Poly(N-arylenbenzimidazoles) via aromatic nucleophilic displacement

NASA Technical Reports Server (NTRS)

Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Smith, Joseph G., Jr. (Inventor)

1995-01-01

Novel poly(N-arylenebenzimidazole)s (PNABIs) are prepared by the aromatic nucleophilic displacement reaction of novel di(hydroxyphenyl-N-arylene benzimidazole) monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N,N-dimethylacetamide using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. The di(hydroxyphenyl N-arylenebenzimidazole) monomers are synthesized by reacting phenyl 4-hydroxybenzoate with bis(2-aminoanilino) arylenes in diphenylsulfone. Moderate molecular weight PNABIs of new chemical structures were prepared that exhibit a favorable combination of physical and mechanical properties. The use of the novel di(hydroxyphenyl N-arylenebenzimidazole)s permits a more economical and easier way to prepare PNABIs than previous routes.

Poly(N-arylenebenzimidazole)s via aromatic nucleophilic displacement

NASA Technical Reports Server (NTRS)

Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Smith, Jr., Joseph G. (Inventor)

1996-01-01

Novel poly(N-arylenebenzimidazole)s (PNABls) are prepared by the aromatic nucleophilic displacement reaction of novel di(hydroxyphenyl-N-arylene benzimidazole) monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N,N-dimethylacetamide using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. The di(hydroxyphenyl-N-arylenebenzimidazole) monomers are synthesized by reacting phenyl-4-hydroxybenzoate with bis(2-aminoanilino)arylenes in diphenylsulfone. Moderate molecular weight PNABIs of new chemical structures were prepared that exhibit a favorable combination of physical and mechanical properties. The use of the novel di(hydroxyphenyI-N-arylenebenzimidazole)s permits a more economical and easier way to prepare PNABIs than previous routes.

The hydrothermolysis of the picrate anion: Kinetics and mechanism

USGS Publications Warehouse

Ross, D.S.; Jayaweera, I.

2002-01-01

The hydrothermolysis of the picrate anion in aqueous solution has been studied at 260-325??C in liquid water. At starting pH values above 12, the disappearance of picrate begins immediately and is first order in OH-. At lower pH, there is an induction period preceding the disappearance, and over the pH range 6.7-11.9 there is no pH dependence in the developed reaction phase. Added borate and silicate salts promote the reaction, suggesting their acting as nucleophiles at hydrothermal conditions. Nitrite is an initial product, while acetate is a final product and reflective of a vigorous oxidative sequence consuming the intermediate products. A reaction sequence consistent with the results at the lower pH includes initiation of a chain process by displacement of nitrite by water, followed by nucleophilic displacement of nitrite by nitrite such that a nitro group is replaced by an O-N=O group. The ester then rapidly hydrolyzes, and the net reaction is the production of an additional nitrite with each cycle. A simple modeling of this system satisfactorily fits the experimental findings. ?? 2002 Elsevier Science B.V. All rights reserved.

Redox and Lewis acid relay catalysis: a titanocene/zinc catalytic platform in the development of multicomponent coupling reactions.

PubMed

Gianino, Joseph B; Campos, Catherine A; Lepore, Antonio J; Pinkerton, David M; Ashfeld, Brandon L

2014-12-19

A titanocene-catalyzed multicomponent coupling is described herein. Using catalytic titanocene, phosphine, and zinc dust, zinc acetylides can be generated from the corresponding iodoalkynes to affect sequential nucleophilic additions to aromatic aldehydes. The intermediate propargylic alkoxides are trapped in situ with acetic anhydride, which are susceptible to a second nucleophilic displacement upon treatment with a variety of electron-rich species, including acetylides, allyl silanes, electron-rich aromatics, silyl enol ethers, and silyl ketene acetals. Additionally, employing cyclopropane carboxaldehydes led to ring-opened products resulting from iodine incorporation. Taken together, these results form the basis for a new mode of three-component coupling reactions, which allows for rapid access to value added products in a single synthetic operation.

Poly(1,3,4-oxadiazoles) via aromatic nucleophilic displacement

NASA Technical Reports Server (NTRS)

Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Wolf, Peter (Inventor)

1992-01-01

Poly(1,3,4-oxadiazoles) (POX) are prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenyl) 1,3,4-oxadiazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The polymerizations are carried out in polar aprotic solvents such as sulfolane or diphenylsulfone using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. The di(hydroxyphenyl) 1,3,4-oxadiazole monomers are synthesized by reacting 4-hydroxybenzoic hydrazide with phenyl 4-hydrobenzoate in the melt and also by reacting aromatic dihydrazides with two moles of phenyl 4-hydroxybenzoate in the melt. This synthetic route has provided high molecular weight POX of new chemical structure, is economically and synthetically more favorable than other routes, and allows for facile chemical structure variation due to the large variety of activated aromatic dihalides which are available.

Poly(arylene ether)s That Resist Atomic Oxygen

NASA Technical Reports Server (NTRS)

Connell, John W.; Hergenrother, Paul; Smith, Joseph G., Jr.

1994-01-01

Novel poly(arylene ether)s containing phosphine oxide (PAEPO's) made via aromatic nucleophilic displacement reactions of activated aromatic dihalides (or, in some cases, activated aromatic dinitro compounds) with new bisphenol monomers containing phosphine oxide. Exhibited favorable combination of physical and mechanical properties and resistance to monatomic oxygen in oxygen plasma environment. Useful as adhesives, coatings, films, membranes, moldings, and composite matrices.

Deuterium and oxygen-18 isotope effects on nucleophilic displacement by water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, J.

1981-01-01

Kinetic deuterium isotope effects (k/sub H/sub 2/O//k/sub D/sub 2/O/) have been measured for nucleophilic attack by water at primary alkyl carbon (S-methylthiophenium ion (MeTh+), methyl trifluoromethane-sulfonate (MeOTf), methyl and ethyl perchlorate (MeOClO/sub 3/, EtOClO/sub 3/)) in aprotic solvents (acetonitrile (MeCN) and tetrahydrothiophene-1, 1-dioxide (TMSO/sub 2/; solfolane)) and L/sub 2/O. In L/sub 2/O solvent k/sub H/sub 2/O//k/sub D/sub 2/O/ is significantly greater than unity while it is reduced to near unity in aprotic solvents. The oxygen-18 isotope effect has also been observed to be 1.002 +- 0.004 for the reaction of MeTh/sup +/ with dilute H/sub 2/O in TMSO/sub 2/ atmore » 35/sup 0/C. For the reaction of MeTh/sup +/ and MeOClO/sub 3/ in aprotic solvents the chemical reaction kinetics are discussed.« less

Using heteroaryl-lithium reagents as hydroxycarbonyl anion equivalents in conjugate addition reactions with (S,S)-(+)-pseudoephedrine as chiral auxiliary; enantioselective synthesis of 3-substituted pyrrolidines.

PubMed

Alonso, Beatriz; Ocejo, Marta; Carrillo, Luisa; Vicario, Jose L; Reyes, Efraim; Uria, Uxue

2013-01-18

We have developed an efficient protocol for carrying out the stereocontrolled formal conjugate addition of hydroxycarbonyl anion equivalents to α,β-unsaturated carboxylic acid derivatives using (S,S)-(+)-pseudoephedrine as chiral auxiliary, making use of the synthetic equivalence between the heteroaryl moieties and the carboxylate group. This protocol has been applied as key step in the enantioselective synthesis of 3-substituted pyrrolidines in which, after removing the chiral auxiliary, the heteroaryl moiety is converted into a carboxylate group followed by reduction and double nucleophilic displacement. Alternatively, the access to the same type of heterocyclic scaffold but with opposite absolute configuration has also been accomplished by making use of the regio- and diastereoselective conjugate addition of organolithium reagents to α,β,γ,δ-unsaturated amides derived from the same chiral auxiliary followed by chiral auxiliary removal, ozonolysis, and reductive amination/intramolecular nucleophilic displacement sequence.

Is nucleophilic cleavage chemistry practical for 4-membered heterocycles?

PubMed

Banks, Harold D

2009-11-07

A computational study at the MP2(Full)/6-311++G(d,p)//MP2(Full)/6-31+G(d) level of the ammonolysis of halogen substituted azetidines, oxetanes and thietanes was performed in the gas phase and in the commonly used solvent, acetonitrile. Using the free energy of activation of a benchmark reaction for evaluation of synthetic viability, several haloazetidines and oxetanes that possessed the required reactivity were identified; however, no substituted thietane investigated herein was determined to be synthetically useful under the mild conditions selected for this study. In the case of the azetidines, the side reaction of displacement of halide ion was determined to be the preferred reaction course in acetonitrile; however, the amino product of the reactions of the 2-haloazetidines cleaved at an acceptable rate under mild conditions. For the oxetane derivatives investigated, 2-fluorooxetane proved to be a direct source of ring cleavage product. Nucleophilic cleavage of halogen-substituted azetidines and oxetanes is predicted to be a viable source of functionalized three-carbon moieties under mild conditions in organic synthesis.

Erosion of stereochemical control with increasing nucleophilicity: O-glycosylation at the diffusion limit.

PubMed

Beaver, Matthew G; Woerpel, K A

2010-02-19

Nucleophilic substitution reactions of 2-deoxyglycosyl donors indicated that the reactivity of the oxygen nucleophile has a significant impact on stereoselectivity. Employing ethanol as the nucleophile resulted in a 1:1 (alpha:beta) ratio of diastereomers under S(N)1-like reaction conditions. Stereoselective formation of the 2-deoxy-alpha-O-glycoside was only observed when weaker nucleophiles, such as trifluoroethanol, were employed. The lack of stereoselectivity observed in reactions of common oxygen nucleophiles can be attributed to reaction rates of the stereochemistry-determining step that approach the diffusion limit. In this scenario, both faces of the prochiral oxocarbenium ion are subject to nucleophilic addition to afford a statistical mixture of diastereomeric products. Control experiments confirmed that all nucleophilic substitution reactions were performed under kinetic control.

Mechanism and stereochemistry for nucleophilic attack at carbon of platinum (iv) alkyls: Model reactions for hydrocarbon oxidation with aqueous platinum chlorides. Technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luinstra, G.A.; Labinger, J.A.; Bercaw, J.E.

1992-10-01

Reactions of PtCl4(2-) with RI (R = CH3, CH2CH2OH) in water yield PtCl5R(2-) which were isolated as their NMe4 salts. They decompose in aqueous chloride solution to give ROH and RCL. erythro- and threo-PtCl5(CHDCHDOH)(2-) are obtained by oxidation of PtCl3(cis- and trans CHD=CHD)(-) respectively. Kinetic rate laws and stereochemistry support SN2 displacement by Cl(-) or H[sub 2]O as the mechanism of the decomposition reactions.

Di(hydroxyphenyl)- benzimidazole monomers

NASA Technical Reports Server (NTRS)

Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Smith, Joseph G. (Inventor)

1993-01-01

Di(hydroxyphenyl)benzimidazole monomers were prepared from phenyl-hydroxybenzoate and aromatic bis(o-diamine)s. These monomers were used in the synthesis of soluble polybenzimidazoles. The reaction involved the aromatic nucleophilic displacement of various di(hydroxyphenyl)benzimidazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds in the presence of an alkali metal base. These polymers exhibited lower glass transition temperatures, improved solubility, and better compression moldability over their commercial counterparts.

Hydrolysis of Nerve Agents by Model Nucleophiles: A Computational Study

PubMed Central

Beck, Jeremy M.

2008-01-01

Density functional theory calculations were employed to study the reaction of five nerve agents with model nucleophiles, including EtX− and EtXH (X = O, S, Se) for serine, cysteine and selenocysteine, respectively. Calculations at the B3LYP/6-311++G(2d,p) level of theory predict an exothermic reaction between ethoxide and all of the nerve agents studied. As compared to EtO− as a nucleophile, these reactions become ~30 kcal/mol more endothermic for EtS−, and by ~40 kcal/mol for EtSe−. The equivalent reactions with the neutral nucleophiles (EtXH) were more endothermic. The effect of solvation on the reaction thermochemistry was determined using a polarizable continuum model simulating the dielectric constant of chloroform. While there was a large exothermic shift for reactions involving charged nucleophiles with solvation modeling, the corresponding shift was minimal for the reaction with neutral nucleophiles. PMID:18538754

Fundamental studies of gas phase ionic reactions by ion mobility spectrometry

NASA Technical Reports Server (NTRS)

Giles, K.; Knighton, W. B.; Sahlstrom, K. E.; Grimsrud, E. P.

1995-01-01

Ion mobility spectrometry (IMS) provides a promising approach to the study of gas phase ionic reactions in buffer gases at unusually high pressures. This point is illustrated here by studies of the Sn2 nucleophilic displacement reaction, Cl(-) + CH3Br yields Br + CH3Br, using IMS at atmospheric pressure. The equilibrium clustering reaction, Cl(-)(CHCI3)(n - 1) + CHCI3 yields Cl(-)(CHCI3)(n), where n = 1 and 2, and the effect of clustering on the Sn2 reaction with CH3Br have also been characterized by this IMS-based kinetic method. Present problems and anticipated improvements in the application of ion mobility spectrometry to studies of other gas phase ionic processes are discussed.

Role of choline and glycine betaine in the formation of N,N-dimethylpiperidinium (mepiquat) under Maillard reaction conditions.

PubMed

Bessaire, Thomas; Tarres, Adrienne; Stadler, Richard H; Delatour, Thierry

2014-01-01

This study is the first to examine the role of choline and glycine betaine, naturally present in some foods, in particular in cereal grains, to generate N,N-dimethylpiperidinium (mepiquat) under Maillard conditions via transmethylation reactions involving the nucleophile piperidine. The formation of mepiquat and its intermediates piperidine - formed by cyclisation of free lysine in the presence of reducing sugars - and N-methylpiperidine were monitored over time (240°C, up to 180 min) using high-resolution mass spectrometry in a model system comprised of a ternary mixture of lysine/fructose/alkylating agent (choline or betaine). The reaction yield was compared with data recently determined for trigonelline, a known methylation agent present naturally in coffee beans. The role of choline and glycine betaine in nucleophilic displacement reactions was further supported by experiments carried out with stable isotope-labelled precursors (¹³C- and deuterium-labelled). The results unequivocally demonstrated that the piperidine ring of mepiquat originates from the carbon chain of lysine, and that either choline or glycine betaine furnishes the N-methyl groups. The kinetics of formation of the corresponding demethylated products of both choline and glycine betaine, N,N-demethyl-2-aminoethanol and N,N-dimethylglycine, respectively, were also determined using high-resolution mass spectrometry.

Study of quinones reactions with wine nucleophiles by cyclic voltammetry.

PubMed

Oliveira, Carla M; Barros, António S; Ferreira, António C S; Silva, Artur M S

2016-11-15

Quinones are electrophilic species which can react with various nucleophiles, like wine antioxidants, such as sulfur dioxide or ascorbic acid, thiols, amino acids, and numerous polyphenols. These reactions are very important in wine aging because they mediate oxygen reactions during both production and bottle aging phases. In this work, the major challenge was to determine the interaction between ortho-quinones and wine nucleophiles (amino acids, thiols, and the antioxidants SO2 and ascorbic acid), by cyclic voltammetry. Wine-model solutions with gallic acid, caffeic acid, or (+)-catechin and nucleophilic compounds were used. To understand the effect of nucleophilic addition in wine, a white wine with the same added nucleophiles was also analysed. Cyclic voltammograms were taken with glassy carbon electrode or screen-printed carbon electrodes, respectively, for wine-model and white wines solutions, in the absence and in the presence of nucleophiles. A nucleophilic order profile related to the cathodic current intensity decrease was observed. Copyright © 2016 Elsevier Ltd. All rights reserved.

A quantitative approach to nucleophilic organocatalysis

PubMed Central

Lakhdar, Sami; Maji, Biplab; Ofial, Armin R

2012-01-01

Summary The key steps in most organocatalytic cyclizations are the reactions of electrophiles with nucleophiles. Their rates can be calculated by the linear free-energy relationship log k(20 °C) = s N(E + N), where electrophiles are characterized by one parameter (E) and nucleophiles are characterized by the solvent-dependent nucleophilicity (N) and sensitivity (s N) parameters. Electrophilicity parameters in the range –10 < E < –5 were determined for iminium ions derived from cinnamaldehyde and common organocatalysts, such as pyrrolidines and imidazolidinones, by studying the rates of their reactions with reference nucleophiles. Iminium activated reactions of α,β-unsaturated aldehydes can, therefore, be expected to proceed with nucleophiles of 2 < N < 14, because such nucleophiles are strong enough to react with iminium ions but weak enough not to react with their precursor aldehydes. With the N parameters of enamines derived from phenylacetaldehyde and MacMillan’s imidazolidinones one can rationalize why only strong electrophiles, such as stabilized carbenium ions (–8 < E < –2) or hexachlorocyclohexadienone (E = –6.75), are suitable electrophiles for enamine activated reactions with imidazolidinones. Several mechanistic controversies concerning iminium and enamine activated reactions could thus be settled by studying the reactivities of independently synthesized intermediates. Kinetic investigations of the reactions of N-heterocyclic carbenes (NHCs) with benzhydrylium ions showed that they have similar nucleophilicities to common organocatalysts (e.g., PPh3, DMAP, DABCO) but are much stronger (100–200 kJ mol–1) Lewis bases. While structurally analogous imidazolylidenes and imidazolidinylidenes have comparable nucleophilicities and Lewis basicities, the corresponding deoxy Breslow intermediates differ dramatically in reactivity. The thousand-fold higher nucleophilicity of 2-benzylidene-imidazoline relative to 2-benzylidene-imidazolidine is explained by the gain of aromaticity during electrophilic additions to the imidazoline derivatives. O-Methylated Breslow intermediates are a hundred-fold less nucleophilic than deoxy Breslow intermediates. PMID:23019481

One-pot facile synthesis of 4-amino-1,8-naphthalimide derived Tröger's bases via a nucleophilic displacement approach.

PubMed

Shanmugaraju, Sankarasekaran; McAdams, Deirdre; Pancotti, Francesca; Hawes, Chris S; Veale, Emma B; Kitchen, Jonathan A; Gunnlaugsson, Thorfinnur

2017-09-13

We report here a novel one-pot synthetic strategy for the synthesis of a family of N-alkyl-1,8-naphthalimide based Tröger's bases via a nucleophilic substitution reaction of a common 'precursor' (or a 'synthon') N-aryl-1,8-naphthalimide Tröger's base heated at 80 °C in neat aliphatic primary amine, in overall yield of 65-96%. This methodology provides an efficient and one-step facile route to design 1,8-naphthalimide derived Tröger's base structures in analytically pure form without the use of column chromatography purification, that can be used in medicinal chemistry and as supramolecular scaffolds. We also report the formation of the corresponding anhydride, and the crystallographic analysis of two of the resulting products, that of the N-phenyl-4-amino-1,8-naphthalimide and the anhydride derived Tröger's bases.

Revisiting the Dielectric Constant Effect on the Nucleophile and Leaving Group of Prototypical Backside Sn2 Reactions: a Reaction Force and Atomic Contribution Analysis.

PubMed

Pedraza-González, Laura Milena; Galindo, Johan Fabian; Gonzalez, Ronald; Reyes, Andrés

2016-10-09

The solvent effect on the nucleophile and leaving group atoms of the prototypical F - + CH 3 Cl → CH 3 F + Cl - backside bimolecular nucleophilic substitution reaction (S N 2) is analyzed employing the reaction force and the atomic contributions methods on the intrinsic reaction coordinate (IRC). Solvent effects were accounted for using the polarizable continuum solvent model. Calculations were performed employing eleven dielectric constants, ε, ranging from 1.0 to 78.5, to cover a wide spectrum of solvents. The reaction force data reveals that the solvent mainly influences the region of the IRC preceding the energy barrier, where the structural rearrangement to reach the transition state occurs. A detailed analysis of the atomic role in the reaction as a function of ε reveals that the nucleophile and the carbon atom are the ones that contribute the most to the energy barrier. In addition, we investigated the effect of the choice of nucleophile and leaving group on the ΔE 0 and ΔE ↕ of Y - + CH 3 X → YCH 3 + X - (X,Y= F, Cl, Br, I) in aqueous solution. Our analysis allowed us to find relationships between the atomic contributions to the activation energy and leaving group ability and nucleophilicity.

Major mechanistic differences between the reactions of hydroxylamine with phosphate di- and tri-esters.

PubMed

Medeiros, Michelle; Wanderlind, Eduardo H; Mora, José R; Moreira, Raphaell; Kirby, Anthony J; Nome, Faruk

2013-10-07

Hydroxylamine reacts as an oxygen nucleophile, most likely via its ammonia oxide tautomer, towards both phosphate di- and triesters of 2-hydroxypyridine. But the reactions are very different. The product of the two-step reaction with the triester TPP is trapped by the NH2OH present in solution to generate diimide, identified from its expected disproportionation and trapping products. The reaction with H3N(+)-O(-) shows general base catalysis, which calculations show is involved in the breakdown of the phosphorane addition-intermediate of a two-step reaction. The reactivity of the diester anion DPP(-) is controlled by its more basic pyridyl N. Hydroxylamine reacts preferentially with the substrate zwitterion DPP(±) to displace first one then a second 2-pyridone, in concerted S(N)2(P) reactions, forming O-phosphorylated products which are readily hydrolysed to inorganic phosphate. The suggested mechanisms are tested and supported by extensive theoretical calculations.

A Substrate-Assisted Mechanism of Nucleophile Activation in a Ser-His-Asp Containing C-C Bond Hydrolase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruzzini, Antonio C.; Bhowmik, Shiva; Ghosh, Subhangi

The meta-cleavage product (MCP) hydrolases utilize a Ser–His–Asp triad to hydrolyze a carbon–carbon bond. Hydrolysis of the MCP substrate has been proposed to proceed via an enol-to-keto tautomerization followed by a nucleophilic mechanism of catalysis. Ketonization involves an intermediate, ES red, which possesses a remarkable bathochromically shifted absorption spectrum. We investigated the catalytic mechanism of the MCP hydrolases using DxnB2 from Sphingomonas wittichii RW1. Pre-steady-state kinetic and LC ESI/MS evaluation of the DxnB2-mediated hydrolysis of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid to 2-hydroxy-2,4-pentadienoic acid and benzoate support a nucleophilic mechanism catalysis. In DxnB2, the rate of ES red decay and product formation showed amore » solvent kinetic isotope effect of 2.5, indicating that a proton transfer reaction, assigned here to substrate ketonization, limits the rate of acylation. For a series of substituted MCPs, this rate was linearly dependent on MCP pK a2 (β nuc ~ 1). Structural characterization of DxnB2 S105A:MCP complexes revealed that the catalytic histidine is displaced upon substrate-binding. The results provide evidence for enzyme-catalyzed ketonization in which the catalytic His–Asp pair does not play an essential role. The data further suggest that ES red represents a dianionic intermediate that acts as a general base to activate the serine nucleophile. This substrate-assisted mechanism of nucleophilic catalysis distinguishes MCP hydrolases from other serine hydrolases.« less

An unprecedented chemospecific and stereoselective tandem nucleophilic addition/cycloaddition reaction of nucleophilic carbenes with ketenimines.

PubMed

Cheng, Ying; Ma, Yang-Guang; Wang, Xiao-Rong; Mo, Jun-Ming

2009-01-16

The first study of the reaction between nucleophilic carbenes and ketenimines is reported. The interaction of thiazole and benzothiazole carbenes with ketenimines proceeded in a chemospecific and stereoselective manner to produce thiazole- and benzothiazole-spiro-pyrrole derivatives generally in good yields. The reaction was proposed to proceed via a tandem nucleophilic addition of carbene to the C=N bond of ketenimine followed by a stepwise [3+2] cycloaddition of the 1,3-dipolar intermediate with the C=C bond of ketenimine. This reaction provides a powerful protocol for the construction of novel polyfunctional thiazole-spiro-pyrrole or benzothiazole-spiro-pyrrole compounds that are not readily accessible by other methods.

Preparation and characterization of poly (arylene ether isoxazole)s by fluoride ion-mediated aromatic nucleophilic displacement reactions

NASA Technical Reports Server (NTRS)

Herbert, C. G.; Bass, R. G.

1994-01-01

As part of a continuing effort to prepare novel thermally stable high-performance polymers, poly(arylene ether isoxazole)s have been prepared by fluoride ion-catalyzed aromatic nucleophilic substitution reactions with bis(trimethylsiloxyphenyl) isoxazoles and activated bisarylhalides in diphenyl sulfone. Initial investigation involving the preparation of these materials with isoxazole bisphenols and activated bisarylhalides in the presence of potassium carbonate indicated that, under reaction conditions necessary to prepare high-molecular-weight materials, the isoxazole monomer was converted to an enamino ketone. This side reaction was avoided by using fluoride as a base. However, trimethylsilyl ether derivatives of the isoxazole bisphenols were required in these polymerizations for the preparation of high-molecular-weight materials. Moderate to high inherent viscosity eta(sub inh): 0.43-0.87 dl/g) materials with good thermal stability (air: 409-477 C, helium: 435-512 C) can be prepared by the silyl ether method. Glass transition temperatures ranged from 182 to 225 C for polymers with phenyl pendants and from 170 to 214 C for those without. Molecular weight control by 2% endcapping and the incorporation of a phenyl pendant at the 4 position of the isoxazole is necessary to yield polymers soluble in polar aprotic solvents at room temperature. There is evidence, however, indicating the existence of crosslinks between the polymer chains when the silyl ether approach is utilized.

Oxidative trifluoromethylation and trifluoromethylthiolation reactions using (trifluoromethyl)trimethylsilane as a nucleophilic CF3 source.

PubMed

Chu, Lingling; Qing, Feng-Ling

2014-05-20

The trifluoromethyl group is widely prevalent in many pharmaceuticals and agrochemicals because its incorporation into drug candidates could enhance chemical and metabolic stability, improve lipophilicity and bioavailability, and increase the protein bind affinity. Consequently, extensive attention has been devoted toward the development of efficient and versatile methods for introducing the CF3 group into various organic molecules. Direct trifluoromethylation reaction has become one of the most efficient and important approaches for constructing carbon-CF3 bonds. Traditionally, the nucleophilic trifluoromethylation reaction involves an electrophile and the CF3 anion, while the electrophilic trifluoromethylation reaction involves a nucleophile and the CF3 cation. In 2010, we proposed the concept of oxidative trifluoromethylation: the reaction of nucleophilic substrates and nucleophilic trifluoromethylation reagents in the presence of oxidants. In this Account, we describe our recent studies of oxidative trifluoromethylation reactions of various nucleophiles with CF3SiMe3 in the presence of oxidants. We have focused most of our efforts on constructing carbon-CF3 bonds via direct trifluoromethylation of various C-H bonds. We have demonstrated copper-mediated or -catalyzed or metal-free oxidative C-H trifluoromethylation of terminal alkynes, tertiary amines, arenes and heteroarenes, and terminal alkenes. Besides various C-H bonds, aryl boronic acids proved to be viable nucleophilic coupling partners for copper-mediated or -catalyzed cross-coupling reactions with CF3SiMe3. To further expand the reaction scope, we also applied H-phosphonates to the oxidative trifluoromethylation system to construct P-CF3 bonds. Most recently, we developed silver-catalyzed hydrotrifluoromethylation of unactivated olefins. These studies explore boronic acids, C-H bonds, and P-H bonds as novel nucleophiles in transition-metal-mediated or -catalyzed cross-coupling reactions with CF3SiMe3, opening new viewpoints for future trifluoromethylation reactions. Furthermore, we also achieved the oxidative trifluoromethylthiolation reactions of aryl boronic acids and terminal alkynes to construct carbon-SCF3 bonds by using CF3SiMe3 and elemental sulfur as the nucleophilic trifluoromethylthiolating reagent. These oxidative trifluoromethylation and trifluoromethylthiolation reactions tolerate a wide range of functional groups, affording a diverse array of CF3- and CF3S-containing compounds with high efficiencies, and provide elegant and complementary alternatives to classical trifluoromethylation and trifluoromethylthiolation reactions. Because of the importance of the CF3 and SCF3 moieties in pharmaceuticals and agrochemicals, these reactions would have potential applications in the life science fields.

Five- and six-membered ring opening of pyroglutamic diketopiperazine.

PubMed

Parrish, Dennis A; Mathias, Lon J

2002-03-22

A variety of ring-opening reactions of pyroglutamic diketopiperazine at both the five-membered and six-membered rings is described. Mild, basic conditions facilitate nucleophilic attack by amines at the diketopiperazine carbonyls giving pyroglutamides in excellent yield. Reaction with nucleophiles under acidic conditions give bis-glutamate derivatives of 2,5-diketopiperazine (DKP). These reactions provide simple, two-step sequences to pyroglutamides and symmetrical diketopiperazines from commercial pyroglutamic acid with control of product dictated by reaction conditions, catalyst, and nucleophile.

Reactions of aromatic diazonium salts with unsaturated compounds in the presence of nucleophiles

NASA Astrophysics Data System (ADS)

Grishchuk, B. D.; Gorbovoi, P. M.; Ganushchak, N. I.; Dombrovskii, A. V.

1994-03-01

The review surveys the reactions of aromatic diazonium salts with diene and monounsaturated compounds in the presence of nucleophiles. Certain further reactions of the reaction products and their application are considered. The bibliography includes 63 references.

Nucleophilic Substitution Reactions Using Phosphine Nucleophiles: An Introduction to Phosphorus-31 NMR

ERIC Educational Resources Information Center

Sibbald, Paul A.

2015-01-01

Nuclear magnetic resonance (NMR) spectroscopy is commonly used in modern synthetic chemistry to monitor the conversion of reactants to products. Since instruction in the use of NMR spectroscopy typically does not occur until after the introduction of nucleophilic substitution reactions, organic chemistry students are not able to take advantage of…

Polybenzoxazole via aromatic nucleophilic displacement

NASA Technical Reports Server (NTRS)

Hergenrother, Paul M. (Inventor); Connell, John W. (Inventor); Smith, Joseph G., Jr. (Inventor)

1993-01-01

Polybenzoxazoles (PBO) are heterocyclic macromolecules which were first synthesized in a two-step process by the initial formation of aromatic diacid chlorides with bis(o-aminophenol)s through solution condensation of aromatic diacid chlorides with bis(o-aminophenol)s followed by thermal cyclodehydration. Since then several methods were utilized in their synthesis. The most common synthetic method for PBO involves a polycondensation of bis(o-aminophenol)s with aromatic diacid diphenyl esters. Another preparative route involves the solution polycondensation of the hydrochloride salts of bis(o-amino phenol)s with aromatic diacids in polyphosphoric acid. Another synthetic method involves the initial formation of poly(o-hydroxy amide)s from silylated bis(o-aminophenol)s with aromatic diacid chlorides followed by thermal cyclodehydration to PBO. A recent preparative route involves the reaction of aromatic bisphenols with bis(fluorophenyl) benzoxazoles by the displacement reaction to form PBO. The novelty of the present invention is that high molecular weight PBO of new chemical structures are prepared that exhibit a favorable combination of physical and mechanical properties.

Citrus Peel Additives for One-Pot Triazole Formation by Decarboxylation, Nucleophilic Substitution, and Azide-Alkyne Cycloaddition Reactions

ERIC Educational Resources Information Center

Mendes, Desiree E.; Schoffstall, Allen M.

2011-01-01

This undergraduate organic laboratory experiment consists of three different reactions occurring in the same flask: a cycloaddition reaction, preceded by decarboxylation and nucleophilic substitution reactions. The decarboxylation and cycloaddition reactions occur using identical Cu(I) catalyst and conditions. Orange, lemon, and other citrus fruit…

Chemoselective reductive nucleophilic addition to tertiary amides, secondary amides, and N-methoxyamides.

PubMed

Nakajima, Minami; Oda, Yukiko; Wada, Takamasa; Minamikawa, Ryo; Shirokane, Kenji; Sato, Takaaki; Chida, Noritaka

2014-12-22

As the complexity of targeted molecules increases in modern organic synthesis, chemoselectivity is recognized as an important factor in the development of new methodologies. Chemoselective nucleophilic addition to amide carbonyl centers is a challenge because classical methods require harsh reaction conditions to overcome the poor electrophilicity of the amide carbonyl group. We have successfully developed a reductive nucleophilic addition of mild nucleophiles to tertiary amides, secondary amides, and N-methoxyamides that uses the Schwartz reagent [Cp2 ZrHCl]. The reaction took place in a highly chemoselective fashion in the presence of a variety of sensitive functional groups, such as methyl esters, which conventionally require protection prior to nucleophilic addition. The reaction will be applicable to the concise synthesis of complex natural alkaloids from readily available amide groups. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dehalogenation of arenes via SN2 reactions at bromine: competition with nucleophilic aromatic substitution.

PubMed

Gronert, Scott; Garver, John M; Nichols, Charles M; Worker, Benjamin B; Bierbaum, Veronica M

2014-11-21

The gas-phase reactions of carbon- and nitrogen-centered nucleophiles with polyfluorobromobenzenes were examined in a selected-ion flow tube (SIFT) and modeled computationally at the MP2/6-31+G(d,p)//MP2/6-31+G(d) level. In the gas-phase experiments, rate constants and branching ratios were determined. The carbon nucleophiles produce expected nucleophilic aromatic substitution (SNAr) and proton transfer products along with unexpected products that result from SN2 reactions at the bromine center (polyfluorophenide leaving group). With nitrogen nucleophiles, the SN2 at bromine channel is suppressed. In the SNAr channels, the "element effect" is observed, and fluoride loss competes with bromide loss. The computational modeling indicates that all the substitution barriers are well below the entrance channel and that entropy and dynamics effects control the product distributions.

The α-Effect and Competing Mechanisms: The Gas-Phase Reactions of Microsolvated Anions with Methyl Formate

NASA Astrophysics Data System (ADS)

Thomsen, Ditte L.; Nichols, Charles M.; Reece, Jennifer N.; Hammerum, Steen; Bierbaum, Veronica M.

2014-02-01

The enhanced reactivity of α-nucleophiles, which contain an electron lone pair adjacent to the reactive site, has been demonstrated in solution and in the gas phase and, recently, for the gas-phase SN2 reactions of the microsolvated HOO-(H2O) ion with methyl chloride. In the present work, we continue to explore the significance of microsolvation on the α-effect as we compare the gas-phase reactivity of the microsolvated α-nucleophile HOO-(H2O) with that of microsolvated normal alkoxy nucleophiles, RO-(H2O), in reactions with methyl formate, where three competing reactions are possible. The results reveal enhanced reactivity of HOO-(H2O) towards methyl formate, and clearly demonstrate the presence of an overall α-effect for the reactions of the microsolvated α-nucleophile. The association of the nucleophiles with a single water molecule significantly lowers the degree of proton abstraction and increases the SN2 and BAC2 reactivity compared with the unsolvated analogs. HOO-(H2O) reacts with methyl formate exclusively via the BAC2 channel. While microsolvation lowers the overall reaction efficiency, it enhances the BAC2 reaction efficiency for all anions compared with the unsolvated analogs. This may be explained by participation of the solvent water molecule in the BAC2 reaction in a way that continuously stabilizes the negative charge throughout the reaction.

Mechanism of alkoxy groups substitution by Grignard reagents on aromatic rings and experimental verification of theoretical predictions of anomalous reactions.

PubMed

Jiménez-Osés, Gonzalo; Brockway, Anthony J; Shaw, Jared T; Houk, K N

2013-05-01

The mechanism of direct displacement of alkoxy groups in vinylogous and aromatic esters by Grignard reagents, a reaction that is not observed with expectedly better tosyloxy leaving groups, is elucidated computationally. The mechanism of this reaction has been determined to proceed through the inner-sphere attack of nucleophilic alkyl groups from magnesium to the reacting carbons via a metalaoxetane transition state. The formation of a strong magnesium chelate with the reacting alkoxy and carbonyl groups dictates the observed reactivity and selectivity. The influence of ester, ketone, and aldehyde substituents was investigated. In some cases, the calculations predicted the formation of products different than those previously reported; these predictions were then verified experimentally. The importance of studying the actual system, and not simplified models as computational systems, is demonstrated.

Mechanism of Alkoxy Groups Substitution by Grignard Reagents on Aromatic Rings and Experimental Verification of Theoretical Predictions of Anomalous Reactions

PubMed Central

Jiménez-Osés, Gonzalo; Brockway, Anthony J.; Shaw, Jared T.; Houk, K. N.

2013-01-01

The mechanism of direct displacement of alkoxy groups in vinylogous and aromatic esters by Grignard reagents, a reaction that is not observed with expectedly better tosyloxy leaving groups, is elucidated computationally. The mechanism of this reaction has been determined to proceed through the inner-sphere attack of nucleophilic alkyl groups from magnesium to the reacting carbons via a metalaoxetane transition state. The formation of a strong magnesium chelate with the reacting alkoxy and carbonyl groups dictates the observed reactivity and selectivity. The influence of ester, ketone and aldehyde substituents was investigated. In some cases, the calculations predicted the formation of products different than those previously reported; these predictions were then verified experimentally. The importance of studying the actual system, and not simplified models as computational systems, is demonstrated. PMID:23601086

Substituted 1,1,1-Triaryl-2,2,2-Trifluoroethanes and Processes for their Synthesis

NASA Technical Reports Server (NTRS)

Alston, William B. (Inventor); Gratz, Roy F. (Inventor)

1999-01-01

Synthetic procedures to tetraalkyls. tetraacids and dianhydrides substituted 1,1,1-triaryl-2,2,2-trifluoroethanes which comprises: (1) 1.1-bis(dialkylaryl)-1-aryl-2,2,2 -trifluoroethane, (2) 1,1-bis(dicarboxyaryl)-1-aryl-2.2,2- trifluoroethane or (3) cyclic dianhydride or diamine of 1,1-bis(dialkylaryl)-1-aryl-2,2,2- trifluoroethanes. The synthesis of (1) is accomplished by the condensation reaction of an aryltrifluoromethyl ketone with a dialkylaryl compound. The synthesis of (2) is accomplished by oxidation of (1). The synthesis dianhydride of (3) is accomplished by the conversion of (2) to its corresponding cyclic dianhydride. The synthesis of the diamine is accomplished by the similar reaction of an aryltrifluoromethyl ketone with aniline or alkyl substituted or disubstituted anihnes. Also, other derivatives of the above are formed by nucleophilic displacement reactions.

Substituted 1,1,1-triaryl 2,2,2-trifluoroethanes and processes for their synthesis

NASA Technical Reports Server (NTRS)

Alston, William B. (Inventor); Gratz, Roy F. (Inventor)

1992-01-01

Synthetic procedures to tetraalkyls, tetraacids, and dianhydrides substituted 1,1,1-triaryl 2,2,2-trifluoroethanes which comprises: (1) 1,1-bis(dialkylaryl) 1-aryl-2,2,2-trifluoroethane, (2) 1,1-bis(dicarboxyaryl) 1-aryl-2,2,2-trifluoroethane, or (3) cyclic dianhydride or diamine of 1,1-bis(dialkylaryl) 1-aryl-2,2,2-trifluoroethanes. The synthesis of (1) is accomplished by the condensation reaction of an aryltrifluoromethyl ketone with a dialkylaryl compound. The synthesis of (2) is accomplished by oxidation of (1). The synthesis dianhydride of (3) is accomplished by the conversion of (2) to its corresponding cyclic dianhydride. The synthesis of the diamine is accomplished by the similar reaction of an aryltrifluoromethyl ketone with aniline or alkyl substituted or disubstituted anilines. Also, other derivatives of the above are formed by nucleophilic displacement reactions.

Polyimides containing pendent trifluoromethyl groups

NASA Technical Reports Server (NTRS)

Havens, S. J.; Hergenrother, P. M.

1993-01-01

Several new polyimides containing trifluoromethyl groups were prepared from the reaction of various aromatic dianhydrides and two new diamines containing trifluoromethyl groups, 4,4'-bis(3-amino-5-trifluoromethylphenoxy)biphenyl and l,4-bis(3-amino-5-trifluoromethylphenoxy)benzene. The diamines were prepared from the aromatic nucleophilic displacement of the disodium salts of 4,4'-biphenol or hydroquinone with 3,5-dinitrobenzotrifluoride followed by hydrogenation of the resultant dinitro compounds. The thermally cured polyimides exhibited glass transition temperatures between 186 and 262 C. By thermogravimetric analysis, the polyimides exhibited 5 percent weight losses at 484-527 C in nitrogen and 452-506 C in air.

Deciphering Front-Side Complex Formation in SN2 Reactions via Dynamics Mapping.

PubMed

Szabó, István; Olasz, Balázs; Czakó, Gábor

2017-07-06

Due to their importance in organic chemistry, the atomistic understanding of bimolecular nucleophilic substitution (S N 2) reactions shows exponentially growing interest. In this publication, the effect of front-side complex (FSC) formation is uncovered via quasi-classical trajectory computations combined with a novel analysis method called trajectory orthogonal projection (TOP). For both F - + CH 3 Y [Y = Cl,I] reactions, the lifetime distributions of the F - ···YCH 3 front-side complex revealed weakly trapped nucleophiles (F - ). However, only the F - + CH 3 I reaction features strongly trapped nucleophiles in the front-side region of the prereaction well. Interestingly, both back-side and front-side attack show propensity to long-lived FSC formation. Spatial distributions of the nucleophile demonstrate more prominent FSC formation in case of the F - + CH 3 I reaction compared to F - + CH 3 Cl. The presence of front-side intermediates and the broad spatial distribution in the back-side region may explain the indirect nature of the F - + CH 3 I reaction.

Ring opening of epoxides with C-nucleophiles.

PubMed

Faiz, Sadia; Zahoor, Ameer Fawad

2016-11-01

Ring opening of epoxides has been an area of interest for organic chemists, owing to their reactivity toward nucleophiles. Such reactions yield important products depending on the type of nucleophiles used. This review article covers the synthetic approaches (1991-2015) used for the ring opening of epoxides via carbon nucleophiles.

Origin of Enhanced Reactivity of a Microsolvated Nucleophile in Ion Pair SN2 Reactions: The Cases of Sodium p-Nitrophenoxide with Halomethanes in Acetone.

PubMed

Li, Qiang-Gen; Xu, Ke; Ren, Yi

2015-04-30

In a kinetic experiment on the SN2 reaction of sodium p-nitrophenoxide with iodomethane in acetone-water mixed solvent, Humeres et al. (J. Org. Chem. 2001, 66, 1163) found that the reaction depends strongly on the medium, and the fastest rate constant was observed in pure acetone. The present work tries to explore why acetone can enhance the reactivity of the title reactions. Accordingly, we make a mechanistic study on the reactions of sodium p-nitrophenoxide with halomethanes (CH3X, X = Cl, Br, I) in acetone by using a supramolecular/continuum model at the PCM-MP2/6-311+G(d,p)//B3LYP/6-311+G(d,p) level, in which the ion pair nucleophile is microsolvated by one to three acetone molecules. We compared the reactivity of the microsolvated ion pair nucleophiles with solvent-free ion pair and anionic ones. Our results clearly reveal that the microsolvated ion pair nucleophile is favorable for the SN2 reactions; meanwhile, the origin of the enhanced reactivity induced by microsolvation of the nucleophile is discussed in terms of the geometries of transition state (TS) structures and activation strain model, suggesting that lower deformation energies and stronger interaction energies between the deformed reactants in the TS lead to the lower overall reaction barriers for the SN2 reaction of microsolvated sodium p-nitrophenoxide toward halomethanes in acetone.

Non-stabilized nucleophiles in Cu-catalysed dynamic kinetic asymmetric allylic alkylation

NASA Astrophysics Data System (ADS)

You, Hengzhi; Rideau, Emeline; Sidera, Mireia; Fletcher, Stephen P.

2015-01-01

The development of new reactions forming asymmetric carbon-carbon bonds has enabled chemists to synthesize a broad range of important carbon-containing molecules, including pharmaceutical agents, fragrances and polymers. Most strategies to obtain enantiomerically enriched molecules rely on either generating new stereogenic centres from prochiral substrates or resolving racemic mixtures of enantiomers. An alternative strategy--dynamic kinetic asymmetric transformation--involves the transformation of a racemic starting material into a single enantiomer product, with greater than 50 per cent maximum yield. The use of stabilized nucleophiles (pKa < 25, where Ka is the acid dissociation constant) in palladium-catalysed asymmetric allylic alkylation reactions has proved to be extremely versatile in these processes. Conversely, the use of non-stabilized nucleophiles in such reactions is difficult and remains a key challenge. Here we report a copper-catalysed dynamic kinetic asymmetric transformation using racemic substrates and alkyl nucleophiles. These nucleophiles have a pKa of >=50, more than 25 orders of magnitude more basic than the nucleophiles that are typically used in such transformations. Organometallic reagents are generated in situ from alkenes by hydrometallation and give highly enantioenriched products under mild reaction conditions. The method is used to synthesize natural products that possess activity against tuberculosis and leprosy, and an inhibitor of para-aminobenzoate biosynthesis. Mechanistic studies indicate that the reaction proceeds through a rapidly isomerizing intermediate. We anticipate that this approach will be a valuable complement to existing asymmetric catalytic methods.

FACTORS AFFECTING THE ELECTROPHILICITY AND NUCLEOPHILICITY OF REAGENTS.

DTIC Science & Technology

The apparent simplicity of the reactions of Malachite Green cation (bis-(p-dimethylaminophenyl), phenylmethyl cation) with nucleophilic reagents...initiated to study the rates of the reactions of a series of Malachite Green cations with a number of nucleophilies in several dipolar aprotic solvents, and the same reactions in water for comparison. (Author)

Dehalogenation of aromatics by nucleophilic aromatic substitution.

PubMed

Sadowsky, Daniel; McNeill, Kristopher; Cramer, Christopher J

2014-09-16

Nucleophilic aromatic substitution has been implicated as a mechanism for both the biotic and abiotic hydrodehalogenation of aromatics. Two mechanisms for the aqueous dehalogenation of aromatics involving nucleophilic aromatic substitution with hydride as a nucleophile are investigated using a validated density functional and continuum solvation protocol. For chlorinated and brominated aromatics, nucleophilic addition ortho to carbon-halogen bonds via an anionic intermediate is predicted to be the preferred mechanism in the majority of cases, while concerted substitution is predicted to be preferred for most fluorinated aromatics. Nucleophilic aromatic substitution reactions with the hydroxide and hydrosulfide anions as nucleophiles are also investigated and compared.

Substituted 1,1,1-triaryl-2,2,2-trifluoroethanes and processes for their synthesis

NASA Technical Reports Server (NTRS)

Alston, William B. (Inventor); Gratz, Roy F. (Inventor)

1994-01-01

Synthetic procedures are given for tetraalkyl, tetraacid and dianhydrides substituted 1,1,1-triaryl-2,2,2-trifluoroethanes which comprises: (1) 1,1-bis (dialkylaryl) 1-aryl-2,2,2 trifluoroethane; (2) 1,1-bis (dicarboxyaryl) 1-aryl-2,2,2 trifluoroethane; or (3) cyclic dianhydride or diamine of 1,1-bis (dialkylaryl) 1-aryl-2,2,2 trifluoroethanes. The synthesis of (1) is accomplished by the condensation reaction of an aryltrifluoromethyl ketone with a dialkylaryl compound. The synthesis of (2) is accomplished by oxidation of (1). The synthesis dianhydride of (3) is accomplished by the conversion of (2) to its corresponding cyclic dianhydride. The synthesis of the diamine is accomplished by the similar reaction of an aryltrifluoromethyl ketone with aniline or alkyl substituted or disubstituted anilines. Also, other derivatives of the above are formed by nucleophilic displacement reactions.

Substituted 1,1,1-triaryl-2,2,2-trifluoroethanes and processes for their synthesis

NASA Technical Reports Server (NTRS)

Alston, William B. (Inventor); Gratz, Roy F. (Inventor)

1989-01-01

Synthetic procedures are disclosed for tetraalkyls, tetraacids, and dianhydrides substituted 1,1,1-triaryl 2,2,2-trifluoroethanes which comprises: (1) 1,1-bis (dialkylaryl) 1-aryl 2,2,2-trifluoroethane, (2) 1,1-bis (dicarboxyaryl) 1-aryl 2,2,2-trifluoroethane, or (3) cyclic dianhydride or diamine of 1,1-bis (dialkylaryl) 1-aryl 2,2,2-trifluoroethanes. The synthesis of (1) is accomplished by the condensation reaction of an aryltrifluoromethyl ketone with a dialkylaryl compound. The synthesis of (2) is accomplished by the oxidation of (1). The synthesis dianhydride of (3) is accomplished by the conversion of (2) to its corresponding cyclic dianhydride. The synthesis of the diamine is accomplished by the similar reaction of an aryltrifluoromethyl ketone with aniline or aklyl substituted or disubstituted anilines. Also, other derivatives of the above are formed by nucleophilic displacement reactions.

The α-effect in gas-phase SN2 reactions of microsolvated anions: methanol as a solvent.

PubMed

Thomsen, Ditte L; Reece, Jennifer N; Nichols, Charles M; Hammerum, Steen; Bierbaum, Veronica M

2014-09-18

The α-effect, an enhanced reactivity of nucleophiles with a lone-pair adjacent to the reaction center, has been studied in solution for several decades. The gas-phase α-effect has recently been documented in studies of SN2 reactions as well as in competing reactions for both bare and microhydrated anions. In the present work we extend our studies of the significance of microsolvation on the α-effect, employing methanol as the solvent, in the expectation that the greater stability of the methanol cluster relative to the water cluster will lower the reactivity and thereby allow studies over a wider efficiency range. We compare the gas-phase reactivity of the microsolvated α-nucleophile HOO(-)(CH3OH) to that of microsolvated normal alkoxy nucleophiles, RO(-)(CH3OH) in reactions with CH3Cl and CH3Br. The results reveal enhanced reactivity of HOO(-)(CH3OH) toward both methyl halides relative to the normal nucleophiles, and clearly demonstrate the presence of an α-effect for the microsolvated α-nucleophile. The highly exothermic reactions with methyl bromide result in a smaller Brønsted βnuc value than observed for methyl chloride, and the α-effect in turn influences the reactions with methyl chloride more than with methyl bromide. Computational investigations reveal that reactions with methyl bromide proceed through earlier transition states with less advanced bond formation compared to the related reactions of methyl chloride. In addition, solvent interactions for HOO(-) are quite different from those with the normal nucleophiles at the transition state, indicating that differential solvation may well contribute to the α-effect. The greater thermodynamic and kinetic stability of the anion-methanol clusters relative to the anion-water clusters accounts well for the differences in the influence of solvation with the two protic polar solvents.

Nucleophilic Substitution in Solution: Activation Strain Analysis of Weak and Strong Solvent Effects

PubMed Central

Hamlin, Trevor A.; van Beek, Bas; Wolters, Lando P.

2018-01-01

Abstract We have quantum chemically studied the effect of various polar and apolar solvents on the shape of the potential energy surface (PES) of a diverse collection of archetypal nucleophilic substitution reactions at carbon, silicon, phosphorus, and arsenic by using density functional theory at the OLYP/TZ2P level. In the gas phase, all our model SN2 reactions have single‐well PESs, except for the nucleophilic substitution reaction at carbon (SN2@C), which has a double‐well energy profile. The presence of the solvent can have a significant effect on the shape of the PES and, thus, on the nature of the SN2 process. Solvation energies, charges on the nucleophile or leaving group, and structural features are compared for the various SN2 reactions in a spectrum of solvents. We demonstrate how solvation can change the shape of the PES, depending not only on the polarity of the solvent, but also on how the charge is distributed over the interacting molecular moieties during different stages of the reaction. In the case of a nucleophilic substitution at three‐coordinate phosphorus, the reaction can be made to proceed through a single‐well [no transition state (TS)], bimodal barrier (two TSs), and then through a unimodal transition state (one TS) simply by increasing the polarity of the solvent. PMID:29457865

Chemistry and properties of new poly(arylene ether imidazoles)

NASA Technical Reports Server (NTRS)

Connell, J. W.; Hergenrother, P. M.

1990-01-01

As part of a program to develop high-temperature high-performance structural resins for aerospace applications, the chemistry and properties of new poly(arylene ether imidazoles) were investigated. The polymers were prepared by the nucleophilic displacement reaction of aromatic bis(imidazolephenols) with activated aromatic difluoro compounds. The amorphous thermoplastic polymers exhibited glass transition temperatures from 230 to 301 C, inherent viscosities from 0.46 to 1.46 dL/g, and number-average molecular weights as high as 59,300 g/mole. The polymers exhibit good toughness, adhesive, composite, and film properties. The chemical, physical, and mechanical properties of these materials are discussed.

Palladium-catalyzed heteroannulation of 1,3-dienes to form alpha-alkylidene-gamma-butyrolactones.

PubMed

Gagnier, S V; Larock, R C

2000-03-10

alpha-Alkylidene-gamma-butyrolactones are readily prepared by the palladium-catalyzed heteroannulation of a variety of 1,3-dienes by alpha-iodo and alpha-bromo acrylic acids. The best results are obtained by employing a catalytic amount of the sterically hindered chelating alkyl phosphine D-t-BPF [(di-tert-butylphosphino)ferrocene]. In most cases, this process is highly regioselective. The reaction is believed to proceed via (1) oxidative addition of the vinylic halide to Pd(0), (2) organopalladium addition to the less hindered end of the 1,3-diene to form a pi-allylpalladium intermediate, and (3) nucleophilic displacement of the palladium by the carboxylate ion.

Synthesis of uniform cyclodextrin thioethers to transport hydrophobic drugs

PubMed Central

Becker, Lisa F; Schwarz, Dennis H

2014-01-01

Summary Methyl and ethyl thioether groups were introduced at all primary positions of α-, β-, and γ-cyclodextrin by nucleophilic displacement reactions starting from the corresponding per-(6-deoxy-6-bromo)cyclodextrins. Further modification of all 2-OH positions by etherification with iodo terminated triethylene glycol monomethyl ether (and tetraethylene glycol monomethyl ether, respectively) furnished water-soluble hosts. Especially the β-cyclodextrin derivatives exhibit very high binding potentials towards the anaesthetic drugs sevoflurane and halothane. Since the resulting inclusion compounds are highly soluble in water at temperatures ≤37 °C they are good candidates for new aqueous dosage forms which would avoid inhalation anaesthesia. PMID:25550759

Some chemical and physical properties of nisin, a small-protein antibiotic produced by Lactococcus lactis.

PubMed Central

Liu, W; Hansen, J N

1990-01-01

Nisin is a small gene-encoded antimicrobial protein produced by Lactococcus lactis that contains unusual dehydroalanine and dehydrobutyrine residues. The reactivity of these residues toward nucleophiles was explored by reacting nisin with a variety of mercaptans. The kinetics of reaction with 2-mercaptoethane-sulfonate and thioglycolate indicated that the reaction pathway includes a binding step. Reaction of nisin at high pH resulted in the formation of multimeric products, apparently as a result of intramolecular and intermolecular reactions between nucleophilic groups and the dehydro residues. One of the nucleophiles had a pKa of about 9.8. The unique vinyl protons of the dehydro residues that give readily identifiable proton nuclear magnetic resonances were used to observe the addition of nucleophiles to the dehydro moiety. After reaction with nucleophiles, nisin lost its antibiotic activity and no longer showed the dehydro resonances, indicating that the dehydro groups had been modified. The effect of pH on the solubility of nisin was determined; the solubility was quite high at low pH (57 mg/ml at pH 2) and was much lower at high pH (0.25 mg/ml at pH 8 to 12), as measured before significant pH-induced chemical modification had occurred. High-performance liquid chromatography on a C18 column was an effective technique for separating unmodified nisin from its reaction products. The cyanogen bromide cleavage products of nisin were about 90% less active toward inhibition of bacterial spore outgrowth than was native nisin. These results are consistent with earlier observations, which suggested that the dehydro residues of nisin have a role in the mechanism of antibiotic action, in which they act as electrophilic Michael acceptors toward nucleophiles in the cellular target. Images PMID:2119570

A Redox-Nucleophilic Dual-Reactable Probe for Highly Selective and Sensitive Detection of H2S: Synthesis, Spectra and Bioimaging

NASA Astrophysics Data System (ADS)

Zhang, Changyu; Wang, Runyu; Cheng, Longhuai; Li, Bingjie; Xi, Zhen; Yi, Long

2016-07-01

Hydrogen sulfide (H2S) is an important signalling molecule with multiple biological functions. The reported H2S fluorescent probes are majorly based on redox or nucleophilic reactions. The combination usage of both redox and nucleophilic reactions could improve the probe’s selectivity, sensitivity and stability. Herein we report a new dual-reactable probe with yellow turn-on fluorescence for H2S detection. The sensing mechanism of the dual-reactable probe was based on thiolysis of NBD (7-nitro-1,2,3-benzoxadiazole) amine (a nucleophilic reaction) and reduction of azide to amine (a redox reaction). Compared with its corresponding single-reactable probes, the dual-reactable probe has higher selectivity and fluorescence turn-on fold with magnitude of multiplication from that of each single-reactable probe. The highly selective and sensitive properties enabled the dual-reactable probe as a useful tool for efficiently sensing H2S in aqueous buffer and in living cells.

Theoretical Investigation of the Gas-Phase SN2 Reactions of Anionic and Neutral Nucleophiles with Chloramines.

PubMed

Liu, Jieqing; Dong, Meng; Zhang, Shuo; Liu, Yong Dong; Zhong, Rugang

2018-03-22

The S N 2 reactions at nitrogen center (S N 2@N) play a significant role in organic synthesis, carcinogenesis, and the formation of some environmentally toxic compounds. However, the S N 2@N reactions specifically for neutral compounds as nucleophiles are less known. In this work, reactions of dimethylamine (DMA) and F - with NH 2 Cl were investigated as model reactions to validate an accurate functional from 24 DFT functionals by comparing with the CCSD(T) reference data. M06-2X functional was found to perform best and applied to systematically explore the trends in reactivity for halides (F - and Cl - ) and simple amines toward the substrates NH 2 Cl and NHCl 2 (S N 2@N) as well as CH 3 Cl and CH 2 Cl 2 (S N 2@C). The computational results show that the backside inversion channel dominates most the S N 2@N reactions except for the case of F - + NHCl 2 , which reacts preferentially via proton transfer. The overall activation free energies (Δ G ‡ ) of the inversion channel for the S N 2 reactions of F - and Cl - with chloramines are negative, whereas those for amines as nucleophiles are around 30-44 kcal/mol. The S N 2@N reactions for all the nucleophiles investigated here are faster than the corresponding S N 2@C. Moreover, amines react faster when they have a higher extent of methyl substitution. Additionally, the energy gap between the HOMO of nucleophile and LUMO of substrate generally correlates well with Δ G ‡ of the corresponding S N 2 reactions, which is consistent with previous results.

First kinetic discrimination between carbon and oxygen reactivity of enols.

PubMed

García-Río, Luis; Mejuto, Juan C; Parajó, Mercedes; Pérez-Lorenzo, Moisés

2008-11-07

Nitrosation of enols shows a well-differentiated behavior depending on whether the reaction proceeds through the carbon (nucleophilic catalysis is observed) or the oxygen atom (general acid-base catalysis is observed). This is due to the different operating mechanisms for C- and O-nitrosation. Nitrosation of acetylacetone (AcAc) shows a simultaneous nucleophilic and acid-base catalysis. This simultaneous catalysis constitutes the first kinetic evidence of two independent reactions on the carbon and oxygen atom of an enol. The following kinetic study allows us to determine the rate constants for both reaction pathways. A similar reactivity of the nucleophilic centers with the nitrosonium ion is observed.

No Acid Required: 4π and 6π Electrocyclization Reactions of Dienyl Diketones for the Synthesis of Cyclopentenones and 2H-Pyrans

PubMed Central

2015-01-01

The 1,6-conjugate addition of nucleophiles to dienyl diketones produces either cyclopentenone or 2H-pyran products with high selectivity through either Nazarov (4π) or 6π electrocyclization, respectively. The outcome of the reaction is dependent upon the nature of the nucleophile used. Nucleophiles that are anionic or easily deprotonated exclusively produce cyclopentenones via Nazarov cyclization, whereas the neutral nucleophile DABCO promotes 6π cyclization to afford 2H-pyrans. Experimental evidence is presented for both retro-4π and -6π electrocyclization in these systems, lending support to the bifurcated mechanistic hypothesis proposed for these cyclizations. PMID:25325706

Nucleophilic Aromatic Substitution Between Halogenated Benzene Dopants and Nucleophiles in Atmospheric Pressure Photoionization.

PubMed

Kauppila, Tiina J; Haack, Alexander; Kroll, Kai; Kersten, Hendrik; Benter, Thorsten

2016-03-01

In a preceding work with dopant assisted-atmospheric pressure photoionization (DA-APPI), an abundant ion at [M + 77](+) was observed in the spectra of pyridine and quinoline with chlorobenzene dopant. This contribution aims to reveal the identity and route of formation of this species, and to systematically investigate structurally related analytes and dopants. Compounds containing N-, O-, and S-lone pairs were investigated with APPI in the presence of fluoro-, chloro-, bromo-, and iodobenzene dopants. Computational calculations on a density functional theory (DFT) level were carried out to study the reaction mechanism for pyridine and the different halobenzenes. The experimental and computational results indicated that the [M + 77](+) ion was formed by nucleophilic aromatic ipso-substitution between the halobenzene radical cation and nucleophilic analytes. The reaction was most efficient for N-heteroaromatic compounds, and it was weakened by sterical effects and enhanced by resonance stabilization. The reaction was most efficient with chloro-, bromo-, and iodobenzenes, whereas with fluorobenzene the reaction was scarcely observed. The calculated Gibbs free energies for the reaction between pyridine and the halobenzenes were shown to increase in the order I < Br < Cl < F. The reaction was found endergonic for fluorobenzene due to the strong C-F bonding, and exergonic for the other halobenzenes. For fluoro- and chlorobenzenes the reaction was shown to proceed through an intermediate state corresponding to [M + dopant](+), which was highly stable for fluorobenzene. For the bulkier bromine and iodine, this intermediate did not exist, but the halogens were shown to detach already during the approach by the nucleophile.

Oxidative cyclization reactions: controlling the course of a radical cation-derived reaction with the use of a second nucleophile.

PubMed

Redden, Alison; Perkins, Robert J; Moeller, Kevin D

2013-12-02

Construction of new ring systems: Oxidative cyclizations (see picture; RVC=reticulated vitreous carbon) have been conducted that use two separate intramolecular nucleophiles to trap an enol ether-derived radical cation intermediate. The reactions provide a means for rapidly trapping the radical cation intermediate in a manner that avoids competitive decomposition reactions. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Safer, Discovery-Based Nucleophilic Substitution Experiment

ERIC Educational Resources Information Center

Horowitz, Gail

2009-01-01

A discovery-based nucleophilic substitution experiment is described in which students compare the reactivity of chloride and iodide ions in an S[subscript N]2 reaction. This experiment improves upon the well-known "Competing Nucleophiles" experiment in that it does not involve the generation of hydrogen halide gas. The experiment also introduces…

Experimental Determination of Activation Energy of Nucleophilic Aromatic Substitution on Porphyrins

ERIC Educational Resources Information Center

Rizvi, Waqar; Khwaja, Emaad; Siddiqui, Saim; Bhupathiraju, N. V. S. Dinesh K.; Drain, Charles Michael

2018-01-01

A physical organic chemistry experiment is described for second-year college students. Students performed nucleophilic aromatic substitution (NAS) reactions on 5,10,15,20-tetrakis(2,3,4,5,6-pentafluorophenyl)porphyrin (TPPF[subscript 20]) using three different nucleophiles. Substitution occurs preferentially at the 4-position ("para")…

Complications of modeling glycosylation reactions: can the anomeric conformation of a donor determine the glycopyranosyl oxacarbenium ring conformation?

PubMed

Whitfield, Dennis M

2012-07-15

That the ring conformation of glycopyranosyl oxacarbenium ions can influence the stereochemical outcome of glycosylation reactions has been postulated for some time. Some new ionization calculations show that the ultimate conformation (4)H(3) or (5)S(1) of D-glucopyranosyl oxacarbenium ions depends on the initial ϕ(H) (CH-1-C-1-S(+)-SCH(3)) conformation of anomeric thiosulfonium ions. Evidence is also presented that nucleophile:electrophile hydrogen bonded complexes, 1,6-anhydro-carbenium ions and electron rich carbon nucleophile:oxacarbenium ion complexes are all probably artifacts of neglecting counter ions or nucleophiles in the DFT calculation. All three cationic species are likely important for glycosylation reaction side reactions but not as productive species. Copyright © 2012. Published by Elsevier Ltd.

Nucleophilic substitution reaction for post-functionalization of polyoxometalates

DOE PAGES

Yin, Panchao; Li, Qiang; Zhang, Jin; ...

2015-07-06

In this study, a hexamolybdate-based organic inorganic hybrid molecule containing a chloralkane fragment is synthesized and its Cl atom can be substituted by iodine and nitrate through nucleophilic substitution reactions in high yields, which provide a post-functionalization protocol to bring in various additional functional groups into polyoxometalate-based hybrid materials under mild conditions.

Nucleophilic Influences and Origin of the SN2 Allylic Effect.

PubMed

Galabov, Boris; Koleva, Gergana; Schaefer, Henry F; Allen, Wesley D

2018-05-27

The potential energy surfaces for the SN2 reactions of allyl and propyl chlorides with 21 anionic and neutral nucleophiles have been studied using ωB97X-D/6-311++G(3df,2pd) computations. The "allylic effect" on SN2 barriers is well manifested for all reactions and ranges between -0.2 and -4.5 kcal mol-1 in the gas phase. Strong correlations of the SN2 net activation barriers with cation affinities, proton affinities, and electrostatic potentials at nuclei (EPN) demonstrate the powerful influence of electrostatics on these reactions. For the reactions of anionic (but not neutral) nucleophiles with allyl chloride, some of the incoming negative charge (0.2% - 18%) migrates into the carbon chains, which may provide some secondary stabilization of the SN2 transition states. Activation strain analysis provides additional insight into the allylic effect by showing that the energy of geometric distortion for the reactants to reach the SN2 transition state (ΔEstrain) is smaller for each allylic reaction in comparison to its propyl analogue. In many cases the interaction energies (ΔEint) between the substrate and nucleophile in this analysis are more favorable for propyl chloride reactions, but this compensation does not overcome the predominant strain energy effect. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemistry and properties of poly(arylene ether benzoxazole)s

NASA Technical Reports Server (NTRS)

Smith, J. G., Jr.; Connell, J. W.; Hergenrother, P. M.

1992-01-01

Several new poly(arylene ether benzoxazole)s (PAEBs) were prepared by the nucleophilic displacement reaction of activated aromatic difluorides with two novel bis(hydroxyphenyl benzoxazole), using potassium carbonate. The 6F-containing PAEBs exhibited better solubility and higher Tgs than did the 6,6'-bis-(2-(4-hydroxyphenyl)benzoxazole)-derived polymers. Several of the 6,6'bis(2-(4-hydroxyphenyl)benzoxazole)-derived polymers exhibited crystallinity by DSC and wide-angle X-ray diffraction. Unorientated thin film properties of the 6F-containing PAEBs were comparable to those of other 6F-containing PAEBS that were previously reported. The chemistry and the physical and mechanical properties of the above polymers are discussed.

Solubilization and spore recovery from silicone polymers. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Hsiao, Y. C.

1974-01-01

A non-sporicidal technique for solvent degradation of cured silicone polymers was developed which involves chemical degradation of cured silicone polymers by amine solvents at room temperature. Substantial improvements were obtained in the recovery of seeded spores from room temperature cured polymers as compared to the standard recovery procedures, which indicates that the curing process is not sufficiently exothermic to reduce spore viability. The dissolution reaction of cured silicone polymers whith amine solvents is proposed to occur by bimolecular nucleophilic displacement. The chemical structure of silicone polymers was determined by spectroscopic methods. The phenyl to methyl ratio, R/Si ratio, molecular weight, and hydroxyl content of the silicone resins were determined.

[Synthesis, biotransformation and pharmacodynamics of a new theophylline derivative].

PubMed

Oelschläger, H; Harsche, C; Engel, J

1991-09-01

7-[(RS)2-((S)-1-Methyl-2-phenyl-ethylamino)propyl]-theophylline (3) was not described until now. This fenetylline analogue is available by reaction of 7 with an excess of 2 at 150 degrees C. If 2 reacts with 4, an E2-elimination overwhelms SN-nucleophilic displacement yielding compound 5. In vivo studies with male White-Wistar rats, comparing biotransformation of 3 and 1, demonstrate, that the amount of 2 is decreased from 4.7% of (RS)-2 to 1%, probably due to steric hindrance of the attacking monooxygenases by the methyl group at C-11 of 3. Pharmacodynamic studies of 3, tested with mice, gave similar results to those obtained with 1.

Analysis of the Nucleophilic Solvation Effects in Isopropyl Chlorothioformate Solvolysis

PubMed Central

D’Souza, Malcolm J.; Mahon, Brian P.; Kevill, Dennis N.

2010-01-01

Correlation of the solvent effects through application of the extended Grunwald-Winstein equation to the solvolysis of isopropyl chlorothioformate results in a sensitivity value of 0.38 towards changes in solvent nucleophilicity (l) and a sensitivity value of 0.72 towards changes in solvent ionizing power (m). This tangible l value coupled with the negative entropies of activation observed indicates a favorable predisposition towards a modest rear-side nucleophilic solvation of a developing carbocation. Only in 100% ethanol was the bimolecular pathway dominant. These observations are very different from those obtained for the solvolysis of isopropyl chloroformate, where dual reaction channels were proposed, with the addition-elimination reaction favored in the more nucleophilic solvents and a unimolecular fragmentation-ionization mechanism favored in the highly ionizing solvents. PMID:20717524

Deuterium and oxygen-18 isotope effects on nucleophilic displacement by monomeric water in aprotic solvents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurz, J.L.; Lee, J.

1980-07-30

The H/sub 2/O/D/sub 2/O rate-constant ratio for nucleophilic attack by water at a methyl carbon (eq 1) is reduced to very near unity when the water is a dilute solute in L/sub 2/O+CH/sub 3/X..-->..L/sub 2/O/sup +/CH/sub 3/+X/sup -/ a dipolar aprotic solvent. This effect was observed for three leaving groups (CH/sub 3/X equals 1-methylthiophenium ion (MeTh/sup +/), methyl perchlorate (MeOCl/sub 3/), and methyl trifluoromethanesulfonate (MeOTf)) and for two aprotic solvents acetonitrile (MeCn), and tetrahydrothiophene 1,1-dioxide (TMSO:'';sulfolane). It was also observed that the corresponding H/sub 2//sup 16/O/H/sub 2//sup 18/O rate-constant ratio is 1.002 +- 0.004 (95% confidence limits) for the reactionmore » of MeTh/sup +/ with dilute H/sub 2/O in TMSO/sub 2/ at 35/sup 0/C. Although alternative explanations exist (vide infra), these observations are consistent with a mechanism in which no significant positive charge is present on the L/sub 2/O oxygen in the rate-determining transition state and thus in which the rate-determining process does not involve (and is not preceded by) any significant covalent-bonding interaction between the nucleophile and the methyl carbon. All reactions were followed by uv spectroscopy in a Cary 16K spectrophotometer.« less

Activation of the SN2 Reaction by Adjacent π Systems: The Critical Role of Electrostatic Interactions and of Dissociative Character.

PubMed

Robiette, Raphaël; Trieu-Van, Tran; Aggarwal, Varinder K; Harvey, Jeremy N

2016-01-27

The activation of the SN2 reaction by π systems is well documented in textbooks. It has been shown previously that this is not primarily due to classical (hyper)conjugative effects. Instead, π-conjugated substituents enhance favorable substrate-nucleophile electrostatic interactions, with electron-withdrawing groups (EWG) on the sp(2) system leading to even stronger activation. Herein we report computational and experimental results which show that this activation by sp(2) EWG-substitution only occurs in a fairly limited number of cases, when the nucleophile involves strong electrostatic interactions (usually strongly basic negatively charged nucleophiles). In other cases, where bond breaking is more advanced than bond making at the transition state, electrophile-nucleophile electrostatic interactions are less important. In such cases, (hyper)conjugative electronic effects determine the reactivity, and EWG-substitution leads to decreased reactivity. The basicity of the nucleophile as well as solvent effects can help to determine which of these two regimes occurs for a given electrophile.

Regio- and Enantioselective Sequential Dehalogenation of rac-1,3-Dibromobutane by Haloalkane Dehalogenase LinB.

PubMed

Gross, Johannes; Prokop, Zbyněk; Janssen, Dick; Faber, Kurt; Hall, Mélanie

2016-08-03

The hydrolytic dehalogenation of rac-1,3-dibromobutane catalyzed by the haloalkane dehalogenase LinB from Sphingobium japonicum UT26 proceeds in a sequential fashion: initial formation of intermediate haloalcohols followed by a second hydrolytic step to produce the final diol. Detailed investigation of the course of the reaction revealed favored nucleophilic displacement of the sec-halogen in the first hydrolytic event with pronounced R enantioselectivity. The second hydrolysis step proceeded with a regioselectivity switch at the primary position, with preference for the S enantiomer. Because of complex competition between all eight possible reactions, intermediate haloalcohols formed with moderate to good ee ((S)-4-bromobutan-2-ol: up to 87 %). Similarly, (S)-butane-1,3-diol was formed at a maximum ee of 35 % before full hydrolysis furnished the racemic diol product. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nucleotides as nucleophiles: Reactions of nucleotides with phosphoimidazolide activated guanosine

NASA Astrophysics Data System (ADS)

Kanavarioti, Anastassia; Rosenbach, Morgan T.; Brian Hurley, T.

1992-07-01

An earlier study of the reaction of phosphoimidazolide activated nucleosides (ImpN) in aqueous phosphate buffers indicated two modes of reaction of the phosphate monoanion and dianion. The first mode is catalysis of the hydrolysis of the P-N bond in ImpN's which leads to imidazole and nucleoside 5'-monophosphate. The second represents a nucleophilic substitution of the imidazole to yield the nucleoside 5'-diphosphate. This earlier study thus served as a model for the reaction of ImpN with nucleoside monophosphates (pN) because the latter can be regarded as phosphate derivatives. In the present study we investigated the reaction of guanosine 5'-phosphate-2-methylimidazolide, 2-MeImpG, in the presence of pN (N=guanosine, adenosine and uridine) in the range 6.9 ≤ pH ≤ 7.7. We observed that pN's do act as nucleophiles to form NppG, and as general base to enhance the hydrolysis of the P-N bond in 2-MeImpG, i.e. pN show the same behavior as inorganic phosphate. The kinetic analysis yields the following rate constants for the dianion pN2-:k {/n pN}=0.17±0.02 M-1 h-1 for nucleophilic attack andk {/h pN}=0.11±0.07 M-1 h-1 for general base catalysis of the hydrolysis. These rate constants which are independent of the nucleobase compare withk p 2=0.415 M-1 h-1 andk_h^{p^2 } =0.217 M-1 h-1 for the reactions of HPO{4/2-}. In addition, this study shows that under conditions where pN presumably form stacks, the reaction mechanism remains unchanged although in quantitative terms stacked pN are somewhat less reactive. Attack by the 2'-OH and 3'-OH groups of the ribose moiety in amounts ≥1% is not observed; this is attributed to the large difference in nucleophilicity in the neutral pH range between the phosphate group and the ribose hydroxyls. This nucleophilicity rank is not altered by stacking.

Nucleotides as nucleophiles: reactions of nucleotides with phosphoimidazolide activated guanosine

NASA Technical Reports Server (NTRS)

Kanavarioti, A.; Rosenbach, M. T.; Hurley, T. B.

1991-01-01

An earlier study of the reaction of phosphoimidazolide activated nucleosides (ImpN) in aqueous phosphate buffers indicated two modes of reaction of the phosphate monoanion and dianion. The first mode is catalysis of the hydrolysis of the P-N bond in ImpN's which leads to imidazole and nucleoside 5'-monophosphate. The second represents a nucleophilic substitution of the imidazole to yield the nucleoside 5'-diphosphate. This earlier study thus served as a model for the reaction of ImpN with nucleoside monophosphates (pN) because the latter can be regarded as phosphate derivatives. In the present study we investigated the reaction of guanosine 5'-phosphate-2-methylimidazolide, 2-MeImpG, in the presence of pN (N = guanosine, adenosine and uridine) in the range 6.9 less than or equal to pH less than or equal to 7.7. We observed that pN's do act as nucleophiles to form NppG, and as general base to enhance the hydrolysis of the P-N bond in 2-MeImpG, i.e. pN show the same behavior as inorganic phosphate. The kinetic analysis yields the following rate constants for the dianion pN2-: knpN = 0.17 +/- 0.02 M-1 h-1 for nucleophilic attack and khpN = 0.11 +/- 0.07 M-1 h-1 for general base catalysis of the hydrolysis. These rate constants which are independent of the nucleobase compare with kp.2 = 0.415 M-1 h-1 and khp2. = 0.217 M-1 h-1 for the reactions of HPO4(2-). In addition, this study shows that under conditions where pN presumably form stacks, the reaction mechanism remains unchanged although in quantitative terms stacked pN are somewhat less reactive. Attack by the 2'-OH and 3'-OH groups of the ribose moiety in amounts greater than or equal to 1% is not observed; this is attributed to the large difference in nucleophilicity in the neutral pH range between the phosphate group and the ribose hydroxyls. This nucleophilicity rank is not altered by stacking.

Detection of Electrophilic and Nucleophilic Chemical Agents

DOEpatents

McElhanon, James R.; Shepodd, Timothy J.

2008-11-11

A "real time" method for detecting electrophilic and nucleophilic species generally by employing tunable, precursor sensor materials that mimic the physiological interaction of these agents to form highly florescent berberine-type alkaloids that can be easily and rapidly detected. These novel precursor sensor materials can be tuned for reaction with both electrophilic (chemical species, toxins) and nucleophilic (proteins and other biological molecules) species.

Laboratory determination of the carbon kinetic isotope effects (KIEs) for reactions of methyl halides with various nucleophiles in solution

USGS Publications Warehouse

Baesman, S.M.; Miller, L.G.

2005-01-01

Large carbon kinetic isotope effects (KIEs) were measured for reactions of methyl bromide (MeBr), methyl chloride (MeCl), and methyl iodide (MeI) with various nucleophiles at 287 and 306 K in aqueous solutions. Rates of reaction of MeBr and MeI with H2O (neutral hydrolysis) or Cl- (halide substitution) were consistent with previous measurements. Hydrolysis rates increased with increasing temperature or pH (base hydrolysis). KIEs for hydrolysis were 51 ?? 6??? for MeBr and 38 ?? 8??? for MeI. Rates of halide substitution increased with increasing temperature and greater reactivity of the attacking nucleophile, with the fastest reaction being that of MeI with Br-. KIEs for halide substitution were independent of temperature but varied with the reactant methyl halide and the attacking nucleophile. KIEs were similar for MeBr substitution with Cl- and MeCl substitution with Br- (57 ?? 5 and 60 ?? 9??? respectively). The KIE for halide exchange of MeI was lower overall (33 ?? 8??? and was greater for substitution with Br- (46 ?? 6???) than with Cl- (29 ?? 6???). ?? Springer Science + Business Media, Inc. 2005.

Reactions of glycidyl derivatives with ambident nucleophiles; part 2: amino acid derivatives

PubMed Central

Dyker, Gerald; Thöne, Andreas; Henkel, Gerald

2007-01-01

A three-step procedure for the synthesis of multifunctionalized heterocycles from a pyroglutamic acid derivative, glycidyl components and anilines by nucleophilic substitution and cobalt catalysis is presented. PMID:17900352

Regio- and Enantioselective N-Allylations of Imidazole, Benzimidazole, and Purine Heterocycles Catalyzed by Single-Component Metallacyclic Iridium Complexes

PubMed Central

Stanley, Levi M.

2010-01-01

Highly regio- and enantioselective iridium-catalyzed N-allylations of benzimidazoles, imidazoles, and purines have been developed. N-Allylated benzimidazoles and imidazoles were isolated in high yields (up to 97%) with high branched-to-linear selectivity (up to 99:1) and enantioselectivity (up to 98% ee) from the reactions of benzimidazole and imidazole nucleophiles with unsymmetrical allylic carbonates in the presence of single component, ethylene-bound, metallacyclic iridium catalysts. N-Allylated purines were also obtained in high yields (up to 91%) with high N9:N7 selectivity (up to 96:4), high branched-to-linear selectivity (98:2), and high enantioselectivity (up to 98% ee) under similar conditions. The reactions encompass a range of benzimidazole, imidazole, and purine nucleophiles, as well as a variety of unsymmetrical aryl, heteroaryl, and aliphatic allylic carbonates. Competition experiments between common amine nucleophiles and the heterocyclic nitrogen nucleophiles studied in this work illustrate the effect of nucleophile pKa on the rate of iridium-catalyzed N-allylation reactions. Kinetic studies on the allylation of benzimidazole catalyzed by metallacyclic iridium-phosphoramidite complexes, in combination with studies on the deactivation of these catalysts in the presence of heterocyclic nucleophiles, provide insight into the effects of the structure of the phosphoramidite ligands on the stability of the metallacyclic catalysts. The data obtained from these studies has led to the development of N-allylations of benzimidazoles and imidazoles in the absence of an exogenous base. PMID:19480431

Nucleophilic ring opening reactions of aziridines.

PubMed

Akhtar, Rabia; Naqvi, Syed Ali Raza; Zahoor, Ameer Fawad; Saleem, Sameera

2018-05-04

Aziridine ring opening reactions have gained tremendous importance in the synthesis of nitrogen containing biologically active molecules. During recent years, a great effort has been put forward by scientists toward unique bond construction methodologies via ring opening of aziridines. In this regard, a wide range of chiral metal- and organo-catalyzed desymmetrization reactions of aziridines have been reported with carbon, sulfur, oxygen, nitrogen, halogen, and other nucleophiles. In this review, an outline of methodologies adopted by a number of scientists during 2013-2017 for aziridine ring opening reactions as well as their synthetic applications is described.

Microsolvation effects on the reactivity of oxy-nucleophiles: the case of gas-phase SN2 reactions of YO-(CH3OH) n=1,2 towards CH3Cl.

PubMed

Yun-Yun, Liu; Fang-Zhou, Qiu; Jun, Zhu; Yi, Ren; Kai-Chung, Lau

2017-06-01

The modified G4(MP2) method was applied to explore microsolvation effects on the reactivity of four solvated normal oxy-nucleophiles YO - (CH 3 OH) n=1,2 (Y = CH 3 , C 2 H 5 , FC 2 H 4 , ClC 2 H 4 ), and five α-oxy-nucleophiles YO - (CH 3 OH) n=1,2 (Y = HO, CH 3 O, F, Cl, Br), in gas-phase S N 2 reactions towards the substrate CH 3 Cl. Based on a Brønsted-type plot, our calculations reveal that the overall activation barriers of five microsolvated α-oxy-nucleophiles are obviously smaller than the prediction from the correlation line constructed by four normal microsolvated ones to different degrees, and clearly demonstrate the existence of an α-effect in the presence of one or two methanol molecule(s). Moreover, it was found that the α-effect of the mono-methanol microsolvated α-nucleophile is stronger than that of the monohydrated α-nucleophile. However, the α-effect of YO - (CH 3 OH) 2 becomes weaker for Y = HO and CH 3 O, whereas it becomes stronger for Y = F, Cl, Br than that of YO - (H 2 O) 2 , which can be explained by analyses of the activation strain model in the two cases. It was also found that the rationale about the low ionization energy of α-nucleophile inducing the α-effect was not widely significant. Graphical abstract Variation of alpha-effect in the gas-phase S N 2 reaction with the microsolvation.

Divergent palladium iodide catalyzed multicomponent carbonylative approaches to functionalized isoindolinone and isobenzofuranimine derivatives.

PubMed

Mancuso, Raffaella; Ziccarelli, Ida; Armentano, Donatella; Marino, Nadia; Giofrè, Salvatore V; Gabriele, Bartolo

2014-04-18

2-Alkynylbenzamides underwent different reaction pathways when allowed to react under PdI2-catalyzed oxidative carbonylation conditions, depending on the nature of the external nucleophile and reaction conditions. Thus, oxidative carbonylation of 2-ethynylbenzamides, bearing a terminal triple bond, carried out in the presence of a secondary amine as external nucleophile, selectively led to the formation of 3-[(dialkylcarbamoyl)methylene]isoindolin-1-ones through the intermediate formation of the corresponding 2-ynamide derivatives followed by intramolecular nucleophilic attack by the nitrogen of the benzamide moiety on the conjugated triple bond. On the other hand, 3-[(alkoxycarbonyl)methylene]isobenzofuran-1(3H)imines were selectively obtained when the oxidative carbonylation of 2-alkynylbenzamides, bearing a terminal or an internal triple bond, was carried out in the presence of an alcohol R'OH (such as methanol or ethanol) as the external nucleophile and HC(OR')3 as a dehydrating agent, necessary to avoid substrate hydrolysis. In this latter case, the reaction pathway leading to the isobenzofuranimine corresponded to the 5-exo-dig intramolecular nucleophilic attack of the oxygen of the benzamide moiety on the triple bond coordinated to the metal center followed by alkoxycarbonylation. The structures of representative products have been confirmed by X-ray crystallographic analysis.

Interstrand cross-linking of DNA by 1,3-bis(2-chloroethyl)-1-nitrosourea and other 1-(2-haloethyl)-1-nitrosoureas.

PubMed

Kohn, K W

1977-05-01

Bifunctional alkylating agents are known to cross-link DNA by simultaneously alkylating two guanine residues located on opposite strands. Despite this apparent requirement for bifunctionality, 1-(2-chloroethyl)-1-nitrosoureas bearing a single alkylating function were found to cross-link DNA in vitro. Cross-linking was demonstrated by showing inhibition of alkali-induced strand separation. Extensive cross-linking was observed in DNA treated with 1-(2-chloroethyl)-1-nitrosourea, 1,3-bis-(2-chloroethyl)-1-nitrosourea, and 1-(2-chloroethyl(-3-cyclohexyl-1-nitrosourea. The reaction occurs in two steps, an intital binding followed by a second step which can proceed after removal of unbound drug. It is suggested that the first step is chloroethylation of a nucleophilic site on one strand and that the second step involves displacement of Cl- by a nucleophilic site on the opposite strand, resulting in an ethyl bridge between the strands. Consistent with this possibility, 1-(2-fluoroethyl)-3-cyclohexyl-1-nitrosourea produced much less cross-linking, as expected from the known low activity of F-, compared with Cl-, as leaving group. 1-Methyl-1-nitrosourea, which is known to depurinate DNA, produced no detectable cross-linking.

The Preparation of Lucigenin.

ERIC Educational Resources Information Center

Amiet, R. G.

1982-01-01

Outlines and discusses procedures for the preparation of lucigenin, a powerfully chemiluminescent compound. Major techniques (requiring three 4-hour sessions) involving nucleophilic and electrophilic aromatic substitution, nucleophilic aliphatic substitution, reductive coupling, and oxidation reactions include steam distillation, decolorization…

Tandem Cu-catalyzed ketenimine formation and intramolecular nucleophile capture: Synthesis of 1,2-dihydro-2-iminoquinolines from 1-(o-acetamidophenyl)propargyl alcohols

PubMed Central

Kant, Ruchir

2014-01-01

Summary The copper-catalyzed ketenimine formation reaction of 1-(o-acetamidophenyl)propargyl alcohols with various sulfonyl azides is found to undergo a concomitant intramolecular nucleophile attack to generate 1,2-dihydro-2-iminoquinolines after aromatization (via elimination of acetyl and hydroxy groups) and tautomerization. The reaction produces 4-substituted and 3,4-unsubstituted title compounds in moderate to good yields under mild reaction conditions. PMID:24991276

Nucleophile Assisting Leaving Groups: A Strategy for Aliphatic 18F-Fluorination

PubMed Central

Lu, Shuiyu; Lepore, Salvatore D.; Li, Song Ye; Mondal, Deboprosad; Cohn, Pamela C.; Bhunia, Anjan K.; Pike, Victor W.

2009-01-01

A series of arylsulfonate nucleophile assisting leaving groups (NALGs) were prepared in which the metal chelating unit is attached to the aryl ring via an ether linker. These NALGs exhibited significant rate enhancements in halogenation reactions using metal halides. Studies with a NALG containing a macrocyclic ether unit suggest that rate enhancements of these nucleophilic halogenation reactions are facilitated by stabilization of charge in the transition state rather than through strong pre-complexation with metal cation. In several cases, a primary substrate containing one of the new leaving groups rivaled or surpassed the reactivity of triflates when exposed to nucleophile but was otherwise highly stable and isolable. These and previously disclosed chelating leaving groups were used in 18F-fluorination reactions using no-carrier-added [18F]fluoride ion (t1/2 = 109.7 min, β+ = 97%) in CH3CN. Under microwave irradiation and without the assistance of a cryptand, such as K2.2.2, primary substrates with select NALGs led to a substantial improvement (2 to 3 fold) in radiofluorination yields over traditional leaving groups. PMID:19572583

Multifunctional Pt(II) Reagents: Covalent Modifications of Pt Complexes Enable Diverse Structural Variation and In-Cell Detection.

PubMed

White, Jonathan D; Haley, Michael M; DeRose, Victoria J

2016-01-19

To enhance the functionality of Pt-based reagents, several strategies have been developed that utilize Pt compounds modified with small, reactive handles. This Account encapsulates work done by us and other groups regarding the use of Pt(II) compounds with reactive handles for subsequent elaboration with fluorophores or other functional moieties. Described strategies include the incorporation of substituents for well-known condensation or nucleophilic displacement-type reactions and their use, for example, to tether spectroscopic handles to Pt reagents for in vivo investigation. Other chief uses of displacement-type reactions have included tethering various small molecules exhibiting pharmacological activity directly to Pt, thus adding synergistic effects. Click chemistry-based ligation techniques have also been applied, primarily with azide- and alkyne-appended Pt complexes. Orthogonally reactive click chemistry reactions have proven invaluable when more traditional nucleophilic displacement reactions induce side-reactivity with the Pt center or when systematic functionalization of a larger number of Pt complexes is desired. Additionally, a diverse assortment of Pt-fluorophore conjugates have been tethered via click chemistry conjugation. In addition to providing a convenient synthetic path for diversifying Pt compounds, the use of click-capable Pt complexes has proved a powerful strategy for postbinding covalent modification and detection with fluorescent probes. This strategy bypasses undesirable influences of the fluorophore camouflaged as reactivity due to Pt that may be present when detecting preattached Pt-fluorophore conjugates. Using postbinding strategies, Pt reagent distributions in HeLa and lung carcinoma (NCI-H460) cell cultures were observed with two different azide-modified Pt compounds, a monofunctional Pt(II)-acridine type and a difunctional Pt(II)-neutral complex. In addition, cellular distribution was observed with an alkyne-appended difunctional Pt(II)-neutral complex analogous in structure to the aforementioned difunctional azide-Pt(II) reagent. In all cases, significant accumulation of Pt in the nucleolus of cells was observed, in addition to broader localization in the nucleus and cytoplasm of the cell. Using the same strategy of postbinding click modification with fluorescent probes, Pt adducts were detected and roughly quantified on rRNA and tRNA from Pt-treated Saccharomyces cerevisiae; rRNA adducts were found to be relatively long-lived and not targeted for immediate degradation. Finally, the utility and feasibility of the alkyne-appended Pt(II) compound has been further demonstrated with a turn-on fluorophore, dansyl azide, in fluorescent detection of DNA in vitro. In all, these modifications utilizing reactive handles have allowed for the diversification of new Pt reagents, as well as providing cellular localization information on the modified Pt compounds.

Chemical Modification of Polysaccharides

PubMed Central

Cumpstey, Ian

2013-01-01

This review covers methods for modifying the structures of polysaccharides. The introduction of hydrophobic, acidic, basic, or other functionality into polysaccharide structures can alter the properties of materials based on these substances. The development of chemical methods to achieve this aim is an ongoing area of research that is expected to become more important as the emphasis on using renewable starting materials and sustainable processes increases in the future. The methods covered in this review include ester and ether formation using saccharide oxygen nucleophiles, including enzymatic reactions and aspects of regioselectivity; the introduction of heteroatomic nucleophiles into polysaccharide chains; the oxidation of polysaccharides, including oxidative glycol cleavage, chemical oxidation of primary alcohols to carboxylic acids, and enzymatic oxidation of primary alcohols to aldehydes; reactions of uronic-acid-based polysaccharides; nucleophilic reactions of the amines of chitosan; and the formation of unsaturated polysaccharide derivatives. PMID:24151557

Unusual reaction paths of SN2 nucleophile substitution reactions CH4 + H- → CH4 + H- and CH4 + F- → CH3F + H-: Quantum chemical calculations

NASA Astrophysics Data System (ADS)

Minyaev, Ruslan M.; Quapp, Wolfgang; Schmidt, Benjamin; Getmanskii, Ilya V.; Koval, Vitaliy V.

2013-11-01

Quantum chemical (CCSD(full)/6-311++G(3df,3pd), CCSD(T)(full)/6-311++G(3df,3pd)) and density function theory (B3LYP/6-311++G(3df,3pd)) calculations were performed for the SN2 nucleophile substitution reactions CH4 + H- → CH4 + H- and CH4 + F- → CH3F + H-. The calculated gradient reaction pathways for both reactions have an unusual behavior. An unusual stationary point of index 2 lies on the gradient reaction path. Using Newton trajectories for the reaction path, we can detect VRI point at which the reaction path branches.

The thriving chemistry of ketenimines.

PubMed

Lu, Ping; Wang, Yanguang

2012-09-07

Ketenimines are an important class of reactive species and useful synthetic intermediates. During the last two decades several practical and versatile approaches to ketenimines have been developed, leading to exhaustive investigations on ketenimine chemistry and the discovery of a variety of highly efficient reactions. Five types of reactions for ketenimines have been reported, including nucleophilic additions (ketenimines can be used as both electrophiles and nucleophiles), radical additions, cycloaddition reactions, electrocyclic ring closure reactions, and σ rearrangements. Furthermore, numerous complex organic compounds, particularly the biologically interesting heterocycles, have been constructed using these methodologies. The review of these accomplishments is presented here.

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles

PubMed Central

Chattopadhyay, Kalicharan; Fenster, Erik; Grenning, Alexander J

2012-01-01

Summary The palladium-catalyzed nucleophilic substitution of (coumarinyl)methyl acetates is described. The reaction proceeds though a palladium π-benzyl-like complex and allows for many different types of C-, N-, and S-nucleophiles to be regioselectively added to the biologically active coumarin motif. This new method was utilized to prepare a 128-membered library of aminated coumarins for biological screening. PMID:23019448

Determination of acidity and nucleophilicity in thiols by reaction with monobromobimane and fluorescence detection.

PubMed

Sardi, Florencia; Manta, Bruno; Portillo-Ledesma, Stephanie; Knoops, Bernard; Comini, Marcelo A; Ferrer-Sueta, Gerardo

2013-04-01

A method based on the differential reactivity of thiol and thiolate with monobromobimane (mBBr) has been developed to measure nucleophilicity and acidity of protein and low-molecular-weight thiols. Nucleophilicity of the thiolate is measured as the pH-independent second-order rate constant of its reaction with mBBr. The ionization constants of the thiols are obtained through the pH dependence of either second-order rate constant or initial rate of reaction. For readily available thiols, the apparent second-order rate constant is measured at different pHs and then plotted and fitted to an appropriate pH function describing the observed number of ionization equilibria. For less available thiols, such as protein thiols, the initial rate of reaction is determined in a wide range of pHs and fitted to the appropriate pH function. The method presented here shows excellent sensitivity, allowing the use of nanomolar concentrations of reagents. The method is suitable for scaling and high-throughput screening. Example determinations of nucleophilicity and pK(a) are presented for captopril and cysteine as low-molecular-weight thiols and for human peroxiredoxin 5 and Trypanosoma brucei monothiol glutaredoxin 1 as protein thiols. Copyright © 2013 Elsevier Inc. All rights reserved.

Reaction of rat liver glutathione S-transferases and bacterial dichloromethane dehalogenase with dihalomethanes.

PubMed

Blocki, F A; Logan, M S; Baoli, C; Wackett, L P

1994-03-25

Dichloromethane dehalogenase from Methylophilus sp. DM11 is a glutathione S-transferase homolog that is specifically active with dihalomethane substrates. This bacterial enzyme and rat liver glutathione S-transferases were purified to investigate their relative reactivity with CH2Cl2 and related substrates. Rat liver alpha class glutathione transferases were inactive and mu class enzymes showed low activity (7-23 nmol/min/mg of protein) with CH2Cl2. theta class glutathione transferase 5-5 from rat liver and Methylophilus sp. dichloromethane dehalogenase showed specific activities of > or = 1 mumol/min/mg of protein. Apparent Kcat/Km were determined to be 3.3 x 10(4) and 6.0 x 10(4) L M-1 S-1 for the two enzymes, respectively. Dideutero-dichloromethane was processed to dideutereo-formaldehyde, consistent with a nucleophilic halide displacement mechanism. The possibility of a GSCH2X reaction intermediate (GS, glutathione; X, halide) was probed using CH2ClF to generate a more stable halomethylglutathione species (GSCH2F). The reaction of CH2ClF with dichloromethane dehalogenase produced a kinetically identifiable intermediate that decomposed to formaldehyde at a similar rate to synthetic HOCH2CH2SCH2F. 19F-NMR revealed the transient formation of an intermediate identified as GSCH2F by its chemical shift, its triplet resonance, and H-F coupling constant consistent with a fluoromethylthioether. Its decomposition was matched by a stoichiometric formation of fluoride. These studies indicated that the bacterial dichloromethane dehalogenase directs a nucleophilic attack of glutathione on CH2Cl2 to produce a halomethylthioether intermediate. This focuses attention on the mechanism used by theta class glutathione transferases to generate a halomethylthioeter from relatively unreactive dihalomethanes.

Oxidations of Organic and Inorganic Substrates by Superoxo-, hydroperoxo-, and oxo-compounds of the transition metals.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vasbinder, Michael John

2006-01-01

Chapters 1 and 2 dealt with the chemistry of superoxo-, hydroperoxo-, and oxo- complexes of chromium, rhodium and cobalt. Chapter 3 dealt with the mechanism of oxygen-atom transfer catalyzed by an oxo-complex of rhenium. In Chapter 1, it was shown that hydroperoxometal complexes of cobalt and rhodium react with superoxochromium and chromyl ions, generating reduced chromium species while oxidizing the hydroperoxometal ions to their corresponding superoxometal ions. It was shown that the chromyl and superoxochromium ions are the more powerful oxidants. Evidence supports hydrogen atom transfer from the hydroperoxometal ion to the oxidizing superoxochromium or chromyl ion as the reactionmore » mechanism. There is a significant H/D kinetic isotope effect. Comparisons to the rate constants of other known hydrogen atom transfer reactions show the expected correlation with bond dissociation energies. In Chapter 2, it was found that the superoxometal complexes Cr{sub aq}OO 2+ and Rh(NH 3) 4(H 2O)OO 2+ oxidize stable nitroxyl radicals of the TEMPO series with rate constants that correlate with the redox potentials of both the oxidant and reductant. These reactions fit the Marcus equation for electron transfer near the theoretical value. Acid catalysis is important to the reaction, especially the thermodynamically limited cases involving Rh(NH 3) 4(H 2O)OO 2+ as the oxidant. The rate constants are notably less than those measured in the reaction between the same nitroxyl radicals and other strong free-radical oxidants, an illustration of the delocalized and stabilized nature of the superoxometal ions. Chapter 3 showed that oxo-rhenium catalysts needed a nucleophile to complete the catalytic oxygen-atom transfer from substituted pyridine-N-oxides to triphenylphosphine. The reaction was studied by introducing various pyridine-derived nucleophiles and monitoring their effect on the rate, then fitting the observed rate constants to the Hammett correlation. It was found that the values of the Hammett reaction constant PN were -1.0(1) for 4-nitro-2-methylpyridine-N-oxide and -2.6(4) for 4-methylpyridine-N-oxide as substrates. The negative value confirms pyridine is acting as a nucleophile. Nucleophiles other than pyridine derivatives were also tested. In the end, it was found that the most effective nucleophiles were the pyridine-N-oxides themselves, meaning that a second equivalent of substrate serves as the most efficient promoter of this oxygen-atom transfer reaction. This relative nucleophilicity of pyridines and pyridine-N-oxides is similar to what is observed in other OAT reactions generating high-valent metal-oxo species.« less

Covalent binding of aniline to humic substances. 2. 15N NMR studies of nucleophilic addition reactions

USGS Publications Warehouse

Thorn, K.A.; Pettigrew, P.J.; Goldenberg, W.S.; Weber, E.J.

1996-01-01

Aromatic amines are known to undergo covalent binding with humic substances in the environment. Although previous studies have examined reaction conditions and proposed mechanisms, there has been no direct spectroscopic evidence for the covalent binding of the amines to the functional groups in humic substances. In order to further elucidate the reaction mechanisms, the Suwannee River and IHSS soil fulvic and humic acids were reacted with 15N-labeled aniline at pH 6 and analyzed using 15N NMR spectrometry. Aniline underwent nucleophilic addition reactions with the quinone and other carbonyl groups in the samples and became incorporated in the form of anilinohydroquinone, anilinoquinone, anilide, imine, and heterocyclic nitrogen, the latter comprising 50% or more of the bound amine. The anilide and anilinohydroquinone nitrogens were determined to be susceptible to chemical exchange by ammonia. In the case of Suwannee River fulvic acid, reaction under anoxic conditions and pretreatment with sodium borohydride or hydroxylamine prior to reaction under oxic conditions resulted in a decrease in the proportion of anilinohydroquinone nitrogen incorporated. The relative decrease in the incorporation of anilinohydroquinone nitrogen with respect to anilinoquinone nitrogen under anoxic conditions suggested that inter- or intramolecular redox reactions accompanied the nucleophilic addition reactions.

Nucleophilic substitution at silicon (SN2@Si) via a central reaction barrier.

PubMed

Bento, A Patrícia; Bickelhaupt, F Matthias

2007-03-16

It is textbook knowledge that nucleophilic substitution at carbon (SN2@C) proceeds via a central reaction barrier which disappears in the corresponding nucleophilic substitution reaction at silicon (SN2@Si). Here, we address the question why the central barrier disappears from SN2@C to SN2@Si despite the fact that these processes are isostructural and isoelectronic. To this end, we have explored and analyzed the potential energy surfaces (PES) of various Cl-+CR3Cl (R=H, CH3) and Cl-+SiR3Cl model reactions (R=H, CH3, C2H5, and OCH3). Our results show that the nature of the SN2 reaction barrier is in essence steric, but that it can be modulated by electronic factors. Thus, simply by increasing the steric demand of the substituents R around the silicon atom, the SN2@Si mechanism changes from its regular single-well PES (with a stable intermediate transition complex, TC), via a triple-well PES (with a pre- and a post-TS before and after the central TC), to a double-well PES (with a TS; R=OCH3), which is normally encountered for SN2@C reactions.

Determining the transition-state structure for different SN2 reactions using experimental nucleophile carbon and secondary alpha-deuterium kinetic isotope effects and theory.

PubMed

Westaway, Kenneth C; Fang, Yao-ren; MacMillar, Susanna; Matsson, Olle; Poirier, Raymond A; Islam, Shahidul M

2008-10-16

Nucleophile (11)C/ (14)C [ k (11)/ k (14)] and secondary alpha-deuterium [( k H/ k D) alpha] kinetic isotope effects (KIEs) were measured for the S N2 reactions between tetrabutylammonium cyanide and ethyl iodide, bromide, chloride, and tosylate in anhydrous DMSO at 20 degrees C to determine whether these isotope effects can be used to determine the structure of S N2 transition states. Interpreting the experimental KIEs in the usual fashion (i.e., that a smaller nucleophile KIE indicates the Nu-C alpha transition state bond is shorter and a smaller ( k H/ k D) alpha is found when the Nu-LG distance in the transition state is shorter) suggests that the transition state is tighter with a slightly shorter NC-C alpha bond and a much shorter C alpha-LG bond when the substrate has a poorer halogen leaving group. Theoretical calculations at the B3LYP/aug-cc-pVDZ level of theory support this conclusion. The results show that the experimental nucleophile (11)C/ (14)C KIEs can be used to determine transition-state structure in different reactions and that the usual method of interpreting these KIEs is correct. The magnitude of the experimental secondary alpha-deuterium KIE is related to the nucleophile-leaving group distance in the S N2 transition state ( R TS) for reactions with a halogen leaving group. Unfortunately, the calculated and experimental ( k H/ k D) alpha's change oppositely with leaving group ability. However, the calculated ( k H/ k D) alpha's duplicate both the trend in the KIE with leaving group ability and the magnitude of the ( k H/ k D) alpha's for the ethyl halide reactions when different scale factors are used for the high and the low energy vibrations. This suggests it is critical that different scaling factors for the low and high energy vibrations be used if one wishes to duplicate experimental ( k H/ k D) alpha's. Finally, neither the experimental nor the theoretical secondary alpha-deuterium KIEs for the ethyl tosylate reaction fit the trend found for the reactions with a halogen leaving group. This presumably is found because of the bulky (sterically hindered) leaving group in the tosylate reaction. From every prospective, the tosylate reaction is too different from the halogen reactions to be compared.

Unravelling the reaction mechanism of matrix metalloproteinase 3 using QM/MM calculations

NASA Astrophysics Data System (ADS)

Feliciano, Gustavo Troiano; da Silva, Antônio José Roque

2015-07-01

The matrix metalloproteinase family (MMP) constitutes a family of zinc (Zn) proteases that catalyze the breaking of peptide bonds in proteins. These enzymes are very promising drug targets, since they are involved in remodeling and degradation of the extracellular matrix, which is a key process required for cancer metastasis, and thus, their reaction mechanism has been an area of intensive research. Early proposal based on acid base catalyzed hydrolysis, suggested that a conserved zinc bound water molecule acted as the nucleophile attacking the peptide bond carbon, after being activated by essential glutamate. The possibility of a direct nucleophilic attack by the enzyme, performed by the glutamate was also suggested. These are the key yet unsolved issues about MMP reaction mechanism. In the present work, we used hybrid quantum/classical calculations to analyze the structure and energetics of different possible hydrolysis reaction paths. The results support a water mediated mechanism, where both the nucleophile water molecule and the carbonyl oxygen of the scissile peptide bond are coordinated to zinc in the reactive configuration, while the essential glutamate acts as the base accepting the proton from the nucleophilic water. Formation of the carbon-oxygen bond and breaking of carbon-nitrogen bond were found to be concerted events, with a computed barrier of 14.8 kcal/mol. Substrate polarization was found to be important for the observed reaction mechanism, and a substantial change in the metal coordination environment was observed, particularly, regarding the zinc-histidine coordination.

REVISITING NUCLEOPHILIC SUBSTITUTION REACTIONS: MICROWAVE-ASSISTED SYNTHESIS OF AZIDES, THIOCYANATES AND SULFONES IN AQUEOUS MEDIUM

EPA Science Inventory

A practical, rapid and efficient microwave (MW) promoted synthesis of various azides, thiocyanates and sulfones, is described in aqueous medium. This general and expeditious MW-enhanced nucleophilic substitution approach uses easily accessible starting materials such as halides o...

Di(hydroxyphenyl)- 1,2,4-triazole monomers

NASA Technical Reports Server (NTRS)

Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Wolf, Peter (Inventor)

1993-01-01

The di(hydroxyphenyl)- 1,2,4-triazole monomers were first synthesized by reacting bis (4-hydroxyphenyl) hydrazide with aniline hydrochloride at 250 C in the melt and also by reacting 1,3 or 1,4-bis- (4-hydroxyphenyl)- phenylene- dihydrazide with 2 moles of aniline hydrochloride in the melt. Purification of the di(hydroxyphenyl)- 1,2,4-triazole monomers was accomplished by recrystallization. Poly (1,2,4-triazoles) (PT) were prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenyl)- 1,2,4-triazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The reactions were carried out in polar aprotic solvents such as sulfolane or diphenylsulfone using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. This synthetic route has provided high molecular weight PT of new chemical structure, is economically and synthetically more favorable than other routes, and allows for facile chemical structure variation due to the availability of a large variety of activated aromatic dihalides.

High-pressure ion source combined with an in-axis ion trap mass spectrometer. 1. Instrumentation and applications

PubMed

Mathurin; Faye; Brunot; Tabet; Wells; Fuche

2000-10-15

A new combination of a dual EI/CI ion source with a quadrupole ion trap mass spectrometer has been realized in order to efficiently produce negative ions in the reaction cell. Analysis of volatile compounds was performed under negative ion chemical ionization (NICI) during a reaction period where selected reactant negative ions, previously produced in the external ion source, were allowed to interact with molecules, introduced by hyphenated techniques such as gas chromatography. The O2*-, CH3O-, and Cl- reactant ions were used in this study to ensure specific ion/molecule interactions such as proton transfer, nucleophilic displacement, or charge exchange processes, respectively leading to even-electron species, i.e., deprotonated [M - H]- molecules, diagnostic [M - R]- ions, or odd-electron M*- molecular species. The reaction orientation depends on the thermochemistry of reactions within kinetic controls. First analytical results are presented here for the trace-level detection of several contaminants under NICI/Cl- conditions. Phosphorus-containing compounds (malathion, ethyl parathion, and methyl parathion as representative for pesticides) and nitro-containing compounds (2,4,6-trinitrotoluene for explosive material) have been chosen in order to explore the analytical ability of this promising instrumental coupling.

Tandem SN2' nucleophilic substitution/oxidative radical cyclization of aryl substituted allylic alcohols with 1,3-dicarbonyl compounds.

PubMed

Zhang, Zhen; Li, Cheng; Wang, Shao-Hua; Zhang, Fu-Min; Han, Xue; Tu, Yong-Qiang; Zhang, Xiao-Ming

2017-04-11

A novel and efficient tandem S N 2' nucleophilic substitution/oxidative radical cyclization reaction of aryl substituted allylic alcohols with 1,3-dicarbonyl compounds has been developed by using Mn(OAc) 3 as an oxidant, which enables the expeditious synthesis of polysubstituted dihydrofuran (DHF) derivatives in moderate to high yields. The use of weakly acidic hexafluoroisopropanol (HFIP) as the solvent rather than AcOH has successfully improved the yields and expanded the substrate scope of this type of radical cyclization reactions. Mechanistic studies confirmed the cascade reaction process involving a final radical cyclization.

REVISITING CLASSICAL NUCLEOPHILIC SUBSTITUTIONS IN AQUEOUS MEDIUM: MICROWAVE-ASSISTED SYNTHESIS OF ALKYL AZIDES

EPA Science Inventory

An efficient and clean synthesis of alkyl azides using microwave (MW) radiation is described in aqueous medium by reacting alkyl halides or tosylates with alkali azides. This general and expeditious MW-enhanced approach to nucleophilic substitution reactions is applicable to the ...

Effect of carbonates/phosphates as nucleophilic catalysts in dimethylformamide for efficient cyanosilylation of aldehydes and ketones

PubMed Central

Prakash, G. K. Surya; Vaghoo, Habiba; Panja, Chiradeep; Surampudi, Vijayalakshmi; Kultyshev, Roman; Mathew, Thomas; Olah, George A.

2007-01-01

Cyanosilylation of aldehydes and aliphatic ketones can be carried out in dimethylformamide even without the use of any catalyst. In the presence of nucleophilic catalysts such as carbonate and phosphate salts, the reaction rate is significantly enhanced. PMID:17360603

Detection of electrophilic and nucleophilic chemical agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

McElhanon, James R.; Shepodd, Timothy J.

2014-08-12

A "real time" method for detecting chemical agents generally and particularly electrophilic and nucleophilic species by employing tunable, precursor sensor materials that mimic the physiological interaction of these agents to form highly florescent berberine-type alkaloids that can be easily and rapidly detected. These novel precursor sensor materials can be tuned for reaction with both electrophilic (chemical species, toxins) and nucleophilic (proteins and other biological molecules) species. By bonding or otherwise attaching these precursor molecules to a surface or substrate they can be used in numerous applications.

Alkali-metal-ion catalysis and inhibition in the nucleophilic displacement reaction of y-substituted phenyl diphenylphosphinates and diphenylphosphinothioates with alkali-metal ethoxides: effect of changing the electrophilic center from P=O to P=S.

PubMed

Um, Ik-Hwan; Shin, Young-Hee; Park, Jee-Eun; Kang, Ji-Sun; Buncel, Erwin

2012-01-16

A kinetic study of the nucleophilic substitution reaction of Y-substituted phenyl diphenylphosphinothioates 2 a-g with alkali-metal ethoxides (MOEt; M = Li, Na, K) in anhydrous ethanol at (25.0±0.1) °C is reported. Plots of pseudo-first-order rate constants (k(obsd)) versus [MOEt], the alkali ethoxide concentration, show distinct upward (KOEt) and downward (LiOEt) curvatures, respectively, pointing to the importance of ion-pairing phenomena and a differential reactivity of dissociated EtO(-) and ion-paired MOEt. Based on ion-pairing treatment of the kinetic data, the k(obsd) values were dissected into k EtO - and k(MOEt), the second-order rate constants for the reaction with the dissociated EtO(-) and ion-paired MOEt, respectively. The reactivity of MOEt toward 2 b (Y = 4-NO(2)) increases in the order LiOEtNaOEt>KOEt>EtO(-). The current study based on Yukawa-Tsuno analysis has revealed that the reactions of 2 a-g (P=S) and Y-substituted phenyl diphenylphosphinates 1 a-g (P=O) with MOEt proceed through the same concerted mechanism, which indicates that the contrasting selectivity patterns are not due to a difference in reaction mechanism. The P=O compounds 1 a-g are approximately 80-fold more reactive than the P=S compounds 2 a-g toward the dissociated EtO(-) (regardless of the electronic nature of substituent Y) but are up to 3.1×10(3)-fold more reactive toward ion-paired LiOEt. The origin of the contrasting selectivity patterns is further discussed on the basis of competing electrostatic effects and solvational requirements as a function of anionic electric field strength and cation size (Eisenman's theory). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Water Assisted Reaction Mechanism of OH- with CCl4 in Aqueous Solution - Hybrid Quantum Mechanical and Molecular Mechanics Investigation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Jie; Yin, Hongyun; Wang, Dunyou

2013-02-20

The OH- (H2O) + CCl4 reaction in aqueous solution was investigated using the combined quantum mechanical and molecular mechanics approach. The reaction mechanism of OH- (H2O) + CCl4 consists of two concerted steps - formation of OH- in the favorable attack conformation via the proton transfer process, and the nucleophilic substitution process in which the newly formed OH- attacks the CCl4. The free energy activation barrier is 38.2 kcal/mol at CCSD(T)/MM level of theory for this reaction, which is about 10.3 kcal/mol higher than that of the direct nucleophilic substitution mechanism of the OH- + CCl4 reaction in aqueous solution.

Hyperbranched Polycarbosilanes via Nucleophilic Substitution Reactions

NASA Astrophysics Data System (ADS)

Interrante, L.; Shen, Q.

Nucleophilic substitution reactions involving organomagnesium (Grignard) [1] and organolithium reagents have been used extensively for many years to form Si—C bonds (see Reaction Scheme 12.1). However, their use for the construction of hyperbranched polymers whose backbone contains, as a major structural component, silicon—carbon bonds, i.e., polycarbosilanes [2] is relatively more recent. (12.1) begin{array}{l} {{R}}_3 {{SiX + MR'}} to {{R}}_3 {{SiR' + MX}} \\ left({{{R,R' = alkyl}} {{or aryl;}} {{M = Mg(X),}} {{Li,}} {{Na}};{{X = halogen, OR''}}} right) \\ This chapter focuses on the application of such nucleophilic substitution reactions toward the synthesis of hyperbranched polycarbosilanes, with particular emphasis on those preparations that have resulted in relatively well characterized products. These syntheses are organized by the type of ABn monomer unit used (see Section 1.2), where A and B refer to the (C)X and (Si)Xn, respectively, functional ends of the monomer unit and where the nature of the coupling reaction leads to entirely or primarily Si—C bond formation. In most cases, these are “one-pot” reactions that employ monomers that bear halogen or alkoxy groups on the C and Si ends of the unit. Indeed, hyperbranched polycarbosilanes have been described, in general, as “obtained in one synthetic step via a random, one-pot polymerization of multifunctional monomers of AB n type” [2]. Treatment of the ABn monomer with either elemental Mg or an organolithium reagent, ideally (but not always) forms a complexed carbanion (the nucleophile) by reaction with the C-X end of the monomer unit, resulting in an intermediate of the type, (XxM)CSiXn, where M = Mg or Li, X = halogen or alkoxy, and x = 1 (Mg) or 0 (Li). Self-coupling of this reagent via reactions of the type shown in Reaction Scheme 12.1 leads to oligomeric and polymeric products that are connected primarily through Si—C bonds and yield an inorganic MXx by-product.

Silyl Ketene Imines: Highly Versatile Nucleophiles for Catalytic, Asymmetric Synthesis

PubMed Central

Denmark, Scott E.; Wilson, Tyler W.

2012-01-01

This Minireview provides an overview on the development of silyl ketene imines and their recent applications in catalytic, enantioselective reactions. The unique structure of the ketene imine allows a diverse range of reactivity patterns and provides solutions to existing challenges in the enantioselective construction of quaternary stereogenic carbon centers and cross-benzoin adducts. A variety of reactions for which silyl ketene imines have been applied are presented with an overall goal of inspiring new uses for these underutilized nucleophiles. PMID:22968901

A model SN2 reaction ‘on water’ does not show rate enhancement

NASA Astrophysics Data System (ADS)

Nelson, Katherine V.; Benjamin, Ilan

2011-05-01

Molecular dynamics calculations of the benchmark nucleophilic substitution reaction (SN2) Cl- + CH3Cl are carried out at the water liquid/vapor interface. The reaction free energy profile and the activation free energy are determined as a function of the reactants' location normal to the surface. The activation free energy remains almost constant relative to that in bulk water, despite the fact that the barrier is expected to significantly decrease as the reaction is carried out near the vapor phase. We show that this is due to the combined effects of a clustering of water molecules around the nucleophile and a relatively weak hydration of the transition state.

Stereoinversion of tertiary alcohols to tertiary-alkyl isonitriles and amines.

PubMed

Pronin, Sergey V; Reiher, Christopher A; Shenvi, Ryan A

2013-09-12

The SN2 reaction (bimolecular nucleophilic substitution) is a well-known chemical transformation that can be used to join two smaller molecules together into a larger molecule or to exchange one functional group for another. The SN2 reaction proceeds in a very predictable manner: substitution occurs with inversion of stereochemistry, resulting from the 'backside attack' of the electrophilic carbon by the nucleophile. A significant limitation of the SN2 reaction is its intolerance for tertiary carbon atoms: whereas primary and secondary alcohols are viable precursor substrates, tertiary alcohols and their derivatives usually either fail to react or produce stereochemical mixtures of products. Here we report the stereochemical inversion of chiral tertiary alcohols with a nitrogenous nucleophile facilitated by a Lewis-acid-catalysed solvolysis. The method is chemoselective against secondary and primary alcohols, thereby complementing the selectivity of the SN2 reaction. Furthermore, this method for carbon-nitrogen bond formation mimics a putative biosynthetic step in the synthesis of marine terpenoids and enables their preparation from the corresponding terrestrial terpenes. We expect that the general attributes of the methodology will allow chiral tertiary alcohols to be considered viable substrates for stereoinversion reactions.

Amino acids as novel nucleophiles for silver nanoparticle-luminol chemiluminescence.

PubMed

Li, Na; Ni, Shubiao

2014-12-01

The use of noble metal nanoparticles (NPs) as reductants in chemiluminescence (CL) has been reported only rarely owing to their high oxidation potentials. Interestingly, nucleophiles could dramatically lower the oxidation potential of Ag NPs, such that in the presence of nucleophiles Ag NPS could be used as reductants to induce the CL emission of luminol, an important CL reagent widely used in forensic analysis for the detection of trace amounts of blood. Although nucleophiles are indispensible in Ag NP-luminol CL, only inorganic nucleophiles such as Cl(-), Br(-), I(-) and S2O3 (2-) have been shown to be efficient. The effects of organic nucleophiles on CL remain unexplored. In this study, 20 standard amino acids were evaluated as novel organic nucleophiles in Ag NP-luminol CL. Histidine, lysine and arginine could initiate CL emission; the others could not. It is proposed that the different behaviors of 20 standard amino acids in the CL reactions derive from the interface chemistry between Ag NPs and these amino acids. UV/vis absorption spectra were studied to validate the interface chemistry. In addition, imidazole and histidine were chosen as a model pair to compare the behavior of the monodentate nucleophile with that of the corresponding multidentate nucleophile in Ag NP-luminol CL. Copyright © 2014 John Wiley & Sons, Ltd.

Fine-tuning the nucleophilic reactivities of boron ate complexes derived from aryl and heteroaryl boronic esters.

PubMed

Berionni, Guillaume; Leonov, Artem I; Mayer, Peter; Ofial, Armin R; Mayr, Herbert

2015-02-23

Boron ate complexes derived from thienyl and furyl boronic esters and aryllithium compounds have been isolated and characterized by X-ray crystallography. Products and mechanisms of their reactions with carbenium and iminium ions have been analyzed. Kinetics of these reactions were monitored by UV/Vis spectroscopy, and the influence of the aryl substituents, the diol ligands (pinacol, ethylene glycol, neopentyl glycol, catechol), and the counterions on the nucleophilic reactivity of the boron ate complexes were examined. A Hammett correlation confirmed the polar nature of their reactions with benzhydrylium ions, and the correlation lg k(20 °C)=sN (E+N) was employed to determine the nucleophilicities of the boron ate complexes and to compare them with those of other borates and boronates. The neopentyl and ethylene glycol derivatives were found to be 10(4) times more reactive than the pinacol and catechol derivatives. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

δ-Deuterium Isotope Effects as Probes for Transition-State Structures of Isoprenoid Substrates

PubMed Central

2015-01-01

The biosynthetic pathways to isoprenoid compounds involve transfer of the prenyl moiety in allylic diphosphates to electron-rich (nucleophilic) acceptors. The acceptors can be many types of nucleophiles, while the allylic diphosphates only differ in the number of isoprene units and stereochemistry of the double bonds in the hydrocarbon moieties. Because of the wide range of nucleophilicities of naturally occurring acceptors, the mechanism for prenyltransfer reactions may be dissociative or associative with early to late transition states. We have measured δ-secondary kinetic isotope effects operating through four bonds for substitution reactions with dimethylallyl derivatives bearing deuterated methyl groups at the distal (C3) carbon atom in the double bond under dissociative and associative conditions. Computational studies with density functional theory indicate that the magnitudes of the isotope effects correlate with the extent of bond formation between the allylic moiety and the electron-rich acceptor in the transition state for alkylation and provide insights into the structures of the transition states for associative and dissociative alkylation reactions. PMID:24665882

Organic Chemistry Students' Ideas about Nucleophiles and Electrophiles: The Role of Charges and Mechanisms

ERIC Educational Resources Information Center

Anzovino, Mary E.; Bretz, Stacey Lowery

2015-01-01

Organic chemistry students struggle with reaction mechanisms and the electron-pushing formalism (EPF) used by practicing organic chemists. Faculty have identified an understanding of nucleophiles and electrophiles as one conceptual prerequisite to mastery of the EPF, but little is known about organic chemistry students' knowledge of nucleophiles…

Chiral phosphines in nucleophilic organocatalysis

PubMed Central

Xiao, Yumei; Sun, Zhanhu

2014-01-01

Summary This review discusses the tertiary phosphines possessing various chiral skeletons that have been used in asymmetric nucleophilic organocatalytic reactions, including annulations of allenes, alkynes, and Morita–Baylis–Hillman (MBH) acetates, carbonates, and ketenes with activated alkenes and imines, allylic substitutions of MBH acetates and carbonates, Michael additions, γ-umpolung additions, and acylations of alcohols. PMID:25246969

Synthesis of a Fluorescent Acridone Using a Grignard Addition, Oxidation, and Nucleophilic Aromatic Substitution Reaction Sequence

ERIC Educational Resources Information Center

Goodrich, Samuel; Patel, Miloni; Woydziak, Zachary R.

2015-01-01

A three-pot synthesis oriented for an undergraduate organic chemistry laboratory was developed to construct a fluorescent acridone molecule. This laboratory experiment utilizes Grignard addition to an aldehyde, alcohol oxidation, and iterative nucleophilic aromatic substitution steps to produce the final product. Each of the intermediates and the…

Phosphorus-containing nucleophiles in reactions with polyfluorinated organic compounds

NASA Astrophysics Data System (ADS)

Furin, Georgii G.

1993-03-01

The review presents a compilation of new expelimental data on the reactions of phosphorus-containing nucleophiles [triphenylphosphine, trialkylphosphines, trialkyl phosphites, phosphorus tris(diethylamide), etc.] with perfluorinated olefins and aromatic and heterocyclic compounds, leading to substances both with and without a phosphorus atom. It is shown that the interaction of phosphorus tris(diethylamide) and trialkylphosphines with organic polyfluoro-compounds and perfluoroolefins leads to the formation of phosphoranes, the decomposition of which is accompanied by the generation of aryl and alkenyl anions. The reactions of these anions with C-electrophiles and compounds containing mobile halogen atoms are examined. In addition, the pathways in the Arbuzov reaction involving a series of unsaturated perfluorinated compounds are analysed. Possible applications of these reactions in organic synthesis are demonstrated. The bibliography includes 120 references.

Synthesis, Electrochemistry, and Reactivity of the Actinide Trisulfides [K(18-crown-6)][An(η(3)-S3)(NR2)3] (An = U, Th; R = SiMe3).

PubMed

Smiles, Danil E; Wu, Guang; Hayton, Trevor W

2016-09-19

The reaction of [Th(I)(NR2)3] (R = SiMe3) with [K(18-crown-6)]2[S4] results in the formation of [K(18-crown-6)][Th(η(3)-S3)(NR2)3] (2). Oxidation of 2, or its uranium analogue, [K(18-crown-6)][U(η(3)-S3)(NR2)3] (1), with AgOTf, in an attempt to generate an [S3](•-) complex, results in the formation of [K(18-crown-6)][An(OTf)2(NR2)3] (3, An = U; 4, An = Th) as the only isolable products. These results suggest that the putative [S3](•-) ligand is only weakly coordinating and can be easily displaced by nucleophiles.

Enantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studies

PubMed Central

Behenna, Douglas C.; Mohr, Justin T.; Sherden, Nathaniel H.; Marinescu, Smaranda C.; Harned, Andrew M.; Tani, Kousuke; Seto, Masaki; Ma, Sandy; Novák, Zoltán; Krout, Michael R.; McFadden, Ryan M.; Roizen, Jennifer L.; Enquist, John A.; White, David E.; Levine, Samantha R.; Petrova, Krastina V.; Iwashita, Akihiko; Virgil, Scott C.; Stoltz, Brian M.

2012-01-01

α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursors: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center. PMID:22083969

Mechanistic Study of Oxygen Atom Transfer Catalyzed by Rhenium Compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shan, Xiaopeng

2003-01-01

Two ionic and one neutral methyl(oxo)rhenium(V) compounds were synthesized and structurally characterized. They were compared in reactivity towards the ligands triphenylphosphane, pyridines, pyridine N-oxides. Assistance from Broensted bases was found on ligand displacement of ionic rhenium compounds as well as nucleophile assistance on oxidation of all compounds. From the kinetic data, crystal structures, and an analysis of the intermediates, a structural formula of PicH +3 - and mechanisms of ligand displacement and oxidation were proposed.

Heterobimetallic Pd-Sn catalysis: Michael addition reaction with C-, N-, O-, and S-nucleophiles and in situ diagnostics.

PubMed

Das, Debjit; Pratihar, Sanjay; Roy, Sujit

2013-03-15

An efficient Michael addition reaction of differently substituted enones with carbon, sulfur, oxygen, and nitrogen nucleophiles has been achieved by a new heterobimetallic "Pd-Sn" catalyst system. The nature of the catalytically relevant species and their interactions with the enone moiety has been examined by spectroscopy. The effect of ligand and the coordination mode of enone with "Pd-Sn" heterobimetallic system have been investigated by kinetics and DFT studies. A straightforward application of this methodology is shown in the synthesis of 1,4-oxathiepane core.

Mechanism of the sulfurisation of phosphines and phosphites using 3-amino-1,2,4-dithiazole-5-thione (xanthane hydride).

PubMed

Hanusek, Jirí; Russell, Mark A; Laws, Andrew P; Jansa, Petr; Atherton, John H; Fettes, Kevin; Page, Michael I

2007-02-07

Contrary to a previous report, the sulfurisation of phosphorus(III) derivatives by 3-amino-1,2,4-dithiazole-5-thione (xanthane hydride) does not yield carbon disulfide and cyanamide as the additional reaction products. The reaction of xanthane hydride with triphenyl phosphine or trimethyl phosphite yields triphenyl phosphine sulfide or trimethyl thiophosphate, respectively, and thiocarbamoyl isothiocyanate which has been trapped with nucleophiles. The reaction pathway involves initial nucleophilic attack of the phosphorus at sulfur next to the thiocarbonyl group of xanthane hydride followed by decomposition of the phosphonium intermediate formed to products. The Hammett rho-values for the sulfurisation of substituted triphenyl phosphines and triphenyl phosphites in acetonitrile are approximately -1.0. The entropies of activation are very negative (-114+/-15 J mol-1 K-1) with little dependence on solvent which is consistent with a bimolecular association step leading to the transition state. The negative values of DeltaS(not equal) and rho values indicate that the rate limiting step of the sulfurisation reaction is formation of the phosphonium ion intermediate which has an early transition state with little covalent bond formation. The site of nucleophilic attack has been also confirmed using computational calculations.

Organic Chemistry Students' Fragmented Ideas about the Structure and Function of Nucleophiles and Electrophiles: A Concept Map Analysis

ERIC Educational Resources Information Center

Anzovino, Mary E.; Bretz, Stacey Lowery

2016-01-01

Organic chemistry students struggle with multiple aspects of reaction mechanisms and the curved arrow notation used by organic chemists. Many faculty believe that an understanding of nucleophiles and electrophiles, among other concepts, is required before students can develop fluency with the electronpushing formalism (EPF). An expert concept map…

Transition-Metal Catalysis of Nucleophilic Substitution Reactions: A Radical Alternative to SN1 and SN2 Processes.

PubMed

Fu, Gregory C

2017-07-26

Classical methods for achieving nucleophilic substitutions of alkyl electrophiles (S N 1 and S N 2) have limited scope and are not generally amenable to enantioselective variants that employ readily available racemic electrophiles. Radical-based pathways catalyzed by chiral transition-metal complexes provide an attractive approach to addressing these limitations.

Transition-Metal Catalysis of Nucleophilic Substitution Reactions: A Radical Alternative to SN1 and SN2 Processes

PubMed Central

2017-01-01

Classical methods for achieving nucleophilic substitutions of alkyl electrophiles (SN1 and SN2) have limited scope and are not generally amenable to enantioselective variants that employ readily available racemic electrophiles. Radical-based pathways catalyzed by chiral transition-metal complexes provide an attractive approach to addressing these limitations. PMID:28776010

Characterization of labelling and de-labelling reagents for detection and recovery of tyrosine residue in peptide.

PubMed

Toyo'oka, Toshimasa; Mantani, Tomomi; Kato, Masaru

2003-01-01

This paper characterized the labelling and de-labelling reagents for reversible labelling of tyrosine (Tyr)-containing peptide, which involves detection and recovery. The phenolic hydroxyl group (-OH) in Tyr structure reacted with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (DBD-F), and 1-fluoro-2,4-dinitrobenzene (DNFB) under mild conditions at room temperature at pH 9.3. The labels in the resulting derivatives were removed with the treatment of nucleophiles, such as thiols (cysteine, N-acetyl-L-cysteine and dithiothreitol) and amines (dimethylamine, methylamine, diethylamine, ethylamine and pyrrolidine). The de-labelling reactions of NBD-labelled N-acetyl-L-tyrosine (N-AcTyr) with the nucleophiles produced N-AcTyr, accompanied by NBD-nucleophile. Although DBD-F and DNFB also successfully labeled the -OH group in N-AcTyr, the efficiency of Cbond;O bond cleavage and recovery of N-AcTyr by the nucleophiles was relatively low compared with NBD-label. Among the de-labelling reagents, N-acetyl-L-cysteine and dimethylamine were recommended for the elimination of NBD moiety, with respect to the reaction rate, the side reaction, and the yield of recovery. The proposed procedure, which includes the labelling with NBD-F and the removal of NBD moiety by the nucleophiles, was successfully applied to the reversible labelling of N-terminal amine-blocked peptides, i.e. N-AcTyr-Val-Gly, Z-Glu-Tyr, Z-Phe-Tyr, N-Formyl-Met-Leu-Tyr, and N-AcArg-Pro-Pro-Gly-Phe-Ser-Pro-Tyr-Arg. Copyright 2003 John Wiley & Sons, Ltd.

Redox homeostasis: The Golden Mean of healthy living

PubMed Central

Ursini, Fulvio; Maiorino, Matilde; Forman, Henry Jay

2016-01-01

The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve “reactive oxygen species” rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles (parahormesis). In summary, while hormesis, although globally protective, results in setting up of a new phenotype, parahormesis contributes to health by favoring maintenance of homeostasis. PMID:26820564

Eco-friendly polyethylene glycol promoted Michael addition reactions of α,β-unsaturated carbonyl compounds

EPA Science Inventory

Abstract- Intra- and inter-nucleophilic addition reactions of different unsaturated compounds were found to be highly effective without any additives in PEG-400 as a recyclable reaction medium under neutral conditions.

Bond formations by intermolecular and intramolecular trappings of acylketenes and their applications in natural product synthesis†

PubMed Central

Reber, Keith P.; Tilley, S. David

2011-01-01

The reactive intermediates known as acylketenes exhibit a rich chemistry and have been extensively utilized for many types of inter- and intramolecular bond-forming reactions within the field of organic synthesis. Characteristic reactions of acylketenes include cycloadditions, carbon–carbon bond-forming reactions, and nucleophilic capture with alcohols or amines to give β-keto acid derivatives. In particular, the intramolecular capture of acylketene intermediates with pendant nucleophiles represents a powerful method for forming both medium-sized rings and macrocycles, often in high yield. This tutorial review examines the history, generation, and reactivity of acylketenes with a special focus on their applications in the synthesis of natural products. PMID:19847338

Photo-oxidation of 6-thioguanine by UVA: the formation of addition products with low molecular weight thiol compounds.

PubMed

Ren, Xiaolin; Xu, Yao-Zhong; Karran, Peter

2010-01-01

The thiopurine, 6-thioguanine (6-TG) is present in the DNA of patients treated with the immunosuppressant and anticancer drugs azathioprine or mercaptopurine. The skin of these patients is selectively sensitive to UVA radiation-which comprises >90% of the UV light in incident sunlight-and they suffer high rates of skin cancer. UVA irradiation of DNA 6-TG produces DNA lesions that may contribute to the development of cancer. Antioxidants can protect 6-TG against UVA but 6-TG oxidation products may undergo further reactions. We characterize some of these reactions and show that addition products are formed between UVA-irradiated 6-TG and N-acetylcysteine and other low molecular weight thiol compounds including β-mercaptoethanol, cysteine and the cysteine-containing tripeptide glutathione (GSH). GSH is also adducted to 6-TG-containing oligodeoxynucleotides in an oxygen- and UVA-dependent nucleophilic displacement reaction that involves an intermediate oxidized 6-TG, guanine sulfonate (G(SO3) ). These photochemical reactions of 6-TG, particularly the formation of a covalent oligodeoxynucleotide-GSH complex, suggest that crosslinking of proteins or low molecular weight thiol compounds to DNA may be a previously unrecognized hazard in sunlight-exposed cells of thiopurine-treated patients. © 2010 The Authors. Journal Compilation. The American Society of Photobiology.

Easy access to nucleophilic boron through diborane to magnesium boryl metathesis

NASA Astrophysics Data System (ADS)

Pécharman, Anne-Frédérique; Colebatch, Annie L.; Hill, Michael S.; McMullin, Claire L.; Mahon, Mary F.; Weetman, Catherine

2017-04-01

Organoboranes are some of the most synthetically valuable and widely used intermediates in organic and pharmaceutical chemistry. Their synthesis, however, is limited by the behaviour of common boron starting materials as archetypal Lewis acids such that common routes to organoboranes rely on the reactivity of boron as an electrophile. While the realization of convenient sources of nucleophilic boryl anions would open up a wealth of opportunity for the development of new routes to organoboranes, the synthesis of current candidates is generally limited by a need for highly reducing reaction conditions. Here, we report a simple synthesis of a magnesium boryl through the heterolytic activation of the B-B bond of bis(pinacolato)diboron, which is achieved by treatment of an easily generated magnesium diboranate complex with 4-dimethylaminopyridine. The magnesium boryl is shown to act as an unambiguous nucleophile through its reactions with iodomethane, benzophenone and N,N'-di-isopropyl carbodiimide and by density functional theory.

Felinine stability in the presence of selected urine compounds.

PubMed

Rutherfurd, S M; Kitson, T M; Woolhouse, A D; McGrath, M C; Hendriks, W H

2007-02-01

The stability of felinine, an amino acid present in feline urine, was investigated. Synthetic felinine was unstable in the urine of a selection of mammals. Felinine was found to stable in feline urine in which urea had been degraded. Synthetic felinine was found to react specifically with urea and did not react with urea analogues such as biuret or thiourea or other nucleophilic compounds such as ammonia which is more nucleophilic or acetamide and water which are less nucleophilic than urea. The reaction of urea and felinine was independent of pH over the range of 3-10. Urea did not react with N-acetyl-felinine suggesting a felinine N-terminal interaction with urea. Mass spectral analysis of the reaction products showed the presence of carbamylated felinine and fragmentation ions derived from carbamyl-felinine. The physiological relevance of felinine carbamylation is yet to be determined.

Ligand-Controlled Regioselective Copper-Catalyzed Trifluoromethylation To Generate (Trifluoromethyl)allenes.

PubMed

Ambler, Brett R; Peddi, Santosh; Altman, Ryan A

2015-05-15

"Cu-CF3" species have been used historically for a broad spectrum of nucleophilic trifluoromethylation reactions. Although recent advancements have employed ligands to stabilize and harness the reactivity of this key organometallic intermediate, the ability of a ligand to differentiate a regiochemical outcome of a Cu-CF3-mediated or -catalyzed reaction has not been previously reported. Herein, we report the first example of a Cu-catalyzed trifluoromethylation reaction in which a ligand controls the regiochemical outcome. More specifically, we demonstrate the ability of bipyridyl-derived ligands to control the regioselectivity of the Cu-catalyzed nucleophilic trifluoromethylation reactions of propargyl electrophiles to generate (trifluoromethyl)allenes. This method provides a variety of di-, tri-, and tetrasubstituted (trifluoromethyl)allenes, which can be further modified to generate complex fluorinated substructures.

A Pictet-Spengler ligation for protein chemical modification

PubMed Central

Agarwal, Paresh; van der Weijden, Joep; Sletten, Ellen M.; Rabuka, David; Bertozzi, Carolyn R.

2013-01-01

Aldehyde- and ketone-functionalized proteins are appealing substrates for the development of chemically modified biotherapeutics and protein-based materials. Their reactive carbonyl groups are typically conjugated with α-effect nucleophiles, such as substituted hydrazines and alkoxyamines, to generate hydrazones and oximes, respectively. However, the resulting C=N linkages are susceptible to hydrolysis under physiologically relevant conditions, which limits the utility of such conjugates in biological systems. Here we introduce a Pictet-Spengler ligation that is based on the classic Pictet-Spengler reaction of aldehydes and tryptamine nucleophiles. The ligation exploits the bioorthogonal reaction of aldehydes and alkoxyamines to form an intermediate oxyiminium ion; this intermediate undergoes intramolecular C–C bond formation with an indole nucleophile to form an oxacarboline product that is hydrolytically stable. We used the reaction for site-specific chemical modification of glyoxyl- and formylglycine-functionalized proteins, including an aldehyde-tagged variant of the therapeutic monoclonal antibody Herceptin. In conjunction with techniques for site-specific introduction of aldehydes into proteins, the Pictet-Spengler ligation offers a means to generate stable bioconjugates for medical and materials applications. PMID:23237853

Theoretical study on the identity ion pair SN2 reactions of LiX with CH3SX (X=Cl, Br, and I): structure, mechanism, and potential energy surface.

PubMed

Ren, Yi; Gai, Jing-Gang; Xiong, Yan; Lee, Kuo-Hsing; Chu, San-Yan

2007-07-26

Three archetypal ion pair nucleophilic substitution reactions at the methylsulfenyl sulfur atom LiX+CH3SX-->XSCH3+LiX (X=Cl, Br, and I) are investigated by the modified Gaussian-2 theory. Including lithium cation in the anionic models makes the ion pair reactions proceed along an SN2 mechanism, contrary to the addition-elimination pathway occurring in the corresponding anionic nucleophilic substitution reactions X-+CH3SX-->XSCH3+X-. Two reaction pathways for the ion pair SN2 reactions at sulfur, inversion and retention, are proposed. Results indicate the inversion pathway is favorable for all the halogens. Comparison of the transition structures and energetics for the ion pair SN2 at sulfur with the potential competition ion pair SN2 reactions at carbon LiX+CH3SX-->XCH3+LiXS shows that the SN2 reactions at carbon are not favorable from the viewpoints of kinetics and thermodynamics.

Reactions of l-ergothioneine and some other aminothiones with 2,2′- and 4,4′-dipyridyl disulphides and of l-ergothioneine with iodoacetamide. 2-Mercaptoimidazoles, 2- and 4-thiopyridones, thiourea and thioacetamide as highly reactive neutral sulphur nucleophiles

PubMed Central

Carlsson, Jan; Kierstan, Marek P. J.; Brocklehurst, Keith

1974-01-01

1. The reactions of 2,2′- and 4,4′-dipyridyl disulphide (2-Py–S–S–2-Py and 4-Py–S–S–4-Py) with l-ergothioneine (2-mercapto-l-histidine betaine), 2-mercaptoimidazole, 1-methyl-2-mercaptoimidazole, thiourea, thioacetamide, 2-thiopyridone (Py–2-SH) and 4-thiopyridone (Py–4-SH) were investigated spectrophotometrically in the pH range approx. 1–9. 2. These reactions involve two sequential reversible thiol–disulphide interchanges. 3. The reaction of l-ergothioneine with 2-Py–S–S–2-Py and/or with the l-ergothioneine–Py–2-SH mixed disulphide, both of which provide Py–2-SH, is characterized by at least three reactive protonic states. This provides definitive evidence that neutral l-ergothioneine is a reactive nucleophile, particularly towards the highly electrophilic protonated disulphides. 4. A similar situation appears to obtain in the reactions of l-ergothioneine and Py–2-SH with 4-Py–S–S–4-Py and in the reactions of the other 2-mercaptoimidazoles, thiourea and Py–4-SH with 2-Py–S–S–2-Py. The nucleophilic reactivity of Py–4-SH suggests that general base catalysis provided by the disulphide in a cyclic or quasi-cyclic transition state is not necessary to generate nucleophilic reactivity in the other amino-thiones whose geometry could permit such catalysis. 5. The existence of a positive deuterium isotope effect in the l-ergothioneine–2-Py–S–S–2-Py system at pH6–7 provides no evidence for general base catalysis but is in accord with a mechanism involving specific acid catalysis and post-transition-state proton transfer. 6. The pH-dependences of the overall equilibrium positions of the various thiol–disulphide interchanges are described. 7. Reaction of thioacetamide with a stoicheiometric quantity of 2-Py–S–S–2-Py at pH1 provides 2 molecules of Py–2-SH per molecule of thioacetamide and elemental sulphur; these findings can be accounted for by thiol–disulphide interchange to provide a thioacetamide–Py–2-SH mixed disulphide followed by fragmentation to provide CH3CN, S and Py–2-SH. 8. Provision of high reactivity in the neutral forms of the members of this series of sulphur nucleophiles by electron donation by the amino group is compared with the well known α effect that provides enhanced nucleophilicity in compounds containing an electronegative atom adjacent to the nucleophilic atom. 9. The decrease in the u.v. absorption of l-ergothioneine at 257nm consequent on transformation of its aminothione moiety into an S-alkyl-2-mercaptoimidazole moiety provides a convenient method of following the alkylation of l-ergothioneine by iodoacetamide. 10. The pH dependence of the extinction coefficient of l-ergothioneine at 257nm is described by ε257={8×103/(1+Ka/[H+]} +6×103m−1·cm−1 in which pKa=10.8. 11. In the pH range 3–11 the reaction is characterized by two reactive protonic states (X and XH). 12. The X state, reaction of the ionized 2-mercaptoimidazole moiety of the l-ergothioneine dianion with neutral iodoacetamide, is characterized by the second-order rate constant 4.0m−1·s−1 (25.0°C, I=0.05). The XH state, characterized by the second-order rate constant 0.03m−1·s−1, is interpreted as reaction of the thione form of the neutral 2-mercaptoimidazole moiety of the l-ergothioneine monoanion with neutral iodoacetamide. 13. The XH state of the alkylation reaction does not exhibit a deuterium isotope effect. PMID:4463944

[Development of boomerang-type intramolecular cascade reactions and application to natural product synthesis].

PubMed

Takasu, K

2001-12-01

Intramolecular cascade reaction has received much attention as a powerful methodology to construct a polycyclic framework in organic synthesis. We have been developing "boomerang-type cascade reaction" to construct a variety of polycyclic skeletons efficiently. In the above reactions, a nucleophilic function of substrates changes the character into an electrophile after the initial reaction, and the electrophilic group acts as a nucleophile in the second reaction. That is, the reaction center stepwise moves from one functional group back to the same one via other functional groups. The stream of the electron concerning the cascade reaction is like a locus of boomerang. We show here three different boomerang-type reactions via ionic species or free radicals. 1) Diastereoselective Michael-aldol reaction based on the chiral auxiliary method and enantioselective Michael-aldol reaction by the use of external chiral sources. 2) Short and efficient total syntheses of longifolane sesquiterpenes utilizing intramolecular double Michael addition as a key step. 3) Development of boomerang-type radical cascade reaction of halopolyenes to construct terpenoid skeletons and its regioselectivity.

Improved strategies for postoligomerization synthesis of oligodeoxynucleotides bearing structurally defined adducts at the N2 position of deoxyguanosine.

PubMed

DeCorte, B L; Tsarouhtsis, D; Kuchimanchi, S; Cooper, M D; Horton, P; Harris, C M; Harris, T M

1996-01-01

Improved methodology has been developed for preparation of oligodeoxynucleotides bearing adducts on the N2 position of guanine in which the adduction reaction is carried out in homogeneous solution rather than while the oligonucleotide is immobilized on a solid matrix. The methodology utilizes a new synthon, 2-fluoro-O6-(trimethylsilylethyl)-2'-deoxyinosine (3). Nucleoside 3 is stable to the conditions of oligonucleotide synthesis, but the O6 protection is eliminated under very mild conditions following displacement of the 2-fluoro group by amine nucleophiles. Oligonucleotides containing 3 could be removed from the solid support by treatment with 0.1 M NaOH (8 h, rt) without disruption of 3. Reaction of the crude, partially deprotected oligonucleotide with (R)-2-amino-2-phenylethanol in homogeneous solution, followed by removal of the remaining protective groups with NH4OH (60 degrees C, 8 h) and then 0.1% acetic acid, gave the adducted oligonucleotide in good purity and yield. Alternatively, fully deprotected oligonucleotide containing 3 could be prepared by use of labile phenoxyacetyl-type protecting groups on the exocyclic amino groups.

Mechanism of tungsten-dependent acetylene hydratase from quantum chemical calculations.

PubMed

Liao, Rong-Zhen; Yu, Jian-Guo; Himo, Fahmi

2010-12-28

Acetylene hydratase is a tungsten-dependent enzyme that catalyzes the nonredox hydration of acetylene to acetaldehyde. Density functional theory calculations are used to elucidate the reaction mechanism of this enzyme with a large model of the active site devised on the basis of the native X-ray crystal structure. Based on the calculations, we propose a new mechanism in which the acetylene substrate first displaces the W-coordinated water molecule, and then undergoes a nucleophilic attack by the water molecule assisted by an ionized Asp13 residue at the active site. This is followed by proton transfer from Asp13 to the newly formed vinyl anion intermediate. In the subsequent isomerization, Asp13 shuttles a proton from the hydroxyl group of the vinyl alcohol to the α-carbon. Asp13 is thus a key player in the mechanism, but also W is directly involved in the reaction by binding and activating acetylene and providing electrostatic stabilization to the transition states and intermediates. Several other mechanisms are also considered but the energetic barriers are found to be very high, ruling out these possibilities.

α-Oxo-Ketenimines from Isocyanides and α-Haloketones: Synthesis and Divergent Reactivity.

PubMed

Mamboury, Mathias; Wang, Qian; Zhu, Jieping

2017-09-18

The palladium-catalyzed reaction of α-haloketones with isocyanides afforded α-oxo-ketenimines through β-hydride elimination of the β-oxo-imidoyl palladium intermediates. Reaction of these relatively stable α-oxo-ketenimines with nucleophiles such as hydrazines, hydrazoic acid, amines, and Grignard reagent afforded pyrazoles, tetrazole, β-keto amidines, and enaminone, respectively, with high chemoselectivity. Whereas amines attack exclusively on the ketenimine functions, the formal [3+2] cycloaddition between N-monosubstituted hydrazines and α-oxo-ketenimines was initiated by nucleophilic addition to the carbonyl group. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Secondary benzylation with benzyl alcohols catalyzed by a high-valent heterobimetallic Ir-Sn complex.

PubMed

Podder, Susmita; Choudhury, Joyanta; Roy, Sujit

2007-04-13

A highly efficient secondary benzylation procedure has been demonstrated using a high-valent heterobimetallic complex [Ir2(COD)2(SnCl3)2(Cl)2(mu-Cl)2] 1 as the catalyst in 1,2-dichloroethane to afford the corresponding benzylated products in moderate to excellent yields. The reaction was performed not only with carbon nucleophiles (arenes and heteroarenes) but also with oxygen (alcohol), nitrogen (amide and sulfonamide), and sulfur (thiol) nucleophiles. Mechanistic investigation showed the intermediacy of the ether in this reaction. An electrophilic mechanism is proposed from Hammett correlation.

Polar Diels-Alder reactions using electrophilic nitrobenzothiophenes. A combined experimental and DFT study

NASA Astrophysics Data System (ADS)

Della Rosa, Claudia D.; Mancini, Pedro M. E.; Kneeteman, Maria N.; Lopez Baena, Anna F.; Suligoy, Melisa A.; Domingo, Luis R.

2015-01-01

The reactions between 2- and 3-nitrobenzothiophenes with three dienes of different nucleophilicity, 1-methoxy-3-trimethylsilyloxy-1,3-butadiene, 1-trimethylsilyloxy-1,3-butadiene and isoprene developed in anhydrous benzene and alternative under microwave irradiation with molecular solvents or in free solvent conditions, respectively, for produce dibenzothiophenes permit to conclude that both nitroheterocycles act as electrophile with the cited dienes. In the cases of the dienes 1-methoxy-3-trimethylsilyloxy-1,3-butadiene and 1-trimethylsilyloxy-1,3-butadiene which posses major nucleophilicity the observed product is the normal cycloaddition one. However when the diene is isoprene the product with both electrophiles follow the hetero Diels-Alder way. These reactions are considered polar cycloaddition reactions and the yields are reasonables. Moreover the polar Diels-Alder reactions of nitrobenzothiophenes with electron rich dienes 1-trimethylsilyloxy-1,3-butadiene have been theoretically studied using DFT methods.

Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols.

PubMed

Tait, Katrina; Horvath, Alysia; Blanchard, Nicolas; Tam, William

2017-01-01

The acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicylic alkene using alcohol nucleophiles were investigated. Although this acid-catalyzed ring-opening reaction did not cleave the cyclopropane unit as planned, this represent the first examples of ring-openings of cyclopropanated 3-aza-2-oxabicyclo[2.2.1]alkenes that lead to the cleavage of the C-O bond instead of the N-O bond. Different acid catalysts were tested and it was found that pyridinium toluenesulfonate in methanol gave the best yields in the ring-opening reactions. The scope of the reaction was successfully expanded to include primary, secondary, and tertiary alcohol nucleophiles. Through X-ray crystallography, the stereochemistry of the product was determined which confirmed an S N 2-like mechanism to form the ring-opened product.

Probing the reactivation process of sarin-inhibited acetylcholinesterase with α-nucleophiles: hydroxylamine anion is predicted to be a better antidote with DFT calculations.

PubMed

Khan, Md Abdul Shafeeuulla; Lo, Rabindranath; Bandyopadhyay, Tusar; Ganguly, Bishwajit

2011-08-01

Inactivation of acetylcholinesterase (AChE) due to inhibition by organophosphorus (OP) compounds is a major threat to human since AChE is a key enzyme in neurotransmission process. Oximes are used as potential reactivators of OP-inhibited AChE due to their α-effect nucleophilic reactivity. In search of more effective reactivating agents, model studies have shown that α-effect is not so important for dephosphylation reactions. We report the importance of α-effect of nucleophilic reactivity towards the reactivation of OP-inhibited AChE with hydroxylamine anion. We have demonstrated with DFT [B3LYP/6-311G(d,p)] calculations that the reactivation process of sarin-serine adduct 2 with hydroxylamine anion is more efficient than the other nucleophiles reported. The superiority of hydroxylamine anion to reactivate the sarin-inhibited AChE with sarin-serine adducts 3 and 4 compared to formoximate anion was observed in the presence and absence of hydrogen bonding interactions of Gly121 and Gly122. The calculated results show that the rates of reactivation process of adduct 4 with hydroxylamine anion are 261 and 223 times faster than the formoximate anion in the absence and presence of such hydrogen bonding interactions. The DFT calculated results shed light on the importance of the adjacent carbonyl group of Glu202 for the reactivation of sarin-serine adduct, in particular with formoximate anion. The reverse reactivation reaction between hydroxylamine anion and sarin-serine adduct was found to be higher in energy compared to the other nucleophiles, which suggests that this α-nucleophile can be a good antidote agent for the reactivation process. Copyright © 2011 Elsevier Inc. All rights reserved.

Structure-function studies of adenylosuccinate synthetase from Escherichia coli.

PubMed

Honzatko, R B; Fromm, H J

1999-10-01

Adenylosuccinate synthetase catalyzes the first committed step in the de novo biosynthesis of AMP, thermodynamically coupling the hydrolysis of GTP to the formation of adenylosuccinate from l-aspartate and IMP. The enzyme from Esherichia coli undergoes a ligand-induced dimerization, which leads to the assembly of a complete active site. The binding of IMP causes conformational changes over distances of 30 A, the end result of which is the activation of essential catalytic elements and the organization of the binding pocket for Mg(2+)-GTP. The enzyme promotes first a phosphoryl transfer from GTP to the 6-oxygen atom of IMP, by way of a transition state that has characteristics of both associative and dissociative reaction pathways. Following the formation of 6-phosphoryl-IMP, the enzyme then catalyzes the nucleophilic displacement of the 6-phosphoryl group by the alpha-amino group of l-aspartate in a transition state, which requires two metal cations. Copyright 1999 Academic Press.

Chemistry and properties of poly(arylene ether 1,3,4-oxadiazole)s and poly(arylene ether 1,2,4-triazole)s

NASA Technical Reports Server (NTRS)

Connell, J. W.; Hergenrother, P. M.; Wolf, P.

1992-01-01

Poly(arylene ether)s containing l,3,4-oxadiazole and 1,2,4-triazole units were prepared by the aromatic nucleophilic displacement reaction of bisphenol oxadiazole and bisphenol triazole compounds with activated aromatic dihalides. The polymers exhibited glass transition temperatures (Tg) ranging from 182 to 242 C, and several polymers exhibited melting transitions (Tm) ranging from 265 to 390 C. Inherent viscosities ranged from 1.02 to 3.40 dl/g, indicating relatively high molecular weights. Thin films exhibited tensile strengths, moduli, and elongations at 23 C of 90-110 MPa, 2.7-3.6 GPa, and 4-7 percent, respectively. Titanium-to-titanium tensile shear specimens of a poly(arylene ether 1,3,4-oxadiazole) exhibited tensile shear strengths at 23 and 150 C of 22.1 and 17.9 MPa, respectively.

Prediction of the chemo- and regioselectivity of Diels-Alder reactions of o-benzoquinone derivatives with thiophenes by means of DFT-based reactivity indices

NASA Astrophysics Data System (ADS)

Ghomri, Amina; Mekelleche, Sidi Mohamed

2014-03-01

Global and local reactivity indices derived from density functional theory were used to elucidate the regio- and chemoselectivity of Diels-Alder reactions of masked o-benzoquinones with thiophenes acting as dienophiles. The polarity of the studied reactions is evaluated in terms of the difference of electrophilicity powers between the diene and dienophile partners. Preferential cyclisation modes of these cycloadditions are predicted using Domingo's polar model based on the local electrophilicity index, ωk, of the electrophile and the local nucleophilicity index, Nuk, of the nucleophile. The theoretical calculations, carried out at the B3LYP/6-311G(d,p) level of theory, are in good agreement with experimental findings.

Aromatic Substitution Reactions: When You've Said Ortho, Meta, and Para, You Haven't Said It All.

ERIC Educational Resources Information Center

Traynham, James G.

1983-01-01

Recent investigations show that the ipso position competes effectively with unsubstituted positions in many aromatic substitution reactions, regardless of charge type of reaction. Selected examples available for nucleophilic, electrophilic, and free radical reactions are reviewed to suggest the range of ipso reactions. (JN)

An Unusual Salt Effect in an Interfacial Nucleophilic Substitution Reaction.

PubMed

Li, Shuheng; Mrksich, Milan

2018-06-12

This paper reports a kinetic characterization of the interfacial reaction of N-methylpyrrolidine with a self-assembled monolayer presenting an iodoalkyl group. SAMDI (self-assembled monolayers for matrix-assisted laser desorption/ionization) mass spectrometry was used to determine the extent of reaction for monolayers that were treated with a range of concentrations of the nucleophile for a range of times. These data revealed a second-order rate constant for the reaction that was approximately 100-fold greater than that for the analogous solution-phase reaction. However, addition of sodium iodide to the reaction mixture resulted in a 7-fold decrease in the reaction rate. Addition of bromide and chloride salts also gave slower rate constants for the reaction, but only at 100- and 1000-fold higher concentrations than was observed with iodide, respectively. The corresponding solution-phase reactions, by contrast, had rate constants that were unaffected by the concentration of halide salts. This work provides a well-characterized example illustrating the extent to which the kinetics and properties of an interfacial reaction can depart substantially from their better-understood solution-phase counterparts.

The Preparation and Reaction of Phenyl-Substituted Pyrylium and Pyridinium Salts.

ERIC Educational Resources Information Center

Awartani, Radi; And Others

1986-01-01

Describes this reaction sequence involving reactivity and synthesis of heterocycles: (1) synthesis of 2,4,6-triphenylpyrylium tetrafluoroborate, II; (2) its reaction with nucleophiles; (3) reaction of pyrylium salt II with a primary amine (benzylamine, p-methoxybenzylamine, and furfurylamine) to form the N-substituted-2,4,6-triphenylpyridinium…

Copper-Catalyzed Electrophilic Amination of Organoaluminum Nucleophiles with O-Benzoyl Hydroxylamines.

PubMed

Zhou, Shuangliu; Yang, Zhiyong; Chen, Xu; Li, Yimei; Zhang, Lijun; Fang, Hong; Wang, Wei; Zhu, Xiancui; Wang, Shaowu

2015-06-19

A copper-catalyzed electrophilic amination of aryl and heteroaryl aluminums with N,N-dialkyl-O-benzoyl hydroxylamines that affords the corresponding anilines in good yields has been developed. The catalytic reaction proceeds very smoothly under mild conditions and exhibits good substrate scope. Moreover, the developed catalytic system is also well suited for heteroaryl aluminum nucleophiles, providing facile access to heteroaryl amines.

Nucleophile Promiscuity of Natural and Engineered Aldolases.

PubMed

Clapes, Pere; Hernández, Karel; Szekrenyi, Anna

2018-04-12

Asymmetric aldol addition reaction mediated by aldolases is recognized as a green and sustainable way for carbon-carbon bond formation. Research in this line has unveiled their unprecedented synthetic potentiality toward diverse new chemical structures, novel product families and even as a technology for industrial manufacturing processes. Despite that, aldolases have long been regarded as strictly selective catalysts, particularly for the nucleophilic substrate, limiting their broad applicability. In recent years, the advances in screening technologies and metagenomics uncovered novel C-C biocatalysts from superfamilies of widely known lyases. Moreover, protein engineering revealed the extraordinary malleability of different carboligases, offering a toolbox of biocatalysts active towards a large structural diversity of nucleophile substrates. In this paper, the nucleophile ambiguity of native and engineered aldolases is discussed with recent examples proving this novel concept. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Metal ion-promoted cleavage of nucleoside diphosphosugars: a model for reactions of phosphodiester bonds in carbohydrates.

PubMed

Dano, Meisa; Elmeranta, Marjukka; Hodgson, David R W; Jaakkola, Juho; Korhonen, Heidi; Mikkola, Satu

2015-12-01

Cleavage of five different nucleoside diphosphosugars has been studied in the presence of Cu(2+) and Zn(2+) complexes. The results show that metal ion catalysts promote the cleavage via intramolecular transesterification whenever a neighbouring HO group can adopt a cis-orientation with respect to the phosphate. The HO group attacks the phosphate and two monophosphate products are formed. If such a nucleophile is not available, Cu(2+) complexes are able to promote a nucleophilic attack of an external nucleophile, e.g. a water molecule or metal ion coordinated HO ligand, on phosphate. With the Zn(2+) complex, this was not observed.

Influence of the leaving group on the dynamics of a gas-phase SN2 reaction

NASA Astrophysics Data System (ADS)

Stei, Martin; Carrascosa, Eduardo; Kainz, Martin A.; Kelkar, Aditya H.; Meyer, Jennifer; Szabó, István; Czakó, Gábor; Wester, Roland

2016-02-01

In addition to the nucleophile and solvent, the leaving group has a significant influence on SN2 nucleophilic substitution reactions. Its role is frequently discussed with respect to reactivity, but its influence on the reaction dynamics remains unclear. Here, we uncover the influence of the leaving group on the gas-phase dynamics of SN2 reactions in a combined approach of crossed-beam imaging and dynamics simulations. We have studied the reaction F- + CH3Cl and compared it to F- + CH3I. For the two leaving groups, Cl and I, we find very similar structures and energetics, but the dynamics show qualitatively different features. Simple scaling of the leaving group mass does not explain these differences. Instead, the relevant impact parameters for the reaction mechanisms are found to be crucial and the differences are attributed to the relative orientation of the approaching reactants. This effect occurs on short timescales and may also prevail in solution-phase conditions.

Influence of the leaving group on the dynamics of a gas-phase SN2 reaction.

PubMed

Stei, Martin; Carrascosa, Eduardo; Kainz, Martin A; Kelkar, Aditya H; Meyer, Jennifer; Szabó, István; Czakó, Gábor; Wester, Roland

2016-02-01

In addition to the nucleophile and solvent, the leaving group has a significant influence on SN2 nucleophilic substitution reactions. Its role is frequently discussed with respect to reactivity, but its influence on the reaction dynamics remains unclear. Here, we uncover the influence of the leaving group on the gas-phase dynamics of SN2 reactions in a combined approach of crossed-beam imaging and dynamics simulations. We have studied the reaction F(-) + CH3Cl and compared it to F(-) + CH3I. For the two leaving groups, Cl and I, we find very similar structures and energetics, but the dynamics show qualitatively different features. Simple scaling of the leaving group mass does not explain these differences. Instead, the relevant impact parameters for the reaction mechanisms are found to be crucial and the differences are attributed to the relative orientation of the approaching reactants. This effect occurs on short timescales and may also prevail in solution-phase conditions.

Probing the reactivity of nucleophile residues in human 2,3-diphosphoglycerate/deoxy-hemoglobin complex by aspecific chemical modifications.

PubMed

Scaloni, A; Ferranti, P; De Simone, G; Mamone, G; Sannolo, N; Malorni, A

1999-06-11

The use of aspecific methylation reaction in combination with MS procedures has been employed for the characterization of the nucleophilic residues present on the molecular surface of the human 2,3-diphosphoglycerate/deoxy-hemoglobin complex. In particular, direct molecular weight determinations by ESMS allowed to control the reaction conditions, limiting the number of methyl groups introduced in the modified globin chains. A combined LCESMS-Edman degradation approach for the analysis of the tryptic peptide mixtures yielded to the exact identification of methylation sites together with the quantitative estimation of their degree of modification. The reactivities observed were directly correlated with the pKa and the relative surface accessibility of the nucleophilic residues, calculated from the X-ray crystallographic structure of the protein. The results here described indicate that this methodology can be efficiently used in aspecific modification experiments directed to the molecular characterization of the surface topology in proteins and protein complexes.

Direct sp(3)C-H acroleination of N-aryl-tetrahydroisoquinolines by merging photoredox catalysis with nucleophilic catalysis.

PubMed

Feng, Zhu-Jia; Xuan, Jun; Xia, Xu-Dong; Ding, Wei; Guo, Wei; Chen, Jia-Rong; Zou, You-Quan; Lu, Liang-Qiu; Xiao, Wen-Jing

2014-04-07

Sequence catalysis merging photoredox catalysis (PC) and nucleophilic catalysis (NC) has been realized for the direct sp(3) C-H acroleination of N-aryl-tetrahydroisoquinoline (THIQ). The reaction was performed under very mild conditions and afforded products in 50-91% yields. A catalytic asymmetric variant was proved to be successful with moderate enantioselectivities (up to 83 : 17 er).

The relationship between RNA catalytic processes

NASA Astrophysics Data System (ADS)

Cedergren, Robert; Lang, B. Franz; Gravel, Denis

1988-09-01

Proposals that an RNA-based genetic system preceeded DNA, stem from the ability of RNA to store genetic information and to promote simple catalysis. However, to be a valid basis for the RNA world, RNA catalysis must demonstrate or be related to intrinsic chemical properties which could have existed in primordial times. We analyze this question by first classifying RNA catalysis and related processes according to their mechanism. We define: (A) thedisjunct nucleophile class which leads to 5'-phosphates. These include Group I and II intron splicing, nuclear mRNA splicing and RNase P reactions. Although Group I introns and its excision mechanism is likely to have existed in primordial times, present-day examples have arisen independently in different phyla much more recently. Comparative methodology indicates that RNase P catalysis originated before the divergence of the major kingdoms. In addition, alldisjunct nucleophile reactions can be interrelated by a proposed mechanism involving a distant 2-OH nucleophile. (B) theconjunct nucleophile class leading to 3'-phosphates. This class is composed of self-cleaving RNAs found in plant viruses and the newt. We propose that tRNA splicing is related to this mechanism rather than the previous one. The presence of introns in tRNA genes of eukaryotes and archaebacteria supports the idea that tRNA splicing predates the divergence of these cell types.

Organic Reaction Mechanisms in the Sixth Form Part 2.

ERIC Educational Resources Information Center

Simpson, Peter

1989-01-01

Presents the mechanistic ideas underlying reactions between nucleophiles and carbonyl compounds as well as some popular misconceptions. Relates reactions of carboxylic acid derivatives to those of aldehydes and ketones. Discusses leaving group ability and the ability of carbonyl oxygen to accept a negative charge. (Author/MVL)

C-glycosylation reactions of sulfur-substituted glycosyl donors: evidence against the role of neighboring-group participation.

PubMed

Beaver, Matthew G; Billings, Susan B; Woerpel, K A

2008-02-13

Nucleophilic substitution reactions of C-4 sulfur-substituted tetrahydropyran acetals revealed that neighboring-group participation does not control product formation. Spectroscopic evidence for the formation of an intermediate sulfonium ion is provided, as are data from nucleophilic substitution reactions demonstrating that products are formed from oxocarbenium ion intermediates. The selectivity was not sensitive to solvent or to which Lewis acid was employed. The identity of the heteroatom at the C-4 position also did not significantly impact diastereoselectivity. Consequently, neighboring-group participation was not responsible for the formation of either the major or the minor products. These studies implicate a Curtin-Hammett kinetic scenario in which the formation of a low-energy intermediate does not necessitate its involvement in the product-forming pathway.

A New Domain of Reactivity for High-Valent Dinuclear [M(μ-O)2 M'] Complexes in Oxidation Reactions.

PubMed

Engelmann, Xenia; Yao, Shenglai; Farquhar, Erik R; Szilvási, Tibor; Kuhlmann, Uwe; Hildebrandt, Peter; Driess, Matthias; Ray, Kallol

2017-01-02

The strikingly different reactivity of a series of homo- and heterodinuclear [(M III )(μ-O) 2 (M III )'] 2+ (M=Ni; M'=Fe, Co, Ni and M=M'=Co) complexes with β-diketiminate ligands in electrophilic and nucleophilic oxidation reactions is reported, and can be correlated to the spectroscopic features of the [(M III )(μ-O) 2 (M III )'] 2+ core. In particular, the unprecedented nucleophilic reactivity of the symmetric [Ni III (μ-O) 2 Ni III ] 2+ complex and the decay of the asymmetric [Ni III (μ-O) 2 Co III ] 2+ core through aromatic hydroxylation reactions represent a new domain for high-valent bis(μ-oxido)dimetal reactivity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The role of an active site Mg(2+) in HDV ribozyme self-cleavage: insights from QM/MM calculations.

PubMed

Mlýnský, Vojtěch; Walter, Nils G; Šponer, Jiří; Otyepka, Michal; Banáš, Pavel

2015-01-07

The hepatitis delta virus (HDV) ribozyme is a catalytic RNA motif embedded in the human pathogenic HDV RNA. It catalyzes self-cleavage of its sugar-phosphate backbone with direct participation of the active site cytosine C75. Biochemical and structural data support a general acid role of C75. Here, we used hybrid quantum mechanical/molecular mechanical (QM/MM) calculations to probe the reaction mechanism and changes in Gibbs energy along the ribozyme's reaction pathway with an N3-protonated C75H(+) in the active site, which acts as the general acid, and a partially hydrated Mg(2+) ion with one deprotonated, inner-shell coordinated water molecule that acts as the general base. We followed eight reaction paths with a distinct position and coordination of the catalytically important active site Mg(2+) ion. For six of them, we observed feasible activation barriers ranging from 14.2 to 21.9 kcal mol(-1), indicating that the specific position of the Mg(2+) ion in the active site is predicted to strongly affect the kinetics of self-cleavage. The deprotonation of the U-1(2'-OH) nucleophile and the nucleophilic attack of the resulting U-1(2'-O(-)) on the scissile phosphodiester are found to be separate steps, as deprotonation precedes the nucleophilic attack. This sequential mechanism of the HDV ribozyme differs from the concerted nucleophilic activation and attack suggested for the hairpin ribozyme. We estimate the pKa of the U-1(2'-OH) group to range from 8.8 to 11.2, suggesting that it is lowered by several units from that of a free ribose, comparable to and most likely smaller than the pKa of the solvated active site Mg(2+) ion. Our results thus support the notion that the structure of the HDV ribozyme, and particularly the positioning of the active site Mg(2+) ion, facilitate deprotonation and activation of the 2'-OH nucleophile.

Redox homeostasis: The Golden Mean of healthy living.

PubMed

Ursini, Fulvio; Maiorino, Matilde; Forman, Henry Jay

2016-08-01

The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve "reactive oxygen species" rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles (parahormesis). In summary, while hormesis, although globally protective, results in setting up of a new phenotype, parahormesis contributes to health by favoring maintenance of homeostasis. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Insertion of Isocyanides into N-Si Bonds: Multicomponent Reactions with Azines Leading to Potent Antiparasitic Compounds.

PubMed

Kishore, Kranti G; Ghashghaei, Ouldouz; Estarellas, Carolina; Mestre, M Mar; Monturiol, Cristina; Kielland, Nicola; Kelly, John M; Francisco, Amanda Fortes; Jayawardhana, Shiromani; Muñoz-Torrero, Diego; Pérez, Belén; Luque, F Javier; Gámez-Montaño, Rocío; Lavilla, Rodolfo

2016-07-25

Trimethylsilyl chloride is an efficient activating agent for azines in isocyanide-based reactions, which then proceed through a key insertion of the isocyanide into a N-Si bond. The reaction is initiated by N activation of the azine, followed by nucleophilic attack of an isocyanide in a Reissert-type process. Finally, a second equivalent of the same or a different isocyanide inserts into the N-Si bond leading to the final adduct. The use of distinct nucleophiles leads to a variety of α-substituted dihydroazines after a selective cascade process. Based on computational studies, a mechanistic hypothesis for the course of these reactions was proposed. The resulting products exhibit significant activity against Trypanosoma brucei and T. cruzi, featuring favorable drug-like properties and safety profiles. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemoenzymatic synthesis of new derivatives of glycyrrhetinic acid with antiviral activity. Molecular docking study.

PubMed

Zígolo, M Antonela; Salinas, Maximiliano; Alché, Laura; Baldessari, Alicia; Liñares, Guadalupe García

2018-08-01

We present an efficient approach to the synthesis of a series of glycyrrhetinic acid derivatives. Six derivatives, five of them new compounds, were obtained through chemoenzymatic reactions in very good to excellent yield. In order to find the optimal reaction conditions, the influence of various parameters such as enzyme source, nucleophile:substrate ratio, enzyme:substrate ratio, solvent and temperature was studied. The excellent results obtained by lipase catalysis made the procedure very efficient considering their advantages such as mild reaction conditions and low environmental impact. Moreover, in order to explain the reactivity of glycyrrhetinic acid and the acetylated derivative to different nucleophiles in the enzymatic reactions, molecular docking studies were carried out. In addition, one of the synthesized compounds exhibited remarkable antiviral activity against TK + and TK- strains of Herpes simplex virus type 1 (HSV-1), sensitive and resistant to acyclovir (ACV) treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Synthetic Studies on Tricyclic Diterpenoids: Direct Allylic Amination Reaction of Isopimaric Acid Derivatives†

PubMed Central

Timoshenko, Mariya A.; Kharitonov, Yurii V.; Shakirov, Makhmut M.; Bagryanskaya, Irina Yu.

2015-01-01

Abstract A selective synthesis of 7‐ or 14‐nitrogen containing tricyclic diterpenoids was completed according to a strategy in which the key step was the catalyzed direct allylic amination of methyl 14α‐hydroxy‐15,16‐dihydroisopimarate with a wide variety of nitrogenated nucleophiles. It was revealed that the selectivity of the reaction depends on the nature of nucleophile. The catalyzed reaction of the mentioned diterpenoid allylic alcohol with 3‐nitroaniline, 3‐(trifluoromethyl)aniline, and 4‐(trifluoromethyl)aniline yield the subsequent 7α‐, 7β‐ and 14αnitrogen‐containing diterpenoids. The reaction with 2‐nitroaniline, 4‐nitro‐2‐chloroaniline, 4‐methoxy‐2‐nitroaniline, phenylsulfamide, or tert‐butyl carbamate proceeds with the formation of 7α‐nitrogen‐substituted diterpenoids as the main products. PMID:27308214

Gas Phase Reactivity of Carboxylates with N-Hydroxysuccinimide Esters

PubMed Central

Peng, Zhou; McGee, William M.; Bu, Jiexun; Barefoot, Nathan Z.; McLuckey, Scott A.

2015-01-01

N-hydroxysuccinimide (NHS) esters have been used for gas phase conjugation reactions with peptides at nucleophilic sites, such as primary amines (N-terminus, ε-amine of lysine) or guanidines, by forming amide bonds through a nucleophilic attack on the carbonyl carbon. The carboxylate has recently been found to also be a reactive nucleophile capable of initiating a similar nucleophilic attack to form a labile anhydride bond. The fragile bond is easily cleaved, resulting in an oxygen transfer from the carboxylate-containing species to the reagent, nominally observed as a water transfer. This reactivity is shown for both peptides and non-peptidic species. Reagents isotopically labeled with O18 were used to confirm reactivity. This constitutes an example of distinct differences in reactivity of carboxylates between the gas-phase, where they are shown to be reactive, and the solution-phase, where they are not regarded as reactive with NHS esters. PMID:25338221

A facile synthesis of the basic steroidal skeleton using a Pauson-Khand reaction as a key step.

PubMed

Kim, Do Han; Kim, Kwang; Chung, Young Keun

2006-10-13

A high-yield synthesis of steroid-type molecules under mild reaction conditions is achieved in two steps involving nucleophilic addition of alkynyl cerium reagent to an easily enolizable carbonyl compound (beta-tetralone) followed by an intramolecular Pauson-Khand reaction.

Mechanistic insights into the dehalogenation reaction of fluoroacetate/fluoroacetic acid

NASA Astrophysics Data System (ADS)

Miranda-Rojas, Sebastián; Toro-Labbé, Alejandro

2015-05-01

Fluoroacetate is a toxic compound whose environmental accumulation may represent an important contamination problem, its elimination is therefore a challenging issue. Fluoroacetate dehalogenase catalyzes its degradation through a two step process initiated by an SN2 reaction in which the aspartate residue performs a nucleophilic attack on the carbon bonded to the fluorine; the second step is hydrolysis that releases the product as glycolate. In this paper, we present a study based on density functional theory calculations of the SN2 initiation reaction modeled through the interaction between the substrate and the propionate anion as the nucleophile. Results are analyzed within the framework of the reaction force and using the reaction electronic flux to identify and characterize the electronic activity that drives the reaction. Our results reveal that the selective protonation of the substrate catalyzes the reaction by decreasing the resistance of the structural and electronic reorganization needed to reach the transition state. Finally, the reaction energy is modulated by the degree of stabilization of the fluoride anion formed after the SN2 reaction. In this way, a site-induced partial protonation acts as a chemical switch in a key process that determines the output of the reaction.

Bonding reactivity descriptor from conceptual density functional theory and its applications to elucidate bonding formation

NASA Astrophysics Data System (ADS)

Zhou, Pan-Pan; Liu, Shubin; Ayers, Paul W.; Zhang, Rui-Qin

2017-10-01

Condensed-to-atom Fukui functions which reflect the atomic reactivity like the tendency susceptible to either nucleophilic or electrophilic attack demonstrate the bonding trend of an atom in a molecule. Accordingly, Fukui functions based concepts, that is, bonding reactivity descriptors which reveal the bonding properties of molecules in the reaction were put forward and then applied to pericyclic and cluster reactions to confirm their effectiveness and reliability. In terms of the results from the bonding descriptors, a covalent bond can readily be predicted between two atoms with large Fukui functions (i.e., one governs nucleophilic attack while the other one governs electrophilic attack, or both of them govern radical attacks) for pericyclic reactions. For SinOm clusters' reactions, the clusters with a low O atom ratio readily form a bond between two Si atoms with big values of their Fukui functions in which they respectively govern nucleophilic and electrophilic attacks or both govern radical attacks. Also, our results from bonding descriptors show that Si—Si bonds can be formed via the radical mechanism between two Si atoms, and formations of Si—O and O—O bonds are possible when the O content is high. These results conform with experimental findings and can help experimentalists design appropriate clusters to synthesize Si nanowires with high yields. The approach established in this work could be generalized and applied to study reactivity properties for other systems.

Electron and Oxygen Atom Transfer Chemistry of Co(II) in a Proton Responsive, Redox Active Ligand Environment.

PubMed

Cook, Brian J; Pink, Maren; Pal, Kuntal; Caulton, Kenneth G

2018-05-21

The bis-pyrazolato pyridine complex LCo(PEt 3 ) 2 serves as a masked form of three-coordinate Co II and shows diverse reactivity in its reaction with several potential outer sphere oxidants and oxygen atom transfer reagents. N-Methylmorpholine N-oxide (NMO) oxidizes coordinated PEt 3 from LCo(PEt 3 ) 2 , but the final cobalt product is still divalent cobalt, in LCo(NMO) 2 . The thermodynamics of a variety of oxygen atom transfer reagents, including NMO, are calculated by density functional theory, to rank their oxidizing power. Oxidation of LCo(PEt 3 ) 2 with AgOTf in the presence of LiCl as a trapping nucleophile forms the unusual aggregate [LCo(PEt 3 ) 2 Cl(LiOTf) 2 ] 2 held together by Li + binding to very nucleophilic chloride on Co(III) and triflate binding to those Li + . In contrast, Cp 2 Fe + effects oxidation to trivalent cobalt, to form (HL)Co(PEt 3 ) 2 Cl + ; proton and the chloride originate from solvent in a rare example of CH 2 Cl 2 dehydrochlorination. An unexpected noncomplementary redox reaction is reported involving attack by 2e reductant PEt 3 nucleophile on carbon of the 1e oxidant radical Cp 2 Fe + , forming a P-C bond and H + ; this reaction competes in the reaction of LCo(PEt 3 ) 2 with Cp 2 Fe + .

Development of Selective Colorimetric Probes for Hydrogen Sulfide Based on Nucleophilic Aromatic Substitution

PubMed Central

Montoya, Leticia A.; Pearce, Taylor F.; Hansen, Ryan J.; Zakharov, Lev N.; Pluth, Michael D.

2013-01-01

Hydrogen sulfide is an important biological signalling molecule and an important environmental target for detection. A major challenge in developing H2S detection methods is separating the often similar reactivity of thiols and other nucleophiles from H2S. To address this need, the nucleophilic aromatic substitution (SNAr) reaction of H2S with electron-poor aromatic electrophiles was developed as a strategy to separate H2S and thiol reactivity. Treatment of aqueous solutions of nitrobenzofurazan (7-nitro-1,2,3-benzoxadiazole, NBD) thioethers with H2S resulted in thiol extrusion and formation of nitrobenzofurazan thiol (λmax = 534 nm). This reactivity allows for unwanted thioether products to be converted to the desired nitrobenzofurazan thiol upon reaction with H2S. The scope of the reaction was investigated using a Hammett linear free energy relationship study, and the determined ρ = +0.34 is consistent with the proposed SN2Ar reaction mechanism. The efficacy of the developed probes was demonstrated in buffer and in serum with associated sub-micromolar detection limits as low as 190 nM (buffer) and 380 nM (serum). Furthermore, the sigmoidal response of nitrobenzofurazan electrophiles with H2S can be fit to accurately quantify H2S. The developed detection strategy offers a manifold for H2S detection that we foresee being applied in various future applications. PMID:23735055

Development of selective colorimetric probes for hydrogen sulfide based on nucleophilic aromatic substitution.

PubMed

Montoya, Leticia A; Pearce, Taylor F; Hansen, Ryan J; Zakharov, Lev N; Pluth, Michael D

2013-07-05

Hydrogen sulfide is an important biological signaling molecule and an important environmental target for detection. A major challenge in developing H2S detection methods is separating the often similar reactivity of thiols and other nucleophiles from H2S. To address this need, the nucleophilic aromatic substitution (SNAr) reaction of H2S with electron-poor aromatic electrophiles was developed as a strategy to separate H2S and thiol reactivity. Treatment of aqueous solutions of nitrobenzofurazan (7-nitro-1,2,3-benzoxadiazole, NBD) thioethers with H2S resulted in thiol extrusion and formation of nitrobenzofurazan thiol (λmax = 534 nm). This reactivity allows for unwanted thioether products to be converted to the desired nitrobenzofurazan thiol upon reaction with H2S. The scope of the reaction was investigated using a Hammett linear free energy relationship study, and the determined ρ = +0.34 is consistent with the proposed SN2Ar reaction mechanism. The efficacy of the developed probes was demonstrated in buffer and in serum with associated submicromolar detection limits as low as 190 nM (buffer) and 380 nM (serum). Furthermore, the sigmoidal response of nitrobenzofurazan electrophiles with H2S can be fit to accurately quantify H2S. The developed detection strategy offers a manifold for H2S detection that we foresee being applied in various future applications.

The effect of varying the anion of an ionic liquid on the solvent effects on a nucleophilic aromatic substitution reaction.

PubMed

Hawker, Rebecca R; Haines, Ronald S; Harper, Jason B

2018-05-09

A variety of ionic liquids, each containing the same cation but a different anion, were examined as solvents for a nucleophilic aromatic substitution reaction. Varying the proportion of ionic liquid was found to increase the rate constant as the mole fraction of ionic liquid increased demonstrating that the reaction outcome could be controlled through varying the ionic liquid. The solvent effects were correlated with the hydrogen bond accepting ability (β) of the ionic liquid anion allowing for qualitative prediction of the effect of changing this component of the solute. To determine the microscopic origins of the solvent effects, activation parameters were determined through temperature-dependent kinetic analyses and shown to be consistent with previous studies. With the knowledge of the microscopic interactions in solution, an ionic liquid was rationally chosen to maximise rate enhancement demonstrating that an ionic solvent can be selected to control reaction outcome for this reaction type.

Mechanistic Basis for High Reactivity of (salen)Co–OTs in the Hydrolytic Kinetic Resolution of Terminal Epoxides

PubMed Central

Nielsen, Lars P. C.; Zuend, Stephan J.; Ford, David D.; Jacobsen, Eric N.

2012-01-01

The (salen)Co(III)-catalyzed hydrolytic kinetic resolution (HKR) of terminal epoxides is a bimetallic process with a rate controlled by partitioning between a nucleophilic (salen)Co–OH catalyst and a Lewis acidic (salen)Co–X catalyst. The commonly used (salen)Co–OAc and (salen)Co–Cl precatalysts undergo complete and irreversible counterion addition to epoxide during the course of the epoxide hydrolysis reaction, resulting in quantitative formation of weakly Lewis acidic (salen)Co–OH, and severely diminished reaction rates in the late stages of HKR reactions. In contrast, (salen)Co–OTs maintains high reactivity over the entire course of HKR reactions. We describe here an investigation of catalyst partitioning with different (salen)Co–X precatalysts, and demonstrate that counterion addition to epoxide is reversible in the case of the (salen)Co–OTs. This reversible counterion addition results in stable partitioning between nucleophilic and Lewis acidic catalyst species, allowing highly efficient catalysis throughout the course of the HKR reaction. PMID:22292515

Mechanistic basis for high reactivity of (salen)Co-OTs in the hydrolytic kinetic resolution of terminal epoxides.

PubMed

Nielsen, Lars P C; Zuend, Stephan J; Ford, David D; Jacobsen, Eric N

2012-03-02

The (salen)Co(III)-catalyzed hydrolytic kinetic resolution (HKR) of terminal epoxides is a bimetallic process with a rate controlled by partitioning between a nucleophilic (salen)Co-OH catalyst and a Lewis acidic (salen)Co-X catalyst. The commonly used (salen)Co-OAc and (salen)Co-Cl precatalysts undergo complete and irreversible counterion addition to epoxide during the course of the epoxide hydrolysis reaction, resulting in quantitative formation of weakly Lewis acidic (salen)Co-OH and severely diminished reaction rates in the late stages of HKR reactions. In contrast, (salen)Co-OTs maintains high reactivity over the entire course of HKR reactions. We describe here an investigation of catalyst partitioning with different (salen)Co-X precatalysts and demonstrate that counterion addition to epoxide is reversible in the case of the (salen)Co-OTs. This reversible counterion addition results in stable partitioning between nucleophilic and Lewis acidic catalyst species, allowing highly efficient catalysis throughout the course of the HKR reaction.

Structure and reactivity of boron-ate complexes derived from primary and secondary boronic esters.

PubMed

Feeney, Kathryn; Berionni, Guillaume; Mayr, Herbert; Aggarwal, Varinder K

2015-06-05

Boron-ate complexes derived from primary and secondary boronic esters and aryllithiums have been isolated, and the kinetics of their reactions with carbenium ions studied. The second-order rate constants have been used to derive nucleophilicity parameters for the boron-ate complexes, revealing that nucleophilicity increased with (i) electron-donating aromatics on boron, (ii) neopentyl glycol over pinacol boronic esters, and (iii) 12-crown-4 ether.

α-Carbamoylsulfides as N-Carbamoylimine Precursors in the Visible Light Photoredox-Catalyzed Synthesis of α,α-Disubstituted Amines.

PubMed

Lebée, Clément; Languet, Morgan; Allain, Clémence; Masson, Géraldine

2016-03-18

A general and practical photoredox-promoted addition of nucleophiles to N-acylimines generated in situ from α-amidosulfides using Ru(bpy)3(PF6)2 as the photocatalyst is reported. The broad scope of the reaction toward various nucleophiles and amidosulfide derivatives was explored. This novel protocol provides a rapid, mild, and efficient access to valuable α,α-disubstituted amines in respectable yields.

Replacing Conventional Carbon Nucleophiles with Electrophiles: Nickel-Catalyzed Reductive Alkylation of Aryl Bromides and Chlorides

PubMed Central

2012-01-01

A general method is presented for the synthesis of alkylated arenes by the chemoselective combination of two electrophilic carbons. Under the optimized conditions, a variety of aryl and vinyl bromides are reductively coupled with alkyl bromides in high yields. Under similar conditions, activated aryl chlorides can also be coupled with bromoalkanes. The protocols are highly functional-group tolerant (−OH, −NHTs, −OAc, −OTs, −OTf, −COMe, −NHBoc, −NHCbz, −CN, −SO2Me), and the reactions are assembled on the benchtop with no special precautions to exclude air or moisture. The reaction displays different chemoselectivity than conventional cross-coupling reactions, such as the Suzuki–Miyaura, Stille, and Hiyama–Denmark reactions. Substrates bearing both an electrophilic and nucleophilic carbon result in selective coupling at the electrophilic carbon (R–X) and no reaction at the nucleophilic carbon (R–[M]) for organoboron (−Bpin), organotin (−SnMe3), and organosilicon (−SiMe2OH) containing organic halides (X–R–[M]). A Hammett study showed a linear correlation of σ and σ(−) parameters with the relative rate of reaction of substituted aryl bromides with bromoalkanes. The small ρ values for these correlations (1.2–1.7) indicate that oxidative addition of the bromoarene is not the turnover-frequency determining step. The rate of reaction has a positive dependence on the concentration of alkyl bromide and catalyst, no dependence upon the amount of zinc (reducing agent), and an inverse dependence upon aryl halide concentration. These results and studies with an organic reductant (TDAE) argue against the intermediacy of organozinc reagents. PMID:22463689

New Synthesis Of Poly(1,3,4-Oxadiazoles)

NASA Technical Reports Server (NTRS)

Connell, John W.; Hergenrother, Paul M.; Wolf, Peter

1992-01-01

Synthesis via aromatic nucleophilic displacement yields new high-molecular-weight polymers. Polymers exhibited good mechanical and thermal properties. Synthetic route provided high-molecular-weight POX of new chemical structure, potentially more economical. Availability of large variety of activated aromatic dihalides, facilitates variation of chemical structures. Exhibit properties making them useful as films. Also useful in coatings, adhesives, moldings, and composites.

Contract W911NF-07-1-0139 (Massachusetts Institute of Technology)

DTIC Science & Technology

2013-07-09

materials were effective in nucleophilic degradation of organophosphorous (OP) esters represented by CWA simulants and pesticides. Studies demonstrated...separate the cells effectively from suspension using a magnet. A fluorescence dye displacement assay shows strong affinities of the nanoparticles...as other imidazole groups, in its proximity. In that regard, we were interested in potential neighboring effects of the imidazole groups concentrated

Heterobimetallic Catalysis: Platinum-Gold-Catalyzed Tandem Cyclization/C-X Coupling Reaction of (Hetero)Arylallenes with Nucleophiles.

PubMed

Alonso, José Miguel; Muñoz, María Paz

2018-04-16

Heterobimetallic catalysis offers new opportunities for reactivity and selectivity but still presents challenges, and only a few metal combinations have been explored so far. Reported here is a Pt-Au heterobimetallic catalyst system for the synthesis of a family of multi-heteroaromatic structures through tandem cyclization/C-X coupling reaction. Au-catalyzed 6-endo-cyclization takes place as the first fast step. Pt-Au clusters are proposed to be responsible for the increased reactivity in the second step, that is, the intermolecular nucleophilic addition which occurs through an outer-sphere mechanism by hybrid homogeneous-heterogeneous catalysis. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemoselective covalent coupling of oligonucleotide probes to self-assembled monolayers.

PubMed

Devaraj, Neal K; Miller, Gregory P; Ebina, Wataru; Kakaradov, Boyko; Collman, James P; Kool, Eric T; Chidsey, Christopher E D

2005-06-22

A chemoselective route to routinely and rapidly attach oligonucleotide probes to well-defined surfaces is presented. Cu(I) tris(benzyltriazolylmethyl)amine-catalyzed coupling of terminal acetylenes to azides on a self-assembled monolayer is used instead of traditional nucleophilic-electrophilic coupling reactions. The reaction proceeds well even in the presence of purposely introduced nucleophilic and electrophilic impurities. The density of oligonucleotide probes can be controlled by controlling the amount of azide functionality. Although most of our work was done on gold surfaces, this technique should be readily applicable to any surface on which an azide-containing monolayer can be assembled as we have preliminarily demonstrated by derivatizing azidotrimethoxysilane-modified glass slides with fluorescein-containing oligonucleotides.

Pyrimidine Nucleosides with a Reactive (β-Chlorovinyl)sulfone or (β-Keto)sulfone Group at the C5 Position, Their Reactions with Nucleophiles and Electrophiles, and Their Polymerase-Catalyzed Incorporation into DNA

PubMed Central

2018-01-01

Transition-metal-catalyzed chlorosulfonylation of 5-ethynylpyrimidine nucleosides provided (E)-5-(β-chlorovinyl)sulfones A, which undergo nucleophilic substitution with amines or thiols affording B. The treatment of vinyl sulfones A with ammonia followed by acid-catalyzed hydrolysis of the intermediary β-sulfonylvinylamines gave 5-(β-keto)sulfones C. The latter reacts with electrophiles, yielding α-carbon-alkylated or -sulfanylated analogues D. The 5′-triphosphates of A and C were incorporated into double-stranded DNA, using open and one-nucleotide gap substrates, by human or Escherichia coli DNA-polymerase-catalyzed reactions. PMID:29732453

Application of the Hard and Soft, Acids and Bases (HSAB) theory to toxicant--target interactions.

PubMed

Lopachin, Richard M; Gavin, Terrence; Decaprio, Anthony; Barber, David S

2012-02-20

Many chemical toxicants and/or their active metabolites are electrophiles that cause cell injury by forming covalent bonds with nucleophilic targets on biological macromolecules. Covalent reactions between nucleophilic and electrophilic reagents are, however, discriminatory since there is a significant degree of selectivity associated with these interactions. Over the course of the past few decades, the theory of Hard and Soft, Acids and Bases (HSAB) has proven to be a useful tool in predicting the outcome of such reactions. This concept utilizes the inherent electronic characteristic of polarizability to define, for example, reacting electrophiles and nucleophiles as either hard or soft. These HSAB definitions have been successfully applied to chemical-induced toxicity in biological systems. Thus, according to this principle, a toxic electrophile reacts preferentially with biological targets of similar hardness or softness. The soft/hard classification of a xenobiotic electrophile has obvious utility in discerning plausible biological targets and molecular mechanisms of toxicity. The purpose of this perspective is to discuss the HSAB theory of electrophiles and nucleophiles within a toxicological framework. In principle, covalent bond formation can be described by using the properties of their outermost or frontier orbitals. Because these orbital energies for most chemicals can be calculated using quantum mechanical models, it is possible to quantify the relative softness (σ) or hardness (η) of electrophiles or nucleophiles and to subsequently convert this information into useful indices of reactivity. This atomic level information can provide insight into the design of corroborative laboratory research and thereby help investigators discern corresponding molecular sites and mechanisms of toxicant action. The use of HSAB parameters has also been instrumental in the development and identification of potential nucleophilic cytoprotectants that can scavenge toxic electrophiles. Clearly, the difficult task of delineating molecular sites and mechanisms of toxicant action can be facilitated by the application of this quantitative approach.

APPLICATION OF THE HARD AND SOFT, ACIDS AND BASES (HSAB) THEORY TO TOXICANT-TARGET INTERACTIONS

PubMed Central

LoPachin, Richard M.; Gavin, Terrence; DeCaprio, Anthony; Barber, David S.

2011-01-01

Many chemical toxicants and/or their active metabolites are electrophiles that cause cell injury by forming covalent bonds with nucleophilic targets on biological macromolecules. Covalent reactions between nucleophilic and electrophilic reagents are however discriminatory, since there is a significant degree of selectivity associated with these interactions. Over the course of the past few decades, the theory of Hard and Soft, Acid and Bases (HSAB) has proven to be a useful tool in predicting the outcome of such reactions. This concept utilizes the inherent electronic characteristic of polarizability to define, for example, reacting electrophiles and nucleophiles as either hard or soft. These HSAB definitions have been successfully applied to chemical-induced toxicity in biological systems. Thus, according to this principle, a toxic electrophile reacts preferentially with biological targets of similar hardness or softness. The soft/hard classification of a xenobiotic electrophile has obvious utility in discerning plausible biological targets and molecular mechanisms of toxicity. The purpose of this Perspective is to discuss the HSAB theory of electrophiles and nucleophiles within a toxicological framework. In principle, covalent bond formation can be described by using the properties of their outermost or frontier orbitals. Because these orbital energies for most chemicals can be calculated using quantum mechanical models, it is possible to quantify the relative softness (σ) or hardness (η) of electrophiles or nucleophiles and to subsequently convert this information into useful indices of reactivity. This atomic level information can provide insight into the design of corroborative laboratory research and thereby help investigators discern corresponding molecular sites and mechanisms of toxicant action. The use of HSAB parameters has also been instrumental in the development and identification of potential nucleophilic cytoprotectants that can scavenge toxic electrophiles. Clearly, the difficult task of delineating molecular sites and mechanisms of toxicant action can be facilitated by the application of this quantitative approach. PMID:22053936

Aza-Michael Reaction for an Undergraduate Organic Chemistry Laboratory

ERIC Educational Resources Information Center

Nigam, Manisha; Rush, Brittney; Patel, Jay; Castillo, Raul; Dhar, Preeti

2016-01-01

A green, aza-Michael reaction is described that can be used to teach undergraduate students conjugate addition of nitrogen nucleophile to an a,ß-unsaturated ester. Students analyze spectral data of the product obtained from the assigned reaction to determine product structure and propose the mechanism of its formation. The experiment requires…

Reactivity III: An Advanced Course in Integrated Organic, Inorganic, and Biochemistry

ERIC Educational Resources Information Center

Schaller, Chris P.; Graham, Kate J.; Jakubowski, Henry V.

2017-01-01

Reactivity III is a new course that presents chemical reactions from the domains of organic, inorganic, and biochemistry that are not readily categorized by electrophile-nucleophile interactions. Many of these reactions involve the transfer of a single electron, in either an intermolecular fashion in the case of oxidation/reduction reactions or an…

N-heterocyclic carbene-catalyzed tandem aza-benzoin/Michael reactions: on site reversal of the reactivity of N-Boc imines.

PubMed

Wu, Ke-Jia; Li, Gong-Qiang; Li, Yi; Dai, Li-Xin; You, Shu-Li

2011-01-07

A tandem NHC-catalyzed aza-benzoin/Michael reaction has been developed as a method to efficiently produce dihydroindenones and pyrrolidinone-containing tricycles. The novel reaction pattern involves tert-butyl aryl(tosyl)methylcarbamates reacting as both electrophile and nucleophile on the same carbon.

Evidence That Nucleophile Deprotonation Exceeds Bond Formation in the HDV Ribozyme Transition State.

PubMed

Lu, Jun; Koo, Selene C; Weissman, Benjamin P; Harris, Michael E; Li, Nan-Sheng; Piccirilli, Joseph A

2018-06-26

Steric constraints imposed by the active sites of protein and RNA enzymes pose major challenges to the investigation of structure-function relationships within these systems. As a strategy to circumvent such constraints in the HDV ribozyme, we have synthesized phosphoramidites from propanediol derivatives and incorporated them at the 5'-termini of RNA and DNA oligonucleotides to generate a series of novel substrates with nucleophiles perturbed electronically through geminal fluorination. In nonenzymatic, hydroxide-catalyzed intramolecular transphosphorylation of the DNA substrates, pH-rate profiles revealed that fluorine substitution reduces the maximal rate and the kinetic p K a , consistent with the expected electron-withdrawing effect. In HDV ribozyme reactions, we observed that the RNA substrates undergo transphosphorylation relatively efficiently, suggesting that the conformational constraints imposed by a ribofuranose ring are not strictly required for ribozyme catalysis. In contrast to the nonenzymatic reactions, however, substrate fluorination modestly increases the ribozyme reaction rate, consistent with a mechanism in which (1) the 2'-hydroxyl nucleophile exists predominantly in its neutral, protonated form in the ground state and (2) the 2'-hydroxyl bears some negative charge in the rate-determining step, consistent with a transition state in which the extent of 2'-OH deprotonation exceeds the extent of P-O bond formation.

Synthesis of 6-alkyluridines from 6-cyanouridine via zinc(II) chloride-catalyzed nucleophilic substitution with alkyl Grignard reagents.

PubMed

Shih, Yu-Chiao; Yang, Ya-Ying; Lin, Chun-Chi; Chien, Tun-Cheng

2013-04-19

6-Cyanouracil derivatives underwent a direct nucleophilic substitution reaction with alkyl Grignard reagents in the presence of zinc(II) chloride as a catalyst to form the corresponding 6-alkyluracils. This methodology is applicable to sugar-protected 6-cyanouridine and 6-cyano-2'-deoxyuridine without the protection at the N(3)-imide and provides a facile and general access to versatile 6-alkyluracil and 6-alkyluridine derivatives.

Barbier Continuous Flow Preparation and Reactions of Carbamoyllithiums for Nucleophilic Amidation.

PubMed

Ganiek, Maximilian A; Becker, Matthias R; Berionni, Guillaume; Zipse, Hendrik; Knochel, Paul

2017-08-01

An ambient temperature continuous flow method for nucleophilic amidation and thioamidation is described. Deprotonation of formamides by lithium diisopropylamine (LDA) affords carbamoyllithium intermediates that are quenched in situ with various electrophiles such as ketones, allyl bromides, Weinreb and morpholino amides. The nature of the reactive lithium intermediates and the thermodynamics of the metalation were further investigated by ab initio calculations and kinetic experiments. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Transition-state charge transfer reveals electrophilic, ambiphilic, and nucleophilic carbon-hydrogen bond activation.

PubMed

Ess, Daniel H; Nielsen, Robert J; Goddard, William A; Periana, Roy A

2009-08-26

Absolutely localized molecular orbital energy decomposition analysis of C-H activation transition states (TSs), including Pt, Au, Ir, Ru, W, Sc, and Re metal centers, shows an electrophilic, ambiphilic, and nucleophilic charge transfer (CT) continuum irrespective of the bonding paradigm (oxidative addition, sigma-bond metathesis, oxidative hydrogen migration, 1,2-substitution). Pt(II) insertion and Au(III) substitution TSs are highly electrophilic and dominated by C-H bond to metal/ligand orbital stabilization, while Ir-X and Ru-X (X = R, NH(2), OR, or BOR(2)) substitution TSs are ambiphilic in nature. In this ambiphilic activation regime, an increase in one direction of CT typically leads to a decrease in the reverse direction. Comparison of Tp(CO)Ru-OH and Tp(CO)Ru-NH(2) complexes showed no evidence for the classic d(pi)-p(pi) repulsion model. Complexes such as and Cp(CO)(2)W-B(OR)(2), (PNP)Ir(I), Cp(2)ScMe, and (acac-kappaO,kappaO)(2)Re(III)-OH were found to mediate nucleophilic C-H activation, where the CT is dominated by the metal/ligand orbital to C-H antibonding orbital interaction. This CT continuum ultimately affects the metal-alkyl intermediate polarization and possible functionalization reactions. This analysis will impact the design of new activation reactions and stimulate the discovery of more nucleophilic activation complexes.

Homologation chemistry with nucleophilic α-substituted organometallic reagents: chemocontrol, new concepts and (solved) challenges.

PubMed

Castoldi, Laura; Monticelli, Serena; Senatore, Raffaele; Ielo, Laura; Pace, Vittorio

2018-05-31

The transfer of a reactive nucleophilic CH2X unit into a preformed bond enables the introduction of a fragment featuring the exact and desired degree of functionalization through a single synthetic operation. The instability of metallated α-organometallic species often poses serious questions regarding the practicability of using this conceptually intuitive and simple approach for forming C-C or C-heteroatom bonds. A deep understanding of processes regulating the formation of these nucleophiles is a precious source of inspiration not only for successfully applying theoretically feasible transformations (i.e. determining how to employ a given reagent), but also for designing new reactions which ultimately lead to the introduction of molecular complexity via short experimental sequences.

How Do Nutritional Antioxidants Really Work: Nucleophilic Tone and Para-Hormesis Versus Free Radical Scavenging in vivo

PubMed Central

Forman, Henry Jay; Davies, Kelvin J. A.; Ursini, Fulvio

2013-01-01

We present arguments for an evolution in our understanding of how antioxidants in fruits and vegetables exert their health-protective effects. There is much epidemiological evidence for disease prevention by dietary antioxidants and chemical evidence that such compounds react in one-electron reactions with free radicals in vitro. Nonetheless, kinetic constraints indicate that in vivo scavenging of radicals is ineffective in antioxidant defense. Instead, enzymatic removal of non-radical electrophiles, such as hydroperoxides, in two-electron redox reactions is the major antioxidant mechanism. Furthermore, we propose that a major mechanism of action for nutritional antioxidants is the paradoxical oxidative activation of the Nrf2 (NF-E2-related factor 2) signaling pathway, which maintains protective oxidoreductases and their nucleophilic substrates. This maintenance of ‘Nucleophilic Tone,’ by a mechanism that can be called ‘Para-Hormesis,’ provides a means for regulating physiological non-toxic concentrations of the non-radical oxidant electrophiles that boost antioxidant enzymes, and damage removal and repair systems (for proteins, lipids, and DNA), at the optimal levels consistent with good health. PMID:23747930

Phosphoester hydrolysis: the incoming substrate turns the bridging hydroxido nucleophile into a terminal one.

PubMed

Gouré, Eric; Carboni, Michaël; Troussier, Angélique; Lebrun, Colette; Pécaut, Jacques; Jacquot, Jean-François; Dubourdeaux, Patrick; Clémancey, Martin; Blondin, Geneviève; Latour, Jean-Marc

2015-05-26

Identifying the active nucleophile in hydrolysis reactions catalyzed by binuclear hydrolases is a recurrent problem and a matter of intense debate. We report on the phosphate ester hydrolysis by a Fe(III)Fe(II) complex of a binucleating ligand. This complex presents activities in the range of those observed for similar biomimetic compounds in the literature. The specific electronic properties of the Fe(III)Fe(II) complex allowed us to use (1)H NMR and Mössbauer spectroscopies to investigate the nature of the various species present in the solution in the pH range of 5-10. Both techniques showed that the hydrolysis activity is associated to a μ-hydroxido Fe(III)Fe(II) species. Further (1)H NMR experiments show that binding of anions or the substrate changes this bonding mode suggesting that a terminal hydroxide is the likely nucleophile in these hydrolysis reactions. This view is further supported by the structure determination of the hydrolysis product. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The scope and limitations of intramolecular Nicholas and Pauson-Khand reactions for the synthesis of tricyclic oxygen- and nitrogen-containing heterocycles.

PubMed

Closser, Kristina D; Quintal, Miriam M; Shea, Kevin M

2009-05-15

We studied the scope and limitations of a tandem intramolecular Nicholas/Pauson-Khand strategy for the synthesis of tricyclic oxygen- and nitrogen-containing heterocycles. This methodology enables conversion of simple acyclic starting materials into a series of previously unknown heterocyclic architectures. For the preparation of cyclic ethers (Z = O), tricyclic [5,6,5]- through [5,9,5]-systems (m = 1, n = 1-4) are available with the [5,7,5]- and [5,8,5]-systems amenable to quick and efficient synthesis. Tricyclic [5,7,5]- and [5,8,5]-amine-containing (Z = NTs) heterocycles can be successfully prepared. Attempts to make larger ring systems (Z = O, m = 2; Z = O, n = 5; or Z = NTs, n = 4-5) or prepare lactones via Nicholas reactions with carboxylic acid nucleophiles (available via oxidation of alcohol nucleophiles, Z = O) result in decomposition or dimerization. The latter process enables formation of 14-, 16-, and 18-membered ring diolides when using carboxylic acid nucleophiles. We also investigated the use of chiral amine promoters in the Pauson-Khand step but found no asymmetric induction.

Dechlorination of chloropicrin and 1,3-dichloropropene by hydrogen sulfide species: redox and nucleophilic substitution reactions.

PubMed

Zheng, Wei; Yates, Scott R; Papiernik, Sharon K; Guo, Mingxin; Gan, Jianying

2006-03-22

The chlorinated fumigants chloropicrin (trichloronitromethane) and 1,3-dichloropropene (1,3-D) are extensively used in agricultural production for the control of soilborne pests. The reaction of these two fumigants with hydrogen sulfide species (H2S and HS-) was examined in well-defined anoxic aqueous solutions. Chloropicrin underwent an extremely rapid redox reaction in the hydrogen sulfide solution. Transformation products indicated reductive dechlorination of chloropicrin by hydrogen sulfide species to produce dichloro- and chloronitromethane. The transformation of chloropicrin in hydrogen sulfide solution significantly increased with increasing pH, indicating that H2S is less reactive toward chloropicrin than HS- is. For both 1,3-D isomers, kinetics and transformation products analysis revealed that the reaction between 1,3-D and hydrogen sulfide species is an S(N)2 nucleophilic substitution process, in which the chlorine at C3 of 1,3-D is substituted by the sulfur nucleophile to form corresponding mercaptans. The 50% disappearance time (DT50) of 1,3-D decreased with increasing hydrogen sulfide species concentration at a constant pH. Transformation of 1,3-D was more rapid at high pH, suggesting that the reactivity of hydrogen sulfide species in the experimental system stems primarily from HS-. Because of the relatively low smell threshold values and potential environmental persistence of organic sulfur products yielded by the reaction of 1,3-D and HS-, the effects of reduced sulfide species should be considered in the development of alternative fumigation practices, especially in the integrated application of sulfur-containing fertilizers.

Alternative Nucleophilic Substrates for the Endonuclease Activities of Human Immunodeficiency Virus Type 1 Integrase

PubMed Central

Ealy, Julie B.; Sudol, Malgorzata; Krzeminski, Jacek; Amin, Shantu; Katzman, Michael

2012-01-01

Retroviral integrase can use water or some small alcohols as the attacking nucleophile to nick DNA. To characterize the range of compounds that human immunodeficiency virus type 1 integrase can accommodate for its endonuclease activities, we tested 45 potential electron donors (having varied size and number or spacing of nucleophilic groups) as substrates during site-specific nicking at viral DNA ends and during nonspecific nicking reactions. We found that integrase used 22 of the 45 compounds to nick DNA, but not all active compounds were used for both activities. In particular, 13 compounds were used for site-specific and nonspecific nicking, 5 only for site-specific nicking, and 4 only for nonspecific nicking; 23 other compounds were not used for either activity. Thus, integrase can accommodate a large number of nucleophilic substrates but has selective requirements for its different activities, underscoring its dynamic properties and providing new information for modeling and understanding integrase. PMID:22910593

Newly proposed proton-abstraction roundabout with backside attack mechanism for the SN2 reaction at the nitrogen center in F- + NH2Cl.

PubMed

Li, Yongfang; Wang, Dunyou

2018-05-07

Recent studies have improved our understanding of the mechanism and dynamics of the bimolecular nucleophilic substitution (S N 2) reaction at the carbon center. Nonetheless, the S N 2 reaction at the nitrogen center has received scarce attention and is less understood. Herein, we propose a new reaction mechanism for the S N 2 reaction at the nitrogen center in the F - + NH 2 Cl reaction using ab initio molecular dynamics calculations. The newly proposed mechanism involves the rotation of NHCl with one proton of NH 2 Cl abstracted by the nucleophile, followed by the classical backside-attack process. The double-inversion mechanism revealed recently for the S N 2 reaction at the carbon center is also observed for the title reaction at the nitrogen center. In contrast to the F - + CH 3 Cl reaction with a proton abstraction-induced first inversion transition state, the F - + NH 2 Cl reaction is a hydrogen bond-induced inversion. This newly proposed reaction mechanism opens a reaction channel to avoid the proton abstraction mechanism at low collision energy. The double-inversion mechanism of the title reaction with a negative first-inversion transition relative to the energy of the reactants is expected to have larger contribution to the reaction rate than the F - + CH 3 Cl reaction with a positive first-inversion transition state.

Catalysts and Initiators as Instruments Controlling Structure of Polymers with Inorganic Backbone.

DTIC Science & Technology

1991-05-02

lipophobic, electron reach/poor, mesogenic, bioactive , etc. Most modifications have been performed on polyphosphazenes (nucleophilic displacement of...chlorines) and on partially hydrogenated siloxanes (hydrosilylation). Modifications of polysilanes is also known. In this aiticle the main emphasis will...groups6 ,7 . Poly(dimethylsiloxane) is probably the only siloxane polymer which does not form a mesophase and has only one first order thermal

Theoretical studies of the nucleophilic substitution of halides and amine at a sulfonyl center.

PubMed

Sung, Dae Dong; Kim, Tae Joon; Lee, Ikchoon

2009-06-25

Gas-phase nucleophilic substitution reactions, F(-) + CH(3)SO(2)F, Cl(-) + CH(3)SO(2)Cl, Cl(-) + CH(3)SO(2)F, and NH(3) + CH(3)SO(2)Cl, have been investigated at the B3LYP/6-311+G** and MP2/6-31+G* levels of theory. A very shallow well for the reaction intermediate in a triple-well potential energy surface (PES) was observed for the identity fluoride exchange, but double well PESs were obtained for the other three reactions with three different PES profiles. NBO analyses of the transition states showed substantial charge transfer interactions in all cases which provided a much larger amount of stabilization energy compared with the corresponding species at the carbon center of methyl halides. This difference is primarily caused by the strong electropositive nature of the sulfur center. The F-S-F axial linkage in the distorted TBP type intermediate in the identity fluoride exchange reaction exhibited a weak three-center, four-electron omega-bonding, which is considered to provide stability of the intermediate. All the reactant (RC) and product complexes (PC) have Cs symmetry. The symmetry plane bisects angles HCH (of methyl group), OSO (of sulfonyl group), and HNH (of ammonia). Vicinal charge transfer interactions between the two out-of-plane C-H, S-O, and N-H bonds provide extra stabilization to the ion-dipole complexes together with H-bond formation of in-plane H atom with the nucleophile and/or leaving group.

Alkaline Hydrolysis/Polymerization of 2,4,6-Trinitrotoluene: Characterization of Products by 13C and 15N NMR

USGS Publications Warehouse

Thorn, K.A.; Thorne, P.G.; Cox, L.G.

2004-01-01

Alkaline hydrolysis has been investigated as a nonbiological procedure for the destruction of 2,4,6-trinitrotoluene (TNT) in explosives contaminated soils and munitions scrap. Nucleophilic substitutions of the nitro and methyl groups of TNT by hydroxide ion are the initial steps in the alkaline degradation of TNT. Potential applications of the technique include both in situ surface liming and ex situ alkaline treatment of contaminated soils. A number of laboratory studies have reported the formation of an uncharacterized polymeric material upon prolonged treatment of TNT in base. As part of an overall assessment of alkaline hydrolysis as a remediation technique, and to gain a better understanding of the chemical reactions underlying the hydrolysis/polymerization process, the soluble and precipitate fractions of polymeric material produced from the calcium hydroxide hydrolysis of unlabeled and 15N-labeled TNT were analyzed by elemental analysis and 13C and 15N nuclear magnetic resonance spectroscopy. Spectra indicated that reactions leading to polymerization included nucleophilic displacement of nitro groups by hydroxide ion, formation of ketone, carboxyl, alcohol, ether, and other aliphatic carbons, conversion of methyl groups to diphenyl methylene carbons, and recondensation of aromatic amines and reduced forms of nitrite, including ammonia and possibly hydroxylamine, into the polymer. Compared to the distribution of carbons in TNT as 14% sp 3- and 86% sp2-hybridized, the precipitate fraction from hydrolysis of unlabeled TNT contained 33% sp3- and 67% sp 2-hybridized carbons. The concentration of nitrogen in the precipitate was 64% of that in TNT. The 15N NMR spectra showed that, in addition to residual nitro groups, forms of nitrogen present in the filtrate and precipitate fractions include aminohydroquinone, primary amide, indole, imine, and azoxy, among others. Unreacted nitrite was recovered in the filtrate fraction. The toxicities and susceptibilities to microbial or chemical degradation of the polymeric materials remain unknown.

Alkaline hydrolysis/polymerization of 2,4,6-Trinitrotoluene:  Characterization of products by 13C and 15N NMR

USGS Publications Warehouse

Thorn, Kevin A.; Thorne, Philip G.; Cox, Larry G.

2004-01-01

Alkaline hydrolysis has been investigated as a nonbiological procedure for the destruction of 2,4,6-trinitrotoluene (TNT) in explosives contaminated soils and munitions scrap. Nucleophilic substitutions of the nitro and methyl groups of TNT by hydroxide ion are the initial steps in the alkaline degradation of TNT. Potential applications of the technique include both in situ surface liming and ex situ alkaline treatment of contaminated soils. A number of laboratory studies have reported the formation of an uncharacterized polymeric material upon prolonged treatment of TNT in base. As part of an overall assessment of alkaline hydrolysis as a remediation technique, and to gain a better understanding of the chemical reactions underlying the hydrolysis/polymerization process, the soluble and precipitate fractions of polymeric material produced from the calcium hydroxide hydrolysis of unlabeled and 15N-labeled TNT were analyzed by elemental analysis and 13C and 15N nuclear magnetic resonance spectroscopy. Spectra indicated that reactions leading to polymerization included nucleophilic displacement of nitro groups by hydroxide ion, formation of ketone, carboxyl, alcohol, ether, and other aliphatic carbons, conversion of methyl groups to diphenyl methylene carbons, and recondensation of aromatic amines and reduced forms of nitrite, including ammonia and possibly hydroxylamine, into the polymer. Compared to the distribution of carbons in TNT as 14% sp3- and 86% sp2-hybridized, the precipitate fraction from hydrolysis of unlabeled TNT contained 33% sp3- and 67% sp2-hybridized carbons. The concentration of nitrogen in the precipitate was 64% of that in TNT. The 15N NMR spectra showed that, in addition to residual nitro groups, forms of nitrogen present in the filtrate and precipitate fractions include aminohydroquinone, primary amide, indole, imine, and azoxy, among others. Unreacted nitrite was recovered in the filtrate fraction. The toxicities and susceptibilities to microbial or chemical degradation of the polymeric materials remain unknown.

The Experimental Evidence in Support of Glycosylation Mechanisms at the SN1-SN2 Interface.

PubMed

Adero, Philip Ouma; Amarasekara, Harsha; Wen, Peng; Bohé, Luis; Crich, David

2018-05-30

A critical review of the state-of-the-art evidence in support of the mechanisms of glycosylation reactions is provided. Factors affecting the stability of putative oxocarbenium ions as intermediates at the S N 1 end of the mechanistic continuum are first surveyed before the evidence, spectroscopic and indirect, for the existence of such species on the time scale of glycosylation reactions is presented. Current models for diastereoselectivity in nucleophilic attack on oxocarbenium ions are then described. Evidence in support of the intermediacy of activated covalent glycosyl donors is reviewed, before the influences of the structure of the nucleophile, of the solvent, of temperature, and of donor-acceptor hydrogen bonding on the mechanism of glycosylation reactions are surveyed. Studies on the kinetics of glycosylation reactions and the use of kinetic isotope effects for the determination of transition-state structure are presented, before computational models are finally surveyed. The review concludes with a critical appraisal of the state of the art.

Steric Effects of Solvent Molecules on SN2 Substitution Dynamics.

PubMed

Liu, Xu; Xie, Jing; Zhang, Jiaxu; Yang, Li; Hase, William L

2017-04-20

Influences of solvent molecules on S N 2 reaction dynamics of microsolvated F - (H 2 O) n with CH 3 I, for n = 0-3, are uncovered by direct chemical dynamics simulations. The direct substitution mechanism, which is important without microsolvation, is quenched dramatically upon increasing hydration. The water molecules tend to force reactive encounters to proceed through the prereaction collision complex leading to indirect reaction. In contrast to F - (H 2 O), reaction with higher hydrated ions shows a strong propensity for ion desolvation in the entrance channel, diminishing steric hindrance for nucleophilic attack. Thus, nucleophilic substitution avoids the potential energy barrier with all of the solvent molecules intact and instead occurs through the less solvated barrier, which is energetically unexpected because the former barrier has a lower energy. The work presented here reveals a trade-off between reaction energetics and steric effects, with the latter found to be crucial in understanding how hydration influences microsolvated S N 2 dynamics.

Functionalization of metallabenzenes through nucleophilic aromatic substitution of hydrogen.

PubMed

Clark, George R; Ferguson, Lauren A; McIntosh, Amy E; Söhnel, Tilo; Wright, L James

2010-09-29

The cationic metallabenzenes [Ir(C(5)H(4){SMe-1})(κ(2)-S(2)CNEt(2))(PPh(3))(2)]PF(6) (1) and [Os(C(5)H(4){SMe-1})(CO)(2)(PPh(3))(2)][CF(3)SO(3)] (2) undergo regioselective nucleophilic aromatic substitution of hydrogen at the metallabenzene ring position γ to the metal in a two-step process that first involves treatment with appropriate nucleophiles and then oxidation. Thus, reaction between compound 1 and NaBH(4), MeLi, or NaOEt gives the corresponding neutral iridacyclohexa-1,4-diene complexes Ir(C(5)H(3){SMe-1}{H-3}{Nu-3})(κ(2)-S(2)CNEt(2))(PPh(3))(2) (Nu = H (3), Me (4), OEt (5)). Similarly, reaction between 2 and NaBH(4) or MeLi gives the corresponding osmacyclohexa-1,4-diene complexes Os(C(5)H(3){SMe-1}{H-3}{Nu-3})(CO)(2)(PPh(3))(2) (Nu = H (8), Me (9)). The metallacyclohexa-1,4-diene rings in all these compounds are rearomatized on treatment with the oxidizing agent O(2), CuCl(2), or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Accordingly, the cationic metallabenzene 1 or 2 is returned after reaction between 3 and DDQ/NEt(4)PF(6) or between 8 and DDQ/NaO(3)SCF(3), respectively. The substituted cationic iridabenzene [Ir(C(5)H(3){SMe-1}{Me-3})(κ(2)-S(2)CNEt(2))(PPh(3))(2)]PF(6) (6) or [Ir(C(5)H(4){SMe-1}{OEt-3})(κ(2)-S(2)CNEt(2))(PPh(3))(2)]PF(6) (7) is produced in a similar manner through reaction between 4 or 5, respectively, and DDQ/NEt(4)PF(6), and the substituted cationic osmabenzene [Os(C(5)H(3){SMe-1}{Me-3})(CO)(2)(PPh(3))(2)]Cl (10) is formed in good yield on treatment of 9 with CuCl(2). The starting cationic iridabenzene 1 is conveniently prepared by treatment of the neutral iridabenzene Ir(C(5)H(4){SMe-1})Cl(2)(PPh(3))(2) with NaS(2)CNEt(2) and NEt(4)PF(6), and the related starting cationic osmabenzene 2 is obtained by treatment of Os(C(5)H(4){S-1})(CO)(PPh(3))(2) with CF(3)SO(3)CH(3) and CO. The stepwise transformations of 1 into 6 or 7 as well as 2 into 10 provide the first examples in metallabenzene chemistry of regioselective nucleophilic aromatic substitutions of hydrogen by external nucleophiles. DFT calculations have been used to rationalize the preferred sites for nucleophilic attack at the metallabenzene rings of 1 and 2. The crystal structures of 1, 3, 6, and 7 have been obtained.

Navy-ASEE (American Society for Engineering Education) Summer Faculty Research Program for 1983 with a Summary of Statistics and a Cumulative Compilation of Data on Later Research Fallouts from the First Five Years of the Program, 1979-1983.

DTIC Science & Technology

1983-01-01

POLYMER FORMATION VIA NUCLEOPHILIC ADDITION TO ACETYLENES Carl L. Bumgardner Department of Chemistry North Carolina...State University Raleigh, North Carolina ABSTRACT Utilizing the ability of acetylenes to add nucleophiles, two new polymer - forming reactions were...examined. The first involved hydroquinone and 1, 4-diethynylbenzene, which, under base calatysis, gave a new semiconducting polymer having the

Chiral Brønsted Acid‐Catalyzed Enantioselective α‐Amidoalkylation Reactions: A Joint Experimental and Predictive Study

PubMed Central

Aranzamendi, Eider; Arrasate, Sonia; Sotomayor, Nuria

2016-01-01

Abstract Enamides with a free NH group have been evaluated as nucleophiles in chiral Brønsted acid‐catalyzed enantioselective α‐amidoalkylation reactions of bicyclic hydroxylactams for the generation of quaternary stereocenters. A quantitative structure–reactivity relationship (QSRR) method has been developed to find a useful tool to rationalize the enantioselectivity in this and related processes and to orient the catalyst choice. This correlative perturbation theory (PT)‐QSRR approach has been used to predict the effect of the structure of the substrate, nucleophile, and catalyst, as well as the experimental conditions, on the enantioselectivity. In this way, trends to improve the experimental results could be found without engaging in a long‐term empirical investigation. PMID:28032023

Reference scales for the characterization of cationic electrophiles and neutral nucleophiles.

PubMed

Mayr, H; Bug, T; Gotta, M F; Hering, N; Irrgang, B; Janker, B; Kempf, B; Loos, R; Ofial, A R; Remennikov, G; Schimmel, H

2001-10-03

Twenty-three diarylcarbenium ions and 38 pi-systems (arenes, alkenes, allyl silanes and stannanes, silyl enol ethers, silyl ketene acetals, and enamines) have been defined as basis sets for establishing general reactivity scales for electrophiles and nucleophiles. The rate constants of 209 combinations of these benzhydrylium ions and pi-nucleophiles, 85 of which are first presented in this article, have been subjected to a correlation analysis to determine the electrophilicity parameters E and the nucleophilicity parameters N and s as defined by the equation log k(20 degrees C) = s(N + E) (Mayr, H.; Patz, M. Angew. Chem., Int. Ed. Engl. 1994, 33, 938-957). Though the reactivity scales thus obtained cover more than 16 orders of magnitude, the individual rate constants are reproduced with a standard deviation of a factor of 1.19 (Table 1). It is shown that the reactivity parameters thus derived from the reactions of diarylcarbenium ions with pi-nucleophiles (Figure 3) are also suitable for characterizing the nucleophilic reactivities of alkynes, metal-pi-complexes, and hydride donors (Table 2) and for characterizing the electrophilic reactivities of heterosubstituted and metal-coordinated carbenium ions (Table 3). The reactivity parameters in Figure 3 are, therefore, recommended for the characterization of any new electrophiles and nucleophiles in the reactivity range covered. The linear correlation between the electrophilicity parameters E of benzhydryl cations and the corresponding substituent constants sigma(+) provides Hammett sigma(+) constants for 10 substituents from -1.19 to -2.11, i.e., in a range with only very few previous entries.

Surfactants-aided syntheses of different sizes and triangular shape of gold nanoparticles using trisodium citrate in environmentally friendly and photoinduced methods.

PubMed

Su, Yen Hsun; Lai, Wei Hao; Chang, Shih-Hui; Hon, Min Hsiung

2007-09-01

We prepared gold nanoparticles (Au NPs) by only using trisodium citrate as the stabilizer. The detailed reaction mechanisms of S(N)1 and E1 reactions are examined and evidenced in this study by FTIR data. Citric acid is a kind of tertiary substrate. In aqueous solution, the substitution nucleophile path 1 (S(N)1) reaction and Elimination path 1 (E1) reaction usually occur simultaneously. Chloride ions, the substitution nucleophile, play a very important role to launch the mechanisms of S(N)1 and E1 reactions. Controlling the concentration of the chloride ions with the addition of HCl(aq) according to Le Chatelier theory, the average particle size of Au NPs (5.5 nm) was achieved to overcome the minimum limited size (approximately 10 nm). Two stages of the photoinduced method, aggregation into triangular conglomerates and growth into triangular particles, were determined form TEM observations. This preparation of Au NPs has potential in tuning the size, shape, and mechanism of Au NP formation by using only environmentally friendly trisodium citrate and the photoinduced method.

METABOLISM OF 1,1- AND 1,3- DICHLOROPROPENE: A MECHANISM OF BIOACTIVATION BY GLUTATHIONE

EPA Science Inventory

Glutathione transferases (GST) catalyze the reaction of glutathione (GSH) with haloalkenes via a nucleophilic vinylic substitution mechanism (SNV reaction). The source water contaminants 1,1-dichloropropene and 1,3-dichloropropene, which are under scrutiny by the U.S.EPA, were...

Facile Synthesis and Proposed Mechanism of α,ω-Oxetanyl-Telechelic Poly(3-nitratomethyl-3-methyl oxetane) by an SN2(i) Nitrato Displacement Method in Basic Media

NASA Astrophysics Data System (ADS)

Desai, Hemant J.; Acheampong, Daniel O.; Hudson, Robert; Lacey, Richard; Stanley, Claire; Turner, Helen; Whitmore, Hannah; Torry, Simon; Golding, Peter; Erothu, Harikrishna; Topham, Paul

2017-01-01

The synthesis of a novel heterocyclic-telechelic polymer, α,ω-oxetanyl-telechelic poly(3-nitratomethyl-3-methyl oxetane), is described. Infrared spectroscopy (IR), gel permeation chromatography (GPC), and nuclear magnetic resonance (NMR) spectroscopy have been used to confirm the successful synthesis, demonstrating the presence of the telechelic-oxetanyl moieties. Synthesis of the terminal functionalities has been achieved via displacement of nitrato groups, in a manner similar to that employed with other leaving groups such as azido, bromo, and nitro, initiated by nucleophiles. In the present case, displacement occurs on the ends of a nitrato-functionalized polymer driven by the formation of sodium nitrate, which is supported by the polar aprotic solvent N,N-dimethyl formamide. The formation of an alkoxide at the polymer chain ends is favored and allows internal back-biting to the nearest carbon bearing the nitrato group, intrinsically in an SN2(i) reaction, leading to α,ω-oxetanyl functionalization. The telechelic-oxetanyl moieties have the potential to be cross-linked by chemical (e.g., acidic) or radiative (e.g., ultraviolet) curing methods without the use of high temperatures, usually below 100°C. This type of material was designed for future use as a contraband simulant, whereby it would form the predominant constituent of elastomeric composites comprising rubbery polymer with small quantities of solids, typically crystals of contraband substances, such as explosives or narcotics. This method also provides an alternative approach to ring closure and synthesis of heterocycles.

Generation of N-Heterocycles via Tandem Reactions of N '-(2-Alkynylbenzylidene)hydrazides.

PubMed

Qiu, Guanyinsheng; Wu, Jie

2016-02-01

As a powerful synthon, N '-(2-alkynylbenzylidene)hydrazides have been utilized efficiently for the construction of N-heterocycles. Since N '-(2-alkynylbenzylidene)hydrazides can easily undergo intramolecular 6-endo cyclization promoted by silver triflate or electrophiles, the resulting isoquinolinium-2-yl amides can proceed through subsequent transformations including [3 + 2] cycloaddition, nucleophilic addition, and [3 + 3] cycloaddition. Several unexpected rearrangements via radical processes were observed in some cases, which afforded nitrogen-containing heterocycles with molecular complexity. Reactive partners including internal alkynes, arynes, ketenimines, ketenes, allenoates, and activated alkenes reacted through [3 + 2] cycloaddition and subsequent aromatization, leading to diverse H-pyrazolo[5,1-a]isoquinolines with high efficiency. Nucleophilic addition to the in situ generated isoquinolinium-2-yl amide followed by aromatization also produced H-pyrazolo[5,1-a]isoquinoline derivatives when terminal alkynes, carbonyls, enamines, and activated methylene compounds were used as nucleophiles. Isoquinoline derivatives were obtained when indoles or phosphites were employed as nucleophiles in the reactions of N '-(2-alkynylbenzylidene)hydrazides. A tandem 6-endo cyclization and [3 + 3] cycloaddition of cyclopropane-1,1-dicarboxylates with N '-(2-alkynylbenzylidene)hydrazides was observed as well. Small libraries of these compounds were constructed. Biological evaluation suggested that some compounds showed promising activities for inhibition of CDC25B, TC-PTP, HCT-116, and PTP1B. © 2015 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optical fiber-based on-line UV/Vis spectroscopic monitoring of chemical reaction kinetics under high pressure in a capillary microreactor.

PubMed

Benito-Lopez, Fernando; Verboom, Willem; Kakuta, Masaya; Gardeniers, J Han G E; Egberink, Richard J M; Oosterbroek, Edwin R; van den Berg, Albert; Reinhoudt, David N

2005-06-14

With a miniaturized (3 microL volume) fiber-optics based system for on-line measurement by UV/Vis spectroscopy, the reaction rate constants (at different pressures) and the activation volumes (deltaV(not =)) were determined for a nucleophilic aromatic substitution and an aza Diels-Alder reaction in a capillary microreactor.

Insights into the mechanism and catalysis of oxime coupling chemistry at physiological pH.

PubMed

Wang, Shujiang; Gurav, Deepanjali; Oommen, Oommen P; Varghese, Oommen P

2015-04-07

The dynamic covalent-coupling reaction involving α-effect nucleophiles has revolutionized bioconjugation approaches, due to its ease and high efficiency. Key to its success is the discovery of aniline as a nucleophilic catalyst, which made this reaction feasible under physiological conditions. Aniline however, is not so effective for keto substrates. Here, we investigate the mechanism of aniline activation in the oxime reaction with aldehyde and keto substrates. We also present carboxylates as activating agents that can promote the oxime reaction with both aldehyde and keto substrates at physiological pH. This rate enhancement circumvents the influence of α-effect by forming H-bonds with the rate-limiting intermediate, which drives the reaction to completion. The combination of aniline and carboxylates had a synergistic effect, resulting in a ∼14-31-fold increase in reaction rate at pD 7.4 with keto substrates. The biocompatibility and efficiency of carboxylate as an activating agent is demonstrated by performing cell-surface oxime labeling at physiological pH using acetate, which showed promising results that were comparable with aniline. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification and Characterization of Novel Catalytic Bioscavengers of Organophosphorus Nerve Agents

DTIC Science & Technology

2013-01-01

hydrolase activity . These strains are Ammoniphilus oxalaticus, Haloarcula sp., and Micromonospora aurantiaca. Lysates from A. oxalaticus had...warfare agents [1–3]. OP nerve agents readily bind covalently to the active site serine in acetylcho- linesterase (AChE), thereby inhibiting the ability...muscarinic receptors, whereas 2-pralidoxime chloride, an oxime nucleophile, reactivates AChE by displacing the phospho- nyl group left on the active site

The development of catalytic nucleophilic additions of terminal alkynes in water.

PubMed

Li, Chao-Jun

2010-04-20

One of the major research endeavors in synthetic chemistry over the past two decades is the exploration of synthetic methods that work under ambient atmosphere with benign solvents, that maximize atom utilization, and that directly transform natural resources, such as renewable biomass, from their native states into useful chemical products, thus avoiding the need for protecting groups. The nucleophilic addition of terminal alkynes to various unsaturated electrophiles is a classical (textbook) reaction in organic chemistry, allowing the formation of a C-C bond while simultaneously introducing the alkyne functionality. A prerequisite of this classical reaction is the stoichiometric generation of highly reactive metal acetylides. Over the past decade, our laboratory and others have been exploring an alternative, the catalytic and direct nucleophilic addition of terminal alkynes to unsaturated electrophiles in water. We found that various terminal alkynes can react efficiently with a wide range of such electrophiles in water (or organic solvent) in the presence of simple and readily available catalysts, such as copper, silver, gold, iron, palladium, and others. In this Account, we describe the development of these synthetic methods, focusing primarily on results from our laboratory. Our studies include the following: (i) catalytic reaction of terminal alkynes with acid chloride, (ii) catalytic addition of terminal alkynes to aldehydes and ketones, (iii) catalytic addition of alkynes to C=N bonds, and (iv) catalytic conjugate additions. Most importantly, these reactions can tolerate various functional groups and, in many cases, perform better in water than in organic solvents, clearly defying classical reactivities predicated on the relative acidities of water, alcohols, and terminal alkynes. We further discuss multicomponent and enantioselective reactions that were developed. These methods provide an alternative to the traditional requirement of separate steps in classical alkyne reactions, including the pregeneration of metal acetylides with stoichiometric, highly basic reagents and the preprotection of sensitive functional groups. Accordingly, these techniques have greatly enhanced overall synthetic efficiencies and furthered our long-term objective of developing Grignard-type reactions in water.

Kinetic Analysis of Haloacetonitrile Stability in Drinking Waters.

PubMed

Yu, Yun; Reckhow, David A

2015-09-15

Haloacetonitriles (HANs) are an important class of drinking water disinfection byproducts (DBPs) that are reactive and can undergo considerable transformation on time scales relevant to system distribution (i.e., from a few hours to a week or more). The stability of seven mono-, di-, and trihaloacetonitriles was examined under a variety of conditions including different pH levels and disinfectant doses that are typical of drinking water distribution systems. Results indicated that hydroxide, hypochlorite, and their protonated forms could react with HANs via nucleophilic attack on the nitrile carbon, forming the corresponding haloacetamides (HAMs) and haloacetic acids (HAAs) as major reaction intermediates and end products. Other stable intermediate products, such as the N-chloro-haloacetamides (N-chloro-HAMs), may form during the course of HAN chlorination. A scheme of pathways for the HAN reactions was proposed, and the rate constants for individual reactions were estimated. Under slightly basic conditions, hydroxide and hypochlorite are primary reactants and their associated second-order reaction rate constants were estimated to be 6 to 9 orders of magnitude higher than those of their protonated conjugates (i.e., neutral water and hypochlorous acid), which are much weaker but more predominant nucleophiles at neutral and acidic pHs. Developed using the estimated reaction rate constants, the linear free energy relationships (LFERs) summarized the nucleophilic nature of HAN reactions and demonstrated an activating effect of the electron withdrawing halogens on nitrile reactivity, leading to decreasing HAN stability with increasing degree of halogenation of the substituents, while subsequent shift from chlorine to bromine atoms has a contrary stabilizing effect on HANs. The chemical kinetic model together with the reaction rate constants that were determined in this work can be used for quantitative predictions of HAN concentrations depending on pH and free chlorine contact times (CTs), which can be applied as an informative tool by drinking water treatment and system management engineers to better control these emerging nitrogenous DBPs, and can also be significant in making regulatory decisions.

Stereocontrolled Cyanohydrin Ether Synthesis through Chiral Brønsted Acid-Mediated Vinyl Ether Hydrocyanation

PubMed Central

Lu, Chunliang; Su, Xiaoge; Floreancig, Paul E.

2013-01-01

Vinyl ethers can be protonated to generate oxocarbenium ions that react with Me3SiCN to form cyanohydrin alkyl ethers. Reactions that form racemic products proceed efficiently upon converting the vinyl ether to an α-chloro ether prior to cyanide addition in a pathway that proceeds through Brønsted acid-mediated chloride ionization. Enantiomerically enriched products can be accessed by directly protonating the vinyl ether with a chiral Brønsted acid to form a chiral ion pair. Me3SiCN acts as the nucleophile and PhOH serves as a stoichiometric proton source in a rare example of an asymmetric bimolecular nucleophilic addition reaction into an oxocarbenium ion. Computational studies provide a model for the interaction between the catalyst and the oxocarbenium ion. PMID:23968162

N-Heterocyclic Olefins as Robust Organocatalyst for the Chemical Conversion of Carbon Dioxide to Value-Added Chemicals.

PubMed

Saptal, Vitthal B; Bhanage, Bhalchandra M

2016-08-09

In this report, the activity of N-heterocyclic olefins (NHOs) as a newly emerging class of organocatalyst is investigated for the chemical fixation of carbon dioxide through reactions with aziridines to form oxazolidinones and the N-formylation of amines with polymethylhydrosiloxane (PMHS) or 9-borabicyclo[3.3.1]nonane (9-BBN) as the reducing agent under mild conditions. The exocyclic carbon atoms of NHOs are highly nucleophilic owing to the electron-donating ability of the two nitrogen atoms. This high nucleophilicity of the NHOs activates CO2 molecules to form zwitterionic NHO-carboxylate (NHO-CO2 ) adducts, which are active in formylation reactions as well as the carboxylation of aziridines to oxazolidinones. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Photometric Characterization of the Reductive Amination Scope of the Imine Reductases from Streptomyces tsukubaensis and Streptomyces ipomoeae.

PubMed

Matzel, Philipp; Krautschick, Lukas; Höhne, Matthias

2017-10-18

Imine reductases (IREDs) have emerged as promising enzymes for the asymmetric synthesis of secondary and tertiary amines starting from carbonyl substrates. Screening the substrate specificity of the reductive amination reaction is usually performed by time-consuming GC analytics. We found two highly active IREDs in our enzyme collection, IR-20 from Streptomyces tsukubaensis and IR-Sip from Streptomyces ipomoeae, that allowed a comprehensive substrate screening with a photometric NADPH assay. We screened 39 carbonyl substrates combined with 17 amines as nucleophiles. Activity data from 663 combinations provided a clear picture about substrate specificity and capabilities in the reductive amination of these enzymes. Besides aliphatic aldehydes, the IREDs accepted various cyclic (C 4 -C 8 ) and acyclic ketones, preferentially with methylamine. IR-Sip also accepted a range of primary and secondary amines as nucleophiles. In biocatalytic reactions, IR-Sip converted (R)-3-methylcyclohexanone with dimethylamine or pyrrolidine with high diastereoselectivity (>94-96 % de). The nucleophile acceptor spectrum depended on the carbonyl substrate employed. The conversion of well-accepted substrates could also be detected if crude lysates were employed as the enzyme source. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Heterobimetallic Pd-Sn catalysis: a Suzuki, tandem ring-closing sequence toward indeno[2,1-b]thiophenes and indeno[2,1-b]indoles.

PubMed

Das, Debjit; Pratihar, Sanjay; Roy, Sujit

2012-09-21

Indeno[2,1-b]thiophene and indeno[1,2-b]indole motifs have been obtained in moderate to good yields from easily available substituted boronic acids, 2-bromo aryl/vinyl aldehydes, and nucleophiles such as arenes/heteroarenes and others using a catalytic combination of bimetallic "Pd-Sn" and AgPF(6). This formal three-component coupling involves a Suzuki reaction followed by nucleophile assisted tandem ring closure. The sequential synthesis of substituted heterocycle-fused indenes, benzofluorene, and fluorenes was also accomplished.

Nucleophilic addition of Grignard reagents to 3-acylindoles: stereoselective synthesis of highly substituted indoline scaffolds.

PubMed

Wang, Lu; Shao, Yushang; Liu, Yuanhong

2012-08-03

3-Acylindoles undergo nucleophilic-type reactions with Grignard reagents to efficiently afford either cis- or trans-substituted indolines, depending on the different quenching procedures. The enolate intermediate could be trapped by aryl acyl chlorides to provide indolines bearing a quaternary carbon center with high stereoselectivity. In contrast, the use of benzyl bromide as an electrophile results in the fragmentation of the indole ring. The indoline products could be easily transformed into indoles through oxidation with DDQ in a one-pot manner.

Electronic forces as descriptors of nucleophilic and electrophilic regioselectivity and stereoselectivity.

PubMed

Liu, Shubin; Rong, Chunying; Lu, Tian

2017-01-04

One of the main tasks of theoretical chemistry is to rationalize computational results with chemical insights. Key concepts of such nature include nucleophilicity, electrophilicity, regioselectivity, and stereoselectivity. While computational tools are available to predict barrier heights and other reactivity properties with acceptable accuracy, a conceptual framework to appreciate above quantities is still lacking. In this work, we introduce the electronic force as the fundamental driving force of chemical processes to understand and predict molecular reactivity. It has three components but only two are independent. These forces, electrostatic and steric, can be employed as reliable descriptors for nucleophilic and electrophilic regioselectivity and stereoselectivity. The advantages of using these forces to evaluate molecular reactivity are that electrophilic and nucleophilic attacks are featured by distinct characteristics in the electrostatic force and no knowledge of quantum effects included in the kinetic and exchange-correlation energies is required. Examples are provided to highlight the validity and general applicability of these reactivity descriptors. Possible applications in ambident reactivity, σ and π holes, frustrated Lewis pairs, and stereoselective reactions are also included in this work.

Magnesium Induced Nucleophile Activation in the Guanylyltransferase mRNA Capping Enzyme

PubMed Central

Swift, Robert V.; Ong, Chau D.; Amaro, Rommie E.

2012-01-01

The messenger RNA guanylyltransferase, or mRNA capping enzyme, co-transcriptionally caps the 5′-end of nascent mRNA with GMP during the second in a set of three enzymatic reactions that result in the formation of an N7-methyl guanosine cap during mRNA maturation. The mRNA capping enzyme is characterized, in part, by a conserved lysine nucleophile that attacks the alpha-phosphorous atom of GTP, forming a lysine-GMP intermediate. Experiments have firmly established that magnesium is required for efficient intermediate formation, but have provided little insight into the requirement’s molecular origins. Using empirical and thermodynamic integration pKa estimates, along with conventional MD simulations, we show that magnesium binding likely activates the lysine nucleophile by increasing its acidity and by biasing the deprotonated nucleophile into conformations conducive to intermediate formation. These results provide additional functional understanding of an important enzyme in the mRNA transcript life cycle and allow functional analogies to be drawn that affect our understanding of the metal dependence of related superfamily members. PMID:23205906

Understanding thio-effects in simple phosphoryl systems: role of solvent effects and nucleophile charge† †Electronic supplementary information (ESI) available: A breakdown of calculated activation free energies shown in Table 1, as well as absolute energies and Cartesian coordinates of all key species in this work are presented as ESI. See DOI: 10.1039/c5ob00309a Click here for additional data file.

PubMed Central

Carvalho, Alexandra T. P.; O'Donoghue, AnnMarie C.; Hodgson, David R. W.

2015-01-01

Recent experimental work (J. Org. Chem., 2012, 77, 5829) demonstrated pronounced differences in measured thio-effects for the hydrolysis of (thio)phosphodichloridates by water and hydroxide nucleophiles. In the present work, we have performed detailed quantum chemical calculations of these reactions, with the aim of rationalizing the molecular bases for this discrimination. The calculations highlight the interplay between nucleophile charge and transition state solvation in SN2(P) mechanisms as the basis of these differences, rather than a change in mechanism. PMID:25797408

Synthesis and Late-Stage Functionalization of Complex Molecules through C–H Fluorination and Nucleophilic Aromatic Substitution

PubMed Central

2015-01-01

We report the late-stage functionalization of multisubstituted pyridines and diazines at the position α to nitrogen. By this process, a series of functional groups and substituents bound to the ring through nitrogen, oxygen, sulfur, or carbon are installed. This functionalization is accomplished by a combination of fluorination and nucleophilic aromatic substitution of the installed fluoride. A diverse array of functionalities can be installed because of the mild reaction conditions revealed for nucleophilic aromatic substitutions (SNAr) of the 2-fluoroheteroarenes. An evaluation of the rates for substitution versus the rates for competitive processes provides a framework for planning this functionalization sequence. This process is illustrated by the modification of a series of medicinally important compounds, as well as the increase in efficiency of synthesis of several existing pharmaceuticals. PMID:24918484

Nucleophilic fluorination of aromatic compounds

DOEpatents

Satyamurthy, Nagichettiar; Barrio, Jorge R

2014-03-18

Iodylbenzene derivatives substituted with electron donating as well as electron withdrawing groups on the aromatic ring are used as precursors in aromatic nucleophilic substitution reactions. The iodyl group (IO.sub.2) is regiospecifically substituted by nucleophilic fluoride to provide the corresponding fluoroaryl derivatives. No-carrier-added [F-18]fluoride ion derived from anhydrous [F-18](F/Kryptofix, [F-18]CsF or a quaternary ammonium fluoride (e.g., Me.sub.4NF, Et.sub.4NF, n-Bu.sub.4NF, (PhCH.sub.2).sub.4NF) exclusively substitutes the iodyl moiety in these derivatives and provides high specific activity F-18 labeled fluoroaryl analogs. Iodyl derivatives of a benzothiazole analog and 6-iodyl-L-dopa derivatives have been synthesized as precursors and have been used in the preparation of no-carrier-added [F-18]fluorobenzothiazole as well as 6-[F-18]fluoro-L-dopa.

Novel Reagents for Multi-Component Reactions

NASA Astrophysics Data System (ADS)

Wang, Yanguang; Basso, Andrea; Nenajdenko, Valentine G.; Gulevich, Anton V.; Krasavin, Mikhail; Bushkova, Ekaterina; Parchinsky, Vladislav; Banfi, Luca; Basso, Andrea; Cerulli, Valentina; Guanti, Giuseppe; Riva, Renata; Rozentsveig, Igor B.; Rozentsveig, Gulnur N.; Popov, Aleksandr V.; Serykh, Valeriy J.; Levkovskaya, Galina G.; Cao, Song; Shen, Li; Liu, Nianjin; Wu, Jingjing; Li, Lina; Qian, Xuhong; Chen, Xiaopeng; Wang, Hongbo; Feng, Jinwu; Wang, Yanguang; Lu, Ping; Heravi, Majid M.; Sadjadi, Samaheh; Kazemizadeh, Ali Reza; Ramazani, Ali; Kudyakova, Yulia S.; Goryaeva, Marina V.; Burgart, Yanina V.; Saloutin, Victor I.; Mossetti, Riccardo; Pirali, Tracey; Tron, Gian Cesare; Rozhkova, Yulia S.; Mayorova, Olga A.; Shklyaev, Yuriy V.; Zhdanko, Alexander G.; Nenajdenko, Valentine G.; Stryapunina, Olga G.; Plekhanova, Irina V.; Glushkov, Vladimir A.; Shklyaev, Yurii V.

Ketenimines are a class of versatile and highly reactive intermediates that can participate in a variety of organic reactions, such as nucleophilic additions, radical additions, [2 + 2] and [2 + 4] cycloadditions, and sigmatropic rearrangements. In this presentation, we report on a series of multi-component reactions that involve a ketenimine intermediate. These reactions could furnish diverse heterocyclic compounds, including functionalized iminocoumarin, iminodihydroqunolines, iminothiochromens, pyrrolines, isoquinolines, pyridines, β-lactams, imino-1,2-dihydrocoumarins, and benzimidazoles.

Microwave-Assisted Synthesis of Phenothiazine and Quinoline Derivatives

PubMed Central

Găină, Luiza; Cristea, Castelia; Moldovan, Claudia; Porumb, Dan; Surducan, Emanoil; Deleanu, Călin; Mahamoud, Abdalah; Barbe, Jacques; Silberg, Ioan A.

2007-01-01

Application of a dynamic microwave power system in the chemical synthesis of some phenothiazine and quinoline derivatives is described. Heterocyclic ring formation, aromatic nucleophilic substitution and heterocyclic aldehydes/ketones condensation reactions were performed on solid support, or under solvent free reaction conditions. The microwave-assisted Duff formylation of phenothiazine was achieved. Comparison of microwave-assisted synthesis with the conventional synthetic methods demonstrates advantages related to shorter reaction times and in some cases better reaction yields.

A Fluorogenic Aromatic Nucleophilic Substitution Reaction for Demonstrating Normal-Phase Chromatography and Isolation of Nitrobenzoxadiazole Chromophores

ERIC Educational Resources Information Center

Key, Jessie A.; Li, Matthew D.; Cairo, Christopher W.

2011-01-01

Normal-phase chromatography is an essential technique for monitoring chemical reactions, identifying the presence of specific components, as well as the purification of organic compounds. An experiment to facilitate the instruction and understanding of the concepts behind normal-phase chromatography at the introductory and intermediate…

A Conversion of Methyl Ketones into Acetylenes: A Project for a Problem-Oriented or Microscale Organic Chemistry Course.

ERIC Educational Resources Information Center

Silveira, Augustine, Jr.; Orlando, Steven C.

1988-01-01

Describes a process for producing terminal or internal alkynes from ketones. Recommends using the experiment to aid in understanding acid-base strength, enolate anion chemistry, reaction at carbon versus oxygen, use of polar aprotic solvents, and elimination and nucleophilic substitution reactions. (ML)

Thiolysis and alcoholysis of phosphate tri- and monoesters with alkyl and aryl leaving groups. An ab initio study in the gas phase.

PubMed

Arantes, Guilherme Menegon; Chaimovich, Hernan

2005-06-30

Phosphate esters are important compounds in living systems. Their biological reactions with alcohol and thiol nucleophiles are catalyzed by a large superfamily of phosphatase enzymes. However, very little is known about the intrinsic reactivity of these nucleophiles with phosphorus centers. We have performed ab initio calculations on the thiolysis and alcoholysis at phosphorus of trimethyl phosphate, dimethyl phenyl phosphate, methyl phosphate, and phenyl phosphate. Results in the gas phase are a reference for the study of the intrinsic reactivity of these compounds. Thiolysis of triesters was much slower and less favorable than the corresponding alcoholysis. Triesters reacted through an associative mechanism. Monoesters can react by both associative and dissociative mechanisms. The basicity of the attacking and leaving groups and the possibility of proton transfers can modulate the reaction mechanisms. Intermediates formed along associative reactions did not follow empirically proposed rules for ligand positioning. Our calculations also allow re-interpretation of some experimental results, and new experiments are proposed to trace reactions that are normally not observed, both in the gas phase and in solution.

CO- and HCl-free synthesis of acid chlorides from unsaturated hydrocarbons via shuttle catalysis

NASA Astrophysics Data System (ADS)

Fang, Xianjie; Cacherat, Bastien; Morandi, Bill

2017-11-01

The synthesis of carboxylic acid derivatives from unsaturated hydrocarbons is an important process for the preparation of polymers, pharmaceuticals, cosmetics and agrochemicals. Despite its industrial relevance, the traditional Reppe-type carbonylation reaction using pressurized CO is of limited applicability to laboratory-scale synthesis because of: (1) the safety hazards associated with the use of CO, (2) the need for special equipment to handle pressurized gas, (3) the low reactivity of several relevant nucleophiles and (4) the necessity to employ different, often tailor-made, catalytic systems for each nucleophile. Herein we demonstrate that a shuttle-catalysis approach enables a CO- and HCl-free transfer process between an inexpensive reagent, butyryl chloride, and a wide range of unsaturated substrates to access the corresponding acid chlorides in good yields. This new transformation provides access to a broad range of carbonyl-containing products through the in situ transformation of the reactive acid chloride intermediate. In a broader context, this work demonstrates that isodesmic shuttle-catalysis reactions can unlock elusive catalytic reactions.

Presidential Green Chemistry Challenge: 1998 Greener Synthetic Pathways Award

EPA Pesticide Factsheets

Presidential Green Chemistry Challenge 1998 award winner, Flexsys America, developed nucleophilic aromatic substitution for hydrogen to eliminate waste from a common reaction and to produce 4-ADPA, a high-volume chemical.

A two-metal ion mechanism operates in the hammerhead ribozyme-mediated cleavage of an RNA substrate

PubMed Central

Lott, William B.; Pontius, Brian W.; von Hippel, Peter H.

1998-01-01

Evidence for a two-metal ion mechanism for cleavage of the HH16 hammerhead ribozyme is provided by monitoring the rate of cleavage of the RNA substrate as a function of La3+ concentration in the presence of a constant concentration of Mg2+. We show that a bell-shaped curve of cleavage activation is obtained as La3+ is added in micromolar concentrations in the presence of 8 mM Mg2+, with a maximal rate of cleavage being attained in the presence of 3 μM La3+. These results show that two-metal ion binding sites on the ribozyme regulate the rate of the cleavage reaction and, on the basis of earlier estimates of the Kd values for Mg2+ of 3.5 mM and >50 mM, that these sites bind La3+ with estimated Kd values of 0.9 and >37.5 μM, respectively. Furthermore, given the very different effects of these metal ions at the two binding sites, with displacement of Mg2+ by La3+ at the stronger (relative to Mg2+) binding site activating catalysis and displacement of Mg2+ by La3+ at the weaker (relative to Mg2+) (relative to Mg2+) binding site inhibiting catalysis, we show that the metal ions at these two sites play very different roles. We argue that the metal ion at binding site 1 coordinates the attacking 2′-oxygen species in the reaction and lowers the pKa of the attached proton, thereby increasing the concentration of the attacking alkoxide nucleophile in an equilibrium process. In contrast, the role of the metal ion at binding site 2 is to catalyze the reaction by absorbing the negative charge that accumulates at the leaving 5′-oxygen in the transition state. We suggest structural reasons why the Mg2+–La3+ ion combination is particularly suited to demonstrating these different roles of the two-metal ions in the ribozyme cleavage reaction. PMID:9435228

Synthesis of Aminofuran-Linked Benzimidazoles and Cyanopyrrole-Fused Benzimidazoles by Condition-Based Skeletal Divergence.

PubMed

Hsu, Wei-Shun; Tsai, Min-Huan; Barve, Indrajeet J; Yellol, Gorakh S; Sun, Chung-Ming

2017-07-10

A condition-based skeletal divergent synthesis was explored to achieve skeletal diversity in two component condensation reaction. Cyanomethyl benzimidazole was reacted with α-bromoketone under thermal conditions to furnish 2-aminofuranyl-benzimidazoles, while the same reaction afforded 3-cyano-benzopyrrolo-imidazoles under microwave irradiation. Two nonequivalent nucleophilic centers on benzimidazole moiety were manipulated elegantly by different reaction conditions to achieve the skeletal diversity.

Some Addition and Complexation Reactions of a Silylated Amino(Methylene)Phosphine.

DTIC Science & Technology

1984-12-12

0 ., . % , ’ - - o= . *.- . ° , % , - . -° , .° ..% . . . -= •% .°• - " . = . 4 reagents to the P=C bond 3 , and possible cycloaddition reactions...example, the reaction of 1 with alkyllithium reagents occurs with both nucleophilic substitution and addition leading to trialkylphosphines or P-C-P...such °" as 1 as synthetic reagents in organophosphorus and organometallic chemistry. A secondary objective of this study was to more closely compare

Electron transfer from nucleophilic species to N,N,N prime ,N prime -tetramethylbenzidine cation in micellar media: Effect of interfacial electrical potential on cation decay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grand, D.; Hautecloque, S.

1990-01-25

Electron-transfer reaction between N,N,N{prime},N{prime}-tetramethylbenzidine cation (TMB{sup +}) and neutral nucleophiles, pyridine (Py) and triethylamine (Et{sub 3}N), is studied in NaLS micellar media. A biphasic decay of TMB{sup +} follows the laser-induced TMB photoionization. The very fast decay is attributed to an electron transfer between reactants located in the core of the micelle. The slow decay would correspond to an electron transfer from the nucleophile solubilized in the aqueous phase to TMB{sup +} embedded in the lipidic phase. The role of the electrical interfacial potential {Delta}{psi} is evidenced. The rate constant of the TMB{sup +} slow decay displays an exponential functionmore » of {Delta}{psi}. The effect of the localization and distance of the reactants is emphasized.« less

Palladium-catalyzed three-component reaction of N-tosyl hydrazones, isonitriles and amines leading to amidines.

PubMed

Dai, Qiang; Jiang, Yan; Yu, Jin-Tao; Cheng, Jiang

2015-12-04

A palladium-catalyzed three-component reaction between N-tosyl hydrazones, aryl isonitriles and amines was developed, leading to amidines in moderate to good yields. This procedure features the rapid construction of amidine frameworks with high diversity and complexity. Ketenimines serve as intermediates, which encounter nucleophilic attack by amines to produce amidines.

Cyclization Reactions through DDQ-Mediated Vinyl Oxazolidinone Oxidation

PubMed Central

Liu, Lei; Floreancig, Paul E.

2009-01-01

Vinyl oxazolidinones react with DDQ to form α,β-unsaturated acyliminium ions in a new method for forming electrophiles under oxidative conditions. Appended nucleophiles undergo 1,4-addition reactions with these intermediates to form cyclic vinyl oxazolidinones with good levels of diastereocontrol, highlighting a new approach to utilizing oxidative carbon–hydrogen bond functionalization to increase molecular complexity. PMID:19552390

Absence of S[subscript N]1 Involvement in the Solvolysis of Secondary Alkyl Compounds

ERIC Educational Resources Information Center

Murphy, Thomas J.

2009-01-01

There are significant contradictions in undergraduate organic chemistry textbooks as to the mechanism of nucleophilic substitution reactions at saturated secondary carbons. Some texts say that only the S[subscript N]2 mechanism operates, others say that solvolysis reactions go entirely by the S[subscript N]1 mechanism, while most texts say that…

Nucleophilic substitution at phosphorus centers (SN2@p).

PubMed

van Bochove, Marc A; Swart, Marcel; Bickelhaupt, F Matthias

2007-12-03

We have studied the characteristics of archetypal model systems for bimolecular nucleophilic substitution at phosphorus (SN2@P) and, for comparison, at carbon (SN2@C) and silicon (SN2@Si) centers. In our studies, we applied the generalized gradient approximation (GGA) of density functional theory (DFT) at the OLYP/TZ2P level. Our model systems cover nucleophilic substitution at carbon in X(-)+CH3Y (SN2@C), at silicon in X(-)+SiH3Y (SN2@Si), at tricoordinate phosphorus in X(-)+PH2Y (SN2@P3), and at tetracoordinate phosphorus in X(-)+POH2Y (SN2@P4). The main feature of going from SN2@C to SN2@P is the loss of the characteristic double-well potential energy surface (PES) involving a transition state [X--CH3--Y]- and the occurrence of a single-well PES with a stable transition complex, namely, [X--PH2--Y]- or [X--POH2--Y](-). The differences between SN2@P3 and SN2@P4 are relatively small. We explored both the symmetric and asymmetric (i.e. X, Y=Cl, OH) SN2 reactions in our model systems, the competition between backside and frontside pathways, and the dependence of the reactions on the conformation of the reactants. Furthermore, we studied the effect, on the symmetric and asymmetric SN2@P3 and S(N)2@P4 reactions, of replacing hydrogen substituents at the phosphorus centers by chlorine and fluorine in the model systems X(-)+PR2Y and X(-)+POR2Y, with R=Cl, F. An interesting phenomenon is the occurrence of a triple-well PES not only in the symmetric, but also in the asymmetric SN2@P4 reactions of X(-)+POCl2--Y.

The Electrode as Organolithium Reagent: Catalyst-Free Covalent Attachment of Electrochemically Active Species to an Azide-Terminated Glassy Carbon Electrode Surface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, Atanu K.; Engelhard, Mark H.; Liu, Fei

2013-12-02

Glassy carbon electrodes have been activated for modification with azide groups and subsequent coupling with ferrocenyl reagents by a catalyst-free route using lithium acetylide-ethylenediamine complex, and also by the more common Cu(I)-catalyzed alkyne-azide coupling (CuAAC) route, both affording high surface coverages. Electrodes were preconditioned at ambient temperature under nitrogen, and ferrocenyl surface coverages obtained by CuAAC were comparable to those reported with preconditioning at 1000 °C under hydrogen/nitrogen. The reaction of lithium acetylide-ethylenediamine with the azide-terminated electrode affords a 1,2,3-triazolyllithium-terminated surface that is active toward covalent C-C coupling reactions including displacement at an aliphatic halide and nucleophilic addition at anmore » aldehyde. For example, surface ferrocenyl groups were introduced by reaction with (6-iodohexyl)ferrocene; the voltammetry shows narrow, symmetric peaks indicating uniform attachment. Coverages are competitive with those obtained by the CuAAC route. X-ray photoelectron spectroscopic data, presented for each synthetic step, are consistent with the proposed reactions. This research was supported as part of the Center for Molecular Electrocatalysis, an Energy Frontier Research Center funded by the US Department of Energy, Office of Science, Office of Basic Energy Sciences. Pacific Northwest National Laboratory is operated by Battelle for the US Department of Energy. A portion of the research was performed using EMSL, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory.« less

Copper-Catalyzed Carbonylative Coupling of Cycloalkanes and Amides.

PubMed

Li, Yahui; Dong, Kaiwu; Zhu, Fengxiang; Wang, Zechao; Wu, Xiao-Feng

2016-06-13

Carbonylation reactions are a most powerful method for the synthesis of carbonyl-containing compounds. However, most known carbonylation procedures still require noble-metal catalysts and the use of activated compounds and good nucleophiles as substrates. Herein, we developed a copper-catalyzed carbonylative transformation of cycloalkanes and amides. Imides were prepared in good yields by carbonylation of a C(sp(3) )-H bond of the cycloalkane with the amides acting as weak nucleophiles. Notably, this is the first report of copper-catalyzed carbonylative C-H activation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reactivity of nitrido complexes of ruthenium(VI), osmium(VI), and manganese(V) bearing Schiff base and simple anionic ligands.

PubMed

Man, Wai-Lun; Lam, William W Y; Lau, Tai-Chu

2014-02-18

Nitrido complexes (M≡N) may be key intermediates in chemical and biological nitrogen fixation and serve as useful reagents for nitrogenation of organic compounds. Osmium(VI) nitrido complexes bearing 2,2':6',2″-terpyridine (terpy), 2,2'-bipyridine (bpy), or hydrotris(1-pyrazolyl)borate anion (Tp) ligands are highly electrophilic: they can react with a variety of nucleophiles to generate novel osmium(IV)/(V) complexes. This Account describes our recent results studying the reactivity of nitridocomplexes of ruthenium(VI), osmium(VI), and manganese(V) that bear Schiff bases and other simple anionic ligands. We demonstrate that these nitrido complexes exhibit rich chemical reactivity. They react with various nucleophiles, activate C-H bonds, undergo N···N coupling, catalyze the oxidation of organic compounds, and show anticancer activities. Ruthenium(VI) nitrido complexes bearing Schiff base ligands, such as [Ru(VI)(N)(salchda)(CH3OH)](+) (salchda = N,N'-bis(salicylidene)o-cyclohexyldiamine dianion), are highly electrophilic. This complex reacts readily at ambient conditions with a variety of nucleophiles at rates that are much faster than similar reactions using Os(VI)≡N. This complex also carries out unique reactions, including the direct aziridination of alkenes, C-H bond activation of alkanes and C-N bond cleavage of anilines. The addition of ligands such as pyridine can enhance the reactivity of [Ru(VI)(N)(salchda)(CH3OH)](+). Therefore researchers can tune the reactivity of Ru≡N by adding a ligand L trans to nitride: L-Ru≡N. Moreover, the addition of various nucleophiles (Nu) to Ru(VI)≡N initially generate the ruthenium(IV) imido species Ru(IV)-N(Nu), a new class of hydrogen-atom transfer (HAT) reagents. Nucleophiles also readily add to coordinated Schiff base ligands in Os(VI)≡N and Ru(VI)≡N complexes. These additions are often stereospecific, suggesting that the nitrido ligand has a directing effect on the incoming nucleophile. M≡N is also a potential platform for the design of new oxidation catalysts. For example, [Os(VI)(N)Cl4](-) catalyzes the oxidation of alkanes by a variety of oxidants, and the addition of Lewis acids greatly accelerates these reactions. [Mn(V)(N)(CN)4]2(-) is another highly efficient oxidation catalyst, which facilitates the epoxidation of alkenes and the oxidation of alcohols to carbonyl compounds using H2O2. Finally, M≡N can potentially bind to and exert various effects on biomolecules. For example, a number of Os(VI)≡N complexes exhibit novel anticancer properties, which may be related to their ability to bind to DNA or other biomolecules.

Triple Nucleophilic Attack of Nitromethane on (2-Iminoaryl)divinyl Ketones: A Domino Synthetic Strategy for Hexahydrophenanthridinones.

PubMed

Feng, Chengjie; Li, Yifei; Xu, Qi; Pan, Ling; Liu, Qun; Xu, Xianxiu

2018-02-02

A novel domino reaction of (2-iminoaryl)divinyl ketones with nitromethane was developed for the efficient synthesis of hexahydrophenanthridin-9(5H)-ones. The reaction proceeded smoothly from readily available starting materials under mild reaction conditions to construct three new bonds and two rings with high diastereoselectivities in good to excellent yields in a single step. A mechanism is proposed, involving a stepwise double Michael addition/aza-Henry reaction cascade, and in this transformation, nitromethane acts as a trinucleophile.

Recent advances in copper-catalyzed asymmetric coupling reactions

PubMed Central

2015-01-01

Summary Copper-catalyzed (or -mediated) asymmetric coupling reactions have received significant attention over the past few years. Especially the coupling reactions of aryl or alkyl halides with nucleophiles became a very powerful tool for the formation of C–C, C–N, C–O and other carbon–heteroatom bonds as well as for the construction of heteroatom-containing ring systems. This review summarizes the recent progress in copper-catalyzed asymmetric coupling reactions for the formation of C–C and carbon–heteroatom bonds. PMID:26734106

Study of improved resins for advanced supersonic technology composites. Part 1: Heteroaromatic polymers containing ether groups. Part 2: Curing chemistry of aromatic polymers and composite studies

NASA Technical Reports Server (NTRS)

Takekoshi, T.; Hillig, W. B.; Mellinger, G. A.

1975-01-01

Fourteen ether-containing, aromatic dianhydrides have been synthesized from N-phenyl-3 or 4-nitrophthalimide and various bisphenols. The process involves nucleophilic displacement of activated nitro groups with bisphenolate ions. Ether-containing dianhydrides were indefinitely stable in the presence of atmospheric moisture. One-step, high temperature solution polymerization of the ether-containing dianhydrides with m-phenylene diamine, 4,4'-oxydianiline and 1, 3-bis(4-aminophenoxy)benzene afforded 42 polyetherimides. The polyetherimides were all soluble in m-cresol except two which were found to be crystalline. The glass transition temperatures of the polyetherimides ranged from 178 to 277 C. Soluble polybenzimidazopyrrolones containing ether groups were also prepared from the same ether-containing dianhydrides and aromatic tetraamines by one-step solution polymerization. Using low molecular weight polyetherimides, various thermoset resin systems were developed and tested as matrices for fiber-reinforced composites. The curing chemistry involving reaction of the phthalonitrile group and the o-diaminophenyl group was found to be generally applicable to crosslinking various aromatic polymers other than polyimides.

Quantum chemical study of leaving group activation in T. vivax nucleoside hydrolase

NASA Astrophysics Data System (ADS)

Loverix, Stefan; Versees, Wim; Steyaert, Jan; Geerlings, Paul

General acid catalysis is a powerful and widely used strategy in enzymatic nucleophilic displacement reactions. However, in the nucleoside hydrolase of the parasite Trypanosoma vivax, crystallographic and mutagenesis studies failed to identify a general acid. The only groups in the vicinity of the leaving group that contribute to catalysis are (i) the indole side chain of Trp260, and (ii) the 5'-group of the substrate's ribose moiety. The x-ray structure of the slow Asp10Ala mutant of nucleoside hydrolase with the substrate inosine bound in the active site displays a face-to-face aromatic stacking interaction between Trp260 and the purine base of the substrate, as well as a peculiar C4'-endo ribose pucker that allows the 5'-OH group to accept an intramolecular hydrogen bond from the C8 of the purine. The first interaction (aromatic stacking) has been shown to raise the pKa of the leaving purine. Here, we present a DFT study showing that the 5'-OH group of ribose fulfills a similar role, rather than stabilizing the oxocarbenium-like transition state.

Nucleophilic catalysis of MeON-neoglycoside formation by aniline derivatives.

PubMed

Loskot, Steven A; Zhang, Jianjun; Langenhan, Joseph M

2013-12-06

Neoglycosylations are increasingly being employed in the synthesis of natural products, drug candidates, glycopeptide mimics, oligosaccharide analogues, and other applications, but the efficiency of these reactions is usually limited by slow reaction times. Here, we show that aniline derivatives such as 2-amino-5-methoxybenzoic acid enhance the rate of acid-catalyzed neoglycosylation for a range of sugar substrates up to a factor of 32 relative to the uncatalyzed reaction.

Carbene Catalysts

NASA Astrophysics Data System (ADS)

Moore, Jennifer L.; Rovis, Tomislav

The use of N-heterocyclic carbenes as catalysts for organic transformations has received increased attention in the past 10 years. A discussion of catalyst development and nucleophilic characteristics precedes a description of recent advancements and new reactions using N-heterocyclic carbenes in catalysis.

New natural product -an efficient antimicrobial applications of new newly synthesized pyrimidine derivatives by the electrochemical oxidation of hydroxyl phenol in the presence of 2-mercapto-6-(trifluoromethyl) pyrimidine-4-ol as nucleophile.

PubMed

Khan, Zia Ul Haq; Khan, Amjad; Wan, Pingyu; Khan, Arif Ullah; Tahir, Kamran; Muhammad, Nawshad; Khan, Faheem Ullah; Shah, Hidayat Ullah; Khan, Zia Ullah

2018-05-01

Some new pyrimidine derivatives have been synthesised by electrochemical oxidation of catechol (1a) in the existence of 2-mercapto-6-(trifluoromethyl) pyrimidine-4-ol (3) as a nucleophile in aqueous solution using Cyclic Voltammetric and Controlled Potential Coulometry. The catechol has been oxidised to o-quinone through electrochemical method and participative in Michael addition reaction, leading to the development of some new pyrimidine derivatives. The products were achieved in good yield with high pureness. The mechanism of the reaction has been conformed from the Cyclic Voltammetric data and Controlled Potential Coulometry. After purification, the compounds were characterised using modern techniques. The synthesised materials were screened for antimicrobial actions using Gram positive and Gram negative strain of bacteria. These new synthesised pyrimidine derivatives showed very good antimicrobial activity.

Aliphatic C-C Bond Cleavage in α-Hydroxy Ketones by a Dioxygen-Derived Nucleophilic Iron-Oxygen Oxidant.

PubMed

Bhattacharya, Shrabanti; Rahaman, Rubina; Chatterjee, Sayanti; Paine, Tapan K

2017-03-17

A nucleophilic iron-oxygen oxidant, formed in situ in the reaction between an iron(II)-benzilate complex and O 2 , oxidatively cleaves the aliphatic C-C bonds of α-hydroxy ketones. In the cleavage reaction, α-hydroxy ketones without any α-C-H bond afford a 1:1 mixture of carboxylic acid and ketone. Isotope labeling studies established that one of the oxygen atoms from dioxygen is incorporated into the carboxylic acid product. Furthermore, the iron(II) complex cleaves an aliphatic C-C bond of 17-α-hydroxyprogesterone affording androstenedione and acetic acid. The O 2 -dependent aliphatic C-C bond cleavage of α-hydroxy ketones containing no α-C-H bond bears similarity to the lyase activity of the heme enzyme, cytochrome P450 17A1 (CYP17A1). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases. Part 3: Michael addition reactions and miscellaneous transformations.

PubMed

Aceña, José Luis; Sorochinsky, Alexander E; Soloshonok, Vadim

2014-09-01

The major goal of this review is a critical discussion of the literature data on asymmetric synthesis of α-amino acids via Michael addition reactions involving Ni(II)-complexes of amino acids. The material covered is divided into two conceptually different groups dealing with applications of: (a) Ni(II)-complexes of glycine as C-nucleophiles and (b) Ni(II)-complexes of dehydroalanine as Michael acceptors. The first group is significantly larger and consequently subdivided into four chapters based on the source of stereocontrolling element. Thus, a chiral auxiliary can be used as a part of nucleophilic glycine Ni(II) complex, Michael acceptor or both, leading to the conditions of matching vs. mismatching stereochemical preferences. The particular focus of the review is made on the practical aspects of the methodology under discussion and mechanistic considerations.

Photoluminescent silicon nanocrystals with chlorosilane surfaces - synthesis and reactivity

NASA Astrophysics Data System (ADS)

Höhlein, Ignaz M. D.; Kehrle, Julian; Purkait, Tapas K.; Veinot, Jonathan G. C.; Rieger, Bernhard

2014-12-01

We present a new efficient two-step method to covalently functionalize hydride terminated silicon nanocrystals with nucleophiles. First a reactive chlorosilane layer was formed via diazonium salt initiated hydrosilylation of chlorodimethyl(vinyl)silane which was then reacted with alcohols, silanols and organolithium reagents. With organolithium compounds a side reaction is observed in which a direct functionalization of the silicon surface takes place.We present a new efficient two-step method to covalently functionalize hydride terminated silicon nanocrystals with nucleophiles. First a reactive chlorosilane layer was formed via diazonium salt initiated hydrosilylation of chlorodimethyl(vinyl)silane which was then reacted with alcohols, silanols and organolithium reagents. With organolithium compounds a side reaction is observed in which a direct functionalization of the silicon surface takes place. Electronic supplementary information (ESI) available: Detailed experimental procedures and additional NMR, PL, EDX, DLS and TEM data. See DOI: 10.1039/C4NR05888G

Attempts to counteract phosgene-induced acute lung injury by instant high-dose aerosol exposure to hexamethylenetetramine, cysteine or glutathione.

PubMed

Pauluhn, Jürgen; Hai, Chun Xue

2011-01-01

Phosgene is an important high-production-volume intermediate with widespread industrial use. Consistent with other lung irritants causing ALI (acute lung injury), mode-of-action-based countermeasures remain rudimentary. This study was conducted to analyze whether extremely short high-level exposure to phosgene gas could be mitigated using three different inhaled nucleophiles administered by inhalation instantly after exposure to phosgene. Groups of young adult male Wistar rats were acutely exposed to carbonyl chloride (phosgene) using a directed-flow nose-only mode of exposure of 600 mg/m³ for 1.5 min (225 ppm × min). Immediately after exposure to phosgene gas the rats were similarly exposed to three strong nucleophiles with and without antioxidant properties for 5 or 15 min. The following nucleophiles were used: hexamethylenetetramine (HMT), l-cysteine (Cys), and l-glutathione (GSH). The concentration of the aerosol (mass median aerodynamic diameter 1.7-2 µm) was targeted to be in the range of 1 mg/L. Cys and GSH have antioxidant properties in addition. The calculated alveolar molar dosage of phosgene was 9 µmol/kg. At 15-min exposure duration, the respective inhaled dose of HMT, Csy, and GSH were 111, 103, and 46 µmol/kg, respectively. The alveolar dose of drugs was ~10-times lower. The efficacy of treatment was judged by protein concentrations in bronchoalveolar lavage fluid (BALF) collected 1 day post-exposure. In spite of using optimized aerosolization techniques, none of the nucleophiles chosen had any mitigating effect on BALF-protein extravasation. This finding appear to suggest that inhaled phosgene gas acylates instantly nucleophilic moieties at the site of initial deposition and that the resultant reaction products can not be reactivated even following instant inhalation treatment with competing nucleophilic agents. In spite of using maximal technically attainable concentrations, it appears to be experimentally challenging to deliver such nucleophiles to the lower respiratory tract at high dosages.

Mechanistic insights on the cycloisomerization of polyunsaturated precursors catalyzed by platinum and gold complexes.

PubMed

Soriano, Elena; Marco-Contelles, José

2009-08-18

Organometallic chemistry provides powerful tools for the stereocontrolled synthesis of heterocycles and carbocycles. The electrophilic transition metals Pt(II) and Au(I, III) are efficient catalysts in these transitions and promote a variety of organic transformations of unsaturated precursors. These reactions produce functionalized cyclic and acyclic scaffolds for the synthesis of natural and non-natural products efficiently, under mild conditions, and with excellent chemoselectivity. Because these transformations are strongly substrate-dependent, they are versatile and may yield diverse molecular scaffolds. Therefore, synthetic chemists need a mechanistic interpretation to optimize this reaction process and design a new generation of catalysts. However, so far, no intermediate species has been isolated or characterized, so the formulated mechanistic hypotheses have been primarily based on labeling studies or trapping reactions. Recently, theoretical DFT studies have become a useful tool in our research, giving us insights into the key intermediates and into a variety of plausible reaction pathways. In this Account, we present a comprehensive mechanistic overview of transformations promoted by Pt and Au in a non-nucleophilic medium based on quantum-mechanical studies. The calculations are consistent with the experimental observations and provide fundamental insights into the versatility of these reaction processes. The reactivity of these metals results from their peculiar Lewis acid properties: the alkynophilic character of these soft metals and the pi-acid activation of unsaturated groups promotes the intra- or intermolecular attack of a nucleophile. 1,n-Enynes (n = 3-8) are particularly important precursors, and their transformation may yield a variety of cycloadducts depending on the molecular structure. However, the calculations suggest that these different cyclizations would have closely related reaction mechanisms, and we propose a unified mechanistic picture. The intramolecular nucleophilic attack of the double bond on the activated alkyne takes place by an endo-dig or exo-dig pathway to afford a cyclopropyl-metallocarbenoid. Through divergent routes, the cyclopropyl intermediate formed by exo-cyclopropanation could yield the metathesis adduct or bicyclic compounds. The endo-cyclization may be followed by a [1,2]-migration of the propargyl moiety to the internal acetylenic position to afford bicyclic [n.1.0] derivatives. This reaction mechanism is applicable for functional groups ranging from H to carboxylate propargyl substituents (Rautenstrauch reaction). In intramolecular reactions in which a shorter enyne bears a propargyl ester or in intermolecular reactions of an ester with an alkene, the ester preferentially attacks the activated alkyne because of enthalpic (ring strain) and entropic effects. Our calculations can predict the correct stereochemical outcome, which may aid the rational design of further stereoselective syntheses. The alkynes activated by electrophilic species can also react with other nucleophiles, such as aromatic rings. The calculations account for the high endo-selectivity observed and suggest that this transformation takes place through a Friedel-Crafts-type alkenylation mechanism, where the endo-dig cyclization promoted by PtCl(2) may involve a cyclopropylmetallacarbene as intermediate before the formation of the expected Wheland-type intermediate. These comparisons of the computational approach with experiment demonstrate the value of theory in the development of a solid mechanistic understanding of these reaction processes.

Changing the chemical and physical properties of high valent heterobimetallic bis-(μ-oxido) Cu-Ni complexes by ligand effects.

PubMed

Kafentzi, Maria-Chrysanthi; Orio, Maylis; Réglier, Marius; Yao, Shenglai; Kuhlmann, Uwe; Hildebrandt, Peter; Driess, Matthias; Simaan, A Jalila; Ray, Kallol

2016-10-12

Two new heterobimetallic [LNiO 2 Cu(RPY2)] + (RPY2 = N-substituted bis 2-pyridyl(ethylamine) ligands with R = indane, 3a or R = Me, 3b) complexes have been spectroscopically trapped at low temperatures. They were prepared by reacting the mononuclear side-on LNi II superoxo precursor bearing a β-diketiminate ligand (L = [HC-(CMeNC 6 H 3 (iPr) 2 ) 2 ]) with the Cu(i) complexes. In contrast to the oxo groups in known high-valent [M 2 (μ-O) 2 ] n+ (M = Fe, Co, Ni, Cu) cores that display electrophilic reactivities, 3a and 3b display rather nucleophilic oxo cores active in aldehyde deformylation reactions. However, the spectroscopic and reactivity properties of 3a/3b are found to be distinct relative to that of the previously reported [LNiO 2 Cu(MeAN)] + complex containing a more basic (nucleophilic) N,N,N',N',N'-pentamethyl-dipropylenetriamine (MeAN) ligand at the copper centre. The geometry and electronic properties of the copper ligands affect the electron density of the oxygen atoms of the heterodinuclear {Ni(μ-O) 2 } core and 3a/3b undergo slower nucleophilic and faster electrophilic reactions than the previously reported [LNiO 2 Cu(MeAN)] + intermediate. The present study therefore demonstrates the tuning of the electrophilicity/nucleophilicity of the oxygen atoms of the heterobimetallic [Ni(μ-O) 2 Cu] 2+ cores by controlling the electron donation from the ancillary ligands, and underlines the significance of subtle electronic changes in the physical and chemical properties of the biologically relevant heterobimetallic metal-dioxygen intermediates.

Regiospecific attack of nitrogen and sulfur nucleophiles on quinones derived from poison oak/ivy catechols (urushiols) and analogues as models for urushiol-protein conjugate formation.

PubMed

Liberato, D J; Byers, V S; Dennick, R G; Castagnoli, N

1981-01-01

Attempts to characterize potential biologically important covalent interactions between electrophilic quinones derived from catechols present in poison oak/ivy (urushiol) and biomacromolecules have led to the analysis of model reactions involving sulfur and amino nucleophiles with 3-heptadecylbenzoquinone. Characterization of the reaction products indicates that this quinone undergoes regiospecific attack by (S)-N-acetylcysteine at C-6 and by 1-aminopentane at C-5. The red solid obtained with 1-aminopentane proved to be 3-heptadecyl-5-(pentylamino)-1,2-benzoquinone. Analogous aminobenzoquinones were obtained with the quinones derived from the 4- and 6-methyl analogues of 3-pentadecylcatechol. All three adducts absorbed visible light at different wavelengths. When the starting catechols were incubated with human serum albumin almost identical chromophores were formed. These results establish that cathechols responsible for the production of the poison oak/ivy contact dermatitis in humans undergo a sequence of reactions in the presence of human serum albumin that lead to covalent attachment of the catechols to the protein via carbon-nitrogen bonds. Estimations of the extent of this binding indicate that, at least with human serum albumin, the reaction is quantitative.

Surface-active ionic liquids in micellar catalysis: impact of anion selection on reaction rates in nucleophilic substitutions† †Electronic supplementary information (ESI) available: Formulae for calculating aggregation parameters and fitting of kinetic constants and copies of NMR spectra. See DOI: 10.1039/c6cp00493h Click here for additional data file.

PubMed Central

Cognigni, Alice; Gaertner, Peter; Zirbs, Ronald; Peterlik, Herwig; Prochazka, Katharina; Schröder, Christian

2016-01-01

A series of surface-active ionic liquids based on the 1-dodecyl-3-methylimidazolium cation and different anions such as halides and alkylsulfates was synthesized. The aggregation behavior of these ionic liquids in water was characterized by surface tension, conductivity measurements and UV-Vis spectroscopy in order to determine the critical micelle concentration (CMC) and to provide aggregation parameters. The determination of surface activity and aggregation properties of amphiphilic ionic liquids was accompanied by SAXS studies on selected surface-active ionic liquids. The application of these surface-active ionic liquids with different anions was tested in nucleophilic substitution reactions for the degradation of organophosphorus compounds. Kinetic studies via UV-Vis spectrophotometry showed a strong acceleration of the reaction in the micellar system compared to pure water. In addition, an influence of the anion was observed, resulting in a correlation between the anion binding to the micelle and the reaction rate constants, indicating that the careful choice of the surface-active ionic liquid can considerably affect the outcome of reactions. PMID:27121134

Rates of proton transfer to Fe-S-based clusters: comparison of clusters containing {MFe(mu(2)-S)(2)}n+ and {MFe(3)(mu(3)-S)(4)}n+ (M = Fe, Mo, or W) cores.

PubMed

Bates, Katie; Garrett, Brendan; Henderson, Richard A

2007-12-24

The rates of proton transfer from [pyrH]+ (pyr = pyrrolidine) to the binuclear complexes [Fe2S2Cl4]2- and [S2MS2FeCl2]2- (M = Mo or W) are reported. The reactions were studied using stopped-flow spectrophotometry, and the rate constants for proton transfer were determined from analysis of the kinetics of the substitution reactions of these clusters with the nucleophiles Br- or PhS- in the presence of [pyrH]+. In general, Br- is a poor nucleophile for these clusters, and proton transfer occurs before Br- binds, allowing direct measure of the rate of proton transfer from [pyrH]+ to the cluster. In contrast, PhS- is a better nucleophile, and a pathway in which PhS- binds preferentially to the cluster prior to proton transfer from [pyrH]+ usually operates. For the reaction of [Fe2S2Cl4]2- with PhS- in the presence of [pyrH]+ both pathways are observed. Comparison of the results presented in this paper with analogous studies reported earlier on cuboidal Fe-S-based clusters allows discussion of the factors which affect the rates of proton transfer in synthetic clusters including the nuclearity of the cluster core, the metal composition, and the nature of the terminal ligands. The possible relevance of these findings to the protonation sites of natural Fe-S-based clusters, including FeMo-cofactor from nitrogenase, are presented.

Characterization of solution-phase and gas-phase reactions in on-line electrochemistry-thermospray tandem mass spectrometry.

PubMed

Volk, K J; Yost, R A; Brajter-Toth, A

1989-07-14

Electrochemistry was used on-line with high-performance liquid chromatography-thermospray tandem mass spectrometry to provide insight into the solution-phase decomposition reactions of electrochemically generated oxidation products. Products formed during electrooxidation were monitored as the electrode potential was varied. The solution reactions which follow the initial electron transfer at the electrode are affected by the vaporizer tip temperature of the thermospray probe and the composition of the thermospray buffer. Either hydrolysis or ammonolysis reactions of the initial electrochemical oxidation products can occur with pH 7 ammonium acetate buffer. Both the electrochemically generated and the synthesized disulfide of 6-thiopurine decompose under thermospray conditions to produce 6-thiopurine and purine-6-sulfinate. Solution-phase studies indicate that nucleophilic and electrophilic substitution reactions with purine-6-sulfinate result in the formation of purine, adenine, and hypoxanthine. Products were identified and characterized by tandem mass spectrometry. This work shows the first example of high-performance liquid chromatography used on-line with electrochemistry to separate stable oxidation products prior to analysis by thermospray tandem mass spectrometry. In addition, solution-phase and gas-phase studies with methylamine show that the site of the nucleophilic and electrophilic reactions is probably inside the thermospray probe. Most importantly, these results also show that the on-line combination of electrochemistry with thermospray tandem mass spectrometry provides valuable information about redox and associated chemical reactions of biological molecules such as the structures of intermediates or products as well as providing insight into reaction pathways.

Electrochemical synthesis of azanucleoside derivatives using a lithium perchlorate-nitromethane system.

PubMed

Kim, Shokaku; Shoji, Takao; Kitano, Yoshikazu; Chiba, Kazuhiro

2013-07-25

We have developed a highly efficient synthetic method for azanucleosides using a lithium perchlorate-nitromethane reaction medium, allowing direct and exclusive installation of various nucleophiles, including protected nucleobases into prolinol derivatives at the preferred 5-position.

Nucleophilic Chiral Phosphines: Powerful and Versatile Catalysts for Asymmetric Annulations

PubMed Central

Xiao, Yumei; Guo, Hongchao; Kwon, Ohyun

2016-01-01

Recent advances in chiral-phosphine-catalyzed asymmetric annulation reactions; including annulations of allenes, alkynes, Morita–Baylis–Hillman (MBH) carbonates, and ketenes; and their applications in the synthesis of bioactive molecules and natural products are reviewed. PMID:28077882

A new family of nucleophiles for photoinduced, copper-catalyzed cross-couplings via single-electron transfer: reactions of thiols with aryl halides under mild conditions (O °C).

PubMed

Uyeda, Christopher; Tan, Yichen; Fu, Gregory C; Peters, Jonas C

2013-06-26

Building on the known photophysical properties of well-defined copper-carbazolide complexes, we have recently described photoinduced, copper-catalyzed N-arylations and N-alkylations of carbazoles. Until now, there have been no examples of the use of other families of heteroatom nucleophiles in such photoinduced processes. Herein, we report a versatile photoinduced, copper-catalyzed method for coupling aryl thiols with aryl halides, wherein a single set of reaction conditions, using inexpensive CuI as a precatalyst without the need for an added ligand, is effective for a wide range of coupling partners. As far as we are aware, copper-catalyzed C-S cross-couplings at 0 °C have not previously been achieved, which renders our observation of efficient reaction of an unactivated aryl iodide at -40 °C especially striking. Mechanistic investigations are consistent with these photoinduced C-S cross-couplings following a SET/radical pathway for C-X bond cleavage (via a Cu(I)-thiolate), which contrasts with nonphotoinduced, copper-catalyzed processes wherein a concerted mechanism is believed to occur.

The Michael Reaction

NASA Astrophysics Data System (ADS)

Poon, Thomas; Mundy, Bradford P.; Shattuck, Thomas W.

2002-02-01

A brief account of the Michael reaction is provided, illustrating its versatility as a topic in undergraduate chemistry courses. Included is a short biography of the reaction's namesake, examples of its use in organic synthesis, and its unique role in the defense mechanism of the bacterium Micromonospora echinospora. A computational rationale for the selectivity of 1,4 versus 1,2 addition of nucleophiles to a,b-unsaturated carbonyls is discussed and links to animations suitable for an introductory organic chemistry course are provided.

Microdroplets Accelerate Ring Opening of Epoxides

NASA Astrophysics Data System (ADS)

Lai, Yin-Hung; Sathyamoorthi, Shyam; Bain, Ryan M.; Zare, Richard N.

2018-05-01

The nucleophilic opening of an epoxide is a classic organic reaction that has widespread utility in both academic and industrial applications. We have studied the reaction of limonene oxide with morpholine to form 1-methyl-2-morpholino-4-(prop-1-en-2-yl) cyclohexan-1-ol in bulk solution and in electrosprayed microdroplets with a 1:1 v/ v water/methanol solvent system. We find that even after 90 min at room temperature, there is no product detected by nuclear magnetic resonance spectroscopy in bulk solution whereas in room-temperature microdroplets (2-3 μm in diameter), the yield is already 0.5% in a flight time of 1 ms as observed by mass spectrometry. This constitutes a rate acceleration of 105 in the microdroplet environment, if we assume that as much as 5% of product is formed in bulk after 90 min of reaction time. We examine how the reaction rate depends on droplet size, solvent composition, sheath gas pressure, and applied voltage. These factors profoundly influence the extent of reaction. This dramatic acceleration is not limited to just one system. We have also found that the nucleophilic opening of cis-stilbene oxide by morpholine is similarly accelerated. Such large acceleration factors in reaction rates suggest the use of microdroplets for ring opening of epoxides in other systems, which may have practical significance if such a procedure could be scaled. [Figure not available: see fulltext.

Benzoylation of Ergosterol through Nucleophilic Acyl Substitution and Subsequent Formation of Ergosterol Benzoate Endoperoxide by Reaction with Singlet Oxygen Generated by Photosensitization

ERIC Educational Resources Information Center

Roslaniec, Mary C.; Sanford, Elizabeth M.

2011-01-01

Reactive oxygen species such as singlet oxygen have been a major focus of research in medicine. The effect of singlet oxygen on sterols within biological membranes is becoming increasingly more important. Ergosterol, a vitamin D precursor, is one such sterol. The benzoylation of ergosterol and subsequent reaction with singlet oxygen to form an…

Ion chemistry of phosphorus in hydrocarbon flames : Part 1. electron scavenging by negative ion formation

NASA Astrophysics Data System (ADS)

Goodings, John M.; Hassanali, Carl S.

1990-12-01

Premixed methane--oxygen flames at atmospheric pressure of both fuel-rich (FR) and fuel-lean (FL; i.e. oxygen-rich) composition were doped with small amounts ( < 0.1 mol %) of volatile phosphorus alkyl triesters. It was demonstrated that these organo phosphorus compounds lead to efficient scavenging of the free electrons, normally present in the burnt gas of hydrocarbon flames, by negative ion formation. The anions produced by chemical ionization reactions were observed by sampling the flame gas through a nozzle into a mass spectrometer. Under both FR and FL conditions, the mass spectrum of phosphorus anions was dominated by PO-3, with a lesser contribution from PO-2. Also, H2PO-4 and PO- were observed below 100 u, as well as HPO-4 and PO-4 in the FL flame, and H2CPO-2 in the FR case. Above 100 u, the identity of the additive survivedin the FR flame to give anions of the type (RO)xPOy(OH)-z, where R is the alkyl group. However, these were replaced in the FL flame by anions of the type PO-n (n = 5-8) below 160 u. The formation chemistry of this considerable variety of phosphorus anions is discussed in detail, involving mainly three-body association, nucleophilic displacement (SN2) and proton abstraction reactions.

SEDIMENT-ASSOCIATED REACTIONS OF AROMATIC AMINES. 2. QSAR DEVELOPMENT

EPA Science Inventory

The fate of aromatic amines in soils and sediments is dominated by irreversible binding through nucleophilic addition and oxidative radical coupling. Despite the common occurrence of the aromatic amine functional group in organic chemicals, the molecular properties useful for pr...

Catalytic Nucleophilic Glyoxylation of Aldehydes

PubMed Central

Steward, Kimberly M.; Johnson, Jeffrey S.

2010-01-01

β-Silyloxy-α-ketoesters are prepared through a cyanide-catalyzed benzoin-type reaction with silyl glyoxylates and aldehydes. The products undergo a dynamic kinetic resolution to provide enantioenriched orthogonally protected alcohols and can be converted to the corresponding β-silyloxy-α-aminoesters. PMID:20481613

The Gabriel Synthesis of Benzylamine

ERIC Educational Resources Information Center

Nigh, W. G.

1975-01-01

Describes an undergraduate organic chemistry laboratory experiment which utilizes the Gabriel Synthesis to demonstrate the acidity of imides and to provide an example of nucleophilic substitution reactions. The experiment also demonstrates the laboratory techniques involved in simple and steam distillation, filtration, extraction, and…

A general ligand design for gold catalysis allowing ligand-directed anti-nucleophilic attack of alkynes.

PubMed

Wang, Yanzhao; Wang, Zhixun; Li, Yuxue; Wu, Gongde; Cao, Zheng; Zhang, Liming

2014-04-07

Most homogenous gold catalyses demand ≥ 0.5 mol% catalyst loading. Owing to the high cost of gold, these reactions are unlikely to be applicable in medium- or large-scale applications. Here we disclose a novel ligand design based on the privileged (1,1'-biphenyl)-2-ylphosphine framework that offers a potentially general approach to dramatically lowering catalyst loading. In this design, an amide group at the 3'-position of the ligand framework directs and promotes nucleophilic attack at the ligand gold complex-activated alkyne, which is unprecedented in homogenous gold catalysis considering the spatial challenge of using ligand to reach anti-approaching nucleophile in a linear P-Au-alkyne centroid structure. With such a ligand, the gold(I) complex becomes highly efficient in catalysing acid addition to alkynes, with a turnover number up to 99,000. Density functional theory calculations support the role of the amide moiety in directing the attack of carboxylic acid via hydrogen bonding.

A General Ligand Design for Gold Catalysis allowing Ligand-Directed Anti Nucleophilic Attack of Alkynes

PubMed Central

Wang, Yanzhao; Wang, Zhixun; Li, Yuxue; Wu, Gongde; Cao, Zheng; Zhang, Liming

2014-01-01

Most homogenous gold catalyses demand ≥0.5 mol % catalyst loading. Due to the high cost of gold, these reactions are unlikely to be applicable in medium or large scale applications. Here we disclose a novel ligand design based on the privileged biphenyl-2-phosphine framework that offers a potentially general approach to dramatically lowering catalyst loading. In this design, an amide group at the 3’ position of the ligand framework directs and promotes nucleophilic attack at the ligand gold complex-activated alkyne, which is unprecedented in homogeneous gold catalysis considering the spatial challenge of using ligand to reach antiapproaching nucleophile in a linear P-Au-alkyne centroid structure. With such a ligand, the gold(I) complex becomes highly efficient in catalyzing acid addition to alkynes, with a turnover number up to 99,000. Density functional theory calculations support the role of the amide moiety in directing the attack of carboxylic acid via hydrogen bonding. PMID:24704803

Linear free energy relationship and deuterium kinetic isotope effect observed on phospho and thiophosphoryl transfer reactions in some organophosphorous compounds

NASA Astrophysics Data System (ADS)

Lumbiny, B. J.; Hui, Z.; Islam, M. A.; Quader, M. A.; Rahman, M.

2014-04-01

Tetracoordinated organophosphorous compounds were synthesized, characterized and nucleophilic substitution reaction were investigated by varying substituents around phosphorous centre or in nucleophile considering its utility in biological and environmental system. The reactivity is expressed in terms of second-order rate constant, k2 and measured conductometrically. Linear Free Energy Relationship (LFER) tools mainly Hammett (ρ), Brönsted (β) LFER coefficients and deuterium kinetic isotope effects (KIEs) being determined for the pyridinolysis of 4 - chlorophenyl 4 - methoxy phenyl chlorophosphate, 1 in acetonitrile at 5.0 °C. The experimental data's were compared with those of structurally similar organophosphorous compounds reported earlier in quest for the mechanistic information. Nice linear correlation being found for Hammett (logk2 vs σx), having negative value of the ρX = -5.85 and Brönsted (logk2 vs pKa(x)) plots having large positive value for βX = 1.18 for 1 can be interpreted as SN2 process with greater extent of bond formation in transition state (TS) of 1. The observed kH/kD values of 1 is 1.00 ± 0.05 and net KIE, 1.32 suggests the primary KIE and indicates frontside nucleophilic attack through the partial deprotonation of pyridine occurs by the hydrogen bonding in the rate-determining step.

A Novel Computational Method to Reduce Leaky Reaction in DNA Strand Displacement.

PubMed

Li, Xin; Wang, Xun; Song, Tao; Lu, Wei; Chen, Zhihua; Shi, Xiaolong

2015-01-01

DNA strand displacement technique is widely used in DNA programming, DNA biosensors, and gene analysis. In DNA strand displacement, leaky reactions can cause DNA signals decay and detecting DNA signals fails. The mostly used method to avoid leakage is cleaning up after upstream leaky reactions, and it remains a challenge to develop reliable DNA strand displacement technique with low leakage. In this work, we address the challenge by experimentally evaluating the basic factors, including reaction time, ratio of reactants, and ion concentration to the leakage in DNA strand displacement. Specifically, fluorescent probes and a hairpin structure reporting DNA strand are designed to detect the output of DNA strand displacement, and thus can evaluate the leakage of DNA strand displacement reactions with different reaction time, ratios of reactants, and ion concentrations. From the obtained data, mathematical models for evaluating leakage are achieved by curve derivation. As a result, it is obtained that long time incubation, high concentration of fuel strand, and inappropriate amount of ion concentration can weaken leaky reactions. This contributes to a method to set proper reaction conditions to reduce leakage in DNA strand displacement.

Variational Flooding Study of a SN2 Reaction.

PubMed

Piccini, GiovanniMaria; McCarty, James J; Valsson, Omar; Parrinello, Michele

2017-02-02

We have studied the reaction dynamics of a prototypical organic reaction using a variationally optimized truncated bias to accelerate transitions between educt and product reactant states. The asymmetric S N 2 nucleophilic substitution reaction of fluoromethane and chloromethane CH 3 F + Cl - ⇌ CH 3 Cl + F - is considered, and many independent biased molecular dynamics simulations have been performed at 600, 900, and 1200 K, collecting several hundred transitions at each temperature. The transition times and relative rate constants have been obtained for both reaction directions. The activation energies extracted from an Arrhenius plot compare well with standard static calculations.

Metal Vinylidenes as Catalytic Species in Organic Reactions

PubMed Central

McClory, Andrew

2008-01-01

Organic vinylidene species have found limited use in organic synthesis due to their inaccessibility. In contrast, metal vinylidenes are much more stable, and may be readily accessed through transition metal activation of terminal alkynes. These electrophilic species may be trapped by a number of nucleophiles. Additionally, metal vinylidenes can participate in pericyclic reactions and processes involving migration of a metal ligand to the vinylidene species. This review addresses the reactions and applications of metal vinylidenes in organic synthesis. PMID:18172846

Copper-catalyzed domino reactions for the synthesis of cyclic compounds.

PubMed

Liao, Qian; Yang, Xianghua; Xi, Chanjuan

2014-09-19

Copper-catalyzed domino reactions are one of the most useful strategies for the construction of various cyclic compounds. In this Synopsis, we mainly focus on the latest advances in copper-catalyzed cross-coupling or addition-initiated domino reactions in the synthesis of cyclic compounds, including double alkenylation of N- or S-nucleophiles, alkenylation or alkynlation followed by cyclization of amides or amines, addition and cyclization of heteroallenes affording heterocycles, and coupling and cyclization of 1,3-dicarbonyl compounds toward heterocycles.

α-Ketophosphonic Acid Esters — Synthesis, Structure, and Reactions

NASA Astrophysics Data System (ADS)

Zhdanov, Yu A.; Uzlova, L. A.; Glebova, Z. I.

1980-09-01

Studies on the synthesis and properties of α-ketophosphonic acid esters (KPE) — a class of highly reactive organophosphorus compounds — are surveyed. Data are presented concerning instances of the anomalous course of the process in the synthesis of KPE by the Arbuzov reaction. The reactions of KPE with nucleophiles, including those which lead to the rupture of the phosphorus-carbon bond, are examined in detail. The problems of the stereochemistry of KPE are dealt with briefly. The bibliography includes 162 references.

N-Triflylthiophosphoramide Catalyzed Enantioselective Mukaiyama Aldol Reaction of Aldehydes with Silyl Enol Ethers of Ketones

PubMed Central

Cheon, Cheol Hong; Yamamoto, Hisashi

2010-01-01

The first Brønsted acid catalyzed asymmetric Mukaiyama aldol reaction of aldehydes using silyl enol ethers of ketones as nucleophiles has been reported. A variety of aldehydes and silyl enol ethers of ketones afforded the aldol products in excellent yields and good to excellent enantioselectivities. Mechanistic studies revealed that the actual catalyst may be changed from the silylated Brønsted acid to Brønsted acid itself depending on the reaction temperature. PMID:20465277

N-triflylthiophosphoramide catalyzed enantioselective Mukaiyama aldol reaction of aldehydes with silyl enol ethers of ketones.

PubMed

Cheon, Cheol Hong; Yamamoto, Hisashi

2010-06-04

The first Brønsted acid catalyzed asymmetric Mukaiyama aldol reaction of aldehydes using silyl enol ethers of ketones as nucleophiles has been reported. A variety of aldehydes and silyl enol ethers of ketones afforded the aldol products in excellent yields and good to excellent enantioselectivities. Mechanistic studies revealed that the actual catalyst may be changed from the silylated Brønsted acid to the Brønsted acid itself depending on the reaction temperature.

Origins of the different metal preferences of Escherichia coli peptide deformylase and Bacillus thermoproteolyticus thermolysin: a comparative quantum mechanical/molecular mechanical study.

PubMed

Dong, Minghui; Liu, Haiyan

2008-08-21

The Escherichia coli peptide deformylase (PDF) and Bacillus thermoproteolyticus thermolysin (TLN) are two representative metal-requiring peptidases having remarkably similar active centers but distinctively different metal preferences. Zinc is a competent catalytic cofactor for TLN but not for PDF. Reaction pathways and the associated energetics for both enzymes were determined using combined semiempirical and ab initio quantum mechanical/molecular mechanical modeling, without presuming reaction coordinates. The results confirmed that both enzymes catalyze via the same chemical steps, and reproduced their different preferences for zinc or iron as competent cofactors. Further analyses indicated that different feasibility of the nucleophilic attack step leads to different metal preferences of the two enzymes. In TLN, the substrate is strongly activated and can serve as the fifth coordination ligand of zinc prior to the chemical steps. In PDF, the substrate carbonyl is activated by the chemical step itself, and becomes the fifth coordination partner of zinc only in a later stage of the nucleophilic attack. These leads to a much more difficult nucleophilic attack in PDF than in TLN. Different from some earlier suggestions, zinc has no difficulty in accepting an activated substrate as the fifth ligand to switch from tetra- to penta-coordination in either PDF or TLN. When iron replaces zinc, its stronger interaction with the hydroxide ligand may lead to higher activation barrier in TLN. In PDF, the stronger interactions of iron with ligands allow iron-substrate coordination to take place either before or at a very early stage of the chemical step, leading to effective catalysis. Our calculations also show combined semiempirical and ab initio quantum mechanical modeling can be efficient approaches to explore complicated reaction pathways in enzyme systems.

Bacterial dehalogenases: biochemistry, genetics, and biotechnological applications.

PubMed Central

Fetzner, S; Lingens, F

1994-01-01

This review is a survey of bacterial dehalogenases that catalyze the cleavage of halogen substituents from haloaromatics, haloalkanes, haloalcohols, and haloalkanoic acids. Concerning the enzymatic cleavage of the carbon-halogen bond, seven mechanisms of dehalogenation are known, namely, reductive, oxygenolytic, hydrolytic, and thiolytic dehalogenation; intramolecular nucleophilic displacement; dehydrohalogenation; and hydration. Spontaneous dehalogenation reactions may occur as a result of chemical decomposition of unstable primary products of an unassociated enzyme reaction, and fortuitous dehalogenation can result from the action of broad-specificity enzymes converting halogenated analogs of their natural substrate. Reductive dehalogenation either is catalyzed by a specific dehalogenase or may be mediated by free or enzyme-bound transition metal cofactors (porphyrins, corrins). Desulfomonile tiedjei DCB-1 couples energy conservation to a reductive dechlorination reaction. The biochemistry and genetics of oxygenolytic and hydrolytic haloaromatic dehalogenases are discussed. Concerning the haloalkanes, oxygenases, glutathione S-transferases, halidohydrolases, and dehydrohalogenases are involved in the dehalogenation of different haloalkane compounds. The epoxide-forming halohydrin hydrogen halide lyases form a distinct class of dehalogenases. The dehalogenation of alpha-halosubstituted alkanoic acids is catalyzed by halidohydrolases, which, according to their substrate and inhibitor specificity and mode of product formation, are placed into distinct mechanistic groups. beta-Halosubstituted alkanoic acids are dehalogenated by halidohydrolases acting on the coenzyme A ester of the beta-haloalkanoic acid. Microbial systems offer a versatile potential for biotechnological applications. Because of their enantiomer selectivity, some dehalogenases are used as industrial biocatalysts for the synthesis of chiral compounds. The application of dehalogenases or bacterial strains in environmental protection technologies is discussed in detail. PMID:7854251

Chlorotrimethylsilane activation of acylcyanamides for the synthesis of mono-N-acylguanidines

PubMed Central

Haussener, Travis J.; Mack, James B. C.

2011-01-01

A simple and efficient one-pot method for the synthesis of mono-protected guanidines is presented. Treatment of an acylcyanamide with chlorotrimethylsilane generates a reactive N-silylcarbodiimide capable of guanylating a variety of amines. Typically the reaction is complete in 15 min for primary and secondary aliphatic amines at rt. Hindered amines and anilines are also competent nucleophiles but require extended reaction times. PMID:21732649

A beta-keto ester as a novel, efficient, and versatile ligand for copper(I)-catalyzed C-N, C-O, and C-S coupling reactions.

PubMed

Lv, Xin; Bao, Weiliang

2007-05-11

Employing ethyl 2-oxocyclohexanecarboxylate as a novel, efficient, and versatile ligand, the copper-catalyzed coupling reactions of various N/O/S nucleophilic reagents with aryl halides could be successfully carried out under mild conditions. A variety of products including N-arylamides, N-arylimidazoles, aryl ethers, and aryl thioethers were synthesized in good to excellent yields.

Enhancing the efficiency of sortase-mediated ligations through nickel-peptide complex formation.

PubMed

David Row, R; Roark, Travis J; Philip, Marina C; Perkins, Lorena L; Antos, John M

2015-08-14

A modified sortase A recognition motif containing a masked Ni(2+)-binding peptide was employed to boost the efficiency of sortase-catalyzed ligation reactions. Deactivation of the Ni(2+)-binding peptide using a Ni(2+) additive improved reaction performance at low to equimolar ratios of the glycine amine nucleophile and sortase substrate. The success of this approach was demonstrated with both peptide and protein substrates.

Oxygen anion (O- ) and hydroxide anion (HO- ) reactivity with a series of old and new refrigerants.

PubMed

Le Vot, Clotilde; Lemaire, Joël; Pernot, Pascal; Heninger, Michel; Mestdagh, Hélène; Louarn, Essyllt

2018-04-01

The reactivity of a series of commonly used halogenated compounds (trihalomethanes, chlorofluorocarbon, hydrochlorofluorocarbon, fluorocarbons, and hydrofluoroolefin) with hydroxide and oxygen anion is studied in a compact Fourier transform ion cyclotron resonance. O - is formed by dissociative electron attachment to N 2 O and HO - by a further ion-molecule reaction with ammonia. Kinetic experiments are performed by increasing duration of introduction of the studied molecule at a constant pressure. Hydroxide anion reactions mainly proceed by proton transfer for all the acidic compounds. However, nucleophilic substitution is observed for chlorinated and brominated compounds. For fluorinated compounds, a specific elimination of a neutral fluorinated alkene is observed in our results in parallel with the proton transfer reaction. Oxygen anion reacts rapidly and extensively with all compounds. Main reaction channels result from nucleophilic substitution, proton transfer, and formal H 2 + transfer. We highlight the importance of transfer processes (atom or ion) in the intermediate ion-neutral complex, explaining part of the observed reactivity and formed ions. In this paper, we present the first reactivity study of anions with HFO 1234yf. Finally, the potential of O - and HO - as chemical ionization reagents for trace analysis is discussed. Copyright © 2017 John Wiley & Sons, Ltd.

Glycoconjugate Oxime Formation Catalyzed at Neutral pH: Mechanistic Insights and Applications of 1,4-Diaminobenzene as a Superior Catalyst for Complex Carbohydrates.

PubMed

Østergaard, Mads; Christensen, Niels Johan; Hjuler, Christian T; Jensen, Knud J; Thygesen, Mikkel B

2018-04-18

The reaction of unprotected carbohydrates with aminooxy reagents to provide oximes is a key method for the construction of glycoconjugates. Aniline and derivatives serve as organocatalysts for the formation of oximes from simple aldehydes, and we have previously reported that aniline also catalyzes the formation of oximes from the more complex aldehydes, carbohydrates. Here, we present a comprehensive study of the effect of aniline analogues on the formation of carbohydrate oximes and related glycoconjugates depending on organocatalyst structure, pH, nucleophile, and carbohydrate, covering more than 150 different reaction conditions. The observed superiority of the 1,4-diaminobenzene (PDA) catalyst at neutral pH is rationalized by NMR analyses and DFT studies of reaction intermediates. Carbohydrate oxime formation at pH 7 is demonstrated by the formation of a bioactive glycoconjugate from a labile, decorated octasaccharide originating from exopolysaccharides of the soil bacterium Mesorhizobium loti. This study of glycoconjugate formation includes the first direct comparison of aniline-catalyzed reaction rates and equilibrium constants for different classes of nucleophiles, including primary oxyamines, secondary N-alkyl oxyamines, as well as aryl and arylsulfonyl hydrazides. We identified 1,4-diaminobenzene as a superior catalyst for the construction of oxime-linked glycoconjugates under mild conditions.

Kinetic Control in the Cleavage of Unsymmetrical Disilanes.

PubMed

Hevesi, Làszlò; Dehon, Michael; Crutzen, Raphael; Lazarescu-Grigore, Adriana

1997-04-04

A series of 12 phenyl-substituted arylpentamethyldisilanes 1a-l have been synthesized in order to examine the regioselectivity of their nucleophilic Si,Si bond cleavage reactions under Still's conditions (MeLi/HMPA/0 degrees C). It has been found that the sensitivity of these reactions to the electronic effects of the substituents in the phenyl ring could be described by the Hammett-type equation log(k(A)/k(B)) = 0.4334 + 2.421(Sigmasigma); (correlation coefficient R = 0.983). The k(A)/k(B) ratio represents the relative rate of attack at silicon atom A (linked to the aryl ring) or at silicon atom B (away from the aryl ring) of the unsymmetrical disilanes. Thus, the present investigation shows that the earlier belief according to which the nucleophilic cleavage of unsymmetrical disilanes always produces the more stable silyl anionic species (thermodynamic control) should be abandoned, or at least seriously amended: kinetic factors appear to exert a primary influence on the regioselectivity of such reactions. Since the two major kinetic factors (i.e., electrophilic character of and steric hindrance at a given silicon atom) have opposite effects on the orientation of the reaction, it may happen that kinetic and thermodynamic control lead to the same result. For some of the unsymmetrical disilanes studied, the major reaction path was not the Si,Si bond cleavage; instead, Si-aryl bond breaking occurred, producing the corresponding aryl anions.

Covalent binding of aniline to humic substances. 1. Kinetic studies

USGS Publications Warehouse

Weber, E.J.; Spidle, D.L.; Thorn, K.A.

1996-01-01

The reaction kinetics for the covalent binding of aniline with reconstituted IHSS humic and fulvic acids, unfractionated DOM isolated from Suwannee River water, and whole samples of Suwannee River water have been investigated. The reaction kinetics in each of these systems can be adequately described by a simple second-order rate expression. The effect of varying the initial concentration of aniline on reaction kinetics suggested that approximately 10% of the covalent binding sites associated with Suwannee River fulvic acid are highly reactive sites that are quickly saturated. Based on the kinetic parameters determined for the binding of aniline with the Suwannee River fulvic and humic acid isolates, it was estimated that 50% of the aniline concentration decrease in a Suwannee River water sample could be attributed to reaction with the fulvic and humic acid components of the whole water sample. Studies with Suwannee River fulvic acid demonstrated that the rate of binding decreased with decreasing pH, which parallels the decrease in the effective concentration of the neutral form, or reactive nucleophilic species of aniline. The covalent binding of aniline with Suwannee River fulvic acid was inhibited by prior treatment of the fulvic acid with hydrogen sulfide, sodium borohydride, or hydroxylamine. These observations are consistent with a reaction pathway involving nucleophilic addition of aniline to carbonyl moieties present in the fulvic acid.

Hydrolysis and nucleophilic substitution of model and ultimate carcinogens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Helmick, J.S.

1992-01-01

The hydrolysis reaction of the Model Carcinogen O-pivaloyl-N-(4-chlorophenyl)hydroxylamine in aqueous buffer (pH 7.0-10.0) proceeds by was of a nitrenium ion intermediate. The products formed from this process are predominately 2,4-dichloroaniline, and 2-hydroxy-4-chloro-pivalanilide. At pH 10-13 the rate becomes dependent upon hydroxide. The product that is formed is 4-chlorophenylhydroxylamine. 4-Chlorophenyl-hydroxylamine is formed by basic ester hydrolysis determined by an [sup 18]O GC-MS experiment. The reaction of O-pivaloyl-N-(4-chlorophenyl)hydroxylamine in an aqueous diethylamine (pH 11.3) buffer gave 4-chlorophenyl-N,N-diethylhydrazine as the substitution product in a 16% yield. The reaction of O-pivaloyl-N-(4-methylphenyl)hydroxylamine with diethylamine gave a 1% yield of the hydrazine product. The reaction ofmore » N,N-dimethylanline and aniline with ring-substituted O-pivaloyl-N-arylhydroxylamines in MeOH generates products of nucleophilic attack on the nitrogen of the hydroxylamine derivative. The hydrolysis of the ultimate carcinogen N-(sulfonatooxy)-N-4-aminobiphenyl proceeds by two consecutive pseudo-first-order processes and generates predominately a product of nucleophilic attack by chloride ion at the ortho position of the aromatic ring. A labile intermediate identified as N-acetypl-4-hydroxy-4-phenyl-2,5-cyclohexadienone imine has been detected by NMR. This intermediate rearranges to form 4-hydroxy-3-phenylacetanilide. The hydrolysis of N-benzoyl-4-hydroxy-4-hydroxy-4-phenyl-2,5-cyclohexadienone imine proceeds by way of two consecutive pseudo-first-order processes. The hydrolysis of N-benzoyl-4-methoxy-4-phenyl-2,5-cyclohexadienone imine also proceeds by two consecutive pseudo-first-order processes. Spectroscopic evidence of two diastereomeric intermediates formed from the hydrolysis of the N-benzoyl imines were tentatively identified as N-benzoyl-N-hydroxy-4-hydroxy-4-phenyl-2,5-cyclohexadienone imine.« less

Synthesis, structure and reaction chemistry of a nucleophilic aluminyl anion.

PubMed

Hicks, Jamie; Vasko, Petra; Goicoechea, Jose M; Aldridge, Simon

2018-05-01

The reactivity of aluminium compounds is dominated by their electron deficiency and consequent electrophilicity; these compounds are archetypal Lewis acids (electron-pair acceptors). The main industrial roles of aluminium, and classical methods of synthesizing aluminium-element bonds (for example, hydroalumination and metathesis), draw on the electron deficiency of species of the type AlR 3 and AlCl 3 1,2 . Whereas aluminates, [AlR 4 ] - , are well known, the idea of reversing polarity and using an aluminium reagent as the nucleophilic partner in bond-forming substitution reactions is unprecedented, owing to the fact that low-valent aluminium anions analogous to nitrogen-, carbon- and boron-centred reagents of the types [NX 2 ] - , [CX 3 ] - and [BX 2 ] - are unknown 3-5 . Aluminium compounds in the +1 oxidation state are known, but are thermodynamically unstable with respect to disproportionation. Compounds of this type are typically oligomeric 6-8 , although monomeric systems that possess a metal-centred lone pair, such as Al(Nacnac) Dipp (where (Nacnac) Dipp  = (NDippCR) 2 CH and R =  t Bu, Me; Dipp = 2,6- i Pr 2 C 6 H 3 ), have also been reported 9,10 . Coordination of these species, and also of (η 5 -C 5 Me 5 )Al, to a range of Lewis acids has been observed 11-13 , but their primary mode of reactivity involves facile oxidative addition to generate Al(III) species 6-8,14-16 . Here we report the synthesis, structure and reaction chemistry of an anionic aluminium(I) nucleophile, the dimethylxanthene-stabilized potassium aluminyl [K{Al(NON)}] 2 (NON = 4,5-bis(2,6-diisopropylanilido)-2,7-di-tert-butyl-9,9-dimethylxanthene). This species displays unprecedented reactivity in the formation of aluminium-element covalent bonds and in the C-H oxidative addition of benzene, suggesting that it could find further use in both metal-carbon and metal-metal bond-forming reactions.

A Novel Computational Method to Reduce Leaky Reaction in DNA Strand Displacement

PubMed Central

Li, Xin; Wang, Xun; Song, Tao; Lu, Wei; Chen, Zhihua; Shi, Xiaolong

2015-01-01

DNA strand displacement technique is widely used in DNA programming, DNA biosensors, and gene analysis. In DNA strand displacement, leaky reactions can cause DNA signals decay and detecting DNA signals fails. The mostly used method to avoid leakage is cleaning up after upstream leaky reactions, and it remains a challenge to develop reliable DNA strand displacement technique with low leakage. In this work, we address the challenge by experimentally evaluating the basic factors, including reaction time, ratio of reactants, and ion concentration to the leakage in DNA strand displacement. Specifically, fluorescent probes and a hairpin structure reporting DNA strand are designed to detect the output of DNA strand displacement, and thus can evaluate the leakage of DNA strand displacement reactions with different reaction time, ratios of reactants, and ion concentrations. From the obtained data, mathematical models for evaluating leakage are achieved by curve derivation. As a result, it is obtained that long time incubation, high concentration of fuel strand, and inappropriate amount of ion concentration can weaken leaky reactions. This contributes to a method to set proper reaction conditions to reduce leakage in DNA strand displacement. PMID:26491602

Substrate-Controlled Product Divergence: Conversion of CO2 into Heterocyclic Products.

PubMed

Rintjema, Jeroen; Epping, Roel; Fiorani, Giulia; Martín, Eddy; Escudero-Adán, Eduardo C; Kleij, Arjan W

2016-03-14

Substituted epoxy alcohols and amines allow substrate-controlled conversion of CO2 into a wide range of heterocyclic structures through different mechanistic manifolds. This new approach results in an unusual scope of CO2-derived products by initial activation of CO2 through either the amine or alcohol unit, thus providing nucleophiles for intramolecular epoxy ring opening under mild reaction conditions. Control experiments support the crucial role of the amine/alcohol fragment in this process with the nucleophile-assisted ring-opening step following an SN i pathway, and a 5-exo-tet cyclization, thus leading to heterocyclic scaffolds. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Progress and developments in the turbo Grignard reagent i-PrMgCl·LiCl: a ten-year journey.

PubMed

Bao, Robert Li-Yuan; Zhao, Rong; Shi, Lei

2015-04-25

Over the past decade, the effectiveness of i-PrMgCl·LiCl has been constantly highlighted by a number of research groups. Its enhanced nucleophilicity brings prosperity to highly functionalized Grignard reagents, other useful bimetallic (alkali-metal) agents and nucleophilic alkylation products under mild reaction conditions. In this feature article, a comprehensive, systematical and in-depth overview of i-PrMgCl·LiCl is provided in a multidisciplinary idea. It involves the structural and kinetic perspectives of i-PrMgCl·LiCl as well as its unique reactivity and selectivity, with knowledge of the former helping to rationalize trends of the later.

Orthogonal Discrimination among Functional Groups in Ullmann-Type C-O and C-N Couplings.

PubMed

Rovira, Mireia; Soler, Marta; Güell, Imma; Wang, Ming-Zheng; Gómez, Laura; Ribas, Xavi

2016-09-02

The copper-catalyzed arylation of nucleophiles has been established as an efficient methodology for the formation of C-C and C-heteroatom bonds. Considering the advances during the last two decades, the ligand choice plays a key role in such transformations and can strongly influence the catalytic efficiency. The applicability of these Ullmann-type coupling reactions regarding the orthogonal selectivity of different functional groups constitutes a challenging subject for current synthetic strategies. Herein, we report a useful toolkit of Cu-based catalysts for the chemoselective arylation of a wide-range of nucleophiles in competitive reactions using aryl iodides and bromides. We show in this work that the arylation of all kinds of amides can be orthogonal to that of amines (aliphatic or aromatic) and phenol derivatives. This high chemoselectivity can be governed by the use of different ligands, yielding the desired coupling products under mild conditions. The selectivity trends are maintained for electronically biased iodobenzene and bromobenzene electrophiles. Radical clock experiments discard the occurrence of radical-based mechanisms.

A Catalytic Mechanism for Cysteine N-Terminal Nucleophile Hydrolases, as Revealed by Free Energy Simulations

PubMed Central

Lodola, Alessio; Branduardi, Davide; De Vivo, Marco; Capoferri, Luigi; Mor, Marco; Piomelli, Daniele; Cavalli, Andrea

2012-01-01

The N-terminal nucleophile (Ntn) hydrolases are a superfamily of enzymes specialized in the hydrolytic cleavage of amide bonds. Even though several members of this family are emerging as innovative drug targets for cancer, inflammation, and pain, the processes through which they catalyze amide hydrolysis remains poorly understood. In particular, the catalytic reactions of cysteine Ntn-hydrolases have never been investigated from a mechanistic point of view. In the present study, we used free energy simulations in the quantum mechanics/molecular mechanics framework to determine the reaction mechanism of amide hydrolysis catalyzed by the prototypical cysteine Ntn-hydrolase, conjugated bile acid hydrolase (CBAH). The computational analyses, which were confirmed in water and using different CBAH mutants, revealed the existence of a chair-like transition state, which might be one of the specific features of the catalytic cycle of Ntn-hydrolases. Our results offer new insights on Ntn-mediated hydrolysis and suggest possible strategies for the creation of therapeutically useful inhibitors. PMID:22389698

Nucleophilic substitution between polysulfides and binders unexpectedly stabilizing lithium sulfur battery

DOE PAGES

Ling, Min; Zhang, Liang; Zheng, Tianyue; ...

2017-05-10

Polysulfide shuttling has been the primary cause of failure in lithium-sulfur (Li-S) battery cycling. In this paper, we demonstrate an nucleophilic substitution reaction between polysulfides and binder functional groups can unexpectedly immobilizes the polysulfides. The substitution reaction is verified by UV–visible spectra and X-ray photoelectron spectra. The immobilization of polysulfide is in situ monitored by synchrotron based sulfur K-edge X-ray absorption spectra. The resulting electrodes exhibit initial capacity up to 20.4 mAh/cm 2, corresponding to 1199.1 mAh/g based on a micron-sulfur mass loading of 17.0 mg/cm 2. The micron size sulfur transformed into nano layer coating on the cathode bindermore » during cycling. Directly usage of nano-size sulfur promotes higher capacity of 33.7 mAh/cm 2, which is the highest areal capacity reported in Li-S battery. Finally, this enhance performance is due to the reduced shuttle effect by covalently binding of the polysulfide with the polymer binder.« less

Nucleophilic substitution between polysulfides and binders unexpectedly stabilizing lithium sulfur battery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ling, Min; Zhang, Liang; Zheng, Tianyue

Polysulfide shuttling has been the primary cause of failure in lithium-sulfur (Li-S) battery cycling. In this paper, we demonstrate an nucleophilic substitution reaction between polysulfides and binder functional groups can unexpectedly immobilizes the polysulfides. The substitution reaction is verified by UV–visible spectra and X-ray photoelectron spectra. The immobilization of polysulfide is in situ monitored by synchrotron based sulfur K-edge X-ray absorption spectra. The resulting electrodes exhibit initial capacity up to 20.4 mAh/cm 2, corresponding to 1199.1 mAh/g based on a micron-sulfur mass loading of 17.0 mg/cm 2. The micron size sulfur transformed into nano layer coating on the cathode bindermore » during cycling. Directly usage of nano-size sulfur promotes higher capacity of 33.7 mAh/cm 2, which is the highest areal capacity reported in Li-S battery. Finally, this enhance performance is due to the reduced shuttle effect by covalently binding of the polysulfide with the polymer binder.« less

Aldolase-catalysed stereoselective synthesis of fluorinated small molecules.

PubMed

Windle, Claire L; Berry, Alan; Nelson, Adam

2017-04-01

The introduction of fluorine has been widely exploited to tune the biological functions of small molecules. Indeed, around 20% of leading drugs contain at least one fluorine atom. Yet, despite profound effects of fluorination on conformation, there is only a limited toolkit of reactions that enable stereoselective synthesis of fluorinated compounds. Aldolases are useful catalysts for the stereoselective synthesis of bioactive small molecules; however, despite fluoropyruvate being a viable nucleophile for some aldolases, the potential of aldolases to control the formation of fluorine-bearing stereocentres has largely been untapped. Very recently, it has been shown that aldolase-catalysed stereoselective carboncarbon bond formation with fluoropyruvate as nucleophile enable the synthesis of many α-fluoro β-hydroxy carboxyl derivatives. Furthermore, an understanding of the structural basis for the stereocontrol observed in these reactions is beginning to emerge. Here, we review the application of aldolase catalysis in the stereocontrolled synthesis of chiral fluorinated small molecules, and highlight likely areas for future developments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reinterpretation of curved Hammett plots in reaction of nucleophiles with aryl benzoates: change in rate-determining step or mechanism versus ground-state stabilization.

PubMed

Um, Ik-Hwan; Han, Hyun-Joo; Ahn, Jung-Ae; Kang, Swan; Buncel, Erwin

2002-11-29

A kinetic study is reported for the reaction of the anionic nucleophiles OH-, CN-, and N 3 - with aryl benzoates containing substituents on the benzoyl as well as the aryloxy moiety, in 80 mol % H2O - 20 mol % dimethyl sulfoxide at 25.0 degrees C. Hammett log k vs sigma plots for these systems are consistently nonlinear. However, a possible traditional explanation in terms of a mechanism involving a tetrahedral intermediate with curvature resulting from a change in rate-determining step is considered but rejected. The proposed explanation involves ground-state stabilization through resonance interaction between the benzoyl substituent and the electrophilic carbonyl center in the two-stage mechanism. Accordingly, the data are nicely accommodated on the basis of the Yukawa-Tsuno equation, which gives linear plots for all three nuceophiles. Literature reports of the mechanism of acyl transfer processes are reconsidered in this light.

C- and N-Metalated Nitriles: The Relationship between Structure and Selectivity.

PubMed

Yang, Xun; Fleming, Fraser F

2017-10-17

Metalated nitriles are exceptional nucleophiles capable of forging highly hindered stereocenters in cases where enolates are unreactive. The excellent nucleophilicity emanates from the powerful inductive stabilization of adjacent negative charge by the nitrile, which has a miniscule steric demand. Inductive stabilization is the key to understanding the reactivity of metalated nitriles because this permits a continuum of structures that range from N-metalated ketenimines to nitrile anions. Solution and solid-state analyses reveal two different metal coordination sites, the formally anionic carbon and the nitrile nitrogen, with the site of metalation depending intimately on the solvent, counterion, temperature, and ligands. The most commonly encountered structures, C- and N-metalated nitriles, have either sp 3 or sp 2 hybridization at the nucleophilic carbon, which essentially translates into two distinct organometallic species with similar but nonidentical stereoselectivity, regioselectivity, and reactivity preferences. The hybridization differences are particularly important in S N i displacements of cyclic nitriles because the orbital orientations create very precise trajectories that control the cyclization selectivity. Harnessing the orbital differences between C- and N-metalated nitriles allows selective cyclization to afford nitrile-containing cis- or trans-hydrindanes, decalins, or bicyclo[5.4.0]undecanes. Similar orbital constraints favor preferential S N i displacements with allylic electrophiles on sp 3 centers over sp 2 centers. The strategy permits stereoselective displacements on secondary centers to set contiguous tertiary and quaternary stereocenters or even contiguous vicinal quaternary centers. Stereoselective alkylations of acyclic nitriles are inherently more challenging because of the difficulty in creating steric differentiation in a dynamic system with rotatable bonds. However, judicious substituent placement of vicinal dimethyl groups and a trisubstituted alkene sufficiently constrains C- and N-metalated nitriles to install quaternary stereocenters with excellent 1,2-induction. The structural differences between C- and N-metalated nitriles permit a rare series of chemoselective alkylations with bifunctional electrophiles. C-Magnesiated nitriles preferentially react with carbonyl electrophiles, whereas N-lithiated nitriles favor S N 2 displacement of alkyl halides. The chemoselective alkylations potentially provide a strategy for late-stage alkylations of polyfunctional electrophiles en route to bioactive targets. In this Account, the bonding of metalated nitriles is summarized as a prelude to the different strategies for selectively preparing C- and N-metalated nitriles. With this background, the Account then transitions to applications in which C- or N-metalated nitriles allow complementary diastereoselectivity in alkylations and arylations, and regioselective alkylations and arylations, with acyclic and cyclic nitriles. In the latter sections, a series of regiodivergent cyclizations are described that provide access to cis- and trans-hydrindanes and decalins, structural motifs embedded within a plethora of natural products. The last section describes chemoselective alkylations and acylations of C- and N-metalated nitriles that offer the tantalizing possibility of selectively manipulating functional groups in bioactive medicinal leads without recourse to protecting groups. Collectively, the unusual reactivity profiles of C- and N-metalated nitriles provide new strategies for rapidly and selectively accessing valuable synthetic precursors.

Design of a Photoredox Catalyst that Enables the Direct Synthesis of Carbamate-Protected Primary Amines via Photoinduced, Copper-Catalyzed N-Alkylation Reactions of Unactivated Secondary Halides.

PubMed

Ahn, Jun Myun; Peters, Jonas C; Fu, Gregory C

2017-12-13

Despite the long history of S N 2 reactions between nitrogen nucleophiles and alkyl electrophiles, many such substitution reactions remain out of reach. In recent years, efforts to develop transition-metal catalysts to address this deficiency have begun to emerge. In this report, we address the challenge of coupling a carbamate nucleophile with an unactivated secondary alkyl electrophile to generate a substituted carbamate, a process that has not been achieved effectively in the absence of a catalyst; the product carbamates can serve as useful intermediates in organic synthesis as well as bioactive compounds in their own right. Through the design and synthesis of a new copper-based photoredox catalyst, bearing a tridentate carbazolide/bisphosphine ligand, that can be activated upon irradiation by blue-LED lamps, we can achieve the coupling of a range of primary carbamates with unactivated secondary alkyl bromides at room temperature. Our mechanistic observations are consistent with the new copper complex serving its intended role as a photoredox catalyst, working in conjunction with a second copper complex that mediates C-N bond formation in an out-of-cage process.

Mechanistic studies on the phosphoramidite coupling reaction in oligonucleotide synthesis. I. Evidence for nucleophilic catalysis by tetrazole and rate variations with the phosphorus substituents.

PubMed Central

Dahl, B H; Nielsen, J; Dahl, O

1987-01-01

Tetrazole catalyzed reactions of a series of phosphoramidites, 5'-O-DMTdT-3'-O-P(OR1)NR2(2) (1a-h), with 3'-O-SiButPh2-6-N-benzoyl-dA (2a) in acetonitrile solution have been studied. It is found that the coupling rate depends very much on whether tetrazole is added before or after 2a, and that dialkylammonium tetrazolide salts are inhibitors. These and other facts are evidence that the reactions are subjected to nucleophilic catalysis by tetrazole, in addition to acid catalysis. The rate variations with phosphorus substituents of 1a-h are NEt2 greater than NPri2 greater than N(CH2CH2)O greater than NMePh, and OMe greater than OCH2CH2CN greater than OCHMeCH2CN greater than OCMe2CH2CN much greater than OC6H4Cl. The inhibitor properties of dialkylammonium tetrazolides have practical consequences for the efficiency of DNA syntheses, when in situ prepared phosphoramidites are used; the same would apply for segmented, simultaneous syntheses or syntheses where recycling is performed. PMID:3822837

Chemical dynamics simulations of X- + CH3Y → XCH3 + Y- gas-phase S(N)2 nucleophilic substitution reactions. Nonstatistical dynamics and nontraditional reaction mechanisms.

PubMed

Manikandan, Paranjothy; Zhang, Jiaxu; Hase, William L

2012-03-29

Extensive classical chemical dynamics simulations of gas-phase X(-) + CH(3)Y → XCH(3) + Y(-) S(N)2 nucleophilic substitution reactions are reviewed and discussed and compared with experimental measurements and predictions of theoretical models. The primary emphasis is on reactions for which X and Y are halogen atoms. Both reactions with the traditional potential energy surface (PES), which include pre- and postreaction potential energy minima and a central barrier, and reactions with nontraditional PESs are considered. These S(N)2 reactions exhibit important nonstatistical atomic-level dynamics. The X(-) + CH(3)Y → X(-)---CH(3)Y association rate constant is less than the capture model as a result of inefficient energy transfer from X(-)+ CH(3)Y relative translation to CH(3)Y rotation and vibration. There is weak coupling between the low-frequency intermolecular modes of the X(-)---CH(3)Y complex and higher frequency CH(3)Y intramolecular modes, resulting in non-RRKM kinetics for X(-)---CH(3)Y unimolecular decomposition. Recrossings of the [X--CH(3)--Y](-) central barrier is important. As a result of the above dynamics, the relative translational energy and temperature dependencies of the S(N)2 rate constants are not accurately given by statistical theory. The nonstatistical dynamics results in nonstatistical partitioning of the available energy to XCH(3) +Y(-) reaction products. Besides the indirect, complex forming atomic-level mechanism for the S(N)2 reaction, direct mechanisms promoted by X(-) + CH(3)Y relative translational or CH(3)Y vibrational excitation are possible, e.g., the roundabout mechanism.

The Chemistry of Photographic Color Dye Formation

ERIC Educational Resources Information Center

Kahn, Bruce E.

2004-01-01

A laboratory activity that can be used at a number of levels from high school to college is discussed. This activity can be used to teach chemical concepts such as oxidation and reduction, stoichiometry, acids and bases, pH, nucleophilic reactions, conjugation, leaving groups, complexation, solubility, and reversibility.

NUCLEOPHILIC AROMATIC SUBSTITUTION REACTIONS OF CHLOROAZINES WITH BISULFIDE (HS-) AND POLYSULFIDES (SN2-). (R826269)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Installation of a reactive site for covalent wiring onto an intrinsically conductive poly(ionic liquid)

DOE PAGES

Brombosz, Scott M.; Lee, Sungwon; Firestone, Millicent A.

2014-11-04

We describe post-polymerization radical bromination of a nanostructured poly(ionic liquid) that selectively introduces a reactive bromo-group onto the polyalkylthiophene backbone. Raman and FT-IR spectroscopy proves that the bromine is successfully introduced at the 3-methyl position of the thiophene and that the molecular structure of the polymer remains largely intact with only minimal chain scission detected. FT-IR and Vis-NIR spectroscopy indicates that incorporation of the bromine induces twisting (loss of co-planarity) of the polythiophene backbone. WAXS confirms retention of an ordered lamellar structure with minor lattice spacing contraction. Cyclic voltammetry confirms spectroscopic findings that the bromination reaction yields a stable p-dopedmore » polymer. The installed bromine is susceptible to nucleophilic displacement permitting the covalent attachment of other functional molecules, such as a dialkylphosphonate. Elemental analysis of such a transformation established that 100 % functionalization can be achieved. These results collectively demonstrate that post-modification of a π-conjugated polymer can be used to both tune electronic and photonic properties, as well as install a chemoselective attachment point for the covalent wiring of other molecules.« less

A colorimetric detection of acrylamide in potato chips based on nucleophile-initiated thiol-ene Michael addition.

PubMed

Hu, Qinqin; Fu, Yingchun; Xu, Xiahong; Qiao, Zhaohui; Wang, Ronghui; Zhang, Ying; Li, Yanbin

2016-02-07

Acrylamide (AA), a neurotoxin and a potential carcinogen, has been found in various thermally processed foods such as potato chips, biscuits, and coffee. Simple, cost-effective, and sensitive methods for the rapid detection of AA are needed to ensure food safety. Herein, a novel colorimetric method was proposed for the visual detection of AA based on a nucleophile-initiated thiol-ene Michael addition reaction. Gold nanoparticles (AuNPs) were aggregated by glutathione (GSH) because of a ligand-replacement, accompanied by a color change from red to purple. In the presence of AA, after the thiol-ene Michael addition reaction between GSH and AA with the catalysis of a nucleophile, the sulfhydryl group of GSH was consumed by AA, which hindered the subsequent ligand-replacement and the aggregation of AuNPs. Therefore, the concentration of AA could be determined by the visible color change caused by dispersion/aggregation of AuNPs. This new method showed high sensitivity with a linear range from 0.1 μmol L(-1) to 80 μmol L(-1) and a detection limit of 28.6 nmol L(-1), and especially revealed better selectivity than the fluorescence sensing method reported previously. Moreover, this new method was used to detect AA in potato chips with a satisfactory result in comparison with the standard methods based on chromatography, which indicated that the colorimetric method can be expanded for the rapid detection of AA in thermally processed foods.

Phosphodiester Cleavage in Ribonuclease H Occurs via an Associative Two-Metal-Aided Catalytic Mechanism

PubMed Central

De Vivo, Marco; Dal Peraro, Matteo; Klein, Michael L.

2009-01-01

Ribonuclease H (RNase H) belongs to the nucleotidyl-transferase (NT) superfamily and hydrolyzes the phosphodiester linkages that form the backbone of the RNA strand in RNA·DNA hybrids. This enzyme is implicated in replication initiation and DNA topology restoration and represents a very promising target for anti-HIV drug design. Structural information has been provided by high-resolution crystal structures of the complex RNase H/RNA·DNA from Bacillus halodurans (Bh), which reveals that two metal ions are required for formation of a catalytic active complex. Here, we use classical force field-based and quantum mechanics/molecular mechanics calculations for modeling the nucleotidyl transfer reaction in RNase H, clarifying the role of the metal ions and the nature of the nucleophile (water versus hydroxide ion). During the catalysis, the two metal ions act cooperatively, facilitating nucleophile formation and stabilizing both transition state and leaving group. Importantly, the two Mg2+ metals also support the formation of a meta-stable phosphorane intermediate along the reaction, which resembles the phosphorane intermediate structure obtained only in the debated β-phosphoglucomutase crystal. The nucleophile formation (i.e., water deprotonation) can be achieved in situ, after migration of one proton from the water to the scissile phosphate in the transition state. This proton transfer is actually mediated by solvation water molecules. Due to the highly conserved nature of the enzymatic bimetal motif, these results might also be relevant for structurally similar enzymes belonging to the NT superfamily. PMID:18662000

Clathrochelates meet phosphorus. New thio- and phosphorylation reactions of an iron(II) dichloroclathrochelate precursor and preparation of its first phosphorus(III)-containing macrobicyclic derivative.

PubMed

Artyushin, Oleg I; Matveeva, Ekaterina V; Vologzhanina, Anna V; Voloshin, Yan Z

2016-03-28

Phosphorylation reactions of an iron(II) dichloroclathrochelate FeBd2(Cl2Gm)(BF)2 (where Bd(2-) and Cl2Gm(2-) are α-benzildioxime and dichloroglyoxime dianions, respectively) with diphenylphosphine oxide and diethyl thiophosphite were performed under phase-transfer conditions. In the case of diethyl thiophosphite as a P-nucleophile, the best yields were obtained in the dichloromethane-50% NaOH aqueous solution-5 mol% triethylbenzylammonium chloride (TEBAC) system. The use of different molar ratios of a macrobicycle precursor and this thiophosphorylating agent allowed us to obtain both the mono- and the diphosphorylated cage complexes. Nucleophilic substitution with diphenylphosphine oxide was performed in the K2CO3-acetonitrile-5 mol% TEBAC system, giving only the corresponding monophosphorylated iron(II) complex in high yield even in the presence of an excess of this P-nucleophile. The phosphorus(v)-containing clathrochelate product was reduced with an excess of silicoform to give an iron(II) macrobicycle with an inherent diphenylphosphine group in an almost quantitative yield, which was then characterized by (31)P{(1)H} NMR and single-crystal X-ray diffraction; it easily undergoes re-oxidation to the initial clathrochelate. The synthesized phosphorus(v)-containing cage complexes were characterized using elemental analysis, MALDI-TOF mass, IR, UV-Vis, (1)H, (11)B, (13)C{(1)H}, (19)F{(1)H} and (31)P{(1)H} NMR spectra, and by single-crystal X-ray diffraction.

Gold(III) chloride catalyzed synthesis of chiral substituted 3-formyl furans from carbohydrates: application in the synthesis of 1,5-dicarbonyl derivatives and furo[3,2-c]pyridine.

PubMed

Mal, Kanchan; Sharma, Abhinandan; Das, Indrajit

2014-09-08

This report describes a gold(III)-catalyzed efficient general route to densely substituted chiral 3-formyl furans under extremely mild conditions from suitably protected 5-(1-alkynyl)-2,3-dihydropyran-4-one using H2 O as a nucleophile. The reaction proceeds through the initial formation of an activated alkyne-gold(III) complex intermediate, followed by either a domino nucleophilic attack/anti-endo-dig cyclization, or the formation of a cyclic oxonium ion with subsequent attack by H2 O. To confirm the proposed mechanistic pathway, we employed MeOH as a nucleophile instead of H2 O to result in a substituted furo[3,2-c]pyran derivative, as anticipated. The similar furo[3,2-c]pyran skeleton with a hybrid carbohydrate-furan derivative has also been achieved through pyridinium dichromate (PDC) oxidation of a substituted chiral 3-formyl furan. The corresponding protected 5-(1-alkynyl)-2,3-dihydropyran-4-one can be synthesized from the monosaccharides (both hexoses and pentose) following oxidation, iodination, and Sonogashira coupling sequences. Furthermore, to demonstrate the potentiality of chiral 3-formyl furan derivatives, a TiBr4 -catalyzed reaction of these derivatives has been shown to offer efficient access to 1,5-dicarbonyl compounds, which on treatment with NH4 OAc in slightly acidic conditions afforded substituted furo[3,2-c]pyridine. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

CuO nanoparticles catalyzed C-N, C-O, and C-S cross-coupling reactions: scope and mechanism.

PubMed

Jammi, Suribabu; Sakthivel, Sekarpandi; Rout, Laxmidhar; Mukherjee, Tathagata; Mandal, Santu; Mitra, Raja; Saha, Prasenjit; Punniyamurthy, Tharmalingam

2009-03-06

CuO nanoparticles have been studied for C-N, C-O, and C-S bond formations via cross-coupling reactions of nitrogen, oxygen, and sulfur nucleophiles with aryl halides. Amides, amines, imidazoles, phenols, alcohols and thiols undergo reactions with aryl iodides in the presence of a base such as KOH, Cs(2)CO(3), and K(2)CO(3) at moderate temperature. The procedure is simple, general, ligand-free, and efficient to afford the cross-coupled products in high yield.

Selenium as an electron acceptor during the catalytic mechanism of thioredoxin reductase.

PubMed

Lothrop, Adam P; Snider, Gregg W; Ruggles, Erik L; Patel, Amar S; Lees, Watson J; Hondal, Robert J

2014-02-04

Mammalian thioredoxin reductase (TR) is a pyridine nucleotide disulfide oxidoreductase that uses the rare amino acid selenocysteine (Sec) in place of the more commonly used amino acid cysteine (Cys) in the redox-active tetrapeptide Gly-Cys-Sec-Gly motif to catalyze thiol/disulfide exchange reactions. Sec can accelerate the rate of these exchange reactions (i) by being a better nucleophile than Cys, (ii) by being a better electrophile than Cys, (iii) by being a better leaving group than Cys, or (iv) by using a combination of all three of these factors, being more chemically reactive than Cys. The role of the selenolate as a nucleophile in the reaction mechanism was recently demonstrated by creating a mutant of human thioredoxin reductase-1 in which the Cys497-Sec498 dyad of the C-terminal redox center was mutated to either a Ser497-Cys498 dyad or a Cys497-Ser498 dyad. Both mutant enzymes were incubated with human thioredoxin (Trx) to determine which mutant formed a mixed disulfide bond complex. Only the mutant containing the Ser497-Cys498 dyad formed a complex, and this structure has been determined by X-ray crystallography [Fritz-Wolf, K., Kehr, S., Stumpf, M., Rahlfs, S., and Becker, K. (2011) Crystal structure of the human thioredoxin reductase-thioredoxin complex. Nat. Commun. 2, 383]. This experimental observation most likely means that the selenolate is the nucleophile initially attacking the disulfide bond of Trx because a complex resulted only when Cys was present in the second position of the dyad. As a nucleophile, the selenolate of Sec helps to accelerate the rate of this exchange reaction relative to Cys in the Sec → Cys mutant enzyme. Another thiol/disulfide exchange reaction that occurs in the enzymatic cycle of the enzyme is the transfer of electrons from the thiolate of the interchange Cys residue of the N-terminal redox center to the eight-membered selenosulfide ring of the C-terminal redox center. The selenium atom of the selenosulfide could accelerate this exchange reaction by being a good leaving group (attack at the sulfur atom) or by being a good electrophile (attack at the selenium atom). Here we provide strong evidence that the selenium atom is attacked in this exchange step. This was shown by creating a mutant enzyme containing a Gly-Gly-Seccoo- motif that had 0.5% of the activity of the wild-type enzyme. This mutant lacks the adjacent, resolving Cys residue, which acts by attacking the mixed selenosulfide bond that occurs between the enzyme and substrate. A similar result was obtained when Sec was replaced with homocysteine. These results highlight the role of selenium as an electron acceptor in the catalytic mechanism of thioredoxin reductase as well as its established role as a donor of an electron to the substrate.

Nitropyrroles, Diels-Alder reactions assisted by microwave irradiation and solvent effect. An experimental and theoretical study

NASA Astrophysics Data System (ADS)

Mancini, Pedro M. E.; Kneeteman, María N.; Cainelli, Mauro; Ormachea, Carla M.; Domingo, Luis R.

2017-11-01

The behaviors of N-tosylnitropyrroles acting as electrophilic dienophiles in polar Diels-Alder reactions joint to different dienes of increeased nucleophilicity are analyzed. The reactions were developed under microwave irradiation using toluene or protic ionic liquids (PILs) as solvents and in free solvent conditions. In all the cases explored we observed good yields in short reaction times. For these reactions, the free solvent condition and the use of protic ionic liquids as solvents offer similar results. However, the free solvent conditions favor environmental sustainability. The role of PILs in these polar Diels-Alder reactions has been theoretically studied within the Molecular Electron Density Theory.

Catalysis of hydrolysis and nucleophilic substitution at the P-N bond of phosphoimidazolide-activated nucleotides in phosphate buffers

NASA Technical Reports Server (NTRS)

Kanavarioti, A.; Rosenbach, M. T.

1991-01-01

Phosphoimidazolide-activated derivatives of guanosine and cytidine 5'-monophosphates, henceforth called ImpN's, exhibit enhanced rates of degradation in the presence of aqueous inorganic phosphate in the range 4.0 < or = pH < or = 8.6. This degradation is been attributed to (i) nucleophilic substitution of the imidazolide and (ii) catalysis of the P-N bond hydrolysis by phosphate. The first reaction results in the formation of nucleoside 5'-diphosphate and the second in nucleoside 5'-monophosphate. Analysis of the observed rates as well as the product ratios as a function of pH and phosphate concentration allow distinction between various mechanistic possibilities. The results show that both H2PO4- and HPO4(2-) participate in both hydrolysis and nucleophilic substitution. Statistically corrected biomolecular rate constants indicate that the dianion is 4 times more effective as a general base than the monoanion, and 8 times more effective as nucleophile. The low Bronsted value beta = 0.15 calculated for these phosphate species, presumed to act as general bases in facilitating water attack, is consistent with the fact that catalysis of the hydrolysis of the P-N bond in ImpN's has not been detected before. The beta nuc = 0.35 calculated for water, H2PO4-, HPO4(2-), and hydroxide acting as nucleophiles indicates a more associative transition state for nucleotidyl (O2POR- with R = nucleoside) transfers than that observed for phosphoryl (PO3(2-)) transfers (beta nuc = 0.25). With respect to the stability/reactivity of ImpN's under prebiotic conditions, our study shows that these materials would not suffer additional degradation due to inorganic phosphate, assuming the concentrations of phosphate, Pi, on prebiotic Earth were similar to those in the present oceans ([Pi] approximately 2.25 micromoles).

Transition State Analysis of Thymidine Hydrolysis by Human Thymidine Phosphorylase*

PubMed Central

Schwartz, Phillip A.; Vetticatt, Mathew; Schramm, Vern L.

2010-01-01

Human thymidine phosphorylase (hTP) is responsible for thymidine (dT) homeostasis and its action promotes angiogenesis. In the absence of phosphate, hTP catalyzes a slow hydrolytic depyrimidination of dT yielding thymine and 2-deoxyribose (dRib). Its transition state was characterized using multiple kinetic isotope effect (KIE) measurements. Isotopically enriched thymidines were synthesized enzymatically from glucose or (deoxy)ribose and intrinsic KIEs were used to interpret the transition state structure. KIEs from [1′-14C]-, [1-15N]-, [1′-3H]-, [2′R-3H]-, [2′S-3H]-, [4′-3H]-, [5′-3H]dTs provided values of 1.033 ± 0.002, 1.004 ± 0.002, 1.325 ± 0.003, 1.101 ± 0.004, 1.087 ± 0.005, 1.040 ± 0.003, and 1.033 ± 0.003, respectively. Transition state analysis revealed a stepwise mechanism with a 2-deoxyribocation formed early and a higher energetic barrier for nucleophilic attack of a water molecule on the high energy intermediate. An equilibrium exists between the deoxyribocation and reactants prior to the irreversible nucleophilic attack by water. The results establish activation of the thymine leaving group without requirement for phosphate. A transition state constrained to match the intrinsic KIEs was found using density functional theory. An active site histidine (His116) is implicated as the catalytic base for activation of the water nucleophile at the rate-limiting transition state. The distance between the water nucleophile and the anomeric carbon (rC-O) is predicted to be 2.3 Å at the transition state. The transition state model predicts that deoxyribose adopts a mild 3′-endo confirmation during nucleophilic capture. These results differ from the concerted bimolecular mechanism reported for the arsenolytic reaction PMID:20804144

Novel organophosphorus scaffolds of urease inhibitors obtained by substitution of Morita-Baylis-Hillman adducts with phosphorus nucleophiles.

PubMed

Ntatsopoulos, Vassilis; Vassiliou, Stamatia; Macegoniuk, Katarzyna; Berlicki, Łukasz; Mucha, Artur

2017-06-16

The reactivity of Morita-Baylis-Hillman allyl acetates was employed to introduce phosphorus-containing functionalities to the side chain of the cinnamic acid conjugated system by nucleophilic displacement. The proximity of two acidic groups, the carboxylate and phosphonate/phosphinate groups, was necessary to form interactions in the active site of urease by recently described inhibitor frameworks. Several organophosphorus scaffolds were obtained and screened for inhibition of the bacterial urease, an enzyme that is essential for survival of urinary and gastrointestinal tract pathogens. α-Substituted phosphonomethyl- and 2-phosphonoethyl-cinnamate appeared to be the most potent and were further optimized. As a result, one of the most potent organophosphorus inhibitors of urease, α-phosphonomethyl-p-methylcinnamic acid, was identified, with K i  = 0.6 μM for Sporosarcina pasteurii urease. High complementarity to the enzyme active site was achieved with this structure, as any further modifications significantly decreased its affinity. Finally, this work describes the challenges faced in developing ligands for urease. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Kinetics of degradation of sulfur mustard and sarin simulants on HKUST-1 metal organic framework.

PubMed

Roy, Anuradha; Srivastava, Avanish K; Singh, Beer; Shah, Dilip; Mahato, Timir Haran; Srivastava, Anchal

2012-10-28

The applicability of HKUST-1 for the degradation of sulfur mustard and sarin simulants was studied with and without coadsorbed water. Degradation was found to be via hydrolysis and dependent on the nucleophilic substitution reaction, vapour pressure and molecular diameter of the toxicants.

Counting ions and other nucleophiles at surfaces by chemical trapping.

PubMed

Cuccovia, Iolanda Midea; da Silva Lima, Filipe; Chaimovich, Hernan

2017-10-01

The interfaces of membranes and other aggregates are determined by the polarity, electrical charge, molecular volume, degrees of motional freedom and packing density of the head groups of the amphiphiles. These properties also determine the type of bound ion (ion selectivity) and its local density, i.e. concentration defined by choosing an appropriate volume element at the aggregate interface. Bulk and local ion concentrations can differ by orders of magnitude. The relationships between ion (or other compound) concentrations in the bulk solvent and in the interface are complex but, in some cases, well established. As the local ion concentration, rather than that in the bulk, controls a variety of properties of membranes, micelles, vesicles and other objects of theoretical and applied interests, measurement of local (interfacial, bound) ion concentrations is of relevance for understanding and characterizing such aggregates. Many experimental methods for estimating ion distributions between the bulk solution and the interface provide indirect estimates because they are based on concentration-dependent properties, rather than concentration measurements. Dediazoniation, i.e. the loss of N 2 , of a substituted diazophenyl derivative provides a tool for determining the number of nucleophiles (including neutral or negatively charged ions) surrounding the diazophenyl derivative prior to the dediazoniation event. This reaction, defined as chemical trapping, and the appropriate reference points obtained in bulk solution allow direct measurements of local concentrations of a variety of nucleophiles at the surface of membranes and other aggregates. Here we review our contributions of our research group to the use, and understanding, of this method and applications of chemical trapping to the description of local concentrations of ions and other nucleophiles in micelles, reverse micelles, vesicles and solvent mixtures. Among other results, we have shown that interfacial water determines micellar shape, zwitterionic vesicle-forming amphiphiles display ion selectivity and urea does not accumulate at micellar interfaces. We have also shown that reaction products can be predicted from the composition of the initial state, even in non-ideal solvent mixtures, supporting the usefulness of chemical trapping as a method to determine local concentrations. In addition, we have analysed the mechanism of dediazoniation, both on theoretical and experimental basis, and concluded that the formation of a free phenyl cation is not a necessary part of the reaction pathway.

A halogenophilic pathway in the reactions of transition metal carbonyl anions with [(η⁶-iodobenzene)Cr(CO)₃].

PubMed

Sazonov, Petr K; Ivushkin, Vasiliy A; Khrustalev, Victor N; Kolotyrkina, Natal'ya G; Beletskaya, Irina P

2014-09-21

The paper provides the first example of formal nucleophilic substitution by the halogenophilic pathway in Cr(CO)3 complexes of haloarenes with metal carbonyl anions. All metal carbonyl anions examined attack [(η(6)-iodobenzene)Cr(CO)3] at halogen, which is shown by aryl carbanion scavenging with t-BuOH. The reaction with K[CpFe(CO)2] gives only the dehalogenated arene, but the reaction with K[Cp*Fe(CO)2] (Cp* = η(5)-C5Me5) results in nucleophilic substitution to give [(η(6)-C6H5FeCp*(CO)2)Cr(CO)3]. Reaction with Na[Re(CO)5] quantitatively gives the iodo(acyl)rhenate anion Na[(η(6)-C6H5C(O)ReI(CO)4)Cr(CO)3] and in the case of K[Mn(CO)5] a mixture of σ-aryl complexes [(η(6)-C6H5Mn(CO)5)Cr(CO)3] and K[(η(6)-C6H5Mn(CO)4I)Cr(CO)3]. An analogous rhenium complex Na[(η(6)-C6H5Re(CO)4I)Cr(CO)3] is formed from the initial iodo(acyl)rhenate upon prolonged standing at 20 °C, and its structure (in the form of [NEt4](+) salt) is established by X-ray diffraction analysis. The reaction of [(η(6)-chlorobenzene)Cr(CO)3] with K[CpFe(CO)2], in contrast, proceeds by the common S(N)2Ar mechanism.

Hydrolysis mechanisms of BNPP mediated by facial copper(II) complexes bearing single alkyl guanidine pendants: cooperation between the metal centers and the guanidine pendants.

PubMed

Zhang, Xuepeng; Liu, Xueping; Phillips, David Lee; Zhao, Cunyuan

2016-01-28

The hydrolysis mechanisms of DNA dinucleotide analogue BNPP(-) (bis(p-nitrophenyl) phosphate) catalyzed by mononuclear/dinuclear facial copper(ii) complexes bearing single alkyl guanidine pendants were investigated using density functional theory (DFT) calculations. Active catalyst forms have been investigated and four different reaction modes are proposed accordingly. The [Cu2(L(1))2(μ-OH)](3+) (L(1) is 1-(2-guanidinoethyl)-1,4,7-triazacyclononane) complex features a strong μ-hydroxo mediated antiferromagnetic coupling between the bimetallic centers and the corresponding more stable open-shell singlet state. Three different reaction modes involving two catalysts and a substrate were proposed for L(1) entries and the mode 1 in which an inter-complex nucleophilic attack by a metal bound hydroxide was found to be more favorable. In the L(3)-involved reactions (L(3) is 1-(4-guanidinobutyl)-1,4,7-triazacyclononane), the reaction mode in which an in-plane intracomplex scissoring-like nucleophilic attack by a Cu(ii)-bound hydroxide was found to be more competitive. The protonated guanidine pendants in each proposed mechanism were found to play crucial roles in stabilizing the reaction structures via hydrogen bonds and in facilitating the departure of the leaving group via electrostatic attraction. The calculated results are consistent with the experimental observations that the Cu(ii)-L(3) complexes are hydrolytically more favorable than their L(1)-involved counterparts.

Highly Stereoselective Intermolecular Haloetherification and Haloesterification of Allyl Amides

PubMed Central

Soltanzadeh, Bardia; Jaganathan, Arvind; Staples, Richard J.

2016-01-01

An organocatalytic and highly regio-, diastereo-, and enantioselective intermolecular haloetherification and haloesterification reaction of allyl amides is reported. A variety of alkene substituents and substitution patterns are compatible with this chemistry. Notably, electronically unbiased alkene substrates exhibit exquisite regio- and diastereoselectivity for the title transformation. We also demonstrate that the same catalytic system can be used in both chlorination and bromination reactions of allyl amides with a variety of nucleophiles with little or no modification. PMID:26110812

The Comparative Nucleophilicity of Naphthoxide Derivatives in Reactions with a Fast-Red TR Dye: A Discovery-Oriented Capstone Project for the Second-Year Organic Laboratory

ERIC Educational Resources Information Center

Mascarenhas, Cheryl M.

2008-01-01

In this experiment, organic chemistry students perform reactions between three naphthyl acetate derivatives and the diazonium salt Fast-Red TR, under basic conditions. The three naphthyl acetate derivatives used in this study are 2-naphthyl acetate (1a), 6-bromo-2-naphthyl acetate (1b) and 1,6-dibromo-2-naphthyl acetate (1c). The two-step, one-pot…

Dienamine and Friedel-Crafts one-pot synthesis, and antitumor evaluation of diheteroarylalkanals.

PubMed

Frías, María; Padrón, José M; Alemán, José

2015-05-26

An asymmetric synthesis of diheteroarylalkanals through one-pot dienamine and Friedel-Crafts reaction is presented. The reaction tolerates a large variety of substituents at different positions of the starting aldehyde and also in the indole nucleophile, and a range of diheterocyclic alkanals can be achieved. Furthermore, we have studied the antiproliferative activity of these new compounds in representative cancer tumor cell lines. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dual palladium- and proline-catalyzed allylic alkylation of enolizable ketones and aldehydes with allylic alcohols.

PubMed

Usui, Ippei; Schmidt, Stefan; Breit, Bernhard

2009-03-19

The dual Pd/proline-catalyzed alpha-allylation reaction of a variety of enolizable ketones and aldehydes with allylic alcohols is described. In this reaction, the choice of a large-bite angle ligand Xantphos and proline as the organocatalyst was essential for generation of the crucial pi-allyl Pd intermediate from allylic alcohol, followed by nucleophilic attack of the enamine formed in situ from the corresponding enolizable carbonyl substrate and proline.

Thio-arylglycosides with Various Aglycon Para-Substituents, a Probe for Studying Chemical Glycosylation Reactions

PubMed Central

Li, Xiaoning; Huang, Lijun; Hu, Xiche; Huang, Xuefei

2009-01-01

Summary Three series of thioglycosyl donors differing only in their respective aglycon substituents within each series have been prepared as representatives of typical glycosyl donors. The relative anomeric reactivities of these donors were quantified under competitive glycosylation conditions with various reaction time, promoters, solvents and acceptors. Over three orders of magnitude reactivity difference were generated by simple transformation of the para-substituent on the aglycon with methanol as the acceptor, while chemoselectivities became lower with carbohydrate acceptors. Excellent linear correlations were attained between relative reactivity values of donors and σp values of the substituents in the Hammett plots. This indicates that the glycosylation mechanism remains the same over a wide range of reactivities and glycosylation conditions. The negative slopes of the Hammett plots suggested that electron donating substituents expedite the reactions and the magnitudes of slopes can be rationalized by neighboring group participation as well as electronic properties of the glycon protective groups. Within the same series of donors, less nucleophilic acceptors gave smaller slopes in their Hammett plots. This is consistent with the notion that acceptor nucleophilic attack onto the reactive intermediate is part of the rate limiting step of the glycosylation reaction. Excellent linear Hammett correlations were obtained between relative reactivity values of three series of donors differing only in their aglycon substituents and σp values of the substituents. PMID:19081954

Action mechanism of tyrosinase on meta- and para-hydroxylated monophenols.

PubMed

Fenoll, L G; Rodríguez-López, J N; Varón, R; García-Ruiz, P A; García-Cánovas, F; Tudela, J

2000-04-01

The relationship between the structure and activity of meta- and para-hydroxylated monophenols was studied during their tyrosinase-catalysed hydroxylation and the rate-limiting steps of the reaction mechanism were identified. The para-hydroxylated substrates permit us to study the effect of a substituent (R) in the carbon-1 position (C-1) of the benzene ring on the nucleophilic attack step, while the meta group permits a similar study of the effect on the electrophilic attack step. Substrates with a -OCH3 group on C-1, as p-hydroxyanisol (4HA) and m-hydroxyanisol (3HA), or with a -CH2OH group, as p-hydroxybenzylalcohol (4HBA) and m-hydroxybenzylalcohol (3HBA), were used because the effect of the substituent (R) size was assumed to be similar. However, the electron-donating effect of the -OCH3 group means that the carbon-4 position (C-4) is favoured for nucleophilic attack (para-hydroxylated substrates) or for electrophilic attack (meta-hydroxylated substrates). The electron-attracting effect of the -CH2OH group has the opposite effect, hindering nucleophilic (para) or electrophilic (meta) attack of C-4. The experimental data point to differences between the maximum steady-state rate (V(M)Max) of the different substrates, the value of this parameter depends on the nucleophilic and electrophilic attack. However, differences are greatest in the Michaelis constants (K(M)m), with the meta-hydroxylated substrates having very large values. The catalytic efficiency k(M)cat/K(M)m is much greater for thepara-hydroxylated substrates although it varies greatly between one substrate and the other. However, it varies much less in the meta-hydroxylated substrates since this parameter describes the power of the nucleophilic attack, which is weaker in the meta OH. The large increase in the K(M)m of the meta-hydroxylated substrates might suggest that the phenolic OH takes part in substrate binding. Since this is a weaker nucleophil than the para-hydroxylated substrates, the binding constant decreases, leading to an increase in K(M)m. The catalytic efficiency of tyrosinase on a monophenol (para or meta) is directly related to the nucleophilic power of the oxygen of the phenolic OH. The oxidation step is not limiting since if this were the case, the para and meta substrates would have the same V(M)max. The small difference between the absolute values of V(M)max suggests that the rate constants of the nucleophilic and electrophilic attacks are on the same order of magnitude.

Conferring specificity in redox pathways by enzymatic thiol/disulfide exchange reactions.

PubMed

Netto, Luis Eduardo S; de Oliveira, Marcos Antonio; Tairum, Carlos A; da Silva Neto, José Freire

2016-01-01

Thiol-disulfide exchange reactions are highly reversible, displaying nucleophilic substitutions mechanism (S(N)2 type). For aliphatic, low molecular thiols, these reactions are slow, but can attain million times faster rates in enzymatic processes. Thioredoxin (Trx) proteins were the first enzymes described to accelerate thiol-disulfide exchange reactions and their high reactivity is related to the high nucleophilicity of the attacking thiol. Substrate specificity in Trx is achieved by several factors, including polar, hydrophobic, and topological interactions through a groove in the active site. Glutaredoxin (Grx) enzymes also contain the Trx fold, but they do not share amino acid sequence similarity with Trx. A conserved glutathione binding site is a typical feature of Grx that can reduce substrates by two mechanisms (mono and dithiol). The high reactivity of Grx enzymes is related to the very acid pK(a) values of reactive Cys that plays roles as good leaving groups. Therefore, although distinct oxidoreductases catalyze similar thiol–disulfide exchange reactions, their enzymatic mechanisms vary. PDI and DsbA are two other oxidoreductases, but they are involved in disulfide bond formation, instead of disulfide reduction, which is related to the oxidative environment where they are found. PDI enzymes and DsbC are endowed with disulfide isomerase activity, which is related with their tetra-domain architecture. As illustrative description of specificity in thiol-disulfide exchange, redox aspects of transcription activation in bacteria, yeast, and mammals are presented in an evolutionary perspective. Therefore, thiol-disulfide exchange reactions play important roles in conferring specificity to pathways, a required feature for signaling.

Silver versus gold catalysis in tandem reactions of carbonyl functions onto alkynes: a versatile access to furoquinoline and pyranoquinoline cores.

PubMed

Godet, Thomas; Vaxelaire, Carine; Michel, Carine; Milet, Anne; Belmont, Philippe

2007-01-01

An efficient and versatile tandem process of acetalization and cycloisomerization reactions has been developed for the reactions of 1-alkynyl-2-carbonylquinoline substrates. The reaction occurs thanks to Au(I) and Ag(I) catalysis. Silver(I) catalysis has been extensively studied (11 different silver species) on a broad range of quinoline derivatives (variation of alkyne substituent, of carbonyl function and of nucleophiles), leading to a variety of furoquinoline and pyranoquinoline moieties. An insight is given for the presumed mechanism along with DFT-B3 LYP/6-31G** calculations to address the 6-endo and 5-exo regioselectivities observed.

Synthesis of water-soluble multidentate aminoalcohol β-cyclodextrin derivatives via epoxide opening.

PubMed

Martina, K; Caporaso, M; Tagliapietra, S; Heropoulos, G; Rosati, O; Cravotto, G

2011-12-13

New highly soluble β-aminoalcohol β-cyclodextrin (β-CD) derivatives have been synthesized via nucleophilic epoxide opening reactions with mono-6-amino mono-6-deoxy-permethyl-β-CD and mono-6-amino mono-6-deoxy-β-CD. The binding properties of the β-CD were enhanced by linking aminoalcohol subunits which caused its solubility to improve markedly. The reaction conditions were optimised using microwave irradiation giving moderate-to-good yields with a series of epoxides. A regioselective epoxide opening reaction was observed in the reaction with styrene oxide while the stereoselectivity was strictly dependent on substrate structure. Copyright © 2011 Elsevier Ltd. All rights reserved.

Comparison of group transfer, inner sphere and outer sphere electron transfer mechanisms for organometallic complexes

NASA Astrophysics Data System (ADS)

Our studies of reactions of metal carbonyl cations and anions have shown that metal carbonyl cations can catalyze CO exchange reactions on metal carbonyl anions. This result provides further evidence for a mechanism involving attack of the metal carbonyl anion on a carbon of the metal carbonyl cation in CO(exp 2+) transfer reactions. Reaction of metal carbonyl anions with metal carbonyl halides is a common approach to formation of metal-metal bonds. We have begun to use kinetic data and product analysis to understand the formation of homobimetallic versus heterobimetallic products in such reactions. Initial data indicate a nucleophilic attack, possibly through a ring-slippage mechanism.

Ion-Molecule Reaction Dynamics

NASA Astrophysics Data System (ADS)

Meyer, Jennifer; Wester, Roland

2017-05-01

We review the recent advances in the investigation of the dynamics of ion-molecule reactions. During the past decade, the combination of single-collision experiments in crossed ion and neutral beams with the velocity map ion imaging detection technique has enabled a wealth of studies on ion-molecule reactions. These methods, in combination with chemical dynamics simulations, have uncovered new and unexpected reaction mechanisms, such as the roundabout mechanism and the subtle influence of the leaving group in anion-molecule nucleophilic substitution reactions. For this important class of reactions, as well as for many fundamental cation-molecule reactions, the information obtained with crossed-beam imaging is discussed. The first steps toward understanding micro-solvation of ion-molecule reaction dynamics are presented. We conclude with the presentation of several interesting directions for future research.

Electrophilic trifluoromethylselenolation of terminal alkynes with Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate.

PubMed

Ghiazza, Clément; Tlili, Anis; Billard, Thierry

2017-01-01

Herein the nucleophilic addition of Se -(trifluoromethyl) 4-methylbenzenesulfonoselenoate, a stable and easy-to-handle reagent, to alkynes is described. This reaction provides trifluoromethylselenylated vinyl sulfones with good results and the method was extended also to higher fluorinated homologs. The obtained compounds are valuable building blocks for further syntheses of fluoroalkylselenolated molecules.

What Happens when Representations Fail to Represent? Graduate Students' Mental Models of Organic Chemistry Diagrams

ERIC Educational Resources Information Center

Strickland, Amanda M.; Kraft, Adam; Bhattacharyya, Gautam

2010-01-01

As part of our investigations into the development of representational competence, we report results from a study in which we elicited sixteen graduate students' expressed mental models of commonly-used terms for describing organic reactions--functional group, nucleophile/electrophile, acid/base--and for diagrams of transformations and their…

Advanced Biosensors for Amino Acid Detection

DTIC Science & Technology

1990-04-18

when (II) was dissolved in CHCl 3 , and found effective for extracting phenylethylamine (C 6 H5CH2 CH2 NH)) and di-phenylglycine ethyl ester (C 6 H6...reaction was promoted. Since reson nce effects are important in aromatic amines and since p-nitroanilive is an extremely weak nucleophile, lack of

Synthesis of Functionalized Organotrifluoroborates via Halomethyltrifluoroborates

PubMed Central

Molander, Gary A.; Ham, Jungyeob

2008-01-01

Potassium bromo- and iodomethyltrifluoroborates have been prepared via in situ reaction of n-BuLi with dibromo- and diiodomethane, respectively, in the presence of trialkyl borates, followed by treatment with KHF2. Moreover, a new synthetic method for the preparation of potassium organotrifluoroborates through nucleophilic substitution of the halide in these potassium halomethyltrifluoroborates is described. PMID:16671774

Double Reformatsky reaction: divergent synthesis of δ-hydroxy-β-ketoesters.

PubMed

Mineno, Masahiro; Sawai, Yasuhiro; Kanno, Kazuaki; Sawada, Naotaka; Mizufune, Hideya

2013-06-21

The double Reformatsky reaction, tandem addition of two molecules of zinc alkanoate to a carbonyl compound, and its synthetic application to a series of δ-hydroxy-β-ketoesters has been developed. The key to accelerate the double Reformatsky reaction is considered to be a complex-induced proximity effect of the in situ generated zinc alkoxide coordinated with the pyridyl group of the substrate or bidentate amines. A noteworthy feature of the reaction system is its high tolerance of functional groups due to the moderate nucleophilicity of organozinc reagents and the mild reaction conditions. Moreover, spectroscopic and crystallographic analyses of the zinc complex of the double Reformatsky product support the proposed mechanism of reaction site discrimination for ketones, aldehydes, nitriles, carboxylic acid anhydrides, and esters.

Ethers on Si(001): A Prime Example for the Common Ground between Surface Science and Molecular Organic Chemistry.

PubMed

Pecher, Lisa; Laref, Slimane; Raupach, Marc; Tonner, Ralf

2017-11-20

By using computational chemistry it has been shown that the adsorption of ether molecules on Si(001) under ultrahigh vacuum conditions can be understood with classical concepts of organic chemistry. Detailed analysis of the two-step reaction mechanism-1) formation of a dative bond between the ether oxygen atom and a Lewis acidic surface atom and 2) nucleophilic attack of a nearby Lewis basic surface atom-shows that it mirrors acid-catalyzed ether cleavage in solution. The O-Si dative bond is the strongest of its kind, and the reactivity in step 2 defies the Bell-Evans-Polanyi principle. Electron rearrangement during C-O bond cleavage has been visualized with a newly developed method for analyzing bonding, which shows that the mechanism of nucleophilic substitutions on semiconductor surfaces is identical to molecular S N 2 reactions. Our findings illustrate how surface science and molecular chemistry can mutually benefit from each other and unexpected insight can be gained. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Substituents on Quinone Methides Strongly Modulate Formation and Stability of Their Nucleophilic Adducts

PubMed Central

Weinert, Emily E.; Dondi, Ruggero; Colloredo-Melz, Stefano; Frankenfield, Kristen N.; Mitchell, Charles H.; Freccero, Mauro; Rokita, Steven E.

2008-01-01

Electronic perturbation of quinone methides (QM) greatly influences their stability and in turn alters the kinetics and product profile of QM reaction with deoxynucleosides. Consistent with the electron deficient nature of this reactive intermediate, electron-donating substituents are stabilizing and electron-withdrawing substituents are destabilizing. For example, a dC N3-QM adduct is made stable over the course of observation (7 days) by the presence of an electron-withdrawing ester group that inhibits QM regeneration. Conversely, a related adduct with an electron donating methyl group is very labile and regenerates its QM with a half-life of approximately 5 hr. The generality of these effects is demonstrated with a series of alternative quinone methide precursors (QMP) containing a variety of substituents attached at different positions with respect to the exocyclic methylene. The rates of nucleophilic addition to substituted QMs measured by laser flash photolysis similarly span five orders of magnitude with electron rich species reacting most slowly and electron deficient species reacting most quickly. The reversibility of QM reaction can now be predictably adjusted for any desired application. PMID:16953635

From Metal Thiobenzoates to Metal Sulfide Nanocrystals: An Experimental and Theoretical Investigation

PubMed Central

Zhang, Zhihua; Lim, Wen Pei; Wong, Chiong Teck; Xu, Hairuo; Yin, Fenfang; Chin, Wee Shong

2012-01-01

A simple preparation of metal sulfide nanoparticles via the decomposition of thiobenzoate precursors at room temperature is presented and discussed. Long chain alkylamines were found to mediate the breakdown of metal thiobenzoates, such as those containing Ag, Cu, In and Cd, to produce uniform Ag2S, Cu2−xS, In2S3 and CdS nanoparticles respectively. The long chain amines are assumed to play dual roles as the nucleophilic reagent and the capping agent. It was found that sizes of the nanoparticles can be controlled by changing the type of amine used, as well as the molar ratio between amine and the precursor. We performed DFT calculations on a proposed mechanism involving an initial nucleophilic addition of amine molecule onto the thiocarboxylates. The proposed reaction was also confirmed through the analysis of by-products via infrared spectroscopy. On the basis of this understanding, we propose to manipulate the stability of the precursors by coordination with suitable stabilizing groups, such that the reaction kinetics can be modified to generate different nanostructures of interest. PMID:28348299

Rhodium Phosphine-π-Arene Intermediates in the Hydroamination of Alkenes

PubMed Central

Liu, Zhijian; Yamamichi, Hideaki; Madrahimov, Sherzod T.; Hartwig, John F.

2011-01-01

A detailed mechanistic study of the intramolecular hydroamination of alkenes with amines catalyzed by rhodium complexes of a biaryldialkylphosphine are reported. The active catalyst is shown to contain the phosphine ligand bound in a κ1, η6 form in which the arene is π-bound to rhodium. Addition of deuterated amine to an internal olefin showed that the reaction occurs by trans addition of the N-H bond across the C=C bond, and this stereochemistry implies that the reaction occurs by nucleophilic attack of the amine on a coordinated alkene. Indeed, the cationic rhodium fragment binds the alkene over the secondary amine, and the olefin complex was shown to be the catalyst resting state. The reaction was zero-order in substrate, when the concentration of olefin was high, and a primary isotope effect was observed. The primary isotope effect, in combination with the observation of the alkene complex as the resting state, implies that nucleophilic attack of the amine on the alkene is reversible and is followed by turnover-limiting protonation. This mechanism constitutes an unusual pathway for rhodium-catalyzed additions to alkenes and is more closely related to the mechanism for palladium-catalyzed addition of amide N-H bonds to alkenes. PMID:21309512

Numerical simulation of miscible viscous fingering with viscosity change in a displacing fluid by chemical reaction

NASA Astrophysics Data System (ADS)

Omori, Keiichiro; Nagatsu, Yuichiro

2017-11-01

Viscous fingering (VF) with viscosity changes by chemical reactions in case of miscible systems have been investigated both experimentally and theoretically in the recent years. Nagatsu et al. investigated experimentally miscible VF in which viscosity of the displaced fluid or the displacing one is changed by fast chemical reaction They showed that VF was more dense by the viscosity increase whereas less dense by the viscosity increase regardless of whether the viscosity change occurs in the displaced fluid or displacing one. From a theoretical viewpoint, numerical simulation performed on the reactive VF where viscosity of the displaced fluid is changed by instantaneously fast chemical reaction. The results had a good agreement with those in the corresponding experiment. In this work, we have conducted numerical simulation on such reactive VF where viscosity of the displacing fluid is changed. We have found the results have a good agreement with the corresponding experimental ones.

Crystal structure of glycoside hydrolase family 127 β-L-arabinofuranosidase from Bifidobacterium longum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ito, Tasuku; Saikawa, Kyo; Kim, Seonah

2014-04-25

Graphical abstract: - Highlights: • HypBA1 β-L-arabinofuranosidase belongs to glycoside hydrolase family 127. • Crystal structure of HypBA1 was determined. • HypBA1 consists of a catalytic barrel and two additional β-sandwich domains. • The active site contains a Zn{sup 2+} coordinated by glutamate and three cysteines. • A possible reaction mechanism involving cysteine as the nucleophile is proposed. - Abstract: Enzymes acting on β-linked arabinofuranosides have been unknown until recently, in spite of wide distribution of β-L-arabinofuranosyl oligosaccharides in plant cells. Recently, a β-L-arabinofuranosidase from the glycoside hydrolase family 127 (HypBA1) was discovered in the newly characterized degradation system ofmore » hydroxyproline-linked β-L-arabinooligosaccharides in the bacterium Bifidobacterium longum. Here, we report the crystal structure of HypBA1 in the ligand-free and β-L-arabinofuranose complex forms. The structure of HypBA1 consists of a catalytic barrel domain and two additional β-sandwich domains, with one β-sandwich domain involved in the formation of a dimer. Interestingly, there is an unprecedented metal-binding motif with Zn{sup 2+} coordinated by glutamate and three cysteines in the active site. The glutamate residue is located far from the anomeric carbon of the β-L-arabinofuranose ligand, but one cysteine residue is appropriately located for nucleophilic attack for glycosidic bond cleavage. The residues around the active site are highly conserved among GH127 members. Based on biochemical experiments and quantum mechanical calculations, a possible reaction mechanism involving cysteine as the nucleophile is proposed.« less

The ligand effect on the hydrolytic reactivity of Zn(II) complexes toward phosphate diesters.

PubMed

Bonfá, Lodovico; Gatos, Maddalena; Mancin, Fabrizio; Tecilla, Paolo; Tonellato, Umberto

2003-06-16

The catalytic effects of the Zn(II) complexes of a series of poliaminic ligands in the hydrolysis of the activated phosphodiesters bis-p-nitrophenyl phosphate (BNP) and 2-hydroxypropyl-p-nitrophenyl phosphate (HPNP) have been investigated. The reactions show first-order rate dependency on both substrate and metal ion complex and a pH dependence which is diagnostic of the acid dissociation of the reactive species. The mechanism of the metal catalyzed transesterification of HPNP has been assessed by solvent isotopic kinetic effect studies and involves the intramolecular nucleophilic attack of the substrate alcoholic group, activated by metal ion coordination. The intrinsic reactivity of the different complexes is controlled by the nature and structure of the ligand: complexes of tridentate ligands, particularly if characterized by a facial coordination mode, are more reactive than those of tetradentate ligands which can hardly allow binding sites for the substrate. In the case of tridentate ligands that form complexes with a facial coordination mode, a linear Brønsted correlation between the reaction rate (log k) and the pK(a) of the active nucleophile is obtained. The beta(nuc) values are 0.75 for the HPNP transesterification and 0.20 for the BNP hydrolysis. These values are indicated as the result of the combination of two opposite Lewis acid effects of the Zn(II) ion: the activation of the substrate and the efficiency of the metal coordinated nucleophile. The latter factor apparently prevails in determining the intrinsic reactivity of the Zn(II) complexes.

Exploiting the oxidizing capabilities of laccases exploiting the oxidizing capabilities of laccases for sustainable chemistry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cannatelli, Mark D.

Part one of this dissertation research has focused on harnessing the ability of laccases to generate reactive para-quinones in situ from the corresponding hydroquinones, followed by reaction with a variety of nucleophiles to perform novel carbon-carbon, carbon-nitrogen, and carbon-sulfur bond forming reactions for the synthesis of new and existing compounds. In part two of this dissertation, the fundamental laccase-catalyzed coupling chemistry developed in part one was applied to functionalize the surface of kraft lignin.

Concise Access to 2-Aroylbenzothiazoles by Redox Condensation Reaction between o-Halonitrobenzenes, Acetophenones, and Elemental Sulfur.

PubMed

Nguyen, Thanh Binh; Pasturaud, Karine; Ermolenko, Ludmila; Al-Mourabit, Ali

2015-05-15

A wide range of 2-aroylbenzothiazoles 3 including some pharmacologically relevant derivatives can be obtained in high yields by simply heating o-halonitrobenzenes 1, acetophenones 2, elemental sulfur, and N-methylmorpholine. This three-component nitro methyl coupling was found to occur in an excellent atom-, step-, and redox-efficient manner in which elemental sulfur played the role of nucleophile building block and redox moderating agent to fulfill electronic requirements of the global reaction.

Enantioselective N-Heterocyclic Carbene Catalysis via the Dienyl Acyl Azolium.

PubMed

Gillard, Rachel M; Fernando, Jared E M; Lupton, David W

2018-04-16

Herein we report the enantioselective N-heterocyclic carbene catalyzed (4+2) annulation of the dienyl acyl azolium with enolates. The reaction exploits readily accessible acyl fluorides and TMS enol ethers to give a range of highly enantio- and diastereo-enriched cyclohexenes (most >97:3 er and >20:1 dr). The reaction was found to require high nucleophilicity NHC catalysts with mechanistic studies supporting a stepwise 1,6-addition/β-lactonization. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

One-pot stereoselective synthesis of α,β-differentiated diamino esters via the sequence of aminochlorination, aziridination and intermolecular SN2 reaction.

PubMed

Xiong, Yiwen; Qian, Ping; Cao, Chenhui; Mei, Haibo; Han, Jianlin; Li, Guigen; Pan, Yi

2014-01-01

We report here an efficient one-pot method for the synthesis of α,β-differentiated diamino esters directly from cinnamate esters using N,N-dichloro-p-toluenesulfonamide and benzylamine as nitrogen sources. The key transformations include a Cu-catalyzed aminohalogenation and aziridination, followed by an intermolecular SN2 nucleophilic ring opening by benzylamine. The reactions feature a wide scope of substrates and proceed with excellent stereo- and regioselectivity (anti:syn >99:1) .

A new reactivity mode for the diazo group: diastereoselective 1,3-aminoalkylation reaction of β-amino-α-diazoesters to give triazolines.

PubMed

Kuznetsov, Alexey; Gulevich, Anton V; Wink, Donald J; Gevorgyan, Vladimir

2014-08-18

A novel mode of reactivity for the diazo group, the 1,3-addition of a nucleophile and an electrophile to the diazo group, has been realized in the intramolecular aminoalkylation of β-amino-α-diazoesters to form tetrasubstituted 1,2,3-triazolines. The reaction exhibited a broad scope, good functional group tolerance, and excellent diastereoselectivity. In addition, a new Au-catalyzed intramolecular transannulation reaction of the obtained propargyl triazolines to give pyrroles has been discovered. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification of ortho-Substituted Benzoic Acid/Ester Derivatives via the Gas-Phase Neighboring Group Participation Effect in (+)-ESI High Resolution Mass Spectrometry.

PubMed

Blincoe, William D; Rodriguez-Granillo, Agustina; Saurí, Josep; Pierson, Nicholas A; Joyce, Leo A; Mangion, Ian; Sheng, Huaming

2018-04-01

Benzoic acid/ester/amide derivatives are common moieties in pharmaceutical compounds and present a challenge in positional isomer identification by traditional tandem mass spectrometric analysis. A method is presented for exploiting the gas-phase neighboring group participation (NGP) effect to differentiate ortho-substituted benzoic acid/ester derivatives with high resolution mass spectrometry (HRMS 1 ). Significant water/alcohol loss (>30% abundance in MS 1 spectra) was observed for ortho-substituted nucleophilic groups; these fragment peaks are not observable for the corresponding para and meta-substituted analogs. Experiments were also extended to the analysis of two intermediates in the synthesis of suvorexant (Belsomra) with additional analysis conducted with nuclear magnetic resonance (NMR), density functional theory (DFT), and ion mobility spectrometry-mass spectrometry (IMS-MS) studies. Significant water/alcohol loss was also observed for 1-substituted 1, 2, 3-triazoles but not for the isomeric 2-substituted 1, 2, 3-triazole analogs. IMS-MS, NMR, and DFT studies were conducted to show that the preferred orientation of the 2-substituted triazole rotamer was away from the electrophilic center of the reaction, whereas the 1-subtituted triazole was oriented in close proximity to the center. Abundance of NGP product was determined to be a product of three factors: (1) proton affinity of the nucleophilic group; (2) steric impact of the nucleophile; and (3) proximity of the nucleophile to carboxylic acid/ester functional groups. Graphical Abstract ᅟ.

Identification of ortho-Substituted Benzoic Acid/Ester Derivatives via the Gas-Phase Neighboring Group Participation Effect in (+)-ESI High Resolution Mass Spectrometry

NASA Astrophysics Data System (ADS)

Blincoe, William D.; Rodriguez-Granillo, Agustina; Saurí, Josep; Pierson, Nicholas A.; Joyce, Leo A.; Mangion, Ian; Sheng, Huaming

2018-02-01

Benzoic acid/ester/amide derivatives are common moieties in pharmaceutical compounds and present a challenge in positional isomer identification by traditional tandem mass spectrometric analysis. A method is presented for exploiting the gas-phase neighboring group participation (NGP) effect to differentiate ortho-substituted benzoic acid/ester derivatives with high resolution mass spectrometry (HRMS1). Significant water/alcohol loss (>30% abundance in MS1 spectra) was observed for ortho-substituted nucleophilic groups; these fragment peaks are not observable for the corresponding para and meta-substituted analogs. Experiments were also extended to the analysis of two intermediates in the synthesis of suvorexant (Belsomra) with additional analysis conducted with nuclear magnetic resonance (NMR), density functional theory (DFT), and ion mobility spectrometry-mass spectrometry (IMS-MS) studies. Significant water/alcohol loss was also observed for 1-substituted 1, 2, 3-triazoles but not for the isomeric 2-substituted 1, 2, 3-triazole analogs. IMS-MS, NMR, and DFT studies were conducted to show that the preferred orientation of the 2-substituted triazole rotamer was away from the electrophilic center of the reaction, whereas the 1-subtituted triazole was oriented in close proximity to the center. Abundance of NGP product was determined to be a product of three factors: (1) proton affinity of the nucleophilic group; (2) steric impact of the nucleophile; and (3) proximity of the nucleophile to carboxylic acid/ester functional groups. [Figure not available: see fulltext.

Sensitive fluorescence detection of nucleic acids based on isothermal circular strand-displacement polymerization reaction.

PubMed

Guo, Qiuping; Yang, Xiaohai; Wang, Kemin; Tan, Weihong; Li, Wei; Tang, Hongxing; Li, Huimin

2009-02-01

Here we have developed a sensitive DNA amplified detection method based on isothermal strand-displacement polymerization reaction. This method takes advantage of both the hybridization property of DNA and the strand-displacement property of polymerase. Importantly, we demonstrate that our method produces a circular polymerization reaction activated by the target, which essentially allows it to self-detect. Functionally, this DNA system consists of a hairpin fluorescence probe, a short primer and polymerase. Upon recognition and hybridization with the target ssDNA, the stem of the hairpin probe is opened, after which the opened probe anneals with the primer and triggers the polymerization reaction. During this process of the polymerization reaction, a complementary DNA is synthesized and the hybridized target is displaced. Finally, the displaced target recognizes and hybridizes with another probe, triggering the next round of polymerization reaction, reaching a target detection limit of 6.4 x 10(-15) M.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Christopher M. Leavitt; Garold L. Gresham; Michael T. Benson

Diphenyldithiophosphinate (DTP) ligands modified with electron-withdrawing trifluoromethyl (TFM) substitutents are of high interest because they have demonstrated potential for exceptional separation of Am3+ from lanthanide3+ cations. Specifically, the bis(ortho-TFM) (L1-) and (ortho-TFM)(meta-TFM) (L2-) derivatives have shown excellent separation selectivity, while the bis(meta-TFM) (L3)- and unmodified DTP (Lu-) did not. Factors responsible for selective coordination have been investigated using density functional theory (DFT) calculations in concert with competitive dissociation reactions in the gas phase. To evaluate the role of (DTP+H) acidity, density functional calculations were used to predict pKa values, which followed the trend of L3 < L2 < L1 L1- > L2- > L3-.« less

Reactive Metabolites in the Biotransformation of Molecules Containing a Furan Ring

PubMed Central

Peterson, Lisa A.

2012-01-01

Many xenobiotics containing a furan ring are toxic and/or carcinogenic. The harmful effects of these compounds require furan ring oxidation. This reaction generates an electrophilic intermediate. Depending on the furan ring substituents, the intermediate is either an epoxide or a cis-enedione with more ring substitution favoring epoxide formation. Either intermediate reacts with cellular nucleophiles such as protein or DNA to trigger toxicities. The reactivity of the metabolite determines which cellular nucleophiles are targeted. The toxicity of a particular furan is also influenced by the presence of competing metabolic pathways or efficient detoxification routes. GSH plays an important role in modulating the harmful effects of this class of compound by reacting with the reactive metabolite. However, this may not represent a detoxification step in all cases. PMID:23061605

Photoredox Generated Radicals in Csp2-Csp3 Bond Construction

NASA Astrophysics Data System (ADS)

Primer, David Neal

The routine application of Csp3-hybridized nucleophiles in cross-coupling has been an ongoing pursuit in the agrochemical, pharmaceutical, and materials science industries for over 40 years. Unfortunately, despite numerous attempts to circumvent the problems associated with alkyl nucleophiles, application of these reagents in transition metal-catalyzed C-C bond-forming reactions has remained largely restricted. In recent years, many chemists have noted the lack of reliable, turnkey reactions that exist for the installation of Csp3-hybridized centers--reactions that would be useful for delivering molecules with enhanced three-dimensional topology and altered chemical properties. As such, a general method for alkyl nucleophile activation in cross-coupling would offer access to a host of compounds inaccessible by other means. From a mechanistic standpoint, the continued failure of alkylmetallics is inherent to the high energy intermediates associated with a traditional transmetalation. To overcome this problem, we have pioneered an alternate, single-electron pathway involving 1) initial oxidation of an alkylmetallic reagent, 2) oxidative alkyl radical capture at a metal center, and 3) subsequent reduction of the metal center to return its initial oxidation state. This series of steps constitutes a formal transmetalation that avoids the energy-demanding steps that plague a traditional anionic approach. Under this enabling paradigm, a host of alkyl precursors (alkyl-trifluoroborates and -silicates) have been generally used in cross-coupling for the first time. In summary, the synergistic use of an Ir photoredox catalyst and a Ni cross-coupling catalyst to mediate the cross-coupling of (hetero)aryl bromides with diverse alkyl radical precursors will be discussed. Methods for coupling various trifluoroborate classes (alpha-alkoxy, alpha-trifluoromethyl, secondary and tertiary alkyl) will be covered, focusing on their complementarity to traditional protocols. Finally, a discussion of novel silicate radical precursors and their advantages in a single-electron transmetalation regime will be included.

DNA logic gate based on metallo-toehold strand displacement.

PubMed

Deng, Wei; Xu, Huaguo; Ding, Wei; Liang, Haojun

2014-01-01

DNA is increasingly being used as an ideal material for the construction of nanoscale structures, circuits, and machines. Toehold-mediated DNA strand displacement reactions play a very important role in these enzyme-free constructions. In this study, the concept of metallo-toehold was utilized to further develop a mechanism for strand displacement driven by Ag+ ions, in which the intercalation of cytosine-cytosine mismatched base pairs on the toeholds provides additional control by varying of the concentration of Ag+ ions. The characteristics of displacement reaction in response to different concentration of Ag+ ions are investigated by fluorescence spectral and non-denaturing polyacrylamide gel electrophoresis. The reaction can successfully occur when the concentration of Ag+ ions is suitabe; excess Ag+ ions block the reaction. Furthermore, the displacement reaction can be tuned and controlled most efficiently under the condition of two C:C mismatched base pairs placed on the six-nt toehold. Based on our research, a mechanism was developed to construct Boolean logic gate AND and OR by employing strand displacement reaction as a tool, Ag+ and Hg2+ as input.

The trans influence in the modulation of platinum anticancer agent biology: the effect of nitrite leaving group on aquation, reactions with S-nucleophiles and DNA binding of dinuclear and trinuclear compounds.

PubMed

Montero, Eva I; Zhang, Junyong; Moniodis, Joseph J; Berners-Price, Susan J; Farrell, Nicholas P

2010-08-09

To examine the effect of leaving group and trans influence on the general reactivity of polynuclear platinum antitumor agents we investigated substitution of the chloride leaving groups with nitrite ion, which forms strong bonds to Pt. It was of interest to explore whether nitrite could be used to modulate biological properties of these agents, in particular the deactivating reactions that occur on reaction with S-nucleophiles, involving loss of the linking diamine under the trans influence of sulfur. Reported herein is a study of the synthesis, aquation, DNA binding and reactions with glutathione (GSH), methionine (Met) and acetylmethione (AcMet) of nitrito derivatives of di- and trinuclear platinum antitumor compounds: [{trans-PtNO(2)(NH(3))(2)}(2)(mu-NH(2)(CH(2))(6)NH(2))](NO(3))(2) (1-NO(2)) and [{trans-PtNO(2)(NH(3))(2)}(2)(mu-trans-Pt(NH(3))(2){NH(2)(CH(2))(6)NH(2)}(2))](NO(3))(4) (1'-NO(2)). {(1)H,(15)N}-HSQC NMR studies revealed that 1-NO(2) is inert to aquation reactions, even after prolonged incubation at physiological pH. Monitoring of the interaction of 1-NO(2) with the duplex 5'-d(ATATGTACATAT)(2) (I) showed only unreacted complex, consistent with activation by aquation being a requirement for covalent DNA binding. The reaction of 1-NO(2) with GSH was studied by (1)H, (195)Pt, (15)N and {(1)H,(15)N}-HSQC NMR spectroscopy. For the parent dichlorido compounds (1 and 1') substitution of chloride by GS(-) leads to drug degradation involving liberation of the diamine linker. While the same final products trans-[Pt(SG)(2)(NH(3))(2)] (5) and trans-[{Pt(SG)(NH(3))(2)}(2)-mu-SG] (6) are formed, different mechanisms are involved, consistent with the trans influence NO(2)(-) > Cl(-); the half-life is slightly longer for 1-NO(2) (1.8 h) compared with 1 (1.3 h). Identification of the intermediate trans-[Pt(NH(3))(2)(NO(2))(SG)] (4) shows that the nitrito group remains coordinated while the linker amine is substituted by coordination of GS(-), and then trans labilization of the nitrito group occurs leading to 5 and 6. Reaction of the trinuclear 1'-NO(2) with GSH follows essentially the same reaction pathway. Reaction of 1-NO(2) with Met and AcMet is much slower and only 20 % liberated amine was observed after reaction with Met for 24 h at 37 degrees C. The final product from reaction with AcMet is trans-[Pt(NH(3))(2)(NO(2))(AcMet)], as in this case coordination of the S-nucleophile does not lead to trans labilization of the nitrito group.

A front-face 'SNi synthase' engineered from a retaining 'double-SN2' hydrolase.

PubMed

Iglesias-Fernández, Javier; Hancock, Susan M; Lee, Seung Seo; Khan, Maola; Kirkpatrick, Jo; Oldham, Neil J; McAuley, Katherine; Fordham-Skelton, Anthony; Rovira, Carme; Davis, Benjamin G

2017-08-01

S N i-like mechanisms, which involve front-face leaving group departure and nucleophile approach, have been observed experimentally and computationally in chemical and enzymatic substitution at α-glycosyl electrophiles. Since S N i-like, S N 1 and S N 2 substitution pathways can be energetically comparable, engineered switching could be feasible. Here, engineering of Sulfolobus solfataricus β-glycosidase, which originally catalyzed double S N 2 substitution, changed its mode to S N i-like. Destruction of the first S N 2 nucleophile through E387Y mutation created a β-stereoselective catalyst for glycoside synthesis from activated substrates, despite lacking a nucleophile. The pH profile, kinetic and mutational analyses, mechanism-based inactivators, X-ray structure and subsequent metadynamics simulations together suggest recruitment of substrates by π-sugar interaction and reveal a quantum mechanics-molecular mechanics (QM/MM) free-energy landscape for the substitution reaction that is similar to those of natural, S N i-like glycosyltransferases. This observation of a front-face mechanism in a β-glycosyltransfer enzyme highlights that S N i-like pathways may be engineered in catalysts with suitable environments and suggests that 'β-S N i' mechanisms may be feasible for natural glycosyltransfer enzymes.

Gold (I)-Catalyzed Diastereo- and Enantioselective 1,3-Dipolar Cycloaddition and Mannich Reactions of Azlactones

PubMed Central

Melhado, Asa D.; Amarante, Giovanni W.; Wang, Z. Jane; Luparia, Marco; Toste, F. Dean

2011-01-01

Azlactones participate in stereoselective reactions with electron-deficient alkenes and N-sulfonyl aldimines to give products of 1,3-dipolar cycloaddition and Mannich addition reactions respectively. Both of these reactions proceed with good to excellent diastereo- and enantioselectivity using a single class of gold-catalysts, namely C2-symmetric bis(phosphinegold(I) carboxylate)complexes. The development of the azlactone Mannich reaction to provide fully protected anti-α,β-diamino acid derivatives is described. 1,3-Dipolar cycloaddition reactions of several acyclic 1,2-disubstituted alkenes, and the chemistry of the resultant cycloadducts, are examined to probe the stereochemical course of this reaction. Reaction kinetics and tandem MS studies of both the cycloaddition and Mannich reactions are reported. These studies support a mechanism in which the gold complexes catalyze addition reactions through nucleophile activation rather than the more typical activation of the electrophilic reaction component. PMID:21341677

Fundamental Reaction Pathway for Peptide Metabolism by Proteasome: Insights from First-principles Quantum Mechanical/Molecular Mechanical Free Energy Calculations

PubMed Central

Wei, Donghui; Fang, Lei; Tang, Mingsheng; Zhan, Chang-Guo

2013-01-01

Proteasome is the major component of the crucial nonlysosomal protein degradation pathway in the cells, but the detailed reaction pathway is unclear. In this study, first-principles quantum mechanical/molecular mechanical free energy calculations have been performed to explore, for the first time, possible reaction pathways for proteasomal proteolysis/hydrolysis of a representative peptide, succinyl-leucyl-leucyl-valyl-tyrosyl-7-amino-4-methylcoumarin (Suc-LLVY-AMC). The computational results reveal that the most favorable reaction pathway consists of six steps. The first is a water-assisted proton transfer within proteasome, activating Thr1-Oγ. The second is a nucleophilic attack on the carbonyl carbon of a Tyr residue of substrate by the negatively charged Thr1-Oγ, followed by the dissociation of the amine AMC (third step). The fourth step is a nucleophilic attack on the carbonyl carbon of the Tyr residue of substrate by a water molecule, accompanied by a proton transfer from the water molecule to Thr1-Nz. Then, Suc-LLVY is dissociated (fifth step), and Thr1 is regenerated via a direct proton transfer from Thr1-Nz to Thr1-Oγ. According to the calculated energetic results, the overall reaction energy barrier of the proteasomal hydrolysis is associated with the transition state (TS3b) for the third step involving a water-assisted proton transfer. The determined most favorable reaction pathway and the rate-determining step have provided a reasonable interpretation of the reported experimental observations concerning the substituent and isotopic effects on the kinetics. The calculated overall free energy barrier of 18.2 kcal/mol is close to the experimentally-derived activation free energy of ~18.3–19.4 kcal/mol, suggesting that the computational results are reasonable. PMID:24111489

Driving Chemical Reactions in Plasmonic Nanogaps with Electrohydrodynamic Flow.

PubMed

Thrift, William J; Nguyen, Cuong Q; Darvishzadeh-Varcheie, Mahsa; Zare, Siavash; Sharac, Nicholas; Sanderson, Robert N; Dupper, Torin J; Hochbaum, Allon I; Capolino, Filippo; Abdolhosseini Qomi, Mohammad Javad; Ragan, Regina

2017-11-28

Nanoparticles from colloidal solution-with controlled composition, size, and shape-serve as excellent building blocks for plasmonic devices and metasurfaces. However, understanding hierarchical driving forces affecting the geometry of oligomers and interparticle gap spacings is still needed to fabricate high-density architectures over large areas. Here, electrohydrodynamic (EHD) flow is used as a long-range driving force to enable carbodiimide cross-linking between nanospheres and produces oligomers exhibiting sub-nanometer gap spacing over mm 2 areas. Anhydride linkers between nanospheres are observed via surface-enhanced Raman scattering (SERS) spectroscopy. The anhydride linkers are cleavable via nucleophilic substitution and enable placement of nucleophilic molecules in electromagnetic hotspots. Atomistic simulations elucidate that the transient attractive force provided by EHD flow is needed to provide a sufficient residence time for anhydride cross-linking to overcome slow reaction kinetics. This synergistic analysis shows assembly involves an interplay between long-range driving forces increasing nanoparticle-nanoparticle interactions and probability that ligands are in proximity to overcome activation energy barriers associated with short-range chemical reactions. Absorption spectroscopy and electromagnetic full-wave simulations show that variations in nanogap spacing have a greater influence on optical response than variations in close-packed oligomer geometry. The EHD flow-anhydride cross-linking assembly method enables close-packed oligomers with uniform gap spacings that produce uniform SERS enhancement factors. These results demonstrate the efficacy of colloidal driving forces to selectively enable chemical reactions leading to future assembly platforms for large-area nanodevices.

Mode-Specific SN2 Reaction Dynamics.

PubMed

Wang, Yan; Song, Hongwei; Szabó, István; Czakó, Gábor; Guo, Hua; Yang, Minghui

2016-09-01

Despite its importance in chemistry, the microscopic dynamics of bimolecular nucleophilic substitution (SN2) reactions is still not completely elucidated. In this publication, the dynamics of a prototypical SN2 reaction (F(-) + CH3Cl → CH3F + Cl(-)) is investigated using a high-dimensional quantum mechanical model on an accurate potential energy surface (PES) and further analyzed by quasi-classical trajectories on the same PES. While the indirect mechanism dominates at low collision energies, the direct mechanism makes a significant contribution. The reactivity is found to depend on the specific reactant vibrational mode excitation. The mode specificity, which is more prevalent in the direct reaction, is rationalized by a transition-state-based model.

Mechanism and stem-cell activity of 5-carboxycytosine decarboxylation determined by isotope tracing.

PubMed

Schiesser, Stefan; Hackner, Benjamin; Pfaffeneder, Toni; Müller, Markus; Hagemeier, Christian; Truss, Matthias; Carell, Thomas

2012-06-25

Eraserhead: Stem cells seem to erase epigenetic information by decarboxylation of the newly discovered epigenetic base 5-carboxycytosine (caC; see picture). This reaction is likely to involve a nucleophilic attack of the C5-C6 double bond. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electrostatic Potential Maps and Natural Bond Orbital Analysis: Visualization and Conceptualization of Reactivity in Sanger's Reagent

ERIC Educational Resources Information Center

Mottishaw, Jeffery D.; Erck, Adam R.; Kramer, Jordan H.; Sun, Haoran; Koppang, Miles

2015-01-01

Frederick Sanger's early work on protein sequencing through the use of colorimetric labeling combined with liquid chromatography involves an important nucleophilic aromatic substitution (S[subscript N]Ar) reaction in which the N-terminus of a protein is tagged with Sanger's reagent. Understanding the inherent differences between this S[subscript…

Invasive reaction assisted strand-displacement signal amplification for sensitive DNA detection.

PubMed

Zou, Bingjie; Song, Qinxin; Wang, Jianping; Liu, Yunlong; Zhou, Guohua

2014-11-18

A novel DNA detection assay was proposed by invasive reaction coupled with molecular beacon assisted strand-displacement signal amplification (IRASA). Target DNAs are firstly hybridized to two probes to initiate invasive reaction to produce amplified flaps. Then these flaps are further amplified by strand-displacement signal amplification. The detection limit was around 0.2 pM.

Reactions of small organic molecules on silver(110)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ayre, C.R.

1992-01-01

The interaction of two pairs of molecules (1) acetone (CH[sub 3])[sub 2]C=O and isobutylene (CH[sub 3])[sub 2] C=CH[sub 2] and (2) 1,2-propanediol CH[sub 3] CH (OH)CH[sub 2]OH and 1,3-propanediol HOCH[sub 2]CH[sub 2]CH[sub 2]OH with clean and oxygen-activated Ag(110) has been explored to investigate the effects of molecular structure on reactivity. Experimental techniques employed include temperature programmed reaction spectroscopy, isotopic labelling, surface displacement reactions, and electron energy loss spectroscopy. Acetone and isobutylene were studied to explore the relative importance of C=O and C=C bonds in governing the reactivity of structurally similar compounds. Nucleophilic attack by oxygen at the electron-deficient carbonyl carbonmore » in acetone results in reversible formation of the metallacycle (CH[sub 3])[sub 2]COO[sub (a)] at 110 K. Upon heating C-H bond activation by O[sub (a)] occurs near 215 K to yield acetone enolate CH[sub 2]=C(CH[sub 3])O[sub (a)] and evolve H[sub 2]O[sub (g)]. Atomic oxygen activates methyl C-H bonds in isobutylene via an acid-base mechanism. Although the major products are CO[sub 2(g)] and H[sub 2]O[sub (g)], a small amount of (CH[sub 3])[sub 2]C=CH[sub 2(g)] evolves near 310 K. Evidence for the formation of [pi]-2-methylallyl CH[sub 3]C(CH[sub 2])[sub 2(a)] and trimethylenementhane C(CH[sub 2])[sub 3(a)] is presented. The reaction of 1,2-propanediol CH[sub 3] CH(OH)CH[sub 2] OH with oxygen-activated Ag(110) has been compared with that of 1,3-propanediol HOCH[sub 2]CH[sub 2]CH[sub 2]OH to evaluate the effects of varying the position of O-H bonds in both diols to produce the corresponding dialkoxides.« less

Control of DNA strand displacement kinetics using toehold exchange.

PubMed

Zhang, David Yu; Winfree, Erik

2009-12-02

DNA is increasingly being used as the engineering material of choice for the construction of nanoscale circuits, structures, and motors. Many of these enzyme-free constructions function by DNA strand displacement reactions. The kinetics of strand displacement can be modulated by toeholds, short single-stranded segments of DNA that colocalize reactant DNA molecules. Recently, the toehold exchange process was introduced as a method for designing fast and reversible strand displacement reactions. Here, we characterize the kinetics of DNA toehold exchange and model it as a three-step process. This model is simple and quantitatively predicts the kinetics of 85 different strand displacement reactions from the DNA sequences. Furthermore, we use toehold exchange to construct a simple catalytic reaction. This work improves the understanding of the kinetics of nucleic acid reactions and will be useful in the rational design of dynamic DNA and RNA circuits and nanodevices.

Rice Os9BGlu31 Is a Transglucosidase with the Capacity to Equilibrate Phenylpropanoid, Flavonoid, and Phytohormone Glycoconjugates*

PubMed Central

Luang, Sukanya; Cho, Jung-Il; Mahong, Bancha; Opassiri, Rodjana; Akiyama, Takashi; Phasai, Kannika; Komvongsa, Juthamath; Sasaki, Nobuhiro; Hua, Yan-ling; Matsuba, Yuki; Ozeki, Yoshihiro; Jeon, Jong-Seong; Cairns, James R. Ketudat

2013-01-01

Glycosylation is an important mechanism of controlling the reactivities and bioactivities of plant secondary metabolites and phytohormones. Rice (Oryza sativa) Os9BGlu31 is a glycoside hydrolase family GH1 transglycosidase that acts to transfer glucose between phenolic acids, phytohormones, and flavonoids. The highest activity was observed with the donors feruloyl-glucose, 4-coumaroyl-glucose, and sinapoyl-glucose, which are known to serve as donors in acyl and glucosyl transfer reactions in the vacuole, where Os9BGlu31 is localized. The free acids of these compounds also served as the best acceptors, suggesting that Os9BGlu31 may equilibrate the levels of phenolic acids and carboxylated phytohormones and their glucoconjugates. The Os9BGlu31 gene is most highly expressed in senescing flag leaf and developing seed and is induced in rice seedlings in response to drought stress and treatment with phytohormones, including abscisic acid, ethephon, methyljasmonate, 2,4-dichlorophenoxyacetic acid, and kinetin. Although site-directed mutagenesis of Os9BGlu31 indicated a function for the putative catalytic acid/base (Glu169), catalytic nucleophile residues (Glu387), and His386, the wild type enzyme displays an unusual lack of inhibition by mechanism-based inhibitors of GH1 β-glucosidases that utilize a double displacement retaining mechanism. PMID:23430256

Phosphine-catalyzed cycloadditions of allenic ketones: new substrates for nucleophilic catalysis.

PubMed

Wallace, Debra J; Sidda, Rachel L; Reamer, Robert A

2007-02-02

A range of phosphine-catalyzed cycloaddition reactions of allenic ketones have been studied, extending the scope of these processes from the more widely used 2,3-butadienoates to allow access to a number of synthetically useful products. Reaction of allenyl methyl ketone 4 with exo-enones afforded spirocyclic compounds in good regioselectivity and promising enantioselectivity via a [2 + 3] cycloaddtion. Aromatic allenyl ketones undergo a phosphine-promoted dimerization to afford functionalized pyrans, leading to a formal [2 + 4] Diels-Alder product, but did not react in the [2 + 3] cycloaddition. The results from other reactions that had found utility with 2,3-butadienoates are also reported.

Biological detection and tagging using tailorable, reactive, highly fluorescent chemosensors.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shepodd, Timothy J.; Zifer, Thomas; McElhanon, James Ross

2006-11-01

This program was focused on the development of a fluorogenic chemosensor family that could tuned for reaction with electrophilic (e.g. chemical species, toxins) and nucleophilic (e.g. proteins and other biological molecules) species. Our chemosensor approach utilized the fluorescent properties of well-known berberine-type alkaloids. In situ chemosensor reaction with a target species transformed two out-of-plane, weakly conjugated, short-wavelength chromophores into one rigid, planar, conjugated, chromophore with strong long wavelength fluorescence (530-560 nm,) and large Stokes shift (100-180 nm). The chemosensor was activated with an isourea group which allowed for reaction with carboxylic acid moieties found in amino acids.

Iminoboronate Formation Leads to Fast and Reversible Conjugation Chemistry of α-Nucleophiles at Neutral pH

PubMed Central

Bandyopadhyay, Anupam

2015-01-01

Bioorthogonal reactions that are fast and reversible under physiologic conditions are in high demand for biological applications. Herein, we show that an ortho boronic acid substituent makes aryl ketones to rapidly conjugate with α-nucleophiles at neutral pH. Specifically, 2-acetylphenylboronic acid and derivatives were found to conjugate with phenylhydrazine with rate constants of 102 to 103 M−1 s−1, comparable to the fastest bioorthogonal conjugations known to date. 11B-NMR analysis reveals varied extent of iminoboronate formation of the conjugates, in which the imine nitrogen forms a dative bond with boron. The iminoboronate formation activates the imines for hydrolysis and exchange, rendering these oxime/hydrazone conjugations reversible and dynamic under physiologic conditions. The fast and dynamic nature of the iminoboronate chemistry should find wide applications in biology. PMID:26311464

Constructing a Catalytic Cycle for C-F to C-X (X = O, S, N) Bond Transformation Based on Gold-Mediated Ligand Nucleophilic Attack.

PubMed

Hu, Ji-Yun; Zhang, Jing; Wang, Gao-Xiang; Sun, Hao-Ling; Zhang, Jun-Long

2016-03-07

A tricoordinated gold(I) chloride complex, tBuXantphosAuCl, supported by a sterically bulky 9,9-dimethyl-4,5-bis(di-tert-butylphosphino)xanthene ligand (tBuXantphos) was synthesized. This complex features a remarkably longer Au-Cl bond length [2.632(1) Å] than bicoordinated linear gold complexes (2.27-2.30 Å) and tricoordinated XantphosAuCl [2.462(1) Å]. Single-crystal X-ray diffraction analysis of a cocrystal of tBuXantphosAuCl and pentafluoronitrobenzene (PFNB) and UV-vis spectroscopic titration experiments revealed the existence of an anion-π interaction between the Cl anion ligand and PFNB. Stoichiometric reaction between PFNB and tBuXantphosAuOtBu, after replacement of Cl by a more nucleophilic tBuO anion ligand, showed higher reactivity and para selectivity in the transformation of C-F to C-OtBu bond, distinctively different from that when only KOtBu was used (ortho selectivity) under the identical condition. Mechanistic studies including density functional theory calculations suggested a gold-mediated nucleophilic ligand attack of the C-F bond pathway via an SNAr process. On the basis of these results, using trimethylsilyl derivatives TMS-X (X = OMe, SEt, NEt2) as the nucleophilic ligand source and the fluorine acceptor, catalytic transformation of the C-F bond of aromatic substrates to the C-X (X = O, S, N) bond was achieved with tBuXantphosAuCl as the catalyst (up to 20 turnover numbers).

A mechanistic investigation into the irreversible protein binding and antigenicity of p-phenylenediamine.

PubMed

Jenkinson, Claire; Jenkins, Rosalind E; Maggs, James L; Kitteringham, Neil R; Aleksic, Maja; Park, B Kevin; Naisbitt, Dean J

2009-06-01

Exposure to the skin sensitizer p-phenylenediamine (PPD) is associated with allergic contact dermatitis; however, the ability of PPD to modify protein has not been fully investigated. The aims of this study were to characterize the reactions of PPD and the structurally related chemical 2,5-dimethyl-1,4-benzoquinonediamine with model nucleophiles, a synthetic peptide (DS3) containing each of the naturally occurring amino acids and His-tagged glutathione-S-transferase pi (GSTP), and to explore the effect of dimethyl substitution on PPD-specific T-cell responses using lymphocytes from allergic patients. The reductive soft nucleophiles N-acetyl cysteine and glutathione prevented PPD self-conjugation reactions and Bandrowski's base formation, but no adducts were detected. N-Acetyl lysine, a hard nucleophile, did not alter the rate of PPD degradation or form PPD adducts. With PPD and 2,5-dimethyl-1,4-benzoquinonediamine, only cysteine was targeted in the DS3 peptide. PPD and 2,5-dimethyl-1,4-benzoquinonediamine were also found to selectively modify the reactive Cys 47 residue of GSTP, which has a pK(a) of 3.5-4.2 and therefore exists in a largely protonated form. Glutathione formed mixed disulfides with the DS3 peptide, reducing levels of PPD binding. Lymphocytes from PPD allergic patients proliferated in the presence of PPD but not with 2,5-dimethyl-1,4-benzoquinonediamine. These results reveal that PPD and 2,5-dimethyl-1,4-benzoquinonediamine bind selectively to specific cysteine residues in peptides and proteins. Lymphocytes from PPD allergic patients were capable of discriminating between the different haptenic structures, suggesting that the hapten, but not the peptide moiety associated with MHC, is an important determinant for T-cell recognition.

Determinants of reactivity and selectivity in soluble epoxide hydrolase from quantum mechanics/molecular mechanics modeling.

PubMed

Lonsdale, Richard; Hoyle, Simon; Grey, Daniel T; Ridder, Lars; Mulholland, Adrian J

2012-02-28

Soluble epoxide hydrolase (sEH) is an enzyme involved in drug metabolism that catalyzes the hydrolysis of epoxides to form their corresponding diols. sEH has a broad substrate range and shows high regio- and enantioselectivity for nucleophilic ring opening by Asp333. Epoxide hydrolases therefore have potential synthetic applications. We have used combined quantum mechanics/molecular mechanics (QM/MM) umbrella sampling molecular dynamics (MD) simulations (at the AM1/CHARMM22 level) and high-level ab initio (SCS-MP2) QM/MM calculations to analyze the reactions, and determinants of selectivity, for two substrates: trans-stilbene oxide (t-SO) and trans-diphenylpropene oxide (t-DPPO). The calculated free energy barriers from the QM/MM (AM1/CHARMM22) umbrella sampling MD simulations show a lower barrier for phenyl attack in t-DPPO, compared with that for benzylic attack, in agreement with experiment. Activation barriers in agreement with experimental rate constants are obtained only with the highest level of QM theory (SCS-MP2) used. Our results show that the selectivity of the ring-opening reaction is influenced by several factors, including proximity to the nucleophile, electronic stabilization of the transition state, and hydrogen bonding to two active site tyrosine residues. The protonation state of His523 during nucleophilic attack has also been investigated, and our results show that the protonated form is most consistent with experimental findings. The work presented here illustrates how determinants of selectivity can be identified from QM/MM simulations. These insights may also provide useful information for the design of novel catalysts for use in the synthesis of enantiopure compounds.

Ionizing power and nucleophilicity in water in oil AOT-based microemulsions.

PubMed

García-Río, Luis; Hervella, Pablo; Leis, José Ramón

2005-08-16

A study was carried out on the solvolysis of substituted phenyl chloroformates in AOT/isooctane/water microemulsions. (AOT is the sodium salt of bis(2-ethyhexyl)sulfosuccinate.) The results obtained have been interpreted by taking into account the distribution of the chloroformates between the continuous medium and the interface of the microemulsions, where the reactions take place. The values obtained for the rate constant in the interface, k(i), decreases as the water content of the microemulsions increases, as a consequence of the decrease in its nucleophilic capacity. This behavior is consistent with a rate-determining step of water addition to the carbonyl group. The values of k(i) allow us to obtain the slopes of the Hammett correlations at the interface of the microemulsions, rho = 2.25, whose values are greater than those obtained in an aqueous medium, rho = 0.82. This increase in the Hammett slope is similar to that observed in ethanol/water mixtures and is a consequence of a variation in the structure of the transition state of the reaction where there is a smaller extension of the expulsion of the leaving group. The values of the rate constants at the interface of the microemulsions have allowed us, by means of the Grunwald-Winstein equation, to obtain the solvent ionizing power and the nucleophilicity of the solvent. The values obtained for Y(Cl) increase together with the water content of the microemulsion, whereas the values of N(T) decrease. These variations are a consequence of the interaction between the AOT headgroups and the interfacial water, where the water molecules act like electronic acceptors. The intensity of this interaction is greater if the system has a small water content, which explains the variation of Y(Cl) and N(T).

Synthesis and evaluation of 3-modified 1D-myo-inositols as inhibitors and substrates of phosphatidylinositol synthase and inhibitors of myo-inositol uptake by cells.

PubMed

Johnson, S C; Dahl, J; Shih, T L; Schedler, D J; Anderson, L; Benjamin, T L; Baker, D C

1993-11-12

A number of 3-substituted 1D-myo-inositols were synthesized and evaluated as substrates for phosphatidylinositol synthase and uptake by intact cells. 1D-3-Amino-, -3-chloro-, and -3-(acetylthio)-3-deoxy-myo-inositols were all synthesized by nucleophilic displacement of the 6-O-(trifluoromethyl)sulfonyl group of 1L-1,2:3,4-di-O-cyclohexylidene-5-O-methyl-6-O-[(trifluoromethyl)-sulfon yl] - chiro-inositol (which was prepared from L-quebrachitol), respectively, by reaction with LiN3, followed by reduction of the azido function, and with LiCl and KSAc to give the O-protected compounds. O-Demethylation using BBr3 and concomitant acetal hydrolysis furnished the free-hydroxy 3-amino- and 3-chloro-3-deoxy-1D-myo-inositols. The 3-mercapto analogue was obtained by removal of the acetal groups of the acetylthio analogue, followed by acetylation and purification of the peracetate, and subsequent O-demethylation and deacetylation. The 3-deoxy derivative was synthesized from the 6-O-(imidazol-1-ylthiocarbonyl) compound via Barton-McCombie deoxygenation. The 3-azido derivative was directly synthesized from 1L-1-O-tosyl-chiro-inositol via displacement with azide. The 3-keto analogue was prepared by Pt-catalyzed air oxidation of 1L-chiro-inositol. The compounds were all evaluated as substrates for phosphatidylinositol (PtdIns) synthase from mouse brain. The 3-NH2, 3-F, 3-deoxy, and 3-keto analogues all showed activity as substrates, as measured by liberation of cytidine monophosphate. These compounds also showed inhibition of the reaction of myo-[3H]inositol with PtdIns synthase. These results taken together indicate that these compounds are likely to be incorporated into phospholipids. As a further indication that these compounds might be useful as probes for the PtdIns pathway, it was demonstrated that the 3-NH2, 3-F, and 3-deoxy compounds are taken up by intact fibroblast cells as evidenced by their competing with myo-[3H]inositol uptake.

Synthesis and Side Chain Liquid Crystal Polymers by Living Ring Opening Metathesis Polymerization. 5. Influence of Mesogenic Group and Interconnecting Group on the Thermotropic Behavior of the Resulting Polymers

DTIC Science & Technology

1992-07-22

Scheme I. The first nucleophilic displacement of halide of an n-haloalkan-l-ol with 4-cyano-4’-hydroxybiphenyl employed potassium carbonate in...21 𔃼 polysiloxanes, 23.24 and polyacrylates . 2- All these polymers exhibit an odd-even effect. If one considers the total number of atoms between the...0.019 mol) and 4’-methoxy-4-hydroxybiphenyl (4.0g, 0.020 tool) were heated at 100°C in 40 mL of dimethylformamide in the presence of potassium carbonate

Simple catalytic mechanism for the direct coupling of α-carbonyls with functionalized amines: a one-step synthesis of Plavix.

PubMed

Evans, Ryan W; Zbieg, Jason R; Zhu, Shaolin; Li, Wei; MacMillan, David W C

2013-10-30

The direct α-amination of ketones, esters, and aldehydes has been accomplished via copper catalysis. In the presence of catalytic copper(II) bromide, a diverse range of carbonyl and amine substrates undergo fragment coupling to produce synthetically useful α-amino-substituted motifs. The transformation is proposed to proceed via a catalytically generated α-bromo carbonyl species; nucleophilic displacement of the bromide by the amine then delivers the α-amino carbonyl adduct while the catalyst is reconstituted. The practical value of this transformation is highlighted through one-step syntheses of two high-profile pharmaceutical agents, Plavix and amfepramone.

A Simple Catalytic Mechanism for the Direct Coupling of α-Carbonyls with Functionalized Amines: A One-Step Synthesis of Plavix

PubMed Central

Evans, Ryan W.; Zbieg, Jason R.; Zhu, Shaolin; Li, Wei; MacMillan, David W. C.

2014-01-01

The direct α-amination of ketones, esters, and aldehydes has been accomplished via copper catalysis. In the presence of catalytic copper(II) bromide, a diverse range of carbonyl and amine substrates undergo fragment coupling to produce synthetically useful α-amino substituted motifs. The transformation is proposed to proceed via a catalytically generated α-bromo carbonyl species; nucleophilic displacement of the bromide by the amine then delivers the α-amino carbonyl adduct while the catalyst is reconstituted. The practical value of this transformation is highlighted through one-step syntheses of two high–profile pharmaceutical agents, Plavix and amfepramone. PMID:24107144

Allylic and Allenic Halide Synthesis via NbCl5- and NbBr5-Mediated Alkoxide Rearrangements

PubMed Central

Ravikumar, P. C.; Yao, Lihua; Fleming, Fraser F.

2009-01-01

Addition of NbCl5, or NbBr5, to a series of magnesium, lithium, or potassium allylic or propargylic alkoxides directly provides allylic or allenic halides. Halogenation formally occurs through a metalla-halo-[3,3] rearrangement although concerted, ionic, and direct displacement mechanisms appear to operate competitively. Transposition of the olefin is equally effective for allylic alkoxides prepared by nucleophilic addition, deprotonation, or reduction. Experimentally, the niobium pentahalide halogenations are rapid, afford essentially pure E-allylic or allenic halides after extraction, and are applicable to a range of aliphatic and aromatic alcohols, aldehydes, and ketones. PMID:19739606

A practical deca-gram scale ring expansion of (R)-(-)-carvone to (R)-(+)-3-methyl-6-isopropenyl-cyclohept-3-enone-1.

PubMed

Alves, Leandro de C; Desiderá, André L; de Oliveira, Kleber T; Newton, Sean; Ley, Steven V; Brocksom, Timothy J

2015-07-28

A route to enantiopure (R)-(+)-3-methyl-6-isopropenyl-cyclohept-3-enone-1, an intermediate for terpenoids, has been developed and includes a highly chemo- and regioselective Tiffeneau-Demjanov reaction. Starting from readily available (R)-(-)-carvone, this robust sequence is available on a deca-gram scale and uses flow chemistry for the initial epoxidation reaction. The stereochemistry of the addition of two nucleophiles to the carbonyl group of (R)-(-)-carvone has been determined by X-ray diffraction studies and chemical correlation.

A Highly-Reduced Cobalt Terminal Carbyne: Divergent Metal- and α-Carbon-Centered Reactivity.

PubMed

Mokhtarzadeh, Charles C; Moore, Curtis E; Rheingold, Arnold L; Figueroa, Joshua S

2018-06-15

Reported here is the isolation of a dianionic cobalt terminal carbyne derived from chemical reduction of an encumbering isocyanide ligand. Crystallographic, spectroscopic and computational data reveal that this carbyne possesses a low-valent cobalt center with an extensively-filled d-orbital manifold. This electronic character renders the cobalt center the primary site of nucleophilicity upon reaction with protic substrates and silyl electrophiles. However, reactions with internal alkynes result in [2+2] cycloaddition with the carbyne carbon to form a new C-C bond.

Exploiting the Electrophilic and Nucleophilic Dual Role of Nitrile Imines: One-Pot, Three-Component Synthesis of Furo[2,3-d]pyridazin-4(5H)-ones.

PubMed

Giustiniano, Mariateresa; Mercalli, Valentina; Amato, Jussara; Novellino, Ettore; Tron, Gian Cesare

2015-08-21

An expeditious multicomponent reaction to synthesize tetrasubstituted furo[2,3-d]pyridazin-4(5H)-ones is reported. In brief, hydrazonoyl chlorides react with isocyanoacetamides, in the presence of TEA, to give 1,3-oxazol-2-hydrazones which, without being isolated, can react with dimethylacetylene dicarboxylate to afford furo[2,3-d]pyridazin-4(5H)-ones with an unprecedented level of complexity in a triple domino Diels-Alder/retro-Diels-Alder/lactamization reaction sequence.

An investigation of the preparation of high molecular weight perfluorocarbon polyethers

NASA Technical Reports Server (NTRS)

Watts, R. O.; Tarrant, P.

1972-01-01

High molecular weight perfluorocarbon polyether gums were obtained by photolysis of perfluorodienes and discyl fluorides containing a perfluorocarbon polyether backbond. The materials obtained are represented by chemical formulas. A method was developed whereby reactive acyl fluoride and trifluorovinyl end groups are converted into inert structures. In order to investigate the possible preparation of difunctional molecules which may be useful in polymer synthesis, the reactions of hexafluoropropene oxide (HFPO) with Grignard and organolithium reagents have been studied. Reactions of various nucleophilic reagents with HFPO were also investigated.

Catalytic Isonitrile Insertions and Condensations Initiated by RNC–X Complexation

PubMed Central

Fleming, Fraser F.

2014-01-01

Isonitriles are delicately poised chemical entities capable of being coaxed to react as nucleophiles or electrophiles. Directing this tunable reactivity with metal and non-metal catalysts provides rapid access to a large array of complex nitrogenous structures ideally functionalized for medicinal applications. Isonitrile insertion into transition metal complexes has featured in numerous synthetic and mechanistic studies, leading to rapid deployment of isonitriles in numerous catalytic processes, including multicomponent reactions (MCR). Covering the literature from 1990–2014, the present review collates reaction types to highlight reactivity trends and allow catalyst comparison. PMID:25484847

Characteristics of Growth Inhibition of Lactobacillus casei by 4-Nitroquinoline-n-Oxide

PubMed Central

Bond, T. J.; Young, Kamie Law; Andrus, Teresa Tarbell

1970-01-01

The bacteriostatic action of 4-nitroquinoline-n-oxide (4-NQO) for Lactobacillus casei is substantially reversed by d-and l-cysteine, glutathione, and 2,2-dihydroxy-1,4-dithiolbutane (dithioerythritol). The action appears to involve a chemical reaction between carbon atom 4 of 4-NQO and nucleophilic centers, such as -SH groups, located on essential cell constituents. The evidence presented indicates that the protective effect of d- and l-cysteine, glutathione, and dithioerythritol against the action involves reactions between 4-NQO and -SH compounds. PMID:5498599

Cyclization Cascades Initiated by 1,6-Conjugate Addition

PubMed Central

Brooks, Joshua L.; Frontier, Alison J.

2012-01-01

Dienyl diketones containing tethered acetates selectively undergo two different 1,6-conjugate addition-initiated cyclization cascades. One is a 1,6-conjugate addition/cyclization sequence with incorporation of the nucleophile, and the other is catalyzed by DABCO and is thought to proceed via a cyclic acetoxonium intermediate. The reaction behavior of substrates lacking the tethered acetate was also studied. The scope of both types of cyclization cascades, the role of the amine additive, and the factors controlling reactivity and selectivity in the two different reaction pathways is discussed. PMID:23004564

How does binuclear zinc amidohydrolase FwdA work in the initial step of methanogenesis: From formate to formyl-methanofuran.

PubMed

Zhang, Xue-Wei; Chen, Shi-Lu

2018-05-11

The initial step of methanogenesis is the fixation of CO 2 to formyl-methanofuran (formyl-MFR) catalyzed by formyl-MFR dehydrogenase, which can be divided into two half reactions. Herein, the second half reaction catalyzed by FwdA (formyl-methanofuran dehydrogenase subunit A), i.e., from formate to formyl-methanofuran, has been investigated using density functional theory and a chemical model based on the X-ray crystal structure. The calculations indicate that, compared with other well-known di-zinc hydrolases, the FwdA reaction employs a reverse mechanism, including the nucleophilic attack of MFR amine on formate carbon leading to a tetrahedral gem-diolate intermediate, two steps of proton transfer from amine to formate moieties assisted by the Asp385, and the CO bond dissociation to form the formyl-MFR product. The second step of proton transfer from the amine moiety to the Asp385 is rate-limiting with an overall barrier of 21.2 kcal/mol. The two zinc ions play an important role in stabilizing the transition states and intermediates, in particular the negative charge at the formate moiety originated from the nucleophilic attack of the MFR amine. The work here appends a crucial piece in the methanogenic mechanistics and advances the understanding of the global carbon cycle. Copyright © 2018 Elsevier Inc. All rights reserved.

Virtually complete control of simple and face diastereoselectivity in the Michael addition reactions between achiral equivalents of a nucleophilic glycine and (S)- or (R)-3-(E-enoyl)-4-phenyl-1,3-oxazolidin-2-ones: practical method for preparation of beta-substituted pyroglutamic acids and prolines.

PubMed

Soloshonok, Vadim A; Ueki, Hisanori; Tiwari, Rohit; Cai, Chaozhong; Hruby, Victor J

2004-07-23

This study demonstrates a new strategy for controlling the stereochemical outcome of the Michael addition reactions between nucleophilic glycine equivalents and alpha,beta-unsaturated carboxylic acid derivatives: The addition reactions between achiral Ni(II)-complex of the Schiff base of glycine with o-[N-alpha-pycolylamino]acetophenone and (S)- or (R)-3-(E-enoyl)-4-phenyl-1,3-oxazolidin-2-ones were shown to occur at room temperature in the presence of nonchelating organic bases and, most notably, with very high stereoselectivity at both newly formed stereogenic centers. Thus, the chiral 4-phenyl-1,3-oxazolidin-2-one moiety was found to control efficiently both face diastereoselectivities of the glycine derived enolate and the C,C double bond of the Michael acceptor. The new strategy developed in this work is methodologically superior to previous methods, most notably in terms of generality and synthetic efficiency. Excellent chemical yields and diastereoselectivities, combined with the simplicity of the experimental procedures, render the present method of immediate use for preparing various 3-substituted pyroglutamic acids and related amino acids (glutamic acids, glutamines, prolines, etc.) available via conventional transformations of the former.

Steric and electronic ligand perturbations in catalysis: asymmetric allylic substitution reactions using C2-symmetrical phosphorus-chiral (bi)ferrocenyl donors.

PubMed

Nettekoven, U; Widhalm, M; Kalchhauser, H; Kamer, P C; van Leeuwen, P W; Lutz, M; Spek, A L

2001-02-09

Three series of P-chiral diphosphines based on ferrocene (1a-f, 2a-c) and biferrocenyl skeletons (3a-c), including novel ligands 1f and 3c, were employed in palladium-catalyzed allylic substitution reactions. Steric effects imposed by the phosphine residues were studied using C2-symmetrical donors 1 (1 = 1,1'-bis(arylphenylphosphino)ferrocene with aryl groups a = 1-naphthyl, b = 2-naphthyl, c = 2-anisyl, d = 2-biphenylyl, e = 9-phenanthryl, and f = ferrocenyl), whereas para-methoxy- and/or para-trifluoromethyl substitution of the phenyl moieties in 1a enabled investigation of ligand electronic effects applying ferrocenyl diphosphines 2a-c. Ligands 3 (3 = 2,2'-bis- (arylphenylphosphino)-1,1'-biferrocenyls with aryl substituents a,c = 1-naphthyl (diastereomers) and b = 2-biphenylyl) allowed for comparison of backbone structure effects (bite angle variation) in catalysis. Linear and cyclic allylic acetates served as substrates in typical test reactions; upon attack of soft carbon and nitrogen nucleophiles on (E)-1,3-diphenylprop-2-ene-1-yl acetate the respective malonate, amine, or imide products were obtained in enantioselectivities of up to 99% ee. A crystal structure analysis of a palladium 1,3-diphenyl-eta 3-allyl complex incorporating ligand (S,S)-1a revealed a marked distortion of the allyl fragment, herewith defining the regioselectivity of nucleophile addition.

Substrate-Directed Catalytic Selective Chemical Reactions.

PubMed

Sawano, Takahiro; Yamamoto, Hisashi

2018-05-04

The development of highly efficient reactions at only the desired position is one of the most important subjects in organic chemistry. Most of the reactions in current organic chemistry are reagent- or catalyst-controlled reactions, and the regio- and stereoselectivity of the reactions are determined by the inherent nature of the reagent or catalyst. In sharp contrast, substrate-directed reaction determines the selectivity of the reactions by the functional group on the substrate and can strictly distinguish sterically and electronically similar multiple reaction sites in the substrate. In this Perspective, three topics of substrate-directed reaction are mainly reviewed: (1) directing group-assisted epoxidation of alkenes, (2) ring-opening reactions of epoxides by various nucleophiles, and (3) catalytic peptide synthesis. Our newly developed synthetic methods with new ligands including hydroxamic acid derived ligands realized not only highly efficient reactions but also pinpointed reactions at the expected position, demonstrating the substrate-directed reaction as a powerful method to achieve the desired regio- and stereoselective functionalization of molecules from different viewpoints of reagent- or catalyst-controlled reactions.

Cu(II)-catalyzed esterification reaction via aerobic oxidative cleavage of C(CO)-C(alkyl) bonds.

PubMed

Ma, Ran; He, Liang-Nian; Liu, An-Hua; Song, Qing-Wen

2016-02-04

A novel Cu(II)-catalyzed aerobic oxidative esterification of simple ketones for the synthesis of esters has been developed with wide functional group tolerance. This process is assumed to go through a tandem sequence consisting of α-oxygenation/esterification/nucleophilic addition/C-C bond cleavage and carbon dioxide is released as the only byproduct.

Ion-Molecule Association in Acrylonitrile

NASA Technical Reports Server (NTRS)

Wilson, Paul F.; Milligan, Daniel B.; McEwan, Murray J.

1997-01-01

Acrylonitrile (propernenitrile or vinyl cyanide) polymerizes readily via a radical mechanism in solution at room temparature. The propensity to polymerize is sufficiently strong that it is usual to add a radical scavenger to the solution to prevent polymerization when oxygen (an inhibitor) is removed. Polymerization of acrylonitrile is also know to occur via nucleophilic addition of an anion by a michael-type reaction.

Stereoselective Synthesis of Tetrasubstituted Furylalkenes via Gold-Catalyzed Cross-Coupling of Enynones with Diazo Compounds.

PubMed

Liu, Pei; Sun, Jiangtao

2017-07-07

A stereoselective, gold-catalyzed, cross-coupling reaction of enynones with diazo compounds has been developed, affording 2-alkenylfurans in moderate to good yields with excellent E-stereoselectivity. Upon using diazo compounds as nucleophiles to trap the in situ formed gold furyl carbene, this protocol provides a novel path toward the formation of unsymmetrical tetrasubstituted alkenes.

Methacrylate monolithic columns functionalized with epinephrine for capillary electrochromatography applications.

PubMed

Carrasco-Correa, Enrique Javier; Ramis-Ramos, Guillermo; Herrero-Martínez, José Manuel

2013-07-12

Epinephrine-bonded polymeric monoliths for capillary electrochromatography (CEC) were developed by nucleophilic substitution reaction of epoxide groups of poly(glycidyl-methacrylate-co-ethylenedimethacrylate) (poly(GMA-co-EDMA)) monoliths using epinephrine as nucleophilic reagent. The ring opening reaction under dynamic conditions was optimized. Successful chemical modification of the monolith surface was ascertained by in situ Raman spectroscopy characterization. In addition, the amount of epinephrine groups that was bound to the monolith surface was evaluated by oxidation of the catechol groups with Ce(IV), followed by spectrophotometric measurement of unreacted Ce(IV). About 9% of all theoretical epoxide groups of the parent monolith were bonded to epinephrine. The chromatographic behavior of the epinephrine-bonded monolith in CEC conditions was assessed with test mixtures of alkyl benzenes, aniline derivatives and substituted phenols. In comparison to the poly(GMA-co-EDMA) monoliths, the epinephrine-bonded monoliths exhibited a much higher retention and slight differences in selectivity. The epinephrine-bonded monolith was further modified by oxidation with a Ce(IV) solution and compared with the epinephrine-bonded monoliths. The resulting monolithic stationary phases were evaluated in terms of reproducibility, giving RSD values below 9% in the parameters investigated. Copyright © 2013 Elsevier B.V. All rights reserved.

A facile synthesis of highly stable multiblock poly(arylene ether)s based alkaline membranes for fuel cells

NASA Astrophysics Data System (ADS)

Jasti, Amaranadh; Shahi, Vinod K.

2014-12-01

Herein, we are disclosing simple route for the preparation of alkaline membranes (AMs) based on aminated multiblock poly(arylene ether)s (AMPEs) synthesized by nucleophilic substitution-poly condensation followed by quaternization and alkalization reactions. In this procedure, four quaternary ammonium groups are successfully introduced without use of carcinogenic reagents such as chloromethylmethyl ether (CMME). Hydrophilic/hydrophobic phase separation is responsible for their high hydroxide conductivity (∼150 mS cm-1 at 80 °C) due to development of interconnected ion transport pathway. AMs are exhibiting good alkaline stability due to the presence of two vicinal quaternary ammonium groups and avoid degradation such as Sommelet-Hauser rearrangement and Hofmann elimination. Vicinal quaternary ammonium groups also resist nucleophilic (OH-) attack and suppress the Stevens rearrangement as well as SN2 substitution reaction due to stearic hindrance. Optimized AM (AMPE-M20N15 (55% DCM)) exhibits about 0.95 V open circuit voltage (OCV) and 48.8 mW cm-2 power density at 65 °C in alkaline direct methanol fuel cell (ADMFC) operation. These results suggest promising begin for the preparation of stable and conductive AMs for ADMFC applications and useful for developing hydroxide conductive materials.

N-silyl oxyketene imines are underused yet highly versatile reagents for catalytic asymmetric synthesis

NASA Astrophysics Data System (ADS)

Denmark, Scott E.; Wilson, Tyler W.

2010-11-01

The reactions of acyl anion equivalents (d1 synthons) with carbonyl electrophiles allow for the construction of a wide range of molecules useful for the synthesis of biologically active compounds, natural products and chiral ligands. Despite their utility, significant challenges still exist for developing catalytic, enantioselective variants of these reactions. For example, the asymmetric benzoin process, arguably the most characteristic reaction of d synthetic equivalents, finds no general solution for reactions involving aliphatic acyl anions. In this Article, we introduce a new class of stable, isolable silyl ketene imines derived from protected cyanohydrins. These nucleophiles serve as acyl anion equivalents in Lewis base catalysed aldol addition reactions and allow for the preparation of cross-benzoin and glycolate-aldol products in high yield and with exceptional diastereo- and enantioselectivities.

Fundamental Reaction Pathway and Free Energy Profile for Butyrylcholinesterase-Catalyzed Hydrolysis of Heroin

PubMed Central

Qiao, Yan; Han, Keli; Zhan, Chang-Guo

2013-01-01

The pharmacological function of heroin requires an activation process which transforms heroin into 6-monoacetylmorphine (6-MAM) which is the most active form. The primary enzyme responsible for this activation process in human plasma is butyrylcholinesterase (BChE). The detailed reaction pathway of the activation process via BChE-catalyzed hydrolysis has been explored computationally, for the first time, in the present study by performing molecular dynamics simulation and first-principles quantum mechanical/molecular mechanical free energy calculations. It has been demonstrated that the whole reaction process includes acylation and deacylation stages. The acylation consists of two reaction steps, i.e. the nucleophilic attack on the carbonyl carbon of 3-acetyl group of heroin by the hydroxyl oxygen of Ser198 side chain and the dissociation of 6-MAM. The deacylation also consists of two reaction steps, i.e. the nucleophilic attack on the carbonyl carbon of the acyl-enzyme intermediate by a water molecule and the dissociation of the acetic acid from Ser198. The calculated free energy profile reveals that the second transition state (TS2) should be rate-determining. The structural analysis reveals that the oxyanion hole of BChE plays an important role in the stabilization of the rate-determining transition state TS2. The free energy barrier (15.9±0.2 or 16.1±0.2 kcal/mol) calculated for the rate-determining step is in good agreement with the experimentally-derived activation free energy (~16.2 kcal/mol), suggesting that the mechanistic insights obtained from the present computational study are reliable. The obtained structural and mechanistic insights could be valuable for use in future rational design of a novel therapeutic treatment of heroin abuse. PMID:23992153

A Theoretical Study of 8-Chloro-9-Hydroxy-Aflatoxin B₁, the Conversion Product of Aflatoxin B₁ by Neutral Electrolyzed Water.

PubMed

Escobedo-González, René; Méndez-Albores, Abraham; Villarreal-Barajas, Tania; Aceves-Hernández, Juan Manuel; Miranda-Ruvalcaba, René; Nicolás-Vázquez, Inés

2016-07-21

Theoretical studies of 8-chloro-9-hydroxy-aflatoxin B₁ (2) were carried out by Density Functional Theory (DFT). This molecule is the reaction product of the treatment of aflatoxin B₁ (1) with hypochlorous acid, from neutral electrolyzed water. Determination of the structural, electronic and spectroscopic properties of the reaction product allowed its theoretical characterization. In order to elucidate the formation process of 2, two reaction pathways were evaluated-the first one considering only ionic species (Cl⁺ and OH(-)) and the second one taking into account the entire hypochlorous acid molecule (HOCl). Both pathways were studied theoretically in gas and solution phases. In the first suggested pathway, the reaction involves the addition of chlorenium ion to 1 forming a non-classic carbocation assisted by anchimeric effect of the nearest aromatic system, and then a nucleophilic attack to the intermediate by the hydroxide ion. In the second studied pathway, as a first step, the attack of the double bond from the furanic moiety of 1 to the hypochlorous acid is considered, accomplishing the same non-classical carbocation, and again in the second step, a nucleophilic attack by the hydroxide ion. In order to validate both reaction pathways, the atomic charges, the highest occupied molecular orbital and the lowest unoccupied molecular orbital were obtained for both substrate and product. The corresponding data imply that the C₉ atom is the more suitable site of the substrate to interact with the hydroxide ion. It was demonstrated by theoretical calculations that a vicinal and anti chlorohydrin is produced in the terminal furan ring. Data of the studied compound indicate an important reduction in the cytotoxic and genotoxic potential of the target molecule, as demonstrated previously by our research group using different in vitro assays.

What Controls the "Off/On Switch" in the Toehold-Mediated Strand Displacement Reaction on DNA Conjugated Gold Nanoparticles?

PubMed

Yao, Dongbao; Wang, Bei; Xiao, Shiyan; Song, Tingjie; Huang, Fujian; Liang, Haojun

2015-06-30

In DNA dynamic nanotechnology, a toehold-mediated DNA strand-displacement reaction has demonstrated its capability in building complex autonomous system. In most cases, the reaction is performed in pure DNA solution that is essentially a one-phase system. In the present work, we systematically investigated the reaction in a heterogeneous media, in which the strand that implements a displacing action is conjugated on gold nanoparticles. By monitoring the kinetics of spherical nucleic acid (SNA) assembly driven by toehold-mediated strand displacement reaction, we observed significant differences, i.e., the abrupt jump in behavior of an "off/on switch", in the reaction rate when the invading toehold was extended to eight bases from seven bases. These phenomena are attributed to the effect of steric hindrance arising from the high density of invading strand conjugated to AuNPs. Based on these studies, an INHIBIT logic gate presenting good selectivity was developed.

Silyl Glyoxylates. Conception and Realization of Flexible Conjunctive Reagents for Multicomponent Coupling

PubMed Central

Boyce, Gregory R.; Greszler, Stephen N.; Linghu, Xin; Malinowski, Justin T.; Nicewicz, David A.; Satterfield, Andrew D.; Schmitt, Daniel C.; Steward, Kimberly M.

2012-01-01

This Perspective describes the discovery and development of silyl glyoxylates, a new family of conjunctive reagents for use in multicomponent coupling reactions. The selection of the nucleophilic and electrophilic components determines whether the silyl glyoxylate reagent will function as a synthetic equivalent to the dipolar glycolic acid synthon, the glyoxylate anion synthon, or the α-keto ester homoenolate synthon. The ability to select for any of these reaction modes has translated to excellent structural diversity in the derived three- and four-component coupling adducts. Preliminary findings on the development of catalytic reactions using these reagents are detailed, as are the design and discovery of new reactions directed toward particular functional group arrays embedded within bioactive natural products. PMID:22414181

Computer-assisted study on the reaction between pyruvate and ylide in the pathway leading to lactyl-ThDP.

PubMed

Alvarado, Omar; Jaña, Gonzalo; Delgado, Eduardo J

2012-08-01

In this study the formation of the lactyl-thiamin diphosphate intermediate (L-ThDP) is addressed using density functional theory calculations at X3LYP/6-31++G(d,p) level of theory. The study includes potential energy surface scans, transition state search, and intrinsic reaction coordinate calculations. Reactivity is analyzed in terms of Fukui functions. The results allow to conclude that the reaction leading to the formation of L-ThDP occurs via a concerted mechanism, and during the nucleophilic attack on the pyruvate molecule, the ylide is in its AP form. The calculated activation barrier for the reaction is 19.2 kcal/mol, in agreement with the experimental reported value.

A reagent for safe and efficient diazo-transfer to primary amines: 2-azido-1,3-dimethylimidazolinium hexafluorophosphate.

PubMed

Kitamura, Mitsuru; Kato, So; Yano, Masakazu; Tashiro, Norifumi; Shiratake, Yuichiro; Sando, Mitsuyoshi; Okauchi, Tatsuo

2014-07-07

Organic azides were prepared from primary amines in high yields by a metal free diazo-transfer reaction using 2-azido-1,3-dimethylimidazolinium hexafluorophosphate (ADMP), which is safe and stable crystalline. The choice of base was important in the diazo-transfer reaction. In general, 4-(N,N-dimethyl)aminopyridine (DMAP) was efficient, but a stronger base such as alkylamine or DBU was more appropriate for the reaction of nucleophilic primary amines. X-ray single crystal structural analysis and geometry optimization using density functional theory (B3LYP/6-31G**) were conducted to study the ADMP structure, and the diazo-transfer reaction mechanism was explained with the help of the results of these analyses.

Lewis Acid-Assisted Photoinduced Intermolecular Coupling between Acylsilanes and Aldehydes: A Formal Cross Benzoin-Type Condensation.

PubMed

Ishida, Kento; Tobita, Fumiya; Kusama, Hiroyuki

2018-01-12

Intermolecular carbon-carbon bond-forming reaction between readily available acylsilanes and aldehydes was achieved under photoirradiation conditions with assistance of a catalytic amount of Lewis acid. Nucleophilic addition of photochemically generated siloxycarbenes to aldehydes followed by 1,4-silyl migration afforded synthetically useful α-siloxyketones. Electrophilic activation of aldehydes by Lewis acid is highly important to realize this reaction efficiently, otherwise the yield of the desired coupling products were significantly decreased. Noteworthy is that a formal cross benzoin-type reaction using acylsilanes was achieved under Lewis acidic conditions. This is the first example of Lewis acid-catalyzed reaction of photochemically generated siloxycarbenes with electrophiles. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Maillard reaction versus other nonenzymatic modifications in neurodegenerative processes.

PubMed

Pamplona, Reinald; Ilieva, Ekaterina; Ayala, Victoria; Bellmunt, Maria Josep; Cacabelos, Daniel; Dalfo, Esther; Ferrer, Isidre; Portero-Otin, Manuel

2008-04-01

Nonenzymatic protein modifications are generated from direct oxidation of amino acid side chains and from reaction of the nucleophilic side chains of specific amino acids with reactive carbonyl species. These reactions give rise to specific markers that have been analyzed in different neurodegenerative diseases sharing protein aggregation, such as Alzheimer's disease, Pick's disease, Parkinson's disease, dementia with Lewy bodies, Creutzfeldt-Jakob disease, and amyotrophic lateral sclerosis. Collectively, available data demonstrate that oxidative stress homeostasis, mitochondrial function, and energy metabolism are key factors in determining the disease-specific pattern of protein molecular damage. In addition, these findings suggest the lack of a "gold marker of oxidative stress," and, consequently, they strengthen the need for a molecular dissection of the nonenzymatic reactions underlying neurodegenerative processes.

DFT Studies of SN2 Dechlorination of Polychlorinated Biphenyls.

PubMed

Krzemińska, Agnieszka; Paneth, Piotr

2016-06-21

Nucleophilic dechlorination of all 209 PCBs congeners by ethylene glycol anion has been studied theoretically at the DFT level. The obtained Gibbs free energies of activation are in the range 7-22 kcal/mol. The reaction Gibbs free energies indicate that all reactions are virtually irreversible. Due to geometric constrains these reactions undergo rather untypical attack with attacking oxygen atom being nearly perpendicular to the attacked C-Cl bond. The most prone to substitution are chlorine atoms that occupy ortho- (2, 2', 6, 6') positions. These results provide extensive information on the PEG/KOH dependent PCBs degradation. They can also be used in further developments of reaction class transition state theory (RC-TST) for description of complex reactive systems encountered for example in combustion processes.

Electrode Reaction Mechanism of Ag 2VO 2PO 4 Cathode

DOE PAGES

Zhang, Ruibo; Abtew, Tesfaye A.; Quackenbush, Nicholas F.; ...

2016-05-09

In this study, the high capacity of primary lithium-ion cathode Ag 2VO 2PO 4 is facilitated by both displacement and insertion reaction mechanisms. Whether the Ag extrusion (specifically, Ag reduction with Ag metal displaced from the host crystal) and V reduction are sequential or concurrent remains unclear. A microscopic description of the reaction mechanism is required for developing design rules for new multimechanism cathodes, combining both displacement and insertion reactions. However, the amorphization of Ag 2VO 2PO 4 during lithiation makes the investigation of the electrode reaction mechanism difficult with conventional characterization tools. For addressing this issue, a combination ofmore » local probes of pair-distribution function and X-ray spectroscopy were used to obtain a description of the discharge reaction. We determine that the initial reaction is dominated by silver extrusion with vanadium playing a supporting role. In addition, once sufficient Ag has been displaced, the residual Ag + in the host can no longer stabilize the host structure and V–O environment (i.e., onset of amorphization). After amorphization, silver extrusion continues but the vanadium reduction dominates the reaction. As a result, the crossover from primarily silver reduction displacement to vanadium reduction is facilitated by the amorphization that makes vanadium reduction increasingly more favorable.« less

Electrode Reaction Mechanism of Ag 2VO 2PO 4 Cathode

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Ruibo; Abtew, Tesfaye A.; Quackenbush, Nicholas F.

In this study, the high capacity of primary lithium-ion cathode Ag 2VO 2PO 4 is facilitated by both displacement and insertion reaction mechanisms. Whether the Ag extrusion (specifically, Ag reduction with Ag metal displaced from the host crystal) and V reduction are sequential or concurrent remains unclear. A microscopic description of the reaction mechanism is required for developing design rules for new multimechanism cathodes, combining both displacement and insertion reactions. However, the amorphization of Ag 2VO 2PO 4 during lithiation makes the investigation of the electrode reaction mechanism difficult with conventional characterization tools. For addressing this issue, a combination ofmore » local probes of pair-distribution function and X-ray spectroscopy were used to obtain a description of the discharge reaction. We determine that the initial reaction is dominated by silver extrusion with vanadium playing a supporting role. In addition, once sufficient Ag has been displaced, the residual Ag + in the host can no longer stabilize the host structure and V–O environment (i.e., onset of amorphization). After amorphization, silver extrusion continues but the vanadium reduction dominates the reaction. As a result, the crossover from primarily silver reduction displacement to vanadium reduction is facilitated by the amorphization that makes vanadium reduction increasingly more favorable.« less

Predicting Hydride Donor Strength via Quantum Chemical Calculations of Hydride Transfer Activation Free Energy.

PubMed

Alherz, Abdulaziz; Lim, Chern-Hooi; Hynes, James T; Musgrave, Charles B

2018-01-25

We propose a method to approximate the kinetic properties of hydride donor species by relating the nucleophilicity (N) of a hydride to the activation free energy ΔG ⧧ of its corresponding hydride transfer reaction. N is a kinetic parameter related to the hydride transfer rate constant that quantifies a nucleophilic hydridic species' tendency to donate. Our method estimates N using quantum chemical calculations to compute ΔG ⧧ for hydride transfers from hydride donors to CO 2 in solution. A linear correlation for each class of hydrides is then established between experimentally determined N values and the computationally predicted ΔG ⧧ ; this relationship can then be used to predict nucleophilicity for different hydride donors within each class. This approach is employed to determine N for four different classes of hydride donors: two organic (carbon-based and benzimidazole-based) and two inorganic (boron and silicon) hydride classes. We argue that silicon and boron hydrides are driven by the formation of the more stable Si-O or B-O bond. In contrast, the carbon-based hydrides considered herein are driven by the stability acquired upon rearomatization, a feature making these species of particular interest, because they both exhibit catalytic behavior and can be recycled.

Assessing the issue of instability due to Michael adduct formation in novel chemical entities possessing a carbon-carbon double bond during early drug development--applicability of common laboratory analytical protocols.

PubMed

Polepally, Akshanth Reddy; Kumar, Venkata V Pavan; Bhamidipati, Ravikanth; Kota, Jagannath; Naveed, Shaik Abdul; Reddy, Karnati Harinder; Mamidi, Rao N V S; Selvakumar, N; Mullangi, Ramesh; Srinivas, Nuggehally R

2008-09-01

The discovery of small-molecule novel chemical entities (NCEs) is often a complex play between appropriate structural requirements and optimization of the desired efficacy, safety and pharmacokinetic properties. One of the typical structural variants such as having an active carbon-carbon double bond (alpha, beta-unsaturated carbonyl group) in xenobiotics may lead to stability issues. Such functionalities are extremely reactive, paving way to nucleophilic attack by endogenously occurring and ubiquitous nucleophiles like thiols. While it is easy to make a unilateral decision to not pursue the development of xenobiotics with such functionalities, we question the wisdom of such a decision. In this report, we present in vitro methodologies with appropriate examples to illustrate the ease of assessing the reactivity of the xenobiotics containing double bonds with a known nucleophile. The protocols involve simple reaction procedures followed by measurements using standard laboratory equipments (UV spectrophotometer, HPLC and LC-MS). Our data suggests that not all xenobiotics with carbon-carbon double bonds readily form a Michael's adduct product with glutathione. Hence, the criterion for dropping discovery compounds because of alpha,beta-unsaturated double bonds needs to be reconsidered.

Ankle-Dorsiflexion Range of Motion and Landing Biomechanics

PubMed Central

Fong, Chun-Man; Blackburn, J. Troy; Norcross, Marc F.; McGrath, Melanie; Padua, Darin A.

2011-01-01

Abstract Context: A smaller amount of ankle-dorsiflexion displacement during landing is associated with less knee-flexion displacement and greater ground reaction forces, and greater ground reaction forces are associated with greater knee-valgus displacement. Additionally, restricted dorsiflexion range of motion (ROM) is associated with greater knee-valgus displacement during landing and squatting tasks. Because large ground reaction forces and valgus displacement and limited knee-flexion displacement during landing are anterior cruciate ligament (ACL) injury risk factors, dorsiflexion ROM restrictions may be associated with a greater risk of ACL injury. However, it is unclear whether clinical measures of dorsiflexion ROM are associated with landing biomechanics. Objective: To evaluate relationships between dorsiflexion ROM and landing biomechanics. Design: Descriptive laboratory study. Setting: Research laboratory. Patients or Other Participants: Thirty-five healthy, physically active volunteers. Intervention(s): Passive dorsiflexion ROM was assessed under extended-knee and flexed-knee conditions. Landing biomechanics were assessed via an optical motion-capture system interfaced with a force plate. Main Outcome Measure(s): Dorsiflexion ROM was measured in degrees using goniometry. Knee-flexion and knee-valgus displacements and vertical and posterior ground reaction forces were calculated during the landing task. Simple correlations were used to evaluate relationships between dorsiflexion ROM and each biomechanical variable. Results: Significant correlations were noted between extended-knee dorsiflexion ROM and knee-flexion displacement (r  =  0.464, P  =  .029) and vertical (r  =  −0.411, P  =  .014) and posterior (r  =  −0.412, P  =  .014) ground reaction forces. All correlations for flexed-knee dorsiflexion ROM and knee-valgus displacement were nonsignificant. Conclusions: Greater dorsiflexion ROM was associated with greater knee-flexion displacement and smaller ground reaction forces during landing, thus inducing a landing posture consistent with reduced ACL injury risk and limiting the forces the lower extremity must absorb. These findings suggest that clinical techniques to increase plantar-flexor extensibility and dorsiflexion ROM may be important additions to ACL injury-prevention programs. PMID:21214345

An improved radiosynthesis of [18F]AV-133: a PET imaging agent for vesicular monoamine transporter 2.

PubMed

Zhu, Lin; Liu, Yajing; Plössl, Karl; Lieberman, Brian; Liu, Jingying; Kung, Hank F

2010-02-01

Recently, a PET tracer, 9-[(18)F]fluoropropyl-(+)-dihydrotetrabenazine ([(18)F]AV-133), targeting vesicular monoamine transporter 2 (VMAT2) in the central nervous system has been reported. It is currently under Phase II clinical trials to establish its usefulness in the diagnosis of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. The radiolabeling of [(18)F]AV-133, nucleophilic fluorination reaction and potential effects of pseudo-carrier were evaluated by in vivo biodistribution. The preparation of [(18)F]AV-133 was evaluated under different conditions, specifically by employing different precursors (-OTs or -Br as the leaving group at the 9-propoxy position), reagents (K222/K(2)CO(3) vs. tributylammonium bicarbonate) and solvents (acetonitrile vs. DMSO), reaction temperature and reaction time. With optimized conditions from these experiments, radiosynthesis and purification with solid-phase extraction (SPE) of [(18)F]AV-133 were performed by an automated nucleophilic [(18)F]fluorination module. In vivo biodistribution in mice on [(18)F]AV-133 purified by either HPLC (no-carrier-added) or the SPE method (containing a pseudo-carrier) was performed and the results compared. Under a mild fluorination condition (heating at 115 degrees C for 5 min in dimethyl sulfoxide), [(18)F]AV-133 was obtained in a high yield using either -OTs or -Br as the leaving group. However, the -OTs precursor gave better radiochemical yields (>70%, thin layer chromatography analysis) compared to those of the -Br precursor. The optimized reaction conditions were successfully implemented to an automated nucleophilic fluorination module. Labeling and purification of [(18)F]AV133 were readily achieved via this automatic module in good radiochemical yield of 21-41% (n=10) in 40 min. The radiochemical purity was larger than 95%. Biodistribution of SPE-purified product (containing a pseudo-carrier) in mice showed a high striatum/cerebellum ratio (4.18+/-0.51), which was comparable to that of HPLC-purified [(18)F]AV-133 (4.51+/-0.10). The formation of [(18)F]AV-133 was evaluated under different labeling conditions. These improved labeling conditions and SPE purification were successfully implemented into an automated synthesis module. This offers a short preparation time (about 40 min), simplicity in operation and ready applicability for routine clinical operation. (c) 2010 Elsevier Inc. All rights reserved.

Integrating a DNA Strand Displacement Reaction with a Whispering Gallery Mode Sensor for Label-Free Mercury (II) Ion Detection.

PubMed

Wu, Fengchi; Wu, Yuqiang; Niu, Zhongwei; Vollmer, Frank

2016-07-29

Mercury is an extremely toxic chemical pollutant of our environment. It has attracted the world's attention due to its high mobility and the ease with which it accumulates in organisms. Sensitive devices and methods specific for detecting mercury ions are, hence, in great need. Here, we have integrated a DNA strand displacement reaction with a whispering gallery mode (WGM) sensor for demonstrating the detection of Hg(2+) ions. Our approach relies on the displacement of a DNA hairpin structure, which forms after the binding of mercury ions to an aptamer DNA sequence. The strand displacement reaction of the DNA aptamer provides highly specific and quantitative means for determining the mercury ion concentration on a label-free WGM sensor platform. Our approach also shows the possibility for manipulating the kinetics of a strand displacement reaction with specific ionic species.

Integrating a DNA Strand Displacement Reaction with a Whispering Gallery Mode Sensor for Label-Free Mercury (II) Ion Detection

PubMed Central

Wu, Fengchi; Wu, Yuqiang; Niu, Zhongwei; Vollmer, Frank

2016-01-01

Mercury is an extremely toxic chemical pollutant of our environment. It has attracted the world’s attention due to its high mobility and the ease with which it accumulates in organisms. Sensitive devices and methods specific for detecting mercury ions are, hence, in great need. Here, we have integrated a DNA strand displacement reaction with a whispering gallery mode (WGM) sensor for demonstrating the detection of Hg2+ ions. Our approach relies on the displacement of a DNA hairpin structure, which forms after the binding of mercury ions to an aptamer DNA sequence. The strand displacement reaction of the DNA aptamer provides highly specific and quantitative means for determining the mercury ion concentration on a label-free WGM sensor platform. Our approach also shows the possibility for manipulating the kinetics of a strand displacement reaction with specific ionic species. PMID:27483277

Real-time monitoring of enzyme-free strand displacement cascades by colorimetric assays

NASA Astrophysics Data System (ADS)

Duan, Ruixue; Wang, Boya; Hong, Fan; Zhang, Tianchi; Jia, Yongmei; Huang, Jiayu; Hakeem, Abdul; Liu, Nannan; Lou, Xiaoding; Xia, Fan

2015-03-01

The enzyme-free toehold-mediated strand displacement reaction has shown potential for building programmable DNA circuits, biosensors, molecular machines and chemical reaction networks. Here we report a simple colorimetric method using gold nanoparticles as signal generators for the real-time detection of the product of the strand displacement cascade. During the process the assembled gold nanoparticles can be separated, resulting in a color change of the solution. This assay can also be applied in complex mixtures, fetal bovine serum, and to detect single-base mismatches. These results suggest that this method could be of general utility to monitor more complex enzyme-free strand displacement reaction-based programmable systems or for further low-cost diagnostic applications.The enzyme-free toehold-mediated strand displacement reaction has shown potential for building programmable DNA circuits, biosensors, molecular machines and chemical reaction networks. Here we report a simple colorimetric method using gold nanoparticles as signal generators for the real-time detection of the product of the strand displacement cascade. During the process the assembled gold nanoparticles can be separated, resulting in a color change of the solution. This assay can also be applied in complex mixtures, fetal bovine serum, and to detect single-base mismatches. These results suggest that this method could be of general utility to monitor more complex enzyme-free strand displacement reaction-based programmable systems or for further low-cost diagnostic applications. Electronic supplementary information (ESI) available: Experimental procedures and analytical data are provided. See DOI: 10.1039/c5nr00697j

Alternative strategy for converting an inverting glycoside hydrolase into a glycosynthase.

PubMed

Honda, Yuji; Fushinobu, Shinya; Hidaka, Masafumi; Wakagi, Takayoshi; Shoun, Hirofumi; Taniguchi, Hajime; Kitaoka, Motomitsu

2008-04-01

The tyrosine residue Y198 is known to support a nucleophilic water molecule with the general base residue, D263, in the reducing-end xylose-releasing exo-oligoxylanase (Rex). A mutation in the tyrosine residue changing it into phenylalanine caused a drastic decrease in the hydrolytic activity and a small increase in the F(-) releasing activity from alpha-xylobiosyl fluoride in the presence of xylose. In contrast, mutations at D263 resulted in the decreased F(-) releasing activity. As a result of the high F(-) releasing activity and low hydrolytic activity, Y198F of Rex accumulates a large amount of product during the glycosynthase reaction. We propose a novel method for producing a glycosynthase from an inverting glycoside hydrolase by mutating a residue that holds the nucleophilic water molecule with the general base residue while keeping the general base residue intact.

Correlation of the rates of solvolysis of neopentyl chloroformate-a recommended protecting agent.

PubMed

D'Souza, Malcolm J; Carter, Shannon E; Kevill, Dennis N

2011-02-15

The specific rates of solvolysis of neopentyl chloroformate (1) have been determined in 21 pure and binary solvents at 45.0 °C. In most solvents the values are essentially identical to those for ethyl and n-propyl chloroformates. However, in aqueous-1,1,1,3,3,3-hexafluoro-2-propanol mixtures (HFIP) rich in fluoroalcohol, 1 solvolyses appreciably faster than the other two substrates. Linear free energy relationship (LFER) comparison of the specific rates of solvolysis of 1 with those for phenyl chloroformate and those for n-propyl chloroformate are helpful in the mechanistic considerations, as is also the treatment in terms of the Extended Grunwald-Winstein equation. It is proposed that the faster reaction for 1 in HFIP rich solvents is due to the influence of a 1,2-methyl shift, leading to a tertiary alkyl cation, outweighing the only weak nucleophilic solvation of the cation possible in these low nucleophilicity solvents.

Organocatalytic asymmetric arylation of indoles enabled by azo groups

NASA Astrophysics Data System (ADS)

Qi, Liang-Wen; Mao, Jian-Hui; Zhang, Jian; Tan, Bin

2018-01-01

Arylation is a fundamental reaction that can be mostly fulfilled by electrophilic aromatic substitution and transition-metal-catalysed aryl functionalization. Although the azo group has been used as a directing group for many transformations via transition-metal-catalysed aryl carbon-hydrogen (C-H) bond activation, there remain significant unmet challenges in organocatalytic arylation. Here, we show that the azo group can effectively act as both a directing and activating group for organocatalytic asymmetric arylation of indoles via formal nucleophilic aromatic substitution of azobenzene derivatives. Thus, a wide range of axially chiral arylindoles have been achieved in good yields with excellent enantioselectivities by utilizing chiral phosphoric acid as catalyst. Furthermore, highly enantioenriched pyrroloindoles bearing two contiguous quaternary chiral centres have also been obtained via a cascade enantioselective formal nucleophilic aromatic substitution-cyclization process. This strategy should be useful in other related research fields and will open new avenues for organocatalytic asymmetric aryl functionalization.

Organocatalytic asymmetric arylation of indoles enabled by azo groups.

PubMed

Qi, Liang-Wen; Mao, Jian-Hui; Zhang, Jian; Tan, Bin

2018-01-01

Arylation is a fundamental reaction that can be mostly fulfilled by electrophilic aromatic substitution and transition-metal-catalysed aryl functionalization. Although the azo group has been used as a directing group for many transformations via transition-metal-catalysed aryl carbon-hydrogen (C-H) bond activation, there remain significant unmet challenges in organocatalytic arylation. Here, we show that the azo group can effectively act as both a directing and activating group for organocatalytic asymmetric arylation of indoles via formal nucleophilic aromatic substitution of azobenzene derivatives. Thus, a wide range of axially chiral arylindoles have been achieved in good yields with excellent enantioselectivities by utilizing chiral phosphoric acid as catalyst. Furthermore, highly enantioenriched pyrroloindoles bearing two contiguous quaternary chiral centres have also been obtained via a cascade enantioselective formal nucleophilic aromatic substitution-cyclization process. This strategy should be useful in other related research fields and will open new avenues for organocatalytic asymmetric aryl functionalization.

Iminoboronate Formation Leads to Fast and Reversible Conjugation Chemistry of α-Nucleophiles at Neutral pH.

PubMed

Bandyopadhyay, Anupam; Gao, Jianmin

2015-10-12

Bioorthogonal reactions that are fast and reversible under physiological conditions are in high demand for biological applications. Herein, it is shown that an ortho boronic acid substituent makes aryl ketones rapidly conjugate with α-nucleophiles at neutral pH. Specifically, 2-acetylphenylboronic acid and derivatives were found to conjugate with phenylhydrazine with rate constants of 10(2) to 10(3) M(-1) s(-1) , comparable to the fastest bioorthogonal conjugations known to date. (11) B NMR analysis revealed the varied extent of iminoboronate formation of the conjugates, in which the imine nitrogen forms a dative bond with boron. The iminoboronate formation activates the imines for hydrolysis and exchange, rendering these oxime/hydrazone conjugations reversible and dynamic under physiological conditions. The fast and dynamic nature of the iminoboronate chemistry should find wide applications in biology. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enzymatic Addition of Alcohols to Terpenes by Squalene Hopene Cyclase Variants.

PubMed

Kühnel, Lisa C; Nestl, Bettina M; Hauer, Bernhard

2017-11-16

Squalene-hopene cyclases (SHCs) catalyze the polycyclization of squalene into a mixture of hopene and hopanol. Recently, amino-acid residues lining the catalytic cavity of the SHC from Alicyclobacillus acidocaldarius were replaced by small and large hydrophobic amino acids. The alteration of leucine 607 to phenylalanine resulted in increased enzymatic activity towards the formation of an intermolecular farnesyl-farnesyl ether product from farnesol. Furthermore, the addition of small-chain alcohols acting as nucleophiles led to the formation of non-natural ether-linked terpenoids and, thus, to significant alteration of the product pattern relative to that obtained with the wild type. It is proposed that the mutation of leucine at position 607 may facilitate premature quenching of the intermediate by small alcohol nucleophiles. This mutagenesis-based study opens the field for further intermolecular bond-forming reactions and the generation of non-natural products. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evidence for Interfacial Halogen Bonding.

PubMed

Swords, Wesley B; Simon, Sarah J C; Parlane, Fraser G L; Dean, Rebecca K; Kellett, Cameron W; Hu, Ke; Meyer, Gerald J; Berlinguette, Curtis P

2016-05-10

A homologous series of donor-π-acceptor dyes was synthesized, differing only in the identity of the halogen substituents about the triphenylamine (TPA; donor) portion of each molecule. Each Dye-X (X=F, Cl, Br, and I) was immobilized on a TiO2 surface to investigate how the halogen substituents affect the reaction between the light-induced charge-separated state, TiO2 (e(-) )/Dye-X(+) , with iodide in solution. Transient absorption spectroscopy showed progressively faster reactivity towards nucleophilic iodide with more polarizable halogen substituents: Dye-F < Dye-Cl < Dye-Br < Dye-I. Given that all other structural and electronic properties for the series are held at parity, with the exception of an increasingly larger electropositive σ-hole on the heavier halogens, the differences in dye regeneration kinetics for Dye-Cl, Dye-Br, and Dye-I are ascribed to the extent of halogen bonding with the nucleophilic solution species. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis, crystal structures, computational studies and antimicrobial activity of new designed bis((5-aryl-1,3,4-oxadiazol-2-yl)thio)alkanes

NASA Astrophysics Data System (ADS)

Ahmed, Muhammad Naeem; Sadiq, Beenish; Al-Masoudi, Najim A.; Yasin, Khawaja Ansar; Hameed, Shahid; Mahmood, Tariq; Ayub, Khurshid; Tahir, Muhammad Nawaz

2018-03-01

A new series of bis((5-aryl-1,3,4-oxadiazol-2-yl)thio)alkanes 4-14 have been synthesized via nucleophilic substitution reaction of dihaloalkanes with respective 1,3,4-oxadiazole-2-thiols 3a-f, and characterized by spectroscopic techniques. The structures of 4 and 12 were unambiguously confirmed by single-crystal X-ray diffraction analysis. Density functional theory calculations at B3LYP/6-31 + G(d) level of theory were performed for comparison of X-ray geometric parameters, molecular electrostatic potential (MEP) and frontier molecular orbital analyses of synthesized compounds. MEP analysis revealed that these compounds are nucleophilic in nature. Frontier molecular orbitals (FMOs) analysis of 4-14 was performed for evaluation of kinetic stability. All synthesized compounds were screened in vitro for antimicrobial activity against three bacterial and three fungal strains and showed promising results.

Copper-Catalyzed Chan-Lam Cyclopropylation of Phenols and Azaheterocycles.

PubMed

Derosa, Joseph; O'Duill, Miriam L; Holcomb, Matthew; Boulous, Mark N; Patman, Ryan L; Wang, Fen; Tran-Dubé, Michelle; McAlpine, Indrawan; Engle, Keary M

2018-04-06

Small molecules containing cyclopropane-heteroatom linkages are commonly needed in medicinal chemistry campaigns yet are problematic to prepare using existing methods. To address this issue, a scalable Chan-Lam cyclopropylation reaction using potassium cyclopropyl trifluoroborate has been developed. With phenol nucleophiles, the reaction effects O-cyclopropylation, whereas with 2-pyridones, 2-hydroxybenzimidazoles, and 2-aminopyridines the reaction brings about N-cyclopropylation. The transformation is catalyzed by Cu(OAc) 2 and 1,10-phenanthroline and employs 1 atm of O 2 as the terminal oxidant. This method is operationally convenient to perform and provides a simple, strategic disconnection toward the synthesis of cyclopropyl aryl ethers and cyclopropyl amine derivatives bearing an array of functional groups.

The Study of Substitution and Elimination Reactions Using Gas Chromatography: An Examination of the Effects of Alkane and Base Structure on Product Distributions

ERIC Educational Resources Information Center

Wharry, Donald L.

2011-01-01

An experiment that compares product distribution obtained by either substitution or elimination utilizing alkyl bromides and methoxide, ethoxide, or t-butoxide as the base (or nucleophile) is described. The change in product distribution caused by steric effects of the base and substrate are readily apparent. Prior work on this experiment focused…

An iron/amine-catalyzed cascade process for the enantioselective functionalization of allylic alcohols.

PubMed

Quintard, Adrien; Constantieux, Thierry; Rodriguez, Jean

2013-12-02

Three is a lucky number: An enantioselective transformation of allylic alcohols into β-chiral saturated alcohols has been developed by combining two distinct metal- and organocatalyzed catalytic cycles. This waste-free triple cascade process merges an iron-catalyzed borrowing-hydrogen step with an aminocatalyzed nucleophilic addition reaction. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

United States Air Force Academy, Department of Chemistry Research: AY 1982-83.

DTIC Science & Technology

1984-03-01

9 𔃼 0 Several reactions have been run using grignard reagents but initial results have not been examined in enough detail to make com- ments at this...potential in aromatic nucleophilic substitution and are useful reagents for the preparation of unsymmetrically substituted biaryls and benzoic acids...aromatic monofluorinated compounds suffers several disadvantages. First, several of the conventional fluori- nating reagents are ineffective in

Thiourea in the Construction of C-S Bonds as Part of an Undergraduate Organic Chemistry Laboratory Course

ERIC Educational Resources Information Center

Lu, Guo-ping; Chen, Fei; Cai, Chun

2017-01-01

The nucleophilic aromatic substitution reaction and thia-Michael addition using thiourea as an odorless, cheap, and easy-to-handle sulfur source in water are described, which can be used to teach upper-division undergraduates the role of thiourea in the formation of C-S bonds and the principles of green chemistry. The use of a cheap, nontoxic…

Acyl Meldrum's acid derivatives: application in organic synthesis

NASA Astrophysics Data System (ADS)

Janikowska, K.; Rachoń, J.; Makowiec, S.

2014-07-01

This review is focused on an important class of Meldrum's acid derivatives commonly known as acyl Meldrum's acids. The preparation methods of these compounds are considered including the recently proposed and rather rarely used ones. The chemical properties of acyl Meldrum's acids are described in detail, including thermal stability and reactions with various nucleophiles. The possible mechanisms of these transformations are analyzed. The bibliography includes 134 references.

Stereospecific Ni-Catalyzed Cross-Coupling of Potassium Alkenyltrifluoroborates with Alkyl Halides

PubMed Central

2015-01-01

A general method for the alkenylation of alkyl electrophiles using nearly stoichiometric amounts of the air- and moisture-stable potassium organotrifluoroborates has been developed. Various functional groups were tolerated on both the nucleophilic and electrophilic partner. Reactions of highly substituted E- and Z-alkenyltrifluoroborates, as well as vinyl- and propenyltrifluoroborates, were successful, and no loss of stereochemistry or regiochemistry was observed. PMID:24666316

Probing the Catalytic Mechanism of Vibrio harveyi GH20 β-N-Acetylglucosaminidase by Chemical Rescue

PubMed Central

Meekrathok, Piyanat; Suginta, Wipa

2016-01-01

Background Vibrio harveyi GH20 β-N-acetylglucosaminidase (VhGlcNAcase) is a chitinolytic enzyme responsible for the successive degradation of chitin fragments to GlcNAc monomers, activating the onset of the chitin catabolic cascade in marine Vibrios. Methods Two invariant acidic pairs (Asp303-Asp304 and Asp437-Glu438) of VhGlcNAcase were mutated using a site-directed mutagenesis strategy. The effects of these mutations were examined and the catalytic roles of these active-site residues were elucidated using a chemical rescue approach. Enhancement of the enzymic activity of the VhGlcNAcase mutants was evaluated by a colorimetric assay using pNP-GlcNAc as substrate. Results Substitution of Asp303, Asp304, Asp437 or Glu438 with Ala/Asn/Gln produced a dramatic loss of the GlcNAcase activity. However, the activity of the inactive D437A mutant was recovered in the presence of sodium formate. Our kinetic data suggest that formate ion plays a nucleophilic role by mimicking the β-COO-side chain of Asp437, thereby stabilizing the reaction intermediate during both the glycosylation and the deglycosylation steps. Conclusions Chemical rescue of the inactive D437A mutant of VhGlcNAcase by an added nucleophile helped to identify Asp437 as the catalytic nucleophile/base, and hence its acidic partner Glu438 as the catalytic proton donor/acceptor. General Significance Identification of the catalytic nucleophile of VhGlcNAcases supports the proposal of a substrate-assisted mechanism of GH20 GlcNAcases, requiring the catalytic pair Asp437-Glu438 for catalysis. The results suggest the mechanistic basis of the participation of β-N-acetylglucosaminidase in the chitin catabolic pathway of marine Vibrios. PMID:26870945

A theoretical investigation of substituent effects on the stability and reactivity of N-heterocyclic olefin carboxylates.

PubMed

Dong, Liang; Wen, Jun; Li, Weiyi

2015-08-21

A theoretical study of substituent effects on the stability and reactivity of novel synthesized N-heterocyclic olefin (NHO) carboxylates has been performed using a combination of density functional theory (DFT) calculations, molecular electrostatic potential (MESP) minimum and nucleophilicity index analyses. These calculations demonstrate that the nucleophilicity of free NHO is stronger than that of the NHO-CO2 adduct and, hence, the thermally unstable NHO-CO2 adduct should be a more efficient organocatalyst for nucleophile-mediated reactions. The stability of the NHO-CO2 adduct, as well as the reactivity of free NHO, is strongly dependent on the electronic and steric effects of the C- and N-substituents on the imidazole ring. This dependency is reflected by the measured MESP minimum for the carboxylate moiety, the NHO-CO2 adduct (Vmin1), and the terminal carbon atom of free NHO (Vmin2). C-Substituents exert only electronic effects while N-substituents exert both electronic and steric effects. In general, the electron-withdrawing groups on the C- and N-positions favor decarboxylation while weakening the reactivity of NHO. These positions favor decarboxylation due to the simultaneous decrease of the electronic density on the carboxyl moiety of the NHO-CO2 and the terminal carbon atom of olefins. Additionally, the balance between the stability of the NHO-CO2 and the reactivity of free NHO can be tuned by the combined effects of the C- and N-substituents. The introduction of weak electron-withdrawing groups at the C-position and aromatic substituents or similar ring-strained entities at the N-position favors decarboxylation of the NHO-CO2 adduct and ensures the free NHO as a strong nucleophile.

Atherton–Todd reaction: mechanism, scope and applications

PubMed Central

Le Corre, Stéphanie S; Berchel, Mathieu; Couthon-Gourvès, Hélène; Haelters, Jean-Pierre

2014-01-01

Summary Initially, the Atherton–Todd (AT) reaction was applied for the synthesis of phosphoramidates by reacting dialkyl phosphite with a primary amine in the presence of carbon tetrachloride. These reaction conditions were subsequently modified with the aim to optimize them and the reaction was extended to different nucleophiles. The mechanism of this reaction led to controversial reports over the past years and is adequately discussed. We also present the scope of the AT reaction. Finally, we investigate the AT reaction by means of exemplary applications, which mainly concern three topics. First, we discuss the activation of a phenol group as a phosphate which allows for subsequent transformations such as cross coupling and reduction. Next, we examine the AT reaction applied to produce fire retardant compounds. In the last section, we investigate the use of the AT reaction for the production of compounds employed for biological applications. The selected examples to illustrate the applications of the Atherton–Todd reaction mainly cover the past 15 years. PMID:24991268

Optical reaction cell and light source for ›18F! fluoride radiotracer synthesis

DOEpatents

Ferrieri, Richard A.; Schlyer, David; Becker, Richard J.

1998-09-15

Apparatus for performing organic synthetic reactions, particularly no-carrier-added nucleophilic radiofluorination reactions for PET radiotracer production. The apparatus includes an optical reaction cell and a source of broadband infrared radiant energy, which permits direct coupling of the emitted radiant energy with the reaction medium to heat the reaction medium. Preferably, the apparatus includes means for focusing the emitted radiant energy into the reaction cell, and the reaction cell itself is preferably configured to reflect transmitted radiant energy back into the reaction medium to further improve the efficiency of the apparatus. The apparatus is well suited to the production of high-yield syntheses of 2-›.sup.18 F!fluoro-2-deoxy-D-glucose. Also provided is a method for performing organic synthetic reactions, including the manufacture of ›.sup.18 F!-labeled compounds useful as PET radiotracers, and particularly for the preparation of 2-›.sup.18 F!fluoro-2-deoxy-D-glucose in higher yields than previously possible.

Optical reaction cell and light source for [18F] fluoride radiotracer synthesis

DOEpatents

Ferrieri, R.A.; Schlyer, D.; Becker, R.J.

1998-09-15

An apparatus is disclosed for performing organic synthetic reactions, particularly no-carrier-added nucleophilic radiofluorination reactions for PET radiotracer production. The apparatus includes an optical reaction cell and a source of broadband infrared radiant energy, which permits direct coupling of the emitted radiant energy with the reaction medium to heat the reaction medium. Preferably, the apparatus includes means for focusing the emitted radiant energy into the reaction cell, and the reaction cell itself is preferably configured to reflect transmitted radiant energy back into the reaction medium to further improve the efficiency of the apparatus. The apparatus is well suited to the production of high-yield syntheses of 2-[{sup 18}F]fluoro-2-deoxy-Dglucose. Also provided is a method for performing organic synthetic reactions, including the manufacture of [{sup 18}F]-labeled compounds useful as PET radiotracers, and particularly for the preparation of 2-[{sup 18}F]fluoro-2-deoxy-D-glucose in higher yields than previously possible. 4 figs.

Strand displacement by DNA polymerase III occurs through a tau-psi-chi link to single-stranded DNA-binding protein coating the lagging strand template.

PubMed

Yuan, Quan; McHenry, Charles S

2009-11-13

In addition to the well characterized processive replication reaction catalyzed by the DNA polymerase III holoenzyme on single-stranded DNA templates, the enzyme possesses an intrinsic strand displacement activity on flapped templates. The strand displacement activity is distinguished from the single-stranded DNA-templated reaction by a high dependence upon single-stranded DNA binding protein and an inability of gamma-complex to support the reaction in the absence of tau. However, if gamma-complex is present to load beta(2), a truncated tau protein containing only domains III-V will suffice. This truncated protein is sufficient to bind both the alpha subunit of DNA polymerase (Pol) III and chipsi. This is reminiscent of the minimal requirements for Pol III to replicate short single-stranded DNA-binding protein (SSB)-coated templates where tau is only required to serve as a scaffold to hold Pol III and chi in the same complex (Glover, B., and McHenry, C. (1998) J. Biol. Chem. 273, 23476-23484). We propose a model in which strand displacement by DNA polymerase III holoenzyme depends upon a Pol III-tau-psi-chi-SSB binding network, where SSB is bound to the displaced strand, stabilizing the Pol III-template interaction. The same interaction network is probably important for stabilizing the leading strand polymerase interactions with authentic replication forks. The specificity constant (k(cat)/K(m)) for the strand displacement reaction is approximately 300-fold less favorable than reactions on single-stranded templates and proceeds with a slower rate (150 nucleotides/s) and only moderate processivity (approximately 300 nucleotides). PriA, the initiator of replication restart on collapsed or misassembled replication forks, blocks the strand displacement reaction, even if added to an ongoing reaction.

Tandem catalytic allylic amination and [2,3]-Stevens rearrangement of tertiary amines.

PubMed

Soheili, Arash; Tambar, Uttam K

2011-08-24

We have developed a catalytic allylic amination involving tertiary aminoesters and allylcarbonates, which is the first example of the use of tertiary amines as intermolecular nucleophiles in metal-catalyzed allylic substitution chemistry. This process is employed in a tandem ammonium ylide generation/[2,3]-rearrangement reaction, which formally represents a palladium-catalyzed Stevens rearrangement. Low catalyst loadings and mild reaction conditions are compatible with an unprecedented substrate scope for the ammonium ylide functionality, and products are generated in high yields and diastereoselectivities. Mechanistic studies suggested the reversible formation of an ammonium intermediate.

A review on chemistry of a powerful organic electron acceptor 7, 7, 8, 8, tetracynoquinodimethane (TCNQ)

NASA Astrophysics Data System (ADS)

Singh, Yadunath

2018-05-01

Organic semiconductors have so far found extensive practical applications similar to inorganic semiconductors. Interest in these compounds has been stimulated by the synthesis of several powerful electron acceptors, such as tetracynoethylene (TCNE), 7, 7, 8, 8, tetracynoquinodimethane (TCNQ) and cyno-p-benzoquinone. In this connection TCNQ is of particular interest, due to presence of four powerful electron accepting groups in its molecule. Nucleophillic addition reactions, which are rarely encountered among unsaturated compounds, as well as addition reactions proceeding via a one electron transfer stage are characteristic of this substance.

Highly stereoselective three-component reactions of phenylselenomagnesium bromide, acetylenic sulfones, and saturated aldehydes/ketones or alpha,beta-unsaturated enals or enones.

PubMed

Huang, Xian; Xie, Meihua

2002-12-13

beta-Phenylseleno-alpha-tolylsulfonyl-substituted alkenes were synthesized via the three-component conjugate-nucleophilic addition of acetylenic sulfones, phenylselenomagnesium bromide, and carbonyl compounds, such as aldehydes, aliphatic ketones, or alpha,beta-unsaturated enals or enones. The reaction is highly regio- and stereoselective with moderate to good yields. Functionalized allylic alcohols were obtained in the case of aldehydes and aliphatic ketones. In the case of alpha,beta-unsaturated enones, functionalized allylic alcohols or functionalized gamma,delta-unsaturated ketones were obtained, depending on the structures of the ketones.

Spectator Ions ARE Important! A Kinetic Study of the Copper-Aluminum Displacement Reaction

ERIC Educational Resources Information Center

Sobel, Sabrina G.; Cohen, Skyler

2010-01-01

Surprisingly, spectator ions are responsible for unexpected kinetics in the biphasic copper(II)-aluminum displacement reaction, with the rate of reaction dependent on the identity of the otherwise ignored spectator ions. Application of a published kinetic analysis developed for a reaction between a rotating Al disk and a Cu(II) ion solution to the…

Palladium/N-heterocyclic carbene catalysed regio and diastereoselective reaction of ketones with allyl reagents via inner-sphere mechanism

PubMed Central

Bai, Da-Chang; Yu, Fei-Le; Wang, Wan-Ying; Chen, Di; Li, Hao; Liu, Qing-Rong; Ding, Chang-Hua; Chen, Bo; Hou, Xue-Long

2016-01-01

The palladium-catalysed allylic substitution reaction is one of the most important reactions in transition-metal catalysis and has been well-studied in the past decades. Most of the reactions proceed through an outer-sphere mechanism, affording linear products when monosubstituted allyl reagents are used. Here, we report an efficient Palladium-catalysed protocol for reactions of β-substituted ketones with monosubstituted allyl substrates, simply by using N-heterocyclic carbene as ligand, leading to branched products with up to three contiguous stereocentres in a (syn, anti)-mode with excellent regio and diastereoselectivities. The scope of the protocol in organic synthesis has been examined preliminarily. Mechanistic studies by both experiments and density functional theory (DFT) calculations reveal that the reaction proceeds via an inner-sphere mechanism—nucleophilic attack of enolate oxygen on Palladium followed by C–C bond-forming [3,3']-reductive elimination. PMID:27283477

Palladium/N-heterocyclic carbene catalysed regio and diastereoselective reaction of ketones with allyl reagents via inner-sphere mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bai, Da -Chang; Yu, Fei -Le; Wang, Wan -Ying

The palladium-catalysed allylic substitution reaction is one of the most important reactions in transition-metal catalysis and has been well-studied in the past decades. Most of the reactions proceed through an outer-sphere mechanism, affording linear products when monosubstituted allyl reagents are used. Here, we report an efficient Palladium-catalysed protocol for reactions of beta-substituted ketones with monosubstituted allyl substrates, simply by using N-heterocyclic carbene as ligand, leading to branched products with up to three contiguous stereocentres in a ( syn, anti)-mode with excellent regio and diastereoselectivities. The scope of the protocol in organic synthesis has been examined preliminarily. As a result, mechanisticmore » studies by both experiments and density functional theory ( DFT) calculations reveal that the reaction proceeds via an inner-sphere mechanism-nucleophilic attack of enolate oxygen on Palladium followed by C-C bond-forming [3,3']-reductive elimination.« less

Palladium/N-heterocyclic carbene catalysed regio and diastereoselective reaction of ketones with allyl reagents via inner-sphere mechanism

DOE PAGES

Bai, Da -Chang; Yu, Fei -Le; Wang, Wan -Ying; ...

2016-06-10

The palladium-catalysed allylic substitution reaction is one of the most important reactions in transition-metal catalysis and has been well-studied in the past decades. Most of the reactions proceed through an outer-sphere mechanism, affording linear products when monosubstituted allyl reagents are used. Here, we report an efficient Palladium-catalysed protocol for reactions of beta-substituted ketones with monosubstituted allyl substrates, simply by using N-heterocyclic carbene as ligand, leading to branched products with up to three contiguous stereocentres in a ( syn, anti)-mode with excellent regio and diastereoselectivities. The scope of the protocol in organic synthesis has been examined preliminarily. As a result, mechanisticmore » studies by both experiments and density functional theory ( DFT) calculations reveal that the reaction proceeds via an inner-sphere mechanism-nucleophilic attack of enolate oxygen on Palladium followed by C-C bond-forming [3,3']-reductive elimination.« less

Polyaryl ethers and related polysiloxane copolymer molecular coatings preparation and radiation degrdation

NASA Technical Reports Server (NTRS)

Mcgrath, J. E.; Hedrick, J. L.; Webster, D. C.; Johnson, B. C.; Mohanty, D. K.; Yilgor, I.

1983-01-01

Poly(arylene ether sulfones) comprise a class of materials known as engineering thermoplastics which have a variety of important applications. These polymers are tough, rigid materials with good mechanical properties over a wide temperature range, and they are processed by conventional methods into products typically having excellent hydrolytic, thermal, oxidative and dimensional stability. Wholly aromatic random copolymers of hydroquinone and biphenol with 4.4 prime dichlorodiphenyl sulfone were synthesized via mechanical nucleophilic displacement. Their structures were characterized and mechanical behavior studied. These tough, ductile copolymers show excellent radiation resistance to electron beam treatment and retain much of the mechanical properties up to at least 700 Mrads under argon.

Simple, rapid method for the preparation of isotopically labeled formaldehyde

DOEpatents

Hooker, Jacob Matthew [Port Jefferson, NY; Schonberger, Matthias [Mains, DE; Schieferstein, Hanno [Aabergen, DE; Fowler, Joanna S [Bellport, NY

2011-10-04

Isotopically labeled formaldehyde (*C.sup..sctn.H.sub.2O) is prepared from labeled methyl iodide (*C.sup..sctn.H.sub.3I) by reaction with an oxygen nucleophile having a pendant leaving group. The mild and efficient reaction conditions result in good yields of *C.sup..sctn.H.sub.2O with little or no *C isotopic dilution. The simple, efficient production of .sup.11CH.sub.2O is described. The use of the .sup.11CH.sub.2O for the formation of positron emission tomography tracer compounds is described. The reaction can be incorporated into automated equipment available to radiochemistry laboratories. The isotopically labeled formaldehyde can be used in a variety of reactions to provide radiotracer compounds for imaging studies as well as for scintillation counting and autoradiography.

Reactions of ortho-lithiophenyl (-hetaryl) isocyanides with carbonyl compounds: rearrangements of 2-metalated 4H-3,1-benzoxazines.

PubMed

Lygin, Alexander V; de Meijere, Armin

2009-06-19

ortho-Lithiophenyl (-hetaryl) isocyanides react with aldehydes and ketones providing isocyanoalcohols 8 (36-89%, nine examples), 4H-3,1-benzoxazines 9 (45-78%, six examples) or, after two types of rearrangements, isobenzofuran-1(3H)-imines (iminophthalanes) 18 (52-75%, four examples), or indolin-2-ones 19 (42-79%, two examples), depending on the reaction conditions and substitution patterns. Isocyanoalcohols 8, in turn, were converted to 9 or 18 under Cu(I) catalysis (66-86%, eight examples). 4H-3,1-Benzoxazin-4-ones 39-Nu and isatoic anhydride 40 were obtained by the reaction of 2 with carbon dioxide followed by trapping of the lithiated intermediate with iodine and subsequent reactions with nucleophiles (45-60%, three examples).

Nitrous Oxide-dependent Iron-catalyzed Coupling Reactions of Grignard Reagents.

PubMed

Döhlert, Peter; Weidauer, Maik; Enthaler, Stephan

2015-01-01

The formation of carbon-carbon bonds is one of the fundamental transformations in chemistry. In this regard the application of palladium-based catalysts has been extensively investigated during recent years, but nowadays research focuses on iron catalysis, due to sustainability, costs and toxicity issues; hence numerous examples for iron-catalyzed cross-coupling reactions have been established, based on the coupling of electrophiles (R(1)-X, X = halide) with nucleophiles (R(2)-MgX). Only a small number of protocols deals with the iron-catalyzed oxidative coupling of nucleophiles (R(1)-MgX + R(2)-MgX) with the aid of oxidants (1,2-dihaloethanes). However, some issues arise with these oxidants; hence more recently the potential of the industrial waste product nitrous oxide (N(2)O) was investigated, because the unproblematic side product N(2) is formed. Based on that, we demonstrate the catalytic potential of easily accessible iron complexes in the oxidative coupling of Grignard reagents. Importantly, nitrous oxide was essential to obtain yields up to >99% at mild conditions (e.g. 1 atm, ambient temperature) and low catalyst loadings (0.1 mol%) Excellent catalyst performance is realized with turnover numbers of up to 1000 and turnover frequencies of up to 12000 h(-1). Moreover, a good functional group tolerance is observed (e.g. amide, ester, nitrile, alkene, alkyne). Afterwards the reaction of different Grignard reagents revealed interesting results with respect to the selectivity of cross-coupling product formation.

Spectroscopic investigations of humic-like acids formed via polycondensation reactions between glycine, catechol and glucose in the presence of natural zeolites

NASA Astrophysics Data System (ADS)

Fukuchi, Shigeki; Miura, Akitaka; Okabe, Ryo; Fukushima, Masami; Sasaki, Masahide; Sato, Tsutomu

2010-10-01

Polycondensation reactions between low-molecular-weight compounds, such as amino acids, sugars and phenols, are crucially important processes in the formation of humic substances, and clay minerals have the ability to catalyze these reactions. In the present study, catechol (CT), glycine (Gly) and glucose (Gl) were used as representative phenols, amino acids and sugars, respectively, and the effects of the catalytic activities of natural zeolites on polycondensation reactions between these compounds were investigated. The extent of polycondensation was evaluated by measuring the specific absorbance at 600 nm ( E600) as an index of the degree of darkening. After a 3-week incubation period, the E600 values for solutions that contained zeolite samples were 4-10 times greater than those measured in the absence of zeolite, suggesting that the zeolite had, in fact, catalyzed the polycondensation reaction. The humic-like acids (HLAs) produced in the reactions were isolated, and their elemental composition and molecular weights determined. When formed in the presence of a zeolite, the nitrogen contents and molecular weights for the HLAs were significantly higher, compared to the HLA sample formed in the absence of zeolite. In addition, solid-state CP-MAS 13C NMR spectra and carboxylic group analyses of the HLA samples indicated that the concentration of carbonyl carbon species for quinones and ketones produced in the presence of zeolite were higher than the corresponding values for samples produced in the absence of a zeolite. Carbonyl carbons in quinones and ketones indicate the nucleophilic characteristics of the samples. Therefore, a nitrogen atom in Gly, which serves as nucleophile, is incorporated into quinones and ketones in CT and Gl. The differences in the catalytic activities of the zeolite samples can be attributed to differences in their transition metal content (Fe, Mn and Ti), which function as Lewis acids.

Covalently Bound Monomolecular Layers on Si Single Crystals

NASA Astrophysics Data System (ADS)

Chidsey, Christopher E. D.

1996-03-01

Methods and reagents borrowed from the molecular synthetic chemistry of silicon compounds have been used to form covalently bound monomolecular layers on silicon single crystals. Organic monolayers bound covalently to silicon could form the basis for silicon/organic interfaces useful in sensor structures. In a representative reaction, alkyl monolayers with densities approaching that of crystalline polyethylene have been prepared by the radical-initiated insertion of 1-alkenes into the Si-H bonds of hydrogen-terminated Si(111) surfaces footnote M. R. Linford, P. Fenter, P. M. Eisenberger and C. E. D Chidsey, J. Am. Chem. Soc. 117, 3145-3155 (1995). It has recently been found that this insertion reaction can also be initiated by illumination with UV light having sufficient energy to break the Si-H bond. Synchrotron-based high-resolution photoelectron spectroscopy and diffraction have demonstrated the expected Si-C bond in such monolayers footnote J. H. Terry, R. Cao, P. A. Pianetta, M. R. Linford and C. E. D. Chidsey, unpublished results. An alternate approach to similar monolayers has been found to be the chlorination of hydrogen-terminated Si(111) with Cl_2, followed by the nucleophilic displacement of chlorine with alkyl lithium reagents. The well-behaved chemical transformations of the hydrogen-terminated silicon surfaces appear to result from the essentially bulk termination of the silicon lattice with closed-shell silicon hydride "functional groups" on the surface. In addition to the formation of novel organic layers, a full understanding of the reactivity of the hydrogen-terminated silicon surfaces should lead to better control of key technological silicon interfaces such as Si/SiO_2, Si/epi-Si, and Si/metal.

Dual role of allylsamarium bromide as a Grignard reagent and a single electron transfer reagent in the one-pot synthesis of terminal olefins.

PubMed

Li, Ying; Hu, Yuan-Yuan; Zhang, Song-Lin

2013-11-21

The utility of allylsamarium bromide, both as a nucleophilic reagent and a single-electron transfer reagent, in the reaction of carbonyl compounds with allylsamarium bromide in the presence of diethyl phosphate is reported in this communication. From a synthetic point of view, a simple one-pot method for the preparation of terminal olefins is developed.

Regioselective SN2 reactions for rapid syntheses of azido-inositols by one-pot sequence-specific nucleophilysis.

PubMed

Ravi, Arthi; Hassan, Syed Zahid; Vanikrishna, Ajithkumar N; Sureshan, Kana M

2017-04-04

Triflates of myo-inositol undergo facile solvolysis in DMSO and DMF yielding S N 2 products substituted with O-nucleophiles; DMF showed slower kinetics. Axial O-triflate undergoes faster substitution than equatorial O-triflate. By exploiting this difference in kinetics, solvent-tuning and sequence-controlled nucleophilysis, rapid synthesis of three azido-inositols of myo-configuration from myo-inositol itself has been achieved.

Efficient palladium-catalyzed asymmetric allylic alkylation of ketones and aldehydes.

PubMed

Zhao, Xiaohu; Liu, Delong; Xie, Fang; Liu, Yangang; Zhang, Wanbin

2011-03-21

Palladium-catalyzed asymmetric allylic alkylation of ketones, via enamines generated in situ as nucleophiles, were carried out smoothly with chiral metallocene-based P,N-ligands. Under the same conditions, however, reactions of aldehydes could hardly be observed. Subsequently, this obstacle was resolved by using chiral metallocene-based P,P-ligands. Both ketones and aldehydes afforded excellent enantioselectivities with up to 98% ee and 94% ee, respectively.

Protein alkylation, transcriptional responses and cytochrome c release during acrolein toxicity in A549 cells: influence of nucleophilic culture media constituents.

PubMed

Thompson, Colin A; Burcham, Philip C

2008-06-01

Acrolein is a toxic combustion product that elicits apoptotic and/or necrotic cell death depending on the conditions under which exposure occurs. As a strong electrophile, side-reactions with nucleophilic media constituents seem likely to accompany study of its toxicity in vitro, but these reactions are poorly characterized. We have thus examined the effect of media composition on the toxicity of acrolein in A549 cells. Cells were exposed to acrolein in either Dulbecco's buffered saline (DBS) or F12 supplemented with various concentrations of fetal bovine serum. Cell viability was assessed using the MTT assay, while heme oxygenase-1 (HO-1) and cytoplasmic cytochrome c were measured as respective markers of transcriptional response and apoptosis. Protein damage was evaluated using the protein carbonyl assay. Compared to F12 media (with or without serum), maximal cell death as evaluated using the MTT assay, as well as adduction of intracellular proteins, occurred when cells were exposed to acrolein in DBS. In contrast, cytochrome c release was maximal in cells exposed to acrolein in serum-containing F12, conditions which inhibited protein modification and overt cell death. These findings highlight the need for careful attention to experimental conditions when conducting in vitro toxicological studies of reactive substances.

Quinone Methide Signal Amplification: Covalent Reporter Labeling of Cancer Epitopes using Alkaline Phosphatase Substrates.

PubMed

Polaske, Nathan W; Kelly, Brian D; Ashworth-Sharpe, Julia; Bieniarz, Christopher

2016-03-16

Diagnostic assays with the sensitivity required to improve cancer therapeutics depend on the development of new signal amplification technologies. Herein, we report the development and application of a novel amplification system which utilizes latent quinone methides (QMs) activated by alkaline phosphatase (AP) for signal amplification in solid-phase immunohistochemical (IHC) assays. Phosphate-protected QM precursor substrates were prepared and conjugated to either biotin or a fluorophore through an amine-functionalized linker group. Upon reaction with AP, the phosphate group is cleaved, followed by elimination of the leaving group and formation of the highly reactive and short-lived QM. The QMs either react with tissue nucleophiles in close proximity to their site of generation, or are quenched by nucleophiles in the reaction media. The reporter molecules that covalently bind to the tissue were then detected visually by fluorescence microscopy in the case of fluorophore reporters, or brightfield microscopy using diaminobenzidine (DAB) in the case of biotin reporters. With multiple reporters deposited per enzyme, significant signal amplification was observed utilizing QM precursor substrates containing either benzyl difluoro or benzyl monofluoro leaving group functionalities. However, the benzyl monofluoro leaving group gave superior results with respect to both signal intensity and discretion, the latter of which was found to be imperative for use in diagnostic IHC assays.

Modelling toehold-mediated RNA strand displacement.

PubMed

Šulc, Petr; Ouldridge, Thomas E; Romano, Flavio; Doye, Jonathan P K; Louis, Ard A

2015-03-10

We study the thermodynamics and kinetics of an RNA toehold-mediated strand displacement reaction with a recently developed coarse-grained model of RNA. Strand displacement, during which a single strand displaces a different strand previously bound to a complementary substrate strand, is an essential mechanism in active nucleic acid nanotechnology and has also been hypothesized to occur in vivo. We study the rate of displacement reactions as a function of the length of the toehold and temperature and make two experimentally testable predictions: that the displacement is faster if the toehold is placed at the 5' end of the substrate; and that the displacement slows down with increasing temperature for longer toeholds. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Photolysis of oxyfluorfen in aqueous methanol.

PubMed

Chakraborty, Subhasish K; Chakraborty, Savitri; Bhattacharyya, Anjan; Chowdhury, Ashim

2013-01-01

Photolysis of oxyfluorfen, an herbicide of the nitrodiphenyl ether class, was studied in aqueous methanol under UV and sunlight. UV irradiation was carried out in a borosilicate glass photoreactor (containing 250 ppm oxyfluorfen in 50% aqueous methanol) equipped with a quartz filter and 125 watt mercury lamp (maximum output 254 nm) at 25 ± 1°C. Sunlight irradiation was conducted at 28 ± 1°C in borosilicate Erlenmeyer flasks containing 250 ppm oxyfluorfen in 50% aqueous methanol. The samples from both the irradiated conditions were withdrawn at a definite time interval and extracted to measure oxyfluorfen content by gas chromatography-flame ionization detector for rate study. The half-life values were 20 hours and 2.7 days under UV and sunlight exposure, respectively. Photolysis of oxyfluorfen yielded 13 photoproducts of which three were characterized by infrared spectrophotometer and (1)H NMR and (13)C NMR spectroscopy. The rest of the photoproducts were identified by gas chromatography-mass spectrometry (GC-MS) and thin layer chromatography (TLC). An ionization potential 70 eV was used for electron impact-mass spectrometry (EI-MS) and methane was used as reagent gas for chemical ionization-mass spectrometry (CI-MS). Two of the photoproducts were also synthesized for comparison. The main phototransformation pathways of oxyfluorfen involved nitro reduction, dechlorination, and hydrolysis as well as nucleophiles displacement reaction.

Mechanism of papain-catalyzed synthesis of oligo-tyrosine peptides.

PubMed

Mitsuhashi, Jun; Nakayama, Tsutomu; Narai-Kanayama, Asako

2015-01-01

Di-, tri-, and tetra-tyrosine peptides with angiotensin I-converting enzyme inhibitory activity were synthesized by papain-catalyzed polymerization of L-tyrosine ethyl ester in aqueous media at 30 °C. Varying the reaction pH from 6.0 to 7.5 and the initial concentration of the ester substrate from 25 to 100 mM, the highest yield of oligo-tyrosine peptides (79% on a substrate basis) was produced at pH 6.5 and 75 mM, respectively. In the reaction initiated with 100 mM of the substrate, approx. 50% yield of insoluble, highly polymerized peptides accumulated. At less than 15 mM, the reaction proceeded poorly; however, from 30 mM to 120 mM a dose-dependent increase in the consumption rate of the substrate was observed with a sigmoidal curve. Meanwhile, each of the tri- and tetra-tyrosine peptides, even at approx. 5mM, was consumed effectively by papain but was not elongated to insoluble polymers. For deacylation of the acyl-papain intermediate through which a new peptide bond is made, L-tyrosine ethyl ester, even at 5mM, showed higher nucleophilic activity than di- and tri-tyrosine. These results indicate that the mechanism through which papain polymerizes L-tyrosine ethyl ester is as follows: the first interaction between papain and the ester substrate is a rate-limiting step; oligo-tyrosine peptides produced early in the reaction period are preferentially used as acyl donors, while the initial ester substrate strongly contributes as a nucleophile to the elongation of the peptide product; and the balance between hydrolytic fragmentation and further elongation of oligo-tyrosine peptides is dependent on the surrounding concentration of the ester substrate. Copyright © 2015 Elsevier Inc. All rights reserved.

Catalyzed Atomic Layer Deposition of Silicon Oxide at Ultralow Temperature Using Alkylamine.

PubMed

Mayangsari, Tirta R; Park, Jae-Min; Yusup, Luchana L; Gu, Jiyeon; Yoo, Jin-Hyuk; Kim, Heon-Do; Lee, Won-Jun

2018-06-12

We report the catalyzed atomic layer deposition (ALD) of silicon oxide using Si 2 Cl 6 , H 2 O, and various alkylamines. The density functional theory (DFT) calculations using the periodic slab model of the SiO 2 surface were performed for the selection of alternative Lewis base catalysts with high catalytic activities. During the first half-reaction, the catalysts with less steric hindrance such as pyridine would be more effective than bulky alkylamines despite lower nucleophilicity. On the other hand, during the second half-reaction, the catalysts with a high nucleophilicity such as triethylamine (Et 3 N) would be more efficient because the steric hindrance is less critical. The in situ process monitoring shows that the calculated atomic charge is a good indicator for expecting the catalyst activity in the ALD reaction. The use of Et 3 N in the second half-reaction was essential to improving the growth rate as well as the step coverage of the film because the Et 3 N-catalyzed process deposited a SiO 2 film with a step coverage of 98% that is better than 93% of the pyridine-catalyzed process. The adsorption of pyridine, ammonia (NH 3 ), or trimethylamine (Me 3 N) salts was more favorable than that of Et 3 N, n-Pr 3 N, or i Pr 3 N salts. Therefore, Et 3 N was expected to incorporate less amine salts in the film as compared to pyridine, and the compositional analyses confirmed that the concentrations of Cl and N by the Et 3 N-catalyzed process were significantly lower than those by the pyridine-catalyzed process.

Assessing the reactivation efficacy of hydroxylamine anion towards VX-inhibited AChE: a computational study.

PubMed

Khan, Md Abdul Shafeeuulla; Ganguly, Bishwajit

2012-05-01

Oximate anions are used as potential reactivating agents for OP-inhibited AChE because of they possess enhanced nucleophilic reactivity due to the α-effect. We have demonstrated the process of reactivating the VX-AChE adduct with formoximate and hydroxylamine anions by applying the DFT approach at the B3LYP/6-311 G(d,p) level of theory. The calculated results suggest that the hydroxylamine anion is more efficient than the formoximate anion at reactivating VX-inhibited AChE. The reaction of formoximate anion and the VX-AChE adduct is a three-step process, while the reaction of hydroxylamine anion with the VX-AChE adduct seems to be a two-step process. The rate-determining step in the process is the initial attack on the VX of the VX-AChE adduct by the nucleophile. The subsequent steps are exergonic in nature. The potential energy surface (PES) for the reaction of the VX-AChE adduct with hydroxylamine anion reveals that the reactivation process is facilitated by the lower free energy of activation (by a factor of 1.7 kcal mol(-1)) than that of the formoximate anion at the B3LYP/6-311 G(d,p) level of theory. The higher free energy of activation for the reverse reactivation reaction between hydroxylamine anion and the VX-serine adduct further suggests that the hydroxylamine anion is a very good antidote agent for the reactivation process. The activation barriers calculated in solvent using the polarizable continuum model (PCM) for the reactivation of the VX-AChE adduct with hydroxylamine anion were also found to be low. The calculated results suggest that V-series compounds can be more toxic than G-series compounds, which is in accord with earlier experimental observations.

Oxidation of a guanine derivative coordinated to a Pt(IV) complex initiated by intermolecular nucleophilic attacks.

PubMed

Choi, Sunhee; Personick, Michelle L; Bogart, Justin A; Ryu, DaWeon; Redman, Romany M; Laryea-Walker, Edith

2011-03-28

In this study we report that fac-[Pt(IV)(dach)(9-EtG)Cl(3)](+) (dach = d,l-1,2-diaminocyclohexane, 9-EtG = 9-ethylguanine) in high pH (pH 12) or phosphate solution (pH 7.4) produces 8-oxo-9-EtG and Pt(II) species. The reaction in H(2)(18)O revealed that the oxygen atom in hydroxide or phosphate ends up at the C8 position of 8-oxo-G. The kinetics of the redox reaction was first order with respect to both Pt(IV)-G and free nucleophiles (OH(-) and phosphate). The oxidation of G initiated by hydroxide was approximately 30∼50 times faster than by phosphate in 100 mM NaCl solutions. The large entropy of activation of OH(-1) (ΔS(‡) = 26.6 ± 4.3 J mol(-1) K(-1)) due to the smaller size of OH(-) is interpreted to be responsible for the faster kinetics compared to phosphate (ΔS(‡) = -195.5 ± 11.1 J mol(-1) K(-1)). The enthalpy of activation for phosphate reaction is more favorable relative to the OH(-) reaction (ΔH(‡) = 35.4 ± 3.5 kJ mol(-1) for phosphate vs. 96.6 ± 11.4 kJ mol(-1) for OH(-1)). The kinetic isotope effect of H8 was determined to be 7.2 ± 0.2. The rate law, kinetic isotope effect, and isotopic labeling are consistent with a mechanism involving proton ionization at the C8 position as the rate determining step followed by two-electron transfer from G to Pt(IV).

Real-time monitoring of enzyme-free strand displacement cascades by colorimetric assays.

PubMed

Duan, Ruixue; Wang, Boya; Hong, Fan; Zhang, Tianchi; Jia, Yongmei; Huang, Jiayu; Hakeem, Abdul; Liu, Nannan; Lou, Xiaoding; Xia, Fan

2015-03-19

The enzyme-free toehold-mediated strand displacement reaction has shown potential for building programmable DNA circuits, biosensors, molecular machines and chemical reaction networks. Here we report a simple colorimetric method using gold nanoparticles as signal generators for the real-time detection of the product of the strand displacement cascade. During the process the assembled gold nanoparticles can be separated, resulting in a color change of the solution. This assay can also be applied in complex mixtures, fetal bovine serum, and to detect single-base mismatches. These results suggest that this method could be of general utility to monitor more complex enzyme-free strand displacement reaction-based programmable systems or for further low-cost diagnostic applications.

Unusual solvent effect on a SN2 reaction. A quantum-mechanical and kinetic study of the Menshutkin reaction between 2-amino-1-methylbenzimidazole and iodomethane in the gas phase and in acetonitrile.

PubMed

Melo, André; Alfaia, António J I; Reis, João Carlos R; Calado, António R T

2006-02-02

The quaternization reaction between 2-amino-1-methylbenzimidazole and iodomethane was investigated in the gas phase and in liquid acetonitrile. Both experimental and theoretical techniques were used in this study. In the experimental part of this work, accurate second-order rate constants were obtained for this reaction in acetonitrile from conductivity data in the 293-323 K temperature range and at ambient pressure. From two different empirical equations describing the effect of temperature on reaction rates, thermodynamic functions of activation were calculated. In the theoretical part of this work, the mechanism of this reaction was investigated in the gas phase and in acetonitrile. Two different quantum levels (B3LYP/[6-311++G(3df,3pd)/LanL2DZ]//B3LYP/[6-31G(d)/LanL2DZ] and B3LYP/[6-311++G(3df,3pd)/LanL2DZ]//B3LYP/[6-31+G(d)/LanL2DZ]) were used in the calculations, and the acetonitrile environment was modeled using the polarized continuum model (PCM). In addition, an atoms in molecules (AIM) analysis was made aiming to characterize possible hydrogen bonding. The results obtained by both techniques are in excellent agreement and lead to new insight into the mechanism of the reaction under examination. These include the identification and thermodynamic characterization of the relevant stationary species, the rationalization of the mechanistic role played by the solvent and the amine group adjacent to the nucleophile nitrogen atom, the proposal of alternative paths on the modeled potential energy surfaces, and the origin of the marked non-Arrhenius behavior of the kinetic data in solvent acetonitrile. In particular, the AIM analysis confirmed the operation of intermolecular hydrogen bonds between reactants and between products, both in the gas phase and in solution. It is also concluded that the unusual solvent effect on this Menshutkin reaction stems from the conjunction of a nucleophile possessing a relatively complex chemical structure with a dipolar aprotic solvent that is protophobic.

Reversible and irreversible reactions of three oxygen precursors on InAs(0 0 1)-(4 × 2)/ c(8 × 2)

NASA Astrophysics Data System (ADS)

Clemens, Jonathon B.; Droopad, Ravi; Kummel, Andrew C.

2010-10-01

The substrate reactions of three common oxygen sources for gate oxide deposition on the group III rich InAs(0 0 1)-(4 × 2)/ c(8 × 2) surface are compared: water, hydrogen peroxide (HOOH), and isopropyl alcohol (IPA). Scanning tunneling microscopy reveals that surface atom displacement occurs in all cases, but via different mechanisms for each oxygen precursor. The reactions are examined as a function of post-deposition annealing temperature. Water reaction shows displacement of surface As atoms, but it does not fully oxidize the As; the reaction is reversed by high temperature (450 °C) annealing. Exposure to IPA and subsequent low-temperature annealing (100 °C) show the preferential reaction on the row features of InAs(0 0 1)-(4 × 2)/ c(8 × 2), but higher temperature anneals result in permanent surface atom displacement/etching. Etching of the substrate is observed with HOOH exposure for all annealing temperatures. While nearly all oxidation reactions on group IV semiconductors are irreversible, the group III rich surface of InAs(0 0 1) shows that oxidation displacement reactions can be reversible at low temperature, thereby providing a mechanism of self-healing during oxidation reactions.

Macrocyclic bis-thioureas catalyze stereospecific glycosylation reactions.

PubMed

Park, Yongho; Harper, Kaid C; Kuhl, Nadine; Kwan, Eugene E; Liu, Richard Y; Jacobsen, Eric N

2017-01-13

Carbohydrates are involved in nearly all aspects of biochemistry, but their complex chemical structures present long-standing practical challenges to their synthesis. In particular, stereochemical outcomes in glycosylation reactions are highly dependent on the steric and electronic properties of coupling partners; thus, carbohydrate synthesis is not easily predictable. Here we report the discovery of a macrocyclic bis-thiourea derivative that catalyzes stereospecific invertive substitution pathways of glycosyl chlorides. The utility of the catalyst is demonstrated in the synthesis of trans-1,2-, cis-1,2-, and 2-deoxy-β-glycosides. Mechanistic studies are consistent with a cooperative mechanism in which an electrophile and a nucleophile are simultaneously activated to effect a stereospecific substitution reaction. Copyright © 2017, American Association for the Advancement of Science.

Proton donor acidity controls selectivity in nonaromatic nitrogen heterocycle synthesis.

PubMed

Duttwyler, Simon; Chen, Shuming; Takase, Michael K; Wiberg, Kenneth B; Bergman, Robert G; Ellman, Jonathan A

2013-02-08

Piperidines are prevalent in natural products and pharmaceutical agents and are important synthetic targets for drug discovery and development. We report on a methodology that provides highly substituted piperidine derivatives with regiochemistry selectively tunable by varying the strength of acid used in the reaction. Readily available starting materials are first converted to dihydropyridines via a cascade reaction initiated by rhodium-catalyzed carbon-hydrogen bond activation. Subsequent divergent regio- and diastereoselective protonation of the dihydropyridines under either kinetic or thermodynamic control provides two distinct iminium ion intermediates that then undergo highly diastereoselective nucleophilic additions. X-ray structural characterization of both the kinetically and thermodynamically favored iminium ions along with density functional theory calculations provide a theoretical underpinning for the high selectivities achieved for the reaction sequences.

Regioselective and enantiospecific rhodium-catalyzed allylic alkylation reactions using copper(I) enolates: synthesis of (-)-sugiresinol dimethyl ether.

PubMed

Evans, P Andrew; Leahy, David K

2003-07-30

The transition metal-catalyzed allylic alkylation represents a fundamentally important cross-coupling reaction for the construction of ternary carbon stereogenic centers. We have developed a regioselective and enantiospecific rhodium-catalyzed allylic alkylation of acyclic unsymmetrical allylic alcohol derivatives using copper(I) enolates to prepare beta-substituted ketones. This protocol represents a convenient asymmetric Claisen rearrangement surrogate in which alpha-substituted enolates permit the introduction of an additional stereogenic center. The synthetic utility of this transformation was highlighted in the construction of a trans-1,2-disubstituted cyclohexene and the total synthesis of (-)-sugiresinol dimethyl ether. Finally, we anticipate that copper(I) enolates may prove useful nucleophiles in related metal-catalyzed reactions.

Diastereoselective reactions in glycine templates containing an ent-ardeemin fragment.

PubMed

Martín-Santamaría, Sonsoles; Corzo-Suárez, Raúl; Avendaño, Carmen; Espada, Modesta; Gago, Federico; García-Granda, Santiago; Rzepa, Henry S

2002-04-05

Self-consistent reaction field solvation models derived from SCF-MO calculations are shown to be reliable in modeling the diastereoselectivity of the reactions of the anion and cation derived from (4S)-2,4-dimethyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-dione (1) at C(1) with electrophiles and nucleophiles, respectively. The found anti/syn ratio of compound 8, which is a seco-ent-ardeemin analogue obtained by alkylation of 1 with gramine methiodide, confirms this computational model. A close similarity between the calculated geometry of the piperazine ring in the anti isomers of 1,2,4-trialkyl derivatives and that deduced from their (1)H NMR (solution) and X-ray data has been also established.

A DFT study of the mechanism and the regioselectivity of [3 + 2] cycloaddition reactions of nitrile oxides with α,β-acetylenic aldehyde

NASA Astrophysics Data System (ADS)

Sobhi, Chafia; Nacereddine, Abdelmalek Khorief; Nasri, Lilia; Lechtar, Zohra; Djerourou, Abdelhafid

2016-11-01

A DFT study of the (32CA) reaction of a series of some nitrile oxides with electron-deficient alkyne (3-phenylpropionlaldehyde) in gas phase and in toluene has been carried out using B3LYP functional with 6-31G(d) basis set. Two reactive channels 4- and 5-associated with the two regioisomeric modes have been located and characterised. These 32CA reactions are characterised by a low asynchronous one-step mechanism with a low-polar character. Analysis of the DFT reactivity indices indicates that the nucleophilic centre of the different nitrile oxides accounts for the 4-regioselectivity. Our calculations are in a good agreement with the experimental findings.

Organic reactions mediated by electrochemically generated ArS+.

PubMed

Matsumoto, Kouichi; Suga, Seiji; Yoshida, Jun-ichi

2011-04-21

Low-temperature electrochemical oxidation of ArSSAr was carried out to generate a pool of "ArS(+)". Spectroscopic studies ((1)H NMR and CSI-MS) of the resulting solution revealed the accumulation of ArS(ArSSAr)(+). The resulting "ArS(+)" pool reacted with alkenes and alkynes to give diarylthio-substituted products. The "ArS(+)" pool rapidly reacted with thioacetals to give the corresponding alkoxycarbenium ion pools, which reacted with various carbon nucleophiles (indirect cation pool method). The reaction of the alkoxycarbenium ion pools with stilbene derivatives in the presence of ArSSAr gave thiochroman derivatives. In addition to such stoichiometric reactions, a catalytic amount of "ArS(+)" serves as an initiator and a chain carrier of some cationic chain reactions involving intramolecular carbon-carbon bond formation. In situ generation of "ArS(+)" by electrochemical oxidation of ArSSAr with a catalytic amount of electricity in the presence of a substrate is also effective for such cationic chain reactions.

The Piancatelli reaction and its variants: recent applications to high added-value chemicals and biomass valorization.

PubMed

Verrier, Charlie; Moebs-Sanchez, Sylvie; Queneau, Yves; Popowycz, Florence

2018-01-31

The Piancatelli reaction, also called the Piancatelli rearrangement, consists in the direct conversion of furfuryl alcohols to cyclopentenone derivatives through a furan ring opening-electrocyclization process. Discovered in the late 70's, this reaction has been scarcely used for more than 40 years but recently has been the focus of particular interest from the scientific community and an increasing number of publications on the topic have emerged in the last few years. The first part of this review provides an overview of the recent achievements in classical Piancatelli reactions, discussing reaction conditions and catalytic systems, whereas the second part focuses on the variants recently developed, including the use of new nucleophiles in the process. Finally, the third part of this review deals with the recent application of this transformation to the production of commodity chemicals from renewable carbon feedstocks based on sugar-derived furanic platforms.

Galvanic displacement reaction and rapid thermal annealing in size/shape controlling silver nanoparticles on silicon substrate

NASA Astrophysics Data System (ADS)

Ghosh, Tapas; Satpati, Biswarup

2017-05-01

The effect of the thermal annealing on silver nanoparticles deposited on silicon surface has been studied. The silver nanoparticles have been deposited by the galvanic displacement reaction. Rapid thermal annealing (RTA) has been performed on the Si substrate, containing the silver nanoparticles. The scanning transmission electron microscopy (STEM), energy dispersive X-ray (EDX) spectroscopy and scanning electron microscopy (SEM) study show that the galvanic displacement reaction and subsequent rapid thermal annealing could lead to well separated and spherical shaped larger silver nanoparticles on silicon substrate.

Implementing Nonlinear Feedback Controllers Using DNA Strand Displacement Reactions.

PubMed

Sawlekar, Rucha; Montefusco, Francesco; Kulkarni, Vishwesh V; Bates, Declan G

2016-07-01

We show how an important class of nonlinear feedback controllers can be designed using idealized abstract chemical reactions and implemented via DNA strand displacement (DSD) reactions. Exploiting chemical reaction networks (CRNs) as a programming language for the design of complex circuits and networks, we show how a set of unimolecular and bimolecular reactions can be used to realize input-output dynamics that produce a nonlinear quasi sliding mode (QSM) feedback controller. The kinetics of the required chemical reactions can then be implemented as enzyme-free, enthalpy/entropy driven DNA reactions using a toehold mediated strand displacement mechanism via Watson-Crick base pairing and branch migration. We demonstrate that the closed loop response of the nonlinear QSM controller outperforms a traditional linear controller by facilitating much faster tracking response dynamics without introducing overshoots in the transient response. The resulting controller is highly modular and is less affected by retroactivity effects than standard linear designs.

C-C bond formation and related reactions at the CNC backbone in (smif)FeX (smif = 1,3-di-(2-pyridyl)-2-azaallyl): dimerizations, 3 + 2 cyclization, and nucleophilic attack; transfer hydrogenations and alkyne trimerization (X = N(TMS)2, dpma = (di-(2-pyridyl-methyl)-amide)).

PubMed

Frazier, Brenda A; Williams, Valerie A; Wolczanski, Peter T; Bart, Suzanne C; Meyer, Karsten; Cundari, Thomas R; Lobkovsky, Emil B

2013-03-18

Molecular orbital analysis depicts the CNC(nb) backbone of the smif (1,3-di-(2-pyridyl)-2-azaallyl) ligand as having singlet diradical and/or ionic character where electrophilic or nucleophilic attack is plausible. Reversible dimerization of (smif)Fe{N(SiMe3)2} (1) to [{(Me3Si)2N}Fe]2(μ-κ(3),κ(3)-N,py2-smif,smif) (2) may be construed as diradical coupling. A proton transfer within the backbone-methylated, and o-pyridine-methylated smif of putative ((b)Me2(o)Me2smif)FeN(SiMe3)2 (8) provides a route to [{(Me3Si)2N}Fe]2(μ-κ(4),κ(4)-N,py2,C-((b)Me,(b)CH2,(o)Me2(smif)H))2 (9). A 3 + 2 cyclization of ditolyl-acetylene occurs with 1, leading to the dimer [{2,5-di(pyridin-2-yl)-3,4-di-(p-tolyl-2,5-dihydropyrrol-1-ide)}FeN(SiMe3)2]2 (11), and the collateral discovery of alkyne cyclotrimerization led to a brief study that identified Fe(N(SiMe3)2(THF) as an effective catalyst. Nucleophilic attack by (smif)2Fe (13) on (t)BuNCO and (2,6-(i)Pr2C6H3)NCO afforded (RNHCO-smif)2Fe (14a, R = (t)Bu; 14b, 2,6-(i)PrC6H3). Calculations suggested that (dpma)2Fe (15) would favorably lose dihydrogen to afford (smif)2Fe (13). H2-transfer to alkynes, olefins, imines, PhN═NPh, and ketones was explored, but only stoichiometric reactions were affected. Some physical properties of the compounds were examined, and X-ray structural studies on several dinuclear species were conducted.

Revealing a double-inversion mechanism for the F⁻+CH₃Cl SN2 reaction.

PubMed

Szabó, István; Czakó, Gábor

2015-01-19

Stereo-specific reaction mechanisms play a fundamental role in chemistry. The back-side attack inversion and front-side attack retention pathways of the bimolecular nucleophilic substitution (SN2) reactions are the textbook examples for stereo-specific chemical processes. Here, we report an accurate global analytic potential energy surface (PES) for the F(-)+CH₃Cl SN2 reaction, which describes both the back-side and front-side attack substitution pathways as well as the proton-abstraction channel. Moreover, reaction dynamics simulations on this surface reveal a novel double-inversion mechanism, in which an abstraction-induced inversion via a FH···CH₂Cl(-) transition state is followed by a second inversion via the usual [F···CH₃···Cl](-) saddle point, thereby opening a lower energy reaction path for retention than the front-side attack. Quasi-classical trajectory computations for the F(-)+CH₃Cl(ν1=0, 1) reactions show that the front-side attack is a fast direct, whereas the double inversion is a slow indirect process.

SN2 fluorination reactions in ionic liquids: a mechanistic study towards solvent engineering.

PubMed

Oh, Young-Ho; Jang, Hyeong Bin; Im, Suk; Song, Myoung Jong; Kim, So-Yeon; Park, Sung-Woo; Chi, Dae Yoon; Song, Choong Eui; Lee, Sungyul

2011-01-21

In the catalysis of S(N)2 fluorination reactions, the ionic liquid anion plays a key role as a Lewis base by binding to the counterion Cs(+) and thereby reducing the retarding Coulombic influence of Cs(+) on the nucleophile F(-). The reaction rates also depend critically on the structures of ionic liquid cation, for example, n-butyl imidazolium gives no S(N)2 products, whereas n-butylmethyl imidazolium works well. The origin of the observed phenomenal synergetic effects by the ionic liquid [mim-(t)OH][OMs], in which t-butanol is bonded covalently to the cation [mim], is that the t-butanol moiety binds to the leaving group of the substrate, moderating the retarding interactions between the acidic hydrogen and F(-). This work is a significant step toward designing and engineering solvents for promoting specific chemical reactions.

Global and Local Partitioning of the Charge Transferred in the Parr-Pearson Model.

PubMed

Orozco-Valencia, Angel Ulises; Gázquez, José L; Vela, Alberto

2017-05-25

Through a simple proposal, the charge transfer obtained from the cornerstone theory of Parr and Pearson is partitioned, for each reactant, in two channels: an electrophilic, through which the species accepts electrons, and the other, a nucleophilic, where the species donates electrons. It is shown that this global model allows us to determine unambiguously the charge-transfer mechanism prevailing in a given reaction. The partitioning is extended to include local effects through the Fukui functions of the reactants. This local model is applied to several emblematic reactions in organic and inorganic chemistry, and we show that besides improving the correlations obtained with the global model it provides valuable information concerning the atoms in the reactants playing the most important roles in the reaction and thus improving our understanding of the reaction under study.

Degradation of methyl bromide in anaerobic sediments

USGS Publications Warehouse

Oremland, R.S.; Miller, L.G.; Strohmaler, F.E.

1994-01-01

Methyl bromide (MeBr) was anaerobically degraded in saltmarsh sediments after reaction with sulfide. The product of this nucleophilic substitution reaction was methanethiol, which underwent further chemical and bacterial reactions to form dimethyl sulfide. These two gases appeared transiently during sediment incubations because they were metabolized by methanogenic and sulfate-reducing bacteria. A second, less significant reaction of MeBr was the exchange with chloride, forming methyl chloride, which was also susceptible to attack by sulfide. Incubation of 14C-labeled methyl iodide as an analogue of MeBr resulted in the formation of 14CH4 and 14CO2 and also indicated that sulfate-reducing bacteria as well as methanogens metabolized the methylated sulfur intermediates. These results suggest that exposed sediments with abundant free sulfide, such as coastal salt-marshes, may constitute a sink for atmospheric MeBr.

Ionic liquids as transesterification catalysts: applications for the synthesis of linear and cyclic organic carbonates

PubMed Central

Perosa, Alvise; Guidi, Sandro; Cattelan, Lisa

2016-01-01

Summary The use of ionic liquids (ILs) as organocatalysts is reviewed for transesterification reactions, specifically for the conversion of nontoxic compounds such as dialkyl carbonates to both linear mono-transesterification products or alkylene carbonates. An introductory survey compares pros and cons of classic catalysts based on both acidic and basic systems, to ionic liquids. Then, innovative green syntheses of task-specific ILs and their representative applications are introduced to detail the efficiency and highly selective outcome of ILs-catalyzed transesterification reactions. A mechanistic hypothesis is discussed by the concept of cooperative catalysis based on the dual (electrophilic/nucleophilic) activation of reactants. PMID:27829898

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

PubMed Central

Sallio, Romain; Lebrun, Stéphane; Capet, Frédéric; Agbossou-Niedercorn, Francine

2018-01-01

A new asymmetric organocatalyzed intramolecular aza-Michael reaction by means of both a chiral auxiliary and a catalyst for stereocontrol is reported for the synthesis of optically active isoindolinones. A selected cinchoninium salt was used as phase-transfer catalyst in combination with a chiral nucleophile, a Michael acceptor and a base to provide 3-substituted isoindolinones in good yields and diastereomeric excesses. This methodology was applied to the asymmetric synthesis of a new pazinaclone analogue which is of interest in the field of benzodiazepine-receptor agonists. PMID:29623121