Cluster Quantum Chemical Study of the Grignard Reagent Formation

NASA Astrophysics Data System (ADS)

Tulub, A. V.; Porsev, V. V.

The main stages of the Grignard reagent formation are described in a framework of quantum chemical cluster model. We have established two kinds of the adsorption of CH3Hal on Mgn clusters, one of which leads to radical formation and the second is responsible for radical free dissociate adsorption. The charge redistribution in cluster CH3MgnHal result to the strong electrostatic interaction with ether and Grignard reagent formation without any activation barrier.

Diastereoselective addition of Grignard reagents to α-epoxy N-sulfonyl hydrazones

NASA Astrophysics Data System (ADS)

Uteuliyev, Maulen M.; Nguyen, Thien T.; Coltart, Don M.

2015-12-01

The α-alkylation of ketones and their derivatives by the addition of their corresponding enolates to alkyl halides is a fundamental synthetic transformation, but its utility is limited because the key bond-forming step proceeds in a bimolecular nucleophilic substitution fashion. Here we describe how an umpolung strategy that involves the addition of Grignard reagents to α-epoxy N-sulfonyl hydrazones—directed by the alkoxide of the 1-azo-3-alkoxy propenes formed in situ via base-induced ring opening of the epoxide—leads to the syn-selective production of α-alkyl-β-hydroxy N-sulfonyl hydrazones with α-quaternary centres. This transformation is remarkable in its ability to incorporate an unprecedented range of carbon-based substituents, which include primary, secondary and tertiary alkyl, as well as alkenyl, aryl, allenyl and alkynyl groups. Subsequent hydrolysis of the β-hydroxy N-sulfonyl hydrazone products produces the corresponding β-hydroxy ketones. In addition to hydrolysis, the hydrazone products are poised to undergo numerous different known synthetic transformations via well-established chemistry, which would provide access to a wide array of useful structures.

Arylation, alkenylation, and alkylation of 2-halopyridine N-oxides with grignard reagents: a solution to the problem of C2/C6 regioselective functionalization of pyridine derivatives.

PubMed

Zhang, Song; Liao, Lian-Yan; Zhang, Fang; Duan, Xin-Fang

2013-03-15

A facile arylation, alkenylation, and alkylation of functionalized 2-halopyridine N-oxides with various Grignard reagents was developed. It represented a highly efficient and selective C-H bond functionalization of pyridine derivatives in the presence of reactive C-Cl or C-Br bonds. Using Cl or Br as a blocking group, C2/C6 site-controllable functionalization of pyridine derivatives has been achieved. Various pyridine compounds can be prepared as illustrated in the total syntheses of Onychine, dielsine, and PARP-1 inhibitor GPI 16539.

Iron- and cobalt-catalyzed arylation of azetidines, pyrrolidines, and piperidines with Grignard reagents.

PubMed

Barré, Baptiste; Gonnard, Laurine; Campagne, Rémy; Reymond, Sébastien; Marin, Julien; Ciapetti, Paola; Brellier, Marie; Guérinot, Amandine; Cossy, Janine

2014-12-05

Iron- and cobalt-catalyzed cross-couplings between iodo-azetidines, -pyrrolidines, -piperidines, and Grignard reagents are disclosed. The reaction is efficient, cheap, chemoselective and tolerates a large variety of (hetero)aryl Grignard reagents.

How to prepare a chiral Grignard reagent: a theoretical proposal.

PubMed

Chen, Zhe-Ning; Fu, Gang; Xu, Xin

2011-04-15

It is shown that two competitive pathways (T2 vs T4) exist for Grignard reagent formation. While the nonradical pathway T2 leads to retention of the configuration, the radical pathway T4 gives racemization. Our calculations suggest the way that T2 can be enhanced, which should be of significance to prompt new synthesis approaches for the preparation of chiral Grignard reagents. © 2011 American Chemical Society

Reactions of in situ generated N-Boc nitrones with aromatic and heteroaromatic grignard reagents: application to the synthesis of zileuton.

PubMed

Guinchard, Xavier; Denis, Jean-Noël

2008-03-07

A new class of alpha-aromatic-N-hydroxylamines has been prepared by reaction of tert-butyl (phenylsulfonyl)alkyl-N-hydroxycarbamates with aromatic and heteroaromatic Grignard reagents. Reactions proceed via a base-assisted elimination of the phenylsulfonyl group leading to N-Boc nitrones. This methodology has been applied to the synthesis of zileuton.

Regioselective copper-catalyzed alkylation of [2.2.2]-acylnitroso cycloadducts: remarkable effect of the halide of Grignard reagents.

PubMed

Crotti, Stefano; Bertolini, Ferruccio; di Bussolo, Valeria; Pineschi, Mauro

2010-04-16

Ring opening with organometallic reagents of [2.2.2]-acylnitroso cycloadducts, including an enantioselective kinetic resolution of these compounds, has been accomplished for the first time. By the careful choice of reaction conditions, it was possible to obtain new cyclohexenyl hydroxamic acids with complete anti-stereoselectivity and a nice regioalternating control. A remarkable effect of the halogen of the Grignard reagent was observed during ring opening.

A unified model of Grignard reagent formation.

PubMed

Shao, Yunqi; Liu, Zhen; Huang, Pan; Liu, Boping

2018-04-25

Grignard reagents are among the most fundamental reagents in organic synthesis, yet studies have hitherto failed to fully explain the selectivity and kinetics of Grignard reagent formation (GRF). The present study provides new insights into the intermediates and pathways of GRF using density functional theory (DFT) calculations. Potential energy surfaces of RX dissociation along different directions reveal the origin of configuration retention of alkenyl and aromatic halides. Radical intermediates participate solely in the dissociation stage, and depend on the geometry of the reactant halide. Dissociation of organic halides yields stabilized surface anions, and the rest of the reaction is ionic in nature. MgX+/RMg+ were proposed as the key intermediates of Mg leaving from the surface in the self-activation of GRF, which explains the accelerated kinetics upon addition of RMgX or MgX2. The intermediacy of the cations was supported by a simple electrochemical experiment. To the best of our knowledge, this is the first unified ionic model (I-model) developed for resolving the controversial issues of GRF.

Theoretical studies on Grignard reagent formation: radical mechanism versus non-radical mechanism.

PubMed

Chen, Zhe-Ning; Fu, Gang; Xu, Xin

2012-12-21

Here we present a systematic theoretical investigation on the mechanisms of Grignard reagent formation (GRF) for CH(3)Cl reacting with Mg atom, Mg(2) and a series of Mg clusters (Mg(4)-Mg(20)). Our calculations reveal that the ground state Mg atom is inactive under matrix condition, whereas it is active under metal vapor synthesis (MVS) conditions. On the other hand, the excited state Mg ((3)P) atom, as produced by laser-ablation, can react with CH(3)Cl barrierlessly, and hence is active under matrix condition. We predict that the bimagnesium Grignard reagent, though often proposed, can barely be observed experimentally, due to its high reactivity towards additional CH(3)Cl to produce more stable Grignard reagent dimer, and that the cluster Grignard reagent RMg(4)X possesses a flat Mg(4) unit rather than a tetrahedral geometry. Our calculations further reveal that the radical pathway (T4) is prevalent on Mg, Mg(2) and Mg(n) clusters of small size, while the no-radical pathway (T2), which starts at Mg(4), becomes competitive with T4 as the cluster size increases. A structure-reactivity relationship between barrier heights and ionization potentials of Mg(n) is established. These findings not only resolve controversy in experiment and theory, but also provide insights which can be used in the design of effective synthesis approaches for the preparation of chiral Grignard reagents.

Do dihydroxymagnesium carboxylates form Grignard-type reagents? A theoretical investigation on decarboxylative fragmentation.

PubMed

Ruf, Alexander; Kanawati, Basem; Schmitt-Kopplin, Philippe

2018-03-27

Dihydroxymagnesium carboxylates [(OH) 2 MgO 2 CR] were probed for decarboxylation on a theoretical level, by utilizing both Møller-Plesset perturbation theory (MP2) and density functional theory (B3LYP-DFT) computations. This study is connected to the question of whether this recently introduced, astrobiologically relevant chemical class may form Grignard-type reagent molecules. To extract trends for a broad molecular mass range, different linear alkyl chain lengths between C 4 and C 11 were computed. The forward energy barrier for decarboxylation reactions increases linearly as a function of the ligand's chain length. Decarboxylation-type fragmentations of these organomagnesium compounds seem to be improbable in non-catalytic, low energetic environments. A high forward energy barrier (E MP2  > 55 kcal mol -1 ) towards a described transition state restricts the release of CO 2 . Nevertheless, we propose the release of CO 2 on a theoretical level, as been revealed via an intramolecular nucleophilic attack mechanism. Once the challenging transition state for decarboxylation is overcome, a stable Mg-C bond is formed. These mechanistic insights were gained by help of natural bond orbital analysis. The Cα atom (first carbon atom in the ligand chain attached to the carboxyl group) is thought to prefer binding towards the electrophilic magnesium coordination center, rather than towards the electrophilic CO 2 -carbon atom. Additionally, the putatively formed Grignard-type OH-bearing product molecules possess a more polarized Mg-C bond in comparison to RMgCl species. Therefore, carbanion formation from OH-bearing Grignard-type molecules is made feasible for triggering C-C bond formation reactions. Graphical abstract This study asks whether recently introduced, astrobiologically dihydroxymagnesium carboxylates form Grignard-type reagent molecules via decarboxylative fragmentation.

Highly versatile enantioselective conjugate addition of Grignard reagents to alpha,beta-unsaturated thioesters.

PubMed

Ruiz, Beatriz Maciá; Geurts, Koen; Fernández-Ibáñez, M Angeles; ter Horst, Bjorn; Minnaard, Adriaan J; Feringa, Ben L

2007-11-22

Herein, we report efficient catalysts for the asymmetric copper-catalyzed conjugate addition of Grignard reagents to alpha,beta-unsaturated thioesters. MeMgBr adds to aromatic alpha,beta-unsaturated thioesters with excellent enantioselectivities and moderate to good yields using Josiphos/CuBr and Tol-BINAP/CuI complexes. The use of bulky Grignard reagents leads to unprecedented enantioselectivities in the 1,4-addition to a broad range of aromatic and aliphatic alpha,beta-unsaturated thioesters using Tol-BINAP/CuI. The highest enantioselectivities reported so far for the addition of Grignard reagents to crowded beta-substituted aliphatic substrates are achieved with Tol-BINAP/CuI.

Formation of Hydridocyclotriphosphazenes Via the Reactions of Organocopper Reagents with Halocyclotriphosphazenes: The Reaction Mechanism.

DTIC Science & Technology

1979-04-26

synthesized by th. new reaction of hexachlorocyclotniphosphazene, (NPC12)3, with alkyl Grignard reagents in the presence of [(~—C4H9)3PCuIJ4, followed by...NPC12)3 was allowed to react with alkyl Grignard reagents in the presence of (~—Bu3PCuI] 4, 34 followed by treatment with 2—propano...mixture.46 Surprisingly, it was found that although the (NPC12)3 was consumed in direct proportion to the amount of Grignard reagent added (up to 3—3.5

Nucleophilic substitution by grignard reagents on sulfur mustards.

PubMed

Converso, Antonella; Saaidi, Pierre-Loïc; Sharpless, K Barry; Finn, M G

2004-10-15

With proper activation of the leaving group, sulfur mustards react with Grignard reagents with neighboring group participation of the sulfur atom. 2,6-Dichloro-9-thiabicyclo[3.3.1]nonane is especially useful in this regard, providing clean reactivity with organomagnesium nucleophiles on a topologically constrained scaffold.

Synthesis of 1,4-amino alcohols by Grignard reagent addition to THF and N-tosyliminobenzyliodinane.

PubMed

Tejo, Ciputra; See, Yang Feng Anders; Mathiew, Mitch; Chan, Philip Wai Hong

2016-01-21

The synthesis of 1,4-amino alcohols from THF treated with N-tosyliminobenzyliodinane (PhINTs) followed by a Grignard reagent under mild reaction conditions at room temperature is described herein. Various Grignard reagents were shown to be compatible, furnishing the corresponding 4-substituted-N-1,4-tosylamino alcohols in good to excellent yields. A partial or full detosylation of the N-tosyl-1,4-amino alcohol was observed in instances involving a sterically bulky Grignard reagent, leading to the deprotected 1,4-amino alcohol product in moderate to good yields. The synthetic utility of this protocol was demonstrated by the synthesis of a 5-substituted-N-tosyl-1,5-amino alcohol from THP and the conversion of two examples to their corresponding γ-lactam and pyrrolidine adducts.

Nickel-catalyzed coupling reaction of alkyl halides with aryl Grignard reagents in the presence of 1,3-butadiene: mechanistic studies of four-component coupling and competing cross-coupling reactions† †Electronic supplementary information (ESI) available: Detailed experimental and computational results, procedures, characterization data, copies of NMR charts, and crystallographic data. CCDC 1572238. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc04675h

PubMed Central

Fukuoka, Asuka; Yokoyama, Wataru; Min, Xin; Hisaki, Ichiro; Kuniyasu, Hitoshi

2018-01-01

We describe the mechanism, substituent effects, and origins of the selectivity of the nickel-catalyzed four-component coupling reactions of alkyl fluorides, aryl Grignard reagents, and two molecules of 1,3-butadiene that affords a 1,6-octadiene carbon framework bearing alkyl and aryl groups at the 3- and 8-positions, respectively, and the competing cross-coupling reaction. Both the four-component coupling reaction and the cross-coupling reaction are triggered by the formation of anionic nickel complexes, which are generated by the oxidative dimerization of two molecules of 1,3-butadiene on Ni(0) and the subsequent complexation with the aryl Grignard reagents. The C–C bond formation of the alkyl fluorides with the γ-carbon of the anionic nickel complexes leads to the four-component coupling product, whereas the cross-coupling product is yielded via nucleophilic attack of the Ni center toward the alkyl fluorides. These steps are found to be the rate-determining and selectivity-determining steps of the whole catalytic cycle, in which the C–F bond of the alkyl fluorides is activated by the Mg cation rather than a Li or Zn cation. ortho-Substituents of the aryl Grignard reagents suppressed the cross-coupling reaction leading to the selective formation of the four-component products. Such steric effects of the ortho-substituents were clearly demonstrated by crystal structure characterizations of ate complexes and DFT calculations. The electronic effects of the para-substituent of the aryl Grignard reagents on both the selectivity and reaction rates are thoroughly discussed. The present mechanistic study offers new insight into anionic complexes, which are proposed as the key intermediates in catalytic transformations even though detailed mechanisms are not established in many cases, and demonstrates their synthetic utility as promising intermediates for C–C bond forming reactions, providing useful information for developing efficient and straightforward

Using a Premade Grignard Reagent to Synthesize Tertiary Alcohols in a Convenient Investigative Organic Laboratory Experiment

ERIC Educational Resources Information Center

Berg, Michael A. G.; Pointer, Roy D.

2007-01-01

A commercially available Grignard reagent (3.0 M solution of phenyl magnesium bromide in ether) was used in a convenient Grignard synthesis in a second-year organic chemistry laboratory without any of the typical failures associated with the Grignard reaction. The reaction setup used oven-dried glassware and no extraordinary measures were taken to…

Chemical bonding and the equilibrium composition of Grignard reagents in ethereal solutions.

PubMed

Henriques, André M; Barbosa, André G H

2011-11-10

A thorough analysis of the electronic structure and thermodynamic aspects of Grignard reagents and its associated equilibrium composition in ethereal solutions is performed. Considering methylmagnesium halides containing fluorine, chlorine, and bromine, we studied the neutral, charged, and radical species associated with their chemical equilibrium in solution. The ethereal solvents considered, tetrahydrofuran (THF) and ethyl ether (Et(2)O), were modeled using the polarizable continuum model (PCM) and also by explicit coordination to the Mg atoms in a cluster. The chemical bonding of the species that constitute the Grignard reagent is analyzed in detail with generalized valence bond (GVB) wave functions. Equilibrium constants were calculated with the DFT/M06 functional and GVB wave functions, yielding similar results. According to our calculations and existing kinetic and electrochemical evidence, the species R(•), R(-), (•)MgX, and RMgX(2)(-) must be present in low concentration in the equilibrium. We conclude that depending on the halogen, a different route must be followed to produce the relevant equilibrium species in each case. Chloride and bromide must preferably follow a "radical-based" pathway, and fluoride must follow a "carbanionic-based" pathway. These different mechanisms are contrasted against the available experimental results and are proven to be consistent with the existing thermodynamic data on the Grignard reagent equilibria.

Preparation and reactions of enantiomerically pure α-functionalized Grignard reagents.

PubMed

Rayner, Peter J; O'Brien, Peter; Horan, Richard A J

2013-05-29

A strategy for the generation of enantiomerically pure α-functionalized chiral Grignard reagents is presented. The approach involves the synthesis of α-alkoxy and α-amino sulfoxides in ≥99:1 dr and ≥99:1 er via asymmetric deprotonation (s-BuLi/chiral diamine) and trapping with Andersen's sulfinate (menthol derived). Subsequent sulfoxide → Mg exchange (room temperature, 1 min) and electrophilic trapping delivers a range of enantiomerically pure α-alkoxy and α-amino substituted products. Using this approach, either enantiomer of products can be accessed in 99:1 er from asymmetric deprotonation protocols without the use of (-)-sparteine as the chiral ligand. Two additional discoveries are noteworthy: (i) for the deprotonation and trapping with Andersen's sulfinate, there is a lack of stereospecificity at sulfur due to attack of a lithiated intermediate onto the α-alkoxy and α-amino sulfoxides as they form, and (ii) the α-alkoxy-substituted Grignard reagent is configurationally stable at room temperature for 30 min.

Substitution of the nitro group with Grignard reagents: facile arylation and alkenylation of pyridine N-oxides.

PubMed

Zhang, Fang; Zhang, Song; Duan, Xin-Fang

2012-11-02

The unprecedented substitution of a nitro group with aryl or alkenyl groups of Grignard reagents affords 2-aryl or alkenylpyridine N-oxides in modest to high yields with high chemoselectivity. This protocol allows a simple and clean synthesis of various 2-substituted pyridine N-oxides and the corresponding pyridine derivatives. Furthermore, straightforward one-pot iterative functionality of pyridine N-oxides could also be achieved simply by successive applications of two Grignard reagents.

Copper-catalyzed synthesis of phenanthridine derivatives under an oxygen atmosphere starting from biaryl-2-carbonitriles and Grignard reagents.

PubMed

Zhang, Line; Ang, Gim Yean; Chiba, Shunsuke

2010-08-20

A copper-catalyzed synthesis of phenanthridine derivatives was developed starting from biaryl-2-carbonitriles and Grignard reagents. The present transformation is carried out by a sequence of nucleophilic addition of Grignard reagents to biaryl-2-carbonitriles to form N-H imines and their Cu-catalyzed C-N bond formation on the aromatic C-H bond, where molecular oxygen is a prerequisite to achieve the catalytic process.

Copper-catalyzed asymmetric conjugate addition of Grignard reagents to trisubstituted enones. Construction of all-carbon quaternary chiral centers.

PubMed

Martin, David; Kehrli, Stefan; d'Augustin, Magali; Clavier, Hervé; Mauduit, Marc; Alexakis, Alexandre

2006-07-05

The copper-catalyzed asymmetric conjugate addition of Grignard reagents to trisubstituted cyclic enones affords enantioenriched all-carbon quaternary centers with up to 96% ee. The chiral ligand is a diaminocarbene, directly generated in situ. The combination of Grignard reagent and diaminocarbene is unprecedented in conjugate addition, and the additon of the phenyl group, on such enones, cannot be done by other conjugate addition methods.

Iron-catalyzed cross-coupling of imidoyl chlorides with Grignard reagents.

PubMed

Ottesen, Lars K; Ek, Fredrik; Olsson, Roger

2006-04-27

[reaction: see text] A general, high yielding rapid iron-catalyzed cross-coupling reaction between Grignard reagents and imidoyl chlorides is described. These reactions are typically completed within 5 min, resulting in high yields of 71-96% using 5% iron catalyst in a THF-NMP solvent mixture. Functionalized imidoyl chlorides (e.g., R = CO(2)Me) gave excellent yields (89%).

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.

Iron-Catalyzed Enantioselective Cross-Coupling Reactions of α-Chloroesters with Aryl Grignard Reagents.

PubMed

Jin, Masayoshi; Adak, Laksmikanta; Nakamura, Masaharu

2015-06-10

The first iron-catalyzed enantioselective cross-coupling reaction between an organometallic compound and an organic electrophile is reported. Synthetically versatile racemic α-chloro- and α-bromoalkanoates were coupled with aryl Grignard reagents in the presence of catalytic amounts of an iron salt and a chiral bisphosphine ligand, giving the products in high yields with acceptable and synthetically useful enantioselectivities (er up to 91:9). The produced α-arylalkanoates were readily converted to the corresponding α-arylalkanoic acids with high optical enrichment (er up to >99:1) via simple deprotections/recrystallizations. The results of radical probe experiments are consistent with a mechanism that involves the formation of an alkyl radical intermediate, which undergoes subsequent enantioconvergent arylation in an intermolecular manner. The developed asymmetric coupling offers not only facile and practical access to various chiral α-arylalkanoic acid derivatives, which are of significant pharmaceutical importance, but also a basis of controlling enantioselectivity in an iron-catalyzed organometallic transformation.

Iron-catalyzed, directed oxidative arylation of olefins with organozinc and Grignard reagents.

PubMed

Ilies, Laurean; Okabe, Jun; Yoshikai, Naohiko; Nakamura, Eiichi

2010-06-18

Chelation-controlled arylation of olefins with organozinc or Grignard reagents proceeds in the presence of an iron catalyst, under mild conditions and typically without the need of external ligands, to afford substituted olefins in high yield and with complete regio- and stereocontrol.

Microwave-induced electrostatic etching: generation of highly reactive magnesium for application in Grignard reagent formation.

PubMed

van de Kruijs, Bastiaan H P; Dressen, Mark H C L; Meuldijk, Jan; Vekemans, Jef A J M; Hulshof, Lumbertus A

2010-04-07

A detailed study regarding the influence of microwave irradiation on the formation of a series of Grignard reagents in terms of rates and selectivities has revealed that these heterogeneous reactions may display a beneficial microwave effect. The interaction between microwaves and magnesium turnings generates violent electrostatic discharges. These discharges on magnesium lead to melting of the magnesium surface, thus generating highly active magnesium particles. As compared to conventional operation the microwave-induced discharges on the magnesium surface lead to considerably shorter initiation times for the insertion of magnesium in selected substrates (i.e. halothiophenes, halopyridines, octyl halides, and halobenzenes). Thermographic imaging and surface characterization by scanning electron microscopy showed that neither selective heating nor a "specific" microwave effect was causing the reduction in initiation times. This novel and straightforward initiation method eliminates the use of toxic and environmentally adverse initiators. Thus, this initiation method limits the formation of by-products. We clearly demonstrated that microwave irradiation enables fast Grignard reagent formation. Therefore, microwave technology is promising for process intensification of Grignard based coupling reactions.

Synthesis of aryl thioethers through the N-chlorosuccinimide-promoted cross-coupling reaction of thiols with Grignard reagents.

PubMed

Cheng, Jun-Hao; Ramesh, Chintakunta; Kao, Hsin-Lun; Wang, Yu-Jen; Chan, Chien-Ching; Lee, Chin-Fa

2012-11-16

A convenient one-pot approach for the synthesis of aryl sulfides through the coupling of thiols with Grignard reagents in the presence of N-chlorosuccinimide is described. The sulfenylchlorides were formed when thiols were treated with N-chlorosuccinimide, and the resulting sulfenylchlorides were then directly reacted with Grignard reagents to provide aryl sulfides in good to excellent yields under mild reaction conditions. Functional groups including ester, fluoro, and chloro are tolerated by the reaction conditions employed. It is important to note that this method has a short reaction time (30 min in total) and represents an alternative approach for the synthesis of aryl sulfides over the existing protocols.

Improved synthesis of aryltrialkoxysilanes via treatment of aryl Grignard or lithium reagents with tetraalkyl orthosilicates.

PubMed

Manoso, Amy S; Ahn, Chuljin; Soheili, Arash; Handy, Christopher J; Correia, Reuben; Seganish, W Michael; Deshong, Philip

2004-11-26

General reaction conditions for the synthesis of aryl(trialkoxy)silanes from aryl Grignard and lithium reagents and tetraalkyl orthosilicates (Si(OR)(4)) have been developed. Ortho-, meta-, and para-substituted bromoarenes underwent efficient metalation and silylation at low temperature to provide aryl siloxanes. Mixed results were obtained with heteroaromatic substrates: 3-bromothiophene, 3-bromo-4-methoxypyridine, 5-bromoindole, and N-methyl-5-bromoindole underwent silylation in good yield, whereas a low yield of siloxane was obtained from 2-bromofuran, and 2-bromopyridine failed to give silylated product. The synthesis of siloxanes via organolithium and magnesium reagents was limited by the formation of di- and triarylated silanes (Ar(2)Si(OR)(2) and Ar(3)SiOR, respectively) and dehalogenated (Ar-H) byproducts. Silylation at low temperature gave predominantly monoaryl siloxanes, without requiring a large excess of the electrophile. Optimal reaction conditions for the synthesis of siloxanes from aryl Grignard reagents entailed addition of arylmagnesium reagents to 3 equiv of tetraethyl- or tetramethyl orthosilicate at -30 degrees C in THF. Aryllithium species were silylated using 1.5 equiv of tetraethyl- or tetramethyl orthosilicate at -78 degrees C in ether.

Catalytic enantioselective addition of Grignard reagents to aromatic silyl ketimines

NASA Astrophysics Data System (ADS)

Rong, Jiawei; Collados, Juan F.; Ortiz, Pablo; Jumde, Ravindra P.; Otten, Edwin; Harutyunyan, Syuzanna R.

2016-12-01

α-Chiral amines are of significant importance in medicinal chemistry, asymmetric synthesis and material science, but methods for their efficient synthesis are scarce. In particular, the synthesis of α-chiral amines with the challenging tetrasubstituted carbon stereocentre is a long-standing problem and catalytic asymmetric additions of organometallic reagents to ketimines that would give direct access to these molecules are underdeveloped. Here we report a highly enantioselective catalytic synthesis of N-sulfonyl protected α-chiral silyl amines via the addition of inexpensive, easy to handle and readily available Grignard reagents to silyl ketimines. The key to this success was our ability to suppress any unselective background addition reactions and side reduction pathway, through the identification of an inexpensive, chiral Cu-complex as the catalytically active structure.

Routes to ultra-pure alkyls of indium and gallium and their adducts with ethers, phosphines and amines

NASA Astrophysics Data System (ADS)

Jones, Anthony C.; Holliday, A. Kenneth; Cole-Hamilton, David J.; Ahmad, M. Munir; Gerrard, Neil D.

1984-09-01

Electrolysis of tetrahydrofuran (thf) solutions of dimethylmagnesium containing tetraethylammonium percholrate using a gallium anode gives [Me 3Ga·thf], but higher yields of both [Me 3Ga·thf] and [Me 3In·thf] are obtained on electrolysis of thf solutions of Grignard reagents with sacrificial metal anodes in the absence of a carrying electrolyte. The thf adducts can be converted into adducts with other Lewis bases, [ Me3M· L], M = Ga or In, L = PMe 3, PEt 3, NEt 3, by simple base exchange reactions. Base-free trimethylgallium can be prepared from: (i) reaction of methyl iodide with the intermetallic compound [Mg 5Ga 2] in a high boiling ether; (ii) electrolysis of Grignard reagents in high boiling ethers using sacrificial gallium anodes; (iii) reactions of GaCl 3 with Grignard reagents in high boiling ethers or (iv) ether exchange reaction between [Me 3Ga·OEt 2] and high boiling ethers. All of these reactions lead to adducts between trimethylgallium and the high boiling ether which, on heating, decompose to give base-free trimethylgallium. [Me 3Ga·OEt 2] can be prepared from reaction of Grignard reagents with gallium trichloride in diethylether or from electrolysis of Grignard reagents in diethyl ether using a sacrificial gallium anode. Similar reactions using an indium anode lead to [Me 3In·OEt 2] from which base-free trimethylindium can be liberated using known chemistry. The use of alkyls prepared in this way for vapour phase epitaxy as well as the purity of the alkyls are discussed.

Copper-catalyzed oxidative homo- and cross-coupling of Grignard reagents using diaziridinone.

PubMed

Zhu, Yingguang; Xiong, Tao; Han, Wenyong; Shi, Yian

2014-12-05

Transition-metal-catalyzed cross-coupling reactions are among the most powerful synthetic transformations. This paper describes an efficient copper-catalyzed homo- and cross-coupling of Grignard reagents with di-tert-butyldiaziridinone as oxidant under mild conditions, giving the coupling products in good to excellent yields. The reaction process has a broad substrate scope and is also effective for the C(sp)-C(sp(3)) coupling.

Inverse temperature dependence in the diastereoselective addition of Grignard reagents to a tetrahydrofurfural.

PubMed

Mowat, Jeffrey; Kang, Baldip; Fonovic, Branden; Dudding, Travis; Britton, Robert

2009-05-21

A remarkable example of inverse-temperature-dependent diastereoselectivity was uncovered while investigating the addition of Grignard reagents to a 3-hydroxytetrahydrofurfural. The free hydroxyl group in the tetrahydrofurfural was found to play a key role in these processes, a result corroborated through a series of DFT calculations that also highlighted an entropic preference for the formation of one diastereomer.

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.

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

Copper-Catalyzed Oxidative Homo- and Cross-Coupling of Grignard Reagents Using Diaziridinone

PubMed Central

2015-01-01

Transition-metal-catalyzed cross-coupling reactions are among the most powerful synthetic transformations. This paper describes an efficient copper-catalyzed homo- and cross-coupling of Grignard reagents with di-tert-butyldiaziridinone as oxidant under mild conditions, giving the coupling products in good to excellent yields. The reaction process has a broad substrate scope and is also effective for the C(sp)–C(sp3) coupling. PMID:25420218

Enantiomerically Pure Acetals in Organic Synthesis: Resolutions and Diastereoselective Alkylations of Alpha-Hydroxy Esters

DTIC Science & Technology

1990-01-01

sensitivity of the alkylating agent to the reaction conditions. In either case , a decision was made to use 5-iodo-2- methyl -l-pentene as the alkylating ...agent, and the reaction conditions. In most cases the diastereomeric products of the alkylation were also separated by column chromatography. This...equatorially substituted product. Oxidation of the alcohol to the ketone followed by treatment with an alkyl Grignard reagent gave only the product which

Oxonitriles: A Grignard Addition-Acylation Route to Enamides

PubMed Central

Wei, Guoqing; Zhang, Zhiyu; Steward, Omar W.

2008-01-01

Sequential addition of three different Grignard reagents and pivaloyl chloride to 3-oxo-1-cyclohexene-1-carbonitrile installs four new bonds to generate a diverse array of cyclic enamides. Remarkably, formation of the C-magnesiated nitrile intermediate is followed by preferential acylation by pivaloyl chloride rather than consumption by in situ Grignard reagent. Rapid N-acylation of the C-magnesiated nitrile generates an acyl ketenimine that reacts readily with Grignard reagents, or a trialkyl zincate, effectively assembling highly substituted, cyclic enamides. PMID:17020332

Association and Dissociation of Grignard Reagents RMgCl and Their Turbo Variant RMgCl⋅LiCl.

PubMed

Schnegelsberg, Christoph; Bachmann, Sebastian; Kolter, Marlene; Auth, Thomas; John, Michael; Stalke, Dietmar; Koszinowski, Konrad

2016-06-01

Grignard reagents RMgCl and their so-called turbo variant, the highly reactive RMgCl⋅LiCl, are of exceptional synthetic utility. Nevertheless, it is still not fully understood which species these compounds form in solution and, in particular, in which way LiCl exerts its reactivity-enhancing effect. A combination of electrospray-ionization mass spectrometry, electrical conductivity measurements, NMR spectroscopy (including diffusion-ordered spectroscopy), and quantum chemical calculations is used to analyze solutions of RMgCl (R=Me, Et, Bu, Hex, Oct, Dec, iPr, tBu, Ph) in tetrahydrofuran and other ethereal solvents in the absence and presence of stoichiometric amounts of LiCl. In tetrahydrofuran, RMgCl forms mononuclear species, which are converted into trinuclear anions as a result of the concentration increase experienced during the electrospray process. These trinuclear anions are theoretically predicted to adopt open cubic geometries, which remarkably resemble structural motifs previously found in the solid state. The molecular constituents of RMgCl and RMgCl⋅LiCl are interrelated via Schlenk equilibria and fast intermolecular exchange processes. A small portion of the Grignard reagent also forms anionic ate complexes in solution. The abundance of these more electron-rich and hence supposedly more nucleophilic ate complexes strongly increases upon the addition of LiCl, thus rationalizing its beneficial effect on the reactivity of Grignard reagents. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

"Anti-Michael addition" of Grignard reagents to sulfonylacetylenes: synthesis of alkynes.

PubMed

Esteban, Francisco; Boughani, Lazhar; García Ruano, José L; Fraile, Alberto; Alemán, José

2017-05-10

In this work, the addition of Grignard reagents to arylsulfonylacetylenes, which undergoes an "anti-Michael addition", resulting in their alkynylation under very mild conditions is described. The simplicity of the experimental procedure and the functional group tolerance are the main features of this methodology. This is an important advantage over the use of organolithium at -78 °C that we previously reported. Moreover, the synthesis of diynes and other examples showing functional group tolerance in this anti-Michael reaction is also presented.

Iron-catalyzed oxidative biaryl cross-couplings via mixed diaryl titanates: significant influence of the order of combining aryl Grignard reagents with titanate.

PubMed

Liu, Kun Ming; Wei, Juan; Duan, Xin Fang

2015-03-18

The mixed diaryl titanates were used for the first time to modify the reactivity of two aryl Grignard reagents. Two titanate intermediates, Ar[Ar'Ti(OR)3]MgX and Ar'[ArTi(OR)3]MgX, formed via alternating the sequence of combining Grignard reagents with ClTi(OR)3 showed a significant reactivity difference. Taking advantage of such different reactivity, two highly structurally similar aryl groups could be facilely assembled through iron-catalyzed oxidative cross-couplings using oxygen as the oxidant.

Oxonitriles: a grignard addition-acylation route to enamides.

PubMed

Fleming, Fraser F; Wei, Guoqing; Zhang, Zhiyu; Steward, Omar W

2006-10-12

[reaction: see text] Sequential addition of three different Grignard reagents and pivaloyl chloride to 3-oxo-1-cyclohexene-1-carbonitrile installs four new bonds to generate a diverse array of cyclic enamides. Remarkably, formation of the C-magnesiated nitrile intermediate is followed by preferential acylation by pivaloyl chloride rather than consumption by an in situ Grignard reagent. Rapid N-acylation of the C-magnesiated nitrile generates an acyl ketenimine that reacts readily with Grignard reagents or a trialkylzincate, effectively assembling highly substituted, cyclic enamides.

An unusual reaction of α-alkoxyphosphonium salts with Grignard reagents under an O2 atmosphere.

PubMed

Fujioka, Hiromichi; Goto, Akihiro; Otake, Kazuki; Kubo, Ozora; Sawama, Yoshinari; Maegawa, Tomohiro

2011-09-21

An unusual and novel reaction of α-alkoxyphosphonium salts, generated from O,O-acetals and Ph(3)P, with Grignard reagents under an O(2) atmosphere afforded alcohols in moderate to high yields. It was clarified by isotopic labelling experiments that the reaction proceeded via a novel radical pathway.

Vinylation of nitro-substituted indoles, quinolinones, and anilides with grignard reagents.

PubMed

Egris, Riccardo; Villacampa, Mercedes; Menéndez, J Carlos

2009-10-19

The reaction of vinyl Grignard reagents with o-methoxynitroarenes containing an electron-releasing substituent para to the nitro group proceeds through a pathway that is different from the initially expected Bartoli indole synthesis. Thus, instead of giving fused indole derivatives, these reactions provide a very mild and efficient new procedure for the synthesis of synthetically relevant aromatic systems containing an o-nitrovinyl moiety, such as 5-nitro-4-vinylindoles, 6-nitro-7-vinylindoles, 6-nitro-5-vinyl-2(1H)quinolinones, and 4-nitro-3-vinylanilines.

Cyclopropylamines from N,N-dialkylcarboxamides and Grignard reagents in the presence of titanium tetraisopropoxide or methyltitanium triisopropoxide.

PubMed

de Meijere, Armin; Chaplinski, Vladimir; Winsel, Harald; Kordes, Markus; Stecker, Björn; Gazizova, Vesta; Savchenko, Andrei I; Boese, Roland; Schill, Farina

2010-12-10

Thirty-three different N,N-dialkyl- and N-alkyl-N-phosphorylalkyl-substituted carboxamides 9-17 were treated with unsubstituted as well as with 2-alkyl-, 2,2-dialkyl-, and 3-alkenyl-substituted ethylmagnesium bromides 6 in the presence of stoichiometric amounts of titanium tetraisopropoxide or methyltitanium triisopropoxide to furnish substituted cyclopropylamines 20-25 in 20-98% yield, depending on the substituents with no (1:1) to excellent (>25:1) diastereoselectivities. Generally higher yields (up to 98%) of the cyclopropylamines 20-28 without loss of the diastereoselectivity were obtained with methyltitanium triisopropoxide as the titanium mediator. Under these conditions, even dioxolane-protected ketones and halogen-substituted and chiral as well as achiral alkyloxyalkyl-substituted carboxamides could be converted to the correspondingly substituted cyclopropylamines with unsubstituted as well as phenyl- and a variety of alkyl-substituted ethylmagnesium bromides in addition to numerous heteroatom-containing (e.g., halogen-, trityloxy-, tetrahydropyranyloxy-substituted) Grignard reagents (62 examples altogether). The transformation of N,N-diformylalkylamines 54 with ethylmagnesium bromide in the presence of methyltitanium triisopropoxide to N,N-dicyclopropyl-N-alkylamines 55 can be brought about in up to 82% yield (6 examples). An asymmetric variant of the titanium-mediated cyclopropanation of N,N-dialkylcarboxamides has been developed by applying chiral titanium mediators generated from stoichiometric amounts of titanium tetraisopropoxide and chiral diamino or diol ligands, respectively. The most efficient chiral mediators turned out to be titanium bistaddolates that provided the corresponding cyclopropylamines with enantiomeric excesses (ee) of up to 84%. Evaluation of several silyl-based additives revealed that the reaction can also efficiently be carried out with substoichiometric amounts (down to 25 mol%) of the titanium reagent, as long as 2-aryl- or 2

Enantioselective synthesis of substituted piperidines by addition of aryl Grignard reagents to pyridine N-oxides.

PubMed

Hussain, Munawar; Banchelin, Thomas Sainte-Luce; Andersson, Hans; Olsson, Roger; Almqvist, Fredrik

2013-01-04

The synthesis of optically active piperidines by enantioselective addition of aryl Grignard reagents to pyridine N-oxides and lithium binolate followed by reduction is reported for the first time. The reaction results in high yields (51-94%) in combination with good ee (54-80%). Some of these products were subsequently recrystallized, affording enhanced optical purities (>99% ee).

Efficient preparation of terminal conjugated dienes by coupling of dienol phosphates with grignard reagents under iron catalysis.

PubMed

Cahiez, Gérard; Habiak, Vanessa; Gager, Olivier

2008-06-19

An efficient new route to prepare stereoselectively terminal conjugated dienes by coupling Grignard reagents and dienol phosphates in the presence of Fe(acac)3 is described. The synthetic utility of this new iron-catalyzed procedure is illustrated by the synthesis of the pheromone of Diparopsis castanea according to a very expeditious strategy.

Continuous-flow synthesis of functionalized phenols by aerobic oxidation of Grignard reagents.

PubMed

He, Zhi; Jamison, Timothy F

2014-03-24

Phenols are important compounds in chemical industry. An economical and green approach to phenol preparation by the direct oxidation of aryl Grignard reagents using compressed air in continuous gas-liquid segmented flow systems is described. The process tolerates a broad range of functional groups, including oxidation-sensitive functionalities such as alkenes, amines, and thioethers. By integrating a benzyne-mediated in-line generation of arylmagnesium intermediates with the aerobic oxidation, a facile three-step, one-flow process, capable of preparing 2-functionalized phenols in a modular fashion, is established. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Use of [superscript 1]H, [superscript 13]C, and [superscript 19]F-NMR Spectroscopy and Computational Modeling to Explore Chemoselectivity in the Formation of a Grignard Reagent

ERIC Educational Resources Information Center

Hein, Sara M.; Kopitzke, Robert W.; Nalli, Thomas W.; Esselman, Brian J.; Hill, Nicholas J.

2015-01-01

A discovery-based Grignard experiment for a second-year undergraduate organic chemistry course is described. The exclusive Grignard reagent formed by the reaction of 1-bromo-4-fluorobenzene (1) with Mg is 4-fluorophenylmagnesium bromide (2), which is treated with either benzophenone or CO[subscript 2] to produce the corresponding fluorinated…

Palladium- and nickel-catalyzed Kumada cross-coupling reactions of gem-difluoroalkenes and monofluoroalkenes with Grignard reagents.

PubMed

Dai, Wenpeng; Xiao, Juan; Jin, Guanyi; Wu, Jingjing; Cao, Song

2014-11-07

A novel Kumada-Tamao-Corriu cross-coupling reaction of gem-di- or monofluoroalkenes with Grignard reagents, with or without β-hydrogen atoms, in the presence of a catalytic amount of palladium- or nickel-based catalysts has been developed. The reaction is performed under mild conditions (room temperature or reflux in diethyl ether for 1-2 h) and leads to di-cross- or mono-cross-coupled products in good to high yields.

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.

Chemoselective chromium(II)-catalyzed cross-coupling reactions of dichlorinated heteroaromatics with functionalized aryl grignard reagents.

PubMed

Steib, Andreas K; Kuzmina, Olesya M; Fernandez, Sarah; Malhotra, Sushant; Knochel, Paul

2015-01-26

Chromium(II) chloride catalyzes the chemoselective cross-coupling reaction of dichloropyridines with a range of functionalized (hetero)aromatic Grignard reagents at room temperature. Functional groups, such as esters and acetals, are well tolerated in this transformation. Previously challenging substrates, quinolines and isoquinolines, participate in the selective Cr-catalyzed cross-coupling in cyclopentyl methyl ether (CPME) as the solvent. The effective purging of Cr salts is demonstrated by using various solid supports. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tandem cyclopropanation with dibromomethane under Grignard conditions.

PubMed

Brunner, Gerhard; Eberhard, Laura; Oetiker, Jürg; Schröder, Fridtjof

2008-10-03

Tertiary Grignard reagents and dibromomethane efficiently cyclopropanate allylic (and certain homoallylic) magnesium and lithium alcoholates at ambient temperature in ether solvents. Lithium (homo)allyl alcoholates are directly cyclopropanated with magnesium and CH2Br2 under Barbier conditions at higher temperatures. The reaction rates depend on the substitution pattern of the (homo)allylic alcoholates and on the counterion with lithium giving best results. Good to excellent syn-selectivities are obtained from alpha-substituted substrates, which are in accord with a staggered Houk model. In tandem reactions, cyclopropyl carbinols are obtained from allyloxylithium or -magnesium intermediates, generated in situ by alkylation of conjugated aldehydes, ketones, and esters as well as from allyl carboxylates or vinyloxiranes. Using this methodology, numerous fragrance ingredients and their precursors were efficiently converted to the corresponding cyclopropyl carbinols.

Transnitrilation from Dimethylmalononitrile to Aryl Grignard and Lithium Reagents: A Practical Method for Aryl Nitrile Synthesis.

PubMed

Reeves, Jonathan T; Malapit, Christian A; Buono, Frederic G; Sidhu, Kanwar P; Marsini, Maurice A; Sader, C Avery; Fandrick, Keith R; Busacca, Carl A; Senanayake, Chris H

2015-07-29

An electrophilic cyanation of aryl Grignard or lithium reagents, generated in situ from the corresponding aryl bromides or iodides, by a transnitrilation with dimethylmalononitrile (DMMN) was developed. DMMN is a commercially available, bench-stable solid. The transnitrilation with DMMN avoids the use of toxic reagents and transition metals and occurs under mild reaction conditions, even for extremely sterically hindered substrates. The transnitrilation of aryllithium species generated by directed ortho-lithiation enabled a net C-H cyanation. The intermediacy of a Thorpe-type imine adduct in the reaction was supported by isolation of the corresponding ketone from the quenched reaction. Computational studies supported the energetic favorability of retro-Thorpe fragmentation of the imine adduct.

Nickel-catalyzed sp2 C-H bonds arylation of N-aromatic heterocycles with Grignard reagents at room temperature.

PubMed

Qu, Gui-Rong; Xin, Peng-Yang; Niu, Hong-Ying; Wang, Dong-Chao; Ding, Rui-Fang; Guo, Hai-Ming

2011-10-21

A novel protocol for nickel-catalyzed direct sp(2) C-H bond arylation of purines has been developed. This new reaction proceeded efficiently at room temperature using Grignard reagent as the coupling partner within 5 hours in good to high yields. This approach provides a new access to a variety of C8-arylpurines which are potentially of great importance in medicinal chemistry.

Regioselective 1,4- and 1,6-Conjugate Additions of Grignard Reagent-Derived Organozinc(II)ates to Polyconjugated Esters.

PubMed

Hatano, Manabu; Mizuno, Mai; Ishihara, Kazuaki

2016-09-16

Regioselective synthetic methods were developed for 1,4- and 1,6-conjugate additions of Grignard reagent-derived organozinc(II)ates to malonate-derived polyconjugated esters. By taking advantage of the tight ion-pair control of organozinc(II)ates, it was possible to switch between 1,4- and 1,6-conjugate additions by introducing a terminal ethoxy moiety in the conjugation.

Analytical RISM-MP2 free energy gradient method: Application to the Schlenk equilibrium of Grignard reagent

NASA Astrophysics Data System (ADS)

Mori, Toshifumi; Kato, Shigeki

2007-03-01

We present a method to evaluate the analytical gradient of reference interaction site model Møller-Plesset second order free energy with respect to solute nuclear coordinates. It is applied to calculate the geometries and energies in the equilibria of the Grignard reagent (CH 3MgCl) in dimethylether solvent. The Mg-Mg and Mg-Cl distances as well as the binding energies of solvents are largely affected by the dynamical electron correlation. The solvent effect on the Schlenk equilibrium is examined.

Synthesis of 1,1-diarylethylenes via efficient iron/copper co-catalyzed coupling of 1-arylvinyl halides with Grignard reagents.

PubMed

Hamze, Abdallah; Brion, Jean-Daniel; Alami, Mouad

2012-06-01

An efficient access to 1,1-diarylethylenes of biological interest by coupling functionalized aryl Grignard reagents and 1-arylvinyl halides in the presence of FeCl(3)/CuTC is described. This bimetallic system proved to be superior to the use of Fe or Cu catalyst alone. The synthetic utility of this protocol is illustrated in the field of steroid chemistry.

High Pulse Energy Flashlamp Pumpable Laser Dyes

DTIC Science & Technology

1990-04-09

on a large scale, and the difficult alkylation to 35 accomplished with 1-iodopropane with sodium hydroxide in acetone. Coupling the Grignard reagent ...dialkylated with 4-(chloromethyl)stilbene (47), which recently became available from Aldrich, to give 48b. The attempt to couple the Grignard reagent from 4...search turned up a useful procedure for coupling aryl Grignard reagents with benzyl halides, the process in Scheme E was largely completed. The Grignard

Direct synthesis of anti-1,3-diols through nonclassical reaction of aryl Grignard reagents with isopropenyl acetate.

PubMed

Jiao, Yinchun; Cao, Chenzhong; Zhou, Zaichun

2011-01-21

A series of symmetrical aromatic 1,3-diols were efficiently synthesized from substituted aryl Grignard reagents and isopropenyl acetate in a one-step reaction that formed anti products as the major species. Both experimental and theoretical studies suggested that the reaction involves the formation of a relatively stable intermediate E containing a six-membered ring from intermediate A. The stereoselectivity of the reactions and the molecular structure of the products were confirmed by NMR spectroscopy, X-ray diffraction, and gas chromatography.

Synthesis of (Silylamino)phosphines by the Wilburn Method.

DTIC Science & Technology

1982-08-01

by the addi- tion of two equivalents of an alkyl Grignard reagent at 0 0C affords the [bis(trimethylsilyl)aminoldialkylphosphines 1 -3 (eq 1). Simi...larly, the use of dichlorophenylphosphine and one equivalent of Grignard reagent permits the convenient preparation of the corres- ponding alkyl(phenyl...Received The importance of (silylamino)phosphines, e.g. (Me3Si)2NPMe2, as reagents for the synthesis of organo-substituted phosphazene 1 2,3 polymers

Asymmetric synthesis of α-alkenyl homoallylic primary amines via 1,2-addition of Grignard reagent to α,β-unsaturated phosphonyl imines.

PubMed

Xiong, Yiwen; Mei, Haibo; Xie, Chen; Han, Jianlin; Li, Guigen; Pan, Yi

2013-01-01

A series of chiral N -phosphonyl protected α-alkenyl homoallylic primary amines were synthesized by asymmetric addition of allylmagnesium bromide Grignard reagent towards chiral α,β-unsaturated imines. Only 1,2-adduct was obtained for all the imines with good yields and excellent diastereoselectivities. The chiral auxiliary could be easily removed under simple conditions, giving free multiple functionalized primary amines.

Stereochemical inversion of a cyano-stabilized grignard reagent: remarkable effects of the ethereal solvent structure and concentration.

PubMed

Gao, Ming; Patwardhan, Neeraj N; Carlier, Paul R

2013-09-25

Chiral organometallic reagents are useful in asymmetric synthesis, and configurational stability of these species is critical to success. In this study we followed the epimerization of a chiral Grignard reagent, prepared by Mg/Br exchange of bromonitrile trans-2b. This compound underwent highly retentive Mg/Br exchange in Et2O; less retention was observed in 2-MeTHF and THF. Epimerization rate constants k(tc) were determined at 195 K by measuring the diastereomer ratio of deuteration product d1-3b as a function of the delay time before quench. Studies were also performed at varying concentrations of Et2O in toluene. Remarkable dynamic range in k(tc) was seen: relative to reaction at 0.12 M Et2O in toluene, epimerization was 26-, 800-, and 1300-fold faster in Et2O, 2-MeTHF, and THF, respectively. Thus, the identity and concentration of an ethereal solvent can dramatically affect configurational stability. Reaction stoichiometry experiments suggested that, in Et2O, the Grignard reagent derived from trans-2b exists as an i-PrMgCl heterodimer; the invariance of k(tc) over a 20-fold range in [Mg]total ruled out mandatory deaggregation (or aggregation) on the epimerization path. Analysis of the dependency of k(tc) on [Et2O] and temperature in Et2O/toluene solution at 195, 212, and 231 K indicated fast incremental solvation before rate-limiting ion-pair separation and provided an estimate of the entropic cost of capturing a solvent ligand (-13 ± 3 eu). Calculations at the MP2/6-31G*(PCM)//B3LYP/6-31G* level provide support for these conclusions and map out a possible "ionogenic conducted tour" pathway for epimerization.

Iron-catalyzed stereospecific activation of olefinic C-H bonds with Grignard reagent for synthesis of substituted olefins.

PubMed

Ilies, Laurean; Asako, Sobi; Nakamura, Eiichi

2011-05-25

The reaction of an aryl Grignard reagent with a cyclic or acyclic olefin possessing a directing group such as pyridine or imine results in the stereospecific substitution of the olefinic C-H bond syn to the directing group. The reaction takes place smoothly and without isomerization of the product olefin in the presence of a mild oxidant (1,2-dichloro-2-methylpropane) and an aromatic cosolvent. Several lines of evidence suggest that the reaction proceeds via iron-catalyzed olefinic C-H bond activation rather than an oxidative Mizoroki-Heck-type reaction.

Photochemical grafting of methyl groups on a Si(111) surface using a Grignard reagent.

PubMed

Herrera, Marvin Ustaris; Ichii, Takashi; Murase, Kuniaki; Sugimura, Hiroyuki

2013-12-01

The photochemical grafting of methyl groups onto an n-type Si(111) substrate was successfully achieved using a Grignard reagent. The preparation involved illuminating a hydrogen-terminated Si(111) that was immersed in a CH3MgBr-THF solution. The success was attributed to the ability of the n-type hydrogenated substrate to produce holes on its surface when illuminated. The rate of grafting methyl groups onto the silicon surface was higher when a larger illumination intensity or when a substrate with lower dopant concentration was used. In addition, the methylated layer has an atomically flat structure, has a hydrophobic surface, and has electron affinity that was lower than the bulk Si. Copyright © 2013 Elsevier Inc. All rights reserved.

Reactions involving the heterolytic cleavage of carbon-element σ-bonds by Grignard reagents

NASA Astrophysics Data System (ADS)

Polivin, Yurii N.; Karakhanov, Robert A.; Postnov, Victor N.

1990-03-01

The reactions involving the heterolysis of the C-O, C-C, C-N, C-S, C-Cl, etc. bonds by organomagnesium compounds are examined and the nature of this interesting phenomenon is analysed. On the basis of the analysis of the characteristic features of the cleavage under discussion, it is shown that the heterolysis of the carbon-element bond is, firstly, a general reaction for all classes of organic compounds (provided that two conditions are observed: the substrate molecule must fragment into two stable species — a carbonium ion and an anion — and the strength of the Lewis acid properties should be adequate for the occurrence of the above reaction) and, secondly, the heterolysis of the carbon-element bond is one of the independent pathways in the reactions of the Grignard reagents. The bibliography includes 158 references.

Complete regioselective addition of grignard reagents to pyrazine N-oxides, toward an efficient enantioselective synthesis of substituted piperazines.

PubMed

Andersson, Hans; Banchelin, Thomas Sainte-Luce; Das, Sajal; Gustafsson, Magnus; Olsson, Roger; Almqvist, Fredrik

2010-01-15

A conceptually new one-pot strategy for the synthesis of protected substituted piperazines via the addition of Grignard reagents to pyrazine N-oxides is presented. This strategy is high yielding (33-91% over three steps), step-efficient, and fast. The synthesized N,N-diprotected piperazines are convenient to handle and allow for orthogonal deprotection at either nitrogen for selective transformations. In addition, this is a synthetic route to enantiomerically enriched piperazines by using a combination of phenyl magnesium chloride and (-)-sparteine, which resulted in enantiomeric excesses up to 83%.

A Grignard-like Organic Reaction in Water

NASA Astrophysics Data System (ADS)

Breton, Gary W.; Hughey, Christine A.

1998-01-01

The addition of a Grignard reagent to a carbonyl-containing compound to form an alcohol is an important reaction to demonstrate in organic chemistry laboratory courses. However, the reaction presents several practical problems for the lab instructor including the need for anhydrous solvents (e.g., ether), dry glassware, and the occasional problem of slow reaction initiation. We have scaled, and tested, a known Grignard-like reaction between allyl bromide and benzaldehyde mediated by zinc metal in aqueous media. The procedure retains the desirable features of the traditional Grignard reaction, while eliminating some of the commonly encountered difficulties. Thus, addition of allyl bromide (1.2 eq) to benzaldehyde and zinc in a two-phase mixture of THF and saturated aqueous NH4Cl afforded addition product 1-phenyl-3-buten-1-ol in 70-85% yields.

[Pd(μ-Cl)Cl(IPr*)]2: a highly hindered pre-catalyst for the synthesis of tetra-ortho-substituted biaryls via Grignard reagent cross-coupling.

PubMed

Lesieur, Mathieu; Slawin, Alexandra M Z; Cazin, Catherine S J

2014-08-14

The new well-defined catalyst [Pd(μ-Cl)Cl(IPr*)]2 enables the efficient Grignard reagent cross-coupling for the synthesis of tetra-ortho-substituted biaryls. The high reactivity of the complex is associated with the important bulkiness of the IPr* ligand. The dimer represents the most efficient catalyst reported to date for this challenging transformation.

Concentration determination of methyl magnesium chloride and other Grignard reagents by potentiometric titration with in-line characterization of reaction species by FTIR spectroscopy.

PubMed

Chen, Yadan; Wang, Tao; Helmy, Roy; Zhou, George X; LoBrutto, Rosario

2002-07-01

A potentiometric titration method for methyl magnesium chloride and other Grignard reagents based on the reaction with 2-butanol in THF has been developed and validated. The method employs a commercially available platinum electrode, using an electrolyte compatible with non-aqueous solvents. Well-defined titration curves were obtained, along with excellent method precision. The endpoint was precisely determined based on the first derivative of the titration curve. Different solvents such as THF, diethyl ether and methylene chloride provided similar results with regard to sharpness of the endpoint and method precision. The method was applied to a wide array of Grignard reagents including methyl magnesium bromide, ethyl magnesium chloride, propyl magnesium chloride, vinyl magnesium chloride, phenyl magnesium chloride, and benzyl magnesium chloride with similar precision and accuracy. Application of in-line FTIR was demonstrated for in situ monitoring of the titration reaction, allowing characterization of the reaction species. An authentic spectrum of the MeMgCl-THF complex was obtained using spectral subtraction and the vibrational absorbance bands were identified. FTIR also provided an alternative for detecting the titration endpoint, and the titration results so obtained, provided a cross-validation of the accuracy of the potentiometric titration.

Two palladium-catalyzed domino reactions from one set of substrates/reagents: efficient synthesis of substituted indenes and cis-stilbenoid hydrocarbons from the same internal alkynes and hindered Grignard reagents.

PubMed

Dong, Cheng-Guo; Yeung, Pik; Hu, Qiao-Sheng

2007-01-18

Two types of domino reactions from the same internal alkynes and hindered Grignard reagents based on carbopalladation, Pd-catalyzed cross-coupling reaction, and a C-H activation strategy are described. The realization of these domino reactions relied on the control of the use of the ligand and the reaction temperature. Our study provides efficient access to useful polysubstituted indenes and cis-substituted stilbenes and may offer a new means of development of tandem/domino reactions in a more efficient way. [reaction: see text].

Two Palladium-Catalyzed Domino Reactions from One Set of Substrates/Reagents: Efficient Synthesis of Substituted Indenes and cis-Stilbenoid Hydrocarbons from the Same Internal Alkynes and Hindered Grignard Reagents

PubMed Central

Dong, Cheng-Guo; Yeung, Pik; Hu, Qiao-Sheng

2008-01-01

Two types of domino reactions from the same internal alkynes and hindered Grignard reagents based on carbopalladation, Pd-catalyzed cross-coupling reaction and C-H activation strategy are described. The realization of these domino reactions relied on the control of the use of the ligand and the reaction temperature. Our study provides an efficient access to useful polysubstituted indenes and cis-substituted stilbenes, and may offer new means to the development of tandem/domino reactions in a more efficient way. PMID:17217305

Preparation and Degradation of Polysilylenes

DTIC Science & Technology

1991-05-02

Grignard reagent formation from Mg and alkyl iodides in comparison with less reactive alkyl chlorides 2 3 . Electron transfer to the chlorides occur at...stoichiometric balance of reagents and nearly complete conversions (e.g. DPN-100 at 99% conversion in a homogeneous polycondensation with exact stoichiometric...the magnesium surface, whereas alkyl iodides accept electrons through Ŝ. larger distance and could not efficiently form organomagneslum reagents but

Investigating a Chemoselective Grignard Reaction in an Undergraduate Discovery Lab to Predict Reactivity and Final Products

ERIC Educational Resources Information Center

Maher, Michael J.; Hayes, Colin O.; Vaccaro, Francesca A.; Flynn, Cailyn B.; Thedford, R. Paxton; Stephenson, Clifton J.

2016-01-01

A discovery-based Grignard experiment that emphasizes several important concepts in organic chemistry is reported. The Grignard reagent from 1- bromo-4-chlorobenzene was prepared and reacted with dimethylformamide (DMF) to synthesize 4-chlorobenzaldehyde. Students were tasked with predicting halogen reactivity in the formation of the Grignard…

Facile Modulation of FLP Properties: A Phosphinylvinyl Grignard Reagent and Ga/P- and In/P2 -Based Frustrated Lewis Pairs.

PubMed

Backs, Jana; Lange, Merten; Possart, Josephine; Wollschläger, Agnes; Mück-Lichtenfeld, Christian; Uhl, Werner

2017-03-06

An Al/P-based frustrated Lewis pair (FLP) reacted with PhMgCl by an unexpected transmetalation and formation of a phosphinylvinyl Grignard reagent. This compound is well suited for the transfer of the basic FLP component to other Lewis acidic metal atoms and allowed the generation of a Ga/P and an In/P 2 FLP. The Ga FLP showed a behavior different to that of the corresponding Al FLP, the In FLP allowed the chelating coordination of an Au atom by Au-Cl bond activation. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

C(2) symmetric chiral NHC ligand for asymmetric quaternary carbon constructing copper-catalyzed conjugate addition of grignard reagents to 3-substituted cyclohexenones.

PubMed

Matsumoto, Yasumasa; Yamada, Ken-ichi; Tomioka, Kiyoshi

2008-06-20

The asymmetric construction of quaternary carbon centers by conjugate addition of Grignard reagents to 3-methyl- and 3-ethylcyclohexenones was realized in a maximum enantioselectivity of 80% by using a C 2 symmetric chiral N-heterocyclic carbene (NHC)-copper catalyst, generated from (4 S,5 S)-1,3-bis(2-methoxyphenyl)-4,5-diphenyl-4,5-dihydro-1 H-imidazol-3-ium tetrafluoroborate and copper(II) triflate. The stereostructures of the NHC-Au complexes were analyzed by X-ray crystallography, which rationalized the good stereocontrolling ability of N-aryl NHCs.

Stereoselective Synthesis of trans-Olefins by the Copper-Mediated SN2′ Reaction of Vinyl Oxazines with Grignard Reagents. Asymmetric Synthesis of D-threo-Sphingosines

PubMed Central

Singh, Om V.; Han, Hyunsoo

2007-01-01

The SN2′ reaction of 6-vinyl-5,6-dihydro-4H-[1,3]oxazines with Grignard reagents in the presence of CuCN was studied, and high trans selectivity for the formation of double bond was observed with a variety of RMgX. The SN2′ reaction, coupled with regioselective asymmetric aminohydroxylation reaction, provided a highly efficient route for the asymmetric synthesis of D-threo-N-acetylsphingosine. PMID:18958293

Asymmetric conjugate addition of Grignard reagents to 3-silyl unsaturated esters for the facile preparation of enantioenriched β-silylcarbonyl compounds and allylic silanes.

PubMed

Zhao, Kai; Loh, Teck-Peng

2014-12-08

A highly enantioselective conjugate addition of Grignard reagents to 3-silyl unsaturated esters to deliver synthetically useful chiral β-silylcarbonyl compounds was developed. The synthetic value of this methodology was further illustrated by the synthesis of enantioenriched β-hydroxyl esters and the facile access granted to various α-chiral allylic silanes. A plethora of diastereoselective transformations of β-silylenolates were also investigated and afforded manifold organosilanes that contained contiguous stereogenic centers with excellent enantioselectivity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and Reactivity of a New (Methylene)Phosphine.

DTIC Science & Technology

1981-01-27

the synthesis of a variety of alkyl(silylamino)- 8phosphines Similarly, if two equivalents of the silylmethyl Grignard reagent were used (eq 3), the...n-BuLi (hexane solution), and t-BuLi (pentane solution). The Grignard reagent Me 3SiCH2 MgCl was prepared in Et 0 2 2 solution from Me3SiCH 2C and Mg...trimethylsilyl)amino] (chloro)- (trimethylsilylmethyl)phosphine (1) was prepared by the "one-pot" Grignard method (eqs 1 and 2) which we have used previously for

Convenient Route to Di- and Triorganosilyl Ethyl Ethers and the Corresponding Di- and Triorganosilanes

DTIC Science & Technology

1993-11-22

example R2 R’SiH. Early reports indicated that formation of R3SiCI or R2SiCI 2 compounds by the addition of organolithium or Grignard reagents to...corresponding Grignard reagents are far less effective for the substiution reactions. 7 3 Table I. Conversion of (CH3 CH20) 4Si to Organosilyl Ethyl Ethers (X...ABSTRACT (Maximum 200 words) Tetraethoxysilane was treated with alkyl- and aryllithium reagents for the preparation of organosilyl ethyl ethers of the

Pd(OAc)2-Catalyzed Domino Reactions of 1-Chloro-2-Haloarenes and 2-Haloaryl Tosylates with Hindered Grignard Reagents via Palladium Associated Arynes

PubMed Central

Dong, Cheng-Guo; Hu, Qiao-Sheng

2008-01-01

The palladium associated aryne generation strategy and Pd(OAc)2-catalyzed annulative Domino reactions of 1-chloro-2-halobenzenes and 2-haloaryl tosylates with hindered Grignard reagents via palladium associated arynes are described. The palladium associated aryne generation strategy described here not only allows the high yield, one-step access to potentially useful substituted fluorenes from readily available 1-chloro-2-halobenzenes and 2-haloaryl tosylates, but may also lead to the development of other tandem reactions based on these readily available o-leaving group bearing haloarenes PMID:17048842

Grignard reagent/CuI/LiCl-mediated stereoselective cascade addition/cyclization of diynes: a novel pathway for the construction of 1-methyleneindene derivatives.

PubMed

Li, De-Yao; Wei, Yin; Shi, Min

2013-11-11

Diynes containing a cyclopropane group smoothly undergo a novel intramolecular and stereoselective cascade addition/cyclization reaction to produce the corresponding 1-methyleneindene derivatives in moderate to good yields. This interesting transformation is mediated by Grignard reagent/CuI with LiCl as an additive under mild conditions. The obtained product can easily be further functionalized through cyclopropyl ring opening. A plausible reaction mechanism has also been presented on the basis of deuterium labeling and control experiments. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pd(OAc)(2)-catalyzed Domino reactions of 1-chloro-2-haloarenes and 2-haloaryl tosylates with hindered Grignard reagents via palladium-associated arynes.

PubMed

Dong, Cheng-Guo; Hu, Qiao-Sheng

2006-10-26

The palladium-associated aryne generation strategy and Pd(OAc)(2)-catalyzed annulative Domino reactions of 1-chloro-2-halobenzenes and 2-haloaryl tosylates with hindered Grignard reagents via palladium-associated arynes are described. The palladium-associated aryne generation strategy described here not only allows the high yield, one-step access to potentially useful substituted fluorenes from readily available 1-chloro-2-halobenzenes and 2-haloaryl tosylates, but may also lead to the development of other tandem reactions based on these readily available ortho leaving group bearing haloarenes. [reaction: see text

Palladium-catalyzed Kumada coupling reaction of bromoporphyrins with silylmethyl Grignard reagents: preparation of silylmethyl-substituted porphyrins as a multipurpose synthon for fabrication of porphyrin systems.

PubMed

Sugita, Noriaki; Hayashi, Satoshi; Hino, Fumio; Takanami, Toshikatsu

2012-12-07

We have developed an efficient method for preparing silylmethyl-substituted porphyrins via the palladium-catalyzed Kumada cross-coupling reaction of bromoporphyrins with silylmethyl Grignard reagents. We demonstrated the synthetic utility of these silylmethylporphyrins as a multipurpose synthon for fabricating porphyrin derivatives through a variety of transformations of the silylmethyl groups, including the DDQ-promoted oxidative conversion to CHO, CH(2)OH, CH(2)OMe, and CH(2)F functionalities and the fluoride ion-mediated desilylative introduction of carbon-carbon single and double bonds.

Control of diastereoselectivity by solvent effects in the addition of Grignard reagents to enantiopure t-butylsulfinimine: syntheses of the stereoisomers of the hydroxyl derivatives of sibutramine.

PubMed

Lu, Bruce Z; Senanayake, Chris; Li, Nansheng; Han, Zhengxu; Bakale, Roger P; Wald, Stephen A

2005-06-23

[reaction: see text] An efficient method has been developed to prepare all four isomers of the hydroxyl derivatives of sibutramine by addition of Grignard reagents (R)- or (S)-5 to a single enantiomer of sulfinyl imine (R)-1 simply by tuning the reaction solvent. The phenomenon of the reversed diastereoselectivity in CH(2)Cl(2) and THF implied that the reaction may proceed through a chelated cyclic transition state in CH(2)Cl(2) and nonchelated acyclic transition state in THF.

Application of a Heterogeneous Chiral Titanium Catalyst Derived from Silica-Supported 3-Aryl H8-BINOL to Enantioselective Alkylation and Arylation of Aldehydes.

PubMed

Akai, Junichiro; Watanabe, Satoshi; Michikawa, Kumiko; Harada, Toshiro

2017-07-07

A 3-aryl H 8 -BINOL was grafted on the surface of silica gel using a hydrosilane derivative as a precursor, and the resulting silica-supported ligand (6 mol %) was employed in the enantioselective alkylation and arylation of aldehydes in the presence of Ti(O i Pr) 4 . The reactions using Et 2 Zn, Et 3 B, and aryl Grignard reagents all afforded the corresponding adducts in high enantioselectivities and yields. The silica-immobilized titanium catalyst could be reused up to 14 times without appreciable deterioration of the activity.

Synthesis of enyne and aryl vinyl sulfoxides: functionalization via Pummerer rearrangement.

PubMed

Souza, Frederico B; Shamim, Anwar; Argomedo, Luiz M Z; Pimenta, Daniel C; Stefani, Hélio A

2015-11-01

An efficient methodology for the synthesis of aryl-substituted vinyl sulfoxides through direct substitution of aryl-substituted alkynyl grignard reagents on menthyl-p-toluenesulfinate followed by Suzuki-Miyaura cross-coupling reaction has been developed. It has also been described that the reaction of alkyl-substituted and cycloalkyl-substituted alkynyl grignard reagents with menthyl-p-toluenesulfinate led to two products, i.e., alkynyl sulfoxide derivatives, as a result of substitution, and enyne sulfoxide derivatives, which resulted from substitution followed by Michael type addition. It was possible to selectively synthesize the enyne sulfoxide derivatives by changing the concentration of the grignard reagent. These alkenyl sulfoxides were transformed into the corresponding [Formula: see text]-thio aldehydes in high yields via additive Pummerer rearrangement.

The GC-MS Observation of Intermediates in a Stepwise Grignard Addition Reaction

ERIC Educational Resources Information Center

Latimer, Devin

2007-01-01

Preparation of phenylmagnesium bromide described by Eckert, addition of three equivalents of Grignard reagent to diethyl carbonate to form triphenylmethanol and a series of GC-MS procedures that form intermediates. The analysis is consistent with a gas chromatogram and mass spectrum for each of the expected intermediates and final product of the…

Flotation selectivity of novel alkyl dicarboxylate reagents for apatite-calcite separation.

PubMed

Karlkvist, Tommy; Patra, Anuttam; Rao, Kota Hanumantha; Bordes, Romain; Holmberg, Krister

2015-05-01

The investigation aims to demonstrate the conceptual thoughts behind developing mineral specific reagents for use in flotation of calcium containing ores. For this purpose, a series of dicarboxylate-based surfactants with varying distance between the carboxylate groups (one, two or three methylene groups) was synthesized. A surfactant with the same alkyl chain length but with only one carboxylate group was also synthesized and evaluated. The adsorption behavior of these new reagents on pure apatite and pure calcite surfaces was studied using Hallimond tube flotation, FTIR and ζ potential measurements. The relation between the adsorption behavior of a given surfactant at a specific mineral surface and its molecular structure over a range of concentrations and pH values, as well as the region of maximum recovery, was established. It was found that one of the reagents, with a specific distance between the carboxylate groups, was much more selective for a particular mineral surface than the other homologues. For example, out of the four compounds synthesized, only the one where the carboxylate groups were separated by a single methylene group floated apatite but not calcite, whereas calcite was efficiently floated with the monocarboxylic reagent, but not with the other reagents synthesized. This selective adsorption of a given surfactant to a particular mineral surface relative to other mineral surfaces as evidenced in the flotation studies was substantiated by ζ potential and infra-red spectroscopy data. Copyright © 2014 Elsevier Inc. All rights reserved.

Transition-metal-free one-pot synthesis of biaryls from Grignard reagents and substituted cyclohexanones.

PubMed

Zhou, Feng; Simon, Marc-Oliver; Li, Chao-Jun

2013-05-27

A new strategy for the construction of biaryls by a transition-metal-free process is presented. A sequence of a Grignard reaction, dehydration, and oxidative aromatization affords the desired products in a one-pot fashion. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A covalent modification for graphene by adamantane groups through two-step chlorination-Grignard reactions

NASA Astrophysics Data System (ADS)

Sun, Xuzhuo; Li, Bo; Lu, Mingxia

2017-07-01

Chemical modification of graphene is a promising approach to manipulate its properties for its end applications. Herein we designed a two-step route through chlorination-Grignard reactions to covalently decorate the surface of graphene with adamantane groups. The chemically modified graphene was characterized by Raman spectroscopy, atomic force microscopy, and X-ray photoelectron spectroscopy. Chlorination of graphene occurred rapidly, and the substitution of chlorine atoms on chlorinated graphene by adamantane Grignard reagent afforded adamantane graphene in almost quantitative yield. Adamantane groups were found to be covalently bonded to the graphene carbons. The present two-step procedure may provide an effective and facile route for graphene modification with varieties of organic functional groups.

Synthesis of γ-hydroxypropyl P-chirogenic (±)-phosphorus oxide derivatives by regioselective ring-opening of oxaphospholane 2-oxide precursors

PubMed Central

Binyamin, Iris; Meidan-Shani, Shoval

2015-01-01

Summary The synthesis of P-chirogenic (±)-phosphine oxides and phosphinates via selective nucleophilic ring opening of the corresponding oxaphospholanes is described. Two representative substrates: the phosphonate 2-ethoxy-1,2-oxaphospholane 2-oxide and the phosphinate 2-phenyl-1,2-oxaphospholane 2-oxide were reacted with various Grignard reagents to produce a single alkyl/aryl product. These products may possess further functionalities in addition to the phosphorus center such as the γ-hydroxypropyl group which results from the ring opening and π-donor moieties such as aryl, allyl, propargyl and allene which originates from the Grignard reagent. PMID:26425187

In situ formation of pyridyl-functionalized poly(3-hexylthiophene)s via quenching of the Grignard metathesis polymerization: Toward ligands for semiconductor quantum dots

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

Kochemba, William Michael; Pickel, Deanna L.; Sumpter, Bobby G.

The synthesis of well-defined, end-functional poly(3-hexylthiophene)s (P3HTs) by in situ quenching of the Grignard metathesis (GRIM) polymerization is complicated by the extreme tendency to favor difunctional products in all but a few cases. A facile one-pot method for preparing 2-pyridyl and 3-pyridyl P3HTs with high abundance of monofunctional products is established via an examination of the kinetics of the end-functionalization quenching reaction with lithium chloride complexes of 2- and 3-pyridyl Grignard reagents. Density functional theory calculations guide the selection of pyridine as the end group, which provides the capacity to ligate cadmium selenide (CdSe) nanocrystals and arrests aggregation upon thermalmore » annealing when dispersed in a P3HT matrix. The relative abundances of various end-functional products, as ascertained by high-resolution matrix assisted laser desorption ionization time-of-flight mass spectrometry, can be altered through the use of 1-pentene as an additive: GRIM polymerizations quenched with 3-pyridyl and 2-pyridyl Grignard reagents show 5% and 18% abundances of difunctional, pyridyl-capped P3HTs, respectively, when 1-pentene is present at 1000:1 relative to the nickel catalyst. This represents a significant improvement compared to quenching with aryl Grignard reagents, where difunctional products predominate. Furthermore, the ability to manipulate end group compositions coupled with the propensity of pyridyl-functionalized P3HTs to ligate semiconductor quantum dots (SQDs) opens new possibilities for tuning the morphology of conjugated polymer/SQD blends.« less

Addition of CFCl 3 to Aromatic Aldehydes via in Situ Grignard Reaction

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

Barkakaty, Balaka; Talukdar, Bandana; Lokitz, Bradley

In the case of synthetic modification of trichlorofluoromethane (CFCl 3) to non-volatile and useful fluorinated precursors, we realized that it is a cost-effective and an environmentally benign strategy for the safe consumption/destruction of the ozone depleting potential of the reagent. In our report, we present a novel method for in situ Grignard reaction using magnesium powder and CFCl 3 for synthesis of dichlorofluoromethyl aromatic alcohols.

Addition of CFCl 3 to Aromatic Aldehydes via in Situ Grignard Reaction

DOE PAGES

Barkakaty, Balaka; Talukdar, Bandana; Lokitz, Bradley

2015-08-18

In the case of synthetic modification of trichlorofluoromethane (CFCl 3) to non-volatile and useful fluorinated precursors, we realized that it is a cost-effective and an environmentally benign strategy for the safe consumption/destruction of the ozone depleting potential of the reagent. In our report, we present a novel method for in situ Grignard reaction using magnesium powder and CFCl 3 for synthesis of dichlorofluoromethyl aromatic alcohols.

Alkylation of Silicon(111) surfaces

NASA Astrophysics Data System (ADS)

Rivillon, S.; Chabal, Y. J.

2006-03-01

Methylation of chlorine-terminated silicon (111) (Si-Cl) is investigated by Infra Red Absorption Spectroscopy (IRAS). Starting from an atomically flat H-terminated Si(111), the surface is first chlorinated by a gas phase process, then methylated using a Grignard reagent. Methyl groups completely replace Cl, and are oriented normal to the surface. The surface remains atomically flat with no evidence of etching.

Synthesis of High-Load, Hybrid Silica-Immobilized Heterocyclic Benzyl Phosphate (Si–OHBP) and Triazolyl Phosphate (Si–OHTP) Alkylating Reagents

PubMed Central

2016-01-01

The development of new ROMP-derived silica-immobilized heterocyclic phosphate reagents and their application in purification-free protocols is reported. Grafting of norbornenyl norbornenyl-functionalized (Nb-tagged) silica particles with functionalized Nb-tagged heterocyclic phosphate monomers efficiently yield high-load, hybrid silica-immobilized oligomeric heterobenzyl phosphates (Si–OHBP) and heterotriazolyl phosphates (Si–OHTP) as efficient alkylation agents. Applications of these reagents for the diversification of N-, O-, and S-nucleophilic species, for efficient heterobenzylation and hetero(triazolyl)methylation have been validated. PMID:27300761

Highly stereoselective construction of the C2 stereocentre of α-tocopherol (vitamin E) by asymmetric addition of Grignard reagents to ketones.

PubMed

Bieszczad, Bartosz; Gilheany, Declan G

2017-08-09

Tertiary alcohol precursors of both C2 diastereoisomers of α-tocopherol were prepared in three ways by our recently reported asymmetric Grignard synthesis. The versatility of Grignard chemistry inherent in its three-way disconnection was exploited to allow the synthesis of three product grades: 77 : 23 dr (5 steps), 81 : 19 dr (5 steps) and 96 : 4 dr (7 steps, one gram scale) from readily available and abundant starting materials. The products were converted to their respective α-tocopherols in 3 steps, which allowed a definitive re-assignment of their absolute configurations.

Stereospecific nickel-catalyzed cross-coupling reactions of alkyl ethers: enantioselective synthesis of diarylethanes.

PubMed

Taylor, Buck L H; Swift, Elizabeth C; Waetzig, Joshua D; Jarvo, Elizabeth R

2011-01-26

Secondary benzylic ethers undergo stereospecific substitution reactions with Grignard reagents in the presence of nickel catalysts. Reactions proceed with inversion of configuration and high stereochemical fidelity. This reaction allows for facile enantioselective synthesis of biologically active diarylethanes from readily available optically enriched carbinols.

Highly selective biaryl cross-coupling reactions between aryl halides and aryl Grignard reagents: a new catalyst combination of N-heterocyclic carbenes and iron, cobalt, and nickel fluorides.

PubMed

Hatakeyama, Takuji; Hashimoto, Sigma; Ishizuka, Kentaro; Nakamura, Masaharu

2009-08-26

Combinations of N-heterocyclic carbenes (NHCs) and fluoride salts of the iron-group metals (Fe, Co, and Ni) have been shown to be excellent catalysts for the cross-coupling reactions of aryl Grignard reagents (Ar(1)MgBr) with aryl and heteroaryl halides (Ar(2)X) to give unsymmetrical biaryls (Ar(1)-Ar(2)). Iron fluorides in combination with SIPr, a saturated NHC ligand, catalyze the biaryl cross-coupling between various aryl chlorides and aryl Grignard reagents in high yield and high selectivity. On the other hand, cobalt and nickel fluorides in combination with IPr, an unsaturated NHC ligand, exhibit interesting complementary reactivity in the coupling of aryl bromides or iodides; in contrast, with these substrates the iron catalysts show a lower selectivity. The formation of homocoupling byproducts is suppressed markedly to less than 5% in most cases by choosing the appropriate metal fluoride/NHC combination. The present catalyst combinations offer several synthetic advantages over existing methods: practical synthesis of a broad range of unsymmetrical biaryls without the use of palladium catalysts and phosphine ligands. On the basis of stoichiometric control experiments and theoretical studies, the origin of the unique catalytic effect of the fluoride counterion can be ascribed to the formation of a higher-valent heteroleptic metalate [Ar(1)MF(2)]MgBr as the key intermediate in our proposed catalytic cycle. First, stoichiometric control experiments revealed the stark differences in chemical reactivity between the metal fluorides and metal chlorides. Second, DFT calculations indicate that the initial reduction of di- or trivalent metal fluoride in the wake of transmetalation with PhMgCl is energetically unfavorable and that formation of a divalent heteroleptic metalate complex, [PhMF(2)]MgCl (M = Fe, Co, Ni), is dominant in the metal fluoride system. The heteroleptic ate-complex serves as a key reactive intermediate, which undergoes oxidative addition with Ph

Ultrasound promoted N-alkylation of pyrrole using potassium superoxide as base in crown ether.

PubMed

Yim, E S; Park, M K; Han, B H

1997-04-01

Ultrasound accelerates the N-alkylation of pyrrole by alkylating reagents using potassium superoxide as base in the presence of 18-crown-6. A much lower yield of N-alkylated pyrrole was realized in the absence of ultrasound. N-alkylating reagents employed for pyrrole are methyl iodide, ethyl bromide, benzyl bromide, as well as acrylonitrile allyl cyanide and methyl acrylate. In an extension of this work, we have found that ultrasound was not necessary for the N-alkylation of indole and alkyl amine, such as diphenyl amine and piperidine with alkyl halides using our reagents. In all cases we observed that the 18-crown-6 catalyzed N-alkylation reaction gives higher yields of N-alkylated products than that without crown ether, when potassium superoxide was used as base. These observations are probably due to the potassium-crown complex which can be released when the reaction goes to completion.

Iron-mediated and -catalyzed metalative cyclization of electron-withdrawing-group-substituted alkynes and alkenes with Grignard reagents.

PubMed

Hata, Takeshi; Sujaku, Shiro; Hirone, Naoki; Nakano, Kirihiro; Imoto, Junsuke; Imade, Haduki; Urabe, Hirokazu

2011-12-16

Treatment of ethyl (E)-5,5-bis[(benzyloxy)methyl]-8-(N,N-diethylcarbamoyl)-2-octen-7-ynoate with an iron reagent generated from FeCl(2) and tBuMgCl in a ratio of 1:4 (abbreviated as FeCl(2)/4 tBuMgCl) afforded ethyl [4,4-bis[(benzyloxy)methyl]-2-[(E)-(N,N-diethylcarbamoyl)methylene]cyclopent-1-yl]acetate in good yield. Deuteriolysis of an identical reaction mixture afforded the bis-deuterated product ethyl [4,4-bis[(benzyloxy)methyl]-2-[(E)-(N,N-diethylcarbamoyl)deuteriomethylene]cyclopent-1-yl]deuterioacetate, thus confirming the existence of the corresponding dimetalated intermediate. The latter intermediate can react with halogens or aldehydes to facilitate further synthetic transformations. The amount of FeCl(2) was reduced to catalytic levels (10 mol % relative to enyne), and catalytic cyclizations of this sort proceeded with yields comparable to those of the aforementioned stoichiometric reactions. The cyclization of diethyl (E,E)-2,7-nonadienedioate with a stoichiometric amount of FeCl(2)/4 tBuMgCl, followed by the addition of sBuOH as a proton source, afforded a mixture of 2-(ethoxycarbonyl)-3-bicyclo[3.3.0]octanone and its enol form in good yield. The use of aldehyde or ketone in place of sBuOH afforded 2-(ethoxycarbonyl)-3-bicyclo[3.3.0]octanone, which has an additional hydroxyalkyl side chain. Additionally, the metalation of a carbon-carbon unsaturated bond in N,N-diethyl-5,5-bis[(benzyloxy)methyl]-7,8-epoxy-2-octynamide or (E)-3,3-dimethyl-6-(N,N-diethylcarbamoyl)-5-hexenyl p-toluenesulfonate with FeCl(2)/4 tBuMgCl or FeCl(2)/4 PhMgBr was followed by an intramolecular alkylation with an epoxide or alkyl p-toluenesulfonate to afford 5,5-bis[(benzyloxy)methyl]-3-[(E)-(N,N-diethylcarbamoyl)methylene]-1-cyclohexanol or N,N-diethyl(3,3-dimethylcyclopentyl)acetamide after hydrolysis. In both cases, the remaining metalated portion α to the amide group was confirmed by deuteriolysis and could be utilized for an alkylation with methyl iodide. Copyright �

Diastereoselective Synthesis of (+/-)-1,2-Diphenyl-1,2-propanediol. A Discovery-Based Grignard Reaction Suitable for a Large Organic Lab Course

NASA Astrophysics Data System (ADS)

Ciaccio, James A.; Bravo, Roxana P.; Drahus, Antoinette L.; Biggins, John B.; Concepcion, Rosalyn V.; Cabrera, David

2001-04-01

We have developed an undergraduate organic laboratory experiment that probes the diastereoselectivity of the reaction between a Grignard reagent and a common, inexpensive a-chiral ketone. Students isolate a single diastereomer of (+/-)-1,2-diphenyl-1,2-propanediol by treatment of (+/-)-benzoin with MeMgI. Since the mp ranges of the two possible diol diastereomers differ by 10 °C, the reaction's diastereoselectivity can be established by mp determination alone, and it can be rationalized by the preferential addition of MeMgI to the least sterically hindered face of the carbonyl group in a rigid, five-membered cyclic intermediate (the "Cram chelate model"). This experiment is an interesting alternative to traditional Grignard experiments, is operationally straightforward and easily performed in large lab courses, and introduces students to p-facial discrimination by having them establish the stereochemical course of kinetically controlled nucleophilic addition to a carbonyl.

Extension of Branches for Orthogonally Fused Molecular Switches

DTIC Science & Technology

1991-05-16

converted to its Grignard reagent . Treatment of the Grignard reagent of 7 with the bromide 6 and (diphenylphosphino)- propanenickel(II) dichloride catalysis...6 afforded the dimer which was deprotonation with LDA and quenched with iodine to give the dimer iodide 8. Treatment of the Grignard reagent of 7 with

Many Mg-Mg bonds form the core of the Mg16Cp*8Br4K cluster anion: the key to a reassessment of the Grignard reagent (GR) formation process?

PubMed

Kruczyński, T; Henke, F; Neumaier, M; Bowen, K H; Schnöckel, H

2016-02-01

It caused a sensation eight years ago, when the first room temperature stable molecular compound with a Mg-Mg bond (LMgMgL, L = chelating ligand) containing magnesium in the oxidation state +1 was prepared. Here, we report the preparation of a [Mg 16 Cp*8Br 4 K] - cluster anion (Cp* = pentamethylcyclopentadiene) with 27 Mg-Mg bonds. It has been obtained through the reaction of KCp* with a metastable solution of MgBr in toluene. A highly-resolved Fourier transform mass spectrum (FT-MS) of this cluster anion, brought into vacuum by electrospraying its solution in THF, provides the title cluster's stoichiometry. This Mg 16 cluster together with experiments on the metastable solution of MgBr show that: during the formation process of GRs (Grignard reagents) which are involved in most of sophisticated syntheses of organic products, not the highly reactive MgBr radical as often presumed, but instead the metalloid Mg 16 Cp*8Br 4 cluster anion and its related cousins that are the operative intermediates along the pathway from Mg metal to GRs ( e.g. Cp*MgBr).

The Impact of Commonly Used Alkylating Agents on Artifactual Peptide Modification.

PubMed

Hains, Peter G; Robinson, Phillip J

2017-09-01

Iodoacetamide is by far the most commonly used agent for alkylation of cysteine during sample preparation for proteomics. An alternative, 2-chloroacetamide, has recently been suggested to reduce the alkylation of residues other than cysteine, such as the N-terminus, Asp, Glu, Lys, Ser, Thr, and Tyr. Here we show that although 2-chloroacetamide reduces the level of off-target alkylation, it exhibits a range of adverse effects. The most significant of these is methionine oxidation, which increases to a maximum of 40% of all Met-containing peptides, compared with 2-5% with iodoacetamide. Increases were also observed for mono- and dioxidized tryptophan. No additional differences between the alkylating reagents were observed for a range of other post-translational modifications and digestion parameters. The deleterious effects were observed for 2-chloroacetamide from three separate suppliers. The adverse impact of 2-chloroacetamide on methionine oxidation suggests that it is not the ideal alkylating reagent for proteomics.

Design and Synthesis of Candidate Prophylactic and Therapeutic Compounds for Use in the Management of Organophosphorus Poisoning.

DTIC Science & Technology

1985-01-01

resynthesis. The Grignard reagent , prepared from 4- chlorobromobenzene and magnesium metal, was treated with NN-diethyl-P- methylphosphonamidic chloride and the...ref. 26-28). Thus, diethylaminodichlorophosphine was treated with two equivalents of butyl Grignard reagent to give phosphinous amide 1 in 63% yield...compound following a general method developed by Ash Stevens Inc. for the synthesis of substituted aryl methylphosphinates. Thus, the Grignard reagent

Prophylactic and Treatment Drugs for Organophosphorus Poisoning

DTIC Science & Technology

1991-01-01

our study, however, this procedure gave extremely low yields (9), so an alternate route to intermediate 2, was developed. The Grignard reagent , prepared...substituted methylphosphinates. The Grignard reagent , prepared from l-bromonaphthalene, was treated with N,N-diethyl-P-methylphosphonamidic, chloride and the...The Grignard reagent prepared from l-bromo-4-methyl- naphthalene was treated with N,N-diethyl-P-methylphosphonamidic chloride. The resulting amide was

Alcohols as alkylating agents in heteroarene C-H functionalization

NASA Astrophysics Data System (ADS)

Jin, Jian; MacMillan, David W. C.

2015-09-01

Redox processes and radical intermediates are found in many biochemical processes, including deoxyribonucleotide synthesis and oxidative DNA damage. One of the core principles underlying DNA biosynthesis is the radical-mediated elimination of H2O to deoxygenate ribonucleotides, an example of `spin-centre shift', during which an alcohol C-O bond is cleaved, resulting in a carbon-centred radical intermediate. Although spin-centre shift is a well-understood biochemical process, it is underused by the synthetic organic chemistry community. We wondered whether it would be possible to take advantage of this naturally occurring process to accomplish mild, non-traditional alkylation reactions using alcohols as radical precursors. Because conventional radical-based alkylation methods require the use of stoichiometric oxidants, increased temperatures or peroxides, a mild protocol using simple and abundant alkylating agents would have considerable use in the synthesis of diversely functionalized pharmacophores. Here we describe the development of a dual catalytic alkylation of heteroarenes, using alcohols as mild alkylating reagents. This method represents the first, to our knowledge, broadly applicable use of unactivated alcohols as latent alkylating reagents, achieved via the successful merger of photoredox and hydrogen atom transfer catalysis. The value of this multi-catalytic protocol has been demonstrated through the late-stage functionalization of the medicinal agents, fasudil and milrinone.

Alcohols as alkylating agents in heteroarene C-H functionalization.

PubMed

Jin, Jian; MacMillan, David W C

2015-09-03

Redox processes and radical intermediates are found in many biochemical processes, including deoxyribonucleotide synthesis and oxidative DNA damage. One of the core principles underlying DNA biosynthesis is the radical-mediated elimination of H2O to deoxygenate ribonucleotides, an example of 'spin-centre shift', during which an alcohol C-O bond is cleaved, resulting in a carbon-centred radical intermediate. Although spin-centre shift is a well-understood biochemical process, it is underused by the synthetic organic chemistry community. We wondered whether it would be possible to take advantage of this naturally occurring process to accomplish mild, non-traditional alkylation reactions using alcohols as radical precursors. Because conventional radical-based alkylation methods require the use of stoichiometric oxidants, increased temperatures or peroxides, a mild protocol using simple and abundant alkylating agents would have considerable use in the synthesis of diversely functionalized pharmacophores. Here we describe the development of a dual catalytic alkylation of heteroarenes, using alcohols as mild alkylating reagents. This method represents the first, to our knowledge, broadly applicable use of unactivated alcohols as latent alkylating reagents, achieved via the successful merger of photoredox and hydrogen atom transfer catalysis. The value of this multi-catalytic protocol has been demonstrated through the late-stage functionalization of the medicinal agents, fasudil and milrinone.

Tandem Carbocupration/Oxygenation of Terminal Alkynes

PubMed Central

Zhang, Donghui; Ready, Joseph M.

2008-01-01

A direct and general synthesis of α-branched aldehydes and their enol derivatives is described. Carbocupration of terminal alkynes and subsequent oxygenation with lithium tert-butyl peroxide generates a metallo-enolate. Trapping with various electrophiles provides α-branched aldehydes or stereo-defined trisubstituted enol esters or silyl ethers. The tandem carbocupration/oxygenation tolerates alkyl and silyl ethers, esters and tertiary amines. The reaction is effective with organocopper complexes derived from primary, secondary and tertiary Grignard reagents and from n-butyllithium. PMID:16321021

Synthesis and Reactivity of Backfluorinated NHC Carbene Complexes (Briefing Charts)

DTIC Science & Technology

2015-07-01

Distribution A: Approved for public release 13 Preparation of Perfluoroalkyl Grignard Reagents F(CF2CF2)nCH2CH2I Mg, Et2O ref lux F(CF2CF2)nCH2CH2MgI F...Synthetic Method #1 Grignard Addition/Reduction/Cyclization • Very general reaction pathway: suitable for all Grignard reagents • Attempts at...dialkylation unsuccessful • Slight excess of Grignard reagent ensures complete monoalkylation N N MesMes N N MesMes F2 C MgX Et2O, rt N N MesMes CF2 MgX 2

Synthesis and Characterization of a Novel Reactive Perfluorinated Alkynyl Silane Monomer

DTIC Science & Technology

2010-10-21

8217 For practical purposes, alkoxy- and th loro-silanes arc the most convenient precurwrs to alkynylsilanes because an alkynyl Grignard or lith ium reagent ...of alkoxy silanes has been accomplished by the treatment of Grignard or organa-lithium reagents with eithet" SiC!.. (followed by alcoholysis)," CI_Si...procedure. Grignard reagents nave been rc:poncd to have significantly lowcr re~ctivity than the litbium rcagents, wbicb rapidly decompose at ambient

Synthesis of Aromatic Polyhedral Oligomeric Silsesquioxane (POSS) Dianilines for Use in High-Temperature Polyimides

DTIC Science & Technology

2012-05-01

In all cases, a Grignard reagent of a para- or meta- substituted, protected aniline was reacted with a chlorosilane. Control of the reaction is...one equivalent of Grignard reagent with a small excess of tetrachlorosilane generates a good yield of monosubstituted trichlorosilane (6a). It must...methyltrichlorosilane. It is possible to add either 1 equivalent (to make 4a and 4b) or 2 equivalents of the protected aniline Grignard reagent (to make 5a

Alcohols as alkylating agents in heteroarene C–H functionalization

PubMed Central

Jin, Jian; MacMillan, David W. C.

2015-01-01

Redox processes and radical intermediates are found in many biochemical processes, including deoxyribonucleotide synthesis and oxidative DNA damage1. One of the core principles that underlies DNA biosynthesis is the radical-mediated elimnation of H2O to deoxygenate ribonucleotides, an example of ‘spin-center shift’ (SCS)2, during which an alcohol C–O bond is cleaved, resulting in a carbon-centered radical intermediate. While SCS is a well-understood biochemical process, it is underutilized by the synthetic organic chemistry community. We wondered whether it would be possible to take advantage of this naturally occurring process to accomplish mild, non-traditional alkylations using alcohols as radical precursors. Considering traditional radical-based alkylation methods require the use of stoichiometric oxidants, elevated temperatures, or peroxides3–7, the development of a mild protocol using simple and abundant alkylating agents would have significant utility in the synthesis of diversely functionalized pharmacophores. In this manuscript, we describe the successful execution of this idea via the development of a dual catalytic alkylation of heteroarenes using alcohols as mild alkylating reagents. This method represents the first broadly applicable use of unactivated alcohols as latent alkylating reagents, achieved via the successful merger of photoredox and hydrogen atom transfer (HAT) catalysis. The utility of this multi-catalytic protocol has been demonstrated through the late-stage functionalization of the medicinal agents, fasudil and milrinone. PMID:26308895

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.

Hydrogen sulfide deactivates common nitrobenzofurazan-based fluorescent thiol labeling reagents.

PubMed

Montoya, Leticia A; Pluth, Michael D

2014-06-17

Sulfhydryl-containing compounds, including thiols and hydrogen sulfide (H2S), play important but differential roles in biological structure and function. One major challenge in separating the biological roles of thiols and H2S is developing tools to effectively separate the reactivity of these sulfhydryl-containing compounds. To address this challenge, we report the differential responses of common electrophilic fluorescent thiol labeling reagents, including nitrobenzofurazan-based scaffolds, maleimides, alkylating agents, and electrophilic aldehydes, toward cysteine and H2S. Although H2S reacted with all of the investigated scaffolds, the photophysical response to each scaffold was significantly different. Maleimide-based, alkylating, and aldehydic thiol labeling reagents provided a diminished fluorescence response when treated with H2S. By contrast, nitrobenzofurazan-based labeling reagents were deactivated by H2S addition. Furthermore, the addition of H2S to thiol-activated nitrobenzofurazan-based reagents reduced the fluorescence signal, thus establishing the incompatibility of nitrobenzofurazan-based thiol labeling reagents in the presence of H2S. Taken together, these studies highlight the differential reactivity of thiols and H2S toward common thiol-labeling reagents and suggest that sufficient care must be taken when labeling or measuring thiols in cellular environments that produce H2S due to the potential for both false-positive and eroded responses.

1,6-Conjugate addition of zinc alkyls to para-quinone methides in a continuous-flow microreactor.

PubMed

Jadhav, Abhijeet S; Anand, Ramasamy Vijaya

2016-12-20

An efficient method for the synthesis of alkyl diarylmethanes through the 1,6-conjugate addition of dialkylzinc reagents to para-quinone methides (p-QMs) has been developed under continuous flow conditions using a microreactor. This protocol allows to access unsymmetrical alkyl diarylmethanes in moderate to excellent yields using a wide range of p-QMs and dialkylzinc reagents. Interestingly, this transformation worked well without the requirement of a catalyst.

Reduction of C Bonds Proceeds with Retention of Configuration: Stereochemical Investigation of the Heterogeneous Reduction by Dideuterium of (Homohypostrophene)Neopentyl(2-Norbornyl)Platinum(II) Complexes on Platinum Black.

DTIC Science & Technology

1991-04-23

ClIH16: C, 89.12; H, 10.88; Found: C, 88.85; H, 10.90. Synthesis of Grignard Reagents . Neopentylmagnesium chloride. Into a 500-mL round-bottomed flask... Grignard reagent several times using the following procedure. We placed 5.0 g (0.206 mol) of magnesium chips and a magnetic stir bar to a 200-mL round...Norbornylmagnesium bromide. This Grignard reagent was synthesized using a variation on established procedures. 58,60 We transferred under argon 50.0 mL (30.0 mmol

Curing and Characterization of Siloxanecarbonate Polymers

DTIC Science & Technology

1980-01-01

to 93 percent yields of p-bromophenol-Z-tetrahydropyranyl ether. The Grignard reagent made from the protected phenol in tetrahydrofuran was added to...iodomethane and heating. When all of the magnesium appeared to have been consumed, the resulting Grignard reagent was added via a double-tipped needle...7-dichlorooctamethyltetrasiloxane via the Grignard reaction. Workup of the reaction product with aqueous ammonium chloride solution kept the molecule

Reichardt's dye and its reactions with the alkylating agents 4-chloro-1-butanol, ethyl methanesulfonate, 1-bromobutane and Fast Red B - a potentially useful reagent for the detection of genotoxic impurities in pharmaceuticals.

PubMed

Corrigan, Damion K; Whitcombe, Michael J; McCrossen, Sean; Piletsky, Sergey

2009-04-01

Alkylating agents are potentially genotoxic impurities that may be present in drug products. These impurities occur in pharmaceuticals as by-products from the synthetic steps involved in drug production, as impurities in starting materials or from in-situ reactions that take place in the final drug product. Currently, analysis for genotoxic impurities is typically carried out using either HPLC/MS or GC/MS. These techniques require specialist expertise, have long analysis times and often use sample clean-up procedures. Reichardt's dye is well known for its solvatochromic properties. In this paper the dye's ability to undergo alkylation is reported. The reaction between Reichardt's dye and alkylating agents such as 4-chloro-1-butanol and ethyl methanesulfonate was monitored spectrophotometrically at 618 nm in acetonitrile and 624 nm in N,N-dimethylformamide. Changes in absorption were observed using low levels of alkylating agent (5-10 parts per million). Alkylation of the dye with 4-chloro-1-butanol and ethyl methanesulfonate was confirmed. Reichardt's dye, and its changing UV absorption, was examined in the presence of paracetamol (10 and 100 mg/ml). Whilst the alkylation-induced changes in UV absorption were not as pronounced as with standard solutions, detection of alkylation was still possible. Using standard solutions and in the presence of a drug matrix, Reichardt's dye shows promise as a reagent for detection of low levels of industrially important alkylating agents.

Thermal Transitions and Reaction Kinetics of Polyhederal Silsesquioxane Containing Phenylethynylphthalimides (Preprint)

DTIC Science & Technology

2010-03-18

Grignard reagent was added drop-wise to a well-stirred THF solution (10 mL) of trichloromethylsilane (5.431 g, 36.3 mmol) in a 250 mL flask. After...chloromethylsilane) The Grignard reagent , (Me3Si)2NC6H4MgBr was prepared exactly as previously described from 37.6 mmol of magnesium and 30 mmol of (N...trimethylsilyl)2-4-bromoaniline in THF (25 mL). This Grignard reagent was added drop-wise to a well-stirred THF solution (10 mL) of trichloromethylsilane

Chemical Durability Improvement and Static Fatigue of Glasses.

DTIC Science & Technology

1982-05-01

Specifically, the replacement of hydroxyl groups on the glass surface with silane or Grignard reagent nearly completely eliminated stress rate dependence...CK3SiC13 in Heptane solution Cc) 2 vol % (CR3)3SIC1 in Heptane solution (d) 0.1 M CH3MgBr ( Grignard reagent ) in n-Buthyl ether solution • Corning 7900...C113)3- SiCl or C13MgBr ( Grignard reagent ) solution while it remains practi- cally unchanged in CH3SiCI3 solution. In CH3SICI3 , the strength is

Synthesis and properties of photochromic biindenylidenedione derivatives containing thiophene groups, and new insights into the reaction of 2,2‧-biindanylidene-1,1‧,3,3‧-tetraone with Grignard reagent

NASA Astrophysics Data System (ADS)

Liu, Juyan; Han, Jie; Song, Zhiyi; Wei, Yongheng; Pang, Meili; Meng, Jiben

2008-11-01

Three indenone derivatives ( 1: 2-[3'-hydroxy-3'-(2-thienyl)indanone-2'-yl]-3-(2-thienyl)indenone; 2: trans- anti-3,3'-(2-thienyl)-3,3'-dihydroxy-[2,2'-bi-1H-indene]-1,1'-dione and 3: trans- syn-3,3'-(2-thienyl)-3,3'-dihydroxy-[2,2'-bi-1H-indene]-1,1'-dione) were obtained in a one-pot reaction of 2,2'-biindanylidene-1,1',3,3'-tetraone with 2-thienylmagnesium bromide. Their structures were characterized by means of IR, 1H NMR, MS, elemental analysis, and X-ray crystallography. The photochromic and photo-induced radical behaviors of these compounds were investigated by means of solid UV-vis spectroscopy and electron spin resonance (ESR) spectroscopy. The results show that compounds 2 and 3 exhibit photochromism in the solid state, whereas compound 1 does not. The relationship between the crystal structures and photochemical properties is also discussed. Based on the formation and product distribution of compounds 1, 2, and 3, a plausible pathway is suggested for the reaction of 2,2'-biindanylidene-1,1',3,3'-tetraone with 2-thienylmagnesium bromide. The findings obtained in this study also provide new insights into the addition-oxidation mechanism for the reaction of 2,2'-biindanylidene-1,1',3,3'-tetraone with Grignard reagent.

Stereocontrolled Alkylative Construction of Quaternary Carbon Centers

PubMed Central

Kummer, David A.; Chain, William J.; Morales, Marvin R.; Quiroga, Olga; Myers, Andrew G.

2009-01-01

Protocols for the stereodefined formation of α,α-disubstituted enolates of pseudoephedrine amides are presented followed by the implementation of these in diastereoselective alkylation reactions. Direct alkylation of α,α-disubstituted pseudoephedrine amide substrates is demonstrated to be both efficient and diastereoselective across a range of substrates, as exemplified by alkylation of the diastereomeric pseudoephedrine α-methylbutyramides, where both substrates are found to undergo stereospecific replacement of the α-C-H bond with α-C-alkyl, with retention of stereochemistry. This is shown to arise by sequential stereospecific enolization and alkylation reactions, with the alkyl halide attacking a common π-face of the E- and Z-enolates, proposed to be that opposite the pseudoephedrine alkoxide side-chain. Pseudoephedrine α-phenylbutyramides are found to undergo highly stereoselective but not stereospecific α-alkylation reactions, which evidence suggests is due to facile enolate isomerization. Also, we show that α, α-disubstituted pseudoephedrine amide enolates can be generated in a highly stereocontrolled fashion by conjugate addition of an alkyllithium reagent to the s-cis-conformer of an α-alkyl-α,β-unsaturated pseudoephedrine amide, providing α,α-disubstituted enolate substrates that undergo alkylation in the same sense as those formed by direct deprotonation. Methods are presented to transform the α-quaternary pseudoephedrine amide products into optically active carboxylic acids, ketones, primary alcohols, and aldehydes. PMID:18788739

When alcohol is the answer: trapping, identifying and quantifying simple alkylating species in aqueous environments

PubMed Central

Penketh, P. G.; Shyam, K.; Baumann, R. P; Zhu, Rui; Ishiguro, K.; Sartorelli, A. C.; Ratner, E. S.

2016-01-01

Alkylating agents are a significant class of environmental carcinogens as well as commonly used anticancer therapeutics. Traditional alkylating activity assays have utilized the colorimetric reagent 4-(4-nitrobenzyl)pyridine (4NBP). However, 4NBP based assays have a relatively low sensitivity towards harder, more oxophilic alkylating species and are not well suited for the identification of the trapped alkyl moiety due to adduct instability. Herein we describe a method using water as the trapping agent which permits the trapping of simple alkylating electrophiles with a comparatively wide range of softness/hardness and permits the identification of donated simple alkyl moieties. PMID:27188264

Synthesis of High Molecular Weight Fluoroalkylarylene-siloxanylene (FASIL) Polymer

DTIC Science & Technology

1979-01-01

impurity component" is shown in Figure 4. 6 When methyl(3,3,3-trifluoropropyl)diethoxysilane was added to the Grignard reagent at reflux instead of at...only a 34% yield. Inverse addi- tion, where the Grignard reagent was added to the diethoxysilane,gave a 43% yield. An impurity, ethoxymethyl(3,3,3...CH 2 CH2CF 3 Treatment of methyl(3,3,3-trifluoropropyl)dichlorosilane with excess ethanol gave methyl(3,3,3-trifluoropropyl)diethoxysilane. A Grignard

The synthesis of 1,2-bis(1,5,9-triazacyclododecyl)ethane: a showcase for the importance of the linker length within bis(alkylating) reagents.

PubMed

Medina-Molner, Alfredo; Blacque, Olivier; Spingler, Bernhard

2007-11-08

The synthesis of 1,2-bis(1,5,9-triazacyclododecyl)ethane (1) showcases how different bis(alkylating) reagents change the reaction from an intra- to an intermolecular pathway. The isolation of the intermediate hexahydro-3a,6a-ethano-1H,4H,7H,9bH-9a-aza-3a,6a-diazoniaphenalene-3a,6a-diium (2) explained why initially the synthesis of 1 was not possible. Both isomers of 2 were found in solution. DFT calculations revealed that isomer 2a is 4.6 kcal/mol lower in energy than 2b. Synthesis of 1 was finally achieved by using oxalyl chloride.

Development of Novel Environmentally Sustainable Binders for Energetic Formulations

DTIC Science & Technology

2015-06-01

Senenayake, C. H., Addition of Grignard reagents to aryl acid chlorides: an efficient synthesis of aryl ketones, Org. Lett. 2005, 7, 5593- 5595. (b) Gowda...M. S.; Pande, S. S.; Ramakrishna, R. A.; Prabhu, K. R., Acylation of Grignard reagents mediated by N-methylpyrrolidinone: a remarkable selectivity...acid moiety to introduce the necessary linker. Although the standard isocyanates- based reagents induce significant toxicity, the isocyanate function

When alcohol is the answer: Trapping, identifying and quantifying simple alkylating species in aqueous environments.

PubMed

Penketh, Philip G; Shyam, Krishnamurthy; Baumann, Raymond P; Zhu, Rui; Ishiguro, Kimiko; Sartorelli, Alan C; Ratner, Elena S

2016-09-01

Alkylating agents are a significant class of environmental carcinogens as well as commonly used anticancer therapeutics. Traditional alkylating activity assays have utilized the colorimetric reagent 4-(4-nitrobenzyl)pyridine (4NBP). However, 4NBP based assays have a relatively low sensitivity towards harder, more oxophilic alkylating species and are not well suited for the identification of the trapped alkyl moiety due to adduct instability. Herein we describe a method using water as the trapping agent which permits the trapping of simple alkylating electrophiles with a comparatively wide range of softness/hardness and permits the identification of donated simple alkyl moieties. Copyright © 2016 Elsevier Inc. All rights reserved.

Asymmetric Synthesis of 1,2,9,9a-Tetrahydrocyclopropa[c]benzo[e]indol-4-one (CBI)

PubMed Central

Lajiness, James P.; Boger, Dale L.

2011-01-01

A short, asymmetric synthesis of the 1,2,9,9a-tetrahydrocyclopropa[c]benzo[e]indol-4-one (CBI) analogue of the CC-1065 and duocarmycin DNA alkylation subunits is described. Treatment of iodo-epoxide 5, prepared by late-stage alkylation of 4 with (S)-glycidal-3-nosylate, with EtMgBr at room temperature directly provides the optically pure alcohol 6 in 87% yield (99% ee) derived from selective metal–halogen exchange and subsequent regioselective intramolecular 6-endo-tet cyclization. The use of MeMgBr or i-PrMgBr also provides the product in high yields (82–87%), but requires larger amounts of the Grignard reagent to effect metal–halogen exchange and cyclization. Direct transannular spirocyclization of 7 following O-debenzylation of 6 provides N-Boc-CBI. This approach represents the most efficient (9-steps, 31% overall) and effective (99% ee) route to the optically pure CBI alkylation subunit yet described. PMID:21192653

Photodissociation Dye Laser Studies and High Pressure Discharge Conditioning Studies

DTIC Science & Technology

1976-11-01

overnight to complete the formation of the Grignard reagent . The mixture was then cooled to room temperature and the solution was decanted ’.rom the...the Grignard reagent . A solution of the commercially available bromodiphenyl- methane (12.35 g) in the minimum quantity of dry benzene was then added...fairly rapidly into the reformed Hrignard reagent . A moderate exotherm was noted during this addition. The mixture was refluxed for two hours

Room-temperature chromium(II)-catalyzed direct arylation of pyridines, aryl oxazolines, and imines using arylmagnesium reagents.

PubMed

Kuzmina, Olesya M; Knochel, Paul

2014-10-03

We report a CrCl2-catalyzed oxidative arylation of various pyridines, aryl oxazolines, and aryl imines using aromatic Grignard reagents in the presence of 2,3-dichlorobutane (DCB). Most of the reactions proceed rapidly at 25 °C and do not require any additional ligand. Benzo[h]quinoline, 2-arylpyridine, aryl oxazoline, and imines were successfully arylated in good yields under these conditions. A TMS-substituent was used to prevent double arylation. After oxidative cross-coupling the TMS-group was further converted to a second ortho-aryl substituent. Remarkably, inexpensive aryl N-butylimine derivatives are excellent substrates for this oxidative arylation.

Synthesis and Modification of Carboxylated Polyphenylenes and Phenylated Polyimides

DTIC Science & Technology

1976-03-01

corresponding grignard reagent , which was allowed to react with DMF19 to provide the benzalde- hyde 50. This aldehyde, however, failed to undergo a benzoin...bromophenylethynyl )-trimethyl- silane in 100 ml THF was refluxed 2 hr with 1.6 g (0.066 g atm) of magnesium to form the Grignard reagent . To the...toluene (Table 2). The crown other reagent , however, could not be completely removed from the resulting ionomer. Treatment of the carboxylated

Synthesis of Soluble Alpha-Thiophene Oligomers. Monomer to Octamer

DTIC Science & Technology

1992-04-25

by forming the Grignard reagent of 5 [Mg (1.5 3 Schemne I a... Me3Si- -SMe 3 (1 1 2 Brj3-B ----m MeSi- 4 j 3 -- X d~-e me3Si J- SiW 3 (2) 3 4, X =Br 6...1.03 equiv), C6 H6 , 0* C to 230 C, 0.5 h, 94 %] and then to the corresponding Grignard reagent [Mg (1.5 equiv), ether, 23*C to 350 C] which was...PPh3)4 (5 mol %), toluene, reflux, 14 h] afforded the pentamer 1 in 47 % yield (eq g).25 The Grignard reagent of 13 was coupled with the iodide 16

Asymmetric Aryl Polyhedral Oligomeric SilSesquioxanes (ArPOSS) with Enhanced Solubility (Preprint)

DTIC Science & Technology

2011-03-23

by reaction of an aryl Grignard or lithium reagent with SiCl4 under reaction conditions s imilar to those previously reported [22]. The aryl...cooling to room temperature, this Grignard reagent w as added via canula to a SiCl 4 (25.1 g, 0.148 m ol) THF (70 mL) solution and stirred overnight

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

PubMed Central

Focken, Thilo

2014-01-01

Summary A review of the synthesis of natural products and bioactive compounds adopting phosphonamide anion technology is presented highlighting the utility of phosphonamide reagents in stereocontrolled bond-forming reactions. Methodologies utilizing phosphonamide anions in asymmetric alkylations, Michael additions, olefinations, and cyclopropanations will be summarized, as well as an overview of the synthesis of the employed phosphonamide reagents. PMID:25246946

Feasibility of Biomonitoring of Exposure to Permethrin Through Analysis of Long-Lived (Metabolite) Adducts to Proteins

DTIC Science & Technology

2009-04-01

BaCO3 N2 koeler Ba(OH)2 opl. ventiel Figure 2. Manifold for preparation of [14C] 3-PBA. Preparation of the Grignard reagent To flask E...The entire system was kept under nitrogen. The preparation of the Grignard reagent was initiated by applying heat using a heat gun. When the reaction...all reagents were present in the manifold prior to the beginning of the experiment. 24 A B E D C drukmetervacuumH2SO4

Feasibility of Biomonitoring of Exposure to Permethrin Through Analysis of Long-Lived (Metabolite) Adducts to Proteins

DTIC Science & Technology

2007-09-01

Preparation of the Grignard reagent To flask E, containing magnesium (52 mg, 2 mmol) and a few crystals of iodine was added a solution of 3...bromodiphenylether (750 mg, 3 mmol) in diethyl ether (3 mL). The entire system was kept under nitrogen. The preparation of the Grignard reagent was initiated by...device represented below was used for the multi-step synthesis of 3-PBA; all reagents were present in the manifold prior to the beginning of the

New synthetic possibilities for the preparation of liquid crystalline dicyclohexyl derivatives

NASA Astrophysics Data System (ADS)

Sasnouski, Genadz; Bezborodov, Vladimir; Dabrowski, Roman S.; Dziaduszek, Jerzy

2000-05-01

A new synthetic approach for the preparation of two- and three ring liquid crystalline compounds possessing trans,trans-dicyclohexyl moiety is proposed and realized. Recently discovered reaction of Grignard reagents with esters leading to 1-substituted cyclopropanoles in the presence of tetraisopropoxytitanium was used as a key stage. Starting from ethyl trans-4-alkylcyclohexancarboxylates the corresponding 6-(4-alkylcyclohexyl)-3-alkyl (or aryl) cyclohex-2-en-1-ones have been prepared. Their catalytic hydrogenation in the base media gave mainly saturated trans, trans-ketones which are liquid crystalline and have been used also as a promising intermediate products for the preparation of different kinds of other LC compounds.

Structure-biocompatibility and transfection activity relationships of cationic polyaspartamides with (dialkylamino)alkyl and alkyl or hydroxyalkyl side groups.

PubMed

Salakhieva, Diana; Shevchenko, Vesta; Németh, Csaba; Gyarmati, Benjámin; Szilágyi, András; Abdullin, Timur

2017-01-30

A series of 14 cationic derivatives of poly(aspartic acid) i.e. cationic polyaspartamides with different (dialkylamino)alkyl and alkyl or hydroxyalkyl side groups was synthesized by nucleophilic addition on polysuccinimide. The resulting polyaspartamides have moderate amphiphilic properties. Relationships between the structure and ratio of side groups and in vitro properties of polyaspartamides, including their cytotoxic and membrane-damaging activity towards human cell lines, primary skin fibroblasts and erythrocytes, were established and discussed. Cationic polyaspartamides vary in their DNA-binding, condensing and nuclease-protecting characteristics depending on the concentration ratio of (dialkylamino)alkyl and alkyl or hydroxyalkyl side groups. Effective cell transfection was achieved upon polyaspartamide-mediated plasmid DNA delivery in serum-free medium in the presence of chloroquine. Effect of serum proteins adsorption onto polyaspartamide based polyplexes, and the role of concentration of polyplexes in culture medium in their colloidal stability and transfection process were demonstrated. Synthesized polyaspartamides are biocompatible and long-acting gene carriers, which are applied to cells after dilution and without washing, thus providing transfection level comparable to that of commercial transfection reagent. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthesis of Bridged Oligophenylene Laser Dyes

DTIC Science & Technology

1991-05-10

the Grignard formation. Pure 22 as the free base could then be coulpled with the Grignard reagent from bromonaphthalene 20 using nickel acetoacetate as...preparation of 22 free of any positional isomer. We were able to prepare quite pure 22 by the Grignard coupling reaction of an excess p-chlorophenylmagnesium...fluorene 14 into the methoxyterphenyl 23 by the palladium-catalyzed Grignard coupling. Bromination of 23 was not clean as both the activated 7-position on

Enantioconvergent Cross-Couplings of Racemic Alkylmetal Reagents with Unactivated Secondary Alkyl Electrophiles: Catalytic Asymmetric Negishi α-Alkylations of N-Boc-pyrrolidine

PubMed Central

Cordier, Christopher J.; Lundgren, Rylan J.; Fu, Gregory C.

2013-01-01

Although enantioconvergent alkyl-alkyl couplings of racemic electrophiles have been developed, there have been no reports of the corresponding reactions of racemic nucleophiles. Herein, we describe Negishi cross-couplings of racemic α-zincated N-Boc-pyrrolidine with unactivated secondary halides, thus providing a one-pot, catalytic asymmetric method for the synthesis of a range of 2-alkylpyrrolidines (an important family of target molecules) from N-Boc-pyrrolidine, a commercially available precursor. Preliminary mechanistic studies indicate that two of the most straightforward mechanisms for enantioconvergence (a dynamic kinetic resolution of the organometallic coupling partner and a simple β-hydride elimination/β-migratory insertion pathway) are unlikely to be operative. PMID:23869442

Chemically modified electrodes by nucleophilic substitution of chlorosilylated platinum oxide surfaces

NASA Astrophysics Data System (ADS)

Chen, Chun-Hsien; Hutchison, James H.; Postlethwaite, Timothy A.; Richardson, John N.; Murray, R. W.

1994-07-01

Chlorosilylated platinum oxide electrode surfaces can be generated by reaction of SiCl4 vapor with an electrochemically prepared monolayer of platinum oxide. A variety of nucleophilic agents (such as alcohols, amines, thiols, and Grignard reagents) can be used to displace chloride and thereby functionalize the metal surface. Electroactive surfaces prepared with ferrocene methanol as the nucleophile show that derivatization by small molecules can achieve coverages on the order of a full monolayer. Surfaces modified with long-chain alkyl groups efficiently block electrode reactions of redox probes dissolved in the contacting solution, but other electrochemical (double layer capacitance and surface coverage) and contact angle measurements suggest that these molecule films are not highly ordered, self-assembled monolayers.

Stereospecific nickel-catalyzed cross-coupling reactions of benzylic ethers and esters.

PubMed

Tollefson, Emily J; Hanna, Luke E; Jarvo, Elizabeth R

2015-08-18

This Account presents the development of a suite of stereospecific alkyl-alkyl cross-coupling reactions employing nickel catalysts. Our reactions complement related nickel-catalyzed stereoconvergent cross-coupling reactions from a stereochemical and mechanistic perspective. Most reactions of alkyl electrophiles with low-valent nickel complexes proceed through alkyl radicals and thus are stereoablative; the correct enantioselective catalyst can favor the formation of one enantiomer. Our reactions, in contrast, are stereospecific. Enantioenriched ethers and esters are cleanly converted to cross-coupled products with high stereochemical fidelity. While mechanistic details are still to be refined, our results are consistent with a polar, two-electron oxidative addition that avoids the formation of radical intermediates. This reactivity is unusual for a first-row transition metal. The cross-coupling reactions engage a range of benzylic ethers and esters, including methyl ethers, tetrahydropyrans, tetrahydrofurans, esters, and lactones. Coordination of the arene substituent to the nickel catalyst accelerates the reactions. Arenes with low aromatic stabilization energies, such as naphthalene, benzothiophene, and furan, serve as the best ligands and provide the highest reactivity. Traceless directing groups that accelerate reactions of sluggish substrates are described, providing partial compensation for arene coordination. Kumada, Negishi, and Suzuki reactions provide incorporation of a broad range of transmetalating agents. In Kumada coupling reactions, a full complement of Grigard reagents, including methyl, n-alkyl, and aryl Grignard reagents, are employed. In reactions employing methylmagnesium iodide, ligation of the nickel catalyst by rac-BINAP or DPEphos provides the highest yield and stereospecificity. For all other Grignard reagents, Ni(dppe)Cl2 has emerged as the best catalyst. Negishi cross-coupling reactions employing dimethylzinc are reported as a strategy to

Acid Chlorides as Formal Carbon Dianion Linchpin Reagents in the Aluminum Chloride-Mediated Dieckmann Cyclization of Dicarboxylic Acids.

PubMed

Armaly, Ahlam M; Bar, Sukanta; Schindler, Corinna S

2017-08-04

The development of acid chlorides as formal dianion linchpin reagents that enable access to cyclic 2-alkyl- and 2-acyl-1,3-alkanediones from dicarboxylic acids is described herein. Mechanistic experiments relying on 13 C-labeling studies confirm the role of acid chlorides as carbon dianion linchpin reagents and have led to a revised reaction mechanism for the aluminum(III)-mediated Dieckmann cyclization of dicarboxylic acids with acid chlorides.

Synthesis of prostaglandins by conjugate addition and alkylation of a directed enolate ion. 4,5-allenyl prostaglandins

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

Patterson, J.W.

1990-09-28

Over the previous two decades many elegant syntheses of prostaglandins, which in more sophisticated forms, allow the stereospecific introduction of the various asymmetric carbons have been accomplished. However, among these approaches the cuprate addition/enolate alkylation of suitable cyclopentenone {sup 2} stands out because of brevity and convergence. The recent reports by Noyori{sup 3} and Corey{sup 4} and their colleagues have reduced to practice the conversion of 4-alkoxycyclopentenones to prostaglandin E{sub 2} (PGE{sub 2}) by conjugate addition of an organocopper derivative of the lower side chain followed by alkylation of the resulting carbanion with methyl 7-halohept-2-enoate. The subject of this papermore » is application of the Tardella tin enolate alkylation developed by Noyori to the synthesis of 4, 5-allenic prostaglandins, a pharmacologically important class of compounds. The authors results demonstrate that the tandem alkylation of an enone precursor with a cuprate reagent followed by alkylation of the corresponding tin enolate with bromide reagent is a viable synthetic method for 4,5-didehydro-PGE{sub 2}. Because the optically active forms of 1 and the vinyl iodide precursor of the PGE{sub 2} lower side chain have been employed to produce a single enantiomer of PGE{sub 2}, the extension of the methodology described here to the synthesis of single enantiomers of 4a awaits only the preparation of the separate enantiomers of allene 14.« less

Alkyl halide-free heteroatom alkylation and epoxidation facilitated by a recyclable polymer-supported oxidant for the in-flow preparation of diazo compounds.

PubMed

Nicolle, Simon M; Hayes, Christopher J; Moody, Christopher J

2015-03-16

Highly reactive metal carbenes, generated from simple ketones via diazo compounds, including diazo-amides and -phosphonates, using a recyclable reagent in-flow, are transient but versatile electrophiles for heteroatom alkylation reactions and for epoxide formation. The method produces no organic waste, with the only by-products being water, KI and nitrogen, without the attendant hazards of isolation of intermediate diazo compounds. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of geminal difluorides by oxidative desulfurization-difluorination of alkyl aryl thioethers with halonium electrophiles in the presence of fluorinating reagents and its application for 18F-radiolabeling.

PubMed

Hugenberg, Verena; Wagner, Stefan; Kopka, Klaus; Schober, Otmar; Schäfers, Michael; Haufe, Günter

2010-09-17

Various ω-substituted 1,1-difluoroalkanes are synthesized in good yields from alkyl aryl thioethers by a new oxidative desulfurization-difluorination protocol with the reagents combination of 1,3-dibromo-5,5-dimethylhydantoin (DBH) as an oxidizer and pyridine·9HF (Py·9HF) as a fluoride source. The reaction proceeds via a fluoro-Pummerer-type rearrangement followed by an oxidative desulfurization-fluorination step. Starting from α-fluorinated thioethers, this reaction is promising for (18)F-labeling (τ(1/2) = 110 min) of ligands applicable for positron emission tomography (PET). Using the combination of DBH and carrier-added Py·9H[(18)F]F, an (18)F-labeled difluoride was synthesized from the corresponding α-fluoro thioether with a radiochemical yield of 9%.

Reactions of Mono(disilylamino)phosphines with Carbon Tetrachloride.

DTIC Science & Technology

1984-05-18

and LiN(SiMe 3 )2 . Allyl and benzyl Grignard reagents were used in the Wilburn synthesis 6 to prepare phosphines L5-18. Compounds 15, 16, and 17, each...Section General Procedures. The following reagents were purchased from commercial sources and used without further purification: MeMgBr(Et20), PhCH...2.7 M, 99 mmol) was added dropwise via the addition funnel. The mixture was allowed to warm to room temperature and to stir overnight. The Grignard

Synthesis and Performance of a Biomimetic Indicator for Alkylating Agents.

PubMed

Provencher, Philip A; Love, Jennifer A

2015-10-02

4-(4-Nitrobenzyl)pyridine (NBP) is a colorimetric indicator compound for many types of carcinogenic alkylating agents. Because of the similar reactivity of NBP and guanine in DNA, NBP serves as a DNA model. NBP assays are used in the toxicological screening of pharmaceutical compounds, detection of chemical warfare agents, environmental hygiene technology, preliminary toxicology tests, mutagenicity of medicinal compounds, and other chemical analyses. Nevertheless, the use of NBP as a DNA model suffers from the compound's low water solubility, its lack of reactive oxygen sites, and dissimilar steric encumbrance compared to DNA. We report herein the design and synthesis of NBP derivatives that address some of these issues. These derivatives have been tested in solution and found to be superior in the colorimetric assay of the alkylating anticancer drug cyclophosphamide. The derivatives have also been integrated into a polymeric silica material which changes color upon the exposure to dangerous alkylating agents, such as iodomethane vapor, without the need for an exogenous base. This material modernizes the NBP assay from a time-consuming laboratory analysis to a real-time solid state sensor, which requires neither solvent nor additional reagents and can detect both gas- and solution-phase alkylating agents.

Potential impurities in drug substances: Compound-specific toxicology limits for 20 synthetic reagents and by-products, and a class-specific toxicology limit for alkyl bromides.

PubMed

Bercu, J P; Galloway, S M; Parris, P; Teasdale, A; Masuda-Herrera, M; Dobo, K; Heard, P; Kenyon, M; Nicolette, J; Vock, E; Ku, W; Harvey, J; White, A; Glowienke, S; Martin, E A; Custer, L; Jolly, R A; Thybaud, V

2018-04-01

This paper provides compound-specific toxicology limits for 20 widely used synthetic reagents and common by-products that are potential impurities in drug substances. In addition, a 15 μg/day class-specific limit was developed for monofunctional alkyl bromides, aligning this with the class-specific limit previously defined for monofunctional alkyl chlorides. Both the compound- and class-specific toxicology limits assume a lifetime chronic exposure for the general population (including sensitive subpopulations) by all routes of exposure for pharmaceuticals. Inhalation-specific toxicology limits were also derived for acrolein, formaldehyde, and methyl bromide because of their localized toxicity via that route. Mode of action was an important consideration for a compound-specific toxicology limit. Acceptable intake (AI) calculations for certain mutagenic carcinogens assumed a linear dose-response for tumor induction, and permissible daily exposure (PDE) determination assumed a non-linear dose-response. Several compounds evaluated have been previously incorrectly assumed to be mutagenic, or to be mutagenic carcinogens, but the evidence reported here for such compounds indicates a lack of mutagenicity, and a non-mutagenic mode of action for tumor induction. For non-mutagens with insufficient data to develop a toxicology limit, the ICH Q3A qualification thresholds are recommended. The compound- and class-specific toxicology limits described here may be adjusted for an individual drug substance based on treatment duration, dosing schedule, severity of the disease and therapeutic indication. Copyright © 2018. Published by Elsevier Inc.

Synthesis of Improved Polyester Resins.

DTIC Science & Technology

1979-07-05

p-phenylene bis(magnesium bromide) dispersed in 70 ml of hexane was added over a period of one hour. Residual Grignard reagent was washed from the...was prepared from p-phenylenedi(phenylphosphonyl chloride) (PPPC). The PPPC monomer was made from the p-phenylene bis(magnesium bromide) Grignard ...phenylphosphonyl dichloride removal. On cooling, the product was a viscous glassy liquid. It weighed 12.5 grams (113 percent based on 8g of Grignard

Parallel and automated library synthesis of 2-long alkyl chain benzoazoles and azole[4,5-b]pyridines under microwave irradiation.

PubMed

Martínez-Palou, Rafael; Zepeda, L Gerardo; Höpfl, Herbert; Montoya, Ascensión; Guzmán-Lucero, Diego J; Guzmán, Javier

2005-01-01

A versatile route to 40-membered library of 2-long alkyl chain substituted benzoazoles (1 and 2) and azole[4,5-b]pyridines (3 and 4) via microwave-assisted combinatorial synthesis was developed. The reactions were carried out in both monomode and multimode microwave oven. With the latter, all reactions were performed in high-throughput experimental settings consisting of an 8 x 5 combinatorial library designed to synthesize 40 compounds. Each step, from the addition of reagents to the recovery of final products, was automated. The microwave-assisted N-long chain alkylation reactions of 2-alkyl-1H-benzimidazole (1) and 2-alkyl-1H-benzimidazole[4,5-b] pyridines (3) were also studied.

Composite Materials with Improved Properties in Compression: Synthesis of 3-Methylene-1,1-Dichlorosilacyclobutane and 1,1-Dichlorosilacyclopent-3-ene

DTIC Science & Technology

1990-05-09

reagents may in fact be involved. Of synthetic interest, V undergoes intramolecular Grignard ring closure to yield III (10%). While the yield of III is low...VII) as the major product along with 1,4-bis(trichlorosilyl)- cis-2-butene (VIII). VII undergoes cyclization by an intramolec- ular Grignard ring...addition of methyl Grignard to III. The 1H 8 am NMR chemical shifts of I in diethyl ether are consistently about 0.4 ppm downfield from those previously

Room temperature alkynylation of H-phosphi(na)tes and secondary phosphine oxides with ethynylbenziodoxolone (EBX) reagents.

PubMed

Chen, C Chun; Waser, Jerome

2014-11-04

Highly efficient protocols for the alkynylation of H-phosphi(na)tes and secondary phosphine oxides with silyl, aryl and alkyl ethynyl-benziodoxolone (EBX) reagents are reported. Alkynyl phosphorus compounds were obtained in 69-93% yield without the need for a transition metal catalyst at room temperature under open flask conditions.

Reductive alkylation of ribosomes as a probe to the topography of ribosomal proteins*

PubMed Central

Moore, Graham; Crichton, Robert R.

1974-01-01

Escherichia coli ribosomes were treated with a number of different aldehydes of various sizes in the presence of NaBH4. After incorporation of either 3H or 14C, the ribosomal proteins were separated by two-dimensional polyacrylamide-gel electrophoresis and the extent of alkylation of the lysine residues in each protein was measured. The same pattern of alkylation was observed with the four reagents used, namely formaldehyde, acetone, benzaldehyde and 3,4,5-trimethoxybenzaldehyde. Every protein in 30S and 50S subunits was modified, although there was considerable variation in the degree of alkylation of individual proteins. A topographical classification of ribosomal proteins is presented, based on the degree of exposure of lysine residues. The data indicate that every protein of the ribosome has at least one lysine residue exposed at or near the surface of the ribonucleo-protein complex. PMID:4462744

Metallaphotoredox-catalysed sp3-sp3 cross-coupling of carboxylic acids with alkyl halides

NASA Astrophysics Data System (ADS)

Johnston, Craig P.; Smith, Russell T.; Allmendinger, Simon; MacMillan, David W. C.

2016-08-01

In the past 50 years, cross-coupling reactions mediated by transition metals have changed the way in which complex organic molecules are synthesized. The predictable and chemoselective nature of these transformations has led to their widespread adoption across many areas of chemical research. However, the construction of a bond between two sp3-hybridized carbon atoms, a fundamental unit of organic chemistry, remains an important yet elusive objective for engineering cross-coupling reactions. In comparison to related procedures with sp2-hybridized species, the development of methods for sp3-sp3 bond formation via transition metal catalysis has been hampered historically by deleterious side-reactions, such as β-hydride elimination with palladium catalysis or the reluctance of alkyl halides to undergo oxidative addition. To address this issue, nickel-catalysed cross-coupling processes can be used to form sp3-sp3 bonds that utilize organometallic nucleophiles and alkyl electrophiles. In particular, the coupling of alkyl halides with pre-generated organozinc, Grignard and organoborane species has been used to furnish diverse molecular structures. However, the manipulations required to produce these activated structures is inefficient, leading to poor step- and atom-economies. Moreover, the operational difficulties associated with making and using these reactive coupling partners, and preserving them through a synthetic sequence, has hindered their widespread adoption. A generically useful sp3-sp3 coupling technology that uses bench-stable, native organic functional groups, without the need for pre-functionalization or substrate derivatization, would therefore be valuable. Here we demonstrate that the synergistic merger of photoredox and nickel catalysis enables the direct formation of sp3-sp3 bonds using only simple carboxylic acids and alkyl halides as the nucleophilic and electrophilic coupling partners, respectively. This metallaphotoredox protocol is suitable for

Chemoselective synthesis of ketones and ketimines by addition of organometallic reagents to secondary amides

NASA Astrophysics Data System (ADS)

Bechara, William S.; Pelletier, Guillaume; Charette, André B.

2012-03-01

The development of efficient and selective transformations is crucial in synthetic chemistry as it opens new possibilities in the total synthesis of complex molecules. Applying such reactions to the synthesis of ketones is of great importance, as this motif serves as a synthetic handle for the elaboration of numerous organic functionalities. In this context, we report a general and chemoselective method based on an activation/addition sequence on secondary amides allowing the controlled isolation of structurally diverse ketones and ketimines. The generation of a highly electrophilic imidoyl triflate intermediate was found to be pivotal in the observed exceptional functional group tolerance, allowing the facile addition of readily available Grignard and diorganozinc reagents to amides, and avoiding commonly observed over-addition or reduction side reactions. The methodology has been applied to the formal synthesis of analogues of the antineoplastic agent Bexarotene and to the rapid and efficient synthesis of unsymmetrical diketones in a one-pot procedure.

Exploiting Carvone to Demonstrate Both Stereocontrol and Regiocontrol: 1,2- vs 1,4-Addition of Grignard Reagents and Organocuprates

ERIC Educational Resources Information Center

Truong, Thai Phat; Bailey, Sophia J.; Golliher, Alexandra E.; Monroy, Erika Y.; Shrestha, Uttar K.; Maio, William A.

2018-01-01

The ability of certain organometallic reagents to react via 1,2- or 1,4-addition to an a,ß-unsaturated ketone is a fundamental example of regioselectivity at the second-year undergraduate organic level. The following two experiments were designed to demonstrate this preference by exploiting carvone as an inexpensive chiral, nonracemic substrate.…

Use of (S)-trans-gamma-monocyclofarnesol as a useful chiral building block for the stereoselective synthesis of diterpenic natural products.

PubMed

Serra, Stefano; Cominetti, Alessandra A; Lissoni, Veronica

2014-03-01

A comprehensive study of the exploitation of (S)-trans-gamma-monocyclofarnesol as a useful chiral building block for the stereoselective synthesis of natural diterpene derivatives is here described. The farnesol derivative (+)-1 was used as starting material in the preparation of the diterpenes (S)-dehydroambliol-A and (S)-trixagol, as well as for the syntheses of the dinorditerpene (S)-dinortrixagone and of the guanidine-interrupted terpenoid (S)-dotofide. Key steps of the presented syntheses were the cross-coupling between an allyl acetate and a Grignard reagent, the Wittig reaction, the selective preparation ofa diacylguanidine derivative and the alkylation of a sulfone derivative, followed by the reductive removal of the same functional group. It is worth noting that the natural products (+)-8, (+)-12 and (+)-15 were prepared stereoselectively for the first time, thus allowing the unambiguous assignment of their absolute configuration.

Metal-Free-Visible Light C-H Alkylation of Heteroaromatics via Hypervalent Iodine-Promoted Decarboxylation.

PubMed

Genovino, Julien; Lian, Yajing; Zhang, Yuan; Hope, Taylor O; Juneau, Antoine; Gagné, Yohann; Ingle, Gajendra; Frenette, Mathieu

2018-05-16

A metal-free photoredox C-H alkylation of heteroaromatics from readily available carboxylic acids using an organic photocatalyst and hypervalent iodine reagents under blue LED light is reported. The developed methodology tolerates a broad range of functional groups and can be applied to the late-stage functionalization of drugs and drug-like molecules. The reaction mechanism was investigated with control experiments and photophysical experiments as well as DFT calculations.

Total Synthesis of Natural Products Using Hypervalent Iodine Reagents

NASA Astrophysics Data System (ADS)

Maertens, Gaetan; L'homme, Chloe; Canesi, Sylvain

2014-12-01

We present a review of natural product syntheses accomplished in our laboratory during the last five years. Each synthetic route features a phenol dearomatization promoted by an environmentally benign hypervalent iodine reagent. The dearomatizations demonstrate the “aromatic ring umpolung” concept, and involve stereoselective remodeling of the inert unsaturations of a phenol into a highly functionalized key intermediate that may contain a quaternary carbon center and a prochiral dienone system. Several new oxidative strategies were employed, including transpositions (1,3-alkyl shift and Prins-pinacol), a polycyclization, an ipso rearrangement, and direct nucleophilic additions at the phenol para position. Several alkaloids, heterocyclic compounds, and a polycyclic core have been achieved, including sceletenone (a serotonin reuptake inhibitor), acetylaspidoalbidine (an antitumor agent), fortucine (antiviral and antitumor), erysotramidine (curare-like effect), platensimycin (an antibiotic), and the main core of a kaurane diterpene (immunosuppressive agent and stimulator of apoptosis). These concise and in some cases enantioselective syntheses effectively demonstrate the importance of hypervalent iodine reagents in the total synthesis of bioactive natural products.

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

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…

Inducible Alkylation of DNA by a Quinone Methide-Peptide Nucleic Acid Conjugate†

PubMed Central

Liu, Yang; Rokita, Steven E.

2012-01-01

The reversibility of alkylation by a quinone methide intermediate (QM) avoids the irreversible consumption that plagues most reagents based on covalent chemistry and allows for site specific reaction that is controlled by the thermodynamics rather than kinetics of target association. This characteristic was originally examined with an oligonucleotide QM conjugate but broad application depends on alternative derivatives that are compatible with a cellular environment. Now, a peptide nucleic acid (PNA) derivative has been constructed and shown to exhibit an equivalent ability to delivery the reactive QM in a controlled manner. This new conjugate demonstrates high selectivity for a complementary sequence of DNA even when challenged with an alternative sequence containing a single T/T mismatch. Alkylation of non-complementary sequences is only possible when a template strand is present to co-localize the conjugate and its target. For efficient alkylation in this example, a single-stranded region of the target is required adjacent to the QM conjugate. Most importantly, the intrastrand self adducts formed between the PNA and its attached QM remained active and reversible over more than eight days in aqueous solution prior to reaction with a chosen target added subsequently. PMID:22243337

SYNTHESES, REACTIONS, AND STRUCTURES OF CERTAIN SULFUR-NITROGEN COMPOUNDS.

DTIC Science & Technology

and nuclear magnetic resonance spectroscopy. The reactions of trichlorophosphazo-substituted phosphonitrilic chloride trimers with phenyl Grignard reagents have been explored and the products characterized similarly. (Author)

Alkylation of Staurosporine to Derive a Kinase Probe for Fluorescence Applications.

PubMed

Disney, Alexander J M; Kellam, Barrie; Dekker, Lodewijk V

2016-05-06

The natural product staurosporine is a high-affinity inhibitor of nearly all mammalian protein kinases. The labelling of staurosporine has proven effective as a means of generating protein kinase research tools. Most tools have been generated by acylation of the 4'-methylamine of the sugar moiety of staurosporine. Herein we describe the alkylation of this group as a first step to generate a fluorescently labelled staurosporine. Following alkylation, a polyethylene glycol linker was installed, allowing subsequent attachment of fluorescein. We report that this fluorescein-staurosporine conjugate binds to cAMP-dependent protein kinase in the nanomolar range. Furthermore, its binding can be antagonised with unmodified staurosporine as well as ATP, indicating it targets the ATP binding site in a similar fashion to native staurosporine. This reagent has potential application as a screening tool for protein kinases of interest. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Copper-catalyzed aerobic spirocyclization of biaryl-N-H-imines via 1,4-aminooxygenation of benzene rings.

PubMed

Tnay, Ya Lin; Chen, Cheng; Chua, Yi Yuan; Zhang, Line; Chiba, Shunsuke

2012-07-06

A synthetic method of azaspirocyclohexadienones has been developed through copper-catalyzed aerobic spirocyclization of biaryl-N-H-imines prepared by the reaction of biarylcarbonitriles and Grignard reagents.

Quantitative chemoproteomics for site-specific analysis of protein alkylation by 4-hydroxy-2-nonenal in cells.

PubMed

Yang, Jing; Tallman, Keri A; Porter, Ned A; Liebler, Daniel C

2015-03-03

Protein alkylation by 4-hydroxy-2-nonenal (HNE), an endogenous lipid derived electrophile, contributes to stress signaling and cellular toxicity. Although previous work has identified protein targets for HNE alkylation, the sequence specificity of alkylation and dynamics in a cellular context remain largely unexplored. We developed a new quantitative chemoproteomic platform, which uses isotopically tagged, photocleavable azido-biotin reagents to selectively capture and quantify the cellular targets labeled by the alkynyl analogue of HNE (aHNE). Our analyses site-specifically identified and quantified 398 aHNE protein alkylation events (386 cysteine sites and 12 histidine sites) in intact cells. This data set expands by at least an order of magnitude the number of such modification sites previously reported. Although adducts formed by Michael addition are thought to be largely irreversible, we found that most aHNE modifications are lost rapidly in situ. Moreover, aHNE adduct turnover occurs only in intact cells and loss rates are site-selective. This quantitative chemoproteomics platform provides a versatile general approach to map bioorthogonal-chemically engineered post-translational modifications and their cellular dynamics in a site-specific and unbiased manner.

Metallaphotoredox-Catalyzed sp3–sp3 Cross-Coupling of Carboxylic Acids with Alkyl Halides

PubMed Central

Johnston, Craig P.; Smith, Russell T.; Allmendinger, Simon; MacMillan, David W. C.

2017-01-01

Over the last half-century, transition metal-mediated cross-coupling reactions have changed the way in which complex organic molecules are synthesized. Indeed, the predictable and chemoselective nature of these transformations has led to their widespread adoption across a vast array of chemical research areas1. However, the construction of sp3–sp3 bonds, a fundamental unit of organic chemistry, remains an important yet elusive objective for cross-coupling reaction engineering2. In comparison to related procedures with sp2-hybridized species, the development of methods for sp3–sp3 bond formation via transition metal catalysis has been historically hampered by deleterious side-reactions, such as β-hydride elimination with Pd-catalysis, and the reluctance of alkyl halides to undergo oxidative addition3,4. To address this issue, a number of research groups have demonstrated the feasibility of nickel-catalyzed cross-coupling processes to form sp3–sp3 bonds that utilize organometallic nucleophiles and alkyl electrophiles5–7. In particular, the coupling of alkyl halides with pregenerated organozinc8–10, Grignard11,12, and organoborane13 species has been used to furnish diverse molecular structures. However, the poor step and atom economies along with the operational difficulties associated with making, carrying, and using these sensitive coupling partners has hindered their widespread adoption. The prospect of establishing a generically useful sp3–sp3 coupling technology that employs bench-stable, native organic functional groups, without the need for pre-functionalization or substrate derivatization, would therefore be a valuable addition to fields of research that rely on organic molecule construction. Here, we demonstrate that the synergistic merger of photoredox and nickel catalysis enables the direct formation of sp3–sp3 bonds using only simple carboxylic acids and alkyl halides as the nucleophilic and electrophilic coupling partners, respectively. The

Selectivity in the Addition Reactions of Organometallic Reagents to Aziridine-2-carboxaldehydes: The Effects of Protecting Groups and Substitution Patterns

PubMed Central

Kulshrestha, Aman; Schomaker, Jennifer M.; Holmes, Daniel; Staples, Richard J.; Jackson, James E.; Borhan, Babak

2014-01-01

Good to excellent stereo-selectivity has been found in the addition reactions of Grignard and organo-zinc reagents to N-protected aziridine-2-carboxaldehydes. Specifically, high syn selectivity was obtained with benzyl-protected cis, tert-butyloxycar-bonyl-protected trans, and tosyl-pro-tected 2,3-disubstituted aziridine-2-car-boxaldehydes. Furthermore, rate and selectivity effects of ring substituents, temperature, solvent, and Lewis acid and base modifiers were studied. The diastereomeric preference of addition is dominated by the substrate aziri-dines’ substitution pattern and especially the electronic character and conformational preferences of the nitrogen protecting groups. To help rationalize the observed stereochemical outcomes, conformational and electronic structural analyses of a series of model systems representing the various substitution patterns have been explored by density functional calculations at the B3LYP/6–31G* level of theory with the SM8 solvation model to account for solvent effects. PMID:21928447

Alkyl–Alkyl Suzuki Cross-Couplings of Unactivated Secondary Alkyl Chlorides**

PubMed Central

Lu, Zhe; Fu, Gregory C.

2010-01-01

The first method for achieving alkyl–alkyl Suzuki reactions of unactivated secondary alkyl chlorides has been developed. Carbon–carbon bond formation occurs under mild conditions (at room temperature) with the aid of commercially available catalyst components. This method has proved to be versatile: without modification, it can be applied to Suzuki reactions of secondary and primary alkyl bromides and iodides, as well as primary alkyl chlorides. Mechanistic investigations suggest that oxidative addition is not the turnover-limiting step of the catalytic cycle for unactivated secondary alkyl iodides and bromides, whereas it may be (partially) for chlorides. PMID:20715038

The Electrochemical Behavior in Aqueous Media of Conducting Polymers. 2. The Insoluble Fractions Obtained on the Cu(II) Catalyzed Polymerization of (2,5-Dibromo-3-Group IV Substituted) Thiophenes.

DTIC Science & Technology

1986-07-30

Grignard compounds derived from 2,5-dibromothiophene and 2,5-dibromo-3- m-thyI thiophene have been reported by Yarmamctc’ et al. (20,21). After iodine...modification of the synthetic route by employing the 2,5-dilithiothiophenes in place of the bis- Grignard compounds. Subsequent anhydrous metal salts promoted...acknowledge the Lithium Corporation for • the donation of n-butyllithium reagent . •o. , References i. G. Wagner, Angew. Chem. Int. Ed. Engi., 20 361 (1981

Bisphosphine dioxides

DOEpatents

Moloy, Kenneth G.

1990-01-01

A process for the production of organic bisphosphine dioxides from organic bisphosphonates. The organic bisphosphonate is reacted with a Grignard reagent to give relatively high yields of the organic bisphosphine dioxide.

40 CFR 721.9595 - Alkyl benzene sulfonic acids and alkyl sulfates, amine salts (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkyl benzene sulfonic acids and alkyl... Significant New Uses for Specific Chemical Substances § 721.9595 Alkyl benzene sulfonic acids and alkyl...) The chemical substances identified generically as alkyl benzene sulfonic acids and alkyl sulfates...

40 CFR 721.9595 - Alkyl benzene sulfonic acids and alkyl sulfates, amine salts (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl benzene sulfonic acids and alkyl... Significant New Uses for Specific Chemical Substances § 721.9595 Alkyl benzene sulfonic acids and alkyl...) The chemical substances identified generically as alkyl benzene sulfonic acids and alkyl sulfates...

40 CFR 721.9595 - Alkyl benzene sulfonic acids and alkyl sulfates, amine salts (generic).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkyl benzene sulfonic acids and alkyl... Significant New Uses for Specific Chemical Substances § 721.9595 Alkyl benzene sulfonic acids and alkyl...) The chemical substances identified generically as alkyl benzene sulfonic acids and alkyl sulfates...

40 CFR 721.9595 - Alkyl benzene sulfonic acids and alkyl sulfates, amine salts (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl benzene sulfonic acids and alkyl... Significant New Uses for Specific Chemical Substances § 721.9595 Alkyl benzene sulfonic acids and alkyl...) The chemical substances identified generically as alkyl benzene sulfonic acids and alkyl sulfates...

40 CFR 721.9595 - Alkyl benzene sulfonic acids and alkyl sulfates, amine salts (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl benzene sulfonic acids and alkyl... Significant New Uses for Specific Chemical Substances § 721.9595 Alkyl benzene sulfonic acids and alkyl...) The chemical substances identified generically as alkyl benzene sulfonic acids and alkyl sulfates...

40 CFR 721.1875 - Boric acid, alkyl and substituted alkyl esters (generic name).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Boric acid, alkyl and substituted... Significant New Uses for Specific Chemical Substances § 721.1875 Boric acid, alkyl and substituted alkyl... chemical substance boric acid, alkyl and substituted alkyl esters (PMN P-86-1252) is subject to reporting...

40 CFR 721.1875 - Boric acid, alkyl and substituted alkyl esters (generic name).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Boric acid, alkyl and substituted... Significant New Uses for Specific Chemical Substances § 721.1875 Boric acid, alkyl and substituted alkyl... chemical substance boric acid, alkyl and substituted alkyl esters (PMN P-86-1252) is subject to reporting...

40 CFR 721.1875 - Boric acid, alkyl and substituted alkyl esters (generic name).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Boric acid, alkyl and substituted... Significant New Uses for Specific Chemical Substances § 721.1875 Boric acid, alkyl and substituted alkyl... chemical substance boric acid, alkyl and substituted alkyl esters (PMN P-86-1252) is subject to reporting...

40 CFR 721.1875 - Boric acid, alkyl and substituted alkyl esters (generic name).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Boric acid, alkyl and substituted... Significant New Uses for Specific Chemical Substances § 721.1875 Boric acid, alkyl and substituted alkyl... chemical substance boric acid, alkyl and substituted alkyl esters (PMN P-86-1252) is subject to reporting...

40 CFR 721.1875 - Boric acid, alkyl and substituted alkyl esters (generic name).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Boric acid, alkyl and substituted... Significant New Uses for Specific Chemical Substances § 721.1875 Boric acid, alkyl and substituted alkyl... chemical substance boric acid, alkyl and substituted alkyl esters (PMN P-86-1252) is subject to reporting...

Olefin Metathesis in Peptidomimetics, Dynamic Combinatorial Chemistry, and Molecular Imprinting

DTIC Science & Technology

2006-08-01

aryl iodide to the Grignard reagent . Treatment of the magnesium compound with allyl bromide and CuCN·2LiCl afforded benzoate 4-11, which was then...cyclization of a linear peptide by conventional coupling agents to form a new amide bond (Scheme 1-12)36,44 Some common reagents are...dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC), and expensive reagents such as HATU or PyBroP, which are more efficient.44 Racemization of the chiral

Bisphosphine dioxides

DOEpatents

Moloy, K.G.

1990-02-20

A process is described for the production of organic bisphosphine dioxides from organic bisphosphonates. The organic bisphosphonate is reacted with a Grignard reagent to give relatively high yields of the organic bisphosphine dioxide.

Distributed Drug Discovery, Part 2: Global Rehearsal of Alkylating Agents for the Synthesis of Resin-Bound Unnatural Amino Acids and Virtual D3 Catalog Construction

PubMed Central

2008-01-01

Distributed Drug Discovery (D3) proposes solving large drug discovery problems by breaking them into smaller units for processing at multiple sites. A key component of the synthetic and computational stages of D3 is the global rehearsal of prospective reagents and their subsequent use in the creation of virtual catalogs of molecules accessible by simple, inexpensive combinatorial chemistry. The first section of this article documents the feasibility of the synthetic component of Distributed Drug Discovery. Twenty-four alkylating agents were rehearsed in the United States, Poland, Russia, and Spain, for their utility in the synthesis of resin-bound unnatural amino acids 1, key intermediates in many combinatorial chemistry procedures. This global reagent rehearsal, coupled to virtual library generation, increases the likelihood that any member of that virtual library can be made. It facilitates the realistic integration of worldwide virtual D3 catalog computational analysis with synthesis. The second part of this article describes the creation of the first virtual D3 catalog. It reports the enumeration of 24 416 acylated unnatural amino acids 5, assembled from lists of either rehearsed or well-precedented alkylating and acylating reagents, and describes how the resulting catalog can be freely accessed, searched, and downloaded by the scientific community. PMID:19105725

Synthesis of 1,1-Diphenylethylene (DPE): The Marriage of a Grignard Reaction and a Column Chromatography Experiment

ERIC Educational Resources Information Center

Alty, Lisa T.; France, Marcia B.; Alty, Isaac G.; Saber, Christine A.; Smith, Donna M.

2016-01-01

The synthesis of 1,1-diphenylethylene (DPE) via a Grignard reaction, followed by an acid-catalyzed dehydration reaction, yields a mixture of compounds. DPE is a high boiling liquid that cannot be purified using simple distillation. However, it is easily separated from the more polar starting material and intermediate alcohol using both thin layer…

E- or Z-Selective synthesis of 4-fluorovinyl-1,2,3-triazoles with fluorinated second-generation Julia-Kocienski reagents.

PubMed

Kumar, Rakesh; Singh, Govindra; Todaro, Louis J; Yang, Lijia; Zajc, Barbara

2015-02-07

A highly modular approach to N-substituted 4-(1-fluorovinyl)triazoles is described. In situ desilylation and Cu-catalyzed ligation reaction of TMS-protected α-fluoropropargyl benzothiazole sulfone with aryl, alkyl, and metallocenyl azides furnished second-generation Julia-Kocienski reagents in good to excellent yields. Condensation reactions of these reagents with aldehydes can be tuned to yield E or Z-alkenes selectively. Under mild conditions with DBU as the base, reactions of aldehydes furnished E-alkenes as the major isomer. On the other hand, in condensation reactions with LHMDS as the base and in appropriate solvents, both aldehydes and ketones reacted to yield fluoroalkenes with Z-selectivity. Stereochemical assignment of E/Z olefins obtained in the reaction of a ketone with two Julia reagents was performed via X-ray crystallographic analysis and comparisons of NMR data. The method allows efficient and ready diversification of the N1-substituent and substituents at the double bond.

E- or Z-selective synthesis of 4-fluorovinyl-1,2,3-triazoles with fluorinated second-generation Julia-Kocienski reagents

PubMed Central

Kumar, Rakesh; Singh, Govindra; Todaro, Louis J.; Yang, Lijia; Zajc, Barbara

2016-01-01

A highly modular approach to N-substituted 4-(1-fluorovinyl)triazoles is described. In situ desilylation and Cu-catalyzed ligation reaction of TMS-protected α-fluoropropargyl benzothiazole sulfone with aryl, alkyl, and metallocenyl azides furnished second-generation Julia-Kocienski reagents in good to excellent yields. Condensation reactions of these reagents with aldehydes can be tuned to yield E or Z-alkenes selectively. Under mild conditions with DBU as base, reactions of aldehydes furnished E-alkenes as the major isomer. On the other hand, in condensations with LHMDS as base and in appropriate solvents, both aldehydes and ketones reacted to yield fluoroalkenes with Z-selectivity. Stereochemical assignment to E/Z olefins obtained in the reaction of a ketone with two Julia reagents was performed via X-ray crystallographic analysis and comparisons of NMR data. The method allows efficient and ready diversification of N1-substituent and substituents at the double bond. PMID:25491086

Processable Electronically Conducting Polymers

DTIC Science & Technology

1991-01-01

polyheterocycles and will be discussed in detail later. The Grignard coupling reaction of alkyl substituted 1,4- dibromobenzenes was initially employed, as...R 2 ,R 3 ) along with alkyl , aryl, benzyl, and -CH 2 CN substituents on the nitrogen (R I ). Since aniline preferentially oxidatively polymerizes at...but, in the case of N-aryl substituted anilines , an alternative mecha- nism has been proposed [171], which is outlined in Scheme 9. Both poly(N

Azidoimidazolinium Salts: Safe and Efficient Diazo-transfer Reagents and Unique Azido-donors.

PubMed

Kitamura, Mitsuru

2017-07-01

2-Azido-1,3-dimethylimidazolinium chloride (ADMC) and its corresponding hexafluorophosphate (ADMP) were found to be efficient diazo-transfer reagents to various organic compounds. ADMC was prepared by the reaction of 2-chloro-1,3-dimethylimidazolinium chloride (DMC) and sodium azide. ADMP was isolated as a crystal having good thermal stability and low explosibility. ADMC and ADMP reacted with 1,3-dicarbonyl compounds under mild basic conditions to give 2-diazo-1,3-dicarbonyl compounds in high yields, which were easily isolated in virtue of the high water solubility of the by-products. ADMP showed high diazo-transfer ability to primary amines even in the absence of metal salt such as Cu(II). Using this diazotization approach, various alkyl/aryl azides were directly obtained from their corresponding primary amines in high yields. Furthermore, naphthols reacted with ADMC to give the corresponding diazonaphthoquinones in good to high yields. In addition, 2-azido-1,3-dimethylimidazolinium salts were employed as azide-transfer and migratory amidation reagents. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of derivatization reagents consisting of n-alkyl chloroformate/n-alcohol combinations in LC-ESI-MS/MS analysis of zwitterionic antiepileptic drugs.

PubMed

Kostić, Nađa; Dotsikas, Yannis; Malenović, Anđelija; Medenica, Mirjana

2013-11-15

In the current study, three antiepileptic drugs with zwitterionic properties, namely vigabatrin, pregabalin and gabapentin, were chosen as model analytes to undergo derivatization by applying various n-alkyl chloroformate/n-alcohol combinations, followed by LC-ESI-MS/MS analysis. The employment of 16 combinations per drug using methyl, ethyl, propyl or butyl chloroformate coupled with methanol, ethanol, propanol or butanol, greatly affected a series of parameters of the derivatives, such as retention time on C8 column, signal expressed via areas, limit of detection values, as well as the yields of the main and side reactions. Practically, even slight modification of n-alkyl group of either chloroformate or alcohol resulted in significant changes in the chromatographic and mass spectrometric behavior of the novel derivative. It was clearly demonstrated that all the estimated parameters were highly correlated with the length of n-alkyl groups of the involved chloroformate and alcohol. The most significant influence was monitored in peak area values, indicating that the length of the n-alkyl chain plays an important role in electrospray ionization efficiency. For this parameter, increasing the n-alkyl chain from methyl to butyl led to increment up to 2089%, 508.7% and 1075% for area values of derivatized vigabatrin, pregabalin and gabapentin, respectively. These changes affected also the corresponding values of limits of detection, with the estimated improvements up to 1553%, 397.7% and 875.0% for the aforementioned derivatized drugs, respectively. Besides the obvious utilization of these conclusions in the development of bioanalytical methods for these analytes with the current protocol, this study offers valuable data which can be useful in more general approaches, giving insights into the effects of this derivatization reaction and its performances. Copyright © 2013 Elsevier B.V. All rights reserved.

Engaging unactivated alkyl, alkenyl and aryl iodides in visible-light-mediated free radical reactions

NASA Astrophysics Data System (ADS)

Nguyen, John D.; D'Amato, Erica M.; Narayanam, Jagan M. R.; Stephenson, Corey R. J.

2012-10-01

Radical reactions are a powerful class of chemical transformations. However, the formation of radical species to initiate these reactions has often required the use of stoichiometric amounts of toxic reagents, such as tributyltin hydride. Recently, the use of visible-light-mediated photoredox catalysis to generate radical species has become popular, but the scope of these radical precursors has been limited. Here, we describe the identification of reaction conditions under which photocatalysts such as fac-Ir(ppy)3 can be utilized to form radicals from unactivated alkyl, alkenyl and aryl iodides. The generated radicals undergo reduction via hydrogen atom abstraction or reductive cyclization. The reaction protocol utilizes only inexpensive reagents, occurs under mild reaction conditions, and shows exceptional functional group tolerance. Reaction efficiency is maintained upon scale-up and decreased catalyst loading, and the reaction time can be significantly shortened when the reaction is performed in a flow reactor.

Materials For Second and Third Order Nonlinear Optical Applications.

DTIC Science & Technology

1996-02-05

the ,Ieneral reaction scheme below in Fig. 1 is reminiscent of the synthetic method of Jutz, using Grignard reagents which were treated with N-methyl...N- phenylpropen-l-al (1[1]) or its higher vinylog, 1[2] in yields of 5-95%. In our procedure, we used a wide variety of organolithium reagents ...be synthesized from a facile high yield procedure for bromination of julolidine. Here we demonstrated that organolithium reagents add to known co-N,N

[Alkylating agents].

PubMed

Pourquier, Philippe

2011-11-01

With the approval of mechlorethamine by the FDA in 1949 for the treatment of hematologic malignancies, alkylating agents are the oldest class of anticancer agents. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in specific indications and sometimes represent the unique option for the treatment of refractory diseases. Here, we are reviewing the major classes of alkylating agents and their mechanism of action, with a particular emphasis for the new generations of alkylating agents. As for most of the chemotherapeutic agents used in the clinic, these compounds are derived from natural sources. With a complex but original mechanism of action, they represent new interesting alternatives for the clinicians, especially for tumors that are resistant to conventional DNA damaging agents. We also briefly describe the different strategies that have been or are currently developed to potentiate the use of classical alkylating agents, especially the inhibition of pathways that are involved in the repair of DNA lesions induced by these agents. In this line, the development of PARP inhibitors is a striking example of the recent regain of interest towards the "old" alkylating agents.

Exploiting Deep Eutectic Solvents and Organolithium Reagent Partnerships: Chemoselective Ultrafast Addition to Imines and Quinolines Under Aerobic Ambient Temperature Conditions.

PubMed

Vidal, Cristian; García-Álvarez, Joaquín; Hernán-Gómez, Alberto; Kennedy, Alan R; Hevia, Eva

2016-12-23

Shattering the long-held dogma that organolithium chemistry needs to be performed under inert atmospheres in toxic organic solvents, chemoselective addition of organolithium reagents to non-activated imines and quinolines has been accomplished in green, biorenewable deep eutectic solvents (DESs) at room temperature and in the presence of air, establishing a novel and sustainable access to amines. Improving on existing methods, this approach proceeds in the absence of additives; occurs without competitive enolization, reduction or coupling processes; and reactions were completed in seconds. Comparing RLi reactivities in DESs with those observed in pure glycerol or THF suggests a kinetic anionic activation of the alkylating reagents occurs, favoring nucleophilic addition over competitive hydrolysis. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nickel-Catalyzed Coupling Reactions of Alkyl Electrophiles, Including Unactivated Tertiary Halides, to Generate Carbon–Boron Bonds

PubMed Central

Dudnik, Alexander S.

2012-01-01

Through the use of a catalyst formed in situ from NiBr2•diglyme and a pybox ligand (both of which are commercially available), we have achieved our first examples of coupling reactions of unactivated tertiary alkyl electrophiles, as well as our first success with nickel-catalyzed couplings that generate bonds other than C–C bonds. Specifically, we have determined that this catalyst accomplishes Miyaura-type borylations of unactivated tertiary, secondary, and primary alkyl halides with diboron reagents to furnish alkylboronates, a family of compounds with substantial (and expanding) utility, under mild conditions; indeed, the umpolung borylation of a tertiary alkyl bromide can be achieved at a temperature as low as −10 °C. The method exhibits good functional-group compatibility and is regiospecific, both of which can be issues with traditional approaches to the synthesis of alkylboronates. In contrast to seemingly related nickel-catalyzed C–C bond-forming processes, tertiary halides are more reactive than secondary or primary halides in this nickel-catalyzed C–B bond-forming reaction; this divergence is particularly noteworthy in view of the likelihood that both transformations follow an inner-sphere electron-transfer pathway for oxidative addition. PMID:22668072

Electronic and Ionic Transport in Processable Conducting Polymers. Symmetry Effects on the Physical and Electrically Conducting, Substituted Poly(di-2-thienylphenylenes)

DTIC Science & Technology

1991-10-21

incorporated using a Grignard coupling reaction. 19 The derivatives with long alkoxy side groups were successfully halogenated with elemental bromine in CC14...transmetallation reaction of 2-thienyllithium with 7 anhydrous zinc chloride. This reagent was treated with the 1,4-dibromo-2,5- disubstitutedbenzene...were attributed to the steric effects in polymer 7c and the regiospecificity in the alkoxy substituted polymers. Experimental Section Reagents and

Facile insertion of a cyclic alkyl(amino) carbene carbon into the B-B bond of diboron(4) reagents.

PubMed

Eichhorn, Antonius F; Kuehn, Laura; Marder, Todd B; Radius, Udo

2017-10-24

We report herein the room temperature insertion of the carbene carbon atom of the cyclic (alkyl)(amino) carbene cAAC Me into the B-B single bonds of the diboron(4) compounds B 2 pin 2 , B 2 cat 2 , B 2 neop 2 , and B 2 eg 2 (pin = pinacolato, cat = catecholato, neop = neopentylglycolato, eg = ethyleneglycolato).

Ion/Ion Reactions with "Onium" Reagents: An Approach for the Gas-phase Transfer of Organic Cations to Multiply-Charged Anions

NASA Astrophysics Data System (ADS)

Gilbert, Joshua D.; Prentice, Boone M.; McLuckey, Scott A.

2015-05-01

The use of ion/ion reactions to effect gas-phase alkylation is demonstrated. Commonly used fixed-charge "onium" cations are well-suited for ion/ion reactions with multiply deprotonated analytes because of their tendency to form long-lived electrostatic complexes. Activation of these complexes results in an SN2 reaction that yields an alkylated anion with the loss of a neutral remnant of the reagent. This alkylation process forms the basis of a general method for alkylation of deprotonated analytes generated via electrospray, and is demonstrated on a variety of anionic sites. SN2 reactions of this nature are demonstrated empirically and characterized using density functional theory (DFT). This method for modification in the gas phase is extended to the transfer of larger and more complex R groups that can be used in later gas-phase synthesis steps. For example, N-cyclohexyl- N'-(2-morpholinoethyl)carbodiimide (CMC) is used to transfer a carbodiimide functionality to a peptide anion containing a carboxylic acid. Subsequent activation yields a selective reaction between the transferred carbodiimide group and a carboxylic acid, suggesting the carbodiimide functionality is retained through the transfer process. Many different R groups are transferable using this method, allowing for new possibilities for charge manipulation and derivatization in the gas phase.

Critical ligand binding reagent preparation/selection: when specificity depends on reagents.

PubMed

Rup, Bonita; O'Hara, Denise

2007-05-11

Throughout the life cycle of biopharmaceutical products, bioanalytical support is provided using ligand binding assays to measure the drug product for pharmacokinetic, pharmacodynamic, and immunogenicity studies. The specificity and selectivity of these ligand binding assays are highly dependent on the ligand binding reagents. Thus the selection, characterization, and management processes for ligand binding reagents are crucial to successful assay development and application. This report describes process considerations for selection and characterization of ligand binding reagents that are integral parts of the different phases of assay development. Changes in expression, purification, modification, and storage of the ligand binding reagents may have a profound effect on the ligand binding assay performance. Thus long-term management of the critical ligand binding assay reagents is addressed including suggested characterization criteria that allow ligand binding reagents to be used in as consistent a manner as possible. Examples of challenges related to the selection, modification, and characterization of ligand binding reagents are included.

Alkaline degradation studies of anion exchange polymers to enable new membrane designs

NASA Astrophysics Data System (ADS)

Nunez, Sean Andrew

Current performance targets for anion-exchange membrane (AEM) fuel cells call for greater than 95% alkaline stability for 5000 hours at temperatures up to 120 °C. Using this target temperature of 120 °C, an incisive 1H NMR-based alkaline degradation method to identify the degradation products of n-alkyl spacer tetraalkylammonium cations in various AEM polymers and small molecule analogs. Herein, the degradation mechanisms and rates of benzyltrimethylammonium-, n-alkyl interstitial spacer- and n-alkyl terminal pendant-cations are studied on several architectures. These findings demonstrate that benzyltrimethylammonium- and n-alkyl terminal pendant cations are more labile than an n-alkyl interstitial spacer cation and conclude that Hofmann elimination is not the predominant mechanism of alkaline degradation. Additionally, the alkaline stability of an n-alkyl interstitial spacer cation is enhanced when combined with an n-alkyl terminal pendant. Interestingly, at 120 °C, an inverse trend was found in the overall alkaline stability of AEM poly(styrene) and AEM poly(phenylene oxide) samples than was previously shown at 80 °C. Successive small molecule studies suggest that at 120 °C, an anion-induced 1,4-elimination degradation mechanism may be activated on styrenic AEM polymers bearing an acidic alpha-hydrogen. In addition, an ATR-FTIR based method was developed to assess the alkaline stability of solid membranes and any added resistance to degradation that may be due to differential solubilities and phase separation. To increase the stability of anion exchange membranes, Oshima magnesate--halogen exchange was demonstrated as a method for the synthesis of new anion exchange membranes that typically fail in the presence of organolithium or Grignard reagents alone. This new chemistry, applied to non-resinous polymers for the first time, proved effective for the n-akyl interstitial spacer functionalization of poly(phenylene oxide) and poly(styrene- co

Alkylation of deoxyribonucleic acid by carcinogens dimethyl sulphate, ethyl methanesulphonate, N-ethyl-N-nitrosourea and N-methyl-N-nitrosourea. Relative reactivity of the phosphodiester site thymidylyl(3'-5')thymidine.

PubMed Central

Swenson, D H; Lawley, P D

1978-01-01

1. The ethyl phosphotriester of thymidylyl(3'-5')thymidine, dTp(Et)dT, was identified as a product from reaction of DNA with N-ethyl-N-nitrosourea, by procedures parallel to those reported previously for the methyl homologue produced by N-methyl-N-nitrosourea. 2. Enzymic degradation to yield alkyl phosphotriesters from DNA alkylated by these carcinogens and by dimethyl sulphate and ethyl methanesulphonate was studied quantitatively, and the relative yields of the triesters dTp(Alk)dT were determined. The relative reactivity of the phosphodiester group dTpdT to each of the four carcinogens was thus obtained, and compared with that of DNA overall, or with that of the N-7 atom of guanine in DNA. Relative reactivity of the phosphodiester group was lowest towards dimethyl sulphate, the least electrophilic of the reagents used, and was highest towards N-ethyl-N-nitrosourea, the most electrophilic reagent. 3. The nature of the alkyl group transferred also influenced reactivity of the phosphodiester site, since this site was relatively more reactive towards ethylation than would be predicted simply from the known Swain-Scott s values of the alkylating agents. It was therefore suggested that the steric accessibility of the weakly nucleophilic phosphodiester group on the outside of the DNA macromolecule favours its reaction with ethylating, as opposed to methylating, reagents. 4. Taking a value of the Swain-Scott nucleophilicity (n) of 2.5 for an average DNA nucleotide unit [Walles & Ehrenberg (1969) Acta Chem. Scand. 23, 1080-1084], a value of n of about 1 for the phosphodiester group was deduced, and this value was found to be 2-3 units less than that for the N-7 atom of guanine in DNA. 5. The reactivity of DNA overall was markedly high towards the alkylnitrosoureas, despite their relatively low s values. This was ascribed to an electrostatic factor that favoured reaction of the negatively charged polymer with alkyldiazonium cation intermediates. PMID:208508

The Two Faces of Sulfinates: Illustrating Umpolung Reactivity

ERIC Educational Resources Information Center

Tapia-Pineda, Adabelia; Perez-Arrieta, Carlos; Silva-Cuevas, Carolina; Paleo, Ehecatl; Lujan-Montelongo, J. Armando

2016-01-01

A simple, microscale experiment was developed with the aim of demonstrating the concept of umpolung in synthetic organic chemistry. Starting from a common alkyl sulfinate, students perform a polarity inversion by performing a Grignard-based sulfoxide synthesis and a Mannich-type formamide synthesis. The products are purified without chromatography…

Effects of redox and sulfhydryl reagents on the bioelectric properties of the giant axon of the squid.

PubMed

Huneeus-Cox, F; Fernandez, H L; Smith, B H

1966-09-01

The effects of internally and externally applied sulfhydryl reagents on the bioelectric properties of the giant axon of the squid Loligo pealeii and Dosidicus gigas were studied. Cysteine-HCl (400 mM, pH 7.3) was used to remove axoplasm from the perfusion channel. Oxidizing agents (1 to 60 mM) tended to increase the duration of the action potential and had a slow, irreversible blocking effect when perfused internally; the membrane potential was little affected. Reducing agents applied internally caused a decrease in the spike duration without affecting its height or the membrane potential, although at high concentrations there was reversible deterioration of the action potential. Both external and internal perfusion of mercaptide-forming reagents caused deterioration in the action and membrane potentials with conduction block occurring in 5 to 45 min. 2-mercaptoethanol reversed the effects. Thiol alkylating reagents, iodoacetate and iodoacetamide, were without effect. N-ethylmaleimide did, however, block. Tests with chelating agents for nonheme iron in the membrane brought about no change in the electrical parameters. The implications of the present findings with regard to the macromolecular mechanism of excitation are discussed.

Effects of Redox and Sulfhydryl Reagents on the Bioelectric Properties of the Giant Axon of the Squid

PubMed Central

Huneeus-Cox, F.; Fernandez, H. L.; Smith, B. H.

1966-01-01

The effects of internally and externally applied sulfhydryl reagents on the bioelectric properties of the giant axon of the squid Loligo pealeii and Dosidicus gigas were studied. Cysteine-HCl (400 mM, pH 7.3) was used to remove axoplasm from the perfusion channel. Oxidizing agents (1 to 60 mM) tended to increase the duration of the action potential and had a slow, irreversible blocking effect when perfused internally; the membrane potential was little affected. Reducing agents applied internally caused a decrease in the spike duration without affecting its height or the membrane potential, although at high concentrations there was reversible deterioration of the action potential. Both external and internal perfusion of mercaptide-forming reagents caused deterioration in the action and membrane potentials with conduction block occurring in 5 to 45 min. 2-mercaptoethanol reversed the effects. Thiol alkylating reagents, iodoacetate and iodoacetamide, were without effect. N-ethylmaleimide did, however, block. Tests with chelating agents for nonheme iron in the membrane brought about no change in the electrical parameters. The implications of the present findings with regard to the macromolecular mechanism of excitation are discussed. ImagesFigure 1 PMID:5970570

Enhanced control of end-group composition in poly(3-hexylthiophene)s prepared by GRIM

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

Kochemba, William Michael; Kilbey, II, S Michael; Pickel, Deanna L

The ability to prepare well-defined semiconducting polymers is essential for understanding the link between structure and function in organic photovoltaic devices. A general method for enhanced control of the degree of functionality of end-functionalized poly(3-hexylthiophene)s (P3HT) prepared by Grignard Metathesis (GRIM) polymerization has been developed. In the absence of additives, the degree of functionality of end-functional P3HTs prepared by quenching of the GRIM polymerization with a Grignard reagent is dependent on the Grignard reagent utilized. In this study, additives such as styrene and 1-pentene are shown to alter the end-group composition of tolyl-functionalized P3HTs as determined by MALDI-TOF MS. Inmore » particular, when quenching the GRIM polymerization with tolylmagnesium bromide a modest decrease in the difunctional product is observed, and the yield of the monofunctional product increases significantly. Temperature and lithium chloride (LiCl) addition also play impactful roles. Monofunctional P3HT is found to be the major product (65%) when the functionalization is done in the presence of LiCl and styrene at 0oC, whereas in the absence of additives the monofunctional product is present at only 20%.« less

The Scarlet Letter of Alkylation: A Mini Review of Selective Alkylating Agents

PubMed Central

Oronsky, Bryan T; Reid, Tony; Knox, Susan J; Scicinski, Jan J

2012-01-01

If there were a stigma scale for chemotherapy, alkylating agents would be ranked at the top of the list. The chemical term alkylation is associated with nonselective toxicity, an association that dates back to the use of nitrogen mustards during World War I as chemical warfare agents. That this stigma persists and extends to compounds that, through selectivity, attempt to “tame” the indiscriminate destructive potential of alkylation is the subject of this review. Selective alkylation, as it is referred to herein, constitutes an extremely nascent and dynamic field in oncology. The pharmacodynamic response to this selective strategy depends on a delicate kinetic balance between specificity and the rate and extent of binding. Three representative compounds are presented: RRx-001, 3-bromopyruvate, and TH-302. The main impetus for the development of these compounds has been the avoidance of the serious complications of traditional alkylating agents; therefore, it is the thesis of this review that they should not experience stigma by association. PMID:22937173

A practical derivatization LC/MS approach for determination of trace level alkyl sulfonates and dialkyl sulfates genotoxic impurities in drug substances.

PubMed

An, Jianguo; Sun, Mingjiang; Bai, Lin; Chen, Ted; Liu, David Q; Kord, Alireza

2008-11-04

Derivatization LC/MS methodology has been developed for the determination of a group of commonly encountered alkyl esters of sulfonates or sulfates in drug substances at low ppm levels. This general method uses trimethylamine as the derivatizing reagent for ethyl/propyl/isopropyl esters and triethylamine for methyl esters. The resulting quaternary ammonium derivatization products are highly polar (ionic) and can be retained by a hydrophilic interaction liquid chromatography (HILIC) column and readily separated from the main interfering active pharmaceutical ingredient (API) peak that is usually present at very high concentration. The method gives excellent sensitivity for all the alkyl esters at typical target analyte level of 1-2 ppm when the API samples were prepared at 5mg/mL. The recoveries at 1-2 ppm were generally above 85% for all the alkyl esters in the various APIs tested. The injection precisions of the lowest concentration standards were excellent with R.S.D.=0.4-4%. A linear range for concentrations from 0.2 to 20 ppm has been established with R(2)>or=0.99. This general method has been tested in a number of API matrices and used successfully for determination of alkyl sulfonates or dialkyl sulfates in support of API batch releases at GlaxoSmithKline.

A comparison between the electrochemical behavior of reversible magnesium and lithium electrodes

NASA Astrophysics Data System (ADS)

Aurbach, D.; Gofer, Y.; Schechter, A.; Chusid, O.; Gizbar, H.; Cohen, Y.; Moshkovich, M.; Turgeman, R.

This paper describes briefly the difference between reversible lithium and magnesium electrodes. In the case of lithium, the active metal is always covered by surface films. Li dissolution-deposition is reversible only when the surface films contain elastomers and are flexible. Hence, they can accommodate the morphological changes of the electrode during the electrochemical processes without breaking down. In an ideal situation, lithium is deposited beneath the surface films, while being constantly protected in a way that prevents reactions between freshly deposited lithium and solution species. In contrast to lithium, magnesium electrodes are reversible only in solutions where surface film free conditions exist. Mg does not react with ethers, and thus, in ethereal solutions of Grignard reagents (RMgX, where R=alkyl, aryl, X=halide) and complexes of the following type: Mg(AlX 4- nR n' R n″ ') 2, R and R'=alkyl groups, X=halide, A=Al, 0< n<4 and n'+ n''= n, magnesium electrodes behave reversibly. However, it should be noted that the above stoichiometry of the Mg salts does not reflect the true structure of the active ions in solutions. Mg deposition does not occur via electron transfer to simply solvated Mg 2+ ions. The behavior of Mg electrodes in these solutions is discussed in light of studies by EQCM, EIS, FTIR, XPS, STM and standard electrochemical techniques.

Fully methylated, atomically flat (111) silicon surface

NASA Astrophysics Data System (ADS)

Fidélis, A.; Ozanam, F.; Chazalviel, J.-N.

2000-01-01

The atomically flat hydrogenated (111) silicon surface has been methylated by anodization in a Grignard reagent and the surface obtained characterized by infrared spectroscopy. 100% substitution of the hydrogen atoms by methyl groups is observed. The resulting surface exhibits preserved ordering and superior chemical stability.

U. S. Veterinary Immune Reagents Network: Progress with poultry immune reagents development

USDA-ARS?s Scientific Manuscript database

A major obstacle to advances in veterinary immunology and disease research is the lack of sufficient immunological reagents specific for veterinary animal species. In 2006, U. S. Veterinary Immune Reagent Network (VIRN) Consortium (www.vetimm.org) was developed to develop immune reagents against ma...

Multifunctional silicon surfaces: reaction of dichlorocarbene generated from Seyferth reagent with hydrogen-terminated silicon (111) surfaces.

PubMed

Liu, Wenjun; Sharp, Ian D; Tilley, T Don

2014-01-14

Insertion of dichlorocarbene (:CCl2), generated by decomposition of the Seyferth reagent PhHgCCl2Br, into the Si-H bond of a tertiary silane to form a Si-CCl2H group is an efficient homogeneous, molecular transformation. A heterogeneous version of this reaction, between PhHgCCl2Br and a silicon (111) surface terminated by tertiary Si-H bonds, was studied using a combination of surface-sensitive infrared and X-ray photoelectron spectroscopies. The insertion of dichlorocarbene into surface Si-H bonds parallels the corresponding reaction of silanes in solution, to produce surface-bound dichloromethyl groups (Si-CCl2H) covering ∼25% of the silicon surface sites. A significant fraction of the remaining Si-H bonds on the surface was converted to Si-Cl/Br groups during the same reaction, with PhHgCCl2Br serving as a halogen atom source. The presence of two distinct environments for the chlorine atoms (Si-CCl2H and Si-Cl) and one type of bromine atom (Si-Br) was confirmed by Cl 2p, Br 3d, and C 1s X-ray photoelectron spectroscopy. The formation of reactive, halogen-terminated atop silicon sites was also verified by reaction with sodium azide or the Grignard reagent (CH3MgBr), to produce Si-N3 or Si-Me functionalities, respectively. Thus, reaction of a hydrogen-terminated silicon (111) surface with PhHgCCl2Br provides a facile route to multifunctional surfaces possessing both stable silicon-carbon and labile silicon-halogen sites, in a single pot synthesis. The reactive silicon-halogen groups can be utilized for subsequent transformations and, potentially, the construction of more complex organic-silicon hybrid systems.

Complex amine-based reagents

NASA Astrophysics Data System (ADS)

Suslov, S. Yu.; Kirilina, A. V.; Sergeev, I. A.; Zezyulya, T. V.; Sokolova, E. A.; Eremina, E. V.; Timofeev, N. V.

2017-03-01

Amines for a long time have been applied to maintaining water chemistry conditions (WCC) at power plants. However, making use of complex reagents that are the mixture of neutralizing and the filmforming amines, which may also contain other organic components, causes many disputes. This is mainly due to lack of reliable information about these components. The protective properties of any amine with regard to metal surfaces depend on several factors, which are considered in this article. The results of applying complex reagents to the protection of heating surfaces in industrial conditions and estimated behavior forecasts for various reagents under maintaining WCC on heat-recovery boilers with different thermal circuits are presented. The case of a two-drum heat-recovery boiler with in-line drums was used as an example, for which we present the calculated pH values for various brands of reagents under the same conditions. Work with different reagent brands and its analysis enabled us to derive a composition best suitable for the conditions of their practical applications in heat-recovery boilers at different pressures. Testing the new amine reagent performed at a CCPP power unit shows that this reagent is an adequate base for further development of reagents based on amine compounds. An example of testing a complex reagent is shown created with the participation of the authors within the framework the program of import substitution and its possible use is demonstrated for maintaining WCC of power-generating units of combined-cycle power plants (CCPP) and TPP. The compliance of the employed reagents with the standards of water chemistry conditions and protection of heating surfaces were assessed. The application of amine-containing reagents at power-generating units of TPP makes it possible to solve complex problems aimed at ensuring the sparing cleaning of heating surfaces from deposits and the implementation of conservation and management of water chemistry condition

Method of making alkyl esters

DOEpatents

Elliott, Brian

2010-09-14

Methods of making alkyl esters are described herein. The methods are capable of using raw, unprocessed, low-cost feedstocks and waste grease. Generally, the method involves converting a glyceride source to a fatty acid composition and esterifying the fatty acid composition to make alkyl esters. In an embodiment, a method of making alkyl esters comprises providing a glyceride source. The method further comprises converting the glyceride source to a fatty acid composition comprising free fatty acids and less than about 1% glyceride by mass. Moreover, the method comprises esterifying the fatty acid composition in the presence of a solid acid catalyst at a temperature ranging firm about 70.degree. C. to about 120.degree. C. to produce alkyl esters, such that at least 85% of the free fatty acids are converted to alkyl esters. The method also incorporates the use of packed bed reactors for glyceride conversion and/or fatty acid esterification to make alkyl esters.

New Approaches to the Synthesis of Novel Organosilanes.

DTIC Science & Technology

1988-01-05

temperature, atmospheric pressure and short reaction times (2-5 hrs). Moreover, the reagents are inexpensive and readily available. 2 Hvdrogenation of...bromomethyl)cyclohexane. Evidence for a Soluble Tri- Grignard ", P. Boudjou&, R. Sooriyakumaran and 4 C.A. Kapfer, J. Organometal. Chem., 281, (1985) C21. 47

Stereoconvergent Amine-Directed Alkyl–Alkyl Suzuki Reactions of Unactivated Secondary Alkyl Chlorides

PubMed Central

Lu, Zhe; Wilsily, Ashraf; Fu, Gregory C.

2011-01-01

A new family of stereoconvergent cross-couplings of unactivated secondary alkyl electrophiles has been developed, specifically, arylamine-directed alkyl–alkyl Suzuki reactions. This represents the first such investigation to be focused on the use of alkyl chlorides as substrates. Structure-enantioselectivity studies are consistent with the nitrogen, not the aromatic ring, serving as the primary site of coordination of the arylamine to the catalyst. The rate law for this asymmetric cross-coupling is compatible with transmetalation being the turnover-limiting step of the catalytic cycle. PMID:21553917

Evaluating the Significance of CDK2-PELP1 Axis in Tumorigenesis and Hormone Therapy Resistance

DTIC Science & Technology

2011-02-01

reagents an breast cancer cells MCF7, ZR75, IMR-90, NIH3T3, 93T were obtained from the American Type Culture tion. All stable cell lines were generated...galactosidase activity or tal protein concentration. ime PCR and cell cycle microarray s were harvested with Trizol Reagent (Invitrogen), and NA was isolated...Margue, F Huselstein, G, Grignard , W Dippel, M, Nathan, S Giacchi, R Scheiden. ILK as a potential marker gene to ascertain specific adenocarcinoma

Alkylation of enolates: An electrophilicity perspective

NASA Astrophysics Data System (ADS)

Elango, M.; Parthasarathi, R.; Subramanian, V.; Chattaraj, P. K.

Enolates are ambient nucleophiles, and alkylation can occur either at a carbon or at an oxygen site. It is known that the ratio of C/O alkylation depends significantly on various factors, including the type of enolate, alkylating agent, site of alkylation, and solvent environment. Analysis of regioselectivity and solvent effects on alkylation of lithium enolates is investigated using various reactivity descriptors, including generalized philicity. These results point out the reliability of both global and local reactivity descriptors in providing significant information about site selectivity and chemical reactivity of lithium enolates.

Thioimidazolium Ionic Liquids as Tunable Alkylating Agents.

PubMed

Guterman, Ryan; Miao, Han; Antonietti, Markus

2018-01-19

Alkylating ionic liquids based on the thioimidazolium structure combine the conventional properties of ionic liquids, including low melting point and nonvolatility, with the alkylating function. Alkyl transfer occurs exclusively from the S-alkyl position, thus allowing for easy derivatization of the structure without compromising specificity. We apply this feature to tune the electrophilicty of the cation to profoundly affect the reactivity of these alkylating ionic liquids, with a caffeine-derived compound possessing the highest reactivity. Anion choice was found to affect reaction rates, with iodide anions assisting in the alkylation reaction through a "shuttling" process. The ability to tune the properties of the alkylating agent using the toolbox of ionic liquid chemistry highlights the modular nature of these compounds as a platform for alkylating agent design and integration in to future systems.

Preparation of pyrrolizinone derivatives via sequential transformations of cyclic allyl imides: synthesis of quinolactacide and marinamide.

PubMed

Simic, Milena; Tasic, Gordana; Jovanovic, Predrag; Petkovic, Milos; Savic, Vladimir

2018-03-28

A facile synthetic route has been developed for the preparation of pyrrolizinone derivatives employing N-allyl imides as starting materials. The nucleophilic addition of a vinyl Grignard reagent/RCM/elimination sequence afforded pyrrolizinones in good yields and has been applied for the preparation of naturally occurring quinolactacide and marinamide.

A novel reduction of diketones with i-RMgBr catalyzed by Cp2TiCl2 and deoxygenation of sulfoxides by Cp2TiCl2/Al system*

PubMed Central

Zhang, Yong-min; Lin, Mao-qin; Yu, Yong-ping

2004-01-01

α-diketones and β-diketones react with Grignard reagents in the presence of a catalytic amount of Cp2TiCl2 to yield α-ketols and corresponding ketones respectively. Sulfoxides can be deoxygenated by Cp2TiCl2/Al system. The possible mechanisms are also discussed. PMID:15362186

Facile preparation of oxazole-4-carboxylates and 4-ketones from aldehydes using 3-oxazoline-4-carboxylates as intermediates.

PubMed

Murai, Kenichi; Takahara, Yusuke; Matsushita, Tomoyo; Komatsu, Hideyuki; Fujioka, Hiromichi

2010-08-06

A novel 2-step synthesis of oxazole-4-carboxylates from aldehydes was developed, which is characterized by the utilization of 3-oxazoline-4-carboxylates as synthetic intermediates. The facile preparation of 4-keto-oxazole derivatives from 3-oxazoline-4-carboxylates based on their interesting reactivity toward Grignard reagents is also described.

Transition-Metal-Catalyzed C-H Alkylation Using Alkenes.

PubMed

Dong, Zhe; Ren, Zhi; Thompson, Samuel J; Xu, Yan; Dong, Guangbin

2017-07-12

Alkylation reactions represent an important organic transformation to form C-C bonds. In addition to conventional approaches with alkyl halides or sulfonates as alkylating agents, the use of unactivated olefins for alkylations has become attractive from both cost and sustainability viewpoints. This Review summarizes transition-metal-catalyzed alkylations of various carbon-hydrogen bonds (addition of C-H bonds across olefins) using regular olefins or 1,3-dienes up to May 2016. According to the mode of activation, the Review is divided into two sections: alkylation via C-H activation and alkylation via olefin activation.

Photoinduced, copper-catalyzed alkylation of amides with unactivated secondary alkyl halides at room temperature.

PubMed

Do, Hien-Quang; Bachman, Shoshana; Bissember, Alex C; Peters, Jonas C; Fu, Gregory C

2014-02-05

The development of a mild and general method for the alkylation of amides with relatively unreactive alkyl halides (i.e., poor substrates for SN2 reactions) is an ongoing challenge in organic synthesis. We describe herein a versatile transition-metal-catalyzed approach: in particular, a photoinduced, copper-catalyzed monoalkylation of primary amides. A broad array of alkyl and aryl amides (as well as a lactam and a 2-oxazolidinone) couple with unactivated secondary (and hindered primary) alkyl bromides and iodides using a single set of comparatively simple and mild conditions: inexpensive CuI as the catalyst, no separate added ligand, and C-N bond formation at room temperature. The method is compatible with a variety of functional groups, such as an olefin, a carbamate, a thiophene, and a pyridine, and it has been applied to the synthesis of an opioid receptor antagonist. A range of mechanistic observations, including reactivity and stereochemical studies, are consistent with a coupling pathway that includes photoexcitation of a copper-amidate complex, followed by electron transfer to form an alkyl radical.

Polyimides with pendant alkyl groups

NASA Technical Reports Server (NTRS)

Jensen, B. J.; Young, P. R.

1982-01-01

The effect on selected polyimide properties when pendant alkyl groups were attached to the polymer backbone was investigated. A series of polymers were prepared using benzophenone tetracarboxylic acid dianhydride (BTDA) and seven different p-alkyl-m,p'-diaminobenzophenone monomers. The alkyl groups varied in length from C(1) (methyl) to C(9) (nonyl). The polyimide prepared from BTDA and m,p'-diaminobenzophenone was included as a control. All polymers were characterized by various chromatographic, spectroscopic, thermal, and mechanical techniques. Increasing the length of the pendant alkyl group resulted in a systematic decrease in glass transition temperature (Tg) for vacuum cured films. A 70 C decrease in Tg to 193 C was observed for the nonyl polymer compared to the Tg for the control. A corresponding systematic increase in Tg indicative of crosslinking, was observed for air cured films. Thermogravimetric analysis revealed a slight sacrifice in thermal stability with increasing alkyl length. No improvement in film toughness was observed.

Aliphatic long chain quaternary ammonium compounds analysis by ion-pair chromatography coupled with suppressed conductivity and UV detection in lysing reagents for blood cell analysers.

PubMed

Giovannelli, D; Abballe, F

2005-08-26

A method has been developed which allows simultaneous determination of three linear alkyl trimethylammonium salts. Dodecyltrimethylammonium chloride, tetradecyltrimethylammonium bromide and hexadecyltrimethylammonium chloride are widely used as main active ingredients of lysing reagents for blood cell analyzers which perform white blood cells differential determination into two or more sub-populations by impedance analysis. The ion-pair on styrene-divinyl benzene chromatographic phase looks like a suitable, reliable and long term stable tool for separation of such quaternary compounds. The detection based on suppressed conductivity was chosen because of the lack of significance chromophores. A micromembrane suppressor device compatible with high solvent concentration (up to 80%) was used in order to minimize the conductivity background before the detection. In the present work we show how the chemical post column derivatization makes the alkyl chain detectable also by UV direct detection at 210 nm.

Molecular design of sequence specific DNA alkylating agents.

PubMed

Minoshima, Masafumi; Bando, Toshikazu; Shinohara, Ken-ichi; Sugiyama, Hiroshi

2009-01-01

Sequence-specific DNA alkylating agents have great interest for novel approach to cancer chemotherapy. We designed the conjugates between pyrrole (Py)-imidazole (Im) polyamides and DNA alkylating chlorambucil moiety possessing at different positions. The sequence-specific DNA alkylation by conjugates was investigated by using high-resolution denaturing polyacrylamide gel electrophoresis (PAGE). The results showed that polyamide chlorambucil conjugates alkylate DNA at flanking adenines in recognition sequences of Py-Im polyamides, however, the reactivities and alkylation sites were influenced by the positions of conjugation. In addition, we synthesized conjugate between Py-Im polyamide and another alkylating agent, 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI). DNA alkylation reactivies by both alkylating polyamides were almost comparable. In contrast, cytotoxicities against cell lines differed greatly. These comparative studies would promote development of appropriate sequence-specific DNA alkylating polyamides against specific cancer cells.

Mass spectral analysis of long chain alkyl aromatic compounds synthesized from alpha-olefin alkylation

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

Cheng, M.T.; Hudson, J.D.

1994-12-31

Long chain alkyl aromatic compounds are important petrochemicals with many applications. They are generally synthesized by alkylating the corresponding aromatic nucleus. In this report, the authors will describe the mass spectral fragmentation of alkylphenols and alkylsalicylates.

40 CFR 721.9892 - Alkylated urea.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkylated urea. 721.9892 Section 721... Alkylated urea. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as an alkylated urea (PMN P-93-1649) is subject to reporting under this...

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.

Long Range Materials Research

DTIC Science & Technology

1975-06-01

for forming Si-C bonds; the two most general are Grignard reactions (eq. 3) and hydrosilylations of olefins (eq. 4); -76- wm RMgX + R3SiY Y...October, 1973. (4) D. N. Marquardt, Ph.D. Thesis, Stanford University, May, 1974. (5) L. F. Fieser and M. Fieser, Reagents for Organic Synthesis, John

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.

Photoinduced, Copper-Catalyzed Carbon-Carbon Bond Formation with Alkyl Electrophiles: Cyanation of Unactivated Secondary Alkyl Chlorides at Room Temperature.

PubMed

Ratani, Tanvi S; Bachman, Shoshana; Fu, Gregory C; Peters, Jonas C

2015-11-04

We have recently reported that, in the presence of light and a copper catalyst, nitrogen nucleophiles such as carbazoles and primary amides undergo C-N coupling with alkyl halides under mild conditions. In the present study, we establish that photoinduced, copper-catalyzed alkylation can also be applied to C-C bond formation, specifically, that the cyanation of unactivated secondary alkyl chlorides can be achieved at room temperature to afford nitriles, an important class of target molecules. Thus, in the presence of an inexpensive copper catalyst (CuI; no ligand coadditive) and a readily available light source (UVC compact fluorescent light bulb), a wide array of alkyl halides undergo cyanation in good yield. Our initial mechanistic studies are consistent with the hypothesis that an excited state of [Cu(CN)2](-) may play a role, via single electron transfer, in this process. This investigation provides a rare example of a transition metal-catalyzed cyanation of an alkyl halide, as well as the first illustrations of photoinduced, copper-catalyzed alkylation with either a carbon nucleophile or a secondary alkyl chloride.

Silica-Supported Catalyst for Enantioselective Arylation of Aldehydes under Batch and Continuous-Flow Conditions.

PubMed

Watanabe, Satoshi; Nakaya, Naoyuki; Akai, Junichiro; Kanaori, Kenji; Harada, Toshiro

2018-05-04

A silica-supported 3-aryl H 8 -BINOL-derived titanium catalyst exhibited high performance in the enantioselective arylation of aromatic aldehydes using Grignard and organolithium reagents not only under batch conditions but also under continuous-flow conditions. Even with a simple pipet reactor packed with the heterogeneous catalyst, the enantioselective production of chiral diarylmethanols could be achieved through a continuous introduction of aldehydes and mixed titanium reagents generated from the organometallic precursors. The pipet reactor could be used repeatedly in different reactions without appreciable deterioration of the activity.

Palladium-Catalyzed Borylation of Primary Alkyl Bromides

PubMed Central

Joshi-Pangu, Amruta; Ma, Xinghua; Diane, Mohamed; Iqbal, Sidra; Kribs, Robert J.; Huang, Richard; Wang, Chao-Yuan

2012-01-01

A mild Pd-catalyzed process for the borylation of alkyl bromides has been developed using bis(pinacolato)diboron as a boron source. This process accommodates the use of a wide range of functional groups on the alkyl bromide substrate. Primary bromides react with complete selectivity in the presence of a secondary bromide. The generality of this approach is demonstrated by its extension to the use of alkyl iodides and alkyl tosylates, as well as borylation reactions employing bis(neopentyl glycolato)diboron as the boron source. PMID:22774861

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

Aryl sulfonate based anticancer alkylating agents.

PubMed

Sheikh, Hamdullah Khadim; Arshad, Tanzila; Kanwal, Ghazala

2018-05-01

This research work revolves around synthesis of antineoplastic alkylating sulfonate esters with dual alkylating sites for crosslinking of the DNA strands. These molecules were evaluated as potential antineoplastic cross linking alkylating agents by reaction with the nucleoside of Guanine DNA nucleobase at both ends of the synthesized molecule. Synthesis of the alkylating molecules and the crosslinking with the guanosine nucleoside was monitored by MALDITOF mass spectroscopy. The synthesized molecule's crosslinking or adduct forming rate with the nucleoside was compared with that of 1,4 butane disulfonate (busulfan), in form of time taken for the appearance of [M+H] + . It was found that aryl sulfonate leaving group was causing higher rate of nucleophilic attack by the Lewis basic site of the nucleobase. Furthermore, the rate was also found to be a function of electron withdrawing or donating nature of the substituent on the aryl ring. Compound with strong electron withdrawing substituent on the para position of the ring reacted fastest. Hence, new alkylating agents were synthesized with optimized or desired reactivity.

Enhancement of alkylation catalysts for improved supercritical fluid regeneration

DOEpatents

Ginosar, Daniel M [Idaho Falls, ID; Petkovic, Lucia [Idaho Falls, ID

2009-09-22

A method of modifying an alkylation catalyst to reduce the formation of condensed hydrocarbon species thereon. The method comprises providing an alkylation catalyst comprising a plurality of active sites. The plurality of active sites on the alkylation catalyst may include a plurality of weakly acidic active sites, intermediate acidity active sites, and strongly acidic active sites. A base is adsorbed to a portion of the plurality of active sites, such as the strongly acidic active sites, selectively poisoning the strongly acidic active sites. A method of modifying the alkylation catalyst by providing an alkylation catalyst comprising a pore size distribution that sterically constrains formation of the condensed hydrocarbon species on the alkylation catalyst or by synthesizing the alkylation catalyst to comprise a decreased number of strongly acidic active sites is also disclosed, as is a method of improving a regeneration efficiency of the alkylation catalyst.

Enhancement of alkylation catalysts for improved supercritical fluid regeneration

DOEpatents

Ginosar, Daniel M.; Petkovic, Lucia M.

2010-12-28

A method of modifying an alkylation catalyst to reduce the formation of condensed hydrocarbon species thereon. The method comprises providing an alkylation catalyst comprising a plurality of active sites. The plurality of active sites on the alkylation catalyst may include a plurality of weakly acidic active sites, intermediate acidity active sites, and strongly acidic active sites. A base is adsorbed to a portion of the plurality of active sites, such as the strongly acidic active sites, selectively poisoning the strongly acidic active sites. A method of modifying the alkylation catalyst by providing an alkylation catalyst comprising a pore size distribution that sterically constrains formation of the condensed hydrocarbon species on the alkylation catalyst or by synthesizing the alkylation catalyst to comprise a decreased number of strongly acidic active sites is also disclosed, as is a method of improving a regeneration efficiency of the alkylation catalyst.

Alkylated hydroxylamine derivatives eliminate peripheral retinylidene Schiff bases but cannot enter the retinal binding pocket of light-activated rhodopsin.

PubMed

Piechnick, Ronny; Heck, Martin; Sommer, Martha E

2011-08-23

Besides Lys-296 in the binding pocket of opsin, all-trans-retinal forms adducts with peripheral lysine residues and phospholipids, thereby mimicking the spectral and chemical properties of metarhodopsin species. These pseudophotoproducts composed of nonspecific retinylidene Schiff bases have long plagued the investigation of rhodopsin deactivation and identification of decay products. We discovered that, while hydroxylamine can enter the retinal binding pocket of light-activated rhodopsin, the modified hydroxylamine compounds o-methylhydroxylamine (mHA), o-ethylhydroxylamine (eHA), o-tert-butylhydroxylamine (t-bHA), and o-(carboxymethyl)hydroxylamine (cmHA) are excluded. However, the alkylated hydroxylamines react quickly and efficiently with exposed retinylidene Schiff bases to form their respective retinal oximes. We further investigated how t-bHA affects light-activated rhodopsin and its interaction with binding partners. We found that both metarhodopsin II (Meta II) and Meta III are resistant to t-bHA, and neither arrestin nor transducin binding is affected by t-bHA. This discovery suggests that the hypothetical solvent channel that opens in light-activated rhodopsin is extremely stringent with regard to size and/or polarity. We believe that alkylated hydroxylamines will prove to be extremely useful reagents for the investigation of rhodopsin activation and decay mechanisms. Furthermore, the use of alkylated hydroxylamines should not be limited to in vitro studies and could help elucidate visual signal transduction mechanisms in the living cells of the retina. © 2011 American Chemical Society

Iodine(III) Reagents in Radical Chemistry

PubMed Central

2017-01-01

Conspectus The chemistry of hypervalent iodine(III) compounds has gained great interest over the past 30 years. Hypervalent iodine(III) compounds show valuable ionic reactivity due to their high electrophilicity but also express radical reactivity as single electron oxidants for carbon and heteroatom radical generation. Looking at ionic chemistry, these iodine(III) reagents can act as electrophiles to efficiently construct C–CF3, X–CF3 (X = heteroatom), C–Rf (Rf = perfluoroalkyl), X–Rf, C–N3, C–CN, S–CN, and C–X bonds. In some cases, a Lewis or a Bronsted acid is necessary to increase their electrophilicity. In these transformations, the iodine(III) compounds react as formal “CF3+”, “Rf+”, “N3+”, “Ar+”, “CN+”, and “X+” equivalents. On the other hand, one electron reduction of the I(III) reagents opens the door to the radical world, which is the topic of this Account that focuses on radical reactivity of hypervalent iodine(III) compounds such as the Togni reagent, Zhdankin reagent, diaryliodonium salts, aryliodonium ylides, aryl(cyano)iodonium triflates, and aryl(perfluoroalkyl)iodonium triflates. Radical generation starting with I(III) reagents can also occur via thermal or light mediated homolysis of the weak hypervalent bond in such reagents. This reactivity can be used for alkane C–H functionalization. We will address important pioneering work in the area but will mainly focus on studies that have been conducted by our group over the last 5 years. We entered the field by investigating transition metal free single electron reduction of Togni type reagents using the readily available sodium 2,2,6,6-tetramethylpiperidine-1-oxyl salt (TEMPONa) as an organic one electron reductant for clean generation of the trifluoromethyl radical and perfluoroalkyl radicals. That valuable approach was later successfully also applied to the generation of azidyl and aryl radicals starting with the corresponding benziodoxole (Zhdankin reagent

Production of latex agglutination reagents for pneumococcal serotyping

PubMed Central

2013-01-01

Background The current ‘gold standard’ for serotyping pneumococci is the Quellung test. This technique is laborious and requires a certain level of training to correctly perform. Commercial pneumococcal latex agglutination serotyping reagents are available, but these are expensive. In-house production of latex agglutination reagents can be a cost-effective alternative to using commercially available reagents. This paper describes a method for the production and quality control (QC) of latex reagents, including problem solving recommendations, for pneumococcal serotyping. Results Here we describe a method for the production of latex agglutination reagents based on the passive adsorption of antibodies to latex particles. Sixty-five latex agglutination reagents were made using the PneuCarriage Project (PCP) method, of which 35 passed QC. The other 30 reagents failed QC due to auto-agglutination (n=2), no reactivity with target serotypes (n=8) or cross-reactivity with non-target serotypes (n=20). Dilution of antisera resulted in a further 27 reagents passing QC. The remaining three reagents passed QC when prepared without centrifugation and wash steps. Protein estimates indicated that latex reagents that failed QC when prepared using the PCP method passed when made with antiserum containing ≤ 500 μg/ml of protein. Sixty-one nasopharyngeal isolates were serotyped with our in-house latex agglutination reagents, with the results showing complete concordance with the Quellung reaction. Conclusions The method described here to produce latex agglutination reagents allows simple and efficient serotyping of pneumococci and may be applicable to latex agglutination reagents for typing or identification of other microorganisms. We recommend diluting antisera or removing centrifugation and wash steps for any latex reagents that fail QC. Our latex reagents are cost-effective, technically undemanding to prepare and remain stable for long periods of time, making them ideal for

Sorbate-nitrite interactions: acetonitrile oxide as an alkylating agent.

PubMed

Pérez-Prior, M Teresa; Gómez-Bombarelli, Rafael; González-Pérez, Marina; Manso, José A; García-Santos, M Pilar; Calle, Emilio; Casado, Julio

2009-07-01

Because chemical species with DNA-damaging and mutagenic activity are formed in sorbate-nitrite mixtures and because sorbic acid sometimes coexists with nitrite occurring naturally or incorporated as a food additive, the study of sorbate-nitrite interactions is important. Here, the alkylating potential of the products resulting from such interactions was investigated. Drawn were the following conclusions: (i) Acetonitrile oxide (ACNO) is the compound responsible for the alkylating capacity of sorbate-nitrite mixtures; (ii) ACNO alkylates 4-(p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to those of DNA bases, forming an adduct (AD; epsilon = 1.4 x 10(4) M(-1) cm(-1); lambda = 519 nm); (iii) the NBP alkylation reaction complies with the rate equation, r = d[AD]/dt = k(alk)(ACNO)[ACNO][NBP]-k(hyd)(AD)[AD], k(alk)(ACNO) being the NBP alkylation rate constant for ACNO and k(hyd)(AD) the rate constant for the adduct hydrolysis reaction; (iv) the small fraction of ACNO forming the adduct with NBP, as well as the small magnitude of the quotient (k(alk) (ACNO)/k(hyd)(ACNO)) as compared with those reported for other alkylating agents, such as some lactones and N-alkyl-N-nitrosoureas, reveals the ACNO effective alkylating capacity to be less significant; (v) the low value of the NBP-ACNO adduct life (defined as the total amount of adduct present along the progression of the NBP alkylation per unit of alkylating agent concentration) points to the high instability of this adduct; and (vi) the obtained results are in accordance with the low carcinogenicity of ACNO.

The formation of quasi-alicyclic rings in alkyl-aromatic compounds

NASA Astrophysics Data System (ADS)

Straka, Pavel; Buryan, Petr; Bičáková, Olga

2018-02-01

The alkyl side chains of n-alkyl phenols, n-alkyl benzenes and n-alkyl naphthalenes are cyclised, as demonstrated by GC measurements, FTIR spectroscopy and molecular mechanics calculations. Cyclisation occurs due to the intramolecular interaction between an aromatic ring (-δ) and a hydrogen of the terminal methyl group (+δ) of an alkyl chain. In fact, conventional molecules are not aliphatic-aromatic, but quasi-alicyclic-aromatic. With the aromatic molecules formed with a quasi-alicyclic ring, the effect of van der Waals attractive forces increases not only intramolecularly but also intermolecularly. This effect is strong in molecules with propyl and higher alkyl substituents. The increase of intermolecular van der Waals attractive forces results in bi-linearity in the GC retention time of the compounds in question, observed in the dependence of the logarithm of the relative retention time on the number of carbons in a molecule in both polar and nonpolar stationary phases with both capillary and packed columns. The role of van der Waals forces has been demonstrated using the potential energies of covalent and noncovalent interactions for 2-n-alkyl phenols, n-alkyl benzenes and 1-n-alkyl- and 2-n-alkyl naphthalenes.

Trichloroacetimidates as Alkylating Reagents and Their Application in the Synthesis of Pyrroloindoline Natural Products and Synthesis of Small Molecule Inhibitors of Src Homology 2 Domain-Containing Inositol Phosphatase (SHIP)

NASA Astrophysics Data System (ADS)

Adhikari, Arijit A.

Trichloroacetimidates are known to be excellent alkylating agents when activated by a catalytic amount of a Bronsted or Lewis acid. Work described herein involved taking advantage of the favorable reactivity of trichloroacetimidates to establish several different synthetic protocols, including the application of these reagents in the synthesis of pyrroloindoline based natural products, 3,3'-disubstituted indolenines and benzylic trichloroacetamides. Initial investigations on the utilization of the reactivity of trichloroacetimidates found that diphenylmethyl trichloroacetimidate, which is a precursor to a highly stabilized carbocation, undergoes facile displacement with carboxylic acids providing the ester product without the need of any exogenous catalyst. Both hindered and unhindered carboxylic acids were esterified with high yields, with no preference for aromatic or aliphatic carboxylic acids. Carboxylic acids with unprotected hydroxyl groups or beta-lactam rings were esterified efficiently. Substrates that are highly prone to elimination or retro-aldol were also esterified in high yields. Carboxylic acids with highly enolizable alpha-stereocenters were esterified without any racemization. Mechanistic studies indicate that the carboxylic acid substrate itself is acidic enough to be effective at promoting the esterification reaction. During our studies on esterification with imidates it was found that these imidates also showed a tendency to undergo rearrangement to the corresponding trichloroacetamides. Two different sets of conditions, thermal and Lewis acid catalyzed, were established which provided these rearranged products with high yields. Various benzylic trichloroacetimidates were shown to undergo these transformations under the established conditions. Based on the observations discussed in this work a cationic mechanism is proposed. After the preliminary studies on alkylation of benzylic trichloroacetimidate with different nucleophiles, this chemistry

Alkylsilyl Peroxides as Alkylating Agents in the Copper-Catalyzed Selective Mono-N-Alkylation of Primary Amides and Arylamines.

PubMed

Sakamoto, Ryu; Sakurai, Shunya; Maruoka, Keiji

2017-07-06

The copper-catalyzed selective mono-N-alkylation of primary amides or arylamines using alkylsilyl peroxides as alkylating agents is reported. The reaction proceeds under mild reaction conditions and exhibits a broad substrate scope with respect to the alkylsilyl peroxides, as well as to the primary amides and arylamines. Mechanistic studies suggest that the present reaction should proceed through a free-radical process that includes alkyl radicals generated from the alkylsilyl peroxides. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reactions of Tributylstannyl Anioniods with Alkyl Bromides.

DTIC Science & Technology

1981-09-28

g (12 mmol) of cesium tert-butoxide was added to the reaction vessel before the addition of n-butyllithium. Alkylation of Tributylstannyl Anionoids...Dry reaction vessels were purged with argon. The desired alkyl halide (1.0 mmol unless noted) and any desired additive were added to the reaction ...OFFICE OF NAVAL RESEARCH Contract N00014-79-C-0584 Task No. NR 053-714 TECHNICAL REPORT No. 2 Reactions of Tributylstannyl Anionoids with Alkyl

Alkylation Damage by Lipid Electrophiles Targets Functional Protein Systems*

PubMed Central

Codreanu, Simona G.; Ullery, Jody C.; Zhu, Jing; Tallman, Keri A.; Beavers, William N.; Porter, Ned A.; Marnett, Lawrence J.; Zhang, Bing; Liebler, Daniel C.

2014-01-01

Protein alkylation by reactive electrophiles contributes to chemical toxicities and oxidative stress, but the functional impact of alkylation damage across proteomes is poorly understood. We used Click chemistry and shotgun proteomics to profile the accumulation of proteome damage in human cells treated with lipid electrophile probes. Protein target profiles revealed three damage susceptibility classes, as well as proteins that were highly resistant to alkylation. Damage occurred selectively across functional protein interaction networks, with the most highly alkylation-susceptible proteins mapping to networks involved in cytoskeletal regulation. Proteins with lower damage susceptibility mapped to networks involved in protein synthesis and turnover and were alkylated only at electrophile concentrations that caused significant toxicity. Hierarchical susceptibility of proteome systems to alkylation may allow cells to survive sublethal damage while protecting critical cell functions. PMID:24429493

Alkylating agents for Waldenstrom's macroglobulinaemia.

PubMed

Yang, Kun; Tan, Jianlong; Wu, Taixiang

2009-01-21

Waldenstrom's macroglobulinaemia (WM) is an uncommon B-cell lymphoproliferative disorder characterized by bone marrow infiltration and production of monoclonal immunoglobulin. Uncertainty remains if alkylating agents, such as chlorambucil, melphalan or cyclophosphamide, are an effective form of management. To assess the effects and safety of the alkylating agents on Waldenstrom's macroglobulinaemia (WM). We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2008), MEDLINE (1966 to 2008), EMBASE (1980 to 2008), the Chinese Biomedical Base (1982 to 2008) and reference lists of articles.We also handsearched relevant conference proceedings from 1990 to 2008. Randomised controlled trials (RCTs) comparing alkylating agents given concomitantly with radiotherapy, splenectomy, plasmapheresis, stem-cell transplantation in patients with a confirmed diagnosis of WM. Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials. One trial involving 92 participants with pretreated/relapsed WM compared the effect of fludarabine versus the combination of cyclophosphamide (the alkylating agent), doxorubicin and prednisone (CAP). Compared to CAP, the Hazard ratio (HR) for deaths of treatment with fludarabine was estimated to be 1.04, with a standard error of 0.30 (95% CI 0.58 to 1.48) and it indicated that the mean difference of median survival time was -4.00 months, and 16.00 months for response duration. The relative risks (RR) of response rate was 2.80 (95% CI 1.10 to 7.12). There were no statistically difference in overall survival rate and median survival months, while on the basis of response rate and response duration, fludarabine seemed to be superior to CAP for pretreated/relapsed patients with macroglobulinaemia. Although alkylating agents have been used for decades they have never actually been tested in a proper randomised trial. This

40 CFR 160.83 - Reagents and solutions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Reagents and solutions. 160.83 Section 160.83 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS GOOD LABORATORY PRACTICE STANDARDS Testing Facilities Operation § 160.83 Reagents and solutions. All reagents and...

Palladium-Catalyzed Asymmetric Alkylation in the Synthesis of Cyclopentanoid and Cycloheptanoid Core Structures Bearing All-Carbon Quaternary Stereocenters

PubMed Central

Hong, Allen Y.; Bennett, Nathan B.; Krout, Michael R.; Jensen, Thomas; Harned, Andrew. M.

2011-01-01

General catalytic asymmetric routes toward cyclopentanoid and cycloheptanoid core structures embedded in numerous natural products have been developed. The central stereoselective transformation in our divergent strategies is the enantioselective decarboxylative alkylation of seven-membered β-ketoesters to form α-quaternary vinylogous esters. Recognition of the unusual reactivity of β-hydroxyketones resulting from the addition of hydride or organometallic reagents enabled divergent access to γ-quaternary acylcyclopentenes through a ring contraction pathway or γ-quaternary cycloheptenones through a carbonyl transposition pathway. Synthetic applications of these compounds were explored through the preparation of mono-, bi-, and tricyclic derivatives that can serve as valuable intermediates for the total synthesis of complex natural products. This work complements our previous work with cyclohexanoid systems. PMID:22347731

Alkyl phosphonic acids and sulfonic acids in the Murchison meteorite

NASA Technical Reports Server (NTRS)

Cooper, George W.; Onwo, Wilfred M.; Cronin, John R.

1992-01-01

Homologous series of alkyl phosphonic acids and alkyl sulfonic acids, along with inorganic orthophosphate and sulfate, are identified in water extracts of the Murchison meteorite after conversion to their t-butyl dimethylsilyl derivatives. The methyl, ethyl, propyl, and butyl compounds are observed in both series. Five of the eight possible alkyl phosphonic acids and seven of the eight possible alkyl sulfonic acids through C4 are identified. Abundances decrease with increasing carbon number as observed of other homologous series indigenous to Murchison. Concentrations range downward from approximately 380 nmol/gram in the alkyl sulfonic acid series, and from 9 nmol/gram in the alkyl phosphonic acid series.

Chemistry of alkali cation exchanged faujasite and mesoporous NaX using alkyl halides and phosphates

NASA Astrophysics Data System (ADS)

Lee, Min-Hong

the length of the alkyl chain. Although introduced mesopores alleviated the limited reagent diffusion to reactive sites due to the microporosity of the NaX zeolites, no marked improvement in the product yields was achieved with either the 1-chloroalkanes or the trialkyl phosphates test compounds, regardless of alkyl chain length. The disappointing results have been attributed to lack of substantial net increase in the numbers of zeolite nucleophilic sites accompanying mesopore introduction.

Polyborylated reagents for modern organic synthesis

PubMed Central

SHIMIZU, Masaki; HIYAMA, Tamejiro

2008-01-01

Diverse kinds of gem- and vic-diborylated compounds are now readily available thanks to advances in gem-diborylation of lithium carbenoids as well as vic-diborylation of carbon–carbon multiple bonds with diboron compounds. These diborylated reagents lead to invention of polyborylated reagents and many novel and useful synthetic methods for supreme stereocontrol. This review summarizes preparative methods and synthetic reactions of di- and polyborylated reagents with the emphasis on multiple bond formation. PMID:18941288

40 CFR 721.2420 - Alkoxylated dialkyldiethylenetriamine, alkyl sulfate salt.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., alkyl sulfate salt. 721.2420 Section 721.2420 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.2420 Alkoxylated dialkyldiethylenetriamine, alkyl sulfate salt. (a... generically as an alkoxylated dialkyldiethylenetriamine, alkyl sulfate salt (PMN P-91-288) is subject to...

40 CFR 721.2420 - Alkoxylated dialkyldiethylenetriamine, alkyl sulfate salt.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., alkyl sulfate salt. 721.2420 Section 721.2420 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.2420 Alkoxylated dialkyldiethylenetriamine, alkyl sulfate salt. (a... generically as an alkoxylated dialkyldiethylenetriamine, alkyl sulfate salt (PMN P-91-288) is subject to...

40 CFR 721.2410 - Alkoxylated alkyldiethylenetriamine, alkyl sulfate salts.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., alkyl sulfate salts. 721.2410 Section 721.2410 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.2410 Alkoxylated alkyldiethylenetriamine, alkyl sulfate salts. (a... generically as alkoxylated dialkyldiethylenetriamine, alkyl sulfate salts (PMN P-94-325, 326, and 327) are...

40 CFR 721.2410 - Alkoxylated alkyldiethylenetriamine, alkyl sulfate salts.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., alkyl sulfate salts. 721.2410 Section 721.2410 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.2410 Alkoxylated alkyldiethylenetriamine, alkyl sulfate salts. (a... generically as alkoxylated dialkyldiethylenetriamine, alkyl sulfate salts (PMN P-94-325, 326, and 327) are...

40 CFR 721.2420 - Alkoxylated dialkyldiethylenetriamine, alkyl sulfate salt.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., alkyl sulfate salt. 721.2420 Section 721.2420 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.2420 Alkoxylated dialkyldiethylenetriamine, alkyl sulfate salt. (a... generically as an alkoxylated dialkyldiethylenetriamine, alkyl sulfate salt (PMN P-91-288) is subject to...

40 CFR 721.2420 - Alkoxylated dialkyldiethylenetriamine, alkyl sulfate salt.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., alkyl sulfate salt. 721.2420 Section 721.2420 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.2420 Alkoxylated dialkyldiethylenetriamine, alkyl sulfate salt. (a... generically as an alkoxylated dialkyldiethylenetriamine, alkyl sulfate salt (PMN P-91-288) is subject to...

40 CFR 721.2410 - Alkoxylated alkyldiethylenetriamine, alkyl sulfate salts.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., alkyl sulfate salts. 721.2410 Section 721.2410 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.2410 Alkoxylated alkyldiethylenetriamine, alkyl sulfate salts. (a... generically as alkoxylated dialkyldiethylenetriamine, alkyl sulfate salts (PMN P-94-325, 326, and 327) are...

40 CFR 721.2410 - Alkoxylated alkyldiethylenetriamine, alkyl sulfate salts.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., alkyl sulfate salts. 721.2410 Section 721.2410 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.2410 Alkoxylated alkyldiethylenetriamine, alkyl sulfate salts. (a... generically as alkoxylated dialkyldiethylenetriamine, alkyl sulfate salts (PMN P-94-325, 326, and 327) are...

21 CFR 864.8540 - Red cell lysing reagent.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8540 Red cell lysing reagent. (a) Identification. A red cell lysing reagent is a device used to lyse (destroy) red blood cells for... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Red cell lysing reagent. 864.8540 Section 864.8540...

21 CFR 864.8540 - Red cell lysing reagent.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8540 Red cell lysing reagent. (a) Identification. A red cell lysing reagent is a device used to lyse (destroy) red blood cells for... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Red cell lysing reagent. 864.8540 Section 864.8540...

21 CFR 864.8540 - Red cell lysing reagent.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8540 Red cell lysing reagent. (a) Identification. A red cell lysing reagent is a device used to lyse (destroy) red blood cells for... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Red cell lysing reagent. 864.8540 Section 864.8540...

21 CFR 864.8540 - Red cell lysing reagent.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8540 Red cell lysing reagent. (a) Identification. A red cell lysing reagent is a device used to lyse (destroy) red blood cells for... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Red cell lysing reagent. 864.8540 Section 864.8540...

21 CFR 864.8540 - Red cell lysing reagent.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Red cell lysing reagent. 864.8540 Section 864.8540...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8540 Red cell lysing reagent. (a) Identification. A red cell lysing reagent is a device used to lyse (destroy) red blood cells for...

21 CFR 864.8100 - Bothrops atrox reagent.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Bothrops atrox reagent. 864.8100 Section 864.8100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8100 Bothrops atrox reagent. (a...

21 CFR 864.8100 - Bothrops atrox reagent.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Bothrops atrox reagent. 864.8100 Section 864.8100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8100 Bothrops atrox reagent. (a...

21 CFR 864.8100 - Bothrops atrox reagent.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Bothrops atrox reagent. 864.8100 Section 864.8100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8100 Bothrops atrox reagent. (a...

Polymerization of Conducting Polymers Confined to Free Surfaces: A comparison of the Langmuir-Blodgett Polymerization of 3-Alkyl Pyrroles and 2- Alkyl Anilines

DTIC Science & Technology

1992-05-19

Confined to Free Surfaces: A Comparison of the Langmuir-Blodgett Polymerization of 3- Alkyl Pyrroles and 2- Alkyl Anilines Submitted for Publication in...Surfaces: A Comparison of the Langmuir Blodgett Polymerizations of 3- alkyl pyrroles and 2- alkyl anilines R. S. Duran and H.C. Zhou Dept. of Chemistry...polymerization reactions in more detail and compare them. To do this, the polymerization reactions were run under two conditions. In the first case

21 CFR 660.30 - Reagent Red Blood Cells.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Reagent Red Blood Cells. 660.30 Section 660.30 Food... ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Reagent Red Blood Cells § 660.30 Reagent Red Blood Cells. (a) Proper name and definition. The proper name of the product shall be Reagent Red...

21 CFR 176.120 - Alkyl ketene dimers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... section. (a) The alkyl ketene dimers are manufactured by the dehydrohalogenation of the acyl halides derived from the fatty acids of animal or vegetable fats and oils. (b) The alkyl ketene dimers are used as...

A Concentration-Dependent Insulin Immobilization Behavior of Alkyl-Modified Silica Vesicles: The Impact of Alkyl Chain Length.

PubMed

Zhang, Jun; Zhang, Long; Lei, Chang; Huang, Xiaodan; Yang, Yannan; Yu, Chengzhong

2018-05-01

The insulin immobilization behaviors of silica vesicles (SV) before and after modification with hydrophobic alkyl -C 8 and -C 18 groups have been studied and correlated to the grafted alkyl chain length. In order to minimize the influence from the other structural parameters, monolayered -C 8 or -C 18 groups are grafted onto SV with controlled density. The insulin immobilization capacity of SV is dependent on the initial insulin concentrations (IIC). At high IIC (2.6-3.0 mg/mL), the trend of insulin immobilization capacity of SV is SV-OH > SV-C 8 > SV-C 18 , which is determined mainly by the surface area of SV. At medium IIC (0.6-1.9 mg/mL), the trend changes to SV-C 8 ≥ SV-C 18 > SV-OH as both the surface area and alkyl chain length contribute to the insulin immobilization. At an extremely low IIC, the hydrophobic-hydrophobic interaction between the alkyl group and insulin molecules plays the most significant role. Consequently, SV-C 18 with longer alkyl groups and the highest hydrophobicity show the best insulin enrichment performance compared to SV-C 8 and SV-OH, as evidenced by an insulin detection limit of 0.001 ng/mL in phosphate buffered saline (PBS) and 0.05 ng/mL in artficial urine determined by mass spectrometry (MS).

IONIC LIQUID-CATALYZED ALKYLATION OF ISOBUTANE WITH 2-BUTENE

EPA Science Inventory

A detailed study of the alkylation of isobutane with 2-butene in ionic liquid media has been conducted using 1-alkyl-3-methylimidazolium halides?aluminum chloride encompassing various alkyl groups (butyl-, hexyl-, and octyl-) and halides (Cl, Br, and I) on its cations and anions,...

21 CFR 660.20 - Blood Grouping Reagent.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Blood Grouping Reagent. 660.20 Section 660.20 Food... ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Blood Grouping Reagent § 660.20 Blood Grouping Reagent. (a) Proper name and definition. The proper name of this product shall be Blood Grouping...

21 CFR 660.20 - Blood Grouping Reagent.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Blood Grouping Reagent. 660.20 Section 660.20 Food... ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Blood Grouping Reagent § 660.20 Blood Grouping Reagent. (a) Proper name and definition. The proper name of this product shall be Blood Grouping...

21 CFR 660.20 - Blood Grouping Reagent.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Blood Grouping Reagent. 660.20 Section 660.20 Food... ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Blood Grouping Reagent § 660.20 Blood Grouping Reagent. (a) Proper name and definition. The proper name of this product shall be Blood Grouping...

21 CFR 660.20 - Blood Grouping Reagent.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Blood Grouping Reagent. 660.20 Section 660.20 Food... ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Blood Grouping Reagent § 660.20 Blood Grouping Reagent. (a) Proper name and definition. The proper name of this product shall be Blood Grouping...

21 CFR 660.20 - Blood Grouping Reagent.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Blood Grouping Reagent. 660.20 Section 660.20 Food... ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Blood Grouping Reagent § 660.20 Blood Grouping Reagent. (a) Proper name and definition. The proper name of this product shall be Blood Grouping...

40 CFR 721.1878 - Alkali metal alkyl borohydride (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkali metal alkyl borohydride... Specific Chemical Substances § 721.1878 Alkali metal alkyl borohydride (generic). (a) Chemical substance... alkali metal alkyl borohydride (PMN P-00-1089) is subject to reporting under this section for the...

40 CFR 721.1878 - Alkali metal alkyl borohydride (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkali metal alkyl borohydride... Specific Chemical Substances § 721.1878 Alkali metal alkyl borohydride (generic). (a) Chemical substance... alkali metal alkyl borohydride (PMN P-00-1089) is subject to reporting under this section for the...

Extended 3{beta}-alkyl steranes and 3-alkyl triaromatic steroids in crude oils and rock extracts

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

Dahl, J.; Moldowan, J.M.; Summons, R.E.

1995-09-01

In oils and Precambian- to Miocene-age source rocks from varying depositional environments, we have conclusively identified several novel 3-alkyl sterane and triaromatic steroid series, including (1) 3{beta}-n-pentyl steranes, (2) 3{beta}-isopentyl steranes, (3) 3{beta}-n-hexyl steranes, (4) 3{beta}-n-hepatyl steranes, (5) 3,4-dimethyl steranes, (6) 3{beta}-butyl,4-methyl steranes, (7) triaromatic 3-n-pentyl steroids, and (8) triaromatic 3-isopentyl steroids. We have also tentatively identified additional homologs with 3-alkyl substituents as large as C{sub 11}. The relative abundances of these compounds vary substantially between samples, as indicated by (1) the ratio of 3{beta}-n-pentyl steranes to 3{beta}-isopentyl steranes and (2) the ratio of 3-n-pentyl triaromatic steroids to 3-isopentyl triaromaticmore » steroids. These data suggest possible utility for these parameters as tools for oil-source rock correlations and reconstruction of depositional environments. Although no 3-alkyl steroid natural products are currently known, several lines of evidence suggest that 3{beta}-alkyl steroids result from bacterial side-chain additions to diagenetic {delta}{sup 2}-sterenes.« less

Polyimide characterization studies - Effect of pendant alkyl groups

NASA Technical Reports Server (NTRS)

Jensen, B. J.; Young, P. R.

1984-01-01

The effect on selected polyimide properties when pendant alkyl groups were attached to the polymer backbone was investigated. A series of polymers were prepared using benzophenone tetracarboxylic acid dianhydride (BTDA) and seven different p-alkyl-m,p'-diaminobenzophenone monomers. The alkyl groups varied in length from C(1) (methyl) to C(9) (nonyl). The polyimide prepared from BTDA and m,p'-diaminobenzophenone was included as a control. All polymers were characterized by various chromatographic, spectroscopic, thermal, and mechanical techniques. Increasing the length of the pendant alkyl group resulted in a systematic decrease in glass transition temperature (Tg) for vacuum cured films. A 70 C decrease in Tg to 193 C was observed for the nonyl polymer compared to the Tg for the control. A corresponding systematic increase in Tg indicative of crosslinking, was observed for air cured films. Thermogravimetric analysis revealed a slight sacrifice in thermal stability with increasing alkyl length. No improvement in film toughness was observed.

Isomeric Detergent Comparison for Membrane Protein Stability: Importance of Inter-Alkyl-Chain Distance and Alkyl Chain Length

PubMed Central

Cho, Kyung Ho; Hariharan, Parameswaran; Mortensen, Jonas S.; Du, Yang; Nielsen, Anne K.; Byrne, Bernadette; Kobilka, Brian K.; Loland, Claus J.; Guan, Lan

2017-01-01

Membrane proteins encapsulated by detergent micelles are widely used for structural study. Because of their amphipathic property, detergents have the ability to maintain protein solubility and stability in an aqueous medium. However, conventional detergents have serious limitations in their scope and utility, particularly for eukaryotic membrane proteins and membrane protein complexes. Thus, a number of new agents have been devised; some have made significant contributions to membrane protein structural studies. However, few detergent design principles are available. In this study, we prepared meta and ortho isomers of the previously reported para-substituted xylene-linked maltoside amphiphiles (XMAs), along with alkyl chain-length variation. The isomeric XMAs were assessed with three membrane proteins, and the meta isomer with a C12 alkyl chain was most effective at maintaining solubility/stability of the membrane proteins. We propose that interplay between the hydrophile–lipophile balance (HLB) and alkyl chain length is of central importance for high detergent efficacy. In addition, differences in inter-alkyl-chain distance between the isomers influence the ability of the detergents to stabilise membrane proteins. PMID:27981750

Synthesis of Quaternary Carbon Stereogenic Centers through Enantioselective Cu-Catalyzed Allylic Substitutions with Vinylaluminum Reagents

PubMed Central

Gao, Fang; McGrath, Kevin P.; Lee, Yunmi; Hoveyda, Amir H.

2010-01-01

Catalytic enantioselective allylic substitution (EAS) reactions, which involve the use of alkyl- or aryl-substituted vinylaluminum reagents and afford 1,4-dienes containing a quaternary carbon stereogenic center at their C-3 site, are disclosed. The C–C bond forming transformations are promoted by 0.5–2.5 mol % of sulfonate bearing chiral bidentate N-heterocyclic carbene (NHC) complexes, furnishing the desired products efficiently (66–97% yield of isolated products) and in high site- (>98% SN2′) and enantioselectivity [up to 99:1 enantiomer ratio (er)]. To the best of our knowledge, the present report puts forward the first cases of allylic substitution reactions that result in the generation of all-carbon quaternary stereogenic centers through the addition of a vinyl unit. The aryl- and vinyl-substituted vinylaluminum reagents, which cannot be prepared in high efficiency through direct reaction with diisobutylaluminum hydride, are accessed through a recently introduced Ni-catalyzed reaction of the corresponding terminal alkynes with the same inexpensive metal-hydride agent. Sequential Ni-catalyzed hydrometallations and Cu-catalyzed C–C bond forming reactions allow for efficient and selective synthesis of a range of enantiomerically enriched EAS products, which cannot cannot be accessed by previously disclosed strategies (due to inefficient vinylmetal synthesis or low reactivity and/or selectivity with Si-substituted derivatives). The utility of the protocols developed is demonstrated through a concise enantioselective synthesis of natural product bakuchiol. PMID:20860365

A Convenient Approach to Synthesizing Peptide C-Terminal N-Alkyl Amides

PubMed Central

Fang, Wei-Jie; Yakovleva, Tatyana; Aldrich, Jane V.

2014-01-01

Peptide C-terminal N-alkyl amides have gained more attention over the past decade due to their biological properties, including improved pharmacokinetic and pharmacodynamic profiles. However, the synthesis of this type of peptide on solid phase by current available methods can be challenging. Here we report a convenient method to synthesize peptide C-terminal N-alkyl amides using the well-known Fukuyama N-alkylation reaction on a standard resin commonly used for the synthesis of peptide C-terminal primary amides, the PAL-PEG-PS (Peptide Amide Linker-polyethylene glycol-polystyrene) resin. The alkylation and oNBS deprotection were conducted under basic conditions and were therefore compatible with this acid labile resin. The alkylation reaction was very efficient on this resin with a number of different alkyl iodides or bromides, and the synthesis of model enkephalin N-alkyl amide analogs using this method gave consistently high yields and purities, demonstrating the applicability of this methodology. The synthesis of N-alkyl amides was more difficult on a Rink amide resin, especially the coupling of the first amino acid to the N-alkyl amine, resulting in lower yields for loading the first amino acid onto the resin. This method can be widely applied in the synthesis of peptide N-alkyl amides. PMID:22252422

A novel direct screening method for alkyl glucoside production by glucosidases expressed in E. coli in 96-well plates.

PubMed

Gräber, Martin; Andersson, Mats; Rundbäck, Fabian; Pozzo, Tania; Karlsson, Eva Nordberg; Adlercreutz, Patrick

2010-01-15

The present work describes the development of a novel direct screening method, assayed in 96-well format, for evaluation of enzymatic alkyl glycoside production in a hexanol-water two-phase system. Alkyl glycosides are surfactants with a range of applications and with good biodegradability and low toxicity. Enzymatic synthesis makes it possible to prepare beta-d-glucopyranosides with high purity. In the developed screening assay, hexyl-beta-d-glucopyranoside was chosen as a model product to be synthesised by reversed hydrolysis in a water-hexanol two-phase system. In a first step the model product is produced by glucosidases expressed in E. coli cells in 96-deep-well plates. After phase separation, the hexyl-beta-d-glucopyranoside in the organic phase is degraded enzymatically and the released glucose detected spectrophotometrically at 405nm utilizing peroxidase/glucose oxidase, and the reagent 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS). The aqueous phase is used to monitor hydrolysis of p-NPG at 405nm, allowing use of a ratio of the two assays to compensate for expression differences. The complete method was used for comparison of two different beta-glucosidases, classified under glycoside hydrolase family 1 and 3, respectively, showing a significant difference in their ability to synthesise hexyl-beta-d-glucopyranoside by reversed hydrolysis.

40 CFR 721.10677 - Alkyl phosphonate (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10677 Alkyl phosphonate (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as alkyl phosphonate (PMN P-12-584...

Inactivation of rabies diagnostic reagents by gamma radiation

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

Gamble, W.C.; Chappell, W.A.; George, E.H.

1980-11-01

Treatment of CVS-11 rabies adsorbing suspensions and street rabies infected mouse brains with gamma radiation resulted in inactivated reagents that are safer to distribute and use. These irradiated reagents were as sensitive and reactive as the nonirradiated control reagents.

PREPARATION OF ALKYL PYROPHOSPHATE EXTRACTANTS

DOEpatents

Levine, C.A.; Skiens, W.E.; Moore, G.R.

1960-08-01

A process for providing superior solvent extractants for metal recovery processes is given wherein the extractant comprises an alkyl pyrophosphoric acid ester dissolved in an organic solvent diluent. Finely divided solid P/sub 2/O/ sub 5/ is slurried in an organic solvent-diluent selected from organic solvents such as kerosene, benzene, chlorobenzene, toluene, etc. An alcohol selected from the higher alcohols having 4 to 17 carbon atoms. e.g.. hexanol-1. heptanol-3, octanol-1. 2.6-dimethyl-heptanol-4, and decanol-1, is rapidly added to the P/sub 2/O/sub 5/ slurry in the amount of about 2 moles of alcohol to 1 mole of P/sub 2/ O/sub 5/. The temperature is maintained below about 110 deg C during the course of the P/sub 2/O/sub 5/-alcohol reaction. An alkyl pyrophosphate extractant compound is formed as a consequence of the reaction process. The alkyl pyrophosphate solvent-diluent extractant phase is useful in solvent extraction metal recovery processes.

Antioxidant activity of alkyl gallates and glycosyl alkyl gallates in fish oil in water emulsions: relevance of their surface active properties and of the type of emulsifier.

PubMed

González, María J; Medina, Isabel; Maldonado, Olivia S; Lucas, Ricardo; Morales, Juan C

2015-09-15

The antioxidant activity of gallic acid and a series of alkyl gallates (C4-C18) and glycosylated alkyl gallates (C4-C18) on fish oil-in-water emulsions was studied. Three types of emulsifiers, lecithin, Tween-20 and sodium dodecyl sulphate (SDS) were tested. A nonlinear behavior of the antioxidant activity of alkyl gallates when increasing alkyl chain length was observed for emulsions prepared with lecithin. Medium-size alkyl gallates (C6-C12) were the best antioxidants. In contrast, for emulsions prepared with Tween-20, the antioxidants seem to follow the polar paradox. Glucosyl alkyl gallates were shown previously to be better surfactants than alkyl gallates. Nevertheless, they exhibited a worse antioxidant capacity than their corresponding alkyl gallates, in emulsions prepared with lecithin or Tween-20, indicating the greater relevance of having three OH groups at the polar head in comparison with having improved surfactant properties but just a di-ortho phenolic structure in the antioxidant. Copyright © 2015 Elsevier Ltd. All rights reserved.

The pyruvic acid analog 3-bromopyruvate interferes with the tetrazolium reagent MTS in the evaluation of cytotoxicity.

PubMed

Ganapathy-Kanniappan, Shanmugasundaram; Geschwind, Jean-Francois H; Kunjithapatham, Rani; Buijs, Manon; Syed, Labiq H; Rao, Pramod P; Ota, Shinichi; Vali, Mustafa

2010-04-01

3-Bromopyruvate (3BrPA) is a pyruvate analog known for its alkylating property. Recently, several reports have documented the antiglycolytic and anticancer effects of 3BrPA and its potential for therapeutic applications. 3BrPA-mediated cytotoxicity has been evaluated in vitro by various methods including tetrazolium salt (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)-based assays such as MTT, MTS, and so on. However, growing body of evidences has shown that tetrazolium reagent may interfere with the test compounds. In this study, we investigated whether the tetrazolium reagent interferes with the assessment of 3BrPA cytotoxicity. The results of the tetrazolium-based MTS assay were compared with 3 distinct cell viability detection methods, that is, Trypan Blue staining, ATP depletion, and Annexin V staining in 2 different cell lines, Vx-2 and HepG2. The MTS assay data showed false positive results by indicating increased cell viability at 1 mM and 2 mM 3BrPA whereas the other cell viability assays demonstrated that both Vx-2 and HepG2 cells are not viable at the same treatment conditions. In order to validate the direct interaction of 3BrPA with MTS reagent, we tested cell-free media incubated with different concentrations of 3BrPA. The results of cell-free media showed an increase in absorbance in a dose-dependent manner confirming the interaction of MTS with 3BrPA. Thus, our data clearly demonstrate that 3BrPA interferes with the accuracy of MTS-based cytotoxicity evaluation. Hence, we suggest that employing multiple methods of biochemical as well as morphological cytotoxicity assays is critical to evaluate 3BrPA-mediated cell death.

Effect of the C-2 hydroxyl group on the mesomorphism of alkyl glycosides: synthesis and thermotropic behavior of alkyl 2-deoxy-D-arabino-hexopyranosides.

PubMed

Singh, Madan Kumar; Jayaraman, Narayanaswamy; Rao, D S Shankar; Prasad, S Krishna

2008-10-01

A homologous series of alkyl 2-deoxy-alpha-d-arabino-hexopyranosides and alkyl 2-deoxy-beta-d-arabino-hexopyranosides were synthesized, upon glycosylation of 1-alkanols (from C8 to C18 alkanols) with ethyl 2-deoxy-3,4,6-tri-O-acetyl-1-thio-d-arabino-hexopyranoside, followed by a deprotection. The thermotropic behavior of these new types of alkyl glycosides was investigated. It was observed that the beta-anomers of these alkyl glycosides, bearing nonyl to tetradecyl alkyl chain are mesomorphic, exhibiting monotropic smectic A phase. In contrast, the alpha-anomers are all non-mesomorphic. An effort to identify the liquid crystalline behavior of binary mixtures of the alpha- and beta-anomers was undertaken and it was found that mixtures containing equimolar amounts of the anomers exhibited mesomorphic behavior. A fine balance of the hydrophilic and hydrophobic components within the molecule is also found to be important for the alkyl 2-deoxy glycosides to form the mesophase.

Direct N-alkylation of unprotected amino acids with alcohols

PubMed Central

Yan, Tao; Feringa, Ben L.; Barta, Katalin

2017-01-01

N-alkyl amino acids find widespread application as highly valuable, renewable building blocks. However, traditional synthesis methodologies to obtain these suffer from serious limitations, providing a major challenge to develop sustainable alternatives. We report the first powerful catalytic strategy for the direct N-alkylation of unprotected α-amino acids with alcohols. This method is highly selective, produces water as the only side product leading to a simple purification procedure, and a variety of α-amino acids are mono- or di-N-alkylated, in most cases with excellent retention of optical purity. The hydrophobicity of the products is tunable, and even simple peptides are selectively alkylated. An iron-catalyzed route to mono-N-alkyl amino acids using renewable fatty alcohols is also described that represents an ideal green transformation for obtaining fully bio-based surfactants. PMID:29226249

Isomeric Detergent Comparison for Membrane Protein Stability: Importance of Inter-Alkyl-Chain Distance and Alkyl Chain Length.

PubMed

Cho, Kyung Ho; Hariharan, Parameswaran; Mortensen, Jonas S; Du, Yang; Nielsen, Anne K; Byrne, Bernadette; Kobilka, Brian K; Loland, Claus J; Guan, Lan; Chae, Pil Seok

2016-12-14

Membrane proteins encapsulated by detergent micelles are widely used for structural study. Because of their amphipathic property, detergents have the ability to maintain protein solubility and stability in an aqueous medium. However, conventional detergents have serious limitations in their scope and utility, particularly for eukaryotic membrane proteins and membrane protein complexes. Thus, a number of new agents have been devised; some have made significant contributions to membrane protein structural studies. However, few detergent design principles are available. In this study, we prepared meta and ortho isomers of the previously reported para-substituted xylene-linked maltoside amphiphiles (XMAs), along with alkyl chain-length variation. The isomeric XMAs were assessed with three membrane proteins, and the meta isomer with a C 12 alkyl chain was most effective at maintaining solubility/stability of the membrane proteins. We propose that interplay between the hydrophile-lipophile balance (HLB) and alkyl chain length is of central importance for high detergent efficacy. In addition, differences in inter-alkyl-chain distance between the isomers influence the ability of the detergents to stabilise membrane proteins. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Salvage of failed protein targets by reductive alkylation.

PubMed

Tan, Kemin; Kim, Youngchang; Hatzos-Skintges, Catherine; Chang, Changsoo; Cuff, Marianne; Chhor, Gekleng; Osipiuk, Jerzy; Michalska, Karolina; Nocek, Boguslaw; An, Hao; Babnigg, Gyorgy; Bigelow, Lance; Joachimiak, Grazyna; Li, Hui; Mack, Jamey; Makowska-Grzyska, Magdalena; Maltseva, Natalia; Mulligan, Rory; Tesar, Christine; Zhou, Min; Joachimiak, Andrzej

2014-01-01

The growth of diffraction-quality single crystals is of primary importance in protein X-ray crystallography. Chemical modification of proteins can alter their surface properties and crystallization behavior. The Midwest Center for Structural Genomics (MCSG) has previously reported how reductive methylation of lysine residues in proteins can improve crystallization of unique proteins that initially failed to produce diffraction-quality crystals. Recently, this approach has been expanded to include ethylation and isopropylation in the MCSG protein crystallization pipeline. Applying standard methods, 180 unique proteins were alkylated and screened using standard crystallization procedures. Crystal structures of 12 new proteins were determined, including the first ethylated and the first isopropylated protein structures. In a few cases, the structures of native and methylated or ethylated states were obtained and the impact of reductive alkylation of lysine residues was assessed. Reductive methylation tends to be more efficient and produces the most alkylated protein structures. Structures of methylated proteins typically have higher resolution limits. A number of well-ordered alkylated lysine residues have been identified, which make both intermolecular and intramolecular contacts. The previous report is updated and complemented with the following new data; a description of a detailed alkylation protocol with results, structural features, and roles of alkylated lysine residues in protein crystals. These contribute to improved crystallization properties of some proteins.

Salvage of Failed Protein Targets by Reductive Alkylation

PubMed Central

Tan, Kemin; Kim, Youngchang; Hatzos-Skintges, Catherine; Chang, Changsoo; Cuff, Marianne; Chhor, Gekleng; Osipiuk, Jerzy; Michalska, Karolina; Nocek, Boguslaw; An, Hao; Babnigg, Gyorgy; Bigelow, Lance; Joachimiak, Grazyna; Li, Hui; Mack, Jamey; Makowska-Grzyska, Magdalena; Maltseva, Natalia; Mulligan, Rory; Tesar, Christine; Zhou, Min; Joachimiak, Andrzej

2014-01-01

The growth of diffraction-quality single crystals is of primary importance in protein X-ray crystallography. Chemical modification of proteins can alter their surface properties and crystallization behavior. The Midwest Center for Structural Genomics (MCSG) has previously reported how reductive methylation of lysine residues in proteins can improve crystallization of unique proteins that initially failed to produce diffraction-quality crystals. Recently, this approach has been expanded to include ethylation and isopropylation in the MCSG protein crystallization pipeline. Applying standard methods, 180 unique proteins were alkylated and screened using standard crystallization procedures. Crystal structures of 12 new proteins were determined, including the first ethylated and the first isopropylated protein structures. In a few cases, the structures of native and methylated or ethylated states were obtained and the impact of reductive alkylation of lysine residues was assessed. Reductive methylation tends to be more efficient and produces the most alkylated protein structures. Structures of methylated proteins typically have higher resolution limits. A number of well-ordered alkylated lysine residues have been identified, which make both intermolecular and intramolecular contacts. The previous report is updated and complemented with the following new data; a description of a detailed alkylation protocol with results, structural features, and roles of alkylated lysine residues in protein crystals. These contribute to improved crystallization properties of some proteins. PMID:24590719

Balancing repair and tolerance of DNA damage caused by alkylating agents.

PubMed

Fu, Dragony; Calvo, Jennifer A; Samson, Leona D

2012-01-12

Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity.

Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases; Part 1: alkyl halide alkylations.

PubMed

Sorochinsky, Alexander E; Aceña, José Luis; Moriwaki, Hiroki; Sato, Tatsunori; Soloshonok, Vadim A

2013-10-01

Alkylations of chiral or achiral Ni(II) complexes of glycine Schiff bases constitute a landmark in the development of practical methodology for asymmetric synthesis of α-amino acids. Straightforward, easy preparation as well as high reactivity of these Ni(II) complexes render them ready available and inexpensive glycine equivalents for preparing a wide variety of α-amino acids, in particular on a relatively large scale. In the case of Ni(II) complexes containing benzylproline moiety as a chiral auxiliary, their alkylation proceeds with high thermodynamically controlled diastereoselectivity. Similar type of Ni(II) complexes derived from alanine can also be used for alkylation providing convenient access to quaternary, α,α-disubstituted α-amino acids. Achiral type of Ni(II) complexes can be prepared from picolinic acid or via recently developed modular approach using simple secondary or primary amines. These Ni(II) complexes can be easily mono/bis-alkylated under homogeneous or phase-transfer catalysis conditions. Origin of diastereo-/enantioselectivity in the alkylations reactions, aspects of practicality, generality and limitations of this methodology is critically discussed.

Identification of alkyl carbazoles and alkyl benzocarbazoles in Brazilian petroleum derivatives.

PubMed

Oliveira, Eniz Conceição; Vaz de Campos, Maria Cecília; Rodrigues, Maria Regina Alves; Pérez, Valéria Flores; Melecchi, Maria Inês Soares; Vale, Maria Goreti Rodrigues; Zini, Cláudia Alcaraz; Caramão, Elina Bastos

2006-02-10

Carbozoles are important compounds in crude oils, as they may be used as geochemical tracers, being the major type of nitrogen compounds in petroleum. At the same time, they are regarded as undesirable due to the problems they may cause in the refining process, such as catalyst poisoning, corrosion, gum or color formation in final products. As separation and identification of carbazoles are challenging goals, this work presents a chromatographic method, made of a pre-fractionation on neutral alumina followed by the separation and identification of two classes of carbazoles using FeCl(3)/Chromossorb W and gas chromatograph with mass spectrometer (GC/MS) (SIM-single ion monitoring mode) analysis. For the first time, a series of alkyl carbazoles and alkyl benzocarbazoles were identified in heavy gas oil (HGO) and atmospheric residue of distillation (ARD) obtained from Brazilian petroleum.

Artificial Solid Electrolyte Interphase-Protected LixSi Nanoparticles: An Efficient and Stable Prelithiation Reagent for Lithium-Ion Batteries.

PubMed

Zhao, Jie; Lu, Zhenda; Wang, Haotian; Liu, Wei; Lee, Hyun-Wook; Yan, Kai; Zhuo, Denys; Lin, Dingchang; Liu, Nian; Cui, Yi

2015-07-08

Prelithiation is an important strategy to compensate for lithium loss in lithium-ion batteries, particularly during the formation of the solid electrolyte interphase (SEI) from reduced electrolytes in the first charging cycle. We recently demonstrated that LixSi nanoparticles (NPs) synthesized by thermal alloying can serve as a high-capacity prelithiation reagent, although their chemical stability in the battery processing environment remained to be improved. Here we successfully developed a surface modification method to enhance the stability of LixSi NPs by exploiting the reduction of 1-fluorodecane on the LixSi surface to form a continuous and dense coating through a reaction process similar to SEI formation. The coating, consisting of LiF and lithium alkyl carbonate with long hydrophobic carbon chains, serves as an effective passivation layer in the ambient environment. Remarkably, artificial-SEI-protected LixSi NPs show a high prelithiation capacity of 2100 mA h g(-1) with negligible capacity decay in dry air after 5 days and maintain a high capacity of 1600 mA h g(-1) in humid air (∼10% relative humidity). Silicon, tin, and graphite were successfully prelithiated with these NPs to eliminate the irreversible first-cycle capacity loss. The use of prelithiation reagents offers a new approach to realize next-generation high-energy-density lithium-ion batteries.

40 CFR 721.10548 - Mixed alkyl phosphate esters alkoxylated (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Mixed alkyl phosphate esters... Specific Chemical Substances § 721.10548 Mixed alkyl phosphate esters alkoxylated (generic). (a) Chemical... as mixed alkyl phosphate esters alkoxylated (PMN P-04-624) is subject to reporting under this section...

40 CFR 721.10548 - Mixed alkyl phosphate esters alkoxylated (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Mixed alkyl phosphate esters... Specific Chemical Substances § 721.10548 Mixed alkyl phosphate esters alkoxylated (generic). (a) Chemical... as mixed alkyl phosphate esters alkoxylated (PMN P-04-624) is subject to reporting under this section...

40 CFR 721.5380 - Mixed alkyl phenolic novolak resin (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Mixed alkyl phenolic novolak resin... Specific Chemical Substances § 721.5380 Mixed alkyl phenolic novolak resin (generic). (a) Chemical... as mixed alkyl phenolic novolak resin (PMN P-98-718) is subject to reporting under this section for...

40 CFR 721.5380 - Mixed alkyl phenolic novolak resin (generic).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Mixed alkyl phenolic novolak resin... Specific Chemical Substances § 721.5380 Mixed alkyl phenolic novolak resin (generic). (a) Chemical... as mixed alkyl phenolic novolak resin (PMN P-98-718) is subject to reporting under this section for...

40 CFR 721.5380 - Mixed alkyl phenolic novolak resin (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Mixed alkyl phenolic novolak resin... Specific Chemical Substances § 721.5380 Mixed alkyl phenolic novolak resin (generic). (a) Chemical... as mixed alkyl phenolic novolak resin (PMN P-98-718) is subject to reporting under this section for...

40 CFR 721.5380 - Mixed alkyl phenolic novolak resin (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Mixed alkyl phenolic novolak resin... Specific Chemical Substances § 721.5380 Mixed alkyl phenolic novolak resin (generic). (a) Chemical... as mixed alkyl phenolic novolak resin (PMN P-98-718) is subject to reporting under this section for...

40 CFR 721.5380 - Mixed alkyl phenolic novolak resin (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Mixed alkyl phenolic novolak resin... Specific Chemical Substances § 721.5380 Mixed alkyl phenolic novolak resin (generic). (a) Chemical... as mixed alkyl phenolic novolak resin (PMN P-98-718) is subject to reporting under this section for...

40 CFR 721.10493 - Tris-alkyl-alkoxy melamine polymer (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Tris-alkyl-alkoxy melamine polymer... Specific Chemical Substances § 721.10493 Tris-alkyl-alkoxy melamine polymer (generic). (a) Chemical... as tris-alkyl-alkoxy melamine polymer (PMN P-05-417) is subject to reporting under this section for...

40 CFR 721.10493 - Tris-alkyl-alkoxy melamine polymer (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Tris-alkyl-alkoxy melamine polymer... Specific Chemical Substances § 721.10493 Tris-alkyl-alkoxy melamine polymer (generic). (a) Chemical... as tris-alkyl-alkoxy melamine polymer (PMN P-05-417) is subject to reporting under this section for...

Selective alkylation of T–T mismatched DNA using vinyldiaminotriazine–acridine conjugate

PubMed Central

Onizuka, Kazumitsu; Usami, Akira; Yamaoki, Yudai; Kobayashi, Tomohito; Hazemi, Madoka E; Chikuni, Tomoko; Sato, Norihiro; Sasaki, Kaname; Katahira, Masato

2018-01-01

Abstract The alkylation of the specific higher-order nucleic acid structures is of great significance in order to control its function and gene expression. In this report, we have described the T–T mismatch selective alkylation with a vinyldiaminotriazine (VDAT)–acridine conjugate. The alkylation selectively proceeded at the N3 position of thymidine on the T–T mismatch. Interestingly, the alkylated thymidine induced base flipping of the complementary base in the duplex. In a model experiment for the alkylation of the CTG repeats DNA which causes myotonic dystrophy type 1 (DM1), the observed reaction rate for one alkylation increased in proportion to the number of T–T mismatches. In addition, we showed that primer extension reactions with DNA polymerase and transcription with RNA polymerase were stopped by the alkylation. The alkylation of the repeat DNA will efficiently work for the inhibition of replication and transcription reactions. These functions of the VDAT–acridine conjugate would be useful as a new biochemical tool for the study of CTG repeats and may provide a new strategy for the molecular therapy of DM1. PMID:29309639

Modern affinity reagents: Recombinant antibodies and aptamers.

PubMed

Groff, Katherine; Brown, Jeffrey; Clippinger, Amy J

2015-12-01

Affinity reagents are essential tools in both basic and applied research; however, there is a growing concern about the reproducibility of animal-derived monoclonal antibodies. The need for higher quality affinity reagents has prompted the development of methods that provide scientific, economic, and time-saving advantages and do not require the use of animals. This review describes two types of affinity reagents, recombinant antibodies and aptamers, which are non-animal technologies that can replace the use of animal-derived monoclonal antibodies. Recombinant antibodies are protein-based reagents, while aptamers are nucleic-acid-based. In light of the scientific advantages of these technologies, this review also discusses ways to gain momentum in the use of modern affinity reagents, including an update to the 1999 National Academy of Sciences monoclonal antibody production report and federal incentives for recombinant antibody and aptamer efforts. In the long-term, these efforts have the potential to improve the overall quality and decrease the cost of scientific research. Copyright © 2015 Elsevier Inc. All rights reserved.

TREATMENT OF MTBE USING FENTON'S REAGENT

EPA Science Inventory

This paper addresses the removal of MTBE from water, using Fenton's Reagent. Although complete mineralization of MTBE by Fenton's Reagent was not achieved, greater than 99% destruction of MTBE was realized. This was accomplished at a Fe+2:H2O2 ratio of 1:1 and one hour of contact...

21 CFR 660.30 - Reagent Red Blood Cells.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Reagent Red Blood Cells. 660.30 Section 660.30...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Reagent Red Blood Cells § 660.30 Reagent Red Blood Cells. (a) Proper name and definition. The proper name of the product shall be...

21 CFR 660.30 - Reagent Red Blood Cells.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Reagent Red Blood Cells. 660.30 Section 660.30...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Reagent Red Blood Cells § 660.30 Reagent Red Blood Cells. (a) Proper name and definition. The proper name of the product shall be...

21 CFR 660.30 - Reagent Red Blood Cells.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Reagent Red Blood Cells. 660.30 Section 660.30...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Reagent Red Blood Cells § 660.30 Reagent Red Blood Cells. (a) Proper name and definition. The proper name of the product shall be...

21 CFR 660.30 - Reagent Red Blood Cells.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Reagent Red Blood Cells. 660.30 Section 660.30...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Reagent Red Blood Cells § 660.30 Reagent Red Blood Cells. (a) Proper name and definition. The proper name of the product shall be...

Alkyl chitosan film-high strength, functional biomaterials.

PubMed

Lu, Li; Xing, Cao; Xin, Shen; Shitao, Yu; Feng, Su; Shiwei, Liu; Fusheng, Liu; Congxia, Xie

2017-11-01

Biofilm with strong tensile strength is a topic item in the area of tissue engineering, medicine engineering, and so forth. Here we introduced an alkyl chitosan film with strong tensile strength and its possibility for an absorbable anticoagulation material in vivo was tested in the series of blood test, such as dynamic coagulation time, plasma recalcification time and hemolysis. Alkyl chitosan film was a better biomaterial than traditional chitosan film in the anticoagulation, tissue compatibility and cell compatibility. The unique trait of alkyl chitosan film may be for its greater contact angle and hydrophobicity ability to reduce the adsorption capacity for the blood component and the activity of fibrinolytic enzymes, enhance the antibacterial capacity than chitosan film. Moreover, none of chitosan film or butyl chitosan film exhibited quick inflammation or other disadvantage and degraded quickly by implanted test. Therefore, Alkyl chitosan film is of prospective properties as an implantable, absorbable agent for tissue heals, and this material need further research. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3034-3041, 2017. © 2017 Wiley Periodicals, Inc.

40 CFR 721.2565 - Alkylated sulfonated diphenyl oxide, alkali and amine salts.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkylated sulfonated diphenyl oxide... New Uses for Specific Chemical Substances § 721.2565 Alkylated sulfonated diphenyl oxide, alkali and... substances identified as alkylated sulfonated diphenyl oxide, alkali salt (PMN P-93-352) and alkylated...

40 CFR 721.2565 - Alkylated sulfonated diphenyl oxide, alkali and amine salts.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkylated sulfonated diphenyl oxide... New Uses for Specific Chemical Substances § 721.2565 Alkylated sulfonated diphenyl oxide, alkali and... substances identified as alkylated sulfonated diphenyl oxide, alkali salt (PMN P-93-352) and alkylated...

Detection and identification of alkylating agents by using a bioinspired "chemical nose".

PubMed

Hertzog-Ronen, Carmit; Borzin, Elena; Gerchikov, Yulia; Tessler, Nir; Eichen, Yoav

2009-10-12

Alkylating agents are simple and reactive molecules that are commonly used in many and diverse fields such as organic synthesis, medicine, and agriculture. Some highly reactive alkylating species are also being used as blister chemical-warfare agents. The detection and identification of alkylating agents is not a trivial issue because of their high reactivity and simple structure. Herein, we report on a new multispot luminescence-based approach to the detection and identification of alkylating agents. In order to demonstrate the potential of the approach, seven pi-conjugated oligomers and polymers bearing nucleophilic pyridine groups, 1-7, were adsorbed onto a solid support and exposed to vapors of alkylators 8-15. The alkylation-induced color-shift patterns of the seven-spot array allow clear discrimination of the different alkylators. The spots are sensitive to minute concentrations of alkylators and, because the detection is based on the formation of new covalent bonds, these spots saturate at about 50 ppb.

Mechanisms of chemoresistance to alkylating agents in malignant glioma.

PubMed

Sarkaria, Jann N; Kitange, Gaspar J; James, C David; Plummer, Ruth; Calvert, Hilary; Weller, Michael; Wick, Wolfgang

2008-05-15

Intrinsic or acquired chemoresistance to alkylating agents is a major cause of treatment failure in patients with malignant brain tumors. Alkylating agents, the mainstay of treatment for brain tumors, damage the DNA and induce apoptosis, but the cytotoxic activity of these agents is dependent on DNA repair pathways. For example, O6-methylguanine DNA adducts can cause double-strand breaks, but this is dependent on a functional mismatch repair pathway. Thus, tumor cell lines deficient in mismatch repair are resistant to alkylating agents. Perhaps the most important mechanism of resistance to alkylating agents is the DNA repair enzyme O6-methylguanine methyltransferase, which can eliminate the cytotoxic O6-methylguanine DNA adduct before it causes harm. Another mechanism of resistance to alkylating agents is the base excision repair (BER) pathway. Consequently, efforts are ongoing to develop effective inhibitors of BER. Poly(ADP-ribose)polymerase plays a pivotal role in BER and is an important therapeutic target. Developing effective strategies to overcome chemoresistance requires the identification of reliable preclinical models that recapitulate human disease and which can be used to facilitate drug development. This article describes the diverse mechanisms of chemoresistance operating in malignant glioma and efforts to develop reliable preclinical models and novel pharmacologic approaches to overcome resistance to alkylating agents.

40 CFR 721.10711 - Alkyl substituted catechol (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10711 Alkyl substituted catechol (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as alkyl...

40 CFR 721.840 - Alkyl substituted diaromatic hydrocarbons.

Code of Federal Regulations, 2010 CFR

2010-07-01

... hydrocarbons. 721.840 Section 721.840 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.840 Alkyl substituted diaromatic hydrocarbons. (a) Chemical substance... alkyl substituted di-aro-matic hydrocarbons (PMN P-91-710) is subject to reporting under this section...

40 CFR 721.840 - Alkyl substituted diaromatic hydrocarbons.

Code of Federal Regulations, 2011 CFR

2011-07-01

... hydrocarbons. 721.840 Section 721.840 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.840 Alkyl substituted diaromatic hydrocarbons. (a) Chemical substance... alkyl substituted di-aro-matic hydrocarbons (PMN P-91-710) is subject to reporting under this section...

Effect of alkyl chain length on the rotational diffusion of nonpolar and ionic solutes in 1-alkyl-3-methylimidazolium-bis(trifluoromethylsulfonyl)imides.

PubMed

Gangamallaiah, V; Dutt, G B

2013-10-10

Rotational diffusion of a nonpolar solute 9-phenylanthracene (9-PA) and a cationic solute rhodamine 110 (R110) has been examined in a series of 1-alkyl-3-methylimidazolium (alkyl = octyl, decyl, dodecyl, tetradecyl, hexadecyl, and octadecyl) bis(trifluoromethylsulfonyl)imides to understand the influence of alkyl chain length on solute rotation. In this study, reorientation times (τr) have been measured as a function of viscosity (η) by varying the temperature (T) of the solvents. These results have been analyzed using the Stokes-Einstein-Debye (SED) hydrodynamic theory along with the ones obtained for the same solutes in 1-alkyl-3-methylimidazolium (alkyl = methyl, ethyl, propyl, butyl, and hexyl) bis(trifluoromethylsulfonyl)imides (Gangamallaiah and Dutt, J. Phys. Chem. B 2012, 116, 12819-12825). It has been noticed that the data for 9-PA and R110 follows the relation τr = A(η/T)(n) with A being the ratio of hydrodynamic volume of the solute to the Boltzmann constant and n = 1 as envisaged by the SED theory. However, upon increasing the alkyl chain length from methyl to octadecyl significant deviations from the SED theory have been observed especially from the octyl derivative onward. From methyl to octadecyl derivatives, the value of A decreases by a factor of 3 for both the solutes and n by a factor of 1.4 and 1.6 for 9-PA and R110, respectively. These observations have been rationalized by taking into consideration the organized structure of the ionic liquids, whose influence appears to be pronounced when the number of carbon atoms in the alkyl chain attached to the imidazolium cation exceeds eight.

Copper-catalyzed radical carbooxygenation: alkylation and alkoxylation of styrenes.

PubMed

Liao, Zhixiong; Yi, Hong; Li, Zheng; Fan, Chao; Zhang, Xu; Liu, Jie; Deng, Zixin; Lei, Aiwen

2015-01-01

A simple copper-catalyzed direct radical carbooxygenation of styrenes is developed utilizing alkyl bromides as radical resources. This catalytic radical difunctionalization accomplishes both alkylation and alkoxylation of styrenes in one pot. A broad range of styrenes and alcohols are well tolerated in this transformation. The EPR experiment shows that alkyl halides could oxidize Cu(I) to Cu(II) in this transformation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lithium perchlorate-nitromethane-promoted alkylation of anilines with arylmethanols.

PubMed

Zhou, Jun; Mao, Hai-Feng; Wang, Lu; Zou, Jian-Ping; Zhang, Wei

2011-11-01

A new application of lithium perchlorate-nitromethane (LPNM) for the formation of aromatic C-N and C-C bonds is introduced. LPNM-promoted reactions of anilines with diarylmethanols selectively generate N-alkylated anilines or mono and double Friedel-Crafts alkylation products under different conditions by changing the reaction time, reaction temperature, and the ratio of the reactants. This method does not require the use of transition metal catalysts to prepare alkylated aniline derivatives.

Facile synthesis of multisubstituted buta-1,3-dienes via Suzuki-Miyaura and Kumada cross-coupling strategy of 2,4-diiodo-buta-1-enes with arylboronic acids and Grignard reagents.

PubMed

Shao, Li-Xiong; Shi, Min

2005-05-21

One-pot Suzuki-Miyaura-type and Kumada-type cross-coupling reactions of 2,4-diiodo-buta-1-enes with arylboronic acids and alkyl/aryl magnesium bromides were carried out in the presence of accessibly simple catalysts under mild conditions. As a result, some 1,1,2-trisubstituted buta-1,3-dienes were obtained including the Tamoxifen-type, which have potential adjuvant therapy in women who have suffered from breast cancer and cyclooxygenase-2-type (COX-2-type) inhibitors, some of which have been proved to elicit efficient anti-inflammatory analgesic activities and less adverse gastrointestinal side effects and to be very useful in the prophylactic treatment of a wide variety of cancers and neurodegenerative disorders.

Chiral Brønsted Base-Promoted Nitroalkane Alkylation: Enantioselective Synthesis of sec-Alkyl-3-Substituted Indoles

PubMed Central

Dobish, Mark C.; Johnston, Jeffrey N.

2010-01-01

A Brønsted base-catalyzed reaction of nitroalkanes with alkyl electrophiles provides indole heterocycles substituted at C3 bearing a sec-alkyl group with good enantioselectivity (up to 90% ee). Denitration by hydrogenolysis provides a product with equally high ee. An indolenine intermediate is implicated in the addition step, and surprisingly, water cosolvent was found to have a beneficial effect in this step, leading to a one-pot protocol for elimination/enantioselective addition using PBAM, a bis(amidine) chiral nonracemic base. PMID:21090654

Virus inactivation by nucleic acid extraction reagents.

PubMed

Blow, Jamie A; Dohm, David J; Negley, Diane L; Mores, Christopher N

2004-08-01

Many assume that common methods to extract viral nucleic acids are able to render a sample non-infectious. It may be that inactivation of infectious virus is incomplete during viral nucleic acid extraction methods. Accordingly, two common viral nucleic acid extraction techniques were evaluated for the ability to inactivate high viral titer specimens. In particular, the potential for TRIzol LS Reagent (Invitrogen Corp., Carlsbad, CA) and AVL Buffer (Qiagen, Valencia, CA) were examined to render suspensions of alphaviruses, flaviviruses, filoviruses and a bunyavirus non-infectious to tissue culture assay. The dilution series for both extraction reagents consistently caused cell death through a 100-fold dilution. Except for the DEN subtype 4 positive control, all viruses had titers of at least 10(6)pfu/ml. No plaques were detected in any extraction reagent plus virus combination in this study, therefore, the extraction reagents appeared to inactivate completely each of the high-titer viruses used in this study. These results support the reliance upon either TRIzol LS Reagent or AVL Buffer to render clinical or environmental samples non-infectious, which has implications for the handling and processing of samples under austere field conditions and low level containment.

Grafting of functionalized polymer on porous silicon surface using Grignard reagent

NASA Astrophysics Data System (ADS)

Tighilt, F.-Z.; Belhousse, S.; Sam, S.; Hamdani, K.; Lasmi, K.; Chazalviel, J. N.; Gabouze, N.

2017-11-01

Recently, considerable attention has been paid to the manipulation and the control of the physicochemical properties of porous silicon surfaces because of their crucial importance to the modern microelectronics industry. Hybrid structures consisting of deposited polymer on porous silicon surfaces are important to applications in microelectronics, photovoltaics and sensors (Ensafi et al., 2016; Kashyout et al., 2015; Osorio et al.; 2015; Hejjo et al., 2002) [1-4]. In many cases, the polymer can provide excellent mechanical and chemical protection of the substrate, changes the electrochemical interface characteristics of the substrate, and provides new ways to the functionalization of porous silicon surfaces for molecular recognition and sensing. In this work, porous silicon surface was modified by anodic treatment in ethynylmagnesium bromide electrolyte leading to the formation of a polymeric layer bearing some bromine substituents. Subsequently, the formed polymer is functionalized with amine molecules containing functional groups (carboxylic acid or pyridine) by a substitution reaction between bromine sites and amine groups (Hofmann reaction). The chemical composition of the modified porous silicon surfaces was investigated and the grafting of polymeric chains and functional groups on the porous silicon surface was confirmed by Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) which displayed the principal characteristic peaks attributed to the different functional groups. Furthermore, the surface of the material was examined by scanning electron microscopy (SEM).

Direct displacement of alkoxy groups of vinylogous esters by Grignard reagents.

PubMed

Brockway, Anthony J; González-López, Marcos; Fettinger, James C; Shaw, Jared T

2011-05-06

The direct displacement of alkoxy groups from the β position of aromatic and unsaturated esters and ketones is described. The reaction is chemo- and regioselective, displaying wide substrate scope. © 2011 American Chemical Society

Direct Displacement of Alkoxy Groups of Vinylogous Esters by Grignard Reagents

PubMed Central

Brockway, Anthony J.; González-López, Marcos; Fettinger, James C.

2011-01-01

The direct displacement of alkoxy groups from the beta position of aromatic and unsaturated esters and ketones is described. The reaction is chemo- and regioselective, displaying wide substrate scope. PMID:21446670

Preparation of an Ester-Containing Grignard Reagent by Halogen-Metal Exchange

ERIC Educational Resources Information Center

Snider, Barry B.

2015-01-01

In this experiment, students carry out a halogen-metal exchange reaction of methyl 2-iodobenzoate with isopropylmagnesium chloride in THF at 0°C to afford 2-carbomethoxyphenylmagnesium chloride, which is treated with "p"-methoxybenzaldehyde to give a lactone (phthalide) product. This reaction introduces students to the modern method of…

Constructing New Bioorthogonal Reagents and Reactions.

PubMed

Row, R David; Prescher, Jennifer A

2018-05-15

Chemical tools are transforming our understanding of biomolecules and living systems. Included in this group are bioorthogonal reagents-functional groups that are inert to most biological species, but can be selectively ligated with complementary probes, even in live cells and whole organisms. Applications of these tools have revealed fundamental new insights into biomolecule structure and function-information often beyond the reach of genetic approaches. In many cases, the knowledge gained from bioorthogonal probes has enabled new questions to be asked and innovative research to be pursued. Thus, the continued development and application of these tools promises to both refine our view of biological systems and facilitate new discoveries. Despite decades of achievements in bioorthogonal chemistry, limitations remain. Several reagents are too large or insufficiently stable for use in cellular environments. Many bioorthogonal groups also cross-react with one another, restricting them to singular tasks. In this Account, we describe our work to address some of the voids in the bioorthogonal toolbox. Our efforts to date have focused on small reagents with a high degree of tunability: cyclopropenes, triazines, and cyclopropenones. These motifs react selectively with complementary reagents, and their unique features are enabling new pursuits in biology. The Account is organized by common themes that emerged in our development of novel bioorthogonal reagents and reactions. First, natural product structures can serve as valuable starting points for probe design. Cyclopropene, triazine, and cyclopropenone motifs are all found in natural products, suggesting that they would be metabolically stable and compatible with a variety of living systems. Second, fine-tuning bioorthogonal reagents is essential for their successful translation to biological systems. Different applications demand different types of probes; thus, generating a collection of tools that span a continuum of

Sleep-inducing N-alkyl-5-[m-(trifluoromethyl)phenyl]-5-hydroxy-2-pyrrolidinones and N-alkyl-3-(trifluoromethyl)cinnamamides.

PubMed

Houlihan, W J; Gogerty, J H; Ryan, E A; Schmitt, G

1985-01-01

A series of N-alkyl-3-[m-(trifluoromethyl)phenyl]-5-hydroxy-2-pyrrolidinones and N-alkyl-3-(trifluoromethyl)-cinnamamides were prepared and screened in a series of tests designed to detect potential sleep inducers. The more active members of the series were evaluated for their ability to induce sleep in Cebus monkeys. The most active compound, N-methyl-5-[m-(trifluoromethyl)phenyl]-5-hydroxy-2-pyrrolidinone, was equal to methaqualone.

Synthesis and characterization of chitosan alkyl urea.

PubMed

Wang, Jing; Jiang, Ji-Zhou; Chen, Wei; Bai, Zheng-Wu

2016-07-10

Chitosan is a versatile material employed for various purposes in many fields including the development of chiral stationary phases for enantioseparation. Chitosan alkyl urea is a kind of intermediate used to prepare enantioseparation materials. In order to synthesize the intermediates, in the present work, a new way to prepare chitosan alkyl urea has been established: chitosan was first reacted with methyl chloroformate yielding N-methoxyformylated chitosan, which was then converted to chitosan alkyl urea through amine-ester exchange reaction. With a large excess of methyl chloroformate and primary amine of low stereohindrance, the amino group in chitosan could be almost completely converted to ureido group. The as-prepared chitosan alkyl urea derivatives were characterized by IR, (1)H NMR, (13)C NMR,(1)H-(1)H COSY and (1)H-(13)C HSQC NMR spectra. The chemical shifts of hydrogen and carbon atoms of glucose unit were assigned. It was found that the degree of substitution was obviously lower if cyclopropyl amine, aniline, tert-butyl amine and diethyl amine were used as reactants for the amine-ester exchange reaction. The reason was explained with the aid of theoretical calculations. Copyright © 2016 Elsevier Ltd. All rights reserved.

21 CFR 866.3900 - Varicella-zoster virus serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Varicella-zoster virus serological reagents. 866... Varicella-zoster virus serological reagents. (a) Identification. Varicella-zoster virus serological reagents... viruses and provides epidemiological information on these diseases. Varicella (chicken pox) is a mild...

21 CFR 866.3900 - Varicella-zoster virus serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Varicella-zoster virus serological reagents. 866... Varicella-zoster virus serological reagents. (a) Identification. Varicella-zoster virus serological reagents... viruses and provides epidemiological information on these diseases. Varicella (chicken pox) is a mild...

21 CFR 866.3900 - Varicella-zoster virus serological reagents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Varicella-zoster virus serological reagents. 866... Varicella-zoster virus serological reagents. (a) Identification. Varicella-zoster virus serological reagents... viruses and provides epidemiological information on these diseases. Varicella (chicken pox) is a mild...

21 CFR 866.3900 - Varicella-zoster virus serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Varicella-zoster virus serological reagents. 866... Varicella-zoster virus serological reagents. (a) Identification. Varicella-zoster virus serological reagents... viruses and provides epidemiological information on these diseases. Varicella (chicken pox) is a mild...

21 CFR 866.3900 - Varicella-zoster virus serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Varicella-zoster virus serological reagents. 866... Varicella-zoster virus serological reagents. (a) Identification. Varicella-zoster virus serological reagents... viruses and provides epidemiological information on these diseases. Varicella (chicken pox) is a mild...

Alkylation of a bioinspired high spin Ni(II)N{sub 3}S{sub 2} complex with bifunctional reagents

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

Chohan, B. S., E-mail: bsc12@psu.edu

2013-12-15

Crystal structures of two S-alkylated complexes generated from the reaction of iodoacetamide and iodoethanol with an air and moisture sensitive high spin Ni(II) pentacoordinate triaminodithiolate complex, 1 are determined by X-ray structure analysis. Crystals of complex 2, [NiC{sub 16}H{sub 31}N{sub 5}O{sub 2}S{sub 2}]I{sub 2}, are triclinic, sp. gr. P-bar1 , Z = 2. Crystals of complex 3, [NiC{sub 16}H{sub 28}N{sub 3}O{sub 2}S{sub 2}]I{sub 2}, are monoclinic, sp. gr. P2{sub 1}/c, Z = 4. Structures of complexes 2 and 3 are very similar: one of the S-acetamide (2) or S-ethanol (3) groups coordinates to the Ni center through the oxygen atom formingmore » N{sub 3}S{sub 2}O hexacoordination; the other group remains unbound to the Ni and left dangling. Crystal packing shows that complexes 2 and 3 interact with the iodide counterions, and that only complex 2 interact with neighboring molecules; some of these close intermolecular contacts include H-bonding interactions.« less

Detection of Alkylating Agents using Electrical and Mechanical Means

NASA Astrophysics Data System (ADS)

Gerchikov, Yulia; Borzin, Elena; Gannot, Yair; Shemesh, Ariel; Meltzman, Shai; Hertzog-Ronen, Carmit; Tal, Shay; Stolyarova, Sara; Nemirovsky, Yael; Tessler, Nir; Eichen, Yoav

2011-08-01

Alkylating agents are reactive molecules having at least one polar bond between a carbon atom and a good leaving group. These often simple molecules are frequently used in organic synthesis, as sterilizing agents in agriculture and even as anticancer agents in medicine. Unfortunately, for over a century, some of the highly reactive alkylating agents are also being used as blister chemical warfare agents. Being relatively simple to make, the risk is that these will be applied by terrorists as poor people warfare agents. The detection and identification of such alkylating agents is not a simple task because of their high reactivity and simple structure of the reactive site. Here we report on new approaches to the detection and identification of such alkylating agents using electrical (organic field effect transistors) and mechanical (microcantilevers) means.

Safety Assessment of Alkyl PEG/PPG Ethers as Used in Cosmetics.

PubMed

Fiume, Monice M; Heldreth, Bart; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

2016-07-01

The Cosmetic Ingredient Review (CIR) Expert Panel assessed the safety of 131 alkyl polyethylene glycol (PEG)/polypropylene glycol ethers as used in cosmetics, concluding that these ingredients are safe in the present practices of use and concentration described in this safety assessment when formulated to be nonirritating. Most of the alkyl PEG/PPG ethers included in this review are reported to function in cosmetics as surfactants, skin-conditioning agents, and/or emulsifying agents. The alkyl PEG/PPG ethers share very similar physiochemical properties as the alkyl PEG ethers, which were reviewed previously by the CIR Expert Panel and found safe when formulated to be nonirritating. The alkyl PEG ethers differ by the inclusion of PPG repeat units, which are used to fine-tune the surfactant properties of this group. The Panel relied heavily on data on analogous ingredients, extracted from the alkyl PEG ethers and PPG reports, when making its determination of safety. © The Author(s) 2016.

Chemical Amplification with Encapsulated Reagents

NASA Technical Reports Server (NTRS)

Chen, Jian; Koemer, Steffi; Craig, Stephen; Lin, Shirley; Rudkevich, Dmitry M.; Rebek, Julius, Jr.

2002-01-01

Autocatalysis and chemical amplification are characteristic properties of living systems, and they give rise to behaviors such as increased sensitivity, responsiveness, and self-replication. Here we report a synthetic system in which a unique form of compartmentalization leads to nonlinear, autocatalytic behavior. The compartment is a reversibly formed capsule in which a reagent is sequestered. Reaction products displace the reagent from the capsule into solution and the reaction rate is accelerated. The resulting self-regulation is sensitive to the highly selective molecular recognition properties of the capsule.

Synthesis of enantiopure trans-2,5-disubstituted trifluoromethylpyrrolidines and (2S,5R)-5-trifluoromethylproline.

PubMed

Lubin, Hodney; Pytkowicz, Julien; Chaume, Grégory; Sizun-Thomé, Gwenaëlle; Brigaud, Thierry

2015-03-06

Enantiopure trans-2,5-disubstituted trifluoromethylpyrrolidines were prepared on a several gram scale starting from a readily available chiral fluorinated oxazolidine (Fox). A pure oxazolopyrrolidine intermediate could be obtained after an efficient separation by selective diastereomer destruction. The addition of various Grignard reagents on this oxazolopyrrolidine provided disubstituted pyrrolidines with moderate to complete trans diastereoselectivity. The highly valuable compound (2S,5R)-5-trifluoromethylproline could be synthesized from the same oxazolopyrrolidine intermediate via a Strecker-type reaction.

40 CFR 792.83 - Reagents and solutions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 31 2010-07-01 2010-07-01 true Reagents and solutions. 792.83 Section 792.83 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) GOOD LABORATORY PRACTICE STANDARDS Testing Facilities Operation § 792.83 Reagents and...

21 CFR 866.3175 - Cytomegalovirus serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cytomegalovirus serological reagents. 866.3175 Section 866.3175 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3175...

21 CFR 866.3145 - Coxsackievirus serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Coxsackievirus serological reagents. 866.3145 Section 866.3145 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3145...

21 CFR 866.3175 - Cytomegalovirus serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cytomegalovirus serological reagents. 866.3175 Section 866.3175 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3175...

21 CFR 866.3145 - Coxsackievirus serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Coxsackievirus serological reagents. 866.3145 Section 866.3145 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3145...

21 CFR 866.3145 - Coxsackievirus serological reagents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Coxsackievirus serological reagents. 866.3145 Section 866.3145 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3145...

21 CFR 866.3145 - Coxsackievirus serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Coxsackievirus serological reagents. 866.3145 Section 866.3145 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3145...

21 CFR 866.3175 - Cytomegalovirus serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cytomegalovirus serological reagents. 866.3175 Section 866.3175 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3175...

21 CFR 866.3145 - Coxsackievirus serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Coxsackievirus serological reagents. 866.3145 Section 866.3145 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3145...

21 CFR 866.3175 - Cytomegalovirus serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cytomegalovirus serological reagents. 866.3175 Section 866.3175 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3175...

21 CFR 58.83 - Reagents and solutions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES Testing Facilities Operation § 58.83 Reagents and solutions. All reagents and solutions in the laboratory areas shall be labeled to indicate identity, titer...

21 CFR 866.3940 - West Nile virus serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false West Nile virus serological reagents. 866.3940... virus serological reagents. (a) Identification. West Nile virus serological reagents are devices that consist of antigens and antisera for the detection of anti-West Nile virus IgM antibodies, in human serum...

21 CFR 866.3940 - West Nile virus serological reagents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false West Nile virus serological reagents. 866.3940... virus serological reagents. (a) Identification. West Nile virus serological reagents are devices that consist of antigens and antisera for the detection of anti-West Nile virus IgM antibodies, in human serum...

21 CFR 866.3940 - West Nile virus serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false West Nile virus serological reagents. 866.3940... virus serological reagents. (a) Identification. West Nile virus serological reagents are devices that consist of antigens and antisera for the detection of anti-West Nile virus IgM antibodies, in human serum...

21 CFR 866.3940 - West Nile virus serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false West Nile virus serological reagents. 866.3940... virus serological reagents. (a) Identification. West Nile virus serological reagents are devices that consist of antigens and antisera for the detection of anti-West Nile virus IgM antibodies, in human serum...

21 CFR 866.3940 - West Nile virus serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false West Nile virus serological reagents. 866.3940... virus serological reagents. (a) Identification. West Nile virus serological reagents are devices that consist of antigens and antisera for the detection of anti-West Nile virus IgM antibodies, in human serum...

Alkylation of 6-mercaptopurine (6-MP) with N-alkyl-N-alkoxycarbonylaminomethyl chlorides: S6-(N-alkyl-N-alkoxycarbonyl)aminomethyl-6-MP prodrug structure effect on the dermal delivery of 6-MP.

PubMed

Siver, K G; Sloan, K B

1990-01-01

The S6-(N-alkyl-N-alkoxycarbonyl)aminomethyl-6-MP (6-CARB-6-MP) prodrugs 5-20 were synthesized from the reaction of 6-MP with N-alkyl-N-alkyoxycarbonylaminomethyl chlorides (4) in dimethyl sulfoxide in overall yields of 5-62%, depending on the N-alkyl and the alkoxy groups involved. The derivatives were fully characterized by spectral and microanalyses. The assignment of the substitution pattern as S6-alkyl was based on comparisons of the UV, 1H NMR and 13C NMR spectra with model compounds. A S6, 9-bis-alkyl derivative was obtained from the reaction of 2 equivalents of 4 with 6-MP but the product was unstable and decomposed on standing to a 9-alkyl derivative. The 6-CARB-6-MP prodrugs reverted to 6-MP in water by an SN1-type mechanism involving unimolecular charge separation in the transition state of the rate determining step. There was no effect of dermal enzymes on the rate of hydrolysis. The solubilities in isopropyl myristate (IPM) for all of the 6-CARB-6-MP prodrugs were significantly greater than the solubility of 6-MP in IPM but only one prodrug (5) was apparently even as soluble as 6-MP in water. Selected 6-CARB-6-MP prodrugs were examined in diffusion cell experiments. Only the N-methyl-N-methoxycarbonyl derivative 5 gave a steady-state rate of delivery of 6-MP from IPM that was significantly greater than the steady-state rate of delivery of 6-MP from 6-MP in IPM. All the other derivatives gave steady-state rates of delivery of 6-MP from IPM that were either not significantly different, or were significantly lower than the rate obtained from 6-MP in IPM. In all cases, the effect of the 6-CARB-6-MP:IPM suspensions on the permeability of the skin, as determined by the second application flux of theophylline:propylene glycol, was of the same magnitude as the effect of IPM alone.

Strategies to prepare and use functionalized organometallic reagents.

PubMed

Klatt, Thomas; Markiewicz, John T; Sämann, Christoph; Knochel, Paul

2014-05-16

Polyfunctional zinc and magnesium organometallic reagents occupy a central position in organic synthesis. Most organic functional groups are tolerated by zinc organometallic reagents, and Csp(2)-centered magnesium organometallic reagents are compatible with important functional groups, such as the ester, aryl ketone, nitro, cyano, and amide functions. This excellent chemoselectivity gives zinc- and magnesium-organometallic reagents a central position in modern organic synthesis. Efficient and general preparations of these organometallic reagents, as well as their most practical and useful reactions, are presented in this Perspective. As starting materials, a broad range of organic halides (iodides, bromides, and also to some extent chlorides) can be used for the direct insertion of magnesium or zinc powder; the presence of LiCl very efficiently promotes such insertions. Alternatively, aromatic or heterocyclic bromides also undergo a smooth bromine-magnesium exchange when treated with i-PrMgCl·LiCl. Alternative precursors of zinc and magnesium reagents are polyfunctionalized aryl and heteroaryl molecules, which undergo directed metalations with sterically hindered TMP bases (TMP = 2,2,6,6-tetramethylpiperide) of magnesium and zinc. This powerful C-H functionalization method gives access to polyfunctional heterocyclic zinc and magnesium reagents, which undergo efficient reactions with numerous electrophiles. The compatibility of the strong TMP-bases with BF3·OEt2 (formation of frustrated Lewis pairs) dramatically increases the scope of these metalations, giving for example, a practical access to magnesiated pyridines and pyrazines, which can be used as convenient building blocks for the preparation of biologically active molecules.

Bifunctional Molybdenum Polyoxometalates for the Combined Hydrodeoxygenation and Alkylation of Lignin-Derived Model Phenolics.

PubMed

Anderson, Eric; Crisci, Anthony; Murugappan, Karthick; Román-Leshkov, Yuriy

2017-05-22

Reductive catalytic fractionation of biomass has recently emerged as a powerful lignin extraction and depolymerization method to produce monomeric aromatic oxygenates in high yields. Here, bifunctional molybdenum-based polyoxometalates supported on titania (POM/TiO 2 ) are shown to promote tandem hydrodeoxygenation (HDO) and alkylation reactions, converting lignin-derived oxygenated aromatics into alkylated benzenes and alkylated phenols in high yields. In particular, anisole and 4-propylguaiacol were used as model compounds for this gas-phase study using a packed-bed flow reactor. For anisole, 30 % selectivity for alkylated aromatic compounds (54 % C-alkylation of the methoxy groups by methyl balance) with an overall 72 % selectivity for HDO at 82 % anisole conversion was observed over H 3 PMo 12 O 40 /TiO 2 at 7 h on stream. Under similar conditions, 4-propylguaiacol was mainly converted into 4-propylphenol and alkylated 4-propylphenols with a selectivity to alkylated 4-propylphenols of 42 % (77 % C-alkylation) with a total HDO selectivity to 4-propylbenzene and alkylated 4-propylbenzenes of 4 % at 92 % conversion (7 h on stream). Higher catalyst loadings pushed the 4-propylguaiacol conversion to 100 % and resulted in a higher selectivity to propylbenzene of 41 %, alkylated aromatics of 21 % and alkylated phenols of 17 % (51 % C-alkylation). The reactivity studies coupled with catalyst characterization revealed that Lewis acid sites act synergistically with neighboring Brønsted acid sites to simultaneously promote alkylation and hydrodeoxygenation activity. A reaction mechanism is proposed involving activation of the ether bond on a Lewis acid site, followed by methyl transfer and C-alkylation. Mo-based POMs represent a versatile catalytic platform to simultaneously upgrade lignin-derived oxygenated aromatics into alkylated arenes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

40 CFR 721.5985 - Fatty alkyl phosphate, alkali metal salt (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Fatty alkyl phosphate, alkali metal... Specific Chemical Substances § 721.5985 Fatty alkyl phosphate, alkali metal salt (generic). (a) Chemical... as a fatty alkyl phosphate, alkali metal salt (PMN P-99-0385) is subject to reporting under this...

40 CFR 721.5985 - Fatty alkyl phosphate, alkali metal salt (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Fatty alkyl phosphate, alkali metal... Specific Chemical Substances § 721.5985 Fatty alkyl phosphate, alkali metal salt (generic). (a) Chemical... as a fatty alkyl phosphate, alkali metal salt (PMN P-99-0385) is subject to reporting under this...

40 CFR 721.2094 - N,N′-di(alkyl heteromonocycle)amino chlorotriazine.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false N,Nâ²-di(alkyl heteromonocycle)amino... Specific Chemical Substances § 721.2094 N,N′-di(alkyl heteromonocycle)amino chlorotriazine. (a) Chemical... as N,N′-di(alkyl heteromonocycle)amino chlorotriazine (PMN P-93-1369) is subject to reporting under...

40 CFR 721.2094 - N,N′-di(alkyl heteromonocycle)amino chlorotriazine.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false N,Nâ²-di(alkyl heteromonocycle)amino... Specific Chemical Substances § 721.2094 N,N′-di(alkyl heteromonocycle)amino chlorotriazine. (a) Chemical... as N,N′-di(alkyl heteromonocycle)amino chlorotriazine (PMN P-93-1369) is subject to reporting under...

21 CFR 866.3405 - Poliovirus serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Poliovirus serological reagents. 866.3405 Section 866.3405 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3405 Poliovirus...

21 CFR 866.3405 - Poliovirus serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Poliovirus serological reagents. 866.3405 Section 866.3405 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3405 Poliovirus...

21 CFR 866.3490 - Rhinovirus serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Rhinovirus serological reagents. 866.3490 Section 866.3490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3490 Rhinovirus...

21 CFR 866.3205 - Echovirus serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Echovirus serological reagents. 866.3205 Section 866.3205 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3205 Echovirus...

21 CFR 866.3405 - Poliovirus serological reagents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Poliovirus serological reagents. 866.3405 Section 866.3405 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3405 Poliovirus...

21 CFR 866.3490 - Rhinovirus serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Rhinovirus serological reagents. 866.3490 Section 866.3490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3490 Rhinovirus...

21 CFR 866.3020 - Adenovirus serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Adenovirus serological reagents. 866.3020 Section 866.3020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3020 Adenovirus...

21 CFR 866.3500 - Rickettsia serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Rickettsia serological reagents. 866.3500 Section 866.3500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3500 Rickettsia...

21 CFR 866.3395 - Norovirus serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Norovirus serological reagents. 866.3395 Section 866.3395 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3395 Norovirus...

21 CFR 866.3470 - Reovirus serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Reovirus serological reagents. 866.3470 Section 866.3470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3470 Reovirus...

21 CFR 866.3500 - Rickettsia serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Rickettsia serological reagents. 866.3500 Section 866.3500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3500 Rickettsia...

21 CFR 866.3500 - Rickettsia serological reagents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rickettsia serological reagents. 866.3500 Section 866.3500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3500 Rickettsia...

21 CFR 866.3020 - Adenovirus serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Adenovirus serological reagents. 866.3020 Section 866.3020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3020 Adenovirus...

21 CFR 866.3490 - Rhinovirus serological reagents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rhinovirus serological reagents. 866.3490 Section 866.3490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3490 Rhinovirus...

21 CFR 866.3020 - Adenovirus serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Adenovirus serological reagents. 866.3020 Section 866.3020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3020 Adenovirus...

21 CFR 866.3020 - Adenovirus serological reagents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Adenovirus serological reagents. 866.3020 Section 866.3020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3020 Adenovirus...

21 CFR 866.3500 - Rickettsia serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Rickettsia serological reagents. 866.3500 Section 866.3500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3500 Rickettsia...

21 CFR 866.3500 - Rickettsia serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Rickettsia serological reagents. 866.3500 Section 866.3500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3500 Rickettsia...

21 CFR 866.3120 - Chlamydia serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Chlamydia serological reagents. 866.3120 Section 866.3120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3120 Chlamydia...

21 CFR 866.3205 - Echovirus serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Echovirus serological reagents. 866.3205 Section 866.3205 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3205 Echovirus...

21 CFR 866.3490 - Rhinovirus serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Rhinovirus serological reagents. 866.3490 Section 866.3490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3490 Rhinovirus...

21 CFR 866.3120 - Chlamydia serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Chlamydia serological reagents. 866.3120 Section 866.3120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3120 Chlamydia...

21 CFR 866.3205 - Echovirus serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Echovirus serological reagents. 866.3205 Section 866.3205 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3205 Echovirus...

21 CFR 866.3205 - Echovirus serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Echovirus serological reagents. 866.3205 Section 866.3205 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3205 Echovirus...

21 CFR 866.3490 - Rhinovirus serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Rhinovirus serological reagents. 866.3490 Section 866.3490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3490 Rhinovirus...

21 CFR 866.3020 - Adenovirus serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Adenovirus serological reagents. 866.3020 Section 866.3020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3020 Adenovirus...

21 CFR 866.3395 - Norovirus serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Norovirus serological reagents. 866.3395 Section 866.3395 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3395 Norovirus...

21 CFR 866.3470 - Reovirus serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Reovirus serological reagents. 866.3470 Section 866.3470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3470 Reovirus...

21 CFR 866.3120 - Chlamydia serological reagents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Chlamydia serological reagents. 866.3120 Section 866.3120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3120 Chlamydia...

21 CFR 866.3120 - Chlamydia serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Chlamydia serological reagents. 866.3120 Section 866.3120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3120 Chlamydia...

21 CFR 866.3395 - Norovirus serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Norovirus serological reagents. 866.3395 Section 866.3395 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3395 Norovirus...

21 CFR 866.3120 - Chlamydia serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Chlamydia serological reagents. 866.3120 Section 866.3120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3120 Chlamydia...

21 CFR 866.3205 - Echovirus serological reagents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Echovirus serological reagents. 866.3205 Section 866.3205 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3205 Echovirus...

21 CFR 866.3405 - Poliovirus serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Poliovirus serological reagents. 866.3405 Section 866.3405 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3405 Poliovirus...

21 CFR 866.3470 - Reovirus serological reagents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Reovirus serological reagents. 866.3470 Section 866.3470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3470 Reovirus...

21 CFR 866.3405 - Poliovirus serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Poliovirus serological reagents. 866.3405 Section 866.3405 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3405 Poliovirus...

21 CFR 866.3470 - Reovirus serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Reovirus serological reagents. 866.3470 Section 866.3470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3470 Reovirus...

21 CFR 866.3470 - Reovirus serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Reovirus serological reagents. 866.3470 Section 866.3470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3470 Reovirus...

40 CFR 721.520 - Alanine, N-(2-carboxyethyl)-N-alkyl-, salt.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alanine, N-(2-carboxyethyl)-N-alkyl... Specific Chemical Substances § 721.520 Alanine, N-(2-carboxyethyl)-N-alkyl-, salt. (a) Chemical substance... alanine, N-(2-carboxyethyl)-N- alkyl-, salt (P-89-336) is subject to reporting under this section for the...

40 CFR 721.520 - Alanine, N-(2-carboxyethyl)-N-alkyl-, salt.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alanine, N-(2-carboxyethyl)-N-alkyl... Specific Chemical Substances § 721.520 Alanine, N-(2-carboxyethyl)-N-alkyl-, salt. (a) Chemical substance... alanine, N-(2-carboxyethyl)-N- alkyl-, salt (P-89-336) is subject to reporting under this section for the...

21 CFR 864.4010 - General purpose reagent.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false General purpose reagent. 864.4010 Section 864.4010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Specimen Preparation Reagents § 864.4010 General purpose...

21 CFR 864.4010 - General purpose reagent.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false General purpose reagent. 864.4010 Section 864.4010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Specimen Preparation Reagents § 864.4010 General purpose...

21 CFR 864.4010 - General purpose reagent.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false General purpose reagent. 864.4010 Section 864.4010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Specimen Preparation Reagents § 864.4010 General purpose...

Affimer proteins are versatile and renewable affinity reagents

PubMed Central

Tiede, Christian; Bedford, Robert; Heseltine, Sophie J; Smith, Gina; Wijetunga, Imeshi; Ross, Rebecca; AlQallaf, Danah; Roberts, Ashley PE; Balls, Alexander; Curd, Alistair; Hughes, Ruth E; Martin, Heather; Needham, Sarah R; Zanetti-Domingues, Laura C; Sadigh, Yashar; Peacock, Thomas P; Tang, Anna A; Gibson, Naomi; Kyle, Hannah; Platt, Geoffrey W; Ingram, Nicola; Taylor, Thomas; Coletta, Louise P; Manfield, Iain; Knowles, Margaret; Bell, Sandra; Esteves, Filomena; Maqbool, Azhar; Prasad, Raj K; Drinkhill, Mark; Bon, Robin S; Patel, Vikesh; Goodchild, Sarah A; Martin-Fernandez, Marisa; Owens, Ray J; Nettleship, Joanne E; Webb, Michael E; Harrison, Michael; Lippiat, Jonathan D; Ponnambalam, Sreenivasan; Peckham, Michelle; Smith, Alastair; Ferrigno, Paul Ko; Johnson, Matt; McPherson, Michael J; Tomlinson, Darren Charles

2017-01-01

Molecular recognition reagents are key tools for understanding biological processes and are used universally by scientists to study protein expression, localisation and interactions. Antibodies remain the most widely used of such reagents and many show excellent performance, although some are poorly characterised or have stability or batch variability issues, supporting the use of alternative binding proteins as complementary reagents for many applications. Here we report on the use of Affimer proteins as research reagents. We selected 12 diverse molecular targets for Affimer selection to exemplify their use in common molecular and cellular applications including the (a) selection against various target molecules; (b) modulation of protein function in vitro and in vivo; (c) labelling of tumour antigens in mouse models; and (d) use in affinity fluorescence and super-resolution microscopy. This work shows that Affimer proteins, as is the case for other alternative binding scaffolds, represent complementary affinity reagents to antibodies for various molecular and cell biology applications. DOI: http://dx.doi.org/10.7554/eLife.24903.001 PMID:28654419

40 CFR 721.644 - Amines, C12-14-tert-alkyl, sulfonates.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Amines, C12-14-tert-alkyl, sulfonates... Substances § 721.644 Amines, C12-14-tert-alkyl, sulfonates. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as amines, C12-14-tert-alkyl, sulfonates (PMN...

40 CFR 721.644 - Amines, C12-14-tert-alkyl, sulfonates.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Amines, C12-14-tert-alkyl, sulfonates... Substances § 721.644 Amines, C12-14-tert-alkyl, sulfonates. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as amines, C12-14-tert-alkyl, sulfonates (PMN...

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.

U. S. VETERINARY IMMUNE REAGENTS NETWORK: PROGRESS WITH POULTRY IMMUNE REAGENTS

USDA-ARS?s Scientific Manuscript database

This poster will present a progress report on the CSREES-funded NRI grant to support a broad community approach to systematically address the immunological reagent gap for the US veterinary immunology research community including for the following groups: ruminants (concentrating on cattle but inclu...

21 CFR 58.83 - Reagents and solutions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Reagents and solutions. 58.83 Section 58.83 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL GOOD... solutions. All reagents and solutions in the laboratory areas shall be labeled to indicate identity, titer...

Novel Reagents for Chemical Vapor Deposition of Intermetallic Alloys

DTIC Science & Technology

1994-10-31

ly bonded heterobimetallic intermediates with no alkyl exchange. Reacti n with A1H3 NMe3 yielded AI(CH2SiMe )3 . NMe3 and "Hf(CH,,SiMe_)H " warbon...3 were consistent with formation of a thermally unstable, alkyl bridged heterobimetallic complex, 1, present In a 5:1 ratio to the starting materials

Alkylation sensitivity screens reveal a conserved cross-species functionome

PubMed Central

Svilar, David; Dyavaiah, Madhu; Brown, Ashley R.; Tang, Jiang-bo; Li, Jianfeng; McDonald, Peter R.; Shun, Tong Ying; Braganza, Andrea; Wang, Xiao-hong; Maniar, Salony; St Croix, Claudette M.; Lazo, John S.; Pollack, Ian F.; Begley, Thomas J.; Sobol, Robert W.

2013-01-01

To identify genes that contribute to chemotherapy resistance in glioblastoma, we conducted a synthetic lethal screen in a chemotherapy-resistant glioblastoma derived cell line with the clinical alkylator temozolomide (TMZ) and an siRNA library tailored towards “druggable” targets. Select DNA repair genes in the screen were validated independently, confirming the DNA glycosylases UNG and MYH as well as MPG to be involved in the response to high dose TMZ. The involvement of UNG and MYH is likely the result of a TMZ-induced burst of reactive oxygen species. We then compared the human TMZ sensitizing genes identified in our screen with those previously identified from alkylator screens conducted in E. coli and S. cerevisiae. The conserved biological processes across all three species composes an Alkylation Functionome that includes many novel proteins not previously thought to impact alkylator resistance. This high-throughput screen, validation and cross-species analysis was then followed by a mechanistic analysis of two essential nodes: base excision repair (BER) DNA glycosylases (UNG, human and mag1, S. cerevisiae) and protein modification systems, including UBE3B and ICMT in human cells or pby1, lip22, stp22 and aim22 in S. cerevisiae. The conserved processes of BER and protein modification were dual targeted and yielded additive sensitization to alkylators in S. cerevisiae. In contrast, dual targeting of BER and protein modification genes in human cells did not increase sensitivity, suggesting an epistatic relationship. Importantly, these studies provide potential new targets to overcome alkylating agent resistance. PMID:23038810

Regulation of DNA Alkylation Damage Repair: Lessons and Therapeutic Opportunities

PubMed Central

Soll, Jennifer M.; Sobol, Robert W.; Mosammaparast, Nima

2016-01-01

Alkylation chemotherapy is one of the most widely used systemic therapies for cancer. While somewhat effective, clinical responses and toxicities of these agents are highly variable. A major contributing factor for this variability is the numerous distinct lesions that are created upon alkylation damage. These adducts activate multiple repair pathways. There is mounting evidence that the individual pathways function cooperatively, suggesting that coordinated regulation of alkylation repair is critical to prevent toxicity. Furthermore, some alkylating agents produce adducts that overlap with newly discovered methylation marks, making it difficult to distinguish between bona fide damaged bases and so called ‘epigenetic’ adducts. We discuss new efforts aimed at deciphering the mechanisms that regulate these repair pathways, emphasizing their implications for cancer chemotherapy. PMID:27816326

Palladium-catalyzed Heck-type cross-couplings of unactivated alkyl iodides.

PubMed

McMahon, Caitlin M; Alexanian, Erik J

2014-06-02

A palladium-catalyzed, intermolecular Heck-type coupling of alkyl iodides and alkenes is described. This process is successful with a variety of primary and secondary unactivated alkyl iodides as reaction partners, including those with hydrogen atoms in the β position. The mild catalytic conditions enable intermolecular C-C bond formations with a diverse set of alkyl iodides and alkenes, including substrates containing base- or nucleophile-sensitive functionality. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Highly enantioselective synthesis of γ-, δ-, and ε-chiral 1-alkanols via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA)–Cu- or Pd-catalyzed cross-coupling

PubMed Central

Xu, Shiqing; Oda, Akimichi; Kamada, Hirofumi; Negishi, Ei-ichi

2014-01-01

Despite recent advances of asymmetric synthesis, the preparation of enantiomerically pure (≥99% ee) compounds remains a challenge in modern organic chemistry. We report here a strategy for a highly enantioselective (≥99% ee) and catalytic synthesis of various γ- and more-remotely chiral alcohols from terminal alkenes via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction)–Cu- or Pd-catalyzed cross-coupling. ZACA–in situ oxidation of tert-butyldimethylsilyl (TBS)-protected ω-alkene-1-ols produced both (R)- and (S)-α,ω-dioxyfunctional intermediates (3) in 80–88% ee, which were readily purified to the ≥99% ee level by lipase-catalyzed acetylation through exploitation of their high selectivity factors. These α,ω-dioxyfunctional intermediates serve as versatile synthons for the construction of various chiral compounds. Their subsequent Cu-catalyzed cross-coupling with various alkyl (primary, secondary, tertiary, cyclic) Grignard reagents and Pd-catalyzed cross-coupling with aryl and alkenyl halides proceeded smoothly with essentially complete retention of stereochemical configuration to produce a wide variety of γ-, δ-, and ε-chiral 1-alkanols of ≥99% ee. The MαNP ester analysis has been applied to the determination of the enantiomeric purities of δ- and ε-chiral primary alkanols, which sheds light on the relatively undeveloped area of determination of enantiomeric purity and/or absolute configuration of remotely chiral primary alcohols. PMID:24912191

A review of reagents for fluorescence microscopy of cellular compartments and structures, part I: BacMam labeling and reagents for vesicular structures.

PubMed

Dolman, Nick J; Kilgore, Jason A; Davidson, Michael W

2013-07-01

Fluorescent labeling of vesicular structures in cultured cells, particularly for live cells, can be challenging for a number of reasons. The first challenge is to identify a reagent that will be specific enough where some structures have a number of potential reagents and others very few options. The emergence of BacMam constructs has allowed more easy-to-use choices. Presented here is a discussion of BacMam constructs as well as a review of commercially-available reagents for labeling vesicular structures in cells, including endosomes, peroxisomes, lysosomes, and autophagosomes, complete with a featured reagent for each structure, recommended protocol, troubleshooting guide, and example image. © 2013 by John Wiley & Sons, Inc.

Chiral Alkyl Halides: Underexplored Motifs in Medicine

PubMed Central

Gál, Bálint; Bucher, Cyril; Burns, Noah Z.

2016-01-01

While alkyl halides are valuable intermediates in synthetic organic chemistry, their use as bioactive motifs in drug discovery and medicinal chemistry is rare in comparison. This is likely attributable to the common misconception that these compounds are merely non-specific alkylators in biological systems. A number of chlorinated compounds in the pharmaceutical and food industries, as well as a growing number of halogenated marine natural products showing unique bioactivity, illustrate the role that chiral alkyl halides can play in drug discovery. Through a series of case studies, we demonstrate in this review that these motifs can indeed be stable under physiological conditions, and that halogenation can enhance bioactivity through both steric and electronic effects. Our hope is that, by placing such compounds in the minds of the chemical community, they may gain more traction in drug discovery and inspire more synthetic chemists to develop methods for selective halogenation. PMID:27827902

Selective sp3 C-H alkylation via polarity-match-based cross-coupling.

PubMed

Le, Chip; Liang, Yufan; Evans, Ryan W; Li, Ximing; MacMillan, David W C

2017-07-06

The functionalization of carbon-hydrogen (C-H) bonds is one of the most attractive strategies for molecular construction in organic chemistry. The hydrogen atom is considered to be an ideal coupling handle, owing to its relative abundance in organic molecules and its availability for functionalization at almost any stage in a synthetic sequence. Although many C-H functionalization reactions involve C(sp 3 )-C(sp 2 ) coupling, there is a growing demand for C-H alkylation reactions, wherein sp 3 C-H bonds are replaced with sp 3 C-alkyl groups. Here we describe a polarity-match-based selective sp 3 C-H alkylation via the combination of photoredox, nickel and hydrogen-atom transfer catalysis. This methodology simultaneously uses three catalytic cycles to achieve hydridic C-H bond abstraction (enabled by polarity matching), alkyl halide oxidative addition, and reductive elimination to enable alkyl-alkyl fragment coupling. The sp 3 C-H alkylation is highly selective for the α-C-H of amines, ethers and sulphides, which are commonly found in pharmaceutically relevant architectures. This cross-coupling protocol should enable broad synthetic applications in de novo synthesis and late-stage functionalization chemistry.

mTOR target NDRG1 confers MGMT-dependent resistance to alkylating chemotherapy.

PubMed

Weiler, Markus; Blaes, Jonas; Pusch, Stefan; Sahm, Felix; Czabanka, Marcus; Luger, Sebastian; Bunse, Lukas; Solecki, Gergely; Eichwald, Viktoria; Jugold, Manfred; Hodecker, Sibylle; Osswald, Matthias; Meisner, Christoph; Hielscher, Thomas; Rübmann, Petra; Pfenning, Philipp-Niklas; Ronellenfitsch, Michael; Kempf, Tore; Schnölzer, Martina; Abdollahi, Amir; Lang, Florian; Bendszus, Martin; von Deimling, Andreas; Winkler, Frank; Weller, Michael; Vajkoczy, Peter; Platten, Michael; Wick, Wolfgang

2014-01-07

A hypoxic microenvironment induces resistance to alkylating agents by activating targets in the mammalian target of rapamycin (mTOR) pathway. The molecular mechanisms involved in this mTOR-mediated hypoxia-induced chemoresistance, however, are unclear. Here we identify the mTOR target N-myc downstream regulated gene 1 (NDRG1) as a key determinant of resistance toward alkylating chemotherapy, driven by hypoxia but also by therapeutic measures such as irradiation, corticosteroids, and chronic exposure to alkylating agents via distinct molecular routes involving hypoxia-inducible factor (HIF)-1alpha, p53, and the mTOR complex 2 (mTORC2)/serum glucocorticoid-induced protein kinase 1 (SGK1) pathway. Resistance toward alkylating chemotherapy but not radiotherapy was dependent on NDRG1 expression and activity. In posttreatment tumor tissue of patients with malignant gliomas, NDRG1 was induced and predictive of poor response to alkylating chemotherapy. On a molecular level, NDRG1 bound and stabilized methyltransferases, chiefly O(6)-methylguanine-DNA methyltransferase (MGMT), a key enzyme for resistance to alkylating agents in glioblastoma patients. In patients with glioblastoma, MGMT promoter methylation in tumor tissue was not more predictive for response to alkylating chemotherapy in patients who received concomitant corticosteroids.

Aag DNA Glycosylase Promotes Alkylation-Induced Tissue Damage Mediated by Parp1

PubMed Central

Calvo, Jennifer A.; Moroski-Erkul, Catherine A.; Lake, Annabelle; Eichinger, Lindsey W.; Shah, Dharini; Jhun, Iny; Limsirichai, Prajit; Bronson, Roderick T.; Christiani, David C.; Meira, Lisiane B.; Samson, Leona D.

2013-01-01

Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER) is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG) mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag −/− mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage. PMID:23593019

mTOR target NDRG1 confers MGMT-dependent resistance to alkylating chemotherapy

PubMed Central

Weiler, Markus; Blaes, Jonas; Pusch, Stefan; Sahm, Felix; Czabanka, Marcus; Luger, Sebastian; Bunse, Lukas; Solecki, Gergely; Eichwald, Viktoria; Jugold, Manfred; Hodecker, Sibylle; Osswald, Matthias; Meisner, Christoph; Hielscher, Thomas; Rübmann, Petra; Pfenning, Philipp-Niklas; Ronellenfitsch, Michael; Kempf, Tore; Schnölzer, Martina; Abdollahi, Amir; Lang, Florian; Bendszus, Martin; von Deimling, Andreas; Winkler, Frank; Weller, Michael; Vajkoczy, Peter; Platten, Michael; Wick, Wolfgang

2014-01-01

A hypoxic microenvironment induces resistance to alkylating agents by activating targets in the mammalian target of rapamycin (mTOR) pathway. The molecular mechanisms involved in this mTOR-mediated hypoxia-induced chemoresistance, however, are unclear. Here we identify the mTOR target N-myc downstream regulated gene 1 (NDRG1) as a key determinant of resistance toward alkylating chemotherapy, driven by hypoxia but also by therapeutic measures such as irradiation, corticosteroids, and chronic exposure to alkylating agents via distinct molecular routes involving hypoxia-inducible factor (HIF)-1alpha, p53, and the mTOR complex 2 (mTORC2)/serum glucocorticoid-induced protein kinase 1 (SGK1) pathway. Resistance toward alkylating chemotherapy but not radiotherapy was dependent on NDRG1 expression and activity. In posttreatment tumor tissue of patients with malignant gliomas, NDRG1 was induced and predictive of poor response to alkylating chemotherapy. On a molecular level, NDRG1 bound and stabilized methyltransferases, chiefly O6-methylguanine-DNA methyltransferase (MGMT), a key enzyme for resistance to alkylating agents in glioblastoma patients. In patients with glioblastoma, MGMT promoter methylation in tumor tissue was not more predictive for response to alkylating chemotherapy in patients who received concomitant corticosteroids. PMID:24367102

Selective sp3 C-H alkylation via polarity-match-based cross-coupling

NASA Astrophysics Data System (ADS)

Le, Chip; Liang, Yufan; Evans, Ryan W.; Li, Ximing; MacMillan, David W. C.

2017-07-01

The functionalization of carbon-hydrogen (C-H) bonds is one of the most attractive strategies for molecular construction in organic chemistry. The hydrogen atom is considered to be an ideal coupling handle, owing to its relative abundance in organic molecules and its availability for functionalization at almost any stage in a synthetic sequence. Although many C-H functionalization reactions involve C(sp3)-C(sp2) coupling, there is a growing demand for C-H alkylation reactions, wherein sp3 C-H bonds are replaced with sp3 C-alkyl groups. Here we describe a polarity-match-based selective sp3 C-H alkylation via the combination of photoredox, nickel and hydrogen-atom transfer catalysis. This methodology simultaneously uses three catalytic cycles to achieve hydridic C-H bond abstraction (enabled by polarity matching), alkyl halide oxidative addition, and reductive elimination to enable alkyl-alkyl fragment coupling. The sp3 C-H alkylation is highly selective for the α-C-H of amines, ethers and sulphides, which are commonly found in pharmaceutically relevant architectures. This cross-coupling protocol should enable broad synthetic applications in de novo synthesis and late-stage functionalization chemistry.

Rapid Peptide Reagent Isolation in a Disposable Microfluidic Cartridge

DTIC Science & Technology

2010-09-01

Rapid Peptide Reagent Isolation in a Disposable Microfluidic Cartridge by Dimitra N. Stratis-Cullum, Joshua M. Kogot, and Paul M...Adelphi, MD 20783-1197 ARL-TR-5357 September 2010 Rapid Peptide Reagent Isolation in a Disposable Microfluidic Cartridge Dimitra N...Peptide Reagent Isolation in a Disposable Microfluidic Cartridge 5a. CONTRACT NUMBER DAAD19-03-D-004 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER

The Chemiluminescence of Organometallic Compounds

NASA Astrophysics Data System (ADS)

Tolstikov, Genrikh A.; Bulgakov, Ramil G.; Kazakov, Valeri P.

1985-11-01

Studies on the liquid-phase and gas-phase reactions of organometallic compounds accompanied by the emission of light are described systematically and discussed. The influence of the magnetic field on the chemiluminescence of Grignard reagents and the study of the electrochemiluminescence of solutions of organometallic compounds are examined. The ways leading to further development of the field of the chemiluminescence of organometallic compounds and certain possible applications of the phenomenon in the monitoring of industrial processes are discussed. The bibliography includes 80 references.

Non-aqueous electrolyte for high voltage rechargeable magnesium batteries

DOEpatents

Doe, Robert Ellis; Lane, George Hamilton; Jilek, Robert E; Hwang, Jaehee

2015-02-10

An electrolyte for use in electrochemical cells is provided. The properties of the electrolyte include high conductivity, high Coulombic efficiency, and an electrochemical window that can exceed 3.5 V vs. Mg/Mg.sup.+2. The use of the electrolyte promotes the electrochemical deposition and dissolution of Mg without the use of any Grignard reagents, other organometallic materials, tetraphenyl borate, or tetrachloroaluminate derived anions. Other Mg-containing electrolyte systems that are expected to be suitable for use in secondary batteries are also described.

Physically absorbable reagents-collectors in elementary flotation

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

S.A. Kondrat'ev; I.G. Bochkarev

2007-09-15

Based on the reviewed researches held at the Institute of Mining, Siberian Branch, Russian Academy of Sciences, the effect of physically absorbable reagents-collectors on formation of a flotation complex and its stability in turbulent pulp flows in flotation machines of basic types is considered. The basic requirements for physically absorbable reagents-collectors at different flotation stages are established.

Stibathiolanes: Synthesis, solid state structure, and solution behavior

NASA Astrophysics Data System (ADS)

Fisher, Richard A.; Nielsen, Ralph B.; Davis, William M.; Buchwald, Stephen L.

1990-06-01

Interest in organometallic compounds of the main group metals has recently grown tremendously, due in part to the wide variety of applications of these compounds in the materials sciences. Despite this new activity, the synthetic strategies for main group organometallics have remained relatively undeveloped. The majority of syntheses of these compounds involve classical metathesis reactions between a main group halide and an organometallic compound such as an organolithium or Grignard reagent and are limited by a lack of selectivity and by the availability of suitable organometallic precursors. The latter limitation is severe for main group metallacycles because of the paucity of suitable 1, n(n=3,4,5)-dianionic reagents or their equivalents, which are most often used for the synthesis of this class of molecules.

A One-Pot Synthesis of m-Terphenyls: A Guided Exploration of Reaction Chemistry, Chromatography, and Spectroscopy. A Miniproject for the Advanced Organic Chemistry Laboratory

NASA Astrophysics Data System (ADS)

Anam, Kishorekumar T.; Curtis, Michael P.; Irfan, Muhammad J.; Johnson, Michael P.; Royer, Andrew P.; Shahmohammadi, Kianor; Vinod, Thottumkara K.

2002-05-01

This four-week project-based laboratory exercise, developed for advanced organic chemistry students, involves a one-pot synthesis of m-terphenyls. Chemistry of aryl diazonium salts and Grignard reagents and reactivity of aryne intermediates toward nucleophilic reagents form the reaction chemistry basis for the project. The project exposes students to a number of important laboratory techniques (thin-layer chromatography, gas chromatography-mass spectrometry, and column chromatography) for monitoring reaction progress and product isolation. A variety of spectroscopic techniques, including IR, 1H NMR, 13C NMR, and attached proton test are used for product characterization. Students are also introduced to a useful empirical relationship to help predict (with considerable accuracy) the 13C chemical shift values of carbon atoms of substituted benzenes.

21 CFR 864.1860 - Immunohistochemistry reagents and kits.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Immunohistochemistry reagents and kits. (a) Identification. Immunohistochemistry test systems (IHC's) are in vitro... performance claims, which may be packaged with ancillary reagents in kits. Their intended use is to identify, by immunological techniques, antigens in tissues or cytologic specimens. Similar devices intended for...

21 CFR 864.1860 - Immunohistochemistry reagents and kits.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Immunohistochemistry reagents and kits. (a) Identification. Immunohistochemistry test systems (IHC's) are in vitro... performance claims, which may be packaged with ancillary reagents in kits. Their intended use is to identify, by immunological techniques, antigens in tissues or cytologic specimens. Similar devices intended for...

IN-PLACE REGENERATION OF GAC USING FENTON'S REAGENTS

EPA Science Inventory

This paper evaluates the feasibility of using Fenton’s reagents for in-place recovery of spent granular activated carbon (GAC). Fenton’s reagents are cycled through spent GAC to degrade sorbed chlorinated hydrocarbons with little loss of carbon capacity. Seven chlorinated compou...

21 CFR 866.3370 - Mycobacterium tuberculosis immunofluorescent reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Mycobacterium tuberculosis immunofluorescent reagents. 866.3370 Section 866.3370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents...

21 CFR 866.3370 - Mycobacterium tuberculosis immunofluorescent reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Mycobacterium tuberculosis immunofluorescent reagents. 866.3370 Section 866.3370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents...

21 CFR 866.3370 - Mycobacterium tuberculosis immunofluorescent reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Mycobacterium tuberculosis immunofluorescent reagents. 866.3370 Section 866.3370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents...

21 CFR 866.3370 - Mycobacterium tuberculosis immunofluorescent reagents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Mycobacterium tuberculosis immunofluorescent reagents. 866.3370 Section 866.3370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents...

21 CFR 866.3370 - Mycobacterium tuberculosis immunofluorescent reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Mycobacterium tuberculosis immunofluorescent reagents. 866.3370 Section 866.3370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents...

Alkyl gallates, intensifiers of beta-lactam susceptibility in methicillin-resistant Staphylococcus aureus.

PubMed

Shibata, Hirofumi; Kondo, Kyoko; Katsuyama, Ryo; Kawazoe, Kazuyoshi; Sato, Yoichi; Murakami, Kotaro; Takaishi, Yoshihisa; Arakaki, Naokatu; Higuti, Tomihiko

2005-02-01

We found that ethyl gallate purified from a dried pod of tara (Caesalpinia spinosa) intensified beta-lactam susceptibility in methicillin-resistant and methicillin-sensitive strains of Staphylococcus aureus (MRSA and MSSA strains, respectively). This compound and several known alkyl gallates were tested with MRSA and MSSA strains to gain new insights into their structural functions in relation to antimicrobial and beta-lactam susceptibility-intensifying activities. The maximum activity of alkyl gallates against MRSA and MSSA strains occurred at 1-nonyl and 1-decyl gallate, with an MIC at which 90% of the isolates tested were inhibited of 15.6 microg/ml. At concentrations lower than the MIC, alkyl gallates synergistically elevated the susceptibility of MRSA and MSSA strains to beta-lactam antibiotics. Such a synergistic activity of the alkyl gallates appears to be specific for beta-lactam antibiotics, because no significant changes were observed in the MICs of other classes of antibiotics examined in this study. The length of the alkyl chain was also associated with the modifying activity of the alkyl gallates, and the optimum length was C5 to C6. The present work clearly demonstrates that the length of the alkyl chain has a key role in the elevation of susceptibility to beta-lactam antibiotics.

40 CFR 721.10517 - Alkyl methacrylates, polymer with substituted carbomonocycle, hydroxymethyl acrylamide and...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl methacrylates, polymer with... Substances § 721.10517 Alkyl methacrylates, polymer with substituted carbomonocycle, hydroxymethyl acrylamide... reporting. (1) The chemical substance identified generically as alkyl methacrylates, polymer with...

Ultrasonic Relaxation Study of 1-Alkyl-3-methylimidazolium-Based Room-Temperature Ionic Liquids: Probing the Role of Alkyl Chain Length in the Cation.

PubMed

Zorębski, Michał; Zorębski, Edward; Dzida, Marzena; Skowronek, Justyna; Jężak, Sylwia; Goodrich, Peter; Jacquemin, Johan

2016-04-14

Ultrasound absorption spectra of four 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imides were determined as a function of the alkyl chain length on the cation from 1-propyl to 1-hexyl from 293.15 to 323.15 K at ambient pressure. Herein, the ultrasound absorption measurements were carried out using a standard pulse technique within a frequency range from 10 to 300 MHz. Additionally, the speed of sound, density, and viscosity have been measured. The presence of strong dissipative processes during the ultrasound wave propagation was found experimentally, i.e., relaxation processes in the megahertz range were observed for all compounds over the whole temperature range. The relaxation spectra (both relaxation amplitude and relaxation frequency) were shown to be dependent on the alkyl side chain length of the 1-alkyl-3-methylimidazolium ring. In most cases, a single-Debye model described the absorption spectra very well. However, a comparison of the determined spectra with the spectra of a few other imidazolium-based ionic liquids reported in the literature (in part recalculated in this work) shows that the complexity of the spectra increases rapidly with the elongation of the alkyl chain length on the cation. This complexity indicates that both the volume viscosity and the shear viscosity are involved in relaxation processes even in relatively low frequency ranges. As a consequence, the sound velocity dispersion is present at relatively low megahertz frequencies.

Systematic trends in photonic reagent induced reactions in a homologous chemical family.

PubMed

Tibbetts, Katharine Moore; Xing, Xi; Rabitz, Herschel

2013-08-29

The growing use of ultrafast laser pulses to induce chemical reactions prompts consideration of these pulses as "photonic reagents" in analogy to chemical reagents. This work explores the prospect that photonic reagents may affect systematic trends in dissociative ionization reactions of a homologous family of halomethanes, much as systematic outcomes are often observed for reactions between homologous families of chemical reagents and chemical substrates. The experiments in this work with photonic reagents of varying pulse energy and linear spectral chirp reveal systematic correlations between observable ion yields and the following set of natural variables describing the substrate molecules: the ionization energy of the parent molecule, the appearance energy of each fragment ion, and the relative strength of carbon-halogen bonds in molecules containing two different halogens. The results suggest that reactions induced by photonic reagents exhibit systematic behavior analogous to that observed in reactions driven by chemical reagents, which provides a basis to consider empirical "rules" for predicting the outcomes of photonic reagent induced reactions.

A reagent strip for measuring the specific gravity of urine.

PubMed

Burkhardt, A E; Johnston, K G; Waszak, C E; Jackson, C E; Shafer, S R

1982-10-01

A solid-phase reagent for determination of urinary specific gravity (relative density) is described. This reagent strip, similar to others in the "N-Multistix" series (Ames), contains a polyacid whose acidity is sensitive to the ionic concentration in the urine in which it is immersed. As the acidity of the polyacid changes, pH changes are detected by a pH indicator within the reagent strip. In comparison studies, 84.4% of relative densities as measured with these reagent strips were within 0.005 of the corresponding results with a total-solids meter, and 89.9% were within 0.005 of the corresponding urinometer results. Adding a correction of +0.005 to the reagent-strip results for urines with high pH increased the percentage of results within 0.005 of the comparison method to 90.7% (TS meter) and 92.9% (urinometer). Lot-to-lot variability and reader-to-reader variability were both low. Reagent strip results are not affected by glucose, may be increased by albumin, and correlate with urea concentrations.

21 CFR 866.3850 - Trichinella spiralis serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Trichinella spiralis serological reagents. 866.3850 Section 866.3850 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3850...

21 CFR 866.3400 - Parainfluenza virus serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Parainfluenza virus serological reagents. 866.3400 Section 866.3400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3400 Parainfluenza...

21 CFR 866.3250 - Erysipelothrix rhusiopathiae serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Erysipelothrix rhusiopathiae serological reagents. 866.3250 Section 866.3250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3250...

21 CFR 866.3270 - Flavobacterium spp. serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Flavobacterium spp. serological reagents. 866.3270 Section 866.3270 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3270...

21 CFR 866.3125 - Citrobacter spp. serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Citrobacter spp. serological reagents. 866.3125 Section 866.3125 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3125 Citrobacter...

21 CFR 866.3600 - Schistosoma spp. serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Schistosoma spp. serological reagents. 866.3600 Section 866.3600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3600 Schistosoma...

21 CFR 866.3140 - Corynebacterium spp. serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Corynebacterium spp. serological reagents. 866.3140 Section 866.3140 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3140...

21 CFR 866.3135 - Coccidioides immitis serological reagents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Coccidioides immitis serological reagents. 866.3135 Section 866.3135 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3135...

21 CFR 866.3280 - Francisella tularensis serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Francisella tularensis serological reagents. 866.3280 Section 866.3280 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3280...

21 CFR 866.3135 - Coccidioides immitis serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Coccidioides immitis serological reagents. 866.3135 Section 866.3135 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3135...

21 CFR 866.3375 - Mycoplasma spp. serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Mycoplasma spp. serological reagents. 866.3375 Section 866.3375 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3375 Mycoplasma...

21 CFR 866.3270 - Flavobacterium spp. serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Flavobacterium spp. serological reagents. 866.3270 Section 866.3270 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3270...

21 CFR 866.3680 - Sporothrix schenckii serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Sporothrix schenckii serological reagents. 866.3680 Section 866.3680 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3680...

21 CFR 866.3330 - Influenza virus serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Influenza virus serological reagents. 866.3330 Section 866.3330 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3330 Influenza...

21 CFR 866.3415 - Pseudomonas spp. serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Pseudomonas spp. serological reagents. 866.3415 Section 866.3415 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3415 Pseudomonas...

21 CFR 866.3300 - Haemophilus spp. serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Haemophilus spp. serological reagents. 866.3300 Section 866.3300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3300 Haemophilus...

21 CFR 866.3550 - Salmonella spp. serological reagents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Salmonella spp. serological reagents. 866.3550 Section 866.3550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3550 Salmonella...

21 CFR 866.3460 - Rabiesvirus immuno-fluorescent reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Rabiesvirus immuno-fluorescent reagents. 866.3460 Section 866.3460 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3460 Rabiesvirus...

21 CFR 866.3780 - Toxoplasma gondii serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Toxoplasma gondii serological reagents. 866.3780 Section 866.3780 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3780 Toxoplasma...

21 CFR 866.3065 - Bordetella spp. serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Bordetella spp. serological reagents. 866.3065 Section 866.3065 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3065 Bordetella...

21 CFR 866.3400 - Parainfluenza virus serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Parainfluenza virus serological reagents. 866.3400 Section 866.3400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3400 Parainfluenza...

21 CFR 866.3350 - Leptospira spp. serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Leptospira spp. serological reagents. 866.3350 Section 866.3350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3350 Leptospira...

21 CFR 866.3110 - Campylobacter fetus serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Campylobacter fetus serological reagents. 866.3110 Section 866.3110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3110 Campylobacter...

21 CFR 866.3220 - Entamoeba histolytica serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Entamoeba histolytica serological reagents. 866.3220 Section 866.3220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3220...

21 CFR 866.3110 - Campylobacter fetus serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Campylobacter fetus serological reagents. 866.3110 Section 866.3110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3110 Campylobacter...