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Sample records for 18f-labelled pyridine-based alkylating

  1. 18F-labeling using click cycloadditions.

    PubMed

    Kettenbach, Kathrin; Schieferstein, Hanno; Ross, Tobias L

    2014-01-01

    Due to expanding applications of positron emission tomography (PET) there is a demand for developing new techniques to introduce fluorine-18 (t 1/2 = 109.8 min). Considering that most novel PET tracers are sensitive biomolecules and that direct introduction of fluorine-18 often needs harsh conditions, the insertion of (18)F in those molecules poses an exceeding challenge. Two major challenges during (18)F-labeling are a regioselective introduction and a fast and high yielding way under mild conditions. Furthermore, attention has to be paid to functionalities, which are usually present in complex structures of the target molecule. The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) and several copper-free click reactions represent such methods for radiolabeling of sensitive molecules under the above-mentioned criteria. This minireview will provide a quick overview about the development of novel (18)F-labeled prosthetic groups for click cycloadditions and will summarize recent trends in copper-catalyzed and copper-free click (18)F-cycloadditions. PMID:25003110

  2. One-step (18)F labeling of biomolecules using organotrifluoroborates.

    PubMed

    Liu, Zhibo; Lin, Kuo-Shyan; Bénard, François; Pourghiasian, Maral; Kiesewetter, Dale O; Perrin, David M; Chen, Xiaoyuan

    2015-09-01

    Herein we present a general protocol for the functionalization of biomolecules with an organotrifluoroborate moiety so that they can be radiolabeled with aqueous (18)F fluoride ((18)F(-)) and used for positron emission tomography (PET) imaging. Among the β(+)-emitting radionuclides, fluorine-18 ((18)F) is the isotope of choice for PET, and it is produced, on-demand, in many hospitals worldwide. Organotrifluoroborates can be (18)F-labeled in one step in aqueous conditions via (18)F-(19)F isotope exchange. This protocol features a recently designed ammoniomethyltrifluoroborate, and it describes the following: (i) a synthetic strategy that affords modular synthesis of radiolabeling precursors via a copper-catalyzed 'click' reaction; and (ii) a one-step (18)F-labeling method that obviates the need for HPLC purification. Within 30 min, (18)F-labeled PET imaging probes, such as peptides, can be synthesized in good chemical and radiochemical purity (>98%), satisfactory radiochemical yield of 20-35% (n > 20, non-decay corrected) and high specific activity of 40-111 GBq/μmol (1.1-3.0 Ci/μmol). The entire procedure, including the precursor preparation and (18)F radiolabeling, takes 7-10 d. PMID:26313478

  3. 18F-Labelled Intermediates for Radiosynthesis by Modular Build-Up Reactions: Newer Developments

    PubMed Central

    Ermert, Johannes

    2014-01-01

    This brief review gives an overview of newer developments in 18F-chemistry with the focus on small 18F-labelled molecules as intermediates for modular build-up syntheses. The short half-life (<2 h) of the radionuclide requires efficient syntheses of these intermediates considering that multistep syntheses are often time consuming and characterized by a loss of yield in each reaction step. Recent examples of improved synthesis of 18F-labelled intermediates show new possibilities for no-carrier-added ring-fluorinated arenes, novel intermediates for tri[18F]fluoromethylation reactions, and 18F-fluorovinylation methods. PMID:25343144

  4. Tetrazine-trans-cyclooctene ligation for the rapid construction of 18F labeled probes.

    PubMed

    Li, Zibo; Cai, Hancheng; Hassink, Matthew; Blackman, Melissa L; Brown, Richard C D; Conti, Peter S; Fox, Joseph M

    2010-11-14

    A radiolabeling method for bioconjugation based on the Diels-Alder reaction between 3,6-diaryl-s-tetrazines and an (18)F-labeled trans-cyclooctene is described. The reaction proceeds with exceptionally fast rates, making it an effective conjugation method within seconds at low micromolar concentrations.

  5. Convergent synthesis and evaluation of 18F-labeled azulenic COX2 probes for cancer imaging

    PubMed Central

    Nolting, Donald D.; Nickels, Michael; Tantawy, Mohammed N.; Yu, James Y. H.; Xie, Jingping; Peterson, Todd E.; Crews, Brenda C.; Marnett, Larry; Gore, John C.; Pham, Wellington

    2013-01-01

    The overall objectives of this research are to (i) develop azulene-based positron emission tomography (PET) probes and (ii) image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel 18F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8 + 2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional 18F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an 18F labeling strategy that employed a much milder phosphate buffer. The 18F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for cancer imaging and

  6. Enhanced Aqueous Suzuki–Miyaura Coupling Allows Site-Specific Polypeptide 18F-Labeling

    PubMed Central

    2013-01-01

    The excesses of reagents used in protein chemistry are often incompatible with the reduced or even inverse stoichiometries used for efficient radiolabeling. Analysis and screening of aqueous Pd(0) ligand systems has revealed the importance of a guanidine core and the discovery of 1,1-dimethylguanidine as an enhanced ligand for aqueous Suzuki–Miyaura cross-coupling. This novel Pd catalyst system has now allowed the labeling of small molecules, peptides, and proteins with the fluorine-18 prosthetic [18F]4-fluorophenylboronic acid. These findings now enable site-specific protein 18F-labeling under biologically compatible conditions using a metal-triggered reaction. PMID:23991754

  7. Efficient 18F labeling of cysteine-containing peptides and proteins using tetrazine-trans-cyclooctene ligation.

    PubMed

    Liu, Shuanglong; Hassink, Matthew; Selvaraj, Ramajeyam; Yap, Li-Peng; Park, Ryan; Wang, Hui; Chen, Xiaoyuan; Fox, Joseph M; Li, Zibo; Conti, Peter S

    2013-01-01

    18F positron emission tomography (PET) has a number of attributes that make it clinically attractive, including nearly 100% positron efficiency, very high specific radioactivity, and a short half-life of ≈ 110 minutes. However, the short half-life of 18F and the poor nucleophilicity of fluoride introduce challenges for the incorporation of 18F into complex molecules. Recently, the tetrazine-trans-cyclooctene ligation was introduced as a novel 18F labeling method that proceeds with fast reaction rates without catalysis. Herein we report an efficient method for 18F labeling of free cysteines of peptides and proteins based on sequential ligation with a bifunctional tetrazinyl-maleimide and an 18F-labeled trans-cyclooctene. The newly developed method was tested for site-specific labeling of both c(RGDyC) peptide and vascular endothelial growth factor (VEGF)-SH protein. Starting with 4 mCi of 18F-trans-cyclooctene and only 10 μg of tetrazine-RGD (80-100 μM) or 15 μg of tetrazine-VEGF (6.0 μM), 18F-labeled RGD peptide and VEGF protein could be obtained within 5 minutes in 95% yield and 75% yield, respectively. The obtained tracers were then evaluated in mice. In conclusion, a highly efficient method has been developed for site-specific 18F labeling of cysteine-containing peptides and proteins. The special characteristics of the tetrazine-trans-cyclooctene ligation provide unprecedented opportunities to synthesize 18F-labeled probes with high specific activity for PET applications.

  8. (18)F-Labeling of Mannan for Inflammation Research with Positron Emission Tomography.

    PubMed

    Li, Xiang-Guo; Hagert, Cecilia; Siitonen, Riikka; Virtanen, Helena; Sareila, Outi; Liljenbäck, Heidi; Tuisku, Jouni; Knuuti, Juhani; Bergman, Jörgen; Holmdahl, Rikard; Roivainen, Anne

    2016-09-01

    Recently mannan from Saccharomyces cerevisiae has been shown to be able to induce psoriasis and psoriatic arthritis in mice, and the phenotypes resemble the corresponding human diseases. To investigate the pathological processes, we set out to label mannan with fluorine-18 ((18)F) and study the (18)F-labeled mannan in vitro and in vivo with positron emission tomography (PET). Accordingly, mannan has been transformed into (18)F-fluoromannan with (18)F-bicyclo[6.1.0]nonyne. In mouse aorta, the binding of [(18)F]fluoromannan to the atherosclerotic lesions was clearly visualized and was significantly higher compared to blocking assays (P < 0.001) or healthy mouse aorta (P < 0.001). In healthy rats the [(18)F]fluoromannan radioactivity accumulated largely in the macrophage-rich organs such as liver, spleen, and bone marrow and the excess excreted in urine. Furthermore, the corresponding (19)F-labeled mannan has been used to induce psoriasis and psoriatic arthritis in mice, which indicates that the biological function of mannan is preserved after the chemical modifications. PMID:27660685

  9. (18)F-Labeling of Mannan for Inflammation Research with Positron Emission Tomography.

    PubMed

    Li, Xiang-Guo; Hagert, Cecilia; Siitonen, Riikka; Virtanen, Helena; Sareila, Outi; Liljenbäck, Heidi; Tuisku, Jouni; Knuuti, Juhani; Bergman, Jörgen; Holmdahl, Rikard; Roivainen, Anne

    2016-09-01

    Recently mannan from Saccharomyces cerevisiae has been shown to be able to induce psoriasis and psoriatic arthritis in mice, and the phenotypes resemble the corresponding human diseases. To investigate the pathological processes, we set out to label mannan with fluorine-18 ((18)F) and study the (18)F-labeled mannan in vitro and in vivo with positron emission tomography (PET). Accordingly, mannan has been transformed into (18)F-fluoromannan with (18)F-bicyclo[6.1.0]nonyne. In mouse aorta, the binding of [(18)F]fluoromannan to the atherosclerotic lesions was clearly visualized and was significantly higher compared to blocking assays (P < 0.001) or healthy mouse aorta (P < 0.001). In healthy rats the [(18)F]fluoromannan radioactivity accumulated largely in the macrophage-rich organs such as liver, spleen, and bone marrow and the excess excreted in urine. Furthermore, the corresponding (19)F-labeled mannan has been used to induce psoriasis and psoriatic arthritis in mice, which indicates that the biological function of mannan is preserved after the chemical modifications.

  10. Sultone opening with [18F]fluoride: an efficient 18F-labelling strategy for PET imaging.

    PubMed

    Schmitt, Sébastien; Bouteiller, Cédric; Barré, Louisa; Perrio, Cécile

    2011-11-01

    Sultones were subject to ring opening by nucleophilic attack with [(18)F]fluoride to afford easily purified (18)F-labelled hydrophilic sulfonated products in high yields. A two-step sequence including radiofluorination and coupling to lysine was then developed from a bis-sultone precursor as a model approach for the labelling of biopolymers.

  11. Synthesis of [18F]-labelled Maltose Derivatives as PET Tracers for Imaging Bacterial Infection

    PubMed Central

    Namavari, Mohammad; Gowrishankar, Gayatri; Hoehne, Aileen; Jouannot, Erwan; Gambhir, Sanjiv S

    2015-01-01

    Purpose To develop novel positron emission tomography (PET) agents for visualization and therapy monitoring of bacterial infections. Procedures It is known that maltose and maltodextrins are energy sources for bacteria. Hence, 18F-labelled maltose derivatives could be a valuable tool for imaging bacterial infections. We have developed methods to synthesize 4-O-(α-D-glucopyranosyl)-6-deoxy-6-[18F]fluoro-D-glucopyranoside (6-[18F]fluoromaltose) and 4-O-(α-D-glucopyranosyl)-1-deoxy-1-[18F]fluoro-D-glucopyranoside (1-[18F]fluoromaltose) as bacterial infection PET imaging agents. 6-[18F]fluoromaltose was prepared from precursor 1,2,3-tri-O-acetyl-4-O-(2′,3′,-di-O-acetyl-4′,6′-benzylidene-α-D-glucopyranosyl)-6-deoxy-6-nosyl-D-glucopranoside (5). The synthesis involved the radio-fluorination of 5 followed by acidic and basic hydrolysis to give 6-[18F]fluoromaltose. In an analogous procedure, 1-[18F]fluoromaltose was synthesized from 2,3, 6-tri-O-acetyl-4-O-(2′,3′,4′,6-tetra-O-acetyl-α-D-glucopyranosyl)-1-deoxy-1-O-triflyl-D-glucopranoside (9). Stability of 6-[18F]fluoromaltose in phosphate-buffered saline (PBS) and human and mouse serum at 37 °C was determined. Escherichia coli uptake of 6-[18F]fluoromaltose was examined. Results A reliable synthesis of 1- and 6-[18F]fluoromaltose has been accomplished with 4–6 and 5–8 % radiochemical yields, respectively (decay-corrected with 95 % radiochemical purity). 6-[18F]fluoromaltose was sufficiently stable over the time span needed for PET studies (~96 % intact compound after 1-h and ~65 % after 2-h incubation in serum). Bacterial uptake experiments indicated that E. coli transports 6-[18F]fluoromaltose. Competition assays showed that the uptake of 6-[18F]fluoromaltose was completely blocked by co-incubation with 1 mM of the natural substrate maltose. Conclusion We have successfully synthesized 1- and 6-[18F]fluoromaltose via direct fluorination of appropriate protected maltose precursors. Bacterial uptake

  12. (18) F-labeled folic acid derivatives for imaging of the folate receptor via positron emission tomography.

    PubMed

    Schieferstein, Hanno; Ross, Tobias L

    2013-01-01

    The folate receptor (FR) is already known as a proven target in diagnostics and therapy of cancer. Furthermore, the FR is involved in inflammatory and autoimmune diseases. The major advantage as a valuable target is its strongly limited expression in healthy tissues. Over the past two decades, several folic acid-based radiopharmaceuticals addressing the FR have been developed, and some of them show great potential for applications in clinical routine. However, most of these radiofolates were developed for single photon emission computed tomography imaging, and only a few can be used for positron emission tomography (PET) imaging. The development of suitable (18) F-labeled derivatives for PET imaging of the FR has aroused great interest and recent studies revealed very promising candidates for further development and translation into human applications. In this review, we focus on the development of (18) F-labeled folic acid derivatives for PET imaging of the FR and discuss various radiochemical strategies and approaches towards (18) F-folates. Besides radiochemistry and (18) F-labeling, we briefly look into the crucial pharmacological parameters and the preclinical in vivo performance of those (18) F-folates.

  13. (18)F-labeled positron emission tomographic radiopharmaceuticals in oncology: an overview of radiochemistry and mechanisms of tumor localization.

    PubMed

    Vallabhajosula, Shankar

    2007-11-01

    Molecular imaging is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in a living system. At present, positron emission tomography/computed tomography (PET/CT) is one the most rapidly growing areas of medical imaging, with many applications in the clinical management of patients with cancer. Although [(18)F]fluorodeoxyglucose (FDG)-PET/CT imaging provides high specificity and sensitivity in several kinds of cancer and has many applications, it is important to recognize that FDG is not a "specific" radiotracer for imaging malignant disease. Highly "tumor-specific" and "tumor cell signal-specific" PET radiopharmaceuticals are essential to meet the growing demand of radioisotope-based molecular imaging technology. In the last 15 years, many alternative PET tracers have been proposed and evaluated in preclinical and clinical studies to characterize the tumor biology more appropriately. The potential clinical utility of several (18)F-labeled radiotracers (eg, fluoride, FDOPA, FLT, FMISO, FES, and FCH) is being reviewed by several investigators in this issue. An overview of design and development of (18)F-labeled PET radiopharmaceuticals, radiochemistry, and mechanism(s) of tumor cell uptake and localization of radiotracers are presented here. The approval of clinical indications for FDG-PET in the year 2000 by the Food and Drug Administration, based on a review of literature, was a major breakthrough to the rapid incorporation of PET into nuclear medicine practice, particularly in oncology. Approval of a radiopharmaceutical typically involves submission of a "New Drug Application" by a manufacturer or a company clearly documenting 2 major aspects of the drug: (1) manufacturing of PET drug using current good manufacturing practices and (2) the safety and effectiveness of a drug with specific indications. The potential routine clinical utility of (18)F-labeled PET radiopharmaceuticals depends also on

  14. Comparison of two site-specifically (18)F-labeled affibodies for PET imaging of EGFR positive tumors.

    PubMed

    Su, Xinhui; Cheng, Kai; Jeon, Jongho; Shen, Bin; Venturin, Gianina Teribele; Hu, Xiang; Rao, Jianghong; Chin, Frederick T; Wu, Hua; Cheng, Zhen

    2014-11-01

    The epidermal growth factor receptor (EGFR) serves as an attractive target for cancer molecular imaging and therapy. Our previous positron emission tomography (PET) studies showed that the EGFR-targeting affibody molecules (64)Cu-DOTA-ZEGFR:1907 and (18)F-FBEM-ZEGFR:1907 can discriminate between high and low EGFR-expression tumors and have the potential for patient selection for EGFR-targeted therapy. Compared with (64)Cu, (18)F may improve imaging of EGFR-expression and is more suitable for clinical application, but the labeling reaction of (18)F-FBEM-ZEGFR:1907 requires a long synthesis time. The aim of the present study is to develop a new generation of (18)F labeled affibody probes (Al(18)F-NOTA-ZEGFR:1907 and (18)F-CBT-ZEGFR:1907) and to determine whether they are suitable agents for imaging of EGFR expression. The first approach consisted of conjugating ZEGFR:1907 with NOTA and radiolabeling with Al(18)F to produce Al(18)F-NOTA-ZEGFR:1907. In a second approach the prosthetic group (18)F-labeled-2-cyanobenzothiazole ((18)F-CBT) was conjugated to Cys-ZEGFR:1907 to produce (18)F-CBT-ZEGFR:1907. Binding affinity and specificity of Al(18)F-NOTA-ZEGFR:1907 and (18)F-CBT-ZEGFR:1907 to EGFR were evaluated using A431 cells. Biodistribution and PET studies were conducted on mice bearing A431 xenografts after injection of Al(18)F-NOTA-ZEGFR:1907 or (18)F-CBT-ZEGFR:1907 with or without coinjection of unlabeled affibody proteins. The radiosyntheses of Al(18)F-NOTA-ZEGFR:1907 and (18)F-CBT-ZEGFR:1907 were completed successfully within 40 and 120 min with a decay-corrected yield of 15% and 41% using a 2-step, 1-pot reaction and 2-step, 2-pot reaction, respectively. Both probes bound to EGFR with low nanomolar affinity in A431 cells. Although (18)F-CBT-ZEGFR:1907 showed instability in vivo, biodistribution studies revealed rapid and high tumor accumulation and quick clearance from normal tissues except the bones. In contrast, Al(18)F-NOTA-ZEGFR:1907 demonstrated high in

  15. Site-specific (18)F-labeling of the protein hormone leptin using a general two-step ligation procedure.

    PubMed

    Flavell, Robert R; Kothari, Paresh; Bar-Dagan, Maya; Synan, Michael; Vallabhajosula, Shankar; Friedman, Jeffrey M; Muir, Tom W; Ceccarini, Giovanni

    2008-07-16

    The protein hormone leptin acts to regulate body fat and energy expenditure. Resistance to this hormone is implicated in human obesity and its pathophysiological consequences. In order to gain insight into the mechanism of leptin resistance, an (18)F-labeled derivative was developed to study the biodistribution of the hormone using positron emission tomography (PET). A two-step, site specific ligation approach was developed for this purpose, in which an aminooxy-reactive group was incorporated at the C-terminus of leptin using expressed protein ligation (EPL), which was subsequently derivatized with [ (18)F]fluorobenzaldehyde using an aniline-accelerated radiochemical oximation reaction. The modified hormone was shown to be biologically active in vitro and in vivo, and it was applied to PET imaging in ob/ ob mice. These protocols will allow for the routine production of site-specifically (18)F radiolabeled leptin, as well as other proteins, for use in PET imaging in systems from mouse to man.

  16. Radiosynthesis and preliminary biological evaluation of a new (18)F-labeled triethylene glycol derivative of triphenylphosphonium.

    PubMed

    Tominaga, Takahiro; Ito, Hiroaki; Ishikawa, Yoichi; Iwata, Ren; Ishiwata, Kiichi; Furumoto, Shozo

    2016-03-01

    Delocalized lipophilic cations such as [(18)F]fluorobenzyltriphenylphosphonium ([(18)F]FBnTP) can accumulate in mitochondria and have been used in myocardial perfusion imaging (MPI). In this study, we established a simplified method for [(18)F]FBnTP synthesis using triphenylphosphine hydrobromide (PPh3 •HBr) without preparing an intermediate that contains benzyl bromide structure. Applying this new method, we synthesized and evaluated a novel (18)F-labeled PEGylated BnTP derivative ([(18)F]FPEGBnTP). In vitro cellular uptake study demonstrated that [(18)F]FPEGBnTP accumulated in cells in proportion to the relative intensity of mitochondrial membrane potential. Biodistribution study revealed that the heart : liver uptake ratio of [(18)F]FPEGBnTP (4.00 at 60 min) was superior to that of [(18)F]FBnTP (1.50 at 60 min). However, [(18)F]FPEGBnTP showed slow blood clearance and high radioactivity uptake in bone at 120-min post-injection. These results imply the possibility of [(18)F]FPEGBnTP being used as a MPI agent. However, there is a need of further structural optimization and flow-dependent uptake study. PMID:26861736

  17. Design, synthesis and evaluation of (18)F-labeled bradykinin B1 receptor-targeting small molecules for PET imaging.

    PubMed

    Zhang, Zhengxing; Kuo, Hsiou-Ting; Lau, Joseph; Jenni, Silvia; Zhang, Chengcheng; Zeisler, Jutta; Bénard, François; Lin, Kuo-Shyan

    2016-08-15

    Two fluorine-18 ((18)F) labeled bradykinin B1 receptor (B1R)-targeting small molecules, (18)F-Z02035 and (18)F-Z02165, were synthesized and evaluated for imaging with positron emission tomography (PET). Z02035 and Z02165 were derived from potent antagonists, and showed high binding affinity (0.93±0.44 and 2.80±0.50nM, respectively) to B1R. (18)F-Z02035 and (18)F-Z02165 were prepared by coupling 2-[(18)F]fluoroethyl tosylate with their respective precursors, and were obtained in 10±5 (n=4) and 22±14% (n=3), respectively, decay-corrected radiochemical yield with >99% radiochemical purity. (18)F-Z02035 and (18)F-Z02165 exhibited moderate lipophilicity (LogD7.4=1.10 and 0.59, respectively), and were stable in mouse plasma. PET imaging and biodistribution studies in mice showed that both tracers enabled visualization of the B1R-positive HEK293T::hB1R tumor xenografts with better contrast than control B1R-negative HEK293T tumors. Our data indicate that small molecule antagonists can be used as pharmacophores for the design of B1R-targeting PET tracers. PMID:27390067

  18. Design, synthesis and evaluation of (18)F-labeled bradykinin B1 receptor-targeting small molecules for PET imaging.

    PubMed

    Zhang, Zhengxing; Kuo, Hsiou-Ting; Lau, Joseph; Jenni, Silvia; Zhang, Chengcheng; Zeisler, Jutta; Bénard, François; Lin, Kuo-Shyan

    2016-08-15

    Two fluorine-18 ((18)F) labeled bradykinin B1 receptor (B1R)-targeting small molecules, (18)F-Z02035 and (18)F-Z02165, were synthesized and evaluated for imaging with positron emission tomography (PET). Z02035 and Z02165 were derived from potent antagonists, and showed high binding affinity (0.93±0.44 and 2.80±0.50nM, respectively) to B1R. (18)F-Z02035 and (18)F-Z02165 were prepared by coupling 2-[(18)F]fluoroethyl tosylate with their respective precursors, and were obtained in 10±5 (n=4) and 22±14% (n=3), respectively, decay-corrected radiochemical yield with >99% radiochemical purity. (18)F-Z02035 and (18)F-Z02165 exhibited moderate lipophilicity (LogD7.4=1.10 and 0.59, respectively), and were stable in mouse plasma. PET imaging and biodistribution studies in mice showed that both tracers enabled visualization of the B1R-positive HEK293T::hB1R tumor xenografts with better contrast than control B1R-negative HEK293T tumors. Our data indicate that small molecule antagonists can be used as pharmacophores for the design of B1R-targeting PET tracers.

  19. A (18)F-labeled glucose analog: synthesis using a click labeling method and in vitro evaluation.

    PubMed

    Kim, Dong Hyun; Choe, Yearn Seong; Jung, Kyung-Ho; Lee, Kyung-Han; Choi, Joon Young; Choi, Yong; Kim, Byung-Tae

    2008-05-01

    A (18)F-labeled glucose analog, 4-[(2-[(18)F]fluoroethyl)-1-(beta-D: -glucopyranosyl)]-1H-1,2,3-triazole ([(18)F]1), was synthesized using a click labeling method and evaluated in vitro for its cellular transportation via glucose transporter (Glut-1) and its potential as a hexokinase substrate. The click labeling method was superior to conventional labeling method, due to a higher decay-corrected radiochemical yield (30% vs. 21%), higher specific activity (59.9 GBq/mumol vs. 23.5 GBq/mumol), and shorter synthesis time (75-80 min vs. 95-100 min). In vitro evaluation demonstrated that [(18)F]1 does not act as a hexokinase substrate and has low and non-specific uptake by SNU-C5 cells. These results suggest that click chemistry offers a rapid and efficient radiolabeling method which does not require the protection of functional groups, although a triazole moiety at C1 of [(18)F]1 is incompatible for hexokinase phosphorylation and facilitative diffusion via Glut-1. PMID:18481013

  20. Fluorine-18 labeling of small molecules: the use of 18F-labeled aryl fluorides derived from no-carrier-added [18F]fluoride as labeling precursors.

    PubMed

    Wuest, F

    2007-01-01

    The favourable long-half life, the ease of production and the low energy of the emitted positron make 18F an ideal radionuclide for PET imaging. Radiochemistry of 18F basically relies on two distinctive types of reactions: nucleophilic and electrophilic reactions. All syntheses of 18F-labeled radiotracers are based on either [18F]fluoride ion or [18F]fluorine gas as simple primary labeling precursors which are obtained directly from the cyclotron. They can be applied either directly to the radiosynthesis or they can be transformed into more complex labeling precursors enabling the multi-step build-up of organic tracer molecules. The topic of this review is a survey on the application of several 18F-labeled aryl fluorides as building blocks derived from no-carrier-added (n.c.a.) [18F] fluoride to build up small monomeric PET radiotracers at high specific radioactivity by multi-step synthesis procedures.

  1. A high-affinity [18F]-labeled phosphoramidate peptidomimetic PSMA-targeted inhibitor for PET imaging of prostate cancer

    PubMed Central

    Ganguly, Tanushree; Dannoon, Shorouk; Hopkins, Mark R.; Murphy, Stephanie; Cahaya, Hendry; Blecha, Joseph E.; Jivan, Salma; Drake, Christopher R.; Barinka, Cyril; Jones, Ella F.; VanBrocklin, Henry F.; Berkman, Clifford E.

    2015-01-01

    Introduction In this study, a structurally modified phosphoramidate scaffold, with improved prostate-specific membrane antigen (PSMA) avidity, stability and in vivo characteristics, as a PET imaging agent for prostate cancer (PCa), was prepared and evaluated. Methods p-Fluorobenzoyl-aminohexanoate and 2-(3-hydroxypropyl)glycine were introduced into the PSMA-targeting scaffold yielding phosphoramidate 5. X-ray crystallography was performed on the PSMA/5 complex. [18F]5 was synthesized, and cell uptake and internalization studies were conducted in PSMA(+) LNCaP and CWR22Rv1 cells and PSMA(−) PC-3 cells. In vivo PET imaging and biodistribution studies were performed at 1 and 4 h post injection in mice bearing CWR22Rv1 tumor, with or without blocking agent. Results The crystallographic data showed interaction of the p-fluorobenzoyl group with an arene-binding cleft on the PSMA surface. In vitro studies revealed elevated uptake of [18F]5 in PSMA(+) cells (2.2% in CWR22Rv1 and 12.1% in LNCaP) compared to PSMA(−) cells (0.08%) at 4 h. In vivo tumor uptake of 2.33% ID/g and tumor-to-blood ratio of 265:1 was observed at 4 h. Conclusions We have successfully synthesized, radiolabeled and evaluated a new PSMA-targeted PET agent. The crystal structure of the PSMA/5 complex highlighted the interactions within the arene-binding cleft contributing to the overall complex stability. The high target uptake and rapid non-target clearance exhibited by [18F]5 in PSMA(+) xenografts substantiates its potential use for PET imaging of PCa. Advances in Knowledge The only FDA-approved imaging agent for PCa, Prostascint®, targets PSMA but suffers from inherent shortcomings. The data acquired in this manuscript confirmed that our new generation of [18F]-labeled PSMA inhibitor exhibited promising in vivo performance as a PET imaging agent for PCa and is well-positioned for subsequent clinical trials. Implications for Patient Care Our preliminary data demonstrate that this tracer possesses

  2. Synthesis of a Potent Aminopyridine-Based nNOS-Inhibitor by Two Recent No-Carrier-Added (18)F-Labelling Methods.

    PubMed

    Drerup, Christian; Ermert, Johannes; Coenen, Heinz H

    2016-01-01

    Nitric oxide (NO), an important multifunctional signaling molecule, is produced by three isoforms of NO-synthase (NOS) and has been associated with neurodegenerative disorders. Selective inhibitors of the subtypes iNOS (inducible) or nNOS (neuronal) are of great interest for decoding neurodestructive key factors, and (18)F-labelled analogues would allow investigating the NOS-function by molecular imaging with positron emission tomography. Especially, the highly selective nNOS inhibitor 6-((3-((3-fluorophenethylamino)methyl)phenoxy)methyl)-4-methylpyridin-2-amine (10) lends itself as suitable compound to be (18)F-labelled in no-carrier-added (n.c.a.) form. For preparation of the (18)F-labelled nNOS-Inhibitor [(18)F]10 a "build-up" radiosynthesis was developed based on a corresponding iodonium ylide as labelling precursor. The such activated phenethyl group of the compound was efficiently and regioselectively labelled with n.c.a. [(18)F]fluoride in 79% radiochemical yield (RCY). After conversion by reductive amination and microwave assisted displacement of the protecting groups, the desired nNOS-inhibitor was obtained in about 15% total RCY. Alternatively, for a simplified "late-stage" (18)F-labelling procedure a corresponding boronic ester precursor was synthesized and successfully used in a newer, copper(II) mediated n.c.a. (18)F-fluoro-deboroniation reaction, achieving the same total RCY. Thus, both methods proved comparatively suited to provide the highly selective NOS-inhibitor [(18)F]10 as probe for preclinical in vivo studies. PMID:27598109

  3. Synthesis of a Potent Aminopyridine-Based nNOS-Inhibitor by Two Recent No-Carrier-Added (18)F-Labelling Methods.

    PubMed

    Drerup, Christian; Ermert, Johannes; Coenen, Heinz H

    2016-09-01

    Nitric oxide (NO), an important multifunctional signaling molecule, is produced by three isoforms of NO-synthase (NOS) and has been associated with neurodegenerative disorders. Selective inhibitors of the subtypes iNOS (inducible) or nNOS (neuronal) are of great interest for decoding neurodestructive key factors, and (18)F-labelled analogues would allow investigating the NOS-function by molecular imaging with positron emission tomography. Especially, the highly selective nNOS inhibitor 6-((3-((3-fluorophenethylamino)methyl)phenoxy)methyl)-4-methylpyridin-2-amine (10) lends itself as suitable compound to be (18)F-labelled in no-carrier-added (n.c.a.) form. For preparation of the (18)F-labelled nNOS-Inhibitor [(18)F]10 a "build-up" radiosynthesis was developed based on a corresponding iodonium ylide as labelling precursor. The such activated phenethyl group of the compound was efficiently and regioselectively labelled with n.c.a. [(18)F]fluoride in 79% radiochemical yield (RCY). After conversion by reductive amination and microwave assisted displacement of the protecting groups, the desired nNOS-inhibitor was obtained in about 15% total RCY. Alternatively, for a simplified "late-stage" (18)F-labelling procedure a corresponding boronic ester precursor was synthesized and successfully used in a newer, copper(II) mediated n.c.a. (18)F-fluoro-deboroniation reaction, achieving the same total RCY. Thus, both methods proved comparatively suited to provide the highly selective NOS-inhibitor [(18)F]10 as probe for preclinical in vivo studies.

  4. Synthesis and in vitro and in vivo evaluation of an (18)F-labeled neuropeptide Y analogue for imaging of breast cancer by PET.

    PubMed

    Hofmann, Sven; Maschauer, Simone; Kuwert, Torsten; Beck-Sickinger, Annette G; Prante, Olaf

    2015-04-01

    Imaging of Y1R expression in breast cancer is still a challenging task. Herein, we report a suitable (18)F-labeled high-molecular-weight glycopeptide for imaging of peripheral neuropeptide Y (NPY) Y1 receptor (Y1R)-positive tumors by preclinical small-animal positron emission tomography (PET). The Y1R-preferring NPY [F(7),P(34)]NPY analogue was functionalized with an alkyne-bearing propargylglycine (Pra) in position 4. The corresponding fluoroglycosylated (FGlc) peptide analogue [Pra(4)(FGlc),F(7),P(34)]NPY and its (18)F-labeled analogue were synthesized by click chemistry-based fluoroglycosylation. The radiosynthesis was performed by (18)F-fluoroglycosylation starting from the 2-triflate of the β-mannosylazide and the alkyne peptide [Pra(4),F(7),P(34)]NPY. The radiosynthesis of the(18)F-labeled analogue was optimized using a minimum amount of peptide precursor (40 nmol), proceeding with an overall radiochemical yield of 20-25% (nondecay corrected) in a total synthesis time of 75 min with specific activities of 40-70 GBq/μmol. In comparison to NPY and [F(7),P(34)]NPY, in vitro Y1R and Y2R activation studies with the cold [Pra(4)(FGlc),F(7),P(34)]NPY on stably transfected COS-7 cells displayed a high potency for the induction of Y1R-specific inositol accumulation (pEC50 = 8.5 ± 0.1), whereas the potency at Y2R was significantly decreased. Internalization studies on stably transfected HEK293 cells confirmed a strong glycopeptide-mediated Y1R internalization and a substantial Y1R subtype selectivity over Y2R. In vitro autoradiography with Y1R-positive MCF-7 tumor tissue slices indicated high specific binding of the (18)F-labeled glycopeptide, when binding was reduced by 95% ([Pra(4),F(7),P(34)]NPY) and by 86% (BIBP3226 Y1R antagonist) in competition studies. Biodistribution and small-animal PET studies on MCF-7 breast tumor-bearing nude mice revealed radiotracer uptake in the MCF-7 tumor of 1.8%ID/g at 20 min p.i. and 0.7%ID/g at 120 min p.i. (n = 3-4), increasing

  5. 27 CFR 21.122 - Pyridine bases.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Pyridine bases. 21.122....122 Pyridine bases. (a) Alkalinity. One ml of pyridine bases dissolved in 10 ml of water is titrated... soon disappears. A minimum of 9.5 ml of the acid must be required for the end point. (Congo...

  6. 27 CFR 21.122 - Pyridine bases.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Pyridine bases. 21.122....122 Pyridine bases. (a) Alkalinity. One ml of pyridine bases dissolved in 10 ml of water is titrated... soon disappears. A minimum of 9.5 ml of the acid must be required for the end point. (Congo...

  7. 27 CFR 21.122 - Pyridine bases.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Pyridine bases. 21.122....122 Pyridine bases. (a) Alkalinity. One ml of pyridine bases dissolved in 10 ml of water is titrated... soon disappears. A minimum of 9.5 ml of the acid must be required for the end point. (Congo...

  8. 27 CFR 21.122 - Pyridine bases.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Pyridine bases. 21.122....122 Pyridine bases. (a) Alkalinity. One ml of pyridine bases dissolved in 10 ml of water is titrated... soon disappears. A minimum of 9.5 ml of the acid must be required for the end point. (Congo...

  9. 27 CFR 21.122 - Pyridine bases.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Pyridine bases. 21.122....122 Pyridine bases. (a) Alkalinity. One ml of pyridine bases dissolved in 10 ml of water is titrated... soon disappears. A minimum of 9.5 ml of the acid must be required for the end point. (Congo...

  10. In vivo biodistribution of two ( sup 18 F)-labelled muscarinic cholinergic receptor ligands: 2-( sup 18 F)- and 4-( sup 18 F)-fluorodexetimide

    SciTech Connect

    Wilson, A.A.; Scheffel, U.A.; Dannals, R.F.; Stathis, M.; Ravert, H.T.; Wagner, H.N. Jr. )

    1991-01-01

    Two ({sup 18}F)-labelled analogues of the potent muscarinic cholinergic receptor (m-AChR) antagonist, dexetimide, were evaluated as potential ligands for imaging m-AChR by positron emission tomography (PET). Intravenous administration of both 2-({sup 18}F)- or 4-({sup 18}F)-fluorodexetimide resulted in high brain uptake of radioactivity in mice. High binding levels were observed in m-AChR rich areas, such as cortex and striatum, with low levels in the receptor-poor cerebellum. Uptake of radioactivity was saturable and could be blocked by pre-administration of dexetimide or atropine. Drugs with different sites of action were ineffective at blocking receptor binding. The results indicate that both radiotracers are promising candidates for use in PET studies.

  11. Synthesis and Evaluation of 4-[18F]Fluoropropoxy-3-iodobenzylguanidine ([18F]FPOIBG): A Novel 18F-labeled Analogue of MIBG

    PubMed Central

    Vaidyanathan, Ganesan; McDougald, Darryl; Koumarianou, Eftychia; Choi, Jaeyeon; Hens, Marc; Zalutsky, Michael R.

    2015-01-01

    Introduction Radioiodinated meta-iodobenzylguanidine (MIBG), a norepinephrine transporter (NET) substrate, has been extensively used as an imaging agent to study the pathophysiology of the heart and for the diagnosis and treatment of neuroendocrine tumors. The goal of this study was to develop an 18F-labeled analogue of MIBG that like MIBG itself could be synthesized in a single radiochemical step. Towards this end, we designed 4-fluoropropoxy-3-iodobenzylguanidine (FPOIBG). Methods Standards of FPOIBG and 4-fluoropropoxy-3-bromobenzylguanidine (FPOBBG) as well as their tosylate precursors for labeling with 18F, and a tin precursor for the preparation of radioiodinated FPOIBG were synthesized. Radiolabeled derivatives were synthesized by nucleophilic substitution and electrophilic iododestannylation from the corresponding precursors. Labeled compounds were evaluated for NET transporter recognition in in vitro assays using three NET-expressing cell lines and in biodistribution experiments in normal mice, with all studies performed in a paired-label format. Competitive inhibition of [125I]MIBG uptake by unlabeled benzylguanidine compounds was performed in UVW-NAT cell line to determine IC50 values. Results [18F]FPOIBG was synthesized from the corresponding tosylate precursor in 5.2 ± 0.5% (n = 6) overall radiochemical yields starting with aqueous fluoride in about 105 min. In a paired-label in vitro assay, the uptake of [18F]FPOIBG at 2 h was 10.2 ± 1.5%, 39.6 ± 13.4%, and 13.3 ± 2.5%, in NET-expressing SK-N-SH, UVW-NAT, and SK-N-BE(2c) cells, respectively, while these values for [125I]MIBG were 57.3 ± 8.1%, 82.7 ± 8.9%, and 66.3 ± 3.6%. The specificity of uptake of both tracers was demonstrated by blocking with desipramine. The 125I-labeled congener of FPOIBG gave similar results. On the other hand, [18F]FPOBBG, a compound recently reported in the literature, demonstrated much higher uptake, albeit less than that of co-incubated [125I]MIBG. IC50 values for

  12. In vivo biodistribution of two [18F]-labelled muscarinic cholinergic receptor ligands: 2-[18F]- and 4-[18F]-fluorodexetimide.

    PubMed

    Wilson, A A; Scheffel, U A; Dannals, R F; Stathis, M; Ravert, H T; Wagner, H N

    1991-01-01

    Two [18F]-labelled analogues of the potent muscarinic cholinergic receptor (m-AChR) antagonist, dexetimide, were evaluated as potential ligands for imaging m-AChR by positron emission tomography (PET). Intravenous administration of both 2-[18F]- or 4-[18F]-fluorodexetimide resulted in high brain uptake of radioactivity in mice. High binding levels were observed in m-AChR rich areas, such as cortex and striatum, with low levels in the receptor-poor cerebellum. Uptake of radioactivity was saturable and could be blocked by pre-administration of dexetimide or atropine. Drugs with different sites of action were ineffective at blocking receptor binding. The results indicate that both radiotracers are promising candidates for use in PET studies. PMID:2008155

  13. Synthesis and pre-clinical evaluation of an (18)F-labeled single-chain antibody fragment for PET imaging of epithelial ovarian cancer.

    PubMed

    Sharma, Sai Kiran; Wuest, Melinda; Way, Jenilee D; Bouvet, Vincent R; Wang, Monica; Wuest, Frank R

    2016-01-01

    Anti-CA125 antibodies have been used in immunoassays to quantify levels of shed antigen in the serum of patients who are under surveillance for epithelial ovarian cancer (EOC). However, there is currently no molecular imaging probe in the clinic for the assessment of CA125 expression in vivo. The present study describes the development of an (18)F-labeled single-chain variable fragment (scFv) for PET imaging of CA125 in preclinical EOC models. Anti-CA125 scFv was derived from MAb-B43.13 by recombinant expression of the fragment in E.coli. Fragment scFv-B43.13 was purified via immobilized metal affinity chromatography and characterized for antigen binding via immuno-staining and flow cytometry. Prosthetic group N-succinimidyl 4-[(18)F]fluorobenzoate ([(18)F]SFB) was used for radiolabeling of scFv-B43.13. Preclinical ovarian cancer models were developed based on ovarian cancer cell lines OVCAR3 (CA125-positive) and SKOV3 (CA125-negative) in NIH-III mice. The radiopharmacological profile of (18)F-labeled scFv-B43.13 ([(18)F]FBz-scFv-B43.13) was studied with PET. [(18)F]FBz-scFv-B43.13 was prepared in radiochemical yields of 3.7 ± 1.8% (n = 5) at an effective specific activity of 3.88 ± 0.76 GBq/µmol (n = 5). The radiotracer demonstrated selective uptake in CA125-positive OVCAR3 cells and virtually no uptake in CA125-negative SKOV3 cells. Standardized uptake values (SUV) of radioactivity uptake in OVCAR3 tumors was 0.5 (n = 3) and 0.3 (n = 2) in SKOV3 tumors after 60 min post injection (p.i.). PMID:27508105

  14. Synthesis and pre-clinical evaluation of an 18F-labeled single-chain antibody fragment for PET imaging of epithelial ovarian cancer

    PubMed Central

    Sharma, Sai Kiran; Wuest, Melinda; Way, Jenilee D; Bouvet, Vincent R; Wang, Monica; Wuest, Frank R

    2016-01-01

    Anti-CA125 antibodies have been used in immunoassays to quantify levels of shed antigen in the serum of patients who are under surveillance for epithelial ovarian cancer (EOC). However, there is currently no molecular imaging probe in the clinic for the assessment of CA125 expression in vivo. The present study describes the development of an 18F-labeled single-chain variable fragment (scFv) for PET imaging of CA125 in preclinical EOC models. Anti-CA125 scFv was derived from MAb-B43.13 by recombinant expression of the fragment in E.coli. Fragment scFv-B43.13 was purified via immobilized metal affinity chromatography and characterized for antigen binding via immuno-staining and flow cytometry. Prosthetic group N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) was used for radiolabeling of scFv-B43.13. Preclinical ovarian cancer models were developed based on ovarian cancer cell lines OVCAR3 (CA125-positive) and SKOV3 (CA125-negative) in NIH-III mice. The radiopharmacological profile of 18F-labeled scFv-B43.13 ([18F]FBz-scFv-B43.13) was studied with PET. [18F]FBz-scFv-B43.13 was prepared in radiochemical yields of 3.7 ± 1.8% (n = 5) at an effective specific activity of 3.88 ± 0.76 GBq/µmol (n = 5). The radiotracer demonstrated selective uptake in CA125-positive OVCAR3 cells and virtually no uptake in CA125-negative SKOV3 cells. Standardized uptake values (SUV) of radioactivity uptake in OVCAR3 tumors was 0.5 (n = 3) and 0.3 (n = 2) in SKOV3 tumors after 60 min post injection (p.i.). PMID:27508105

  15. Fully automated production of diverse 18F-labeled PET tracers on the ELIXYS multi-reactor radiosynthesizer without hardware modification

    PubMed Central

    Lazari, Mark; Collins, Jeffrey; Shen, Bin; Farhoud, Mohammed; Yeh, Daniel; Maraglia, Brandon; Chin, Frederick T.; Nathanson, David A.; Moore, Melissa; van Dam, R. Michael

    2015-01-01

    Fully-automated radiosynthesizers are continuing to be developed to meet the growing need for the reliable production of positron emission tomography (PET) tracers made under current good manufacturing practice (cGMP) guidelines. There is a current trend towards supporting “kit-like” disposable cassettes that come preconfigured for particular tracers, thus eliminating the need for cleaning protocols between syntheses and enabling quick transitions to synthesizing other tracers. Though ideal for production, these systems are often limited for the development of novel tracers due to pressure, temperature, and chemical compatibility considerations. This study demonstrates the versatile use of the ELIXYS fully-automated radiosynthesizer to adapt and produce eight different 18F-labeled PET tracers of varying complexity. Methods Three reactor syntheses of D-[18F]FAC, L-[18F]FMAU, and D-[18F]FEAU along with the one reactor syntheses of D-[18F]FEAU, [18F]FDG, [18F]FLT, [18F]Fallypride, [18F]FHBG, and [18F]SFB were all produced using ELIXYS without the need for any hardware modifications or reconfiguration. Synthesis protocols were adapted, and slightly modified from literature, but not fully optimized. Furthermore, [18F]FLT, [18F]FDG, and [18F]Fallypride were produced sequentially on the same day and used for preclinical imaging of A431 tumor-bearing SCID mice and wild-type BALB/c mice, respectively. To assess future translation to the clinical setting, several batches of tracers were subjected to a full set of quality control tests. Results All tracers were produced with radiochemical yields comparable to those in literature. [18F]FLT, [18F]FDG, and [18F]Fallypride were successfully used to image the mice with results consistent with literature. All tracers subjected to clinical quality control tests passed. Conclusion The ELIXYS radiosynthesizer facilitates rapid tracer development and is capable of producing multiple 18F-labeled PET tracers suitable for clinical

  16. Synthesis of a potent and selective (18)F-labeled delta-opioid receptor antagonist derived from the Dmt-Tic pharmacophore for positron emission tomography imaging.

    PubMed

    Ryu, Eun Kyoung; Wu, Zhanhong; Chen, Kai; Lazarus, Lawrence H; Marczak, Ewa D; Sasaki, Yusuke; Ambo, Akihiro; Salvadori, Severo; Ren, Chuancheng; Zhao, Heng; Balboni, Gianfranco; Chen, Xiaoyuan

    2008-03-27

    Identification and pharmacological characterization of two new selective delta-opioid receptor antagonists, derived from the Dmt-Tic pharmacophore, of potential utility in positron emission tomography (PET) imaging are described. On the basis of its high delta selectivity, H-Dmt-Tic--Lys(Z)-OH (reference compound 1) is a useful starting point for the synthesis of (18)F-labeled compounds prepared by the coupling of N-succinimidyl 4-[ (18)F]fluorobenzoate ([(18)F]SFB) with Boc-Dmt-Tic--Lys(Z)-OH under slightly basic conditions at 37 degrees C for 15 min, deprotection with TFA, and HPLC purification. The total synthesis time was 120 min, and the decay-corrected radiochemical yield of [(18)F]- 1 was about 25-30% ( n = 5) starting from [(18)F]SFB ( n = 5) with an effective specific activity about 46 GBq/micromol. In vitro autoradiography studies showed prominent uptake of [ (18)F]- 1 in the striatum and cortex with significant blocking by 1 and UFP-501 (selective delta-opioid receptor antagonist), suggesting high specific binding of [(18)F]- 1 to delta-opioid receptors. Noninvasive microPET imaging studies revealed the absence of [(18)F]- 1 in rat brain, since it fails to cross the blood-brain barrier. This study demonstrates the suitability of [ (18)F]- 1 for imaging peripheral delta-opioid receptors.

  17. Improved radiosynthesis and preliminary in vivo evaluation of a (18)F-labeled glycopeptide-peptoid hybrid for PET imaging of neurotensin receptor 2.

    PubMed

    Maschauer, Simone; Greff, Cornelia; Einsiedel, Jürgen; Ott, Julian; Tripal, Philipp; Hübner, Harald; Gmeiner, Peter; Prante, Olaf

    2015-07-15

    The neurotensin receptor 2 (NTS2) is an attractive target for cancer imaging, as it is overexpressed in a variety of tumor types including prostate, pancreas and breast carcinoma. The aim of this study was the development of the first NTS2 subtype selective (18)F-labeled radioligand for imaging NTS2 expression in vivo by positron emission tomography (PET). The radiosynthesis of glycopeptoid (18)F-4 was realized by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), applying the prosthetic group 6-deoxy-6-[(18)F]fluoroglucosyl azide for (18)F-fluoroglycosylation of the alkyne-terminated NT(8-13) analog Pra-N-Me-Arg-Arg-Pro-N-homo-Tyr-Ile-Leu-OH. The binding affinity of the peptide-peptoid 4 for NTS2 was 7nM with excellent subtype selectivity over NTS1 (260-fold). In vitro autoradiography studies of rat brain slices confirmed the high selectivity of (18)F-4 for NTS2. Biodistribution experiments using HT29 and PC3 tumor-bearing nude mice revealed high renal and only moderate tumor uptake, while PET imaging experiments revealed specific binding of (18)F-4 in NTS2-positive tumors. As (18)F-4 displayed high stability in vitro but fast degradation in vivo, future work will focus on the development of metabolically more stable NT(8-13) analogs.

  18. Synthesis and Evaluation of (18)F-labeled Pyridaben Analogues for Myocardial Perfusion Imaging in Mice, Rats and Chinese mini-swine.

    PubMed

    Mou, Tiantian; Zhao, Zuoquan; You, Linyi; Li, Yesen; Wang, Qian; Fang, Wei; Lu, Jie; Peng, Cheng; Zhang, Xianzhong

    2016-01-01

    This study reports three novel (18)F-labeled pyridaben analogues for potential myocardial perfusion imaging (MPI). Three precursors and the corresponding nonradioactive compounds were synthesized and characterized. The radiolabeled tracers were obtained by substituting tosyl with (18)F. The total radiosynthesis time of these tracers was 70-90 min. Typical decay-corrected radiochemical yields were 47-58%, with high radiochemical purities (>98%). Tracers were evaluated as MPI agents in vitro, ex vivo and in vivo. In the mouse biodistribution study, all three radiotracers showed high initial heart uptake (34-54% ID/g at 2 min after injection) and fast liver clearance. In the microPET imaging study, [(18)F]Fmpp2 produced heart images with good quality in both mice and rats. In the whole-body PET/CT images of mini-swine, [(18)F]Fmpp2 showed excellent initial heart standardized uptake value (SUV) (7.12 at 5 min p.i.) and good retention (5.75 at 120 min p.i.). The heart/liver SUV ratios were 4.12, 5.42 and 5.99 at 30, 60 and 120 min after injection, respectively. The favorable biological properties of [(18)F]Fmpp2 suggest that it is worth further investigation as a potential MPI agent. PMID:27646847

  19. Single-step High-yield Radiosynthesis and Evaluation of a Sensitive 18F-Labeled Ligand for Imaging Brain Peripheral Benzodiazepine Receptors with PET

    PubMed Central

    Briard, Emmanuelle; Zoghbi, Sami S.; Siméon, Fabrice G.; Imaizumi, Masao; Gourley, Jonathan P.; Shetty, H. Umesha; Lu, Shuiyu; Fujita, Masahiro; Innis, Robert B.; Pike, Victor W.

    2009-01-01

    Elevated levels of peripheral benzodiazepine receptors (PBR) are associated with activated microglia in their response to inflammation. Hence, PBR imaging in vivo is valuable for investigating brain inflammatory conditions. Sensitive, easily prepared and readily available radioligands for imaging with positron emission tomography (PET) are desirable for this purpose. We describe a new 18F-labeled PBR radioligand, namely [18F]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ([18F]9). [18F]9 was produced easily through a single and highly efficient step, the reaction of [18F]fluoride ion with the corresponding bromo precursor, 8. Ligand 9 exhibited high affinity for PBR in vitro. PET showed that [18F]9 was avidly taken into monkey brain and gave a high ratio of PBR-specific to nonspecific binding. [18F]9 was devoid of defluorination in rat and monkey and gave predominantly polar radiometabolite(s). In rat, a low level radiometabolite of intermediate lipophilicity was identified as [18F]2-fluoro-N-(2-phenoxyphenyl)acetamide ([18F]11). [18F]9 is a promising radioligand for future imaging of PBR in living human brain. PMID:19119848

  20. Radiosynthesis and Evaluation of an 18F-Labeled Positron Emission Tomography (PET) Radioligand for Metabotropic Glutamate Receptor Subtype 4 (mGlu4)

    PubMed Central

    2015-01-01

    Four 4-phthalimide derivatives of N-(3-chlorophenyl)-2-picolinamide were synthesized as potential ligands for the PET imaging of mGlu4 in the brain. Of these compounds, N-(3-chloro-4-(4-fluoro-1,3-dioxoisoindolin-2-yl)phenyl)-2-picolinamide (3, KALB001) exhibited improved binding affinity (IC50 = 5.1 nM) compared with ML128 (1) and was subsequently labeled with 18F. When finally formulated in 0.1 M citrate buffer (pH 4) with 10% ethanol, the specific activity of [18F]3 at the end of synthesis (EOS) was 233.5 ± 177.8 GBq/μmol (n = 4). The radiochemical yield of [18F]3 was 16.4 ± 4.8% (n = 4), and the purity was over 98%. In vivo imaging studies in a monkey showed that the radiotracer quickly penetrated the brain with the highest accumulation in the brain areas known to express mGlu4. Despite some unfavorable radiotracer properties like fast washout in rodent studies, [18F]3 is the first 18F-labeled mGlu4 radioligand, which can be further modified to improve pharmacokinetics and brain penetrability for future human studies. PMID:25330258

  1. Synthesis and Evaluation of 18F-labeled Pyridaben Analogues for Myocardial Perfusion Imaging in Mice, Rats and Chinese mini-swine

    PubMed Central

    Mou, Tiantian; Zhao, Zuoquan; You, Linyi; Li, Yesen; Wang, Qian; Fang, Wei; Lu, Jie; Peng, Cheng; Zhang, Xianzhong

    2016-01-01

    This study reports three novel 18F-labeled pyridaben analogues for potential myocardial perfusion imaging (MPI). Three precursors and the corresponding nonradioactive compounds were synthesized and characterized. The radiolabeled tracers were obtained by substituting tosyl with 18F. The total radiosynthesis time of these tracers was 70–90 min. Typical decay-corrected radiochemical yields were 47–58%, with high radiochemical purities (>98%). Tracers were evaluated as MPI agents in vitro, ex vivo and in vivo. In the mouse biodistribution study, all three radiotracers showed high initial heart uptake (34–54% ID/g at 2 min after injection) and fast liver clearance. In the microPET imaging study, [18F]Fmpp2 produced heart images with good quality in both mice and rats. In the whole-body PET/CT images of mini-swine, [18F]Fmpp2 showed excellent initial heart standardized uptake value (SUV) (7.12 at 5 min p.i.) and good retention (5.75 at 120 min p.i.). The heart/liver SUV ratios were 4.12, 5.42 and 5.99 at 30, 60 and 120 min after injection, respectively. The favorable biological properties of [18F]Fmpp2 suggest that it is worth further investigation as a potential MPI agent. PMID:27646847

  2. Synthesis and evaluation of (18)F-labeled ATP competitive inhibitors of topoisomerase II as probes for imaging topoisomerase II expression.

    PubMed

    Daumar, Pierre; Zeglis, Brian M; Ramos, Nicholas; Divilov, Vadim; Sevak, Kuntal Kumar; Pillarsetty, NagaVaraKishore; Lewis, Jason S

    2014-10-30

    Type II topoisomerase (Topo-II) is an ATP-dependent enzyme that is essential in the transcription, replication, and chromosome segregation processes and, as such, represents an attractive target for cancer therapy. Numerous studies indicate that the response to treatment with Topo-II inhibitors is highly dependent on both the levels and the activity of the enzyme. Consequently, a non-invasive assay to measure tumoral Topo-II levels has the potential to differentiate responders from non-responders. With the ultimate goal of developing a radiofluorinated tracer for positron emission tomography (PET) imaging, we have designed, synthesized, and evaluated a set of fluorinated compounds based on the structure of the ATP-competitive Topo-II inhibitor QAP1. Compounds 18 and 19b showed inhibition of Topo-II in in vitro assays and exhibited moderate, Topo-II level dependent cytotoxicity in SK-BR-3 and MCF-7 cell lines. Based on these results, (18)F-labeled analogs of these two compounds were synthesized and evaluated as PET probes for imaging Topo-II overexpression in mice bearing SK-BR-3 xenografts. [(18)F]-18 and [(18)F]-19b were synthesized from their corresponding protected tosylated derivatives by fluorination and subsequent deprotection. Small animal PET imaging studies indicated that both compounds do not accumulate in tumors and exhibit poor pharmacokinetics, clearing from the blood pool very rapidly and getting metabolized over. The insights gained from the current study will surely aid in the design and construction of future generations of PET agents for the non-invasive delineation of Topo-II expression.

  3. Synthesis and evaluation of 18F-labeled ATP competitive inhibitors of topoisomerase II as probes for imaging topoisomerase II expression

    PubMed Central

    Daumar, Pierre; Zeglis, Brian M.; Ramos, Nicholas; Divilov, Vadim; Sevak, Kuntal Kumar; Pillarsetty, NagaVaraKishore; Lewis, Jason S.

    2015-01-01

    Type II topoisomerase (Topo-II) is an ATP-dependent enzyme that is essential in the transcription, replication, and chromosome segregation processes and, as such, represents an attractive target for cancer therapy. Numerous studies indicate that the response to treatment with Topo-II inhibitors is highly dependent on both the levels and the activity of the enzyme. Consequently, a non-invasive assay to measure tumoral Topo-II levels has the potential to differentiate responders from non-responders. With the ultimate goal of developing a radiofluorinated tracer for positron emission tomography (PET) imaging, we have designed, synthesized, and evaluated a set of fluorinated compounds based on the structure of the ATP-competitive Topo-II inhibitor QAP1. Compounds 18 and 19b showed inhibition of Topo-II in in vitro assays and exhibited moderate, Topo-II level dependent cytotoxicity in SK-BR-3 and MCF-7 cell lines. Based on these results, 18F-labeled analogs of these two compounds were synthesized and evaluated as PET probes for imaging Topo-II overexpression in mice bearing SK-BR-3 xenografts. [18F]-18 and [18F]-19b were synthesized from their corresponding protected tosylated derivatives by fluorination and subsequent deprotection. Small animal PET imaging studies indicated that both compounds do not accumulate in tumors and exhibit poor pharmacokinetics, clearing from the blood pool very rapidly and getting metabolized over. The insights gained from the current study will surely aid in the design and construction of future generations of PET agents for the non-invasive delineation of Topo-II expression. PMID:25240701

  4. Noninvasive positron emission tomography imaging of cell death using a novel small-molecule probe, (18)F labeled bis(zinc(II)-dipicolylamine) complex.

    PubMed

    Wang, Hongliang; Tang, Xiaolan; Tang, Ganghua; Huang, Tingting; Liang, Xiang; Hu, Kongzhen; Deng, Huaifu; Yi, Chang; Shi, Xinchong; Wu, Kening

    2013-08-01

    The synthetic bis(zinc(II)-dipicolylamine) (DPAZn2) coordination complexes are known to have a high specific and selective affinity to target the exposed phosphatidylserine (PS) on the surface of dead and dying cells. An (18)F-labeled DPAZn2 complex (4-(18)F-Fluoro-benzoyl-bis(zinc(II)-dipicolylamine), (18)F-FB-DPAZn2) as positron emission tomography (PET) tracer was developed and evaluated for in vivo imaging of tumor treated with a chemical agent. The in vitro cell stain studies revealed that fluorescent DPAZn2 complexes (Dansyl-DPAZn2) stained the same cells (apoptotic and necrotic cells) as fluorescein isothiocyanate (FITC) labeled Annexin V (FITC-Annexin V). The radiosynthesis of (18)F-FB-DPAZn2 was achieved through the amidation the precursor bis(2,2'-dipicolylamine) derivative (DPA2) with the prosthetic group N-succinimidyl-4-[(18)F]-fluorobenzoate ((18)F-SFB) and chelation with zinc nitrate. In the biodistribution study, the fast clearance of (18)F-FB-DPAZn2 from blood and kidney was observed and high uptake in liver and intestine within 90 min postinjection was also found. For the PET imaging, significantly higher tumor uptake of (18)F-FB-DPAZn2 was observed in the adriamycin (ADM)-treated Hepa1-6 hepatocellular carcinoma-bearing mice than that in the untreated tumor-model mice, while a slightly decreased tumor uptake of (18)F-FDG was found in the ADM-treated tumor-bearing mice. The results indicate that (18)F-FB-DPAZn2 has the similar capability of apoptosis detection as FITC-Annexin V and seems to be a potential PET tracer for noninvasive evaluation and monitoring of anti-tumor chemotherapy. The high uptake of (18)F-FB-DPAZn2 in the abdomen needs to optimize the structure for improving its pharmacokinetics characteristics in the future work.

  5. Synthesis and evaluation of new (18)F-labelled acetamidobenzoxazolone-based radioligands for imaging of the translocator protein (18 kDa, TSPO) in the brain.

    PubMed

    Tiwari, Anjani K; Fujinaga, Masayuki; Yui, Joji; Yamasaki, Tomoteru; Xie, Lin; Kumata, Katsushi; Mishra, Anil K; Shimoda, Yoko; Hatori, Akiko; Ji, Bin; Ogawa, Masanao; Kawamura, Kazunori; Wang, Feng; Zhang, Ming-Rong

    2014-12-21

    The visualization of the activated microglia/TSPO is one of the main aspects of neuroimaging. Here we describe two new (18)F-labelled molecules, 2-[5-(4-[(18)F]fluoroethoxyphenyl)- ([(18)F]2) and 2-[5-(4-[(18)F]fluoropropyloxyphenyl)- ([(18)F]3) -2-oxo-1,3-benzoxazol-3(2H)-yl]-N-methyl-N-phenylacetamide as novel PET ligands for imaging the translocator protein (18 kDa, TSPO) in the brain. The three-D pharmacophore evaluation and docking studies suggested their high affinity for the TSPO and in vitro binding assays of the TSPO showed binding affinities 6.6 ± 0.7 nM and 16.7 ± 2.5 nM for 2 and 3, respectively. The radiochemical yields for [(18)F]2 and [(18)F]3 were found to be 22 ± 4% (n = 8) and 5 ± 2% (n = 5), respectively at EOB. The radiochemical purity for both was found ≥98% and the specific activity was in the range of 98-364 GBq μmol(-1) at EOS. In vitro autoradiography with an ischemic rat brain showed significantly increased binding on the ipsilateral side compared to the contralateral side. The specificity of [(18)F]2 and [(18)F]3 for binding TSPO was confirmed using the TSPO ligands PK11195 and MBMP. The biodistribution patterns of both PET ligands were evaluated in normal mice by 1 h dynamic PET imaging. In the brain, regional radioactivity reached the maximum very rapidly within 0-4 min for both ligands, similar to (R)[(11)C]PK11195. The metabolite study of [(18)F]2 also favoured a more favourable profile for quantification in comparison to (R)[(11)C]PK11195. In summary, these data indicated that [(18)F]2 and [(18)F]3 have good potential to work as PET ligands, therefore there are merits to use these radioligands for the in vivo evaluation in animal models to see their efficacy in the living brain.

  6. 18F-Labeled NaF PET-CT in Detection of Bone Metastases in Patients With Preoperative Lung Cancer

    PubMed Central

    Rao, Liangjun; Zong, Zhen; Chen, Zhifeng; Wang, Xiaoyan; Shi, Xinchong; Yi, Chang; Zhang, Xiangsong

    2016-01-01

    Abstract We compared the diagnostic accuracy of 18F-labeled sodium fluoride (18F-NaF) PET-CT with 99m-technetium methylene diphosphonate (99mTc-MDP) single photon emission computed tomography (SPECT) to detect bone metastases (BMs) in patients with preoperative lung cancer. Patients with lung cancer (n = 181) were examined with 18F-NaF PET-CT, and another 167 patients with lung cancer were examined with 99mTc-MDP SPECT. 18F-NaF PET-CT and 99mTc-MDP SPECT were evaluated by 2 experienced readers. Lesions were graded on a scale of 0 (degenerative lesion) to 4 (definite BM), and equivocal lesions were determined as indifferent (grade 3). Based on patient-based analysis, there were only 4 equivocal patients in 18F-NaF PET-CT detection. However, in 99mTc-MDP SPECT detection, there were 19 equivocal patients, which indicated a significant difference in terms of occurrence ratio (χ2 = 9.005, P = 0.03). Sensitivity and specificity of PET-CT was significantly better than that of SPECT when equivocal reading was categorized as malignant or benign (P < 0.05). Based on lesions-based analysis, SPECT produced 26 equivocal lesions of 333 lesions, but PET-CT produced only 5 equivocal lesions of 991 lesions. PET-CT was significantly better than SPECT in the aspect of producing equivocal patients (χ2 = 58.141, P < 0.001). Sensitivity and specificity of PET-CT was significantly better than that of SPECT when equivocal reading was categorized as malignant or benign (P < 0.05). 18F-NaF PET-CT is a highly sensitive and specific modality for the detection of BM in patients with preoperative lung cancer. It is better than conventional 99mTc-MDP SPECT in detecting BM in patients with preoperative lung cancer. PMID:27100456

  7. Radiosynthesis and preliminary PET evaluation of (18)F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile for imaging AMPA receptors.

    PubMed

    Yuan, Gengyang; Jones, Graham B; Vasdev, Neil; Liang, Steven H

    2016-10-01

    To prompt the development of (18)F-labeled positron emission tomography (PET) tracers for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, we have prepared (18)F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile ([(18)F]8). The radiosynthesis was achieved by a one-pot two-step method that utilized a spirocyclic hypervalent iodine(III) mediated radiofluorination to prepare the (18)F-labeled 1-bromo-3-fluorobenzene ([(18)F]15) intermediate with K(18)F. A subsequent copper(I) iodide mediated coupling reaction was carried out with 2-(2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile (10) to [(18)F]8 in 10±2% uncorrected radiochemical yield relative to starting (18)F-fluoride with >99% radiochemical purity and 29.6±7.4Gbq/μmol specific activity at the time of injection. PET imaging studies with the title radiotracer in normal mice demonstrated good brain uptake (peak standardized uptake value (SUV)=2.3±0.1) and warrants further in vivo validation. PMID:27546294

  8. Radiosynthesis and preliminary PET evaluation of (18)F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile for imaging AMPA receptors.

    PubMed

    Yuan, Gengyang; Jones, Graham B; Vasdev, Neil; Liang, Steven H

    2016-10-01

    To prompt the development of (18)F-labeled positron emission tomography (PET) tracers for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, we have prepared (18)F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile ([(18)F]8). The radiosynthesis was achieved by a one-pot two-step method that utilized a spirocyclic hypervalent iodine(III) mediated radiofluorination to prepare the (18)F-labeled 1-bromo-3-fluorobenzene ([(18)F]15) intermediate with K(18)F. A subsequent copper(I) iodide mediated coupling reaction was carried out with 2-(2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile (10) to [(18)F]8 in 10±2% uncorrected radiochemical yield relative to starting (18)F-fluoride with >99% radiochemical purity and 29.6±7.4Gbq/μmol specific activity at the time of injection. PET imaging studies with the title radiotracer in normal mice demonstrated good brain uptake (peak standardized uptake value (SUV)=2.3±0.1) and warrants further in vivo validation.

  9. Distribution and binding of 18F-labeled and 125I-labeled analogues of ACI-80, a prospective molecular imaging biomarker of disease: a whole hemisphere post mortem autoradiography study in human brains obtained from Alzheimer's disease patients.

    PubMed

    Gulyás, Balázs; Spenger, Christian; Beliczai, Zsuzsa; Gulya, Károly; Kása, Péter; Jahan, Mahabuba; Jia, Zhisheng; Weber, Urs; Pfeifer, Andrea; Muhs, Andreas; Willbold, Dieter; Halldin, Christer

    2012-01-01

    One of the major pathological landmarks of Alzheimer's disease and other neurodegenerative diseases is the presence of amyloid deposits in the brain. The early non-invasive visualization of amyloid is a major objective of recent diagnostic neuroimaging approaches, including positron emission tomography (PET), with an eye on follow-up of disease progression and/or therapy efficacy. The development of molecular imaging biomarkers with binding affinity to amyloid in the brain is therefore in the forefront of imaging biomarker and radiochemistry research. Recently, a dodecamer peptide (amino acid sequence=QSHYRHISPAQV; denominated D1 or ACI-80) was identified as a prospective ligand candidate, binding with high ex vivo affinity to L-Aβ-amyloid (K(d): 0.4 μM). In order to assess the ligand's capacity to visualize amyloid in Alzheimer's disease (AD), two (125)I labeled and three (18)F labeled analogues of the peptide were synthesized and tested in post mortem human autoradiography experiments using whole hemisphere brain slices obtained from deceased AD patients and age matched control subjects. The (18)F-labeled radioligands showed more promising visualization capacity of amyloid that the (125)I-labeled radioligands. In the case of each (18)F radioligands the grey matter uptake in the AD brains was significantly higher than that in control brains. Furthermore, the grey matter: white matter uptake ratio was over ~2, the difference being significant for each (18)F-radioligands. The regional distribution of the uptake of the various radioligands systematically shows a congruent pattern between the high uptake regions and spots in the autoradiographic images and the disease specific signals obtained in adjacent or identical brain slices labeled with histological, immunohistochemical or autoradiographic stains for amyloid deposits or activated astrocytes. The present data, using post mortem human brain autoradiography in whole hemisphere human brains obtained from deceased

  10. Synthesis and Evaluation of Two 18F-Labeled 6-Iodo-2-(4′-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine Derivatives as Prospective Radioligands for β-Amyloid in Alzheimer’s Disease

    PubMed Central

    Cai, Lisheng; Chin, Frederick T.; Pike, Victor W.; Toyama, Hiroshi; Liow, Jeih-San; Zoghbi, Sami S.; Modell, Kendra; Briard, Emmanuelle; Shetty, H. Umesha; Sinclair, Kathryn; Donohue, Sean; Tipre, Dnyanesh; Kung, Mei-Ping; Dagostin, Claudio; Widdowson, David A.; Green, Michael; Gao, Weiyi; Herman, Mary M.; Ichise, Masanori; Innis, Robert B.

    2014-01-01

    This study evaluated 18F-labeled IMPY [6-iodo-2-(4′-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine] derivatives as agents for imaging β-amyloid plaque with positron emission tomography (PET). The precursor for radiolabeling and reference compounds was synthesized in up to five steps from commercially accessible starting materials. One of the two N-methyl groups of IMPY was substituted with either a 3-fluoropropyl (FPM-IMPY) or a 2-fluoroethyl (FEM-IMPY) group. FPM-IMPY and FEM-IMPY were found to have moderate affinity for Aβ- aggregates with Ki = 27 ± 8 and 40 ± 5 nM, respectively. A “one-pot” method for 18F-2-fluoroethylation and 18F-3-fluoropropylation of the precursor was developed. The overall decay-corrected radiochemical yields were 26–51%. In PET experiments with normal mouse, high uptake of activity was obtained in the brain after iv injection of each probe: 6.4% ID/g for [18F]FEM-IMPY at 1.2 min, and 5.7% ID/g for [18F]FPM-IMPY at 0.8 min. These values were similar to those of [123I/125I]IMPY (7.2% ID/g at 2 min). Polar and nonpolar radioactive metabolites were observed in both plasma and brain homogenates after injection of [18F]FEM or [18F]FPM-IMPY. In contrast to the single-exponential washout of [123I/125I]IMPY, the washouts of brain activity for the two fluorinated analogues were biphasic, with an initial rapid phase over 20 min and a subsequent much slower phase. Residual brain activity at 2 h, which may represent polar metabolites trapped in the brain, was 4.5% ID/g for [18F]FEM-IMPY and 2.1% ID/g for [18F]FPM-IMPY. Substantial skull uptake of [18F]fluoride was also clearly observed. With a view to slow the metabolism of [18F]FEM-IMPY, an analogue was prepared with deuteriums substituted for the four ethyl hydrogens. However, D4-[18F]FEM-IMPY showed the same brain uptake and clearance as the protio analogue. Metabolism of the [18F]FEM-IMPY was appreciably slower in rhesus monkey than in mouse. Autoradiography of postmortem brain sections

  11. Aligning Potency and Pharmacokinetic Properties for Pyridine-Based NCINIs.

    PubMed

    Fader, Lee D; Bailey, Murray; Beaulieu, Eric; Bilodeau, François; Bonneau, Pierre; Bousquet, Yves; Carson, Rebekah J; Chabot, Catherine; Coulombe, René; Duan, Jianmin; Fenwick, Craig; Garneau, Michel; Halmos, Ted; Jakalian, Araz; James, Clint; Kawai, Stephen H; Landry, Serge; LaPlante, Steven R; Mason, Stephen W; Morin, Sebastien; Rioux, Nathalie; Simoneau, Bruno; Surprenant, Simon; Thavonekham, Bounkham; Thibeault, Carl; Trinh, Thao; Tsantrizos, Youla; Tsoung, Jennifer; Yoakim, Christiane; Wernic, Dominik

    2016-08-11

    Optimization of pyridine-based noncatalytic site integrase inhibitors (NCINIs) based on compound 2 has led to the discovery of molecules capable of inhibiting virus harboring N124 variants of HIV integrase (IN) while maintaining minimal contribution of enterohepatic recirculation to clearance in rat. Structure-activity relationships at the C6 position established chemical space where the extent of enterohepatic recirculation in the rat is minimized. Desymmetrization of the C4 substituent allowed for potency optimization against virus having the N124 variant of integrase. Combination of these lessons led to the discovery of compound 20, having balanced serum-shifted antiviral potency and minimized excretion in to the biliary tract in rat, potentially representing a clinically viable starting point for a new treatment option for individuals infected with HIV. PMID:27563405

  12. 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%. PMID:20738143

  13. Anticancer efficacy of unique pyridine-based tetraindoles.

    PubMed

    Fu, Chih-Wei; Hsieh, Yun-Jung; Chang, Tzu Ting; Chen, Chia-Ling; Yang, Cheng-Yu; Liao, Anne; Hsiao, Pei-Wen; Li, Wen-Shan

    2015-11-01

    Results of previous studies demonstrated that the tetraindole, SK228, which has a high lipid but low water solubility, displayed moderate anticancer efficacy in a xenograft model of breast cancer. This finding led to the proposal that new, pyridine based tetraindole (PBT) analogs of SK228, containing tetraindole moieties distributed about central protonated pyridine cores, would have enhanced bioavailabilities and anticancer efficacies. Among the PBTs prepared and subjected to biological studies, 3f (FCW81) was observed to display the highest antiproliferative activity against the two triple negative breast cancer (TNBCs) cell lines, MDA-MB-231 and BT549. In addition, its mode of action was shown to involve G2/M arrest of the cell cycle along with the promotion of increased levels of cyclin B1 and p-chk2 and a decreased level of p-cdc2. DNA damage and induction of apoptosis caused by FCW81 was found to be associated with a decrease in DNA repair. Significantly, FCW81 displays therapeutic efficacy in a xenograft model of human breast cancer by not only serving to inhibit markedly the growth of cancer cells but also to block effectively cancer cell metastasis. Collectively, the results of these studies have led to the identification of novel pyridine-tetraindole based anticancer agents with potential use in TNBC therapy. PMID:26457743

  14. N-Succinimidyl 3-((4-(4-[18F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate ([18F]SFBTMGMB): A Residualizing Label for 18F-labeling of internalizing biomolecules

    PubMed Central

    Vaidyanathan, Ganesan; McDougald, Darryl; Choi, Jaeyeon; Pruszynski, Marek; Koumarianou, Eftychia; Zhou, Zhengyuan; Zalutsky, Michael R.

    2015-01-01

    Residualizing labeling methods for internalizing peptides and proteins are designed to trap the radionuclide inside the cell after intracellular degradation of the biomolecule. The goal of this work was to develop a residualizing label for the 18F-labeling of internalizing biomolecules based on a template used successfully for radioiodination. N-succinimidyl 3-((4-(4-[18F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(bis-Boc-guanidinomethyl)benzoate (Boc2-[18F]SFBTMGMB) was synthesized by click reaction of an azide precursor and [18F]fluorohexyne in 8.5 ± 2.8% average decay-corrected radiochemical yield (n =15). An anti-HER2 nanobody 5F7 was labeled with 18F using [18F]SFBTMGMB ([18F]RL-I), obtained by the deprotection of Boc2-[18F]SFBTMGMB, in 31.2 ± 6.7% (n =5) conjugation efficiency. Thus labeled nanobody had a radiochemical purity of >95%, bound to the HER2-expressing BT474M1 breast cancer cells with an affinity of 4.7 ± 0.9 nM, and had an immunoreactive fraction of 62–80%. In summary, a novel residualizing prosthetic agent for labeling biomolecules with 18F has been developed. An anti-HER2 nanobody was labeled using this prosthetic group with retention of affinity and immunoreactivity to HER2. PMID:26645790

  15. N-Succinimidyl 3-((4-(4-[(18)F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate ([(18)F]SFBTMGMB): a residualizing label for (18)F-labeling of internalizing biomolecules.

    PubMed

    Vaidyanathan, Ganesan; McDougald, Darryl; Choi, Jaeyeon; Pruszynski, Marek; Koumarianou, Eftychia; Zhou, Zhengyuan; Zalutsky, Michael R

    2016-01-28

    Residualizing labeling methods for internalizing peptides and proteins are designed to trap the radionuclide inside the cell after intracellular degradation of the biomolecule. The goal of this work was to develop a residualizing label for the (18)F-labeling of internalizing biomolecules based on a template used successfully for radioiodination. N-Succinimidyl 3-((4-(4-[(18)F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(bis-Boc-guanidinomethyl)benzoate ([(18)F]SFBTMGMB-Boc2) was synthesized by a click reaction of an azide precursor and [(18)F]fluorohexyne in 8.5 ± 2.8% average decay-corrected radiochemical yield (n = 15). An anti-HER2 nanobody 5F7 was labeled with (18)F using [(18)F]SFBTMGMB ([(18)F]RL-I), obtained by the deprotection of [(18)F]SFBTMGMB-Boc2, in 31.2 ± 6.7% (n = 5) conjugation efficiency. The labeled nanobody had a radiochemical purity of >95%, bound to HER2-expressing BT474M1 breast cancer cells with an affinity of 4.7 ± 0.9 nM, and had an immunoreactive fraction of 62-80%. In summary, a novel residualizing prosthetic agent for labeling biomolecules with (18)F has been developed. An anti-HER2 nanobody was labeled using this prosthetic group with retention of affinity and immunoreactivity to HER2.

  16. Alkylating enzymes.

    PubMed

    Wessjohann, Ludger A; Keim, Jeanette; Weigel, Benjamin; Dippe, Martin

    2013-04-01

    Chemospecific and regiospecific modifications of natural products by methyl, prenyl, or C-glycosyl moieties are a challenging and cumbersome task in organic synthesis. Because of the availability of an increasing number of stable and selective transferases and cofactor regeneration processes, enzyme-assisted strategies turn out to be promising alternatives to classical synthesis. Two categories of alkylating enzymes become increasingly relevant for applications: firstly prenyltransferases and terpene synthases (including terpene cyclases), which are used in the production of terpenoids such as artemisinin, or meroterpenoids like alkylated phenolics and indoles, and secondly methyltransferases, which modify flavonoids and alkaloids to yield products with a specific methylation pattern such as 7-O-methylaromadendrin and scopolamine.

  17. Mild copper-catalyzed fluorination of alkyl triflates with potassium fluoride.

    PubMed

    Dang, Hester; Mailig, Melrose; Lalic, Gojko

    2014-06-16

    A chemoselective catalytic fluorination of alkyl triflates is described using potassium fluoride as a fluoride source. Excellent yields of the desired alkyl fluorides are obtained after one hour at 45 °C using 2 mol% of the copper catalyst. With 10 mol% of the catalyst, full conversion can be achieved in less than 10 minutes at 45 °C, and thus makes this procedure potentially suited for the preparation of (18) F-labeled PET probes. As a result of the mild reaction conditions, only the substitution products are observed with no evidence of common side reactions, such as elimination. Reported is a preliminary study of the reaction scope, which demonstrates that the fluorination can be performed in the presence of a wide range of functional groups. Evidence suggests an unusual role of the [IPrCuOTf] catalyst as a phase-transfer catalyst and points to [IPrCuF] as the active fluorinating reagent (IPr=1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene).

  18. Improved 18F Labeling of Peptides with a Fluoride-Aluminum-Chelate Complex

    PubMed Central

    McBride, William J.; D’Souza, Christopher A.; Sharkey, Robert M.; Karacay, Habibe; Rossi, Edmund A.; Chang, Chien-Hsing; Goldenberg, David M.

    2010-01-01

    We reported previously the feasibility to radiolabel peptides with fluorine-18 (18F) using a rapid, one-pot, method that first mixes 18F− with Al3+, and then binds the (Al18F)2+ complex to a NOTA ligand on the peptide. In this report, we examined several new NOTA ligands and determined how temperature, reaction time, and reagent concentration affected the radiolabeling yield. Four structural variations of the NOTA ligand had isolated radiolabeling yields ranging from 5.8% to 87% under similar reaction conditions. All of the Al18F NOTA complexes were stable in vitro in human serum and those that were tested in vivo also were stable. The radiolabeling reactions were performed at 100°C and the peptides could be labeled in as little as five minutes. The IMP467 peptide could be labeled up to 115 GBq/μmol (3100 Ci/mmol), with a total reaction and purification time of 30 min without chromatographic purification. PMID:20540570

  19. Efficient (18)F-Labeling of Synthetic Exendin-4 Analogues for Imaging Beta Cells.

    PubMed

    Keliher, Edmund J; Reiner, Thomas; Thurber, Greg M; Upadhyay, Rabi; Weissleder, Ralph

    2012-08-01

    A number of exendin derivatives have been developed to target glucagon-like peptide 1 (GLP-1) receptors on beta cells in vivo. Modifications of exendin analogues have been shown to have significant effects on pharmacokinetics and, as such, have been used to develop a variety of therapeutic compounds. Here, we show that an exendin-4, modified at position 12 with a cysteine conjugated to a tetrazine, can be labeled with (18)F-trans-cyclooctene and converted into a PET imaging agent at high yields and with good selectivity. The agent accumulates in beta cells in vivo and has sufficiently high accumulation in mouse models of insulinomas to enable in vivo imaging. PMID:23997998

  20. 18F Labeled Nanoparticles for in Vivo PET-CT Imaging

    PubMed Central

    Devaraj, Neal K.; Keliher, Edmund J.; Thurber, Greg M.; Nahrendorf, Matthias; Weissleder, Ralph

    2009-01-01

    We report the synthesis and in vivo characterization of an 18F modified trimodal nanoparticle (18F-CLIO). This particle consists of cross-linked dextran held together in core–shell formation by a superparamagnetic iron oxide core and functionalized with the radionuclide 18F in high yield via “click” chemistry. The particle can be detected with positron emission tomography, fluorescence molecular tomography, and magnetic resonance imaging. The presence of 18F dramatically lowers the detection threshold of the nanoparticles, while the facile conjugation chemistry provides a simple platform for rapid and efficient nanoparticle labeling. PMID:19138113

  1. Efficient 18F-Labeling of Synthetic Exendin-4 Analogues for Imaging Beta Cells

    PubMed Central

    Keliher, Edmund J; Reiner, Thomas; Thurber, Greg M; Upadhyay, Rabi; Weissleder, Ralph

    2012-01-01

    A number of exendin derivatives have been developed to target glucagon-like peptide 1 (GLP-1) receptors on beta cells in vivo. Modifications of exendin analogues have been shown to have significant effects on pharmacokinetics and, as such, have been used to develop a variety of therapeutic compounds. Here, we show that an exendin-4, modified at position 12 with a cysteine conjugated to a tetrazine, can be labeled with 18F-trans-cyclooctene and converted into a PET imaging agent at high yields and with good selectivity. The agent accumulates in beta cells in vivo and has sufficiently high accumulation in mouse models of insulinomas to enable in vivo imaging. PMID:23997998

  2. Synthesis and evaluation of 18F labeled alanine derivatives as potential tumor imaging agents

    PubMed Central

    Wang, Limin; Zha, Zhihao; Qu, Wenchao; Qiao, Hongwen; Lieberman, Brian P.; Plössl, Karl; Kung, Hank F.

    2012-01-01

    Introduction This paper reports the synthesis and labeling of 18F alanine derivatives. We also investigate their biological characteristics as potential tumor imaging agents mediated by alanine-serine-cysteine preferring (ASC) transporter system. Methods Three new 18F alanine derivatives were prepared from corresponding tosylate-precursors through a two-step labelling reaction. In vitro uptake studies to evaluate and to compare these three analogs were carried out in 9L glioma and PC-3 prostate cancer cell lines. Potential transport mechanisms, protein incorporation and stability of 3-(1-[18F]fluoromethyl)-L-alanine (L[18F]FMA) were investigated in 9L glioma cells. Its biodistribution was determined in a rat-bearing 9L tumor model. PET imaging studies were performed on rat bearing 9L glioma tumors and transgenic mouse carrying spontaneous generated M/tomND tumor (mammary gland adenocarcinoma). Results New 18F alanine derivatives were prepared with 7–34% uncorrected radiochemical yields, excellent enantiomeric purity (>99%) and good radiochemical purity (>99%). In vitro uptake of the L-[18F]FMA in 9L glioma and PC-3 prostate cancer cells was higher than those observed for other two alanine derivatives and [18F]FDG in first 1 h. Inhibition of cell uptake studies suggested that L-[18F]FMA uptake in 9L glioma was predominantly via transport system ASC. After entering into cells, L-[18F]FMA remained stable and was not incorporated into protein within 2 h. In vivo biodistribution studies demonstrated that L-[18F]FMA had relatively high uptake in liver and kidney. Tumor uptake was fast, reaching a maximum within 30 min. The tumor-to-muscle, tumor-to-blood and tumor-to-brain ratios at 60 min post injection were 2.2, 1.9 and 3.0, respectively. In PET imaging studies, tumors were visualized with L-[18F]FMA in both 9L rat and transgenic mouse. Conclusion L-[18F]FMA showed promising properties as a PET imaging agent for up-regulated ASC transporter associated with tumor proliferation. PMID:22542392

  3. Synthesis and evaluation of 18F labeled FET prodrugs for tumor imaging

    PubMed Central

    Wang, Limin; Lieberman, Brian P.; Ploessl, Karl; Kung, Hank F.

    2013-01-01

    Introduction O-(2-[18F]fluoroethyl)-L-tyrosine (FET, [18F]1) is a useful amino-acid-based imaging agent for brain tumors. This paper reports the synthesis and evaluation of three FET prodrugs, O-(2-[18F]fluoroethyl)-L-tyrosyl-L-glycine (FET-Gly, [18F]2), O-(2-[18F]fluoroethyl)-L-tyrosyl-L-alanine (FET-Ala, [18F]3) and N-acetyl O-(2-[18F]fluoroethyl)-L-tyrosine (AcFET, [18F]4), which could be readily hydrolyzed to FET in vivo for tumor imaging. We investigated their metabolism in the blood and imaging properties in comparison to FET ([18F]1). Methods Three new [18F]FET derivatives, 2 – 4, were prepared from their corresponding tosylate-precursors through nucleophilic fluorination and subsequent deprotection reactions. In vitro uptake studies were carried out in 9L glioma cancer cell lines. In vitro and in vivo hydrolysis studies were conducted to evaluate the hydrolysis of FET prodrugs in blood and in Fisher 344 rats. Biodistribution and PET imaging studies were then performed in rats bearing 9L tumors. Results New FET prodrugs were prepared with 3 – 28 % decay corrected radiochemical yields, good enantiomeric purity (> 95 %) and high radiochemical purity (> 95 %). FET-Gly ([18F]2), FET-Ala ([18F]3), and AcFET ([18F]4) exhibited negligible uptake in comparison to the high uptake of FET ([18F]1) in 9L cells. Metabolism studies of FET-Gly ([18F]2), FET-Ala ([18F]3), and AcFET ([18F]4) in rat and human blood showed that FET-Ala ([18F]3) was hydrolyzed to FET ([18F]1) faster than FET-Gly ([18F]2) or AcFET ([18F]4). Most of the FET-Ala (79 %) was converted to FET ([18F]1) within 5 min in blood in vivo. Biodistribution studies demonstrated that FET-Ala ([18F]3) displayed the highest tumor uptake. The tumor-to-background ratios of FET-Ala ([18F]3) and FET ([18F]1) were comparable and appeared to be better than those of FET-Gly ([18F]2) and AcFET ([18F]4). PET imaging studies showed that both FET ([18F]1) and FET-Ala ([18F]3) could visualize tumors effectively, and that they share similar imaging characteristics. Conclusions FET-Ala ([18F]3) demonstrated promising properties as a prodrug of FET ([18F]1), which could be used in PET imaging of tumor amino acid metabolism. PMID:24183614

  4. An improved strategy for the synthesis of [18F]-labeled arabinofuranosyl nuclosides

    PubMed Central

    Zhang, Hanwen; Cantorias, Melchor V.; Pillarsetty, NagaVaraKishore; Burnazi, Eva M.; Cai, Shangde; Lewis, Jason S.

    2012-01-01

    The expression of the herpes simplex virus type-1 thymidine kinase (HSV1-tk) gene can be imaged efficaciously using a variety of 2′-[18F]fluoro-2′-deoxy-1-b-D-arabinofuranosyl-uracil derivatives [[18F]-FXAU, X= I(iodo), E(ethyl), and M(methyl)]. However, the application of these derivatives in clinical and translational studies has been impeded by their complicated and long syntheses (3–5 h). To remedy these issues, in the study at hand we have investigated whether microwave or combined catalysts could facilitate the coupling reaction between sugar and nucleobase and, further, have probed the feasibility of establishing a novel approach for [18F]-FXAU synthesis. We have demonstrated that the rate of the trimethylsilyl trifluoromethanesulfonate (TMSOTf)-catalyzed coupling reaction between the 2-deoxy-sugar and uracil derivatives at 90°C can be significantly accelerated by microwave-driven heating or by the addition of Lewis acid catalyst (SnCl4). Further, we have observed that the stability of the α- and β-anomers of [18F]-FXAU derivatives differs during the hydrolysis step. Using the microwave-driven heating approach, overall decay-corrected radiochemical yields of 19–27% were achieved for [18F]-FXAU in 120 min at a specific activity of >22 MBq/nmol (595 Ci/mmol). Ultimately, we believe that these high yielding syntheses of [18F]-FIAU, [18F]-FMAU and [18F]-FEAU will facilitate routine production for clinical applications. PMID:22819195

  5. 18F-Labeled Silicon-Based Fluoride Acceptors: Potential Opportunities for Novel Positron Emitting Radiopharmaceuticals

    PubMed Central

    Bernard-Gauthier, Vadim; Wängler, Carmen; Wängler, Bjoern; Schirrmacher, Ralf

    2014-01-01

    Background. Over the recent years, radiopharmaceutical chemistry has experienced a wide variety of innovative pushes towards finding both novel and unconventional radiochemical methods to introduce fluorine-18 into radiotracers for positron emission tomography (PET). These “nonclassical” labeling methodologies based on silicon-, boron-, and aluminium-18F chemistry deviate from commonplace bonding of an [18F]fluorine atom (18F) to either an aliphatic or aromatic carbon atom. One method in particular, the silicon-fluoride-acceptor isotopic exchange (SiFA-IE) approach, invalidates a dogma in radiochemistry that has been widely accepted for many years: the inability to obtain radiopharmaceuticals of high specific activity (SA) via simple IE. Methodology. The most advantageous feature of IE labeling in general is that labeling precursor and labeled radiotracer are chemically identical, eliminating the need to separate the radiotracer from its precursor. SiFA-IE chemistry proceeds in dipolar aprotic solvents at room temperature and below, entirely avoiding the formation of radioactive side products during the IE. Scope of Review. A great plethora of different SiFA species have been reported in the literature ranging from small prosthetic groups and other compounds of low molecular weight to labeled peptides and most recently affibody molecules. Conclusions. The literature over the last years (from 2006 to 2014) shows unambiguously that SiFA-IE and other silicon-based fluoride acceptor strategies relying on 18F− leaving group substitutions have the potential to become a valuable addition to radiochemistry. PMID:25157357

  6. Neither azeotropic drying, nor base nor other additives: a minimalist approach to (18)F-labeling.

    PubMed

    Richarz, R; Krapf, P; Zarrad, F; Urusova, E A; Neumaier, B; Zlatopolskiy, B D

    2014-10-28

    A novel, efficient, time-saving and reliable radiolabeling procedure via nucleophilic substitution with [(18)F]fluoride is described. Different radiolabeled aliphatic and aromatic compounds were prepared in high radiochemical yields simply by heating of quaternary anilinium, diaryliodonium and triarylsulfonium [(18)F]fluorides in suitable solvents. The latter were obtained via direct elution of (18)F(-) from an anion exchange resin with alcoholic solutions of onium precursors. Neither azeotropic evaporation of water, nor a base, nor any other additives like cryptands or crown ethers were necessary. Due to its simplicity this method should be highly suitable for automated radiosyntheses, especially in microfluidic devices. PMID:25190038

  7. Efficient (18)F-Labeling of Synthetic Exendin-4 Analogues for Imaging Beta Cells.

    PubMed

    Keliher, Edmund J; Reiner, Thomas; Thurber, Greg M; Upadhyay, Rabi; Weissleder, Ralph

    2012-08-01

    A number of exendin derivatives have been developed to target glucagon-like peptide 1 (GLP-1) receptors on beta cells in vivo. Modifications of exendin analogues have been shown to have significant effects on pharmacokinetics and, as such, have been used to develop a variety of therapeutic compounds. Here, we show that an exendin-4, modified at position 12 with a cysteine conjugated to a tetrazine, can be labeled with (18)F-trans-cyclooctene and converted into a PET imaging agent at high yields and with good selectivity. The agent accumulates in beta cells in vivo and has sufficiently high accumulation in mouse models of insulinomas to enable in vivo imaging.

  8. Decarboxylative Alkyl-Alkyl Cross-Coupling Reactions.

    PubMed

    Konev, Mikhail O; Jarvo, Elizabeth R

    2016-09-12

    Alkyl with alkyl: A significant development in alkyl-alkyl cross-coupling reactions, namely the nickel-catalyzed decarboxylative Negishi coupling of N-hydroxyphthalimide esters, was recently reported by Baran and co-workers. This method enables the synthesis of various highly functionalized compounds, including natural product derivatives.

  9. Optoelectronic and Photovoltaic Performances of Pyridine Based Monomer and Polymer Capped ZnO Dye-Sensitized Solar Cells.

    PubMed

    Singh, Satbir; Raj, Tilak; Singh, Amarpal; Kaur, Navneet

    2016-06-01

    The present research work describes the comparative analysis and performance characteristics of 4-pyridine based monomer and polymer capped ZnO dye-sensitized solar cells. The N, N-dimethyl-N4-((pyridine-4yl)methylene) propaneamine (4,monomer) and polyamine-4-pyridyl Schiff base (5, polymer) dyes were synthesized through one step condensation reaction between 4-pyridinecarboxaldehyde 1 and N, N-dimethylpropylamine 2/polyamine 3. Products obtained N, N-dimethyl-N4-((pyridine-4yl)methylene)propaneamine (4) and polyamine-4-pyridyl Schiff base (5) were purified and characterized using 1H, 13C NMR, mass, IR and CHN spectroscopy. Both the dyes 4 and 5 were further coated over ZnO nanoparticles and characterized using SEM, DLS and XRD analysis. Absorption profile and emission profile was monitored using fluorescence and UV-Vis absorption spectroscopy. A thick layer of these inbuilt dye linked ZnO nanoparticles of dyes (4) and (5) was pasted on one of the conductive side of ITO glass followed with a liquid electrolyte and counter electrode of the same conductive glass. Polyamine-4-pyridyl Schiff base polymer (5) decorated dye sensitized solar cell has shown better exciting photovoltaic properties in the form of short circuit current density (J(sc) = 6.3 mA/cm2), open circuit photo voltage (V(oc) = 0.7 V), fill factor (FF = 0.736) than monomer decorated dye sensitized solar cell. Polymer dye (5) based ZnO solar cell has shown a maximum solar power to electrical conversion efficiency of 3.25%, which is enhanced by 2.16% in case of monomer dye based ZnO solar cell under AM 1.5 sun illuminations.

  10. Pro-Oxidant Activity of Amine-Pyridine-Based Iron Complexes Efficiently Kills Cancer and Cancer Stem-Like Cells

    PubMed Central

    González-Bártulos, Marta; Aceves-Luquero, Clara; Qualai, Jamal; Cussó, Olaf; Martínez, Mª Angeles; Fernández de Mattos, Silvia; Menéndez, Javier A.; Villalonga, Priam; Costas, Miquel; Ribas, Xavi; Massaguer, Anna

    2015-01-01

    Differential redox homeostasis in normal and malignant cells suggests that pro-oxidant-induced upregulation of cellular reactive oxygen species (ROS) should selectively target cancer cells without compromising the viability of untransformed cells. Consequently, a pro-oxidant deviation well-tolerated by nonmalignant cells might rapidly reach a cell-death threshold in malignant cells already at a high setpoint of constitutive oxidative stress. To test this hypothesis, we took advantage of a selected number of amine-pyridine-based Fe(II) complexes that operate as efficient and robust oxidation catalysts of organic substrates upon reaction with peroxides. Five of these Fe(II)-complexes and the corresponding aminopyridine ligands were selected to evaluate their anticancer properties. We found that the iron complexes failed to display any relevant activity, while the corresponding ligands exhibited significant antiproliferative activity. Among the ligands, none of which were hemolytic, compounds 1, 2 and 5 were cytotoxic in the low micromolar range against a panel of molecularly diverse human cancer cell lines. Importantly, the cytotoxic activity profile of some compounds remained unaltered in epithelial-to-mesenchymal (EMT)-induced stable populations of cancer stem-like cells, which acquired resistance to the well-known ROS inducer doxorubicin. Compounds 1, 2 and 5 inhibited the clonogenicity of cancer cells and induced apoptotic cell death accompanied by caspase 3/7 activation. Flow cytometry analyses indicated that ligands were strong inducers of oxidative stress, leading to a 7-fold increase in intracellular ROS levels. ROS induction was associated with their ability to bind intracellular iron and generate active coordination complexes inside of cells. In contrast, extracellular complexation of iron inhibited the activity of the ligands. Iron complexes showed a high proficiency to cleave DNA through oxidative-dependent mechanisms, suggesting a likely mechanism of

  11. The discovery and the structural basis of an imidazo[4,5-b]pyridine-based p21-activated kinase 4 inhibitor.

    PubMed

    Park, Jeung Kuk; Kim, Sunmin; Han, Yu Jin; Kim, Seong Hwan; Kang, Nam Sook; Lee, Hyuk; Park, SangYoun

    2016-06-01

    p21-Activated kinases (PAKs) which belong to the family of ste20 serine/threonine protein kinases regulate cytoskeletal reorganization, cell motility, cell proliferation, and oncogenic transformation which are all related to the cellular functions during cancer induction and metastasis. The fact that PAK mutations are detected in multiple tumor tissues makes PAKs a novel therapeutic drug target. In this study, an imidazo[4,5-b]pyridine-based PAK4 inhibitor, KY-04045 (6-Bromo-2-(3-isopropyl-1-methyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridine), was discovered using a virtual site-directed fragment-based drug design and was validated using an inhibition assay. Although PAK4 affinity to KY-04045 seems much weaker than that of the reported PAK4 inhibitors, the location of KY-04045 is clearly defined in the structure of PAK4 co-crystallized with KY-04045. The crystal structure illustrates that the pyrazole and imidazopyridine rings of KY-04045 are sufficient for mediating PAK4 hinge loop interaction. Hence, we believe that KY-04045 can be exploited as a basic building block in designing novel imidazo[4,5-b]pyridine-based PAK4 inhibitors. PMID:27117431

  12. (11)C- and (18)F-Labeled Radioligands for P-Glycoprotein Imaging by Positron Emission Tomography.

    PubMed

    Cantore, Mariangela; Benadiba, Marcel; Elsinga, Philip H; Kwizera, Chantal; Dierckx, Rudi A J O; Colabufo, Nicola Antonio; Luurtsema, Gert

    2016-01-01

    P-Glycoprotein (P-gp) is an efflux transporter widely expressed at the human blood-brain barrier. It is involved in xenobiotics efflux and in onset and progression of neurodegenerative disorders. For these reasons, there is great interest in the assessment of P-gp expression and function by noninvasive techniques such as positron emission tomography (PET). Three radiolabeled aryloxazole derivatives: 2-[2-(2-methyl-((11)C)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline ([(11)C]-5); 2-[2-(2-fluoromethyl-((18)F)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetra-hydroisoquinoline ([(18)F]-6); and 2-[2-(2-fluoroethyl-((18)F)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline ([(18)F]-7), were tested in several in vitro biological assays to assess the effect of the aryl substituent in terms of potency and mechanism of action toward P-gp. Methyl derivative [(11)C]-5 is a potent P-gp substrate, whereas the corresponding fluoroethyl derivative [(18)F]-7 is a P-gp inhibitor. Fluoromethyl compound [(18)F]-6 is classified as a non-transported P-gp substrate, because its efflux increases after cyclosporine A modulation. These studies revealed a promising substrate and inhibitor, [(11)C]-5 and [(18)F]-7, respectively, for in vivo imaging of P-gp by using PET.

  13. Synthesis, uptake mechanism characterization and biological evaluation of 18F labeled fluoroalkyl phenylalanine analogs as potential PET imaging agents

    PubMed Central

    Wang, Limin; Qu, Wenchao; Lieberman, Brian P.; Plössl, Karl; Kung, Hank F.

    2010-01-01

    Introduction Amino acids based tracers represent a promising class of tumor metabolic imaging agents with successful clinical applications. Two new phenylalanine derivatives, p-(2-[18F]fluoroethyl)-L-phenylalanine (FEP, [18F]2) and p-(3-[18F]fluoropropyl)-L-phenylalanine (FPP, [18F]3) were synthesized and evaluated in comparison to clinically utilized O-(2-[18F]fluoroethyl)-L-tyrosine (FET, [18F]1). Methods FEP ([18F]2) and FPP ([18F]3) were successfully synthesized by a rapid and efficient two-step nucleophilic fluorination of tosylate precursors and deprotection reaction. In vitro cell uptake studies were carried out in 9L glioma cells. In vivo studies, 9L tumor xenografts were implanted in Fisher 344 rats. Results FEP ([18F]2) and FPP ([18F]3) could be efficiently labeled within 90 min with good enantiomeric purity (>95%), good yield (11–37%) and high specific activity (21–69 GBq/μmol). Cell uptake studies showed FEP had higher uptake than FPP as well as reference ligand FET ([18F]1). Uptake mechanism studies suggested that FEP is a selective substrate for system L and prefers its subtype LAT1. In vivo biodistribution studies demonstrated FEP had specific accumulation in tumor cells and tumor to background ratio reached 1.45 at 60 min. Small animal PET imaging studies showed FEP was comparable to FET for imaging rats bearing 9L tumor model. FEP had high uptake in 9L tumor compared to surrounding tissue and was quickly excreted through urinary tract. Conclusion Biological evaluations indicate that FEP ([18F]2) is a potential useful tracer for tumor imaging with PET. PMID:21220129

  14. 18F-labeled Single-Stranded DNA Aptamer for PET Imaging of Protein Tyrosine Kinase-7 Expression

    PubMed Central

    Wang, Lu; Wang, Zhe; Yang, Xiangyu; Dewhurst, Andrew; Ma, Ying; Zhu, Guizhi; Niu, Gang; Kiesewetter, Dale O.; Vasdev, Neil; Liang, Steven H.; Chen, Xiaoyuan

    2016-01-01

    Protein tyrosine kinase-7 (PTK7), a member of receptor tyrosine kinase superfamily initially identified as colon carcinoma kinase-4 (CCK-4), is highly expressed in various human malignancies. Its expression was found to correlate with aggressive biological behaviors such as increased cell proliferation, invasiveness and migration. Despite the importance and unmet need of imaging PTK7 in vivo, there is currently no clinically-relevant method to visualize tumoral PTK7 expression noninvasively such as PET or SPECT. This study aims to develop a specific, selective and high affinity PET radioligand based on single-stranded DNA (ssDNA) aptamer to address this challenge. Methods Sgc8, a 41-oligonucleotide that targets to PTK7, was labeled with F-18 using a two-step radiochemical synthesis, which featured a direct one-step radiofluorination on the distinctive spirocyclic hypervalent iodine(III) precursor to give 18F-fluorobenzyl azide followed by copper mediated “click” conjugation with Sgc8-alkyne. 18F-Sgc8 was evaluated in vitro and in vivo in two cell lines, HCT116 and U87MG, which express high and low amounts of PTK7, respectively. Results Sgc8 was labeled efficiently with F-18 in an isolated radiochemical yield of 62 ± 2%, non-decay-corrected (ndc) based on 18F-fluorobenzyl azide. 18F-Tr-Sgc8 was found to possess high affinity binding to both cell lines, with IC50 values for HCT116 as 2.7 ± 0.6 nM and U87MG as 16.9 ± 2.1 nM. In vivo PET imaging clearly visualized PTK7 expression in HCT116 xenografted mice with tumor uptake of 0.76 ± 0.09 %ID/g at 30 min post-injection (p.i.) for the subcutaneous tumor model and greater than 1.5 %ID/g for the liver metastasis model. U87MG xenograft tumors had much lower tracer accumulation (0.13 ± 0.06 %ID/g at 30 min p.i.), which was consistent with the lower expression of PTK7 in this tumor model. The labeled aptamer was rapidly cleared from the blood through the kidneys and bladder to give high tumor-to-blood and tumor-to-muscle ratios of 7.29 ± 1.51 and 10.25 ± 2.08, respectively. Conclusions The F-18 radiolabeling methodology shown here is a very robust procedure for labeling aptamers and similar chemical moieties, and can be applied to many different targets. Quantification of PTK7 using 18F-Tr-Sgc8 may be suitable for clinical translation and might help in the future to select and monitor appropriate therapies. PMID:26315836

  15. Synthesis, In Vitro and In Vivo Evaluation of 18F-labeled PET Ligands for Imaging the Vesicular Acetylcholine Transporter

    PubMed Central

    Tu, Zhude; Efange, Simon M. N.; Xu, Jinbin; Li, Shihong; Jones, Lynne A.; Parsons, Stanley M.; Mach, Robert H.

    2009-01-01

    A new class of vesicular acetylcholine transporter inhibitor that incorporates a carbonyl group into the benzovesamicol structure was synthesized and analogs were evaluated in vitro. (±)-trans-2-Hydroxy-3-(4-(4-[18F]fluorobenzoyl)piperidino)tetralin (9e) has Ki values of 2.70 nM for VAChT, 191 nM for σ1 and 251 nM for σ2. The racemic precursor (9d) was resolved via chiral HPLC and (±)-[18F]9e, (-)-[18F]9e, and (+)-[18F]9e were respectively radiolabeled via microwave irradiation of the appropriate precursors with [18F]/F- and Kryptofix/K2CO3 in DMSO with radiochemical yields ∼50-60% and specific activities >2000 mCi/μmol. (-)-[18F]9e uptake in rat brain was consistent with in vivo selectivity for the VAChT with an initial uptake of 0.911 %ID/g in rat striatum and a striatum: cerebellum ratio of 1.88 by 30 min p.i.. MicroPET imaging of macaques demonstrated a 2.1 ratio of (-)-[18F]9e in putamen versus cerebellum at 2 h. p.i. (-)-[18F]9e has potential to be a PET tracer for clinical imaging of the VAChT. PMID:19203271

  16. 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.

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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.

  3. Luminescent cyclometalated alkynylplatinum(II) complexes with a tridentate pyridine-based N-heterocyclic carbene ligand: synthesis, characterization, electrochemistry, photophysics, and computational studies.

    PubMed

    Leung, Sammual Yu-Lut; Lam, Elizabeth Suk-Hang; Lam, Wai Han; Wong, Keith Man-Chung; Wong, Wing-Tak; Yam, Vivian Wing-Wah

    2013-07-29

    A new class of luminescent alkynylplatinum(II) complexes with a tridentate pyridine-based N-heterocyclic carbene (2,6-bis(1-butylimidazol-2-ylidenyl)pyridine) ligand, [Pt(II)(C^N^C)(C≡CR)][PF6], and their chloroplatinum(II) precursor complex, [Pt(II)(C^N^C)Cl][PF6], have been synthesized and characterized. One of the alkynylplatinum(II) complexes has also been structurally characterized by X-ray crystallography. The electrochemistry, electronic absorption and luminescence properties of the complexes have been studied. Nanosecond transient absorption (TA) spectroscopy has also been performed to probe the nature of the excited state. The origin of the absorption and emission properties has been supported by computational studies. PMID:23788216

  4. Mild Catalytic methods for Alkyl-Alkyl Bond Formation

    SciTech Connect

    Vicic, David A

    2009-08-10

    Overview of Research Goals and Accomplishments for the Period 07/01/06 – 06/30/07: Our overall research goal is to transform the rapidly emerging synthetic chemistry involving alkyl-alkyl cross-couplings into more of a mechanism-based field so that that new, rationally-designed catalysts can be performed under energy efficient conditions. Our specific objectives for the previous year were 1) to obtain a proper electronic description of an active catalyst for alkyl-alkyl cross-coupling reactions and 2) to determine the effect of ligand structure on the rate, scope, selectivity, and functional group compatibility of C(sp3)-C(sp3) cross-coupling catalysis. We have completed both of these initial objectives and established a firm base for further studies. The specific significant achievements of the current grant period include: 1) we have performed magnetic and computational studies on (terpyridine)NiMe, an active catalyst for alkyl-alkyl cross couplings, and have discovered that the unpaired electron resides heavily on the terpyridine ligand and that the proper electronic description of this nickel complex is a Ni(II)-methyl cation bound to a reduced terpyridine ligand; 2) we have for the first time shown that alkyl halide reduction by terpyridyl nickel catalysts is substantially ligand based; 3) we have shown by isotopic labeling studies that the active catalyst (terpyridine)NiMe is not produced via a mechanism that involves the formation of methyl radicals when (TMEDA)NiMe2 is used as the catalyst precursor; 4) we have performed an extensive ligand survey for the alkyl-alkyl cross-coupling reactions and have found that electronic factors only moderately influence reactivity in the terpyridine-based catalysis and that the most dramatic effects arise from steric and solubility factors; 5) we have found that the use of bis(dialkylphosphino)methanes as ligands for nickel does not produce active catalysts for cross-coupling but rather leads to bridging hydride

  5. Chain-amplified photochemical fragmentation of N-alkoxypyridinium salts: proposed reaction of alkoxyl radicals with pyridine bases to give pyridinyl radicals.

    PubMed

    Shukla, Deepak; Adiga, Shashishekar P; Ahearn, Wendy G; Dinnocenzo, Joseph P; Farid, Samir

    2013-03-01

    Photoinduced electron transfer to N-alkoxypyridiniums, which leads to N–O bond cleavage and alkoxyl radical formation, is highly chain amplified in the presence of a pyridine base such as lutidine. Density functional theory calculations support a mechanism in which the alkoxyl radicals react with lutidine via proton-coupled electron transfer (PCET) to produce lutidinyl radicals (BH•). A strong electron donor, BH• is proposed to reduce another alkoxypyridinium cation, leading to chain amplification, with quantum yields approaching 200. Kinetic data and calculations support the formation of a second, stronger reducing agent: a hydrogen-bonded complex between BH• and another base molecule (BH•···B). Global fitting of the quantum yield data for the reactions of four pyridinium salts (4-phenyl and 4-cyano with N-methoxy and N-ethoxy substituents) led to a consistent set of kinetic parameters. The chain nature of the reaction allowed rate constants to be determined from steady-state kinetics and independently determined chain-termination rate constants. The rate constant of the reaction of CH3O• with lutidine to form BH•, k1, is ~6 × 10(6) M(–1) s(–1); that of CH3CH2O• is ~9 times larger. Reaction of CD3O• showed a deuterium isotope effect of ~6.5. Replacing lutidine by 3-chloropyridine, a weaker base, decreases k1 by a factor of ~400.

  6. 40 CFR 721.9892 - Alkylated urea.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 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...

  7. 40 CFR 721.9892 - Alkylated urea.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 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...

  8. 40 CFR 721.9892 - Alkylated urea.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 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...

  9. 40 CFR 721.9892 - Alkylated urea.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 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...

  10. Oil compositions containing alkyl amine or alkyl mercaptan derivatives of copolymers of an alpha olefin or an alkyl vinyl ether

    SciTech Connect

    Le, H.T.

    1990-02-13

    This patent describes an oil composition. It comprises a major amount of an oil selected from a crude oil or fuel oil and a minor amount of an alkyl amine or alkyl mercaptan derivative of an alpha olefin or alkyl vinyl ether and an unsaturated alpha, beta-dicarboxylic compound copolymer having pour point depressant ;properties. The copolymer comprising the reaction product of an alpha olefin having from about 2 to about 30 carbon atoms or mixtures of alpha olefins having from about 2 to about 30 carbon atoms or an alkyl vinyl ether or mixture of alkyl vinyl ethers.

  11. Methods of making alkyl esters

    SciTech Connect

    Elliott, Brian

    2010-08-03

    A method comprising contacting an alcohol, a feed comprising one or more glycerides and equal to or greater than 2 wt % of one or more free fatty acids, and a solid acid catalyst, a nanostructured polymer catalyst, or a sulfated zirconia catalyst in one or more reactors, and recovering from the one or more reactors an effluent comprising equal to or greater than about 75 wt % alkyl ester and equal to or less than about 5 wt % glyceride.

  12. 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.

  13. Structural, magnetic, and redox diversity of first-row transition metal complexes of a pyridine-based macrocycle: well-marked trends supported by theoretical DFT calculations.

    PubMed

    Drahoš, Bohuslav; Herchel, Radovan; Trávníček, Zdeněk

    2015-04-01

    A series of first-row transition metal complexes with 15-membered pyridine-based macrocycle (3,12,18-triaza-6,9-dioxabicyclo[12.3.1]octadeca-1(18),14,16-triene = L) was prepared ([M(II)(L)Cl2], where M = Mn, Co, Ni, Zn (1, 3, 4, 6); [Fe(III)(L)Cl2]Cl (2), [Cu(II)(L)Cl]Cl (5)) and thoroughly characterized. Depending on the complexated metal atom, the coordination number varies from 7 (Mn, Fe, Co), through 5 + 2 for Ni and 4 + 1 for Cu, to 5 for Zn accompanied by changes in the coordination geometry from the pentagonal bipyramid (1-4) to the square pyramid (5 and 6). Along the series, the metal-oxygen distances were prolonged in such manner that their bonding character was investigated, apart from X-ray structural analysis, also by ab initio calculations (Mayer's bond order, electron localization function), which confirmed that, in 4 and 5, two and one oxygen donor atoms are semicoordinated, respectively, and one and two oxygen atoms are uncoordinated in 5, and 6, respectively. On the basis of the temperature variable magnetic susceptibility measurements, 1 and 2 behave as expected for 3d(5) high-spin configuration with negligible zero-field splitting (ZFS). On the other hand, a large axial ZFS (D(Co) ≈ 40 cm(-1), D(Ni) ≈ -6.0 cm(-1)) was found for 3 and 4, and rhombic ZFS (E/D ≈ 0.15) for 4. Antiferromagnetic exchange coupling was observed for 4 and 5 (J(Ni) = -0.48 cm(-1), and J(Cu) = -2.43 cm(-1), respectively). The obtained results correlate well with ab initio calculations of ZFS parameters as well as J-values, which indicate that the antiferromagnetic exchange is mediated by hydrogen bonds. The complexes were also investigated by cyclic voltammetry in water or acetonitrile. A quasi-reversible couple Mn(II)/Mn(III) at 1.13/0.97 V, an almost reversible couple Fe(II)/Fe(III) at 0.51/0.25 V, and a one-step/multistep reduction/oxidation of Cu(II) complex 5 at -0.33 V/0.06-0.61 V were detected. PMID:25761063

  14. Bimetallic oxidative addition involving radical intermediates in nickel-catalyzed alkyl-alkyl Kumada coupling reactions.

    PubMed

    Breitenfeld, Jan; Ruiz, Jesus; Wodrich, Matthew D; Hu, Xile

    2013-08-14

    Many nickel-based catalysts have been reported for cross-coupling reactions of nonactivated alkyl halides. The mechanistic understanding of these reactions is still primitive. Here we report a mechanistic study of alkyl-alkyl Kumada coupling catalyzed by a preformed nickel(II) pincer complex ([(N2N)Ni-Cl]). The coupling proceeds through a radical process, involving two nickel centers for the oxidative addition of alkyl halide. The catalysis is second-order in Grignard reagent, first-order in catalyst, and zero-order in alkyl halide. A transient species, [(N2N)Ni-alkyl(2)](alkyl(2)-MgCl), is identified as the key intermediate responsible for the activation of alkyl halide, the formation of which is the turnover-determining step of the catalysis.

  15. Bimetallic oxidative addition involving radical intermediates in nickel-catalyzed alkyl-alkyl Kumada coupling reactions.

    PubMed

    Breitenfeld, Jan; Ruiz, Jesus; Wodrich, Matthew D; Hu, Xile

    2013-08-14

    Many nickel-based catalysts have been reported for cross-coupling reactions of nonactivated alkyl halides. The mechanistic understanding of these reactions is still primitive. Here we report a mechanistic study of alkyl-alkyl Kumada coupling catalyzed by a preformed nickel(II) pincer complex ([(N2N)Ni-Cl]). The coupling proceeds through a radical process, involving two nickel centers for the oxidative addition of alkyl halide. The catalysis is second-order in Grignard reagent, first-order in catalyst, and zero-order in alkyl halide. A transient species, [(N2N)Ni-alkyl(2)](alkyl(2)-MgCl), is identified as the key intermediate responsible for the activation of alkyl halide, the formation of which is the turnover-determining step of the catalysis. PMID:23865460

  16. 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 alkyl esters (generic name). 721.1875 Section 721.1875 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.1875 Boric acid, alkyl and substituted...

  17. 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 alkyl esters (generic name). 721.1875 Section 721.1875 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.1875 Boric acid, alkyl and substituted...

  18. 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 alkyl esters (generic name). 721.1875 Section 721.1875 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.1875 Boric acid, alkyl and substituted...

  19. 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 alkyl esters (generic name). 721.1875 Section 721.1875 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.1875 Boric acid, alkyl and substituted...

  20. 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 alkyl esters (generic name). 721.1875 Section 721.1875 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.1875 Boric acid, alkyl and substituted...

  1. 40 CFR 721.8673 - [(Disubstituted phenyl)]azo dihydro hydroxy alkyl oxo alkyl-substituted-pyridines (generic name).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false azo dihydro hydroxy alkyl oxo alkyl... Significant New Uses for Specific Chemical Substances § 721.8673 azo dihydro hydroxy alkyl oxo alkyl...) The chemical substances identified generically as azo dihydro hydroxy alkyl oxo...

  2. 40 CFR 721.8673 - [(Disubstituted phenyl)]azo dihydro hydroxy alkyl oxo alkyl-substituted-pyridines (generic name).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false azo dihydro hydroxy alkyl oxo alkyl... Significant New Uses for Specific Chemical Substances § 721.8673 azo dihydro hydroxy alkyl oxo alkyl...) The chemical substances identified generically as azo dihydro hydroxy alkyl oxo...

  3. 40 CFR 721.8673 - [(Disubstituted phenyl)]azo dihydro hydroxy alkyl oxo alkyl-substituted-pyridines (generic name).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false azo dihydro hydroxy alkyl oxo alkyl... Significant New Uses for Specific Chemical Substances § 721.8673 azo dihydro hydroxy alkyl oxo alkyl...) The chemical substances identified generically as azo dihydro hydroxy alkyl oxo...

  4. 40 CFR 721.8673 - [(Disubstituted phenyl)]azo dihydro hydroxy alkyl oxo alkyl-substituted-pyridines (generic name).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false azo dihydro hydroxy alkyl oxo alkyl... Significant New Uses for Specific Chemical Substances § 721.8673 azo dihydro hydroxy alkyl oxo alkyl...) The chemical substances identified generically as azo dihydro hydroxy alkyl oxo...

  5. 40 CFR 721.8673 - [(Disubstituted phenyl)]azo dihydro hydroxy alkyl oxo alkyl-substituted-pyridines (generic name).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false azo dihydro hydroxy alkyl oxo alkyl... Significant New Uses for Specific Chemical Substances § 721.8673 azo dihydro hydroxy alkyl oxo alkyl...) The chemical substances identified generically as azo dihydro hydroxy alkyl oxo...

  6. Mechanistic insights into nickamine-catalyzed alkyl-alkyl cross-coupling reactions.

    PubMed

    Breitenfeld, Jan; Hu, Xile

    2014-01-01

    Within the last decades the transition metal-catalyzed cross-coupling of non-activated alkyl halides has significantly progressed. Within the context of alkyl-alkyl cross-coupling, first row transition metals spanning from iron, over cobalt, nickel, to copper have been successfully applied to catalyze this difficult reaction. The mechanistic understanding of these reactions is still in its infancy. Herein we outline our latest mechanistic studies that explain the efficiency of nickel, in particular nickamine-catalyzed alkyl-alkyl cross-coupling reactions.

  7. Occupational asthma due to alkyl cyanoacrylate

    SciTech Connect

    Nakazawa, T. )

    1990-08-01

    A case of bronchial asthma induced by occupational exposure to alkyl cyanoacrylate, an adhesive, occurred in an assembly operation. Provocative exposure testing induced immediate and delayed asthmatic responses. Alkyl cyanoacrylate seemed to act as an allergen or as an irritant, resulting in the development of asthma.

  8. 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 721.9892 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.9892 Alkylated urea. (a) Chemical...

  9. C-Alkylation by Hydrogen Autotransfer Reactions.

    PubMed

    Obora, Yasushi

    2016-04-01

    The development of practical, efficient, and atom-economical methods for the formation of carbon-carbon bonds remains a topic of considerable interest in current synthetic organic chemistry. In this review, we have summarized selected topics from the recent literature with particular emphasis on C-alkylation processes involving hydrogen transfer using alcohols as alkylation reagents. This review includes selected highlights concerning recent progress towards the modification of catalytic systems for the α-alkylation of ketones, nitriles, and esters. Furthermore, we have devoted a significant portion of this review to the methylation of ketones, alcohols, and indoles using methanol. Lastly, we have also documented recent advances in β-alkylation methods involving the dimerization of alcohols (Guerbet reaction), as well as new developments in C-alkylation methods based on sp (3) C-H activation. PMID:27573136

  10. Alkylation of organic aromatic compounds

    DOEpatents

    Smith, Jr., Lawrence A.; Arganbright, Robert P.; Hearn, Dennis

    1993-01-01

    Aromatic compounds are alkylated in a catalytic distillation, wherein the catalyst structure also serves as a distillation component by contacting the aromatic compound with a C.sub.2 to C.sub.10 olefin in the catalyst bed under 0.25 to 50 atmospheres of pressure and at temperatures in the range of 80.degree. C. to 500.degree. C., using as the catalyst a mole sieve characterized as acidic or an acidic cation exchange resin. For example, ethyl benzene is produced by feeding ethylene to about the mid point of the catalyst bed while benzene is conveniently added through the reflux in molar excess to that required to react with ethylene, thereby reacting substantially all of the ethylene and recovering benzene as the principal overhead and ethyl benzene in the bottoms.

  11. Alkylation of organic aromatic compounds

    DOEpatents

    Smith, Jr., Lawrence A.

    1989-01-01

    Aromatic compounds are alkylated in a catalytic distillation, wherein the catalyst structure also serves as a distillation component by contacting the aromatic compound with a C.sub.2 to C.sub.10 olefin in the catalyst bed under 0.25 to 50 atmospheres of pressure and at temperatures in the range of 80.degree. C. to 500.degree. C., using as the catalyst a mole sieve characterized as acidic or an acidic cation exchange resin. For example, ethyl benzene is produced by feeding ethylene below the catalyst bed while benzene is conveniently added through the reflux in molar excess to that required to react with ethylene, thereby reacting substantially all of the ethylene and recovering benzene as the principal overhead and ethyl benzene in the bottoms.

  12. Alkylation of organic aromatic compounds

    DOEpatents

    Smith, L.A. Jr.; Arganbright, R.P.; Hearn, D.

    1993-09-07

    Aromatic compounds are alkylated in a catalytic distillation, wherein the catalyst structure also serves as a distillation component by contacting the aromatic compound with a C[sub 2] to C[sub 10] olefin in the catalyst bed under 0.25 to 50 atmospheres of pressure and at temperatures in the range of 80 C to 500 C, using as the catalyst a molecular sieve characterized as acidic or an acidic cation exchange resin. For example, ethyl benzene is produced by feeding ethylene to about the mid point of the catalyst bed while benzene is conveniently added through the reflux in molar excess to that required to react with ethylene, thereby reacting substantially all of the ethylene and recovering benzene as the principal overhead and ethyl benzene in the bottoms. 1 figures.

  13. Alkylation of organic aromatic compounds

    DOEpatents

    Smith, Jr., Lawrence A.; Arganbright, Robert P.; Hearn, Dennis

    1993-01-01

    Aromatic compounds are alkylated in a combination reactor/distillation column comprising a vessel suitable for operating between 70.degree. C. and 500.degree. C. and from 0.5 to 20 atmospheres pressure; an inert distillation packing in the lower one-third of said vessel; solid acidic catalytic material such as zeolites or an acidic cation exchange resin supported in the middle one-third of said vessel; and inert distillation packing in the upper one-third of said vessel. A benzene inlet is located near the upper end of the vessel; an olefin inlet is juxtaposed with said solid acidic catalytic material; a bottoms outlet is positioned near the bottom of said vessel for removing said cumene and ethyl benzene; and an overhead outlet is placed at the top of said vessel for removing any unreacted benzene and olefin.

  14. Alkylation of organic aromatic compounds

    DOEpatents

    Smith, Jr., Lawrence A.; Arganbright, Robert P.; Hearn, Dennis

    1994-01-01

    Aromatic compounds are alkylated in a catalytic distillation, wherein the catalyst structure also serves as a distillation component by contacting the aromatic compound with a C.sub.2 to C.sub.10 olefin in the catalyst bed under 0.25 to 50 atmospheres of pressure and at temperatures in the range of 80.degree. C. to 500.degree. C., using as the catalyst a mole sieve characterized as acidic or an acidic cation exchange resin. For example, ethyl benzene is produced by feeding ethylene below the catalyst bed while benzene is conveniently added through the reflux in molar excess to that required to react with ethylene, thereby reacting substantially all of the ethylene and recovering benzene as the principal overhead and ethyl benzene in the bottoms.

  15. Alkylation of organic aromatic compounds

    DOEpatents

    Smith, L.A. Jr.

    1989-07-18

    Aromatic compounds are alkylated in a catalytic distillation, wherein the catalyst structure also serves as a distillation component by contacting the aromatic compound with a C[sub 2] to C[sub 10] olefin in the catalyst bed under 0.25 to 50 atmospheres of pressure and at temperatures in the range of 80 C to 500 C, using as the catalyst a mole sieve characterized as acidic or an acidic cation exchange resin. For example, ethyl benzene is produced by feeding ethylene below the catalyst bed while benzene is conveniently added through the reflux in molar excess to that required to react with ethylene, thereby reacting substantially all of the ethylene and recovering benzene as the principal overhead and ethyl benzene in the bottoms. 1 fig.

  16. Alkylation of organic aromatic compounds

    DOEpatents

    Smith, L.A. Jr.; Arganbright, R.P.; Hearn, D.

    1994-06-14

    Aromatic compounds are alkylated in a catalytic distillation, wherein the catalyst structure also serves as a distillation component by contacting the aromatic compound with a C[sub 2] to C[sub 10] olefin in the catalyst bed under 0.25 to 50 atmospheres of pressure and at temperatures in the range of 80 C to 500 C, using as the catalyst a molecular sieve characterized as acidic or an acidic cation exchange resin. For example, ethyl benzene is produced by feeding ethylene below the catalyst bed while benzene is conveniently added through the reflux in molar excess to that required to react with ethylene, thereby reacting substantially all of the ethylene and recovering benzene as the principal overhead and ethyl benzene in the bottoms. 1 fig.

  17. Alkylation of organic aromatic compounds

    DOEpatents

    Smith, L.A. Jr.; Arganbright, R.P.; Hearn, D.

    1993-01-05

    Aromatic compounds are alkylated in a combination reactor/distillation column comprising a vessel suitable for operating between 70 C and 500 C and from 0.5 to 20 atmospheres pressure; an inert distillation packing in the lower one-third of said vessel; solid acidic catalytic material such as zeolites or an acidic cation exchange resin supported in the middle one-third of said vessel; and inert distillation packing in the upper one-third of said vessel. A benzene inlet is located near the upper end of the vessel; an olefin inlet is juxtaposed with said solid acidic catalytic material; a bottoms outlet is positioned near the bottom of said vessel for removing said cumene and ethyl benzene; and an overhead outlet is placed at the top of said vessel for removing any unreacted benzene and olefin.

  18. Catalytic hydrogenation activity and electronic structure determination of bis(arylimidazol-2-ylidene)pyridine cobalt alkyl and hydride complexes.

    PubMed

    Yu, Renyuan Pony; Darmon, Jonathan M; Milsmann, Carsten; Margulieux, Grant W; Stieber, S Chantal E; DeBeer, Serena; Chirik, Paul J

    2013-09-01

    The bis(arylimidazol-2-ylidene)pyridine cobalt methyl complex, ((iPr)CNC)CoCH3, was evaluated for the catalytic hydrogenation of alkenes. At 22 °C and 4 atm of H2 pressure, ((iPr)CNC)CoCH3 is an effective precatalyst for the hydrogenation of sterically hindered, unactivated alkenes such as trans-methylstilbene, 1-methyl-1-cyclohexene, and 2,3-dimethyl-2-butene, representing one of the most active cobalt hydrogenation catalysts reported to date. Preparation of the cobalt hydride complex, ((iPr)CNC)CoH, was accomplished by hydrogenation of ((iPr)CNC)CoCH3. Over the course of 3 h at 22 °C, migration of the metal hydride to the 4-position of the pyridine ring yielded (4-H2-(iPr)CNC)CoN2. Similar alkyl migration was observed upon treatment of ((iPr)CNC)CoH with 1,1-diphenylethylene. This reactivity raised the question as to whether this class of chelate is redox-active, engaging in radical chemistry with the cobalt center. A combination of structural, spectroscopic, and computational studies was conducted and provided definitive evidence for bis(arylimidazol-2-ylidene)pyridine radicals in reduced cobalt chemistry. Spin density calculations established that the radicals were localized on the pyridine ring, accounting for the observed reactivity, and suggest that a wide family of pyridine-based pincers may also be redox-active.

  19. Cellular accumulation of 18F-labelled boronophenylalanine depending on DNA synthesis and melanin incorporation: a double-tracer microautoradiographic study of B16 melanomas in vivo.

    PubMed

    Kubota, R; Yamada, S; Ishiwata, K; Tada, M; Ido, T; Kubota, K

    1993-04-01

    The cellular distribution of 4-borono-2-[18F]fluoro-L-phenylalanine ([18F]FBPA, an analog of p-boronophenylaline), a potential agent for boron neutron capture therapy (BNCT), and [6-3H]thymidine ([3H]Thd, a DNA precursor) in murine two B16 melanoma sublines and FM3A mammary carcinoma was studied in vivo using double-tracer microautoradiography. Tumour volume, tumour age, cell density in the tissues and the proportion of S phase cells in the cell cycle were the same in the three tumour models. Volume doubling time, which represents tumour growth rate, was fastest in B16F10, followed by B16F1 (P < 0.05), the slowest being in FM3A (P < 0.001). The rate of DNA synthesis in S phase cells corresponded to the volume doubling time. The greatest amount of [18F]FBPA was observed in S phase melanocytes and the lowest amount was found in non-S phase non-melanocytes. The [18F]FBPA accumulation was primarily related to the activity of DNA synthesis and, secondarily, to the degree of pigmentation in melanocytes. The therapeutic efficacy of BNCT with p-boronophenylalanine may be greater in melanoma that exhibits greater DNA synthesis activity and higher melanin content.

  20. Cellular accumulation of 18F-labelled boronophenylalanine depending on DNA synthesis and melanin incorporation: a double-tracer microautoradiographic study of B16 melanomas in vivo.

    PubMed Central

    Kubota, R.; Yamada, S.; Ishiwata, K.; Tada, M.; Ido, T.; Kubota, K.

    1993-01-01

    The cellular distribution of 4-borono-2-[18F]fluoro-L-phenylalanine ([18F]FBPA, an analog of p-boronophenylaline), a potential agent for boron neutron capture therapy (BNCT), and [6-3H]thymidine ([3H]Thd, a DNA precursor) in murine two B16 melanoma sublines and FM3A mammary carcinoma was studied in vivo using double-tracer microautoradiography. Tumour volume, tumour age, cell density in the tissues and the proportion of S phase cells in the cell cycle were the same in the three tumour models. Volume doubling time, which represents tumour growth rate, was fastest in B16F10, followed by B16F1 (P < 0.05), the slowest being in FM3A (P < 0.001). The rate of DNA synthesis in S phase cells corresponded to the volume doubling time. The greatest amount of [18F]FBPA was observed in S phase melanocytes and the lowest amount was found in non-S phase non-melanocytes. The [18F]FBPA accumulation was primarily related to the activity of DNA synthesis and, secondarily, to the degree of pigmentation in melanocytes. The therapeutic efficacy of BNCT with p-boronophenylalanine may be greater in melanoma that exhibits greater DNA synthesis activity and higher melanin content. Images Figure 1 PMID:8471428

  1. PET Imaging of Extracellular pH in Tumors with (64)Cu- and (18)F-Labeled pHLIP Peptides: A Structure-Activity Optimization Study.

    PubMed

    Demoin, Dustin Wayne; Wyatt, Linden C; Edwards, Kimberly J; Abdel-Atti, Dalya; Sarparanta, Mirkka; Pourat, Jacob; Longo, Valerie A; Carlin, Sean D; Engelman, Donald M; Andreev, Oleg A; Reshetnyak, Yana K; Viola-Villegas, Nerissa; Lewis, Jason S

    2016-09-21

    pH (low) insertion peptides (pHLIP peptides) target acidic extracellular environments in vivo due to pH-dependent cellular membrane insertion. Two variants (Var3 and Var7) and wild-type (WT) pHLIP peptides have shown promise for in vivo imaging of breast cancer. Two positron emitting radionuclides ((64)Cu and (18)F) were used to label the NOTA- and NO2A-derivatized Var3, Var7, and WT peptides for in vivo biodistribution studies in 4T1 orthotopic tumor-bearing BALB/c mice. All of the constructs were radiolabeled with (64)Cu or [(18)F]-AlF in good yield. The in vivo biodistribution of the 12 constructs in 4T1 orthotopic allografted female BALB/c mice indicated that NO2A-cysVar3, radiolabeled with either (18)F (4T1 uptake; 8.9 ± 1.7%ID/g at 4 h p.i.) or (64)Cu (4T1 uptake; 8.2 ± 0.9%ID/g at 4 h p.i. and 19.2 ± 1.8% ID/g at 24 h p.i.), shows the most promise for clinical translation. Additional studies to investigate other tumor models (melanoma, prostate, and brain tumor models) indicated the universality of tumor targeting of these tracers. From this study, future clinical translation will focus on (18)F- or (64)Cu-labeled NO2A-cysVar3. PMID:27396694

  2. PET Imaging of Extracellular pH in Tumors with 64Cu- and 18F-Labeled pHLIP Peptides: A Structure–Activity Optimization Study

    PubMed Central

    2016-01-01

    pH (low) insertion peptides (pHLIP peptides) target acidic extracellular environments in vivo due to pH-dependent cellular membrane insertion. Two variants (Var3 and Var7) and wild-type (WT) pHLIP peptides have shown promise for in vivo imaging of breast cancer. Two positron emitting radionuclides (64Cu and 18F) were used to label the NOTA- and NO2A-derivatized Var3, Var7, and WT peptides for in vivo biodistribution studies in 4T1 orthotopic tumor-bearing BALB/c mice. All of the constructs were radiolabeled with 64Cu or [18F]-AlF in good yield. The in vivo biodistribution of the 12 constructs in 4T1 orthotopic allografted female BALB/c mice indicated that NO2A-cysVar3, radiolabeled with either 18F (4T1 uptake; 8.9 ± 1.7%ID/g at 4 h p.i.) or 64Cu (4T1 uptake; 8.2 ± 0.9%ID/g at 4 h p.i. and 19.2 ± 1.8% ID/g at 24 h p.i.), shows the most promise for clinical translation. Additional studies to investigate other tumor models (melanoma, prostate, and brain tumor models) indicated the universality of tumor targeting of these tracers. From this study, future clinical translation will focus on 18F- or 64Cu-labeled NO2A-cysVar3. PMID:27396694

  3. Structure-Activity Relationship of (18)F-Labeled Phosphoramidate Peptidomimetic Prostate-Specific Membrane Antigen (PSMA)-Targeted Inhibitor Analogues for PET Imaging of Prostate Cancer.

    PubMed

    Dannoon, Shorouk; Ganguly, Tanushree; Cahaya, Hendry; Geruntho, Jonathan J; Galliher, Matthew S; Beyer, Sophia K; Choy, Cindy J; Hopkins, Mark R; Regan, Melanie; Blecha, Joseph E; Skultetyova, Lubica; Drake, Christopher R; Jivan, Salma; Barinka, Cyril; Jones, Ella F; Berkman, Clifford E; VanBrocklin, Henry F

    2016-06-23

    A series of phosphoramidate-based prostate specific membrane antigen (PSMA) inhibitors of increasing lipophilicity were synthesized (4, 5, and 6), and their fluorine-18 analogs were evaluated for use as positron emission tomography (PET) imaging agents for prostate cancer. To gain insight into their modes of binding, they were also cocrystallized with the extracellular domain of PSMA. All analogs exhibited irreversible binding to PSMA with IC50 values ranging from 0.4 to 1.3 nM. In vitro assays showed binding and rapid internalization (80-95%, 2 h) of the radiolabeled ligands in PSMA(+) cells. In vivo distribution demonstrated significant uptake in CWR22Rv1 (PSMA(+)) tumor, with tumor to blood ratios of 25.6:1, 63.6:1, and 69.6:1 for [(18)F]4, [(18)F]5, and [(18)F]6, respectively, at 2 h postinjection. Installation of aminohexanoic acid (AH) linkers in the phosphoramidate scaffold improved their PSMA binding and inhibition and was critical for achieving suitable in vivo imaging properties, positioning [(18)F]5 and [(18)F]6 as favorable candidates for future prostate cancer imaging clinical trials. PMID:27228467

  4. 18F-Labeled NaF PET-CT in Detection of Bone Metastases in Patients With Preoperative Lung Cancer.

    PubMed

    Rao, Liangjun; Zong, Zhen; Chen, Zhifeng; Wang, Xiaoyan; Shi, Xinchong; Yi, Chang; Zhang, Xiangsong

    2016-04-01

    We compared the diagnostic accuracy of F-labeled sodium fluoride (F-NaF) PET-CT with 99m-technetium methylene diphosphonate (Tc-MDP) single photon emission computed tomography (SPECT) to detect bone metastases (BMs) in patients with preoperative lung cancer. Patients with lung cancer (n = 181) were examined with F-NaF PET-CT, and another 167 patients with lung cancer were examined with Tc-MDP SPECT. F-NaF PET-CT and Tc-MDP SPECT were evaluated by 2 experienced readers. Lesions were graded on a scale of 0 (degenerative lesion) to 4 (definite BM), and equivocal lesions were determined as indifferent (grade 3). Based on patient-based analysis, there were only 4 equivocal patients in F-NaF PET-CT detection. However, in Tc-MDP SPECT detection, there were 19 equivocal patients, which indicated a significant difference in terms of occurrence ratio (χ = 9.005, P = 0.03). Sensitivity and specificity of PET-CT was significantly better than that of SPECT when equivocal reading was categorized as malignant or benign (P < 0.05). Based on lesions-based analysis, SPECT produced 26 equivocal lesions of 333 lesions, but PET-CT produced only 5 equivocal lesions of 991 lesions. PET-CT was significantly better than SPECT in the aspect of producing equivocal patients (χ = 58.141, P < 0.001). Sensitivity and specificity of PET-CT was significantly better than that of SPECT when equivocal reading was categorized as malignant or benign (P < 0.05). F-NaF PET-CT is a highly sensitive and specific modality for the detection of BM in patients with preoperative lung cancer. It is better than conventional Tc-MDP SPECT in detecting BM in patients with preoperative lung cancer.

  5. Synthesis and evaluation of (18)F-labeled bile acid compound: a potential PET imaging agent for FXR-related diseases.

    PubMed

    Jia, Lina; Jiang, Dawei; Hu, Pengcheng; Li, Xiao; Shi, Hongcheng; Cheng, Dengfeng; Zhang, Lan

    2014-07-01

    The farnesoid-X-receptor (FXR) is a member of the nuclear hormone receptor superfamily. The FXR has critical functions in maintaining bile acid synthesis and homeostasis, liver regeneration and tumorigenesis, intestinal diseases, intestinal tumorigenesis, cholesterol gallstone disease, cholestasis, and atherosclerosis. FXR expression is strongly downregulated in liver fibrosis, hepatocellular adenoma and hepatocellular carcinoma compared to expression levels in adjacent normal tissues. Chenodeoxycholic acid (CDCA) is the most potent physiological ligand for FXR. CDCA was radiolabeled with (18)F based on the efficiency click reaction of 1,3-dipolar cycloaddition of terminal alkynes and organic azides for noninvasively evaluating the relationship between FXR and FXR-related disease. The PET tracer [(18)F]8 was produced by 'click' labeling and showed a high non-decay corrected radiochemical yield (end of synthesis (EOS) yield=42±3% (n=5) from aqueous [(18)F]fluoride), high radiochemical purity ( >99%), and high specific activity (>320GBq/μmol). [(18)F]8 had a high metabolic stability in vitro and in vivo. PET imaging studies in nude mice indicated a rapid uptake of the tracer into liver tissue with uniform distribution of radioactivity in the liver. Significant accumulation of radioactivity was found in the liver, gallbladder, and intestine, while no obvious uptake was observed in other organs, such as the bladder, heart, and brain. Thus, this PET tracer represents a novel tool for early detection of abnormalities in the liver and staging of neoplasms.

  6. Development of Purine-Derived 18F-Labeled Pro-drug Tracers for Imaging of MRP1 Activity with PET

    PubMed Central

    2014-01-01

    Multidrug resistance-associated protein 1 (MRP1) is a drug efflux transporter that has been implicated in the pathology of several neurological diseases and is associated with development of multidrug resistance. To enable measurement of MRP1 function in the living brain, a series of 6-halopurines decorated with fluorinated side chains have been synthesized and evaluated as putative pro-drug tracers. The tracers were designed to undergo conjugation with glutathione within the brain and hence form the corresponding MRP1 substrate tracers in situ. 6-Bromo-7-(2-[18F]fluoroethyl)purine showed good brain uptake and rapid metabolic conversion. Dynamic PET imaging demonstrated a marked difference in brain clearance rates between wild-type and mrp1 knockout mice, suggesting that the tracer can allow noninvasive assessment of MRP1 activity in vivo. PMID:24456310

  7. Radiosynthesis and evaluation of an 18F-labeled positron emission tomography (PET) radioligand for brain histamine subtype-3 receptors based on a nonimidazole 2-aminoethylbenzofuran chemotype

    PubMed Central

    Bao, Xiaofeng; Lu, Shuiyu; Liow, Jeih-San; Zoghbi, Sami S.; Jenko, Kimberly J.; Clark, David T.; Gladding, Robert L.; Innis, Robert B.; Pike, Victor W.

    2012-01-01

    A known chemotype of H3 receptor ligand was explored for development of a radioligand for imaging brain histamine subtype 3 (H3) receptors in vivo with positron emission tomography (PET), namely non-imidazole 2-aminoethylbenzofurans, represented by the compound (R)-(2-(2-(2-methylpyrrolidin-1-yl)ethyl)benzofuran-5-yl)(4-fluorophenyl)methanone (9). Compound 9 was labeled with fluorine-18 (t1/2= 109.7 min) in high specific activity by treating the prepared nitro analog (12) with cyclotron-produced [18F]fluoride ion. [18F]9 was studied with PET in mouse and in monkey after intravenous injection. [18F]9 showed favorable properties as a candidate PET radioligand, including moderately high brain uptake with a high proportion of H3 receptor-specific signal in the absence of radiodefluorination. The nitro compound 12 was found to have even higher H3 receptor affinity, indicating the potential of this chemotype for the development of further promising PET radioligands. PMID:22313227

  8. 18F-Labeled NaF PET-CT in Detection of Bone Metastases in Patients With Preoperative Lung Cancer.

    PubMed

    Rao, Liangjun; Zong, Zhen; Chen, Zhifeng; Wang, Xiaoyan; Shi, Xinchong; Yi, Chang; Zhang, Xiangsong

    2016-04-01

    We compared the diagnostic accuracy of F-labeled sodium fluoride (F-NaF) PET-CT with 99m-technetium methylene diphosphonate (Tc-MDP) single photon emission computed tomography (SPECT) to detect bone metastases (BMs) in patients with preoperative lung cancer. Patients with lung cancer (n = 181) were examined with F-NaF PET-CT, and another 167 patients with lung cancer were examined with Tc-MDP SPECT. F-NaF PET-CT and Tc-MDP SPECT were evaluated by 2 experienced readers. Lesions were graded on a scale of 0 (degenerative lesion) to 4 (definite BM), and equivocal lesions were determined as indifferent (grade 3). Based on patient-based analysis, there were only 4 equivocal patients in F-NaF PET-CT detection. However, in Tc-MDP SPECT detection, there were 19 equivocal patients, which indicated a significant difference in terms of occurrence ratio (χ = 9.005, P = 0.03). Sensitivity and specificity of PET-CT was significantly better than that of SPECT when equivocal reading was categorized as malignant or benign (P < 0.05). Based on lesions-based analysis, SPECT produced 26 equivocal lesions of 333 lesions, but PET-CT produced only 5 equivocal lesions of 991 lesions. PET-CT was significantly better than SPECT in the aspect of producing equivocal patients (χ = 58.141, P < 0.001). Sensitivity and specificity of PET-CT was significantly better than that of SPECT when equivocal reading was categorized as malignant or benign (P < 0.05). F-NaF PET-CT is a highly sensitive and specific modality for the detection of BM in patients with preoperative lung cancer. It is better than conventional Tc-MDP SPECT in detecting BM in patients with preoperative lung cancer. PMID:27100456

  9. (11) C-labeled and (18) F-labeled PET ligands for subtype-specific imaging of histamine receptors in the brain.

    PubMed

    Funke, Uta; Vugts, Danielle J; Janssen, Bieneke; Spaans, Arnold; Kruijer, Perry S; Lammertsma, Adriaan A; Perk, Lars R; Windhorst, Albert D

    2013-01-01

    The signaling molecule histamine plays a key role in the mediation of immune reactions, in gastric secretion, and in the sensory system. In addition, it has an important function as a neurotransmitter in the central nervous system, acting in pituitary hormone secretion, wakefulness, motor and cognitive functions, as well as in itch and nociception. This has raised interest in the role of the histaminergic system for the treatment and diagnosis of various pathologies such as allergy, sleeping and eating disorders, neurodegeneration, neuroinflammation, mood disorders, and pruritus. In the past 20 years, several ligands targeting the four different histamine receptor subtypes have been explored as potential radiotracers for positron emission tomography (PET). This contribution provides an overview of the developments of subtype-selective carbon-11-labeled and fluorine-18-labeled compounds for imaging in the brain. Using specific radioligands, the H1 R expression in human brain could be examined in diseases such as schizophrenia, depression, and anorexia nervosa. In addition, the sedative effects of antihistamines could be investigated in terms of H1 R occupancy. The H3 R is of special interest because of its regulatory role in the release of various other neurotransmitters, and initial H3 R PET imaging studies in humans have been reported. The H4 R is the youngest member of the histamine receptor family and is involved in neuroinflammation and various sensory pathways. To date, two H4 R-specific (11) C-labeled ligands have been synthesized, and the imaging of the H4 R in vivo is in the early stage.

  10. Reusable electrochemical cell for rapid separation of [18F]fluoride from [18O]water for flow-through synthesis of 18F-labeled tracers

    PubMed Central

    Sadeghi, Saman; Liang, Vincent; Cheung, Shilin; Woo, Suh; Wu, Curtis; Ly, Jimmy; Deng, Yuliang; Eddings, Mark; van Dam, R. Michael

    2015-01-01

    A brass-platinum electrochemical micro flow cell was developed to extract [18F]fluoride from an aqueous solution and release it into an organic based solution, suitable for subsequent radio-synthesis, in a fast and reliable manner. This cell does not suffer electrode erosion and is thus reusable while operating faster by enabling increased voltages. By optimizing temperature, trapping and release potentials, flow rates, and electrode materials, an overall [18F]fluoride trapping and release efficiency of 84±5% (n=7) was achieved. X-ray photoelectron spectroscopy (XPS) was used to analyze electrode surfaces of various metal-metal systems and the findings were correlated with the performance of the electrochemical cell. To demonstrate the reactivity of the released [18F]fluoride, the cell was coupled to a flow-through reactor and automated synthesis of [18F]FDG with a repeatable decay-corrected yield of 56±4% (n=4) was completed in <15 min. A multi-human dose of 5.92 GBq [18F]FDG was also demonstrated. PMID:23474380

  11. Synthesis of isomers of 18F-labelled amino acid radiopharmaceutical: position 2- and 3-L-18F-alpha-methyltyrosine using a separation and purification system.

    PubMed

    Tomiyoshi, K; Amed, K; Muhammad, S; Higuchi, T; Inoue, T; Endo, K; Yang, D

    1997-02-01

    To diagnose cancers with radiolabelled amino acid using positron emission tomography, we have constructed a separation and purification system for the production of L-18F-alpha-methyltyrosine (L-18FAmT). This system could provide radioprotection and consistent production of L-18FAmT. L-18FAmT was synthesized and purified and the efficiency of the system was examined. The radiochemical yield of L-18FAmT was 20.3 +/- 5.1% (n = 5) based on the radioactivity trapped in the reaction vessel. The radiochemical purity was greater than 99.4 +/- 0.3% (n = 5). The radiochemical stability in phosphate-buffered saline and human plasma was examined and little decomposition was observed by HPLC analysis. Our results indicate that the separation and purification system gave simple and quick synthesis of L-18FAmT with a large reduction in radiation exposure and consistent production of L-18FAmT.

  12. Regioselectivity of Birch reductive alkylation of biaryls.

    PubMed

    Lebeuf, Raphaël; Robert, Frédéric; Landais, Yannick

    2005-10-13

    [reaction: see text] The regioselectivity of the Birch reductive alkylation of polysubstituted biaryls has been investigated. Results indicate that regioselectivity is affected by the electronic nature of substituents on both aromatic rings. The electron-rich 3,5-dimethoxyphenyl moiety is selectively reduced and then alkylated, while phenols and aniline are not dearomatized under these conditions. Biaryls possessing a phenol moiety are alkylated on the second ring, providing that the acidic proton has been removed prior to the Li/NH3 reduction.

  13. 21 CFR 176.120 - Alkyl ketene dimers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Alkyl ketene dimers. 176.120 Section 176.120 Food... Use Only as Components of Paper and Paperboard § 176.120 Alkyl ketene dimers. Alkyl ketene dimers may... section. (a) The alkyl ketene dimers are manufactured by the dehydrohalogenation of the acyl...

  14. 21 CFR 176.120 - Alkyl ketene dimers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Alkyl ketene dimers. 176.120 Section 176.120 Food... Paperboard § 176.120 Alkyl ketene dimers. Alkyl ketene dimers may be safely used as a component of articles..., transporting, or holding food, subject to the provisions of this section. (a) The alkyl ketene dimers...

  15. 21 CFR 176.120 - Alkyl ketene dimers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Alkyl ketene dimers. 176.120 Section 176.120 Food... Use Only as Components of Paper and Paperboard § 176.120 Alkyl ketene dimers. Alkyl ketene dimers may... section. (a) The alkyl ketene dimers are manufactured by the dehydrohalogenation of the acyl...

  16. 21 CFR 176.120 - Alkyl ketene dimers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Alkyl ketene dimers. 176.120 Section 176.120 Food... Use Only as Components of Paper and Paperboard § 176.120 Alkyl ketene dimers. Alkyl ketene dimers may... section. (a) The alkyl ketene dimers are manufactured by the dehydrohalogenation of the acyl...

  17. 21 CFR 176.120 - Alkyl ketene dimers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Alkyl ketene dimers. 176.120 Section 176.120 Food... Use Only as Components of Paper and Paperboard § 176.120 Alkyl ketene dimers. Alkyl ketene dimers may... section. (a) The alkyl ketene dimers are manufactured by the dehydrohalogenation of the acyl...

  18. N-Alkylation by Hydrogen Autotransfer Reactions.

    PubMed

    Ma, Xiantao; Su, Chenliang; Xu, Qing

    2016-06-01

    Owing to the importance of amine/amide derivatives in all fields of chemistry, and also the green and environmentally benign features of using alcohols as alkylating reagents, the relatively high atom economic dehydrative N-alkylation reactions of amines/amides with alcohols through hydrogen autotransfer processes have received much attention and have developed rapidly in recent decades. Various efficient homogeneous and heterogeneous transition metal catalysts, nano materials, electrochemical methods, biomimetic methods, asymmetric N-alkylation reactions, aerobic oxidative methods, and even certain transition metal-free, catalyst-free, or autocatalyzed methods, have also been developed in recent years. With a brief introduction to the background and developments in this area of research, this chapter focuses mainly on recent progress and technical and conceptual advances contributing to the development of this research in the last decade. In addition to mainstream research on homogeneous and heterogeneous transition metal-catalyzed reactions, possible mechanistic routes for hydrogen transfer and alcohol activation, which are key processes in N-alkylation reactions but seldom discussed in the past, the recent reports on computational mechanistic studies of the N-alkylation reactions, and the newly emerged N-alkylation methods based on novel alcohol activation protocols such as air-promoted reactions and transition metal-free methods, are also reviewed in this chapter. Problems and bottlenecks that remained to be solved in the field, and promising new research that deserves greater future attention and effort, are also reviewed and discussed.

  19. N-Alkylation by Hydrogen Autotransfer Reactions.

    PubMed

    Ma, Xiantao; Su, Chenliang; Xu, Qing

    2016-06-01

    Owing to the importance of amine/amide derivatives in all fields of chemistry, and also the green and environmentally benign features of using alcohols as alkylating reagents, the relatively high atom economic dehydrative N-alkylation reactions of amines/amides with alcohols through hydrogen autotransfer processes have received much attention and have developed rapidly in recent decades. Various efficient homogeneous and heterogeneous transition metal catalysts, nano materials, electrochemical methods, biomimetic methods, asymmetric N-alkylation reactions, aerobic oxidative methods, and even certain transition metal-free, catalyst-free, or autocatalyzed methods, have also been developed in recent years. With a brief introduction to the background and developments in this area of research, this chapter focuses mainly on recent progress and technical and conceptual advances contributing to the development of this research in the last decade. In addition to mainstream research on homogeneous and heterogeneous transition metal-catalyzed reactions, possible mechanistic routes for hydrogen transfer and alcohol activation, which are key processes in N-alkylation reactions but seldom discussed in the past, the recent reports on computational mechanistic studies of the N-alkylation reactions, and the newly emerged N-alkylation methods based on novel alcohol activation protocols such as air-promoted reactions and transition metal-free methods, are also reviewed in this chapter. Problems and bottlenecks that remained to be solved in the field, and promising new research that deserves greater future attention and effort, are also reviewed and discussed. PMID:27573267

  20. Copper-catalyzed reductive cross-coupling of nonactivated alkyl tosylates and mesylates with alkyl and aryl bromides.

    PubMed

    Liu, Jing-Hui; Yang, Chu-Ting; Lu, Xiao-Yu; Zhang, Zhen-Qi; Xu, Ling; Cui, Mian; Lu, Xi; Xiao, Bin; Fu, Yao; Liu, Lei

    2014-11-17

    A copper-catalyzed reductive cross-coupling reaction of nonactivated alkyl tosylates and mesylates with alkyl and aryl bromides was developed. It provides a practical method for efficient and cost-effective construction of aryl-alkyl and alkyl-alkyl CC bonds with stereocontrol from readily available substrates. When used in an intramolecular fashion, the reaction enables convenient access to various substituted carbo- or heterocycles, such as 2,3-dihydrobenzofuran and benzochromene derivatives.

  1. Alkyl rearrangement processes in organozirconium complexes. Observation of internal alkyl complexes during hydrozirconation

    SciTech Connect

    Chirik, P.J.; Day, M.W.; Labinger, J.A.; Bercaw, J.E.

    1999-11-10

    Isotopically labeled alkyl zirconocene complexes of the form (CpR{sub n}){sub 2}Zr(CH{sub 2}CDR{sub 2}{prime})(X) (CpR{sub n} = alkyl-substituted cyclopentadienyl; R{prime} = H, alkyl group; X = H, D, Me) undergo isomerization of the alkyl ligand as well as exchange with free olefin in solution under ambient conditions. Increasing the substitution on the Cp ring results in slower isomerization reactions, but these steric effects are small. In contrast, changing X has a very large effect on the rate of isomerization. Pure {sigma}-bonding ligands such as methyl and hydride promote rapid isomerization, whereas {pi}-donor ligands inhibit {beta}-H elimination and hence alkyl isomerization. For ({eta}{sup 5}-C{sub 5}H{sub 5}){sub 2}Zr(R)(Cl), internal alkyl complexes have been observed for the first time. The rate of isomerization depends on the length of the alkyl group: longer alkyl chains (heptyl, hexyl) isomerize faster than shorter chains (butyl). The transient intermediate species have been identified by a combination of isotopic labeling and {sup 1}H, {sup 2}H, and {sup 13}C NMR experiments. The solid-state structure of the zirconocene cyclopentyl chloride complex, Cp{sub 2}Zr(cyclo-C{sub 5}H{sub 9})(Cl), has been determined by X-ray diffraction.

  2. Palladium-Catalyzed Arylation of Alkyl Sulfenate Anions.

    PubMed

    Jia, Tiezheng; Zhang, Mengnan; Jiang, Hui; Wang, Carol Y; Walsh, Patrick J

    2015-11-01

    A unique palladium-catalyzed arylation of alkyl sulfenate anions is introduced that affords aryl alkyl sulfoxides in high yields. Due to the base sensitivity of the starting sulfoxides, sulfenate anion intermediates, and alkyl aryl sulfoxide products, the use of a mild method to generate alkyl sulfenate anions was crucial to the success of this process. Thus, a fluoride triggered elimination strategy was employed with alkyl 2-(trimethylsilyl)ethyl sulfoxides to liberate the requisite alkyl sulfenate anion intermediates. In the presence of palladium catalysts with bulky monodentate phosphines (SPhos and Cy-CarPhos) and aryl bromides or chlorides, alkyl sulfenate anions were readily arylated. Moreover, the thermal fragmentation and the base promoted elimination of alkyl sulfoxides was overridden. The alkyl sulfenate anion arylation exhibited excellent chemoselectivity in the presence of functional groups, such as anilines and phenols, which are also known to undergo palladium catalyzed arylation reactions.

  3. 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.

  4. Palladium-Catalyzed, Ring-Forming Aromatic C–H Alkylations with Unactivated Alkyl Halides

    PubMed Central

    Venning, Alexander R. O.; Bohan, Patrick T.; Alexanian, Erik J.

    2015-01-01

    A catalytic C–H alkylation using unactivated alkyl halides and a variety of arenes and heteroarenes is described. This ring-forming process is successful with a variety of unactivated primary and secondary alkyl halides, including those with β-hydrogens. In contrast to standard polar or radical cyclizations of aromatic systems, electronic activation of the substrate is not required. The mild, catalytic reaction conditions are highly functional group tolerant and facilitate access to a diverse range of synthetically and medicinally important carbocyclic and heterocyclic systems. PMID:25746442

  5. Enhancement of alkylation catalysts for improved supercritical fluid regeneration

    DOEpatents

    Ginosar, Daniel M.; Petkovic, Lucia

    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.

  6. Enhancement of alkylation catalysts for improved supercritical fluid regeneration

    SciTech Connect

    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.

  7. 40 CFR 721.5769 - Mixture of nitrated alkylated phenols.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Mixture of nitrated alkylated phenols... Substances § 721.5769 Mixture of nitrated alkylated phenols. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as a mixture of nitrated alkylated...

  8. 40 CFR 721.5769 - Mixture of nitrated alkylated phenols.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Mixture of nitrated alkylated phenols... Substances § 721.5769 Mixture of nitrated alkylated phenols. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as a mixture of nitrated alkylated...

  9. 40 CFR 721.4136 - Alkyl heteropolycyclic-aniline (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkyl heteropolycyclic-aniline... Specific Chemical Substances § 721.4136 Alkyl heteropolycyclic-aniline (generic). (a) Chemical substance... alkyl heteropolycyclic-aniline (PMN P-00-0067) is subject to reporting under this section for...

  10. 40 CFR 721.8700 - Halogenated alkyl pyridine.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Halogenated alkyl pyridine. 721.8700... Substances § 721.8700 Halogenated alkyl pyridine. Link to an amendment published at 79 FR 34638, June 18... identified generically as halogenated alkyl pyridine (PMN P-83-237) is subject to reporting under...

  11. 40 CFR 721.9720 - Disubstituted alkyl triazines (generic name).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Disubstituted alkyl triazines (generic... Specific Chemical Substances § 721.9720 Disubstituted alkyl triazines (generic name). Link to an amendment... reporting. (1) The chemical substances identified generically as disubstituted alkyl triazines (PMNs...

  12. 40 CFR 721.1878 - Alkali metal alkyl borohydride (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 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...

  13. 40 CFR 721.10233 - Linear alkyl epoxide (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Linear alkyl epoxide (generic). 721... Substances § 721.10233 Linear alkyl epoxide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as linear alkyl epoxide (PMN...

  14. 40 CFR 721.555 - Alkyl amino nitriles (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkyl amino nitriles (generic). 721... Substances § 721.555 Alkyl amino nitriles (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as alkyl amino nitriles (PMNs...

  15. 40 CFR 721.840 - Alkyl substituted diaromatic hydrocarbons.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl substituted diaromatic... 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...

  16. 40 CFR 721.550 - Alkyl alkenoate, azobis-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl alkenoate, azobis-. 721.550... Substances § 721.550 Alkyl alkenoate, azobis-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as alkyl alkenoate, azobis- (PMN P-88-2470)...

  17. 40 CFR 721.550 - Alkyl alkenoate, azobis-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkyl alkenoate, azobis-. 721.550... Substances § 721.550 Alkyl alkenoate, azobis-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as alkyl alkenoate, azobis- (PMN P-88-2470)...

  18. 40 CFR 721.10053 - Alkyl silane methacrylate (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl silane methacrylate (generic... Specific Chemical Substances § 721.10053 Alkyl silane methacrylate (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as alkyl...

  19. 40 CFR 721.648 - Alkyl dialkylamino phenylsulfonyl alkenoate (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl dialkylamino phenylsulfonyl... Specific Chemical Substances § 721.648 Alkyl dialkylamino phenylsulfonyl alkenoate (generic). (a) Chemical... as alkyl dialkylamino phenylsulfonyl alkenoate (PMN P-00-0816) is subject to reporting under...

  20. 40 CFR 721.2825 - Alkyl ester (generic name).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl ester (generic name). 721.2825... Substances § 721.2825 Alkyl ester (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance alkyl ester (PMN P-84-968) is subject to reporting under this...

  1. 40 CFR 721.1852 - Di-alkyl borane (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Di-alkyl borane (generic). 721.1852... Substances § 721.1852 Di-alkyl borane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as di-alkyl borane (PMN P-00-1087) is...

  2. 40 CFR 721.3485 - Hydrofluorocarbon alkyl ether.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Hydrofluorocarbon alkyl ether. 721... Substances § 721.3485 Hydrofluorocarbon alkyl ether. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as a hydrofluorocarbon alkyl...

  3. 40 CFR 721.2410 - Alkoxylated alkyldiethylenetriamine, alkyl sulfate salts.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., 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)...

  4. 40 CFR 721.10053 - Alkyl silane methacrylate (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkyl silane methacrylate (generic... Specific Chemical Substances § 721.10053 Alkyl silane methacrylate (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as alkyl...

  5. 40 CFR 721.840 - Alkyl substituted diaromatic hydrocarbons.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl substituted diaromatic... 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...

  6. 40 CFR 721.6070 - Alkyl phosphonate ammonium salts.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkyl phosphonate ammonium salts. 721... Substances § 721.6070 Alkyl phosphonate ammonium salts. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substances identified generically as alkyl phosphonate...

  7. 40 CFR 721.555 - Alkyl amino nitriles (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkyl amino nitriles (generic). 721... Substances § 721.555 Alkyl amino nitriles (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as alkyl amino nitriles (PMNs...

  8. 40 CFR 721.3485 - Hydrofluorocarbon alkyl ether.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Hydrofluorocarbon alkyl ether. 721... Substances § 721.3485 Hydrofluorocarbon alkyl ether. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as a hydrofluorocarbon alkyl...

  9. 40 CFR 721.9720 - Disubstituted alkyl triazines (generic name).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Disubstituted alkyl triazines (generic... Specific Chemical Substances § 721.9720 Disubstituted alkyl triazines (generic name). (a) Chemical... as disubstituted alkyl triazines (PMNs P-85-932 and P-85-933) are subject to reporting under...

  10. 40 CFR 721.6490 - Alkyl phenyl polyetheramines.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl phenyl polyetheramines. 721.6490... Substances § 721.6490 Alkyl phenyl polyetheramines. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as alkyl phenyl...

  11. 40 CFR 721.10669 - Tertiary amine alkyl ether (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Tertiary amine alkyl ether (generic... Specific Chemical Substances § 721.10669 Tertiary amine alkyl ether (generic). (a) Chemical substance and... alkyl ether (PMN P-13-78) is subject to reporting under this section for the significant new...

  12. 40 CFR 721.655 - Ethoxylated alkyl quaternary ammonium compound.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Ethoxylated alkyl quaternary ammonium... Specific Chemical Substances § 721.655 Ethoxylated alkyl quaternary ammonium compound. (a) Chemical... as an ethoxylated alkyl quaternary ammonium compound (PMN P-96-573) is subject to reporting...

  13. 40 CFR 721.10385 - Phenoxy alkyl ether (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Phenoxy alkyl ether (generic). 721... Substances § 721.10385 Phenoxy alkyl ether (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as phenoxy alkyl ether (PMN...

  14. 40 CFR 721.840 - Alkyl substituted diaromatic hydrocarbons.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkyl substituted diaromatic... 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...

  15. 40 CFR 721.575 - Substituted alkyl halide.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Substituted alkyl halide. 721.575... Substances § 721.575 Substituted alkyl halide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted alkyl halide (PMN P-83-1222)...

  16. 40 CFR 721.10385 - Phenoxy alkyl ether (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Phenoxy alkyl ether (generic). 721... Substances § 721.10385 Phenoxy alkyl ether (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as phenoxy alkyl ether (PMN...

  17. 40 CFR 721.647 - Alkoxylated alkyl amine (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkoxylated alkyl amine (generic). 721... Substances § 721.647 Alkoxylated alkyl amine (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as an alkoxylated alkyl amine...

  18. 40 CFR 721.10697 - Polyfluorinated alkyl polyamide (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polyfluorinated alkyl polyamide... Specific Chemical Substances § 721.10697 Polyfluorinated alkyl polyamide (generic). (a) Chemical substance... polyfluorinated alkyl polyamide (PMN P-11-487) is subject to reporting under this section for the significant...

  19. 40 CFR 721.2825 - Alkyl ester (generic name).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkyl ester (generic name). 721.2825... Substances § 721.2825 Alkyl ester (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance alkyl ester (PMN P-84-968) is subject to reporting under this...

  20. 40 CFR 721.6070 - Alkyl phosphonate ammonium salts.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl phosphonate ammonium salts. 721... Substances § 721.6070 Alkyl phosphonate ammonium salts. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substances identified generically as alkyl phosphonate...

  1. 40 CFR 721.3485 - Hydrofluorocarbon alkyl ether.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Hydrofluorocarbon alkyl ether. 721... Substances § 721.3485 Hydrofluorocarbon alkyl ether. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as a hydrofluorocarbon alkyl...

  2. 40 CFR 721.3740 - Bisalkylated fatty alkyl amine oxide.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Bisalkylated fatty alkyl amine oxide... Substances § 721.3740 Bisalkylated fatty alkyl amine oxide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as bisalkylated fatty alkyl...

  3. 40 CFR 721.647 - Alkoxylated alkyl amine (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkoxylated alkyl amine (generic). 721... Substances § 721.647 Alkoxylated alkyl amine (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as an alkoxylated alkyl amine...

  4. 40 CFR 721.8700 - Halogenated alkyl pyridine.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Halogenated alkyl pyridine. 721.8700... Substances § 721.8700 Halogenated alkyl pyridine. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified generically as halogenated alkyl pyridine (PMN P-83-237)...

  5. 40 CFR 721.10701 - Polyfluorinated alkyl amine (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polyfluorinated alkyl amine (generic... Specific Chemical Substances § 721.10701 Polyfluorinated alkyl amine (generic). (a) Chemical substance and... polyfluorinated alkyl amine (PMN P-11-532) is subject to reporting under this section for the significant new...

  6. 40 CFR 721.840 - Alkyl substituted diaromatic hydrocarbons.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl substituted diaromatic... 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...

  7. 40 CFR 721.10053 - Alkyl silane methacrylate (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl silane methacrylate (generic... Specific Chemical Substances § 721.10053 Alkyl silane methacrylate (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as alkyl...

  8. 40 CFR 721.10385 - Phenoxy alkyl ether (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Phenoxy alkyl ether (generic). 721... Substances § 721.10385 Phenoxy alkyl ether (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as phenoxy alkyl ether (PMN...

  9. 40 CFR 721.648 - Alkyl dialkylamino phenylsulfonyl alkenoate (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl dialkylamino phenylsulfonyl... Specific Chemical Substances § 721.648 Alkyl dialkylamino phenylsulfonyl alkenoate (generic). (a) Chemical... as alkyl dialkylamino phenylsulfonyl alkenoate (PMN P-00-0816) is subject to reporting under...

  10. 40 CFR 721.10233 - Linear alkyl epoxide (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Linear alkyl epoxide (generic). 721... Substances § 721.10233 Linear alkyl epoxide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as linear alkyl epoxide (PMN...

  11. 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...

  12. 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)...

  13. 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)...

  14. 40 CFR 721.10087 - Substituted alkyl phosphine oxide (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Substituted alkyl phosphine oxide... Specific Chemical Substances § 721.10087 Substituted alkyl phosphine oxide (generic). (a) Chemical... as substituted alkyl phosphine oxide (PMN P-06-332) is subject to reporting under this section...

  15. 40 CFR 721.655 - Ethoxylated alkyl quaternary ammonium compound.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Ethoxylated alkyl quaternary ammonium... Specific Chemical Substances § 721.655 Ethoxylated alkyl quaternary ammonium compound. (a) Chemical... as an ethoxylated alkyl quaternary ammonium compound (PMN P-96-573) is subject to reporting...

  16. 40 CFR 721.550 - Alkyl alkenoate, azobis-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl alkenoate, azobis-. 721.550... Substances § 721.550 Alkyl alkenoate, azobis-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as alkyl alkenoate, azobis- (PMN P-88-2470)...

  17. 40 CFR 721.10087 - Substituted alkyl phosphine oxide (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Substituted alkyl phosphine oxide... Specific Chemical Substances § 721.10087 Substituted alkyl phosphine oxide (generic). (a) Chemical... as substituted alkyl phosphine oxide (PMN P-06-332) is subject to reporting under this section...

  18. 40 CFR 721.648 - Alkyl dialkylamino phenylsulfonyl alkenoate (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl dialkylamino phenylsulfonyl... Specific Chemical Substances § 721.648 Alkyl dialkylamino phenylsulfonyl alkenoate (generic). (a) Chemical... as alkyl dialkylamino phenylsulfonyl alkenoate (PMN P-00-0816) is subject to reporting under...

  19. 40 CFR 721.10087 - Substituted alkyl phosphine oxide (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Substituted alkyl phosphine oxide... Specific Chemical Substances § 721.10087 Substituted alkyl phosphine oxide (generic). (a) Chemical... as substituted alkyl phosphine oxide (PMN P-06-332) is subject to reporting under this section...

  20. 40 CFR 721.6070 - Alkyl phosphonate ammonium salts.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl phosphonate ammonium salts. 721... Substances § 721.6070 Alkyl phosphonate ammonium salts. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substances identified generically as alkyl phosphonate...

  1. 40 CFR 721.10453 - Polyglycerin alkyl ether (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Polyglycerin alkyl ether (generic... Specific Chemical Substances § 721.10453 Polyglycerin alkyl ether (generic). (a) Chemical substance and... alkyl ether (PMN P-02-796) is subject to reporting under this section for the significant new...

  2. 40 CFR 721.1852 - Di-alkyl borane (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Di-alkyl borane (generic). 721.1852... Substances § 721.1852 Di-alkyl borane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as di-alkyl borane (PMN P-00-1087) is...

  3. 40 CFR 721.4136 - Alkyl heteropolycyclic-aniline (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl heteropolycyclic-aniline... Specific Chemical Substances § 721.4136 Alkyl heteropolycyclic-aniline (generic). (a) Chemical substance... alkyl heteropolycyclic-aniline (PMN P-00-0067) is subject to reporting under this section for...

  4. 40 CFR 721.10053 - Alkyl silane methacrylate (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkyl silane methacrylate (generic... Specific Chemical Substances § 721.10053 Alkyl silane methacrylate (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as alkyl...

  5. 40 CFR 721.6070 - Alkyl phosphonate ammonium salts.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkyl phosphonate ammonium salts. 721... Substances § 721.6070 Alkyl phosphonate ammonium salts. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substances identified generically as alkyl phosphonate...

  6. 40 CFR 721.9720 - Disubstituted alkyl triazines (generic name).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Disubstituted alkyl triazines (generic... Specific Chemical Substances § 721.9720 Disubstituted alkyl triazines (generic name). (a) Chemical... as disubstituted alkyl triazines (PMNs P-85-932 and P-85-933) are subject to reporting under...

  7. 40 CFR 721.1852 - Di-alkyl borane (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Di-alkyl borane (generic). 721.1852... Substances § 721.1852 Di-alkyl borane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as di-alkyl borane (PMN P-00-1087) is...

  8. 40 CFR 721.10696 - Polyfluorinated alkyl thiol (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polyfluorinated alkyl thiol (generic... Specific Chemical Substances § 721.10696 Polyfluorinated alkyl thiol (generic). (a) Chemical substances and... polyfluorinated alkyl thiol (PMNs P-11-483 and P-11-528) are subject to reporting under this section for...

  9. 40 CFR 721.4136 - Alkyl heteropolycyclic-aniline (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl heteropolycyclic-aniline... Specific Chemical Substances § 721.4136 Alkyl heteropolycyclic-aniline (generic). (a) Chemical substance... alkyl heteropolycyclic-aniline (PMN P-00-0067) is subject to reporting under this section for...

  10. 40 CFR 721.2825 - Alkyl ester (generic name).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkyl ester (generic name). 721.2825... Substances § 721.2825 Alkyl ester (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance alkyl ester (PMN P-84-968) is subject to reporting under this...

  11. 40 CFR 721.1852 - Di-alkyl borane (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Di-alkyl borane (generic). 721.1852... Substances § 721.1852 Di-alkyl borane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as di-alkyl borane (PMN P-00-1087) is...

  12. 40 CFR 721.575 - Substituted alkyl halide.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Substituted alkyl halide. 721.575... Substances § 721.575 Substituted alkyl halide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted alkyl halide (PMN P-83-1222)...

  13. 40 CFR 721.648 - Alkyl dialkylamino phenylsulfonyl alkenoate (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkyl dialkylamino phenylsulfonyl... Specific Chemical Substances § 721.648 Alkyl dialkylamino phenylsulfonyl alkenoate (generic). (a) Chemical... as alkyl dialkylamino phenylsulfonyl alkenoate (PMN P-00-0816) is subject to reporting under...

  14. 40 CFR 721.10087 - Substituted alkyl phosphine oxide (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Substituted alkyl phosphine oxide... Specific Chemical Substances § 721.10087 Substituted alkyl phosphine oxide (generic). (a) Chemical... as substituted alkyl phosphine oxide (PMN P-06-332) is subject to reporting under this section...

  15. 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...

  16. 40 CFR 721.10700 - Polyfluorinated alkyl thio polyacrylamide (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polyfluorinated alkyl thio... Specific Chemical Substances § 721.10700 Polyfluorinated alkyl thio polyacrylamide (generic). (a) Chemical... as polyfluorinated alkyl thio polyacrylamide (PMNs P-11-530 and P-11-533) are subject to...

  17. 40 CFR 721.575 - Substituted alkyl halide.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Substituted alkyl halide. 721.575... Substances § 721.575 Substituted alkyl halide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted alkyl halide (PMN P-83-1222)...

  18. 40 CFR 721.4136 - Alkyl heteropolycyclic-aniline (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl heteropolycyclic-aniline... Specific Chemical Substances § 721.4136 Alkyl heteropolycyclic-aniline (generic). (a) Chemical substance... alkyl heteropolycyclic-aniline (PMN P-00-0067) is subject to reporting under this section for...

  19. 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)...

  20. 40 CFR 721.550 - Alkyl alkenoate, azobis-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl alkenoate, azobis-. 721.550... Substances § 721.550 Alkyl alkenoate, azobis-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as alkyl alkenoate, azobis- (PMN P-88-2470)...

  1. 40 CFR 721.3485 - Hydrofluorocarbon alkyl ether.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Hydrofluorocarbon alkyl ether. 721... Substances § 721.3485 Hydrofluorocarbon alkyl ether. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as a hydrofluorocarbon alkyl...

  2. 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...

  3. 40 CFR 721.10453 - Polyglycerin alkyl ether (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polyglycerin alkyl ether (generic... Specific Chemical Substances § 721.10453 Polyglycerin alkyl ether (generic). (a) Chemical substance and... alkyl ether (PMN P-02-796) is subject to reporting under this section for the significant new...

  4. 40 CFR 721.10087 - Substituted alkyl phosphine oxide (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted alkyl phosphine oxide... Specific Chemical Substances § 721.10087 Substituted alkyl phosphine oxide (generic). (a) Chemical... as substituted alkyl phosphine oxide (PMN P-06-332) is subject to reporting under this section...

  5. 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...

  6. 40 CFR 721.10053 - Alkyl silane methacrylate (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl silane methacrylate (generic... Specific Chemical Substances § 721.10053 Alkyl silane methacrylate (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as alkyl...

  7. 40 CFR 721.4136 - Alkyl heteropolycyclic-aniline (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkyl heteropolycyclic-aniline... Specific Chemical Substances § 721.4136 Alkyl heteropolycyclic-aniline (generic). (a) Chemical substance... alkyl heteropolycyclic-aniline (PMN P-00-0067) is subject to reporting under this section for...

  8. 40 CFR 721.3485 - Hydrofluorocarbon alkyl ether.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Hydrofluorocarbon alkyl ether. 721... Substances § 721.3485 Hydrofluorocarbon alkyl ether. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as a hydrofluorocarbon alkyl...

  9. 40 CFR 721.9720 - Disubstituted alkyl triazines (generic name).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Disubstituted alkyl triazines (generic... Specific Chemical Substances § 721.9720 Disubstituted alkyl triazines (generic name). (a) Chemical... as disubstituted alkyl triazines (PMNs P-85-932 and P-85-933) are subject to reporting under...

  10. 40 CFR 721.3740 - Bisalkylated fatty alkyl amine oxide.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Bisalkylated fatty alkyl amine oxide... Substances § 721.3740 Bisalkylated fatty alkyl amine oxide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as bisalkylated fatty alkyl...

  11. 40 CFR 721.555 - Alkyl amino nitriles (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl amino nitriles (generic). 721... Substances § 721.555 Alkyl amino nitriles (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as alkyl amino nitriles (PMNs...

  12. 40 CFR 721.10233 - Linear alkyl epoxide (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Linear alkyl epoxide (generic). 721... Substances § 721.10233 Linear alkyl epoxide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as linear alkyl epoxide (PMN...

  13. 40 CFR 721.10692 - Fluorinated alkyl dianiline (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fluorinated alkyl dianiline (generic... Specific Chemical Substances § 721.10692 Fluorinated alkyl dianiline (generic). (a) Chemical substance and... alkyl dianiline (PMN P-13-288) is subject to reporting under this section for the significant new...

  14. 40 CFR 721.3740 - Bisalkylated fatty alkyl amine oxide.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Bisalkylated fatty alkyl amine oxide... Substances § 721.3740 Bisalkylated fatty alkyl amine oxide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as bisalkylated fatty alkyl...

  15. 40 CFR 721.555 - Alkyl amino nitriles (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl amino nitriles (generic). 721... Substances § 721.555 Alkyl amino nitriles (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as alkyl amino nitriles (PMNs...

  16. 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...

  17. 40 CFR 721.6490 - Alkyl phenyl polyetheramines.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl phenyl polyetheramines. 721.6490... Substances § 721.6490 Alkyl phenyl polyetheramines. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as alkyl phenyl...

  18. 40 CFR 721.6490 - Alkyl phenyl polyetheramines.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkyl phenyl polyetheramines. 721.6490... Substances § 721.6490 Alkyl phenyl polyetheramines. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as alkyl phenyl...

  19. 40 CFR 721.648 - Alkyl dialkylamino phenylsulfonyl alkenoate (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkyl dialkylamino phenylsulfonyl... Specific Chemical Substances § 721.648 Alkyl dialkylamino phenylsulfonyl alkenoate (generic). (a) Chemical... as alkyl dialkylamino phenylsulfonyl alkenoate (PMN P-00-0816) is subject to reporting under...

  20. 40 CFR 721.10699 - Polyfluorinated alkyl thio acrylamide (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polyfluorinated alkyl thio acrylamide... Specific Chemical Substances § 721.10699 Polyfluorinated alkyl thio acrylamide (generic). (a) Chemical... as polyfluorinated alkyl thio acrylamide (PMN P-11-529) is subject to reporting under this...

  1. 40 CFR 721.1852 - Di-alkyl borane (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Di-alkyl borane (generic). 721.1852... Substances § 721.1852 Di-alkyl borane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as di-alkyl borane (PMN P-00-1087) is...

  2. 40 CFR 721.2825 - Alkyl ester (generic name).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl ester (generic name). 721.2825... Substances § 721.2825 Alkyl ester (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance alkyl ester (PMN P-84-968) is subject to reporting under this...

  3. 40 CFR 721.655 - Ethoxylated alkyl quaternary ammonium compound.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Ethoxylated alkyl quaternary ammonium... Specific Chemical Substances § 721.655 Ethoxylated alkyl quaternary ammonium compound. (a) Chemical... as an ethoxylated alkyl quaternary ammonium compound (PMN P-96-573) is subject to reporting...

  4. 40 CFR 721.10698 - Polyfluorinated alkyl halide (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polyfluorinated alkyl halide (generic... Specific Chemical Substances § 721.10698 Polyfluorinated alkyl halide (generic). (a) Chemical substance and... polyfluorinated alkyl halide (PMN P-11-527) is subject to reporting under this section for the significant...

  5. 40 CFR 721.550 - Alkyl alkenoate, azobis-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkyl alkenoate, azobis-. 721.550... Substances § 721.550 Alkyl alkenoate, azobis-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as alkyl alkenoate, azobis- (PMN P-88-2470)...

  6. 40 CFR 721.1878 - Alkali metal alkyl borohydride (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 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...

  7. 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)...

  8. 40 CFR 721.6490 - Alkyl phenyl polyetheramines.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl phenyl polyetheramines. 721.6490... Substances § 721.6490 Alkyl phenyl polyetheramines. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as alkyl phenyl...

  9. 40 CFR 721.655 - Ethoxylated alkyl quaternary ammonium compound.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Ethoxylated alkyl quaternary ammonium... Specific Chemical Substances § 721.655 Ethoxylated alkyl quaternary ammonium compound. (a) Chemical... as an ethoxylated alkyl quaternary ammonium compound (PMN P-96-573) is subject to reporting...

  10. 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...

  11. 40 CFR 721.555 - Alkyl amino nitriles (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl amino nitriles (generic). 721... Substances § 721.555 Alkyl amino nitriles (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as alkyl amino nitriles (PMNs...

  12. 40 CFR 721.647 - Alkoxylated alkyl amine (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkoxylated alkyl amine (generic). 721... Substances § 721.647 Alkoxylated alkyl amine (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as an alkoxylated alkyl amine...

  13. 40 CFR 721.1878 - Alkali metal alkyl borohydride (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 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...

  14. 40 CFR 721.840 - Alkyl substituted diaromatic hydrocarbons.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkyl substituted diaromatic... 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...

  15. 40 CFR 721.9720 - Disubstituted alkyl triazines (generic name).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Disubstituted alkyl triazines (generic... Specific Chemical Substances § 721.9720 Disubstituted alkyl triazines (generic name). (a) Chemical... as disubstituted alkyl triazines (PMNs P-85-932 and P-85-933) are subject to reporting under...

  16. 40 CFR 721.655 - Ethoxylated alkyl quaternary ammonium compound.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Ethoxylated alkyl quaternary ammonium... Specific Chemical Substances § 721.655 Ethoxylated alkyl quaternary ammonium compound. (a) Chemical... as an ethoxylated alkyl quaternary ammonium compound (PMN P-96-573) is subject to reporting...

  17. 40 CFR 721.2420 - Alkoxylated dialkyldiethylenetriamine, alkyl sulfate salt.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., 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...

  18. 40 CFR 721.575 - Substituted alkyl halide.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted alkyl halide. 721.575... Substances § 721.575 Substituted alkyl halide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted alkyl halide (PMN P-83-1222)...

  19. 40 CFR 721.3740 - Bisalkylated fatty alkyl amine oxide.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Bisalkylated fatty alkyl amine oxide... Substances § 721.3740 Bisalkylated fatty alkyl amine oxide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as bisalkylated fatty alkyl...

  20. 40 CFR 721.10669 - Tertiary amine alkyl ether (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Tertiary amine alkyl ether (generic... Specific Chemical Substances § 721.10669 Tertiary amine alkyl ether (generic). (a) Chemical substance and... alkyl ether (PMN P-13-78) is subject to reporting under this section for the significant new...

  1. 40 CFR 721.3740 - Bisalkylated fatty alkyl amine oxide.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Bisalkylated fatty alkyl amine oxide... Substances § 721.3740 Bisalkylated fatty alkyl amine oxide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as bisalkylated fatty alkyl...

  2. 40 CFR 721.6490 - Alkyl phenyl polyetheramines.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkyl phenyl polyetheramines. 721.6490... Substances § 721.6490 Alkyl phenyl polyetheramines. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as alkyl phenyl...

  3. 40 CFR 721.647 - Alkoxylated alkyl amine (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkoxylated alkyl amine (generic). 721... Substances § 721.647 Alkoxylated alkyl amine (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as an alkoxylated alkyl amine...

  4. 40 CFR 721.647 - Alkoxylated alkyl amine (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkoxylated alkyl amine (generic). 721... Substances § 721.647 Alkoxylated alkyl amine (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as an alkoxylated alkyl amine...

  5. 40 CFR 721.575 - Substituted alkyl halide.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Substituted alkyl halide. 721.575... Substances § 721.575 Substituted alkyl halide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted alkyl halide (PMN P-83-1222)...

  6. 40 CFR 721.6070 - Alkyl phosphonate ammonium salts.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl phosphonate ammonium salts. 721... Substances § 721.6070 Alkyl phosphonate ammonium salts. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substances identified generically as alkyl phosphonate...

  7. 40 CFR 721.2825 - Alkyl ester (generic name).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl ester (generic name). 721.2825... Substances § 721.2825 Alkyl ester (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance alkyl ester (PMN P-84-968) is subject to reporting under this...

  8. 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,...

  9. 40 CFR 721.10506 - Alkylated phenols (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkylated phenols (generic). 721.10506... Substances § 721.10506 Alkylated phenols (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as alkylated phenols (PMNs...

  10. 40 CFR 721.10506 - Alkylated phenols (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkylated phenols (generic). 721.10506... Substances § 721.10506 Alkylated phenols (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as alkylated phenols (PMNs...

  11. 40 CFR 721.5769 - Mixture of nitrated alkylated phenols.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Mixture of nitrated alkylated phenols... Substances § 721.5769 Mixture of nitrated alkylated phenols. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as a mixture of nitrated alkylated...

  12. 40 CFR 721.5769 - Mixture of nitrated alkylated phenols.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Mixture of nitrated alkylated phenols... Substances § 721.5769 Mixture of nitrated alkylated phenols. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as a mixture of nitrated alkylated...

  13. 40 CFR 721.5769 - Mixture of nitrated alkylated phenols.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Mixture of nitrated alkylated phenols... Substances § 721.5769 Mixture of nitrated alkylated phenols. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as a mixture of nitrated alkylated...

  14. Chelation-driven rearrangement of primary alkyl aminopalladation products to stable trisubstituted alkyl-palladium complexes.

    PubMed

    Rosewall, Carolyn F; Ingalls, Erica L; Kaminsky, Werner; Michael, Forrest E

    2015-04-01

    The formation of highly substituted carbon centers using catalysis has been a widely sought after goal, but complexes of highly substituted carbon atoms with transition metals are rare, and the factors that affect the relative stability of complexes with differentially substituted carbon atoms are poorly understood. In this study, a set of equilibrating alkyl-palladium complexes were subtly tuned to form either a primary or trisubstituted alkyl complex as the more thermodynamically favored state, depending on either the substrate or reaction conditions. An X-ray crystal structure of the trisubstituted alkyl-palladium complex is presented and compared with the corresponding primary alkyl complex. The mechanism for rearrangement and the factors that drive the change in stability are discussed.

  15. 77 FR 72747 - Alkyl(C8

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-06

    ... Classification System (NAICS) codes is not intended to be exhaustive, but rather provides a guide to help readers... . II. Petition for Exemption In the Federal Register of May 2, 2012 (77 FR 25957) (FRL-9346-1), EPA.../reproductive screening test (OECD 422) toxicity study on a representative N- alkyl(C 8 -C...

  16. 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.

  17. Lipoxygenase inhibitory activity of alkyl protocatechuates.

    PubMed

    Ha, Tae Joung; Shimizu, Kuniyoshi; Kubo, Isao

    2014-09-15

    Alkyl 3,4-dihydroxybenzoates (protocatechuates) inhibited linoleic acid peroxidation catalyzed by soybean lipoxygenase-1 (EC 1.13.11.12, Type 1). Their inhibitory activities displayed a parabolic function of their lipophilicity and maximized with alkyl chain lengths of between C11 and C14. Tetradecanyl protocatechuate exhibited the most potent inhibition with an IC50 of 0.05 μM, followed by dodecyl (lauryl) protocatechuate with an IC50 of 0.06 μM. However, their parent compound, protocatechuic acid, did not show this inhibitory activity up to 200 μM, indicating that the alkyl chain length is significantly related to the inhibition activity. The allosteric (or cooperative) inhibition of soybean lipoxygenase-1 of longer alkyl protocatechuates is reversible but in combination with their iron binding ability to disrupt the active site competitively and to interact with the hydrophobic portion surrounding near the active site (sequential action). In the case of dodecyl protocatechuate, the enzyme quickly binds this protocatechuate and then its dodecyl group undergoes a slow interaction with the hydrophobic domain in close proximity to the active site in the enzyme. The inhibition kinetics analyzed by Lineweaver-Burk plots indicates that octyl protocatechuate is a competitive inhibitor and the inhibition constant (Ki) was obtained as 0.23 μM but dodecyl protocatechuate is a slow binding inhibitor.

  18. Xanthine oxidase inhibitory activity of alkyl gallates.

    PubMed

    Masuoka, Noriyoshi; Nihei, Ken-ichi; Kubo, Isao

    2006-08-01

    A series (C1-C12) of alkyl gallates was examined for their effects on the activity of xanthine oxidase. Octyl (C8), decyl (C10), and dodecyl (C12) gallates competitively inhibited uric acid formation generated by xanthine oxidase, and the inhibition increased upon increasing the alkyl chain length. Interestingly, neither menthyl nor bornyl gallates inhibited uric acid formation. These data indicate that the hydrophobic alkyl portion is associated with the xanthine-binding site in the Mo-binding domain. It is likely that the linear alkyl portion interacts with the hydrophobic domain close to the binding site, and the hydrophobic interaction is crucial to inhibit the xanthine oxidase reaction. On the other hand, all of gallic acid and its esters equally suppress superoxide anion generation catalyzed by xanthine oxidase at low concentration. The suppression is not due to scavenging activity of these gallates but due to reduction of xanthine oxidase by these gallates. The reduced enzyme catalyzes the reaction to generate hydrogen peroxide and uric acid.

  19. Poly(ethyleneoxide) functionalization through alkylation

    DOEpatents

    Sivanandan, Kulandaivelu; Eitouni, Hany Basam; Li, Yan; Pratt, Russell Clayton

    2015-04-21

    A new and efficient method of functionalizing high molecular weight polymers through alkylation using a metal amide base is described. This novel procedure can also be used to synthesize polymer-based macro-initiators containing radical initiating groups at the chain-ends for synthesis of block copolymers.

  20. Theoretical study on the mechanism of Ni-catalyzed alkyl-alkyl Suzuki cross-coupling.

    PubMed

    Li, Zhe; Jiang, Yuan-Ye; Fu, Yao

    2012-04-01

    Ni-catalyzed cross-coupling of unactivated secondary alkyl halides with alkylboranes provides an efficient way to construct alkyl-alkyl bonds. The mechanism of this reaction with the Ni/L1 (L1=trans-N,N'-dimethyl-1,2-cyclohexanediamine) system was examined for the first time by using theoretical calculations. The feasible mechanism was found to involve a Ni(I)-Ni(III) catalytic cycle with three main steps: transmetalation of [Ni(I)(L1)X] (X=Cl, Br) with 9-borabicyclo[3.3.1]nonane (9-BBN)R(1) to produce [Ni(I)(L1)(R(1))], oxidative addition of R(2) X with [Ni(I)(L1)(R(1))] to produce [Ni(III)(L1)(R(1))(R(2))X] through a radical pathway, and C-C reductive elimination to generate the product and [Ni(I)(L1)X]. The transmetalation step is rate-determining for both primary and secondary alkyl bromides. KOiBu decreases the activation barrier of the transmetalation step by forming a potassium alkyl boronate salt with alkyl borane. Tertiary alkyl halides are not reactive because the activation barrier of reductive elimination is too high (+34.7 kcal mol(-1)). On the other hand, the cross-coupling of alkyl chlorides can be catalyzed by Ni/L2 (L2=trans-N,N'-dimethyl-1,2-diphenylethane-1,2-diamine) because the activation barrier of transmetalation with L2 is lower than that with L1. Importantly, the Ni(0)-Ni(II) catalytic cycle is not favored in the present systems because reductive elimination from both singlet and triplet [Ni(II)(L1)(R(1))(R(2))] is very difficult.

  1. 40 CFR 721.10218 - 2-Propenoic acid, 2-mehtyl-, C12-15-branched and linear alkyl esters, telomers with alkyl 2...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-branched and linear alkyl esters, telomers with alkyl 2- thio]-2-alkanoate, aminoalkyl methacrylate and alkyl methacrylate, tert-Bu 2-ethylhexanoperoxoate-initiated (generic). 721.10218 Section 721.10218... 2-Propenoic acid, 2-mehtyl-, C12-15-branched and linear alkyl esters, telomers with alkyl 2-...

  2. 40 CFR 721.10218 - 2-Propenoic acid, 2-mehtyl-, C12-15-branched and linear alkyl esters, telomers with alkyl 2...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-branched and linear alkyl esters, telomers with alkyl 2- thio]-2-alkanoate, aminoalkyl methacrylate and alkyl methacrylate, tert-Bu 2-ethylhexanoperoxoate-initiated (generic). 721.10218 Section 721.10218... 2-Propenoic acid, 2-mehtyl-, C12-15-branched and linear alkyl esters, telomers with alkyl 2-...

  3. 40 CFR 721.10218 - 2-Propenoic acid, 2-mehtyl-, C12-15-branched and linear alkyl esters, telomers with alkyl 2...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-branched and linear alkyl esters, telomers with alkyl 2- thio]-2-alkanoate, aminoalkyl methacrylate and alkyl methacrylate, tert-Bu 2-ethylhexanoperoxoate-initiated (generic). 721.10218 Section 721.10218... 2-Propenoic acid, 2-mehtyl-, C12-15-branched and linear alkyl esters, telomers with alkyl 2-...

  4. 40 CFR 721.10218 - 2-Propenoic acid, 2-mehtyl-, C12-15-branched and linear alkyl esters, telomers with alkyl 2...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-branched and linear alkyl esters, telomers with alkyl 2- thio]-2-alkanoate, aminoalkyl methacrylate and alkyl methacrylate, tert-Bu 2-ethylhexanoperoxoate-initiated (generic). 721.10218 Section 721.10218... 2-Propenoic acid, 2-mehtyl-, C12-15-branched and linear alkyl esters, telomers with alkyl 2-...

  5. Synthesis and X-ray crystal structure of isomeric pyridine-based leuco-TAM dyes, 2,2-(2-(pyridinyl)propane-1,3-diylidene)bis(5-chloro-1,3,3-trimethyl indoline) derivatives and unusual stability of 4-pyridinyl compound

    NASA Astrophysics Data System (ADS)

    Ma, So-Young; Keum, Sam-Rok

    2013-09-01

    The solid-state structures and unequivocal stereochemistries of isomeric pyridine-based leuco-triarylmethane (LTAM) dyes 2,2‧-(2-(pyridin-4 or 3-yl)propane-1,3-diylidene)bis(5-chloro-1,3,3-trimethylindoline) derivatives were established by X-ray crystallography. Surprisingly, the EE isomer was formed for the 4-pyridinyl compound, whereas the 3-pyridinyl compound formed ZE isomers. In addition, the latter have a so-called three-bladed propeller conformation, whereas the former possess a Y-shaped conformation. These pyridine-based LTAM compounds stack to form a dimer, adopting either an orthorhombic, with Pcmn space group, or monoclinic crystal system with P21/n space group in the crystal unit cell.

  6. Reaction of Lithium Diethylamide with an Alkyl Bromide and Alkyl Benzenesulfonate: Origins of Alkylation, Elimination, and Sulfonation

    PubMed Central

    Gupta, Lekha; Ramírez, Antonio; Collum, David B.

    2010-01-01

    A combination of NMR, kinetic, and computational methods are used to examine reactions of lithium diethylamide in tetrahydrofuran (THF) with n-dodecyl bromide and n-octyl benzenesulfonate. The alkyl bromide undergoes competitive SN2 substitution and E2 elimination in proportions independent of all concentrations except for a minor medium effect. Rate studies show that both reactions occur via trisolvated-monomer-based transition structures. The alkyl benzenesulfonate undergoes competitive SN2 substitution (minor) and N-sulfonation (major) with N-sulfonation promoted at low THF concentrations. The SN2 substitution is shown to proceed via a disolvated monomer suggested computationally to involve a cyclic transition structure. The dominant N-sulfonation follows a disolvated-dimer-based transition structure suggested computationally to be a bicyclo[3.1.1] form. The differing THF and lithium diethylamide orders for the two reactions explain the observed concentration-dependent chemoselectivities. PMID:21077695

  7. Antifungal activity of alkyl gallates against plant pathogenic fungi.

    PubMed

    Ito, Shinsaku; Nakagawa, Yasutaka; Yazawa, Satoru; Sasaki, Yasuyuki; Yajima, Shunsuke

    2014-04-01

    The antifungal activity of alkyl gallates against plant pathogenic fungi was evaluated. All of the fungi tested in this study were susceptible to some alkyl gallates, and the effect of linear alkyl gallates against plant pathogenic fungi was similar to the previously reported effects against Gram-negative and Gram-positive bacteria. We found that branched alkyl gallates showed stronger activity than did linear alkyl gallates with similar logP values. In addition, the antifungal activity of alkyl gallates was correlated with gallate-induced inhibition of the activity of mitochondrial complex II. The antifungal activity of alkyl gallates likely originates, at least in part, from their ability to inhibit the membrane respiratory chain.

  8. PROCESS FOR PRODUCING ALKYL ORTHOPHOSPHORIC ACID EXTRACTANTS

    DOEpatents

    Grinstead, R.R.

    1962-01-23

    A process is given for producing superior alkyl orthophosphoric acid extractants for use in solvent extraction methods to recover and purify various metals such as uranium and vanadium. The process comprises slurrying P/sub 2/O/ sub 5/ in a solvent diluent such as kerosene, benzene, isopropyl ether, and the like. An alipbatic alcohol having from nine to seventeen carbon atoms, and w- hcrein ihc OH group is situated inward of the terminal carbon atoms, is added to the slurry while the reaction temperature is mainiained below 60 deg C. The alcohol is added in the mole ratio of about 2 to l, alcohol to P/sub 2/O/sub 5/. A pyrophosphate reaotion product is formed in the slurry-alcohol mixture. Subsequently, the pyrophosphate reaction product is hydrolyzed with dilute mineral acid to produce the desired alkyl orthophosphoric aeid extractant. The extraetant may then be separated and utilized in metal-recovery, solvent- extraction processes. (AEC)

  9. In pursuit of homoleptic actinide alkyl complexes.

    PubMed

    Seaman, Lani A; Walensky, Justin R; Wu, Guang; Hayton, Trevor W

    2013-04-01

    This Forum Article describes the pursuit of isolable homoleptic actinide alkyl complexes, starting with the pioneering work of Gilman during the Manhattan project. The initial reports in this area suggested that homoleptic uranium alkyls were too unstable to be isolated, but Wilkinson demonstrated that tractable uranium alkyls could be generated by purposeful "ate" complex formation, which serves to saturate the uranium coordination sphere and provide the complexes with greater kinetic stability. More recently, we reported the solid-state molecular structures of several homoleptic uranium alkyl complexes, including [Li(THF)4][U(CH2(t)Bu)5], [Li(TMEDA)]2[UMe6], [K(THF)]3[K(THF)2][U(CH2Ph)6]2, and [Li(THF)4][U(CH2SiMe3)6], by employing Wilkinson's strategy. Herein, we describe our attempts to extend this chemistry to thorium. The treatment of ThCl4(DME)2 with 5 equiv of LiCH2(t)Bu or LiCH2SiMe3 at -25 °C in THF affords [Th(CH2(t)Bu)5] (1) and [Li(DME)2][Th(CH2SiMe3)5 (2), respectively, in moderate yields. Similarly, the treatment of ThCl4(DME)2 with 6 equiv of K(CH2Ph) produces [K(THF)]2[Th(CH2Ph)6] (3), in good yield. Complexes 1-3 have been fully characterized, while the structures of 1 and 3 were confirmed by X-ray crystallography. Additionally, the electronic properties of 1 and 3 were explored by density functional theory.

  10. ALKYL PYROPHOSPHATE METAL SOLVENT EXTRACTANTS AND PROCESS

    DOEpatents

    Long, R.L.

    1958-09-30

    A process is presented for the recovery of uranium from aqueous mineral acidic solutions by solvent extraction. The extractant is a synmmetrical dialkyl pyrophosphate in which the alkyl substituents have a chain length of from 4 to 17 carbon atoms. Mentioned as a preferred extractant is dioctyl pyrophosphate. The uranium is precipitated irom the organic extractant phase with an agent such as HF, fluoride salts. alcohol, or ammonia.

  11. Alkylation of complementary ribonucleotides in nanoreactors.

    PubMed

    Angelico, Ruggero; Losito, Ilario; Cuomo, Francesca; Ceglie, Andrea; Palmisano, Francesco

    2013-01-14

    The aim of the present study was to provide experimental evidence that base pairing, commonly occurring between nucleic bases in more complex supramolecular arrangements, may affect the reaction pathways associated with the alkylation of bases themselves. In pursuit of this aim, dilute aqueous solutions of Cytidine- (CMP) and Guanosine-Mono-Phosphate (GMP) as single reactants or in an equimolar mixture were treated with the electrophilic alkylating agent 1,2-Dodecyl-Epoxide (DE), which was preventively dispersed into micellar solutions prepared with the cationic surfactant hexadecyltrimethylammonium bromide (CTAB). In the early stage of the reaction, CTAB micelles acted as micro-heterogeneous nanoreactors, but as the reaction progressed the systems evolved toward the formation of polydisperse aggregates, whose size and surface-charge properties were monitored as a function of reaction time. From mass spectrometry analyses, it was found that the deamination of cytosine, a side reaction related to the alkylation of the amino group of CMP, was reduced when both the complementary ribonucleotides were present in the same reaction mixture. The involvement of specific sites able to establish C:G interactions (possibly via H-bonding or π-π stacking) could explain the reduced reactivity occurring at the level of some of the nucleophilic centers responsible for molecular recognition.

  12. DNA-directed alkylating ligands as potential antitumor agents: sequence specificity of alkylation by intercalating aniline mustards.

    PubMed

    Prakash, A S; Denny, W A; Gourdie, T A; Valu, K K; Woodgate, P D; Wakelin, L P

    1990-10-23

    The sequence preferences for alkylation of a series of novel parasubstituted aniline mustards linked to the DNA-intercalating chromophore 9-aminoacridine by an alkyl chain of variable length were studied by using procedures analogous to Maxam-Gilbert reactions. The compounds alkylate DNA at both guanine and adenine sites. For mustards linked to the acridine by a short alkyl chain through a para O- or S-link group, 5'-GT sequences are the most preferred sites at which N7-guanine alkylation occurs. For analogues with longer chain lengths, the preference of 5'-GT sequences diminishes in favor of N7-adenine alkylation at the complementary 5'-AC sequence. Magnesium ions are shown to selectively inhibit alkylation at the N7 of adenine (in the major groove) by these compounds but not the alkylation at the N3 of adenine (in the minor groove) by the antitumor antibiotic CC-1065. Effects of chromophore variation were also studied by using aniline mustards linked to quinazoline and sterically hindered tert-butyl-9-aminoacridine chromophores. The results demonstrate that in this series of DNA-directed mustards the noncovalent interactions of the carrier chromophores with DNA significantly modify the sequence selectivity of alkylation by the mustard. Relationships between the DNA alkylation patterns of these compounds and their biological activities are discussed.

  13. Effects of alkyl parabens on plant pathogenic fungi.

    PubMed

    Ito, Shinsaku; Yazawa, Satoru; Nakagawa, Yasutaka; Sasaki, Yasuyuki; Yajima, Shunsuke

    2015-04-15

    Alkyl parabens are used as antimicrobial preservatives in cosmetics, food, and pharmaceutical products. However, the mode of action of these chemicals has not been assessed thoroughly. In this study, we determined the effects of alkyl parabens on plant pathogenic fungi. All the fungi tested, were susceptible to parabens. The effect of linear alkyl parabens on plant pathogenic fungi was related to the length of the alkyl chain. In addition, the antifungal activity was correlated with the paraben-induced inhibition of oxygen consumption. The antifungal activity of linear alkyl parabens likely originates, at least in part, from their ability to inhibit the membrane respiratory chain, especially mitochondrial complex II. Additionally, we determined that some alkyl parabens inhibit Alternaria brassicicola infection of cabbage.

  14. Photochemical Production of Alkyl Nitrates in the Tropical Pacific Ocean

    NASA Astrophysics Data System (ADS)

    Dahl, E. E.; Yvon-Lewis, S. A.; Saltzman, E. S.

    2005-12-01

    Alkyl nitrates are important to the tropospheric NOx/ozone cycle because they represent a significant fraction of the reactive nitrogen (NOy). Previous work has shown that there is an oceanic source of alkyl nitrates. A photochemical mechanism for the formation of alkyl nitrates in seawater has been proposed. This mechanism involves the reaction of ROO and NO, where ROO is an alkyl peroxy radical. ROO and NO radicals in seawater are derived from the photolysis of DOM and nitrite, respectively. In this study, the photochemical production of low molecular weight alkyl nitrates (C1-C3) was observed in shipboard incubation experiments in the tropical Pacific during the PHASE 1 cruise. Seawater samples from several regions, including high and low-chlorophyll areas, were collected and incubated. Alkyl nitrate production rates as high as 2 nM/hour were observed. The production rate of alkyl nitrates was clearly dependent upon the initial concentration of nitrite, most likely as the source for NO radicals. While the magnitude of production varied between sample locations, the ratios of the production rates of the various alkyl nitrates remained relatively constant. The observed production ratios of methyl, ethyl, isopropyl, and n-propyl nitrate were 5.9:1.0:0.1:0.2. These ratios presumably reflect the speciation of peroxy radicals formed in seawater, and the yield of alkyl nitrates from the ROO+NO reaction. The observed production rate ratios are similar to the concentration ratios of alkyl nitrates observed in ambient seawater and the overlying atmosphere during the study. A comparison of the measured production rates and the observed concentrations, suggests that photochemically produced alkyl nitrates are a major source of atmospheric alkyl nitrates in the surface ocean and marine atmosphere.

  15. Alkylated benzothiophene desulfurization by Rhodococcus sp. strain T09.

    PubMed

    Matsui, T; Onaka, T; Tanaka, Y; Tezuka, T; Suzuki, M; Kurane, R

    2000-03-01

    A benzothiophene desulfurizing bacterium was isolated and identified as Rhodococcus sp. strain T09. Growth assays revealed that this strain assimilated, as the sole sulfur source, various organosulfur compounds that cannot be assimilated by the well-studied dibenzothiophene-desulfurizing Rhodococcus sp. IGTS8. The cellular growth rate of strain T09 for the alkylated benzothiophenes depended on the alkylated position and the length of the alkyl moiety.

  16. 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.

  17. Alkyl substitution effect: A high mobility bistetracene derivatives

    NASA Astrophysics Data System (ADS)

    Liu, Xiaoyan; Liu, Yujuan; Zheng, Yujun

    2016-03-01

    Tetracenes and their derivatives are widely used in organic semiconductors for the advantages of small reorganization energies and large electronic couplings. The influences of long alkyl chain on charge transfer mobility of two bistetracene derivatives are investigated theoretically. The results show that the introduction of long alkyl chains would lead to a more compact packing, and increase electronic coupling, but reduce intermolecular distance. However, the introduction of long alkyl chains has little influence on reorganization energy. This provides a new understanding of the introduction of long alkyl chain on designing new high efficiency organic semiconductors.

  18. A Mechanism for the Aqueous Phase Production of Alkyl Nitrates

    NASA Astrophysics Data System (ADS)

    Dahl, E. E.; Saltzman, E. S.; DeBruyn, W. J.

    2002-05-01

    Measurements of alkyl nitrates in the surface ocean and marine boundary layer indicate that there is an oceanic source of alkyl nitrates to the marine troposphere. Alkyl nitrates make up a portion of the total reactive nitrogen in the troposphere. They can contribute significantly to the NOx budget in the remote marine atmosphere, affecting regional ozone formation. The origin of the alkyl nitrate in the surface ocean is unknown. One possible mechanism for aqueous alkyl nitrate formation is the reaction of alkyl peroxy radicals with NO (ROO + NO -> RONO2). Peroxy radicals and NO have been observed in seawater at levels that make this a viable reaction (Blough 1997) (Zafiriou and McFarland 1981). In this project, steady state irradiations of nitrite and alkane solutions were used to determine the yield of alkyl nitrates from this reaction. The yield for ethyl nitrate has been determined to be 101+/-12% and 102+/-8% total yield for propyl nitrates (n-propyl and iso-propyl) with no evident temperature dependence between 5 and 30° C. Alkyl nitrates were also generated by the irradiation of natural seawater and nitrite-spiked seawater. These results indicate that the proposed mechanism may be a viable source of alkyl nitrates in surface waters.

  19. Biosynthesis of alkyl lysophosphatidic acid by diacylglycerol kinases.

    PubMed

    Gellett, Amanda M; Kharel, Yugesh; Sunkara, Manjula; Morris, Andrew J; Lynch, Kevin R

    2012-06-15

    Lysophosphatidic acid (LPA) designates a family of bioactive phosphoglycerides that differ in the length and degree of saturation of their radyl chain. Additional diversity is provided by the linkage of the radyl chain to glycerol: acyl, alkyl, or alk-1-enyl. Acyl-LPAs are the predominate species in tissues and biological fluids. Alkyl-LPAs exhibit distinct pharmacodynamics at LPA receptors, potently drive platelet aggregation, and contribute to ovarian cancer aggressiveness. Multiple biosynthetic pathways exist for alkyl-LPA production. Herein we report that diacylglycerol kinases (DGKs) contribute to cell-associated alkyl-LPA production involving phosphorylation of 1-alkyl-2-acetyl glycerol and document the biosynthesis of alkyl-LPA by DGKs in SKOV-3 ovarian cancer cells, specifically identifying the contribution of DGKα. Concurrently, we discovered that treating SKOV-3 ovarian cancer cell with a sphingosine analog stimulates conversion of exogenous 1-alkyl-2-acetyl glycerol to alkyl-LPA, indicating that DGKα contributes significantly to the production of alkyl-LPA in SKOV-3 cells and identifying cross-talk between the sphingolipid and glycerol lipid pathways.

  20. Application of secondary alkyl halides to a domino aryl alkylation reaction for the synthesis of aromatic heterocycles.

    PubMed

    Rudolph, Alena; Rackelmann, Nils; Turcotte-Savard, Marc-Olivier; Lautens, Mark

    2009-01-01

    A palladium-catalyzed, norbornene-mediated ortho-alkylation reaction of aryl iodides with secondary alkyl halides is described. Intermolecular or intramolecular ortho-alkylation proceeds in a domino process with various termination steps, generating two new carbon-carbon or carbon-nitrogen bonds in one pot, to afford an array of polycyclic heterocycles. The use of enantioenriched substrates has shown that this palladium-catalyzed reaction is stereospecific, proceeding with minimal erosion of ee.

  1. Alkyl Chlorides as Hydrogen Bond Acceptors

    SciTech Connect

    Nadas, Janos I; Vukovic, Sinisa; Hay, Benjamin

    2012-01-01

    To gain an understanding of the role of an alkyl chloride as a hydrogen bond acceptor, geometries and interaction energies were calculated at the MP2/aug-cc-pVDZ level of theory for complexes between ethyl chloride and representative hydrogen donor groups. The results establish that these donors, which include hydrogen cyanide, methanol, nitrobenzene, pyrrole, acetamide, and N-methylurea, form X-H {hor_ellipsis} Cl hydrogen bonds (X = C, N, O) of weak to moderate strength, with {Delta}E values ranging from -2.8 to -5.3 kcal/mol.

  2. Catalytic Asymmetric Alkylation of Substituted Isoflavanones

    PubMed Central

    Nibbs, Antoinette E.; Baize, Amanda-Lauren; Herter, Rachel M.; Scheidt, Karl A.

    2009-01-01

    The asymmetric alkylation of isoflavanones and protected 3-phenyl-2,3-dihydroquinolin-4(1H)-ones catalyzed by a novel cinchonidine-derived phase transfer catalyst E is reported. This functionalization occurs at the non-activated C3 methine to afford novel products that can easily be functionalized to generate more complex fused ring systems. The process accommodates a variety of isoflavanones and activated electrophiles and installs a stereogenic quaternary center in high yield and with good-to-excellent selectivity. PMID:19658430

  3. Determination of reaction rate constants for alkylation of 4-(p-nitrobenzyl) pyridine by different alkylating agents.

    PubMed

    Walles, S A

    1980-02-01

    The rate constants have been determined for the reaction between some different alkylating agents and 4-(p-nitrobenzyl) pyridine (NBP) in methanol. These constants have been compared with those for alkylation of aniline in water. All the constants were lower in methanol than in water but in different degrees. The rate constants of the different alkylating agents have been calculated at a nucleophilic strength n=2. The genetic risk defined as the degree of alkylation of a nucleophile (n=2) is equivalent to the rate constant kn=2 and the target dose. The dependence of the genetic risk on the rate constant (kn=2) is discussed.

  4. 40 CFR 721.10038 - Trimellitic anhydride, polymer with substituted glycol, alkyl phenols and ethoxylated nonylphenol...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... substituted glycol, alkyl phenols and ethoxylated nonylphenol (generic). 721.10038 Section 721.10038... Trimellitic anhydride, polymer with substituted glycol, alkyl phenols and ethoxylated nonylphenol (generic... identified generically as trimellitic anhydride, polymer with substituted glycol, alkyl phenols...

  5. 40 CFR 721.10038 - Trimellitic anhydride, polymer with substituted glycol, alkyl phenols and ethoxylated nonylphenol...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... substituted glycol, alkyl phenols and ethoxylated nonylphenol (generic). 721.10038 Section 721.10038... Trimellitic anhydride, polymer with substituted glycol, alkyl phenols and ethoxylated nonylphenol (generic... identified generically as trimellitic anhydride, polymer with substituted glycol, alkyl phenols...

  6. 40 CFR 721.10038 - Trimellitic anhydride, polymer with substituted glycol, alkyl phenols and ethoxylated nonylphenol...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... substituted glycol, alkyl phenols and ethoxylated nonylphenol (generic). 721.10038 Section 721.10038... Trimellitic anhydride, polymer with substituted glycol, alkyl phenols and ethoxylated nonylphenol (generic... identified generically as trimellitic anhydride, polymer with substituted glycol, alkyl phenols...

  7. The photodissociation dynamics of alkyl radicals

    SciTech Connect

    Giegerich, Jens; Fischer, Ingo

    2015-01-28

    The photodisscociation dynamics of the alkyl radicals i-propyl (CH(CH{sub 3}){sub 2}) and t-butyl (C(CH{sub 3}){sub 3}) are investigated by H-atom photofragment imaging. While i-propyl is excited at 250 nm, the photodynamics of t-butyl are explored over a large energy range using excitation wavelengths between 347 nm and 233 nm. The results are compared to those obtained previously for ethyl, CH{sub 3}CH{sub 2}, and to those reported for t-butyl using 248 nm excitation. The translational energy (E{sub T}) distribution of the H-atom photofragments is bimodal and appears rather similar for all three radicals. The low E{sub T} part of the distribution shows an isotropic photofragment angular distribution, while the high E{sub T} part is associated with a considerable anisotropy. Thus, for t-butyl, two H-atom loss channels of roughly equal importance have been identified in addition to the CH{sub 3}-loss channel reported previously. A mechanism for the photodissociation of alkyl radicals is suggested that is based on interactions between Rydberg- and valence states.

  8. Radioiodination of Aryl-Alkyl Cyclic Sulfates

    PubMed Central

    Mushti, Chandra; Papisov, Mikhail I.

    2015-01-01

    Among the currently available positron emitters suitable for Positron Emission Tomography (PET), 124I has the longest physical half-life (4.2 days). The long half-life and well-investigated behavior of iodine in vivo makes 124I very attractive for pharmacological studies. In this communication, we describe a simple yet effective method for the synthesis of novel 124I labeled compounds intended for PET imaging of arylsulfatase activity in vivo. Arylsulfatases have important biological functions, and genetic deficiencies of such functions require pharmacological replacement, the efficacy of which must be properly and non-invasively evaluated. These enzymes, even though their natural substrates are mostly of aliphatic nature, hydrolyze phenolic sulfates to phenol and sulfuric acid. The availability of [124I]iodinated substrates is expected to provide a PET-based method for measuring their activity in vivo. The currently available methods of synthesis of iodinated arylsulfates usually require either introducing of a protected sulfate ester early in the synthesis or introduction of sulfate group at the end of synthesis in a separate step. The described method gives the desired product in one step from an aryl-alkyl cyclic sulfate. When treated with iodide, the source cyclic sulfate opens with substitution of iodide at the alkyl center and gives the desired arylsulfate monoester. PMID:23135631

  9. 40 CFR 721.2560 - Alkylated diphenyl oxide (generic name).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkylated diphenyl oxide (generic name). 721.2560 Section 721.2560 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC... Substances § 721.2560 Alkylated diphenyl oxide (generic name). (a) Chemical substance and significant...

  10. Alkylation of refinery C5 streams to lower gasoline volatility

    SciTech Connect

    Cronkright, W.A.; Ditz, J.M.; Newsome, D.S. ); Lerner, H. ); Schorfheide, J.J. ); Libbers, D.D. )

    1994-01-01

    A pilot plant program was carried out to provide precise information about the sulfuric acid alkylation of refinery C5 streams under conditions found in commercial operation of the Exxon stirred, autorefrigerated alkylation process. The study used isobutane to alkylate the full range of pentenes in a C5 cut from an FCC unit as well as the linear olefin concentrate in the raffinate that would be obtained after processing this cut in a TAME unit. A few experiments were conducted with a mixture of C5 olefins matching the composition of the refinery feed in order to highlight the effect of impurities. The results showed that hydrocarbon impurities are a principal factor causing the high acid consumption values reported for pentene alkylation. The results also demonstrated that operating variables that affect acid consumption and alkylate quality in butene alkylation produce directionally similar effects in pentene alkylation, but of different magnitude. It is concluded that sulfur acid alkylation of pentenes produces an excellent isoparaffinic blending stock for the gasoline pool while eliminating volatile olefins and reducing gasoline RVP. Combined with the TAME process, a scheme for adding oxygen and achieving maximum RVP reduction at the same time is realized.

  11. 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...

  12. 40 CFR 721.10341 - Amino alkyl organoborane (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Amino alkyl organoborane (generic... Specific Chemical Substances § 721.10341 Amino alkyl organoborane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as amino...

  13. 40 CFR 721.10430 - Tetra alkyl ammonium salt (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Tetra alkyl ammonium salt (generic... Specific Chemical Substances § 721.10430 Tetra alkyl ammonium salt (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as tetra...

  14. 40 CFR 721.9515 - Aminofunctional alkoxy alkyl siloxane.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Aminofunctional alkoxy alkyl siloxane... Substances § 721.9515 Aminofunctional alkoxy alkyl siloxane. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as an aminofunctional alkoxy...

  15. 40 CFR 721.2155 - Alkoxyamino-alkyl-coumarin (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkoxyamino-alkyl-coumarin (generic... Substances § 721.2155 Alkoxyamino-alkyl-coumarin (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as...

  16. 40 CFR 721.9515 - Aminofunctional alkoxy alkyl siloxane.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Aminofunctional alkoxy alkyl siloxane... Substances § 721.9515 Aminofunctional alkoxy alkyl siloxane. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as an aminofunctional alkoxy...

  17. 40 CFR 721.10317 - Alkyl phosphate derivative (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl phosphate derivative (generic... Specific Chemical Substances § 721.10317 Alkyl phosphate derivative (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as...

  18. 40 CFR 721.10073 - Modified alkyl acrylamide (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Modified alkyl acrylamide (generic... Specific Chemical Substances § 721.10073 Modified alkyl acrylamide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as modified...

  19. 40 CFR 721.9572 - Substituted alkyl sulfonamide (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Substituted alkyl sulfonamide (generic... Substances § 721.9572 Substituted alkyl sulfonamide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted...

  20. 40 CFR 721.10430 - Tetra alkyl ammonium salt (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Tetra alkyl ammonium salt (generic... Specific Chemical Substances § 721.10430 Tetra alkyl ammonium salt (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as tetra...

  1. 40 CFR 721.2155 - Alkoxyamino-alkyl-coumarin (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkoxyamino-alkyl-coumarin (generic... Substances § 721.2155 Alkoxyamino-alkyl-coumarin (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as...

  2. 40 CFR 721.9515 - Aminofunctional alkoxy alkyl siloxane.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Aminofunctional alkoxy alkyl siloxane... Substances § 721.9515 Aminofunctional alkoxy alkyl siloxane. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as an aminofunctional alkoxy...

  3. 40 CFR 721.10341 - Amino alkyl organoborane (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Amino alkyl organoborane (generic... Specific Chemical Substances § 721.10341 Amino alkyl organoborane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as amino...

  4. 40 CFR 721.2155 - Alkoxyamino-alkyl-coumarin (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkoxyamino-alkyl-coumarin (generic... Substances § 721.2155 Alkoxyamino-alkyl-coumarin (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as...

  5. 40 CFR 721.10073 - Modified alkyl acrylamide (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Modified alkyl acrylamide (generic... Specific Chemical Substances § 721.10073 Modified alkyl acrylamide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as modified...

  6. 40 CFR 721.9572 - Substituted alkyl sulfonamide (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Substituted alkyl sulfonamide (generic... Substances § 721.9572 Substituted alkyl sulfonamide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted...

  7. 40 CFR 721.10317 - Alkyl phosphate derivative (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl phosphate derivative (generic... Specific Chemical Substances § 721.10317 Alkyl phosphate derivative (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as...

  8. 40 CFR 721.9572 - Substituted alkyl sulfonamide (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Substituted alkyl sulfonamide (generic... Substances § 721.9572 Substituted alkyl sulfonamide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted...

  9. 40 CFR 721.9515 - Aminofunctional alkoxy alkyl siloxane.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Aminofunctional alkoxy alkyl siloxane... Substances § 721.9515 Aminofunctional alkoxy alkyl siloxane. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as an aminofunctional alkoxy...

  10. 40 CFR 721.10073 - Modified alkyl acrylamide (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Modified alkyl acrylamide (generic... Specific Chemical Substances § 721.10073 Modified alkyl acrylamide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as modified...

  11. 40 CFR 721.10073 - Modified alkyl acrylamide (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Modified alkyl acrylamide (generic... Specific Chemical Substances § 721.10073 Modified alkyl acrylamide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as modified...

  12. 40 CFR 721.9572 - Substituted alkyl sulfonamide (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted alkyl sulfonamide (generic... Substances § 721.9572 Substituted alkyl sulfonamide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted...

  13. 40 CFR 721.10317 - Alkyl phosphate derivative (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkyl phosphate derivative (generic... Specific Chemical Substances § 721.10317 Alkyl phosphate derivative (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as...

  14. 40 CFR 721.10073 - Modified alkyl acrylamide (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Modified alkyl acrylamide (generic... Specific Chemical Substances § 721.10073 Modified alkyl acrylamide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as modified...

  15. 40 CFR 721.10341 - Amino alkyl organoborane (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Amino alkyl organoborane (generic... Specific Chemical Substances § 721.10341 Amino alkyl organoborane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as amino...

  16. 40 CFR 721.9572 - Substituted alkyl sulfonamide (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Substituted alkyl sulfonamide (generic... Substances § 721.9572 Substituted alkyl sulfonamide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as substituted...

  17. 40 CFR 721.9515 - Aminofunctional alkoxy alkyl siloxane.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Aminofunctional alkoxy alkyl siloxane... Substances § 721.9515 Aminofunctional alkoxy alkyl siloxane. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as an aminofunctional alkoxy...

  18. 40 CFR 721.2155 - Alkoxyamino-alkyl-coumarin (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkoxyamino-alkyl-coumarin (generic... Substances § 721.2155 Alkoxyamino-alkyl-coumarin (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as...

  19. 40 CFR 721.2155 - Alkoxyamino-alkyl-coumarin (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkoxyamino-alkyl-coumarin (generic... Substances § 721.2155 Alkoxyamino-alkyl-coumarin (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as...

  20. 40 CFR 721.8700 - Halogenated alkyl pyridine.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.8700 Halogenated alkyl pyridine. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified generically as halogenated alkyl pyridine (PMN P-83-237)...

  1. Ni-Catalyzed C-C Couplings Using Alkyl Electrophiles.

    PubMed

    Iwasaki, Takanori; Kambe, Nobuaki

    2016-10-01

    Much effort has been devoted to developing new methods using Ni catalysts for the cross-coupling reaction of alkyl electrophiles with organometallic reagents, and significant achievements in this area have emerged during the past two decades. Nickel catalysts have enabled the coupling reaction of not only primary alkyl electrophiles, but also sterically hindered secondary and tertiary alkyl electrophiles possessing β-hydrogens with various organometallic reagents to construct carbon skeletons. In addition, Ni catalysts opened a new era of asymmetric cross-coupling reaction using alkyl halides. Recent progress in nickel-catalyzed cross-coupling reaction of alkyl electrophiles with sp(3)-, sp(2)-, and sp-hybridized organometallic reagents including asymmetric variants as well as mechanistic insights of nickel catalysis are reviewed in this chapter. PMID:27580894

  2. β-Alkyl Elimination: Fundamental Principles and Some Applications.

    PubMed

    O'Reilly, Matthew E; Dutta, Saikat; Veige, Adam S

    2016-07-27

    This review describes organometallic compounds and materials that are capable of mediating a rarely encountered but fundamentally important reaction: β-alkyl elimination at the metal-Cα-Cβ-R moiety, in which an alkyl group attached to the Cβ atom is transferred to the metal or to a coordinated substrate. The objectives of this review are to provide a cohesive fundamental understanding of β-alkyl-elimination reactions and to highlight its applications in olefin polymerization, alkane hydrogenolysis, depolymerization of branched polymers, ring-opening polymerization of cycloalkanes, and other useful organic reactions. To provide a coherent understanding of the β-alkyl elimination reaction, special attention is given to conditions and strategies used to facilitate β-alkyl-elimination/transfer events in metal-catalyzed olefin polymerization, which provide the well-studied examples.

  3. 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.

  4. Ni-Catalyzed C-C Couplings Using Alkyl Electrophiles.

    PubMed

    Iwasaki, Takanori; Kambe, Nobuaki

    2016-10-01

    Much effort has been devoted to developing new methods using Ni catalysts for the cross-coupling reaction of alkyl electrophiles with organometallic reagents, and significant achievements in this area have emerged during the past two decades. Nickel catalysts have enabled the coupling reaction of not only primary alkyl electrophiles, but also sterically hindered secondary and tertiary alkyl electrophiles possessing β-hydrogens with various organometallic reagents to construct carbon skeletons. In addition, Ni catalysts opened a new era of asymmetric cross-coupling reaction using alkyl halides. Recent progress in nickel-catalyzed cross-coupling reaction of alkyl electrophiles with sp(3)-, sp(2)-, and sp-hybridized organometallic reagents including asymmetric variants as well as mechanistic insights of nickel catalysis are reviewed in this chapter.

  5. Abuse potential and dopaminergic effect of alkyl nitrites.

    PubMed

    Jeon, Seo Young; Kim, Yun Ji; Kim, Young-Hoon; Shin, Jisoon; Yun, Jaesuk; Han, Kyoungmoon; Park, Hye-Kyung; Kim, Hyung Soo; Cha, Hye Jin

    2016-08-26

    The abuse of alkyl nitrites is common among adolescents and young adults worldwide. However, the information regarding the effects of alkyl nitrites on the central nervous system and the associated psychological abuse potential is scarce. The abuse potential of 3 representative alkyl nitrites - isobutyl nitrite, isoamyl nitrite, and butyl nitrite - was evaluated in mice using conditioned place preference tests with an unbiased method. The dopamine levels released by synaptosomes extracted from the striatal region were measured using high performance liquid chromatography. Mice treated with the test substances (50mg/kg, i.p.) exhibited a significantly increased drug-paired place preference. Moreover, greater levels of dopamine were released by striatal region synaptosomes in response to isobutyl nitrite treatment in mice. Thus, our findings suggest that alkyl nitrites could lead to psychological dependence and dopaminergic effects. Furthermore, these results provide scientific evidence to support the regulation of alkyl nitrites as psychoactive substances in the future.

  6. An efficient copper-catalyzed cross-coupling reaction of alkyl-triflates with alkyl-Grignard reagents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A highly efficient method for the formation of C-C covalent bonds by cross-coupling reaction between alkyl-triflates and alkyl-Grignard reagents catalyzed by copper catalyst, Li2CuCl4, is described. The reaction works with most primary triflates in diethyl ether at low temperature within 0.5-3 h an...

  7. Process for conversion of light paraffins to alkylate in the production of tertiary alkyl ether rich gasoline

    SciTech Connect

    Harandi, M.N.; Owen, H.

    1992-04-21

    This patent describes a continuous integrated process for producing hydrocarbon streams comprising C{sub 5} + gasoline rich in alkyl tertiary alkyl ether and C{sub 5} + alkylated aromatic rich gasoline. It comprises contacting alkanol and C{sub 3} + aliphatic hydrocarbon stream containing alkanes and alkenes rich in iso-olefins with acid etherification catalyst under iso-olefin etherification conditions in an etherification reaction zone; separating etherification effluent to recover an overhead stream comprising unreacted alkanol plus C{sub 4} {minus} aliphatic hydrocarbons and a liquid product stream comprising C{sub 5} + gasoline containing alkyl tertiary-alkyl ether; contacting the overhead stream and a feedstream containing light aromatic hydrocarbons in an alkylation reactor containing acidic, medium pore metallosilicate catalyst under alkylation conditions and conversion conditions sufficient to convert alkanol, alkane and alkene to higher hydrocarbons the conditions comprising a temperature of about 200{degrees} C to 400{degrees} C and a pressure about above 3400 kPa; and separating step (c) reaction products and recovering the C{sub 5} + alkylated aromatic rich gasoline and a stream comprising C{sub 4} {minus} hydrocarbons.

  8. 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.

  9. Copper-catalyzed alkyl-alkyl cross-coupling reactions using hydrocarbon additives: efficiency of catalyst and roles of additives.

    PubMed

    Iwasaki, Takanori; Imanishi, Reiko; Shimizu, Ryohei; Kuniyasu, Hitoshi; Terao, Jun; Kambe, Nobuaki

    2014-09-19

    Cross-coupling of alkyl halides with alkyl Grignard reagents proceeds with extremely high TONs of up to 1230000 using a Cu/unsaturated hydrocarbon catalytic system. Alkyl fluorides, chlorides, bromides, and tosylates are all suitable electrophiles, and a TOF as high as 31200 h(-1) was attained using an alkyl iodide. Side reactions of this catalytic system, i.e., reduction, dehydrohalogenation (elimination), and the homocoupling of alkyl halides, occur in the absence of additives. It appears that the reaction involves the β-hydrogen elimination of alkylcopper intermediates, giving rise to olefins and Cu-H species, and that this process triggers both side reactions and the degradation of the Cu catalyst. The formed Cu-H promotes the reduction of alkyl halides to give alkanes and Cu-X or the generation of Cu(0), probably by disproportionation, which can oxidatively add to alkyl halides to yield olefins and, in some cases, homocoupling products. Unsaturated hydrocarbon additives such as 1,3-butadiene and phenylpropyne play important roles in achieving highly efficient cross-coupling by suppressing β-hydrogen elimination, which inhibits both the degradation of the Cu catalyst and undesirable side reactions.

  10. Ligand redox effects in the synthesis, electronic structure, and reactivity of an alkyl-alkyl cross-coupling catalyst.

    PubMed

    Jones, Gavin D; Martin, Jason L; McFarland, Chris; Allen, Olivia R; Hall, Ryan E; Haley, Aireal D; Brandon, R Jacob; Konovalova, Tatyana; Desrochers, Patrick J; Pulay, Peter; Vicic, David A

    2006-10-11

    The ability of the terpyridine ligand to stabilize alkyl complexes of nickel has been central in obtaining a fundamental understanding of the key processes involved in alkyl-alkyl cross-coupling reactions. Here, mechanistic studies using isotopically labeled (TMEDA)NiMe(2) (TMEDA = N,N,N',N'-tetramethylethylenediamine) have shown that an important catalyst in alkyl-alkyl cross-coupling reactions, (tpy')NiMe (2b, tpy' = 4,4',4' '-tri-tert-butylterpyridine), is not produced via a mechanism that involves the formation of methyl radicals. Instead, it is proposed that (terpyridine)NiMe complexes arise via a comproportionation reaction between a Ni(II)-dimethyl species and a Ni(0) fragment in solution upon addition of a terpyridine ligand to (TMEDA)NiMe(2). EPR and DFT studies on the paramagnetic (terpyridine)NiMe (2a) both suggest that the unpaired electron resides heavily on the terpyridine ligand and that the proper electronic description of this nickel complex is a Ni(II)-methyl cation bound to a reduced terpyridine ligand. Thus, an important consequence of these results is that alkyl halide reduction by (terpyridine)NiR(alkyl) complexes appears to be substantially ligand based. A comprehensive survey investigating the catalytic reactivity of related ligand derivatives suggests that electronic factors only moderately influence reactivity in the terpyridine-based catalysis and that the most dramatic effects arise from steric and solubility factors.

  11. Copper-catalyzed alkyl-alkyl cross-coupling reactions using hydrocarbon additives: efficiency of catalyst and roles of additives.

    PubMed

    Iwasaki, Takanori; Imanishi, Reiko; Shimizu, Ryohei; Kuniyasu, Hitoshi; Terao, Jun; Kambe, Nobuaki

    2014-09-19

    Cross-coupling of alkyl halides with alkyl Grignard reagents proceeds with extremely high TONs of up to 1230000 using a Cu/unsaturated hydrocarbon catalytic system. Alkyl fluorides, chlorides, bromides, and tosylates are all suitable electrophiles, and a TOF as high as 31200 h(-1) was attained using an alkyl iodide. Side reactions of this catalytic system, i.e., reduction, dehydrohalogenation (elimination), and the homocoupling of alkyl halides, occur in the absence of additives. It appears that the reaction involves the β-hydrogen elimination of alkylcopper intermediates, giving rise to olefins and Cu-H species, and that this process triggers both side reactions and the degradation of the Cu catalyst. The formed Cu-H promotes the reduction of alkyl halides to give alkanes and Cu-X or the generation of Cu(0), probably by disproportionation, which can oxidatively add to alkyl halides to yield olefins and, in some cases, homocoupling products. Unsaturated hydrocarbon additives such as 1,3-butadiene and phenylpropyne play important roles in achieving highly efficient cross-coupling by suppressing β-hydrogen elimination, which inhibits both the degradation of the Cu catalyst and undesirable side reactions. PMID:25010426

  12. Antihydrophobic cosolvent effects for alkylation reactions in water solution, particularly oxygen versus carbon alkylations of phenoxide ions.

    PubMed

    Breslow, Ronald; Groves, Kevin; Mayer, M Uljana

    2002-04-10

    Antihydrophobic cosolvents such as ethanol increase the solubility of hydrophobic molecules in water, and they also affect the rates of reactions involving hydrophobic surfaces. In simple reactions of hydrocarbons, such as the Diels-Alder dimerization of 1,3-cyclopentadiene, the rate and solubility data directly reflect the geometry of the transition state, in which some hydrophobic surface becomes hidden. In reactions involving polar groups, such as alkylations of phenoxide ions or S(N)1 ionizations of alkyl halides, cosolvents in water can have other effects as well. However, solvation of hydrophobic surfaces is still important. By the use of structure-reactivity relationships, and comparing the effects of ethanol and DMSO as solvents, it has been possible to sort out these effects. The conclusions are reinforced by an ab initio computer model for hydrophobic solvation. The result is a sensible transition state for phenoxide ion as a nucleophile, using its oxygen n electrons to avoid loss of conjugation. The geometry of alkylation of aniline is very different, involving packing (stacking) of the aniline ring onto the phenyl ring of a benzyl group in the benzylation reaction. The alkylation of phenoxide ions by benzylic chlorides can occur both at the phenoxide oxygen and on ortho and para positions of the ring. Carbon alkylation occurs in water, but not in nonpolar organic solvents, and it is observed only when the phenoxide has at least one methyl substituent ortho, meta, or para. The effects of phenol substituents and of antihydrophobic cosolvents on the rates of the competing alkylation processes indicate that in water the carbon alkylation involves a transition state with hydrophobic packing of the benzyl group onto the phenol ring. The results also support our conclusion that oxygen alkylation uses the n electrons of the phenoxide oxygen as the nucleophile and does not have hydrophobic overlap in the transition state. The mechanisms and explanations for

  13. Perfluorinated Alkyl Compounds: Challenges To Develop Robust And Reliable Methods

    EPA Science Inventory

    An increasing number of studies have been conducted to investigate the environmental distribution of perfluorinated alkyl compounds (PFCs), some of which are known to be toxic in laboratory studies. Despite growing public concerns, environmental monitoring data are still limited...

  14. Copper-catalyzed arylation of alkyl halides with arylaluminum reagents

    PubMed Central

    Shrestha, Bijay

    2015-01-01

    Summary We report a Cu-catalyzed coupling between triarylaluminum reagents and alkyl halides to form arylalkanes. The reaction proceeds in the presence of N,N,N’,N’-tetramethyl-o-phenylenediamine (NN-1) as a ligand in combination with CuI as a catalyst. This catalyst system enables the coupling of primary alkyl iodides and bromides with electron-neutral and electron-rich triarylaluminum reagents and affords the cross-coupled products in good to excellent yields. PMID:26734088

  15. Copper-catalyzed arylation of alkyl halides with arylaluminum reagents.

    PubMed

    Shrestha, Bijay; Giri, Ramesh

    2015-01-01

    We report a Cu-catalyzed coupling between triarylaluminum reagents and alkyl halides to form arylalkanes. The reaction proceeds in the presence of N,N,N',N'-tetramethyl-o-phenylenediamine (NN-1) as a ligand in combination with CuI as a catalyst. This catalyst system enables the coupling of primary alkyl iodides and bromides with electron-neutral and electron-rich triarylaluminum reagents and affords the cross-coupled products in good to excellent yields. PMID:26734088

  16. Use of Trifluoromethyl Groups for Catalytic Benzylation and Alkylation with Subsequent Hydrodefluorination.

    PubMed

    Zhu, Jiangtao; Pérez, Manuel; Caputo, Christopher B; Stephan, Douglas W

    2016-01-22

    The electrophilic organofluorophosphonium catalyst [(C6F5)3PF][B(C6F5)4] is shown to effect benzylation or alkylation by aryl and alkyl CF3 groups with subsequent hydrodefluorination, thus resulting in a net transformation of CF3 into CH2-aryl fragments. In the case of alkyl CF3 groups, Friedel-Crafts alkylation by the difluorocarbocation proceeded without cation rearrangement, in contrast to the corresponding reactions of alkyl monofluorides. PMID:26663711

  17. Alkyl and phenolic glycosides from Saussurea stella.

    PubMed

    Wang, Tian-Min; Wang, Ru-Feng; Chen, Hu-Biao; Shang, Ming-Ying; Cai, Shao-Qing

    2013-07-01

    One alkyl glycoside, saussurostelloside A (1), two phenolic glycosides, saussurostellosides B1 (2) and B2 (3), and 27 known compounds, including eleven flavonoids, seven phenolics, six lignans, one neolignan, one phenethyl glucoside and one fatty acid, were isolated from an ethanol extract of Saussurea stella (Asteraceae). Their structures were elucidated by NMR, MS, UV, and IR spectroscopic analysis. Of the known compounds, (+)-medioresinol-di-O-β-D-glucoside (7), picraquassioside C (10), and diosmetin-3'-O-β-D-glucoside (27) were isolated from the Asteraceae family for the first time, while (+)-pinoresinol-di-O-β-D-glucoside (6), di-O-methylcrenatin (11), protocatechuic acid (14), 1,5-di-O-caffeoylquinic acid (17), formononetin (28), and phenethyl glucoside (29) were isolated from the Saussurea genus for the first time. The anti-inflammatory activities of three new compounds (1-3), five lignans ((-)-arctiin (4), (+)-pinoresinol-4-O-β-D-glucoside (5), (+)-pinoresinol-di-O-β-D-glucoside (6), (+)-medioresinol-di-O-β-D-glucoside (7) and (+)-syringaresinol-4-O-β-D-glucoside (8)), one neolignan (picraquassioside C (10)), and one phenolic glycoside (di-O-methylcrenatin (11)) were evaluated by testing their inhibition of the release of β-glucuronidase from PAF-stimulated neutrophils. Only compound 5 showed moderate inhibition of the release of β-glucuronidase, with an inhibition ratio of 39.1%.

  18. 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. PMID:24590719

  19. Final Technical Report [Development of Catalytic Alkylation and Fluoroalkylation Methods

    SciTech Connect

    Vicic, David A.

    2014-05-01

    In the early stages of this DOE-funded research project, we sought to prepare and study a well-defined nickel-alkyl complex containing tridentate nitrogen donor ligands. We found that reaction of (TMEDA)NiMe2 (1) with terpyridine ligand cleanly led to the formation of (terpyridyl)NiMe (2), which we also determined to be an active alkylation catalyst. The thermal stability of 2 was unlike that seen for any of the active pybox ligands, and enabled a number of key studies on alkyl transfer reactions to be performed, providing new insights into the mechanism of nickel-mediated alkyl-alkyl cross-coupling reactions. In addition to the mechanistic studies, we showed that the terpyridyl nickel compounds can catalytically cross-couple alkyl iodides in yields up to 98% and bromides in yields up to 46 %. The yields for the bromides can be increased up to 67 % when the new palladium catalyst [(tpy’)Pd-Ph]I is used. The best route to the targeted [(tpy)NiBr] (1) was found to involve the comproportionation reaction of [(dme)NiBr{sub 2}] and [Ni(COD){sub 2}] in the presence of two equivalents of terpyridine. This reaction was driven to high yields of product formation (72 % isolated) by the precipitation of 1 from THF solvent.

  20. 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.

  1. 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.

  2. DNA minor groove targeted alkylating agents based on bisbenzimidazole carriers: synthesis, cytotoxicity and sequence-specificity of DNA alkylation.

    PubMed

    Smaill, J B; Fan, J Y; Denny, W A

    1998-12-01

    A series of bisbenzimidazoles bearing a variety of alkylating agents [ortho- and meta-mustards, imidazolebis(hydroxymethyl), imidazolebis(methylcarbamate) and pyrrolebis(hydroxymethyl)], appended by a propyl linker chain, were prepared and investigated for sequence-specificity of DNA alkylation and their cytotoxicity. Previous work has shown that, for para-aniline mustards, a propyl linker is optimal for cytotoxicity. Alkaline cleavage assays using a variety of different labelled oligonucleotides showed that the preferred sequences for adenine alkylation were 5'-TTTANANAANN and 5'-ATTANANAANN (underlined bases show the drug alkylation sites), with AT-rich sequences required on both the 5' and 3' sides of the alkylated adenine. The different aniline mustards showed little variation in alkylation pattern and similar efficiencies of DNA cross-link formation despite the changes in orientation and positioning of the mustard, suggesting that the propyl linker has some flexibility. The imidazole- and pyrrolebis(hydroxymethyl) alkylators showed no DNA strand cleavage following base treatment, indicating that no guanine or adenine N3 or N7 adducts were formed. Using the PCR-based polymerase stop assay, these alkylators showed PCR blocks at 5'-C*G sites (the * nucleotide indicates the blocked site), particularly at 5'-TAC*GA 5'-AGC*GGA, and 5'-AGCC*GGT sequences, caused by guanine 2-NH2 lesions on the opposite strand. Only the (more reactive) imidazolebis(methylcarbamoyl) and pyrrolebis(hydroxymethyl) alkylators demonstrated interstrand cross-linking ability. All of the bifunctional mustards showed large (approximately 100-fold) increases in cytotoxicity over chlorambucil, with the corresponding monofunctional mustards being 20- to 60-fold less cytotoxic. These results suggest that in the mustards the propyl linker provides sufficient flexibility to achieve delivery of the alkylator to favoured (adenine N3) sites in the minor groove, regardless of its exact geometry with

  3. Cu(I)-Catalyzed Enantioselective Friedel-Crafts Alkylation of Indoles with 2-Aryl-N-sulfonylaziridines as Alkylating Agents.

    PubMed

    Ge, Chen; Liu, Ren-Rong; Gao, Jian-Rong; Jia, Yi-Xia

    2016-07-01

    A highly enantioselective Friedel-Crafts alkylation of indoles with N-sulfonylaziridines as alkylating agents has been developed by utilizing the complex of Cu(CH3CN)4BF4/(S)-Segphos as a catalyst. A range of optically active tryptamine derivatives are obtained in good to excellent yields and enantioselectivities (up to >99% ee) via a kinetic resolution process. PMID:27309541

  4. 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. PMID:11237050

  5. Palladium-Catalyzed Cross Coupling of Secondary and Tertiary Alkyl Bromides with a Nitrogen Nucleophile

    PubMed Central

    2016-01-01

    We report a new class of catalytic reaction: the thermal substitution of a secondary and or tertiary alkyl halide with a nitrogen nucleophile. The alkylation of a nitrogen nucleophile with an alkyl halide is a classical method for the construction of C–N bonds, but traditional substitution reactions are challenging to achieve with a secondary and or tertiary alkyl electrophile due to competing elimination reactions. A catalytic process could address this limitation, but thermal, catalytic coupling of alkyl halides with a nitrogen nucleophile and any type of catalytic coupling of an unactivated tertiary alkyl halide with a nitrogen nucleophile are unknown. We report the coupling of unactivated secondary and tertiary alkyl bromides with benzophenone imines to produce protected primary amines in the presence of palladium ligated by the hindered trialkylphosphine Cy2t-BuP. Mechanistic studies indicate that this amination of alkyl halides occurs by a reversible reaction to form a free alkyl radical. PMID:27725963

  6. N-Alkyl-, 1-C-Alkyl-, and 5-C-Alkyl-1,5-dideoxy-1,5-imino-(L)-ribitols as Galactosidase Inhibitors.

    PubMed

    Front, Sophie; Gallienne, Estelle; Charollais-Thoenig, Julie; Demotz, Stéphane; Martin, Olivier R

    2016-01-01

    A series of 1,5-dideoxy-1,5-imino-(l)-ribitol (DIR) derivatives carrying alkyl or functionalized alkyl groups were prepared and investigated as glycosidase inhibitors. These compounds were designed as simplified 4-epi-isofagomine (4-epi-IFG) mimics and were expected to behave as selective inhibitors of β-galactosidases. All compounds were indeed found to be highly selective for β-galactosidases versus α-glycosidases, as they generally did not inhibit coffee bean α-galactosidase or other α-glycosidases. Some compounds were also found to be inhibitors of almond β-glucosidase. The N-alkyl DIR derivatives were only modest inhibitors of bovine β-galactosidase, with IC50 values in the 30-700 μM range. Likewise, imino-L-ribitol substituted at the C1 position was found to be a weak inhibitor of this enzyme. In contrast, alkyl substitution at C5 resulted in enhanced β-galactosidase inhibitory activity by a factor of up to 1000, with at least six carbon atoms in the alkyl substituent. Remarkably, the 'pseudo-anomeric' configuration in this series does not appear to play a role. Human lysosomal β-galactosidase from leukocyte lysate was, however, poorly inhibited by all iminoribitol derivatives tested (IC50 values in the 100 μM range), while 4-epi-IFG was a good inhibitor of this enzyme. Two compounds were evaluated as pharmacological chaperones for a GM1-gangliosidosis cell line (R301Q mutation) and were found to enhance the mutant enzyme activity by factors up to 2.7-fold.

  7. Alkyl polycyclic aromatic hydrocarbons emissions in diesel/biodiesel exhaust

    NASA Astrophysics Data System (ADS)

    Casal, Carina S.; Arbilla, Graciela; Corrêa, Sergio M.

    2014-10-01

    Polycyclic aromatic hydrocarbons (PAHs) are widely studied in environmental matrices, such as air, water, soil and sediment, because of their toxicity, mutagenicity and carcinogenicity. Because of these properties, the environmental agencies of developed countries have listed sixteen PAHs as priority pollutants. Few countries have limits for these compounds for ambient air, but they only limit emissions from stationary and mobile sources and occupational areas. There are several studies to specifically address the 16 priority PAHs and very little for the alkyl PAHs. These compounds are more abundant, more persistent and frequently more toxic than the non-alkylated PAHs, and the toxicity increases with the number of alkyl substitutions on the aromatic ring. In this study, a method was developed for the analysis of PAHs and alkyl PAHs by using a GC-MS and large injection volume injection coupled with program temperature vaporisation, which allows for limits of detection below 1.0 ng μL-1. Several variables were tested, such as the injection volume, injection velocity, injector initial temperature, duration of the solvent split and others. This method was evaluated in samples from particulate matter from the emissions of engines employing standard diesel, commercial diesel and biodiesel B20. Samples were collected on a dynamometer bench for a diesel engine cycle and the results ranged from 0.5 to 96.9 ng mL-1, indicating that diesel/biodiesel makes a significant contribution to the formation of PAHs and alkyl PAHs.

  8. Catalytic synthesis of n-alkyl arenes through alkyl group cross-metathesis.

    PubMed

    Dobereiner, Graham E; Yuan, Jian; Schrock, Richard R; Goldman, Alan S; Hackenberg, Jason D

    2013-08-28

    n-Alkyl arenes were prepared in a one-pot tandem dehydrogenation/olefin metathesis/hydrogenation sequence directly from alkanes and ethylbenzene. Excellent selectivity was observed when ((tBu)PCP)IrH2 was paired with tungsten monoaryloxide pyrrolide complexes such as W(NAr)(C3H6)(pyr)(OHIPT) (1a) [Ar = 2,6-i-Pr2C6H3; pyr = pyrrolide; OHIPT = 2,6-(2,4,6-i-Pr3C6H2)2C6H3O]. Complex 1a was also especially active in n-octane self-metathesis, providing the highest product concentrations reported to date. The thermal stability of selected olefin metathesis catalysts allowed elevated temperatures and extended reaction times to be employed. PMID:23909821

  9. Safety assessment of alkyl PEG 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; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

    2012-01-01

    The CIR Expert Panel assessed the safety of Alkyl PEG Ethers as used in cosmetics. These ingredients primarily function in cosmetics as surfactants, and some have additional functions as skin-conditioning agents, fragrance ingredients, and emulsion stabilizers. The Panel reviewed available relevant animal and clinical data, as well as information from previous CIR reports; when data were not available for individual ingredients, the Panel extrapolated from the existing data to support safety. The Panel concluded that the Alkyl PEG ethers are safe as used when formulated to be nonirritating, and the same applies to future alkyl PEG ether cosmetic ingredients that vary from those ingredients recited herein only by the number of ethylene glycol repeat units.

  10. Preparation and reactivity of macrocyclic rhodium(III) alkyl complexes

    SciTech Connect

    Carraher, Jack M.; Ellern, Arkady; Bakac, Andreja

    2013-09-21

    Macrocyclic rhodium(II) complexes LRh(H2O)(2+) (L = L-1 = cyclam and L-2 = meso-Me-6-cyclam) react with alkyl hydroperoxides RC(CH3)(2)OOH to generate the corresponding rhodium(III) alkyls L(H2O)RhR2+ (R = CH3, C2H5, PhCH2). Methyl and benzyl complexes can also be prepared by bimolecular group transfer from alkyl cobaloximes (dmgH)(2)(H2O) CoR and (dmgBF(2))(2)(H2O) CoR (R = CH3, PhCH2) to LRh(H2O)(2+). The new complexes were characterized by solution NMR and by crystal structure analysis. They exhibit great stability in aqueous solution at room temperature, but undergo efficient Rh-C bond cleavage upon photolysis. (C) 2013 Elsevier B.V. All rights reserved.

  11. Safety Assessment of Alkyl PEG Sulfosuccinates as Used in Cosmetics.

    PubMed

    Johnson, Wilbur; 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

    2015-09-01

    The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) reviewed the safety of alkyl polyethylene glycol (PEG) sulfosuccinates, which function in cosmetics mostly as surfactants/cleansing agents. Although these ingredients may cause ocular and skin irritation, dermal penetration is unlikely because of the substantial polarity and molecular size of these ingredients. The Panel considered the negative oral carcinogenicity and reproductive and developmental toxicity data on chemically related laureths (PEG lauryl ethers) and negative repeated dose toxicity and skin sensitization data on disodium laureth sulfosuccinate supported the safety of these alkyl PEG sulfosuccinates in cosmetic products, but. The CIR Expert Panel concluded that the alkyl PEG sulfosuccinates are safe in the present practices of use and concentration when formulated to be nonirritating.

  12. Safety Assessment of Alkyl Ethylhexanoates as Used in Cosmetics.

    PubMed

    Fiume, Monice; 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

    2015-01-01

    The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of 16 alkyl ethylhexanoates for use in cosmetics, concluding that these ingredients are safe in cosmetic formulations in the present practices of use and concentrations when formulated to be nonirritating. The alkyl ethylhexanoates primarily function as skin-conditioning agents in cosmetics. The highest concentration of use reported for any of the alkyl ethylhexanoates is 77.3% cetyl ethylhexanoate in rinse-off formulations used near the eye, and the highest leave-on use reported is 52% cetyl ethylhexanoate in lipstick formulations. The Panel reviewed available animal and clinical data related to these ingredients, and the similarities in structure, properties, functions, and uses of ingredients from previous CIR assessments on constituent alcohols that allowed for extrapolation of the available toxicological data to assess the safety of the entire group.

  13. Safety Assessment of Alkyl Ethylhexanoates as Used in Cosmetics.

    PubMed

    Fiume, Monice; 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

    2015-01-01

    The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of 16 alkyl ethylhexanoates for use in cosmetics, concluding that these ingredients are safe in cosmetic formulations in the present practices of use and concentrations when formulated to be nonirritating. The alkyl ethylhexanoates primarily function as skin-conditioning agents in cosmetics. The highest concentration of use reported for any of the alkyl ethylhexanoates is 77.3% cetyl ethylhexanoate in rinse-off formulations used near the eye, and the highest leave-on use reported is 52% cetyl ethylhexanoate in lipstick formulations. The Panel reviewed available animal and clinical data related to these ingredients, and the similarities in structure, properties, functions, and uses of ingredients from previous CIR assessments on constituent alcohols that allowed for extrapolation of the available toxicological data to assess the safety of the entire group. PMID:26684798

  14. Alkylation of imidazole under ultrasound irradiation over alkaline carbons

    NASA Astrophysics Data System (ADS)

    Costarrosa, L.; Calvino-Casilda, V.; Ferrera-Escudero, S.; Durán-Valle, C. J.; Martín-Aranda, R. M.

    2006-06-01

    N-Alkyl-imidazole has been synthesized by sonochemical irradiation of imidazole and 1-bromobutane using alkaline-promoted carbons (exchanged with the binary combinations of Na, K and Cs). The catalysts were characterized by X-ray photoelectron spectroscopy, thermal analysis and N 2 adsorption isotherms. Under the experimental conditions, N-alkyl-imidazoles can be prepared with a high activity and selectivity. It is observed that imidazole conversion increases in parallel with increasing the basicity of the catalyst. The influence of the alkaline promoter, the reaction temperature, and the amount of catalyst on the catalytic activity has been studied. For comparison, the alkylation of imidazole has also been performed in a batch reactor system under thermal activation.

  15. Saturation anomalies of alkyl nitrates in the tropical Pacific Ocean

    NASA Astrophysics Data System (ADS)

    Dahl, Elizabeth E.; Yvon-Lewis, Shari A.; Saltzman, Eric S.

    2005-10-01

    This paper reports the first measurements of the saturation state of low molecular weight alkyl nitrates (methyl, ethyl, isopropyl, and n-propyl nitrate) in the tropical Pacific Ocean. These compounds were supersaturated with saturation anomalies as high as 2000%. Air/sea flux estimates based on these measurements suggest that surface ocean emissions are sufficient to account for observed levels of tropospheric alkyl nitrates in this region. Model calculations suggest that atmospheric loss rates are faster than can be explained by photolysis and reaction with OH alone. The implication is that removal via transport is important, and there must be a net export of alkyl nitrates from the tropics to other regions of the atmosphere.

  16. Selective N-Alkylation of Aniline by Micellar Catalysis

    PubMed

    Siswanto; Rathman

    1997-12-01

    Reactions of aniline with 1-bromobutane to form N-butylaniline and N,N-dibutylaniline were performed in single-phase aqueous surfactant systems. Reaction rate, yield, and selectivity of the N-alkyl product were monitored for different initial compositions, and much higher reaction rate, yield, and selectivity were observed in comparison to reactions of neat components. Excess aniline increased yield and selectivity, while excess 1-bromobutane had the opposite effect. The lipophilic reactant (1-bromobutane) and both products are solubilized almost entirely in the surfactant micelles. The formation of relatively small amounts of N,N-dibutylaniline effectively inhibited further alkylation of N-butylaniline, so that high selectivities (>20) of the N-alkyl were obtained. Added sodium hydroxide caused small decreases in yield and selectivity and showed that pH-dependent dissociation equilibria of the various amine species do not have a major influence on reaction characteristics. Copyright 1997 Academic Press. Copyright 1997Academic Press

  17. Structural features of a series of S-alkylated and non-S-alkylated aminothiolate nickel(II) complexes

    NASA Astrophysics Data System (ADS)

    Chohan, B. S.

    2014-12-01

    The structural aspects of a family of S-alkylated complexes, generated by reacting iodoacetamide or iodoethanol with two mononuclear Ni(II) diaminodithiolate complexes are discussed. The S-alkylation reactions were investigated with particular attention paid to the size of the chelate ring that straps the N,N'-methylamine donors. In one complex the N-methyl groups are cis to each other and in the other they are trans. Both complexes undergo S-alkylation with two equivalents of either reagent, that coordinates through the pendant oxygen to the Ni(II), forming dications with an N2S2O2 ligand donor set. Crystal structures of [NiC12H26N4O2S2]I2 · MeOH, [NiC12H28N2O2S2]I2, and [NiC13H30N2O2S2]I2 · 1/2 MeOH, are determined by single crystal X-ray analysis. The N-methyl groups in each of the alkylated derivatives are trans to each other, suggesting that the cis configuration is highly unfavored for such complexes in octahedral conformation. Crystal packing data shows that each of the alkylated complexes interacts closely with the iodide counterions, and with solvent if present; some of these interactions include H-bonds. Only the iodoacetamide derivative shows any significant interaction with a neighboring molecule.

  18. 40 CFR 721.6183 - Amides, from ammonium hydroxide - maleic anhydride polymer and hydrogenated tallow alkyl amines...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... - maleic anhydride polymer and hydrogenated tallow alkyl amines, sodium salts, compds. with ethanolamine... alkyl amines, sodium salts, compds. with ethanolamine. (a) Chemical substance and significant new uses... anhydride polymer and hydrogenated tallow alkyl amines, sodium salts, compds. with ethanolamine (PMN...

  19. Alkyl hydroxybenzoic acid derivatives that inhibit HIV-1 protease dimerization.

    PubMed

    Flausino, O A; Dufau, L; Regasini, L O; Petrônio, M S; Silva, D H S; Rose, T; Bolzani, V S; Reboud-Ravaux, M

    2012-01-01

    The therapeutic potential of gallic acid and its derivatives as anti-cancer, antimicrobial and antiviral agents is well known. We have examined the mechanism by which natural gallic acid and newly synthesized gallic acid alkyl esters and related protocatechuic acid alkyl esters inhibit HIV-1 protease to compare the influence of the aromatic ring substitutions on inhibition. We used Zhang-Poorman's kinetic analysis and fluorescent probe binding to demonstrate that several gallic and protecatechuic acid alkyl esters inhibited HIV-1 protease by preventing the dimerization of this obligate homodimeric aspartic protease rather than targeting the active site. The tri-hydroxy substituted benzoic moiety in gallates was more favorable than the di-substituted one in protocatechuates. In both series, the type of inhibition, its mechanism and the inhibitory efficiency dramatically depended on the length of the alkyl chain: no inhibition with alkyl chains less than 8 carbon atoms long. Molecular dynamics simulations corroborated the kinetic data and propose that gallic esters are intercalated between the two N- and C-monomer ends. They complete the β-sheet and disrupt the dimeric enzyme. The best gallic ester (14 carbon atoms, K(id) of 320 nM) also inhibited the multi-mutated protease MDR-HM. These results will aid the rational design of future generations of non-peptide inhibitors of HIV-1 protease dimerization that inhibit multi-mutated proteases. Finally, our work suggests the wide use of gallic and protocatechuic alkyl esters to dissociate intermolecular β-sheets involved in protein-protein interactions.

  20. Direct β-Alkylation of Aldehydes via Photoredox Organocatalysis

    PubMed Central

    2015-01-01

    Direct β-alkylation of saturated aldehydes has been accomplished by synergistically combining photoredox catalysis and organocatalysis. Photon-induced enamine oxidation provides an activated β-enaminyl radical intermediate, which readily combines with a wide range of Michael acceptors to produce β-alkyl aldehydes in a highly efficient manner. Furthermore, this redox-neutral, atom-economical C–H functionalization protocol can be achieved both inter- and intramolecularly. Mechanistic studies by various spectroscopic methods suggest that a reductive quenching pathway is operable. PMID:24754456

  1. Alkylation of H-Phosphinate Esters under Basic Conditions

    PubMed Central

    Abrunhosa-Thomas, Isabelle; Sellers, Claire E.; Montchamp, Jean-Luc

    2008-01-01

    An efficient and general procedure was developed for the direct alkylation of H-phosphinate esters with LiHMDS at low temperature. The simplicity of the reaction allows the use of various H-phosphinate esters and takes place with a wide range of electrophiles. The approach can be employed to access some GABA analogs or precursors to GABA analogs. The isolated yields are moderate to good. This is the first report of an alkylation with a secondary iodide, or a primary chloride. PMID:17352490

  2. Alkyl phospholipid antihypertensive agents in method of lowering blood pressure

    DOEpatents

    Snyder, Fred L.; Blank, Merle L.; Muirhead, Ernest E.; Leach, deceased, Byron E.; Byers, Lawrence W.

    1988-01-01

    The composition of this invention is 1-O-alkyl-2-acetoyl-sn-glycero-3-phosphocholine, having the ionic structural formula; ##STR1## wherein R is saturated alkyl having 9-21 carbon atoms, or salts or hydrates of the composition. Preferably R has 13-19 carbon atoms and most preferably R has 15 carbon atoms. The composition of this invention is useful for reducing hypertension in warm-blooded animals, including humans, when administered either orally or by injection or innoculation, e.g., intravenous injection. The composition can be prepared from naturally occurring lipids or synthetically from commercially available material.

  3. The effect of alkylating agents on model supported metal clusters

    SciTech Connect

    Erdem-Senatalar, A.; Blackmond, D.G.; Wender, I. . Dept. of Chemical and Petroleum Engineering); Oukaci, R. )

    1988-01-01

    Interactions between model supported metal clusters and alkylating agents were studied in an effort to understand a novel chemical trapping technique developed for identifying species adsorbed on catalyst surfaces. It was found that these interactions are more complex than had previously been suggested. Studies were completed using deuterium-labeled dimethyl sulfate (DMS), (CH{sub 3}){sub 2}SO{sub 4}, as a trapping agent to interact with the supported metal cluster ethylidyne tricobalt enneacarbonyl. Results showed that oxygenated products formed during the trapping reaction contained {minus}OCD{sub 3} groups from the DMS, indicating that the interaction was not a simple alkylation. 18 refs., 1 fig., 3 tabs.

  4. 40 CFR 721.7200 - Perfluoroalkyl aromatic carbamate modified alkyl methacrylate copolymer.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... modified alkyl methacrylate copolymer. 721.7200 Section 721.7200 Protection of Environment ENVIRONMENTAL... alkyl methacrylate copolymer. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as perfluoroalkyl aromatic carbamate modified...

  5. 40 CFR 721.7200 - Perfluoroalkyl aromatic carbamate modified alkyl methacrylate copolymer.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... modified alkyl methacrylate copolymer. 721.7200 Section 721.7200 Protection of Environment ENVIRONMENTAL... alkyl methacrylate copolymer. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as perfluoroalkyl aromatic carbamate modified...

  6. 40 CFR 721.7200 - Perfluoroalkyl aromatic carbamate modified alkyl methacrylate copolymer.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... modified alkyl methacrylate copolymer. 721.7200 Section 721.7200 Protection of Environment ENVIRONMENTAL... alkyl methacrylate copolymer. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as perfluoroalkyl aromatic carbamate modified...

  7. 40 CFR 721.7200 - Perfluoroalkyl aromatic carbamate modified alkyl methacrylate copolymer.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... modified alkyl methacrylate copolymer. 721.7200 Section 721.7200 Protection of Environment ENVIRONMENTAL... alkyl methacrylate copolymer. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as perfluoroalkyl aromatic carbamate modified...

  8. 40 CFR 721.7200 - Perfluoroalkyl aromatic carbamate modified alkyl methacrylate copolymer.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... modified alkyl methacrylate copolymer. 721.7200 Section 721.7200 Protection of Environment ENVIRONMENTAL... alkyl methacrylate copolymer. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as perfluoroalkyl aromatic carbamate modified...

  9. 40 CFR 721.10058 - Reaction product of alkylphenol, aromatic cyclicamine, alkyl diglycidyl dibenzene, and...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Reaction product of alkylphenol... Reaction product of alkylphenol, aromatic cyclicamine, alkyl diglycidyl dibenzene, and formaldehyde... identified generically as reaction product of alkylphenol, aromatic cyclicamine, alkyl diglycidyl...

  10. 40 CFR 721.10058 - Reaction product of alkylphenol, aromatic cyclicamine, alkyl diglycidyl dibenzene, and...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Reaction product of alkylphenol... Reaction product of alkylphenol, aromatic cyclicamine, alkyl diglycidyl dibenzene, and formaldehyde... identified generically as reaction product of alkylphenol, aromatic cyclicamine, alkyl diglycidyl...

  11. 40 CFR 721.10058 - Reaction product of alkylphenol, aromatic cyclicamine, alkyl diglycidyl dibenzene, and...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Reaction product of alkylphenol... Reaction product of alkylphenol, aromatic cyclicamine, alkyl diglycidyl dibenzene, and formaldehyde... identified generically as reaction product of alkylphenol, aromatic cyclicamine, alkyl diglycidyl...

  12. 40 CFR 721.10058 - Reaction product of alkylphenol, aromatic cyclicamine, alkyl diglycidyl dibenzene, and...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Reaction product of alkylphenol... Reaction product of alkylphenol, aromatic cyclicamine, alkyl diglycidyl dibenzene, and formaldehyde... identified generically as reaction product of alkylphenol, aromatic cyclicamine, alkyl diglycidyl...

  13. 40 CFR 721.10058 - Reaction product of alkylphenol, aromatic cyclicamine, alkyl diglycidyl dibenzene, and...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Reaction product of alkylphenol... Reaction product of alkylphenol, aromatic cyclicamine, alkyl diglycidyl dibenzene, and formaldehyde... identified generically as reaction product of alkylphenol, aromatic cyclicamine, alkyl diglycidyl...

  14. Immobilization of Lipases on Alkyl Silane Modified Magnetic Nanoparticles: Effect of Alkyl Chain Length on Enzyme Activity

    PubMed Central

    Wang, Jiqian; Meng, Gang; Tao, Kai; Feng, Min; Zhao, Xiubo; Li, Zhen; Xu, Hai; Xia, Daohong; Lu, Jian R.

    2012-01-01

    Background Biocatalytic processes often require a full recycling of biocatalysts to optimize economic benefits and minimize waste disposal. Immobilization of biocatalysts onto particulate carriers has been widely explored as an option to meet these requirements. However, surface properties often affect the amount of biocatalysts immobilized, their bioactivity and stability, hampering their wide applications. The aim of this work is to explore how immobilization of lipases onto magnetite nanoparticles affects their biocatalytic performance under carefully controlled surface modification. Methodology/Principal Findings Magnetite nanoparticles, prepared through a co-precipitation method, were coated with alkyl silanes of different alkyl chain lengths to modulate their surface hydrophobicity. Candida rugosa lipase was then directly immobilized onto the modified nanoparticles through hydrophobic interaction. Enzyme activity was assessed by catalytic hydrolysis of p-nitrophenyl acetate. The activity of immobilized lipases was found to increase with increasing chain length of the alkyl silane. Furthermore, the catalytic activities of lipases immobilized on trimethoxyl octadecyl silane (C18) modified Fe3O4 were a factor of 2 or more than the values reported from other surface immobilized systems. After 7 recycles, the activities of the lipases immobilized on C18 modified nanoparticles retained 65%, indicating significant enhancement of stability as well through hydrophobic interaction. Lipase immobilized magnetic nanoparticles facilitated easy separation and recycling with high activity retaining. Conclusions/Significance The activity of immobilized lipases increased with increasing alkyl chain length of the alkyl trimethoxy silanes used in the surface modification of magnetite nanoparticles. Lipase stability was also improved through hydrophobic interaction. Alkyl silane modified magnetite nanoparticles are thus highly attractive carriers for enzyme immobilization

  15. 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

  16. Transition-Metal-Free Regioselective Alkylation of Pyridine N-Oxides Using 1,1-Diborylalkanes as Alkylating Reagents.

    PubMed

    Jo, Woohyun; Kim, Junghoon; Choi, Seoyoung; Cho, Seung Hwan

    2016-08-01

    Reported herein is an unprecedented base-promoted deborylative alkylation of pyridine N-oxides using 1,1-diborylalkanes as alkyl sources. The reaction proceeds efficiently for a wide range of pyridine N-oxides and 1,1-diborylalkanes with excellent regioselectivity. The utility of the developed method is demonstrated by the sequential C-H arylation and methylation of pyridine N-oxides. The reaction also can be applied for the direct introduction of a methyl group to 9-O-methylquinine N-oxide, thus it can serve as a powerful method for late-stage functionalization. PMID:27351367

  17. 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...

  18. 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...

  19. 40 CFR 721.10437 - Sulfonic acid, linear xylene alkylate, mono, sodium salts (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Sulfonic acid, linear xylene alkylate... Significant New Uses for Specific Chemical Substances § 721.10437 Sulfonic acid, linear xylene alkylate, mono... chemical substances identified generically as sulfonic acid, linear xylene alkylate, mono, sodium...

  20. 40 CFR 721.10437 - Sulfonic acid, linear xylene alkylate, mono, sodium salts (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Sulfonic acid, linear xylene alkylate... Significant New Uses for Specific Chemical Substances § 721.10437 Sulfonic acid, linear xylene alkylate, mono... chemical substances identified generically as sulfonic acid, linear xylene alkylate, mono, sodium...

  1. 40 CFR 721.644 - Amines, C12-14-tert-alkyl, sulfonates.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 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...

  2. 40 CFR 721.5860 - Methylphenol, bis(sub-sti-tuted)alkyl.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Methylphenol, bis(sub-sti-tuted)alkyl... Substances § 721.5860 Methylphenol, bis(sub-sti-tuted)alkyl. (a) Chemical substance and significant new uses...-ed)alkyl (P-84-417) is subject to reporting under this section for the significant new uses...

  3. 40 CFR 721.3845 - Alkyl substituted aromatic glycidyl ether (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl substituted aromatic glycidyl... Specific Chemical Substances § 721.3845 Alkyl substituted aromatic glycidyl ether (generic). (a) Chemical... as alkyl substituted aromatic glycidyl ether (PMN P-97-661) is subject to reporting under...

  4. 40 CFR 721.10143 - Amines, bis (C11-14-branched and linear alkyl).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... linear alkyl). 721.10143 Section 721.10143 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10143 Amines, bis (C11-14-branched and linear alkyl). (a) Chemical..., bis (C11-14-branched and linear alkyl) (PMN P-06-733; CAS No. 900169-60-0) is subject to...

  5. 40 CFR 721.10316 - Dicyclopentadiene polymer with maleic anhydride and alkyl alcohols (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... anhydride and alkyl alcohols (generic). 721.10316 Section 721.10316 Protection of Environment ENVIRONMENTAL... anhydride and alkyl alcohols (generic). (a) Chemical substance and significant new uses subject to reporting... and alkyl alcohols (PMN P-02-872) is subject to reporting under this section for the significant...

  6. 40 CFR 721.5860 - Methylphenol, bis(sub-sti-tuted)alkyl.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Methylphenol, bis(sub-sti-tuted)alkyl... Substances § 721.5860 Methylphenol, bis(sub-sti-tuted)alkyl. (a) Chemical substance and significant new uses...-ed)alkyl (P-84-417) is subject to reporting under this section for the significant new uses...

  7. 40 CFR 721.3845 - Alkyl substituted aromatic glycidyl ether (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkyl substituted aromatic glycidyl... Specific Chemical Substances § 721.3845 Alkyl substituted aromatic glycidyl ether (generic). (a) Chemical... as alkyl substituted aromatic glycidyl ether (PMN P-97-661) is subject to reporting under...

  8. 40 CFR 721.5860 - Methylphenol, bis(sub-sti-tuted)alkyl.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Methylphenol, bis(sub-sti-tuted)alkyl... Substances § 721.5860 Methylphenol, bis(sub-sti-tuted)alkyl. (a) Chemical substance and significant new uses...-ed)alkyl (P-84-417) is subject to reporting under this section for the significant new uses...

  9. 40 CFR 721.10352 - Dimethyl terephthalate, polymer with alkyl diol and substituted benzoates (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... alkyl diol and substituted benzoates (generic). 721.10352 Section 721.10352 Protection of Environment... with alkyl diol and substituted benzoates (generic). (a) Chemical substance and significant new uses... with alkyl diol and substituted benzoates (PMN P-08-93) is subject to reporting under this section...

  10. 40 CFR 721.10316 - Dicyclopentadiene polymer with maleic anhydride and alkyl alcohols (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... anhydride and alkyl alcohols (generic). 721.10316 Section 721.10316 Protection of Environment ENVIRONMENTAL... anhydride and alkyl alcohols (generic). (a) Chemical substance and significant new uses subject to reporting... and alkyl alcohols (PMN P-02-872) is subject to reporting under this section for the significant...

  11. 40 CFR 721.3845 - Alkyl substituted aromatic glycidyl ether (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl substituted aromatic glycidyl... Specific Chemical Substances § 721.3845 Alkyl substituted aromatic glycidyl ether (generic). (a) Chemical... as alkyl substituted aromatic glycidyl ether (PMN P-97-661) is subject to reporting under...

  12. 40 CFR 721.10417 - Biphenyl alkyl morpholino ketone (generic) (P-11-338).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Biphenyl alkyl morpholino ketone... Specific Chemical Substances § 721.10417 Biphenyl alkyl morpholino ketone (generic) (P-11-338). (a... generically as biphenyl alkyl morpholino ketone (PMN P-11-338) is subject to reporting under this section...

  13. 40 CFR 721.2094 - N,N′-di(alkyl heteromonocycle)amino chlorotriazine.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 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...

  14. 40 CFR 721.4100 - Tris(disubstituted alkyl) het-er-o-cy-cle.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Tris(disubstituted alkyl) het-er-o-cy... Specific Chemical Substances § 721.4100 Tris(disubstituted alkyl) het-er-o-cy-cle. (a) Chemical substance... tris(disubstituted alkyl) heterocycle (P-90-142) is subject to reporting under this section for...

  15. 40 CFR 721.5985 - Fatty alkyl phosphate, alkali metal salt (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 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...

  16. 40 CFR 721.10143 - Amines, bis (C11-14-branched and linear alkyl).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... linear alkyl). 721.10143 Section 721.10143 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10143 Amines, bis (C11-14-branched and linear alkyl). (a) Chemical..., bis (C11-14-branched and linear alkyl) (PMN P-06-733; CAS No. 900169-60-0) is subject to...

  17. 40 CFR 721.644 - Amines, C12-14-tert-alkyl, sulfonates.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 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...

  18. 40 CFR 721.10352 - Dimethyl terephthalate, polymer with alkyl diol and substituted benzoates (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... alkyl diol and substituted benzoates (generic). 721.10352 Section 721.10352 Protection of Environment... with alkyl diol and substituted benzoates (generic). (a) Chemical substance and significant new uses... with alkyl diol and substituted benzoates (PMN P-08-93) is subject to reporting under this section...

  19. 40 CFR 721.10342 - Quaternary ammonium compounds, fatty alkyl dialkyl hydroxide (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... alkyl dialkyl hydroxide (generic). 721.10342 Section 721.10342 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.10342 Quaternary ammonium compounds, fatty alkyl... chemical substance identified generically as quaternary ammonium compounds, fatty alkyl dialkyl...

  20. 40 CFR 721.10359 - Cardanol-based alkyl phosphate (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Cardanol-based alkyl phosphate... Specific Chemical Substances § 721.10359 Cardanol-based alkyl phosphate (generic). (a) Chemical substance... cardanol-based alkyl phosphate (PMN P-09-613) is subject to reporting under this section for...

  1. 40 CFR 721.6475 - Alkyl polycarboxylic acids, esters with ethoxylated fatty alcohols.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkyl polycarboxylic acids, esters... Significant New Uses for Specific Chemical Substances § 721.6475 Alkyl polycarboxylic acids, esters with... chemical substances identified generically as alkyl polycarboxylic acids, esters with ethoxylated...

  2. 40 CFR 721.3845 - Alkyl substituted aromatic glycidyl ether (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl substituted aromatic glycidyl... Specific Chemical Substances § 721.3845 Alkyl substituted aromatic glycidyl ether (generic). (a) Chemical... as alkyl substituted aromatic glycidyl ether (PMN P-97-661) is subject to reporting under...

  3. 40 CFR 721.10497 - Substituted alkyl ester, hydrolysis products with silica and substituted silane (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Substituted alkyl ester, hydrolysis... CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10497 Substituted alkyl... alkyl ester, hydrolysis products with silica and substituted silane (PMNs P-06-276 and P-06-279)...

  4. 40 CFR 721.10486 - Alkyl substituted amino-benzamide (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl substituted amino-benzamide... Specific Chemical Substances § 721.10486 Alkyl substituted amino-benzamide (generic). (a) Chemical... as alkyl substituted amino-benzamide (PMN P-04-591) is subject to reporting under this section...

  5. 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...

  6. 40 CFR 721.10361 - Anthraquinonedicarboximide, diamino-N-alkyl- (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-alkyl- (generic). 721.10361 Section 721.10361 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10361 Anthraquinonedicarboximide, diamino-N-alkyl- (generic). (a... generically as anthraquinonedicarboximide, diamino-N-alkyl- (PMN P-10-15) is subject to reporting under...

  7. 40 CFR 721.6475 - Alkyl polycarboxylic acids, esters with ethoxylated fatty alcohols.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl polycarboxylic acids, esters... Significant New Uses for Specific Chemical Substances § 721.6475 Alkyl polycarboxylic acids, esters with... chemical substances identified generically as alkyl polycarboxylic acids, esters with ethoxylated...

  8. 40 CFR 721.4100 - Tris(disubstituted alkyl) het-er-o-cy-cle.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Tris(disubstituted alkyl) het-er-o-cy... Specific Chemical Substances § 721.4100 Tris(disubstituted alkyl) het-er-o-cy-cle. (a) Chemical substance... tris(disubstituted alkyl) heterocycle (P-90-142) is subject to reporting under this section for...

  9. 40 CFR 721.10635 - Alkyl maleimide substituted bicyclic olefin (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl maleimide substituted bicyclic... Specific Chemical Substances § 721.10635 Alkyl maleimide substituted bicyclic olefin (generic). (a... generically as alkyl maleimide substituted bicyclic olefin (PMN P-12-480) is subject to reporting under...

  10. 40 CFR 721.10498 - Substituted alkyl ester, hydrolysis products with silica (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Substituted alkyl ester, hydrolysis... Significant New Uses for Specific Chemical Substances § 721.10498 Substituted alkyl ester, hydrolysis products... chemical substances identified generically as substituted alkyl ester, hydrolysis products with...

  11. 40 CFR 721.2094 - N,N′-di(alkyl heteromonocycle)amino chlorotriazine.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 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...

  12. 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...

  13. 40 CFR 721.3900 - Alkyl polyethylene glycol phosphate, potassium salt.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkyl polyethylene glycol phosphate... Specific Chemical Substances § 721.3900 Alkyl polyethylene glycol phosphate, potassium salt. (a) Chemical... as alkyl polyethylene glycol phosphate, potassium salt (P-90-481), is subject to reporting under...

  14. 40 CFR 721.10200 - Benzenacetonitrile, cyclohexylidene-alkyl substituted (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-alkyl substituted (generic). 721.10200 Section 721.10200 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.10200 Benzenacetonitrile, cyclohexylidene-alkyl... substance identified generically as benzenacetonitrile, cyclohexylidene-alkyl substituted (PMN P-09-75)...

  15. 40 CFR 721.10350 - Amines, C11-14-branched and linear alkyl.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... alkyl. 721.10350 Section 721.10350 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.10350 Amines, C11-14-branched and linear alkyl. (a) Chemical substance...-branched and linear alkyl (PMN P-06-742; CAS No. 863766-30-7) is subject to reporting under this...

  16. 40 CFR 721.10702 - Polyfluorinated alkyl thio polyacrylic acid-acrylamide (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polyfluorinated alkyl thio polyacrylic... Significant New Uses for Specific Chemical Substances § 721.10702 Polyfluorinated alkyl thio polyacrylic acid... substance identified generically as polyfluorinated alkyl thio polyacrylic acid-acrylamide (PMN P-11-534)...

  17. 40 CFR 721.10498 - Substituted alkyl ester, hydrolysis products with silica (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Substituted alkyl ester, hydrolysis... Significant New Uses for Specific Chemical Substances § 721.10498 Substituted alkyl ester, hydrolysis products... chemical substances identified generically as substituted alkyl ester, hydrolysis products with...

  18. 40 CFR 721.10101 - Copolymer of alkyl acrylate and ethyleneglycol dimethacrylate (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Copolymer of alkyl acrylate and... Significant New Uses for Specific Chemical Substances § 721.10101 Copolymer of alkyl acrylate and...) The chemical substance identified generically as copolymer of alkyl acrylate and...

  19. 40 CFR 721.10359 - Cardanol-based alkyl phosphate (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Cardanol-based alkyl phosphate... Specific Chemical Substances § 721.10359 Cardanol-based alkyl phosphate (generic). (a) Chemical substance... cardanol-based alkyl phosphate (PMN P-09-613) is subject to reporting under this section for...

  20. 40 CFR 721.10101 - Copolymer of alkyl acrylate and ethyleneglycol dimethacrylate (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Copolymer of alkyl acrylate and... Significant New Uses for Specific Chemical Substances § 721.10101 Copolymer of alkyl acrylate and...) The chemical substance identified generically as copolymer of alkyl acrylate and...

  1. 40 CFR 721.10143 - Amines, bis (C11-14-branched and linear alkyl).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... linear alkyl). 721.10143 Section 721.10143 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10143 Amines, bis (C11-14-branched and linear alkyl). (a) Chemical..., bis (C11-14-branched and linear alkyl) (PMN P-06-733; CAS No. 900169-60-0) is subject to...

  2. 40 CFR 721.5985 - Fatty alkyl phosphate, alkali metal salt (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 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...

  3. 40 CFR 721.10143 - Amines, bis (C11-14-branched and linear alkyl).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... linear alkyl). 721.10143 Section 721.10143 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10143 Amines, bis (C11-14-branched and linear alkyl). (a) Chemical..., bis (C11-14-branched and linear alkyl) (PMN P-06-733; CAS No. 900169-60-0) is subject to...

  4. 40 CFR 721.10143 - Amines, bis (C11-14-branched and linear alkyl).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... linear alkyl). 721.10143 Section 721.10143 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10143 Amines, bis (C11-14-branched and linear alkyl). (a) Chemical..., bis (C11-14-branched and linear alkyl) (PMN P-06-733; CAS No. 900169-60-0) is subject to...

  5. 40 CFR 721.10479 - Quaternary ammonium compounds, tris(hydrogenated tallow alkyl)methyl, chlorides.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...(hydrogenated tallow alkyl)methyl, chlorides. 721.10479 Section 721.10479 Protection of Environment..., tris(hydrogenated tallow alkyl)methyl, chlorides. (a) Chemical substance and significant new uses...(hydrogenated tallow alkyl)methyl, chlorides (PMN P-04-335; CAS No. 308074-73-9) is subject to reporting...

  6. 40 CFR 721.10200 - Benzenacetonitrile, cyclohexylidene-alkyl substituted (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-alkyl substituted (generic). 721.10200 Section 721.10200 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.10200 Benzenacetonitrile, cyclohexylidene-alkyl... substance identified generically as benzenacetonitrile, cyclohexylidene-alkyl substituted (PMN P-09-75)...

  7. 40 CFR 721.4100 - Tris(disubstituted alkyl) het-er-o-cy-cle.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Tris(disubstituted alkyl) het-er-o-cy... Specific Chemical Substances § 721.4100 Tris(disubstituted alkyl) het-er-o-cy-cle. (a) Chemical substance... tris(disubstituted alkyl) heterocycle (P-90-142) is subject to reporting under this section for...

  8. 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...

  9. 40 CFR 721.10200 - Benzenacetonitrile, cyclohexylidene-alkyl substituted (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-alkyl substituted (generic). 721.10200 Section 721.10200 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.10200 Benzenacetonitrile, cyclohexylidene-alkyl... substance identified generically as benzenacetonitrile, cyclohexylidene-alkyl substituted (PMN P-09-75)...

  10. 40 CFR 721.10350 - Amines, C11-14-branched and linear alkyl.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... alkyl. 721.10350 Section 721.10350 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.10350 Amines, C11-14-branched and linear alkyl. (a) Chemical substance...-branched and linear alkyl (PMN P-06-742; CAS No. 863766-30-7) is subject to reporting under this...

  11. 40 CFR 721.10361 - Anthraquinonedicarboximide, diamino-N-alkyl- (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-alkyl- (generic). 721.10361 Section 721.10361 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10361 Anthraquinonedicarboximide, diamino-N-alkyl- (generic). (a... generically as anthraquinonedicarboximide, diamino-N-alkyl- (PMN P-10-15) is subject to reporting under...

  12. 40 CFR 721.6475 - Alkyl polycarboxylic acids, esters with ethoxylated fatty alcohols.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl polycarboxylic acids, esters... Significant New Uses for Specific Chemical Substances § 721.6475 Alkyl polycarboxylic acids, esters with... chemical substances identified generically as alkyl polycarboxylic acids, esters with ethoxylated...

  13. 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...

  14. 40 CFR 721.10417 - Biphenyl alkyl morpholino ketone (generic) (P-11-338).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Biphenyl alkyl morpholino ketone... Specific Chemical Substances § 721.10417 Biphenyl alkyl morpholino ketone (generic) (P-11-338). (a... generically as biphenyl alkyl morpholino ketone (PMN P-11-338) is subject to reporting under this section...

  15. 40 CFR 721.10101 - Copolymer of alkyl acrylate and ethyleneglycol dimethacrylate (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Copolymer of alkyl acrylate and... Significant New Uses for Specific Chemical Substances § 721.10101 Copolymer of alkyl acrylate and...) The chemical substance identified generically as copolymer of alkyl acrylate and...

  16. 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...

  17. 40 CFR 721.10200 - Benzenacetonitrile, cyclohexylidene-alkyl substituted (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-alkyl substituted (generic). 721.10200 Section 721.10200 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.10200 Benzenacetonitrile, cyclohexylidene-alkyl... substance identified generically as benzenacetonitrile, cyclohexylidene-alkyl substituted (PMN P-09-75)...

  18. 40 CFR 721.644 - Amines, C12-14-tert-alkyl, sulfonates.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 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...

  19. 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...

  20. 40 CFR 721.10342 - Quaternary ammonium compounds, fatty alkyl dialkyl hydroxide (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... alkyl dialkyl hydroxide (generic). 721.10342 Section 721.10342 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.10342 Quaternary ammonium compounds, fatty alkyl... chemical substance identified generically as quaternary ammonium compounds, fatty alkyl dialkyl...

  1. 40 CFR 721.5860 - Methylphenol, bis(sub-sti-tuted)alkyl.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Methylphenol, bis(sub-sti-tuted)alkyl... Substances § 721.5860 Methylphenol, bis(sub-sti-tuted)alkyl. (a) Chemical substance and significant new uses...-ed)alkyl (P-84-417) is subject to reporting under this section for the significant new uses...

  2. 40 CFR 721.10101 - Copolymer of alkyl acrylate and ethyleneglycol dimethacrylate (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Copolymer of alkyl acrylate and... Significant New Uses for Specific Chemical Substances § 721.10101 Copolymer of alkyl acrylate and...) The chemical substance identified generically as copolymer of alkyl acrylate and...

  3. 40 CFR 721.3845 - Alkyl substituted aromatic glycidyl ether (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkyl substituted aromatic glycidyl... Specific Chemical Substances § 721.3845 Alkyl substituted aromatic glycidyl ether (generic). (a) Chemical... as alkyl substituted aromatic glycidyl ether (PMN P-97-661) is subject to reporting under...

  4. 40 CFR 721.10397 - Alkyl acrylate-polyfluoro methacrylate-poly(oxyalkylenediyl)-methacrylates (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl acrylate-polyfluoro methacrylate... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10397 Alkyl acrylate-polyfluoro... subject to reporting. (1) The chemical substances identified generically as alkyl...

  5. 40 CFR 721.3900 - Alkyl polyethylene glycol phosphate, potassium salt.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkyl polyethylene glycol phosphate... Specific Chemical Substances § 721.3900 Alkyl polyethylene glycol phosphate, potassium salt. (a) Chemical... as alkyl polyethylene glycol phosphate, potassium salt (P-90-481), is subject to reporting under...

  6. 40 CFR 721.10200 - Benzenacetonitrile, cyclohexylidene-alkyl substituted (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-alkyl substituted (generic). 721.10200 Section 721.10200 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.10200 Benzenacetonitrile, cyclohexylidene-alkyl... substance identified generically as benzenacetonitrile, cyclohexylidene-alkyl substituted (PMN P-09-75)...

  7. 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...

  8. 40 CFR 721.10635 - Alkyl maleimide substituted bicyclic olefin (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl maleimide substituted bicyclic... Specific Chemical Substances § 721.10635 Alkyl maleimide substituted bicyclic olefin (generic). (a... generically as alkyl maleimide substituted bicyclic olefin (PMN P-12-480) is subject to reporting under...

  9. 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...

  10. 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...

  11. 40 CFR 721.4100 - Tris(disubstituted alkyl) het-er-o-cy-cle.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Tris(disubstituted alkyl) het-er-o-cy... Specific Chemical Substances § 721.4100 Tris(disubstituted alkyl) het-er-o-cy-cle. (a) Chemical substance... tris(disubstituted alkyl) heterocycle (P-90-142) is subject to reporting under this section for...

  12. 40 CFR 721.5985 - Fatty alkyl phosphate, alkali metal salt (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 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...

  13. 40 CFR 721.6475 - Alkyl polycarboxylic acids, esters with ethoxylated fatty alcohols.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl polycarboxylic acids, esters... Significant New Uses for Specific Chemical Substances § 721.6475 Alkyl polycarboxylic acids, esters with... chemical substances identified generically as alkyl polycarboxylic acids, esters with ethoxylated...

  14. 40 CFR 721.10397 - Alkyl acrylate-polyfluoro methacrylate-poly(oxyalkylenediyl)-methacrylates (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkyl acrylate-polyfluoro methacrylate... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10397 Alkyl acrylate-polyfluoro... subject to reporting. (1) The chemical substances identified generically as alkyl...

  15. 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...

  16. 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...

  17. 40 CFR 721.10486 - Alkyl substituted amino-benzamide (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl substituted amino-benzamide... Specific Chemical Substances § 721.10486 Alkyl substituted amino-benzamide (generic). (a) Chemical... as alkyl substituted amino-benzamide (PMN P-04-591) is subject to reporting under this section...

  18. 40 CFR 721.10352 - Dimethyl terephthalate, polymer with alkyl diol and substituted benzoates (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... alkyl diol and substituted benzoates (generic). 721.10352 Section 721.10352 Protection of Environment... with alkyl diol and substituted benzoates (generic). (a) Chemical substance and significant new uses... with alkyl diol and substituted benzoates (PMN P-08-93) is subject to reporting under this section...

  19. 40 CFR 721.10316 - Dicyclopentadiene polymer with maleic anhydride and alkyl alcohols (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... anhydride and alkyl alcohols (generic). 721.10316 Section 721.10316 Protection of Environment ENVIRONMENTAL... anhydride and alkyl alcohols (generic). (a) Chemical substance and significant new uses subject to reporting... and alkyl alcohols (PMN P-02-872) is subject to reporting under this section for the significant...

  20. 40 CFR 721.2094 - N,N′-di(alkyl heteromonocycle)amino chlorotriazine.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 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...

  1. 40 CFR 721.3900 - Alkyl polyethylene glycol phosphate, potassium salt.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl polyethylene glycol phosphate... Specific Chemical Substances § 721.3900 Alkyl polyethylene glycol phosphate, potassium salt. (a) Chemical... as alkyl polyethylene glycol phosphate, potassium salt (P-90-481), is subject to reporting under...

  2. 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...

  3. 40 CFR 721.10361 - Anthraquinonedicarboximide, diamino-N-alkyl- (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-alkyl- (generic). 721.10361 Section 721.10361 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10361 Anthraquinonedicarboximide, diamino-N-alkyl- (generic). (a... generically as anthraquinonedicarboximide, diamino-N-alkyl- (PMN P-10-15) is subject to reporting under...

  4. 40 CFR 721.5860 - Methylphenol, bis(sub-sti-tuted)alkyl.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Methylphenol, bis(sub-sti-tuted)alkyl... Substances § 721.5860 Methylphenol, bis(sub-sti-tuted)alkyl. (a) Chemical substance and significant new uses...-ed)alkyl (P-84-417) is subject to reporting under this section for the significant new uses...

  5. 40 CFR 721.6475 - Alkyl polycarboxylic acids, esters with ethoxylated fatty alcohols.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkyl polycarboxylic acids, esters... Significant New Uses for Specific Chemical Substances § 721.6475 Alkyl polycarboxylic acids, esters with... chemical substances identified generically as alkyl polycarboxylic acids, esters with ethoxylated...

  6. 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...

  7. 40 CFR 721.10342 - Quaternary ammonium compounds, fatty alkyl dialkyl hydroxide (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... alkyl dialkyl hydroxide (generic). 721.10342 Section 721.10342 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.10342 Quaternary ammonium compounds, fatty alkyl... chemical substance identified generically as quaternary ammonium compounds, fatty alkyl dialkyl...

  8. 40 CFR 721.10417 - Biphenyl alkyl morpholino ketone (generic) (P-11-338).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Biphenyl alkyl morpholino ketone... Specific Chemical Substances § 721.10417 Biphenyl alkyl morpholino ketone (generic) (P-11-338). (a... generically as biphenyl alkyl morpholino ketone (PMN P-11-338) is subject to reporting under this section...

  9. 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...

  10. 40 CFR 721.10359 - Cardanol-based alkyl phosphate (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Cardanol-based alkyl phosphate... Specific Chemical Substances § 721.10359 Cardanol-based alkyl phosphate (generic). (a) Chemical substance... cardanol-based alkyl phosphate (PMN P-09-613) is subject to reporting under this section for...

  11. 40 CFR 721.10350 - Amines, C11-14-branched and linear alkyl.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... alkyl. 721.10350 Section 721.10350 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.10350 Amines, C11-14-branched and linear alkyl. (a) Chemical substance...-branched and linear alkyl (PMN P-06-742; CAS No. 863766-30-7) is subject to reporting under this...

  12. 40 CFR 721.10397 - Alkyl acrylate-polyfluoro methacrylate-poly(oxyalkylenediyl)-methacrylates (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl acrylate-polyfluoro methacrylate... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10397 Alkyl acrylate-polyfluoro... subject to reporting. (1) The chemical substances identified generically as alkyl...

  13. 40 CFR 721.4100 - Tris(disubstituted alkyl) het-er-o-cy-cle.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Tris(disubstituted alkyl) het-er-o-cy... Specific Chemical Substances § 721.4100 Tris(disubstituted alkyl) het-er-o-cy-cle. (a) Chemical substance... tris(disubstituted alkyl) heterocycle (P-90-142) is subject to reporting under this section for...

  14. 40 CFR 721.10479 - Quaternary ammonium compounds, tris(hydrogenated tallow alkyl)methyl, chlorides.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...(hydrogenated tallow alkyl)methyl, chlorides. 721.10479 Section 721.10479 Protection of Environment..., tris(hydrogenated tallow alkyl)methyl, chlorides. (a) Chemical substance and significant new uses...(hydrogenated tallow alkyl)methyl, chlorides (PMN P-04-335; CAS No. 308074-73-9) is subject to reporting...

  15. 40 CFR 721.3900 - Alkyl polyethylene glycol phosphate, potassium salt.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl polyethylene glycol phosphate... Specific Chemical Substances § 721.3900 Alkyl polyethylene glycol phosphate, potassium salt. (a) Chemical... as alkyl polyethylene glycol phosphate, potassium salt (P-90-481), is subject to reporting under...

  16. 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...

  17. Students' Understanding of Alkyl Halide Reactions in Undergraduate Organic Chemistry

    ERIC Educational Resources Information Center

    Cruz-Ramirez de Arellano, Daniel

    2013-01-01

    Organic chemistry is an essential subject for many undergraduate students completing degrees in science, engineering, and pre-professional programs. However, students often struggle with the concepts and skills required to successfully solve organic chemistry exercises. Since alkyl halides are traditionally the first functional group that is…

  18. Nickel-Catalyzed Reductive Amidation of Unactivated Alkyl Bromides.

    PubMed

    Serrano, Eloisa; Martin, Ruben

    2016-09-01

    A user-friendly, nickel-catalyzed reductive amidation of unactivated primary, secondary, and tertiary alkyl bromides with isocyanates is described. This catalytic strategy offers an efficient synthesis of a wide range of aliphatic amides under mild conditions and with an excellent chemoselectivity profile while avoiding the use of stoichiometric and sensitive organometallic reagents. PMID:27357076

  19. Leukemia after therapy with alkylating agents for childhood cancer

    SciTech Connect

    Tucker, M.A.; Meadows, A.T.; Boice, J.D. Jr.; Stovall, M.; Oberlin, O.; Stone, B.J.; Birch, J.; Voute, P.A.; Hoover, R.N.; Fraumeni, J.F. Jr.

    1987-03-01

    The risk of leukemia was evaluated in 9,170 2-or-more-year survivors of childhood cancer in the 13 institutions of the Late Effects Study Group. Secondary leukemia occurred in 22 nonreferred individuals compared to 1.52 expected, based on general population rates (relative risk (RR) = 14; 95% confidence interval (CI), 9-22). The influence of therapy for the first cancer on subsequent leukemia risk was determined by a case-control study conducted on 25 cases and 90 matched controls. Treatment with alkylating agents was associated with a significantly elevated risk of leukemia (RR = 4.8; 95% CI, 1.2-18.9). A strong dose-response relationship was also observed between leukemia risk and total dose of alkylating agents, estimated by an alkylator score. The RR of leukemia reached 23 in the highest dose category. Radiation therapy, however, did not increase risk. Although doxorubicin was also identified as a possible risk factor, the excess risk of leukemia following treatment for childhood cancer appears almost entirely due to alkylating agents.

  20. A Green Alternative to Aluminum Chloride Alkylation of Xylene

    ERIC Educational Resources Information Center

    Sereda, Grigoriy A.; Rajpara, Vikul B.

    2007-01-01

    An acutely less toxic 2-bromobutane is used to develop a simple graphite-promoted procedure of alkylation of p-xylene. It is further demonstrated that aluminum chloride is not required, the need for aqueous workup is eliminated, waste solutions are not produced and the multiple use of the catalyst is allowed.