3222-05-7Relevant articles and documents
Hexabromoacetone as tribromoacetylating agent of alcohols and amines and as mediator in the conversion of carboxylic acids into amides in the presence of triphenylphosphine
Menezes, Fabrício G.,Kolling, Rosane,Bortoluzzi, Adaílton J.,Gallardo, Hugo,Zucco, César
body text, p. 2559 - 2561 (2009/08/09)
Hexabromoacetone has been used as an alternative tribromoacetylating agent of primary alcohols and amines and as mediator in the conversion of carboxylic acids into amides in the presence of triphenylphosphine. The reactions have been performed under mild conditions with moderate to good yields. All the products have been adequately characterized by their physical and spectroscopic properties.
Synthetic approaches to the microtubule-Sabilizing sponge alkaloid ceratamine A and desbromo analogues
Nodwell, Matt,Pereira, Alban,Riffell, Jenna L.,Zimmerman, Carla,Patrick, Brian O.,Roberge, Michel,Andersen, Raymond J.
scheme or table, p. 995 - 1006 (2009/07/18)
Two synthetic approaches to the microtubule-stabilizing ceratamine alkaloids are described. The first approach involved attempts to graft an aminoimidazole moiety onto an azepine ring to form partially hydrogenated versions of the unprecedented aromatic imidazo[4,5-d]azepine core of the ceratamines. This route ultimately failed because it was not possible to aromatize the partially hydrogenated ceratamine intermediates. A second approach started with tribromoimidazole that was sequentially metalated and functionalized to efficiently generate a key imidazole intermediate containing vinyl bromide and amide functionalities. An intramolecular Buchwald vinyl amidation reaction converted this key intermediate into a bicyclic imidazo[4,5-d]azepine that was at the same oxidation state as the aromatic core of the ceratamines. The 2-amino functionality present on the imidazole ring of the ceratamines was installed using a Buchwald/Hartwig amination reaction on a 2-chloroimidazole precursor. Deprotection and aromatization resulted in the first synthesis of desbromoceratamine A (55) and desmethyldesbromoceratamine A (60). An unanticipated addition of atmospheric oxygen was encountered during deprotection of the imidazole ring in the last step of the synthesis leading to C-11 oxygenated ceratamine analogues as byproducts. Evaluation of the synthetic ceratamines in a TG3 cell-based assay for mitotic arrest revealed that the C-14 and C-16 bromine substituents in ceratamine A (1) play a major role in the antimitotic potency of the natural product. The synthetic route to ceratamine analogues has provided sufficient quantities of desbromoceratamine A (55) for testing in mouse models of cancer.
Occurrence, synthesis, and mammalian cell cytotoxicity and genotoxicity of haloacetamides: An emerging class of nitrogenous drinking water disinfection byproducts
Plewa, Michael J.,Muellner, Mark G.,Richardson, Susan D.,Fasano, Francesca,Buettner, Katherine M.,Woo, Yin-Tak,Mckague, A. Bruce,Wagner, Elizabeth D.
, p. 955 - 961 (2008/03/31)
The haloacetamides, a class of emerging nitrogenous drinking water disinfection byproduct (DBPs), were analyzed for their chronic cytotoxicity and for the induction of genomic DNA damage in Chinese hamster ovary cells. The rank order for cytotoxicity of 13 haloacetamides was DIAcAm > IAcAm > BAcAm > TBAcAm > BIAcAm > DBCAcAm > CIAcAm > BDCAcAm > DBAcAm > BCAcAm > CAcAm > DCAcAm > TCAcAm. The rank order of their genotoxicity was TBAcAm > DIAcAm ≈ IAcAm > BAcAm > DBCAcAm > BIAcAm > BDCAcAm > CIAcAm > BCAcAm > DBAcAm > CAcAm > TCAcAm. DCAcAm was not genotoxic. Cytotoxicity and genotoxicity were primarily determined by the leaving tendency of the halogens and followed the order I > Br > > Cl. With the exception of brominated trihaloacetamides, most of the toxicity rank order was consistent with structure-activity relationship expectations. For di- and trihaloacetamides, the presence of at least one good leaving halogen group (I or Br but not Cl) appears to be critical for significant toxic activity. Log P was not a factor for monohaloacetamides but may play a role in the genotoxicity of trihaloacetamides and possible activation of dihaloacetamides by intracellular GSH and -SH compounds. With the advent of the U.S. EPA Stage 2 DBP regulations, water utilities are considering the use of disinfectants that are alternatives to chlorine. The use of these alternative disinfectants will shift the distribution of DBP chemical classes. The emergence of new, highly toxic iodinated, nitrogenous DBPs, as illustrated by the discovery of bromoiodoacetamide as a new DBP, underscores the importance of comparative toxicity studies to assist in the overall goal of safer drinking water practice.
Synthesis of antimitotic analogs of the microtubule stabilizing sponge alkaloid ceratamine A
Nodwell, Matt,Riffell, Jenna L.,Roberge, Michel,Andersen, Raymond J.
body text, p. 1051 - 1054 (2009/04/06)
Antimitotic analogs of the microtubule stabilizing sponge alkaloid ceratamine A (1) have been synthesized starting from tribromoimidazole. A key step In the synthesis Is the formation of the azepine ring via an intramolecular Buchwald coupling between a vinyl bromide and a N-methyl amide. This represents the first synthesis of a fully unsaturated imidazo[4,5,d]azepine. NMR data obtained for the synthetic ceratamine analogs has provided support for the structure assigned to the natural product.
In situ derivatization/solid-phase microextraction for the determination of haloacetic acids in water
Sarrion,Santos,Galceran
, p. 4865 - 4873 (2007/10/03)
An in situ derivatization solid-phase microextraction method has been developed for the determination of haloacetic acids (HAAs) in water. The analytical procedure involves derivatization of HAAs to their methyl esters with dimethyl sulfate, headspace sampling using solid-phase microextraction (SPME), and gas chromatography-ion trap mass spectrometry (GC/ITMS) determination. Parameters affecting both derivatization efficiency and headspace SPME procedure, such as the selection of the SPME coating, derivatization-extraction time and temperature, and ionic strength, were optimized. The commercially available Carboxen-poly(dimethylsiloxane) (CAR-PDMS) fiber appears to be the most suitable for the determination of HAAs. Moreover, the formation of HAA methyl esters was dramatically improved (up to 90-fold) by the addition of tetrabutylammonium hydrogen sulfate (4.7 μmol) to the sample as ion-pairing agent in the derivatization step. The precision of the in situ derivatization/HS-SPME/GC/ITMS method evaluated using an internal standard gave relative standard deviations (RSDs) between 6.3 and 11.4%. The method was linear over 2 orders of magnitude, and detection limits were compound-dependent, but ranged from 10 to 450 ng/L. The method was compared with the EPA method 552.2 for the analysis of HAAs in various water samples, and good agreement was obtained. Consequently, in situ derivatization/HS-SPME/GC/ITMS is proposed for the analysis of HAAs in water.
Carbon-13 NMR Spectra of Bromine-containing Esters
Velichko, F. K.,Dostovalova, V. I.,Vinogradova, L. V.,Freidlina, R Kh.
, p. 442 - 446 (2007/10/02)
13CHBrCOOR fragments of bromine-containing mono- and dicarboxylates show 13C NMR signals in the range 38-45 ppm, at 12-15 ppm to high field of their chloro analogues.The introduction of one bromine atom into the α-CH2 group causes a 6-13 ppm shift of the carbon signal, depending on the type of ester.The replacement of H with Br in 13C2H2(COOR)2 has only a negligible influence on the 13CH2 signal position.The 13CBr2COOR fragment signals appear in the range 40-54 ppm. 13C NMR data, including the chemical shift values, signal multiplicities and spin-spin couplings, make possible the identification of isomers present in isomer mixtures of bromine-containing esters.The 13COOR chemical shifts of diastereomers of α,β-dibromoesters differ noticeably from each other, and the 13C NMR spectra can thus be used to supply preliminary information about the stereochemistry of bromine addition to α,β-unsaturated acids.
