103499-59-8Relevant academic research and scientific papers
Synthesis and reaction of 2-mercapto-3-arylpropanoic acids
Pokhodylo, Nazariy T.,Matiychuk, Vasyl S.,Obushak, Mykola D.
experimental part, p. 850 - 858 (2012/08/07)
Two synthetic pathways for the preparation of 2-mercapto-3-arylpropanoic acids were developed. First, by the reaction of arenediazonium bromides with acrylic esters in the presence of CuBr, alkyl (2-bromo-3-aryl)propanoates were formed. Their cyclization with thiourea produced 5-(R-benzyl)-2-imino-4- thiazolidinones, which yielded 3-aryl-2-mercaptopropanoic acids by alkaline hydrolysis. Second, direct Meerwein arylation of acrylates in the presence of S-nucleophile (NaSH) allowed isolation of 3-phenyl-2-mercaptopropanoic acid in 8% yield. Such acids were used for cyclization with cyanoguanidine and phenyl isothiocyanate yielding 1-[5-(R-benzyl)-4-oxo-1,3-thiazolidin-2-ylidene] guanidines and new 5-(R-benzyl)-3-phenyl-2-thioxo-1,3-thiazolidin-4-one (rhodanine) derivatives correspondingly. Copyright Taylor and Francis Group, LLC 2012.
Reactions of α-mercaptocarboxylic acid hydrazides with triethyl orthoesters: Synthesis of 1,3,4-thiadiazin-5(6H)-ones and 1,3,4-oxadiazoles
Kudelko, Agnieszka
, p. 3616 - 3625 (2012/06/18)
Reactions of α-mercapto-β-phenylpropionic and α-mercaptophenylacetic acid hydrazides with triethyl orthoesters were conducted under N2 in glacial acetic acid and resulted in the formation of two groups of products, derivatives of 1,3,4-thiadiazin-5(6H)-ones and 2-(1-mercaptomethyl)-1,3,4-oxadiazoles. When conducting the same transformations on α-mercaptophenylacetic acid hydrazide in the presence of air, two different products from the 1,3,4-oxadiazole family, the appropriate bis(1,3,4-oxadiazol-2-yl-phenylmethyl) disulfides and 2-benzyl-1,3,4- oxadiazoles, were formed with the liberation of free sulfur. The oxygenated bis(1,3,4-oxadiazol-2-yl-phenylmethyl) disulfides were reduced to the corresponding 2-(1-mercaptomethyl)-1,3,4-oxadiazoles with the use of zinc powder under mild conditions.
Synthesis of (Racemization Prone) Optically Active Thiols by SN2 Substitution Using Cesium Thiocarboxylates
Strijtveen, Bert,Kellogg, Richard M.
, p. 3664 - 3671 (2007/10/02)
The cesium salt of thioacetic acid is prepared by treatment with cesium carbonate.This salt has a solubility of about 0.7 M in DMF (even higher in Me2SO) at 50 deg C.The mesylates of (R)-2-octanol, the ethyl ester and N,N-dimethyl amide of (R)-mandelic acid, (S)-ethyl lactate, (S)-methyl 3-phenyllactate, and (S)-diethyl malate underwent clean SN2 substitution in DMF solution.Racemization occured only in the case of the mesylate of ethyl mandelate when allowed to react in DMF, but complete inversion was achieved on use of absolute ethanol as solvent.Hydrolysis or aminolysis is used to deacylate the thiols (except for aliphatic thioacetates, which are deprotected by treatment with lithium aluminum hydride) to afford 2-mercapto esters or amides.Owing to the sensitivity of mercapto-bearing carbon, some racemization (0-20percent depending on the system) occurs during deprotection.An alternate route to the same materials prepared by the cesium thiocarboxylate method involves treatment of the free alcohol with thioacetic acid in the presence of twofold amount of the preformed salt from diisopropyl azodicarboxylate (DIAD) and triphenylphosphine.This method works well except for ethyl mandelate and N,N-dimethylmandelamide.Scale-up of the reaction is difficult, however, owing to the need for a chromatographic separation.Various NMR methods for determining the enantiomeric excesses of the various products are described.Particularly useful for determination of the high enantiomeric excesses is an internal calibration method based on the use of 13C satellite peaks in the presence of a chiral shift reagent.The enantiomeric excesses of the thiols were determined by conversion to the phosphonodithioates followed by measurement of the meso/d,l ratios obtained from 31P NMR spectra.Attempts to hydrolyze 2-acetylthio esters to the free 2-mercapto carboxylic acids lead to 10-40percent racemization depending on the compound.A partial solution to this problem was found by use of optically pure S bromides obtained from diazotation of (S)-alanine, (S)-phenylalanine, and (S)-valine in the presence of bromide.These bromides, on treatment with cesium thiobenzoate, underwent clean SN2 substitution, and debenzoylation could be brought about without significant racemization
