GB602755A - Improvements in or relating to the manufacture of aryl and alkyl substituted cysteines - Google Patents

Abstract

Aryl and alkyl cysteines of general formula <FORM:0602755/IV(b)/1> (R1=aryl or alkyl; R2=H or alkyl), are obtained by heating under pressure with an aqueous mineral acid, a 5-substituted-thiazolidone- or 5-substituted-thiothiazolidone-4-carboxylic acid of general formula <FORM:0602755/IV(b)/2> (X=oxygen or sulphur). The 5-substituted-thiazolidone-4-carboxylic acids are obtained by boiling with aqueous alkali a 4-substituted-2-substituted mercaptothiazolone of general formula <FORM:0602755/IV(b)/3> (R3=an aliphatic hydrocarbon group, preferably methyl, ethyl or propyl). The 5-substituted thiothiazolidone-4-carboxylic acids are obtained by standing a 4-substituted-2-substituted mercaptothiazolone of the foregoing general formula with a methanol solution of a tertiary amine of molecular weight not substantially exceeding 150, saturating with hydrogen sulphide and hydrolysing the resultant thiolcarboxy thiothiazolidone by warming with a dilute mineral acid. In examples: (1) 2-ethylmercapto - 4 - benzylidene - 5 - thiazolone is boiled with sodium hydroxide and ethanol to obtain 5-phenylthiazolidone-4-carboxylic acid; (2) 5 - phenylthiazolidone - 4 - carboxylic acid is heated with hydrochloric acid and the resulting hydrochloride is treated with pyridine to liberate b -phenylcysteine; (3) 2-ethylmercapto-4-benzylidene-5-thiazolone, in methanolic tri-ethylamine, is saturated with hydrogen sulphide and neutralized to obtain 5-phenyl-4-thiolcarboxy-2-thiothiazolidone, which is hydrolysed to 5-phenyl-4-carboxy-2-thiothiazolidone; (4) 2-ethylmercapto-4-isopropylidene-5-thiazolone is treated as in (3) to obtain 5 : 5-dimethyl-4 - thiolcarboxy - 2 - thiothiazolidone, which is hydrolysed to 5 : 5-dimethyl-4-carboxy-2-thiothiazolidone; (5) the final product of (3) is treated as in (2) to obtain b -phenylcysteine; (6) the final product of (4) is treated as in (2) to obtain b : b - dimethylcysteine hydrochloride (penicillamine hydrochloride), purified via isopropylidenepenicillamine hydrochloride which is treated by (i) warming with aqueous hydrochloric acid, (ii) warming with aqueous mercuric chloride and decomposing by hydrogen sulphide, or (iii) adding pyridine to its aqueous solution to obtain b : b -dimethylcysteine. Specifications 584,813 and 585,439 are referred to. 2 - Ethylmercapto - 4 - benzylidene - thiazolone is obtained by heating together N-dithiocarbethoxyglycine, benzaldehyde and acetic anhydride. 2-Ethylmercapto-4-isopropylidenethiazolone is obtained by heating together N-dithiocarbethoxyglycine, acetone, acetic anhydride and anhydrous sodium acetate.