GB585581A - Improvements in or relating to the manufacture of cysteine derivatives - Google Patents

Abstract

Cysteine derivatives, of possible interest for a synthesis of penicillin and of penicillin-like substances, are obtained by condensation, in the presence of an anhydrous hydrogen halide, of an oxazolone having the general formula <FORM:0585581/IV/1> wherein R1 represents hydrogen or an alkyl or aralkyl group, R2 represents an alkyl or aralkyl group and R3 represents an alkyl, aralkyl or aryl group, with an acid-stable mercapto compound of the type R.SH, wherein R represents an alkyl or aralkyl radical, and effecting fission of the oxazolone ring by adding at least one molecular equivalent of water. When reaction is effected in a strictly anhydrous solvent medium, e.g. glacial acetic acid containing a small quantity of acetic anhydride, the products isolated may be thiol derivatives of the corresponding oxazolone, but addition of at least one molecular equivalent of water results in fission of the oxazolone ring to yield products conforming to the general formula <FORM:0585581/IV/2> wherein R is an alkyl or aralkyl group, R1 and R2 have the significance above defined and R4 represents an acyl group, acid hydrolysis of which produces amino derivatives of general formula <FORM:0585581/IV/3> wherein R, R1 and R2 have the significance above-defined. Fission of the oxazolone ring and acid hydrolysis may be affected concomitantly by adding, e.g. dilute hydrohloric acid to the reaction mixture and heating to convert the -NHR4 group into the -NH2 group, and in some cases mere addition of water and thereafter heating may suffice. In examples: (1) 2-phenyl-4-isopropylidene oxazolone in glacial acetic acid containing acetic anhydride is treated with benzyl mercaptan and the mixture is cooled to 10 DEG C., prior to saturation with dry hydrogen chloride, and subsequent standing of the closed reaction vessel at 25 DEG C. to isolate dl-S-benzyl-N-benzoyl-b : b -dimethylcysteine; (2) 2-phenyl-4-isopropylidene oxazolone in glacial acetic acid containing acetic anhydride is treated with benzyl mercaptan and saturated with dry hydrogen chloride as in (1), setting the mixture aside at room temperature and the mixture is then boiled with dilute hydrochloric acid to isolate dl-S-benzyl-b : b -dimethylcysteine.