GB638513A - Process of preparing penicillamine and its derivatives - Google Patents

Abstract

N : S-Diacyl-dl-penicillamines of the formula <FORM:0638513/IV (b)/1> where R is an alkyl group are prepared by heating the corresponding a -acylamido-b : b -dimethylacrylic acid with an alkane thiolic acid preferably using an excess of the thiolic acid and conducting the reaction at a temperature of 85 DEG C. or above. The reaction time at 90 DEG C. is about sixteen hours. Hydrolysis of the product preferably by mineral acid or by alkaline solution gives penicillamine or its salts. Purification of the penicillamine salts is effected by neutralizing to a pH of about 6, filtering and adding the filtrate to an aqueous solution of a mercuric salt, e.g. mercuric chloride, bromide or acetate to precipitate an insoluble addition compound which is suspended in water and treated with hydrogen sulphide to precipitate mercuric sulphide and leave the corresponding salt, e.g. the chloride, bromide or acetate of penicillamine in solution. This salt is isolated by evaporation under reduced pressure and is converted into penicillamine by treatment with an alkali such as pyridine piperidine or guinoline. In an example, a -acetamido-b : b -dimethylacrylic acid is heated with thioacetic acid, the resultant a -acetamido-b -acet-thioisovaleric acid is hydrolysed by heating with a mixture of hydrochloric acid and acetic acid to give on evaporating to dryness dl-penicillamine hydrochloride, this is neutralized and reacted with mercuric chloride to precipitate the mercuric addition compound, treatment with hydrogen sulphide liberates penicillamine hydrochloride which is converted to the free base by reaction with pyridine and recrystallized from ethyl alcohol to give dl-penicillamine. Specification 16225/45 (as open to inspection under Sect. 91) is referred to.