Penicillamines - mfrg using two stage hydrolysis of thiazolidine carbonitrile to form carboxylic acid intermediate

摘要

Process for penicillamines by reacting isobutyraldehyde with S and NH3 to give delta3-thiazoline, converting this to the carbonitrile with HCN, hydrolysing the nitrile to the carboxylic acid and degrading the acid; the hydrolysis of the nitrile is effected in two stages with conc. acid, one at a low temp. to give the carbonamide, the other at a higher temp. to hydrolyse the amide. The yield of carboxylic acid is increased. Specif. hydrolysis with Conc. HCl alone is effected at 0-20 degrees C or with a solvent e.g. MeOH at 50 degrees C. The second hydrolysis is effected at 105 degrees C.