GB854339A - Penicillamine production process - Google Patents

Abstract

<FORM:0854339/IV(b)/1> Penicillamine hydrohalide is prepared by hydrolysing pencillin under alkaline conditions, decarboxylating the resulting penicilloic acid to form penilloic acid, e.g. by heating to a temperature in the range of about 75 DEG to 95 DEG C. under reduced pressure, reacting the latter acid with a mercuric halide such as meruric chloride or a mercuric salts in the presence of halide ions, separating the resulting pencillamine/mercuric halide complex, decomposing the complex with hydrogen sulphide to form penicillamine hydrohalide, reacting this hydrohalide, preferably in a dry condition, with acetone, preferably substantially dry acetone, to form isopropylidene penicillamine hydrohalide complex, and decomposing said complex. In the above process it is preferably to separate the pencilloic acid before the decarboxylation step, e.g. by extraction into an organic solvent and crystallisation from the solvent such as n-butanol, to hydrolize the penicillin in aqueous sodium hydroxide solution at a pH value in the range of about 10 to 12, to react the acetone and penicillamine hydrohalide at a temperature in the range of 0 DEG to 56,5 DEG C., and to decompose the complex by heating in hydrochloric acid solution at a concentration in the range of about 1 to 3 normal under an inert atmosphere. The concentration of pencillin is preferably in the range of about 2% to 10% weight for volume (c. g. s units) for the initial step. The reaction with the mercuric halide or a mercuric salt is preferably carried out in the presence of sufficient sodium hydroxide to convert substantially the whole of the penilloic acid into a salt. It is preferable to react the pencillamine halide with acetone in the proportion of about 1 part by weight of the amine to about 2 to 3 parts by weight of acetone. A preferred method of carrying out the process is shown in the drawing. A detailed example is given.