Conversion of Thiols into Disulfides with Diethyl Bromomalonate

Abstract

Reactions of aliphatic, aromatic and heterocyclic thiols (2 and 5a-h) with diethyl bromomalonate (1a) gave the corresponding symmetrical disulfides (3 and 6a-h) in high yields. In the case of L-cysteine (5i), glutathione (5j) or thiamine (5k), the reaction also gave L-cystine (6i), oxidized glutathione (6j) or thiamine disulfide (6k) in high yields regardless of the presence of other functional groups. Dithiols (11) were converted into cyclic disulfides (12) by this method. In particular, N-(2-mercapto-2-methylpropionyl)-L-cysteine (9) was converted into (4R)-tetrahydro-7, 7-dimethyl-6-oxo-3H-1, 2, 5-dithiazepine-4-carboxylic acid (10)(obtained in poor yields by general oxidation methods) in good yield. The intermediate in the reaction was considered to be sulfenyl bromide (8).