Synthesis of 3,4-dimethyl-2-iodobenzoic acid

Objective To synthesize 3,4-dimethyl-2-iodobenzoic acid as the key intermediate for the preparation of vadimezana vascular distrupting agent.Methods Glyoxylic acid was treated with acetic anhydride to give 2,2-diacetoxylacetic acid,followed by chlorination with thionyl chloride to obtain the corresponding acid chloride,which was reacted with 2,3-dimethylaniline to provide N-(2,2-diacetoxyl)acetyl-2,3-dimethylaniline,and then oximated with hydroxylamine hydrochloride to afford N-(2-hydroxyimino)acetyl-2,3-dimethylaniline,which was followed by cyclization with methanesulfonic acid and oxidative ring-opening subsequently to yield 2-amino-3,4-dimethylbenzoic acid,from which the target compound was finally obtained by sandmeyer reaction.Results 3,4-Dimethyl-2-iodobenzoic acid was synthesized through a seven-step procedure in a overall yield of 45.0%,and the structure of the target compound was identified by 1H-NMR and ESI-MS.Conclusions The easy availability of the reactants,facile reaction conditions and convenient operation procedures made the process a promising prospect for application in large-scale manufacture..