FACILE PREPARATION OF SUBSTITUTED BENZIMIDAZOLE-2-CARBOXYLATES

摘要

Mild conditions for the preparation of benzimidazole-2-carboxylates have been developed.Condensation of a substituted 1,2-phenylenediamine with methyl trichloroacetamidate in the presence of TFA rapidly affords the 2-trichloromethylbenzimidazole;hydrolysis provides the desired product.The benzimidazole-2-carboxamide moiety is a regular structural motif that appears in compounds possessing activity against a variety of important biological targets.Most commonly,the carboxamides are prepared from the corresponding benzimidazole-2-carboxylates.As indicated in Scheme 1,two main routes have been described for preparation of these acids;i)condensation of the requisite 1,2-phenylenediamine(1)with glycolic acid,followed by KMnO_4 oxidation;ii)condensation of 1 with methyl trichloroacetimidate in neat acetic acid,followed by NaOH hydrolysis to give 4.