Synthesis of 1,2-Bisubstituted Benzimidazole: 1,3-Shift Mechanism Catalyzed by Acid or Base

Benzimidazole ring system is a useful nucleus in medicinal chemistry and is found in many biologically active compounds. An efficient approach for the synthesis of 1,2-bisubstituted benzimidazoles is presented in this article, and the mechanism of the condensation from 2-[(2-aminophenylimino)phenylmethyl]-4-bromophenol, using piperdine or acetic acid as catalyst, is studied. 1,3-Shift of negative hydrogen ion is the key step for this rearrangement reaction, and the influences of catalyst, temperature, substrate, and solvent are also investigated.