Green synthetic approaches to benzimidazole derivatives

The procedures for the synthesis of benzimidazoles have become a focus in synthetic organic chemistry, as they are building blocks of strong interest for the development of compounds with pharmacological activity. Various benzimidazole derivatives exhibit important activities such as antimicrobial, antiviral, anticancer, anti-inflammatory and analgesic.1 Some of the already synthesized compounds from the above mentioned field have found very strong application in medicine praxis.2 Most of the procedures for the synthesis of benzimidazole derivatives involve the condensation of o-phenylenediamine with aldehydes.3,4 However, the reaction is not always selective, affording both 2-substituted (a) and 1,2-di- substituted benzimidazoles (b). We report a simple and sustainable method for the synthesis in green medium of 1,2-di- substituted or 2-substituted benzimidazoles, starting from o-phenylenediamine in the presence of different aldehydes. The use of an ionic liquid (IL) or a deep eutectic solvent (DES) enables to prepare selectively 1,2-disubstituted benzimidazoles or 2-substituted benzimidazoles in high yields and short reaction times (Figure 1).