Facile Protocol for the Synthesis of Electron-Rich Benzimidazole Derivatives

Abstract

A protocol is reported which allows preparation of electron-rich benzimidazole derivatives in good yield. The reaction proceeds directly from dinitrobenzene derivatives without need of isolation of air-sensitive diamines.Benzimidazole-4,7-diones (3) are compounds of interest due to their potential use as anticancer and antifungal agents. [1][2][3][4][5][6][7][8] They are typically prepared by oxidation of the corresponding 4,7-dimethoxybenzimidazoles (2), which in turn are prepared from 3,6-dimethoxybenzene-1,2-diamine (1) (Scheme 1). Both aldehydes 1,2,7,8 and carboxylic acids 7,9,10 have been used for this reaction, with the former requiring oxidation of one of the intermediates, which is often accomplished simply by exposure to air. Scheme 1. Synthesis of benzimidazole-4,7-dionesAs part of another project, we were interested in preparing benzimidazole derivatives 2 by a simple and convenient method. Previous reports describing the synthesis of 3,6-dimethoxybenzene-1,2-diamine 1 have noted its significant air sensitivity, 9,10 which makes working with the compound somewhat