Copper-Catalyzed Synthesis of Benzimidazoles via Cascade Reactions of o-Haloacetanilide Derivatives with Amidine Hydrochlorides

We have developed an efficient method for the synthesis of benzimidazoles via cascade reactions of o-haloacetoanilide derivatives with amidine hydrochlorides. The protocol uses 10 mol % CuBr as the catalyst, Cs₂CO₃ as the base, and DMSO as the solvent, and no ligand is required. The procedure proceeds via the sequential coupling of o-haloacetoanilide derivatives with amidines, hydrolysis of the intermediates (amides), and intramolecular cyclization with the loss of NH₃ to give 2-substituted 1H-benzimidazoles.