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

• Published in: Journal of organic chemistry Vol. 73; no. 19; pp. 7841 - 7844
• Main Authors: Yang, Daoshan, Fu, Hua, Hu, Liming, Jiang, Yuyang, Zhao, Yufen
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 03-10-2008
• Subjects: Acetanilides - chemistry; Amidines - chemistry; Benzimidazoles - chemical synthesis; Catalysis; Catalysts: preparations and properties; Chemistry; Copper - chemistry; Cyclization; Exact sciences and technology; General and physical chemistry; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Hydrolysis; Organic chemistry; Preparations and properties; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry; Cesium carbonate; Intramolecular reaction; Catalytic reaction; Acetanilide; Nitrogen heterocycle; Ligand; Organic halogen compounds; Hydrolysis; Ammonia; Amidine; Methyl sulfoxide; Cyclization; Benzimidazole derivatives; Carboxamide; Copper I Bromides; Chemical synthesis; Solvent; Catalyst; Successive reaction
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo8014984

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.