An Efficient Multi-Functionalized Synthesis of N-Arylated Indole-3-Substituted-2-Benzimidazoles as Anticancer Agents

Abstract: A convenient, efficient method for synthesising indole-3-substituted-2-benzimidazoles and benzothiazoles was carried out using N-arylation followed by condensation-oxidation protocol. N-arylation of 1H-indole-3-carbaldehyde was carried out via CuI/DMED to yield 1-(3-((tert-butylsulfonyl)methyl)phenyl)-1H-indole-3-carbaldehyde. Condensation using various o-phenylenediamines in the presence of CAN/DMF as oxidant furnished the desired 2-(1-(3-((tert-butylsulfonyl)methyl)phenyl)-1H-indol-3-yl)-1H-benzo[d]imidazole. In addition to simple o-phenylenediamines, 1,2-arylenediamines substituted with withdrawing and donating groups, heterocyclic-2,3-phenylene diamines are well tolerated and give good yields of up to 74% yield. As simple reaction between o-phenylenediamines and 1H-substituted indole-3-carboxyaldehyde give indole-3-substituted-2-benzimidazoles with moderate to good yields. These novel indole-derived benzimidazoles and benzothiazoles have shown their efficacy as anti-cancer agents with various cancer K-562, MDA-MB231, colon-205 cell lines.