Synthesis of Quinoline–Benzimidazole Hybrids as Potential Antimycobacterial Agents via Sonogashira‐Hydroamination

Abstract

A series of quinoline–benzimidazole derivatives has been synthesized utilizing a Sonogashira coupling followed by hydroamination cyclization. These derivatives were rigorously evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H 37 Rv. The reaction effectively facilitates the formation of a C(sp 2 )─C(sp) bond and the construction of a five‐membered ring connecting the quinoline and benzimidazole moieties via hydroamination. The optimization of reaction conditions included the systematic examination of various catalysts, ligands, bases, solvents, and temperatures. Under the optimized conditions, the final products were obtained with yields of up to 86%, showcasing a broad substrate scope and a commendable tolerance for diverse functional groups. This methodology presents an efficient model for both Sonogashira coupling and hydroamination cyclization under mild conditions. It provides several noteworthy advantages, such as excellent atom economy and cost‐effectiveness, attributed to the use of an economically viable CuI/L‐proline catalytic system. Furthermore, this approach aligns with green chemistry principles, emphasizing step economy, high efficiency, and minimized waste generation. Consequently, it enables the efficient synthesis of quinoline‐benzimidazole hybrid frameworks that are of significant medicinal interest.