Copper‐Catalyzed One‐Pot, Three‐Component Synthesis of Imidazo[1,2‐c]quinazolines and Benzimidazo[1,2‐c]quinazolines

Abstract

A highly efficient copper‐catalyzed three component, one‐pot reaction has been described for the synthesis of imidazo[1,2‐c]quinazolines and benzimidozo[1,2‐c]quinazolines from 2‐(2‐bromophenyl)‐1H‐imidazoles/benzimidazoles using benzyl alcohol or benzylamine as benzaldehyde surrogate and sodium azide as nitrogen source. Various functional groups were well tolerated and desired products were obtained in moderate to good yields. The reaction involves copper‐catalyzed sequential azidation of 2‐(2‐bromophenyl)‐1H‐imidazoles/benzimidazoles through SNAr reaction and reductive amination followed by oxidative condensation with benzyl alcohols or benzylamines. The significant practical advantages of the protocol are utilization of the readily accessible simple substrates, broad substrate scope, and ligand‐free reaction conditions.

An Extensive Analysis of Current Synthetic Methodologies and Applications of Imidazo/Benzimidazo[1,2‐c]Quinazolines

“…[44] In 2021, Kumar and associates reported an extremely effective micelle mediated copper catalyzed three-component, one-pot procedure for the synthesis of imidazo[1,2c]quinazolines and benzimidazo[1,2-c]quinazolines by combining 2-(2-bromophenyl)-1H-imidazoles/benzimidazoles with benzyl alcohol or benzylamine as a benzaldehyde surrogate and NaN 3 as a nitrogen source (Scheme 32). [45] Several substrates consisting of both electron-donating and electron-withdrawing functional groups reacted, and desirable products were isolated in moderate to excellent yields (54-80 %).…”

Recent Advances in Metal-Catalyzed Approaches for the Synthesis of Quinazoline Derivatives

“…Molecules 2024, 29, x FOR PEER REVIEW benzaldehyde surrogate and sodium azide as a nitrogen source by using green (PEG 400) (Scheme 49b) [106]. In 2015, Fan and colleagues described copper-catalyzed one-pot cascade reac 2-(2-bromo-aryl)-1H indoles (55), aldehydes (18), and aqueous ammonia (41) for thesis of indolo[1,2-c]quinazoline using K2CO3 as a base and L-proline as a li DMSO under a nitrogen atmosphere (Scheme 50) [107].…”

“…The developed also worked well at the gram scale with a 71% yield. Moreover, authors also accom Recently, Nandwana et al described a one-pot three-component strategy for the synthesis of imidazo[1,2-c]quinazolines and benzimidozo[1,2-c]quinazolines from 2-(2-bromophenyl) -1Himid-azoles/benzimidazoles from benzyl alcohol or benzylamine as a benzaldehyde surrogate and sodium azide as a nitrogen source by using green solvent (PEG 400) (Scheme 49b) [106].…”