Microwave Promoted Simple, Efficient and Regioselective Synthesis of Trisubstituted Imidazo[1,2-a]benzimidazoles on Soluble Support

Abstract

An efficient microwave-assisted and soluble polymer-supported synthesis of medicinally important imidazole-fused benzimidazoles has been developed. The protocol involves the rapid condensation of polymer-bound amino benzimidazoles with various α-bromoketones and subsequent in situ intramolecular cyclization under microwave irradiation resulting in a one pot synthesis of imidazole interlacing benzimidazole polymer conjugates. The condensed product was obtained with excellent regioselectivity. The biologically interesting imidazo[1,2-a]benzimidazoles was released from polymer support at ambient temperature. Diversity in the triheterocyclic nucleus was achieved by the different substitutions at its 2, 3, and 9 positions. The new protocol has the advantages of short reaction time, easy workup process, excellent yields, reduced environmental impact, wide substrate scope and convenient procedure.

One-Pot, Two-Step Synthesis of Imidazo[1,2-a]benzimidazoles via A Multicomponent [4 + 1] Cycloaddition Reaction

“…Our exploration starts with the synthesis of various N -alkyl-2-aminobenzimidazoles To obtain various N -alkyl-2-aminobenzimidazoles, we reacted methyl 4-fluoro-3-nitrobenzoate with various alkyl amines followed by reduction to the intermediate diamine 1 { 1 }. Reaction with cyanogen bromide afforded the 2-aminobenzimidazole 2 { 1 } in good yields (Scheme ). , …”

“…We have earlier reported a soluble polymer-supported regioselective synthesis of imidazo[1,2-a]benzimidazoles. 11 A similar protocol was used by Han and co-workers for the synthesis and SAR studies of imidazo[1,2-a]benzimidazoles as corticotrophin-releasing factor 1 receptor antagonists. 3 Langer et al synthesized 2-aminoimidazo[1,2-a]imidazoles by [3 + 2] cycloaddition of dilithiated 2-methylbenzimidazole and oxaldiimidoyl dichlorides.…”

“…We have earlier reported a soluble polymer-supported regioselective synthesis of imidazo[1,2- a ]benzimidazoles . A similar protocol was used by Han and co-workers for the synthesis and SAR studies of imidazo[1,2- a ]benzimidazoles as corticotrophin-releasing factor 1 receptor antagonists .…”

Polycyclic Benzimidazole: Synthesis and Photophysical Properties

“…Benzimidazole 79 could be released from the polymer support inside the biological cells at room temperature. The feasibility of this newly developed methodology could be explained by easy workup process with excellent yield and short reaction time …”

“…The feasibility of this newly developed methodology could be explained by easy workup process with excellent yield and short reaction time. [28] Song and co-workers recently prepared polycyclic benzimidazole 87 via successive nucleophilic additions of benzimidazole 83 derivatives to arynes 84 (Scheme 18). Electron donating and electron withdrawing groups are well tolerated in this methodology in good to excellent yields.…”