A concise synthesis of 2-(2-aminothiophene)-benzimidazoles by one-pot multicomponent reaction

Abstract

A concise synthesis of 2-(2-aminothiophene)benzimidazoles by one-pot multicomponent reaction3

Rapid Two-Step Synthesis of Benzimidazo[1′,2′:1,5]pyrrolo[2,3-c]isoquinolines by a Three-Component Coupling Reaction

“…The condensation of primary amine of 1 with cyanoacetic acid gave a cyanoacetamide 2 that was cyclized under acidic conditions with TFA to obtain the desired 2-cyanomethyl benzimidazoles 3 in good yields. 11,12 Initially, we studied a one pot reaction on 2-cyanomethylbenzinmidazole 3{1}, methyl 2-formyl benzoate, and cyclohexylisonitrile. Heating a dichloroethane solution of reactants in the presence of piperidine catalyst (30 mol %) at 180 °C for 12 h in a sealed tube yielded the desired pentacyclic benzimidazoisoquinolinone 6{1, 1,1} in low yield (25%) along with pyrrolobenzimidazole (35%, PBI) 7 (Scheme 2).…”

“…Treatment of 3-nitro-4-fluorobenzoates with various amines and reduction of the nitro group yielded corresponding 3,4-diaminobenzoates 1 . The condensation of primary amine of 1 with cyanoacetic acid gave a cyanoacetamide 2 that was cyclized under acidic conditions with TFA to obtain the desired 2-cyanomethyl benzimidazoles 3 in good yields. , …”

“…9 Luotonin A III is a pyrroloquinazolinoquinoline alkaloid to work against leukemia by inducing DNA topoisomerase I-dependent cytotoxicity (Figure 1). 10 Recently, we developed multicomponent reactions utilizing 2-cyanomethylbenzimidazoles for the synthesis of pyrrolo[1,2-a]benzimidazoles 11 and benzimidazole-linked 2-aminothiophenes. 12 In continuation with our efforts to establish facile reactions using functionalized benzimidazoles for the synthesis of biologically interesting polyazaheterocycles, we report a two step protocol for the synthesis of novel benzimidazo[1′,2′:1,5]pyrrolo[2,3-c]isoquinolines (BPIs) that contains a benzimidazole and an isoquinolinone pharmacophore fused through a pyrrole ring.…”

Green methodologies for the synthesis of 2-aminothiophene

“…described the synthesis of 2-(2-aminothiophene)-benzimidazoles ( 31a – t ) using 3-multicomponent reactions involving nitriles 29a – f with aldehydes 30a – f , elemental sulfur S 8 and piperidine in ethanol under reflux for 1.5 h, providing 2-aminothiophenes 31a – t in 69–86% yields after purification by silica gel chromatography (Fig. 18 ) (Chen et al 2013 ).

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Diversity oriented synthesis of benzimidazole-based biheterocyclic molecules by combinatorial approach: a critical review

“…In 2013, Sun et al developed a one-pot multicomponent approach to benzimidazole-linked 2-aminothiophenes under solution-phase chemistry. 32 As revealed in Scheme 21, substituted methyl-3,4-diaminobenzoate 107 underwent condensation reaction with cyanoacetic acid 108 at the primary amine functionality to give cyanoacetamide, which was subsequently cyclised using TFA, to give 2-cyanomethyl benzimidazole 109 in good yields. The intermediate 109, treated with aldehydes 74 containing an active methylene group and sulfur powder, under reuxing condition gave biologically relevant benzimidazole-linked 2-aminothiophene 110 in good yields.…”