One‐pot Synthesis of Benzo[4,5]imidazo[1,2‐a]pyridine Derivatives in Aqueous Conditions

Abstract

One‐pot reaction of cyclic 1,3‐diketones, dimethylformamide dimethylacetal (DMFDMA) and 2‐(1H‐benzo[d]imidaz‐2‐yl)acetonitrile was found to be a highly selective process leading to 4‐oxo‐1,2,3,4‐tetrahydrobenzo[4,5]imidazo[1,2‐a]quinolin‐6‐yl cyanides. Optimized reaction conditions using water as solvent at room temperature or under microwave heating allowed high yields of the target products required no additional purification.

Benzo[4,5]imidazo[1,2-a]pyridines and benzo[4,5]imidazo[1,2-a]pyrimidines: recent advancements in synthesis of two diversely important heterocyclic motifs and their derivatives

“…In 2016, Gorobets and co-workers reported a one-pot green synthesis of Benzo[4,5]imidazo[1,2- a ]pyridines ( 74 ) from cyclic 1,3-diketones ( 71 ), DMFDA ( 72 ), and 2-benzoimidazylacetonitrile ( 17 ) in water solvent by microwave irradiation. 63 The reaction was carried out in 2 stages. In stage 1 the enamines ( 73 ) were synthesized by a previously reported methodology.…”

“…Yields were slightly lowered for substrates with aliphatic attachment to alkyne (62g, 75%; 62h, 68%; 62i, 70%). Substrate scope was expanded to a variety of 3-(arylethynyl)benzofuran/benzothieno-2-carbaldehydes (63). These gave Scheme 6 I 2 mediated Synthesis of pyrido[1,2-a]benzimidazoles from cyclohexanones and 2-aminopyridines using O 2 as oxidant.…”

“…[58][59][60][61] or synthesis being performed in the aqueous medium. 62,63 In this review we have discussed the various significant advancements in the synthesis of these motifs and their derivatives which have taken place within the period 2011-2021.…”

TWO-STAGE ONE-POT INTERACTION OF ACYCLIC Β-Ketoesters, DMFDMA AND 2-Cyanomethylbenzimidazole

“…The intermediates 23 were isolated as precipitates and their structure was defined in X-ray diffraction study [9]. In addition the condensation of cyclic 1,3-dicarbonyl compounds of type 1 with DMFDMA 2 and 2-(1H-benzo[d]imidazol-2-yl)acetonitrile 4 (Scheme 1) resulted in selective formation of cyanides 5 and our attempts to isolate other types of reaction products by variation of reaction conditions were unsuccessful [18]. Based on these considerations we assume that the main product obtained in the presence of piperidine (Tables 1,2) is formed by Path B (Scheme 4) and formulated as 8.…”

“…Recently we used its reactivity within the discussed above synthetic approach using cyclic 1,3-dicarbonyl compounds of type 1 as the starting α-CH 2 -carbonyls (Scheme 1). This condensation was found to be a highly selective process leading to 4-oxo-1,2,3,4-tetrahydrobenzo [4,5]imidazo[1,2-a]quinolin-6-yl cyanides (5) [18].…”