Synthesis and Antioxidant Activity of Tiglic Aldehyde-Based Fused Imidazo[1,2-a]Pyridines: A Groebke–Blackburn–Bienaymé Reaction

Abstract

A one-pot catalytic and column-free synthesis of fused imidazo[1,2-a]pyridines(4a-4j), from readily available pyridin-2-amine, various isocyanide, and tiglic aldehyde [2-methylbut-2-enal] as building blocks through the Groebke– Blackburn–Bienaymé reaction (GBBR) is reported. This efficient protocol has the advantages of environmental friendliness in terms of atom economy, high yields, and operational simplicity. The optimization of the process was carried out by various p and d block metal catalysts (particularly, Th(NO3)4, AlCl3, PCl3, La(NO3)3, Sc(OTf)3, ZrCl4, and SrCl2) and found most efficient with Zirconium metal catalyst. The biological evaluation demonstrated that compound 4a(t-butyl isocyanide) and 4h (cyclohexyl isocyanide) showed promising antioxidant activity concerning the used standard (ascorbic acid).