Microwave-promoted One-pot Synthesis of Imidazo[1,2-a]pyridines in Lemon Juice

Abstract

Objective: A simple and highly efficient microwave-promoted procedure for the synthesis of imidazo[1,2-a]pyridine derivatives from the reaction of aromatic ketones, N-bromosuccinimide, and 2-aminopyridines in lemon juice was designed. The main advantages of this protocol, such as clean reaction profile, mild reaction condition, high yield, and minimum reaction time, were compared to other previously developed methods. Method: A mixture of aromatic ketones (1a-m) (0.005 m), N-bromosuccinimide (NBS) (0.005 m), and lemon juice (10 ml) was irradiated by microwave at 400-watt power at 85°C, and the formation of α- bromoketones was monitored by Thin Layer Chromatography (TLC). After completion of α-bromination, 2-aminopyridines (0.005 m) was added to the reaction mixture and it was further irradiated at the same reaction condition. After completion of the reaction, the reaction mass was poured in ice-cold water, the solid product obtained was filtered, washed with cold water, and recrystallized from aqueous ethanol. Result: In the present investigation, we have developed an environmentally benign, easy, and highly efficient one-pot procedure for the synthesis of 2-phenylimidazo [1, 2-a] pyridines from the reaction of aromatic ketones, N-bromosuccinimide, and 2-aminopyridines in lemon juice as a natural acid catalyst and solvent under microwave irradiation. This new protocol offers very attractive features such as minimum reaction time, clean reaction profile, mild reaction condition, and green aspects such as avoid poisonous catalyst, hazardous solvents, ease of the work-up procedure, and higher yield. Conclusion: In the present investigation, we have developed an environmentally benign, easy, and highly efficient one-pot procedure for the synthesis of 2-phenylimidazo [1, 2-a] pyridines from the reaction of aromatic ketones, N-bromosuccinimide, and 2-aminopyridines in lemon juice as a natural acid catalyst and solvent under microwave irradiation. This new protocol offers very attractive features such as minimum reaction time, clean reaction profile, mild reaction condition, and green aspects such as no need for a poisonous catalyst and hazardous solvents, ease of work-up procedure, and higher yield.