One-pot, multicomponent oxidative synthesis of 2,4,5-trisubstituted imidazoles from internal alkenes using an I2/DMSO system.

Abstract

Imidazoles are vital heterocyclic compounds usually incorporated in natural products such as biotin, vitamin B12, histamine, and histidine. 2,4,5-trisubstituted imidazoles, in particular, possess versatile biological and pharmaceutical activities such as antidiabetic, antimalarial, and analgesic properties. A traditional procedure for the synthesis of these elegant compounds involves the cyclocondensation reaction between a 1,2-diketone, an aldehyde, and ammonia in the presence of an acid or metal catalyst. However, this methodology suffers from various shortcomings such as the use of acid or metal catalysts, tedious work-up procedures, use of toxic reagents, and substrate scope limitations. Hence, the development of new methods to synthesize 2,4,5-trisubstituted imidazoles is of vital importance. This study describes the preparation of 2,4,5-trisubstituted imidazoles from alkenes using an environmentally benign iodine/DMSO system. This novel methodology was applied to a broad substrate scope such as substituted benzaldehydes, heterocyclic aldehydes, bulkier aldehydes, and substituted stilbenes, and afforded the target compounds in moderate to high yields under mild reaction conditions. Preliminary mechanistic studies revealed that 1,2-diketone is a key intermediate and that the mechanism is not radical-mediated. It also revealed that the oxygen source is DMSO and that the coupling step is catalyzed by iodine coordination and hydrogen bonding from the solvent. Based on the results obtained from the preliminary mechanistic investigations, a reasonable mechanism is proposed.