A rapid and efficient access to polysubstituted imidazoles via iodine-catalyzed tandem oxidative cyclization

Abstract

Imidazoles represent one of the most important heterocycles which are known to exhibit a wide range of biological and medical activity. Existing methodologies for the synthesis of imidazoles are limited to the generality and accessibility of substrates, and the harsh reaction conditions. The development of milder and more practical protocols should be still desirable and necessary. Here we report a new method for the synthesis of polysubstituted imidazoles. A series of imidazoles was obtained directly from 2-phenylacetaldehyde or acetophenone derivatives and benzylamine derivatives via a metal-free-catalyzed tandem oxidative cyclization. The reaction was performed under mild conditions with iodine as a catalyst and TBHP as an oxidant. The effect of catalyst loading, oxidants, solvents and temperature on this transformation was investigated. The optimal reaction conditions were as follows: 0.3 equiv. of iodine as the catalyst, TBHP as the oxidant, acetonitrile as the solvent and the reaction being carried out at 70°C. Electron-withdrawing group of acetophenone derivatives and benzylamine derivatives benefit the oxidative reaction. Compared with traditional methods, this reaction was conducted under milder conditions with facile starting materials. © 2012 Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences.