Direct synthesis of 2,4,5-trisubstituted imidazoles from alcohols and [alpha]-hydroxyketones by microwave

This article reports a fast, simple and efficient method to synthesize highly substituted imidazoles. Green organic synthesis is needed to face current environmental pollution. For instance the replacement of hazardous organic compounds by safe alternatives is particularly relevant. Ionic liquids are an environmentally friendly alternative to conventional organic solvents due to their unique physicochemical properties. Substituted imidazoles have been widely used to prepare pharmaceuticals. Many synthetic approaches have been developed to produce substituted imidazoles. However, despite considerable efforts only a few green methods are reported for the synthesis of highly substituted imidazoles. Here a straightforward and atom-economic approach is reported to synthesize a series 2,4,5-trisubstituted imidazoles directly from [alpha]-hydroxyketones and alcohols employing 1-methyl-3-H-imidazolium nitrate as a promoter and medium under microwave irradiation. The protocol has several advantages such as high yields of 77-91 %, short reaction times of 6-8 min, easy purification processes, and methodological simplicity due to the formation of carbon-carbon and carbon-heteroatom bonds in a single step. The methodology has been further extended towards the facile synthesis of Trifenagrel in good yield. This method provides new opportunities for the rapid screening of a wide range of compounds, either for the development of new drugs or total synthesis of natural products.[PUBLICATION ABSTRACT]