Research Synthesis of 2,4,5-Trisubstituted Imidazoles from Azido Chalcones and Nitriles

Abstract

A simple and efficient synthetic route for the preparation of 2,4,5- trisubstituted imidazoles has been developed using α-azido chalcones and nitriles as key starting materials under Lewis acid-promoted thermal conditions. The present work explores the utility of α-azido chalcones as versatile intermediates for the synthesis of highly substituted imidazolederivatives. Various α-azido chalcones were reacted with aliphatic, vinyl, and aromatic nitriles in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) as a Lewis acid catalyst under solvent-free conditions at 80 °C. The reactions proceeded smoothly within 2 h to afford the corresponding 2,4,5-trisubstituted imidazoles in good yields (74–79%). The synthesized compounds were purified and characterized by melting point determination, thin-layer chromatography (TLC), infrared spectroscopy (IR), and proton nuclear magnetic resonance (^1H NMR) spectroscopy. Spectral data confirmed the formation of the desired imidazole derivatives, showing characteristic N–H, C=O, aromatic, and aliphatic/vinylic proton signals. The optimized method offers a rapid, efficient, and convenient approach for the synthesis of structurally diverse imidazole derivatives from α-azido chalcones. This protocol may serve as a useful strategy for the preparation of biologically relevant imidazole scaffolds for further medicinal and synthetic applications.