Metal-Free Amine-Mediated Oxidative Synthesis of Polysubstituted Imidazoles from Aryl Methyl Ketones, Ammonium Iodide or Benzylamine, and Hydrogen Peroxide

A hydrogen peroxide (H₂O₂)-promoted amine-mediated oxidative coupling reaction between aryl methyl ketones and ammonium iodide leading to (4 or 5)-aryl-2-benzoyl-imidazole analogs has been developed; these analogs show highly potent antiproliferative activity and can be further developed as promising antitumor agents. This methodology features a one-step process, metal-free conditions, high atom economy, good functional group tolerance, and the use of economic and simple starting materials and oxidant. Moreover, the reaction can be scaled up without significant decrease of the yield. Furthermore, 1,2,4-trisubstituted imidazoles, which are synthetically and pharmaceutically valuable compounds, are produced in the presence of benzylamine. A reasonable mechanism is proposed based on some control experiments.