Design, Synthesis and Characterization of Novel 2,4,5- Trisubstituted Oxazole Derivatives

Abstract

A concise and efficient synthetic methodology for the preparation of substituted oxazole derivatives has been developed using readily accessible α-azido chalcones as key intermediates. The present work describes the synthesis of a series of 2,4,5-trisubstituted oxazole derivatives through a one-pot cyclization reaction involving substituted α-azido chalcones and potassium thiocyanate in the presence of potassium persulfate as an oxidant under mild reaction conditions. The reaction proceeds smoothly in dry acetonitrile under nitrogen atmosphere at 80 °C to afford the corresponding oxazole-2-thiol derivatives in good to excellent yields without the need for column chromatographic purification. Five representative compounds were synthesized and characterized by melting point determination, thin layer chromatography (TLC), infrared spectroscopy (IR), and ^1H NMR spectroscopy. The synthesized compounds showed yields ranging from 89– 95% and exhibited spectral characteristics consistent with the proposed structures. The present methodology offers significant advantages such as operational simplicity, shorter reaction time, high product yield, and broad substrate tolerance. The study demonstrates that α-azido chalcones are useful synthons for the construction of highly substituted oxazole frameworks, which are of considerable importance in medicinal chemistry due to their diverse biological activities. This work provides an efficient route for the synthesis of substituted oxazoles and may facilitate future exploration of their pharmacological potential.