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A convenient one-pot, multi-component and solvent free procedure for the preparation of substituted 2-amino-5-aryl-1,3,4-oxadiazoles has been achieved. The method is a significant improvement over previously reported synthesis. Reaction of acid chlorides with hydrazine hydrate and isothiocynates under microwave-irradiation (MWI) afforded the corresponding 1,3,4-oxadiazole derivatives in high yields with high purity. All synthesized compounds were characterized by FT-IR, proton and carbon NMR, mass spectroscopy and elemental analysis. A possible mechanism is proposed for the cyclodesulfurization based on the results of this study.