Commercial Zinc Oxide: A Facile, Efficient, and Eco-friendly Catalyst for the One-Pot Three-Component Synthesis of Multisubstituted 2‑Aminothiophenes via the Gewald Reaction

An eco-friendly, simple, and effective protocol is developed for the synthesis of various multisubstituted 2-aminothiophenes. In the presence of a catalytic amount of ZnO (5 mol %), ketones or aldehydes, malononitrile and elemental sulfur were converted to the corresponding 2-aminothiophene derivatives in moderate to high yields (27%–70%) under solvent-free conditions at 100 °C. Zinc oxide as an efficient, readily available, and reusable catalyst, showed very good catalytic activity for the synthesis of 2-aminothiophene derivatives. Thus far, little research has been reported on the Gewald reaction under solvent-free conditions; to the best of our knowledge, this is the first time that it has been proposed as an inexpensive and readily available catalyst for use in the target synthetic route.