Innovative Ultrasound‐Assisted Synthesis of Isoxazolo[5,4‐ <i>b</i> ]Pyridines from Aryl Glyoxal, 5‐Aminoisoxazoles, and Malononitrile in Acetic Acid as a Solvent and Catalyst

Abstract In this work, a novel strategy for the straightforward synthesis of isoxazolo[5,4‐ b ]pyridines from a one‐pot reaction of aryl glyoxal, 5‐aminoisoxazoles, and malononitrile under ultrasound (US) irradiation is described. In the reaction, acetic acid has a dual role as solvent and catalyst. The advantages of this reaction include easy purification of products, raw materials with easy access, short reaction time, high efficiency, and green conditions by utilizing ultrasound irradiation as an energy source and using acetic acid as solvent and Lewis acid. The synthesis achieved high yields of isoxazolo[5,4‐ b ]pyridines with a broad substrate scope, successfully producing twelve diverse derivatives. The methodology capitalizes on the benefits of sonochemistry, which accelerates reaction rates and improves selectivity while minimizing waste. The proposed mechanism involves a series of reactions including Knoevenagel condensation, Michael addition, and subsequent cyclization processes. This approach not only streamlines the synthesis of complex heterocycles but also aligns with environmentally friendly practices.