DBUH-I 3 : A next-generation organocatalyst for arylidene isoxazolone synthesis

Abstract A next-generation approach to arylidene isoxazolone synthesis is introduced using the versatile, sustainable 3,5,6,7,8,9-hexahydro-2H-imidazo[1,2-a]azepin-1-ium-iodine-iodide (DBUH-I 3 ) organocatalyst. This one-pot, three-component condensation of ethyl acetoacetate, substituted aryl aldehydes, and hydroxylamine hydrochloride under ethanol reflux yielded excellent results (up to 92%) across a diverse substrate range. DBUH-I 3 showed unparalleled catalytic efficiency and substrate versatility among screened amine–iodine–iodide complexes. The protocol offers operational simplicity, mild conditions, and rapid reaction rates, making it broadly applicable for the synthesis of isoxazolones. All products were structurally confirmed by FT-IR, ¹H NMR, and ¹³C NMR spectroscopy. Importantly, DBUH-I 3 overcomes iodine’s drawbacks, such as sublimation and moisture sensitivity, providing a stable, user-friendly alternative. Its compatibility with both electron-rich and electron-deficient substrates underscores its broad utility. This work establishes DBUH-I 3 as an eco-friendly, cost-effective catalyst that advances the synthesis of biologically relevant isoxazolone scaffolds and supports green chemistry applications..