The three-component cyclocondensation was performed using various frequently available aryl/heteroaryl aldehydes, hydroxylamine hydrochloride, and β-ketoesters in water as a green reaction medium at 80 °C. In this reaction, isoxazol-5(4H)-ones were obtained in the presence of 2-aminopyridine as an efficient and low-cost organocatalyst. The present methodology offers sustainable approach with appreciable yields of the desired heterocycles. This procedure has expectant features, including shorter reaction times, easy separation of pure products, avoiding the hazardous organic solvents, simplicity experimental procedure, operationally simple, and eco-friendly. The heterocyclic structures were characterized using physical properties and analysis of spectral data.Isoxazoles are the top 10% most commonly used heterocycles in drug discovery. 1 Derivatives of this attractive five-membered heterocyclic ring are found in various natural and medicinal products. 1 Isoxazol-5(4H)-ones, on the other hand, have widely been shown antibacterial, antifungal, androgen receptor antagonist, tyrosinase inhibitory, SIRT1 inhibitory, anti-obesity, anti-HIV, antioxidant, anticancer, fungicide and insecticide properties activities. 2 As reported, the compounds have been studied in photovoltaic cells, 3 monochromatic terahertz difference frequency, 4 and laser dyes. 5 Isoxazol-5(4H)-ones are a representative class of isoxazoles that have been used as precursors in the synthesis of other interesting organic molecules. 6 The cyclization of O-propioloyl/propargylic oximes, 7 the reaction of ethyl acetoacetate and hydroxylamine hydrochloride followed condensation with aromatic aldehydes, and condensation of 1,3-dicarbonyls with benzaldoximes 8 are straightforward methods used to synthesis of isoxazol-5(4H)-ones. Significant development has been made in reviewing different routes for the construction of an isoxazol-5(4H)-one skeleton. 9
