Synergistic effect of dual-frequency ultrasound irradiation in the one-pot synthesis of 3,5-disubstituted isoxazoles

Herein is reported a one-pot three-step process for the regioselective synthesis of 3,5-disubstituted isoxazoles based on copper(I)-catalyzed cycloaddition reaction between in situ generated nitrile oxides (from the corresponding aldehydes) and alkynes, using ultrasound irradiation, avoiding toxic reagents and solvents and isolation/purification of intermediates.The combined use of 40 kHz ultrasonic bath and 20 kHz probe in the presence of copper turnings reduced reaction time to 1 h and resulted in only one final purification step with increased yields, clearly indicating that there is a dual-frequency synergistic effect.In addition, under metal free conditions, the 1,3-dipolar cycloaddition was regioselective giving low to modest yields.