Isoxazoles and Isoxazolines by 1,3-Dipolar Cycloaddition. Base-Catalysed Condensation of Primary Nitro compounds with Dipolarophiles to Isoxazole Derivatives

1,4 -Diazabicyclo [2.2.2]octane (DABCO) or other suitable N-bases cause primary activated nitro compounds to condense with alkenes to yield isoxazolines or with alkynes to give isoxazoles. As the molar ratio of the base with respect to the dipolarophile decreased, the reaction became slower, but the nitro compound became more resistant to hydrolytic cleavage. The best results were achieved with a molar ratio of base in the range of 0.05-0.1. The reactions were carried out in chloroform at 60 degrees C; for ethyl nitroacetate and phenylnitromethane, ethanol at 80 degrees C can be employed with better results and shorter reaction times. A catalytic cycle is proposed: in chloroform the hydrogen-bonded ion pair formed between the nitronate and the protonated base undergoes reversible cycloaddition with the dipolarophile and then the hydrogen-bonded intermediate adduct releases water by reaction with a second nitro molecule to give the product and the hydrogen-bonded nitronate.