Synthetic and Mechanistic Aspects of 4-Substituted-3, 5-bis (methoxycarbonyl) isoxazoline N-Oxides and the Corresponding 3, 5-Bis-(butylcarbamoyl) isoxazoles derived therefrom

Abstract

An improved method for the synthesis of 4-substituted-3, 5-bis (methoxycarbonyl)-isoxazoline N-oxides (3) was developed by one-step cyclization of aldehydes with methyl nitroacetate in N, N-dimethylacetamide. The reaction mechanism was found to involve intramolecular nitrite ion displacement by the nitronate anion (9) ; this was confirmed by the formation of 3, 5-bis (methoxycarbonyl)-4-phenylisoxazoline N-oxide-4-d (11), starting from benzaldehyde-1-d and methyl nitroacetate. Conversion of isoxazoline N-oxides (3) to the corresponding 3, 5-bis (butylcarbamoyl) isoxazoles (7) is also discussed.