Studies on Isoxazoles. X. Syntheses of Acylketene S, N-Acetals from 3-Phenylthio-and 3-Alkylthioisoxazolium Salts

Abstract

The reaction of 2-methyl-5-phenyl-3-phenylthioisoxazolium chloride (IIa) with a mixture of optimum amounts of thiophenol (2 eq.) and triethylamine (TEA) (1 eq.) gave benzoylketene S, N-acetal (IIIa) in maximum yield. To determine the reaction mechanism, IIa was treated with tri-n-butylphosphine in the presence of acetic acid (AcOH) to afford N-acetyl-N-methylbenzoylacetamide (VIII). The isolation of VIII provides evidence for the involvement of an intermediate, benzoylketene N-methylimine (VII), in the transformation of IIa to IIIa. Various acylketene S, N-acetals (III) were synthesized by the reaction of 3-chloroisoxazolium chlorides (I) with mixtures of optimum amounts of thiols (3 eq.) and TEA (2 eq.). On the other hand, the S, N-acetal (IIIj) was also prepared by the reduction of 3-ethylthio-2, 5-dimethylisoxazolium iodide (XIII) with zinc in AcOH. Cyclization of IIIj with hydroxylamine or hydrazine afforded 3-methylaminoisoxazole (XIV) or 3-methylaminopyrazole (XV) in good yield.