Synthesis of 5-substituted-3-phenacyloxime-1,2,4-oxadiazoles from acetylated or benzoylated benzoylthiacetamide with hydroxylamine hydrochloride : Spectral evidence for a tetrahedral carbinolamine intermediate

Acetylated and benzoylated benzoylthiacetamide 1a,b reacts with hydroxylamine hydrochloride in refluxing ethanol to yield 3 - acetylamino - and 3 - benzoylamino - 5 - phenyl - isoxazoles 2a,b, while 3 -phenacyloxime - 5 - substituted - 1, 4a,b are formed in the presence of sodium acetate or in pyridine.When refluxed in ethanol containing small amounts of concentrated hydrochloric acid, the above 1,2,4-oxadiazoles 4a, b rearrange to the corresponding isoxazoles 2a, b.The reaction in pyridine has been studied at 35° by using ¹H and ¹³C NMR spectroscopy. It has been possible to detect an adduct between the carbinolamine intermediate, resulting from the addition of hydroxylamine to the keto carbonyl group, and the starting thiamide.