Reaction of hydroxylamine with 5‐aminooxazoles. A new route to isoxazoles

Abstract

The nucleophilic attack of hydroxylamine at the 5 position of 2‐aryl‐4‐trifluoroacetyl‐5‐amino‐oxazoles leads to a mixture of stereoisomeric isoxazolines. Dehydration of these isomeric isoxazolines in the presence of trifluoroacetic anhydride gives 3‐amino‐4‐acylamino‐5‐trifluoromethylisoxazoles. The structures and spectroscopic data of these compounds are discussed.

Five‐Membered Heterocycles: 1,2‐Azoles. Part 2. Isoxazoles and Isothiazoles

“…Nucleophilic attack of hydroxylamine at the five position of 94 leads to ring opening followed by a cyclization to give isoxazoline 95. Subsequent dehydration in the presence of trifluoroacetic anhydride allows the synthesis of isoxazoles in good yields [191].…”

5-Halomethyl-5-Hydroxy-4,5-Dihydroisoxazoles: Synthesis and 13C, 17O,15N, 19F NMR Spectroscopy

“…In 1976, Clerin et al [62] showed an interesting route to synthesize 3-amino-4-acylamino-5-trifluoromethyl-4,5-dihydroisoxazoles 57 from the reaction of 2-aryl-4-trifluoromethyl-5-aminooxazoles 56 with hydroxylamine (Scheme 20). The reaction was carried out in reflux of ethanol, affording the products in high yields (85-92%).…”

Oxazole chemistry. A review of recent advances

“…When ethyl a-isocyanoacetate ( 106) is treated with KOt-Bu and N^V-dimethylcarbamoyl chloride, the intermediate 108 is formed. When 108 cyclizes, bond formation can occur between the isocyanide carbon and the ester carbonyl oxygen or to the amide carbonyl oxygen to give p-Tol either 5-ethoxyoxazole-4-(ArAr-dimethyl)carboxamide (109) or ethyl 5-(Ar,Ar-dimethylamino)oxazole-4-carboxylate (110), respectively. Only the 5-ethoxyoxazole 109 could be isolated in 77% yield (47).…”

“…"2 ^alkylThe position most susceptible to nucleophilic attack by amines in the 4-trifluoroacetyl-5-aminooxazoles 258 is the 5-position. This results in the formation of 1-trifluoroacetyl-l-acylamino-2,2-diaminoethylenes 260 after ring opening of the 2-oxazoline intermediate 259(108).262(48-60%)3-Amino-4-acylamino-5-hydroxy-5-trifluoromethyl-2isoxazolines 264 (85-92%) and ultimately 3-amino-4acylamino-5-trifluoromethylisoxazoles 265 are the products isolated in the reaction of 5-aminooxazoles 258 with hy-droxylamine(109). The reaction most likely proceeds through 260 (R4 = H, R5 = OH) which tautomerizes to the amidoxime 263.…”