Isoxazole-benzisoxazole rearrangement

Upon UV irradiation, the heteroaromatic isoxazoles 35 rearrange similarly—most likely via azirines (293)159—to afford, by photocleavage of 293, nitrilylides (294)140,160 and finally the isomeric 1,3-oxazoles 295.1S7 However, ethyl 5-aminoisoxazole-4-carboxylate (34) isomerizes by another pathway. Similar to some thermal reactions,161 reorganization of the nitrile function in 295 affords the vinylamine 296157 (Scheme 80). Similar results are known for benzisoxazoles.162... 

The isoxazole-to-oxazole rearrangement has been also used in the synthesis of benzocondensed derivatives. The irradiation of benzisoxazoles 81 in water (high-pressure Hg lamp) produces almost quantitative yields of the corresponding ben-zoxazoles 82 (Scheme 12.24) [53]. Benzoxazolin-2-ones 83 are similarly obtained [54], Furthermore, oxazolo[5,4-b]pyridines 84 and oxazolo[5,4-b]quinoline 85 are obtained by preparative-scale photolysis in ether with a high-pressure Hg lamp of the corresponding isoxazolo[5,4-b]pyridines or isoxazolo[5,4-b]quinoline, respectively (Scheme 12.24) [55]. 

Benzisoxazoles could be obtained by cyclization reactions forming N—O, O—C(7), or N—C(3) bonds as well as by heterocyclic rearrangements <84CHEC-I(6)l>. 1,2-Benzisoxazole (313) is synthesized from lithiated 3,5-dimethyl isoxazole (312) and a-oxoketene (311) (Equation (62)) <88TL50I>. Thermal transformations of ethyl nitrophenyl ethanoates (314) resulted in cyclization, to afford 2,1-benzisoxazole (316) via the ketene intermediate (315). Its mechanism has been discussed with evidence <95CC2457>. 

The kinetics of a further series of isoxazole-2//-azirine rearrangements at 165-185°C has been investigated.62 The activation parameters for 3-phenyl-5-methoxyisoxazole (AH = 38 + 1 kcal/mol AS = 3.6 2 eu) are in good accord with the postulated initial N—O bond breakage [DH°(PhO— NR2) = 38-39 kcal/mol63]. The photochemical64 and thermal65 conversion of benzisoxazoles to benzoxazoles appears to involve an intermediate spiroazirine. 

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