Isoxazole-to-oxazole rearrangements

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]. 

In analogy to the isoxazole-to-oxazole rearrangement, thiazoles can be obtained photochemically from irradiation of the corresponding isothiazoles. In several cases, however, irradiations have been conducted for mechanistic purposes only, and mixtures of photoisomers arising from competing reaction mechanisms are often formed [4, 6]. 

This type of rearrangement can also occur as a consequence of in situ formation of a suitable intermediate, such as in the case of tandem or cascade reactions. Examples of the isoxazole-to-oxazole rearrangement have been studied both computationally and experimentally, providing evidence of the involvement of a 1,2,4-oxadiazole intermediate (2009JOC351). Synthetically useful cascade rearrangements have also been reported for the one-pot synthesis of indazoles (2011SL3018) and a series of isoxazolo-pyrimidines (2011OL4749). 

Another rearrangement occurs in the photoisomerization of isoxazoles to oxazoles, which is interpreted in terms of a 1,5-electrocyclization (cf. p 129) involving an isolable 3-acylazirine 25 as an intermediate ... 

Nishimoto and co-workers reported a theoretical smdy on the photochemical rearrangement of isoxazoles to oxazoles. In a later smdy of the thermal and photochemical transposition of oxazoles, the authors concluded that these rearrangements involve the formation of azirine intermediates. ... 

Propose the rearrangement mechanism from isoxazole to oxazole. ... 

The behaviour of /S-oxovinylazides is quite similar to those above. The Z isomer (556), formed from the /S-halo carbonyl compound and sodium azide, is unstable losing N2 and forming the isoxazole (557) in an anchimerically assisted concerted reaction (75AG(E)775, 78H(9)1207). At moderate temperatures (50-80 °C) the E isomer formed acylazirines which at higher temperatures rearranged to oxazoles and isoxazoles. 

Although 2-acyl-2//-azirines are known to give oxazoles upon irradiation, the reaction is wavelength dependent, and isoxazoles are formed at some wavelengths, as they are in the thermal rearrangement of 2-acyl-2//-azirines.<74TL29,75JA4682> Since the thermal reaction of diazocarbonyl compounds with nitriles leads to oxazole formation, it would seem that mechanistic path C is unlikely in these reactions. 

The electron impact mass spectra of 3-methyl-4-nitro-5-styryl-isoxazoles exhibit, on the contrary, only negligible loss of OH"80. This has been interpreted in terms of an isoxazole-to-azirine rearrangement80. The latter fragments directly to an abundant cinnamoyl ion as well as rearranges to oxazole and an epoxide through an intramolecular oxidation of the ethylenic bond by the nitro group80 see Scheme 10. 

Oxazoles are the products of the rearrangement of isoxazoles and of C-acylazirines, these processes being intimately related (81MI41800, 76ACR37I, 77H(6)143). Photolysis of 3-acylazirines gives nitrile ylides which cyclize thermally to oxazoles (equation 131). Flash vacuum pyrolysis of 3,5-diphenylisoxazole yields as major products 2,5-diphenyloxazole, 1,2-diphenylazirine, 2-phenylindole and benzamide. 13C labelling experiments indicate that the first two compounds are formed as shown in Scheme 31. 

The thermal rearrangement of 3-hydroxyindoxazene to benzoxazolin-2-one is temperature-dependent. The indoxazene is inert at 250°C but rearranges quantitatively at 450°C.78 3-Phenylindoxazene under flash vacuum pyrolysis conditions (800°C, 0.1-1 torr) rearranges to 3-phenylbenzoxazole in 80% yield.79 In both reactions a spiroazirine intermediate [59 or 60 (R = Ph)], analogous to those isolated in some isoxazole-oxazole rearrangements,80 is considered likely. 

The photochemically induced isomerization of isoxazole (279) to oxazole (281) is known to proceed via the intermediate keto-azirine (280). An M.O. study of the isomerization reactions of the azirine that are involved has been reported. Irradiation of (280) at >300 nm gives n tt excitation of the CO chromophore to 5i, intersystem crossing to Ti, and then C—N bond rupture, to form (279). Irradiation at 254 nm, however, gives n - n excitation of the C=N chromophore to S2, intersystem crossing to T, and then C—C bond rupture, to form (281). Such an isomerization reaction resulted in the photochemical conversion of isoxazolophane (282) into (283) (40%). Irradiation of (283) at 254 nm produced a quantitative yield of the expected oxazolophane. A new rearrangement was found, however, on irradiation of (283) at >300 nm, when the acyl-ketenimine (284) was formed, which could be converted into (285) by acid hydrolysis. 

Vivona and co-workers also described an unusual base-catalyzed isoxazole-oxazole rearrangement. Here, treatment of 3-(aroylamino)-5-methylisoxazoles 122 with KOtBu/DMF effected rearrangement to 2-(aroylamino)-5-methyloxazoles 125 (Scheme 1.33). The authors proposed initial deprotonation of 122 to generate 123,... 

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