Rearrangements of oxazoles

A microwave assisted Comforth rearrangement of oxazole-4-carboxamides 106 efficiently afforded 5-aminooxazole-4-carboxylates 107. This procedure was applied to the formal synthesis of a natural antibiotic derived from pseudomonic acid <06TL4698>. 

Rearrangements of oxazoles 392 and 393 (Scheme 62). which assume nucleophilic attack of the side-chain at the C(5) position and consequent fission of the ring O—C(5) bond, have been considered [76JCS(PI)315]. Nevertheless, the phenylhydrazide 394 does not rearrange into the expected 395 and remains unchanged under various conditions. In this context, unsuccessful attempts are reported for some structurally related 4-substituted oxazoles, whereas specific examples concerning oxazolium substrates 393 are not mentioned [76JCS(P1)3I5]. 

Thiazoles can be synthesized by a rearrangement of oxazoles, isoxazoles, and isothiazoles these transformations have been covered in CHEC-II(1996) <1996CHEC-II(3)373>. 

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. 

Dewar and Turchi carried out similar rearrangements of secondary and tertiary alkyl and aryl oxazole-4-carboxamides (5a-e) to the corresponding secondary and tertiary 5-aminooxazoles (6a-e). For example, they realized yields > 90% when the amide nitrogen is part of a heterocyclic ring system. 

In studies on l-diazo-2-ketosulfones, Shioiri et at. found that the thermal decomposition of benzoyl(sulfonyl)diazomethanes 6 with benzyl alcohol in acetonitrile also gave two products.<82CPB526> One is the 4-sulfonyloxazole 7 whereas the other product 8 results from rearrangement and reaction with the alcohol. The ratio of products varies with the nature of the sulfone substituent with the benzyl group giving highest yields of oxazole (Scheme 5). 

Oxazole formation can be envisaged as proceeding by three possible pathways 1,3-dipolar cycloaddition of a free ketocarbene to the nitiile (Path A), the formation and subsequent 1,5-cyclisation of a nitrile ylide (Path B) or the formation and subsequent rearrangement of a 2-acyl-2//-azirine (Path C) (Scheme 9). 

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 mass spectra of azolides are not very specific, since they depend to a large extent on the structures of the respective acyl groups. Flash vacuum pyrolyses of azolides has been studied for 1-acyl-1,2,4-triazoles and benzotriazolides by tandem mass spectrometry (MS/MS). 461 Rearrangements of triazolides resulted in the formation of oxazoles. 471... 

Rapi, G. et al., J. Chem. Soc., Chem. Comm., 1982, 1339-1340 Oxidative rearrangement of the oxazole to 4-hydroperoxy-5-hydroxy-4-methylimidazolidin-2-one in presence of iron(II) catalysts at ambient temperature may become explosive if not controlled effectively. 

Conceptually interesting is the synthesis of the oxazole system 94 through a Beckmann rearrangement of a-formyl ketoxime dimethyl acetals 93 which demonstrated the possibility of a non-amino acid pathway in the biosynthesis of marine derived oxazoles <06CC1742>. 

Aromatic pyrrolo[2,l- ]oxazoles are unknown compounds. Dihydro derivatives 228 and 229 have been obtained from the thermal rearrangement of dihydrooxazole 226 through intermediate 227 (Scheme 32) <2003EJ01438>. 

The first syntheses of a-allenic a-amino acids [131,133] took advantage of Steg-lich s [134] protocol for the oxazole-Claisen rearrangement of unsaturated N-ben-zoylamino acid esters (Scheme 18.46). Thus, treatment of the propargylic ester 143 with triphenylphosphine and tetrachlormethane furnished the allenic oxazolone 144, which was converted into the amino acid derivative 145 by methanolysis. Stepwise deprotection finally led to the allenic DOPA analog 146, which shows a much higher decarboxylase-inhibiting activity than a-vinyl- and a-ethynyl-DOPA [133],... 

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. 

Acyclo-C-nucleoside analogs possessing oxazole rings were obtained from the rearrangement of lactoxime o-vinyl ethers or sugar lactoxime o-vinyl ethers [92JCS(P1)2127]. In some cases, epimerization took place at the C-2 position. 

The endoperoxides (49) of oxazoles also undergo clean rearrangements following the path outlined in Scheme 6 <88TL1007>. The initial product is a dioxazole (50) identified at low temperature by NMR spectroscopy <90JCS(P1)1011>. Subsequent products are the imino anhydride (51) followed by... 

The only examples of 1,2,4-trioxolanes containing A-linked substituents arise from photooxygenation of oxazoles. The endoperoxides thus produced are bicyclic, with a 1,2,4-trioxolane ring bridged by an imine moiety and are unstable at ambient temperature. They have been characterized at low temperature and thermal rearrangement is described in Section 4.16.5.1.1. 

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