Azoles Pyrazoles, Isothiazoles, Isoxazoles Reactions and Synthesis

2-Azoles Pyrazoles, Isothiazoles, Isoxazoles Reactions and Synthesis 

Rapid tautomerism, involving switching of hydrogen from one nitrogen to the other, as in imidazoles (see 24.1.1.1), means that substituted pyrazoles are inevitably mixtures, and a nomenclature analogous to that used for imidazoles is employed to signify this 3(5)-methylpyrazole, for example. In some cases, one tautomer is predominant.  

Heterocyclic Chemistry 5th Edition John Joule and Keith Mills 2010 Blackwell Publishing Ltd 

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Azoles pyrazoles, isothiazoles, isoxazoles reactions and synthesis... 

Abstract Synthesis methods of various C- and /V-nitroderivativcs of five-membered azoles - pyrazoles, imidazoles, 1,2,3-triazoles, 1,2,4-triazoles, oxazoles, oxadiazoles, isoxazoles, thiazoles, thiadiazoles, isothiazoles, selenazoles and tetrazoles - are summarized and critically discussed. The special attention focuses on the nitration reaction of azoles with nitric acid or sulfuric-nitric acid mixture, one of the main synthetic routes to nitroazoles. The nitration reactions with such nitrating agents as acetylnitrate, nitric acid/trifluoroacetic anhydride, nitrogen dioxide, nitrogen tetrox-ide, nitronium tetrafluoroborate, V-nitropicolinium tetrafluoroborate are reported. General information on the theory of electrophilic nitration of aromatic compounds is included in the chapter covering synthetic methods. The kinetics and mechanisms of nitration of five-membered azoles are considered. The nitroazole preparation from different cyclic systems or from aminoazoles or based on heterocyclization is the subject of wide speculation. The particular section is devoted to the chemistry of extraordinary class of nitroazoles - polynitroazoles. Vicarious nucleophilic substitution (VNS) reaction in nitroazoles is reviewed in detail. 

There are parallels, but also methods unique to particular 1,2-azoles, in the principal methods available for the construction of pyrazoles, isothiazoles and isoxazoles neither the reaction of propene with sulfur dioxide and ammonia at 350 °C, which gives isothiazole itself in 65% yield, nor a synthesis from propargyl aldehyde and thiosulfate (shown below) have direct counterparts for the other 1,2-azoles. 

Synthesis and reactions of lithiated monocyclic azoles containing two or more hetero-atoms. Part 1 Isoxazoles , Iddon, B., Heterocycles, 1994, 37, 1263 Part III Pyrazoles , Grimmett, M. R. and Iddon, B., ibid., 1994, 37, 2087 Part V Isothiazoles and thiazoles , Iddon, B., ibid., 995,41, 533. Heinisch, G., Holzer, W. and Pock, S., J. Chem. Soc., Perkin Trans. 1, 1990, 1829. 

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