Nucleophilic aromatic substitution 1,3-azoles

Nucleophilic aromatic substitutions 1,3-azoles are more reactive than pyrrole, furan or thiaphene towards nucleophilic attack. Some examples of nucleophilic aromatic substitutions of oxazole, imidazole and thiazoles and their derivatives are given below. In the reaction with imidazole, the presence of a nitro-group in the reactant can activate the reaction because the nitro-group can act as an electron acceptor. 

No activation is required for 2-halo-1,3-azoles, which can undergo nucleophilic aromatic substitutions quite easily. 

In 1,2-type azole N-oxides, leaving groups at the 3- and 5-positions are activated toward nucleophilic aromatic substitution since nucleophilic attack at these positions renders intermediates 28 and 34 in which the positive N-oxide nitrogen atom adopts the negative charge brought to the adduct by the nucleophile. Nucleophilic attack at the 4-substituted isomer 30 would give rise to intermediates like 31 in which such stabilization is impossible (Scheme 6). 

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. 

---