Pyrazole nucleophilic substitutions

If the fV-aryl group is strongly activated, then it can be removed in nucleophilic substitution reactions in which the azole anion acts as leaving group. Thus l-t2,4-dinitrophenyl)pyrazole reacts with N2H4 or NaOMe. 

In the copper catalyzed aromatic nucleophilic substitution of aryl halides bromoindole derivatives were converted to the appropriate cyanoindoles. Both 5-bromoindole and its 7V-tosyl derivative gave excellent yields, when a substoichiometric amount potassium iodide was added to the reaction mixture (6.80.), Pyrazole and benzothiophene showed a similar reactivity. The role of the added iodide is to activate the aromatic system through a bromine-iodine exchange.111... 

Nucleophilic substitution of the terminal halogen in the alkyl groups at G-5 atom is a simple but efficient approach to modification of tetrazole derivatives. Treatment of 1-phenyl-5-chloromethyltetrazole with imidazole or pyrazole (DMSO, NaOH) gave the corresponding products of the halogen /3-substitution 338 and 339 <2002JOC8230>. 

Nucleophilic substitutions in the pyrazole series have been much less studied than electrophilic substitutions. 

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. 

Flash chromatography has been applied to study the vicarious nucleophilic substitution products of nitroazoles (pyrazoles, imidazoles, indazoles, and benzimidazoles) [319], the thermal isomerization of the nitroisoxazoles into nitrooxazoles (with petroleum ether/ethyl acetate 10 1 v/v as eluent) [501, 502],... 

Nucleophilic substitution reactions of 5-chlorop5Tazoles 48 with amines and thiols under mild conditions provided 5-alkyl amino and thioether pyrazoles 49 as selective COX-2 inhibitors <03TL7629>. 4-Chloromethylpyrazoles 50 reacted readily with amides, carbamates, urea, azoles, alcohols, and thiols under neutral conditions to give substituted benzylic products 51 in moderate yields <03H(60)167>. 

Reaction of l-methyl-4-nitropyrazole with 1,1,1-trimethylhydrazinium halides in the presence of sodium methoxide or potassium fert-butoxide afforded 5-amino-l-methyl-4-nitropyrazoles <1999CHE1109>. Specifically, the primary radical anions of substrate in the vicarious nucleophilic substitution of hydrogen in 1-methyl-4-nitropyrazole 192 with 1,1,1-trimethylhydrazinium iodide yielded 5-amino-l-methyl-4-nitropyrazole 193, which was studied by electron spin resonance (ESR) (Equation 31) <2005MRC1023>. Reaction of 3,5-dinitropyrazole 194 with trimethylhydrazinium iodide in DMSO afforded 4-amino-3,5-dinitro-l//-pyrazole 195 via another vicarious nucleophilic substitution (Equation 32) <2001JHC1227>. 

Nucleophilic substitution reactions Neutral pyrazoles and indazoles... 

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