Pyrazoles, phenyl-, nitration

The results are in accord with the observations above i.e., in mixed acid the pyrazole ring in protonated and the pyrazolium cation acts as a para director to the phenyl ring. In acetic anhydride pyrazoles are nitrated as free bases to yield 4-nitropyrazoles. 

The principal results on the nitration of pyrazoles are shown in Scheme 23. If the substituent is a phenyl group, it can compete with the pyrazole ring and para-nitration is often observed (Sections 4.04.2.3.3(ii) and 4.04.2.3.10(i)). 

Electrophilic substitution occurs readily in iV-phenyl groups, e.g., 1-phenyl-pyrazoles, -imidazoles and -pyrazolinones are all nitrated and halogenated at the para position. The aryl group is attacked preferentially when the reactions are carried out in strongly acidic media where the azole ring is protonated. 

The crystal structure of tris(l-phenyl-3,5-dimethylpyrazole)silver(I) nitrate (3) has been determined.63 The Ag+ ion sat at the centre of a triangle of 3 Ns from the pyrazole rings and the Ag—N bond lengths were about 224 pm. The nitrate groups were situated between the silver ions in the crystal lattice but the separations were of the order of 550-700 pm—too far... 

In the nitration of methylphenylpyrazoles, Parrini [57AC(R)929] showed that a mixture of nitric and sulfuric acids leads to nitration first in the para position of the phenyl ring and second in the 4-position of the pyrazole ring. 4-Nitro-(4-nitrophenyl) derivatives were obtained from 3,5-dimethyl-1-phenylpyrazole and 3-methyl-5-phenylpyrazole. 

In strongly acidic media the conjugate acid is nitrated leading to para substitution in the phenyl ring. In acetic anhydride an intermediate such as (28) may be formed, resulting in the favored 4-attack in the pyrazole ring (Fig. 9). 

The nitration (fuming nitric acid) of 5-chloro-3-methyl-l-phenylpyrazole is reported to give a mononitro product (presumably the 4-nitrophenyl derivative) and a dinitro product 5-chloro-3-methyI-4-nitro-l-(4-nitro-phenyl)-pyrazole (1900CB2595 11LA329). 

A comprehensive report has described the nitration of 3-hydroxy-1-phenyl pyrazoles [75JCS(P2)1609]. These hydroxy compounds are tautomeric with pyrazolones but at equilibrium the hydroxy form is favored. 3-Hydroxy-5-methyl-l-phenylpyrazole is nitrated in acetone using pentyl... 

In the case of 1,3-diphenylfuro[3,2-c]pyrazole (58) most electrophilic substitutions, e.g., Vilsmeier formylation, Friedel-Crafts acylation, and monobromination, take place in the furan ring. Excess bromine gives the second bromination in the 4-position of the 1-phenyl group, but nitration gives the l-(4-nitrophenyl) derivative and a second, uncharacterized, product (78YZ204). 

In the case of 5-bromo-3,4-dimethyl-l-phenyl-l/f, 6//-pyrano[2,3-c]pyrazol-6-one (59), mixed acid nitration results not only in para substitution in the phenyl ring, but also in ipso attack at the 5-position to yield... 

A quantitative study has been carried out by Ridd and co-workers126 on the nitration of imidazole and pyrazole in 98% sulfuric acid the partial rate factors for the 4-positions of imidazolium and pyrazolium cations are 3.0 xlO-9 and 2.1 x 10-10, respectively. Thiazole and isoxazole cations are also far less reactive than benzene. As a consequence, phenyl derivatives give products substituted in the benzene ring, on sulfonation or nitration.208-210... 

The introduction of other electron-withdrawing or -donating groups enables nitration of one or another of the rings to be accomplished selectively. Thus, l-phenyl-3-methylpyrazole is nitrated only in the pyrazole ring, whereas 1 -phenylpyrazole-3-carboxylic acid nitrates only in the para position of the benzene ring.586 The only dinitro-pyrazole recorded was obtained from 3-nitro-5-(pyrid-3-yl)-pyrazole.249,587 In the nitration product (54) the nitro group at... 

In some cases l-methyl-5-nitro- and l-methyl-3,5-dinitropyrazole can form as a result of deoxygenation [76], Nevetheless, the nitration of 2-benzylpyrazole 1-oxide by sulfuric-nitric acid mixture leads to 2-benzyl-3-nitropyrazole 1-oxide in quantitative yield. Further nitration takes place in the phenyl 4-position forming 3-nitro-2-(4-nitrobenzyl)pyrazole 1-oxide and then in the pyrazole 5-position to give 3,5-dinitro-2-(4-nitrobenzyl)pyrazole 1-oxide as the final product [77],... 

---