Nitration of pyrazole

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)). 

Preparation of one of the analogues in which benzene is replaced by pyrazole starts by nitration of pyrazole carboxylic acid The product, is then converted to... 

Initial nitration of pyrazole derivatives with nitric acid in acetic or trifluoroacetic anhydrides leads to A-nitropyrazoles, which rearrange to the C-nitrated product on stirring in concentrated sulfuric acid at subambient temperature. This N -> C nitro group rearrangement often occurs in situ when pyrazoles are nitrated with mixed acid. 

Claridge, R. P., Lancaster, N. L., Millar, R. W., Moodie, R. B. and Sandall, J. P. B. Faujasite catalysis of aromatic nitrations with dinitrogen pentoxide. The effect of aluminum content on catalytic activity and regioselectivity. The nitration of pyrazole, J. Chem. Soc., Perkin Trans. 2, 2001, 197-200. 

Scheme 7.11. Standard log rates for nitration of pyrazole and derivatives [74JCS(P2)389 75JCS(P2)1600. 75JCS(P2)I609, 75JCS(P2)I632]. Positions that have underlined values react as the free bases. Where two values are given, the underlined value is for reaction on the free base (at low acidity) the other value refers to reaction on the conjugate acid.

The introduction of such electron-withdrawing groups as 2,4-dinitrophenyl, picryl, or nitroguanidyl at position 1 of pyrazole does not hinder the nitration of pyrazole at position 4 [32, 41, 64],... 

Some examples of the nitration of pyrazole N-oxides are known [75, 76]. The result of nitration is determined by the ratio of the components in the nitrating mixture (Scheme 10). 

Direct nitration of pyrazoles, imidazoles, isoxazoles, and thiazoles has been carried out by Katritzky et al. with a new nitrating agent - nitric acid/trifluoroacetic anhydride [364, 365], This method allows obtaining mononitro derivatives of azoles in good yield (Table 5). 

Elguero et al. (68BSF5019) (Scheme 58) used concentrated nitric acid for the nitration of pyrazol-3-one 177a and obtained 4-nitropyrazol-3-one 178b in 50%... 

Varvounis and co-workers (01JHC1065) (Scheme 60) used 50% aqueous nitric acid for the nitration of pyrazol-3-ones 181a-c. The 4-nitro derivatives 182a-c were obtained in 80, 78 and 70% yield, respectively. 

Nitration of pyrazole is a high energetic reaction. Applying a continuous processing approach using a micro-reactor, 4-nitro-pyrazole was prepared from pyrazole-5-carboxylic acid in 73% yield. ... 

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