4-Nitropyrazoles

Hydroxy-6-methyl-2-phenylpyridazin-3(2Fr)-one and 4-hydroxy-5-nitropyridazin-3(2FT)-one rearrange in acidic medium to 3-methyl-l-phenylpyrazole-5-carboxylic acid and 4-nitropyrazole-5-carboxylic acid. 4-Hydroxypyridazin-3(2FT)-ones with a hydroxy group or other group at positions 5 or 6, which is easily replaced in alkaline medium, are transformed into 5-(or 3-)pyrazolones with hot alkali. An interesting example is ring contraction of 5-chloro-4-(methylthio)-l-phenylpyridazin-6(lFT)-one which gives, besides pyrazole derivative (127), 4-hydroxy-5-methylthio-l-phenylpyridazin-6(lFf)-one (128 Scheme 41). 

Nitropyrazoles rearrange to 4-nitropyrazoles in H2SO4 and to 3-nitropyrazoles thermally. Similar rearrangements are known for 7V-nitro-l,2,4-triazoles. 

The results obtained with methoxypyrazole (247) are attributed to an electronic effect, whereas those obtained with (246) can be explained by taking into account the angular strain in the minor isomer. Reaction of 3(5)-nitropyrazole with l-fluoro-2,4-dinitrobenzene affords exclusively l-(2,4-dinitrophenyl)-3-nitropyrazole (70JHC1237). 

Bromopyrazoles (298) react with fuming nitric acid in 80% sulfuric acid to give 4-nitropyrazoles (ipso nitration Section 4.04.2.3.7). When R was an alkyl group, nitration took place at C-3 giving (299) (a small amount of the dinitro derivative (300) was also obtained) (79AJC1727). Nitrodebromination proceeds from the protonated pyrazolium ion whereas 3-and 5-nitration were expected to involve the free base. 

Dimethylpyrazole 1.4- Dimethyl-3-nitropyrazole The attack at the 3- and 5-positions occurs on the free base. Standard rates 1,4-dimethylpyrazole (attack at the 3-position), log /co = 3.55, l,4-dimethyl-3-nitropyrazole (attack at the 5-position), log /c = -4.73 (deactivating effect of the nitro group) 75JCS(P2)1632... 

With mixed acid 1-methylpyrazole 2-oxide (268) gives high yields of l-methyl-5-nitropyrazole 2-oxide (269) (B-76MI40402). The form undergoing the reaction is the base, for which first-order kinetics are observed in the Hq range from -5 to -6.5 a dinitro derivative is also formed under slightly different conditions. The reaction of indazole with fuming nitric acid affords a nearly quantitative yield of 5-nitroindazole (Section 4.04.2.3.2(i)). 

Nitration in 80% sulfuric acid of 4-bromopyrazoles gives rise to considerable nitro-debromination (formation of 4-nitropyrazoles) (79AJC1727). The reaction takes place on the protonated pyrazolium ion (Section 4.04.2.1.4(ii)). 

Generally the name of a compound should correspond to the most stable tautomer (76AHCS1, p. 5). This is often problematic when several tautomers have similar stabilities, but is a simple and reasonable rule whose violation could lead to naming phenol as cyclohexadienone. Different types of tautomerism use different types of nomenclature. For instance, in the case of annular tautomers both are named, e.g., 4(5)-methylimidazole, while for functional tautomerism, usually the name of an individual tautomer is used because to name all would be cumbersome. In the case of crystal structures, the name should reflect the tautomer actually found therefore, 3-nitropyrazole should be named as such (97JPOC637) and not as 3(5)-nitropyrazole. 

Amino-4//-l,2,4-triazole 16 was employed as an aminating agent in a reaction with l-methyl-4-nitropyrazole 81 the reaction gave a mixture of the 5-amino-4-nitropyrazole 82 and the adduct 83 in low yields of 20% and 13%, respectively (Equation 30) <2000CHE476, 2000KGS551>. 

Various nitropyrazoles and nitroimidazoles have been studied96-99 see Table 1. The loss of OH from methyl-substituted nitropyrazoles and nitroimidazoles appears as a useful probe in determining the actual location of the substituents. Thus, it could be established that in the case of adjacent methyl and nitro groups, the loss of OH originates exclusively from these substituents96-98. In addition to the loss of OH the presence of a mobile N-bonded hydrogen atom leads to the elimination of H2O, as is visualized by the mechanisms for loss of OH and H2O from 3(5)-methyl-4-nitropyrazole and 4-methyl-3(5)-nitropyrazole, respectively98 see Scheme 28. 

Poullain and co-workers ° synthesized Af-substituted-3,5-diamino-4-nitropyrazoles by treating substituted pyrimidines with Af-alkylhydrazines. 3,5-Diamino-4-nitropyrazole (14) has been synthesized by treating the pyrimidine (13) with hydrazine hydrate. This methodology is limited in scope but the products are useful intermediates for the synthesis of insensitive high explosives. 

A common route to nitropyrazoles involves the diazotization of the corresponding amino derivatives in the presence of excess sodium nitrite." Diazotization in the presence of sodium azide allows the introduction of the azido explosophore ."... 

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. 

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