4-nitropyrazole

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. 

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. 

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)). 

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 rare example of desmotropy (two tautomers that crystallize in two different crystals) in azoles, found by X-ray crystallography, concerns 3-methyl-4-nitropyrazole (198) and its tautomer, 5-methyl-4-nitropyrazole (199) (94CC1143). 

Tautomerism of 3,5-bis(4-methylpyrazol-l-yl)-4-methylpyrazole (202) also involves the simultaneous rotation of the two lateral rings and has a value of 12 kcal mol-1 (in methanol), almost the same as 3,5-dimethyl-4-chloropyrazole and 3,5-dimethyl-4-nitropyrazole (93CJC1443). 

Nitro-l-(2-nitrophenyl)pyrazole 4-Nitro-1 -(3-nitrophenyl)pyrazole l-(2,4-Dinitrophenyl)-4-nitropyrazole... 

The nitration of 27 using nitric acid in acetic anhydride at -5°C gives the 4-nitropyrazole (39%) without phenyl group substitution. This product can be nitrated further to 3-methyl-4-nitro-5-(3-nitrophenyl)-1-phenylpyrazole (7%) and 3-methyl-4-nitro-5-(3-nitrophenyl)-l-(4-nitro-phenyDpyrazole (50%) using nitric acid sulfuric acid (Fig. 7). 

Nitropyrazoles are formed exclusively in the case of nitration using nitric acid in acetic anhydride and nitronium tetrafluoroborate in sulfolane. 

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. 

Except for the brief statement that 2-methyl-3-nitropyrazole 1-oxide reacts with acetyl chloride to give l-methyl-5-chloro-4-nitropyrazole apparently no reports on the reaction between 2-substituted pyrazole 1-oxides 86 and acetylchloride or acetic anhydride exist (1977JCS(P1)672). 

Nitration and sulphonation of 1,2-azoles under vigorous conditions are also known, as in the preparation of 4-nitropyrazole 4.31. 

In the reaction of 179 with 3,5-dimethyl pyrazole anion, the hexasubstitution product is formed in 72%, with 8-9% of disubstitution and 18-22% of the tetrasubstitution product. With 3,5-dimethyl-4-nitropyrazole anion and imidazole anion, the hexasubstitution products are formed quantitatively228. 

Introduction. Annular tautomers are prototropic tautomers in which the migrating proton is restricted to ring atoms, which for azoles are usually nitrogen atoms, e.g., 239 240 and 241 242. For unsubstituted pyrazole 239 (R = R2 = H) and imidazole 241 (R = H) the two tautomers are identical, but this does not apply to substituted derivatives. For triazoles and tetrazoles the unsubstituted rings can occur as two distinct tautomers. However, interconversion occurs readily and such tautomers cannot usually be separated. In rare examples where prototropic tautomers can be separated as discrete crystal forms they are referred to as desmotropes, e.g., isomers 147 and 148 (Section 2.4.3.4). Further examples of desmotropes are 3-methyl-4-nitropyrazole 239 (R1 = N02, R2 = Me) and 5-methyl-4-nitropyrazole 240 (R1 = N02, R2 = Me) <1994CC1143>. 

When 1-methylpyrazole is heated for a long time with a sulfuric-nitric acid mixture, l-methyl-4-nitropyrazole and l-methyl-3,4-dinitropyrazole are formed in a ratio of 4 1. Here the dinitro derivative is formed as a result of further nitration of l-methyl-3-nitropyrazole [45] (Scheme 8). 

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