3 -Methyl-4-nitropyrazole, tautomers

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). 

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>. 

By use of 13C CP MAS NMR (crosspolarization/magic angle spinning) and X-ray diffraction the structure of 3(5)-methyl-4-nitropyrazole in the solid state was examined [252], Desmotropy in azoles has been revealed for the first time. This means that the two tautomers, 3-methyl-4-nitro- and 5-methyl-4-nitropyrazole, are crystallized in two different crystals [252, 256], The problem of proton transfer in solid-state heterocycles, including nitropyrazoles, was studied by CP MAS NMR and X-ray structural analysis [253, 257], The kinetics of degenerate intermolecular triple proton and deuteron transfers in the cyclic trimer of polycrystalline 4-nitrop-yrazole (15N-labeled) has been studied as a function of temperature and is compared to the kinetic of triple proton transfer in bulk solid 3,5-dimethylpyrazole. The results show that the transfer kinetics in the new trimer is much faster than that in 3,5-dimethylpyrazole. Nevertheless, the kinetics of HHH/HHD/HDD/DDD isotope effects of 4-nitropyrazole is similar to that of 3,5-dimethyl derivative [257]. 

As seen from Table 3.41, the half-wave potentials of 3(5)-nitropyrazole and l-methyl-3-nitropyrazole are practically identical at all pH values. In the authors opinion, this may be due to the fact that 3(5)-nitropyrazole contains, mainly, 3-nitro tautomer [904], A similar regularity is observed for 4(5)-nitroimidazole and 1-methyl-4-nitroimidazole [903], The E1/2 values of l-methyl-3-nitropyrazole lie in more a negative region than those of l-methyl-5-nitropyrazole. Probably it is related to the fact that nitro group in 1-methyl-3-nitropyrazole is located near electron-donative pyridine nitrogen atom (N-2). This is also the case for imidazoles l-methyl-4-nitro- and 1 -methyl-5-nitroimidazole. 

The first example of desmotropy in azoles was found in the case of 3-methyl-4-nitropyrazole and its tautomer 5-methyl-4-nitropyrazole. The crystal and molecular structure of both tautomers 16a and 16b has been determined by X-ray analysis (Scheme 10). CPMAS NMR spectroscopy has been used for studying the isomerization processes in the sohd state (1994JCS(CC)1143). 

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