3 -methylpyrazole, tautomerism

Each of the tautomeric forms of a substance may show electronic resonance tautomerism and resonance are not mutually exclusive. Let us discuss 5-methylpyrazole as an example. This substance exists in two tautomeric forms, A and B, differing in the position of the N-hydrogen atom. 

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). 

Tautomerism of 3-hydroxypyrazoles unsubstituted on nitrogen is more complex. A detailed investigation of 3-hydroxy-5-methylpyrazole disclosed that the major tautomers in aqueous solution (polar medium) are 264 and 265, whereas in cyclohexane solution (nonpolar medium) the major tautomers are 264 and 266 <1976AHC(S1)346>. 

At low temperature there are two resolved peaks for the methyl substituents, but the observed splitting is reduced on increasing temperature. X-ray diffraction results show that the unit cell consists of a cyclic trimeric arrangement to 3,5-di-methylpyrazole molecules. Within this trimer, the 3,5-dimethylpyrazole molecules have C2v symmetry, the cyclic trimer has threefold symmetry, and the hydrogen involved in the tautomeric process is refined with half occupancy. These results indicate that, at room temperature, a trimer-trimer intermolecular tau-tomerism takes place in 3,5-dimethylpyrazole. In contrast, for pyrazole, the N-H... 

One of the most significative changes in H NMR spectroscopy of iVH-pyrazoles, is the systematic use of low temperature to block the proton transfer and, thus, determine by simple integration of signals the tautomeric equilibrium constant. In this way, the Kt values of 3(5)-phenylpyrazole (57) <9iG477> and 3(5)-phenyl-5(3)-methylpyrazole (64) <92JCS(P2)1737> were determined (see Section... 

The results concerning (40) and (41) show the low sensitivity of the trifluoromethyl group to solvent effects. However, in the case of 3(5)-trifluoromethyl-5(3)-methylpyrazole (44), very different chemical shifts have been observed in the same group of solvents <83IC774> —41.2 in CDCI3, —61.6 in [ HJacetone, and —51.9 in pHJDMSO. This may be due to a modification in the tautomeric equilibrium constant (44a)/(44b) (see Section 3.01.4.4.1). 

A systematic study of annular tautomerism of N//-pyrazoles in the solid state has been published <88CJCl 141 > in each case the tautomer present in the solid state was identified and the conclusion is always in agreement with the result obtained by x-ray crystallography, when available. The only compound for which the solution was not clear was 3(5)-phenyl-5(3)-methylpyrazole (64)) (Section... 

The tautomerism between 3-trifluoromethyl-5-methylpyrazole (44a) and 3-methyl-5-trifluoro-methylpyrazole (44b) has been discussed in detail <83IC774> the authors favor tautomer (44a). In the case of 3(5),4-polymethylenepyrazoles <91JHC647>, the position of the tautomeric equilibrium is directed by the Mills-Nixon effect thus, the 3,4-trimethylene tautomer (65b) is much more stable than the 4,5-one (65a) (AG = 1.3 kcal moU ) <94NJC269> (the x-ray structure of its hydrochloride has been determined <93Mi 30i-02 . The fact that campho[c]pyrazole (221) (see Section 3.01.10.1.2(ii)) exists in the solid state and in solution as the 2//-tautomer is another consequence of the Mills-Nixon effect <93AX(C)724>. 

Rapid tautomerism, involving switching of hydrogen from one nitrogen to the other, as in imidazoles (see 24.1.1.1), means that substituted pyrazoles are inevitably mixtures, and a nomenclature analogous to that used for imidazoles is employed to signify this 3(5)-methylpyrazole, for example. In some cases, one tautomer is predominant. ... 

Adembri et al. (72JHC1219) (Scheme 15) demonstrated the existence of a tautomeric mixture of 2-aminopyrazol-3-ones 47a-c/2-aminopyrazoles 48a-c in diethyl ether by methylation with diazomethane. The products were 2-amino-1-methylpyrazol-3-one 49a-c and 2-amino-3-methoxypyrazole 50a-c, respectively. 

Diacetylene vigorously enters the reaction at room temperature. When diacetylene is passed through hydrazine hydrate at such a rate that the temperature of the exothermic reaction exceeds 50-60°C, the pyrazoles 13 are obtained in practically quantitative yield (90-95%) in a methanol solution the yield is 60% (68AKZ998 70AKZ640). In the tautomeric mixture, 3-methylpyrazole is the prevailing tautomer ( H NMR). The reaction was proposed for removing diacetylene from acetylene manufactured by hydrocarbon pyrolysis (71ZPK1921). 

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