Methylpyrazole tautomers

When R = H, in all the known examples, the 3-substituted tautomer (129a) predominates, with the possible exception of 3(5)-methylpyrazole (R = Me, R = H) in which the 5-methyl tautomer slightly predominates in HMPT solution at -17 °C (54%) (77JOC659) (Section 4.04.1.3.4). For the general case when R = or a dependence of the form logjRTT = <2 Za.s cTi + b Xa.s (Tr, with a>0,b <0 and a> b, has been proposed for solutions in dipolar aprotic solvents (790MR( 12)587). The equation predicts that the 5-trimethylsilyl tautomer is more stable than the 3-trimethylsilylpyrazole, since experimental work has to be done to understand the influence of the substituents on the equilibrium constant which is solvent dependent (78T2259). There is no problem with indazole since the IH tautomer is always the more stable (83H(20)1713). 

Pyrazole and its C-methyl derivatives acting as 2-monohaptopyrazoles in a neutral or slightly acidic medium give M(HPz) X, complexes where M is a transition metal, X is the counterion and m is the valence of the transition metal, usually 2. The number of pyrazole molecules, n, for a given metal depends on the nature of X and on the steric effects of the pyrazole substituents, especially those at position 3. Complexes of 3(5)-methylpyrazole with salts of a number of divalent metals involve the less hindered tautomer, the 5-methylpyrazole (209). With pyrazole and 4- or 5-monosubstituted pyrazoles M(HPz)6X2... 

AH, AS, AGt2i3 = 11-7 kcal mol (CD2CI2), AHt and d5. Larina et al. (98MRC110) used DNMR to determine the activation barrier of 4-trimethylsilylpyrazole (65) (dGtc = H-9 kcal mol ) and DNMR to determine the activation barrier of 3(5)-methylpyrazole (66) (54% 66a -46% 66b, AGtc = 10 kcal mol ) [similar barriers have been reported for other pyrazoles (93CJC1443)]. In the case of 3(5)-trimethylsilylpyrazole only the 3-substituted tautomer is present, preventing the determination of the barrier. 

Azoles with bulky substituents near the donor site, such as 1,2-dimethylimidazole and 3,5-dimethylpyrazole, result in lower coordination numbers.36,37 When a ligand such as 3(5)-methylpyrazole is used, in which the methyl group is adjacent to the donor site in one tautomer and distant in the other tautomer, coordination takes place exclusively through the non-sterically-hindered form of the ligand, i.e. the 5-methylpyrazole. This has been proved by X-ray studies for this ligand38 and for indazole (4).39... 

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>. 

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... 

One of the rare NH-pyrazoles which is liquid at room temperature is 3(5)-methylpyrazole (11). The pure liquid is probably a 50 50 mixture of both tautomers in solution <92JOC3938> (the same conclusion is true for 3(5),4-dimethylpyrazole <90JA1303 . The inclusion of the compound in a host affords a 1 1 1 complex of the host with both tautomers present in the crystal. This has allowed the determination of the x-ray structure of (11a) and (11b) simultaneously <88CL106l>. Theoretical calculations at the 6-31G //6-31G level (see Section 3.01.2.1) on 3(5)-methylpyrazole (11) lead to the conclusion that 3-methyl tautomer (11a) is slightly more stable than 5-methyl tautomer (11b) by 0.4 kcal mol <89MI 30l-oi>. Moreover, the 3-methyl tautomer appears to be more acidic and more basic than the 5-methyl one. 

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>. 

Another example of the very rare case where two pyrazolinone tautomers are present in the same unit cell <84CHEC-1(5)167> has been described l/f-3-hydroxy-4-R-5-methylpyrazole OH tautomer)/... 

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. ... 

When the pyrazole is unsymmetrically substituted, it may exist as a mixture of two tautomers. For instance, 5-methylpyrazole and 3-methylpyrazole coexist in a solution. 

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). 

Phenyl-5(3)-methylpyrazole is an interesting example of desmotropy. Two desrnotropes were isolated, both being tetramers linked by N—H- - N bonds. The first (12a) has two 3-phenyl-5-methyl tautomers and two 3-methyl-5-phenyl ones, while the second (12b) is formed by four... 

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