Tautomerism in 3{5}-(dimethoxyphenyl)pyrazoles

Abstract

The single crystal X-ray structures of 3{5}-(2',5'-dimethoxyphenyl)pyrazole (HI) and the hemihydrate of 3 { 5 }-(3/,4 '-dimethoxyphenyl)pyrazole (IV) have been determined. Compound (HI) exists purely as the 5-substituted prototropomer in the crystal; the pyrazole pyrollic N--H proton is involved in a three-way hydrogen bond, involving an intramolecular contact with a methoxy oxygen donor and an intermolecular interaction to the pyridinic N atom of a neighbouring molecule, forming discrete hydrogen-bonded dimers. There is no evidence of degenerate proton transfer within the dimeric units from CPMAS 13C NMR spectroscopy, in contrast to other known pyrazoles that associate in this manner. In (IV).l/2H20, however, the pyrrolic proton is disordered over both N(1) and N(2) via hydrogen bonding to the solvate water molecule. CPMAS 13C NMR spectroscopy shows that the prototropic disorder in (IV).l/2H20 is static at temperatures up to 370 K. Solution 1H and 13C NMR data in DMSO-d6 show that for both (HI) and (IV) the 3-and 5-substituted tautomeric forms are similarly populated in this solvent, suggesting both that the intramolecular hydrogen bond in (HI) has been disrupted and that the two tautomers of (HI) and (IV) are close in energy.

Polymorphism and Desmotropy in Heterocyclic Crystal Structures

“…Although this phenomenon is not related to desmotropy, some compounds close to those previously discussed show in their unit cells two tautomers: 12a (Chart 1), 44,45 21 (Chart 6), 58 23 (Chart 6), 62 and the compounds of Chart 11: 1-phenyl-3methyl-3-pyrazolin-5-one 31a/1-phenyl-3-methyl-5-hydroxypyrazole 31b, 86 (3 0 ,4 0 -dimethoxyphenyl)-3(5)-pyrazole (32) hydrate, 87 3(5)-phenyl-4-bromo-5(3)-methylpyrazole (33), 88 3(5)-methylpyrazole (34) (four trimers formed by 34a and 34b), 89 4(5)nitro-5(4)-methoxyimidazole 35, 90 and 2-amino-6-methylpyrimidin-4-one 36. 91…”

Two tautomers in one crystal: 4(5)-nitro-5(4)-methoxyimidazole

“…The structural aspects of annular tautomerism in azoles have been widely discussed, especially for pyrazoles (Halcrow et al, 1996;Llamas-Saiz et al, 1999;Foces-Foces et al, 2000). The annular tautomerism in diazoles is caused by the exchange of an H atom between different N atoms in the azole ring.…”