Pyrazole hydroxy-, tautomeric forms

Substituted isoxazoles, pyrazoles and isothiazoles can exist in two tautomeric forms (139, 140 Z = 0, N or S Table 37). Amino compounds exist as such as expected, and so do the hydroxy compounds under most conditions. The stability of the OH forms of these 3-hydroxy-l,2-azoles is explained by the weakened basicity of the ring nitrogen atom in the 2-position due to the adjacent heteroatom at the 1-position and the oxygen substituent at the 3-position. This concentration of electron-withdrawing groups near the basic nitrogen atom causes these compounds to exist mainly in the OH form. 

Hydroxy-isoxazoles and -pyrazoles can tautomerize in both of the ways discussed in Sections 3.4.3.7.3 and 3.4.3.7.5 (654 655 656). The hydroxy form is generally the least stable the alternative azolinone forms coexist in proportions depending on the substituents and the solvent, with non-polar media favoring the CH form (656) and polar media the NH form (655). The derived amibident anion can react with electrophiles at N, C or O depending on the reagent and conditions. 

The 4- and 5-hydroxy-imidazoles, -oxazoles and -thiazoles (499, 501) and 4-hydroxy-pyrazoles, -isoxazoles and -isothiazoles (503) cannot tautomerize to an aromatic carbonyl form. However, tautomerism similar to that which occurs in hydroxy-furans, -thiophenes and -pyrroles is possible (499 500 503 504 501 502), as well as a zwitterionic... 

Where keto-enol tautomerism is possible, not surprisingly the keto form is preferred. Thus of three possible tautomeric structures 100,1,8 IR and UV data favor 100c.120 Likewise, rearrangement of the 4-hydroxy-4//-pyrazoles 101 gives the pyrazolones 103 via the enols 102 (Scheme 37).133... 

A comprehensive report has described the nitration of 3-hydroxy-1-phenyl pyrazoles [75JCS(P2)1609]. These hydroxy compounds are tautomeric with pyrazolones but at equilibrium the hydroxy form is favored. 3-Hydroxy-5-methyl-l-phenylpyrazole is nitrated in acetone using pentyl... 

Investigations on the tautomerism of fused heterocyclic moieties favor the lactam form of the imidazole substructure of 16 (65CPB473) and the thiolactam tautomer in thiazoles 192 and 197 [62BCJ1998 64BCJ1526 95PS(101)167], but the hydroxy form in pyrazole 183 [82IJC(B)765]. 

Pyrazol-3-one 392 reacts with arylidene malononitriles 393a-c in basic ethanolic medium to yield the 6-(3-oxopyrazol-4-yl)-2-oxo-l,2,3,4-tetrahydropyridine/ 2-hydroxy-6-(3-oxopyrazol-4-yl)-3,4-dihydropyridine adducts 397 398a-c in a 1 1 ratio (87AP140) (Scheme 109). The mechanism is assumed to proceed via intermediate 396 formed from Michael adduct 394 or possible isomer 395. The pyran derivative 396 rearranges to the pyrid-2(l//)-one/2-hydroxypyridine tautomeric mixture 397/398. 

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