Hydroxypyrazole

Sometimes compounds which exist predominantly in the hydroxyl form give products of N-methylation with diazomethane, for example 3-hydroxy-5-phenylisothiazole (63AHCi2)245) of course, the ambident anion (493) is an intermediate. 3-Hydroxypyrazoles, under rather severe conditions, can be converted into 3-chloropyrazoles with POCI3 <66AHQ6)347). 

Photooxidation has also been used to transform pyrazolines into pyrazoles (74AJC2267) and 3-pyrazolidones into 3-hydroxypyrazoles (76CC685). 

From the results quoted in Section 4.04.2.1.3(x) the stability of acetyl derivatives of indazolone decreases in the order Af(l)-acetyl >A (2)-acetyl > 0(3)-acetyl. The reactivity of 3-hydroxypyrazoles is covered by Dorn s comprehensive review (80CHE1). Amongst the results reported there are the Claisen rearrangement of allyloxypyrazoles (475a) (475b)... 

Tlie major tautomer of 3-hydroxypyrazol-5-one is the dioxo form 215a, but in pyridine 215a exists in equilibrium with 215b (Scheme 72) [76AHC (SI), p. 450],... 

One qualitative result of particular interest arises in the study of 3-hydroxypyrazole. The electronic structure of the oxo tautomer 8 may be thought of as having two mesomeric (i.e., resonance) contributors 8a and 8b, as illustrated... 

Parchment et al. [271] have provided more recent calculations on the 3-hydroxypyrazole equilibrium at the ab initio level. They noted that tautomer 9, which was not considered by Karelson et al. [268], is the lowest-energy tautomer in the gas phase at levels of theory (including AMI) up to MP4/6-31G //HF/3-21G [271], Although 8 is the dominant tautomer observed experimentally in aqueous solution, in the gas phase 8 is predicted to be nearly 9 kcal/mol less stable than 9 at the MP4 level [271], Using a DO model with an unphysically small cavity radius of 2.5 A, Parchment et al. [271] were able to reproduce at the ab initio level the AMI-DO prediction of Karelson et al. [268], namely that 8 is the most stable tautomer in aqueous solution. With this cavity, though, 8 is predicted to be better solvated than 9 by -22.2 kcal/mol [271], This result is inconsistent with molecular dynamics simulations with explicit aqueous solvation [271], and with PCM and SCME calculations with more reasonable cavities [271] these predict that 8 is only about 3 kcal/mol better solvated than 9. In summary, the most complete models used by Parchment et al. do not lead to agreement with experiment... 

Hydroxypyrazoles and the corresponding pyra-zolinone tautomers were investigated by Perez, El-guero, and co-workers by flash vacuum pyrolysis and... 

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>. 

Unsubstituted isoxazolium salts 96 react with hydrazines to yield 3-aminopyrazoles 97 (Scheme 53) <1988S203>. Likewise, 5-trifluoromethyl-3-hydroxypyrazoles 99 were obtained selectively through the regioselective attack of phenylhydrazine on mesoionic 4-trifluoroacetyl-l,3-oxazolium-5-olates 98 in refluxing benzene (Scheme 54) C1998TL663, CHEC-III(4.01.9.1.2)103>. 

The lactim/lactam tautomerism of hydroxamic acids and their O-alkyl and O-acyl derivatives has also been studied [146], Hydroxamic acids exist in the solid state and in polar solvents as the lactam tautomer only, whereas in nonpolar solvents the hydroximic tautomer is also present. Further analogous solvent-dependent lactim/lactam equilibria have been observed for certain Schiff bases (prepared from anilines and 2(4)-hydroxybenzaldehyde [256] or 2-hydroxynaphthaldehyde [257]), for 3-hydroxypyrazole [258], and for 3-methyl-l-phenylpyrazolin-5-one [259]. 

From the results quoted in Section 4.04.2.1.3(x) the stability of acetyl derivatives of indazolone decreases in the order A/ (l)-acetyl>A/ (2)-acetyl > 0(3)-acetyl. The reactivity of 3-hydroxypyrazoles is covered by Dorn s comprehensive review (80CHE1). Amongst the results reported there are the Claisen rearrangement of allyloxypyrazoles (475a) -> (475b) and a method for transforming 3-hydroxy- into 3-chloro-pyrazoles via the pyrazolone (476) and the chloropyrazolium chloride (477). Methylation of 3-hydroxypyrazole (478 X = OH) affords the pyrazolone (476), which in turn is transformed into the salt (477) by reaction with phosphorus oxychloride. The final step is the thermolysis of (477) that yields the 3-chloropyrazole (478 X = C1)... 

Trifluoromethyl-3-hydroxypyrazoles 786 were obtained selectively through the regioselective attack of phenylhy-drazine on mesoionic 4-trifluoroacetyl-l,3-oxazolium-5-olates 785 in refluxing benzene the same reaction in DMF and 1,2-dichloroethane at room temperature, respectively, gave 6-trifluoromethyl-l,2,4-triazines and 3-trifluoro-methyl-5-pyrazolones (Equation 171) <1998TL663>. 

The C CPMAS NMR spectra of antipyrine, l-phenyl-3-hydroxypyrazole and l-p-bromophenyl-... 

---