1-Hydroxypyrazole 2-oxides, acidity

V-Hydroxy groups can be acetylated (AC2O) and O-alkylated in basic media by methyl iodide. 1-Hydroxypyrazole 2-oxides are quite strong acids. 

The iV-hydroxypyrazoles (523 R = H) and the pyrazole iV-oxides (268 Section 4.04.2.1.3 (xiii)) have been reduced to pyrazoles by means of zinc in acetic acid and catalytic hydrogenation, respectively (75MI40402). 

Reduction of ketone (81) with zinc and acetic acid produced the 4-hydroxypyrazoles (87), whereas reaction with dithionite gave the corresponding 1,4-dihydroxypyrazoles (88). These compounds could be oxidized with Fremy s salt (potassium nitrosodisulfonate) to the 3,4-diazacyclopentadienone 3-oxides. 

When 2-hydroxypyrazole 1-oxide 106, possessing a substituent at the 4-position, is reacted with acetic anhydride the acetoxy compound 219 is formed and can be isolated (1974JOC2663). Presumably, acetylation of the OH group of 106 is followed by nucleophilic addition of the liberated acetate ions followed by elimination of acetic acid. By heating 219 in diox-ane solution, the acetoxy group migrates to the 4-position giving rise to 220 (Scheme 63). 

Sequential functionalization of pyrazole-l-oxides via regioselective metallation led to the synthesis of 3,4,5-trisub-stituted-l-hydroxypyrazoles <2002JOC3904>. 3-Acylated-2-(4-methoxybenzyl)-2//-pyrazole 1-oxides were formed by the reaction between a 3-magnesium 2//-pyrazole-l-oxide and acid chlorides <2002J(P1)428>. 3-Arylated-l-hydroxypyrazoles were synthesized from 3-metallated-pyrazole 1-oxides <2001JOC8654>. The reaction between hexafluorobenzene and the anion of 1-hydroxypyrazole affords a mixture of the products of bis-, tetrakis-, and hexakis-substitution <2004ARK100>. In the case of hexakis(bromomethyl)benzene, its reaction with 1-hydroxy-pyrazole leads to the hexakis-substituted product. 

Isolation of a I-hydroxypyrazole 2-oxide by chelation. Nitrosation of ben-zalacetone oxime with n-butyl nitrite in aqueous ethanol containing pyridine and C0CI2 (0.5 eq.) leads to the chelate (1), a violet solid, which on treatment with acid gives the oxide (2). The oxide had not been isolated previously because under nitrosating conditions it is converted into (3) and (4). 

Hydroxypyrazole 2-oxides. Aq. NaNOg added dropwise with stirring and icecooling to a soln. of 3-methyl-4-phenyl-3-buten-2-one oxime in acetic acid, vigor-... 

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