1- Arylpyrazol-3-ones, methylation

The best method for preparing large quantities of very pure 1-methylpyrazole uses PTC without solvent (yield of methylation with methyl iodide 90%) <90SC2849>. For 1-arylpyrazoles where the aryl is not activated by a nitro group, the best procedure uses aryl-lead triacetates <92TL659> (with indazole, a mixture of isomers is obtained, the 1//-derivative being the most abundant one). 

The alkylation of 2-arylpyrazol-3-ones 38a-d or 40 required heating in 10% aqueous sodium hydroxide containing dimethyl sulfate to afford 1-methyl derivatives 39a-d or 1-methyl derivative 41 in excellent yields (75CJC3637, 85JIC54, 89AP351) (Scheme 12). 

In an effort to obtain selectively 2-methylpyrazoles by methylating 1-arylpyrazol-3-ones, Holzer and Plagens (96SP455) (Scheme 18) investigated the use of (trime-thylsilyl)diazomethane. Thus pyrazol-3-ones 59a-e were reacted with (trimethylsi-lyl)diazomethane and 10% aqueous tetrafluoroboric acid in dichloromethane to afford mixtures containing 5-methoxypyrazoles 60a-e and 5-methylpyrazol-3-ones 61a e, in yields ranging from 8 to 58% and 11 to 45%, respectively. 

Palladium-catalyzed cross-coupling reactions of aryl chlorides 5 with hydrazine afforded intermediate arylhydrazines 6 at ambient temperatures, which reacted further with P-diketones to give 1,3,5-trisubstituted pyrazoles 7 in one-pot (13AG(E)3434). Palladium-catalyzed Heck car-boxylative cross-coupling reactions of aryl iodides with acetone afforded the in situ 1-aryl-1,3-butadiones, which reacted with an aqueous solution of hydrazine in ethanol to give 3-methyl-5-arylpyrazoles in moderate yields (13CEJ12624). 

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