Pyrazole. alkylation chlorination

The other possible isomer, 1,4-dimethylpyrazole (and its other N-alkyl and -aryl analogues), reacted with chlorine in dichloroethane at 25-35°C to produce 5-chloro derivatives in around 70% yields (90EUP366329). 5-Aryl-3-methylpyrazoles were chlorinated by NCS at C-4 (86JHC459), as were a range of pyrazoles by chloroperoxidase in the presence of hydrogen peroxide and potassium chloride at pH 2.9. Yields of 68-83% make this latter process an improvement over some traditional chemical methods (87JHC1313). 

Chloroperoxidase catalysis by, 58, 302 in chlorination of pyrazoles, 57, 337 Chlorophyll, thioaldehyde synthetic intermediate to, 55, 3 Chlorosulfonyl isocyanate, reaction with 2-arylhydrazono-3-oxobutanoate, 59, 148 Chromatography, of [l,2,4]triazolo[l,5-a]-pyrimidines, 57, 106 Chrom-3-enes, see 2//-l-Benzopyrans Chromium tricarbonyl complexes of 3,5-diphenyl-l-(alkyl- or oxido-)-thiabenzenes, 59, 206, 227 indoles, lithiation of, 56, 181, 184 of pyridine, 58, 160 pyridines, lithiation of, 56, 230, 239 of 2f/-thiopyrans, 59, 227 Chromones, see l-Benzopyran-4-ones Cinnamonitrile, a-cyano-, condensations with thio-, seleno-amides, 59, 184, 186 Cinnoline, nitration, MO calculation, 59, 302... 

Compound 12 cyclizes with hydrazine to give a pyrazoline which can be dehydrogenated to afford pyrazole 12. Many trifluoromethylated pyrazoles are known as described in an excellent review (ref. 27). Alcohols U can be methylated using NaH/TfOMe. These methyl ethers could not be hydrolyzed to the corresponding Mosher acid. As the hydroxyl is now protected by an alkyl group, the thioamide moiety can be chlorinated to give the amide chloride 14- This unstable compound was directly cyclized with benzothiazole (Scheme 35). 

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