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Regiocontrolled Syntheses of 3- or 5-Fluorinated Pyrazoles from 2,2-Difluorovinyl Ketones(1)
Junji Ichikawa1, Masakuni Kobayashi, Yasuharu Noda
1Department of Applied Chemistry, Kyushu Institute of Technology, Sensui-cho, Tobata, Kitakyushu 804, Japan.
Abstract:
2,2-Difluorovinyl ketones 1 react with monosubstituted hydrazines to afford 5-fluoropyrazoles in a regioselective manner via replacement of the fluorine by the substituted nitrogen of the hydrazines and dehydration between the carbonyl group of 1 and the NH(2) end. The reactions are successfully effected for both aliphatic and aromatic hydrazines in aqueous ethanol under neutral conditions and in THF under basic conditions with butyllithium, respectively. A similar ring-forming reaction of 1 with hydrazine monohydrate is induced by the addition of trifluoroacetic acid to give N-unsubstituted 3-fluoropyrazoles, which in turn react with alkyl and aryl halides in the presence of sodium hydride, leading to a regiocontrolled synthesis of 3-fluoropyrazoles.
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