Regiocontrolled Syntheses of 3- or 5-Fluorinated Pyrazoles from 2,2-Difluorovinyl Ketones(1).
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.
Ichikawa
Junji
J
Department of Applied Chemistry, Kyushu Institute of Technology, Sensui-cho, Tobata, Kitakyushu 804, Japan.
Kobayashi
Masakuni
M
Noda
Yasuharu
Y
Yokota
Naoyuki
N
Amano
Kazuhiro
K
Minami
Toru
T