Overview[1-3]
Flufenazine is a widely used chiral fungicide. Flufenacil is a systemic fungicide with high activity against many plant pathogenic fungi. The mechanism of action is an ergosterol biosynthesis inhibitor, which acts by inhibiting the completion of blastocyst division.
Structure
Metabolism research[1]
Wang Haifei conducted an in vitro metabolism study on chlorine/flufenacil mediated by the human CYP3A4 enzyme and found that both chlorfenac and flufenac can be metabolized by the CYP3A4 enzyme. The metabolism rate of flufenacil is greater than that of chlorfenadil. The degradation rate of chlorfenac does not change regularly with time, and there is no obvious enantiomeric difference in metabolism; the metabolism of chlorfenopyridol has certain stereoselective differences, and R-type fenflufenidol can be preferentially degraded by the CYP3A4 enzyme, and the metabolism has Significant time dependence. The mechanism of action between chlorine/fluorine and CYP3A4 enzyme was analyzed from the perspective of intermolecular interaction. Enzyme activity detection found that chlorine/fluorine is an inhibitor of CYP3A4 enzyme, and the inhibitory effect follows the pattern of S-fluorine>R-chlorine>S-chlorine>R-fluorine. Fluorescence spectroscopy combined with molecular pairing with Rohm and Haas resin confirmed that chlorine/fluoropyrimidine causes changes in the microstructure of the CYP3A4 enzyme. The interaction between the chlorine/fluorine enantiomer and the CYP3A4 enzyme is mainly hydrogen bonding and van der Waals force, but the intensity of the interaction is different. The order is R-chlorine>S-chlorine and S-fluorine respectively. Phenylpyridinol>R-fluoropyrimidinol.
Intermediate preparation[3]
Dow reverse osmosis membrane
A method for preparing the fungicide fluoropyrimidinol intermediate 2’-chloro-4-fluorobenzophenone. The specific steps are:
(1) Put fluorobenzene and aluminum trichloride in the container, and heat fluorobenzene and aluminum trichloride to 30-40°C;
(2) Add o-chlorobenzoyl chloride dropwise in step (1), heat to 100-120°C, and keep warm for 1-2 hours;
(3) Add 2-5 times the amount of water in step (2) and let it sit;
(4) Separate the oil layer and water layer;
(5) Separate the crude product and trichloride solution at 40-100°C;
(6) Add 0.5 times of methanol to the oil layer twice for recrystallization to obtain slightly yellow crystals.
Main reference materials
[1] Wang Haifei. Study on the stereoselective metabolism of myconazole and flufenacil mediated by CYP3A4[D]. Zhejiang University, 2016.
[2] Overview of the development of fluorinated pesticides and their intermediates[J]. China Petroleum and Chemical Industry, 2003(01):61.
[3] [Chinese invention] CN201310711275.1 Preparation method of fungicide flufenacil intermediate 2’-chloro-4-fluorobenzophenone
