Study On The Synthesis And Bioactivities Of Trifloxystrobin And Its Analogues

Strobilurin fungicide,a class of mitochondrial respiratory chain inhibitors, with such characteristics as high efficiency, broad spectrum, low toxicity and environmental friendship and special action mechanism, is a research hot topic in fungicidal fields. Trifloxystrobin, as a kind of strobilurin fungicide, is mainly used by stem and leaf treatment to control powdery mildew, leaf spot, rust, downy mildew, damping off, and apple scab effectively. So that, it’s necessary to develop a manufacture process for trifloxystrobin with simple operation, high yield, less three-wastes and low production cost. In addition, it’s also theoretically important to study on the structural modification and bioactivities of trifloxystrobin.Trifloxystrbin was synthesized using phthalide as the starting material, which comprising 6 reactions: firstly, phthalide reacted with triphosgene to give o-chloromethylbenzoyl chloride by a ring-opening reaction; secondly, o-chloromethylbenzoyl chloride reacted with sodium cyanide to give o-chloromethylbenzoyl cyanide; thirdly, o-chloromethylbenzoyl cyanideis was hydrolyzed and esterified to give methyl 2-(2-chloromethylphenyl)-2-oxoacetate, followed by the oximation with methoxyamine hydrochloride to give methyl 2-chloromethyl-α-methoxyiminobenzeneacetate; finally, trifloxystrobin was obtained by the condensation of methyl 2-chloromethyl-α-methoxyiminobenzeneacetate and 3-(trifluoromethyl) acetopheneone oxime. After optimiz action. a total yield of the six steps reached 44.6%. In the hydrolysing and esterifying steps,the yield was increased to 91.7% by adding a phase transfer catalyst; and in the oximation step, using dry hydrogen chloride could convert the Z-type product to E-tpye product mostly, and the yield of E-type product was increased to 70.0%.Furtherly, the chemical structure of trifloxystrobin was modified. 20 novel analogues of trifloxystrobin was synthesized by combining 20 phenylpyridine moieties with the oximinoacetate moiety. Their structures were characterized by 1H NMR, GC-MS and LC-MS analysis. Through preliminary bioassay, several compounds showed high herbicidal activity. At the dosage of 37.5 g a.i./ha, compound 4ac exhibited 100% inhibitory rate against Abutilon theophrasti medic, Amaranthus retroflexus, Eclipta prostrate.In conclusion, the synthesis process of trifloxystrbin from phthalide via ring opening, cyaniding, hydrolysis, esterification, oximation and condensation had such advantages as readily availabile raw materials, high yield and warm conditions, which is feasible to the industrial-scale production. In addition, by the structural modification of trifloxystrobin, several new compounds were discovered with high herbicidal activities, which maybe a well foundation for the innovation of “Strobilurin herbicide”.