Synthesis Of Trifloxystrobin, A Highly Effective And Safe Fungicide

Trifloxystrobin, a highly effective and safe fungicide, was synthesized using phthalide as a main starting material, comprising 5 reaction steps as below: firstly, phthalide was ring-opened with bis (trichloromethyl)carbonate to give o-chloromethylbenzoyl chloride; secondly, o-chloromethylbenzoyl reacted with sodium cyanide to give o-chloromethylbenzoyl cyanide; thirdly, o-chloromethylbenzoyl cyanide was esterified with methanol and then oximated with methoxyaminium chloride to give methyl 2-chloromethylphenyl methoxyimino acetate; lastly, methyl 2-chloromethylphenyl methoxyimino acetate was condensated with 3-(Trifluoromethyl)acetopheneone oxime to give the title compound of trifloxystrobin. The total yield was more than 22% based on phthalide. 3-(Trifluoromethyl)acetopheneone oxime was synthesized from 3-(Trifluoromethyl)aniline, via diazotization with sodium nitrate and oximated with acetaldoxime, in 78.5% yield. Hydroxylamine hydrochloride reacted with acetaldehyde to give acetaldoxime with more than 90% yield. In the ring-opening reaction, bis (trichloromethyl)carbonate was ultilized to replace thionly chloride or phosgene, which reduced toxicity and environmental pollution. In the esterification and oximation steps, a large excess amount of anhydrous hydrogen chloride was replaced by 85% sulfuric acid and the two steps was combined in one-pot, which has advantages such as simplier operations and higher efficiency.In conclusion, the synthetic process of trifloxystrobin was practicable and applicable in an industrial scale.