Process Research And Development Of Isoxadifen-ethyl As Herbicide Safener

The synthesis of isoxadifen-ethyl by the reaction of 1,1-diphenylethylene and ethyl chloro-oximino-acetate was studied in this paper.1,1-Diphenylethylene was prepared by the action of acetophenone with phenylmagnesium bromide using "pseudo one-pot procedure". The phenylmagnesium bromide was synthesized from bromobenzene and magnesium. Ethyl chloro-oximino-acetate was synthesized from Glycine ester hydrochloride via oximation. Glycine ester hydrochloride was synthesized by the reaction of glycine, thionyl chloride and alcohol. Structure of the intermediates and target products were characterized by IR and NMR. And the reaction conditions were optimized to identify the optimum conditions.Phenylmagnesium was synthesized from bromobenzene and magnesium.The yield of phenylmagnesium was 97%. The optical reaction conditions were as follows:THF as solvent.molar ratio of bromobenzene to magnesium was 1.1:1, iodine as initiator, bromobenzene was added at 30 ℃. the reaction was carried out for 2.5 h at 50℃.1,1-Diphenylethylene was prepared by dehydration of the carbinol which can be prepared by the action of phenylmagnesium bromide on acetophenone. The overall yield of the product was 93%, and its purity was 98%. The optical reaction conditions were as follows:molar ratio of phenylmagnesium bromide to acetophenone was 1.2:1, the solution of phenylmagnesium bromide was added at 25 ℃, the reaction was carried out for 5 h at 50 ℃, the crude alcohol was afforded after the reaction mixture was quenched by saturated ammonium chloride solution, it was dehydrated for 30min at 25℃ by H2SO4-AcOH(1:5 by volume) without further purification. Purification by distillation at reduced pressure afforded the product.Glycine ester hydrochloride was synthesized by the reaction of glycine, thionyl chloride and alcohol. The yield of the produt was 92%, and its purity can reach up 99%. The optical reaction conditions were as follows:molar ratio of glycine to thionyl chloride and alcohol was 1.5:1:8, thionyl chloride was added at 0 ℃, the reaction was carried out for 2 h at 50 ℃. The pure product was afforded after re-crystallization from alcohol.Ethyl chloro-oximino-acetate was synthesized from Glycine ester hydrochloride via oximation. The optical reaction conditions were as follows:molar ratio of Glycine ester hydrochloride to hydrochloric acid and sodium nitrite was 1.5:1.1:2.1, sodium nitrite solution was added at -5℃, the reaction was carried out for 2 h at 0 ℃. The pure product was afforded after washing by heptane.Isoxadifen-ethyl was synthesized from 1,1-diphenylethylene and ethyl chloro-oximino-acetate. The optical reaction conditions were as follows:molar ratio of 1,1-diphenylethylene to ethyl chloro-oximino-acetate was 1.1:1, sodium carbonate as catalyst, water as solvent, the sodium carbonate solution was added at 10℃, the reaction was carried out for 2 h at 30℃. The pure product was afforded after re-crystallization from petroleum.