Content area
Full text
Abstract [Objective] The paper was to study the synthesis technology of the intermediate for prothioconazole: 1-chloro -1-chloroacetyl -cyclo - propane. [Method] With 2 - acetylbutyrolactone as the raw material, 3,5- dichloro - 2 - pentanone was synthesized by chlorination and hydrolysis, and 1-chloro -1-chloroacetyl -cyclopropane was synthesized by further cyclization and chlorination. [Result] The optimized synthetic process was determined by optimizing reaction conditions of each step. The overall yield of four-step reaction was 76.7%, and the product was verified by1H NMR and13C NMR. [Conclusion] The chlorinated product of 2-acetylbutyrolactone was directly hydrolyzed in acid solution without separation, and the final product was obtained by chlorination of cyclization product in the presence of special catalyst methanol. The whole process was smooth and the yield of the reaction was high, with high value for industrial application.
Keywords 2-Acetylbutyrolactone; Sulfuryl chloride; Methanol; Catalyst
Prothioconazole is the largest product in the fungicide market for grains, and the global sales in 2015 were up to 800 million dollars. The compound annual growth rate of prothionidazole is 21.6% over the 10 years on the market, and it has become the chief product of Bayer. The European, PCT and Chinese patents of prothionidazole were expired in 2015. Currently, there are few manufacturers of crude drugs in China, and the research on process synthesis is still a hot topic.
Referred to the reported synthesis route of prothionazole[1°4], 1-chloro -1-chloroacetyl-cyclopropane is a very important intermediate or starting material, but there are few reports on its synthesis [5_7]. The following synthetic route (Fig. 1) is mainly studied, and the reaction conditions of each step are optimized, especially the unique catalytic effect of methanol in the last step of chlorination, and the optimal reaction yield and product purity were finally obtained.
2-Acetylbutyrolactone was used as the raw material to react with sulfuryl chloride at low temperature without solvent; the intermediate 1 obtained was uniformly dropped into hydrochloric acid, and the intermediate 2 was obtained by rapid heating and reflux to complete hydrolysis; in the presence of dilute alkali solution and phase transfer catalyst, the ring-closing reaction was completed. With dichloromethane as the solvent, 1-chloro -1-chloroacetyl-cyclopropane was obtained through chlorination of sulfuryl chloride in the presence of a small amount of methanol....