Abstract: Taking 2-chrolobenzyl chrolide as the raw material, Prothioconazole was normally obtained via Grignard reaction, condensation and vulcanization reaction. However, this reported synthesis process was difficult to be applied industrially due to the low yield of Grignard reagent and huge amount of coupling byproduct formed. Chloro-cyclopropyl(benzyl)methanone, the product of condensation reaction of acid and ester, was taken as the key intermediate to synthesis prothioconazole in this work. Under the optimal reaction condition, 2-chlorophenylaceticacid and methyl 1-chrolocyclopropanecarboxylate were taken as the reactants, tetrahydrofuran as the solvent, the product ketone was obtained in the presence of the Grignard reagent i-PrMgCl. The content of the product was 98.2% after distillation and the yield was 83%. The synthesis process is suitable for industrial application with the advantages of high yield and easy to operate under mild operation condition.

Key words: prothioconazole, i-PrMgCl, condensation reaction

摘要： 丙硫菌唑的合成报道方法均是以邻氯苄氯为原料, 制备格氏试剂后, 经加成、缩合、硫化得到产物。由于邻氯苄氯反应活性高, 得到的格氏产物收率低, 大量偶联副产物生成, 难以工业化应用。选择环丙基苄基甲酮为原料合成丙硫菌唑的中间体, 以简便高效的中间体制备方法为目的, 研究了酸与酯经缩合反应得到酮的制备方法。经反应工艺条件优化, 在异丙基氯化镁格氏试剂存在下, 以四氢呋喃为反应溶剂, 邻氯苯乙酸和1-氯环丙基甲酸甲酯为原料, n(氯代异丙烷)/n(1-氯环丙基甲酸甲酯)为3.0, 邻氯苯乙酸与1-氯环丙基甲酸甲酯的投料比为1.1 :1.0(摩尔比), 合成得到环丙基苄基甲酮。蒸馏纯化后产品液相色谱检测纯度为98.2%, 收率为83%。该工艺收率高, 操作简单, 条件温和, 适合工业化生产。

关键词: 丙硫菌唑, 异丙基氯化镁, 缩合反应