唑草酮中间体2-(4-氯-2-氟苯基)-5-甲基-1H-1,2,4-三唑-3-酮的合成

Synthesis of carfentrazone-ethyl intermediate 2-(4-chloro-2-fluorophenyl)-5-methyl-1H-1,2,4-triazol-3-one

为了提高唑草酮关键中间体2-(4-氯-2-氟苯基)-5-甲基-1H-1,2,4-三唑-3-酮的产品质量,提升反应收率并降低成本,以4-氯-2-氟苯肼为原料,利用一锅法合成工艺,经脱水缩合、1,3-偶极加成和氧化脱氢反应,得到2-(4-氯-2-氟苯基)-5-甲基-1H-1,2,4-三唑-3-酮。通过筛选反应参数,得到最佳合成条件为:以乙醇-水(质量比4∶1)为溶剂,醋酸作为质子酸,4-氯-2-氟苯肼、乙醛、氰酸钠、醋酸、次氯酸钠的摩尔比为1.0∶1.5∶1.5∶1.6∶1.6,反应温度15℃。采用HPLC进行反应中控,以^(1)H-NMR、^(13)C-NMR、ESI-MS等对产物进行表征,结果显示产物为目标产物,HPLC纯度≥99%,收率为90%。该一锅法合成工艺,操作简便,设备利用率高,节约能耗和工时,适合工业化生产,对类似唑草酮中间体的化合物生产工艺设计具有借鉴意义。

In order to improve the product quality and reaction yield, and reduce costs of 2-(4-chloro-2-fluorophenyl)-5-methyl-1H-1,2,4-triazol-3-one, the key intermediate of carfentrazone-ethyl, this paper uses 4-chloro-2-fluorophenylhydrazine as the raw material, and adopts one-pot method for dehydration condensation, 1,3-dipole addition and oxidative dehydrogenation to obtain 2-(4-chloro-2-fluorophenyl)-5-methyl-1H-1,2,4-triazol-3-one. By screening the reaction parameters, the best synthesis conditions were obtained: ethanol-water(with a mass ratio of 4∶1) was used as the solvent, acetic acid was used as protonic acid, the molar ratio of 4-chloro-2-fluorophenylhydrazine, acetaldehyde, sodium cyanate, acetic acid and sodium hypochlorite was 1.0∶1.5∶1.5∶1.6∶1.6, and the reaction temperature was 15 ℃. The reaction was controlled by HPLC, and the product was characterized by ^(1)H-NMR,^(13)C-NMR, ESI-MS, etc. The results showed that the product was the target product, the HPLC purity was ≥99%, and the yield was 90%. The "one-pot method" synthesis technology, having the advantages of simple operation, high utilization rate of equipment, and energy consumption and man-hour saving, is suitable for industrial production, and has referential significance for the design of the production process of compounds similar to carfentrazone-ethyl intermediates.