异噁唑类杀虫剂氟噁唑酰胺合成工艺研究

Study on synthesis process of isoxazole insecticide fluxametamide

优化合成路线和工艺,合成目的产物氟噁唑酰胺。以3,5-二氯溴苯为原料,经格氏化,与三氟乙酸甲酯反应得到3’,5’-二氯-2,2,2-三氟苯乙酮;在月桂酸钠的催化下,2-甲基-4-乙酰基苯甲酸与3’,5’-二氯-2,2,2-三氟苯乙酮缩合,脱水,再与盐酸羟胺环化得到关键中间体4-[5-(3,5-二氯苯基)-5-三氟甲基-4,5-二氢异噁唑-3-基]-2-甲基苯甲酸;关键中间体经酰氯化后氨解得到4-[5-(3,5-二氯苯基)-5-三氟甲基-4,5-二氢异噁唑-3-基]-2-甲基苯甲酰胺;然后与原甲酸三甲酯,甲氧基胺盐酸盐反应得到目的产物氟噁唑酰胺。产物结构经核磁共振氢谱确证。该工艺简单经济,条件温和,具有工业化应用前景。

The synthesis route and process were optimized to synthesize the target product fluxazolamide.3’,5’-dichloro-2,2,2-trifluoroacetophenone was prepared using 1-bromo-3,5-dichlorobenzene as raw material to react with magnesium metal and methyl trifluoroacetate. Under the present of sodium laurate, 2-methyl-4-acetylbenzoic acid reacted with 3’,5’-dichloro-2,2,2-trifluoroacetophenone to give 4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methylbenzoic acid through these reactions of condensation, dehydration, and cyclization with hydroxylamine hydrochloride. Then, it reacted respectively with thionyl chloride and ammonia to give the 4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methylbenzamide. Finally, 4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methylbenzamide reacted with trimethyl orthoformate and methoxyamine hydrochloride to give the target product fluxametamide. The product thus obtained was identified by1H NMR. This process is simple, warm and economical, which is suitable for industrial scale manufacture.