1-(2,6-二氯-4-三氟甲基苯基)-3-氰基-5-氨基吡唑合成工艺

Techniques for synthesizing 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-3-cyano-5-aminopyrazole

研究了1-（2,6-二氯-4-三氟甲基苯基）-3-氰基-5-氨基吡唑的改进合成工艺：经2,6-二氯-4-三氟甲基苯胺重氮化反应,再与2,3-二氰基丙酸甲酯缩合,在氨气作用下,甲苯溶液中20-25℃下反应3 h,得到1-（2,6-二氯-4-三氟甲基苯基）-3-氰基-5-氨基吡唑.1-（2,6-二氯-4-三氟甲基苯基）-3-氰基-5-氨基吡唑是氟虫腈的重要中间体.产品及重要中间体结构经红外光谱、核磁共振确认,并经高效液相色谱测定产品纯度为98%（HPLC）,收率为89%,均高于文献值.综合考虑了影响反应的因素：投料比、氨气量、溶剂、反应时间、反应温度.最佳反应条件为：2,6-二氯-4-三氟甲基苯胺与2,3-二氰基丙酸甲酯的摩尔比为：1∶1.12,反应温度为3~5℃,反应时间为5 h.产品为淡黄色针状晶体,熔点：141-142℃,工艺条件温和、易操作、原料廉价易得、废水量少,达到绿色清洁化生产,因此有广阔的工业化前景.

Fipronil is increasing worldwide use as insecticide because it is effective against a variety of pests. The intermediates of fipronil are important for its production. In this study, an improved process for the synthesis of 1-[-2,6-dichloro-4-（trifluoromethyl）phenyl]-3-cyano-5-aminopyrazole was investigated. The technique includes diazo-reaction with 2,6-dichlor0-4-trifluoro methylaniline, condensation with methyl 2,3-dicyanopropionate. The reaction was under 20-25℃ for 3h, used toluene as solvent. The target compound and key intermediate were separated and characterized by high performance liquid chromatography （HPLC）, infrared spectrum （IR） and nuclear magnetic resonance （NMR）. The yield of the target compound can be reached 89% （purity of 98%）, which is higher than the literature. The factors of reaction include feed molar ratio, ammonia flow rate, solvent, reaction time and reaction temperature. The optimum conditions were investigated in detail, which include reaction time and reaction mole ratio on yield, etc. The results of optimum conditions show that molar ratio （1 ： 1.12） 2,6-dichloro-4-trifluoro methylaniline/Ethyl 2,3-dicyanopropianate, reaction temperature 3-5℃, reaction time 5h. The product is light yellow needle crystal, m.p. 141-142 ℃. The advantages of the synthetic route proposed are easy operation, mild reaction condition, using cheaper and more reading available raw materials, simpler procedure, higher yield, etc. This method was preferable for green process and the post treatment of the process. So this route had good prospect for industrialization.