3-(4-氯-2-氟-5-甲氧基苯基)-1-甲基-5-三氟甲基-1H-吡唑的合成

Synthesis of 3-(4-Chloro-2-fluoro-5-methoxyphenyl)-1-methyl-5-trifluoromethyl-1H-pyrazole

3 (4 氯 2 氟 5 甲氧基苯基 ) 1 甲基 5 三氟甲基 1H 吡唑是合成除草剂的中间体。它通过以下途径制得 :邻氯对氟苯甲醚在冰水浴下与甲基二氯甲基醚和四氯化钛反应得 4 氯 2 氟 5 甲氧基苯甲醛 ;后者经甲基格氏试剂作用 ,然后在酸性条件下用三氧化铬氧化 ,转变为 4 氯 2 氟 5 甲氧基苯乙酮 ;4 氯 2 氟 5 甲氧基苯乙酮在甲醇钠 /甲醇体系中 ,与三氟乙酸乙酯反应得相应的 β 二酮 ;然后用水合肼闭环 ,再用硫酸二甲酯甲基化即得产品。总收率 6 3 5 %。最后一步用硫酸二甲酯甲基化时 ,反应在酸性条件下进行可减少副产品的生成。产品结构经质谱、核磁共振氢谱。

3-(4-Chloro 2 fluoro 5 methoxyphenyl) 1 methyl 5 trifluoromethyl 1H pyrazole,an intermediate of herbicides,was obtained from the following steps.Treatment of 4 chloro 2 fluoroanisole with dichloromethyl methyl ether and titanium tetrachloride under ice-water bath gave 4 chloro 2 fluoro 5 methoxybenzaldehyde(Ⅰ).I was converted to 4 chloro 2 fluoro 5 methoxyacetophenone(Ⅱ) by treatment with methyl Grignard followed by oxidation using chromium trioxide under acidic condition.Ⅱreacted with ethyl trifluoroacetate in sodium methoxide/methanol solvent to form 1 (4 chloro 2 fluoro 5 methoxyphenyl) 4,4,4 trifluoro 1,3 butandione(Ⅲ).Ⅲreacted with aqueous hydrazine,and then is methylated using dimethylsulfate to obtain the final product.The total yield was 63 5%.In the last step,methylation with dimethylsulfate,the by product could be reduced if the reaction was carried out under acidic condition.Structures of the products were confirmed by CIMS, 1HNMR and 13 CNMR.