3-二氟甲基-1-甲基-1H-吡唑-4-羧酸合成工艺改进  

Improvement of the synthetic process of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid

作　　者：刘倩 孙群芳 于志广 吴国军 LIU Qian;SUN Qunfang;YU Zhiguang;WU Guojun(Shijiazhuang City Sentay Chemical Co.,Ltd.,Shijiazhuang 052500,China;Xingtai Julu Wanghuzhai School,Xingtai 055250,Hebei,China)

机构地区：[1]石家庄市深泰化工有限公司,石家庄052500 [2]邢台市巨鹿县王虎寨校区,河北邢台055250

出　　处：《农药》2024年第11期796-801,共6页Agrochemicals

摘　　要：[目的]对3-二氟甲基-1-甲基-1H-吡唑-4-羧酸的合成工艺进行优化,减少异构体的生成,提高产品的质量和收率。[方法]以4,4-二氟乙酰乙酸乙酯为起始原料,与N,N-二甲基甲酰胺二甲缩醛(DMF-DMA)反应生成2-二氟乙酰基-3-(二甲基氨基)丙烯酸乙酯(EMADFAA);EMADFAA先与水合肼合成吡唑环,之后用DMF-DMA进行选择性N-甲基化;再经水解反应得到高纯度目标化合物。[结果]反应总收率82.4%,产品纯度99.9%,异构体含量≤0.1%(HPLC面积归一值);目标化合物及中间体的结构经LC-MS和1H NMR确证。[结论]此合成方法反应条件温和,操作简单,因增加了区域选择性,减少了异构体的生成,目标产物收率较高。[Aims]This study aims to optimize the process for the preparation of 3-(difluoromethyl)-1-methyl-1Hpyrazole-4-carboxylic acid,so as to reduce the generation of isomers and improve the quality and the yield of the product.[Methods]The starting material ethyl 4,4-difluoroacetoacetate reacted with N,N-dimethylformamide dimethylacetal(DMF-DMA)to generate ethyl 2-(difluoroacetyl)-3-(dimethylamino)acrylate(EMADFAA);EMADFAA reacted with hydrazine hydrate to synthesize a pyrazole ring,and then selectively N-methylated with DMF-DMA.High purity target product was obtained through hydrolysis reaction.[Results]The total process yield was 82.4%,and the product purity(peak area normalization method of HPLC)was 99.9%,with isomer content≤0.1%.The structures of the target product and intermediates were confirmed by LC-MS and 1H NMR.[Conclusions]This synthetic method is mild in reactions and simple in operation.Increasing the regioselectivity and reducing the generation of isomer,it has a high yield of target product.

关 键 词：杀菌剂 3-二氟甲基-1-甲基-1H-吡唑-4-羧酸 N N-二甲基甲酰胺二甲缩醛 合成 

分 类 号：TQ455.4[化学工程—农药化工]