摘要
以廉价易得的2-甲基苯乙酸(2)为原料,经硝化、酰胺化、脱水三步反应成功制备目标产品2-甲基-3-硝基苯乙腈(1),结构经1H NMR和MS确证。实验中以L9(34)正交试验为研究方法,重点讨论了反应物料比、反应温度、反应时间、pH值等关键工艺参数对制备目标产品的影响,获得了适宜的生产工艺:n(二氯亚砜)∶n(氨气)∶n(3)=1.3∶1.4∶1,反应时间2 h;三氟乙酸酐-三乙胺作脱水剂,且n(三氟乙酸酐)∶n(4)=1.4∶1,反应温度40℃及pH值为10。反应总收率为57.0%,纯度高达99.6%,改进后工艺操作简单、反应条件温和,易于放大生产,对2-甲基-3-硝基苯乙腈的工业化生产及下游原料药的研究提供借鉴意义。
The target product 2-methyl-3-nitrophenylacetonitrile(1)was successfully prepared from cheap 2-methylphenylacetic acid(2)with three processes-nitration,amidation and dehydration reaction.Its structure was confirmed by 1H NMR and MS.In the experiment,the main factors influencing the reaction were evaluated by the orthogonal experimental design of L9(34),and the effects of key process parameters such as reaction material ratio,reaction temperature,reaction time and pH value on the preparation of the target product were mainly discussed.The proper production process was obtained:the ratio of n(dichlorosulfoxide)∶n(ammonia)∶n(3)=1.3∶1.4∶1,with reaction time 2 h;with trifluoroacetic anhydride triethylamine as dehydrating agent,and the ratio of n(trifluoroacetic anhydride)∶n(4)=1.4∶1,with reaction temperature 40℃and pH value 10.The total yield of the reaction was 57.0%and the purity was up to 99.6%.With the improvement of the process,the operation of synthesis process is simple,reaction conditions ismild and scale-up production is easy to fulfill,which was referenced for the industrial production of 2-methyl-3-nitrophenylacetonitrile and the research of downstream active pharmaceutical ingredients.
作者
李匡元
李娟
张怡
门靖
Li Kuangyuan;Li Juan;Zhang Yi;Men Jin(Shaanxi Wansheng Health Industry Co.,Ltd,Xi'an 710000;Xi'an WanLong Pharmaceutical Co.,Ltd,Xi'an 710119)
出处
《化工与医药工程》
2020年第2期6-10,共5页
Chemical and Pharmaceutical Engineering
作者简介
李匡元(1973—),男,工程师,主要从事药品生产技术研究。
