多潘立酮的新合成工艺研究  

New Synthetic Process Research of Domperidone

作　　者：王宁 崔建兰 于思源 钟丛杉 王晓 龙义强 WANG Ning;CUI Jian-lan;YU Si-yuan;ZHONG Cong-shan;WANG Xiao;LONG Yi-qiang(School of Chemical Engineering and Technology, North University of China, Taiyuan 030051, China;Sichuan Wuzhou Huapu Engineering Design Co. Ltd. , Luzhou 646000, China)

机构地区：[1]中北大学化学工程与技术学院,山西太原030051 [2]四川五洲华普工程设计有限公司,四川泸州646000

出　　处：《中北大学学报（自然科学版）》2021年第2期159-164,共6页Journal of North University of China(Natural Science Edition)

摘　　要：报道了一种多潘立酮的新合成工艺方法.在反应釜中的氮气氛围下,以1-(3-氯丙基)-2,3-二氢-1H-苯并咪唑-2-酮与5-氯-1-(哌啶-4-基)-1,3-二氢-2H-苯并咪唑-2-酮为原料,KI为催化剂,4-甲基-2-戊酮与二甲基亚砜(DMSO)为溶剂,通过单因素实验和L_(9)(3^(3))正交实验考察了反应物物质的量比、溶剂、反应温度和反应时间对反应的影响.实验结果表明:1-(3-氯丙基)-2,3-二氢-1H-苯并咪唑-2-酮与5-氯-1-(哌啶-4-基)-1,3-二氢-2H-苯并咪唑-2-酮物质的量比为1∶1.1,KI的物质的量为5%,反应温度为100℃,4-甲基-2-戊酮与DMSO为溶剂,体积比为8∶1,可得到最佳效果,收率为67.2%,纯度为99.0%.该合成工艺方法优势在于可以防止反应物以及产物的氧化,减少不必要的副产物的产生,同时使用混合溶剂显著提高了产品质量和收率,缩短了反应时间,之后以活性炭为吸附剂,对产物进行了有效的脱色处理,得到了杂质较少的多潘立酮.In this paper,a new synthetic way for domperidone was reported.The reaction kettle is used as the reaction vessel,under the nitrogen atmosphere,1-(3-chloropropyl)-2,3-dihy-dro-1 H-benzimidaz-ole-2-one and 5-chloro-1-(piperidine-4-yl)-1,3-dihydro-2H-benzimid-azole-2-one as raw material,KI as catalyst,4-methy1-2-pentanone and DMSO as solvents,the effects of the volume ratio,solvent,reaction temperature and reaction time of reactive matter on the reaction were investigated by single factor experiment and L_(9)(3^(3))orthogonal experiment.The results show that:the molar ratio of 1-(3-chloropropyl)-2,3-dihydro-1H-ben-zimidazole-2-one and 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzimidazo1-2-one is 1∶1.1,the amount of KI is 5%,the reaction temperature is 100℃,4-methy1-2-ptanone and DMSO are used as the solvent,volume ratio is 8∶1,the best effect can be obtained,the yield is 67.2%,the purity is 99.0%.The advantages of the synthesis process reported in this paper are that it can prevent the oxidation of reactants and products,reduce the production of unnecessary by-products,at the same time,the mixed solvent is used to significantly improve the product quality and yield,shorten the reaction time,and the active carbon is used as an adsorbent to effectively decolorize the product to obtain domperidone with less impurities.

关 键 词：多潘立酮 1-(3-氯丙基)-2 3-二氢-1H-苯并咪唑-2-酮 混合溶剂 5-氯-1-(哌啶-4-基)-1 3-二氢-2H-苯并咪唑-2-酮 合成工艺 

分 类 号：TQ463[化学工程—制药化工]