摘要
本文主要研究一种柳氮磺吡啶杂质Ⅰ磺酸乙酯杂质的制备方法。此杂质为柳氮磺吡啶杂质I结构上的磺酸基团和生产工艺中用到的乙醇缩合成的磺酸乙酯,化学名为5-((4-(磺酸乙酯)苯基)偶氮)-2-羟基苯甲酸,此杂质具有遗传毒性和致癌性杂质的警示结构,但目前的PubChem的CCRIS等相关数据库并没有此杂质的毒理研究数据,因此合成此柳氮磺吡啶杂质Ⅰ磺酸乙酯杂质,对研究其杂质在人体内的生物代谢及毒理具有重大的价值。本研究以对硝基苯磺酰氯和乙醇钠为起始物料,经过4步反应得到柳氮磺吡啶杂质Ⅰ磺酸乙酯杂质,纯度可达96%,收率可达75%以上。本研究的合成路线,原料易得,工艺路线短,设计合理,合成操作简单安全,收率高纯度高,可实现工业化生产柳氮磺吡啶杂质Ⅰ磺酸乙酯杂质。
The invention discloses a method for preparing sulfasalazine impurity I ethyl sulfonate impurity.The impurity is a compoud that a sulfonic acid group on the structure of sulfasalazine impurity Ⅰ condensed with ethanol which is used in the production process to form ethyl sulfonate.This chemical is called 5-((4-(ethoxysulfonyl)phenyl)diazenyl)-2-hydroxybenzoic acid,which has the warning structure of a genotoxic carcinogenic impurity.At present,there is no toxicological data of this impurity in relevant databases such as CCRIS of PubChem.So invented a method for preparing sulfasalazine impurity I ethyl sulfonate impurity has great value for studying the biological metabolism and toxicology of this impurity in human body.The synthetic route invented in this study is easy access to raw materials,short process route,reasonable design,simple and safe synthesis operation,high yield and high purity,which can realize the industrial production of sulfasalazine impurity Ⅰ ethyl sulfonate impurity.This invention takes 4-Nitrobenzenesulfonyl chloride and Sodium ethoxide as starting materials,obtains sulfasalazine impurity Ⅰ ethyl sulfonate impurity through four steps of reaction,the purity can reach 96%,the yield can reach 75%above.The structure of the title compound was characterized by ^(1 )H NMR,and ^(13)C NMR.
作者
陈伟荣
周刚
陈道新
孟祥亮
Chen Weirong;Zhou Gang;Chen Daoxin;Meng Xiangliang(Zhejiang Hisoar Chuannan Pharmaceutical Co.,Ltd.,Zhejiang Linhai 317000)
出处
《化工时刊》
CAS
2021年第5期12-14,共3页
Chemical Industry Times
关键词
柳氮磺吡啶
杂质Ⅰ磺酸乙酯
杂质合成
sulfasalazine
impurityⅠethyl sulfonate
impurity synthesis
