氯唑沙宗的合成工艺优化  

Improved Synthetic Process of Chlorzoxazone

作　　者：杨文艳 崔建兰[1] 王俊[1] 荆晓荣 刘梦鸽 赵林秀[1] YANG Wenyan;CUI Jianlan;WANG Jun;JING Xiaorong;LIU Mengge;ZHAO Linxiu(North University of China,Taiyuan 030051)

机构地区：[1]中北大学,山西太原030051

出　　处：《中国医药工业杂志》2022年第6期837-839,共3页Chinese Journal of Pharmaceuticals

摘　　要：以对氯苯酚(2)为原料,经硝酸硝化得2-硝基-4-氯苯酚(3),3在二氧化硫脲中还原得2-氨基-4-氯苯酚(4),无需分离,加20%硫酸调至pH 3,然后与尿素直接环合制得氯唑沙宗(1),总收率约76%,纯度99.81%。硝化时加入冰乙酸作溶剂,反应完全,3可均匀分散在体系中析出,反应时间缩短至1 h。还原和环合反应连续进行,避免了中间体4后处理时的氧化问题;还原用二氧化硫脲代替传统的硫化钠或水合肼等,绿色环保,反应时间缩短至20 min;环合用硫酸代替盐酸,避开盐酸挥发对实验操作的影响,缩短反应时间。改进后的工艺条件温和,后处理简单。2-Nitro-4-chlorophenol(3) was obtained from p-chlorophenol(2) by nitration with nitric acid.Compound 3 was reduced to 2-amino-4-chlorophenol(4) in the presence of thiourea dioxide.After adjusted to pH 3 by adding 20% sulfuric acid,chlorzoxazone(1) was obtained by cyclization of 4 and urea.The total yield was about 76%and the purity was 99.81%.When adding acetic acid as solvent,3 could be evenly dispersed and precipitated in the system,so the nitration was complete,and the reaction time was shortened to 1 h.The reduction and cyclization were carried out continuously without oxidation of intermediate 4 in the isolation prcess.The reduction used thiourea dioxide instead of traditional sodium sulfide or hydrazine hydrate,which was green and environmental friendly.Sulfuric acid was used to replace hydrochloric acid in cyclization to avoid the influence of volatilization of hydrochloric acid on the experimental operations,and the reaction time was also shortened.The improved process had mild conditions and simple post-processing steps.

关 键 词：肌肉松弛药 氯唑沙宗 合成 工艺改进 

分 类 号：TQ460.6[化学工程—制药化工] R971[医药卫生—药品]