摘要
美沙拉嗪是一种重要的消炎药,现有间歇合成工艺存在原料毒性大、设备要求高、操作复杂、安全风险高等不足。文中从动力学研究出发,优化美沙拉嗪的连续合成工艺。首先在1 MPa、333—353 K的条件下研究5-硝基水杨酸加氢反应本征动力学。5-硝基水杨酸加氢反应为一级反应,得出此条件下反应速率方程,活化能为23.62 kJ/mol。然后在连续固定床催化加氢反应器中研究和优化催化剂、温度、压强和停留时间等工艺条件,结果表明:当以质量分数0.5%Pd/C为催化剂、反应温度60℃、压强1.0 MPa、停留时间20 min时,母液循环条件下的反应收率达97%。实现美沙拉嗪的连续合成,反应时间缩短为间歇工艺的1/4,原料毒性低、操作简便、安全性高,为其后续生产应用奠定了技术基础。
Mesalazine is a significant anti-inflammatory drug,however,the current batch synthesis process presents several challenges,including the high toxicity of raw materials,stringent equipment requirements,complex operational procedures and elevated safety risks.This study aims to optimize the continuous synthesis process of mesalazine through kinetic research.Initially,the intrinsic kinetics of the hydrogenation reaction of 5-nitrosalicylic acid were examined under 1 MPa and 333-353 K.The hydrogenation reaction was determined to be first-order,with an activation energy of 23.62 kJ/mol,and a reaction rate equation was derived.Subsequently,various process parameters,including catalyst type,temperature,pressure and residence time,were investigated and optimized in a continuous fixed-bed catalytic hydrogenation reactor.The results indicate that using mass fraction 0.5%Pd/C as the catalyst,at reaction temperature of 60℃,pressure of 1.0 MPa and residence time of 20 minutes,the reaction yield reaches 97%under mother liquor circulation conditions.This study successfully achieves the continuous synthesis of mesalazine,reducing the reaction time to one-fourth that of the traditional batch process.The optimized method features lower toxicity of raw materials,simplified operations and enhanced safety,providing a solid technical foundation for future production and application.
作者
李金龙
金晓蓓
施熠
沈介发
严生虎
张跃
LI Jinlong;JIN Xiaobei;SHI Yi;SHEN Jiefa;YAN Shenghu;ZHANG Yue(School of Pharmacy&School of Biological and Food Engineering,Changzhou University,Changzhou 213164,Jiangsu Province,China;Changzhou Tronly New Electronic Material Co.,Ltd.,Changzhou 213164,Jiangsu Province,China;Institute of Chemical Safety Essence,Changzhou University,Changzhou 213164,Jiangsu Province,China)
出处
《化学工程》
北大核心
2025年第7期66-71,共6页
Chemical Engineering(China)
基金
国家重点研发计划(2021YFC3001104)。
关键词
美沙拉嗪
连续固定床反应
工艺优化
催化加氢
反应动力学
mesalazine
continuous fixed-bed reaction
process optimization
catalytic hydrogenation
reaction kinetics
