基于三氧化硫磺化的丹参酮ⅡA磺酸钠的连续化合成  

Continuous Synthesis of Sodium Tanshinone IIA Sulfonate Based on Sulfur Trioxide Sulfonation

作　　者：闵书樑 周长路[1] 王超颖 万海涛 俞伟 辛忠[1] MIN Shuliang;ZHOU Changlu;WANG Chaoying;WAN Haitao;YU Wei;XIN Zhong(Shanghai Key Laboratory of Multiphase Materials Chemical Engineering,East China University of Science and Technology,Shanghai 200237,China;SPH No.1 Biochemical&Pharmaceutical Co.Ltd,Shanghai 201111,China)

机构地区：[1]华东理工大学上海市多相结构材料化学工程重点实验室,上海200237 [2]上海上药第一生化药业有限公司,上海201111

出　　处：《华东理工大学学报（自然科学版）》2024年第6期802-809,共8页Journal of East China University of Science and Technology

基　　金：“超限制造”上海市市级科技重大专项。

摘　　要：利用飞秒激光微加工技术,制作了一种厘米级类卡特彼勒3D微流控芯片,并在微流控芯片内以三氧化硫为磺化剂连续制备丹参酮ⅡA磺酸钠。停留时间分布测试结果表明:微流控芯片内的整体流动状态接近于平推流。最佳磺化条件为:磺化温度25℃,n(SO_(3))/n(丹参酮ⅡA)=2.0,停留时间2 min。与传统硫酸间歇工艺相比,丹参酮ⅡA磺酸钠产率由68.0%提升至92.3%,反应时间由120 min降低至2 min,E因子由27.7降低至2.1。实现了丹参酮IIA磺酸钠的绿色、安全、高效连续制备。A centimeter-scale 3D microfluidic chip with high density and large liquid-holding capacity was fabricated using femtosecond laser micromachining technology,and sodium tanshinone IIA sulfonate was continuously synthesized within the microfluidic chip using sulfur trioxide as the sulfonation agent.The average residence time,factorless variance and various model parameters obtained from the residence time distribution test of the microfluidic chip at different flow rates showed that the actual residence time in the microfluidic chip was close to the theoretical residence time,the overall flow state in the microfluidic chip was close to the pushover flow,and it could effectively inhibit the occurrence of the side reaction in the local area caused by the back-mixing.We also determined that the greater the fluid flow rate,the more pronounced the effect flow.The effects of temperature,residence time and n(SO_(3))/n(tanshinone IIA)on the yield of sodium tanshinone IIA sulfonate and the conversion of tanshinone IIA were investigated by one-way experimental analysis.The optimal process conditions were determined as follows:a sulfonation temperature of 25℃,n(SO3)/n(tanshinone IIA)of 2.0,and residence time of 2 min.The products were analyzed by HPLC,indicating a yield of up to 92.3%,and a conversion rate of 97.2%.Comparing to the traditional batch process,the yield was increased by 35.7%,the ratio of sulfonating agent was reduced from 38 to 2,the reaction time was reduced from 120 min to 2 min,and the E-Factor reduced from 27.7 to 2.1.The generation of waste acid was reduced and production efficiency was improved.The green,safe,and efficient continuous preparation of sodium tanshinone IIA sulfonate was realized.

关 键 词：三氧化硫 丹参酮ⅡA磺酸钠 微流控芯片 停留时间分布 绿色化学 

分 类 号：TQ463[化学工程—制药化工]