Abstract：Tadalafil is an important pharmaceutical raw material. The general method for synthetic tadalafil has many disadvantages. In order to improve the production efficiency of tadalafil， methy (1R,3R)-1-(benzo[d][1,3]dioxol-5-yl)-2-(2-chloroacetyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate (carboline derivatives) were reacted with methylamine to prepare tadalafil using a microreactor in this study. The results showed that， compared with batch reactors， the microreactor significantly improved the yield of tadalafil and shortens the reaction time. When the temperature is 65 ℃， the concentration of tetrahydrocarboline derivatives is 2.5 mL·mol－1 and the molar ratio of methylamine to tetrahydrocarboline derivatives is 5， with the residence time of 20 min and the yield of 88.3%. While in the bath reactor， the best yield of tadalafil is only 79.7%， and the reaction time is 2 h. The reaction kinetic model was established， and the total order of the reaction was 2， with the pre-exponential factor of 6.27×1011 mL·mol－1·s－1， and the activation energy of 38.92 kJ·mol－1. This kinetic model has important theoretical significance and practical value for optimizing reactor design and industrial production.
李军峰,杨红军,毛志鹏,李 闯,宋青明,许 蓉,陈 建. 微反应器中他达拉非的高效合成及其动力学研究[J]. 华中师范大学学报(自然科学版), 2022, 56(5): 812-817.
LI Junfeng,YANG Hongjun,MAO Zhipeng,LI Chuang,SONG Qingming,XU Rong,CHEN Jian. Efficient synthesis of tadalafil and its kinetic study in a microreactor system. journal1, 2022, 56(5): 812-817.
2022, Vol. 56 
