【摘要】 他达拉非是一种重要的医药原料，其传统的合成工艺是在间歇反应釜中进行，具有产率低和反应时间长等缺点.为提高他达拉非的生产效率，该文研究了在微反应器中由（1R,3R）-1,2,3,4-四氢-2-氯乙酰-（3,4-亚甲基苯基）-9H吡啶并[3,4-b]吲哚-3-羧酸甲酯（四氢咔啉衍生物）与甲胺反应制备他达拉非.结果表明，与间歇反应釜相比，微通道反应器显著提高了他达拉非的产率，缩短了反应时间.当温度为65℃,四氢咔啉衍生物浓度为2.5 mmol·mL^-1,甲胺与四氢咔啉衍生物物质的量的比为5,停留时间为20 min时，他达拉非产率达到88.3%.而在间歇釜中，他达拉非最佳产率仅为79.7%,反应时间为2 h.同时该文建立了该反应简化动力学模型，确定该反应总级数为2,指前因子为6.27×10¹¹ mL·mol^-1·s^-1,活化能为38.92 kJ·mol^-1.更多还原

【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（1 R,3 R）-1-（benzo[d][1,3]dioxol-5-yl）-2-（2-chloroacetyl）-2,3,4,9-tetrahydro-1 H-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.更多还原