文献类型：期刊文献

英文题名：Process parameter and kinetic study for the azidation of a zidovudine intermediate with sodium azide in microreactors

作者：Jiang, Rongkun[1,2];Xue, Xiao[2];Zhao, Fang[3];Zhu, Weiping[1];Shang, Minjing[2];Su, Yuanhai[2];Xu, Yufang[1];Qian, Xuhong[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]Shanghai Jiao Tong Univ, Frontiers Sci Ctr Transformat Mol, Sch Chem & Chem Engn, Shanghai 200240, Peoples R China;[3]East China Univ Sci & Technol, State Key Lab Chem Engn, Shanghai 200237, Peoples R China

年份：2022

卷号：429

外文期刊名：CHEMICAL ENGINEERING JOURNAL

收录：;EI(收录号：20213810922722);WOS:【SCI-EXPANDED(收录号:WOS:000729803500001)】；

基金：We want to acknowledge financial support from the National NaturalScience Foundation of China (Nos. 21878088, 21476077 and 21676164) , and Key Project of the Shanghai Science and Technology Committee (No. 18DZ1112703) .

语种：英文

外文关键词：Zidovudine; Azidation; Microreactor; Process safety; Kinetic study

摘要：Zidovudine, i.e., AZT, is an indispensable anti-AIDS drug for highly active antiretroviral therapy. The azidation step is of the most vital importance in the synthetic route of zidovudine. Herein we report the use of microreactors in combination with the simplified azidation system instead of conventional batch reactors, with reducing the usage of solvent and hazardous chemicals, avoiding risk of explosion and increasing process efficiency. First, effects of various parameters such as volumetric flow rate, microreactor diameter, reactant concentration, reaction temperature and residence time on the azidation process were systematically studied. Compared with the batch reactor, the continuous-flow microreactor could achieve comparable AZT-C yield (i.e., 89%) at much shorter time (10 min) under the condition optimized by experimental parameter screening. The reaction rate of the azidation in the microreactor was 360 times faster than that in the batch reactor. Then, the reaction order of each reactant, pre-exponential factors and activation energy values for both the main and side reactions were determined. On the basis of the kinetic study, the reaction mechanism of the azidation from AZT-B to AZT-C was proved for the first time. Finally, we designed a series of validation experiments to show the accuracy of the obtained reaction kinetics, with the indication of its use for the further process optimization and scale-up.