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.

• East China University of Science and Technology
• Shanghai Jiao Tong University

• Intermediate

1. antiretroviral
2. azidation
3. AZT
4. Intermediate
5. Research Article
6. Scale-up
7. Zidovudine