Armstrong Cameron T, Pritchard Cailean Q, Cook Daniel W, Ibrahim Mariam, Desai Bimbisar K, Whitham Patrick J, Marquardt Brian J, Chen Yizheng, Zoueu Jeremie T, Bortner Michael J, Roper Thomas D
Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, VA, 23219 USA.
Department of Chemical Engineering and Macromolecules Innovation Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061 USA. E-mail:
React Chem Eng. 2019 Jan 30;4(3):634-642. doi: 10.1039/c8re00252e.
Continuous flow chemistry has the potential to greatly improve efficiency in the synthesis of active pharmaceutical ingredients (APIs); however, the optimization of these processes can be complicated by a large number of variables affecting reaction success. In this work, a screening design of experiments was used to compare computational fluid dynamics (CFD) simulations with experimental results. CFD simulations and experimental results both identified the reactor residence time and reactor temperature as the most significant factors affecting product yield for this reaction within the studied design space. A point-to-point comparison of the results showed absolute differences in product yield as low as 2.4% yield at low residence times and up to 19.1% yield at high residence times with strong correlation between predicted and experimental percent yields. CFD was found to underestimate the product yields at low residence times and overestimate at higher residence times. The correlation in predicted product yield and the agreement in identifying significant factors in reaction performance reveals the utility of CFD as a valuable tool in the design of continuous flow tube reactors with significantly reduced experimentation.
连续流动化学有潜力极大地提高活性药物成分（API）合成的效率；然而，这些过程的优化可能会因大量影响反应成功的变量而变得复杂。在这项工作中，采用实验筛选设计将计算流体动力学（CFD）模拟与实验结果进行比较。CFD模拟和实验结果均确定，在所研究的设计空间内，反应器停留时间和反应器温度是影响该反应产物收率的最重要因素。结果的点对点比较表明，在低停留时间下，产物收率的绝对差异低至2.4%，在高停留时间下高达19.1%，预测收率与实验收率之间具有很强的相关性。发现CFD在低停留时间下低估产物收率，而在较高停留时间下高估产物收率。预测产物收率的相关性以及在确定反应性能重要因素方面的一致性，揭示了CFD作为一种有价值工具在连续流管式反应器设计中的实用性，可显著减少实验。
