(542d) Using Data-Rich Experimentation to Maximize Productivity of Photochemical Reactions upon Scale-up

Visible light promoted organic reactions access novel reaction pathways, enabling the synthesis of complex organic molecules using mild reagents under ambient reaction conditions. While photochemistry offers green solutions for manufacturing, scaling up reactions beyond the kilo scale remains a challenge due to the complex relationship between reaction conditions and the attenuation of light in finding the optimal operating conditions for productivity. For these reasons, it is important to have a firm grasp of the process kinetics and optical properties of the reactor. Herein we report a case study on the photocatalyzed cross coupling of aryl bromides with pyrrolidine where the interplay between reagent concentrations, pathlength, and light intensity were quickly elucidated. A design of experiments highlighted the optimal reaction conditions to maximize productivity by maximizing yield while minimizing residence time. Statistical or first principles kinetic models provided further insight into the impact of each parameter, and their interactions, on the reaction rate and final yield. These insights were applied in scaling this photoamination reaction and achieving productivities > 10 kg/day in a plug flow photoreactor.