(299e) Improving Reactor Design for Scaling-up Photoredox Reactions in Flow

Authors: 
Harper, K., AbbVie
Bordawekar, S., AbbVie Inc.

Improving Reactor Design for Scaling-Up Photoredox Reactions in Flow

Eric G. Moschetta,* Kaid C. Harper*, Shailendra V. Bordawekar, and Steven J. Wittenberger

AbbVie, Inc. Process R&D, 1401 Sheridan Road North Chicago, IL 60064

*co-corresponding authors: eric.moschetta@abbvie.com, kaid.harper@abbvie.com

Photoredox catalysis has emerged as an innovative methodology for constructing organic molecules in selective fashion. These one-electron chemistries rely on special transition metal and organic photoredox catalysts that absorb photons from sources of visible light to promote the catalysts into electronically excited states. Once energized, the catalysts undergo single electron transfer with organic substrates to afford products. These reactions are attractive from an industrial viewpoint because they operate at mild conditions, use green energy sources in the form of inexpensive visible light, and offer exceptional selectivity and unique reactivity in chemical transformations. Such transformations are especially appealing in the pharmaceutical industry. In spite of these advances in synthetic methodology, reactor technology does not yet exist to execute photoredox reactions on a commercial scale. One promising solution is to implement flow chemistry in photoredox processes. Flow reactors offer the benefits of increased throughput, improved heat and mass transfer properties, and potentially smaller reactor volumes. For photoredox applications, flow reactors also offer improved photon fluxes throughout the volume of the reactor, especially when compared to batch reactors. The major challenge in developing scalable flow reactor technology for photoredox chemistry in the pharmaceutical industry is understanding the fundamental kinetics of these reactions and the other necessary scale-up parameters for rational design of flow reactors to achieve production on the order of kilograms per day.

We present an example of a successful kilogram-per-day scale reaction in a flow reactor for a dual metallaphotoredox C–N coupling using an iridium photoredox catalyst and a nickel cross-coupling catalyst. We show how we collected kinetic data in batch and used simple guidelines for transitioning from the batch reactor to a flow reactor. These guidelines should apply to a broad range of photoredox reactions as well as photoreactors. We also address how the intensity of the light source apparently affects photoredox reactions in different fashions and how that impacts the design of the flow reactor. Finally, with photoreactor-specific scale-up principles established, we reintroduce more conventional principles of chemical reaction engineering to address how flow reactor design may be approached at commercial scales to maximize throughput.

The design, study conduct, and financial support for this research was provided by AbbVie. AbbVie participated in the interpretation of data, writing, reviewing, and approving the publication. All authors are AbbVie employees.