Heuristics for Implementing Photoredox Catalysis in Flow Reactors

Heuristics for Implementing Photoredox Catalysis in Flow Reactors   Eric G. Moschetta,^* Steven M. Richter, and Steven J. Wittenberger   AbbVie, Inc. Process R&D, 1401 Sheridan Road North Chicago, IL 60064   ^*corresponding author: eric.moschetta@abbvie.com               Photoredox catalysis is reemerging in organic synthesis as a powerful method for constructing small molecules under mild conditions. Such transformations often employ transition metal catalysts to absorb visible light, exciting the catalysts into energetic states that facilitate single electron transfer events between the catalysts and organic substrates.^[1] These reactions frequently occur at mild temperatures, including room temperature, using visible light sources such as LEDs that provide intense light with narrow wavelength emissions. As such, materials for conducting photoredox chemistry at the lab scale are readily available for chemists and engineers. However, significant challenges remain in visible-light photoredox catalysis. The primary challenge in industrial applications is scaling up photoredox reactions from laboratory scale batch reactors to reactors that are capable of multi-kilogram scale production. Proper reactor design relies on rigorous understanding of the inherent kinetics of photoredox reactions, which are largely unexplored. The photon flux, the overall observed rate at which photons are received in the reactor, must be high enough to ensure that the inherent kinetics of the reaction are the operating conditions of the reactor. The lamp-reactor geometry, therefore, is a critical design factor in scalable photoredox flow chemistry. Maximizing the photon flux also likely depends on careful tuning of the catalyst concentration, reactant concentration, and light intensity.             Continuous flow reactors can facilitate improved photon fluxes and increased throughput through significantly decreased reaction times compared to batch reactions, which are both necessary for industrial photoredox catalysis.^[2] Flexible fluoropolymer tubing is chemically resistant to many materials and highly transparent to visible light, meaning that tubing can be wrapped around light sources such as LEDs for access to customizable tubular flow reactors for photoredox applications. The short tube diameters allow for shorter path lengths, meaning that photons are more evenly distributed throughout the reactor, increasing the apparent rate of reaction. However, general principles and heuristics for designing such flow reactors are not yet available to process chemists and engineers. This work establishes heuristics for employing flow reactors in photoredox chemistry. The effects of reactant and catalyst concentration, tube diameter, and LED intensity on the observed photon fluxes and rates of reaction will be discussed. The model reaction for establishing the heuristics will be the oxidation of 9,10-diphenylanthracene using molecular oxygen and a common ruthenium photoredox catalyst, Ru(bpy)₃Cl₂. The quantum yield for this reaction is known,^[3] meaning that the photon flux under a given set of reaction conditions can be calculated directly once the rate of reaction is measured. These heuristics will then be examined against a pyrazole synthesis driven by photoredox catalysis, using the same ruthenium catalyst, to see if heuristics accurately predict how the observed rates of reaction change with changes in reaction conditions in flow.   References

[1]        C. K. Prier, D. A. Rankic, D. W. C. MacMillan, Chem. Rev. 2013, 113, 5322-5363.

[2]        Y. Su, N. J. W. Straathof, V. Hessel, T. Noel, Chem. Eur. J. 2014, 20, 10562-10589.

[3]        S. P. Pitre, C. D. McTiernan, W. Vine, R. DiPucchio, M. Grenier, J. C. Scaiano, Sci. Rep. 2015, 5, 16397.   This abstract presentation was sponsored by AbbVie. AbbVie contributed to the design, research, and interpretation of data, writing, reviewing, and approving the publication. All authors are AbbVie employees.