(542f) A Systematic Approach to the Design and Scale-up of Photochemical Reactors

Photochemistry allows efficient access to complex molecular scaffolds with high selectivity, and has

been demonstrated to be a powerful tool in pharmaceutical chemistry applications. Determining

reaction conditions and light intensity requirements for photochemical reactions, however, is

challenging because light distribution through the reactor is highly dependent on reactor geometry and

the absorbance of components. In scaling up these reactions, the effect is especially exacerbated as the

ratio of illuminated area to reactor volume decreases.

Here we present a workflow for optimizing photochemical reaction parameters and reactor geometry to

enable a robust and efficient scale-up in flow. The workflow starts with the characterization of the

photophysical properties of the reaction components, and the irradiation parameters of the reactor and

the light sources. In parallel, we utilize high-throughput experimentation (HTE) to determine reaction

rates and to optimize reaction conditions. We incorporate the intrinsic reaction parameters and the

radiation components to model the kinetics of the desired photochemical reaction for various reactor

geometries and light sources. Through iterations of modeling and experimental work, the reaction

conditions and residence time are selected to optimize productivity for a given photoreactor design.

Using this systematic approach and optimizing reactor geometry and light-source selection accordingly,

we were able to achieve productivities exceeding those achieved in commercially-available laboratory scale

flow reactors. We will present the application of our workflow to both a single component

photocyclization reaction as well as to a more complicated visible-light photoredox catalysis reaction.