Heuristics, Protocol, and Considerations for Flow Chemistry in Photoredox Catalysis

Abstract

Heuristics for employing photoredoxc atalysts in coiled-tube LED reactors for flow chemistry are presented. These heuristics focus on common reaction parameters (for example, reagent concentration, tube diameter and light intensity) designed to encompass as many photoredox systems as possible. A chemicala ctinometerb ased on ac ommon photocatalyst, [Ru(bpy) 3 Cl 2 ], is used to determine how each parameter affects the observed rate of reaction and the photon flux received in the reactor. These heuristics are then demonstrated using a photoredox reaction to see if they accurately predict flow reaction conditions that correspond to increased rates of reaction.Visible-light photoredox catalysis is an emerging field in organic synthesis as ap latformf or small-molecule activation. These transformationsc an be achieved using organometallic complexes, mostc ommonly Ru and Ir polypyridyl complexes, and organic molecules to absorb photons from simple light sources such as commercially available LEDs to facilitate single electron transfer between substrates. Advantages of photoredox catalysis include high stability of catalysts and reagents under ambient conditions, mild reactiont emperatures (with many transformations occurringa tr oom temperature), access to ab road range of substrates due to the high redox potentials of the catalysts, and the use of visible light as an inexpensive green source of energy.M any excellent reviewsa nd perspectives have recently discussed the advances in synthesis, functional groups,and classes of substrates that can be accessed via photoredox catalysis. [1] Other reviewsh ave providedv aluable insight into the photophysics of photoredox catalysts, both organic [2] and organometallic. [3] Althought he synthetic developments and thermodynamic understanding of catalystr edox potentials have advanced the field of photoredox catalysis with respectt oo rganic transformations and catalysts electiona nd design, significant challenges remain.The mostsignificant challenge facing the implementation of photoredox catalysis in industrial applications is scaling up reactions from laboratory batch reactorsw ith small volumes. [4] Efficient photon distribution in the reactor is critical to maintain fast rates of reaction at all points in space within the reactor,m eaning that the geometrica rrangement of the light source and the reactorm ustb ea djusted to maximize the photon flux received (that is, the total number of photons received/absorbed in the reactor that lead to observed chemical reactionp er unit time, given as mol photons s À1 ). [5] Furthermore, understanding the intrinsick inetics and mechanisms of photoredox transformations allows for improved design of scaled-up reactors, yet few reports of thorough kinetic examinations of such reactions exist within the last decade. [6] The reactanta nd catalystc oncentrations, intensity of the light source, and geometry of the reactor likely all contributet ot he photon flux that is received in the reactor. Understanding how changing these properties...

A Laser Driven Flow Chemistry Platform for Scaling Photochemical Reactions with Visible Light

“…Beyond the context of the high intensity laser, we have observed this same trend where decreasing catalyst concentration up to a certain point leads to increased rate of reaction, independent of the light source used. 38,53 Indeed, at the beginning of our evaluation, the system was designed based on the Beer-Lambert law calculation for 0.05 mol % of photocatalyst to give maximum absorption at a reaction depth of 5 cm. We attribute the difference in observed catalyst concentration to that determined from the Beer-Lambert law to significant solution darkening which occurs during the reaction which is equivalent to 50% increase in absorbance at Initially surprised by this counterintuitive trend, we sought to explore the generality of this principle in other reactions.…”

Positioning for a sustainable future—Role of chemical engineers in transforming pharmaceutical process development

“…The geometry of the lighting array and the reactor both significantly impact the performance of the reactor and subtle changes in this geometry can lead to dramatic effects on reactor throughput. The recent innovation of using laser light in a CSTR is a step toward overcoming these barriers and has enabled robust scale‐up of photochemical reactions 33,34 . Our studies indicate that higher intensity light sources lead to increased rates of reaction, thereby increasing throughput and yield.…”

“…The approach of using laser light in a CSTR offers reaction rates superior to those measured in optimized LED tubular flow reactors. We have demonstrated this benefit for a number of reactions of interest in the synthesis of pharmaceutical compounds 33,34 . The example shown here in Figure 13 used a higher power light source (25 W 450 nm fiber coupled laser system) for a CN coupling reaction.…”

Predicting Performance of Photochemical Transformations for Scaling Up in Different Platforms by Combining High-Throughput Experimentation with Computational Modeling

“…The photon flux decays with path length ( z ) as shown in Figure a. This effect is particularly exacerbated when scaling up photochemical reactions in batch reactors, since the illuminated surface area to volume ratio decreases exponentially as reactor volume increases. ,,, Moreover, the distribution of photon flux within the reactor could be time-dependent for the cases where the concentration of the photoactive species is changing with time, either due to the consumption or degradation of the input materials or formation of new photoactive species. Figure b demonstrates the change in overall absorbance and the photon flux through the reactor at residence time τ = t for the cases where the photoactive starting material is consumed to form a product that does not absorb in the wavelength region of interest.…”