The Right Light: De Novo Design of a Robust Modular Photochemical Reactor for Optimum Batch and Flow Chemistry

Bonfield, Holly E.; Mercer, Kayleigh; Díaz‐Rodríguez, Alba; Cook, Gemma C.; McKay, Blandine; Slade, Pawel; Taylor, George M.; Ooi, Wei Xiang; Williams, Jason D.; Roberts, Jack P.M.; Murphy, John A.; Schmermund, Luca; Kroutil, Wolfgang; Mielke, Tamara; Cartwright, Jared; Grogan, Gideon; Edwards, Lee J.

doi:10.1002/cptc.201900203

Cited by 65 publications

(71 citation statements)

References 39 publications

(46 reference statements)

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“…(intensity based on space). We have found that the angle of the LED lens affects this parameter 11 .…”

Section: Additional Considerations For Scalingmentioning

confidence: 88%

“…For literature reactions that we have reproduced, we have discovered that, although the air surrounding a reactor can be at ambient temperature, it is not uncommon for the internal reaction temperature to reach 60°C-80°C 11 . The specific type of reactor used for a reaction affects the internal reaction temperature 11 . Signifying the reactor configuration and any heat transfer elements used is the key.…”

Section: Stark-einstein Law or Photoequivalence Lawmentioning

confidence: 99%

“…Many pharmaceutical companies and external technology suppliers have developed their own photochemistry platforms, meaning that there is a trend towards standardization within companies [11][12][13] . Characterization of equipment within each organization/group is the first step toward the future of photochemistry in the modern era.…”

Section: Beer-lambert Lawmentioning

confidence: 99%

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Photons as a 21st century reagent

et al. 2020

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A pharmaceutical industry viewpoint on how the fundamental laws of photochemistry are used to identify the parameters required to implement photochemistry from lab to scale. Parameters such as photon stoichiometry and light intensity are highlighted within to inform future publications. Photochemistry employs photons to drive chemical transformations. Traditional approaches rely on the direct excitation of bonds with light 1,2. In contrast, photoredox catalysis uses a photosensitizer to facilitate electron transfer, generating reactive intermediates under mild conditions 3. From a pharmaceutical industry point-of-view, photochemistry is a powerful tool to access highenergy intermediates that can provide novel reactivity and enables new disconnections, allowing target-and diversity-oriented synthesis to be explored 4. Photochemistry is extensively used within medicinal chemistry projects, but has not yet been extensively employed for the commercial manufacture of pharmaceutical agents 5. The scientific community has published new and exciting photochemical methods, but in our experience these transformations can be challenging to reproduce 3,6. We believe that this difficulty results from an under-emphasized importance of fundamental photochemical concepts, which renders translation of methods between setups challenging. Most authors try to describe the key features of the photochemical system used in their experiments; however, the description may not be completely sufficient to ensure reproducibility in a different lab or comparable reactor system. It can be quite common to find little technical detail about the equipment setup in the Supplementary Information and many summaries fall short of fully characterizing the photo-physical properties of their setup. We believe that careful characterization and description of the photochemistry equipment is essential; more systematic and better documented experimentation will enable greater mechanistic understanding, leading to facile identification of the key scale-up factors. From a review of the fundamentals of photochemistry, we will detail the minimum information to include in any photochemistry-related publication. This will enable the chemistry community to more readily assess and adopt photochemical transformations. We will then look toward the future of photochemistry for a manufacturing system that applies this technology. Grotthuss-Draper law Light must be absorbed by a chemical substance for a photochemical reaction to occur. Photon absorption excites a molecule from its ground state to an excited state. Chemical substances only absorb at specific wavelengths, so it is critical that the right wavelength is selected for the desired transformation.

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“…(intensity based on space). We have found that the angle of the LED lens affects this parameter 11 .…”

Section: Additional Considerations For Scalingmentioning

confidence: 88%

Section: Stark-einstein Law or Photoequivalence Lawmentioning

confidence: 99%

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Photons as a 21st century reagent

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“…Moreover, it comes to meet the need of the pharmaceutical industry for characterized commercial photoreactors. [16] Experimental Section…”

Section: Discussionmentioning

confidence: 99%

Photon Transport and Hydrodynamics in Gas‐Liquid Flow Part 2: Characterization of Bubbly Flow in an Advanced‐Flow Reactor

et al. 2020

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The Corning® G1 Advanced-Flow™ Reactor (G1 AFR) is a commercially available meso-scale reactor which promotes a bubbly flow regime and was previously used to scale-up gasliquid photoreactions. In this paper, we study how the photon transport and hydrodynamics affects the performance of G1 AFR in gas-liquid flow. This was realized by analyzing the flow pattern, liquid residence time, photon flux per liquid volume and optical pathlength using image analysis, residence time distribution (RTD) experiments and chemical actinometry. While the gas content did not significantly influence the RTD responses and photon flux per liquid volume, it affected the liquid residence time and optical pathlength. An empirical correlation was proposed to predict the optical pathlength in gas-liquid flow. The constant photon flux per liquid volume and hydrodynamics found for bubbly flow in G1 AFR translate into high flexibility to choose the flow conditions without affecting the performance of this photoreactor.

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“…4 A rising interest in photochemistry has been seen from the pharmaceutical industry. 5 Organic photoredox catalysts are growing in popularity due to the avoidance of expensive and toxic metals such as ruthenium and iridium. 6 Acridinium salts are among the most popular of these.…”

mentioning

confidence: 99%