Photons as a 21st century reagent

Abstract

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.

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

“…They discovered that the choice of the PS impacted the selective formation of mono-vs difluorinated products at the benzylic position; 9-fluorenone affords benzylic monofluorination and xanthone affords benzylic difluorination (Scheme 5). Importantly, this metal-free direct C-H fluorination proceeded without the need for any specialized photochemical equipment; under visible-light irradiation by a household (19 W) compact fluorescent light (CFL) bulb (emitting variable wavelengths in the range of ≈365-625 nm) [195] and under mild conditions. Control reactions revealed that both the PS and light were essential for the reaction to occur.…”

Distinct Sustainable Carbon Nanodots Enable Free Radical Photopolymerization, Photo‐ATRP and Photo‐CuAAC Chemistry

“…Light as a reagent and tool [1][2][3][4][5][6][7][8][9][10][11] has received gained interest because it interdisciplinary connects different fields of chemistry, biology and physics resulting in emerging applications related to display technologies based on holography [12] , 2D [13][14] and 3D printing [15][16][17][18] , photopharmacology [19] , dentistry [20] or environmental sciences to clean water and/or air from microbial ballast [21] -just to name a few emerging applications. It requires knowledge about the properties of the excited state such as lifetime, redox potentials and excitation energy to design systems working with appropriate light sources such as LEDs or lasers resulting in generation of initiating radicals or conjugate acid to initiate radical or cationic polymerization, respectively.…”

A method to determine the correct photocatalyst concentration for photooxidation reactions conducted in continuous flow reactors

“…The narrower spectra, while providing many benefits and likely reducing the occurrence of side reactions, also facilitate that other factors become more important. Notably, an exact description of the photoflow setup is now crucial to ensure reproducible experiments [20,21].…”