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.
The combination of kinetic understanding and reaction modeling has been successfully applied to the development of processes from laboratory to manufacturing plant. Although extensively used in bulk chemistry, polymers, and the oil industry
The
development of low-volume continuous processes for the pharmaceutical
industry requires a greater understanding of mixing in microreactors.
In this paper, numerous commercially available micromixers are evaluated
using the Villermaux–Dushman reaction scheme and the interaction
by exchange with the mean (IEM) mixing model to quantify the mixing
time. The work presents the mixing times as a function of flow rate
and energy dissipation for mixers including T-mixers, Ehrfeld Mikrotechnik
BTS micromixers, and Syrris Asia microchips.
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