Issue link: https://www.e-digitaleditions.com/i/1420709
52 Pharmaceutical Technology APIs, EXCIPIENTS, AND MANUFACTURING eBOOK 2021 P h a r mTe c h . c o m Development Each bond in a molecule absorbs photons with a dis- crete wavelength, causing a change in its electronic configuration. Having knowledge of this prior to activation allows chemists to finely tune reactions for the required transformation. These light sources, however, required filters to narrow the wavelength bandwidth, and over irradiation of the reaction mixture often led to decomposition of starting ma- terials and products, resulting in the formation of byproducts via undesired reaction pathways. There has been a surge in research in this area of chemistry and, over the past 15 years, the de- velopment of single—or near enough monochro- matic—wavelength light-emitting diodes (LEDs). LEDs have emerged as a more economical and environmentally friendly alternative to broad spectrum lamps for activating molecules or func- tional groups of interest. Not all organic molecules are photoactive, so the field of photochemistry has moved on to include the use of valuable or- ganic and transition metal photocatalysts such as tris(bipyridine)ruthenium(II) [Ru(bpy) 3 ] 2+ to aid the desired process (5). The photoexcited catalyst generates reactive radicals of the starting materials, therefore offering an alternative reaction pathway via homolytic bond cleavage and single electron transfer processes. Photochemistry—with or with- out a photocatalyst—tuned to a specific wavelength can therefore provide access to transformations in which the user can make and break bonds in a unique fashion. This not only allows for cleaner reaction mixtures that are easier to purify, but also reduces the number of steps required to get to the desired product. Photochemistry also allows access to chemistries that cannot easily be achieved using round bottom f lasks and traditional methods. For example, photocatalyzed carbon–hydrogen (C–H) activation methods have expanded the range of available chemistry for this technique while reduc- ing the number of reagents required. Flow photochemistry reactors to the rescue Parallel to the increasing awareness of new photo- chemistry methods is the growing use of modern flow chemistry techniques to enhance the control of these reactions. Chemists ask many questions when it comes to planning experiments, from specifics about reaction conditions—based on the stereoelectronic properties of the molecules involved and the experi- mental set-up—to the analysis and purification of the target product. They also follow trends of new techniques, transformations, and catalysts, which is exactly what has happened in the area of continuous flow photochemistry, where its uptake is reflected in the dramatic increase of publications and conferences in recent years (1). Benefits of flow photochemistry The benefits of f low chemistry over traditional batch techniques are widely known, and these benefits translate equally to f low photochemis- try. Most of the benefits offered by f low chemistry come from the precise control of reaction param- eters, such as temperature, mixing, stoichiometry, and reaction times, in a chemical reaction. In a f low photochemistry reactor, this control can be further increased over traditional batch photo- chemical techniques by improved irradiation of the reaction for better selectivity, reaction scal- ability, and reproducibility. It is also possible to control reaction exposure times to prevent over ir- radiating, minimize product degradation, and pre- vent unwanted side reactions. Further benefits of particular importance include the increased safety