FLOW CHEMISTRY reactions like carbonylation and catalytic hydrogenations to run at high pressures 3 , 4
• Corrosive reagents : Reagents such as TFA , fuming nitric acid and organometallics are hazardous but useful . Nitration chemistry is a good example of what is achievable in flow . Highly exothermic reactions can be precisely controlled , allowing the use of neat fuming nitric acid and pushing reaction kinetics to their limit 5 , 6
• High pressure reactions : When running high ( 200-250 º C ) temperature reactions with volatile reagents , high system pressures are required to maintain everything in the liquid phase . For this , we need pumps able to pump organic reagents at 200 bar possible to rapidly explore a vast array of compounds . After this , analysing all the products became the limiting step . Integrating inline analysis , such as UV / Vis , IR , Raman spectroscopy or HPLC , can provide an insight into the reaction kinetics by either following product consumption or reagent formation . 9 This live data can also be used to determine which reactions were successful without further offline analysis . All the while , scientists were exploiting the technological advantages of continuous flow , especially in photochemistry . Batch photochemistry has some key limitations : uneven irradiation fields and difficulties in controlling the
Launched in 2006 , the R-Series was Vapourtec ’ s first flow chemistry platform
reaction ’ s temperature make these reactions very difficult to replicate . Scientists developed photoreactors in their labs by simply wrapping a polymer tube around a UV source . 10 These handmade reactors enabled photochemistry to reach a key milestone with the development of an efficient photochemical route for antimalaria drugs . 11 Vapourtec launched its photochemical reactor , the UV- 150 in 2015 . This can control both temperature and UV irradiation from exchangeable sources , from energetic UV ( 220 nm ) to visible light ( up to 700 nm ). It enabled flow chemists to explore photoredox catalysis , singlet oxygen formation and even photobromination with one reactor . 12-14
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• Pumping slurries : Solids can be problematic to handle in flow . Traditional pumps only work with solutions . Free-flowing solids almost invariably risk agglomeration and blockage in any part of the system . We developed a peristaltic pump to handle solids at pressure , operating as either a pump or a BPR , without blocking . Thanks to such features , flow chemistry rapidly expanded as a tool for reaction optimisation . As reactions can be programmed in series , different parameters ( stoichiometric ratio , residence time and temperature ) could be easily evaluated . Planning experiments with statistical tools , such as Design of Experiments , made flow chemistry an even more powerful tool as an optimisation platform or generator of kinetic models . 7 , 8
Automation & analysis
The next logical step was to further automate flow chemistry . The option to handle several different reagents in a flow set-up would allow scientists to expand their research to automated library synthesis . We hit this milestone in 2009 and could then use as many reagents as we wanted , even with just two pumps , which made it
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