Synthetic toolbox: Flow chemistry

Catalysis

Catalysis is an important aspect of green chemistry and there have been many efforts to develop supported catalysts for use on large scale. In small scale batch reactions, the catalyst, reagents, reactants and solvent are mixed together and stirred until reaction completion, after which the bulk liquid is separated by filtration, and the catalyst is collected for re-use or disposal.[1] In continuous systems, the catalyst can be fixed in space over which the reaction mixture is allowed to flow, allowing the reaction and the separation steps to be combined into a single stage.[1] The catalyst remains in the reactor, allowing for ease of recycling; this system also allows the catalyst a longer lifetime as a result of the reduced exposure to the external environment.[2] As a result, reaction rates and catalyst turnover numbers are augmented through use of high catalyst concentrations and continuous recycling.  

An area of chemistry that has been difficult to implement on large scale pharmaceutical production is photochemistry; light has long been considered a valuable tool for performing synthetic reactions, it acts as a traceless agent facilitating the reaction without the production of further waste or the need for removal from the reaction mixture.[1][3][4]Though photochemistry has found application on industrial scale, its use is still uncommon in the pharmaceutical and fine chemicals industry; largely due to the use of batch reactors and the challenges associated with using photochemistry on a large scale, where the sheer volume of the reactor does not allow for complete light penetration.[5][6] Flow chemistry allows better access to photochemistry as a tool at a range of scales using inexpensive equipment:  the reaction mixture is pumped through a transparent tubing or transparent chip microreactor which is irradiated with a light source, the small diameter of the tubes allows for satisfactory light penetration, permitting all reaction molecules to be exposed to the same amount of heat and light. This comprehensive light exposure generally means that photochemical reactions run in flow tend to be orders of magnitude faster than their corresponding batch reactors.[1]

  1. S. G. Newman and K. F. Jensen, The role of flow in green chemistry and engineering, Green Chem., 2013, 15, 1456-1472.
  2. C. G. Frost and L. Mutton, Heterogeneous catalytic synthesis using microreactor technology, Green Chem., 2010, 12, 1687-1703.
  3. J. Xuan and W. - J. Xiao, Visible-Light Photoredox Catalysis, Angew. Chem. Int. Ed., 2012, 51, 6828-6838.
  4. J. M. R. Narayanam and C. R. J. Stephenson, Visible light photoredox catalysis: applications in organic synthesis, Chem. Soc. Rev., 2011, 40, 102-113.
  5. J. P. Knowles, L. D. Elliott and K. I. Booker-Milburn, Flow photochemistry: Old light through new windows, Beilstein J. Org. Chem., 2012, 8, 2025-2052.
  6. M. Oelgemoeller, Highlights of Photochemical Reactions in Microflow Reactors, Chem. Eng. Technol., 2012, 35, 1144-1152.