Mesoscale flow chemistry: A plug-flow approach to reaction optimization

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Organic Process Research & Development 2007, 11 (4), 704-710

  • Rob C. Wheeler, Otman Benali, Martyn Deal, Elizabeth Farrant, Simon J. F. MacDonald, and Brian H. Warrington
  • GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NI, United Kingdom

The work published in this paper was performed on an Africa flow chemistry system (now replaced by Asia). The image below shows the formation of an organic reaction plug (orange solution) in a perfluorinated solvent system in 0.75mm i.d. PFA tubing.

Mesoscale Flow Chemistry: A Plug-Flow Approach to Reaction Optimisation

Abstract: In recent years, chemistry in flowing systems has become more prominent as a method of carrying out chemical transformations, ranging in scale from analytical-scale (microchemistry) through to kilogram-scale synthesis (macrochemistry). The advantages are readily apparent: increased control of conditions leading to greater reproducibility, scalability, and increased safety/reduced loss although its acceptance as a viable synthesis technique has been limited due to its drawbacks, primarily precipitation, liquid handling, and diffusion of the reaction within the reactor. Here, we present details of a system which bridges the gap between micro- and macro-reactors and has enabled fast reaction optimisation (using small amounts of reagents) and subsequent multigram scale-up using a commercial reactor.

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The chemistry was performed on an Africa 2 channel synthesis flow chemistry system (now replaced by Asia).