Bubble flow in a flow reactor
Flow chemistry, sometimes referred to as plug flow, microchemistry or continuous flow chemistry is the process of performing chemical reactions in a tube or pipe. Reactive components are pumped together at a mixing junction and flowed down a temperature controlled pipe or tube.
The major advantages of flow chemistry are faster reactions, cleaner products, safer reactions, quick reaction optimization, easy scale-up, and the integration of typically separate processes (such as synthesis, work-up and analysis).
The Benefits of Flow Chemistry
Mixing of liquids in a Syrris glass microreactor
Flow reactors are easily pressurized (e.g. Asia systems can be pressurized to 300psi). This allows reactions to be heated 100-150ºC above their normal boiling point therefore creating reaction rates that are 1000s of times faster. This process is called superheating.
Flow reactors enable excellent reaction selectivity. The rapid diffusion mixing avoids the issues found in batch reactors. The high surface area to volume ratio (1000x greater than a batch reactor) enables almost instantaneous heating or cooling and therefore ultimate temperature control.
Flow chemistry allows only a small amount of hazardous intermediate to be formed at any instant. The high surface area also allows excellent control of exotherms.
Flow reaction showing mixing in a microreactor
Integrated Synthesis, Work-up and Analysis
Reaction products exiting a flow reactor can be flowed into a flow aqueous work-up system or solid phase scavenger column. From there they can be analysed either in line (e.g. FTIR) or a sample taken, using a sampler and dilutor then and injected onto and LCMS.
Rapid Reaction Optimization
Flow Chemistry with automation enables the quick variation of reaction conditions on a very small scale e.g. 100µl. Parameters such as reaction time, temperature, ratio of reagents, concentration and reagents themselves can all be rapidly varied. One reaction can follow another, separated by solvent, each cleaning out the previous reaction.
Scale up issues are minimized due to maintaining excellent mixing and heat transfer. Higher flow rates and correspondingly larger reactors can be used to easily produce kilogram quantities.
Reaction Conditions Not Possible in Batch
Flow chemistry facilitates reaction conditions not possible in batch such as a 5 second reaction at 250ºC. Multi step procedures such as a rapid low temperature deprotonation followed instantaneously by the addition of an electrophile high temperature are made easy.
This section provides information about the application of flow chemistry. Please use the navigation to the right to access more specialist flow chemistry information.
Examples of Flow Chemistry
Syrris has a range of resources that demonstrate a variety of flow chemistry application notes and reactions using Syrris' flow chemistry systems. Syrris' innovative microreactor based systems include the modular Asia and Africa product ranges. Here are two examples shown below:
Oxidation of a primary alcohol
This paper describes reaction conditions for the oxidation of alcohols in continuous flow using a column reactor packed with polymer-supported tetra-N-alkylammonium perruthenate.
Steven V. Ley, Ian R. Baxendale, Jon Deeley, Charlotte M. Griffiths-Jones, Steen Saaby, Geoffrey K. Tranmer (University of Cambridge)
Williamson Ether Synthesis
This paper describes a multi-step formation of functionalized indoles. This step focuses on a high yielding Williamson ether synthesis using Methanol as a nucleophile.
Thomas Tricotet and Donal O’Shea (University College Dublin)