As this is our first blog post about flow chemistry I thought it might be useful to start with the basics and explain what flow chemistry actually is, and talk a bit about why is flow chemistry so useful.

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. What this means is that reactive components are pumped together at a mixing junction and flowed down a temperature controlled pipe or tube. See the below graph illustrating the principle of mixing.

whats-is-flow-chem

There are lots of advantages to flow chemistry such as 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). But how can you achieve these? 

Faster Reactions The benefit of using flow reactors is that they are easily pressurized. 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.
Cleaner Products 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.
Safer Reactions 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.
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.
Easy Scale-Up 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 is the first post in the series of general topics we plan to cover about flow chemistry, don’t miss our next posts – simply subscribe on the right!

 

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