There are many excellent resources to explain flow chemistry, some of which you can find links to in the section below. However, based on our experience with industrial clients who are exploring flow chemistry for the first time, we would like to list some things to keep in mind before beginning a project in flow chemistry.
A reaction in flow chemistry is typically carried out by pumping the reagents through a mixer and into micro- or mesofluidic tubing. This means that, ideally, the feed solutions containing the reagents should be stable, homogenous liquids. Also, all intermediates and products formed during the reaction should be soluble in the chosen solvent. Alternatives may exist for the treatment of solids, such as the use of pumps that can handle slurries, performing reactions above the melting point, use of sonication, or larger tubing, each alternative comes with limitations that should be taken into consideration.
The feed solution will take time to be fully processed, depending on the volume of the feed solution prepared and the flow rate at which it is pumped. Therefore, reagents that are incompatible should not be mixed in the feed solution. Combining several feed solutions will result in a reaction mixture in which the reagents are more diluted than the original feed solutions. This will affect the reaction mixture concentration, and therefore the throughput and the intensification of the reaction.
As a general guideline, a reaction should have a residence time under 15 minutes for it to be performed in flow in an industrial scale. For most reactions, this means that the conditions must be intensified: higher temperatures, pressures, or concentrations must be adopted than what would typically be used. The precise control of heat and mass transfer that can be obtained using flow chemistry allows such conditions to be used without triggering side reactions. This may mean that solvents may be used in temperatures above their boiling or flash points, while kept under pressure.
A frequent concern arises as to the safety of the conditions used: higher temperatures or pressures that would normally be “allowed” for the chemicals involved. The added safety of the process in flow chemistry arises from the precise control of reaction time (residence time); the possibility of increased heat transfer, avoiding thermal runaways; the lack of headspace in the reactor; the reduced volume of flow reactors compared to batch reactors. When assessing the safety of a flow process, these aspects must be taken into consideration. Incorporating a better understanding of flow chemistry with reglementary agencies is an ongoing effort.
New to flow chemistry? We invite you to consult the following:
Or request a training in flow chemistry.