In flow chemistry, a chemical reaction is running in a continuously flowing stream rather than in batch production. Previously, classical batch chemistry has been simple and effective when discovering new materials but using this method to scale up chemical production can be problematic. There can be issues with waste, for example, heat management or even runaway reactions. Moving to cleaner, more cost effective chemical production is important for sustaining chemical manufacturing in around the world. Flow chemistry is a smarter way of making chemicals.
This is how it works: pumps deliver chemicals to a reactor where chemical reaction takes place inside a continuous stream. Flow chemistry is a well-established technique for use at a large scale when manufacturing large quantities of a given material. However, the term has only been coined recently for its application on a laboratory scale.
- Reaction temperature can be raised above the solvent’s boiling pointas the volume of the laboratory devices is typically small. Typically, non-compressible fluids are used with no gas volume, so that the expansion factor as a function of pressure is small.
- Mixing can be achieved within seconds at the smaller scales used in flow chemistry.
- Heat transfer is intensified. Mostly, because of the area to volume ratio is large. As a result, endothermic and exothermic reactions can be thermostated easily and consistently. The temperature gradient can be steep, allowing efficient control over reaction time.
- Safety is increased:
- Thermal mass of the system is dominated by the apparatus making thermal runaways unlikely.
- Smaller reaction volume is also considered a safety benefit.
- The reactor operates under steady-state
- Flow reactions can be automated with far less effort than batch reactions. This allows for unattended operation and experimental planning. By coupling the output of the reactor to a detector system, it is possible to go further and create an automated system which can sequentially investigate a range of possible reaction parameters (varying stoichiometry, residence time and temperature) and therefore explore reaction parameters with little or no intervention.
Typical drivers are higher yields/selectivities, less needed manpower or a higher safety level.
- Multi step reactionscan be arranged in a continuous sequence. This can be especially beneficial if intermediate compounds are unstable, toxic, or sensitive to air, since they will exist only momentarily and in very small quantities.
- The position along the flowing stream and reaction time point are directly related to one another. This means that it is possible to arrange the system such that further reagents can be introduced into the flowing reaction stream at a precise time point that is desired.
- It is possible to arrange a flowing system such that purification is coupled with the reaction. There are three primary techniques that are used:
- Solid phase scavenging
- Chromatographic separation
- Liquid/Liquid Extraction
- Reactions which involve reagents containing dissolved gases are easily handled, whereas in batch a pressurized “bomb” reactor would be necessary.
- Multi phase liquid reactions (e.g. phase transfer catalysis) can be performed in a straightforward way, with high reproducibility over a range of scales and conditions.
- Scale up of a proven reaction can be achieved rapidly with little or no process development work, by either changing the reactor volume or by running several reactors in parallel, provided that flows are recalculated to achieve the same residence times.
- Dedicated equipment is needed for precise continuous dosing (e.g. pumps), connections, etc.
- Start up and shut down procedures have to be established.
- Scale up of micro effects such as the high area to volume ratio is not possible and economy of scalemay not apply. Typically, a scale up leads to a dedicated plant.
- Safety issues for the storage of reactive material still apply.