What is flow chemistry? How do flow chemistry systems work?

By Andrew Mansfield on April 17th, 2018 in Flow chemistry, The Flow Chemistry Collection

Famous chemistry professors are doing it. Magazines are writing about it. Students are focusing on it. Research and development chemists are perfecting reactions with it, and scale-up chemists are producing products with it.

You’ve undoubtedly heard about flow chemistry, but unless you’ve used our R&D100 Award-winning Asia Flow Chemistry System, you might still be wondering – what, exactly, is flow chemistry?

The basics of flow chemistry

Though it goes by a number of names – “plug flow chemistry”, “microchemistry”, and “continuous flow chemistry” – the principles of flow chemistry are the same.

Flow chemistry is the process of performing chemical reactions in a tube, capillary or micro structured device (a flow reactor).

What this means is that reactive components are pumped first through a mixing device, either a t-junction or a static mixer and then flowed down a temperature-controlled flow reactor; a radically different approach from the traditional chemistry method of performing reactions in glass flasks or jacketed reactors.

Further to maintaining a fixed temperature to promote a reaction flow chemistry lends itself perfectly to using photon or electron flux to mediate continuous reactions.

The differences between plug flow and continuous flow chemistry
Though often used interchangeably, there is a small difference between “plug flow chemistry” and “continuous flow chemistry”.

Continuous flow chemistry is just that – continuous. The reactive materials are continuously pumped with no breaks, resulting in a continuous stream of chemicals, and therefore a continuous stream of end product.

Plug flow chemistry is where alternating “plugs” of reactive materials and solvent are pumped, where each plug is considered as a separate entity (a discrete reaction mixture). These plugs never meet – they are separated by the system solvent – so the conditions in which they go through the flow chemistry system (i.e. temperature, stoichiometry, residence time etc.) can be changed to observe how the reaction changes.

Plug flow lends itself well for method development, reaction optimization, and library synthesis, where smaller amounts of material are required.

Intelligent systems, such as the Asia Flow Chemistry System, can automate these processes. Automation enables a range of reaction conditions, reagents or analogs to be explored with the automated collection of individual plugs, sending the product into one collection vial and the solvent to waste.

What is a mixing junction?

So what do we mean by a “mixing junction”? A mixing junction is where our reagent streams meet before flowing into our flow reactor. Often this is a simple t-piece but if faster more efficient mixing is required, e.g. for reactions needing fast mass transfer, a static mixer can be used. The two types of mixing junctions contribute to different mixing regimes, diffusive and turbulent.

When a fluid is flowing through a closed channel such as a flow reactor, either of two types of flow may occur depending on the velocity and viscosity of the fluid: laminar flow or turbulent flow. Laminar flow tends to occur at lower velocities, below a threshold at which it becomes turbulent. Turbulent flow is a less orderly flow regime that is characterized by eddies or small packets of fluid particles, which result in lateral mixing. In non-scientific terms, laminar flow is smooth, while turbulent flow is rough.

Mixing in laboratory scale flow systems such as Asia mixing will occur through the lateral mixing regime of laminar flow. Diffusion mixing can be slow however the diameter of the tubing used on these scales is small and diffusive mixing is very significant, and more notably reproducible. 

When rapid mixing is required, e.g. in reactions that require fast mass transfer, turbulent flow is necessary. Turbulent mixing is generated in flow generally by a micromixer (static mixer) of some type.

What types of flow reactors are available?

A flow reactor is essentially the equivalent of a round-bottomed flask or a jacketed reactor – it’s where the reaction occurs in a flow chemistry system.

As described earlier two (or more) separate solutions of reactive compounds are brought together, mixed and flowed through a single, temperature-controlled channel in order to react them.

Flow reactors come in a variety of shapes and sizes, but they all perform the same role: to allow chemical reactions to take place continuously. There are a few characteristics that flow reactors should aim to provide:

• Flexibility in volume to allow a large range of residence (reaction) times
• Excellent mixing
• Excellent heat transfer
• Good visibility where possible
• Ability to perform different types of chemistry (i.e. Homogeneous and heterogeneous)

The common types of flow reactor are outlined below and are all available with the Syrris Asia Flow Chemistry System.

Glass microreactor chips

Glass microreactor chips are the most commonly known type of reactor used in a flow chemistry system. A piece of glass is “etched” with a particular design (depending on the application); the design helps determines how wide the mixing channel is and how the mixing occurs. A longer channel enables a longer residence time than a shorter channel (assuming the pump flow rate is the same).

Glass microreactor chips are inserted into chip climate controllers which maintain a set temperature throughout the entire chip and are the perfect system for chemists just starting out in flow chemistry.

Tube reactors

Tube reactors are effectively long tubes wrapped around a heated or cooled coil. The large length of the coil offers far longer residence times than glass microreactor chips (or much faster pump flow rate) if the application requires it.

Tube reactors are available in different materials, depending on the application. Material such as PTFE allows good visibility of the flow reaction but are limited for high-temperature reactions. Stainless Steel and Hastelloy enable higher temperatures and pressures to be achieved.

Column reactors

Column reactors are typically glass columns and allow heterogeneous chemistry to be performed, small diameter tubes don’t like having solids passed through them. Solid-supported reagents, catalysts, enzymes, and scavengers can be employed – this will be explored in further blog posts.

So why are chemists adopting flow chemistry into their reactions?

By saying flow chemistry is essentially one more tool to add to the chemist’s tool-box does not do this synthetic technique the justice it deserves. Flow chemistry techniques allow the precise control of reaction conditions such as stoichiometry, mixing, temperature control, and reaction time. Controlling these factors gives excellent reaction control often leading to greater yields and better selectivity.

FYI – We’ve put a whole blog post and infographic together to explain the 9 main benefits flow chemistry offers. Read it here.

There are a number of reasons chemists across all industries are introducing or switching to, continuous flow chemistry, but in short, the main benefits are;

• Faster reactions
• Safer reactions
• Faster reaction optimization
• Fast serial library synthesis
• Reaction conditions not possible in batch
• Reactions are usually more selective
• Scale up is easier in flow than batch
• Easy integration of reaction analysis
• Reactions are easier to work-up in flow

Conclusion

So now you know what flow chemistry is, how it works, and the different types of mixing junctions available. But if you’re performing chemistry in batch at the moment, why would you bother switching to continuous flow? The “why perform your chemistry in continuous flow?” blog post explains the 9 main reasons chemists in various industries are adopting flow chemistry into their labs.