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10 facts about continuous flow chemistry

Flow Chemistry

1. Do you know what exactly flow chemistry is?

Flow chemistry is the process of performing chemical reactions in a tube, capillary, or a flow reactor. Like traditional batch chemistry reactors, where reagents are mixed in a vessel, flow chemistry systems use a pump to send reagents through tubes and into a flow reactor where they blend and are immediately heated or cooled using a temperature control module.  There are various types of flow reactors available, such as glass micro-reactor chips, tube reactors, and solid-phase column reactors or packed bed reactors.

Flow Chemistry

2. Do you know why it is better to perform your chemistry on continuous flow?

Continuous flow techniques have been adopted by chemists in many industries. However, do you know which advantages your lab will get by performing continuous flow chemistry?

  • Faster reactions: Higher pressures enable higher temperatures, resulting in faster reaction
  • Safer reactions: As there is a reduction in the number of reactions happening at one time, only a small amount of liquid is mixed through glass chips.
  • Faster reaction optimization: Each reaction is flushed out by the next, separated by a solvent, therefore only one continuous flow chemical reactor is required.
  • Fast serial library synthesis: Advanced flow chemistry systems allow fast, serial library synthesis and purification of 10s-100s of compounds a day, with total automation of liquid handling using automatic reagent addition and product collection modules.
  • Reaction conditions not possible in batch: Flow chemistry techniques enable new chemistries. Mixing happens by diffusion, which is considerably faster and more efficient than conventional methods of batch chemistry; Reactors are pre-heated and pre-cooled therefore the reaction temperature can change almost instantly; Heat up and cool down times are much faster than a microwave, so ultra-hot, ultra-fast reactions are viable.
  • Reactions are usually more selective: Due to a high surface area - volume ratio and diffusional mixing, flow chemistry systems permit much better selectivity, due to their exceptional temperature control and minimal concentration gradient.
  • Scale up is easier in flow than batch: The vital principle of a higher surface area to volume ratio means that scaling up in continuous flow decreases the heat transfer effect. The mixing is faster and more reproducible if using static mixers. In summary, continuous flow chemistry can save time and money when scaling up reactions.
  • Easy integration of reaction analysis: In continuous flow chemistry, numerous reactions can flow “under” the same probe. Smart flow chemistry systems can include sampling and diluting modules which automatically divert a tiny amount of each reaction for analysis.
  • Reactions are easier to work-up in flow: In continuous flow chemistry, the reaction is already mobile, enabling in-line (integrated) work-up of liquid to liquid extraction and solid phase reagents/scavengers/filtration.
Flow Chemistry

3. Continuous flow polymerization is possible!

Although the idea of carrying out polymerizations in tubes may sound absurd, chemists around the world are effectively doing that. The objects of the polystyrene production methods are high molecular weight, narrow molecular weight distribution, good productivity, and high conversion rates of the styrene monomer to polymer.

4. Flow chemistry makes electrochemistry and photochemistry easily accessible

Chemistries which don’t use reagents such as electrochemistry and photochemistry – are extremely difficult for chemists to perform precisely. The high levels of control that continuous flow chemistry systems provide allow for these chemistries to happen.

Although these systems can be easily set-up, there has been a reluctance to implement them as in the past, electrochemistry techniques relied on electrolysis in glass reactors leading to poor control of reactions, low selectivity, reproducibility, and sluggish reaction rates.

Electrochemistry is a surface phenomenon, which requires a large surface area to volume ratios, lending itself to continuous flow chemistry systems as flow chemistry reactors have a large surface area to volume ratio compared to equivalent volume batch reactors.

5. Continuous flow biocatalysis is on the rise – for good reason!

Chemists are concentrating on the continuous flow biocatalysis as it can be used in the production of fine chemicals, drugs, biotherapeutics, biofuels etc. The graph below shows the total number of patents and publications in continuous flow biocatalysis since 2000.

Flow Chemistry

Batch stirred tank reactors are the most common approach in traditional biocatalysis systems. Consequently, it is the most widely available type of reactor. However, this method has relatively low volumetric productivity, and the collision of the enzyme with stirrers and impellers causes degradation and attrition of the enzyme. Flow chemistry, though, offers numerous benefits over traditional methods, including:

  • Increased rates of biotransformations:due to its increased mass transfer, flow chemistry makes biocatalysis more economical by decreasing reaction times and increasing throughput of material
  • Immobilization of enzymesallows for better stability, reduces product purification, allows better control of substrate contact time and its recyclability reduces costs and extends their applicability for production

6. Continuous flow nanoparticle synthesis offers multiple benefits over traditional methods

Due to their physical and chemical properties, nanoparticles are used in many fields, leading to an increasing demand that challenges chemists to have a reliable supply of large quantities of nanoparticles of good quality.

In the production of nanoparticles in batches, different chemical methods have been used, but these all present problems: lack of homogeneity in mixing, the importance of ageing, the challenge of precise temperature regulation and uncertain reproducibility from batch to batch. A batch process frequently depends as much on the chemist's knowledge as on the chemistry itself.

When scaling up the production, all these problems are much moredifficult to solve. Flow chemistry provides a range of benefits that help solve these challenges:

  • Fast and reproducible mixing
  • Accurate reaction control
  • Excellent temperature control
  • The ability to carry out pressurized reactions
  • System modularity
  • Easy scale-up

7. Chemists are drastically improving old chemistries through continuous flow

There are several examples that we might use here, but one that really stands out is the work of Kappe Lab researchers who have developed a continuous flow procedure for the synthesis of Ciprofibrate, a drug used for the treatment of different blood diseases, which substituted hours of intense batch stirring with a residence time of 4 minutes. The conversion of batch to flow enhanced safety, speed, yield, and scalability of an existing process.

8. Solid phase catalysis is possible in continuous flow

It is possible to carry out solid-phase catalysis in a continuous flow with the packed bed or column reactors enabling the chemical to flow through a column reactor packed with a solid phase catalyst through the liquid phase.

Flow Chemistry

9. Converting your batch processes to flow – or introducing continuous flow in your existing setup – doesn’t have to be a difficult task

Perhaps the greatest challenge for chemists implementing flow chemistry is the time it takes to turn a batch process into a smooth flow set-up, but it does not have to be!

This blog post addresses the 7 key points to keep in mind when you are looking to transform your batch process to continuous flow, whether you want gradual or immediate adoption.

10. Continuous flow will continuously grow

As the number of regulatory agencies allowing continuous flow processing processes grows, there is an ever-increasing need for laboratories to investigate and adopt continuous flow processes to keep up with competitors, thanks to enhanced production, reduced energy requirements and waste, and the decreased chance of human error generated by continuous flow.

Want to know more about Continuous Flow Chemistry? 

If you’re considering implementing continuous flow techniques into your lab, or even if you’re already working in flow but looking to improve your results, contact our Sales Team today. They will be happy to help you with all your lab needs.


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