News > Building Up a Compound Library in Continuous Flow Chemistry

Building Up a Compound Library in Continuous Flow Chemistry

Syrris is the world leader in flow chemistry, chemical scale-up, batch chemistry reactor systems, and reaction calorimetry solutions. As the dedicated distributor for Syrris in Ireland, Lab Unlimited offers Syrris’s award-winning flow chemistry systems in lab, pilot plant and production scales. We have previously written about Flow Chemistry Reactors and the Reasons to Perform Flow Chemistry. In this article, we will talk about ways of creating new reactions and products that will help you in this process.

One of the main challenges to embracing flow chemistry is the concept of spending time incorporating  and designing  novel chemical reactions. It can be very time-consuming to screen many reaction stoichiometries and numerous conditions, as well as defining the desired reaction and performing additional optimisation.

Plug-flow, or segmented flow chemistry

One of the solutions to these challenges is also the most significant advantage of using flow chemistry, and yet it is frequently ignored, which is the ability to perform flow experiments in segments, also known as “plug-flow” or “segment flow” chemistry.

Plug-flow or segmented flow chemistry involves setting up a flow system to run particular quantities of reagents in line, separated by a volume or carrier solvent. For instance, each input line segmenting each reagent, enables you to automate the development of segments that can run under various stoichiometries and conditions.

Designing the experiment

Consider the reaction:

R + Y → O

Where R and Y are the same volume and concentration (this does not have to always be the case).

This can be set up using a Flow Chemistry system to run each reaction in series to achieve the following reaction profile:

• Reaction 1: 40 ºC, Residence Time: 16 minutes
• Reaction 2: 80 ºC, 10 bar, Residence Time: 4 minutes

Optimizing the experiment

Optimizing the experiment can be set and automated using Design of Experiment (DoE) software, which allows the user to try to create a matrix of possible conditions and variables.

The matrix below is an example of what would be found in DoE software, allowing the user to define the desired conditions and variables for each reaction:

The DoE software programs the matrix and implements the conditions to run consecutively, as below:

Using the conditions in Reaction 1, A and B react to produce product O at low yield and purity.

In Reaction 2, R and Y react to create O in much more favourable conditions and results in a much more optimised reaction.

At the point of collection, however, this would not always be clear. Segmented flow chemistry means you can set up your experiments to ensure the products of reaction 1 and reaction 2 are collected in separate vials to create a sequence of products which can then be analysed together.

Since your reagent only makes up a small portion of the overall volume of your flow system (which is mainly made up of carrier solvent), you can save a substantial volume of reagent per experiment.

Screening various different reactions

As well as building a library for optimising a single reaction, you can also use an automatic reagent injector to run a series of reactions sequentially.

Consider the reactions:

Reaction 3: R + Y → O

Reaction 4: R + B → P

Reaction 5: B + Y → G

All different reagents run different reaction profiles in sequence and are collected in 3 separate vials for analysis, allowing for the creating of a compound library at once, enabling fast and easy analysis.

Discuss your compound library generation needs:

If you’re considering implementing continuous flow techniques into your lab, want to discuss compound library generation 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.