Neal Munyebvu, Technical Support Specialist, Syrris

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Building up a compound library in continuous flow

By on April 18th, 2018 in Flow chemistry
One of the biggest challenges of becoming invested in flow chemistry is often the thought of taking time integrating and developing brand new chemical reactions. Screening of various reaction stoichiometries and various conditions can take time. Alongside the time required to analyze the sample, identify the desired reaction and conduct further optimization.

Plug-flow, or segmented flow chemistry

It is often not considered that one of the solutions to this is, in fact, one of the largest benefits of using flow chemistry. The ability to run flow experiments in segments. This is what we call ‘plug-flow’ or ‘segmented flow’ chemistry.

This is where you set up a flow system to run specific volumes of reagents in line which are separated by a volume of carrier solvent.

This can be the case for each input line, segmenting each reagent. This allows you to create segments which can be set to run under different stoichiometries and conditions in an automated fashion.

Syrris Asia Reagent Injector module for flow chemistry

A reagent injector allows for small samples of reagent to be injected in continuous flow

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 one after the other in series to give 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

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

An example of this is given in the matrix below which is similar to what would be found in DoE software and allows the user to set the desired conditions and variables for each reaction:

Run Name Flow Rate – Reagent Injector 1 Flow Rate – Reagent Injector 2 Temperature Pressure Collection Volume
1 Reaction 1 50 μL/min 50 μL/min 40 °C 0 bar 1600 μL
2 Reaction 2 200 μL/min 200 μL/min 80 °C 10 bar 1600 μL

The DoE software programs this and implements the conditions to run one after the other as below:

Design of Experiment (DoE) software steps for flow chemistry compound library generation

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 favorable conditions and results in a much more optimized 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 analyzed together.

The fact that the volume of your reagent makes up a small amount of the total volume of your flow system (which is made up primarily of carrier solvent) ultimately saves a significant amount of reagent per experiment.

An automated reagent injector allows for small samples of reagent to be injected in flow

The Syrris Automated Reagent injector allows for up to 24 different reagents (12 on each channel) to be injected in continuous flow

Screening various different reactions

Not only can you end up creating a library for optimization of a single reaction, but you can also run an array of different reactions, one after the other using an automated reagent injector.

Consider the reactions:

Reaction 3: R + Y → O

Reaction 4: R + B → P

Reaction 5: B + Y → G

Design of Experiment (DoE) software steps for flow chemistry compound library generation 2

All different reagents running different reaction profiles each set to run one after the other in series and collected in 3 separate vials for analysis.

This allows the creation of a library of compounds all at once which can be analysed quickly and easily.

Discuss your compound library generation needs

Want to discuss compound library generation with a Syrris chemist? Simply fill in the form below and we’ll get back to you.

About Neal Munyebvu (MChem)

As a Flow Chemistry Technical Specialist for the Syrris Support Team, Neal is responsible for installing Asia Flow Chemistry Systems in sites around the world, helping chemists overcome issues, and enabling chemists to get the most out of their flow chemistry equipment.

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