Speciality Chemicals Magazine SEP / OCT 2024 | Page 40

FLOW CHEMISTRY

dependent reactions , affect the reaction rate and the residence time of the slug . This phenomenon can be eliminated by using an immiscible carrier solvent that does not allow dispersion . For example , fluorinated solvents have been used to good effect with organic reaction conditions .

When using a miscible carrier , more dispersion is likely when using small segment volumes and longer residence times . For very small samples showing a large amount of dispersion , there will be a point where steady state conditions are not achieved .

It is therefore advisable to use a smaller volume flow reactor for small samples . The dispersion effect can be minimised by increasing the segment volume , as larger segments will provide better convergence , and generally lead to a steady state condition , giving the desired reaction concentration .

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Figure 5 shows the effect of increasing or decreasing the sample collection volume by adding or subtracting a volume at the front or back of a reaction segment to ensure , or avoid , collection of the transient regions . Diverse pre- and postslug values can be used to capture the heart cut of the sample ( the steady state ).

The total input volume is collected when the values are zero . An additional volume can be added to the front or the rear of the slug to ensure greater recovery , or subtracted for greater purity and less dilution .

Conclusion

Flow chemistry is a valuable technique that can be used to perform several functions in drug discovery , from creating a significant amount of

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Figure 4 – Solute concentrate in ideal ( a ) & nonideal ( b ) cases

the desired material to synthesising just enough material to optimise a process or screen novel compounds against a biological target . The needs of the target application will determine the most appropriate flow chemistry regime , and there are some crucial considerations when selecting the correct equipment and setting up experiments .

There is an increasing desire to use segmented flow approaches to synthesise an ever larger array of compounds , as this enables much smaller reactant volumes to be used . When using segmented flow in this way , it is vital to use a system capable of accurately tracking the segments , giving the user confidence that the segments converge and are collected at the correct times to give the best results .

In addition , software should enable experiments to be adapted to suit the segment yield and purity needs of the intended application . Careful choice of equipment and software will undoubtedly enhance the success of flow chemistry processes . ●

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References : 1 : N . Hawbaker et al ., Org . Process Res . Dev ., 2016 , 20 , 465-473 2 : K . D . Nagy et al ., Org . Process Res . Dev ., 2012 , 16 , 976-981 3 : B . Cerra et al ., ACS Med . Chem . Lett ., 2019 , 10 , 677-681

40 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981