FLOW CHEMISTRY
The carrier fluids can be either liquid or gas , but are generally the same solvent that the reaction is performed in to minimise solubility issues . Segmented flow allows the introduction of small aliquots of reactants to create ‘ segments ’, allowing the screening of reaction conditions or the generation of libraries of compounds .
Reaction optimisation using segmented flow
Any chemical process will require the optimisation of the reaction conditions to achieve maximum yield with minimal by-products . Optimising reaction conditions or designing a new methodology using traditional batch methods can be time-consuming and expensive . A discrete reaction set-up is required to explore different reaction conditions , typically using a single round-bottomed flask or vial .
Reaction optimisation is much easier using flow chemistry . Modern flow chemistry systems with reagent injection modules , such as Syrris ’ modular Asia Flow Chemistry System , enable fully automated , walk-away procedures for both continuous and segmented flow applications .
Continuous flow regimes can be used to explore reaction optimisation rapidly , allowing parameters such as time , temperature and reaction stoichiometry to be easily altered . However , despite its ease of automation , continuous flow may not be the most efficient approach , because returning the system to a steady state between experiments takes time and consumes more material , and additional cleaning is required to avoid cross-contamination .
A segmented flow regime enables the same system set-up to be used to perform multiple reactions in sequence with only one flow reactor . Each reaction is discrete , and the carrier solvent acts as a wash fluid , cleaning the flow reactor between experiments .
Figure 2 – Continuous ( above ) & segmented ( below ) flow optimisation
This makes it easier to explore more chemistries with less material . The use of a reagent injection module to introduce the reactants , and advanced software to control the process , allows more efficient exploration of not only continuous reaction parameters , but also discontinuous variables – such as reagents and catalysts . Figure 2 illustrates continuous and segmented flow regimes for reaction optimisation .
Library generation using segmented flow
Library generation is not a new concept ; established drug discovery techniques encompass everything from single gramscale compound synthesis for screening through the development of combinatorial techniques , and automation is commonly used to generate large numbers of compounds . Automated flow chemistry systems can be combined with process analytical technologies and computational chemistry to generate focused libraries of chemical compounds with minimum human interference , as well as offering faster and more efficient processes when compared to batch chemistry protocols . 3
Segmented flow regimes are ideal for compound synthesis and library generation to aid in the early stages of drug discovery . Automated flow chemistry systems that incorporate reagent injection modules and liquid handling capabilities allow the evaluation of a range of reactants to generate a series of similar or diverse compound sets , depending on what the user wishes to explore .
The use of low-volume segments offers maximum efficiency for applications such as the generation of analytical data for reaction optimisation or the production of sufficient material for library screening . Samples are generally collected via an automated product – or fraction – collector , allowing volumes to be adjusted .
When generating a series of compounds , the reaction conditions are generally optimised for the chemistry being performed . Typically , the same reaction conditions are used to synthesise each unique compound of interest in a series of reaction segments .
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