Theoretical principles of flow chemistry

Chemistry in flow, or continuous flow chemistry, consists of carrying out syntheses in different pieces of equipment, through which the flowing reaction medium passes, and in which reactions and transformations are carried out in a controlled manner. It differs from batch chemistry, which is essentially carried out in a single piece of equipment in transient mode, in which the various stages of synthesis are carried out sequentially.

Compared to batch chemistry, flow chemistry offers a number of advantages.

• Better control and repeatability of reactions thanks to the use of several pieces of equipment placed in series, enabling temperature, pressure, concentration and residence time conditions to be precisely adjusted to the optimum conditions required by the reaction. Continuous flow chemistry equipment is highly modular.

• Intensification of transfers (heat, material and mixing) thanks to the miniaturization of equipment, which makes it possible to do away with limiting stages that very often have a detrimental effect on the conversion and selectivity of reactions.

• New operating conditions in terms of temperature, pressure and concentration can be achieved safely, often with higher productivity or shorter residence times.

  For example, running a continuous reaction under pressure enables reactions to be triggered at higher temperatures than batch reactions, where the solvent often refluxes at room temperature.

• Enhanced process safety. The transition from batch to continuous can reduce the risk of reactions considered too dangerous. Thanks to the intensification of heat transfer, continuous flow makes it much easier to control the temperature of highly exothermic reactions likely to lead to thermal runaway. The quantities of reactants coming into contact are smaller, and manual sampling is eliminated.

• Rapid analysis, optimization and extrapolation of chemical reactions. In continuous flow chemistry, it can be fairly easy and quick to modify reaction conditions (temperature, concentration), with small quantities of substrates and reagents, to search for optimal synthesis conditions.

Real-time, online analysis also enables you to quickly determine the effect of variables on reaction performance.

To understand the advantages of flow chemistry over batch chemistry, it is necessary to understand the fundamental principles that determine the conversions and yields of chemical reactions.

Four fundamental improvement principles are presented:

• heat transfer ;...