Dispersion-generated concentration gradients and cyclic flow for reaction optimisation and kinetic analysis

The use of dynamic flow experiments where variables such as reaction time, light exposure, temperature or component concentration vary during a continuous run rapidly generates reaction data. The variation of concentration of one or more components is a powerful technique but requires dynamic control of flow rates of several pumps, something generally not available in commercial systems. Herein we present a method for varying component concentrations without needing dynamic flow rate control, readily implemented in simple flow systems. Taylor dispersion of a plug of a reaction component as it passes through a tube generates a concentration gradient which, when combined with the other components and passed through a reactor with continuous monitoring of output, allows the effect of all concentrations up to the maximum of the dispersed component to be examined in a single flow experiment. The dynamic flow methodology was successfully applied to kinetic studies of first-order and second-order processes, and to investigate the influence of the concentration of palladium, ligands, and additives on the Heck and Sonogashira coupling reactions. Cyclic reciprocating and unidirectional flow were used alongside dispersion-generated concentration gradients to allow simultaneous investigation of the effect of species concentration and residence time on an S_NAr process. Further methodology refinements include the introduction of concentration gradient clipping, the use of glass bead-filled reactors to reduce dispersion, and the use of multiple concentration gradients of different reactants in a single unidirectional cyclic flow experiment.