Flow Chemistry - Segmented Flow Chemistry

Segmented Flow Chemistry

As discussed above, running experiments in continuous flow systems is difficult, especially when one is developing new chemical reactions, which requires screening of multiple components, varying stoichiometry, temperature and residence time. In continuous flow, experiments are performed serially, which means one experimental condition can be tested. Experimental throughput is highly variable and as typically five times the residence time is needed for obtaining steady state. For temperature variation the thermal mass of the reactor as well as peripherals such as fluid baths need to be considered. More often than not, the analysis time needs to be considered.

Segmented flow is an approach that improves upon the speed in which screening, optimization and libraries can be conducted in flow chemistry. Segmented flow uses a "Plug Flow" approach where specific volumetric experimental mixtures are created and then injected into a high pressure flow reactor. Diffusion of the segment (reaction mixture) is minimized by using immiscible solvent on the leading and rear ends of the segment.

One of the primary benefits of segmented flow chemistry is the ability to run experiments in a serial/parallel manner where experiments that share the same residence time and temperature can be repeatedly created and injected. In addition, the volume of each experiment is independent to that of the volume of the flow tube thereby saving a significant amount of reactant per experiment. When performing reaction screening and libraries, segment composition is typically varied by composition of matter. When performing reaction optimization, segments vary by stoichiometry.

Segmented flow is also used with online LCMS, both analytical and preparative where the segments are detected when exiting the reactor using UV and subsequently diluted for analytical LCMS or injected directly for preparative LCMS.