Liquid–Liquid Microsystems in Organic Synthesis - Liquid–Liquid Biphasic Reactions - Microreactors in Organic Chemistry and Catalysis, Second Edition (2013)

Microreactors in Organic Chemistry and Catalysis, Second Edition (2013)

8. Liquid–Liquid Biphasic Reactions

8.6. Liquid–Liquid Microsystems in Organic Synthesis

Exploiting of liquid–liquid microreactor in organic synthesis offers attractive advantages, including the reduction of diffusion path lengths to maximize the rate of mass transfer and reaction rates. Despite the advantages, interest in liquid–liquid microreactors did not take off until recently, perhaps due to the complication of flow pattern manipulation combined with the limited numbers of liquid–liquid reactions. Initial interest focused on the control of parameters responsible for variation in flow patterns to engineer microemulsions or droplets. However, it was soon realized that liquid–liquid microdevices are more than just a tool for controlling flow patterns and further interest developed.

Liquid–liquid chemical reactions that require enhancement in mixing could take advantage of a flow regime in which the two phases were separated to form a segmented flow pattern. Nevertheless, there are only few examples of reactions conducted in parallel flow regime. There is a reasonable interest on segmented flow because of the easy control of the flow regime, the increase in interfacial area, and the efficient mixing inside the segments because of generation of the internal circulations at low Reynolds number compared to parallel flow.

Most examples describe catalyzed biphasic reactions taking the extra advantage of product isolation and catalyst recycling. De Bellefon et al. [21] published one of the first examples of biphasic reactions performed in a microreactor. The isomerization of allylic alcohols to carbonyl compounds was conducted in a liquid–liquid system using a micromixer combined with a microchannel tube. As there are limited examples of biphasic isomerization reactions, the authors were interested on extending the scope by taking advantage of microsystems. To achieve this, various complexes of transition metals with a library of water-soluble ligands were screened for the isomerization of 1-hexene-3-ol to 3-hexanone using an aqueous/hydrocarbon solvent system (Scheme 8.2). The catalysts and substrates were introduced simultaneously in pulsed injection manner as shown in Figure 8.10. The use of micromixer helped the formation of droplets flow which was then carried through the integrated microchannel tube. The results of screening different catalysts demonstrated clearly the efficiency of a microsystem for rapidly finding an efficient catalyst. In addition, only a very small amount of catalyst had to be used in the rapid screening of many catalysts. This investigation was one of the first high-throughput screening tests conducted in microreactors.

Figure 8.10 Schematic illustration of high-throughput screening used for the isomerization of allylic alcohols to ketones with the illustration of the micromixer used to generate droplet flow. Source: By courtesy of Wiley-VCH Verlag GmbH [21].


Scheme 8.2 Isomerization of 1-hexene-3-ol to ethyl propyl ketone in a microreactor.