Reactions involving solids in continuous flow chemistry

As an emerging technology, flow chemistry technology has received more and more extensive attention and applications in experimental research and industrial production. Compared with the traditional batch-type kettle reaction, the continuous flow reaction has the advantages of high mass transfer and heat transfer efficiency, and can obtain the target compound at a speed faster than the kettle reaction and at a safer temperature than the kettle reaction. In addition, for reactions that generate unstable intermediates and sensitive intermediates, continuous flow reactions immediately generate immediate reactions, which can greatly reduce the risk of the reaction and increase the reaction yield.

The appearance of solids in organic chemical reactions is almost inevitable. How to resolve and treat the solids in the microreactor is a problem that everyone is concerned about. The following is divided into several situations to show you how to deal with the solids in the continuous flow reactor. ‍

1. Reactions with solid participation‍

In a reaction involving solids, the solid material is one of the reactants. You can first see if you can find a suitable solvent to dissolve it and treat it as a liquid, or if it can be heated to melt and feed in a high-temperature melting state. ‍

If neither of these two can be achieved, then the solids need to be dispersed in a solvent or reaction liquid to form a slurry. In the feed system, an external driving field is usually required, and the corresponding dispersion effect depends on the size, density and concentration of the particles. . Our continuous flow microchannel reactor can handle solids below 150 microns. When feeding solids, please note that the diameter of the solid particles should be less than 10% of the equivalent diameter, and the solid content of the reagent should be less than 5%, otherwise the microreactor may be blocked . During the reaction process, it is easy to produce insoluble precipitates (all solvents are insoluble). It is forbidden to carry out in the microreactor, such as the reaction of tert-butyl lithium; at the same time, it is strictly forbidden to freeze the internal materials of the reactor (such as water). freeze).

The behavior of the solids in the reaction channel is controlled by the interaction between the particles, the fluid and the surface of the reactor, and if applicable, external forces (such as ultrasound) can also be considered.

Microreactors have the advantages of small size, fast heat and mass transfer rate, and high safety. They have been widely used in the continuous and green synthesis of various fine chemicals and pharmaceutical intermediates. However, the existing microreactor technology still has problems such as easy clogging, poor operating flexibility, and difficulty in scaling up, which limits its large-scale industrial application. Ultrasound can generate cavitation bubbles in the fluid. The bubbles vibrate and beat vigorously, mixing the fluid quickly like a miniature stirrer; thereby enhancing the mass transfer of gas-liquid, liquid-liquid and other multiphase flows, preventing and dredging the solid particles in the microchannels. Blocked. With these significant advantages, ultrasonic microreactors are expected to replace part of the existing microreactors and are widely used in the fields of nanomaterial synthesis, heterogeneous (catalytic) reactions, and drug crystallization.

2. The solid produced during the reaction

The situation where solids are generated during the reaction is more complicated. According to different situations, we can adopt different response methods.

One of the countermeasures: the process conditions of the kettle type process and the microreactor are quite different. Because the kettle type reaction is limited by mass transfer and heat exchange, the reaction temperature and concentration have certain requirements, and it can only be achieved by extending the reaction time. Control the response. The microreactor has powerful mass transfer and heat exchange functions, and the reaction time is greatly shortened by strengthening the temperature. The increase in temperature has a certain effect on the solubility of the product, and the product during the reaction process may not precipitate solids.

Countermeasure 2: The microreactor has good mass transfer and short reaction residence time, which can well control the selectivity of the reaction. For some solids in the reaction, the reaction produced by the side reaction has a good control effect. ‍

The third response strategy: If the reaction product is indeed a solid, it can be investigated whether the solid can be dissolved by adding a certain solvent in the reaction process. For example, a certain kind of salt is generated, and water is introduced to dissolve it in the middle or back of the reactor. ‍

Coping strategy 4: If the reaction product is indeed a solid, we must carefully study the shape of the solid, the size of the particles, the amount of production and the fluidity of the fluid to determine whether the microchannel reactor is suitable.

Continuous mechanical dynamic stirring reactor

For continuous flow reactions, especially multi-stage continuous flow reactions, the formation of solids has always been a big problem. In the existing standardized microreactors, the solid particles produced by the reaction are very easy to accumulate at the back pressure valve and the corners of the reaction pipeline and eventually cause the pipeline to block. Although there are some solutions (advanced introduction of auxiliary solvents, ultrasound to suppress the formation of solid particles, specific reactors designed for specific reactions, etc.), these methods are not universal and have a wide range of applications. , There is no way to standardize. The continuous mechanical dynamic stirring reactor can better supplement the limitations of the microchannel reactor in the reaction of solid participation/generation.