Boric acid compounds are an extremely important class of organic compounds. Due to their unique structural characteristics, they have good biological activity and pharmacological effects [1-2], and are widely used in the synthesis of potential enzyme inhibitors, Boron neutron capture therapy for cancer [3] and feedback-controlled drug transport polymers, and the boronic acid group is an important active group in the Suzuki reaction and is widely used in chemical industry.
Because microreactors can achieve precise control of reaction temperature, precise proportioning of reaction materials, and instantaneous mixing, they can effectively eliminate restrictions on mass transfer and heat transfer and avoid uneven heating or uneven mixing. Moreover, the controllable fluid performance of the microreactor allows the product to flow out of the reaction system without staying in the reactor for too long, thus inhibiting the occurrence of side reactions, thereby greatly improving the efficiency, productivity, and efficiency of the reaction. Selectivity. At the same time, because of the airtightness of the microreaction calcium bicarbonate device itself, the synthesis reaction of phenylboronic acid can proceed efficiently and smoothly without additional protection. This article describes a synthesis of phenylboronic acid performed in a microreactor.
Synthesis of Phenylboronic Acid in Microreactor 1 Experimental Principle
Figure 1 Experimental Principle
The reaction process is divided into two steps: first, butyllithium reagent is added to generate an intermediate, and then the intermediate reacts with the added triisopropyl borate.
Synthesis 2 process flow of phenylboronic acid in microreactor
The reaction mainly consists of two parts: the feed system and the reaction system. The substrate and n-butyllithium are pumped into the microreactor through a plunger pump. After the reaction is completed in the first half of the microreactor, it reacts with the added triisopropyl borate in the second half of the microreactor to obtain the product.
Picture of the synthetic experimental process of diphenylboronic acid
Synthesis of Phenylboronic Acid in Microreactor 3 Experimental Process
The reaction temperature of MRSF20 is controlled by a low-temperature coolant reaction bath, and the reaction temperature is monitored in real time through a thermocouple on the reaction piece. The internal temperature change of the reaction piece is ±3°C.
Put the reaction solution and n-butyllithium solution into the microreactor at the same time through a metering pump. The microreactor has a pre-heat exchange function. The materials can reach the temperature required for the reaction after pre-heat exchange. The residence time is controlled by adjusting the flow rate of the metering pump and the number of reaction sheets. The reaction temperature is controlled by cooling the reaction bath at low temperature. The two materials are quickly and fully mixed in the microreactor. After the reaction system is stable, take a sample to quench the reaction system at the outlet, extract it with an organic solvent, and then analyze the calcium carbonate with a liquid chromatograph.
Use a microreactor to add triisopropyl borate. Control the residence time by adjusting the flow rate of the metering pump and increasing or decreasing the number of reaction sheets. Control the reaction temperature by cooling the reaction bath at low temperature. After the reaction is completed, quench it and adjust the pH value. to 6, extracted with organic solvent, and analyzed by liquid chromatography.
Synthesis of Phenylboronic Acid in Microreactor 4 Results and Discussion
When performing a reaction in a microreactor, the reaction temperature is a very important factor. Too high or too low a temperature may lead to excessive or incomplete reaction, so it is very important to choose the appropriate reaction temperature.
Table 1 Effect of temperature on reaction results
As can be seen from the table, as the reaction temperature increases, the reaction yield first increases and then decreases. This may be because the reaction is incomplete at low temperatures, resulting in low reaction yield. When the temperature is too high, the by-products of the reaction increase. resulting in a decrease in reaction yield.
Table 2 Effect of residence time on reaction results
As can be seen from the table, as the reaction residence time increases, the reaction yield first increases and then decreases. This is because when the residence time is not enough, the reaction is incomplete and the raw materials are not fully reacted. When the residence time is too long, the reaction by-products increase, resulting in a decrease in reaction yield.
Table 3 Comparison of results between microreactor and kettle reactor
As can be seen from the table, compared with the kettle reactor, the main advantages of the phenylboronic acid synthesis reaction in the microreactor are reflected in four aspects: First, the reaction temperature is greatly increased, from the original -78℃ to -40℃ ; The second is that the reaction time is greatly shortened from the original 2.5h to less than 100s; the third is that the final reaction yield is increased from 87% to 90%; the fourth is that the kettle reaction is changed to continuous production.
Synthesis of Phenylboronic Acid in Microreactor 5 Conclusions
The reaction rate of the phenylboronic acid synthesis reaction in the microreactor is relatively fast. The results show that the microreactor’s efficient heat transfer capacity, precise proportion of materials, and its high sealing characteristics can…�Effectively speed up the reaction speed, increase the reaction temperature, increase the reaction yield, and reduce side reactions. The reaction in the microreactor can be completed in about 100 seconds. At the same time, the reaction temperature is increased by 30°C, the yield is increased to 90%, an increase of 3% compared with the kettle reactor, and the batch reaction is changed into continuous production.
Many advantages of microchannel reactors have been reported, such as high throughput, automated control, improved raw material utilization and product selectivity. Because the microchannel reactor has a small liquid holding capacity, it is especially suitable for chemical reactions with high risk factors and difficult to operate, which can greatly improve the safety of production. Microchannel reactor technology is applied in the process development stage, which can greatly shorten the process development cycle of new products and seize market opportunities, and has great application prospects.
References
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[2] Chen L, Firooznia F, Gillespie P, et al. Aminotetrahydroin-dazoloacetic acids［P］． US: 8,124,641, 2012-2-28.
[3] Soloway A H,Tjarks W,Barnum B A,et al.The chemistry of Neutron Capture Therapy[J].Chem Rev,1998,98(4);1515-1519.
