Synthesis of Methyl Mercaptoacetate by Microreactor

Introduction

Methyl thioglycolate is a colorless and transparent oily liquid, soluble in water, with allicin odor. It is an important intermediate in the synthesis of medicine, pesticides, food flavors and tobacco flavors, and can be used as an organotin heat stabilizer, a polymer molecular weight regulator. Polymercapto methyl acetate can also be used as a low-temperature curing agent for epoxy resins, optical lenses and manufacturing adhesives, etc. The current production and synthesis method of methyl thioglycolate mainly uses thioglycolic acid and methanol as raw materials, and a batch synthesis method using sulfuric acid as catalyst. This process has many problems such as low yield, long reaction time and serious corrosion of equipment. Therefore, it is necessary to find an efficient synthesis process of methyl thioglycolate, and the continuous synthesis of methyl thioglycolate in a microchannel reactor is carried out under this background.

microreactor is a continuous flow pipeline reactor. Its pipe size is much smaller than that of conventional tubular reactors, so it has a large specific surface area, which brings the fundamental advantage of great heat exchange efficiency and mass transfer efficiency. In other words, the reaction temperature can be precisely controlled and the reaction materials can be mixed instantaneously according to the exact ratio. These are the key factors to improve the yield, selectivity, safety, reaction speed and product quality. Recently, many researchers have applied the new process enhancement method of microstructure reactor to esterification reaction. For example, Yao et al. [1] used p-toluenesulfonic acid as a catalyst to synthesize methyl acetate, ethyl acetate, butyl acetate and propyl acetate in a quartz capillary reactor. The results showed that the highest ester yield was over 97.2% within the reaction time of 14.7min. Benito-Lopez et al. [2] studied the esterification process of phthalic anhydride and methanol using an etched glass microreactor. Compared with the traditional reactor, the reaction rate was increased by more than 50 times. Wiles et al. [3] successfully synthesized phenyl acetate and nitrophenyl acetate using a borosilicate glass microreactor. The conversion rate reached 100%, but the reaction time was significantly shortened. It can be seen that the use of microstructured reactors is conducive to improving the esterification reaction efficiency.

1-mercaptoacetic acid esterification reaction

Under the action of the catalyst, thioglycolate methyl ester is obtained from thioglycolic acid and methanol through intermolecular dehydration and condensation reaction. The reaction equation is as follows:

2 Experimental device and method

A certain amount of p-toluenesulfonic acid is dissolved in thioglycolic acid in advance, and methanol and thioglycolic acid solution are injected into a microchannel reactor in a certain proportion by high pressure liquid chromatography pump for reaction. The reaction temperature is controlled by using a hot and cold integrated machine, and the outlet is maintained with an appropriate length of coil intrusion in ice water to terminate the reaction. The residence time is controlled by changing the pump flow rate. The concentration of methyl thioglycolate in the reaction liquid is analyzed by liquid chromatography.

1, 2 - material, 3 - microreactor, 4 - cooler, 5 - collection bottle

Fig. 1 Schematic diagram of a microchannel reaction experimental device

3 Analysis of experimental results

3.1 Effect of residence time on the yield of methyl thioglycolate

The molar ratio of methanol to thioglycolic acid is 3:1, the amount of p-toluenesulfonic acid is 1% of thioglycolic acid, and the reaction temperature is 60 ° C. The residence time is adjusted from 8.2 min to 57.2 min by changing the flow rate. The effects of different residence times on the yield of methyl thioglycolate are investigated, and the results are shown in Table 1.

Table 1 Effect of retention time on the yield of methyl thioglycolate

It can be seen from the results in Table 1 that when the reaction time is 14.3min, a higher yield of methyl thioglycolate can be obtained, while the synthesis of methyl thioglycolate in a conventional kettle reactor achieves similar experimental results, and the reaction time is about 8 hours. Obviously, the esterification rate in the microchannel reactor is significantly higher than that in the conventional kettle reactor. In addition to the high heat and mass transfer efficiency of the microchannel reactor mentioned above, another important reason may be that the reaction solution in the microchannel does not appear backmixing phenomenon, that is, the final reaction product methyl thioglycolate is immiscible with water and continuously flows out of the microchannel, so the esterification reaction in the microchannel reactor can be approximately regarded as an irreversible reaction.

The synthesis of methyl thioglycolate is an endothermic reaction. Increasing the reaction temperature is conducive to the positive direction of the reaction. The boiling points of methanol and thioglycolic acid are 64.7 ° C and 123 ° C. Therefore, the molar ratio of methanol to thioglycolic acid is 3:1, and the amount of p-toluenesulfonic acid is 1% of thioglycolic acid at 30 ° C, 40 ° C, 50 ° C, 60 ° C, 70 ° C, 80 ° C and 90 ° C. The effect of reaction temperature on the yield of methyl thioglycolate was investigated. The results are shown in Figure 2.

Figure 2 Effect of reaction temperature on the yield of methyl thioglycolate

It can be seen from Figure 2 that when the reaction temperature is lower than the boiling point of methanol, the yield increases rapidly with the increase of the reaction temperature, indicating that increasing the temperature is conducive to the forward advancement of the endothermic reaction; when the reaction temperature rises from 60 ° C to 80 ° C, although the yield of thioglycolate methyl ester continues to increase, the increase becomes slow, and when the reaction temperature rises from 80 ° C to 90 ° C, the yield decreases slightly, which may be related to the side reaction of thioglycolic acid that is prone to lactating at higher temperatures. From the above discussion, it can be seen that when the reaction temperature is close to the boiling point of the lowest boiling point component in the esterification system, the reaction is most conducive to the positive direction, which is similar to the conclusion obtained by Yao et al. [1] when using a microchannel reactor to rapidly synthesize propyl acetate.

3.3

For the reversible esterification reaction, from the perspective of chemical equilibrium, increasing the amount of reactants can make the equilibrium proceed in the positive direction, thereby improving the ester yield. Table 2 gives the effect of the molar ratio of methanol to thioglycolic acid on the synthesis of thioglycolic acid methyl ester in the range of 1:1 to 6:1. The reaction conditions are as follows: the amount of p-toluenesulfonic acid is 1% of thioglycolic acid, the reaction temperature is 60 ° C, and the residence time is 14.3min.

Table 2 Effect of molar ratio of methanol to thioglycolate on the yield of methyl thioglycolate

It can be seen from Table 2 that when the molar ratio of methanol to thioglycolic acid is from 1 to 4, the yield of methyl thioglycolate also increases rapidly from 81.3% to 94.6%, and when the molar ratio of methanol to thioglycolic acid increases to 5, the yield of methyl thioglycolate basically does not change, but when the molar ratio of methanol to thioglycolic acid increases to 6, the yield of methyl thioglycolate decreases slightly, which may be related to the decrease in catalyst concentration in the reaction system when the molar ratio of methanol to thioglycolic acid is too high.

4 Halma Microchannel Reactor

Shandong Haomai Chemical Technology Co., Ltd. has independently developed a variety of microchannel reactors with various structures and materials, such as square channel structure and umbrella channel structure, as well as stainless steel and silicon carbide materials. Through different types of organic synthesis experiments, it has been confirmed that microchannel reactors have significant effects in improving mass transfer, heat transfer efficiency and reaction efficiency, and have won unanimous praise from customers. With the wider application of methyl thioglycolate, the various microchannel reactors developed by Haomai Chemical will also be promising.

Figure 3 Silicon carbide microchannel reactor

5 Summary

Compared with the conventional reactor, the method of synthesizing methyl thioglycolate in a microchannel reactor can significantly shorten the reaction time. At the reaction temperature of 60 ° C, the molar ratio of methanol to thioglycolic acid is 4, and the yield reaches 94.6%. It only takes 14.6min, while the conventional reaction yield is only 85% under more suitable process conditions, and the reaction time does take nearly 8 hours. This should be because the reaction solution in the microchannel does not appear backmixing phenomenon, that is, the final reaction product ester is immiscible with water and continuously flows out of the microchannel, so the esterification reaction in the microchannel reactor can be considered an irreversible reaction.

References

[1] Yao X, Yao J, Zhang L, et al. Fast Esterification of Acetic Acids with Short Chain Alcohols in Microchannel Reactors [J]. Catalysis Letters, 2009, 132 (1-2): 147-152.

[2] Benitolopez F, Tiggelaar R M, Salbut K, et al. Substantial rate enhancements of the esterification reaction of phthalic anhydride with methanol at high pressure and using supercritical CO2 as a co-solvent in a glass microreactor. [J]. Lab on A Chip, 2007, 7 (10): 1345-1351.

[3] Wiles C, Watts P, Haswell S J, et al. The aldol reaction of silyl enol ethers within a micro reactor. [J]. Lab on a Chip, 2001, 1 (2): 100.

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