In-depth Study on Continuous Synthesis of Methyl Mercaptoacetate in Microchannel Reactor and In-depth Study on Continuous Synthesis of Methyl Mercaptoacetate in Microchannel Reactor and Industrialization Value Analysis Industrialization Value Analysis

Microreactor Synthesis of Methyl Mercaptoacetate Microreactor Synthesis of Methyl Mercaptoacetate Process

Introduction Introduction

As a sulfur-containing fine chemical intermediate, thioglycolate methyl ester has strong coordination reaction, addition reaction and chain transfer regulation capabilities due to its unique thioglycolyl (-SH) active structure. It is an irreplaceable core fine chemical in pharmaceutical synthesis, pesticide creation, tobacco flavors, polymer material additives, and optical material curing systems. In the polymer industry, it can precisely regulate the molecular weight distribution of polymers and solve the problem of excessive molecular weight dispersion of traditional regulators. In the field of new materials, multiple esterified derivatives can achieve low-temperature and rapid curing of epoxy resins, which is suitable for the low-temperature molding requirements of optical lenses and precision adhesives. The requirements for product purity, color and impurity control in downstream high-end application scenarios continue to tighten. As a sulfur-containing fine chemical intermediate, thioglycolate methyl ester has strong coordination reaction, addition reaction and chain transfer regulation capabilities due to its unique thioglycolyl (-SH) active structure. It is an irreplaceable core fine chemical in pharmaceutical synthesis, pesticide creation, tobacco flavors, polymer material additives, and optical material curing systems. In the polymer industry, it can precisely regulate the molecular weight distribution of polymers and solve the problem of excessive molecular weight dispersion of traditional regulators. In the field of new materials, multiple esterified derivatives can achieve low-temperature and rapid curing of epoxy resins, which is suitable for the low-temperature molding requirements of optical lenses and precision adhesives. The requirements for product purity, chromaticity, and impurity control in downstream high-end application scenarios continue to tighten.

The current domestic industrial production relies entirely on the current domestic industrial production relies entirely on the thioglycolic acid-methanol sulfuric acid catalytic batch kettle esterification process , the defect of this traditional process is not simply low efficiency, but the existence of essential engineering and reaction mechanism shortcomings. The strong corrosiveness of the homogeneous catalytic system of concentrated sulfuric acid will continue to damage the reactor and stirring device, and the equipment depreciation and maintenance costs are high; the batch reaction has serious problems of system backmixing, product retention, and accumulation of side reactions; at the same time, the esterification reaction is a typical reversible equilibrium reaction. The kettle system cannot separate the product and the generated water in time, the equilibrium conversion rate is limited, and there are long-term industry pain points of low yield, poor batch stability, high sulfur impurities in the product, and a large amount of acidic wastewater in the three wastes, making it difficult to adapt to the production standards of high-end electronic, optical, and pharmaceutical grade products. Therefore, the introduction of process strengthening technology to replace the traditional batch process is an inevitable direction for the upgrading of the mercaptoacetate methyl ester industry., the defect of this traditional process is not simply low efficiency, but there are essential engineering and reaction mechanism shortcomings. The strong corrosiveness of the homogeneous catalytic system of concentrated sulfuric acid will continue to damage the reactor and stirring device, and the equipment depreciation and maintenance costs are high; the batch reaction has serious problems of system backmixing, product retention, and accumulation of side reactions; at the same time, the esterification reaction is a typical reversible equilibrium reaction. The kettle system cannot separate the product and the generated water in time, the equilibrium conversion rate is limited, and there are long-term industry pain points of low yield, poor batch stability, high sulfur impurities in the product, and a large amount of acidic wastewater in the three wastes, making it difficult to adapt to the production standards of high-end electronic, optical, and pharmaceutical-grade products. Therefore, the introduction of process strengthening technology to replace the traditional batch process is an inevitable direction for the upgrading of the mercaptoacetate methyl ester industry.

As a new generation of continuous flow process strengthening equipment, the core advantage of microchannel reactor is not volume miniaturization, but microchannel reactor as a new generation of continuous flow process strengthening equipment. The core advantage of microchannel reactor is not volume miniaturization, but specific surface area improvement, heat and mass transfer ultimate enhancement, no backmixing and flat flow characteristics, parameters precise and controllable specific surface area order of magnitude improvement, heat and mass transfer ultimate enhancement, no backmixing and flat flow characteristics, parameters precise and controllable . Compared with conventional kettle reactors, microchannel systems can achieve millisecond-level accurate mixing of materials, constant temperature and no temperature difference reaction, real-time product removal, and two-way optimization of esterification reaction efficiency from the level of reaction kinetics and thermodynamics. In recent years, this technology has achieved efficient verification in the esterification synthesis of short URL esters and aromatic esters, generally achieving dozens of times increase in reaction rate, significant optimization of yield, and significant suppression of side reactions, providing mature technical path support for the green and efficient continuous production of thioglycolate methyl esters... Compared with conventional kettle reactors, the microchannel system can achieve accurate mixing of materials at millisecond level, constant temperature without temperature difference reaction, and real-time removal of products, and optimize the esterification reaction efficiency from the reaction kinetics and thermodynamics. In recent years, this technology has achieved efficient verification in the esterification synthesis of short URL esters and aromatic esters, generally achieving dozens of times increase in reaction rate, significant optimization of yield, and significant inhibition of side reactions, providing a mature technical path for the green and efficient continuous production of thioglycolate methyl esters.

1 thioglycolic acid esterification mechanism depth analysis 1 thioglycolic acid esterification mechanism depth analysis

The esterification reaction of thioglycolic acid and methanol is the esterification reaction of thioglycolic acid and methanol is the acid-catalyzed reversible endothermic condensation reaction. The acid-catalyzed reversible endothermic condensation reaction follows the general mechanism of carboxylic acid alcohol esterification. Under the catalysis of proton acid, the carboxycarbonyl oxygen undergoes protonation, enhances the electrophilicity of carbonyl carbons, and undergoes nucleophilic addition to methanol hydroxyl groups, followed by intermolecular dehydration to generate thioglycolic acid methyl ester and water. In the conventional kettle system, the ester and water generated by the reaction coexist in the system, and the product accumulation will reverse inhibit the forward reaction. At the same time, the backmixing of the system causes the product to stay in a high temperature environment for a long time, which is easy to induce thiol oxidation, lactation, and thioether side reactions, which is the core mechanism of low product purity and limited yield., The core reaction follows the general mechanism of carboxylic acid alcohol esterification. Under the catalysis of protonic acid, the carboxyl carbonyl oxygen undergoes protonation, enhances the electrophilicity of carbonyl carbon, and undergoes nucleophilic addition with methanol hydroxyl group, followed by intermolecular dehydration to generate mercaptoacetate methyl ester and water. In the conventional kettle system, the ester and water generated by the reaction coexist in the system, and the product accumulation will reverse inhibit the forward reaction. At the same time, the backmixing of the system causes the product to stay in a high temperature environment for a long time, which is easy to induce thiol oxidation, lactone, and thioether side reactions. It is the core mechanism of low product purity and limited yield.

However, the parallel flow characteristics of the microchannel reactor completely changed the reaction thermodynamic equilibrium state: thioglycolate methyl ester and water miscibility is extremely poor, in the continuous flow microchannel, the product can be quickly separated from the reaction micro-zone after generation, no product accumulation, no reverse reaction driving force, so that the original reversible esterification reaction and the reverse flow characteristics of the microchannel reactor completely changed the reaction thermodynamic equilibrium state: thioglycolate methyl ester and water miscibility is extremely poor, in the continuous flow microchannel, the product can be quickly separated from the reaction micro-zone after generation, no product accumulation, no reverse reaction driving force, so that the original reversible esterification reaction approaches irreversible unidirectional reaction approaches irreversible unidirectional reaction , breaking through the equilibrium conversion limit of traditional processes from the root It is also the core underlying logic of the micro-channel process yield far exceeding the kettle process., breaking through the balance conversion rate limit of the traditional process from the root, which is also the core underlying logic of the micro-channel process yield far exceeding the kettle process.

2 Experimental device system and system design logic 2 Experimental device system and system design logic

This experiment uses a precise and controllable continuous flow microreaction system to build a full closed-loop continuous process of raw material precise feeding-microchannel reaction-rapid quenching-product collection. The experiment uses p-toluenesulfonic acid as a catalyst instead of traditional concentrated sulfuric acid. Compared with concentrated sulfuric acid, p-toluenesulfonic acid is less corrosive, has fewer side reactions, and is more evenly dissolved in the organic system. It can effectively reduce the risk of equipment corrosion and product carbonation, and adapt to the operation requirements of microchannel precision flow channels to avoid strong corrosive media blockage and damage to microstructure channels. This experiment uses a precise and controllable continuous flow microreaction system to build a full closed-loop continuous process of raw material precise feeding-microchannel reaction-rapid quenching-product collection. In the experiment, p-toluenesulfonic acid was used as a catalyst instead of traditional concentrated sulfuric acid. Compared with concentrated sulfuric acid, p-toluenesulfonic acid is less corrosive, has fewer side reactions, and dissolves in the organic system more evenly, which can effectively reduce the risk of equipment corrosion and product carbonation. It is suitable for the operation requirements of the precision flow channel of the microchannel to avoid the blockage of strong corrosive media and damage to the microstructure channel.

The system uses double high-pressure liquid phase metering pumps to achieve accurate material transportation, which can realize high-precision regulation of the molar ratio of raw materials and avoid batch differences caused by the deviation of intermittent feeding ratio; closed-loop temperature control of the hot-cold integrated machine solves the problems of local overheating, temperature hysteresis, and uneven temperature difference of the traditional kettle reaction, and realizes precise control of the constant temperature of the microchannel reaction system; the rapid quenching design of the end ice-water immersion coil can instantly stop the reaction, inhibit the oxidation and polymerization side reactions of free sulfhydryl groups at high temperatures, and retain the purity of the target product to the greatest extent. Finally, high-performance liquid chromatography is used to accurately quantitatively analyze the concentration of the product, and the data accuracy and experimental reliability are far better than the traditional titr The system uses double high-pressure liquid phase metering pumps to achieve accurate material transportation, which can realize high-precision regulation of the molar ratio of raw materials and avoid batch differences caused by the deviation of intermittent feeding ratio; closed-loop temperature control of the integrated cooling and heating machine solves the problems of local overheating, temperature hysteresis, and uneven temperature difference of the traditional kettle reaction, and realizes precise control of the constant temperature of the microchannel reaction system; the rapid quenching design of the end ice-water immersion coil can instantly stop the reaction, inhibit the oxidation and polymerization side reactions of free sulfhydryl groups at high temperatures, and retain the purity of the target product to the greatest extent. Finally, high-performance liquid chromatography is used to accurately quantitatively analyze the concentration of the product, and the data accuracy and experimental reliability are far better than the traditional titration detection method.

The core design advantages of the whole set of equipment are: the whole process is closed and continuous, no material backmixing, no high temperature retention, and the parameters can be quantified and replicated. It completely solves the defects of large batch differences in traditional batch processes, uncontrollable by-products, and strong operator human interference. It provides accurate basic data support for the development of industrial process packages. The core design advantages of the whole set of equipment are: the whole process is closed and continuous, no material backmixing, no high temperature retention, and parameters can be quantified and replicated. It completely solves the defects of large batch differences in traditional batch processes, uncontrollable by-products, and strong operator human interference. It provides accurate basic data support for the development of industrial process packages.

3 Analysis of the influence mechanism of process parameter variables and the optimal condition mechanism 3 Analysis of the influence mechanism of process parameter variables and the optimal condition mechanism

3.1 Dynamic regulation mechanism of residence time 3.1 Dynamic regulation mechanism of residence time

The reaction residence time was precisely controlled by adjusting the feed flow rate in the experiment, and the variable range was 8.2min~ 57.2min. The data show that the microchannel system can achieve high yield synthesis in only 14.3min, while the traditional kettle process requires more than 8 hours for the same yield level, and the reaction efficiency is increased by more than 30 times. From the kinetic point of view, the traditional kettle reactor relies on mechanical stirring mass transfer, the mass transfer boundary layer is thick, the mixing between phases is uneven, and the effective reaction rate is slow; the fluid at the microchannel microscale is in a laminar flow precise mixing state, the phase interface is continuously updated, the mass transfer resistance is almost eliminated, the effective collision frequency per unit time is greatly increased, and the kinetic rate is significantly accelerated. The experiment precisely controls the reaction residence time by adjusting the feed flow rate, and the variable range is 8.2min~ 57.2min. The data show that the microchannel system can achieve high yield synthesis in only 14.3 minutes, while the traditional kettle process takes more than 8 hours for the same yield level, and the reaction efficiency is increased by more than 30 times. From the perspective of kinetics, the traditional kettle reactor relies on mechanical stirring for mass transfer, with thick mass transfer boundary layer and uneven mixing between phases, and the effective reaction rate is slow; the fluids at the microchannel microscale are in a laminar flow precise mixing state, the phase interface is continuously updated, the mass transfer resistance is almost eliminated, the effective collision frequency per unit time is greatly increased, and the kinetic rate is significantly accelerated.

More importantly, the conventional kettle system has serious backmixing, and some products remain in the reaction system for a long time to cause reverse reactions and side reactions, which lengthen the reaction period and cannot improve the yield; the micro-channel flat stream has no backmixing characteristics, the product is removed in real time, and the equilibrium continues to move forward. The reaction limit conversion rate can be achieved in a short time, and the residence time is too long but there is no obvious gain, achieving the optimal balance of efficiency and energy consumption. More importantly, the conventional kettle system has serious backmixing, and some products remain in the reaction system for a long time to cause reverse reactions and side reactions, which lengthen the reaction cycle and cannot improve the yield; the micro-channel flat push flow has no backmixing characteristics, and the product is removed in real time. The balance continues to move forward, and the reaction limit conversion rate can be reached in a short time. If the residence time is too long, there is no obvious gain, achieving the optimal balance between efficiency and energy consumption.

3.2 Bidirectional Regulation of Reaction Temperature and Side Reaction Suppression Logic 3.2 Bidirectional Regulation of Reaction Temperature and Side Reaction Suppression Logic

The esterification reaction of methyl thioglycolate is an endothermic reaction, and thermodynamic warming is conducive to the forward balance movement, but the system containing sulfhydryl groups has a unique risk of side reactions: under high temperature conditions, sulfhydryl groups are prone to intramolecular cyclization and lactating, oxidative coupling to form disulfide bond by-products, which is the core bottleneck restricting the purity of the product. The experimental data show obvious segmentation characteristics: when the temperature is lower than the boiling point of methanol (64.7 ° C), the temperature increases the reaction rate and yield significantly, and there is no obvious side reaction; in the range of 60 ° C to 80 ° C, the main reaction approaches saturation, and the yield increases slowly; in the high temperature range of 80 ° C to 90 ° C, the side reaction dominates, the lactating impurities increase, and the product yield decreases slightly The esterification of methyl thioglycolate is an endothermic reaction, and thermodynamic heating is conducive to the positive balance movement, but the system containing thiol groups has unique side reaction risks: under high temperature conditions, thiol groups are prone to intracyclination and oxidative coupling to form disulfide bond by-products, which is the core bottleneck restricting the purity of the product. The experimental data show obvious segmentation characteristics: when the temperature is lower than the boiling point of methanol (64.7 ° C), the temperature increases the reaction rate and yield significantly, and there is no obvious side reaction; in the range of 60 ° C to 80 ° C, the main reaction approaches saturation, and the yield increases slowly; in the high temperature range of 80 ° C to 90 ° C, the side reactions dominate, the lactating impurities increase, and the product yield decreases slightly and the color becomes poor.

This conclusion has strong guiding significance for industrialization: the optimal temperature of the microchannel process needs to be locked in. This conclusion has strong guiding significance for industrialization: the optimal temperature of the microchannel process needs to be locked in the critical interval of the boiling point of low boiling point components. The critical interval of the boiling point of low boiling point components not only uses the thermodynamic positive gain of heating up, but also avoids the high-temperature sulfhydryl side reaction, which is different from the extensive operation of the traditional process of blind high-temperature efficiency improvement, to achieve the maximization of the main reaction and the minimization of the side reaction.

3.3 Balance Regulation and Concentration Effect Analysis of Feed Molar Ratio 3.3 Balance Regulation and Concentration Effect Analysis of Feed Molar Ratio

For the reversible esterification reaction, excess methanol can push the equilibrium forward by increasing the concentration of the reactants, but there is a critical threshold for the excess ratio. Experiments show that when the molar ratio of methanol to thioglycolic acid increases from 1:1 to 4:1, the yield increases rapidly from 81.3% to 94.6%; after the molar ratio exceeds 4:1, the yield does not increase, and there is a slight drop at 6:1. The core reason is not that the excess raw material is ineffective, but that for the reversible esterification reaction, excess methanol can push the equilibrium forward by increasing the concentration of the reactants, but there is a critical threshold for the excess ratio. Experiments show that when the molar ratio of methanol to thioglycolic acid increases from 1:1 to 4:1, the yield increases rapidly from 81.3% to 94.6%; when the molar ratio exceeds 4:1, the yield no longer increases, and decreases slightly at 6:1. The core reason is not that the excess of raw materials is ineffective, but the existence of catalyst dilution concentration effect catalyst dilution concentration effect : Excessive methanol ratio is too high, which will greatly dilute the effective concentration of p-toluenesulfonic acid catalyst in the system, reduce the number of catalytic activity check points per unit volume, weaken the catalytic efficiency, and ultimately lead to a small decrease in the reaction rate and yield.: Excessive methanol ratio is too high, which will greatly dilute the effective concentration of p-toluenesulfonic acid catalyst in the system, reduce the number of catalytic activity check points per unit volume, weaken the catalytic efficiency, and finally lead to a small decrease in the reaction rate and yield.

This parameter breaks the traditional cognition that "the more raw materials, the higher the conversion rate", and clarifies the optimal ratio critical value of the microchannel continuous process, providing the core data basis for reducing the energy consumption of methanol recovery, controlling the cost of raw materials, and simplifying the post-processing distillation process in industrialization. This parameter breaks the traditional cognition that "the more raw materials, the higher the conversion rate", and clarifies the optimal ratio critical value of the microchannel continuous process. It provides the core data basis for reducing the energy consumption of methanol recovery, controlling the cost of raw materials, and simplifying the post-processing distillation process in industrialization.

4 Microchannel reactor equipment adaptability and industrialization advantage interpretation 4 Microchannel reactor equipment adaptability and industrialization advantage interpretation

The silicon carbide and stainless steel microchannel reactor independently developed by Shandong Haomai Chemical is perfectly adapted to the production conditions of thioglycolate methyl acetate sulfur-containing acid system. The silicon carbide material has the characteristics of weak acid resistance, sulfur corrosion resistance, hot topic conductivity, and no adsorption residue, which can completely solve the problems of sulfur corrosion, carbon deposition residue, and material adsorption loss of traditional stainless steel equipment; the square and umbrella-shaped composite channel structure can enhance the fluid turbulent mixing effect, further improve mass transfer efficiency, and adapt to the rapid reaction requirements of esterification reaction. The silicon carbide and stainless steel microchannel reactor independently developed by Shandong Haomai Chemical is perfectly adapted to the production conditions of thioglycolate methyl acetate sulfur-containing acid system. The silicon carbide material has the characteristics of weak acid resistance, sulfur corrosion resistance, hot topic conductivity, and no adsorption residue, which can completely solve the problems of sulfur corrosion, carbon deposition residue, and material adsorption loss of traditional stainless steel equipment; the square and umbrella-shaped composite channel structure can strengthen the fluid turbulent mixing effect, further improve the mass transfer efficiency, and adapt to the rapid reaction requirements of esterification reaction.

Compared with traditional kettle-type equipment, the industrialization value of this set of micro-reaction equipment is reflected in three dimensions: first, safety improvement, sulfur-containing organic system high temperature for a long time can easily lead to oxidation, polymerization and even over-temperature risk, micro-channel liquid holding capacity is extremely low, and intrinsic safety is greatly improved; second, cost optimization, reaction time is greatly shortened, methanol unit consumption is reduced, catalyst utilization rate is improved, waste production is sharply reduced, and comprehensive production cost is significantly reduced; third, quality upgrade, continuous non-backmixing system greatly reduces by-products, product purity, chromaticity, and stability are better than batch process, and can be directly adapted to high-end fragrances, optical materials, and pharmaceutical intermediates. Compared with traditional kettle equipment, the industrialization value of this set of micro-reaction equipment is reflected in three dimensions: first, safety improvement, sulfur-containing organic system high temperature for a long time can easily lead to oxidation, polymerization and even over-temperature risk, micro-channel liquid holding capacity is extremely low, and intrinsic safety is greatly improved; second, cost optimization, reaction time is greatly shortened, methanol unit consumption is reduced, catalyst utilization rate is improved, waste production is sharply reduced, and comprehensive production costs are significantly reduced; third, quality upgrade, continuous non-backmixing system greatly reduces by-products, product purity, chromaticity, and stability are better than batch process, and can be directly adapted to high-end fragrances, optical materials, and pharmaceutical intermediates.

5 Process Core Conclusion and Industrial Innovation Value Summary 5 Process Core Conclusion and Industrial Innovation Value Summary

This micro-channel continuous synthesis process realizes an all-round innovation of the traditional process from the three dimensions of reaction mechanism, process parameters, and equipment adaptation. Under the optimal process conditions: reaction temperature of 60 ° C, molar ratio of alkyd to acid 4:1, residence time of 14.3 minutes, the yield of the product can reach 94.6%. Compared with the traditional kettle process, the reaction time is shortened by more than 97%, the yield is increased by more than 9 percentage points, and the pain points of strong acid corrosion, batch fluctuation, excessive by-products, and large amount of three wastes are avoided at the same time. Its core technological breakthrough lies in using the characteristics of microchannel non-return mixing and leveling to transform the traditional reversible esterification reaction into a quasi-irreversible one-way reaction, and break through the upper limit of the conversion rate of the traditional process from the mechanism level. This micro-channel continuous synthesis process realizes an all-round innovation of the traditional process from the three dimensions of reaction mechanism, process parameters, and equipment adaptation. Under the optimal process conditions: reaction temperature 60 ° C, molar ratio of alkyd to acid 4:1, residence time 14.3 minutes, the product yield can reach 94.6%. Compared with the traditional kettle process, the reaction time is shortened by more than 97%, the yield is increased by more than 9 percentage points, and at the same time avoid the pain points of strong acid corrosion, batch fluctuation, excessive by-products, and large amount of three wastes. Its core technological breakthrough lies in the use of the non-return mixing and leveling characteristics of microchannels to transform the traditional reversible esterification reaction into a quasi-irreversible one-way reaction, and break through the upper limit of the conversion rate of the traditional process from the mechanism level.

From the perspective of industrial development, with the continuous expansion of the downstream market for high-end fragrances, optical curing materials, and precision polymer additives, the supply and demand gap of high-quality thioglycolate methyl ester continues to expand. The traditional batch process can no longer meet the dual needs of green production and high-end quality in the industry. From the perspective of industrial development, with the continuous expansion of the downstream market for high-end fragrances, optical curing materials, and precision polymer additives, the supply and demand gap of high-quality thioglycolate methyl ester continues to expand. The traditional batch process can no longer meet the dual needs of green production and high-end quality in the industry. Microchannel continuous chemical technology relies on the core advantages of high efficiency, green, safety, high purity, continuous mass production, high efficiency, green, safety, high purity, continuous mass production , and will become the mainstream direction of technology iteration in the thioglycolate methyl ester industry, providing a general technical paradigm for the continuous, green and high-end production of sulfur-containing fine ester intermediates. The core advantages of will become the mainstream direction of technology iteration in the thioglycolate methyl ester industry, providing a general technical paradigm for the continuous, green and high-end production of sulfur-containing fine ester intermediates.

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