A method for preparing sodium fatty acyl methyl isethionate

Abstract

This application relates to the field of fine chemical synthesis technology, specifically disclosing a method for preparing sodium fatty acylmethyl hydroxyethyl sulfonate. The raw materials for preparing this product include an aqueous solution of sodium bisulfite, propylene oxide, sodium hydroxide solution, fatty acids, activated carbon, and high-purity nitrogen, without the need for any metal catalysts throughout the process. The preparation method comprises five core steps: intermediate synthesis and purity testing, dynamic proportioning and controlled dehydration, staged catalytic-free esterification and endpoint control, product distillation and purification, and drying and granulation. Precise control of the entire process is achieved through microchannel continuous reaction, dynamic raw material proportioning, and staged gradient temperature control. The resulting product is free of heavy metals and chloride ion residues, making it suitable for pharmaceutical excipients or cosmetics. It exhibits excellent foaming and foam stabilization properties and good batch stability. This preparation method completely avoids the drawbacks of catalyst residues, balancing reaction conversion efficiency and overall product quality, and is suitable for large-scale industrial continuous production.

Description

Technical Field

[0001] This application relates to the field of fine chemical synthesis technology, and in particular to a method for preparing high-purity fatty acylmethyl hydroxyethyl sulfonate sodium, which can be used in the field of pharmaceutical excipients. Background Technology

[0002] Sodium fatty acylmethyl hydroxyethyl sulfonate is a high-performance, green anionic surfactant with excellent surface activity, foaming and stabilizing properties, and hard water tolerance. It operates under mild conditions and has low irritation to skin and mucous membranes, making it widely used in personal care products and pharmaceutical cleaning excipients. With the standardization of the pharmaceutical excipients and high-end daily chemical industries, market demands for the purity, safety, and batch stability of these products continue to rise. High-quality products with low impurities and no harmful residues have become a core requirement for large-scale production and application in these industries.

[0003] Currently, the mainstream industrial preparation process for this type of product is catalytic esterification. This typically involves adding metal catalysts such as zinc oxide to lower the activation energy of the esterification reaction, achieving industrially acceptable reaction efficiency and raw material conversion rate. However, this process introduces heavy metal catalyst residues into the final product, making it difficult to meet the stringent safety requirements of high-end fields such as pharmaceutical excipients. Existing attempts to develop catalytic-free esterification processes generally suffer from insufficient reaction activation energy and low conversion efficiency. The prolonged high-temperature reaction mode used to improve conversion rate easily leads to problems such as thermal degradation of raw materials, increased product by-products, and excessive color. Current processes have consistently failed to completely avoid heavy metal catalyst residues while simultaneously ensuring both esterification reaction conversion efficiency and overall product quality. This is a core technical problem that urgently needs to be solved in the industry. Summary of the Invention

[0004] To address the problem that existing processes for preparing sodium fatty acyl methyl hydroxyethyl sulfonate struggle to completely eliminate heavy metal catalyst residues while simultaneously ensuring esterification conversion efficiency and overall product quality, this application provides a method for preparing sodium fatty acyl methyl hydroxyethyl sulfonate.

[0005] In a first aspect, this application provides a method for preparing sodium fatty acylmethyl hydroxyethyl sulfonate, which adopts the following technical solution: A method for preparing sodium fatty acylmethyl hydroxyethyl sulfonate includes the following steps: S1. Intermediate Synthesis and Purity Detection: In a microchannel reactor, a pH-adjusted sodium bisulfite aqueous solution was continuously added to propylene oxide. After the reaction was completed, activated carbon was used for decolorization and filtration. The purity of the resulting purified sodium 2-hydroxypropanesulfonate aqueous solution was tested to obtain the purity data of this batch of intermediates. S2. Dynamic proportioning and controlled dehydration: Fatty acids are added to the reaction vessel and replaced with an inert gas. Based on the purity data obtained in step S1, the molar ratio of pure sodium 2-hydroxypropanesulfonate to fatty acids in this batch is dynamically calculated and adjusted. Under constant temperature conditions, the purified sodium 2-hydroxypropanesulfonate aqueous solution is added dropwise to the molten fatty acids at a uniform rate. During the dropwise addition, a slight negative pressure is applied to the reaction vessel, and the slight negative pressure is adjusted according to the moisture content measurement results to keep the water content of the reaction system below 0.5% during the dropwise addition stage. S3. Staged non-catalyst-free esterification and endpoint control: After the addition is complete, stop applying the micro negative pressure and restore the atmospheric pressure. No catalyst is added throughout the process. Nitrogen gas is introduced into the reactor. The esterification reaction is carried out in a staged gradient heating mode. First, the temperature is rapidly increased to complete the reaction activation. Then, the heating rate is reduced and the temperature is slowly increased to carry out the deep esterification reaction. During the activation stage, a micro positive pressure is applied to the reactor. After entering the deep esterification reaction stage, the pressure is switched to atmospheric pressure or micro negative pressure. The acid value of the reaction product is monitored during the reaction. When the acid value drops to 45-55 mgKOH / g, the esterification reaction is terminated. S4. Product distillation and purification: After the esterification reaction is completed, the distillation starting conditions are determined according to the acid value at the time of termination of the esterification reaction in step S3. Excess fatty acids in the system are removed and recovered by vacuum distillation. S5. Drying and granulation: The distilled material is cooled, dried and granulated to obtain sodium fatty acylmethyl hydroxyethyl sulfonate.

[0006] By adopting the above technical solution, the continuous and stable synthesis of intermediates is achieved by utilizing the plug flow characteristics and precise temperature control capability of the microchannel reactor. Combined with real-time detection of intermediate purity and dynamic adjustment of raw material ratios, the optimal reaction feed ratio for each batch is precisely locked, adapting to the high sensitivity of the catalytic-free esterification system to the raw material ratio. Simultaneously, during the intermediate dropwise addition stage, the system's water content is dynamically controlled by micro-negative pressure to continuously remove water, a byproduct of the esterification reaction, thus clearing the equilibrium barrier for reversible esterification from a reaction kinetic perspective. Furthermore, through a staged gradient temperature esterification process without a catalyst throughout the entire process, coupled with dynamic pressure switching and precise endpoint control of acid value, efficient initiation and deep conversion of the esterification reaction under catalytic-free conditions are achieved. Therefore, while completely avoiding heavy metal catalyst residues, the conversion efficiency of the esterification reaction and the overall quality of the product are considered, ensuring batch stability and safety of use.

[0007] Preferably, in step S1, the microchannel reactor consists of 3-5 reaction chambers connected in series. Along the material flow direction, the temperature of the first two reaction chambers is controlled at 55℃-65℃, and the temperature of the last 1-3 reaction chambers is controlled at 70℃-85℃. The pH value of the sodium bisulfite aqueous solution is adjusted to 3.5-5.5, and the continuous addition reaction is carried out under the conditions that the system pressure does not exceed 0.1MPa and the reaction residence time is 30-60 minutes.

[0008] By adopting the above technical solution, multiple sets of series-connected reaction chambers form a continuous plug flow reaction system, avoiding the backmixing problem of batch reaction. The gradient heating mode set along the material flow direction can match the kinetic characteristics of the addition reaction. In the early stage of the reaction, the hydrolysis and self-polymerization side reactions of propylene oxide are controlled by lower temperature, and in the later stage of the reaction, the complete conversion of raw materials is ensured by increasing the temperature. With precise control of pH value, system pressure and reaction residence time, intermediates with low impurity content and small fluctuations in effective component content can be stably prepared, providing a uniform and stable raw material basis for downstream catalytic non-catalytic esterification reaction.

[0009] Preferably, in step S1, the purity data is detected using near-infrared spectroscopy or liquid chromatography; when the content of sodium 2-hydroxypropanesulfonate is ≥42%, the residue of unreacted sodium bisulfite is ≤0.1%, and the residue of propylene oxide is ≤0.05%, the batch of intermediates is deemed qualified and proceeds to step S2.

[0010] By adopting the above technical solutions, near-infrared spectroscopy can achieve online real-time detection of intermediate purity, while liquid chromatography can complete accurate laboratory quantitative verification. Both detection methods can quickly output quantitative data on the effective components and residual impurities of intermediates. The clear intermediate qualification threshold can provide a unified judgment standard for downstream feed, avoiding the entry of intermediates with excessive unreacted raw material residues into the esterification reaction system. This reduces the factors that induce side reactions during high-temperature esterification from the raw material end, ensuring the stable progress of the catalytic-free esterification reaction.

[0011] Preferably, in step S2, the fatty acid is one of lauric acid, coconut oil acid or stearic acid, the molar ratio of sodium 2-hydroxypropanesulfonate pure substance to fatty acid is controlled at 1:2.5 to 1:3.0, and the constant temperature during the dropping process is controlled at 110℃-150℃.

[0012] By adopting the above technical solution, the selected fatty acid and sodium 2-hydroxypropanesulfonate have good reaction compatibility. The excess fatty acid serves as both the core raw material for the esterification reaction and the reaction medium of the system, improving the mass transfer efficiency of the reaction system and providing sufficient driving force for the catalytic-free esterification reaction. The matched constant temperature dropping temperature can ensure that the corresponding fatty acid is always in a stable molten state, achieving uniform mixing and full contact with the intermediate aqueous solution, while avoiding raw material volatilization and premature side reactions caused by excessively high temperature during the dropping stage, laying the foundation for the smooth start of the esterification reaction.

[0013] Preferably, in step S2, the vacuum degree of the micro-negative pressure applied to the reactor during the dripping process is controlled to be -0.03MPa to -0.05MPa, and the total dripping time is controlled to be 1.5-2.5 hours.

[0014] By adopting the above technical solution, the precisely controlled micro-negative pressure environment can continuously and stably remove the water introduced by the intermediate and the water generated in the early stage of the reaction during the dropping process, while avoiding the loss of fatty acids with water vapor caused by excessive negative pressure; the matched total dropping time can achieve a balance between the dropping rate and the dehydration rate, avoiding the problem of excessively high local water content and uneven reaction system caused by excessively fast dropping, realizing a continuous process of dropping, reacting and dehydrating at the same time, and continuously promoting the positive shift of the esterification reaction equilibrium.

[0015] Preferably, in step S3, the staged gradient heating mode specifically involves: first, heating the system to 180℃-210℃ at a rate of 2℃ / min-4℃ / min and holding for 1-2 hours for rapid activation; then reducing the heating rate to 0.2℃ / min-0.8℃ / min and slowly heating to 230℃-240℃, holding for deep esterification reaction; the micro-positive pressure applied during the activation stage is 0.01MPa to 0.03MPa.

[0016] By adopting the above technical solution, the system is first rapidly raised at a relatively fast heating rate to quickly overcome the high activation energy barrier of the catalytic esterification reaction, thus smoothly initiating the esterification reaction under catalyst-free conditions. At the same time, the residence time of materials in the medium-temperature range where side reactions are prone to occur is significantly shortened. Then, the deep conversion of the esterification reaction is gradually promoted by a slow heating rate, avoiding local overheating, thermal degradation of raw materials, and coking of products caused by rapid heating. The micro-positive pressure environment in the activation stage can increase the boiling point of the system, reduce the loss of fatty acids due to volatilization during rapid heating, and ensure the stability of the material ratio of the reaction system.

[0017] Preferably, in step S4, the starting temperature of the vacuum distillation is determined based on the acid value recorded when the esterification reaction is terminated in step S3: when the terminating acid value is 45-50 mg KOH / g, the starting temperature of distillation is 190℃-210℃; when the terminating acid value is 50-55 mg KOH / g, the starting temperature of distillation is 210℃-230℃.

[0018] By adopting the above technical solution, the acid value at the end of the esterification reaction directly corresponds to the remaining content of free fatty acids in the system. The distillation start temperature is dynamically matched according to the acid value, which can select appropriate distillation start conditions for systems with different free fatty acid contents. When the acid value is high, a higher start temperature is used to ensure the rapid and efficient removal of excess fatty acids. When the acid value is low, a lower start temperature is used to avoid thermal degradation and excessive color caused by the product being in a high-temperature environment for a long time, thus achieving precise and controllable distillation process.

[0019] Preferably, in step S4, the temperature of the vacuum distillation is controlled at 190℃-240℃, and the vacuum degree of the system is controlled at -0.09MPa to -0.1MPa; the excess fatty acids recovered by distillation are decolorized by activated carbon and then recycled to step S2 as part of the fatty acid raw material.

[0020] By adopting the above technical solution, the high-vacuum distillation environment can significantly reduce the boiling point of fatty acids, achieve efficient separation of excess fatty acids from the target product at a relatively mild temperature, and reduce the risk of thermal degradation of the target product. The recovered fatty acids are decolorized by activated carbon, which can effectively remove colored impurities and trace by-products accumulated during the recycling process, ensure the stability of the reaction system after recycling, reduce raw material consumption, reduce waste emissions during the production process, and improve the industrial adaptability of the process.

[0021] Preferably, in step S5, the drying and granulation processes are carried out under vacuum conditions. The vacuum degree during the drying stage is controlled to be -0.08MPa to -0.1MPa. After the material is cooled to 80℃-100℃, it is granulated and sieved to directly obtain finished particles with a particle size of 20-40 mesh.

[0022] By adopting the above technical solutions, vacuum drying can isolate oxygen, avoid oxidation and discoloration and degradation of active ingredients during high-temperature drying, and ensure the stability of product color and active ingredient content. Granulation and sieving are completed in a suitable temperature range, which can avoid material agglomeration at high temperatures and directly obtain finished granules with uniform particle size, good flowability and dispersibility, which facilitates subsequent storage, transportation and formulation of the product, and meets the processing and use requirements of pharmaceutical excipients and cosmetics.

[0023] Secondly, this application provides an application of sodium fatty acylmethyl hydroxyethyl sulfonate, employing the following technical solution: An application of sodium fatty acyl methyl hydroxyethyl sulfonate: the prepared sodium fatty acyl methyl hydroxyethyl sulfonate is used as a raw material in the preparation of pharmaceutical excipients or cosmetics.

[0024] By adopting the above technical solution, the prepared fatty acylmethyl hydroxyethyl sulfonate sodium is free of heavy metal and chloride ion residues, has excellent foaming and foam stability performance and hard water resistance, and is gentle on the skin and mucous membranes. It can be adapted to the formulation system requirements of pharmaceutical excipients and cosmetics, and can be directly used in sulfate-free cleaning products, pharmaceutical external cleaning preparations and other scenarios, meeting the relevant regulatory requirements of pharmaceutical excipients and cosmetic raw materials.

[0025] In summary, this application has the following beneficial effects: 1. This application adopts a staged gradient temperature esterification process without catalysts throughout the entire process, which completely eliminates the metal catalysts commonly used in existing technologies, thus eliminating the industry pain point of heavy metal residues from the source. At the same time, the staged temperature control mode overcomes the technical bias that the reaction efficiency and product quality of the catalyst-free system cannot be balanced, and achieves a balance between high conversion rate and high quality.

[0026] 2. In this application, a microchannel reactor is preferably used to prepare intermediates. Combined with the process of online detection of intermediate purity and dynamic adjustment of raw material feed ratio, the optimal raw material ratio for each batch of reaction can be accurately locked, effectively avoiding the impact of intermediate purity fluctuations on the reaction, and significantly improving the batch stability and reaction consistency of the product.

[0027] 3. The method of this application precisely controls the water content of the system by using micro-negative pressure during the dropping stage, and combined with dynamic pressure switching and nitrogen water-carrying process throughout the esterification reaction, it can continuously promote the positive shift of the esterification reaction equilibrium, effectively reduce the activation energy requirement of the non-catalyst system, and reduce the probability of side reactions.

[0028] 4. The method of this application, through the linkage control of the esterification termination acid value and the distillation start temperature, combined with the decolorization and recycling process of recovered fatty acids, allows the recovered fatty acids to be recycled multiple times without significant degradation of product quality. While ensuring product quality, it reduces raw material consumption and waste emissions, and improves the industrial continuous production adaptability and economy of the process.

[0029] 5. The preferred method used in this application is drying and granulation under vacuum conditions, which can produce finished granules with uniform particle size and stable performance. With precise control of impurities throughout the process, the resulting product is free of chloride ions and heavy metal residues, and can meet the stringent requirements of pharmaceutical excipients and cosmetics. Attached Figure Description

[0030] Figure 1 This is a flowchart of a method for preparing sodium fatty acylmethyl hydroxyethyl sulfonate provided in this application. Detailed Implementation

[0031] The present application will be further described in detail below with reference to embodiments and comparative examples. Unless otherwise specified, the experimental methods used below are conventional methods. Unless otherwise specified, the materials, reagents, methods and instruments used are all conventional materials, reagents, methods and instruments in the art, which can be obtained by those skilled in the art through commercial channels or prepared according to literature methods.

[0032] Technical Concept: Sodium fatty acylmethyl hydroxyethyl sulfonate is a mild, foaming, and hard water resistant anionic surfactant widely used in high-end cosmetics and pharmaceutical cleaning excipients. However, as industry demands for product safety and batch stability continue to rise, the core shortcomings of existing preparation processes are becoming increasingly apparent. Currently, mainstream metal-catalyzed esterification methods easily introduce heavy metal residues, failing to meet the stringent requirements of high-end applications. Existing non-catalyzed processes generally suffer from low conversion efficiency, numerous byproducts, and poor batch stability. The core reasons are insufficient control over intermediate quality and a failure to match the reaction kinetics of non-catalyzed esterification, thus failing to balance the fundamental contradiction between reaction efficiency and side reaction control.

[0033] To address the aforementioned issues, this solution constructs a fully collaborative, green, catalyst-free preparation system. It employs a microchannel reactor for continuous intermediate preparation, coupled with online purity monitoring and dynamic raw material proportioning to precisely determine the optimal feed ratio for each batch. By controlling water flow under slight negative pressure during the dropwise addition stage, obstacles to the esterification reaction equilibrium are eliminated. Staged gradient heating combined with dynamic pressure switching enables efficient initiation and deep conversion of the esterification reaction under catalyst-free conditions. Furthermore, through precise acid value control, integrated distillation purification, and raw material recycling processes, the solution ultimately avoids heavy metal residues while simultaneously ensuring reaction efficiency, product quality, and batch stability, thus meeting the demands of large-scale industrial continuous production.

[0034] Example 1: This example provides a fatty acyl methyl hydroxyethyl sulfonate sodium, with the core target product being lauroyl methyl hydroxyethyl sulfonate sodium. The basic raw materials used in its preparation include: a 35% sodium bisulfite aqueous solution, 99.8% propylene oxide, 32% sodium hydroxide solution, 99% lauric acid, activated carbon, and 99.99% nitrogen.

[0035] The preparation method of the above-mentioned fatty acylmethyl hydroxyethyl sulfonate sodium includes the following steps: S1. Intermediate Synthesis and Purity Detection: In a microchannel reactor, a pH-adjusted aqueous solution of sodium bisulfite was continuously added to propylene oxide. After the reaction was completed, activated carbon was used for decolorization and filtration. The purity of the resulting purified sodium 2-hydroxypropanesulfonate aqueous solution was tested to obtain the purity data of this batch of intermediates.

[0036] The microchannel reactor consists of four reaction chambers connected in series. The temperature of the first two reaction chambers is controlled at 60℃, and the temperature of the last two reaction chambers is controlled at 77.5℃. The pH of the sodium bisulfite aqueous solution is adjusted to 4.5. The continuous addition reaction is carried out under the conditions of system pressure of 0.05MPa and reaction residence time of 45 minutes. The purity data is detected by near-infrared spectroscopy. When the content of sodium 2-hydroxypropanesulfonate is detected to be 45%, the unreacted sodium bisulfite residue is 0.05%, and the propylene oxide residue is 0.02%, the batch of intermediate is judged to be qualified and proceeds to step S2.

[0037] S2. Dynamic Proportioning and Controlled Dehydration: Fatty acids are added to the reaction vessel and replaced with an inert gas. Based on the purity data obtained in step S1, the molar ratio of pure sodium 2-hydroxypropanesulfonate to fatty acids in this batch is dynamically calculated and adjusted. Under constant temperature conditions, the purified sodium 2-hydroxypropanesulfonate aqueous solution is added dropwise to the molten fatty acids at a uniform rate. During the dropwise addition, a slight negative pressure is applied to the reaction vessel, and the slight negative pressure is adjusted according to the moisture content measurement results to maintain the water content of the reaction system at 0.3% during the dropwise addition stage.

[0038] The fatty acid used was lauric acid. The molar ratio of sodium 2-hydroxypropanesulfonate to fatty acid was controlled at 1:2.75. The constant temperature during the dropping process was controlled at 130℃. The vacuum degree of the micro-negative pressure applied to the reactor during the dropping process was controlled at -0.04MPa. The total dropping time was controlled at 2 hours. The reactor was purged with nitrogen three times. The stirring speed was controlled at 250r / min throughout the process. The oil phase after condensation and separation was returned to the reactor, and the aqueous phase was continuously discharged from the system.

[0039] S3. Staged non-catalyst-free esterification and endpoint control: After the addition is complete, stop applying the slight negative pressure and restore the atmospheric pressure. No catalyst is added throughout the process. Nitrogen gas is introduced into the reactor. The esterification reaction is carried out in a staged gradient heating mode. First, the temperature is rapidly increased to complete the reaction activation. Then, the heating rate is reduced and the temperature is slowly increased to carry out the deep esterification reaction. During the activation stage, a slight positive pressure is applied to the reactor. After entering the deep esterification reaction stage, the pressure is switched to atmospheric pressure. The acid value of the reaction product is monitored during the reaction. When the acid value drops to 50 mg KOH / g, the esterification reaction is terminated.

[0040] The phased gradient heating mode is as follows: first, the system is heated to 195℃ at a rate of 3℃ / min and held for 1.5 hours for rapid activation; then, the heating rate is reduced to 0.5℃ / min, and the system is slowly heated to 235℃ and held for deep esterification reaction; the micro-positive pressure applied during the activation stage is 0.02MPa; a small amount of nitrogen is continuously introduced into the reactor throughout the process to remove the water generated in the reaction from the system, and the nitrogen introduction rate is controlled at 50mL / min.

[0041] S4. Product distillation and purification: After the esterification reaction is completed, the distillation starting conditions are determined according to the acid value at the time of termination of the esterification reaction in step S3. Excess fatty acids in the system are removed and recovered by vacuum distillation.

[0042] The starting temperature of vacuum distillation is determined based on the acid value recorded when the esterification reaction is terminated in step S3. The terminating acid value is 50 mg KOH / g, and the starting temperature of distillation is 210℃. The temperature of vacuum distillation is controlled at 215℃, and the vacuum degree of the system is controlled at -0.095 MPa. The excess fatty acids recovered by distillation are decolorized by activated carbon and then recycled to step S2 as part of the fatty acid raw material.

[0043] S5. Drying and granulation: The distilled material is cooled, dried and granulated to obtain sodium fatty acylmethyl hydroxyethyl sulfonate.

[0044] The drying and granulation processes are carried out under vacuum conditions. The vacuum level during the drying stage is controlled at -0.09 MPa. After the material is cooled to 90°C, it is granulated and screened to directly obtain finished particles with a particle size of 30 mesh.

[0045] Example 2: This example provides a fatty acyl methyl hydroxyethyl sulfonate sodium, with the core target product being lauroyl methyl hydroxyethyl sulfonate sodium. The basic raw materials used in its preparation include: a 35% sodium bisulfite aqueous solution, 99.8% propylene oxide, 32% sodium hydroxide solution, 99% lauric acid, activated carbon, and 99.99% nitrogen.

[0046] The preparation method of the above-mentioned fatty acylmethyl hydroxyethyl sulfonate sodium includes the following steps: S1. Intermediate Synthesis and Purity Detection: In a microchannel reactor, a pH-adjusted aqueous solution of sodium bisulfite was continuously added to propylene oxide. After the reaction was completed, activated carbon was used for decolorization and filtration. The purity of the resulting purified sodium 2-hydroxypropanesulfonate aqueous solution was tested to obtain the purity data of this batch of intermediates.

[0047] The microchannel reactor consists of three reaction chambers connected in series. The temperature of the first two reaction chambers is controlled at 55℃, and the temperature of the last reaction chamber is controlled at 70℃. The pH of the sodium bisulfite aqueous solution is adjusted to 3.5. The continuous addition reaction is carried out under the conditions of system pressure of 0.02MPa and reaction residence time of 30 minutes. The purity data is detected by near-infrared spectroscopy. When the content of 2-hydroxypropanesulfonate is detected to be 42%, the unreacted sodium bisulfite residue is 0.1%, and the propylene oxide residue is 0.05%, the batch of intermediate is judged to be qualified and proceeds to step S2.

[0048] S2. Dynamic Proportioning and Controlled Dehydration: Fatty acids are added to the reaction vessel and replaced with an inert gas. Based on the purity data obtained in step S1, the molar ratio of pure sodium 2-hydroxypropanesulfonate to fatty acids in this batch is dynamically calculated and adjusted. Under constant temperature conditions, the purified sodium 2-hydroxypropanesulfonate aqueous solution is added dropwise to the molten fatty acids at a uniform rate. During the dropwise addition, a slight negative pressure is applied to the reaction vessel, and the slight negative pressure is adjusted according to the moisture content measurement results to maintain the water content of the reaction system at 0.45% during the dropwise addition stage.

[0049] The fatty acid used was lauric acid. The molar ratio of sodium 2-hydroxypropanesulfonate to fatty acid was controlled at 1:2.5. The constant temperature during the dropping process was controlled at 110℃. The vacuum degree of the micro-negative pressure applied to the reactor during the dropping process was controlled at -0.03MPa. The total dropping time was controlled at 1.5 hours. The reactor was purged with nitrogen three times. The stirring speed was controlled at 250r / min throughout the process. The oil phase after condensation and separation was returned to the reactor, and the aqueous phase was continuously discharged from the system.

[0050] S3. Staged non-catalyst-free esterification and endpoint control: After the addition is complete, stop applying the slight negative pressure and restore the atmospheric pressure. No catalyst is added throughout the process. Nitrogen gas is introduced into the reactor. The esterification reaction is carried out in a staged gradient heating mode. First, the temperature is rapidly increased to complete the reaction activation. Then, the heating rate is reduced and the temperature is slowly increased to carry out the deep esterification reaction. During the activation stage, a slight positive pressure is applied to the reactor. After entering the deep esterification reaction stage, the pressure is switched to atmospheric pressure. The acid value of the reaction product is monitored during the reaction. When the acid value drops to 45 mg KOH / g, the esterification reaction is terminated.

[0051] The phased gradient heating mode is as follows: first, the system is heated to 180℃ at a rate of 2℃ / min and held for 1 hour for rapid activation; then, the heating rate is reduced to 0.2℃ / min, and the system is slowly heated to 230℃ and held for deep esterification reaction; the micro-positive pressure applied during the activation stage is 0.01MPa; a small amount of nitrogen is continuously introduced into the reactor throughout the process to remove the water generated in the reaction from the system, and the nitrogen introduction rate is controlled at 50mL / min.

[0052] S4. Product distillation and purification: After the esterification reaction is completed, the distillation starting conditions are determined according to the acid value at the time of termination of the esterification reaction in step S3. Excess fatty acids in the system are removed and recovered by vacuum distillation.

[0053] The starting temperature of vacuum distillation is determined based on the acid value recorded when the esterification reaction is terminated in step S3. The terminating acid value is 45 mg KOH / g, and the starting temperature of distillation is 190℃. The temperature of vacuum distillation is controlled at 190℃, and the vacuum degree of the system is controlled at -0.09 MPa. The excess fatty acids recovered by distillation are decolorized by activated carbon and then recycled to step S2 as part of the fatty acid raw material.

[0054] S5. Drying and granulation: The distilled material is cooled, dried and granulated to obtain sodium fatty acylmethyl hydroxyethyl sulfonate.

[0055] The drying and granulation processes are carried out under vacuum conditions. The vacuum level during the drying stage is controlled at -0.08 MPa. After the material is cooled to 80°C, it is granulated and screened to directly obtain finished particles with a particle size of 20 mesh.

[0056] Example 3: This example provides a fatty acyl methyl hydroxyethyl sulfonate sodium, with the core target product being lauroyl methyl hydroxyethyl sulfonate sodium. The basic raw materials used in its preparation include: a 35% sodium bisulfite aqueous solution, 99.8% propylene oxide, 32% sodium hydroxide solution, 99% lauric acid, activated carbon, and 99.99% nitrogen.

[0057] The preparation method of the above-mentioned fatty acylmethyl hydroxyethyl sulfonate sodium includes the following steps: S1. Intermediate Synthesis and Purity Detection: In a microchannel reactor, a pH-adjusted aqueous solution of sodium bisulfite was continuously added to propylene oxide. After the reaction was completed, activated carbon was used for decolorization and filtration. The purity of the resulting purified sodium 2-hydroxypropanesulfonate aqueous solution was tested to obtain the purity data of this batch of intermediates.

[0058] The microchannel reactor consists of five reaction chambers connected in series. The temperature of the first two reaction chambers is controlled at 65°C, and the temperature of the last three reaction chambers is controlled at 85°C. The pH of the sodium bisulfite aqueous solution is adjusted to 5.5. The continuous addition reaction is carried out under the conditions of system pressure of 0.1 MPa and reaction residence time of 60 minutes. The purity data is detected by near-infrared spectroscopy. When the content of sodium 2-hydroxypropanesulfonate is detected to be 48%, the unreacted sodium bisulfite residue is 0.02%, and the propylene oxide residue is 0.01%, the batch of intermediates is judged to be qualified and proceeds to step S2.

[0059] S2. Dynamic Proportioning and Controlled Dehydration: Fatty acids are added to the reaction vessel and replaced with an inert gas. Based on the purity data obtained in step S1, the molar ratio of pure sodium 2-hydroxypropanesulfonate to fatty acids in this batch is dynamically calculated and adjusted. Under constant temperature conditions, the purified sodium 2-hydroxypropanesulfonate aqueous solution is added dropwise to the molten fatty acids at a uniform rate. During the dropwise addition, a slight negative pressure is applied to the reaction vessel, and the slight negative pressure is adjusted according to the moisture content measurement results to maintain the water content of the reaction system at 0.2% during the dropwise addition stage.

[0060] The fatty acid used was lauric acid. The molar ratio of sodium 2-hydroxypropanesulfonate to fatty acid was controlled at 1:3.0. The constant temperature during the dropping process was controlled at 150℃. The vacuum degree of the micro-negative pressure applied to the reactor during the dropping process was controlled at -0.05MPa. The total dropping time was controlled at 2.5 hours. The reactor was purged with nitrogen three times. The stirring speed was controlled at 250r / min throughout the process. The oil phase after condensation and separation was returned to the reactor, and the aqueous phase was continuously discharged from the system.

[0061] S3. Staged, non-catalytic esterification and endpoint control: After the addition is complete, the application of micro-negative pressure is stopped and the pressure is restored to normal. No catalyst is added throughout the process. Nitrogen gas is introduced into the reactor. The esterification reaction is carried out in a staged gradient heating mode. First, the temperature is rapidly increased to complete the reaction activation. Then, the heating rate is reduced and the temperature is slowly increased to carry out the deep esterification reaction. During the activation stage, micro-positive pressure is applied to the reactor. After entering the deep esterification reaction stage, the pressure is switched to micro-negative pressure. The vacuum degree of micro-negative pressure is controlled at -0.03MPa. The acid value of the reaction product is monitored during the reaction. When the acid value drops to 55mgKOH / g, the esterification reaction is terminated.

[0062] The phased gradient heating mode is as follows: first, the system is heated to 210℃ at a rate of 4℃ / min and held for 2 hours for rapid activation; then, the heating rate is reduced to 0.8℃ / min and the system is slowly heated to 240℃ and held for deep esterification reaction; the micro-positive pressure applied during the activation stage is 0.03MPa; a small amount of nitrogen is continuously introduced into the reactor throughout the process to remove the water generated in the reaction from the system, and the nitrogen introduction rate is controlled at 50mL / min.

[0063] S4. Product distillation and purification: After the esterification reaction is completed, the distillation starting conditions are determined according to the acid value at the time of termination of the esterification reaction in step S3. Excess fatty acids in the system are removed and recovered by vacuum distillation.

[0064] The starting temperature of vacuum distillation is determined based on the acid value recorded when the esterification reaction is terminated in step S3. The terminating acid value is 55 mg KOH / g, and the starting temperature of distillation is 230℃. The temperature of vacuum distillation is controlled at 240℃, and the vacuum degree of the system is controlled at -0.1 MPa. The excess fatty acids recovered by distillation are decolorized by activated carbon and then recycled to step S2 as part of the fatty acid raw material.

[0065] S5. Drying and granulation: The distilled material is cooled, dried and granulated to obtain sodium fatty acylmethyl hydroxyethyl sulfonate.

[0066] The drying and granulation processes are carried out under vacuum conditions. The vacuum level during the drying stage is controlled at -0.1 MPa. After the material is cooled to 100°C, it is granulated and screened to directly obtain finished particles with a particle size of 40 mesh.

[0067] The sodium lauroyl methyl hydroxyethyl sulfonate products obtained in Examples 1-3 above are free of chloride ions and heavy metal zinc ions, and can be used as raw materials in the preparation of pharmaceutical excipients or cosmetics.

[0068] Comparative Example 1: The only difference between this comparative example and Example 1 is that in step S3, the staged catalytic esterification and endpoint control, after the addition is completed and the pressure is restored to normal, zinc oxide catalyst accounting for 1.0% of the total mass of lauric acid is added. The remaining steps, parameters, types of raw materials and amounts are completely consistent with Example 1.

[0069] Comparative Example 2: The only difference between this comparative example and Example 1 is that in step S1, intermediate synthesis and purity detection, a microchannel reactor is not used. Instead, a traditional 1000mL four-necked flask is used for the intermittent addition reaction. The reaction temperature, pH, raw material amount, and total reaction time are completely consistent with those of Example 1. All other steps and parameters are exactly the same as those of Example 1.

[0070] Comparative Example 3: The only difference between this comparative example and Example 1 is that in step S2, dynamic proportioning and controlled dehydration, dynamic calculations are not performed based on the intermediate purity data in step S1. Instead, the molar ratio of sodium 2-hydroxypropanesulfonate to lauric acid is directly fixed at 1:2.75. This fixed ratio is used regardless of fluctuations in the purity of the intermediate. All other steps, parameters, types of raw materials, and amounts are completely consistent with Example 1.

[0071] Comparative Example 4: The only difference between this comparative example and Example 1 is that in step S2, dynamic proportioning and controlled dehydration, no slight negative pressure is applied to the reactor during the dripping process, and the dripping is carried out at normal pressure. The water content of the system is not actively controlled, and the water in the reaction system accumulates naturally with the dripping. The other steps, parameters, and raw material dosages are completely consistent with Example 1.

[0072] Comparative Example 5: The only difference between this comparative example and Example 1 is that in step S3, the staged non-catalytic esterification and endpoint control, the staged gradient heating mode is not used. Instead, the system is directly heated from 130°C to 235°C at a single heating rate of 1.5°C / min. The total holding time of the reaction is consistent with the total time of rapid activation + slow heating in Example 1. All other steps, parameters, and raw material amounts are completely consistent with Example 1.

[0073] Comparative Example 6: This comparative example uses commercially available sodium lauroyl methyl hydroxyethyl sulfonate synthesized via the mainstream acyl chloride method. This product is prepared by condensation reaction of lauroyl chloride and sodium 2-hydroxypropanesulfonate under alkaline conditions, followed by desalting and purification. This comparative example serves as a control example of prior art products, and its performance testing methods are completely consistent with those of Example 1.

[0074] I. Detection of Active Ingredient Content and Limits of Key Impurities, Test Standard: GB / T13173-2021 "Test Methods for Surfactants and Detergents"; Following the standardized testing procedures specified in this standard, a systematic test was conducted on the finished sodium lauroyl methyl hydroxyethyl sulfonate products of Examples 1-3 and Comparative Examples 1-6. The active ingredient content was quantitatively determined using the ethanol extraction method specified in the standard; the zinc ion content was quantitatively determined using flame atomic absorption spectrophotometry; the chloride ion content was quantitatively determined using silver nitrate potentiometric titration; the free fatty acid content was determined using acid-base titration; and the product color was determined using the platinum-cobalt colorimetric method. Each sample underwent three parallel tests, and the arithmetic mean of all parallel test results was taken as the final test data. Through horizontal data comparison of multiple groups of samples, the differences in the impact of different preparation processes on the basic purity, key impurity residues, and overall quality of the product were visually verified.

[0075] II. Foaming Performance and Hard Water Stability Testing, Test Standards: GB / T7462-1994 "Determination of Foaming Power of Surfactants - Modified Ross-Miles Method", GB / T13173-2021 "Surfactants - Test Methods for Detergents"; Following the test methods specified in these two standards, the core application performance of sodium lauroyl methyl hydroxyethyl sulfonate products from Examples 1-3 and Comparative Examples 1-6 was tested. First, a 0.25% (w / w) sample aqueous solution was prepared. Distilled water and 250 mg / L standard hard water were used as the test media. All test cycles... The ambient temperature was uniformly controlled at 40℃. The modified Ross-Miles method was used to record the foam height of the sample solution at 0 seconds and 300 seconds after foam formation, thereby characterizing the instantaneous foaming power and foam stability of the sample. At the same time, the transmittance change of the sample after standing in hard water for 24 hours was measured according to the method specified in GB / T13173-2021, thereby characterizing the hard water stability of the sample. Each sample was tested in triplicate, and the arithmetic mean of all parallel test results was taken as the final test data to verify the direct impact of the product's basic purity and impurity residue on the core application performance.

[0076] III. Batch stability and raw material recycling compatibility testing, test standard: GB / T13173-2021 "Test Methods for Surfactants and Detergents"; according to the relevant test methods specified in this standard, parallel scale-up tests were conducted on three consecutive batches of the preparation processes of Examples 1-3, and parallel scale-up tests were conducted on the preparation processes of Comparative Examples 1-5 under the same conditions and batches. The relative standard deviation of the active ingredient content, key impurity content, and foaming performance of each parallel batch sample was detected to quantify the batch stability of different preparation processes. At the same time, five consecutive recycling tests were conducted on the lauric acid recovered by distillation in Example 1, and the same number of recycling tests were conducted on the lauric acid recovered by distillation in Comparative Example 1 under the same conditions. The change range of various performance indicators of the finished product after each recycling test was detected to verify the compatibility of different preparation processes with raw material recycling, and to provide complete data support for the industrial continuous production of the process.

[0077] Table 1: Results of Active Ingredient Content and Limits of Key Impurities Note: "Not detected" means the test result is below the detection limit of the corresponding method, where the detection limit for zinc ions is 0.1 ppm and the detection limit for chloride ions is 0.5 ppm.

[0078] Table 2: Results of foaming performance and hard water stability tests Table 3: Results of Batch Stability and Raw Material Recycling Compatibility Tests Note: "-" indicates that the sample has not been tested for the corresponding item. Comparative Example 6 is a commercially available finished product, and there is no batch stability test data for the corresponding preparation process. Examples 2 and 3 did not carry out cyclic application comparison tests. Only Example 1 was used as the core representative to verify the cyclic compatibility of raw materials.

[0079] As can be seen from Examples 1-3 and Comparative Example 1, and Tables 1-3, the addition or absence of a catalyst in the esterification reaction system directly affects the level of impurities in the product, the adaptability of raw material recycling, and the complexity of the production process. Although metal catalysts can provide activation energy for the esterification reaction, they will introduce heavy metal residues into the product. At the same time, the catalyst will enter the recycling system with the recovered fatty acids, continuously affecting the reaction stability of subsequent batches. The synthesis system without catalyst throughout the entire process avoids these problems from the source. Through the synergistic cooperation of the entire process, it achieves reaction effects and overall product performance that are comparable to or even better than those of the catalytic system.

[0080] As can be seen from Examples 1-3 and Comparative Example 2, and Tables 1-3, the preparation method of the intermediate directly determines the purity, impurity content, and batch stability of the intermediate, which in turn has a chain effect on the effect of the downstream esterification reaction and the performance of the final product. Microchannel continuous reaction can more precisely control the process of addition reaction and system environment, and the quality of the intermediate obtained is more stable, providing a reliable raw material basis for catalytic-free esterification reaction. In contrast, the mass and heat transfer efficiency of traditional batch reactor reaction is limited, and the quality of the prepared intermediate fluctuates greatly, which will directly reduce the purity, application performance, and batch stability of the final product.

[0081] As can be seen from Examples 1-3 and Comparative Example 3, and Tables 1-3, the control method of raw material feeding ratio is directly related to the stability of the catalytic-free esterification reaction and the batch consistency of the final product. Dynamically adjusting the raw material feeding molar ratio based on the actual purity of the intermediate can accurately lock the optimal raw material ratio for each batch of esterification reaction, avoid the imbalance problem caused by the fluctuation of intermediate purity, and ensure the stable progress of the esterification reaction in the catalytic-free system. However, a fixed feeding ratio cannot adapt to the quality fluctuation of the intermediate, which will directly affect the conversion efficiency of the esterification reaction and amplify the performance differences between different batches of products.

[0082] Based on Examples 1-3 and Comparative Example 4, and in conjunction with Tables 1 and 2, it can be seen that controlling the water content of the system during the dropwise addition stage is crucial for the successful initiation and deep progression of the catalytic-free esterification reaction. Esterification is a typical reversible reaction. During the dropwise addition stage, the continuous removal of water from the system by a slight negative pressure can effectively promote the forward shift of the esterification reaction equilibrium, clearing the core obstacle for the esterification reaction under catalytic-free conditions. However, under normal pressure dropwise addition, the water in the system cannot be effectively removed, which will directly inhibit the forward progress of the esterification reaction, significantly reduce the reaction conversion rate, increase the probability of side reactions, and ultimately affect the purity and application performance of the product.

[0083] Based on Examples 1-3 and Comparative Example 5, and in conjunction with Tables 1 and 2, it can be seen that the heating mode during the esterification reaction directly determines the balance between reaction efficiency and product quality in the catalytic-free system. The phased gradient heating mode can quickly overcome the activation energy barrier of the catalytic-free esterification reaction in the early stage of the reaction, smoothly start the reaction, and shorten the residence time of materials in the high-temperature zone of the side reactions. The subsequent slow heating can ensure the deep conversion of the reaction while avoiding the degradation of raw materials and coking of products caused by continuous high temperature. However, the single-rate heating mode cannot adapt to the needs of different stages of the catalytic-free esterification reaction, and will simultaneously cause problems of insufficient reaction conversion and increased by-products, ultimately reducing the overall quality of the product.

[0084] Combining Examples 1-3 and Comparative Example 6 with Tables 1 and 2, it can be seen that different synthetic routes directly determine the types of impurities in the product and the environmental friendliness of the production process. The direct non-catalytic esterification route using fatty acids as raw materials avoids chloride ion byproducts generated during the acyl chloride synthesis process from the source, eliminating the need for additional desalting and purification processes. The prepared product has no chloride ion residue, and has better hard water stability and foaming performance. At the same time, it greatly simplifies the production process and reduces the cost and pressure of waste treatment.

[0085] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. A method for preparing sodium fatty acylmethyl hydroxyethyl sulfonate, characterized in that: Includes the following steps: S1. Intermediate Synthesis and Purity Detection: In a microchannel reactor, a pH-adjusted sodium bisulfite aqueous solution was continuously added to propylene oxide. After the reaction was completed, activated carbon was used for decolorization and filtration. The purity of the resulting purified sodium 2-hydroxypropanesulfonate aqueous solution was tested to obtain the purity data of this batch of intermediates. S2. Dynamic proportioning and controlled dehydration: Fatty acids are added to the reaction vessel and replaced with an inert gas. Based on the purity data obtained in step S1, the molar ratio of pure sodium 2-hydroxypropanesulfonate to fatty acids in this batch is dynamically calculated and adjusted. Under constant temperature conditions, the purified sodium 2-hydroxypropanesulfonate aqueous solution is added dropwise to the molten fatty acids at a uniform rate. During the dropwise addition, a slight negative pressure is applied to the reaction vessel, and the slight negative pressure is adjusted according to the moisture content measurement results to keep the water content of the reaction system below 0.5% during the dropwise addition stage. S3. Staged non-catalyst-free esterification and endpoint control: After the addition is complete, stop applying the micro negative pressure and restore the atmospheric pressure. No catalyst is added throughout the process. Nitrogen gas is introduced into the reactor. The esterification reaction is carried out in a staged gradient heating mode. First, the temperature is rapidly increased to complete the reaction activation. Then, the heating rate is reduced and the temperature is slowly increased to carry out the deep esterification reaction. During the activation stage, a micro positive pressure is applied to the reactor. After entering the deep esterification reaction stage, the pressure is switched to atmospheric pressure or micro negative pressure. The acid value of the reaction product is monitored during the reaction. When the acid value drops to 45-55 mgKOH / g, the esterification reaction is terminated. S4. Product distillation and purification: After the esterification reaction is completed, the distillation starting conditions are determined according to the acid value at the time of termination of the esterification reaction in step S3. Excess fatty acids in the system are removed and recovered by vacuum distillation. S5. Drying and granulation: The distilled material is cooled, dried and granulated to obtain sodium fatty acylmethyl hydroxyethyl sulfonate.

2. The method for preparing sodium fatty acylmethyl hydroxyethyl sulfonate according to claim 1, characterized in that: In step S1, the microchannel reactor consists of 3-5 reaction chambers connected in series. Along the material flow direction, the temperature of the first two reaction chambers is controlled at 55℃-65℃, and the temperature of the last 1-3 reaction chambers is controlled at 70℃-85℃. The pH value of the sodium bisulfite aqueous solution is adjusted to 3.5-5.

5. The continuous addition reaction is carried out under the conditions that the system pressure does not exceed 0.1MPa and the reaction residence time is 30-60 minutes.

3. The method for preparing sodium fatty acylmethyl hydroxyethyl sulfonate according to claim 1, characterized in that: In step S1, the purity data is detected using near-infrared spectroscopy or liquid chromatography. When the content of sodium 2-hydroxypropanesulfonate is ≥42%, the residue of unreacted sodium bisulfite is ≤0.1%, and the residue of propylene oxide is ≤0.05%, the batch of intermediates is deemed qualified and proceeds to step S2.

4. The method for preparing sodium fatty acylmethyl hydroxyethyl sulfonate according to claim 1, characterized in that: In step S2, the fatty acid is one of lauric acid, coconut oil acid or stearic acid, and the molar ratio of sodium 2-hydroxypropanesulfonate pure substance to fatty acid is controlled at 1:2.5 to 1:3.

0. The constant temperature during the dropping process is controlled at 110℃-150℃.

5. The method for preparing sodium fatty acylmethyl hydroxyethyl sulfonate according to claim 1, characterized in that: In step S2, the vacuum degree of the micro-negative pressure applied to the reactor during the dropping process is controlled to be -0.03MPa to -0.05MPa, and the total dropping time is controlled to be 1.5-2.5 hours.

6. The method for preparing sodium fatty acylmethyl hydroxyethyl sulfonate according to claim 1, characterized in that: In step S3, the staged gradient heating mode specifically involves: first, heating the system to 180℃-210℃ at a rate of 2℃ / min-4℃ / min and holding for 1-2 hours for rapid activation; then reducing the heating rate to 0.2℃ / min-0.8℃ / min and slowly heating to 230℃-240℃, holding for deep esterification reaction; the micro-positive pressure applied during the activation stage is 0.01MPa to 0.03MPa.

7. The method for preparing sodium fatty acylmethyl hydroxyethyl sulfonate according to claim 1, characterized in that: In step S4, the starting temperature of the vacuum distillation is determined based on the acid value recorded when the esterification reaction is terminated in step S3: when the terminating acid value is 45-50 mg KOH / g, the starting temperature of distillation is 190℃-210℃; when the terminating acid value is 50-55 mg KOH / g, the starting temperature of distillation is 210℃-230℃.

8. The method for preparing sodium fatty acylmethyl hydroxyethyl sulfonate according to claim 1, characterized in that: In step S4, the temperature of the vacuum distillation is controlled at 190℃-240℃, and the vacuum degree of the system is controlled at -0.09MPa to -0.1MPa. The excess fatty acids recovered by distillation are decolorized by activated carbon and then recycled back to step S2 as part of the fatty acid raw material.

9. The method for preparing sodium fatty acylmethyl hydroxyethyl sulfonate according to claim 1, characterized in that: In step S5, the drying and granulation processes are carried out under vacuum conditions. The vacuum degree during the drying stage is controlled at -0.08MPa to -0.1MPa. After the material is cooled to 80℃-100℃, it is granulated and sieved to directly obtain finished particles with a particle size of 20-40 mesh.

10. An application of a fatty acylmethyl hydroxyethyl sulfonate sodium, characterized in that: The sodium fatty acyl methyl hydroxyethyl sulfonate prepared by any one of claims 1-9 is used as a raw material in the preparation of pharmaceutical excipients or cosmetics.

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