A method for concentrating a solution of bitosulfone by electrodialysis

Abstract

This invention belongs to the field of organic compound purification and concentration technology. It proposes a method for concentrating succinic acid solution using electrodialysis. The method involves pre-treatment by filtration, electrodialysis concentration, and cyclic concentration of a 3-5% succinic acid solution until a 15-18% succinic acid solution is obtained. This invention aims to obtain high-purity pharmaceutical intermediates from high-purity succinic acid solutions containing a strong dibasic organic acid. An optimized concentration range of 15-18% was determined based on the viscosity characteristics of the succinic acid solution, avoiding efficiency reduction and product quality issues caused by excessively high viscosity. The electrodialysis process operates at ambient temperature and pressure, consuming only electrical energy to drive ion migration, eliminating the need for heating and solvent evaporation, thus avoiding the latent heat of phase change of water and resulting in lower energy consumption than evaporation concentration methods. The electrodialysis process does not use chemical reagents, produces no waste residue, and avoids secondary pollution. It also avoids the decomposition and discoloration problems of succinic acid caused by high-temperature evaporation, resulting in a product with good thermal stability and high purity.

Description

Technical Field

[0001] This invention belongs to the field of organic compound purification and concentration technology, and particularly relates to a method for concentrating succinic acid solution by electrodialysis. Background Technology

[0002] Succinic acid is a dibasic strong organic acid containing two sulfonic acid groups. This compound is a colorless to white crystalline solid and is well soluble in water. Succinic acid is a key intermediate in the preparation of S-adenosylmethionine disulfate, and its quality directly affects the purity and stability of the final drug product.

[0003] Succinic acid can be obtained through various synthetic routes. For example, sodium 1,4-succinate undergoes an acidification reaction with hydrogen chloride gas in an organic alcohol solvent. After removing hydrogen chloride and organic acids, crude succinic acid is obtained by crystallization. The crude product is then recrystallized in an organic acid to obtain refined succinic acid. There are also reports of preparing succinic acid by reacting 1,4-butanediol with sulfonic acid, or by chlorinating sulfur and chloroethane in an ether followed by an alkalization reaction. Sodium 1,4-succinate is converted using the H-type cation exchange resin method, yielding high-purity 1,4-succinic acid in one step. However, the concentration is only 3-4%, which is insufficient to reach 15% or higher, and does not meet the requirements for subsequent production.

[0004] Currently, evaporation concentration is the main method used for solution concentration, including atmospheric pressure evaporation and vacuum evaporation. However, as a strong dibasic organic acid, succinic acid presents the following unique technical challenges in its concentration process:

[0005] 1) Succinic acid is extremely sensitive to heat: Under heating and evaporation conditions, high temperature can easily cause succinic acid to decompose, change color or produce side reactions. The impurities generated will directly enter the downstream product S-adenosylmethionine succinate, affecting the quality of the drug. Even if the evaporation temperature is reduced by vacuum evaporation, thermal degradation cannot be completely avoided. Moreover, prolonged heating will cause the solution to darken in color and decrease in purity.

[0006] 2) The viscosity of succinic acid solution increases non-linearly with increasing concentration: Experiments show that when the mass concentration of succinic acid is below 10%, the viscosity of the solution is similar to that of water; when the concentration reaches 15%, the viscosity rises to about 5 mPa·s (25℃); when the concentration exceeds 18%, the viscosity rises sharply to more than 15 mPa·s, resulting in a significant decrease in evaporation efficiency, difficulty in stirring, deterioration of heat transfer, and a sharp increase in energy consumption.

[0007] 3) The evaporation and concentration process involves a phase change process, which requires a large amount of latent heat, resulting in high equipment investment and maintenance costs.

[0008] Electrodialysis, as a membrane separation technology, exhibits unique advantages in the field of solution concentration. This technology drives ion migration through an electric field, combined with the selective permeability of ion exchange membranes, to achieve the separation of solute and solvent, without phase change, with low energy consumption and mild operation.

[0009] Regarding organic acid treatment, patents have reported methods for treating wastewater containing complex organic acids using electrodialysis. For example, Chinese invention patent CN94110704.3 discloses a method for treating wastewater containing organic acids using electrodialysis, where the concentration of organic acids treated is 3-15% (M / M), and the resulting concentrated solution contains 20-40% (M / M) acid. However, this method is designed for mixed wastewater primarily composed of monoprotic organic acids, and the treatment objective is to meet biochemical discharge requirements, falling under the field of environmental remediation. Furthermore, bipolar membrane electrodialysis technology is also used in organic acid production, but its principle is water dissociation, which differs from ordinary electrodialysis concentration.

[0010] Currently, there are no reports of directly applying conventional electrodialysis technology to the concentration of succinic acid solutions. Succinic acid contains two sulfonic acid groups, and its dissociation behavior, ion mobility, membrane flux characteristics, and concentration polarization behavior differ fundamentally from those of monobasic organic acids. Existing electrodialysis techniques for concentrating monobasic organic acids cannot be directly applied to binary strong organic acid systems. This is because binary acids may undergo secondary dissociation, ion valence state changes, and enhanced interactions with membrane materials during electrodialysis, all of which require targeted research and optimization. Summary of the Invention

[0011] This invention addresses the shortcomings of the above-mentioned evaporation concentration method, such as thermal decomposition, high energy consumption, and low efficiency, by proposing a method for concentrating succinic acid solution using electrodialysis. This method solves the problems of thermal decomposition, high energy consumption, and low efficiency of the evaporation concentration method, and achieves efficient, mild, and high-purity concentration of succinic acid solution, concentrating the succinic acid solution from 3-5% to 15-18%.

[0012] To achieve the above objectives, the technical solution adopted by the present invention is as follows: The present invention provides a method for concentrating succinic acid solution by electrodialysis, comprising the following steps:

[0013] S1. Take the raw material solution to be concentrated: the raw material solution is a 3-5% mass concentration succinic acid solution;

[0014] S2. Pretreatment: The raw material liquid is filtered to obtain a filtered succinic acid solution with a filtration accuracy of 0.1~10μm;

[0015] S3. Electrodialysis Concentration: The filtered succinic acid solution is introduced into the concentration chamber, desalination chamber, and electrode chamber of the electrodialysis device. The concentration of the filtered succinic acid solution in the desalination chamber is 3-4%, and the concentration in the electrode chamber is 1-4%. The temperature is controlled at 20-30°C, the operating voltage of the DC electric field is 5-50V, and the current density is 50-500A / m. 2 Under the action of a DC electric field, succinate ions in the desalination chamber migrate to the concentration chamber through the anion exchange membrane, and hydrogen ions migrate to the concentration chamber through the cation exchange membrane.

[0016] S4. Cyclic Concentration: The high-concentration succinic acid solution obtained in the concentration chamber of step S3 is used as a new raw material solution. Step S3 is repeated until a succinic acid solution with a concentration of 15-18% is obtained.

[0017] S5. Product collection: Collect 15-18% succinic acid solution as raw material for the downstream preparation of S-adenosylmethionine succinate.

[0018] Preferably, the concentration of the succinic acid solution in step S1 is 3-4%.

[0019] Preferably, the electrodialysis device described in step S3 includes at least one membrane stack, which comprises alternating cation exchange membranes and anion exchange membranes. The anion exchange membrane is a homogeneous anion exchange membrane with high selective permeability to succinate ions and a membrane surface resistivity ≤ 3 Ω·cm. 2 The migration number is ≥0.95, and the cation exchange membrane is a homogeneous cation exchange membrane.

[0020] Preferably, during the cyclic concentration process described in step S4, the concentration of succinic acid in the concentration chamber is detected every 10 to 30 minutes, the concentration endpoint is 15 to 18%, and the viscosity of the solution is also detected.

[0021] Preferably, the high-concentration succinic acid solution obtained in step S3 is post-treated by decolorizing it with activated carbon to remove trace amounts of colored impurities produced by electrodialysis concentration.

[0022] Preferably, the electrodialysis device employs single-stage electrodialysis or multi-stage series electrodialysis.

[0023] Compared with the prior art, the advantages and positive effects of the present invention are as follows:

[0024] 1. The present invention provides a method for concentrating succinic acid solution by electrodialysis, which is different from the purpose of environmental protection and emission. It is aimed at obtaining high-purity pharmaceutical intermediates from high-purity succinic acid solution, which is a strong organic acid in dibasic form. The optimized concentration range of 15-18% is determined according to the viscosity characteristics of succinic acid solution to avoid the efficiency reduction and product quality problems caused by excessive viscosity.

[0025] 2. This invention operates at ambient temperature and pressure through electrodialysis, consuming only electrical energy to drive ion migration without heating or evaporating the solvent, thus avoiding the consumption of latent heat of phase change of water and having lower energy consumption than the evaporation and concentration method. At the same time, the electrodialysis process does not use chemical reagents, produces no waste residue, and causes no secondary pollution. Furthermore, it avoids the decomposition and discoloration of succinic acid caused by high-temperature evaporation, resulting in products with good thermal stability and high purity.

[0026] 3. This invention fully considers the special properties of succinic acid as a strong dibasic organic acid, selects appropriate anion exchange membranes and operating parameters, and realizes a highly efficient and stable concentration process. It solves the problems that the current electrodialysis parameters of monobasic organic acids may lead to accelerated membrane fouling, decreased current efficiency, and poor concentration effect when directly applied to succinic acid.

[0027] 4. This invention uses an electrodialysis device as the main concentration equipment, which has high space utilization and does not require supporting equipment such as heating and condensation. The equipment investment and maintenance costs are lower than those of the evaporation concentration system.

[0028] 5. This invention enables continuous operation of succinic acid concentration through a multi-stage series electrodialysis device, thereby improving production efficiency. Attached Figure Description

[0029] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the following description of the embodiments will be briefly introduced. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0030] Figure 1 This is a schematic diagram of an electrodialysis apparatus in a method for concentrating succinic acid solution using electrodialysis;

[0031] Figure 2 This is a schematic diagram comparing the electrodialysis behavior of succinic acid and monobasic organic acids. Detailed Implementation

[0032] To better understand the above-mentioned objects, features, and advantages of the present invention, the present invention will be further described below in conjunction with the accompanying drawings and embodiments. It should be noted that, unless otherwise specified, the embodiments and features described in the embodiments of this application can be combined with each other. Many specific details are set forth in the following description to provide a thorough understanding of the present invention; however, the present invention may also be implemented in other ways different from those described herein. Therefore, the present invention is not limited to the specific embodiments disclosed in the following specification.

[0033] The succinic acid raw material processed in this invention can be obtained by acidification: sodium 1,4-succinic acid is deionized by H-type cation exchange resin to obtain a raw material solution with a mass concentration of 3-5%.

[0034] like Figure 2 As shown, the difference in behavior between succinic acid (a strong dibasic organic acid) and lactic acid (a monobasic organic acid) during electrodialysis is illustrated: using the same electrodialysis apparatus (effective membrane area 0.16m²), 2 (10 pairs of membranes) The anion exchange membrane used is a conventional dense anion exchange membrane, and the cation exchange membrane used is a dense cation exchange membrane; 3% succinic acid solution and 3% lactic acid (monobasic weak organic acid) solution were treated respectively under the same voltage of 10V and the same current density of 200A / m 2 And the current efficiency and membrane flux were compared after running at the same temperature of 25°C for 2 hours.

[0035] The results showed that succinic acid concentration using conventional dense anion exchange membranes resulted in low current efficiency, small membrane pore size, and low permeation efficiency, along with a slight tendency for membrane fouling. This indicates that dicarboxylic acids are incompatible with conventional dense anion exchange membranes, necessitating the use of specially optimized anion exchange membranes with slightly larger pore sizes. These differences suggest that existing electrodialysis process parameters for monocarboxylic organic acids cannot be directly applied to succinic acid. Example 1

[0036] S1. Take the raw material solution to be concentrated: the raw material solution is a 3% (w / w) succinic acid solution;

[0037] S2. Pretreatment: The raw material liquid is filtered through a 0.45μm microfiltration membrane for later use. The filtration accuracy is 0.1~10μm.

[0038] S3. Electrodialysis Concentration: The electrodialysis device includes at least one membrane stack, which comprises 10 pairs of alternating cation exchange membranes and anion exchange membranes, with an effective membrane area of ​​0.16 m². 2 The anion exchange membrane is a homogeneous anion exchange membrane with high selective permeability to succinate ions, and a membrane surface resistivity of 2.5 Ω·cm. 2 The migration number is 0.96, and the cation exchange membrane is a homogeneous cation exchange membrane;

[0039] A 3% succinic acid feedstock solution is introduced into the concentration chamber. The filtered succinic acid solution with a concentration of 3% is then introduced into the electrode chamber. The temperature is controlled at 25±2℃. The operating voltage of the DC electric field is 10V, the rated current is 3A, and the current density is 50~500A / m². Figure 1As shown, under the action of a DC electric field, succinate ions in the desalination chamber migrate to the concentration chamber through the anion exchange membrane, and hydrogen ions migrate to the concentration chamber through the cation exchange membrane; the concentration of succinate in the concentration chamber is detected every 15 minutes.

[0040] S4. Cyclic Concentration: The high-concentration succinic acid solution obtained in the concentration chamber in step S3 is used as a new raw material solution, and step S3 is repeated; after 3 hours of treatment, the concentration of succinic acid in the concentration chamber reaches 15.2%; since the concentration in the concentration chamber reaches 16.5% after 3.5 hours of further treatment, the current efficiency drops from 72% to 58%, so the electrodialysis concentration is stopped after 3 hours.

[0041] S5. Product collection: Collect a 15.2% succinic acid solution as a raw material for the downstream preparation of S-adenosylmethionine succinate;

[0042] Testing revealed that the concentrated succinic acid solution was colorless and transparent with no discoloration, exhibiting an HPLC purity of 98.5% and a succinic acid yield of 96.8%. Energy consumption statistics show that the power consumption for processing one ton of succinic acid solution (concentrated from 3% to 15.2%) in this embodiment is approximately 45 kWh, while the power consumption for the same processing capacity using vacuum evaporation concentration method is approximately 115 kWh (including vacuum pump, heating, etc.). Comparatively, this embodiment saves approximately 61% of energy. Example 2

[0043] A 4% succinic acid feed solution was filtered through a 0.45 μm microfiltration membrane and set aside for later use. Using the same electrodialysis apparatus as in Example 1, a 4% filtered succinic acid solution was introduced into the desalination chamber, and a 3% filtered succinic acid solution was introduced into the electrode chamber. The operating voltage was adjusted to 10V, the rated current to 3A, and the solution temperature was controlled at 25±2℃. After 3 hours of cyclic electrodialysis treatment, the succinic acid concentration in the concentration chamber reached 15.7%, and operation was stopped. The concentrated solution was collected; the succinic acid solution was colorless and transparent, with a concentration of 15.7%, an HPLC purity of 98.2%, and a yield of 97.0%. The energy consumption was 46 kW·h / ton of solution. In this example, the succinic acid feed solution was introduced into the concentration chamber, desalination chamber, and electrode chamber. Based on a reasonable concentration design, the independent circulating electrolyte in the electrode chamber was eliminated, and the succinic acid feed solution was used directly as the circulating electrolyte in the electrode chamber, eliminating the introduction of external inorganic electrode liquid ions and avoiding the ion contamination problem caused by conventional electrodialysis from the source. Example 3

[0044] A 4% succinic acid feed solution was filtered through a 0.45 μm microfiltration membrane and set aside for later use. Using the same electrodialysis apparatus as in Example 1, the operating voltage was adjusted to 10V, the rated current to 4A, and the solution temperature was controlled at 28±2℃. After 2.5 hours of cyclic electrodialysis treatment, the succinic acid concentration in the concentration chamber reached 16.1%, at which point operation was stopped. The concentrate was collected, and after decolorization with activated carbon, the succinic acid solution was colorless and transparent, with a concentration of 16.0%, HPLC purity of 98.8%, and a yield of 97.2%. The energy consumption was 48 kW·h / ton of solution. Example 4

[0045] The 3% succinic acid feed solution prepared in Example 1 was continuously concentrated using a two-stage series electrodialysis unit. The first-stage electrodialysis unit was set with an operating voltage of 10V and a rated current of 3A, increasing the succinic acid concentration from 3% to 8%. The second-stage electrodialysis unit was set with an operating voltage of 14V and a rated current of 4A, further increasing the concentration from 8% to 15.5%. The entire process involved continuous feeding and discharging, reducing the processing time to 1.8 hours. The succinic acid yield was 96.5%, the purity was 98.3%, and the energy consumption was 42 kW·h / ton of solution. This example demonstrates how a multi-stage series electrodialysis unit can achieve continuous operation for succinic acid concentration, improving production efficiency. For concentration systems with a concentration factor less than 5, a single-stage circulating electrodialysis unit can suffice. Comparative Example 1

[0046] Evaporation concentration method: 1 L of the 3% succinic acid solution from Example 1 was concentrated under reduced pressure using a rotary evaporator at 60°C and a vacuum of -0.09 MPa. When the solution volume was concentrated to approximately 200 mL, the succinic acid concentration was measured to be 14.8%. However, the concentrated solution was pale yellow, and the HPLC purity decreased to 95.2%, indicating that the succinic acid underwent partial degradation and discoloration during heating. The energy consumption was estimated to be approximately 115 kW·h / ton of solution. Comparative Example 2

[0047] The electrodialysis parameter concentration method for monobasic organic acids was adopted: the same butanedisulfonic acid feed solution as in Example 1 was used, but the anion exchange membrane was selected as a homogeneous anion exchange membrane conventionally used for monobasic organic acids (membrane surface resistivity 4.0 Ω·cm). 2 (No optimization for divalent anions was performed), all other operating conditions were the same. After 2 hours of operation, the membrane flux was found to have decreased to 1.2 L / m. 2 At 1000 h, the current efficiency dropped to 45%, and the concentration in the concentration chamber reached only 9.8%. After stopping operation, the membrane module was inspected, and obvious contaminants were found on the surface of the anion membrane. After cleaning, the performance was restored. This comparative example shows that the electrodialysis membrane and parameters designed for monobasic organic acids cannot be directly applied to succinic acid and must be specifically optimized.

[0048] Industrial Application Example: The method of this invention was applied to a production line with an annual output of 100 tons of S-adenosylmethionine disulfonate. The succinic acid solution was concentrated from 3% to 15-16% as an intermediate for subsequent salt formation reactions. After replacing the original reduced-pressure evaporation concentration process with the electrodialysis process described in Example 1, the production cycle was shortened from 8 hours per batch to 4 hours, energy consumption was reduced by approximately 60%, and the intermediate quality remained stable (colorless and transparent, purity ≥98.5%). The HPLC purity of the final product, S-adenosylmethionine disulfonate, increased from 98.0% to 99.2%, the total related substances decreased from 1.5% to 0.6%, and the product yield increased by approximately 5%, resulting in significant improvements in both economic benefits and product quality.

[0049] In Examples 1 to 4, the present invention uses electrodialysis concentration at room temperature and pressure, which consumes only electrical energy to drive ion migration, without the need for heating to evaporate the solvent, thus avoiding the consumption of latent heat of phase change of water. The energy consumption is lower than that of the evaporation concentration method, only 30 to 50% of the evaporation concentration method. Furthermore, the electrodialysis process does not use chemical reagents, produces no waste residue, and causes no secondary pollution, making it an environmentally friendly concentration technology.

[0050] Furthermore, based on the viscosity-concentration curve of the succinic acid solution, this invention determined an optimized concentration endpoint of 15-18%. When the concentration exceeds 18%, concentration polarization and water permeation from the desalination chamber into the concentration chamber become severe problems, making it unsuitable to continue using electrodialysis to increase the concentration.

[0051] Compared with Comparative Example 1, the products of Examples 1-4 exhibit better thermal stability and higher purity: electrodialysis is conducted at room temperature (20-30℃), completely avoiding the decomposition and discoloration of succinic acid caused by high-temperature evaporation. Experiments show that the succinic acid solution concentrated using the method of this invention is colorless and transparent, with an HPLC purity ≥98.5%, while the evaporation concentration method produces a light yellow solution at 60℃, with purity decreasing to approximately 95%. This provides a high-quality raw material for the downstream preparation of S-adenosylmethionine succinate, increasing the final product purity from 98.0% to 99.2%. This invention uses an electrodialysis device as the main concentration equipment, resulting in high space utilization and eliminating the need for heating, condensation, or other auxiliary equipment. The equipment investment and maintenance costs are lower than those of evaporation concentration systems.

[0052] Compared to Comparative Example 2, Examples 1-4 optimized the process for the characteristics of dibasic strong organic acids, fully considering the special properties of succinic acid as a dibasic strong organic acid, namely, complete dissociation into divalent anions, nonlinear concentration-viscosity relationship, and concentration polarization sensitivity. Appropriate anion exchange membranes and operating parameters were selected, achieving a highly efficient and stable concentration process. In Comparative Example 2, directly applying the electrodialysis parameters of monobasic organic acids to succinic acid leads to problems such as accelerated membrane fouling, decreased current efficiency, and poor concentration effect.

[0053] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any other way. Any person skilled in the art may make changes or modifications to the above-disclosed technical content to create equivalent embodiments for application in other fields. However, any simple modifications, equivalent changes, and modifications made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the protection scope of the present invention.

Claims

1. A method for concentrating succinic acid solution by electrodialysis, characterized in that, Includes the following steps: S1. Take the raw material solution to be concentrated: the raw material solution is a 3-5% mass concentration succinic acid solution; S2. Pretreatment: The raw material liquid is filtered to obtain a filtered succinic acid solution with a filtration accuracy of 0.1~10μm; S3. Electrodialysis Concentration: The filtered succinic acid solution is introduced into the concentration chamber, desalination chamber, and electrode chamber of the electrodialysis device. The mass concentration of the filtered succinic acid solution in the desalination chamber is 3-4%, and the mass concentration in the electrode chamber is 1-4%. The temperature is controlled at 20-30℃, the operating voltage of the DC electric field is 5-50V, and the current density is 50-500A / m. 2 Under the action of a DC electric field, succinate ions in the desalination chamber migrate to the concentration chamber through the anion exchange membrane, and hydrogen ions migrate to the concentration chamber through the cation exchange membrane. S4. Cyclic Concentration: The high-concentration succinic acid solution obtained in the concentration chamber of step S3 is used as a new raw material solution. Step S3 is repeated until a succinic acid solution with a mass concentration of 15~18% is obtained. S5. Product collection: Collect a 15-18% succinic acid solution as a raw material for the downstream preparation of S-adenosylmethionine succinate.

2. The method for concentrating succinic acid solution by electrodialysis according to claim 1, characterized in that, The mass concentration of the succinic acid solution in step S1 is 3-4%.

3. The method for concentrating succinic acid solution by electrodialysis according to claim 2, characterized in that, The electrodialysis device described in step S3 includes at least one membrane stack, which comprises alternating cation exchange membranes and anion exchange membranes. The anion exchange membrane is a homogeneous anion exchange membrane with high selectivity for succinate ions and a surface resistivity ≤ 3 Ω·cm. 2 The migration number is ≥0.95, and the cation exchange membrane is a homogeneous cation exchange membrane.

4. The method for concentrating succinic acid solution by electrodialysis according to claim 3, characterized in that, During the cyclic concentration process described in step S4, the mass concentration of succinic acid in the concentration chamber is detected every 10 to 30 minutes, with the concentration endpoint being 15 to 18%, and the viscosity of the solution is also detected.

5. A method for concentrating succinic acid solution by electrodialysis according to claim 1 or 4, characterized in that, The high-concentration succinic acid solution obtained in step S3 is post-treated by decolorizing it with activated carbon to remove trace amounts of colored impurities produced by electrodialysis concentration.

6. The method for concentrating succinic acid solution by electrodialysis according to claim 1, characterized in that, The electrodialysis device employs single-stage electrodialysis or multi-stage series electrodialysis.

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