Preparation method for mercaptosuccinic acid betaine (1:1)

Abstract

Provided is a preparation method for mercaptosuccinic acid betaine (1:1). In the preparation method, betaine and mercaptosuccinic acid are used as main raw materials, and water is used as a solvent; and the mercaptosuccinic acid and the betaine directly react with each other under a heating condition, thereby obtaining high-purity mercaptosuccinic acid betaine (1:1) represented by formula (I).

Description

Process for the preparation of mercaptosuccinic acid betaine (1:1)

[0001] Cross-reference to Related Applications

[0002] The present disclosure claims priority to and the benefit of Chinese Patent Application No. 202410639054.6, filed May 21, 2024, the entire contents of which are incorporated herein by reference. TECHNICAL FIELD

[0003] The present disclosure relates to a process for the preparation of betaine complex salt, and more particularly, to a process for the preparation of mercaptosuccinic acid betaine (1:1). BACKGROUND

[0004] In recent years, due to the fact that betaine can provide active methyl in the metabolism of living organisms, participate in methyl reactions, its application in the livestock and feed industry is becoming more and more extensive, and new uses are being developed. In view of the fact that betaine has strong hygroscopicity, it is easy to absorb moisture during transportation and storage, thereby affecting the quality of use, and the complex salt of betaine has attracted more and more attention. However, the salt formation process of betaine usually needs to use alcohol-based solvents or more complicated separation processes.

[0005] In GB1240313, a process for the preparation of thiomalic acid betaine is disclosed, in which a methanolic solution of betaine and a methanolic solution of thiomalic acid are used as raw materials to react to produce thiomalic acid betaine. This method not only needs a multi-step separation and purification process, but also has a yield of only 68%.

[0006] In GB987849, a process for the preparation of fumaric acid betaine is disclosed. The inventors still believe that fumaric acid and betaine can only obtain good salt formation results in inert solvents, such as alcohol-based solvents. However, the use of alcohol-based solvents increases the environmental burden.

[0007] In CN110724048, a process for the preparation of malic acid betaine is disclosed. In order to reduce the separation and purification process, the formation of a complex is introduced to improve the directionality of the reaction. Although this method increases the yield, it also increases the complexity of the reaction and equipment, and also increases the process cost.

[0008] In recent years, mercaptosuccinic acid betaine (1:1) has attracted attention due to its unique properties. Mercaptosuccinic acid betaine is not only relatively stable, but also has high water solubility. It greatly reduces the hygroscopicity of betaine while retaining the functions of mercaptosuccinic acid itself, which is conducive to the development of more biochemical functions of the product.

[0009] In view of this, the present disclosure proposes a preparation method of betaine mercaptosuccinate (1 :1), which simplifies the equipment and operation while ensuring the yield, and the product maintains a good ratio of 1 :1. In addition, in the method, the raw materials of each step are commercially available, with appropriate prices and sufficient supply, providing feasibility for industrial mass production of the product. SUMMARY

[0010] The present disclosure aims to provide a preparation method of betaine mercaptosuccinate (1 :1), which is mild in reaction conditions, simple in process and equipment, easy to operate, and environmentally friendly.

[0011] The present disclosure provides a preparation method of betaine mercaptosuccinate (1 :1) represented by formula (I), comprising the following steps:

[0012] a) providing a mixture of mercaptosuccinic acid and water, wherein the weight ratio of mercaptosuccinic acid to water is 1 :2 to 1 :8;

[0013] b) adding betaine to directly react the betaine with the mercaptosuccinic acid, wherein the molar ratio of mercaptosuccinic acid to betaine is 1 :1 to 1 :1.1; and

[0014] c) crystallizing the product of step b) to obtain the betaine mercaptosuccinate (1 :1) represented by formula (I).

[0015] In embodiments, the molar ratio of mercaptosuccinic acid to betaine can be 1 :1 to 1 :1.05, for example, 1 :1, 1 :1.03, or 1 :1.05.

[0016] In embodiments, the weight ratio of mercaptosuccinic acid to water can be 1 :2 to 1 :5, preferably 1 :3 to 1 :5, for example, 1 :3, 1 :4, or 1 :5.

[0017] In embodiments, in step a), the mixture of mercaptosuccinic acid and water can be maintained at a first temperature, and the first temperature can be 45°C to 75°C.

[0018] In embodiments, in step b), the betaine can be directly reacted with the mercaptosuccinic acid at a second temperature, and the second temperature can be 45°C to 75°C.

[0019] In embodiments, the first temperature and the second temperature can be the same, and can be 45°C to 65°C, for example, 45°C, 50°C, 55°C, 60°C, or 65°C.

[0020] Alternatively, the first temperature and the second temperature can be different, and the second temperature can be 45°C to 65°C, for example, 45°C, 50°C, 55°C, 60°C, or 65°C.

[0021] In embodiments, the direct reaction time of betaine with mercaptosuccinic acid can be 6 hours to 10 hours, for example 6 hours, 7 hours, 8 hours, 9 hours or 10 hours.

[0022] In embodiments, step c) can further comprise adding an organic solvent, standing at room temperature, collecting the obtained solid after crystallization no longer increases, and vacuum drying after crushing to obtain the betaine mercaptosuccinic acid (1:1) represented by formula (I).

[0023] In embodiments, the organic solvent can comprise one or more of acetone, ethanol and isopropanol.

[0024] In embodiments, the weight ratio of the organic solvent to mercaptosuccinic acid can be 1:0.9 to 1:1.1, preferably 1:1.

[0025] The preparation method provided by the present disclosure has at least one of the following advantages:

[0026] 1. The reaction directionality is improved, the utilization rate of raw materials is improved, and the purity of betaine mercaptosuccinic acid (1:1) is greatly improved;

[0027] 2. Each step raw material is commercially available, widely sourced and sufficient in supply;

[0028] 3. The reaction conditions are relatively mild and the process is simple, each step reaction is a conventional operation easy to control, which reduces the process cost, and because the mercapto substituent is used, compared with hydroxysuccinic acid, the formation of intermediate complex is avoided, and the process is simplified;

[0029] 4. Environmentally friendly, reduces pollution and realizes green production. DETAILED DESCRIPTION

[0030] In the following, the present disclosure will be further illustrated according to specific embodiments. However, the specific embodiments listed are only for the purpose of illustration, and are not intended to limit the present disclosure to the disclosed specific embodiments. A person skilled in the art will recognize that specific features in any one of the following embodiments can be used in any other embodiment, as long as it does not deviate from the spirit of the present disclosure.

[0031] In the following, unless otherwise defined, all terms used herein (including technical and scientific terms) have the same meaning as commonly understood by a person of ordinary skill in the art to which the present application belongs. Terms such as those defined in a commonly used dictionary should be interpreted in accordance with their meanings in the context of the relevant technology, and should not be interpreted in an idealized or overly formal sense, unless otherwise defined herein.

[0032] The term "direct reaction" as used herein means a reaction that is carried out without the addition of other reaction reagents or reactants to form an intermediate product.

[0033] The term "about" as used herein includes the specified value and means within an acceptable range of deviation of the value as determined by one of ordinary skill in the art considering the associated measurement and error in measurement associated with the measurement of the quantity (i.e., the limitations of the measurement system). For example, "about" can mean within one or more standard deviations, or within ±20%, ±10%, or ±5% of the specified value.

[0034] Herein, the specific temperature of "room temperature" means 22°C to 25°C, and generally means 25°C.

[0035] The present disclosure provides a method for preparing mercaptosuccinic acid betaine (1:1) represented by formula (I), the method comprising the steps of:

[0036] a) providing a mixture of mercaptosuccinic acid and water, wherein the weight ratio of mercaptosuccinic acid to water is 1:2 to 1:8;

[0037] b) adding betaine so that the betaine directly reacts with the mercaptosuccinic acid, wherein the molar ratio of mercaptosuccinic acid to betaine is 1:1 to 1:1.1; and

[0038] c) crystallizing the product of step b) to obtain mercaptosuccinic acid betaine (1:1) represented by formula (I).

[0039] In embodiments, in step a), the mixture of mercaptosuccinic acid and water can be maintained at a first temperature, and the first temperature can be 45°C to 75°C.

[0040] In embodiments, in step a), the mercaptosuccinic acid and water can be added to a reactor, and rapidly warmed to a first temperature under stirring. Wherein the reactor is not particularly limited as long as the above-mentioned reaction can be achieved.

[0041] In embodiments, the weight ratio of mercaptosuccinic acid to water can be about 1 :2 to about 1 :8, preferably about 1 :2 to about 1 :5, more preferably about 1 :3 to about 1 :5. In particular embodiments, the weight ratio of mercaptosuccinic acid to water can be 1 :3, 1 :4, or 1 :5. In one embodiment, the weight ratio of mercaptosuccinic acid to water can be 1 :3. In another embodiment, the weight ratio of mercaptosuccinic acid to water can be 1 :4. In yet another embodiment, the weight ratio of mercaptosuccinic acid to water can be 1 :5. However, the skilled person will appreciate that embodiments of the disclosure are not limited thereto, and the weight ratio of mercaptosuccinic acid to water can be any value from about 1 :2 to about 1 :8, for example 1 :3.5 or 1 :2.6.

[0042] In embodiments, in step b), betaine can be reacted directly with mercaptosuccinic acid at the second temperature, and the second temperature can be 45 °C to 75 °C.

[0043] In embodiments, in step b), betaine can be added in portions under stirring, such that betaine is reacted directly with mercaptosuccinic acid at the second temperature. Here, betaine being reacted directly with mercaptosuccinic acid at the second temperature means that betaine and mercaptosuccinic acid are reacted without the need to add further reaction reagents or reactants to form further intermediates, for example without the need to add further protecting reagents to form further protected intermediates, or without the need to add further reagents to form further complex intermediates.

[0044] In embodiments, the molar ratio of mercaptosuccinic acid to betaine can be about 1 :1 to about 1 :1.1, preferably about 1 :1 to about 1 :1.05, more preferably about 1 :1.03 to about 1 :1.05. In particular embodiments, the molar ratio of mercaptosuccinic acid to betaine can be 1 :1, 1 :1.01, 1 :1.02, 1 :1.03, 1 :1.04, or 1 :1.05. In one embodiment, the molar ratio of mercaptosuccinic acid to betaine can be 1 :1. In another embodiment, the molar ratio of mercaptosuccinic acid to betaine can be 1 :1.03. In yet another embodiment, the molar ratio of mercaptosuccinic acid to betaine can be 1 :1.05. However, the skilled person will appreciate that embodiments of the disclosure are not limited thereto, and the molar ratio of mercaptosuccinic acid to betaine can be any value from about 1 :1 to about 1 :1.1.

[0045] In embodiments, the first temperature and the second temperature can each be about 45 °C to about 65 °C, for example, 45 °C, 50 °C, 55 °C, 60 °C, or 65 °C. In specific embodiments, the first temperature and the second temperature can be the same or different, in other words, the first temperature and the second temperature can be slightly different, but preferably, the first temperature and the second temperature are carried out at the same temperature. In one embodiment, the first temperature and the second temperature can each be 45 °C. In another embodiment, the first temperature and the second temperature can each be 55 °C. In yet another embodiment, the first temperature and the second temperature can each be 65 °C. However, one skilled in the art will appreciate that embodiments of the present disclosure are not limited thereto, and the first temperature and the second temperature can each be any value in the range of about 45 °C to about 65 °C, for example, 45.5 °C or 45.7 °C.

[0046] In embodiments, the reaction time of step b) can be about 6 hours to about 10 hours. In specific embodiments, the reaction time of step b) can be 6 hours, 7 hours, 8 hours, 9 hours, or 10 hours. However, one skilled in the art will appreciate that embodiments of the present disclosure are not limited thereto, and the reaction time of step b) can be any value in the range of about 6 hours to about 10 hours, for example, 6.5 hours, 7.5 hours, or 8.5 hours.

[0047] In embodiments, step c) can further comprise adding an organic solvent, standing at room temperature, collecting the obtained solid, and vacuum drying after crushing, to obtain the mercaptosuccinic acid betaine (1:1) represented by formula (I). In specific embodiments, the organic solvent can comprise one or more of acetone, ethanol, and isopropanol. In one embodiment, the organic solvent can be any one of acetone, ethanol, and isopropanol. In addition, the weight ratio of the organic solvent to mercaptosuccinic acid can be about 1:0.9 to about 1:1.1, preferably 1:1. However, one skilled in the art will appreciate that the method of crystallization in step c) is not limited to the specifically disclosed method above.

[0048] Example

[0049] Example 1

[0050] In the reactor, mercaptosuccinic acid (150 g, 1.0 mol) and water (750 g) were added, and after stirring to homogeneity, the temperature was rapidly increased to 45 °C, and betaine (122.8 g, about 1.05 mol) was added in portions while stirring, and after the addition was completed, the reaction was continued to stir for 10 hours, and after the reaction was completed, the temperature was cooled to room temperature, and the insoluble matter was removed by filtration, and the filtrate was concentrated to remove most of the solvent, and acetone (150 g) was added, and the mixture was allowed to stand at room temperature, and when the crystallization did not increase any more (a small amount of crystals can be added to accelerate the crystallization process), the obtained solid was collected, and after crushing, vacuum drying was performed, to obtain mercaptosuccinic acid betaine (1:1) as a white solid, in an amount of 245.7 g, with a yield of about 92.0%.

[0051] The product was compared with the standard by ion chromatography.

[0052] Example 2

[0053] In a reactor, add mercaptosuccinic acid (150 g, 1.0 mol) and water (450 g), after stirring evenly, quickly warm to 60 °C, add betaine (117 g, 1.0 mol) in batches under stirring, after adding, continue to stir for 6 hours, after the reaction is completed, cool to room temperature, remove the insoluble by filtration, remove most of the solvent by concentration, add ethanol (150 g) at room temperature, stand until the crystallization no longer increases (a small amount of crystal can be added to speed up the crystallization process), collect the obtained solid, crush and dry in vacuum to obtain betaine mercaptosuccinate (1:1) as a white solid, 225.3 g, yield about 84.4%.

[0054] The product was compared with the standard by ion chromatography.

[0055] Example 3

[0056] In a reactor, add mercaptosuccinic acid (150 g, 1.0 mol) and water (600 g), after stirring evenly, quickly warm to 55 °C, add betaine (120.5 g, about 1.03 mol) in batches under stirring, after adding, continue to stir for 8 hours, after the reaction is completed, cool to room temperature, remove the insoluble by filtration, remove most of the solvent by concentration, add acetone (150 g) at room temperature, stand until the crystallization no longer increases (a small amount of crystal can be added to speed up the crystallization process), collect the obtained solid, crush and dry in vacuum to obtain betaine mercaptosuccinate (1:1) as a white solid, 236.5 g, yield about 88.6%.

[0057] The product was compared with the standard by ion chromatography.

[0058] Example 4

[0059] In a reactor, add mercaptosuccinic acid (150 g, 1.0 mol) and water (600 g), after stirring evenly, quickly warm to 55 °C, add betaine (122.8 g, about 1.05 mol) in batches under stirring, after adding, continue to stir for 8 hours, after the reaction is completed, cool to room temperature, remove the insoluble by filtration, remove most of the solvent by concentration, add isopropanol (150 g) at room temperature, stand until the crystallization no longer increases (a small amount of crystal can be added to speed up the crystallization process), collect the obtained solid, crush and dry in vacuum to obtain betaine mercaptosuccinate (1:1) as a white solid, 232.9 g, yield about 87.2%.

[0060] The product was compared with the standard by ion chromatography.

[0061] Example 5

[0062] In a reactor, add mercaptosuccinic acid (150 g, 1.0 mol) and water (600 g), stir well, then quickly warm to 65 °C, add betaine (117 g, 1.0 mol) in batches under stirring, continue to stir after adding, and react for 10 hours. After the reaction is completed, cool to room temperature, filter out the insoluble matter, concentrate the filtrate to remove most of the solvent, add isopropyl alcohol (150 g) at room temperature, and stand until no more crystals are formed (a small amount of crystals can be added to accelerate the crystallization process). Collect the obtained solid, crush it, and then vacuum dry to obtain betaine mercaptosuccinate (1:1) as a white solid, 231.2 g, with a yield of about 86.6%.

[0063] The product is consistent with the standard by ion chromatography.

[0064] Comparative Example 1

[0065] In a reactor, add mercaptosuccinic acid (150 g, 1.0 mol) and water (600 g), stir well, then quickly warm to 65 °C, add betaine (117 g, 1.0 mol) in batches under stirring, continue to stir after adding, and react for 10 hours. After the reaction is completed, cool to room temperature, filter out the insoluble matter, concentrate the filtrate to remove most of the solvent, add isopropyl alcohol (150 g) at room temperature, and stand until no more crystals are formed (a small amount of crystals can be added to accelerate the crystallization process). Collect the obtained solid, crush it, and then vacuum dry to obtain betaine mercaptosuccinate (1:1) as a white solid, 231.2 g, with a yield of about 86.6%.

[0066] The product is consistent with the standard by ion chromatography.

[0067] Comparative Example 2

[0068] In a reactor, add mercaptosuccinic acid (150 g, 1.0 mol) and water (600 g), stir well, then quickly warm to 65 °C, add betaine (117 g, 1.0 mol) in batches under stirring, continue to stir after adding, and react for 10 hours. After the reaction is completed, cool to room temperature, filter out the insoluble matter, concentrate the filtrate to remove most of the solvent, add isopropyl alcohol (150 g) at room temperature, and stand until no more crystals are formed (a small amount of crystals can be added to accelerate the crystallization process). Collect the obtained solid, crush it, and then vacuum dry to obtain betaine mercaptosuccinate (1:1) as a white solid, 231.2 g, with a yield of about 86.6%.

[0069] The product is consistent with the standard by ion chromatography.

[0070] The relevant details of the above experiments are summarized in Table 1 below.

[0071] Table 1. Examples and related data of Examples.

[0072] Comparative Example 1 and Comparative Example 2 employed a preparation method commonly used in the art, which is similar to the method disclosed in GB1240313 mentioned in the background art, and the salt formation reaction of betaine was carried out using an alcohol-based solvent commonly used in the art. However, compared with the method disclosed in GB1240313, the preparation method employed in Comparative Example 1 and Comparative Example 2 appropriately prolonged the reaction time from 1 hour to 4 hours or 6 hours, so that the reaction time of the comparative examples was comparable to that of the examples. It can be seen that under the same molar ratio of mercaptosuccinic acid to betaine, similar reaction temperature and comparable reaction time, the preparation method of the examples can obtain significantly improved yield.

[0073] In addition, the present application employs a direct reaction of aqueous mercaptosuccinic acid with betaine, omitting the intermediate complex generation step, which can more directly and effectively obtain the desired product, thereby simplifying the preparation process and avoiding impurities that may be brought by the intermediate.

[0074] Although the present disclosure has been described with respect to its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present disclosure.

Claims

1. A process for the preparation of mercaptosuccinic acid betaine (1 : 1) represented by formula (I), said process comprising: a) providing a mixture of mercaptosuccinic acid and water, wherein the weight ratio of mercaptosuccinic acid to water is 1 :2 to 1 :8; b) adding betaine, allowing the betaine to directly react with the mercaptosuccinic acid, wherein the molar ratio of mercaptosuccinic acid to betaine is 1 : 1 to 1 : 1.1; and c) crystallizing the product of step b) to obtain said betaine mercaptosuccinate (1 : 1) represented by formula (I).

2. The preparation method of claim 1, wherein the molar ratio of mercaptosuccinic acid to betaine is 1 : 1 to 1 : 1.05, for example, 1 : 1, 1 : 1.03, or 1 : 1.

05.

3. The preparation method of claim 1 or 2, wherein the weight ratio of mercaptosuccinic acid to water is 1 :2 to 1 :5, preferably 1 :3 to 1 :5, for example, 1 :3, 1 :4, or 1 :

5.

4. The preparation method of claim 1 or 2, wherein in step a), the mixture of mercaptosuccinic acid and water is maintained at a first temperature, and the first temperature is 45 °C to 75 °C, and in step b), the betaine directly reacts with the mercaptosuccinic acid at a second temperature, and the second temperature is 45 °C to 75 °C.

5. The preparation method of claim 4, wherein the first temperature and the second temperature are the same, and are 45 °C to 65 °C, for example, 45 °C, 50 °C, 55 °C, 60 °C, or 65 °C.

6. The preparation method of claim 4, wherein the first temperature and the second temperature are different, and the second temperature is 45 °C to 65 °C, for example, 45 °C, 50 °C, 55 °C, 60 °C, or 65 °C.

7. The preparation method of claim 1 or 2, wherein the direct reaction time of betaine with mercaptosuccinic acid is 6 hours to 10 hours, for example, 6 hours, 7 hours, 8 hours, 9 hours, or 10 hours.

8. The preparation method of claim 1 or 2, wherein step c) further comprises adding an organic solvent, standing at room temperature, collecting the obtained solid when crystallization no longer increases, and vacuum drying after crushing to obtain said betaine mercaptosuccinate (1 : 1) represented by formula (I).

9. The preparation method of claim 8, wherein the organic solvent comprises one or more of acetone, ethanol, and isopropanol.

10. The preparation method of claim 8, wherein the weight ratio of the organic solvent to mercaptosuccinic acid is 1 :0.9 to 1 : 1.1, preferably 1 : 1.

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