Novel preparation method of 1: 1 mercaptosuccinic acid betaine

Abstract

The invention provides a novel preparation method of mercaptosuccinic acid betaine (1: 1), and the preparation method adopts betaine and mercaptosuccinic acid as main raw materials, adopts water as a solvent, and enables the mercaptosuccinic acid and the betaine to directly react under a heating condition, so that the mercaptosuccinic acid betaine (1: 1) represented by a formula (I) is obtained with high purity. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to a novel preparation method of betaine composite salt, and more specifically, to a novel preparation method of mercaptosuccinic acid betaine (1:1). Background Art

[0002] In recent years, betaine has been increasingly used in the livestock and poultry industry and feed industry, as it can provide active methyl groups in the metabolism of biological organisms and participate in methyl reactions. New uses are also being developed. In view of the strong hygroscopicity of betaine, it is easy to absorb moisture during transportation and storage, thus affecting the quality of use. Therefore, the complex salt of betaine has received more and more attention. However, the salt formation process of betaine usually requires the use of alcohol-based solvents or more complicated separation processes.

[0003] GB1240313 discloses a method for preparing betaine thiomalate, wherein a methanol solution of betaine and a methanol solution of thiomalic acid are used as raw materials to react and produce betaine thiomalate. This method not only requires multiple steps of separation and purification processes, but also has a yield of only 68%.

[0004] GB987849 discloses a method for preparing betaine fumarate. The inventor still believes that good salt formation results can only be obtained with fumaric acid and betaine in an inert solvent, such as an alcohol-based solvent. However, the use of an alcohol-based solvent increases the burden on the environment.

[0005] CN110724048 discloses a method for preparing malic acid betaine, which, in order to reduce the separation and purification process, improves the directivity of the reaction by introducing the formation of a complex. Although this method increases the yield, it also increases the complexity of the reaction and equipment, and also increases the process cost.

[0006] In recent years, betaine mercaptosuccinate (1:1) has attracted much attention due to its unique properties. Betaine mercaptosuccinate is not only relatively stable but also highly water-soluble. While greatly reducing the hygroscopicity of betaine, it also retains the function of mercaptosuccinic acid itself, which is conducive to the development of more biochemical functions of this product.

[0007] In view of this, the present disclosure proposes a new preparation method of mercaptosuccinic acid betaine (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 this method, the raw materials in each step are commercially available, with suitable prices and sufficient supply, which provides feasibility for industrial mass production of the product. Summary of the invention

[0008] The purpose of the present disclosure is to provide a new preparation method of mercaptosuccinic acid betaine (1:1), which has mild reaction conditions, simple process and equipment, is easy to operate and is environmentally friendly.

[0009] The present disclosure provides a method for preparing mercaptosuccinic acid betaine (1:1) represented by formula (I), the preparation method comprising the following steps:

[0010]

[0011] a) providing a mixture of mercaptosuccinic acid and water, wherein the weight ratio of mercaptosuccinic acid to water is 1:2 to 1:8;

[0012] b) adding betaine to directly react the betaine with mercaptosuccinic acid, wherein the molar ratio of mercaptosuccinic acid to betaine is 1:1 to 1:1.1; and

[0013] c) crystallizing the product of step b) to obtain the mercaptosuccinic acid betaine (1:1) represented by formula (I).

[0014] In embodiments, the molar ratio of mercaptosuccinic acid to betaine may be 1:1 to 1:1.05, eg, 1:1, 1:1.03, or 1:1.05.

[0015] In an embodiment, the weight ratio of mercaptosuccinic acid to water may be 1:2 to 1:5, preferably 1:3 to 1:5, for example, 1:3, 1:4 or 1:5.

[0016] In an embodiment, in step a), the mixture of mercaptosuccinic acid and water may be maintained at a first temperature, and the first temperature may be 45°C to 75°C.

[0017] In an embodiment, in step b), betaine may be directly reacted with mercaptosuccinic acid at a second temperature, and the second temperature may be 45°C to 75°C.

[0018] In an embodiment, the first temperature and the second temperature may be the same and may be 45°C to 65°C, for example, 45°C, 50°C, 55°C, 60°C, or 65°C.

[0019] Alternatively, the first temperature and the second temperature may be different, and the second temperature may be 45°C to 65°C, for example, 45°C, 50°C, 55°C, 60°C or 65°C.

[0020] In an embodiment, the direct reaction time of betaine and mercaptosuccinic acid may be 6 hours to 10 hours, such as 6 hours, 7 hours, 8 hours, 9 hours or 10 hours.

[0021] In an embodiment, step c) may further include adding an organic solvent, standing at room temperature, and collecting the obtained solid until crystallization no longer increases, crushing it and vacuum drying it to obtain the mercaptosuccinic acid betaine (1:1) represented by formula (I).

[0022] In an embodiment, the organic solvent may include one or more of acetone, ethanol, and isopropanol.

[0023] In an embodiment, the weight ratio of the organic solvent to mercaptosuccinic acid may be 1:0.9 to 1:1.1, preferably 1:1.

[0024] The preparation method provided by the present disclosure has at least one of the following advantages:

[0025] 1. The directionality of the reaction is improved, the utilization rate of raw materials is increased, and the purity of mercaptosuccinic acid betaine (1:1) is greatly improved;

[0026] 2. The raw materials in each step are commercially available, with a wide range of sources and sufficient supply;

[0027] 3. The reaction conditions are relatively mild and the process is simple. Each step of the reaction is a conventional operation and is easy to control, which reduces the process cost. In addition, due to the use of a thiol substituent, compared with hydroxysuccinic acid, the formation of an intermediate complex is avoided, simplifying the process;

[0028] 4. Environmentally friendly, reduces pollution and achieves green production. DETAILED DESCRIPTION

[0029] Hereinafter, the present disclosure will be further described according to specific embodiments. However, the specific embodiments listed are only for illustrative purposes, and are not intended to limit the present disclosure to the disclosed specific embodiments. Those skilled in the art will recognize that the specific features in any of the following embodiments can be used for any other embodiment, as long as it does not deviate from the gist of the present disclosure.

[0030] Hereinafter, unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by a person skilled in the art to which the present application belongs. Terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning consistent with their meaning in the context of the relevant technology, and will not be interpreted in an idealized or overly formal sense unless explicitly defined as such herein.

[0031] As used herein, the term "direct reaction" means a reaction that proceeds without the addition of other reagents or reactants to form intermediate products.

[0032] As used herein, the term "about" includes the stated value and means within an acceptable range of deviation of the stated value as determined by one of ordinary skill in the art taking into account the relevant measurements and the errors associated with the measurement of the quantity (i.e., the limitations of the measurement system). For example, "about" can mean within one or more than one standard deviation, or within ±20%, ±10%, or ±5% of the stated value.

[0033] Herein, "room temperature" specifically refers to 22°C to 25°C, usually 25°C.

[0034] The present disclosure provides a method for preparing mercaptosuccinic acid betaine (1:1) represented by formula (I), the preparation method comprising the following steps:

[0035]

[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 reacts directly with 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 represented by formula (I) (1:1).

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

[0040] In an embodiment, in step a), mercaptosuccinic acid and water may be added to a reactor, and the temperature may be rapidly raised to a first temperature under stirring. The reactor is not particularly limited as long as the above reaction can be achieved.

[0041] In an embodiment, 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 a specific embodiment, 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, it will be appreciated by those skilled in the art that embodiments of the present invention 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, such as 1:3.5 or 1:2.6.

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

[0043] In an embodiment, in step b), betaine may be added in batches under stirring, so that betaine and mercaptosuccinic acid react directly at the second temperature. Here, the direct reaction of betaine and mercaptosuccinic acid at the second temperature means that betaine and mercaptosuccinic acid react without adding other reagents or reactants to form other intermediates, for example, without adding other protecting reagents to form other protected intermediates, or without adding other reagents to form other complex intermediates.

[0044] In an embodiment, the molar ratio of mercaptosuccinic acid to betaine can be from about 1:1 to about 1:1.1, preferably from about 1:1 to about 1:1.05, more preferably from about 1:1.03 to about 1:1.05. In a specific embodiment, 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, it should be understood by those skilled in the art that embodiments of the present invention 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 an embodiment, the first temperature and the second temperature may each be about 45°C to about 65°C, for example, 45°C, 50°C, 55°C, 60°C or 65°C. In a specific embodiment, the first temperature and the second temperature may be the same or different, in other words, the first temperature and the second temperature may be slightly different, but preferably carried out at the same temperature. In one embodiment, the first temperature and the second temperature may both be 45°C. In another embodiment, the first temperature and the second temperature may both be 55°C. In yet another embodiment, the first temperature and the second temperature may both be 65°C. However, it will be appreciated by those skilled in the art that embodiments of the present invention are not limited thereto, and the first temperature and the second temperature may each be any value from 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 from 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, it will be appreciated by those skilled in the art that embodiments of the present invention are not limited thereto, and the reaction time of step b) can be any value from about 6 hours to about 10 hours, for example 6.5 hours, 7.5 hours or 8.5 hours.

[0047] In an embodiment, step c) may further include adding an organic solvent, standing at room temperature, waiting for crystallization to no longer increase, collecting the obtained solid, crushing and vacuum drying to obtain the step of obtaining the mercaptosuccinic acid betaine (1:1) represented by formula (I). In a specific embodiment, the organic solvent may include one or more of acetone, ethanol and isopropanol. In one embodiment, the organic solvent may be any one of acetone, ethanol and isopropanol. In addition, the weight ratio of the organic solvent to mercaptosuccinic acid may be from about 1:0.9 to about 1:1.1, preferably 1:1. However, it should be understood by those skilled in the art that the method of crystallization in step c) is not limited to the above-mentioned specific disclosed method.

[0048] Example

[0049] Example 1

[0050] Add mercaptosuccinic acid (150 g, 1.0 mol) and water (750 g) into the reactor, stir evenly and then quickly heat up to 45°C, add betaine (122.8 g, about 1.05 mol) in batches under stirring, continue stirring and react for 10 hours after the addition, and after the reaction is completed, cool to room temperature, filter to remove insoluble matter, concentrate the filtrate to remove most of the solvent, add acetone (150 g) and stand at room temperature until crystallization no longer increases (a small amount of crystals can be added to accelerate the crystallization process), collect the obtained solid, crush and vacuum dry to obtain mercaptosuccinic acid betaine (1:1) as a white solid, 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] Add mercaptosuccinic acid (150 g, 1.0 mol) and water (450 g) into the reactor, stir evenly and then quickly heat up to 60°C, add betaine (117 g, 1.0 mol) in batches under stirring, continue stirring and react for 6 hours after the addition, and after the reaction is completed, cool to room temperature, filter to remove insoluble matter, concentrate the filtrate to remove most of the solvent, add ethanol (150 g) and stand at room temperature until crystallization no longer increases (a small amount of crystals can be added to accelerate the crystallization process), collect the obtained solid, crush and vacuum dry to obtain mercaptosuccinic acid betaine (1:1) as a white solid, 225.3 g, with a yield of about 84.4%.

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

[0055] Example 3

[0056] Add mercaptosuccinic acid (150 g, 1.0 mol) and water (600 g) into the reactor, stir evenly and then quickly heat up to 55° C., add betaine (120.5 g, about 1.03 mol) in batches under stirring, continue stirring and react for 8 hours after the addition, and after the reaction is completed, cool to room temperature, filter to remove insoluble matter, concentrate the filtrate to remove most of the solvent, add acetone (150 g) and stand at room temperature until crystallization no longer increases (a small amount of crystals can be added to accelerate the crystallization process), collect the obtained solid, crush and vacuum dry to obtain mercaptosuccinic acid betaine (1:1) as a white solid, 236.5 g, with a yield of about 88.6%.

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

[0058] Example 4

[0059] Add mercaptosuccinic acid (150 g, 1.0 mol) and water (600 g) into the reactor, stir evenly and then quickly heat up to 55° C., add betaine (122.8 g, about 1.05 mol) in batches under stirring, continue stirring and react for 8 hours after the addition, and after the reaction is completed, cool to room temperature, filter to remove insoluble matter, concentrate the filtrate to remove most of the solvent, add isopropanol (150 g) and stand at room temperature until crystallization no longer increases (a small amount of crystals can be added to accelerate the crystallization process), collect the obtained solid, crush and vacuum dry to obtain mercaptosuccinic acid betaine (1:1) as a white solid, 232.9 g, with a yield of about 87.2%.

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

[0061] Example 5

[0062] Add mercaptosuccinic acid (150 g, 1.0 mol) and water (600 g) into the reactor, stir evenly and then quickly heat up to 65° C., add betaine (117 g, 1.0 mol) in batches under stirring, continue stirring and react for 10 hours after the addition, and after the reaction is completed, cool to room temperature, filter to remove insoluble matter, concentrate the filtrate to remove most of the solvent, add isopropanol (150 g) and stand at room temperature until crystallization no longer increases (a small amount of crystals can be added to accelerate the crystallization process), collect the obtained solid, crush and vacuum dry to obtain mercaptosuccinic acid betaine (1:1) as a white solid, 231.2 g, with a yield of about 86.6%.

[0063] The product was compared with the standard by ion chromatography.

[0064] Comparative Example 1

[0065] Add mercaptosuccinic acid (150 g, 1.0 mol) and methanol (600 g) into the reactor, stir evenly and then quickly heat up to 55°C, add betaine methanol solution (containing 117 g, 1.0 mol of betaine and 400 g of methanol) in batches under stirring, continue stirring and react under reflux for 6 hours after the addition, cool to room temperature after the reaction is completed, stand until crystallization no longer increases (a small amount of crystals can be added to accelerate the crystallization process), collect the obtained solid, crush and vacuum dry to obtain mercaptosuccinic acid betaine (1:1) as a white solid, 165.5 g, with a yield of about 62.0%.

[0066] The product was compared with the standard by ion chromatography.

[0067] Comparative Example 2

[0068] Add mercaptosuccinic acid (150 g, 1.0 mol) and methanol (500 g) into the reactor, stir evenly and then quickly heat up to 55°C, add betaine methanol solution (containing 117 g, 1.0 mol of betaine and 350 g of methanol) in batches under stirring, continue stirring and react under reflux for 4 hours after the addition, cool to room temperature after the reaction is completed, stand until crystallization no longer increases (a small amount of crystals can be added to accelerate the crystallization process), collect the obtained solid, crush and vacuum dry to obtain mercaptosuccinic acid betaine (1:1) as a white solid, 151.3 g, with a yield of about 56.7%.

[0069] The product was compared 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 relevant data of the examples.

[0072]

[0073] Comparative Examples 1 and 2 use a preparation method commonly used in the art, which is similar to the method disclosed in GB1240313 mentioned in the background technology, and uses an alcohol-based solvent commonly used in the art to carry out the salt-forming reaction of betaine, but compared with the method disclosed in GB1240313, the preparation method used in Comparative Examples 1 and 2 appropriately extends the reaction time from 1 hour to 4 hours or 6 hours, so that the reaction time of the comparative example is equivalent to the reaction time of the embodiment. It can be seen from the comparison that under the same molar ratio of mercaptosuccinic acid to betaine, similar reaction temperature and equivalent reaction time, the preparation method of the embodiment can obtain a significantly improved yield.

[0074] In addition, the present application uses a mercaptosuccinic acid aqueous solution to react directly with betaine, omitting the step of generating an intermediate complex, and can obtain the desired product more directly and effectively, thereby simplifying the preparation process and avoiding impurities that may be introduced by the intermediate.

[0075] While the invention has been described with respect to specific embodiments thereof, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of this invention.

Claims

1. A method for preparing mercaptosuccinic acid betaine (1:1) represented by formula (I), the method comprising: include: 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 to directly react the betaine with 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 the mercaptosuccinic acid betaine (1:1) represented by formula (I).

2. The preparation method as claimed in 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 as claimed in 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 according to 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), betaine is directly reacted with mercaptosuccinic acid at a second temperature, and the second temperature is 45°C to 75°C.

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

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

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

10. The preparation method according to 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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