Preparation method of magnesium acetyltaurine salt

Abstract

The invention discloses a preparation method of magnesium acetyltaurine salt, which comprises the following steps: S1, dissolving taurine in water to react with strong base, and concentrating water to obtain corresponding taurine salt; s2, dispersing the taurine salt obtained in the step S1 in acetic acid to react with acetic anhydride, and concentrating the acetic acid to obtain corresponding acetyl taurine salt; and S3, dissolving the acetyl taurine salt obtained in the step S2 in water, adding magnesium salt, adjusting the pH value of a reaction system, adding a single post-treatment solvent, crystallizing, filtering, and drying to obtain the acetyl taurine magnesium salt. According to the preparation method of the magnesium acetyltaurate, provided by the invention, the dosage of acetic anhydride and a post-treatment solvent is effectively reduced, the generation of acid-containing wastewater can be remarkably reduced, the process is simple, the reaction is mild, the raw materials are cheap and easy to obtain, the yield is high, and large-scale industrial production is facilitated.

Description

Technical Field

[0001] The invention relates to the field of medical technology, and in particular to a method for preparing acetyltaurine magnesium salt. Background Art

[0002] Taurine, also known as 2-aminoethanesulfonic acid, is a semi-essential micronutrient and one of the most abundant amino acids in humans and eukaryotes. In the human body, it plays a variety of important biological functions, including promoting the development and function of the nervous system, maintaining the health of the cardiovascular system, and enhancing the body's immunity. N-acetyltaurine is a derivative of taurine and a secondary metabolite in the human body. Recently, a Stanford University team published a research paper in Nature, discovering the first N-acetyltaurine hydrolase (PTER) in mammals, and confirmed the important physiological function of N-acetyltaurine in inhibiting food intake and resisting obesity. As a magnesium salt of acetyltaurine, magnesium acetyltaurine has the advantages of good stability and easy absorption, so it has broad application prospects.

[0003] The existing preparation method of magnesium acetyl taurate usually synthesizes magnesium acetyl taurate by directly reacting taurine and magnesium oxide with acetic anhydride. This process route is short, but there are disadvantages such as large amount of acetic anhydride used, poor atom economy, large amount of acid-containing wastewater, multiple solvents required for post-treatment, high production cost and harsh reaction conditions. Therefore, it is necessary to propose a new preparation method of magnesium acetyl taurate to solve some problems existing in the above process. Summary of the invention

[0004] The technical problem to be solved by the present invention is to provide a method for preparing acetyl taurine magnesium salt in view of the deficiencies in the above-mentioned prior art.

[0005] In order to solve the above technical problems, the technical solution adopted by the present invention is: a method for preparing acetyl taurine magnesium salt, comprising the following steps:

[0006] S1, dissolving taurine in water and reacting with a strong base, and concentrating the water to obtain the corresponding taurate;

[0007] S2, dispersing the taurine obtained in step S1 in acetic acid and reacting with acetic anhydride, and concentrating the acetic acid to obtain the corresponding acetyl taurine;

[0008] S3, dissolving the acetyltaurate obtained in step S2 in water and adding magnesium salt, adjusting the pH of the reaction system, adding a single post-treatment solvent for crystallization, filtering and drying to obtain acetyltaurate magnesium salt. More specifically, the acetyltaurate magnesium salt prepared in the present invention is acetyltaurate magnesium dihydrate containing two inherent water molecules, and the relative molecular weight is about 392.69.

[0009] The reaction route is as follows:

[0010]

[0011] Among them, Ac2O is acetic anhydride and AcOH refers to acetic acid.

[0012] Preferably, the strong base is selected from at least one of sodium hydroxide, potassium hydroxide and lithium hydroxide, and most preferably is sodium hydroxide.

[0013] Preferably, the molar ratio of the strong base to taurine is 1:1.0 to 1:1.3, for example, 1:1.0, 1:1.1, 1:1.2, 1:1.3 or any value between any two of them, and most preferably 1:1.1.

[0014] Preferably, the volume of water used in step S1 is 3 to 10 times the weight of taurine, measured in mL by volume and g by weight, for example, 3, 5, 8, 10 times or any value therebetween, and most preferably 5 times.

[0015] Preferably, the molar ratio of acetic anhydride in step S2 to taurine in step S1 is 0.8:1 to 1.5:1, for example, 0.8:1, 1.0:1, 1.2:1, 1.5:1 or any value between them, and most preferably 1.0:1.

[0016] Preferably, the reaction temperature of step S2 is 20-50°C, for example, 20°C, 30°C, 40°C, 50°C or any value therebetween, and most preferably 40°C.

[0017] Preferably, the reaction time of step S2 is 0.5-2 h, for example, 0.5, 1, 1.5, 2 h or any value therebetween, most preferably 1.5 h.

[0018] Preferably, the volume of acetic acid used in step S2 is 3 to 10 times the weight of taurine in step 1, measured in mL by volume and g by weight, for example, 3, 5, 8, 10 times or any value between them, and most preferably 5 times.

[0019] Preferably, the magnesium salt in step S3 is selected from at least one of magnesium carbonate, magnesium hydroxide and magnesium chloride, and most preferably is magnesium carbonate.

[0020] Preferably, the molar ratio of the magnesium salt in step S3 to the taurine in step S1 is 1:2.0 to 1:2.4, for example, 1:2.0, 1:2.1, 1:2.2, 1:2.3, 1:2.4 or any value therebetween, most preferably 1:2.0.

[0021] Preferably, the single post-treatment solvent in step S3 is selected from at least one of ethanol, methanol, isopropanol, acetone and tetrahydrofuran, and most preferably is ethanol.

[0022] Preferably, the volume of the single post-treatment solvent is 5 to 20 times the weight of the taurine in step S1, measured in mL by volume and g by weight, for example, 5, 10, 15, 20 times or any value therebetween, most preferably 10 times.

[0023] Preferably, the pH value of step S3 is 4.0-7.0, for example, 4.0, 5.0, 6.0, 7.0 or any value between any two of them, and most preferably 5.0.

[0024] Preferably, the reagent used to adjust the pH in step S3 is selected from at least one of sodium bicarbonate, sodium carbonate, sodium hydroxide and sodium acetate, and most preferably sodium bicarbonate.

[0025] The beneficial effects of the present invention are:

[0026] The invention provides a method for preparing acetyltaurine magnesium salt, which uses taurine, which is cheap and easily available in large-scale industrial production, as a raw material, first reacts with taurine to generate a water-soluble salt under alkaline conditions, then reacts with acetic anhydride in acetic acid to prepare acetyltaurate, and finally reacts with a magnesium salt to obtain the final product acetyltaurate magnesium. The process method of the invention effectively reduces the amount of acetic anhydride and post-treatment solvent, can significantly reduce the generation of acid-containing wastewater, and has a simple process, mild reaction, cheap and easily available raw materials, high yield, and is conducive to large-scale industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 This is the NMR spectrum of the finished product of acetyltaurine magnesium salt prepared in Example 2. DETAILED DESCRIPTION

[0028] The present invention is further described in detail below in conjunction with embodiments so that those skilled in the art can implement the invention with reference to the description.

[0029] It should be understood that the terms such as “having”, “including” and “comprising” used herein do not exclude the existence or addition of one or more other elements or combinations thereof.

[0030] The test methods used in the following examples are conventional methods unless otherwise specified. The materials and reagents used in the following examples are all commercially available unless otherwise specified. In the following examples, if no specific conditions are specified, the experiments were carried out under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used, if the manufacturer is not specified, are all conventional products that can be purchased commercially.

[0031] Example 1

[0032] Step S1, preparation of taurate

[0033]

[0034] Add 50 mL of water to a 250 mL three-necked flask, then add taurine (10.0 g, 79.9 mmol), and stir to disperse evenly; then add sodium hydroxide (2.9 g, 72.6 mmol) in batches, and stir to react until it dissolves into a colorless clear liquid; transfer the reaction solution to a rotary evaporator, heat to 60°C, and concentrate to dryness under reduced pressure to obtain taurine sodium salt, which is a white powder to block solid with a wet weight of 15.3 g.

[0035] Step S2, preparation of acetyl taurine sodium salt

[0036]

[0037] Add 50 mL of acetic acid to a 250 mL three-necked flask, then add 15.3 g of the wet taurine sodium salt obtained in step 2, and stir to disperse evenly; then add acetic anhydride (8.2 g, 79.9 mmol), heat to 40°C, and stir for 1.5 h; after TLC monitoring of the reaction is complete, transfer the reaction solution to a rotary evaporator, heat to 60°C, and concentrate to dryness under reduced pressure to obtain acetyl taurate sodium salt as a white block solid with a wet weight of 16.0 g.

[0038] Step S3, preparation of acetyl taurate magnesium salt

[0039]

[0040] Add 50 mL of water to a 250 mL three-necked flask, then add 16.0 g of the wet product of acetyl taurate sodium salt obtained in step 2, and stir to dissolve; then add magnesium carbonate (3.4 g, 40.0 mmol), stir to dissolve to form a colorless clear liquid; add an appropriate amount of sodium bicarbonate to adjust the pH to 5.0, add 100 mL of ethanol, and precipitate a white solid; filter, rinse the wet product with 10 mL of ethanol twice, and dry it with air at 90° C. to obtain 14.7 g of acetyl taurate magnesium salt as a white powder with a yield of 93.63%.

[0041] Example 2

[0042] Step S1, preparation of taurate

[0043]

[0044] Add 25L of water to a 100L reactor, then add taurine (5.00kg, 40.0mol), stir and disperse evenly; then add sodium hydroxide (1.45kg, 36.4mol) in batches, stir and react until it dissolves into a colorless clear liquid; turn on the vacuum pump, raise the temperature to 60°C, and concentrate under reduced pressure until there is basically no droplet, transfer to a rotary evaporator for further evaporation to obtain taurine sodium salt, which is a white powder to a block solid with a wet weight of 7.84kg.

[0045] Step S2, preparation of acetyl taurine sodium salt

[0046]

[0047] Add 25L of acetic acid to a 100L reactor, then add 7.84kg of the wet taurine sodium salt obtained in step 2, stir and disperse evenly; then add acetic anhydride (4.10kg, 40.0mol), raise the temperature to 40°C, and keep stirring for 1.5h; after TLC monitoring, after the reaction is complete, turn on the vacuum pump, raise the temperature to 60°C, and concentrate under reduced pressure until there is almost no droplet, transfer to a rotary evaporator for further evaporation to obtain acetyl taurate sodium salt as a white block solid with a wet weight of 8.21kg.

[0048] Step S3, preparation of acetyl taurate magnesium salt

[0049]

[0050] Add 25L of water to a 100L reactor, then add 8.21kg of the wet product of acetyl taurate sodium salt obtained in step 2, stir to dissolve; then add magnesium carbonate (1.70kg, 20.0mol), stir to dissolve to a colorless clear liquid; add an appropriate amount of sodium bicarbonate to adjust the pH to 5.0, add 50L of ethanol, and precipitate a white solid; filter, rinse the wet product with 5L of ethanol twice, and dry it with air at 90°C to obtain 7.25kg of acetyl taurate magnesium salt, which is a white powder with a yield of 92.47%.

[0051] The NMR spectrum of the finished product of acetyltaurine magnesium salt prepared in this example is as follows Figure 1 As shown, the NMR data are as follows:

[0052] 1 H NMR (400MHz, D2O): δ = 3.47 (t, J = 6.8Hz, 2H), 3.00 (t, J = 6.8Hz, 2H), 1.90 (s, 3H).

[0053] Although the embodiments of the present invention have been disclosed as above, they are not limited to the applications listed in the specification and the implementation modes. They can be fully applied to various fields suitable for the present invention. For those familiar with the art, additional modifications can be easily implemented. Therefore, without departing from the general concept defined by the claims and the scope of equivalents, the present invention is not limited to specific details.

Claims

1. A method for preparing acetyl taurine magnesium salt, characterized in that: The following steps are involved: S1, dissolving taurine in water and reacting with a strong base, and concentrating the water to obtain the corresponding taurate; S2, dispersing the taurine obtained in step S1 in acetic acid and reacting with acetic anhydride, and concentrating the acetic acid to obtain the corresponding acetyl taurine; S3, dissolving the acetyl taurate obtained in step S2 in water and adding magnesium salt, adjusting the pH of the reaction system, adding a single post-treatment solvent for crystallization, filtering and drying to obtain acetyl taurate magnesium salt.

2. The method for preparing acetyltaurine magnesium salt according to claim 1, characterized in that: The strong base is selected from at least one of sodium hydroxide, potassium hydroxide and lithium hydroxide, and the molar ratio of the strong base to taurine is 1:1.0 to 1:1.

3.

3. The method for preparing acetyltaurine magnesium salt according to claim 2, characterized in that: The volume of water used in step S1 is 3 to 10 times the weight of taurine, with the volume unit being mL and the weight unit being g.

4. The method for preparing acetyltaurine magnesium salt according to claim 1, characterized in that: The molar ratio of acetic anhydride in step S2 to taurine in step S1 is 0.8:1 to 1.5:

1.

5. The method for preparing acetyltaurine magnesium salt according to claim 4, characterized in that: The reaction temperature of step S2 is 20-50° C., and the reaction time is 0.5-2 h.

6. The method for preparing acetyltaurine magnesium salt according to claim 5, characterized in that: The volume of acetic acid used in step S2 is 3 to 10 times the weight of taurine in step 1, with volume in mL and weight in g.

7. The method for preparing acetyltaurine magnesium salt according to claim 1, characterized in that: The magnesium salt in step S3 is selected from at least one of magnesium carbonate, magnesium hydroxide and magnesium chloride, and the molar ratio of the magnesium salt to the taurine in step S1 is 1:2.0 to 1:2.

4.

8. The method for preparing acetyltaurine magnesium salt according to claim 7, characterized in that: The single post-treatment solvent in step S3 is selected from at least one of ethanol, methanol, isopropanol, acetone and tetrahydrofuran.

9. The method for preparing acetyltaurine magnesium salt according to claim 8, characterized in that: The volume of the single post-treatment solvent is 5 to 20 times the weight of the taurine in step S1, measured in mL by volume and g by weight.

10. The method for preparing acetyltaurine magnesium salt according to claim 9, characterized in that: The pH value of step S3 is 4.0-7.0, and the reagent used to adjust the pH is selected from at least one of sodium bicarbonate, sodium carbonate, sodium hydroxide and sodium acetate.

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