A process for the preparation of beta-aminopropionic acids

Abstract

The application relates to the technical field of organic synthesis and fine chemical separation and purification, and specifically discloses a preparation method of beta-amino propionic acid. The method comprises the following steps: S1: under an inert atmosphere, ammonia and acrylonitrile are uniformly mixed, and after reaction, the product is subjected to deamination and rectification to obtain refined beta-amino propionitrile; S2: after liquid alkali is added into a reaction kettle and heated, refined beta-amino propionitrile is added, and after mixed hydrolysis, hydrochloric acid is used for neutralization, then an antioxidant is added, a mixed solution containing beta-amino propionic acid is obtained, solid-liquid separation is carried out, beta-amino propionic acid crystal seeds are added into the filtrate, cooling crystallization is carried out, solid-liquid separation is carried out, and beta-amino propionic acid wet products are obtained; S3: the beta-amino propionic acid wet products are uniformly mixed with water, modified activated carbon and modified diatomite are added, mixing is carried out, solid-liquid separation is carried out, methanol is added for alcohol precipitation, solid-liquid separation is carried out, and drying is carried out, so that beta-amino propionic acid is obtained. The beta-amino propionic acid prepared by the method has the advantages of high purity, high total yield, low ignition residue and high light transmittance.

Description

Technical Field

[0001] This application relates to the technical field of organic synthesis and fine chemical separation and purification, and more specifically, it relates to a method for preparing β-aminopropionic acid. Background Technology

[0002] β-Aminopropionic acid, also known as 3-aminopropionic acid or β-alanine, is a precursor in the synthesis of pantothenic acid, calcium pantothenate, and carnosine. It is a crucial component of coenzyme A and is primarily used in pharmaceuticals, animal feed, and food. β-alanine can increase carnosine concentration in human muscles, scavenge reactive oxygen species, and prevent the production of fatigue toxins in working muscles, thus attracting significant attention in food health products, biopharmaceuticals, and feed additives. Currently, the production methods for β-alanine mainly fall into two categories: chemical and biological methods. Biological methods offer advantages such as mild conditions and environmental friendliness, but their industrialization remains limited due to constraints related to enzyme activity, stability, and scalability.

[0003] Traditional chemical methods involve reacting acrylonitrile with ammonia under pressure or high temperature to prepare β-aminopropionitrile, followed by alkali hydrolysis and hydrochloric acid acidification to obtain β-alanine. Regarding purification, patent application CN109851515A discloses a method for preparing β-aminopropionic acid using bipolar membrane electrodialysis. This method uses 3-aminopropionitrile with an aqueous solution of sodium hydroxide or potassium hydroxide as raw material to obtain a sodium 3-aminopropionate solution. The sodium 3-aminopropionate is then directly passed through a bipolar membrane electrodialysis device. The ionized sodium ions combine with hydroxide ions to form sodium hydroxide, while the aminopropionate ions combine with hydrogen ions to form 3-aminopropionic acid. High-purity 3-aminopropionic acid can be obtained through concentration and crystallization.

[0004] This technical solution uses bipolar membrane electrodialysis instead of hydrochloric acid acidification, avoiding the introduction of inorganic salt byproducts. However, the ion migration efficiency during electrodialysis is significantly affected by fluctuations in feed concentration, temperature, and pH, leading to unstable separation of aminopropionic acid and sodium ions and large batch-to-batch fluctuations in product purity. Simultaneously, long-term operation of the membrane stack is prone to concentration polarization and membrane fouling, resulting in a gradual decrease in current efficiency and fluctuations in the recovery rate of the target product. This makes it difficult to consistently achieve both high purity and high yield in large-scale production. Summary of the Invention

[0005] To overcome the shortcomings of existing bipolar membrane electrodialysis methods, which result in large batch-to-batch fluctuations in product purity and yield, this application provides a method for preparing β-aminopropionic acid.

[0006] This application provides a method for preparing β-aminopropionic acid, using the following technical solution: A method for preparing β-aminopropionic acid includes the following steps: S1: Under an inert atmosphere, ammonia water and acrylonitrile are mixed and reacted at 80~100℃ and 2.5~3.5MPa for 4~8h. The product is then deaminated and distilled to obtain purified β-aminopropionitrile. S2: After adding liquid alkali to the reaction vessel, add purified β-aminopropionitrile at a rate of 1.5~2.5 mL / min, control the temperature at 90~100℃, mix and hydrolyze, neutralize with hydrochloric acid, then add an antioxidant to obtain a mixture containing β-aminopropionic acid, concentrate, heat, separate solid and liquid, add β-aminopropionic acid seed crystals to the obtained filtrate, cool to crystallize, separate solid and liquid to obtain wet β-aminopropionic acid; S3: Mix the wet β-aminopropionic acid with water, add modified activated carbon and modified diatomaceous earth, mix for 40-60 min, separate the solid and liquid, add methanol to the obtained filtrate for alcohol precipitation, separate the solid and liquid, and dry to obtain β-aminopropionic acid.

[0007] In this technical solution, high-purity refined β-aminopropionitrile is first prepared and added to liquid alkali at a controlled rate of 1.5~2.5 mL / min to avoid side reactions caused by excessively high local alkali concentration. An antioxidant is added immediately after acid neutralization to block the color-forming reaction during subsequent concentration and heating, ensuring transmittance. After concentration, solid-liquid separation is performed by heating. The low solubility of sodium chloride at high temperatures allows it to precipitate and separate preferentially. Then, β-aminopropionic acid seed crystals are added to induce uniform crystal growth under low supersaturation, reducing mother liquor inclusion. Modified activated carbon and modified diatomaceous earth are then used for adsorption. The former strongly adsorbs polar pigments through its surface oxygen-containing functional groups, while the latter, after modification, combines colloid capture and filtration functions to synergistically remove soluble and colloidal impurities. Finally, methanol precipitation is used to remove residual trace impurities, yielding high-purity β-aminopropionic acid.

[0008] Furthermore, the modified activated carbon is obtained by stepwise oxidation of activated carbon with hydrogen peroxide of varying concentrations.

[0009] Furthermore, the method for preparing the modified activated carbon includes the following steps: Add activated carbon to a 3%~5% hydrogen peroxide solution with a solid-liquid ratio of 1g:(3~5)mL, adjust the pH to 4.0~5.0, heat to 40~60℃, mix for 60~90min, separate the solid and liquid, wash, then add to a 5%~10% hydrogen peroxide solution with a solid-liquid ratio of 1g:(2~4)mL, adjust the pH to 4.0~5.0, heat to 60~80℃, mix for 40~60min, separate the solid and liquid, wash, and dry to obtain modified activated carbon.

[0010] In this technical solution, a step-by-step oxidation method is used. First, a low-concentration hydrogen peroxide is used to gently expand the pores and achieve preliminary oxidation, avoiding excessive etching and loss of specific surface area caused by a one-step high-concentration treatment. Then, a high-concentration hydrogen peroxide is used to deeply introduce polar oxygen-containing groups such as carboxyl groups and phenolic hydroxyl groups, so that the modified activated carbon has both high adsorption capacity and high selectivity for pigment molecules and trace organic impurities in β-aminopropionic acid solution.

[0011] Furthermore, the modified diatomaceous earth is prepared by impregnating diatomaceous earth with aluminum salt, adjusting the pH to 7.0~7.5, allowing it to stand, and then calcining it at 600~700℃ for 3~5 hours.

[0012] Furthermore, the preparation method of the modified diatomaceous earth includes the following steps: Diatomaceous earth was impregnated in an aluminum nitrate solution with a mass concentration of 5%~10% at a solid-liquid ratio of 1g:(3~5)mL for 1.5~2.5h. The pH was adjusted to 7.0~7.5, and the mixture was allowed to stand. The solid and liquid were separated, washed, dried, and calcined at 600~700℃ for 3~5h. After cooling, modified diatomaceous earth was obtained.

[0013] In this technical solution, aluminum oxide active sites are loaded on the surface of diatomaceous earth, which significantly improves the co-adsorption and retention capacity of colloidal particles, while improving the filtration performance and helping to improve the light transmittance of the product.

[0014] Furthermore, the mass concentration of the ammonia water is 18% to 22%.

[0015] Furthermore, the mass concentration of the liquid alkali is 30%~35%.

[0016] Furthermore, the antioxidant is sodium bisulfite or sodium metabisulfite.

[0017] Further, the mass ratio of the ammonia water, acrylonitrile, liquid alkali, antioxidant, β-aminopropionic acid seed crystals, modified activated carbon and modified diatomaceous earth is (62~67):100:(70~78):(0.06~0.15):(0.15~0.35):(0.8~1.5):(0.4~0.8).

[0018] Furthermore, in step S3, when adding the methanol, an organic complexing agent accounting for 3% to 5% of the methanol volume is also added.

[0019] Furthermore, the organic complexing agent is ethylenediaminetetraacetic acid or citric acid.

[0020] In this technical solution, ethylenediaminetetraacetic acid or citric acid can form stable soluble complexes with residual trace metal ions in the feed solution, preventing these metal ions from being incorporated into the crystal lattice or adsorbed onto the crystal surface during the crystallization of β-aminopropionic acid. Simultaneously, it inhibits potential oxidation and color development side reactions catalyzed by metal ions. This further reduces the residue on ignition and ensures better light transmittance.

[0021] Furthermore, in step S3, when adding the methanol, β-aminopropionic acid seed crystals accounting for 1% to 1.5% of the methanol volume are also added.

[0022] In this technical solution, by introducing high-purity crystal nuclei in advance, β-aminopropionic acid is induced to precipitate in an orderly manner in the methanol-water system with the crystal seed as the core, which effectively reduces the supersaturation of crystallization and avoids the phenomenon of crystal inclusion of mother liquor and impurities co-precipitation caused by explosive nucleation, so that the obtained crystals have more uniform particle size and higher purity.

[0023] Further, in step S2, the concentration specifically refers to concentrating to a β-aminopropionic acid mass concentration of 35% to 45%.

[0024] Furthermore, in step S2, the solid-liquid separation by heating specifically involves heating to 80~85℃.

[0025] Further, in step S2, adding β-aminopropionic acid seed crystals to the obtained filtrate specifically involves adding β-aminopropionic acid seed crystals after the obtained filtrate has been cooled to 60~65℃.

[0026] Furthermore, in step S2, the cooling crystallization specifically involves cooling to 3~8℃ and holding at that temperature for 1.5~2.5h.

[0027] Furthermore, in step S3, when methanol is added to the obtained filtrate for alcohol precipitation, the volume ratio of filtrate to methanol is 1:(1.8~2.5).

[0028] Furthermore, in step S3, the alcohol precipitation is cooled to 2-5°C.

[0029] In summary, this application has the following beneficial effects: This application obtains a high-purity intermediate through high-pressure amination and distillation, followed by controlled-rate hydrolysis and antioxidant color protection to effectively suppress side reactions and pigment formation. High-temperature selective desalination combined with slow crystallization using seed crystals is employed, and then modified activated carbon is used in conjunction with modified diatomaceous earth to deeply remove colloids and trace impurities. This is supplemented by complexing agent masking and seed crystal-induced crystallization during the alcohol precipitation stage, ultimately achieving high purity, low ignition residue, and high light transmittance of the target product. Attached Figure Description

[0030] Figure 1 The HPLC chromatogram is shown for calcium pantothenate prepared from β-aminopropionic acid obtained in Example 5. Detailed Implementation

[0031] The present application will be further described in detail below with reference to the embodiments.

[0032] Unless otherwise specified, the raw materials used in the embodiments and comparative examples of this application are all commercially available.

[0033] The activated carbon is food-grade wood-based powder activated carbon with a particle size distribution of 300 mesh. More than 98% of it can pass through a standard sieve. The methylene blue adsorption value is 180~220mg / g, the iodine value is ≥1000mg / g, and the ash content (dry basis) is ≤5%. Diatomaceous earth has a particle size distribution of 200 mesh, with over 95% passing through a standard sieve, a silica content of ≥99%, and a specific surface area of ​​50~60 m². 2 / g, bulk density 0.4~0.5g / cm³ 3 .

[0034] Preparation Examples 1-3: Modified Activated Carbon Preparation Example 1 The method for preparing modified activated carbon in this preparation example includes the following steps: Add 10g of powdered activated carbon to a reactor, set the rotation speed to 200rpm, add 30mL of 3% hydrogen peroxide, adjust the pH of the system to 4.0 with 5% glacial acetic acid, heat to 40℃, stir for 60min, filter, wash with deionized water until neutral, add the filter cake to another reactor, set the rotation speed to 200rpm, add 20mL of 5% hydrogen peroxide, adjust the pH of the system to 4.0 with 5% glacial acetic acid, heat to 60℃, stir for 40min, filter, wash with deionized water until neutral, and vacuum dry at 60℃ to constant weight to obtain modified activated carbon.

[0035] Preparation Example 2 The method for preparing modified activated carbon in this preparation example includes the following steps: Add 10g of powdered activated carbon to a reactor, set the rotation speed to 200rpm, add 40mL of 4% hydrogen peroxide, adjust the pH of the system to 4.5 with 5% glacial acetic acid, heat to 50℃, stir for 75min, filter, wash with deionized water until neutral, add the filter cake to another reactor, set the rotation speed to 200rpm, add 30mL of 8% hydrogen peroxide, adjust the pH of the system to 4.5 with 5% glacial acetic acid, heat to 70℃, stir for 50min, filter, wash with deionized water until neutral, and vacuum dry at 60℃ to constant weight to obtain modified activated carbon.

[0036] Preparation Example 3 The method for preparing modified activated carbon in this preparation example includes the following steps: Add 10g of powdered activated carbon to a reactor, set the rotation speed to 200rpm, add 50mL of 5% hydrogen peroxide, adjust the pH of the system to 5.0 with 5% glacial acetic acid, heat to 60℃, stir for 90min, filter, wash with deionized water until neutral, add the filter cake to another reactor, set the rotation speed to 200rpm, add 40mL of 10% hydrogen peroxide, adjust the pH of the system to 5.0 with 5% glacial acetic acid, heat to 80℃, stir for 60min, filter, wash with deionized water until neutral, and vacuum dry at 60℃ to constant weight to obtain modified activated carbon.

[0037] Preparation Examples 4-6: Modified Diatomaceous Earth Preparation Example 4 The preparation method of the modified diatomaceous earth in this example includes the following steps: 10g of diatomaceous earth was vacuum dried at 120℃ for 2h, cooled to room temperature, and then impregnated in 5% aluminum nitrate solution with a solid-liquid ratio of 1g:3mL. The mixture was stirred at 100rpm for 2h, and then 5% dilute ammonia solution was added dropwise at a rate of 1mL / min until the pH of the system stabilized at 7.0. The mixture was stirred for 30min, allowed to stand and age for 1h, filtered, rinsed twice with deionized water, vacuum dried at 60℃ for 2h, transferred to a muffle furnace, heated to 600℃ at 5℃ / min, calcined for 5h, and cooled to room temperature with the furnace to obtain modified diatomaceous earth.

[0038] Preparation Example 5 The preparation method of the modified diatomaceous earth in this example includes the following steps: 10g of diatomaceous earth was vacuum dried at 120℃ for 2h, cooled to room temperature, and then impregnated in 7% aluminum nitrate solution at a solid-liquid ratio of 1g:4mL. The mixture was stirred at 100rpm for 1.5h, and then 5% dilute ammonia solution was added dropwise at a rate of 1mL / min until the pH of the system stabilized at 7.5. The mixture was stirred for another 30min, allowed to stand and age for 1h, filtered, rinsed twice with deionized water, vacuum dried at 60℃ for 2h, transferred to a muffle furnace, heated to 650℃ at 5℃ / min, calcined for 4h, and cooled to room temperature with the furnace to obtain modified diatomaceous earth.

[0039] Preparation Example 6 The preparation method of the modified diatomaceous earth in this example includes the following steps: 10g of diatomaceous earth was vacuum dried at 120℃ for 2h, cooled to room temperature, and then impregnated in 10% aluminum nitrate solution at a solid-liquid ratio of 1g:5mL. The mixture was stirred at 100rpm for 2.5h, and then 5% dilute ammonia solution was added dropwise at a rate of 1mL / min until the pH of the system stabilized at 7.5. The mixture was stirred for another 30min, allowed to stand and age for 1h, filtered, rinsed twice with deionized water, vacuum dried at 60℃ for 2h, transferred to a muffle furnace, heated to 650℃ at 5℃ / min, calcined for 4h, and cooled to room temperature with the furnace to obtain modified diatomaceous earth.

[0040] Example 1 The preparation method of β-aminopropionic acid in this embodiment includes the following steps: S1: Under a nitrogen atmosphere, 124g of ammonia water with a mass concentration of 18% and 200g of acrylonitrile were added to a high-pressure reactor and stirred at 200rpm to mix evenly. The temperature was raised to 80℃, and the pressure inside the reactor was controlled at 2.5MPa. After reacting at a constant temperature for 8h, the mixture was allowed to cool naturally to room temperature and the pressure was released. The reaction solution was removed, and excess ammonia was removed by distillation at 1 standard atmosphere. The solution was then subjected to vacuum distillation (-0.095MPa) to obtain purified β-aminopropionitrile. S2: Add 140g of 30% liquid alkali to a constant temperature reactor, heat to 90℃, add purified β-aminopropionitrile at 1.5mL / min, and control the system temperature at 90℃ throughout the addition. After the addition is complete, continue to hydrolyze at this temperature for 2 hours. After hydrolysis, neutralize with 30% hydrochloric acid to pH 6.8~7.0, immediately add 0.12g of sodium bisulfite and mix well to obtain a mixture containing β-aminopropionic acid. Concentrate the mixture under reduced pressure to a β-aminopropionic acid concentration of 35%, heat to 80℃ and stir for 10min, filter while hot, cool the filtrate to 60℃, add 0.3g of β-aminopropionic acid seed crystals, stir evenly, cool to 8℃ at a rate of 0.4℃ / min, stir at this temperature for 1.5 hours, filter to obtain wet β-aminopropionic acid. S3: Add the wet β-aminopropionic acid to a beaker, add deionized water at 1.2 times the mass of the wet product, stir and mix evenly, add 1.6 g of modified activated carbon from Preparation Example 1 and 0.8 g of modified diatomaceous earth from Preparation Example 4, stir and mix at 25°C for 40 min, filter, add methanol to the filtrate with a volume ratio of filtrate to methanol of 1:1.8, cool to 5°C at a uniform rate, keep warm and stand for 2 h, filter, wash the filter cake with a small amount of cold methanol, and vacuum dry at 40°C for 4 h to obtain β-aminopropionic acid.

[0041] Product performance testing: purity 99.11%, loss on drying 0.29%, total molar yield 85.7%, residue on ignition 0.19%, transmittance at 430nm 95.6%, heavy metals (as Pb) ≤0.001%.

[0042] Example 2 The preparation method of β-aminopropionic acid in this embodiment includes the following steps: S1: Under a nitrogen atmosphere, 130g of ammonia water with a mass concentration of 18% and 200g of acrylonitrile were added to a high-pressure reactor and stirred at 200rpm to mix evenly. The temperature was raised to 90℃, and the pressure inside the reactor was controlled at 3.0MPa. After reacting at a constant temperature for 6h, the mixture was allowed to cool naturally to room temperature and the pressure was released. The reaction solution was removed, and excess ammonia was removed by distillation at 1 standard atmosphere. The solution was then subjected to vacuum distillation (-0.095MPa) to obtain purified β-aminopropionitrile. S2: 148g of 35% liquid alkali was added to a constant-temperature reactor, and the temperature was raised to 95℃. β-aminopropionitrile was added dropwise at 2.0mL / min, with the system temperature maintained at 95℃ throughout the addition. After the addition was complete, hydrolysis was continued for 2 hours. After hydrolysis, the solution was neutralized to pH 6.8-7.0 with 30% hydrochloric acid. 0.2g of sodium metabisulfite was immediately added and mixed thoroughly to obtain a mixture containing β-aminopropionic acid. The mixture was concentrated under reduced pressure to a β-aminopropionic acid concentration of 40%. The temperature was raised to 85℃ and stirred for 10 minutes. The mixture was then filtered while hot. The filtrate was cooled to 65℃, and 0.5g of β-aminopropionic acid seed crystals were added. After stirring evenly, the mixture was cooled to 5℃ at a rate of 0.4℃ / min and stirred for 2.0 hours. The mixture was then filtered to obtain wet β-aminopropionic acid. S3: Add the wet β-aminopropionic acid to a beaker, add deionized water at 1.2 times the mass of the wet product, stir and mix evenly, add 2.4 g of modified activated carbon from Preparation Example 2 and 1.2 g of modified diatomaceous earth from Preparation Example 5, stir and mix at 25°C for 40 min, filter, add methanol to the filtrate with a volume ratio of filtrate to methanol of 1:2.0, add citric acid at 3% of the volume of methanol, stir evenly, cool to 3°C at a uniform rate, keep warm and stand for 2 h, filter, wash the filter cake with a small amount of cold methanol, and vacuum dry at 40°C for 4 h to obtain β-aminopropionic acid.

[0043] Product performance testing: purity 99.20%, loss on drying 0.28%, total molar yield 86.0%, residue on ignition 0.17%, transmittance at 430nm 95.9%, heavy metals (as Pb) ≤0.001%.

[0044] Example 3 The preparation method of β-aminopropionic acid in this embodiment includes the following steps: S1: Under a nitrogen atmosphere, 134g of ammonia water with a mass concentration of 18% and 200g of acrylonitrile were added to a high-pressure reactor and stirred at 200rpm to mix evenly. The temperature was raised to 100℃, and the pressure inside the reactor was controlled at 3.5MPa. After reacting at a constant temperature for 4h, the mixture was allowed to cool naturally to room temperature and the pressure was released. The reaction solution was removed, and excess ammonia was removed by distillation at 1 standard atmosphere. The solution was then subjected to vacuum distillation (-0.095MPa) to obtain purified β-aminopropionitrile. S2: Add 156g of 35% liquid alkali to a constant temperature reactor, heat to 100℃, add purified β-aminopropionitrile at 2.5mL / min, and control the system temperature at 100℃ throughout the dropwise addition. After the dropwise addition is complete, continue to hydrolyze at this temperature for 2 hours. After hydrolysis, neutralize with 30% hydrochloric acid to a pH of 6.8~7.0, immediately add 0.3g of sodium bisulfite and mix well to obtain a mixture containing β-aminopropionic acid. Concentrate the mixture under reduced pressure to a β-aminopropionic acid concentration of 45%, heat to 85℃ and stir for 10 minutes, filter while hot, cool the filtrate to 65℃, add 0.7g of β-aminopropionic acid seed crystals, stir evenly, cool to 3℃ at a rate of 0.4℃ / min, stir at this temperature for 2.5 hours, filter, and obtain wet β-aminopropionic acid. S3: Add the wet β-aminopropionic acid to a beaker, add deionized water at 1.2 times the mass of the wet product, stir and mix evenly, add 3.0 g of modified activated carbon from Preparation Example 3 and 1.6 g of modified diatomaceous earth from Preparation Example 6, stir and mix at 25°C for 60 min, filter, add methanol to the filtrate with a volume ratio of filtrate to methanol of 1:2.5, add 5% citric acid by volume of methanol and 1% β-aminopropionic acid seed crystals by volume of methanol, stir evenly, cool to 2°C at a uniform rate, keep warm and stand for 2 h, filter, wash the filter cake with a small amount of cold methanol, and vacuum dry at 40°C for 4 h to obtain β-aminopropionic acid.

[0045] Product performance testing: purity 99.18%, loss on drying 0.28%, total molar yield 86.3%, residue on ignition 0.15%, transmittance at 430nm 96.2%, heavy metals (as Pb) ≤0.001%.

[0046] Example 4 The preparation method of β-aminopropionic acid in this embodiment includes the following steps: S1: Under a nitrogen atmosphere, 134g of ammonia water with a mass concentration of 22% and 200g of acrylonitrile were added to a high-pressure reactor and stirred at 200rpm to mix evenly. The temperature was raised to 100℃, and the pressure inside the reactor was controlled at 3.5MPa. After reacting at a constant temperature for 4h, the mixture was allowed to cool naturally to room temperature and the pressure was released. The reaction solution was removed, and excess ammonia was removed by distillation at 1 standard atmosphere. The solution was then subjected to vacuum distillation (-0.095MPa) to obtain purified β-aminopropionitrile. S2: Add 156g of 35% liquid alkali to a constant temperature reactor, heat to 100℃, add purified β-aminopropionitrile at 2.5mL / min, and control the system temperature at 100℃ throughout the dropwise addition. After the dropwise addition is complete, continue to hydrolyze at this temperature for 2 hours. After hydrolysis, neutralize with 30% hydrochloric acid to a pH of 6.8~7.0, immediately add 0.3g of sodium bisulfite and mix well to obtain a mixture containing β-aminopropionic acid. Concentrate the mixture under reduced pressure to a β-aminopropionic acid concentration of 45%, heat to 85℃ and stir for 10 minutes, filter while hot, cool the filtrate to 65℃, add 0.7g of β-aminopropionic acid seed crystals, stir evenly, cool to 3℃ at a rate of 0.4℃ / min, stir at this temperature for 2.5 hours, filter, and obtain wet β-aminopropionic acid. S3: Add the wet β-aminopropionic acid to a beaker, add deionized water at 1.2 times the mass of the wet product, stir and mix evenly, add 3.0 g of modified activated carbon from Preparation Example 3 and 1.6 g of modified diatomaceous earth from Preparation Example 6, stir and mix at 25°C for 60 min, filter, add methanol to the filtrate with a volume ratio of filtrate to methanol of 1:2.5, add 5% citric acid by volume of methanol and 1.2% β-aminopropionic acid seed crystals by volume of methanol, stir evenly, cool to 2°C at a constant rate, keep warm and stand for 2 h, filter, wash the filter cake with a small amount of cold methanol, and vacuum dry at 40°C for 4 h to obtain β-aminopropionic acid.

[0047] Product performance testing: purity 99.22%, loss on drying 0.27%, total molar yield 86.7%, residue on ignition 0.13%, transmittance at 430nm 96.5%, heavy metals (as Pb) ≤0.001%.

[0048] Example 5 The preparation method of β-aminopropionic acid in this embodiment includes the following steps: S1: Under a nitrogen atmosphere, 130g of 20% ammonia solution and 200g of acrylonitrile were added to a high-pressure reactor and stirred at 200rpm until homogeneous. The mixture was heated to 90℃, and the pressure inside the reactor was controlled at 3.0MPa. After reacting at a constant temperature for 6 hours, the mixture was allowed to cool naturally to room temperature and the pressure was released. The reaction solution was then removed and excess ammonia was removed by distillation at 1 standard atmosphere. The solution was then subjected to vacuum distillation (-0.095MPa) to obtain purified β-aminopropionitrile. S2: 148g of 32% liquid alkali was added to a constant-temperature reactor, and the temperature was raised to 95℃. β-aminopropionitrile was added dropwise at 2.0mL / min, with the system temperature maintained at 95℃ throughout the addition. After the addition was complete, hydrolysis was continued for 2 hours. After hydrolysis, the solution was neutralized to pH 6.8-7.0 with 30% hydrochloric acid. 0.2g of sodium metabisulfite was immediately added and mixed thoroughly to obtain a mixture containing β-aminopropionic acid. The mixture was concentrated under reduced pressure to a β-aminopropionic acid concentration of 40%. The temperature was raised to 85℃ and stirred for 10 minutes. The mixture was then filtered while hot. The filtrate was cooled to 60℃, and 0.5g of β-aminopropionic acid seed crystals were added. After stirring evenly, the mixture was cooled to 5℃ at a rate of 0.4℃ / min and stirred for 2.0 hours. The mixture was then filtered to obtain wet β-aminopropionic acid. S3: Add the wet β-aminopropionic acid to a beaker, add deionized water at 1.2 times the mass of the wet product, stir and mix evenly, add 2.4 g of modified activated carbon from Preparation Example 2 and 1.2 g of modified diatomaceous earth from Preparation Example 5, stir and mix at 25°C for 60 min, filter, add methanol to the filtrate with a volume ratio of filtrate to methanol of 1:2.0, add 4% ethylenediaminetetraacetic acid by volume of methanol and 1.5% β-aminopropionic acid seed crystals by volume of methanol, stir evenly, cool to 3°C at a constant rate, keep warm and stand for 2 h, filter, wash the filter cake with a small amount of cold methanol, and dry under vacuum at 40°C for 4 h to obtain β-aminopropionic acid.

[0049] Product performance testing: purity 99.21%, loss on drying 0.27%, total molar yield 87.1%, residue on ignition 0.11%, transmittance at 430nm 96.8%, heavy metals (as Pb) ≤0.001%.

[0050] Comparative Example 1 The difference between this comparative example and Example 1 is as follows: The preparation method of the modified activated carbon in this comparative example includes the following steps: Add 10g of powdered activated carbon to the reactor, set the rotation speed to 200rpm, add 20mL of 5% hydrogen peroxide, adjust the pH of the system to 4.0 with 5% glacial acetic acid, heat to 60℃, stir for 40min, filter, wash with deionized water until neutral, and vacuum dry at 60℃ to constant weight to obtain modified activated carbon.

[0051] Everything else is the same as in Example 1.

[0052] Product performance testing: purity 99.02%, loss on drying 0.30%, total molar yield 84.6%, residue on ignition 0.20%, transmittance at 430nm 95.1%, heavy metals (as Pb) ≤0.001%.

[0053] Comparative Example 2 The difference between this comparative example and Example 1 is as follows: The modified diatomaceous earth was replaced with diatomaceous earth of equal mass. Before use, diatomaceous earth is vacuum dried at 120℃ for 2 hours and then cooled to room temperature for later use.

[0054] Everything else is the same as in Example 1.

[0055] Product performance testing: purity 99.05%, loss on drying 0.30%, total molar yield 84.1%, residue on ignition 0.20%, transmittance at 430nm 95.4%, heavy metals (as Pb) ≤0.001%.

[0056] As can be seen from the product performance test data of Example 1 and Comparative Examples 1-2, the stepwise hydrogen peroxide oxidation modified activated carbon used in this application achieves more efficient removal of organic impurities and colored by-products without increasing product loss compared to the one-step modified activated carbon. The in-situ loaded calcination modified diatomaceous earth process used in this application can significantly reduce the product calcination residue, while simultaneously optimizing product purity and total yield.

[0057] As can be seen from the product performance test data of Examples 1-5, this application, through the optimization of the ammoniation reaction and hydrolysis neutralization parameters, can simultaneously improve product purity and transmittance and reduce ignition residue within a very small yield fluctuation range by introducing citric acid. Adding β-aminopropionic acid seed crystals to the citric acid system can further control the supersaturation of the crystallization process, avoid insufficient purity and product loss caused by explosive nucleation and mother liquor inclusion, and achieve simultaneous improvement in purity and total molar yield. Replacing citric acid with ethylenediaminetetraacetic acid, which has a stronger complexing ability, can further enhance the complexing and masking effect of trace metal ions in the system and optimize the ignition residue and transmittance of the product.

[0058] Application examples The β-aminopropionic acid obtained in Example 5 was added to a methanol system at a stoichiometric ratio of 1:0.55 (the amount of methanol being 6 times the mass of β-aminopropionic acid). The mixture was stirred at 35°C for 4 hours. After centrifugation and plate and frame filtration, a clear β-aminopropionic acid calcium methanol solution was obtained and transferred to a crystallization vessel. The pH of the system was fine-tuned to 9.0 using a 30% sodium methoxide methanol solution. Subsequently, 1.1 times the mass of β-aminopropionic acid was dissolved in methanol and slowly added to the crystallization vessel at 70°C with continuous stirring to carry out a condensation reaction. The pH was controlled within the range of 8.0 to 9.5 until the reaction endpoint was confirmed by HPLC monitoring. The temperature was then uniformly lowered to -3°C at a rate of 1.0°C / min and allowed to stand for 4 hours to grow crystals. After filtration, the filter cake was washed with a small amount of pre-cooled anhydrous methanol and dried under vacuum at 40°C to constant weight to obtain vitamin B5 (calcium pantothenate) product. The mother liquor was recovered and recycled.

[0059] The purity of this product was analyzed using high-performance liquid chromatography (HPLC) as described in the United States Pharmacopeia (USP) at a wavelength of 200 nm. The HPLC chromatogram is shown below. Figure 1 As shown, the retention time of the main peak of calcium pantothenate was 3.529 min. The chromatographic peak baseline was stable, the peak shape was symmetrical and sharp, and there was no tailing or leading edge phenomenon. The relative peak area of ​​the target main peak was 99.83%, while the total relative peak area of ​​other impurity peaks was only 0.17%, and there were no obvious interfering peaks within the entire detection window. The above results indicate that, using the high-purity β-aminopropionic acid from Example 5 of this application as raw material, and condensing it with L-pantolytic acid lactone under the condition of a weakly alkaline environment provided by calcium oxide, the resulting calcium pantothenate product has extremely low impurity content, and all indicators meet the current USP Pharmacopoeia quality requirements for calcium pantothenate.

[0060] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. A method for preparing β-aminopropionic acid, characterized in that, Includes the following steps: S1: Under an inert atmosphere, ammonia water and acrylonitrile are mixed and reacted at 80~100℃ and 2.5~3.5MPa for 4~8h. The product is then deaminated and distilled to obtain purified β-aminopropionitrile. S2: After adding liquid alkali to the reaction vessel, add purified β-aminopropionitrile at a rate of 1.5~2.5 mL / min, control the temperature at 90~100℃, mix and hydrolyze, neutralize with hydrochloric acid, then add an antioxidant to obtain a mixture containing β-aminopropionic acid, concentrate, heat, separate solid and liquid, add β-aminopropionic acid seed crystals to the obtained filtrate, cool to crystallize, separate solid and liquid to obtain wet β-aminopropionic acid; S3: Mix the wet β-aminopropionic acid with water, add modified activated carbon and modified diatomaceous earth, mix for 40-60 min, separate the solid and liquid, add methanol to the obtained filtrate for alcohol precipitation, separate the solid and liquid, and dry to obtain β-aminopropionic acid.

2. The method for preparing β-aminopropionic acid according to claim 1, characterized in that, The modified activated carbon is obtained by stepwise oxidation of activated carbon with hydrogen peroxide of gradient concentration.

3. The method for preparing β-aminopropionic acid according to claim 2, characterized in that, The method for preparing the modified activated carbon includes the following steps: Add activated carbon to a 3%~5% hydrogen peroxide solution with a solid-liquid ratio of 1g:(3~5)mL, adjust the pH to 4.0~5.0, heat to 40~60℃, mix for 60~90min, separate the solid and liquid, wash, then add to a 5%~10% hydrogen peroxide solution with a solid-liquid ratio of 1g:(2~4)mL, adjust the pH to 4.0~5.0, heat to 60~80℃, mix for 40~60min, separate the solid and liquid, wash, and dry to obtain modified activated carbon.

4. The method for preparing β-aminopropionic acid according to claim 1, characterized in that, The modified diatomaceous earth is prepared by impregnating diatomaceous earth with aluminum salt, adjusting the pH to 7.0~7.5, allowing it to stand, and then calcining it at 600~700℃ for 3~5 hours.

5. The method for preparing β-aminopropionic acid according to claim 4, characterized in that, The method for preparing the modified diatomaceous earth includes the following steps: Diatomaceous earth was impregnated in an aluminum nitrate solution with a mass concentration of 5%~10% at a solid-liquid ratio of 1g:(3~5)mL for 1.5~2.5h. The pH was adjusted to 7.0~7.5, and the mixture was allowed to stand. The solid and liquid were separated, washed, dried, and calcined at 600~700℃ for 3~5h. After cooling, modified diatomaceous earth was obtained.

6. The method for preparing β-aminopropionic acid according to claim 1, characterized in that, The antioxidant is sodium bisulfite or sodium metabisulfite.

7. The method for preparing β-aminopropionic acid according to claim 1, characterized in that, The mass ratio of ammonia, acrylonitrile, liquid alkali, antioxidant, β-aminopropionic acid seed crystals, modified activated carbon, and modified diatomaceous earth is (62~67):100:(70~78):(0.06~0.15):(0.15~0.35):(0.8~1.5):(0.4~0.8).

8. The method for preparing β-aminopropionic acid according to claim 1, characterized in that, In step S3, when adding the methanol, an organic complexing agent accounting for 3% to 5% of the methanol volume is also added.

9. The method for preparing β-aminopropionic acid according to claim 1, characterized in that, In step S3, when adding the methanol, β-aminopropionic acid seed crystals accounting for 1% to 1.5% of the methanol volume are also added.

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