A method for efficiently preparing calcium beta-aminopropionate from beta-aminopropionitrile

Abstract

The application discloses a method for efficiently preparing beta-amino propionic acid calcium from beta-amino propionitrile, and comprises the following steps: beta-amino propionitrile and a calcium salt solution are reacted in the presence of a catalyst and an additive, and microwave radiation is used to promote the reaction; after the reaction solution is filtered and deaminated, the solution is concentrated, cooled and alcohol crystallized to obtain beta-amino propionic acid calcium crystals which can be used for the production of calcium pantothenate; wherein the catalyst is a transition metal complex, and the additive is a phase transfer catalyst or a buffer metal salt. The application has the advantages of simple process, high yield and high reaction efficiency.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of chemistry, and particularly relates to a preparation method of calcium beta-aminopropionate. BACKGROUND

[0002] As an important component of coenzyme A, vitamin B5 plays a key role in human metabolism and plays an important role in the manufacture of antibody function, skin and blood health. As its commercial form, calcium pantothenate is widely used in feed additives, medicine, food and daily chemical fields, and has broad market prospects. The production of calcium pantothenate needs a key intermediate, calcium beta-aminopropionate.

[0003] At present, the production method of calcium beta-aminopropionate mainly includes the following steps: calcium beta-aminopropionate is prepared by hydrolysis and crystallization of beta-aminopropionitrile, and then calciumization is performed. The comprehensive yield of the two-step reaction is 70-85%, and the cost is high. In the process of preparing beta-aminopropionic acid from beta-aminopropionitrile, a high temperature and a long time are required, and a large amount of sodium sulfate salt is generated. In addition, high-concentration liquid alkali will increase the corrosion cost and increase the investment cost in industrialization. In addition, the above post-treatment needs to increase the decolorization link, which adds many difficulties to industrialization. SUMMARY

[0004] In view of the problems of long route, low yield and high cost in the prior art, the purpose of the present application is to provide a method for efficiently preparing calcium beta-aminopropionate from beta-aminopropionitrile. In the method, the use of catalyst, additive and microwave radiation technology enables beta-aminopropionitrile to be generated into calcium beta-aminopropionate in one step, avoids the two-step reaction of the original process, avoids the generation of a large amount of waste salt sodium sulfate, and at the same time, the reaction conditions are more mild, the reaction time is shortened to seconds, the process is simple, the corrosion cost of the equipment in the reaction process is also greatly reduced, and it is beneficial to industrial production.

[0005] In order to achieve the above purpose, the technical scheme adopted by the present application is as follows:

[0006] A method for efficiently preparing calcium beta-aminopropionate from beta-aminopropionitrile, comprising: beta-aminopropionitrile and calcium salt solution in the presence of a catalyst, an additive, and microwave radiation to promote the reaction, filtering and deaminating the reaction liquid, and then concentrating, cooling and alcohol crystallizing to obtain calcium beta-aminopropionate crystals.

[0007] In the present application, the catalyst is a transition metal complex coordinated with an organic ligand, wherein the metal includes at least one of cobalt, magnesium, tungsten and zirconium; and the organic ligand includes one or more of 2,2'-bipyridine, 1,10-phenanthroline, BINAP and 1,8-bis(diphenylphosphino)naphthalene.

[0008] The catalyst can be prepared by fully stirring the solution containing the metal salt and the organic ligand, and then concentrated, cooled and crystallized, and dried.

[0009] The metal salt comprises at least one of chlorides, bromides and nitrate of cobalt, magnesium, tungsten and zirconium, and the molar ratio of the metal salt to the organic ligand is 1:0.5-5, preferably 1:1.2-3.5. The reaction temperature is 0-80℃, preferably 20-50℃; the reaction time is 0.5-5h, preferably 1-3h; the concentration temperature is 20-150℃, preferably 30-130℃; and the crystallization temperature is -30-25℃, preferably -20-0℃.

[0010] The catalyst is added in an amount of 0.1-1.5% of the mass of the β-aminopropionitrile, preferably 0.3-0.8%.

[0011] The additive is a phase transfer catalyst or a buffer metal salt, and comprises one or more of pyridine, tributylamine, 18-crown-6, 15-crown-5, sodium bicarbonate and sodium dihydrogen phosphate. The additive is added in an amount of 1-10% of the mass of the β-aminopropionitrile, preferably 3-7%.

[0012] The microwave radiation power is 100-1500W, preferably 400-1000W. The microwave radiation time is 20-500s, preferably 100-300s.

[0013] The calcium salt solution is prepared by mixing a calcium salt and a solvent, wherein the calcium salt comprises one or both of calcium oxide and calcium hydroxide; and the solvent comprises one or more of water, acetonitrile, dimethyl sulfoxide and N,N-dimethylformamide. The mass ratio of the calcium salt to the solvent is 0.05-1.50:1, preferably 0.20-1.00:1.

[0014] The molar ratio of the β-aminopropionitrile to the calcium salt is 1:1-2, preferably 1:1.2-1.7.

[0015] The reaction temperature is 20-80℃, preferably 35-65℃.

[0016] The recrystallization solvent for the crude β-aminopropionic acid is methanol, and the amount of the solvent added is 3-10 times, preferably 4-7 times, of the mass of the product.

[0017] The present application has the advantages that the introduction of the catalyst and the additive and the use of the microwave radiation technology in the present application enable the β-aminopropionitrile to be generated into calcium β-aminopropionate in one step, the two-step reaction in the original process is avoided, a large amount of waste sodium sulfate is not generated, the reaction condition is more moderate, the reaction time is shortened to seconds, the process is simple, the corrosion cost of the equipment in the reaction process is greatly reduced, and the industrial production is facilitated. The conversion rate of the β-aminopropionitrile is greater than 99%, the purity of the obtained product calcium β-aminopropionate is greater than 99%, and the yield is greater than 98%. DETAILED DESCRIPTION

[0018] The present application is further described below in combination with specific examples, and it should be noted that the scope of the present application includes but is not limited to the listed examples.

[0019] Example 1

[0020] The cobalt chloride and 1,10-phenanthroline are put into a reaction bottle in a molar ratio of 1:1.5, an appropriate amount of anhydrous ether is added as a solvent, the reaction temperature is controlled at 20℃, and the constant temperature reaction is performed for 1h. After the 40℃ concentration treatment, the system is put into -20℃ for full crystallization, the crystallized solid is filtered and fully dried to obtain the required catalyst.

[0021] In the reaction bottle fixed in the cavity of the microwave oven, the β-aminopropionitrile, the catalyst, the pyridine, the calcium hydroxide and the water / acetonitrile solvent are mixed at room temperature, the addition amount of the catalyst is 0.4% of the mass of the β-aminopropionitrile, the addition amount of the pyridine is 3.5% of the mass of the β-aminopropionitrile, the molar ratio of the β-aminopropionitrile to the calcium hydroxide is 1:1.5, and the mass ratio of the calcium hydroxide to the solvent is 0.45:1. The reaction temperature is set to 45℃, the microwave radiation power is 700W, and the radiation time is 250s. After the reaction is completed, the reaction liquid is filtered and deaminated, and then the above reaction liquid is concentrated to a viscous state by reduced pressure distillation, 5 times the mass of the theoretical product of methanol is added, and the calcium β-aminopropionate is obtained by filtering and drying after the temperature is lowered and crystallized. The conversion rate of the β-aminopropionitrile is greater than 99%, the purity of the obtained product calcium β-aminopropionate is 99.5%, and the yield is 98.9%.

[0022] Example 2

[0023] The zirconium chloride and 2,2'-bipyridine are put into a reaction bottle in a molar ratio of 1:1.9, an appropriate amount of anhydrous ether is added as a solvent, the reaction temperature is controlled at 30℃, and the constant temperature reaction is performed for 3h. After the 40℃ concentration treatment, the system is put into -15℃ for full crystallization, the crystallized solid is filtered and fully dried to obtain the required catalyst.

[0024] In a reaction bottle fixed in the microwave oven cavity, β-aminopropionitrile, catalyst, 18 crown 6, calcium hydroxide and water were mixed at room temperature, wherein the catalyst was added in an amount of 0.5% of the mass of β-aminopropionitrile, 18 crown 6 was added in an amount of 4.0% of the mass of β-aminopropionitrile, the molar ratio of β-aminopropionitrile to calcium hydroxide was 1:1.7, and the mass ratio of calcium hydroxide to water was 0.25:1. The reaction temperature was set to 45°C, the microwave radiation power was 800W, and the radiation time was 200 seconds. After the reaction was completed, filtration and deamination were performed, and the above reaction liquid was concentrated to a viscous state under reduced pressure, 4 times the mass of the theoretical product of methanol was added, and after crystallization, filtration and drying were performed to obtain β-aminopropionic acid calcium. The conversion rate of β-aminopropionitrile was >99%, the purity of the obtained product β-aminopropionic acid calcium was 99.0%, and the yield was 99.1%.

[0025] Example 3

[0026] The magnesium chloride and 1,8-bis(diphenylphosphino)naphthalene were added to the reaction bottle in a molar ratio of 1:1.2, and an appropriate amount of anhydrous toluene was added as a solvent. The reaction temperature was controlled at 50°C, and the constant temperature reaction was carried out for 3h. After 100°C concentration treatment, the system was sealed and placed at -15°C for full crystallization. The crystallized solid was filtered and dried to obtain the desired catalyst.

[0027] In a reaction bottle fixed in the microwave oven cavity, β-aminopropionitrile, catalyst, 18 crown 6, calcium hydroxide and water were mixed at room temperature, wherein the catalyst was added in an amount of 0.5% of the mass of β-aminopropionitrile, 18 crown 6 was added in an amount of 4.0% of the mass of β-aminopropionitrile, the molar ratio of β-aminopropionitrile to calcium hydroxide was 1:1.7, and the mass ratio of calcium hydroxide to water was 0.25:1. The reaction temperature was set to 45°C, the microwave radiation power was 800W, and the radiation time was 200 seconds. After the reaction was completed, filtration and deamination were performed, and the above reaction liquid was concentrated to a viscous state under reduced pressure, 4 times the mass of the theoretical product of methanol was added, and after crystallization, filtration and drying were performed to obtain β-aminopropionic acid calcium. The conversion rate of β-aminopropionitrile was >99%, the purity of the obtained product β-aminopropionic acid calcium was 99.0%, and the yield was 99.1%.

[0028] Comparative Example 1:

[0029] In a reaction bottle, β-aminopropionitrile, calcium hydroxide and water were mixed at room temperature, wherein the molar ratio of β-aminopropionitrile to calcium hydroxide was 1:1.7, and the mass ratio of calcium hydroxide to water was 0.45:1. The reaction temperature was set at 25°C, and the reaction time was 200 seconds. After the reaction was completed, the reaction solution was concentrated by distillation under reduced pressure to a viscous state, 4 times the mass of the theoretical product of methanol was added, and the product was crystallized by cooling to obtain a crude β-aminopropionitrile calcium product. The conversion rate of β-aminopropionitrile was 15%, the purity of the obtained product β-aminopropionitrile calcium was 41.2%, and the yield was 7.1%.

[0030] Comparative Example 2:

[0031] In a reaction bottle fixed in the cavity of a microwave oven, β-aminopropionitrile, pyridine, calcium hydroxide, water / acetonitrile solvent were mixed uniformly at room temperature, wherein the amount of pyridine added was 3.5% of the mass of β-aminopropionitrile, the molar ratio of β-aminopropionitrile to calcium hydroxide was 1:1.5, and the mass ratio of calcium hydroxide to solvent was 0.45:1. The reaction temperature was set at 45°C, the microwave irradiation power was 700W, and the irradiation time was 250 seconds. After the reaction was completed, the reaction solution was concentrated by distillation under reduced pressure to a viscous state, 5 times the mass of the theoretical product of methanol was added, and the product was crystallized by cooling to obtain a crude β-aminopropionitrile calcium product. The conversion rate of β-aminopropionitrile was 43%, the purity of the obtained product β-aminopropionitrile calcium was 56.2%, and the yield was 19.2%.

[0032] The above specific embodiments do not limit the technical solutions of the present application in any form. Any simple modification, equivalent change and modification made according to the technical essence of the present application to the above embodiments all fall within the protection scope of the present application.

Claims

1. A method for the efficient production of calcium β-aminopropionate from β-aminopropionitrile, comprising: The beta-amino propionitrile and calcium salt solution is reacted in the presence of a catalyst and an additive, and microwave radiation is used to promote the reaction, so as to obtain beta-amino calcium propionate crystals; wherein the catalyst is a transition metal complex, and in the catalyst, the metal includes at least one of cobalt, magnesium and zirconium, and the organic ligand includes one or more of 2,2'-dipyridyl, 1,10-phenanthroline and 1,8-bis(diphenylphosphino)naphthalene; and the additive is one or more of pyridine, tributylamine and 18 crown 6.

2. The method of claim 1, wherein, The catalyst is added in an amount of 0.1-1.5% of the mass of the beta-amino propionitrile.

3. The method of claim 1, wherein, The catalyst is added in an amount of 0.3-0.8% of the mass of the beta-amino propionitrile.

4. The method of claim 1, wherein, The additive is added in an amount of 1-10% of the mass of the beta-amino propionitrile.

5. The method of claim 1, wherein, The additive is added in an amount of 3-7% of the mass of the beta-amino propionitrile.

6. The method of claim 1, wherein, The microwave radiation power is 100-1500W.

7. The method of claim 1, wherein, The microwave radiation power is 400-1000W.

8. The method according to any of claims 1 or 6, characterized in that, The microwave radiation time is 20-500 seconds.

9. The method according to any of claims 1 or 6, characterized in that, The microwave radiation time is 100-300 seconds.

10. The method according to any one of claims 1 to 7, characterized in that, The molar ratio of the beta-amino propionitrile to the calcium salt is 1:1-2.

11. The method of claim 10, wherein, The calcium salt includes calcium oxide and / or calcium hydroxide.

12. The method according to any one of claims 1 to 7, characterized in that, The reaction temperature is 20-80℃.

13. The method according to any one of claims 1 to 7, characterized in that, The reaction temperature is 35-65℃.

14. The method according to any one of claims 1 to 7, characterized in that, The beta-amino calcium propionate recrystallization solvent is methanol, and the amount of addition is 3-10 times the mass of the theoretical product.