CN117567306A - A method for efficiently preparing calcium beta-aminopropionate from beta-aminopropionitrile - Google Patents
A method for efficiently preparing calcium beta-aminopropionate from beta-aminopropionitrile Download PDFInfo
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- CN117567306A CN117567306A CN202311501726.9A CN202311501726A CN117567306A CN 117567306 A CN117567306 A CN 117567306A CN 202311501726 A CN202311501726 A CN 202311501726A CN 117567306 A CN117567306 A CN 117567306A
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
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Abstract
The invention discloses a method for efficiently preparing beta-calcium aminopropionate from beta-aminopropionitrile, which comprises the following steps: in the presence of a catalyst and an additive, the beta-aminopropionitrile and a calcium salt solution are subjected to microwave radiation to promote reaction, the reaction solution is filtered and deaminated, and then concentrated, cooled and crystallized to obtain beta-aminopropionic acid calcium crystals which can be used for calcium pantothenate production; wherein the catalyst is a transition metal complex, and the additive is a phase transfer catalyst or a buffer metal salt. The invention has the advantages of simple process, high yield, high reaction efficiency and the like.
Description
Technical Field
The invention belongs to the technical field of chemistry, and particularly relates to a preparation method of beta-calcium aminopropionate.
Background
Vitamin B5, an important component of coa, plays a critical role in human metabolism, and plays an important role in the manufacture of antibody functions, skin and blood health. Calcium pantothenate is used as a commodity form and widely applied to the fields of feed additives, medicines, foods, daily chemicals and the like, and has wide market prospect. The production of calcium pantothenate requires a key intermediate, calcium beta-aminopropionate.
The existing production method of beta-aminopropionic acid calcium mainly comprises the steps of preparing beta-aminopropionic acid from beta-aminopropionitrile through hydrolysis and crystallization, and then calcification. The comprehensive yield of the two-step reaction is 70-85%, the cost is high, the temperature and time required in the process of preparing the beta-aminopropionic acid from the beta-aminopropionitrile are high, and a large amount of sodium sulfate salt is generated, in addition, the corrosion cost is increased due to high concentration of liquid alkali, the investment cost in industrialization is increased, and the decoloring links are added in the post-treatment, so that a plurality of difficulties are added to the industrialization.
Disclosure of Invention
Aiming at the problems of longer route, lower yield and higher cost in the prior art, the invention aims to provide a method for efficiently preparing beta-calcium aminopropionate from beta-aminopropionitrile. The method uses the catalyst, the additive and the microwave radiation technology, so that the beta-aminopropionitrile can generate the beta-aminopropionic acid calcium in one step, the two-step reaction of the original process is avoided, the generation of a large amount of waste salt sodium sulfate is avoided, the reaction condition is milder, the reaction time is shortened to the second level, the process is simple, the corrosion cost of equipment in the reaction process is also greatly reduced, and the method is beneficial to industrial production.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
a method for efficiently preparing beta-calcium aminopropionate from beta-aminopropionitrile, comprising: in the presence of catalyst and additive, the beta-aminopropionitrile and calcium salt solution utilize microwave radiation to promote reaction, and after the reaction solution is filtered and deaminated, the beta-aminopropionitrile and calcium salt solution are concentrated, cooled and crystallized by alcohol so as to obtain the invented beta-aminopropionic acid calcium crystal.
In the invention, the catalyst is a transition metal complex coordinated by an organic ligand, wherein the metal comprises at least one of cobalt, magnesium, tungsten and zirconium; the organic ligand comprises one or more of 2,2' -bipyridine, 1, 10-phenanthroline, BINAP and 1, 8-bis (diphenylphosphine) naphthalene;
the catalyst can be prepared by fully stirring and reacting a solution containing metal salt and an organic ligand, concentrating, cooling, crystallizing and drying;
wherein the metal salt comprises at least one of chloride, bromide 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 to 5 hours, preferably 1 to 3 hours; the concentration temperature is 20-150deg.C, preferably 30-130deg.C; the crystallization temperature is-30 to 25 ℃, preferably-20 to 0 ℃;
the catalyst of the invention is added in an amount of 0.1 to 1.5% by mass, preferably 0.3 to 0.8% by mass, based on the mass of the beta-aminopropionitrile.
The additive is a phase transfer catalyst or buffer metal salt, and comprises one or more of pyridine, tributylamine, 18 crown 6, 15 crown 5, sodium bicarbonate and sodium dihydrogen phosphate. The addition amount of the additive is 1-10% of the mass of the beta-aminopropionitrile, preferably 3-7%.
The microwave radiation power of the invention is 100-1500W, preferably 400-1000W. The microwave irradiation time is 20 to 500 seconds, preferably 100 to 300 seconds.
The calcium salt solution is formed by mixing calcium salt and a solvent, wherein the calcium salt comprises one or two of calcium oxide and calcium hydroxide; 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.
The molar ratio of the beta-aminopropionitrile to the calcium salt is 1:1-2, preferably 1:1.2-1.7.
The reaction temperature according to the invention is 20-80℃and preferably 35-65 ℃.
The recrystallization solvent of the crude beta-aminopropionic acid is methanol, and the addition amount is 3-10 times, preferably 4-7 times, of the mass of theoretical products.
The method has the beneficial effects that the introduction of the catalyst and the additive and the use of the microwave radiation technology enable the beta-aminopropionitrile to generate the beta-aminopropionic acid calcium in one step, the two-step reaction of the original process is avoided, the generation of a large amount of waste salt sodium sulfate is avoided, meanwhile, the reaction condition is milder, the reaction time is shortened to the second level, the process is simple, the corrosion cost of equipment in the reaction process is also greatly reduced, and the method is beneficial to industrial production. The detection shows that the conversion rate of the beta-aminopropionitrile is more than 99%, the purity of the beta-aminopropionic acid is more than 99%, and the yield is more than 98%.
Detailed Description
The invention will be further illustrated with reference to specific examples, it being noted that the scope of the invention includes, but is not limited to, the examples listed.
Example 1
Cobalt chloride and 1, 10-phenanthroline are put into a reaction bottle according to the mol ratio of 1:1.5, a proper amount of absolute ethyl ether is added as a solvent, the reaction temperature is controlled at 20 ℃, and the constant temperature reaction is carried out for 1h. Concentrating at 40 deg.c, crystallizing at-20 deg.c, filtering the crystallized solid and drying to obtain the catalyst.
In a reaction bottle fixed in a microwave oven cavity, mixing beta-aminopropionitrile, a catalyst, pyridine, calcium hydroxide and a water/acetonitrile solvent at normal temperature, wherein the adding amount of the catalyst is 0.4% of the mass of the beta-aminopropionitrile, the adding amount of the pyridine is 3.5% of the mass of the beta-aminopropionitrile, the molar ratio of the beta-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 was set at 45℃and the microwave radiation power at 700W for 250 seconds. After the reaction is finished, filtering and deaminizing, concentrating the reaction liquid by reduced pressure distillation to be sticky, adding methanol with the mass 5 times of the theoretical product, cooling, crystallizing, filtering and drying to obtain the beta-calcium aminopropionate. The detection shows that the conversion rate of the beta-aminopropionitrile is more than 99%, the purity of the obtained product beta-aminopropionic acid calcium is 99.5%, and the yield is 98.9%.
Example 2
Zirconium chloride and 2,2' -bipyridine are put into a reaction bottle according to the mol ratio of 1:1.9, a proper amount of absolute ethyl ether is added as a solvent, the reaction temperature is controlled at 30 ℃, and the reaction is carried out for 3 hours at constant temperature. Concentrating at 40 deg.c, crystallizing at-15 deg.c, filtering the crystallized solid and drying to obtain the catalyst.
In a reaction bottle fixed on a microwave oven cavity, mixing beta-aminopropionitrile, a catalyst, 18 crown 6, calcium hydroxide and water at normal temperature, wherein the adding amount of the catalyst is 0.5% of the mass of the beta-aminopropionitrile, the adding amount of the 18 crown 6 is 4.0% of the mass of the beta-aminopropionitrile, the mol ratio of the beta-aminopropionitrile to the calcium hydroxide is 1:1.7, and the mass ratio of the calcium hydroxide to the water is 0.25:1. The reaction temperature was set at 45℃and the microwave radiation power at 800W for 200 seconds. After the reaction is finished, filtering and deaminizing, concentrating the reaction liquid by reduced pressure distillation to be sticky, adding methanol with the mass 4 times of the theoretical product, cooling, crystallizing, filtering and drying to obtain the beta-calcium aminopropionate. The detection shows that the conversion rate of the beta-aminopropionitrile is more than 99%, and the purity of the obtained product beta-aminopropionic acid calcium is 99.0%, and the yield is 99.1%.
Example 3
Adding magnesium chloride and 1, 8-bis (diphenylphosphine) naphthalene into a reaction bottle according to the molar ratio of 1:1.2, adding a proper amount of anhydrous toluene as a solvent, controlling the reaction temperature at 50 ℃, and reacting for 3 hours at constant temperature. Concentrating at 100deg.C, hermetically crystallizing at-15deg.C, filtering, and drying to obtain the final product.
In a reaction bottle fixed in a microwave oven cavity, mixing beta-aminopropionitrile, a catalyst, tributyl amine, calcium oxide and N, N-dimethylformamide at normal temperature, wherein the adding amount of the catalyst is 0.8% of the mass of the beta-aminopropionitrile, the adding amount of the tributyl amine is 4.0% of the mass of the beta-aminopropionitrile, the mol ratio of the beta-aminopropionitrile to the calcium oxide is 1:1.4, and the mass ratio of the calcium oxide to the N, N-dimethylformamide is 0.30:1. The reaction temperature was set at 25℃and the microwave radiation power at 1000W for 300 seconds. After the reaction is finished, filtering and deaminizing, concentrating the reaction liquid by reduced pressure distillation to be sticky, adding methanol with the mass 7 times of the theoretical product, cooling, crystallizing, filtering and drying to obtain the beta-calcium aminopropionate. The detection shows that the conversion rate of the beta-aminopropionitrile is more than 99%, the purity of the obtained product beta-aminopropionic acid calcium is 99.1%, and the yield is 95.5%.
Comparative example 1:
beta-aminopropionitrile, calcium hydroxide and water are mixed in a reaction bottle at normal temperature, wherein the molar ratio of the beta-aminopropionitrile to the calcium hydroxide is 1:1.7, and the mass ratio of the calcium hydroxide to the water is 0.45:1. The reaction temperature was set at 25℃and the reaction time was 200 seconds. After the reaction is finished, filtering and deaminizing, concentrating the reaction liquid by reduced pressure distillation to be sticky, adding methanol with the mass 4 times of the theoretical product, and cooling and crystallizing to obtain a crude product of beta-calcium aminopropionate. The detection shows that the conversion rate of the beta-aminopropionitrile is 15%, the purity of the obtained product beta-aminopropionic acid calcium is 41.2%, and the yield is 7.1%.
Comparative example 2:
in a reaction bottle fixed in a microwave oven cavity, uniformly mixing beta-aminopropionitrile, pyridine, calcium hydroxide and water/acetonitrile solvent at normal temperature, wherein the addition amount of the pyridine is 3.5% of the mass of the beta-aminopropionitrile, the molar ratio of the beta-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 was set at 45℃and the microwave radiation power at 700W for 250 seconds. After the reaction is finished, filtering and deaminizing, concentrating the reaction liquid to be sticky by reduced pressure distillation, adding methanol with the mass 5 times of the theoretical product, cooling, crystallizing, filtering and drying to obtain the beta-calcium aminopropionate. The detection shows that the conversion rate of the beta-aminopropionitrile is 43%, the purity of the obtained product beta-aminopropionic acid calcium is 56.2%, and the yield is 19.2%.
The above embodiments are not intended to limit the technical solution of the present invention in any way. Any simple modification, equivalent variation and modification of the above embodiments according to the technical substance of the present invention fall within the protection scope of the present invention.
Claims (10)
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Citations (7)
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|---|---|---|---|---|
| US3935256A (en) * | 1974-09-06 | 1976-01-27 | Thompson-Hayward Chem. Co. | Process for the production of the calcium salt of pantothenic acid |
| US4052451A (en) * | 1976-03-11 | 1977-10-04 | Lekberg Robert D | Preparation of calcium pantothenate |
| JP2000007609A (en) * | 1998-06-24 | 2000-01-11 | Toray Ind Inc | Production of carboxylic acid derivative |
| CN101801915A (en) * | 2007-07-31 | 2010-08-11 | 帝斯曼知识产权资产管理有限公司 | Method for synthesizing beta-sodium alanine and calcium pantothenate |
| CN101948402A (en) * | 2010-08-20 | 2011-01-19 | 新发药业有限公司 | Method for preparing D-calcium pantothenate |
| CN102718645A (en) * | 2012-05-09 | 2012-10-10 | 湖北远成药业有限公司 | Microwave synthesis method of cinnamic acid derivative |
| CN107986979A (en) * | 2017-12-14 | 2018-05-04 | 苏州百福安酶技术有限公司 | A kind of method for synthesizing Beta-alanine calcium and D-VB5 calcium |
-
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- 2023-11-13 CN CN202311501726.9A patent/CN117567306A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3935256A (en) * | 1974-09-06 | 1976-01-27 | Thompson-Hayward Chem. Co. | Process for the production of the calcium salt of pantothenic acid |
| US4052451A (en) * | 1976-03-11 | 1977-10-04 | Lekberg Robert D | Preparation of calcium pantothenate |
| JP2000007609A (en) * | 1998-06-24 | 2000-01-11 | Toray Ind Inc | Production of carboxylic acid derivative |
| CN101801915A (en) * | 2007-07-31 | 2010-08-11 | 帝斯曼知识产权资产管理有限公司 | Method for synthesizing beta-sodium alanine and calcium pantothenate |
| CN101948402A (en) * | 2010-08-20 | 2011-01-19 | 新发药业有限公司 | Method for preparing D-calcium pantothenate |
| CN102718645A (en) * | 2012-05-09 | 2012-10-10 | 湖北远成药业有限公司 | Microwave synthesis method of cinnamic acid derivative |
| CN107986979A (en) * | 2017-12-14 | 2018-05-04 | 苏州百福安酶技术有限公司 | A kind of method for synthesizing Beta-alanine calcium and D-VB5 calcium |
Non-Patent Citations (1)
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| JAIN, N. F. ETAL: "Carboxyl Synthesis from carboxylic acid derivatives", 《SCIENCE OF SYNTHESIS》, 31 December 2006 (2006-12-31), pages 75 - 92 * |
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