CN112321447A - Method for preparing D-sodium pantothenate from D-calcium pantothenate mother liquor - Google Patents
Method for preparing D-sodium pantothenate from D-calcium pantothenate mother liquor Download PDFInfo
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- CN112321447A CN112321447A CN202011035014.9A CN202011035014A CN112321447A CN 112321447 A CN112321447 A CN 112321447A CN 202011035014 A CN202011035014 A CN 202011035014A CN 112321447 A CN112321447 A CN 112321447A
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- pantothenate
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
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- C07C231/24—Separation; Purification
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Abstract
The invention discloses a method for preparing D-sodium pantothenate from D-calcium pantothenate mother liquor. The method comprises the steps of carrying out reflux concentration on D-calcium pantothenate mother liquor, adding water, stirring, adding sodium carbonate, carrying out reaction, filtering, adding dilute sulfuric acid into filtrate, adjusting pH, adding activated carbon, filtering, concentrating the filtrate, adding methanol, cooling, crystallizing, filtering, and drying to obtain the D-sodium pantothenate. The invention utilizes the D-calcium pantothenate with 10-20% of the D-calcium pantothenate remained in the crystallization mother liquor of the D-calcium pantothenate to prepare the D-sodium pantothenate. The solvent used in the reaction is low in price, the mother liquor needing to be recycled is used as a raw material to prepare a new product, the cost is great, the reaction environment is friendly, the safety is high, the reaction time is short, the solvent can be recycled, the steps are simple, and the purity of the obtained D-sodium pantothenate product is high.
Description
Technical Field
The invention belongs to the field of chemical industry, and particularly relates to a method for preparing D-sodium pantothenate from D-calcium pantothenate mother liquor.
Background
Sodium pantothenate, known by the british name D-pantonic Acid Sodium Salt, also known as D-pantonic Acid Sodium Salt, is chemically (R) -N- (2, 4-dihydroxy-3, 3-dimethyl-1-oxobutyl) - β -aminopropionic Acid monosodium Salt, which is the Sodium Salt form of Pantothenic Acid. Pantothenic acid, also known as pantothenic acid and vitamin B3, belongs to a vitamin B group, can help cell formation, maintain normal development and development of central nervous system, maintain normal functions of adrenal gland, are essential substances for energy conversion of fats and saccharides, and are also essential substances for antibody synthesis and utilization of aminobenzoic acid and choline by human body. Two forms of pantothenic acid, calcium and sodium, are commonly used clinically. Calcium pantothenate as a raw material and its tablets have been collected in the 2000 th edition of the Chinese pharmacopoeia, and as pantothenic acid often needs to be combined with other B vitamins such as riboflavin sodium phosphate or other phosphate drugs, calcium pantothenate is required to have a reduced potency due to formation of calcium phosphate, so that the sodium salt of pantothenic acid must be used. With the wide clinical application of sodium pantothenate, the demand for raw materials for medicinal sodium pantothenate is increasing.
The prior art reports on the relevant literature that calcium pantothenate mainly comprises the following two types: (1) obtaining D-pantoic acid lactone by resolution to directly obtain D-calcium pantothenate, and (2) obtaining DL-calcium pantothenate first and then obtaining D-calcium pantothenate by induced resolution. However, calcium pantothenate is obtained by crystallization in the production process of calcium pantothenate, and the crystallization yield is only 80% -85%, so that the mother liquor also contains 10% -20% of calcium pantothenate. If the mother liquor is discarded, not only resource waste is caused, but also environmental pollution is caused. In order to solve such problems, the calcium pantothenate mother liquor is treated.
In the synthesis of sodium D-pantothenate, it is often the case that the finished product of calcium D-pantothenate is purchased to produce sodium D-pantothenate, the steps are complicated, and the final crystallization rate of sodium D-pantothenate is 50% or less, and patent documents mention that the crystallization yield of sodium D-pantothenate can reach 90% using a mixed solvent of ethanol and acetone, but the recovery of the mixed solution causes troubles in the later stage, and acetone is a relatively dangerous solvent, and the types of mixed solvents increase, which also increases the cost, and even more, it is not advisable from the viewpoint of safety after industrialization.
Disclosure of Invention
In order to solve the defects in the prior art, the invention aims to provide a method for effectively treating and utilizing D-calcium pantothenate mother liquor.
The invention provides a method for preparing D-sodium pantothenate from D-calcium pantothenate mother liquor, which comprises the steps of carrying out reflux concentration on the D-calcium pantothenate mother liquor, adding water, stirring, adding sodium carbonate, carrying out reaction, filtering, adding dilute sulfuric acid into filtrate, adjusting pH, adding activated carbon, filtering, concentrating the filtrate, adding methanol, cooling, crystallizing, filtering, and drying to obtain the D-sodium pantothenate.
As a preferable scheme of the invention, after the D-calcium pantothenate mother liquor is concentrated until no liquid reflux exists, water with the mass of 1.5-3 times of that of the concentrate is added, the mixture is uniformly stirred, water with the mass of 2 times of that of the concentrate is preferably added, and the mixture is distilled to 100-120 ℃ under normal pressure, preferably to 100 ℃. In the reflux concentration process, the methanol in the mother liquor can be recycled, so that the resource waste is avoided.
As a preferred scheme of the invention, after the sodium carbonate is added, the mixture is stirred for 0.8 to 1.5 hours, preferably 1 hour, at the temperature of between 80 and 90 ℃ to ensure the stable and complete reaction. After the reaction is finished under the condition of heat preservation, cooling to room temperature and filtering.
As a preferred embodiment of the present invention, sodium carbonate and calcium pantothenate are added in a molar ratio of (1-1.2: 1).
As a preferred embodiment of the present invention, dilute sulfuric acid is added to adjust the pH to 6.8-7.2, preferably 7.0. The pH is adjusted by dilute sulfuric acid, so that the excessive alkali in the solution can be neutralized, and the yield is improved.
As a preferred scheme of the invention, the filtrate filtered after adding the active carbon is concentrated to the water content of 1-10%, and the crystallization solvent is a mixed solution of methanol and water, so that the energy waste is avoided, the residual water is removed, and the high-purity methanol can be used.
As a preferable embodiment of the present invention, methanol is added under stirring in an amount of 3 to 7 times as much as the concentrated solution, preferably 90 to 99% methanol, more preferably 95% methanol.
As a preferable scheme of the invention, the temperature for reducing the temperature and crystallizing is 10-25 ℃.
As a preferable embodiment of the present invention, the drying condition is vacuum drying at 30 ℃ to 45 ℃.
The method of the invention effectively treats the crystallization mother liquor of the D-calcium pantothenate and simultaneously utilizes the 10-20% of the D-calcium pantothenate remained in the crystallization mother liquor of the D-calcium pantothenate to prepare the D-sodium pantothenate. The solvent used in the reaction is low in price, the mother liquor needing to be recycled is used as a raw material to prepare a new product, the cost is great, the reaction environment is friendly, the safety is high, the reaction time is short, the solvent can be recycled, the steps are simple, and the purity of the obtained D-sodium pantothenate product is high.
Compared with the prior art, the invention has the beneficial effects that:
1. the method utilizes the D-calcium pantothenate tail waste mother liquor to synthesize the same kind of pantothenate, namely D-sodium pantothenate, and has simple steps, and compared with other technologies for synthesizing the D-sodium pantothenate, the method has great advantages in cost because the raw material is the tail waste mother liquor. The method not only effectively treats the calcium pantothenate mother liquor, reduces the cost and the process for simply treating the tail waste mother liquor, but also changes waste into valuable, and prepares the high-purity D-sodium pantothenate by using the calcium pantothenate mother liquor as a raw material.
2. The method uses the mixed solvent of methanol and water in the crystallization stage, only contains one organic solvent of methanol, and compared with the two mixed organic solvents of ethanol and acetone adopted in the crystallization in the prior art, the D-calcium pantothenate is easier to crystallize in methanol, the single solvent in production also saves the equipment investment for enterprises, reduces the safety risk, avoids the waste of resources, and the obtained D-sodium pantothenate has higher purity.
Detailed Description
The present invention is further illustrated by the following examples, which should not be construed as limiting the invention.
"D-calcium pantothenate mother liquor" referred to in the following examples: d-calcium pantothenate also known as vitamin B5The D-calcium pantothenate is prepared by salifying 3-aminopropionic acid and calcium oxide in methanol system and then reacting with D-pantoic acid lactoneAcylating to obtain a methanol solution of the D-calcium pantothenate, finally cooling, crystallizing and filtering to obtain the D-calcium pantothenate, wherein the crystallization yield is generally 80-85%, so that the residual 15-20% of the product is still remained in the mother liquor, and the D-calcium pantothenate mother liquor is obtained.
Example 1.
The embodiment provides a method for preparing D-sodium pantothenate from D-calcium pantothenate mother liquor, which specifically comprises the following steps:
taking 1000g D-calcium pantothenate mother liquor, carrying out reflux concentration at 50 ℃ in vacuum, recovering methanol until no liquid flows back in a condenser, adding 150g of water, continuing to distill at normal pressure to 100 ℃, adding 11.5g of sodium carbonate, preserving heat at 80-90 ℃ for one hour, and then filtering; adding dilute sulfuric acid into the filtrate to adjust the pH value to 6.96, adding 0.5g of activated carbon, stirring for 30 minutes, filtering, concentrating at 66 ℃ under reduced pressure until the residual feed liquid is 60g (the water content is 5.5%), adding 180g of 95% methanol, stirring uniformly, continuously cooling, slowly cooling to 10 ℃, filtering, and drying the filtered crystals at 40-45 ℃ in vacuum to obtain 36g of a dried D-sodium pantothenate with the purity of 99.3%.
Example 2.
The embodiment provides a method for preparing D-sodium pantothenate from D-calcium pantothenate mother liquor, which specifically comprises the following steps:
taking 1000g D-calcium pantothenate mother liquor, carrying out reflux concentration at 50 ℃ in vacuum, recovering methanol until no liquid flows back in a condenser, adding 160g of water, continuing to distill at normal pressure to 100 ℃, adding 12.2g of sodium carbonate, preserving heat at 80-90 ℃ for one hour, and then filtering; adding dilute sulfuric acid into the filtrate to adjust the pH value to 7.1, adding 0.5g of activated carbon, stirring for 30 minutes, filtering, concentrating at 63 ℃ under reduced pressure until the residual feed liquid is 63g (the water content is 8.3%), adding 210g of methanol, stirring uniformly, continuously cooling, slowly cooling to 20 ℃, filtering, and drying the filtered crystals at 40 ℃ in vacuum to obtain 33g of a dried D-sodium pantothenate product with the purity of 99.6%.
Example 3.
The embodiment provides a method for preparing D-sodium pantothenate from D-calcium pantothenate mother liquor, which specifically comprises the following steps:
taking 1000g D-calcium pantothenate mother liquor, carrying out reflux concentration at 50 ℃ in vacuum, recovering methanol until no liquid flows back in a condenser, adding 146g of water, continuing to distill at normal pressure to 100 ℃, adding 11.5g of sodium carbonate, preserving heat at 80-90 ℃ for one hour, and then filtering; adding dilute sulfuric acid into the filtrate to adjust the pH value to 7.06, adding 0.5g of activated carbon, stirring for 30 minutes, filtering, concentrating at 65 ℃ under reduced pressure until 65g of the residual feed liquid (the water content is 10.0%), adding 230g of methanol, stirring uniformly, continuously cooling, slowly cooling to 11 ℃, filtering, and drying the filtered crystal at 40 ℃ in vacuum to obtain 39g of a dried D-sodium pantothenate product with the purity of 99.0%.
Comparative example 1.
This comparative example was conducted in the same manner as in the above experimental example 2, except that the water content after concentration was changed and anhydrous methanol was added, and included: adding activated carbon, stirring, filtering, concentrating until the water content of the rest material liquid is 0.5%, adding 210g anhydrous methanol, stirring, cooling, filtering, and vacuum drying to obtain dry D-sodium pantothenate 41g with purity of 82.3%.
Comparative example 2.
This comparative example was conducted in the same manner as in the above experimental example 2, and was different mainly in that the crystallization temperature was changed, including: and adding dilute sulfuric acid into the filtrate to adjust the pH value to 7.0, adding activated carbon, stirring, filtering, concentrating until the water content of the residual feed liquid is 6.8%, adding 210g of methanol, stirring uniformly, continuously cooling, slowly cooling to 0 ℃, filtering, and drying in vacuum to obtain 53g of a dry product of the D-sodium pantothenate with the purity of 66.5%.
As can be seen from the above examples and comparative examples, the purity of sodium D-pantothenate prepared by the method of the present invention was 99.0% or more, while the purity of the product obtained by the comparative example was 82.3% or less, even as low as 66.5%.
Therefore, the method not only effectively treats the D-calcium pantothenate mother liquor, but also obtains the high-purity D-sodium pantothenate, and has the advantages of simple operation, environmental friendliness, reasonable utilization of resources and energy conservation.
The preferred embodiments of the present invention have been described in detail, however, the present invention is not limited to the specific details of the above embodiments, and various simple modifications may be made to the technical solution of the present invention within the technical idea of the present invention, and these simple modifications are within the protective scope of the present invention.
It should be noted that the various technical features described in the above embodiments can be combined in any suitable manner without contradiction, and the invention is not described in any way for the possible combinations in order to avoid unnecessary repetition.
In addition, any combination of the various embodiments of the present invention is also possible, and the same should be considered as the disclosure of the present invention as long as it does not depart from the spirit of the present invention.
Claims (10)
1. A method for preparing D-sodium pantothenate from D-calcium pantothenate mother liquor is characterized by comprising the steps of carrying out reflux concentration on the D-calcium pantothenate mother liquor, adding water, stirring, adding sodium carbonate, carrying out reaction, filtering, adding dilute sulfuric acid into filtrate, adjusting pH, adding activated carbon, filtering, concentrating the filtrate, adding methanol, cooling, crystallizing, filtering, and drying to obtain the D-sodium pantothenate.
2. The method according to claim 1, wherein the D-calcium pantothenate mother liquor is concentrated to no liquid reflux, and then water is added in an amount of 1.5 to 3 times the mass of the concentrate, and the concentrate is distilled at atmospheric pressure to 100 ℃ to 120 ℃.
3. The process of claim 1, wherein the stirring is carried out at 80-90 ℃ for 0.8-1.5h after the addition of sodium carbonate.
4. The process according to any one of claims 1 to 3, wherein the molar ratio of sodium carbonate to calcium pantothenate added is (1-1.2): 1.
5. A method according to any of claims 1-3, characterized in that dilute sulfuric acid is added to adjust the pH to 6.8-7.2, preferably 7.0.
6. A method according to any one of claims 1 to 3, wherein the filtrate after the addition of activated carbon is concentrated to a water content of 1% to 10%.
7. A method according to any one of claims 1 to 3, wherein methanol is added in an amount of 3 to 7 times the concentrate.
8. A process according to any one of claims 1 to 3, wherein the methanol is 90-99% methanol, preferably 95% methanol.
9. A method according to any one of claims 1 to 3, wherein the temperature of the reduced temperature crystallization is from 10 ℃ to 25 ℃.
10. The method according to any one of claims 1 to 3, wherein the drying conditions are vacuum drying at 30 ℃ to 45 ℃.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202011035014.9A CN112321447A (en) | 2020-09-27 | 2020-09-27 | Method for preparing D-sodium pantothenate from D-calcium pantothenate mother liquor |
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| CN202011035014.9A CN112321447A (en) | 2020-09-27 | 2020-09-27 | Method for preparing D-sodium pantothenate from D-calcium pantothenate mother liquor |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB565976A (en) * | 1941-05-26 | 1944-12-07 | Parke Davis & Co | Process for the manufacture of crystalline sodium-d-pantothenate |
| DE2919515A1 (en) * | 1978-05-18 | 1979-11-22 | Hoffmann La Roche | PROCESS FOR THE PRODUCTION OF SODIUM PANTOTHENATE |
| CN104592053A (en) * | 2015-01-16 | 2015-05-06 | 河北一品制药有限公司 | Industrial preparation method of high-purity sodium pantothenate |
| CN111072512A (en) * | 2019-11-13 | 2020-04-28 | 合肥华方医药科技有限公司 | Preparation and detection method of high-purity high-melting-point sodium pantothenate |
-
2020
- 2020-09-27 CN CN202011035014.9A patent/CN112321447A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB565976A (en) * | 1941-05-26 | 1944-12-07 | Parke Davis & Co | Process for the manufacture of crystalline sodium-d-pantothenate |
| DE2919515A1 (en) * | 1978-05-18 | 1979-11-22 | Hoffmann La Roche | PROCESS FOR THE PRODUCTION OF SODIUM PANTOTHENATE |
| CN104592053A (en) * | 2015-01-16 | 2015-05-06 | 河北一品制药有限公司 | Industrial preparation method of high-purity sodium pantothenate |
| CN111072512A (en) * | 2019-11-13 | 2020-04-28 | 合肥华方医药科技有限公司 | Preparation and detection method of high-purity high-melting-point sodium pantothenate |
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Application publication date: 20210205 |