CN110734415B - Aqueous solution crystallization method of D-pantolactone - Google Patents
Aqueous solution crystallization method of D-pantolactone Download PDFInfo
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- CN110734415B CN110734415B CN201911188231.9A CN201911188231A CN110734415B CN 110734415 B CN110734415 B CN 110734415B CN 201911188231 A CN201911188231 A CN 201911188231A CN 110734415 B CN110734415 B CN 110734415B
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- pantolactone
- pantoic acid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Abstract
The invention relates to a method for crystallizing an aqueous solution of D-pantolactone, which comprises the following steps: taking an inorganic saline solution containing 15-23% of D-pantolactone as a raw material, concentrating until the concentration of the D-pantolactone is 28-35%, cooling to 0-5 ℃ at the speed of 2-8 ℃/h, and carrying out heat preservation and crystallization. The method provided by the invention realizes crystallization by adjusting the concentration of D-pantoic acid lactone in an inorganic salt water solution and controlling the cooling speed, and is preferably suitable for a mixed solution which is prepared by using D-pantoic acid as a raw material and adopting a lactonization process to prepare D-pantoic acid lactone. The method has the characteristics of simple steps, easy operation control, high quality and the like, and is an effective method for purifying D-pantolactone crystals.
Description
Technical Field
The invention relates to the field of chemical production, in particular to a method for crystallizing an aqueous solution of D-pantolactone.
Background
The D-pantoic acid lactone is white crystalline powder, is very easy to dissolve in methanol and ethanol, and is easy to dissolve in water. Boiling point of 120-122 ℃ and density of 1.165g/cm3The specific rotation (20 ℃) is-45 to-50.8 (C is 2.5 and water).
D-pantoic acid lactone can be used for producing D-calcium pantothenate, D-panthenol and D-panthenol ethyl ether, and has huge market. For example: the deficiency of calcium D-pantothenate in humans can be manifested by growth arrest, weight loss, sudden death, skin hair disorders, nervous system disorders, disorders of digestive organs, liver dysfunction, influence on antibody formation, and the like. Calcium D-pantothenate is also used as a food additive and a feed additive, plays an important role in the formation of epidermal tissues, is used as an active ingredient in pharmaceutical ingredients, for promoting wound healing and in cosmetics, is an indispensable nutrient for skin health care and beauty, and is also used as an additive for cosmetics, including vitamins such as D-panthenol, D-panthenyl ethyl ether and DL-panthenol, in many foreign countries.
At present, the D-pantoic acid lactone is generally prepared by a chemical or biological resolution method. In the traditional chemical resolution method and the biological resolution method, the microbial enzyme method is adopted to resolve the DL-pantoic acid lactone, and the method becomes an important direction for research due to the characteristics of environmental pollution, low toxicity and the like. Wherein, one method for splitting DL-pantolactone by a microbial enzyme method is to utilize microorganisms producing L-pantolactone to decompose L-pantolactone in DL-pantolactone to obtain undecomposed D-configuration pantolactone.
However, whatever the resolution method, the purification problem of D-pantoic acid sodium lactone is encountered. In the prior art, the traditional method for extracting D-pantoic acid lactone adopts organic solvent for extraction and then refining to obtain qualified D-pantoic acid lactone, and the traditional method uses solvents such as ethyl acetate, dichloromethane, toluene and the like, has the problems of toxicity and pollution, and has complicated steps.
Disclosure of Invention
The invention aims to solve the defects in the prior art and provides an aqueous solution crystallization method for producing high-quality D-pantolactone crystals with simple operation, easy control and high efficiency.
Specifically, the invention provides a method for crystallizing an aqueous solution of D-pantolactone, which comprises the steps of taking an inorganic saline solution containing 15-23% of D-pantolactone as a raw material, concentrating until the concentration of the D-pantolactone is 28-35%, cooling to 0-5 ℃ at the speed of 2-8 ℃/h, and carrying out heat preservation and crystallization.
The concentration of D-pantoic acid lactone refers to the mass volume percentage concentration, namely the gram of D-pantoic acid lactone in each 100ml of aqueous solution. For example, 15 to 23% of D-pantolactone means that the mass of D-pantolactone per 100ml of aqueous solution is 15 to 23 g. For another example, concentration to a concentration of 28 to 35% of D-pantolactone means concentration to a mass of 28 to 35g of D-pantolactone per 100ml of aqueous solution.
The method provided by the invention has the core that the concentration of D-pantoic acid lactone in the inorganic saline solution is controlled and the cooling rate is controlled, so that the D-pantoic acid lactone is efficiently separated out and crystallized, the obtained crystal is large and uniform, the specific rotation degree of the crystallized product D-pantoic acid lactone can reach-45 to-50.5, preferably-49.5 to-50.5, and the method meets the process use standard.
The method provided by the invention is preferably used for preparing the mixed solution of D-pantoic acid lactone by taking D-pantoic acid as a raw material and adopting a lactonization process. The D-pantoic acid can be prepared by taking DL-pantoic acid lactone as a raw material through resolution, and is preferably prepared by adopting a biological resolution method. The crystallization method for the aqueous solution of the inorganic salt containing D-pantolactone provided by the invention is particularly suitable for the product obtained by the process because a large amount of inorganic salt is generated in the mass production process of the process.
The inorganic salts include ammonium sulfate, sodium chloride and ammonium chloride. In the inorganic salt water solution, the mass ratio of D-pantoic acid lactone to inorganic salt is preferably 100: (50-75).
In order to improve the concentration efficiency, the concentration is preferably performed at 55-65 ℃ under reduced pressure. The water solution can be stirred at the rotating speed of 20-40 r/min in the concentration process.
In order to ensure uniform cooling speed so as to efficiently precipitate crystals with excellent quality, the invention preferably stirs the aqueous solution at a rotating speed of 20-40 r/min in the cooling process.
By adopting the method provided by the invention, the thermal insulation crystallization time is about 1-3 h, and large and uniform D-pantolactone crystals can be precipitated. The crystal obtained by the method provided by the invention has the specific rotation degree of-49.5 to-50.5 generally and excellent quality.
As a specific preferred embodiment of the present invention, the method comprises the steps of: taking an inorganic salt water solution containing D-pantolactone as a raw material, concentrating under reduced pressure at 58-62 ℃ to ensure that the concentration of the D-pantolactone is 30-32%, stirring at the rotating speed of 28-32 r/min, cooling to 0-2 ℃ at the speed of 6-8 ℃/h, preserving heat, crystallizing for 2h, and filtering and collecting crystals;
the inorganic salt water solution is a mixed solution of D-pantoic acid solution after lactonization, wherein the concentration of D-pantoic acid lactone is 18-22%, and the concentration of inorganic salt is 13-17%.
Compared with the prior art, the method provided by the invention is preferably suitable for the solution obtained by performing lactonization on the D-pantoic acid solution obtained by chiral resolution, and the qualified D-pantoic acid lactone can be directly obtained from the inorganic salt water solution of the D-pantoic acid lactone without being extracted by an organic solvent, so that the use of a toxic organic solvent is avoided, the steps are simple, the equipment investment is reduced for production, the production steps are reduced, the cost is saved, the most important is environmental protection and no pollution, and the method actively responds to national policies. The method directly crystallizes the D-pantolactone from the inorganic salt water solution, reduces the working procedures, has easily controlled process and simple and convenient operation, obtains large and uniform crystals of the obtained product, ensures that the specific rotation degree of the crystallized product D-pantolactone can reach-45 to-50.5, preferably reaches-49.5 to-50.5, and meets the process use standard.
Detailed Description
The present invention is further illustrated by the following examples, which should not be construed as limiting the invention.
In the following examples, the inorganic salt in the feed solution was composed of ammonium sulfate, sodium chloride, and ammonium chloride.
Example 1
The embodiment provides a method for crystallizing an aqueous solution of D-pantolactone, which comprises the following specific steps:
taking 2L of the feed liquid (containing 20.1 percent of D-pantolactone and 15 percent of inorganic salt) of the D-pantolactone solution after lactonization, carrying out reduced pressure concentration at 60 ℃ to adjust the concentration of the D-pantolactone to be 30.0 percent, reducing the temperature to 1 ℃ at the speed of 8 ℃/h, stirring at the speed of 30r/min at the speed of 1 ℃, preserving the heat for 2h, and carrying out suction filtration to obtain 300g of the feed liquid.
The yield of D-pantoic acid lactone obtained in the embodiment is 75%, the specific rotation is-50.0 degrees, and the crystal is regular and uniform and has large particles.
Example 2
The embodiment provides a method for crystallizing an aqueous solution of D-pantolactone, which comprises the following specific steps:
taking 2L of the feed liquid (containing 18.1 percent of D-pantolactone and 14 percent of inorganic salt) of the lactonized D-pantolactone solution, carrying out reduced pressure concentration at 60 ℃ to adjust the concentration of the D-pantolactone to be 28.0 percent, reducing the temperature to 3 ℃ at the speed of 8 ℃/h, stirring at the speed of 30r/min at the speed of 3 ℃, preserving the temperature for 2h, and carrying out suction filtration to obtain 260g of the feed liquid.
The yield of D-pantoic acid lactone obtained in the embodiment is 72%, the specific rotation is-49.9 degrees, and the crystal is regular and uniform and has large particles.
Example 3
The embodiment provides a method for crystallizing an aqueous solution of D-pantolactone, which comprises the following specific steps:
taking 2L of the feed liquid (containing 19.1 percent of D-pantoic acid lactone and 14.5 percent of inorganic salt) of the lactonized D-pantoic acid solution, carrying out reduced pressure concentration at 60 ℃ to adjust the concentration of the D-pantoic acid lactone to be 30.0 percent, reducing the temperature to 4 ℃ at the speed of 8 ℃/h, stirring at the speed of 30r/min, keeping the temperature at 4 ℃ for 2h, and carrying out suction filtration to obtain 260g of the feed liquid.
The yield of D-pantolactone obtained in this example was 68%, the specific rotation was-50.2%, and the purity was 98.1%. Regular and uniform crystals and large particles.
Example 4
The embodiment provides a method for crystallizing an aqueous solution of D-pantolactone, which comprises the following specific steps:
taking 2L of the feed liquid (containing 18.1 percent of D-pantolactone and 12 percent of inorganic salt) of the lactonized D-pantolactone solution, carrying out reduced pressure concentration at 60 ℃ to adjust the concentration of the D-pantolactone to be 28.0 percent, reducing the temperature to 2 ℃ at the speed of 8 ℃/h, stirring at the speed of 30r/min at the speed of 2 ℃, preserving the heat for 2h, and carrying out suction filtration to obtain 260g of the feed liquid.
The yield of D-pantoic acid lactone obtained in the embodiment is 72%, the specific rotation is-49.9 degrees, and the crystal is regular and uniform and has large particles.
Example 5
The embodiment provides a method for crystallizing an aqueous solution of D-pantolactone, which comprises the following specific steps:
taking 2L of the feed liquid (containing 19.1 percent of D-pantolactone and 10 percent of inorganic salt) of the lactonized D-pantolactone solution, carrying out reduced pressure concentration at 60 ℃ to adjust the concentration of the D-pantolactone to be 30.0 percent, reducing the temperature to 4 ℃ at the speed of 8 ℃/h, keeping the temperature at 4 ℃ at the stirring speed of 30r/min, and carrying out suction filtration to obtain 260g of the feed liquid.
The yield of D-pantolactone obtained in the embodiment is 68%, the specific rotation is-50.2 degrees, and the crystal is regular and uniform and has large particles.
Although the invention has been described in detail hereinabove by way of general description, specific embodiments and experiments, it will be apparent to those skilled in the art that many modifications and improvements can be made thereto based on the invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.
Claims (9)
1. A method for crystallizing an aqueous solution of D-pantolactone is characterized in that an inorganic saline solution containing 15-23% of D-pantolactone is used as a raw material, concentration is carried out to ensure that the concentration of the D-pantolactone is 28-35%, the temperature is reduced to 0-5 ℃ at the speed of 2-8 ℃/h, and crystallization is carried out under the condition of heat preservation;
wherein the inorganic salt water solution containing 15-23% of D-pantoic acid lactone is as follows: d-pantoic acid is taken as a raw material, and a mixed solution obtained by preparing D-pantoic acid lactone by adopting a lactonization process; the inorganic salts include ammonium sulfate, sodium chloride, and ammonium chloride.
2. The process according to claim 1, wherein the D-pantoic acid is prepared by resolution of DL-pantoic acid lactone as a starting material.
3. The method according to claim 2, wherein the D-pantoic acid is prepared by a biological resolution method.
4. The method according to any one of claims 1 to 3, wherein the mass ratio of D-pantolactone to inorganic salt in the aqueous solution of inorganic salt is 100: (50-75).
5. The method according to claim 1, wherein the concentration is performed under reduced pressure at 55-65 ℃.
6. The method according to claim 1 or 5, wherein the aqueous solution is stirred at a rotation speed of 20-40 r/min during the concentration process.
7. The method according to claim 1, wherein the aqueous solution is stirred at a rotation speed of 20-40 r/min during the temperature reduction process.
8. The method according to claim 1, wherein the time for the heat-preservation crystallization is 1-3 h.
9. The method of claim 1, comprising the steps of: taking an inorganic salt water solution containing D-pantolactone as a raw material, concentrating under reduced pressure at 58-62 ℃ to ensure that the concentration of the D-pantolactone is 30-32%, stirring at the rotating speed of 28-32 r/min, cooling to 0-2 ℃ at the speed of 6-8 ℃/h, preserving heat, crystallizing for 2h, and filtering and collecting crystals;
the inorganic salt water solution is a mixed solution of D-pantoic acid solution after lactonization, wherein the concentration of D-pantoic acid lactone is 18-22%, and the concentration of inorganic salt is 13-17%.
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Citations (5)
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|---|---|---|---|---|
| JPS57128683A (en) * | 1981-02-03 | 1982-08-10 | Sumitomo Chem Co Ltd | Production of optically active pantolactone |
| US4359582A (en) * | 1978-03-03 | 1982-11-16 | Basf Aktiengesellschaft | Extraction of pantolactone from its aqueous solutions |
| EP0443406A2 (en) * | 1990-02-17 | 1991-08-28 | Hoechst Aktiengesellschaft | Process for enzymatic racemate separation of pantolacton |
| CN102229584A (en) * | 2011-04-19 | 2011-11-02 | 吴江 | Method for preparing D-(-)- or L-(+)-pantoic acid lactone by splitting pantoic acid lactone |
| CN108117532A (en) * | 2018-01-12 | 2018-06-05 | 重庆市碚圣医药科技股份有限公司 | A kind of synthetic method of the D-VB5 lactone of high-purity |
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2019
- 2019-11-28 CN CN201911188231.9A patent/CN110734415B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4359582A (en) * | 1978-03-03 | 1982-11-16 | Basf Aktiengesellschaft | Extraction of pantolactone from its aqueous solutions |
| JPS57128683A (en) * | 1981-02-03 | 1982-08-10 | Sumitomo Chem Co Ltd | Production of optically active pantolactone |
| EP0443406A2 (en) * | 1990-02-17 | 1991-08-28 | Hoechst Aktiengesellschaft | Process for enzymatic racemate separation of pantolacton |
| CN102229584A (en) * | 2011-04-19 | 2011-11-02 | 吴江 | Method for preparing D-(-)- or L-(+)-pantoic acid lactone by splitting pantoic acid lactone |
| CN108117532A (en) * | 2018-01-12 | 2018-06-05 | 重庆市碚圣医药科技股份有限公司 | A kind of synthetic method of the D-VB5 lactone of high-purity |
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