CN110835309A

CN110835309A - Crystallization method of DL-panthenol

Info

Publication number: CN110835309A
Application number: CN201911188417.4A
Authority: CN
Inventors: 段小瑞; 汪洪湖; 赵毅; 杨鹤; 李涛
Original assignee: ANHUI TIGER BIOTECHNOLOGY Co Ltd
Current assignee: ANHUI TIGER BIOTECHNOLOGY Co Ltd
Priority date: 2019-11-28
Filing date: 2019-11-28
Publication date: 2020-02-25
Anticipated expiration: 2039-11-28
Also published as: CN110835309B

Abstract

The invention relates to a crystallization method of DL-panthenol, which comprises the following steps: (1) carrying out acylation reaction by taking DL-pantolactone and 3-aminopropanol as raw materials and absolute ethyl alcohol as a solvent to obtain a DL-panthenol solution; (2) and concentrating the DL-panthenol solution, standing at-5 ℃ for crystallization, collecting crystals, and drying. The crystallization method provided by the invention has the advantages of simple and convenient operation, high product yield and purity and the like.

Description

Crystallization method of DL-panthenol

Technical Field

The invention relates to the field of chemical production, and particularly relates to a crystallization method of DL-panthenol.

Background

DL-panthenol is a precursor of vitamin B5, and is a white powdery solid with slightly peculiar smell, and is easy to absorb moisture, and is easily soluble in water, ethanol, methanol and propylene glycol, soluble in chloroform and ether, slightly soluble in glycerin, and insoluble in vegetable oil, mineral oil and fat. Is relatively stable in air and under light. The melting point is 64.5-68.5 ℃, the content is 99.0-102.0%, the specific rotation is-0.05- +0.05, and the limit of 3-aminopropanol is less than or equal to 0.1%.

DL-panthenol is racemic mixture of L-panthenol and D-panthenol and may be used widely in medicine, food and cosmetics. In the pharmaceutical industry, it is used as vitamin B medicine and can be directly added into cosmetics. DL-panthenol, D-panthenol and D-panthenol ethyl ether are widely used in cosmetic series, wherein D-panthenol and D-panthenol ethyl ether are in liquid form, and DL-panthenol has solid and liquid forms. Compared with DL-panthenol liquid, the DL-panthenol solid has the advantages of stable property, convenient transportation, simple and convenient packaging and free weighing.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provide a method for crystallizing DL-panthenol.

Specifically, the crystallization method provided by the invention comprises the following steps:

(1) carrying out acylation reaction by taking DL-pantolactone and 3-aminopropanol as raw materials and absolute ethyl alcohol as a solvent to obtain a DL-panthenol solution;

(2) and concentrating the DL-panthenol solution, standing at-5 ℃ for crystallization, collecting crystals, and drying.

In order to ensure that the starting materials react sufficiently to reduce the impurity content in the crystals, the reaction conditions of step (1) are preferably carried out in the present invention. Specifically, the feeding molar ratio of the DL-pantoic acid lactone to the 3-aminopropanol is preferably 1: 1. when the feed weight of the absolute ethyl alcohol is the same as the weight of DL-panthenol, the cost can be saved on the basis of ensuring that the reaction is fully carried out. The acylation reaction is carried out at 65-85 ℃ with reflux stirring, preferably for 4-8 h.

The method provided by the invention firstly concentrates the solution obtained by the reaction, and can improve the crystallization efficiency after removing part of the solvent. According to the invention, a great deal of practice shows that when the concentration is carried out to the extent that the Baume degree of the solution at 30 ℃ is 10-12, the subsequent cooling crystallization is most facilitated and the higher yield of the product is ensured.

The invention further optimizes the crystallization scheme after concentration to ensure that the crystals are fully separated out and improve the yield on the basis of ensuring the purity of the crystals.

As a preferable embodiment of the present invention, the standing crystallization specifically includes: standing at 0-4 ℃, precipitating crystals, stirring and cooling to below 0 ℃, preferably-5 to-3 ℃. The standing time is preferably 20-30 h. According to the preferred scheme, after the system forms stable crystals at low temperature, stirring is started, the effect of crystallization without sticking to walls can be achieved, and further cooling is carried out, so that crystals can be further and fully separated out.

As a preferable embodiment of the present invention, the standing crystallization specifically includes: standing at 0-4 ℃, precipitating crystals, stirring and preserving heat. The standing time is preferably 20-30 h, and the heat preservation time is preferably 10-15 h. The preferred scheme ensures that the system forms stable crystals at low temperature, then starts stirring, can achieve the effect of crystallization without sticking to the wall, continues heat preservation crystallization, and can ensure that the crystals are fully separated out.

As a preferable embodiment of the present invention, the standing crystallization specifically includes: standing at-5 to-3 ℃. The standing time is preferably 20-30 h. In this preferred embodiment, the crystals can be sufficiently precipitated by crystallizing the crystals at a low temperature for a long time in a low temperature environment of 0 ℃ or lower.

As a preferred embodiment of the present invention, the method comprises the steps of:

adding 80-85 parts of absolute ethyl alcohol, 50-55 parts of DL-pantoic acid lactone and 28-32 parts of 3-aminopropanol into a reaction container in sequence, refluxing and stirring for 4-6 hours at 65-70 ℃, concentrating until the Baume degree is 10-12 at 30 ℃, standing for 20-30 hours at 0-4 ℃, precipitating crystals, stirring and cooling to below 0 ℃, pouring out, filtering, and drying. Preferably, the concentrated solution is kept stand at 0 ℃ for 24 hours, crystals are precipitated, and the temperature is reduced to-5 ℃ by stirring.

In the scheme, the parts are parts by mass and can be mass units commonly used in the field such as g, kg and the like.

The crystallization method provided by the invention takes DL-pantoic acid lactone and 3-aminopropanol as raw materials, takes absolute ethyl alcohol as a solvent to carry out acylation reaction to generate DL-panthenol, and carries out low-temperature crystallization after concentration. The invention further controls the proportion of DL-panthenol and ethanol, and the invention achieves the purpose of crystallization without sticking to the wall by starting stirring after stable crystals are formed at low temperature and continuing low-temperature or cooling crystallization. The method provided by the invention is convenient to operate, is beneficial to industrial production and establishes an efficient method, and the quality of the product obtained by crystallization according to the method can reach the quality standard of United states Pharmacopeia.

Detailed Description

The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention.

Example 1

The embodiment provides a crystallization method of DL-panthenol, which specifically comprises the following steps: adding 82g of absolute ethyl alcohol, 52g of DL-pantolactone (value after purity reduction) and 30g of 3-aminopropanol (value after purity reduction) into a dry and clean 500ml single-mouth bottle in sequence, refluxing and stirring for 4h at 65 ℃, concentrating until the Baume degree is 12 at 30 ℃, standing for 24h at 0 ℃, crystallizing, stirring and cooling to-5 ℃, pouring out, filtering, and drying to obtain 60g of a product, wherein the yield is 77%.

The detection shows that the obtained DL-panthenol product has the specific rotation degree of 0, the residual quantity of 3-aminopropanol of less than or equal to 0.1 percent, the melting point of 65 ℃, the content of 99.5 percent, the drying weight loss of less than or equal to 0.5 percent, the heavy metal of less than or equal to 10ppm, and the product has no crystal form and no fluidity.

Example 2

The embodiment provides a crystallization method of DL-panthenol, which specifically comprises the following steps: in a dry and clean 500ml single-mouth bottle, 82g of absolute ethyl alcohol, 52g of DL-pantoic acid lactone (value after purity reduction) and 30g of 3-aminopropanol (value after purity reduction) are sequentially added, reflux and stirring are carried out for 4h at 65 ℃, then concentration is carried out until the Baume degree is 12 at 30 ℃, standing is carried out for 24h at-5 ℃, pouring out, suction filtration and drying are carried out, and 63g of product is obtained, wherein the yield is 73%.

Example 3

The embodiment provides a crystallization method of DL-panthenol, which specifically comprises the following steps: adding 82g of absolute ethyl alcohol, 52 gDL-pantoic acid lactone (after-purity value) and 30g of 3-aminopropanol (after-purity value) into a dry and clean 500ml single-mouth bottle in sequence, refluxing and stirring for 4h at 65 ℃, concentrating until the Baume degree is 12 at 30 ℃, standing for 24h at 0 ℃, crystallizing, stirring, keeping the temperature for 12h, performing suction filtration and drying to obtain 41g of a product, wherein the yield is 50%.

The detection shows that the obtained DL-panthenol product has the specific rotation degree of 0, the residual quantity of 3-aminopropanol of less than or equal to 0.1 percent, the melting point of 65 ℃, the content of 99.5 percent, the drying weight loss of less than or equal to 0.5 percent, the heavy metal of less than or equal to 10ppm, and is crystal-clear and has better fluidity.

Example 4

The embodiment provides a crystallization method of DL-panthenol, which specifically comprises the following steps: in a dry and clean 500ml single-mouth bottle, 82g of absolute ethyl alcohol, 52g of DL-pantoic acid lactone (value after purity reduction) and 30g of 3-aminopropanol (value after purity reduction) are sequentially added, reflux and stirring are carried out for 6h at 75 ℃, concentration is carried out until the Baume degree is 10 at 30 ℃, standing is carried out for 24h at-5 ℃, pouring, suction filtration and drying are carried out, and 63g of product is obtained, wherein the yield is 73%.

Example 5

The embodiment provides a crystallization method of DL-panthenol, which specifically comprises the following steps: adding 82g of absolute ethyl alcohol, 52g of DL-pantoic acid lactone (value after purity reduction) and 30g of 3-aminopropanol (value after purity reduction) into a dry and clean 500ml single-mouth bottle in sequence, refluxing and stirring for 8h at 85 ℃, concentrating until the Baume degree is 12 at 30 ℃, standing for 24h at 0 ℃, crystallizing, stirring, continuously preserving the temperature for 12h, carrying out suction filtration and drying to obtain 41g of material, wherein the yield is 50%.

Through detection, the obtained DL-panthenol product has the specific rotation degree of 0, the residual amount of 3-aminopropanol of less than or equal to 0.1 percent, the melting point of 65 ℃, the content of 99.5 percent, the drying weight loss of less than or equal to 0.5 percent, the heavy metal of less than or equal to 10ppm, and is crystal-clear and has better fluidity.

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

1. A method for crystallizing DL-panthenol, comprising the steps of:

2. The process according to claim 1, wherein the molar ratio of the DL-pantoic acid lactone to 3-aminopropanol is from 1: 1.

3. the process according to claim 1 or 2, wherein the anhydrous ethanol is fed in a weight equal to the weight of DL-panthenol.

4. The process according to claim 1, wherein the acylation reaction is carried out at 65-85 ℃ with reflux stirring, preferably for 4-8 h.

5. The method according to claim 1, wherein the concentration is in particular: concentrating until the Baume degree of the solution is 10-12 at 30 ℃.

6. The method according to any one of claims 1 to 5, wherein the standing crystallization is specifically: standing at 0-4 ℃, separating out crystals, stirring and cooling to below 0 ℃; preferably, the standing time is 20-30 h.

7. The method according to any one of claims 1 to 5, wherein the standing crystallization is specifically: standing at 0-4 ℃, separating out crystals, stirring and preserving heat; preferably, the standing time is 20-30 hours, and the heat preservation time is 10-15 hours.

8. The method according to any one of claims 1 to 5, wherein the standing crystallization is specifically: standing at-5 to-3 ℃; preferably, the standing time is 20-30 h.

9. The method according to claim 1, characterized by comprising the following specific steps: adding 80-85 parts of absolute ethyl alcohol, 50-55 parts of DL-pantoic acid lactone and 28-32 parts of 3-aminopropanol into a reaction container in sequence, refluxing and stirring for 4-6 hours at 65-70 ℃, concentrating until the Baume degree is 10-12 at 30 ℃, standing for 20-30 hours at 0-4 ℃, precipitating crystals, stirring and cooling to below 0 ℃, pouring out, filtering, and drying.

10. The method according to claim 9, wherein the concentration is followed by a standing at 0 ℃ for 24 hours, and after the precipitation of crystals, the mixture is stirred and cooled to-5 ℃.