A method for synthesizing high-purity DL-panthenol

Abstract

The present invention belongs to the field of chemical engineering technology, and particularly relates to a method for synthesizing high-purity DL-panthenol. The method comprises the following steps: S1. Dewatering pretreatment of DL-pantolactone to make the water content in the DL-pantolactone raw material < 0.1%; S2. Using the dewatered DL-pantolactone and 3-aminopropanol as raw materials, with the molar ratio of the two being 1.02 to 1.05:1, and carrying out an acylation reaction in a temperature range of 60 to 90 °C after mixing, controlling the reaction time to be 2 to 3 h to obtain a DL-panthenol reaction solution; S3. After the acylation reaction is completed, adding a mixed solvent composed of ethyl acetate and water to the reaction system, heating to dissolve until clear, and then cooling to 10 to 20 °C for crystallization; filtering the crystallization solution to obtain wet DL-panthenol, and drying the wet product to obtain DL-panthenol. The DL-panthenol obtained by this method has a chromatographic purity > 99.5%, a yield as high as 96 to 98%, and there is no need to cool to a lower temperature during the synthesis.

Description

Technical Field

[0001] The present invention belongs to the technical field of chemical engineering, and particularly relates to a method for synthesizing high-purity DL-panthenol. Background Art

[0002] DL-panthenol is a precursor of provitamin B5, a white crystalline hygroscopic powder, which is easy to absorb moisture, soluble in water, ethanol, methanol, etc., and soluble in chloroform and ether. It can promote the metabolism of human proteins, fats, and sugars, protect the skin and mucous membranes, improve the color and luster of hair, and prevent the occurrence of diseases. It is widely used in the pharmaceutical, food, and cosmetic industries.

[0003] In the traditional process of DL-panthenol, due to the water content in the used DL-pantolactone, during the acylation reaction, DL-pantolactone will hydrolyze into DL-pantothenic acid, and DL-pantothenic acid will be introduced into DL-panthenol during the crystallization process, resulting in an increase in impurity content. In current industrial production, methanol / ethanol is usually used as the crystallization solvent. However, due to the high solubility of DL-panthenol in methanol / ethanol, not only a lower crystallization temperature is required during the crystallization process, which increases energy consumption, but also violent precipitation easily occurs during the crystal precipitation process, leading to an increase in impurity content and difficult filtration; and due to the high solubility of DL-panthenol in methanol / ethanol, the yield in a single batch production is only about 75%. Summary of the Invention

[0004] The purpose of the present invention is to provide a method for synthesizing high-purity DL-panthenol. The DL-panthenol obtained by this method has a chromatographic purity > 99.5%, a yield as high as 96 - 98%, and no need to cool down to a lower temperature during the synthesis, solving the technical problems in the prior art that when using methanol / ethanol as the crystallization solvent, a lower crystallization temperature is required and violent precipitation easily occurs.

[0005] The technical solution adopted by the present invention to solve its technical problems is as follows:

[0006] A method for synthesizing high-purity DL-panthenol, the method comprising the following steps:

[0007] S1. Dewatering pretreatment of DL-pantolactone

[0008] Concentrate DL-pantolactone under negative pressure at a vacuum degree of -0.092 to -0.098 MPa and a temperature of 100 to 120 °C for 2 to 3 h, so that the water content in the DL-pantolactone raw material < 0.1%;

[0009] S2. Using the dewatered DL-pantolactone and 3-aminopropanol as raw materials, the molar ratio of the two in the feed is 1.02 - 1.05:1. After mixing, carry out an acylation reaction within the temperature range of 60 to 90 °C, control the reaction time to be 2 to 3 h, and obtain a DL-panthenol reaction solution;

[0010] The main raw materials for the reaction are DL-pantolactone and 3-aminopropanol, and DL-pantolactone is in excess.

[0011] S3. After the acylation reaction is completed, a mixed solvent composed of ethyl acetate and water is added to the reaction system. After heating to dissolve clearly, the temperature is lowered to 10-20 °C for crystallization; the crystallization liquid is filtered to obtain wet DL-panthenol, and the wet product is dried to obtain DL-panthenol.

[0012] The main impurity residue in DL-panthenol is DL-pantothenic acid. This impurity is caused by the hydrolysis reaction of DL-pantolactone with water. After the moisture in the DL-pantolactone raw material is reduced, the residue of the impurity DL-pantothenic acid is greatly reduced; the present invention reduces the total generation amount of this impurity by reducing the moisture in the material. The main raw materials for the reaction in S2 are DL-pantolactone and 3-aminopropanol, and DL-pantolactone is in excess.

[0013] Preferably, the acylation reaction is a solvent-free reaction.

[0014] Preferably, in S3, in the mixed solvent composed of ethyl acetate and water, the weight ratio of ethyl acetate to the DL-panthenol reaction solution is 1.2-1.5:1, and the optimal value is 1.3:1; the feeding amount of water is 6%-10% of the weight of the DL-panthenol reaction solution, and the optimal value is 8%.

[0015] Preferably, when heating to dissolve clearly in S3, the temperature is raised to 55-65 °C to completely dissolve the reaction solution and the solvent. After the dissolution is completed, the temperature is lowered uniformly and slowly, and seed crystals are added when the temperature is controlled at 45-50 °C during the cooling process.

[0016] The beneficial effects of the present invention are as follows: The present invention mixes DL-pantolactone after pre-treatment of water removal with 3-aminopropanol and reacts at 60-90 °C for 2-3 h. After the reaction is completed, an ethyl acetate and water system is added for dissolution. After the dissolution is completed, the temperature is lowered for crystallization, and after filtration and drying, DL-panthenol is produced. Using the preparation method in the present invention, the obtained DL-panthenol content > 99.5%, the yield is as high as 96-98%, and there is no need to lower the temperature to a relatively low temperature. The operation is simple and suitable for industrial production. Brief Description of the Drawings

[0017] Figure 1 It is the liquid chromatogram of the DL-panthenol product prepared in Example 1 of the present invention. Detailed Description of the Embodiments

[0018] The following are specific examples to further specifically illustrate the technical solutions of the present invention. It should be understood that the implementation of the present invention is not limited to the following examples, and any form of modification and / or change made to the present invention will fall within the protection scope of the present invention.

[0019] In the present invention, unless otherwise specified, all parts and percentages are in weight units, and the equipment and raw materials used can be purchased from the market or are commonly used in the art. The methods in the following examples are conventional methods in the art unless otherwise specified.

[0020] Example 1

[0021] 148 g of DL-pantolactone on a dry basis was charged into a clean and dry reaction flask. After evacuating to a vacuum, the temperature was raised to 100 °C under a vacuum of -0.095 MPa. After the temperature reached 100 °C, it was held for 1 hour to remove moisture. Then, the temperature was lowered to 70 - 75 °C, and 82.1 g of 3-aminopropanol was added dropwise. After the dropwise addition was completed, the reaction temperature was controlled at 80 - 85 °C and the reaction was carried out for 2.5 hours. After the reaction ended, 340 g of ethyl acetate and 14 g of water were added, and the temperature was controlled at 60 °C and stirred until dissolved. After dissolution, the temperature was lowered to 50 °C, 0.2 g of seed crystal was added, and the temperature was slowly lowered to 15 °C. After the temperature reduction ended, it was held for 1 hour for crystallization. Then, the crystallization solution was filtered, and the wet product was dried by blowing air to obtain 218.4 g of DL-panthenol, with a yield of 97.3%. DL-pantolactone residue was not detected, and the purity of DL-panthenol was 99.87% (see Figure 1 ).

[0022] Example 2

[0023] 145 g of DL-pantolactone on a dry basis was charged into a clean and dry reaction flask. After evacuating to a vacuum, the temperature was raised to 100 °C under a vacuum of -0.095 MPa. After the temperature reached 100 °C, it was held for 1 hour to remove moisture. Then, the temperature was lowered to 70 - 75 °C, and 82 g of 3-aminopropanol was added dropwise. After the dropwise addition was completed, the reaction temperature was controlled at 80 - 85 °C and the reaction was carried out for 2.5 hours. After the reaction ended, 300 g of ethyl acetate and 14 g of water were added, and the temperature was controlled at 60 °C and stirred until dissolved. After dissolution, the temperature was lowered to 50 °C, 0.2 g of seed crystal was added, and the temperature was slowly lowered to 18 °C. After the temperature reduction ended, it was held for 1 hour for crystallization. Then, the crystallization solution was filtered, and the wet product was dried by blowing air to obtain 216.2 g of DL-panthenol, with a yield of 96.5%. DL-pantolactone residue was not detected, and the purity of DL-panthenol was 99.9%.

[0024] Example 3

[0025] Into a clean and dry reaction flask, 198 g of DL-pantolactone on an anhydrous basis was charged. After evacuating to a vacuum, the temperature was raised to 100 °C under a vacuum of -0.095 MPa. After the temperature reached 100 °C, it was held for 1 hour to remove moisture. Then the temperature was lowered to 70 - 75 °C, and 110 g of 3-aminopropanol was added dropwise. After the addition was complete, the reaction temperature was controlled at 80 - 85 °C and held for 3 hours. After the reaction was completed, 400 g of ethyl acetate and 21 g of water were added, and the temperature was controlled at 60 °C and stirred until dissolved. After complete dissolution, the temperature was lowered to 47 °C, 0.3 g of seed crystal was added, and the temperature was slowly lowered to 11 °C. After the temperature reduction was completed, it was held for 1 hour for crystallization. Then the crystallization solution was filtered, and the wet product was dried by blowing air to obtain 294.3 g of DL-panthenol, with a yield of 97.9%. Residual DL-pantolactone was not detected, and the purity of DL-panthenol was 99.8%.

[0026] Example 4

[0027] Into a clean and dry reaction flask, 195 g of DL-pantolactone on an anhydrous basis was charged. After evacuating to a vacuum, the temperature was raised to 100 °C under a vacuum of -0.095 MPa. After the temperature reached 100 °C, it was held for 1 hour to remove moisture. Then the temperature was lowered to 70 - 75 °C, and 110 g of 3-aminopropanol was added dropwise. After the addition was complete, the reaction temperature was controlled at 80 - 85 °C and held for 2 hours. After the reaction was completed, 400 g of ethyl acetate and 21 g of water were added, and the temperature was controlled at 60 °C and stirred until dissolved. After complete dissolution, the temperature was lowered to 45 °C, 0.3 g of seed crystal was added, and the temperature was slowly lowered to 14 °C. After the temperature reduction was completed, it was held for 1 hour for crystallization. Then the crystallization solution was filtered, and the wet product was dried by blowing air to obtain 292 g of DL-panthenol, with a yield of 97.1%. Residual DL-pantolactone was not detected, and the purity of DL-panthenol was 99.8%.

[0028] Comparative Example:

[0029] Into a clean and dry reaction flask, 148 g of DL-pantolactone on an anhydrous basis was charged and heated to 70 - 75 °C for stirring and melting. After the DL-pantolactone melted, 82.1 g of 3-aminopropanol was added dropwise. After the addition was complete, the reaction temperature was controlled at 80 - 85 °C and held for 2.5 hours. After the reaction was completed, the temperature was lowered to 40 °C, 225 g of methanol was added, and it was stirred until dissolved. After complete dissolution, the temperature was lowered to 0 °C, and 0.5 g of seed crystal was added. After the seed crystal was added, the temperature was slowly lowered to -10 °C. After the temperature reduction was completed, it was held for 1 hour for crystallization. Then the crystallization solution was filtered to obtain 246.71 g of filtrate and 180.03 g of wet DL-panthenol. The content of DL-panthenol in the filtrate was 22.1%. The wet product was dried by blowing air to obtain 167.79 g of DL-panthenol, with a single-pass yield of 74.6%. Residual DL-pantolactone was 0.21%, and the purity of DL-panthenol was 99.8%.

[0030] The filtrate produced is concentrated under reduced pressure until the remaining weight is 110 g. After concentration, the temperature is lowered to -10 °C for crystallization. 36.8 g of wet DL-panthenol is obtained by filtration. After drying, 34.4 g of DL-panthenol is obtained, with a DL-pantothenic acid residue of 0.48% and a DL-panthenol purity of 99.6%. The filtrate has a relatively dark color and cannot be used further.

[0031] A total of 202.19 g of DL-panthenol is produced by two crystallizations, with a yield of 89.89%.

[0032] In this specification, each embodiment is described in a progressive manner. The key point of each embodiment is to illustrate the differences from other embodiments. For the same or similar parts among the embodiments, reference can be made to each other. For the devices disclosed in the embodiments, since they correspond to the methods disclosed in the embodiments, the description is relatively simple. For the relevant parts, reference can be made to the description in the method section.

[0033] The above has introduced in detail a method for synthesizing high-purity DL-panthenol provided by the present invention. Specific examples are used herein to elaborate on the principle and implementation mode of the present invention. The description of the above embodiments is only used to help understand the method and its core idea of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and modifications can be made to the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention.

Claims

1. A method for synthesizing high-purity DL-panthenol, characterized in that: The method comprises the following steps: S1. Pretreatment of DL-pantolactone for water removal Concentrate DL-pantolactone under negative pressure at a vacuum degree of -0.092 to -0.098 MPa and a temperature of 100 to 120°C for 2 to 3 hours to reduce the moisture content of the DL-pantolactone raw material to less than 0.1%; S2. Using dehydrated DL-pantolactone and 3-aminopropanol as raw materials, the molar ratio of the two is 1.02-1.05:1, mixing them, and conducting an acylation reaction at a temperature range of 60-90° C. for 2-3 hours to obtain a DL-panthenol reaction solution; the acylation reaction is a solvent-free reaction; S3. After the acylation reaction is completed, a mixed solvent consisting of ethyl acetate and water is added to the reaction system, the temperature is raised to dissolve, and then the temperature is lowered to 10-20°C for crystallization; the crystallized liquid is filtered to obtain a DL-panthenol wet product, and the wet product is dried to obtain DL-panthenol; in the mixed solvent consisting of ethyl acetate and water, the weight ratio of ethyl acetate to DL-panthenol reaction liquid is 1.2-1.5:1, and the amount of water added is 6%-10% of the weight of the DL-panthenol reaction liquid.

2. The method for synthesizing high-purity DL-panthenol according to claim 1, wherein: In S3, in the mixed solvent consisting of ethyl acetate and water, the weight ratio of ethyl acetate to the DL panthenol reaction liquid is 1.3:1; and the amount of water added is 8% by weight of the DL panthenol reaction liquid.

3. The method for synthesizing high-purity DL-panthenol according to claim 1, wherein: When S3 is heated to dissolve, the temperature is raised to 55-65°C to completely dissolve the reaction liquid and the solvent. After the dissolution is completed, the temperature is slowly lowered at a uniform speed. During the cooling process, the temperature is controlled at 45-50°C and the seed crystal is added.

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