A crystallization purification method to improve the stability of 3-o-ethyl ascorbic acid

Abstract

This invention relates to the field of purification technology and discloses a crystallization purification method for improving the stability of 3-o-ethyl ascorbic acid. The method includes recrystallizing crude 3-o-ethyl ascorbic acid under the action of a main solvent and an antisolvent to obtain highly stable 3-o-ethyl ascorbic acid. The main solvent is selected from one or more of ethanol, acetone, N,N-dimethylformamide, and N,N-dimethylacetamide; the antisolvent is selected from one or more of petroleum ether, diethyl ether, n-hexane, ethyl acetate, and chloroform. The main solvent is ethanol, and the antisolvent is ethyl acetate. The purification method of this invention exhibits significant advantages in improving solubility, thermal stability, light stability, crystallization yield, and purity, and is suitable for the purification of highly stable 3-o-ethyl ascorbic acid.

Description

Technical Field

[0001] This invention relates to the field of purification technology, specifically to a crystallization purification method for improving the stability of 3-o-ethyl ascorbic acid. Background Technology

[0002] In the cosmetics and skincare industry, 3-o-ethyl ascorbic acid is commonly used as an antioxidant and whitening agent to help reduce oxidative damage and pigmentation in the skin. When this ingredient is added to skincare products, the products require high-temperature manufacturing processes, such as mixing, heating, and sterilization.

[0003] In this context, thermal stability is crucial for the efficacy and maintenance of the activity of 3-o-ethyl ascorbic acid. If 3-o-ethyl ascorbic acid is unstable under high-temperature conditions, it may decompose or lose its antioxidant properties, thereby affecting the product's efficacy.

[0004] Therefore, in the manufacture of cosmetics and skincare products, it is necessary to select 3-o-ethyl ascorbic acid with good thermal stability to ensure its stability and activity under high-temperature conditions. However, the thermal stability of 3-o-ethyl ascorbic acid crystals purified by traditional purification methods is not high. Therefore, those skilled in the art have proposed a crystallization purification method to improve the stability of 3-o-ethyl ascorbic acid. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a crystallization purification method to improve the stability of 3-o-ethyl ascorbic acid, solving the problem of low thermal stability of 3-o-ethyl ascorbic acid crystals purified by traditional purification methods.

[0006] To achieve the above objectives, the present invention provides the following technical solution: a crystallization purification method for improving the stability of 3-o-ethyl ascorbic acid, comprising: recrystallizing crude 3-o-ethyl ascorbic acid under the action of a main solvent and an antisolvent to obtain highly stable 3-o-ethyl ascorbic acid;

[0007] The main solvent is selected from one or more of ethanol, acetone, N,N-dimethylformamide, and N,N-dimethylacetamide; the antisolvent is selected from one or more of petroleum ether, diethyl ether, n-hexane, ethyl acetate, and chloroform.

[0008] Preferably, the main solvent is ethanol and the antisolvent is ethyl acetate.

[0009] Preferably, the specific steps of the method are as follows:

[0010] (1) Dissolve crude 3-o-ethyl ascorbic acid in the main solvent by stirring;

[0011] (2) Add a small amount of 3-o-ethyl ascorbic acid seed crystals of known crystal form to the antisolvent as a crystallization starting point;

[0012] (3) Slowly add the antisolvent to the main solvent to achieve antisolvent precipitation;

[0013] (4) After the crystallization process is completed, the crystals are separated and then cleaned with an antisolvent. After freeze-drying, highly stable 3-o-ethyl ascorbic acid is obtained.

[0014] Preferably, the ratio of the main solvent to crude 3-o-ethyl ascorbic acid in step (1) is 10 to 50:1.

[0015] Preferably, the dissolution temperature in step (1) is 40-80℃ and the stirring speed is 200-500rpm.

[0016] Preferably, the number of seed crystals in step (2) can account for 1 to 5% of the total.

[0017] Preferably, the antisolvent is added at a rate of 1 to 5 mL / min in step (3).

[0018] Preferably, the crystal separation in step (4) is performed by centrifugation at 4000-8000 rpm.

[0019] Preferably, the freeze-drying temperature in step (4) is -50 to -80°C and the pressure is 0.1 to 1 mbar.

[0020] Preferably, step (2) further includes using an ultrasonic device to promote crystallization, with the power of the ultrasonic wave being 20 to 100 W and the operating frequency being 20 to 40 kHz.

[0021] This invention provides a crystallization purification method to improve the stability of 3-o-ethyl ascorbic acid. It has the following beneficial effects:

[0022] The purification method of the present invention exhibits significant advantages in improving solubility, thermal stability, light stability, crystallization yield and purity, and is suitable for the purification process of highly stable 3-o-ethyl ascorbic acid. Detailed Implementation

[0023] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0024] Example 1:

[0025] 1. Dissolve 10 g of crude 3-o-ethyl ascorbic acid in 500 mL of ethanol, stirring at 60 °C and 300 rpm.

[0026] 2. Add 0.5 g of 3-o-ethyl ascorbic acid seed crystals of known crystal form to ethyl acetate (100 mL) as the crystallization starting point.

[0027] 3. Slowly add ethyl acetate to the ethanol at a rate of 2 mL / min to achieve antisolvent precipitation.

[0028] 4. After the crystallization process is complete, separate the crystals and wash them with ethyl acetate.

[0029] 5. Freeze-dry the crystals at a temperature of -70℃ and a pressure of 0.2 mbar.

[0030] 6. Highly stable 3-o-ethyl ascorbic acid was obtained.

[0031] Example 2:

[0032] 1. Dissolve 10g of crude 3-o-ethyl ascorbic acid in 500mL of acetone, stirring at 50℃ and 400rpm.

[0033] 2. Add 0.5 g of 3-o-ethyl ascorbic acid seed crystals of known crystal form to n-hexane (100 mL) as the crystallization starting point.

[0034] 3. Slowly add n-hexane to acetone at a rate of 3 mL / min to achieve antisolvent precipitation.

[0035] 4. After the crystallization process is complete, separate the crystals and wash them with n-hexane.

[0036] 5. Freeze-dry the crystals at a temperature of -60℃ and a pressure of 0.5mbar.

[0037] 6. Highly stable 3-o-ethyl ascorbic acid was obtained.

[0038] Example 3:

[0039] 1. Dissolve 10 g of crude 3-o-ethyl ascorbic acid in 500 mL of ethanol. Stir at 70 °C and 500 rpm.

[0040] 2. Add 0.5 g of 3-o-ethyl ascorbic acid seed crystals of known crystalline form to chloroform (100 mL) as the starting point for crystallization.

[0041] 3. Slowly add chloroform to the ethanol at a rate of 5 mL / min to achieve the precipitation of the antisolvent.

[0042] 4. After the crystallization process is complete, separate the crystals and clean them with chloroform.

[0043] 5. Freeze-dry the crystals at a temperature of -50℃ and a pressure of 0.8mbar.

[0044] 6. Highly stable 3-o-ethyl ascorbic acid was obtained.

[0045] Example 4:

[0046] 1. Dissolve 10 g of crude 3-o-ethyl ascorbic acid in 500 mL of N,N-dimethylformamide. Stir at 55 °C and 300 rpm.

[0047] 2. Add 0.5 g of 3-o-ethyl ascorbic acid seed crystals of known crystalline form to ether (100 mL) as the crystallization starting point.

[0048] 3. Slowly add diethyl ether to N,N-dimethylformamide at a rate of 4 mL / min to achieve antisolvent precipitation.

[0049] 4. After the crystallization process is complete, separate the crystals and clean them with ether.

[0050] 5. The crystals were freeze-dried at a temperature of -65℃ and a pressure of 0.3 mbar.

[0051] 6. Highly stable 3-o-ethyl ascorbic acid was obtained.

[0052] Example 5:

[0053] 1. Dissolve 10 g of crude 3-o-ethyl ascorbic acid in 500 mL of N,N-dimethylacetamide. Stir at 45 °C and 200 rpm.

[0054] 2. Add 0.5 g of 3-o-ethyl ascorbic acid seed crystals of known crystal form to petroleum ether (100 mL) as the crystallization starting point.

[0055] 3. Slowly add petroleum ether to N,N-dimethylacetamide at a rate of 3 mL / min to achieve antisolvent precipitation.

[0056] 4. After the crystallization process is complete, separate the crystals and clean them with petroleum ether.

[0057] 5. The crystals were freeze-dried at a temperature of -55℃ and a pressure of 0.6 mbar.

[0058] 6. Highly stable 3-o-ethyl ascorbic acid was obtained.

[0059] Example 6:

[0060] 1. Dissolve 10 g of crude 3-o-ethyl ascorbic acid in 500 mL of ethanol, stirring at 60 °C and 300 rpm.

[0061] 2. Add 0.5 g of 3-o-ethyl ascorbic acid seed crystals of known crystal form to a mixed solvent of ethyl acetate and petroleum ether (100 mL) as the crystallization starting point.

[0062] 3. Slowly add a mixture of ethyl acetate and petroleum ether to the ethanol at a rate of 4 mL / min to achieve antisolvent precipitation.

[0063] 4. After the crystallization process is complete, separate the crystals and clean them using a mixed solvent of ethyl acetate and petroleum ether.

[0064] 5. Freeze-dry the crystals at a temperature of -70℃ and a pressure of 0.2 mbar.

[0065] 6. Highly stable 3-o-ethyl ascorbic acid was obtained.

[0066] Example 7:

[0067] 1. Dissolve 10 g of crude 3-o-ethyl ascorbic acid in a mixed solvent (500 mL) of ethanol and N,N-dimethylformamide, stirring at 65 °C and 350 rpm.

[0068] 2. Add 0.5 g of 3-o-ethyl ascorbic acid seed crystals of known crystal form to a mixed solvent (100 mL) of n-hexane and ethyl acetate as the crystallization starting point.

[0069] 3. Slowly add a mixture of hexane and ethyl acetate to a mixture of ethanol and N,N-dimethylformamide at a rate of 3 mL / min to achieve antisolvent precipitation.

[0070] 4. After the crystallization process is complete, separate the crystals and clean them using a mixed solvent of n-hexane and ethyl acetate.

[0071] 5. Freeze-dry the crystals at a temperature of -60℃ and a pressure of 0.5mbar.

[0072] 6. Highly stable 3-o-ethyl ascorbic acid was obtained.

[0073] Example 8:

[0074] 1. Dissolve 10 g of crude 3-o-ethyl ascorbic acid in a mixed solvent (500 mL) of acetone and N,N-dimethylacetamide, stirring at 55 °C and 400 rpm.

[0075] 2. Add 0.5 g of 3-o-ethyl ascorbic acid seed crystals of known crystal form to a mixed solvent of chloroform and petroleum ether (100 mL) as the crystallization starting point.

[0076] 3. Slowly add a mixture of chloroform and petroleum ether to a mixture of acetone and N,N-dimethylacetamide at a rate of 4 mL / min to achieve antisolvent precipitation.

[0077] 4. After the crystallization process is complete, separate the crystals and clean them using a mixed solvent of chloroform and petroleum ether.

[0078] 5. The crystals were freeze-dried at a temperature of -65℃ and a pressure of 0.3 mbar.

[0079] 6. Highly stable 3-o-ethyl ascorbic acid was obtained.

[0080] Comparative experimental example:

[0081] The 3-o-ethyl ascorbic acid obtained after purification in Examples 1-8 was determined as follows:

[0082] Solubility: The solubility of each crystal in Examples 1-8 was determined under the same conditions.

[0083] Thermal stability: The weight loss of the crystal during the heating process was determined using a thermogravimetric analyzer.

[0084] Crystallization yield: The crystallization yield is calculated based on the quality of the crystals and the quality of the raw materials.

[0085] Purity analysis: The purity of the crystals was determined using high performance liquid chromatography.

[0086] Photolysis stability: The photolysis stability of a sample is assessed by observing its color change after exposing it to ultraviolet or visible light.

[0087] The measurement results are shown in the table below:

[0088]

[0089]

[0090] Based on the data from comparative experiments and the results of photolysis stability observations, it can be concluded that in the eight examples, when ethanol was used as the main solvent and ethyl acetate as the antisolvent, the purified 3-o-ethyl ascorbic acid exhibited the best stability, including higher solubility, lower thermal weight loss, higher crystallization yield, higher purity, and relatively better photolysis stability. The purification method of this invention demonstrates significant advantages in improving solubility, thermal stability, photostability, crystallization yield, and purity, and is suitable for the purification of highly stable 3-o-ethyl ascorbic acid.

[0091] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A crystallization purification method for improving the stability of 3-o-ethylascorbic acid, characterized in that, include: The crude 3-o-ethyl ascorbic acid was recrystallized under the action of a main solvent and an antisolvent to obtain highly stable 3-o-ethyl ascorbic acid. The main solvent is selected from one or more of ethanol, acetone, N,N-dimethylformamide, and N,N-dimethylacetamide; the antisolvent is selected from one or more of petroleum ether, diethyl ether, n-hexane, ethyl acetate, and chloroform. The specific steps of the method are as follows: (1) Dissolve crude 3-o-ethyl ascorbic acid in the main solvent by stirring; (2) Add a small amount of 3-o-ethyl ascorbic acid seed crystals of known crystal form to the antisolvent as a crystallization starting point; (3) Slowly add the antisolvent to the main solvent to achieve antisolvent precipitation; (4) After the crystallization process is completed, the crystals are separated and then washed with an antisolvent. After freeze-drying, highly stable 3-o-ethyl ascorbic acid is obtained. In step (2), the number of seed crystals accounts for 1-5% of the total. In step (3), the antisolvent is added at a rate of 1 to 5 mL / min.

2. The crystallization and purification method for improving the stability of 3-o-ethylascorbic acid according to claim 1, characterized in that, The main solvent is ethanol, and the antisolvent is ethyl acetate.

3. The crystallization and purification method for improving the stability of 3-o-ethylascorbic acid according to claim 1, characterized in that, In step (1), the ratio of the main solvent to crude 3-o-ethyl ascorbic acid is 10 to 50:

1.

4. The crystallization and purification method for improving the stability of 3-o-ethylascorbic acid according to claim 3, characterized in that, In step (1), the dissolution temperature is 40-80℃ and the stirring speed is 200-500rpm.

5. The crystallization and purification method for improving the stability of 3-o-ethylascorbic acid according to claim 1, characterized in that, In step (4), crystal separation is performed by centrifugation at 4000–8000 rpm.

6. The crystallization and purification method for improving the stability of 3-o-ethylascorbic acid according to claim 1, characterized in that, In step (4), the freeze-drying temperature is -50 to -80°C and the pressure is 0.1 to 1 mbar.

7. The crystallization and purification method for improving the stability of 3-o-ethylascorbic acid according to claim 1, characterized in that, Step (2) also includes using an ultrasonic device to promote crystallization, with the power of the ultrasonic wave being 20 to 100 W and the operating frequency being 20 to 40 kHz.

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