Synthesis process of vitamin C ethyl ether

Abstract

The invention discloses a synthesis process of vitamin C ethyl ether, and belongs to the technical field of vitamin C derivative synthesis. The process comprises the following steps: taking L-ascorbic acid as a raw material, adding acetone, anhydrous cupric sulfate and acetyl chloride, and reacting for 1-2 hours at 38-40 DEG C under the protection of nitrogen to obtain a vitamin C protector; adding alkali, water, an alkylating reagent and absolute ethyl alcohol into the reaction product, reacting for 3 hours at 75-78 DEG C under the protection of nitrogen, and performing reduced pressure distillation to obtain a vitamin C protector etherate; and finally, hydrolyzing by using cationic resin, removing a protecting group, and recrystallizing by using ethyl acetate to obtain the vitamin C ethyl ether. Through the synergistic catalysis of anhydrous cupric sulfate and acetyl chloride, the reaction time is remarkably shortened, and the product purity and yield are improved. Through detection, the product purity is more than 99.5%, the total yield can reach more than 80%, and an efficient and economical method is provided for industrial production of vitamin C ethyl ether.

Description

Technical Field

[0001] The present invention belongs to the technical field of vitamin C derivative synthesis, and specifically relates to a synthesis process of vitamin C ethyl ether. Background Art

[0002] Vitamin C ethyl ether is a very useful vitamin C derivative. It is not only very stable in chemical properties and is a non-discoloring vitamin C derivative, but also an amphiphilic substance with both hydrophilic and lipophilic properties, which greatly expands its scope of application, especially in cosmetics. Vitamin C ethyl ether can easily penetrate into the dermis through the stratum corneum. After entering the body, it is very easy to be decomposed by biological enzymes in the body to exert the biological effects of vitamin C such as whitening, antioxidant and promoting collagen production. Therefore, vitamin C ethyl ether is one of the very important raw materials for anti-aging agents and whitening agents in cosmetics.

[0003] The synthesis methods of vitamin C ethyl ether include one-step method and three-step method. Patent CN100586941C discloses a separation and purification method for preparing 3-O-alkyl ascorbic acid ether from vitamin C by one-step method. The preparation steps include mixing vitamin C, alkali, and alkylating reagent in a solvent for reaction to synthesize 3-O-alkyl ascorbic acid ether. After the reaction, the reaction solvent is recovered, the residue is diluted with water, ion exchange is carried out using a strongly basic anion exchange resin column, washed with water, eluted with dilute acid, concentrated and crystallized to obtain purified vitamin C ethyl ether. The reaction products of this method are relatively complex, the separation and purification are difficult, the yield is low, and it is difficult to realize industrial production. The common method for synthesizing vitamin C ethyl ether is the three-step method. Patent CN103113333B discloses a synthesis method of vitamin C ethyl ether. First, using vitamin C as the raw material, acetone dimethyl acetal as the reactant, DMSO as the solvent, and under the action of a catalyst, the hydroxyl groups at the 5th and 6th positions of vitamin C are protected. Then, alkali and alkylating reagent are added for reaction to form an ether bond at the 3rd hydroxyl group. Finally, the protecting groups at the 5th and 6th positions are removed by acid treatment, and vitamin C ethyl ether is obtained by crystallization with a fat-soluble solvent. The total yield of the three steps is 50%-50.4%. Patent CN113214197B discloses a preparation method of vitamin C ethyl ether. First, using vitamin C as the starting material, cyclopentanone as the reactant and solvent, 5,6-O-cyclopentyl-ascorbic acid is obtained under the catalysis of acetyl chloride. Then, thionyl chloride, ethanol and triethylamine are added for reaction to obtain 3-O-ethyl-5,6-O-cyclopentyl-ascorbic acid ether. Finally, the protecting group is removed by reaction with dilute hydrochloric acid, and recrystallized with ethanol to obtain vitamin C ethyl ether. Patent CN112142697B discloses a production process of vitamin C ethyl ether. Using vitamin C as the starting material, it is protected by acetone, etherified and hydrolyzed to remove the protecting group to obtain vitamin C ethyl ether. The third step is to use concentrated hydrochloric acid for hydrolysis to remove the protecting group, and recrystallize with n-butanol. The yield of vitamin C ethyl ether can reach more than 65%.

[0004] Currently, the reaction time for vitamin C to react with acetone to form the 5,6-O-isopropylidene-L-ascorbic acid intermediate usually takes 3 - 5 hours. This long reaction time not only increases energy consumption but also limits production efficiency. The long reaction time may lead to an increase in by-products, reduce the purity of the target product, and thus affect subsequent purification steps. At the same time, in the prior art, after removing the protecting group through ion exchange resin or dilute hydrochloric acid, multiple crystallizations are required to obtain high-purity vitamin C ethyl ether. This process is time-consuming and complex, resulting in an extended production cycle. In addition, due to multiple crystallization and purification steps, the overall yield of the product is usually only 50% - 60%. This not only increases production costs but also limits the feasibility of large-scale industrial production. Summary of the Invention

[0005] 1. Problems to be Solved

[0006] Aiming at the deficiencies of the prior art, the purpose of the present invention is to provide an improved synthesis process of vitamin C ethyl ether to solve the following key problems:

[0007] Shorten the reaction time: In the existing process, the reaction time for vitamin C to react with acetone to form the 5,6-O-isopropylidene-L-ascorbic acid intermediate is relatively long, usually taking 3 - 5 hours. The present invention aims to significantly reduce the reaction time and improve production efficiency by optimizing the catalyst combination.

[0008] Improve purification efficiency and yield: The prior art requires multiple crystallizations and complex purification steps to obtain high-purity vitamin C ethyl ether, resulting in a low yield (usually 50% - 60%). The present invention improves the purification method, reduces the number of crystallizations, and improves the purity and yield of the final product.

[0009] To achieve the above objectives, during the reaction of vitamin C with acetone, anhydrous copper sulfate and acetyl chloride are introduced as catalysts in the present invention, shortening the reaction time to 1 - 2 hours. In the step of removing the protecting group, cation resin is used for hydrolysis and extraction with a fat-soluble solvent. Only one crystallization is required to obtain vitamin C ethyl ether with a purity greater than 99%, and the overall yield can reach over 80%. Through these improvement measures, the present invention not only improves the production efficiency of vitamin C ethyl ether but also reduces production costs, making it more suitable for large-scale industrial production.

[0010] 2. Technical Solutions

[0011] To solve the above problems, the technical solution provided by the present invention is as follows:

[0012] A synthesis process of vitamin C ethyl ether, comprising the following steps:

[0013] (1) Using L-ascorbic acid as a raw material, acetone as a reactant and solvent, heating to 38 - 40 °C, reacting for 1 - 2 h under the action of anhydrous copper sulfate and acetyl chloride, taking the solid obtained after centrifugation, namely the vitamin C protecting body;

[0014] (2) Adding alkali, water and an alkylating agent into the reaction product vitamin C protecting body in step (1), then adding absolute ethanol, the weight of absolute ethanol is 5 - 8 times the weight of L-ascorbic acid added in step (1), stirring and reacting for 3 h at 75 - 78 °C under nitrogen protection, and obtaining the vitamin C protecting body etherate by vacuum distillation of the reaction solution;

[0015] (3) Dissolving the reaction product vitamin C protecting body etherate in step (2) with a lower alcohol, hydrolyzing the solution in a column filled with cation resin at 55 - 60 °C for 5 h, adding water to the hydrolysis solution and then extracting twice with a fat-soluble solvent, after recovering the solvent of the extract, recrystallizing the obtained solid in ethyl acetate, centrifuging to collect the solid, and drying it under vacuum to obtain vitamin C ethyl ether.

[0016] Preferably, the weight ratio of L-ascorbic acid to acetone in step (1) is 1:1.5.

[0017] Preferably, the dosages of anhydrous copper sulfate and acetyl chloride in step (1) are 3% and 1% of the weight of acetone respectively.

[0018] Preferably, the rotation speed of centrifugation in step (1) is 5000 rpm and the centrifugation time is 10 min.

[0019] Preferably, the molar ratio of alkali to L-ascorbic acid in step (2) is 1:1 - 1.5:1;

[0020] The molar ratio of water to L-ascorbic acid in step (2) is 0.2:1 - 0.3:1;

[0021] The molar ratio of alkylating agent to L-ascorbic acid in step (2) is 1:1 - 1.5:1.

[0022] Preferably, the molar ratio of alkali to L-ascorbic acid in step (2) is 1.2:1;

[0023] The molar ratio of water to L-ascorbic acid in step (2) is 0.3:1;

[0024] The molar ratio of alkylating agent to L-ascorbic acid in step (2) is 1.2:1;

[0025] The weight of absolute ethanol in step (2) is 6 times the weight of L-ascorbic acid added in step (1).

[0026] Preferably, the alkali in step (2) is triethylamine;

[0027] In step (2), the alkylating agent is diethyl carbonate;

[0028] The parameters of vacuum distillation in step (2) are as follows:

[0029] Distillation temperature: 50 °C, condensation temperature: 4 °C, vacuum degree: 20 mmHg.

[0030] Preferably, in step (3), the lower alcohol is isopropyl alcohol or ethanol;

[0031] In step (3), the cation resin is HYA-10 type cation resin of Xi'an Hanyu Resin Technology Co., Ltd. or LXT-142 type cation resin of Xi'an BlueSail New Materials Co., Ltd.;

[0032] It should be additionally noted that in this application, a new modified cation resin is also designed. The LXT-142 type cation resin is soaked in a 5% NaOH solution by mass for 2 h, then rinsed with distilled water until neutral, and then soaked in 5% HCl by mass for 3 h, and then rinsed with distilled water to remove impurities. Finally, it is soaked in a 15% copper chloride solution by mass, the temperature is controlled at 50 °C, and the time is controlled at 4 h. After soaking, a 10% sodium sulfonate solution by mass is immediately added, the temperature is controlled at 60 °C, and the time is controlled at 2 h. After rinsing with distilled water until there is no residue, it is ready.

[0033] In step (3), the fat-soluble solvent is a mixture of petroleum ether and ethyl acetate, and the weight ratio of petroleum ether to ethyl acetate is 1:1 - 1:3;

[0034] The conditions for recrystallization in step (3) are as follows: the amount of ethyl acetate used is 5 times the weight of the solid, dissolved at 60 - 65 °C, left standing at 2 - 8 °C for 4 - 6 h, cooling rate: 2 °C / min, and crystallization temperature is 4 °C;

[0035] The conditions for vacuum drying in step (3) are as follows: drying temperature is 58 - 62 °C, and drying time is 5 h.

[0036] Preferably, the vitamin C ethyl ether obtained in step (3) is subjected to purity detection by high performance liquid chromatography.

[0037] Preferably, the parameter conditions for purity detection in step (3) are as follows:

[0038] Chromatographic column: C18 column, inner diameter of the chromatographic column is 4.6 mm, length of the chromatographic column is 250 mm, filler particle size: 5 μm, column temperature 35 °C, detection wavelength 242 nm, flow rate 0.7 mL / min, time 25 min; for gradient elution, the volume ratio between acetonitrile and 0.1% phosphoric acid aqueous solution by mass ranges from 5:95 to 80:20.

[0039] Through an innovative synthesis process, the present invention significantly improves the production efficiency and product quality of vitamin C ethyl ether. The present invention uses a combination of anhydrous copper sulfate and acetyl chloride as a catalyst to accelerate the reaction process between vitamin C and acetone. This combination not only shortens the reaction time to 1-2 h (less than half of the traditional method), but also improves the purity and yield of the intermediate. This efficient catalyst combination reduces the formation of by-products, optimizes the reaction conditions, and makes the entire reaction process more economical and efficient. During the process of removing the protecting group, the present invention introduces a cation exchange resin for hydrolysis, and then uses a specific lipophilic solvent for extraction. This step not only simplifies the purification process, but also significantly improves the purity (greater than 99%) and yield (up to more than 80%) of vitamin C ethyl ether. By reducing the number of crystallization times, the production cycle is significantly shortened, and the energy consumption and production cost are reduced. By shortening the reaction time and simplifying the purification steps, the present invention effectively reduces the consumption of raw materials and energy, and greatly reduces the production cost. This improvement makes the industrial production of vitamin C ethyl ether more economical, and provides an efficient, environmentally friendly and economical solution for the market.

[0040] 3. Beneficial Effects

[0041] Compared with the traditional method, it has the following significant beneficial effects:

[0042] The reaction time is significantly shortened: By using anhydrous copper sulfate and acetyl chloride as catalysts, the reaction time between vitamin C and acetone is shortened from 3-5 h of the traditional method to 1-2 h. This not only improves the production efficiency, but also reduces the energy consumption and production cost. Improve the product purity and yield: In the step of removing the protecting group of the present invention, through hydrolysis with a cation exchange resin and extraction with a lipophilic solvent, vitamin C ethyl ether with a purity greater than 99% can be obtained with only one crystallization. The total yield is increased to more than 80%, which significantly improves the raw material utilization rate and economic benefits compared with 50%-60% of the traditional method. Simplify the process flow: The optimized process reduces the number of crystallization times and complex purification steps, making the production process more simple and efficient. This improvement not only reduces the operation complexity, but also shortens the production cycle, which is helpful for large-scale industrial production. Reduce environmental impact: Due to the optimization of the reaction and purification steps, the present invention reduces the usage amount of solvents and chemical reagents, thereby reducing the generation of waste and having better environmental friendliness.

[0043] In summary, the present invention provides a more feasible solution for the large-scale application of vitamin C ethyl ether by improving the reaction efficiency, product quality and production economy. Description of the Drawings

[0044] Figure 1 It is the synthesis process route diagram of vitamin C ethyl ether prepared in Example 1 of the present invention.

[0045] Figure 2 It is the original chromatographic analysis report corresponding to the vitamin C ethyl ether prepared in Example 2 of the present invention.

[0046] Figure 3 It is the original infrared analysis report corresponding to the vitamin C ethyl ether prepared in Example 2 of the present invention.

[0047] Figure 4 It is the original carbon spectrum analysis report corresponding to the vitamin C ethyl ether prepared in Example 2 of the present invention.

[0048] Figure 5 It is the original hydrogen spectrum analysis report corresponding to the vitamin C ethyl ether prepared in Example 2 of the present invention. Detailed implementation manners

[0049] Next, the technical solutions in the implementation manners of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the implementation manners of the present invention. Obviously, the described implementation manners are only a part of the implementation manners of the present invention, rather than all of the implementation manners. All other implementation manners obtained by those of ordinary skill in the art based on the implementation manners of the present invention without making creative efforts belong to the scope of protection of the present invention.

[0050] It should be noted that in the present invention, the weight parts or other weight ratios involved are in kilograms, the international standard unit.

[0051] Example 1

[0052] As Figure 1 shown, the synthesis process of vitamin C ethyl ether includes the following steps:

[0053] (1) Weigh 352 g of L-ascorbic acid and 528 g of acetone, put them into a 10-L reaction flask, start stirring, heat up to 38 °C, add 5.28 g of acetyl chloride and 15.84 g of anhydrous copper sulfate, and after reacting for 1 h, centrifuge to obtain the vitamin C protection body;

[0054] (2) Add 202 g of triethylamine, 7.2 g of water and 236 g of diethyl carbonate to the vitamin C protection body, then add 1760 g of absolute ethanol, and under nitrogen protection, stir and react at 75 °C for 3 h, and perform vacuum distillation to obtain the vitamin C protection body etherified product;

[0055] (3) Dissolve the vitamin C protected ether compound with 352 g of isopropanol, and hydrolyze it at 55 °C for 5 h in a column filled with 17.6 g of cation exchange resin (the cation exchange resin is the HYA-10 type cation exchange resin of Xi'an Hanyu Resin Technology Co., Ltd.) to remove the protecting groups at the 5th and 6th positions. Add 352 g of water, and extract twice with 500 g of petroleum ether: ethyl acetate (weight ratio 1:1). After recovering the solvent of the extract, crystallize the obtained solid once with ethyl acetate. The crystallization conditions are as follows: dissolve at 60 °C, stand still at 8 °C for 4 h, centrifuge to collect the solid, and dry it under vacuum at 62 °C for 5 h and then weigh it. 327.2 g of solid is obtained. After analysis and detection, the purity of vitamin C ethyl ether is 99.5%, and the yield of vitamin C ethyl ether is 80.2%.

[0056] Example 2

[0057] The synthesis process of vitamin C ethyl ether includes the following steps:

[0058] (1) Weigh 352 g of L-ascorbic acid and 528 g of acetone, put them into a 10 L reaction flask, start stirring, heat up to 39 °C, add 5.28 g of acetyl chloride and 15.84 g of anhydrous copper sulfate, and after reacting for 2 h, centrifuge to obtain the vitamin C protected body;

[0059] (2) Add 242.4 g of triethylamine, 10.8 g of water and 283.2 g of diethyl carbonate to the vitamin C protected body, then add 2112 g of absolute ethanol, and under nitrogen protection, stir and react at 77 °C for 3 h, and perform vacuum distillation to obtain the vitamin C protected ether compound;

[0060] (3) Dissolve the vitamin C protected ether compound with 352 g of ethanol, and hydrolyze it at 60 °C for 5 h in a column filled with 35.2 g of cation exchange resin (the cation exchange resin is the LXT-142 type cation exchange resin of Xi'an BlueSail New Materials Co., Ltd.) to remove the protecting groups at the 5th and 6th positions. Then add 352 g of water, and extract twice with 500 g of petroleum ether: ethyl acetate (weight ratio 1:3). Remove the solvent of the extract, crystallize the obtained solid once with ethyl acetate. The crystallization conditions are as follows: dissolve at 65 °C, stand still at 2 °C for 6 h, dry it under vacuum at 58 °C for 5 h and then weigh it. 338.3 g of solid is obtained. After analysis and detection, the purity of vitamin C ethyl ether is 99.6%, and the yield of vitamin C ethyl ether is 82.9%.

[0061] Comparative Example 1

[0062] The synthesis process of vitamin C ethyl ether is basically the same as that of Example 2, with the only difference being that in step (1), anhydrous copper sulfate is not added, and only acetyl chloride is used as the catalyst. After reacting for 4 h, 294.2 g of solid is obtained after drying. After analysis and detection, the purity of vitamin C ethyl ether is 99.0%, and the yield of vitamin C ethyl ether is 72.1%.

[0063] The calculation formula is as follows: The yield of vitamin C ethyl ether = (weight of pure vitamin C ethyl ether / theoretical amount of vitamin C ethyl ether generated) × 100%.

[0064] Table 1 Calculation Table of the Yield of Vitamin C Ethyl Ether

[0065]

[0066] Table 1 shows the calculation of the yield of vitamin C ethyl ether in Example 1, Example 2 and Comparative Example 1. In terms of purity, the purity of the products in the examples is above 99.5%, slightly higher than that of the comparative example. This indicates that the synthesis method of the present invention not only improves the product yield but also enhances the product purity. For the first time, the present invention combines anhydrous copper sulfate with acetyl chloride to further optimize the reaction conditions. This combination significantly shortens the reaction time, improves the purity and yield of the target product, and solves the problem of low product purity in traditional methods. By optimizing the catalyst combination, the present invention realizes a more efficient synthesis route. This improvement not only enhances the production efficiency but also reduces the production cost, making the industrial production of vitamin C ethyl ether more competitive. The short reaction time and high-purity products provide more extensive possibilities for subsequent applications, especially in fields with strict product quality requirements, such as the pharmaceutical and cosmetic industries. Therefore, the innovation and practicality of the present invention in the synthesis of vitamin C ethyl ether have been verified, providing an efficient, economical and environmentally friendly solution for the large-scale application of this compound.

[0067] Meanwhile, as Figure 2As shown, taking the vitamin C ethyl ether prepared in Example 2 as an example, the chromatographic peak information is interpreted as follows: As can be seen from the report, three main peaks were detected in the sample (Peak 1, Peak 2, and Peak 3 from left to right in the figure), which appeared at retention times of 7.107 min, 9.942 min, and 15.004 min respectively. Peak 1 (7.107 min): Area percentage: 0.0842%, Area value: 13.59696 mAU*s, which may be impurities or background noise. Peak 2 (9.942 min): Area percentage: 99.6613%, Area value: 16087.4 mAU*s. This peak accounts for the vast majority of the total area and is the target product, vitamin C ethyl ether. Peak 3 (15.004 min): Area percentage: 0.2545%, Area value: 41.08047 mAU*s, which may be by-products or other impurities. Sample purity: According to the area percentage, the purity of the target product (Peak 2) is 99.6613%, indicating that the impurity content in the sample is extremely low. The sum of the remaining impurities (Peak 1 and Peak 3) only accounts for 0.3387%, indicating that the product has a high purity. Retention time analysis: The retention time of Peak 2 is 9.942 min, which is the characteristic retention time of the main target product. The stable and sharp main peak of the retention time indicates good separation effect, and the chromatographic conditions are suitable for the analysis of vitamin C ethyl ether. The total area is 16142.1 mAU*s, indicating a high sample concentration and strong detection signal. Conclusion: The proportion of the target product, vitamin C ethyl ether, in the sample is as high as 99.6613%, with a very high purity, meeting the requirements of industrial production or laboratory research. The impurity content is extremely low, and there are only two small impurity peaks (7.107 min and 15.004 min), which do not cause significant interference to the main component. The chromatographic conditions are good, the separation effect is clear, and it can be used for subsequent quantitative analysis or quality control.

[0068] As Figure 3 shown, the infrared spectrum is mainly used to analyze the functional group characteristics of the molecular structure in the sample. The following is a detailed interpretation of this infrared spectrum: Wavenumber range and corresponding characteristic absorption peaks: 3408.22 cm -1 (broad peak): Corresponding to the stretching vibration of the hydroxyl group (-OH), indicating that there may be free hydroxyl groups or phenolic structures in the sample. 2929.87 cm -1 and 2877.79 cm -1 : Corresponding to the C-H stretching vibration of the alkyl group (methyl and methylene), indicating that the sample contains saturated hydrocarbon chains. 1743.65 cm -1 : Corresponding to the stretching vibration of the ester group (C=O), indicating that there may be ester compounds in the sample. This is an important characteristic peak of vitamin C ethyl ether, verifying the presence of the target product. 1425.50 cm -1 and 1382.96 cm -1: Corresponding to C-H bending vibration, it further confirmed the existence of the alkyl structure. 1271.08 cm -1 and 1187.71 cm -1 : Corresponding to the stretching vibration of the ether bond (C-O-C), it indicated that the sample contained an ether bond. This is one of the important characteristics of vitamin C ethyl ether. 1056.82 cm -1 and 1031.92 cm -1 : Corresponding to the stretching vibration of the C-O bond, it further supported the existence of ether and ester structures in the sample. Combining with the characteristic absorption peaks in the infrared spectrum, the following conclusions can be drawn: There are hydroxyl groups (3408.22 cm -1 ) in the sample, which may be the residues of unreacted vitamin C. The absorption peaks of the ester group (1743.65 cm -1 ) and the ether bond (1271.08 cm -1 , 1187.71 cm -1 ) are clearly visible, indicating that the target product, namely vitamin C ethyl ether, has been successfully synthesized. The characteristic peaks of the saturated hydrocarbon chain (2929.87 cm -1 , 2877.79 cm -1 ) further supported the existence of the alkyl part in the target product structure. The key absorption peaks in the infrared spectrum are consistent with the molecular structure of vitamin C ethyl ether, verifying the successful synthesis of the target product. The appearance of hydroxyl and other impurity peaks may be related to a small amount of unreacted raw materials or by-products, but overall it conforms to the characteristics of high-purity products.

[0069] As Figure 4 shown, the carbon spectrum is used to analyze the chemical environment of carbon atoms in the compound to help confirm the molecular structure. The following is a detailed interpretation of this carbon spectrum: Chemical shift range: The chemical shift (δ) is in ppm, and the horizontal axis represents the chemical environment of different carbon atoms. Multiple clear peaks are shown in the figure, indicating that the sample contains different types of carbon atoms. Main peak positions and corresponding structures:

[0070] Based on the chemical shift range and typical carbon signal characteristics, the following is speculated:

[0071] 170 - 180 ppm: This region usually corresponds to the chemical shift of the carbonyl group (C=O).

[0072] The peaks at 173.42 ppm and 177.86 ppm indicate that there may be ester groups or carboxylic acid groups in the sample, which is consistent with the structure of vitamin C ethyl ether.

[0073] 60 - 100 ppm: This region usually corresponds to the chemical environment of the ether bond (C-O) or saturated carbon connected to oxygen.

[0074] The peaks at 70.02 ppm and 72.04 ppm indicate the presence of ether bonds (C-O-C) in the sample, which is an important characteristic of vitamin C ethyl ether.

[0075] 40 - 60 ppm: Corresponding to the chemical environment of saturated carbons (such as methylene, methyl) connected to electronegative atoms (such as oxygen, nitrogen).

[0076] The peaks at 63.59 ppm and 61.20 ppm may be characteristic signals of the ethyl ether moiety.

[0077] 10 - 40 ppm: This region generally corresponds to the chemical environment of saturated alkyl carbon atoms. The peak at 14.60 ppm may be the signal of the methyl group at the ethyl end.

[0078] The following conclusions can be drawn from the main peaks in the carbon spectrum:

[0079] There are ester groups (C=O) and ether bonds (C-O-C) in the sample, which is consistent with the molecular structure of vitamin C ethyl ether. The saturated alkyl signals indicate that the sample contains an ethyl moiety. The peak distribution in the carbon spectrum is clear and there are no obvious impurity signals, indicating a high purity of the sample. By analyzing the characteristic peaks in the carbon spectrum, it can be confirmed that the sample is vitamin C ethyl ether, and the ester group, ether bond, and ethyl moiety in its molecular structure are all verified. At the same time, the spectrum shows a high purity of the sample and a low impurity content. This result is consistent with the results of liquid chromatography and infrared spectroscopy analysis.

[0080] As Figure 5 shown, the hydrogen spectrum is used to analyze the chemical environment of hydrogen atoms in the compound. The following is a detailed interpretation of this hydrogen spectrum:

[0081] Chemical shift range:

[0082] 0.5 - 5 ppm.

[0083] Main peak positions and corresponding structures:

[0084] ~1.5 ppm: May correspond to methyl or methylene hydrogen atoms in the alkyl chain. This is a common chemical shift in saturated hydrocarbon chains.

[0085] ~3.5 - 4.5 ppm: Corresponding to methylene hydrogen atoms connected to oxygen. Indicating the characteristics of the presence of ether bonds or ester bonds in the sample.

[0086] ~5 ppm: May correspond to an enol structure or other special chemical environments connected to oxygen. The peaks in this region may be key structural characteristics in vitamin C ethyl ether.

[0087] Analysis of sample characteristics:

[0088] Saturated hydrocarbon chain: The signal in the low-field region (~1.5 ppm) indicates that the sample contains a saturated hydrocarbon chain.

[0089] Hydrogen linked to oxygen: The signal in the middle-field region (~3.5 - 4.5 ppm) indicates the presence of an ether or ester structure in the sample.

[0090] High purity: The peaks in the spectrum are clear and there are no obvious impurity signals, indicating a high purity of the sample.

[0091] By analyzing the characteristic peaks in the above hydrogen spectrum, it can be confirmed that the sample has the typical structural characteristics of vitamin C ethyl ether. The signals of the saturated hydrocarbon chain and the hydrogen linked to oxygen are consistent with the expected molecular structure, indicating successful synthesis and high purity.

[0092] Compared with the traditional three-step synthesis process of vitamin C ethyl ether, the present invention has the following remarkable advantages:

[0093] Shorter reaction time, higher purity and yield of the target product: By using anhydrous copper sulfate and acetyl chloride jointly as catalysts, the present invention shortens the reaction time for vitamin C to react with acetone to form an intermediate to 1 - 2 h, which is less than half of the traditional method. This optimization significantly improves the reaction efficiency, reduces the generation of by-products, and thus greatly enhances the purity and yield of the target product. Simplified purification steps, improved production efficiency: In the third step of removing the protecting group, the present invention uses a cation exchange resin for hydrolysis to remove the protecting groups at the 5th and 6th positions. Subsequently, a fat-soluble solvent is used to extract the hydrolysis solution, and the solvent in the extract is recovered. Through this optimization, vitamin C ethyl ether with a purity greater than 99% can be obtained by only one crystallization, and the total yield can reach more than 80%. Compared with the complex operations of multiple crystallizations required by the traditional process, the present invention greatly simplifies the purification process and significantly shortens the production cycle. Reduced production cost: By shortening the reaction time, reducing the purification steps and increasing the yield, the present invention effectively reduces the consumption of raw materials and energy, and significantly reduces the production cost. This improvement makes the industrial production of vitamin C ethyl ether more economical. In summary, the present invention is superior to the traditional process in terms of reaction efficiency, product quality and production cost, providing an efficient, economical and environmentally friendly solution for the large-scale industrial production of vitamin C ethyl ether.

[0094] The above description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be obvious to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A synthesis process of vitamin C ethyl ether, comprising the following steps: (1) Using L-ascorbic acid as a raw material and acetone as a reactant and solvent, heating to 38-40° C., reacting under the action of anhydrous copper sulfate and acetyl chloride for 1-2 hours, and taking the solid obtained after centrifugation, i.e., the vitamin C protected body; (2) adding alkali, water and an alkylating agent to the reaction product of step (1), and then adding anhydrous ethanol, wherein the weight of the anhydrous ethanol is 5-8 times the weight of the L-ascorbic acid added in step (1), stirring and reacting at 75-78° C. for 3 hours under nitrogen protection, and distilling the reaction solution under reduced pressure to obtain the vitamin C protected body etherified product; (3) The reaction product of step (2), vitamin C protected body etherate, is dissolved in a low alcohol, and the solution is hydrolyzed in a column equipped with a cationic resin at 55-60° C. for 5 h. Water is added to the hydrolyzate, and the solution is extracted twice with a fat-soluble solvent. After the solvent of the extract is recovered, the obtained solid is recrystallized in ethyl acetate, the solid is collected by centrifugation, and vacuum dried to obtain vitamin C ethyl ether.

2. The synthesis process of vitamin C ethyl ether according to claim 1, characterized in that: In step (1), the weight ratio of L-ascorbic acid to acetone is 1:1.

5.

3. The synthesis process of vitamin C ethyl ether according to claim 2, characterized in that: In step (1), the amounts of anhydrous copper sulfate and acetyl chloride used are 3% and 1% of the weight of acetone, respectively.

4. The synthesis process of vitamin C ethyl ether according to claim 3, characterized in that: The centrifugal speed in step (1) is 5000 rpm and the centrifugal time is 10 min.

5. The synthesis process of vitamin C ethyl ether according to claim 4, characterized in that: In step (2), the molar ratio of the base to the L-ascorbic acid is 1:1-1.5:1; In step (2), the molar ratio of water to L-ascorbic acid is 0.2:1-0.3:1; In step (2), the molar ratio of the alkylating agent to L-ascorbic acid is 1:1-1.5:

1.

6. The synthesis process of vitamin C ethyl ether according to claim 5, characterized in that: In step (2), the molar ratio of alkali to L-ascorbic acid is 1.2:1; In step (2), the molar ratio of water to L-ascorbic acid is 0.3:1; In step (2), the molar ratio of the alkylating agent to L-ascorbic acid is 1.2:1; The weight of anhydrous ethanol in step (2) is 6 times the weight of L-ascorbic acid added in step (1).

7. The synthesis process of vitamin C ethyl ether according to claim 6, characterized in that: In step (2), the base is triethylamine; In step (2), the alkylating agent is diethyl carbonate; The parameters of the vacuum distillation in step (2) are as follows: Distillation temperature: 50°C, condensation temperature: 4°C, vacuum degree: 20 mmHg.

8. The synthesis process of vitamin C ethyl ether according to claim 7, characterized in that: In step (3), the lower alcohol is isopropanol or ethanol; The cationic resin in step (3) is HYA-10 cationic resin produced by Xi'an Hanyu Resin Technology Co., Ltd. or LXT-142 cationic resin produced by Xi'an Lanxiao Technology New Materials Co., Ltd.; In step (3), the fat-soluble solvent is a mixture of petroleum ether and ethyl acetate, wherein the weight ratio of petroleum ether to ethyl acetate is 1:1-1:3; The conditions for recrystallization in step (3) are as follows: ethyl acetate is used in an amount of 5 times the weight of the solid, dissolved at 60-65°C, allowed to stand at 2-8°C for 4-6h, cooling rate: 2°C / min, crystallization temperature is 4°C; The vacuum drying conditions in step (3) are as follows: drying temperature is 58-62° C., and drying time is 5 h.

9. The synthesis process of vitamin C ethyl ether according to claim 8, characterized in that: The vitamin C ethyl ether obtained in step (3) is subjected to purity detection by high performance liquid chromatography.

10. The synthesis process of vitamin C ethyl ether according to claim 9, characterized in that: The parameter conditions for purity detection in step (3) are as follows: The chromatographic column is C18 column, the inner diameter of the chromatographic column is 4.6 mm, the length of the chromatographic column is 250 mm, the filler particle size is 5 μm, the column temperature is 35° C., the detection wavelength is 242 nm, the flow rate is 0.7 mL / min, and the time is 25 min; the volume ratio of the gradient elution mobile phase between acetonitrile and 0.1% by mass phosphoric acid aqueous solution is from 5:95 to 80:20.

Images