A synthesis process of vitamin c ethyl ether

Abstract

The application 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 raw material, adding acetone, anhydrous copper sulfate and acetyl chloride, and reacting at 38-40 DEG C for 1-2 hours under nitrogen protection to obtain a vitamin C protected body; adding alkali, water, an alkylating agent and anhydrous ethanol into the reaction product, reacting at 75-78 DEG C for 3 hours under nitrogen protection, and performing reduced-pressure distillation to obtain a vitamin C protected body etherate; finally, hydrolysis is carried out by using a cation resin, a protective group is removed, and recrystallization is carried out by using ethyl acetate to obtain the vitamin C ethyl ether. Through the synergistic catalysis of the anhydrous copper sulfate and the acetyl chloride, the reaction time is remarkably shortened, and the product purity and the yield are improved. Through detection, the product purity is greater than 99.5%, and the total yield can reach more than 80%, so that an efficient and economical method is provided for the industrial production of the vitamin C ethyl ether.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of vitamin C derivative synthesis, in particular, relates to a synthesis process of vitamin C ethyl ether. BACKGROUND

[0002] Vitamin C ethyl ether is a very useful vitamin C derivative, which is not only very stable in chemical properties, is a colorless vitamin C derivative, but also is an amphiphilic substance, which greatly expands its application range, especially in cosmetics. Vitamin C ethyl ether can easily enter the dermis through the stratum corneum, and it is very easy to be decomposed by biological enzymes in the body after entering the body, thereby playing the biological effects of vitamin C, such as whitening, antioxidant and promoting collagen production. Therefore, vitamin C ethyl ether is one of the important raw materials for cosmetic anti-aging agents and whitening agents.

[0003] There are one-step and three-step methods for synthesizing vitamin C ethyl ether. 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 agent in a solvent to react, synthesizing 3-O-alkyl ascorbic acid ether, recovering the reaction solvent after the reaction, diluting the residue with water, applying a strong basic anion exchange resin column for ion exchange, washing with water, eluting with dilute acid, concentrating and crystallizing to obtain purified vitamin C ethyl ether. The reaction product of this method is relatively complex, the separation and purification is difficult, the yield is low, and it is difficult to realize industrial production. The general method for synthesizing vitamin C ethyl ether is three-step method. Patent CN103113333B discloses a synthesis method of vitamin C ethyl ether, which first uses vitamin C as a raw material, acetone dimethyl acetal as a reactant, and DMSO as a solvent, and protects the hydroxyl groups at positions 5 and 6 of vitamin C under the action of a catalyst, then adds alkali and alkylating agent to react to form ether bond at position 3 of the hydroxyl group, and finally removes the protecting groups at positions 5 and 6 by acid treatment, and crystallizes vitamin C ethyl ether with a fat-soluble solvent, and the total yield of the three steps is 50%-50.4%. Patent CN113214197B discloses a preparation method of vitamin C ethyl ether, which first uses vitamin C as a starting raw material, and uses cyclopentanone as a reactant and a solvent, and obtains 5,6-O-cyclopentyl-ascorbic acid under the catalysis of acetyl chloride, then adds thionyl chloride, ethanol and triethylamine to react to obtain 3-O-ethyl-5,6-O-cyclopentyl-ascorbic acid ether, and finally removes the protecting groups by reacting with dilute hydrochloric acid, and recrystallizes with ethanol to obtain vitamin C ethyl ether. Patent CN112142697B discloses a production process of vitamin C ethyl ether, which uses vitamin C as a starting raw material, and obtains vitamin C ethyl ether through acetone protection, etherification and hydrolysis deprotection, wherein the third step is hydrolysis deprotection group with concentrated hydrochloric acid, and recrystallization with n-butanol, and the yield of vitamin C ethyl ether can reach more than 65%.

[0004] Currently, the reaction of Vitamin C with acetone to form the 5,6-O-isopropyl-L-ascorbic acid intermediate typically takes 3-5 hours. This long reaction time not only increases energy consumption but also limits production efficiency. Long reaction times can lead to increased side products, reducing the purity of the target product and affecting subsequent purification steps. Meanwhile, in the prior art, after removing the protecting group using 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, leading to a prolonged production cycle. Additionally, due to multiple crystallization and purification steps, the overall yield of the product is typically only 50%-60%. This not only increases production costs but also limits the feasibility of large-scale industrial production. SUMMARY

[0005] 1. Problems to be solved

[0006] To address the shortcomings of the prior art, the purpose of the present invention is to provide an improved synthesis process for Vitamin C ethyl ether to solve the following key problems:

[0007] Shorten reaction time: In the existing process, the reaction of Vitamin C with acetone to form the 5,6-O-isopropyl-L-ascorbic acid intermediate takes a long time, typically 3-5 hours. The present invention aims to significantly reduce the reaction time by optimizing the catalyst combination, improving production efficiency.

[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 low yield (typically 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, in the reaction of Vitamin C with acetone, anhydrous copper sulfate and acetyl chloride are introduced as catalysts, reducing the reaction time to 1-2 hours. In the step of removing the protecting group, cationic resin is used for hydrolysis, and a lipophilic solvent is used for extraction, and only one crystallization is required to obtain Vitamin C ethyl ether with a purity of more than 99%, with a total yield of more than 80%. Through these improvements, 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:

[0012] A synthesis process for Vitamin C ethyl ether, comprising the following steps:

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

[0014] (2) Adding base, water and alkylating agent into the reaction product vitamin C protector of step (1), then adding anhydrous ethanol, the weight of anhydrous ethanol being 5-8 times the weight of L-ascorbic acid added in step (1), stirring and reacting for 3h under nitrogen protection at 75-78°C, distilling the reaction solution under reduced pressure to obtain vitamin C protector etherate;

[0015] (3) Dissolving the reaction product vitamin C protector etherate of step (2) in a low alcohol, hydrolyzing the solution in a column filled with cation resin at 55-60°C for 5h, adding water into the hydrolysis solution and extracting twice with a fat-soluble solvent, recovering the solvent of the extracted solution, recrystallizing the obtained solid in ethyl acetate, collecting the solid by centrifugation and drying 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 amount of anhydrous cupric sulfate and acetyl chloride in step (1) is 3% and 1% of the weight of acetone, respectively.

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

[0019] Preferably, the molar ratio of base 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 base 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 anhydrous ethanol in step (2) is 6 times the weight of L-ascorbic acid added in step (1).

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

[0027] The alkylating agent in step (2) is diethyl carbonate;

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

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

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

[0031] The cationic resin in step (3) is HYA-10 cationic resin from Xi'an Hanyu Resin Technology Co., Ltd. or LXT-142 cationic resin from Xi'an Lanxiao New Material Technology Co., Ltd.

[0032] It is necessary to additionally explain that a new modified cationic resin is designed in the present application. The LXT-142 cationic resin is soaked in a 5% NaOH solution for 2h, then washed with distilled water until neutral, then soaked in a 5% HCl solution for 3h, then washed with distilled water to remove impurities. Finally, it is soaked in a 15% copper chloride solution, the temperature is controlled at 50℃, the time is controlled at 4h, after soaking, a 10% sodium sulfonate solution is immediately added, the temperature is controlled at 60℃, the time is controlled at 2h, and it is washed with distilled water until no residue is left.

[0033] The liposoluble solvent in step (3) 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 of recrystallization in step (3) are as follows: the amount of ethyl acetate is 5 times the weight of the solid, dissolution at 60-65℃, standing at 2-8℃ for 4-6h, cooling rate: 2℃ / min, crystallization temperature is 4℃.

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

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

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

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

[0039] The present invention significantly improves the production efficiency and product quality of Vitamin C ethyl ether through an innovative synthesis process. The invention uses a combination of anhydrous copper sulfate and acetyl chloride as a catalyst to accelerate the reaction process of Vitamin C and acetone. This combination not only shortens the reaction time to 1-2h (less than half of the traditional method), but also improves the purity and yield of the intermediate. This efficient catalyst combination reduces the generation of by-products, optimizes the reaction conditions, and makes the entire reaction process more economical and efficient. In the process of removing the protecting group, the invention introduces cationic resin for hydrolysis, followed by extraction using a specific lipid-soluble solvent. This step not only simplifies the purification process, but also significantly improves the purity (more than 99%) and yield (up to 80%) of Vitamin C ethyl ether. By reducing the number of crystallizations, the production cycle is significantly shortened, reducing energy consumption and production costs. By shortening the reaction time and simplifying the purification steps, the invention effectively reduces raw material and energy consumption, significantly reducing production costs. This improvement makes the industrial production of Vitamin C ethyl ether more economical, providing a high-efficiency, environmentally friendly and economical solution for the market.

[0040] 3. Beneficial effects

[0041] Compared with traditional methods, the following significant beneficial effects are achieved:

[0042] Significant reduction in reaction time: By using anhydrous copper sulfate and acetyl chloride as a catalyst, the reaction time of Vitamin C and acetone is shortened from 3-5h in traditional methods to 1-2h. This not only improves production efficiency, but also reduces energy consumption and production costs. Improve product purity and yield: In the step of removing the protecting group, the invention uses lipid-soluble solvent extraction after cationic resin hydrolysis, and only one crystallization is needed to obtain Vitamin C ethyl ether with a purity of more than 99%. The total yield is increased to more than 80%, significantly improving raw material utilization and economic benefits compared to the traditional method of 50%-60%. Simplify the process flow: The optimized process reduces the number of crystallizations and complex purification steps, making the production process more simple and efficient. This improvement not only reduces the complexity of operation, but also shortens the production cycle, which helps to realize large-scale industrial production. Reduce environmental impact: Due to the optimization of reaction and purification steps, the invention reduces the amount of solvents and chemicals used, thereby reducing waste generation and having better environmental friendliness.

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

[0044] Figure 1 is a synthesis process route map of Vitamin C ethyl ether prepared in Example 1 of the present invention.

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

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

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

[0048] Figure 5 is the original hydrogen spectrum analysis report of vitamin C ethyl ether prepared in Example 2 of the present application. DETAILED DESCRIPTION

[0049] The technical solutions in the embodiments of the present application will be described clearly and completely in combination with the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

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

[0051] Example 1

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

[0053] (1) 352 g of L-ascorbic acid and 528 g of acetone were weighed and put into a 10 L reaction bottle, stirring was started, and the temperature was raised to 38℃. Then 5.28 g of acetyl chloride and 15.84 g of anhydrous copper sulfate were added. After 1 h of reaction, centrifugation was performed to obtain a vitamin C protected body;

[0054] (2) 202 g of triethylamine, 7.2 g of water and 236 g of diethyl carbonate were added to the vitamin C protected body, followed by the addition of 1760 g of anhydrous ethanol. Under nitrogen protection, stirring was performed at 75℃ for 3 h, and then distillation was performed under reduced pressure to obtain a vitamin C protected body etherate;

[0055] ​(3) 352 g of ethanol was used to dissolve the vitamin C protected etherate, and the column was filled with 35.2 g of cationic resin (LXT-142 type cationic resin from Xi'an Blue Sky Technology New Material Co., Ltd.). The column was hydrolyzed at 60°C for 5 h to remove the protecting groups at the 5th and 6th positions. Then, 352 g of water was added, and the mixture was extracted twice with 500 g of petroleum ether: ethyl acetate (1:3 by weight). After removing the solvent from the extract, the obtained solid was crystallized once with ethyl acetate. The crystallization conditions were as follows: dissolution at 65°C, standing at 2°C for 6 h, and vacuum drying at 58°C for 5 h. Then, the weight of the solid was measured, and 338.3 g of solid was obtained. The purity of the vitamin C ethyl ether was 99.6%, and the yield of the vitamin C ethyl ether was 82.9%.

[0056] Example 2

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

[0058] (1) 352 g of L-ascorbic acid and 528 g of acetone were weighed and placed in a 10 L reaction bottle. The stirring was started, and the temperature was raised to 39°C. Then, 5.28 g of acetyl chloride and 15.84 g of anhydrous copper sulfate were added. After 2 h of reaction, the mixture was centrifuged to obtain vitamin C protected body.

[0059] (2) 242.4 g of triethylamine, 10.8 g of water, and 283.2 g of diethyl carbonate were added to the vitamin C protected body. Then, 2112 g of anhydrous ethanol was added. The mixture was stirred at 77°C for 3 h under nitrogen protection. Then, the vitamin C protected etherate was obtained by distillation under reduced pressure.

[0060] (3) 352 g of ethanol was used to dissolve the vitamin C protected etherate, and the column was filled with 35.2 g of cationic resin (LXT-142 type cationic resin from Xi'an Blue Sky Technology New Material Co., Ltd.). The column was hydrolyzed at 60°C for 5 h to remove the protecting groups at the 5th and 6th positions. Then, 352 g of water was added, and the mixture was extracted twice with 500 g of petroleum ether: ethyl acetate (1:3 by weight). After removing the solvent from the extract, the obtained solid was crystallized once with ethyl acetate. The crystallization conditions were as follows: dissolution at 65°C, standing at 2°C for 6 h, and vacuum drying at 58°C for 5 h. Then, the weight of the solid was measured, and 338.3 g of solid was obtained. The purity of the vitamin C ethyl ether was 99.6%, and the yield of the vitamin C ethyl ether was 82.9%.

[0061] Comparative Example 1

[0062] The synthesis process of vitamin C ethyl ether was basically the same as that of Example 2, except that in step (1), no anhydrous copper sulfate was added, and only acetyl chloride was used as the catalyst. The reaction time was 4 h. After drying, 294.2 g of solid was obtained. The purity of the vitamin C ethyl ether was 99.0%, and the yield of the vitamin C ethyl ether was 72.1%.

[0063] wherein the calculation formula is as follows: Vitamin C ethyl ether yield = (weight of pure Vitamin C ethyl ether / theoretical Vitamin C ethyl ether generation) x 100%.

[0064] Table 1 Vitamin C ethyl ether yield calculation table

[0065]

[0066] Table 1 shows the Vitamin C ethyl ether yield calculation of Example 1, Example 2 and Comparative Example 1. In terms of purity, the product purity of the examples is above 99.5%, slightly higher than that of the comparative example, which indicates that the synthesis method of the present application not only improves the product yield, but also improves the product purity. The present application first uses anhydrous copper sulfate and acetyl chloride together, further optimizes 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. The present application realizes a more efficient synthesis path by optimizing the catalyst combination. This improvement not only improves the production efficiency, but also reduces the production cost, making the industrialized production of Vitamin C ethyl ether more competitive. Short reaction time and high purity product provide more extensive possibilities for subsequent applications, especially in fields with strict requirements for product quality, such as the pharmaceutical and cosmetic industries. Therefore, the innovation and practicality of the present application 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] At the same time, 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: The report shows that three main peaks were detected in the sample (peak 1, peak 2, and peak 3 from left to right in the figure), appearing 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. This may be an impurity or background noise. Peak 2 (9.942 min): Area percentage: 99.6613%, Area value: 16087.4 mAU*s. This peak accounts for the 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. This may be a byproduct or other impurities. Sample Purity: Based on the area percentage, the purity of the target product (peak 2) is 99.6613%, indicating extremely low impurity content in the sample. The sum of the remaining impurities (peaks 1 and 3) accounts for only 0.3387%, indicating high product 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 indicates good separation, and the chromatographic conditions are suitable for analyzing vitamin C ethyl ether. The total area is 16142.1 mAU*s, indicating a high sample concentration and strong detection signal. Conclusion: The target product vitamin C ethyl ether accounts for as high as 99.6613% in the sample, with very high purity, meeting the requirements for industrial production or laboratory research. The impurity content is extremely low, with only two small impurity peaks (7.107 min and 15.004 min), which do not significantly interfere with the main component. The chromatographic conditions are good, and the separation effect is clear, suitable for subsequent quantitative analysis or quality control.

[0068] like Figure 3 As shown, infrared spectra are primarily used to analyze the functional group characteristics of molecular structures in samples. The following is a detailed interpretation of this infrared spectrum: wavenumber range and corresponding characteristic absorption peak: 3408.22 cm⁻¹ -1 (Broad peak): Corresponds to the stretching vibration of the hydroxyl group (-OH), indicating the possible presence of free hydroxyl groups or phenolic structures in the sample. 2929.87 cm⁻¹ -1 and 2877.79cm -1 The CH stretching vibration corresponding to alkyl (methyl and methylene) groups indicates the presence of saturated hydrocarbon chains in the sample. 1743.65 cm⁻¹ -1 The stretching vibration corresponding to the ester group (C=O) indicates the possible presence of ester compounds in the sample. This is an important characteristic peak of vitamin C ethyl ether, confirming the presence of the target product. 1425.50 cm⁻¹ -1 and 1382.96cm -1The presence of an alkyl structure was further confirmed by the CH bending vibration. (1271.08 cm) -1 and 1187.71cm -1 The stretching vibration corresponding to the ether bond (COC) indicates the presence of ether bonds in the sample. This is one of the important characteristics of vitamin C ethyl ether. 1056.82 cm⁻¹ -1 and 1031.92cm -1 The stretching vibration corresponding to the CO bond further supports the presence of ether and ester structures in the sample. Combined with the characteristic absorption peaks in the infrared spectrum, the following conclusion can be drawn: hydroxyl groups are present in the sample (3408.22 cm⁻¹). -1 This may be unreacted vitamin C residue. Ester group (1743.65cm) -1 ) and ether bonds (1271.08cm) -1 1187.71cm -1 The absorption peak of ) is clearly visible, indicating that the target product, vitamin C ethyl ether, has been successfully synthesized. The characteristic peak of the saturated hydrocarbon chain (2929.87 cm⁻¹) is also clearly visible. -1 2877.79cm -1 This further supports the presence of the alkyl moiety 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 small amounts of unreacted starting materials or byproducts, but overall, it is consistent with the characteristics of a high-purity product.

[0069] like Figure 4 As shown, carbon nanotube spectra are used to analyze the chemical environment of carbon atoms in compounds, helping to confirm molecular structure. The following is a detailed interpretation of this carbon nanotube spectrum: Chemical shift range: Chemical shift (δ) is in ppm, and the horizontal axis represents the chemical environment of different carbon atoms. The figure shows multiple clear peaks, 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 inferences are made:

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

[0072] The peak values ​​at 173.42 ppm and 177.86 ppm indicate the possible presence of ester or carboxylic acid groups in the sample, consistent with the structure of vitamin C ethyl ether.

[0073] 60-100ppm: This region typically corresponds to a chemical environment with ether bonds (CO) or saturated carbon bonded to oxygen.

[0074] Peaks at 70.02 ppm and 72.04 ppm indicate the presence of ether bonds (C-O-C) in the sample, which is a key feature of vitamin C ethyl ester.

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

[0076] 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 a signal of the terminal methyl group of the ethyl group.

[0078] From the main peaks in the carbon spectrum, the following conclusions can be drawn:

[0079] The presence of ester groups (C=O) and ether bonds (C-O-C) in the sample is consistent with the molecular structure of vitamin C ethyl ester. The saturated alkyl signals indicate that the sample contains an ethyl moiety. The clear peak distribution in the carbon spectrum and the absence of obvious impurity signals indicate that the sample has high purity. By analyzing the characteristic peaks in the carbon spectrum, it can be confirmed that the sample is vitamin C ethyl ester, and the ester group, ether bond and ethyl moiety in its molecular structure are verified. At the same time, the spectrum shows that the sample is pure and has low impurity content. This result is consistent with the results of liquid chromatography and infrared spectroscopy analysis.

[0080] As shown in Figure 5 , 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 position and corresponding structure:

[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: Corresponds to methylene hydrogen atoms connected to oxygen. This indicates the presence of ether bonds or ester bonds in the sample.

[0086] ~5 ppm: May correspond to enol structures or other special chemical environments connected to oxygen. Peaks in this region may be key structural features in vitamin C ethyl ester.

[0087] Sample property analysis:

[0088] Saturated hydrocarbon chain: Signals in the low-field region (~1.5 ppm) indicate the presence of saturated hydrocarbon chains in the sample.

[0089] Oxygen-linked hydrogen: Signals in the mid-field region (~3.5-4.5 ppm) indicate the presence of ether or ester structures in the sample.

[0090] High purity: Clear peaks in the spectrum without significant impurity signals indicate a high purity 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 saturated hydrocarbon chains and oxygen-linked hydrogen are consistent with the expected molecular structure, indicating that the synthesis is successful and the purity is high.

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

[0093] Shortened reaction time, improved purity and yield of target product: The present invention uses anhydrous copper sulfate combined with acetyl chloride as a catalyst to shorten the reaction time of vitamin C and 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 and reduces the generation of by-products, thereby greatly improving the purity and yield of the target product. Simplify purification steps and improve production efficiency: In the process of removing the protecting group in the third step, the present invention uses cationic resin for hydrolysis to remove the protecting groups at positions 5 and 6. Subsequently, the hydrolyzate is extracted with a lipid-soluble solvent, and the solvent in the extract is recovered. Through this optimization, only one crystallization is needed to obtain vitamin C ethyl ether with a purity of more than 99%, and the total yield can reach more than 80%. Compared with the complex operation of multiple crystallizations in the traditional process, the present invention greatly simplifies the purification process and significantly shortens the production cycle. Reducing production costs: The present invention effectively reduces raw material and energy consumption by shortening reaction time, reducing purification steps and improving yield, significantly reducing production costs. 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 large-scale industrial production of vitamin C ethyl ether.

[0094] The above description of disclosed embodiments enables those skilled in the art to carry out or use the present invention. Various modifications to these embodiments will be apparent 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 these embodiments shown herein, but will conform to 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) taking L-ascorbic acid as raw material, taking acetone as reactant and solvent, heating to 38-40℃, reacting for 1-2h under the action of anhydrous copper sulfate and acetyl chloride, taking the obtained solid after centrifugation, i.e. vitamin C protector; (2) adding base, water and alkylating agent into the reaction product vitamin C protector of step (1), then adding anhydrous ethanol, the weight of anhydrous ethanol is 5-8 times of the weight of L-ascorbic acid added in step (1), stirring and reacting for 3h under nitrogen protection at 75-78℃, distilling the reaction solution under reduced pressure to obtain vitamin C protector etherate; (3) dissolving the reaction product vitamin C protector etherate of step (2) with lower alcohol, hydrolyzing the solution in a column filled with cationic resin at 55-60℃ for 5h, adding water into the hydrolysis solution and extracting twice with liposoluble solvent, recovering the solvent of the extracted solution, recrystallizing the obtained solid in ethyl acetate, collecting the solid by centrifugation, and drying under vacuum to obtain vitamin C ethyl ether; the weight ratio of L-ascorbic acid to acetone in step (1) is 1:1.5; the amount of anhydrous copper sulfate and acetyl chloride in step (1) is 3% and 1% of the weight of acetone, respectively.

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

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

1.

4. The synthesis process of vitamin C ethyl ether according to claim 3, characterized in that: the molar ratio of base to L-ascorbic acid in step (2) is 1.2:1; the molar ratio of water to L-ascorbic acid in step (2) is 0.3:1; the molar ratio of alkylating agent to L-ascorbic acid in step (2) is 1.2:1; the weight of anhydrous ethanol in step (2) is 6 times of the weight of L-ascorbic acid added in step (1).

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

6. The synthesis process of vitamin C ethyl ether according to claim 5, characterized in that: the lower alcohol in step (3) is isopropyl alcohol or ethanol; the cationic resin in step (3) is HYA-10 type cationic resin of Xi'an Hanyu Resin Technology Co., Ltd. or LXT-142 type cationic resin of Xi'an Lanxiao New Material Technology Co., Ltd.; the liposoluble solvent in step (3) is a mixture of petroleum ether and ethyl acetate, and the weight ratio of petroleum ether to ethyl acetate is 1:1-1:

3. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ The conditions of recrystallization in step (3) are as follows: the amount of ethyl acetate is 5 times the weight of the solid, dissolution at 60-65°C, standing at 2-8°C for 4-6h, cooling rate: 2°C / min, and the crystallization temperature is 4°C; The conditions of vacuum drying in step (3) are as follows: the drying temperature is 58-62°C, and the drying time is 5h.

7. The synthesis process of vitamin C ethyl ether according to claim 6, characterized in that: The purity of vitamin C ethyl ether obtained in step (3) is detected by high performance liquid chromatography.

8. The synthesis process of vitamin C ethyl ether according to claim 7, characterized in that: The parameter conditions of the purity detection in step (3) are as follows: The column is a C18 column, the inner diameter of the column is 4.6mm, the length of the column is 250mm, the particle size of the filler is 5μm, the column temperature is 35°C, the detection wavelength is 242nm, the flow rate is 0.7mL / min, and the time is 25min; the gradient elution mobile phase is the volume ratio between acetonitrile and 0.1% phosphoric acid aqueous solution from 5:95 to 80:20.

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