Preparation method of high-purity vitamin C ethyl ether

Abstract

The invention relates to the technical field of chemical synthesis, in particular to a synthesis method of vitamin C ethyl ether, which comprises an etherification reaction stage and an extraction, separation and purification post-treatment stage, and is characterized in that in the etherification reaction stage, water, inorganic alkali and an organic phase solvent form a reaction system under the protection of nitrogen, and the vitamin C ethyl ether is synthesized under the action of a two-phase catalyst. The method comprises the following steps: carrying out etherification reaction on vitamin C and an alkylating reagent at 25-60 DEG C for 2-5 hours to generate a vitamin C ethyl ether solution, extracting for multiple times, combining organic phases, concentrating, recrystallizing and drying a solid crude product to obtain a vitamin C ethyl ether crude product, and recrystallizing to obtain the high-purity vitamin C ethyl ether. The yield of the vitamin C ethyl ether prepared by the method is 80%, the purity reaches 99.85%, the preparation cost is effectively reduced, and the effect is obvious; the reaction conditions are mild and easy to control, the post-treatment process is simple and efficient, and the large-scale preparation requirement is met.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of chemical synthesis, and is a synthesis method of vitamin C ethyl ether, in particular to a simple and convenient industrial preparation, separation and purification cosmetic-grade technical scheme of high-purity vitamin C ethyl ether. BACKGROUND

[0002] Vitamin C ethyl ether (3-O-ethyl ascorbic acid ether) is a high-stability vitamin C derivative obtained by chemical modification. Its core feature is excellent stability, light resistance, heat resistance and oxidation resistance, and it is not easy to discolor, avoiding the drawbacks of traditional vitamin C which is easy to lose activity. At the same time, it has water-oil amphiphilic properties, can efficiently penetrate the skin barrier, and directly reach the dermis layer to play a role. In terms of efficacy, it can block melanin production from the source by inhibiting tyrosinase activity, and can also reduce the already formed melanin, achieving high-efficiency whitening and freckle removal. Its strong antioxidant capacity can scavenge free radicals and resist photoaging. In addition, it can also promote collagen synthesis, improve skin quality and enhance skin elasticity. Its advantages are obvious: on the basis of retaining all the biological activities of pure vitamin C, it has high permeability, excellent stability and mildness, and is suitable for various skin types including sensitive skin, and is used in whitening, freckle-removing and anti-aging products such as gels, serums, emulsions, creams, etc. The recommended addition amount is 1-5%.

[0003] The preparation methods of vitamin C ethyl ether mainly include three-step synthesis method and one-step synthesis method. The three-step method generally adopts three steps of protecting the alcohol hydroxyl group on the branched chain with a protecting agent, then performing etherification reaction and deprotection reaction to obtain the target product. For example, the invention patent CN202510314980 adopts the following steps: first, vitamin C is protected by using acetone, anhydrous copper sulfate and acetyl chloride to form a protected body, then performing etherification reaction with diethyl carbonate, and then deprotection with cationic resin, followed by extraction, crystallization and purification. This process uses the traditional acetone protection method, uses anhydrous copper sulfate and acetyl chloride reagents to increase the cost, uses isopropyl alcohol as the eluent to use resin deprotection, increases the equipment maintenance cost in the later stage, and the use of complex organic mixed solvents increases the difficulty of using extractants; the invention patent CN202411560105 adopts the following steps: first, vitamin C is subjected to acetal reaction with benzaldehyde and a catalyst to form a protected intermediate, then neutralization reaction is performed by adding an organic base, followed by alkylation reaction by adding an alkylating agent, then the separated and dried solid is subjected to hydrogenation deprotection under the catalysis of palladium carbon, filtration is performed, the filtrate is collected and crystallized, the precipitate is collected and washed and dried to obtain vitamin C ethyl ether. In the reaction process, benzaldehyde is used as the protection reagent, which has lower molecular effectiveness than acetone, thereby increasing the additional cost, especially in the deprotection stage, the dried intermediate is subjected to catalytic hydrogenation reaction to obtain the target product reaction liquid, thereby increasing the risk of the reaction and the difficulty of cost control; the invention patent CN202110035754 adopts the following steps: first, acetone dimethyl acetal is used as a protecting agent, then diethyl carbonate is used as an alkylating agent, then dilute hydrochloric acid is used for deprotection, and then the final product is prepared by purification. In the reaction process, the protecting agent acetone dimethyl acetal has lower molecular effectiveness and higher cost than the traditional protecting agent acetone, and in addition, stannous chloride with high toxicity is used, thereby increasing the difficulty of post-treatment and bringing great safety hazards. Compared with the traditional three-step method, the one-step synthesis method avoids the protection and deprotection processes, directly performs alkyl etherification reaction, greatly reduces the raw material cost, and has fewer preparation process steps and smaller equipment investment scale, thereby becoming a research hotspot.The one-step synthesis process at the present stage mostly uses organic alcohol as a solvent, organic base as a catalyst, and alkylating agent for etherification reaction. However, due to the selectivity problem of the etherification reaction process, the degree of substitution of the reaction product is relatively complex, which increases the difficulty of separation and purification of the target product and reduces the yield. The literature reports mostly use chromatography column separation and purification of the product. Therefore, optimizing the selectivity of the etherification reaction has become an important research content of the one-step synthesis method. For example, Japanese patent JP2005320310 is to add raw materials vitamin C, base, alkylating agent, and solvent into a reactor for reflux reaction and then concentrate, and then use silica gel column chromatography for subsequent separation and purification. Yasuo Kikugawa et al. published "SYNTHESIS OF 3-O-ALKYLASCORBIC ACIDS FROM L-ASCORBIC ACID IN A SINGLE STEP" is to use ethanol as a solvent, and vitamin C is subjected to alkylating reaction with diethyl sulfate under the action of triethylamine, and then column chromatography is used to separate vitamin C ethyl ether with a yield of 64%. Chen Bingbing et al. published "Simple and regionally selective synthesis of 3-O-ethyl vitamin C" uses microwave reaction conditions, and the optimal reaction conditions are determined by orthogonal test. The optimal yield of the reaction liquid is 79.4% (HPLC detection). Patent CN101824011 is to use vitamin C, sodium methoxide, and diethyl sulfate as raw materials, and ethanol as a solvent, and the reaction is carried out under nitrogen protection. After the reaction is completed, a small polar solvent trichloromethane is added to the reaction liquid, and the solid vitamin C ethyl ether crude product is precipitated at low temperature. Then, one-step recrystallization is carried out to obtain vitamin C ethyl ether with a yield of 40%. The post-processing time of the separation and purification process is as long as 15 hours, and low-boiling organic solvents are used for purification treatment, which greatly reduces the yield and produces a large amount of waste solvent, which is not conducive to the production cost control of the product. Tai et al. published "A simple efficient synthesis and biological evaluation of 3-O-ethylascorbic acid" is to use L-sodium ascorbate as a raw material and bromoethane as an alkylating agent for etherification reaction in dimethyl sulfoxide solvent. The target product is obtained by preliminary purification by column chromatography and then recrystallization with a yield of 51.0%. This method uses dimethyl sulfoxide high-boiling organic solvent and column chromatography separation and purification method, which has high post-processing cost. The above-mentioned one-step preparation of vitamin C ethyl ether technology has the disadvantage of poor selectivity of etherification reaction, which leads to complicated and inefficient post-processing process and is not suitable for large-scale production and preparation of the product. SUMMARY

[0004] In view of the above technical defects, the technical problem to be solved by the present application is to provide a high-selectivity, low-production-cost, high-efficiency, and environmentally-friendly preparation method of vitamin C ethyl ether.

[0005] The technical problem to be solved by the present application is solved by the following technical scheme: a preparation method of high-purity vitamin C ethyl ether, which completes the alkylation reaction in one step under the action of a two-phase catalyst, improves the selectivity and reaction speed of the alkylation in the etherification reaction process through optimized reaction conditions, adopts a reaction system of water and inorganic base to reduce the raw material cost and be more environmentally friendly, realizes mild reaction and high yield, and through the post-treatment of the reaction liquid, the reaction liquid can be directly extracted by adding an extraction agent after being concentrated and being reduced to room temperature, and then the extraction agent is concentrated, precipitated, filtered, and recrystallized to realize simple separation and purification process, which greatly reduces the complexity of the post-treatment, improves the yield and purity of the final product, and reduces the preparation cost. The reaction condition is mild and easy to control, the post-treatment process is simple and efficient, and the preparation method meets the requirements of large-scale preparation.

[0006] The preparation method of high-purity vitamin C ethyl ether comprises an etherification reaction stage and an extraction, separation, and purification post-treatment stage. In the etherification reaction stage, a reaction system composed of water, an inorganic base, and an organic phase solvent is used, and a two-phase catalyst is used to perform etherification reaction on vitamin C and an alkylating agent under the protection of nitrogen. The reaction is performed at 25-60°C for 2-5 hours to generate a vitamin C ethyl ether solution. The organic phase is extracted several times, concentrated, and then the solid crude product is recrystallized and dried to obtain vitamin C ethyl ether crude product. High-purity vitamin C ethyl ether is obtained through recrystallization.

[0007] The inorganic base is one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and sodium bicarbonate. The organic phase solvent is one or more of ethyl acetate, methyl acetate, butyl acetate, butanone, and methyl isobutyl ketone. The two-phase catalyst is one or more of benzyl triethyl ammonium chloride, tetrabutyl ammonium bromide, tetrabutyl ammonium iodide, tetrabutyl ammonium chloride, tetrabutyl phosphonium bromide, and polyethylene glycol 600. The alkylating agent is one or more of diethyl sulfate, diethyl carbonate, ethyl p-toluenesulfonate, bromoethane, and iodoethane.

[0008] In the above preparation method of high-purity vitamin C ethyl ether, the molar ratio of vitamin C: alkylating agent: two-phase catalyst: inorganic base is 1:0.5-1.5:1-5%:1-3, and the mass ratio of water: organic phase solvent is 1:0-2.

[0009] The above preparation method of high-purity vitamin C ethyl ether is characterized in that the extraction, separation, and purification post-treatment stage comprises the following steps: 1) The vitamin C ethyl ether solution is cooled to room temperature, an organic solvent A is added for extraction, the volume ratio of the concentrated organic solvent is 1 / 5-1 / 3 of the total amount of the organic solvent, the temperature is reduced to 0-10°C, and the vitamin C ethyl ether crude product is obtained by filtration. 2) The crude vitamin C ethyl ether product of step 1) is directly added into solvent B without drying, and after being warmed to complete dissolution, the hot filtrate is recrystallized to obtain high-purity vitamin C ethyl ether; the organic solvent A is one or more of ethyl acetate, methyl acetate, butyl acetate, butanone, methyl isobutyl ketone; the solvent B is one or more of ethyl acetate, methyl acetate, ethanol, water.

[0010] The preparation method of the high-purity vitamin C ethyl ether described above, the weight ratio of the organic solvent A to vitamin C is 5-20:1, and the weight ratio of the solvent B to the crude vitamin C ethyl ether product is 0.5-5:1.

[0011] The preparation method of the high-purity vitamin C ethyl ether described above, the two-phase catalyst is tetrabutylammonium bromide.

[0012] The preparation method of the high-purity vitamin C ethyl ether described above, the inorganic base is sodium hydroxide.

[0013] The preparation method of the high-purity vitamin C ethyl ether described above, the organic phase solvent is butanone.

[0014] The preparation method of the high-purity vitamin C ethyl ether described above, the extraction organic solution A is butanone.

[0015] The preparation method of the high-purity vitamin C ethyl ether described above, the recrystallization solvent B is ethyl acetate.

[0016] The beneficial effects of the present application are: The present application is a preparation method of high-purity vitamin C ethyl ether, which completes the alkylation reaction in one step under the action of a two-phase catalyst. The selectivity and reaction speed of the alkylation in the etherification reaction process are improved by optimizing the reaction conditions such as the catalyst, inorganic base, solvent system, molar ratio of reactants, reaction temperature, and feeding mode, so that the reaction time is 2-5 hours, the conversion rate is more than 90%, and the cumbersome degree of the post-treatment is greatly reduced. The reaction liquid can be directly extracted by adding an extractant after being cooled without being concentrated, and then the product is separated and purified through simple processes such as concentration, precipitation, filtration, and recrystallization. The yield of the final product vitamin C ethyl ether is 80%, and the purity reaches 99.85%. The preparation cost is effectively reduced, and the effect is obvious. The reaction conditions are mild and easy to control, the post-treatment process is simple and efficient, and the method meets the requirements of large-scale preparation. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 The HPLC detection graph of the vitamin C ethyl ether prepared in Example 9. DETAILED DESCRIPTION

[0018] The preparation method of high-purity vitamin C ethyl ether comprises an etherification reaction synthesis stage and an extraction, separation and purification post-processing stage. First, under the protection of nitrogen, vitamin C, water, a two-phase catalyst, an organic phase, an alkylating agent and an inorganic base are added, the reaction temperature is 30-60 DEG C, the reaction time is 2-5 hours, and a vitamin C ethyl ether solution is generated. The content of nitrogen is greater than 50%, and the water is industrial deionized water. The two-phase catalyst is one or more of benzyl triethyl ammonium chloride, tetrabutyl ammonium bromide, tetrabutyl ammonium iodide, tetrabutyl ammonium chloride, tetrabutyl phosphonium bromide and polyethylene glycol 600, the organic phase solvent is one or more of ethyl acetate, methyl acetate, butyl acetate, butanone and methyl isobutyl ketone, the alkylating agent is one or more of diethyl sulfate, diethyl carbonate, ethyl p-toluene sulfonate, bromoethane and iodoethane, and the inorganic base is one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and sodium bicarbonate.

[0019] In the above synthesis method of vitamin C ethyl ether, the molar ratio of vitamin C to two-phase catalyst is 1:1-5%, the molar ratio of vitamin C to alkylating agent is 1:0.5-1.5, the molar ratio of vitamin C to inorganic base is 1:1-3, and the mass ratio of water to organic phase solvent is 1:0-2. The extraction, separation and purification post-processing stage comprises the following steps: the reaction solution is cooled to room temperature, one or more of ethyl acetate, methyl acetate, butyl acetate, butanone and methyl isobutyl ketone is added as an organic solvent (extractant), the organic solvent is concentrated to 1 / 5-1 / 3 of the total amount of the extraction liquid, the temperature is lowered to 0-10 DEG C, and the vitamin C ethyl ether crude product is obtained by filtration. The crude product is directly used in the next recrystallization stage without drying, the recrystallization solvent is one or more of ethyl acetate, methyl acetate, ethanol and water, the mass ratio of vitamin C to organic solvent (extractant) is 1:2-20, and the mass ratio of vitamin C ethyl ether crude product to recrystallization solvent is 1:0.5-5. The two-phase catalyst is preferably tetrabutyl ammonium bromide, the organic solvent (reaction liquid) is preferably butanone, the organic solvent (extractant) is preferably ethyl acetate, and the recrystallization solvent is preferably ethyl acetate.

[0020] Example 1

[0021] In 100 ml of ajar, add the rotor, weigh 5.28 g (0.03 mol) of vitamin C, 10 ml of water and 10 ml of butanone, stir and dissolve into a colorless transparent mixed solution under the protection of nitrogen, add diethyl sulfate 5.54 g (0.036 mol) to 50 ℃, slowly add sodium hydroxide 1.44 g (0.036 mol) to 60 ℃, react for 2 hours, end, reduce to room temperature, stand and separate, extract with butanone 10 ml twice, combine the organic phase, concentrate to dryness to get white solid crude product, recrystallize with ethyl acetate, dry to get 2.63 g, purity 94.0%, yield 43%. Melting point: 114-116 ℃ (literature value: 112-116 ℃). Nuclear magnetic resonance hydrogen spectrum data as follows: ESI (m / z): 204; 1 HNMR (600 MHz, D2O): 1.25 (3H, t), 3.64 (1H, d), 3.36-3.43 (2H, m), 4.36-4.43 (2H, m), 4.71 (1H, s).

[0022] Example 2

[0023] In 100 ml of ajar, add the rotor, weigh 5.28 g (0.03 mol) of vitamin C, 0.42 g (0.0015 mol) of tetrabutylammonium chloride, 10 ml of water, stir and dissolve, under the protection of nitrogen, add diethyl sulfate 6.00 g (0.039 mol) at one time to 50 ℃, slowly add 30% potassium hydroxide 2.52 g (0.045 mol) aqueous solution within 2 hours, heat to 60 ℃, react for 1 hour, end, reduce to room temperature, extract with butanone 10 ml three times, combine the organic phase, concentrate to dryness to get white solid crude product, recrystallize with ethyl acetate, dry to get 3.07 g of vitamin C ethyl ether, purity 95.4%, yield 50%.

[0024] Example 3

[0025] In 100 ml of ajar, add the rotor, weigh 5.28 g (0.03 mol) of vitamin C, 0.42 g (0.0015 mol) of tetrabutylammonium chloride, 10 ml of water, stir and dissolve, under the protection of nitrogen, add diethyl sulfate 5.54 g (0.036 mol) to 50 ℃, slowly add 30% sodium hydroxide 1.44 g (0.036 mol) aqueous solution within 2 hours, heat to 60 ℃, react for 1 hour, end, reduce to room temperature, extract with butanone 10 ml three times, combine the organic phase, concentrate to dryness to get white solid crude product, recrystallize with ethyl acetate, dry to get 3.19 g of vitamin C ethyl ether, purity 96.0%, yield 52%.

[0026] Example 4

[0027] In 100 ml of a flask, add a rotor, weigh 5.28 g (0.03 mol) of vitamin C, 0.42 g (0.0015 mol) of tetrabutylammonium chloride, 10 ml of water, and 10 ml of butanone, and stir to dissolve under nitrogen to form a colorless transparent solution. Add 30% sodium hydroxide aqueous solution 1.8 g (0.045 mol) dropwise and diethyl sulfate 6.93 g (0.045 mol) dropwise at 60°C for 2 hours. After 1 hour of reaction, cool to room temperature, extract three times with butanone 10 ml, combine the organic phases, and concentrate to dryness to obtain a white solid crude product. Recrystallize with ethyl acetate, dry, and obtain 3.31 g of vitamin C ethyl ether with a purity of 97.2% and a yield of 54%.

[0028] Example 5

[0029] In 100 ml of a flask, add a rotor, weigh 5.28 g (0.03 mol) of vitamin C, 0.42 g (0.0015 mol) of tetrabutylammonium chloride, 10 ml of water, and 10 ml of butanone, and stir to dissolve under nitrogen to form a colorless transparent solution. Add 30% sodium hydroxide aqueous solution 1.8 g (0.045 mol) dropwise and diethyl sulfate 6.93 g (0.045 mol) dropwise at 60°C for 2 hours. After 1 hour of reaction, cool to room temperature, extract three times with butanone 10 ml, combine the organic phases, and concentrate to dryness to obtain a white solid crude product. Recrystallize with ethyl acetate, dry, and obtain 3.31 g of vitamin C ethyl ether with a purity of 97.2% and a yield of 54%.

[0030] Example 6

[0031] In 100 ml of a flask, add a rotor, weigh 5.28 g (0.03 mol) of vitamin C, 0.42 g (0.0015 mol) of tetrabutylammonium chloride, 10 ml of water, and 10 ml of butanone, and stir to dissolve under nitrogen to form a colorless transparent solution. Add 30% sodium hydroxide aqueous solution 1.8 g (0.045 mol) dropwise and diethyl sulfate 6.93 g (0.045 mol) dropwise at 60°C for 2 hours. After 1 hour of reaction, cool to room temperature, extract three times with butanone 10 ml, combine the organic phases, and concentrate to dryness to obtain a white solid crude product. Recrystallize with ethyl acetate, dry, and obtain 3.31 g of vitamin C ethyl ether with a purity of 97.2% and a yield of 54%.

[0032] Example 7

[0033] In a 100ml round-bottom flask, a rotor was added, and 5.28g (0.03mol) of vitamin C, 0.39g (0.0012mol) of tetrabutylammonium bromide, 10ml of water, and 10ml of butanone were weighed out. Under nitrogen protection, the mixture was stirred and dissolved into a colorless and transparent mixed solution. 9.01g (0.045mol) of ethyl p-toluenesulfonate was added, and the temperature was raised to 50℃. 1.80g (0.045mol) of sodium hydroxide was slowly added, and the temperature was maintained at 60℃ for 2 hours. The mixture was then cooled to room temperature, allowed to stand and separate into layers, and extracted twice with 10ml of butanone. The organic phases were combined and concentrated to dryness to obtain a white solid crude product. Recrystallization from ethyl acetate and drying yielded 4.72g of vitamin C ethyl ether with a purity of 98.4% and a yield of 77%.

[0034] Examples 2-7 verified the effects of not adding a two-phase catalyst, using different two-phase catalysts, different inorganic bases, different organic reaction solvents, different alkylating agents, different feeding methods, and different molar ratios of reactants on the reaction yield and purity. By optimizing the reaction conditions, the process parameters of the reaction were made more suitable for large-scale preparation. At the same time, the most effective post-processing method, namely, continuous extraction without concentration, was explored to achieve the separation and purification of the target product. The key technical indicators of the target product vitamin C ethyl ether, with a yield of 77% and a purity of up to 98.6%, were achieved, laying the foundation for the final industrial scale-up.

[0035] Example 8

[0036] In a 3000L enamel reactor, start stirring, add 500kg water, add vitamin C 264kg (1.5Kmol), tetrabutylammonium bromide 24.2kg (0.075Kmol), add sodium hydroxide 90kg (2.3Kmol) in three batches, control the temperature below 55℃, stir and dissolve, then add butanone 500kg, slowly add diethyl sulfate 323.4kg (2.1Kmol) under nitrogen protection, complete within 3 hours, keep the temperature for 2 hours, after testing, pump the vitamin C ethyl ether reaction liquid and the extracting agent butanone into the continuous extraction device, separate the organic phase to the distillation kettle, reduce the pressure to remove the solvent, the vacuum degree is greater than or equal to 0.085MPa, heat to 45-55℃, continue to reduce the pressure to distill and remove the organic solvent until the extraction liquid is thick (about one fourth of the solvent amount), cool the concentrated liquid to 5-10℃ to precipitate the solid, filter through the centrifuge, then wash the solid with appropriate amount of ethyl acetate to obtain 280kg of crude product; put the wet material into 5 times amount of ethyl acetate, heat the dissolving kettle to 70℃ to completely dissolve, then pump into the preheated crystallization kettle through the filter, start stirring, gradually cool to 60℃, then add the crystal seed, keep the temperature for 0.5 hours to recrystallize, uniformly cool to 45℃, a large amount of solid precipitates, quickly cool to 5-10℃, keep the temperature for 0.5 hours, filter through the centrifuge, then wash the solid with a small amount of ethyl acetate; transfer the refined wet material into the double-cone dryer, the vacuum degree is greater than or equal to 0.085MPa, control the temperature at 45-55℃, dry to constant weight, obtain 230kg of white crystalline powder vitamin C ethyl ether, the yield is 75%, the content is 99.7%

[0037] Example 9

[0038] In a 3000L enamel reactor, start stirring, add 500kg water, add vitamin C 264kg (1.5Kmol), tetrabutylammonium bromide 24.2kg (0.075Kmol), nitrogen protection condition, temperature rise 50-55℃ stirring dissolution, add butanone 500kg, while slowly add diethyl sulfate 323.4kg (2.1Kmol), drop 30% sodium hydroxide aqueous solution 90kg (2.3Kmol), complete within 3 hours, keep warm for 2 hours, after detection, pump the vitamin C ethyl ether reaction liquid and the extracting agent butanone into the continuous extraction device, separate the organic phase to the distillation kettle, reduce pressure to dissolve, vacuum degree ≥0.085MPa, temperature rise to 45-55℃, continue to reduce pressure distillation to remove organic solvent to the extraction liquid sticky (about one fourth of the solvent amount), the concentrated liquid is cooled to 5-10℃ to precipitate solid, filter through centrifuge, then wash the solid with appropriate amount of ethyl acetate to obtain 310kg of crude product; put the wet material into 5 times amount of ethyl acetate, dissolve the kettle to 70℃, completely dissolve, then pump into the preheated crystallization kettle through the filter, open the stirring, through gradient cooling to 60℃, then add seed crystal, keep warm for 0.5 hours, recrystallize, uniform speed cooling to 40℃, a large amount of solid precipitates, rapid cooling to 5-10℃, keep warm for 0.5 hours, filter through centrifuge, then wash the solid with a small amount of ethyl acetate; transfer the refined wet material into the double-cone dryer, vacuum degree ≥0.085MPa, control temperature 45-55℃, dry to constant weight, obtain 245kg of white crystalline powder vitamin C ethyl ether, yield 80%, content 99.85%, HPLC detection as shown in Figure 1 .

[0039] By Examples 8-9, it is verified that under the condition of other process parameters unchanged, using different alkali adding methods, solid powder batch adding or water solution form drop adding, the selective influence on the preparation of target product vitamin C ethyl ether in the process scale-up, finally verify the significant difference of the yield and purity of target product vitamin C ethyl ether, at the same time, verify that using continuous extraction method is suitable for the needs of industrial preparation of this product, which can effectively separate and purify vitamin C ethyl ether, there is no related report on the application of this technology in industrial preparation of this product, through the effect of the above examples, the reaction conditions of the whole preparation process of vitamin C ethyl ether (etherification reaction synthesis stage and treatment stage) are mild, easy to control, the post-treatment process is simple and efficient, which significantly reduces the preparation cost (raw material cost and labor cost), and meets the requirements of large-scale industrial preparation.

Claims

1. A method for preparing high-purity vitamin C ethyl ether, the entire preparation process comprising: The etherification reaction stage and the extraction, separation, and purification post-processing stage are characterized in that: the etherification reaction stage is carried out under nitrogen protection, with a reaction system consisting of water, inorganic base, and organic solvent. Under the action of a two-phase catalyst, vitamin C and alkylating reagent undergo etherification reaction. The reaction is carried out at 25-60℃ for 2-5 hours to generate vitamin C ethyl ether solution. The organic phases are extracted several times, concentrated, and then the solid crude product is recrystallized and dried to obtain crude vitamin C ethyl ether. High-purity vitamin C ethyl ether is then obtained by recrystallization. The inorganic base is one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and sodium bicarbonate; the organic solvent is one or more of ethyl acetate, methyl acetate, butyl acetate, butanone, and methyl isobutyl ketone; the two-phase catalyst is one or more of benzyltriethylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium chloride, tetrabutylphosphonium bromide, and polyethylene glycol 600; and the alkylating agent is one or more of diethyl sulfate, diethyl carbonate, ethyl p-toluenesulfonate, bromoethane, and iodoethane.

2. The method for preparing high-purity vitamin C ethyl ether according to claim 1, characterized in that: The molar ratio of vitamin C: alkylating agent: two-phase catalyst: inorganic base is 1:0.5~1.5:1-5%:1~3; the mass ratio of water: organic phase solvent is 1:0~2.

3. The method for preparing high-purity vitamin C ethyl ether according to claim 1 or claim 2, characterized in that, The extraction, separation, purification, and post-processing steps include: 1) Cool the vitamin C ethyl ether solution to room temperature, add organic solvent A for extraction, concentrate the organic solvent volume ratio to 1 / 5 to 1 / 3 of the total organic solvent volume, cool to 0 to 10°C, and filter to obtain crude vitamin C ethyl ether product; 2) The crude vitamin C ethyl ether product from step 1) is added directly to solvent B without drying, heated until completely dissolved, hot filtered, and then recrystallized to obtain high-purity vitamin C ethyl ether; the organic solvent A is one or more of ethyl acetate, methyl acetate, butyl acetate, butanone, and methyl isobutyl ketone; the solvent B is one or more of ethyl acetate, methyl acetate, ethanol, and water.

4. The method for preparing high-purity vitamin C ethyl ether according to claim 3, characterized in that: The weight ratio of organic solvent A to vitamin C is 5~20:1, and the weight ratio of solvent B to crude vitamin C ethyl ether is 0.5~5:

1.

5. The method for preparing high-purity vitamin C ethyl ether according to claim 1, characterized in that: The two-phase catalyst is tetrabutylammonium bromide.

6. The method for preparing high-purity vitamin C ethyl ether according to claim 1, characterized in that: The inorganic base is sodium hydroxide.

7. The method for preparing high-purity vitamin C ethyl ether according to claim 1, characterized in that: The organic solvent is butanone.

8. The method for preparing high-purity vitamin C ethyl ether according to claim 1, characterized in that: The organic solution A being extracted is butanone.

9. The method for preparing high-purity vitamin C ethyl ether according to claim 1, characterized in that: The recrystallization solvent B is ethyl acetate.

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