A process for the preparation of a vc derivative ascorbyl tetraisopalmitate

Abstract

The application discloses a preparation method of a VC derivative ascorbic acid tetraisopalmitate, and is characterized by the following steps: taking vitamin C and 2-hexyl decanoic acid as raw materials, performing esterification reaction in a supported catalyst and an alkaline eutectic solvent system, and preparing ascorbic acid tetraisopalmitate; the supported catalyst is prepared by the following steps: firstly, reacting 4-dimethylamino pyridine with trifluoromethanesulfonic anhydride to prepare Tf-DMAP, and then loading the Tf-DMAP on a silica carrier with surface grafted polystyrene brush to prepare the supported catalyst; and the alkaline eutectic solvent is a ternary eutectic solvent system composed of choline chloride, urea and an organic base acid-binding agent. The preparation method has the advantages of mild reaction conditions, easy separation and recovery of the catalyst, green environmental protection, simple post-treatment operation, high product yield and the like.

Description

Technical Field

[0001] This invention relates to a method for preparing ascorbic acid tetraisopalmitate, a VC derivative, and belongs to the field of chemical synthesis technology. Background Technology

[0002] Ascorbate tetraisopalmitate (chemical structural formula is) Ascorbyl Tetraisopalmitate (VCIP), also known as tetrahexyldecyl ascorbic acid, VC tetraisopalmitate, tetrahexyldecyl ascorbic acid, tetrahexyldecanoic acid ascorbate, tetrahexyldecyl alcohol ascorbate, and tetrahexyl-2-hexyldecanoate, is an oil-soluble vitamin C derivative. Its molecular structure consists of four hydroxyl groups (positions 2, 3, 5, and 6) on the vitamin C (L-ascorbic acid) molecule replaced by isopalmitoyl residues. VCIP not only retains the antioxidant activity of vitamin C but also exhibits good lipid solubility due to the introduction of long-chain fatty acids, enabling it to effectively penetrate the skin barrier and showing broad application prospects in cosmetics, food, and pharmaceuticals.

[0003] Currently, the main methods for preparing ascorbate tetraisopalmitate are chemical synthesis and bio-enzymatic synthesis. Chemical synthesis mainly includes the acyl chloride method and the esterification method.

[0004] The acyl chloride process involves reacting 2-hexyldecanoic acid with a chlorinating agent (such as thionyl chloride or phosphorus trichloride) to produce 2-hexyldecanoyl chloride. Then, the 2-hexyldecanoyl chloride is esterified with vitamin C in the presence of an acid-binding agent (such as pyridine or triethylamine) to obtain ascorbic acid tetraisopalmitate. The acyl chloride process requires highly corrosive reagents such as thionyl chloride and phosphorus trichloride, placing high demands on equipment and posing significant operational risks. Furthermore, the acyl chloride intermediates generated during the reaction are highly reactive and readily react with water, necessitating a strictly anhydrous reaction system and demanding operating conditions. Additionally, the reaction produces large amounts of acidic wastewater, requiring complex post-treatment and causing severe environmental pollution.

[0005] Esterification methods include direct esterification and oxidative esterification. Direct esterification involves the direct esterification of vitamin C (L-ascorbic acid) with 2-hexyldecanoic acid in the presence of a catalyst. Oxidative esterification involves the oxidative esterification of vitamin C with 2-hexyldecanoic acid in the presence of a catalyst and an oxidant. Esterification methods typically require strong acid (such as concentrated sulfuric acid) catalysts or strong oxidants, resulting in drawbacks such as severe equipment corrosion, numerous side reactions, and complex post-processing.

[0006] Biocatalytic synthesis typically uses enzymes (such as Novozym 435) to catalyze the transesterification reaction of vitamin C with fatty acid esters to synthesize ascorbic acid tetraisopalmitate. Although this method has mild reaction conditions, it suffers from drawbacks such as low catalytic efficiency, high byproduct content, and difficulty in product separation. Furthermore, the enzyme catalyst is expensive, which is not conducive to large-scale industrial production.

[0007] In addition, the catalysts used in the preparation of ascorbate tetraisopalmitate are usually difficult to separate and recover, resulting in high production costs and complex purification operations. Furthermore, organic solvents (such as dichloromethane, chloroform, N-methylpyrrolidone, etc.) are usually used as reaction solvents, which poses an environmental pollution risk.

[0008] Therefore, it is necessary to develop a green, environmentally friendly, easy-to-process, and industrially scalable method for preparing ascorbic acid tetraisopalmitate, a VC derivative. Summary of the Invention

[0009] In view of the above-mentioned problems in the prior art, the purpose of this invention is to provide a method for preparing VC derivative ascorbate tetraisopalmitate.

[0010] To achieve the above objectives, the present invention adopts the following technical solution: A method for preparing a vitamin C derivative, ascorbic acid tetraisopalmitate, involves using vitamin C (i.e., L-ascorbic acid) and 2-hexyldecanoic acid as raw materials, and carrying out an esterification reaction in a supported catalyst and an alkaline eutectic solvent system to obtain ascorbic acid tetraisopalmitate. The supported catalyst is prepared by first reacting 4-dimethylaminopyridine (DMAP) with trifluoromethanesulfonic anhydride (Tf2O) to prepare Tf-DMAP, and then immobilizing Tf-DMAP on a silica support grafted with polystyrene brushes. The alkaline eutectic solvent is a ternary eutectic solvent system composed of choline chloride, urea and an organic base acid binder.

[0011] In one embodiment, during the preparation of ascorbic acid tetraisopalmitate, the molar ratio of vitamin C to 2-hexyldecanoic acid is 1:4-6, the amount of supported catalyst is 5-15% of the mass of vitamin C based on Tf-DMAP, and the amount of alkaline eutectic solvent is 10-30% of the total mass of reactants.

[0012] In one embodiment, during the preparation of ascorbic acid tetraisopalmitate, the esterification reaction temperature is 25-50℃ and the reaction time is 8-24 hours.

[0013] In one embodiment, after the esterification reaction is completed, hexane is added to the reaction system for extraction, and the hexane phase is collected by separation. The supported catalyst is dispersed in an alkaline eutectic solvent phase, and the catalyst is recovered by centrifugation or filtration. The alkaline eutectic solvent phase is recovered by vacuum distillation. The hexane phase is washed successively with saturated sodium bicarbonate solution and saturated brine, dried with anhydrous sodium sulfate, filtered, and distilled under vacuum. The resulting product is recrystallized from hexane to obtain ascorbic acid tetraisopalmitate.

[0014] In one embodiment, the preparation of the supported catalyst includes the following steps: 1) Under nitrogen protection, 4-dimethylaminopyridine (DMAP) was dissolved in dichloromethane, cooled to 0-5°C, and trifluoromethanesulfonic anhydride (Tf2O) was slowly added. After the addition was complete, the mixture was heated to room temperature and stirred for 3-5 hours to obtain Tf-DMAP. 2) The silica support (SiO2@PS) grafted with polystyrene brushes was dispersed in dichloromethane, and the Tf-DMAP prepared in step 1) was added. The mixture was stirred at room temperature for 12-24 hours to obtain a supported catalyst. This invention first synthesizes the active material Tf-DMAP under homogeneous conditions, and then immobilizes the prepared Tf-DMAP on the support. The DMAP and Tf2O are in full contact, resulting in a complete reaction and high conversion rate. This avoids the problems of incomplete reaction and uneven active sites caused by mass transfer limitations and steric hindrance when directly reacting with Tf2O on immobilized DMAP, thus ensuring the integrity and uniformity of the catalyst's active centers. Furthermore, the obtained Tf-DMAP is loaded into the polystyrene brush layer through ionic or hydrogen bonding, maintaining the complete chemical structure and catalytic activity of Tf-DMAP while also giving the catalyst recyclability. When used for the preparation of ascorbic acid tetraisopalmitate, the catalyst can be recovered after the reaction by simple centrifugation or filtration, making post-reaction processing convenient.

[0015] In a preferred embodiment, in step 1), the molar ratio of 4-dimethylaminopyridine (DMAP) to trifluoromethanesulfonic anhydride (Tf2O) is 1:1-1.2.

[0016] In a preferred embodiment, in step 2), the mass ratio of silica carrier to Tf-DMAP is 1:0.5-2.

[0017] In one embodiment, the silica carrier for the surface-grafted polystyrene brush is prepared by first subjecting silica nanoparticles to sequential amylation modification and brominated initiator modification to obtain SiO2@Br, and then using SiO2@Br as an initiator and styrene as a monomer, grafting polymerization is carried out through electron transfer regeneration activated atom transfer radical polymerization technology to obtain polystyrene brush-grafted silica (SiO2@PS); wherein, the amylation modifier used in the amylation modification is 3-aminopropyltriethoxysilane, and the brominated initiator is 2-bromoisobutyryl bromide.

[0018] In the silica carrier grafted with polystyrene brushes, the silica nanoparticles can be commercially available or made using existing technology. The particle size of the silica nanoparticles is 50-200 nm. For example, silica nanoparticles (SiO2) can be made using the Stöber method. The Stöber method for preparing silica nanoparticles involves hydrolyzing and condensing tetraethyl orthosilicate (TEOS) in a mixture of alcohol, water, and ammonia to obtain monodisperse spherical silica nanoparticles. This technology is conventional in the field, and the specific process can be found in existing published literature, which will not be elaborated here.

[0019] In a preferred embodiment, the preparation of the silica carrier with the surface grafted polystyrene brush includes the following steps: ① Disperse silica nanoparticles in an organic solvent (e.g., toluene, xylene, etc.), add 3-aminopropyltriethoxysilane (APTES), and react at 80-130℃ for 24-72 hours under inert gas protection. After the reaction is completed, centrifuge, wash, and dry to obtain aminated silica. ② Disperse aminated silica in an organic solvent (e.g., tetrahydrofuran), add an organic amine (e.g., triethylamine), cool to 0-5℃, slowly add 2-bromoisobutyryl bromide (BiBB), after the addition is complete, heat to room temperature and react for 24-72 hours. After the reaction is complete, centrifuge, wash, and dry to obtain SiO2@Br; ③ Disperse SiO2@Br in a solvent (e.g., N,N-dimethylformamide, toluene, anisole, etc.), add styrene monomer, copper halide catalyst, nitrogen-containing ligand and reducing agent, and react at 70-110℃ for 6-24 hours under inert gas protection; after the reaction is completed, centrifuge, wash and dry to obtain silica support with surface grafted polystyrene brush, denoted as SiO2@PS.

[0020] In a preferred embodiment, in step ①, the mass ratio of silica nanoparticles to 3-aminopropyltriethoxysilane (APTES) is 1:0.5-2.

[0021] In a preferred embodiment, in step ②, the mass ratio of aminated silica to 2-bromoisobutyryl bromide is 1:0.5-2, the organic amine is triethylamine, and the molar ratio of triethylamine to 2-bromoisobutyryl bromide is 1-2:1.

[0022] In a preferred embodiment, in step ③, the mass ratio of SiO2@Br to styrene monomer is 1:5-50, more preferably 1:10-20; the copper halide catalyst is CuBr2, the nitrogen-containing ligand is 1,1,4,7,10,10-hexamethyltriethylenetetramine (HMTETA), and the reducing agent is stannous octoate; the molar ratio of the copper halide catalyst to the nitrogen-containing ligand is 1:3-8; and the thickness of the polystyrene brush layer in the obtained SiO2@PS is 20-50 nm.

[0023] In one embodiment, the molar ratio of choline chloride to urea in the alkaline eutectic solvent is 1:1.5-3; the organic base acid-binding agent is selected from at least one of triethylamine, N,N-diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and tetramethylguanidine, and its addition amount is 1-5% of the total mass of choline chloride and urea. In the alkaline eutectic solvent, choline chloride acts as a hydrogen bond acceptor and urea as a hydrogen bond donor, forming the bulk of the eutectic solvent, which serves as a stabilizer for the reaction medium and catalytic intermediate. The organic base acid-binding agent dissolves in the eutectic solvent and participates in the DES hydrogen bond network as a third component. On the one hand, it endows the system with acid-binding function; on the other hand, its hydrogen bonding with choline chloride and urea further enhances the stability and homogeneity of the system.

[0024] In one embodiment, the alkaline eutectic solvent is prepared by: Choline chloride (ChCl) is mixed with urea and stirred at 70-90°C for 1-3 hours until a homogeneous and transparent liquid is formed. After cooling to room temperature, an organic base acid-binding agent is added and stirred evenly to obtain an alkaline eutectic solvent.

[0025] This invention utilizes an alkaline eutectic solvent, with the bulk of the eutectic solvent formed by choline chloride and urea, instead of traditional organic solvents (such as dichloromethane) as the reaction medium. This eutectic solvent bulk is low in toxicity and non-volatile, overcoming the environmental pollution problems of traditional organic solvents. Furthermore, the organic base acid-binding agent in the alkaline eutectic solvent can neutralize the acids generated during the reaction (e.g., trifluoromethanesulfonic acid generated by the active material Tf-DMAP of the supported catalyst). The neutralized onium salts dissolve and stabilize in the hydrogen bond network of the eutectic solvent. After the reaction, the eutectic solvent phase is recovered by vacuum distillation, solving the defect in the prior art where organic bases as homogeneous acid-binding agents are difficult to recover. The alkaline eutectic solvent and the supported catalyst have a synergistic effect. The supported catalyst provides highly efficient and selective acylation catalytic activity, which is the core driving force for the esterification reaction. The eutectic solvent provides a green reaction medium and stabilizes the catalytic intermediate through the hydrogen bond network. The two work synergistically to achieve a highly efficient esterification reaction under mild conditions (25-50°C).

[0026] Compared with the prior art, the present invention has the following significant advantages: This invention uses vitamin C and 2-hexyldecanoic acid as raw materials to carry out an esterification reaction in a supported catalyst and an alkaline eutectic solvent system to obtain ascorbic acid tetraisopalmitate. The catalyst used can be removed by simple filtration or centrifugation after the reaction. At the same time, an eutectic solvent is used instead of traditional organic solvents as the reaction medium. The entire preparation method has the advantages of mild reaction conditions, easy separation and recovery of catalyst, green and environmentally friendly, simple post-processing operation (no column chromatography required, only simple separation, filtration and recrystallization), high product yield (yield can be higher than 90%), and high product purity (purity can be higher than 98%). It is suitable for industrial production and has great industrial application value. Detailed Implementation

[0027] The technical solution of the present invention will be further described in detail and completely below with reference to the embodiments. It should be understood that these embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention. Experimental methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions or as recommended by the manufacturer. Example 1

[0028] I. Preparation of silica carrier for surface-grafted polystyrene brushes ① Anhydrous ethanol (1.049 L), 25% concentrated ammonia (74 mL), and tetraethyl orthosilicate (TEOS, 44 mL) were added sequentially to the reaction vessel. The mixture was stirred at room temperature for 6 hours. After the reaction was completed, the mixture was centrifuged (9000 rpm). The separated product was washed sequentially with deionized water and anhydrous ethanol, and then dried under vacuum at 60 °C for 12 hours to obtain silica nanoparticles (approximately 12.5 g, with a particle size of approximately 85 nm). 12.0 g of silica nanoparticles were dispersed in 120 mL of anhydrous xylene, and 12.0 g of 3-aminopropyltriethoxysilane (APTES) was added. The mixture was stirred at 120 °C for 48 hours under nitrogen protection. After the reaction was completed, the mixture was centrifuged (9000 rpm). The separated product was washed successively with anhydrous xylene and anhydrous ethanol, and dried under vacuum at 60 °C for 12 hours to obtain aminated silica (approximately 12.8 g). ② Disperse aminated silica (11.0 g) in anhydrous tetrahydrofuran (THF, 150 mL), cool in an ice bath to 0-5 °C, add triethylamine (8.0 mL, 57.4 mmol), and slowly add 2-bromoisobutyryl bromide (BiBB, 5.9 mL, 47.8 mmol). After the addition is complete, remove the ice bath, raise the temperature to room temperature and stir for 48 hours. After the reaction is complete, centrifuge (9000 rpm), wash the separated product with anhydrous THF, deionized water and anhydrous ethanol in sequence, and dry under vacuum at 60 °C for 12 hours to obtain SiO2@Br (approximately 11.5 g). ③ Disperse SiO2@Br in a solvent (e.g., N,N-dimethylformamide, toluene, anisole, etc.), add styrene monomer, copper halide catalyst, nitrogen-containing ligand and reducing agent, and react at 70-110℃ for 6-24 hours under inert gas protection; after the reaction is completed, centrifuge, wash and dry to obtain silica support with surface grafted polystyrene brush, denoted as SiO2@PS.

[0029] SiO2@Br (2.0 g) was dispersed in N,N-dimethylformamide (DMF, 40 mL), and styrene monomer (20.0 g, 192 mmol) was added. Nitrogen gas was bubbled through the mixture for 30 minutes to remove oxygen. CuBr2 (4.5 mg, 0.02 mmol), 1,1,4,7,10,10-hexamethyltriethylenetetramine (HMTETA, 23.0 mg, 0.10 mmol), and stannous octoate (Sn(EH)2, 48.6 mg, 0.12 mmol) were added. The reaction system was sealed and stirred at 90 °C for 12 hours. After the reaction was completed, the mixture was cooled to room temperature and centrifuged (9000 rpm). The separated product was washed successively with toluene, tetrahydrofuran, and methanol, and dried under vacuum at 60 °C for 12 hours to obtain a polystyrene brush-grafted silica support (denoted as SiO2@PS, approximately 2.3 g). Transmission electron microscopy (TEM) showed that the polystyrene brush layer thickness was approximately 35 nm.

[0030] II. Preparation of Supported Catalysts 1) Under nitrogen protection, 4-dimethylaminopyridine (DMAP, 6.1 g, 50 mmol) was dissolved in dichloromethane (100 mL), and the temperature was lowered to 0-5 °C. Trifluoromethanesulfonic anhydride (Tf₂O, 14.1 g, 50 mmol) was dissolved in dichloromethane (50 mL), and slowly added dropwise to the reaction system containing DMAP. The dropping rate was controlled so that the reaction temperature did not exceed 5 °C. After the addition was complete, the mixture was heated to room temperature and stirred for 4 hours. After the reaction was completed, the mixture was centrifuged (9000 rpm), the separated product was washed with petroleum ether, and dried under vacuum at 40 °C for 4 hours to obtain Tf-DMAP (approximately 14.5 g). 2) The silica support (SiO2@PS, 1.0 g) grafted with polystyrene brushes was dispersed in dichloromethane (50 mL), and Tf-DMAP (1.0 g) was added. The mixture was stirred at room temperature for 24 hours. After the reaction was completed, the mixture was filtered. The solid obtained by filtration was washed with dichloromethane and dried under vacuum at 40 °C for 12 hours to obtain a supported catalyst (1.85 g). The nitrogen content was determined by elemental analysis, and the Tf-DMAP loading in the catalyst was calculated to be approximately 0.38 mmol / g.

[0031] III. Preparation of Alkaline Eutectic Solvents Choline chloride (ChCl) and urea were mixed at a molar ratio of 1:2 and stirred at 80°C under nitrogen protection for 60 minutes until a uniform and transparent liquid was formed. After cooling to room temperature, 2% of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) of the total mass of choline chloride and urea was added and stirred until homogeneous to obtain an alkaline eutectic solvent.

[0032] IV. Preparation of ascorbic acid tetraisopalmitate

[0033] In a reaction flask, vitamin C (1.76 g, 10 mmol), 2-hexyldecanoic acid (11.5 g, 48 mmol), a self-made supported catalyst (0.46 g, 10% of the mass of vitamin C based on Tf-DMAP), and a self-made basic eutectic solvent (2.0 g, 15.0% of the total mass of vitamin C and 2-hexyldecanoic acid) were added, the temperature was raised to 40 °C, and the reaction was stirred for 15 hours. After the reaction was completed, n-hexane (30 mL) was added to the system for extraction, and the mixture was separated to obtain the eutectic solvent phase and the n-hexane phase, respectively. The eutectic solvent phase (containing the supported catalyst and the salt generated by the neutralization of the acid-binding agent) is centrifuged (9000 rpm). The lower solid layer is the supported catalyst, thus removing the supported catalyst from the eutectic solvent phase. The supported catalyst is recovered, dried, and weighed, with a catalyst recovery rate of 95.8%. The upper clear liquid is the eutectic solvent phase after removing the catalyst (containing the salt generated by the neutralization of the acid-binding agent and choline chloride / urea). It is then distilled under reduced pressure (80℃, 10 mmHg) to remove residual n-hexane and a small amount of water, thus recovering the eutectic solvent. If the recovered eutectic solvent is to be recycled, since the acid-binding agent in the recovered eutectic solvent has been converted into the corresponding salt and lost its acid-binding ability, fresh acid-binding agent needs to be added before it can be recycled. The hexane phase (ascorbic acid tetraisopalmitate is a long-chain fatty acid ester compound that is highly soluble in hexane) was washed successively with saturated sodium bicarbonate solution (which reacts with unreacted 2-hexyldecanoic acid to form a water-soluble sodium carboxylate salt, thereby removing unreacted 2-hexyldecanoic acid; neutralizes any remaining TfOH; and washes away any trace DBU that accidentally entered the hexane phase by converting it into a water-soluble salt) and saturated brine, dried over anhydrous sodium sulfate, filtered, and distilled under reduced pressure. The crude product was recrystallized from hexane to obtain a white crystalline product, which was ascorbic acid tetraisopalmitate (8.73 g, yield 93.0%, HPLC purity 98.5%). Example 2

[0034] The difference between this embodiment and Example 1 is as follows: In the reaction flask, vitamin C (1.76 g, 10 mmol), 2-hexyldecanoic acid (12.0 g, 50 mmol), the self-made supported catalyst from Example 1 (0.35 g, 7.5% of the mass of L-ascorbic acid based on Tf-DMAP), and the self-made basic eutectic solvent from Example 1 (2.5 g, 18.1% of the total mass of vitamin C and 2-hexyldecanoic acid) were added, the temperature was raised to 35°C, and the reaction was stirred for 20 hours; after the reaction, the post-processing method was the same as in Example 1; the yield of the obtained ascorbic acid tetraisopalmitate was 94.3%, and the HPLC purity was 98.6%. Example 3

[0035] The difference between this embodiment and Example 1 is as follows: In the reaction flask, vitamin C (1.76 g, 10 mmol), 2-hexyldecanoic acid (14.4 g, 60 mmol), the self-made supported catalyst from Example 1 (0.46 g, 10% of the mass of L-ascorbic acid based on Tf-DMAP), and the self-made basic eutectic solvent from Example 1 (3.0 g, 18.5% of the total mass of vitamin C and 2-hexyldecanoic acid) were added, the temperature was raised to 45°C, and the reaction was stirred for 12 hours; after the reaction, the post-processing method was the same as in Example 1; the yield of the obtained ascorbic acid tetraisopalmitate was 90.9%, and the HPLC purity was 98.3%. Example 4

[0036] The difference between this embodiment and Example 1 is that in the preparation of ascorbic acid tetraisopalmitate, the acid-binding agent used in the alkaline eutectic solvent is triethylamine (TEA) instead of DBU. Specifically, choline chloride and urea are mixed at a molar ratio of 1:2 and stirred at 80°C under nitrogen protection for 60 minutes until a uniform and transparent liquid is formed. After cooling to room temperature, 2% of the total mass of choline chloride and urea is added to the triethylamine mixture and stirred until homogeneous to obtain the alkaline eutectic solvent. The remaining conditions are the same as in Example 1. The yield of the obtained ascorbic acid tetraisopalmitate is 91.8%, and the HPLC purity is 98.4%.

[0037] Finally, it should be noted that the above are only some preferred embodiments of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-essential improvements and adjustments made by those skilled in the art based on the above content of the present invention shall fall within the scope of protection of the present invention.

Claims

1. A method for preparing a vitamin C derivative, ascorbate tetraisopalmitate, characterized in that, Ascorbate tetraisopalmitate was prepared by esterification reaction of vitamin C and 2-hexyldecanoic acid in a supported catalyst and alkaline eutectic solvent system. The supported catalyst is prepared by first reacting 4-dimethylaminopyridine with trifluoromethanesulfonic anhydride to prepare Tf-DMAP, and then immobilizing Tf-DMAP on a silica support grafted with polystyrene brushes. The alkaline eutectic solvent is a ternary eutectic solvent system composed of choline chloride, urea and an organic base acid binder.

2. The method for preparing the VC derivative ascorbate tetraisopalmitate according to claim 1, characterized in that, In the preparation of ascorbic acid tetraisopalmitate, the molar ratio of vitamin C to 2-hexyldecanoic acid is 1:4-6, the amount of supported catalyst is 5-15% of the mass of vitamin C based on Tf-DMAP, and the amount of alkaline eutectic solvent is 10-30% of the total mass of reactants.

3. The method for preparing the VC derivative ascorbate tetraisopalmitate according to claim 1, characterized in that, In the preparation of ascorbic acid tetraisopalmitate, the esterification reaction temperature is 25-50℃ and the reaction time is 8-24 hours.

4. The method for preparing the VC derivative ascorbate tetraisopalmitate according to claim 1, characterized in that, The preparation of the supported catalyst includes the following steps: 1) Under nitrogen protection, 4-dimethylaminopyridine was dissolved in dichloromethane, cooled to 0-5°C, and trifluoromethanesulfonic anhydride was slowly added. After the addition was complete, the mixture was heated to room temperature and stirred for 3-5 hours to obtain Tf-DMAP. 2) Disperse the silica support with surface-grafted polystyrene brushes in dichloromethane, add the Tf-DMAP prepared in step 1), and stir at room temperature for 12-24 hours to obtain the supported catalyst.

5. The method for preparing the VC derivative ascorbate tetraisopalmitate according to claim 4, characterized in that, In step 1), the molar ratio of 4-dimethylaminopyridine to trifluoromethanesulfonic anhydride is 1:1-1.

2.

6. The method for preparing the VC derivative ascorbate tetraisopalmitate according to claim 4, characterized in that, In step 2), the mass ratio of silica carrier to Tf-DMAP is 1:0.5-2.

7. The method for preparing the VC derivative ascorbate tetraisopalmitate according to claim 1, characterized in that, The silica carrier for the surface-grafted polystyrene brush is prepared by first subjecting silica nanoparticles to sequential amylation modification and brominated initiator modification to obtain SiO2@Br. Then, using SiO2@Br as the initiator and styrene as the monomer, graft polymerization is carried out through electron transfer regeneration activated atom transfer radical polymerization technology to obtain silica grafted onto the polystyrene brush. Among them, the amylation modifier used in the amylation modification is 3-aminopropyltriethoxysilane, and the brominated initiator is 2-bromoisobutyryl bromide.

8. The method for preparing the VC derivative ascorbate tetraisopalmitate according to claim 7, characterized in that, The preparation of the silica carrier with the surface grafted polystyrene brush includes the following steps: ① Disperse silica nanoparticles in an organic solvent, add 3-aminopropyltriethoxysilane, and react at 80-130℃ for 24-72 hours under inert gas protection. After the reaction is completed, centrifuge, wash, and dry to obtain aminated silica. ② Disperse aminated silica in an organic solvent, add an organic amine, cool to 0-5℃, slowly add 2-bromoisobutyryl bromide, after the addition is complete, heat to room temperature and react for 24-72 hours. After the reaction is complete, centrifuge, wash, and dry to obtain SiO2@Br; ③ Disperse SiO2@Br in a solvent, add styrene monomer, copper halide catalyst, nitrogen-containing ligand and reducing agent, and react at 70-110℃ for 6-24 hours under inert gas protection; after the reaction is completed, centrifuge, wash and dry to obtain silica support with surface grafted polystyrene brush, denoted as SiO2@PS.

9. The method for preparing the VC derivative ascorbate tetraisopalmitate according to claim 1, characterized in that, In the alkaline eutectic solvent, the molar ratio of choline chloride to urea is 1:1.5-3; the organic base acid binder is selected from at least one of triethylamine, N,N-diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, and tetramethylguanidine, and its addition amount is 1-5% of the total mass of choline chloride and urea.

10. The method for preparing the VC derivative ascorbate tetraisopalmitate according to claim 1, characterized in that, The alkaline eutectic solvent is prepared by mixing choline chloride and urea, stirring at 70-90°C for 1-3 hours until a homogeneous transparent liquid is formed, cooling to room temperature, adding an organic base acid-binding agent, and stirring evenly to obtain the alkaline eutectic solvent.

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