Preparation method of vitamin E acetate

Abstract

The invention relates to a preparation method of vitamin E acetate, which comprises the following steps: taking 2, 3, 5-trimethylhydroquinone diacetate and isophytol as basic raw materials, and reacting under the synergistic catalysis of Lewis acid and Bronsted acid to synthesize the vitamin E acetate. According to the preparation method, through proportion coordination of the two acids, namely, the two acids participate in the acid content change based on a substrate in the reaction, the synthesis targets of high reaction selectivity (greater than or equal to 98.5%), low product hydrolysis selectivity (less than or equal to 0.5%) and the like can be achieved.

Description

Technical Field

[0001] This invention belongs to the field of chemical technology, specifically relating to a method for preparing vitamin E acetate. Background Technology

[0002] Vitamin E is a fat-soluble vitamin, and its hydrolysis product is tocopherol. Tocopherol, as one of the most important antioxidants, plays many crucial roles. For men, tocopherol can promote the secretion of sex hormones, thereby increasing sperm motility and count. For women, it can increase estrogen levels, helping to improve fertility and prevent miscarriage. In addition, vitamin E also has applications in preventing and treating male infertility, treating burns and frostbite, relieving capillary bleeding, improving menopausal syndrome, and in cosmetics. Vitamin E acetate, with its unique properties, has shown broad application prospects and significant market value in various fields such as medicine, food, cosmetics, and animal feed.

[0003] German patent document DE2000111402 discloses a method for producing vitamin E acetate. This method uses zinc halide (Lewis acid) and an aqueous protic acid as catalysts, and involves a condensation reaction between trimethylhydroquinone diester and isophytol in a polar solvent and water mixture. Its advantage lies in using a polar solvent to dissolve the catalyst, facilitating subsequent recovery and reuse. However, this method has several problems: the zinc halide-containing wastewater is difficult to treat; the aqueous protic acid easily decomposes some vitamin E acetate into vitamin E and other impurities; and a subsequent re-esterification step is required to obtain vitamin E acetate, making the process complex and cumbersome.

[0004] European patent document EP603695 discloses a process for synthesizing vitamin E in a liquid or supercritical carbon dioxide system. It uses hydrochloric acid, zinc chloride, and an ion exchanger as acidic catalysts to induce a condensation reaction between trimethylhydroquinone and isophytol to produce vitamin E. However, this process is complex, catalyst recovery and reuse are difficult, and it suffers from severe equipment corrosion and troublesome wastewater treatment.

[0005] Domestic patent CN115672378A reports a catalyst recycling method for a reaction system based on trimethylhydroquinone diester and isophytol to prepare vitamin E acetate. This method is applicable to situations using zinc halide and hydrogen halide aqueous solutions as catalysts. By controlling the content of heavy components in the catalyst phase to be recycled to ≤1 wt%, good reaction conversion and product selectivity can be maintained. However, the overall operation process is relatively cumbersome and not conducive to actual production operations.

[0006] Existing methods for preparing vitamin E acetate suffer from problems such as the product decomposition into numerous impurities, difficulty in treating catalyst waste liquid, and cumbersome process operations. Therefore, a new method for synthesizing vitamin E acetate is needed to address these technical issues. Summary of the Invention

[0007] To address the aforementioned problems, the present invention aims to provide a method for preparing vitamin E acetate, using 2,3,5-trimethylhydroquinone diacetate and isophytol as basic raw materials, and synthesizing vitamin E acetate through a reaction catalyzed by Lewis acid and Brønsted acid. This preparation method achieves good reaction selectivity (≥98.5%) and low product hydrolysis selectivity (≤0.5%) by coordinating the ratio of the two acids. Furthermore, the amount of acid used can be selectively controlled by adjusting the reaction temperature and time.

[0008] To achieve the above-mentioned objectives, the present invention adopts the following technical solution:

[0009] A method for preparing vitamin E acetate includes the following steps: using 2,3,5-trimethylhydroquinone diacetate and isophytol as raw materials, a catalytic reaction is carried out in a Lewis acid and Brønsted acid system to synthesize vitamin E acetate;

[0010] The reaction equation is as follows:

[0011]

[0012] In this invention, the Lewis acid is a substance capable of accepting electron pairs, such as containing a simple cation (Fe). 3+ Zn 2 + Substances that are electron-deficient (BF3, AlCl3) and compounds that can expand into octet bodies (PCl5, SF6);

[0013] Preferably, substances containing simple cations, such as ferric chloride or zinc chloride, are used.

[0014] In this reaction, the generation of the main product, hydrolysis product VE, is unavoidable because acetic acid will be released from the reaction network. Acetate groups are prone to losing acetic acid groups under acidic conditions. The side reaction of this process is a known pain point in the industry and can only be controlled by adjusting the reaction parameters (such as temperature, acid concentration, and time).

[0015] In this invention, the Brønsted acid is a proton-releasing acid (H+). + Substances such as inorganic halo acids (HCl, HBr, HI), inorganic non-halo acids (H2SO4, HNO3, H3PO4), and organic acids (CH3COOH, C6H5COOH, p-TsOH, CF3SO3H);

[0016] Preferably, inorganic haloacids such as HCl, HBr, and HI are used; more preferably, HCl is used.

[0017] In this invention, the reaction is carried out in the presence of a solvent, which is selected from alkanes (n-pentane, n-hexane, n-heptane, n-octane) and aromatics (toluene, benzene, p-xylene, m-xylene, o-xylene, and mesitylene).

[0018] Preferably, alkanes are used, such as n-pentane, n-hexane, n-heptane, and n-octane; more preferably, n-heptane is used.

[0019] Preferably, the mass ratio of 2,3,5-trimethylhydroquinone diacetate to solvent is 1:2-10, and more preferably, the mass ratio is 1:3-5.

[0020] In this invention, the molar ratio of 2,3,5-trimethylhydroquinone diacetate to isophytol is 1:1.0-1.5, preferably 1:1.05-1.25.

[0021] In this invention, high reaction selectivity can be achieved by coordinating the ratio of the two acids, and the amount of acid used can be selectively controlled by the reaction temperature and time. The preferred molar ratio of Lewis acid to 2,3,5-trimethylhydroquinone diacetate is 0.2-0.5:1. The preferred molar ratio of Lewis acid to Brønsted acid is 1:0.6-0.8.

[0022] Brønsted acid is a 30% aqueous solution.

[0023] The catalyst concentration (C, expressed as Lewis acid concentration) in the reaction system is controlled to be 225-900 min, the reaction time (t) to be 50-100℃, and the three factors satisfy Equation 1:

[0024]

[0025] In the formula, C is in ppm, t is in min, and T is in °C.

[0026] In this invention, Lewis acids induce the formation of carbocations from the olefins of isophytol, while Brønsted acids facilitate cyclization after protonation. The concentration of the Lewis acid determines the polarity of the carbocation; adding too dilute a concentration hinders the protonation of the Brønsted acid, while adding too high a concentration accelerates the reaction. Because Lewis acid-catalyzed reactions are thermodynamic, their rates are greatly affected by temperature, with higher temperatures promoting the reaction.

[0027] This shows that in the synthesis of vitamin E acetate, 1) at the same temperature, the catalyst concentration C is negatively correlated with the reaction time; 2) at the same concentration, temperature and time are negatively correlated; 3) at the same time, temperature and concentration are negatively correlated.

[0028] For the formation of the main product, hydrolysis product VE, catalyst concentration (C), reaction temperature (T), and reaction time (t) are key variables, and their coupling relationship is as follows: a) Catalyst concentration: If C is too high, the reaction rate increases significantly, and the main reaction and hydrolysis are accelerated simultaneously; if C is too low, the overall rate decreases, and hydrolysis side reactions continue to occur in the system during extended residence time, leading to reduced selectivity. b) Reaction temperature: Since the hydrolysis reaction is thermodynamically controlled, an increase in T shifts the equilibrium towards hydrolysis, increasing the yield of hydrolysis product VE and adversely affecting subsequent purification. Therefore, by synergistically optimizing C, T, and t, high selectivity and high yield of the target product can be achieved while suppressing hydrolysis side reactions.

[0029] In one specific embodiment of the present invention, the reaction is carried out in the following order: a solvent and 2,3,5-trimethylhydroquinone diacetate are placed at the bottom, Lewis acid and Brønsted acid are added after the temperature is raised to a certain level, and finally isophytol is added dropwise to the reaction system.

[0030] Preferably, the feeding time of isophytol is 30-120 min, and the feeding time is not included in the reaction time.

[0031] The beneficial effects of this invention are as follows:

[0032] This invention significantly reduces the selectivity of vitamin E acetate side reactions by controlling the relationship between reaction time, catalyst concentration, and reaction temperature, effectively improving the selectivity of vitamin E acetate to over 98.5%. Detailed Implementation

[0033] The following embodiments will further illustrate the method provided by the present invention, but the present invention is not limited to the listed embodiments, and should also include any other known modifications within the scope of the claims of the present invention.

[0034] High-performance liquid chromatography (HPLC) characterization: Agilent 1260 HPLC system, Sphersorb C8 column (4.6*250mm), Hitachi L7420 UV-Vis detector, Chomatopac C-RIA HPLC workstation data processing system, Zorbax-SIL stationary phase. Chromatographic conditions: mobile phase was methanol / acetonitrile = 7 / 3 (v / v) mixed solvent, detection temperature 40℃, flow rate 1 ml / min, wavelength 455 nm. Qualitative and quantitative analysis of the product composition was performed.

[0035] The main raw materials used in the following examples and comparative examples are as follows:

[0036] 2,3,5-Trimethylhydroquinone diacetate: 99.5%, Wanhua Chemical;

[0037] Isophytol: 97%, Wanhua Chemical;

[0038] Ferric chloride, zinc chloride: >96%, Sigma (Shanghai) Trading Co., Ltd.;

[0039] Alkanes (n-pentane, n-hexane, n-heptane, n-octane): Bailingwei;

[0040] Hydrochloric acid: Beijing Inocare Technology Co., Ltd.

[0041] Example 1:

[0042] In a 1000 mL three-necked reaction flask, 24.1 g of 2,3,5-trimethylhydroquinone diacetate and 96.4 g of n-heptane were added. The oil bath was turned on to raise the temperature of the system to 80 °C. 4.11 g of zinc chloride and 2.20 g of 30% hydrochloric acid were added to the reaction. Then, 32.9 g of isophytol was added dropwise to the reaction flask over 0.5 h. Gas chromatography analysis was performed to detect the conversion rate and product selectivity of 3,5-trimethylhydroquinone diacetate. After 225 min of reaction, the conversion rate of 2,3,5-trimethylhydroquinone diacetate was 99.5%, the selectivity of vitamin E acetate was 98.9%, and the selectivity of hydrolysis side reaction was 0.3%.

[0043] Example 2:

[0044] In a 1000 mL three-necked reaction flask, 24.1 g of 2,3,5-trimethylhydroquinone diacetate and 144.6 g of n-hexane were added. The oil bath was turned on to raise the temperature of the system to 50 °C. 6.48 g of zinc chloride and 4.6 g of 30% hydrochloric acid were added to the reaction. Subsequently, 35.9 g of isophytol was added dropwise to the reaction flask over 1.5 h. Gas chromatography analysis was performed to detect the conversion rate and product selectivity of 3,5-trimethylhydroquinone diacetate. After 400 min of reaction, the conversion rate of 2,3,5-trimethylhydroquinone diacetate was 99.3%, the selectivity of vitamin E acetate was 99.1%, and the selectivity of hydrolysis side reaction was 0.2%.

[0045] Example 3:

[0046] In a 1000 mL three-necked reaction flask, 24.1 g of 2,3,5-trimethylhydroquinone diacetate and 120.5 g of n-heptane were added. The oil bath was turned on to raise the temperature of the system to 50 °C. 5.1 g of zinc chloride and 3.2 g of 30% hydrochloric acid were added to the reaction. Subsequently, 31.4 g of isophytol was added dropwise to the reaction flask over 1.0 h. Gas chromatography analysis was performed to detect the conversion rate and product selectivity of 3,5-trimethylhydroquinone diacetate. After 625 min of reaction, the conversion rate of 2,3,5-trimethylhydroquinone diacetate was 99.7%, the selectivity of vitamin E acetate was 98.6%, and the selectivity of hydrolysis side reaction was 0.4%.

[0047] Example 4:

[0048] In a 1000 mL three-necked reaction flask, 24.1 g of 2,3,5-trimethylhydroquinone diacetate and 72.3 g of n-heptane were added. The oil bath was turned on to raise the temperature of the system to 60 °C. 4.0 g of zinc chloride and 2.2 g of 30% hydrochloric acid were added to the reaction. Subsequently, 32.9 g of isophytol was added dropwise to the reaction flask over 0.5 h. Gas chromatography analysis was performed to detect the conversion rate and product selectivity of 3,5-trimethylhydroquinone diacetate. After 256 min of reaction, the conversion rate of 2,3,5-trimethylhydroquinone diacetate was 98.8%, the selectivity of vitamin E acetate was 99.2%, and the selectivity of hydrolysis side reaction was 0.3%.

[0049] Example 5:

[0050] In a 1000 mL three-necked reaction flask, 24.1 g of 2,3,5-trimethylhydroquinone diacetate and 72.3 g of n-heptane were added. The oil bath was turned on to raise the temperature of the system to 70 °C. 3.0 g of zinc chloride and 2.2 g of 30% hydrochloric acid were then added to the reaction mixture. Subsequently, 32.9 g of isophytol was added dropwise over 0.5 h. Gas chromatography analysis was performed to detect the conversion rate and product selectivity of 3,5-trimethylhydroquinone diacetate. After 900 min of reaction, the conversion rate of 2,3,5-trimethylhydroquinone diacetate was 99.5%, the selectivity of vitamin E acetate was 99.3%, and the selectivity of the hydrolysis side reaction was 0.1%. Comparative Example 1:

[0051] In a 1000 mL three-necked reaction flask, 24.1 g of 2,3,5-trimethylhydroquinone diacetate and 72.3 g of n-heptane were added. The oil bath was turned on to raise the temperature of the system to 100 °C. 2.47 g of zinc chloride and 1.3 g of 30% hydrochloric acid were then added to the reaction mixture. Subsequently, 32.9 g of isophytol was added dropwise over 0.5 h. Gas chromatography analysis was performed to detect the conversion rate and product selectivity of 3,5-trimethylhydroquinone diacetate. After 225 min of reaction, the conversion rate of 2,3,5-trimethylhydroquinone diacetate was 99.6%, the selectivity of vitamin E acetate was 95.5%, and the selectivity of the hydrolysis side reaction was 3.6%. Comparative Example 2:

[0052] In a 1000 mL three-necked reaction flask, 24.1 g of 2,3,5-trimethylhydroquinone diacetate and 72.3 g of n-heptane were added. The oil bath was turned on to raise the temperature of the system to 70 °C. 3.0 g of zinc chloride and 2.2 g of 30% hydrochloric acid were added to the reaction. Subsequently, 32.9 g of isophytol was added dropwise to the reaction flask over 0.5 h. Gas chromatography analysis was performed to detect the conversion rate and product selectivity of 3,5-trimethylhydroquinone diacetate. After 2000 min of reaction, the conversion rate of 2,3,5-trimethylhydroquinone diacetate was 99.5%, the selectivity of vitamin E acetate was 94.3%, and the selectivity of hydrolysis side reaction was 4.2%.

[0053] The above embodiments are merely illustrative of the technical solutions of the present invention and do not constitute a limitation on the claims. Any equivalent substitutions or improvements made by those skilled in the art without departing from the scope defined by the claims of the present invention should fall within the protection scope of the present invention.

Claims

1. A method for preparing vitamin E acetate, comprising the following steps: using 2,3,5-trimethylhydroquinone diacetate and isophytol as raw materials, a catalytic reaction is carried out in a Lewis acid and Brønsted acid system to synthesize vitamin E acetate; The catalyst concentration (C) in the reaction system is controlled as Lewis acid concentration, the reaction time (t) is 225-900 min, and the reaction temperature T is 50-100℃, and the three factors satisfy the following relationship: In the formula, C is in ppm, t is in min, and T is in °C.

2. The preparation method according to claim 1, characterized in that, The Lewis acid is selected from those containing a simple cation (Fe). 3 + Zn 2+ Substances containing electron-deficient molecules (BF3, AlCl3) and compounds that can expand into octet bodies (PCl5, SF6); Preferably, the sample is selected from ferric chloride or zinc chloride.

3. The preparation method according to claim 1, characterized in that, The Brønsted acid is selected from inorganic halo acids (HCl, HBr, HI), inorganic non-halo acids (H2SO4, HNO3, H3PO4), and organic acids (CH3COOH, C6H5COOH, p-TsOH, CF3SO3H). Preferably, the HCl, HBr, or HI are selected.

4. The preparation method according to any one of claims 1-3, characterized in that, The molar ratio of Lewis acid to 2,3,5-trimethylhydroquinone diacetate is 0.2-0.5:

1.

5. The preparation method according to any one of claims 1-4, characterized in that, The molar ratio of Lewis acids to Brønsted acids is 1:0.6-0.8; Preferably, the Brønsted acid is a 30% aqueous solution.

6. The preparation method according to any one of claims 1-5, characterized in that, The reaction is carried out in the presence of a solvent, which is selected from alkanes (n-pentane, n-hexane, n-heptane, n-octane) and aromatics (toluene, benzene, p-xylene, m-xylene, o-xylene, and mesitylene). Preferably, it is selected from n-pentane, n-hexane, n-heptane, and n-octane.

7. The preparation method according to claim 6, characterized in that, The mass ratio of 2,3,5-trimethylhydroquinone diacetate to solvent is 1:2-10, preferably 1:3-5.

8. The preparation method according to any one of claims 1-5, characterized in that, The molar ratio of 2,3,5-trimethylhydroquinone diacetate to isophytol is 1:1.0-1.5, preferably 1:1.05-1.

25.

9. The preparation method according to any one of claims 1-8, characterized in that, The reaction is carried out in the following order: solvent and 2,3,5-trimethylhydroquinone diacetate are placed at the bottom, Lewis acid and Brønsted acid are added after the temperature is raised to a certain level, and finally isophytol is added dropwise to the reaction system.

10. The preparation method according to claim 9, characterized in that, The feeding time for isophytol is 30-120 minutes, and the feeding time is not included in the reaction time.

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