Preparation method of tocopheryl acetate
The method addresses the separation challenges of acetic anhydride and acetic acid in tocopherol acetate production by using a two-stage reaction with controlled molar ratios and catalysts, achieving high purity recovery with reduced energy and equipment needs.
Patent Information
- Application Number
- CN202411332286.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-24
- Publication Date
- 2024-12-27
AI Technical Summary
Existing methods for preparing tocopherol acetate require excessive acetic anhydride, leading to difficulties in separating acetic anhydride and acetic acid, which results in high equipment investment and energy consumption due to the need for distillation with a large number of distillation plates and reflux ratio.
A method involving two stages of reaction with controlled molar ratios and catalysts, where the first stage uses less than the reaction equivalent of acetic anhydride, followed by separation of acetic acid, and the second stage uses an excess of acetic anhydride to ensure complete conversion, followed by simple distillation.
This method achieves high purity of both acetic acid and acetic anhydride recovery, reducing equipment investment and energy consumption while ensuring complete conversion of raw materials, with purities exceeding 99.5% and 85% respectively.
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Abstract
Description
Technical Field
[0001] The invention relates to a method for preparing tocopherol acetate. Background Art
[0002] Vitamin E is a fat-soluble vitamin essential to the human body. It has the functions of anti-oxidation, anti-aging, improving immunity, and preventing infertility. It is widely used in the pharmaceutical, food, feed, health care products, and cosmetics industries. It is one of the nutrients necessary for the normal growth of organisms. In recent years, the feed industry has developed rapidly, and the demand for vitamin E has also increased sharply, with good prospects and extremely high returns.
[0003] Synthetic vitamin E mainly includes dl-α tocopherol and dl-α tocopherol acetate, wherein tocopherol acetate can be prepared by direct esterification of tocopherol or condensation of trimethylhydroquinone diester and isophytol. The specific esterification steps of tocopherol and acetic anhydride under the action of a catalyst to obtain tocopherol acetate are as follows:
[0004]
[0005] US2723278 reports a method for synthesizing α-tocopherol acetate, using excess acetic anhydride as a reactant and a reaction reagent without a catalyst, and refluxing for 3-5 hours to obtain the product tocopherol acetate. The patent also does not further explain the separation of acetic anhydride and acetic acid.
[0006] CN105801551B discloses an esterification reaction of tocopherol and acetic anhydride in the presence of toluene under the catalysis of DMAP, wherein the molar ratio of acetic anhydride to tocopherol is 1.5-2: 1. After the reaction, the mixture of toluene, acetic acid and acetic anhydride is recovered under reduced pressure, but the patent does not further describe the separation operation of the mixed solvent.
[0007] CN108329288A discloses a method for preparing tocopherol acetate, wherein acetic anhydride and pyridine are added to tocopherol, and the mixture is reacted at 40-50°C for 2-3 hours through the heating system. The molar ratio of acetic anhydride to tocopherol is 2.5-3:1, but the patent does not further describe the separation operation of excess acetic anhydride and acetic acid generated by the reaction.
[0008] The above esterifications all require the addition of excessive acetic anhydride to promote the complete esterification of the raw materials. After the unreacted acetic anhydride and the acetic acid generated by the reaction are recovered, a mixture is obtained. It is necessary to separate by high-tower distillation to obtain acetic acid with a purity greater than 99% and acetic anhydride with a purity greater than 98%. Distillation is difficult, the theoretical number of plates of the whole tower needs to reach about 50, and the reflux ratio is controlled at about 3-4. Therefore, the equipment investment for the distillation and separation of acetic anhydride and acetic acid is large and the energy consumption is high. If the number of plates of the distillation tower is reduced, the acetic anhydride recovered by distillation contains 5%-20% of acetic anhydride, which cannot be completely separated, the unit consumption of acetic anhydride is large, and the cost of raw materials is high. Summary of the invention
[0009] The present invention provides a method for preparing tocopherol acetate to solve the problems that an excessive amount of acetic anhydride needs to be added during the ethyl esterification of tocopherol in the prior art, which leads to difficulty in separating acetic anhydride and acetic acid in the product. The preparation method makes full use of acetic anhydride, and the difficulty in separating acetic anhydride and acetic acid in the product is small.
[0010] In order to achieve the above object, the present invention adopts the following technical solutions:
[0011] The present invention provides a method for preparing tocopherol acetate, which comprises the following steps:
[0012] S1. Under the action of a catalyst, reacting a first raw material to obtain a first product; the first raw material comprises tocopherol and acetic anhydride in a molar ratio of 1:x, wherein 0.80≤x≤0.95;
[0013] S2, separating the acetic acid in the first product to obtain a first crude product;
[0014] S3, reacting a second raw material; the second raw material includes newly added acetic anhydride and the first crude product; the molar ratio of tocopherol in step S1 to the newly added acetic anhydride in step S3 is 1:y, wherein x+y≥1.3.
[0015] In the present invention, in step S1, the catalyst is conventionally selected in the art, such as sodium acetate, potassium acetate, zinc bromide or 4-dimethylaminopyridine (DMAP).
[0016] In the present invention, in step S1, the amount of the catalyst is preferably used to promote the reaction. Preferably, the mass of the catalyst may be 0.2wt%-1.0wt% of the mass of the tocopherol, such as 0.2wt%, 0.3wt% or 1.0wt%.
[0017] In the present invention, in step S1, the first raw material may further include acetic acid, and the mass of the acetic anhydride may be more than 80wt% of the sum of the masses of the acetic anhydride and the acetic acid, preferably more than 85wt%, for example, 90wt%.
[0018] Wherein, the acetic acid can be added with the acetic anhydride in the form of a mixture. The mixture can be obtained from the previous reaction step S3. That is, the acetic acid and acetic anhydride mixture obtained in step S3 can be applied to the next reaction step S1.
[0019] In the present invention, in step S1, the reaction temperature is conventionally selected in the art, preferably 60-120°C, more preferably 90-110°C.
[0020] In certain specific embodiments of the present invention, in step S1, the reaction temperature is 70°C, 80°C, 90°C or 110°C.
[0021] In the present invention, in step S1, the reaction time is preferably such that the acetic anhydride reacts as completely as possible, for example, 3 hours.
[0022] In the present invention, in step S1, the reaction may be carried out until the content of acetic anhydride in the reaction system is below 0.5 wt %.
[0023] In the present invention, in step S1, the molar ratio of the tocopherol to the acetic anhydride is preferably 1:(0.85-0.90).
[0024] In certain specific embodiments of the present invention, in step S1, the molar ratio of the tocopherol to the acetic anhydride is 1:0.85, 1:0.90 or 1:0.95.
[0025] In the present invention, in step S2, the separation method is conventional in the art, such as distillation, preferably vacuum distillation.
[0026] In the present invention, in step S2, the vacuum degree of the distillation can be 2000Pa.
[0027] In the present invention, in step S2, the distillation temperature may not exceed 70°C.
[0028] In the present invention, in step S2, the separation can separate the acetic acid as completely as possible.
[0029] In the present invention, in step S3, the reaction temperature is conventionally selected in the art, preferably 60-120°C, more preferably 90-110°C.
[0030] In certain specific embodiments of the present invention, in step S3, the reaction temperature is 70°C, 80°C, 90°C or 110°C.
[0031] In the present invention, in step S3, the reaction time is preferably such that the tocopherol reacts as completely as possible, for example, 3 hours.
[0032] In the present invention, in step S3, the reaction may be carried out until the content of tocopherol in the reaction system is below 0.5 wt %.
[0033] In the present invention, in step S3, x+y may be ≥1.45, for example, x+y=1.45, 1.55, 1.60, 1.75, 1.85, 1.90 or 1.95.
[0034] In the present invention, in step S3, x+0.2y may be ≥1.
[0035] In the present invention, in step S3, x+0.15y may be ≥1.
[0036] In the present invention, in step S3, x+y may be ≤1.95.
[0037] In the present invention, the molar ratio of the tocopherol in step S1 to the acetic anhydride newly added in step S3 can be 1:(0.5-1.0), preferably 1:(0.9-1.0).
[0038] In certain specific embodiments of the present invention, the molar ratio of the tocopherol in step S1 to the acetic anhydride newly added in step S3 is 1:0.5 or 1:0.7.
[0039] In the present invention, in step S3, after the reaction, distillation can be performed until no acetic anhydride or acetic acid is distilled out to obtain a second crude product. The distillation method is conventional in the art, for example, the distillation can be vacuum distillation. The vacuum degree of the distillation can be 2000 Pa. The temperature of the distillation can not exceed 70°C.
[0040] Wherein, the second crude product can be further purified to obtain tocopherol acetate. The purification step may include: adding n-heptane and then washing with water. The ratio of the n-heptane to the tocopherol in step S1 may be 500mL:1000g. The ratio of the amount of water used in the water washing to the amount of tocopherol in step S1 may be 100mL:1000g. The number of times of the water washing may be three times.
[0041] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.
[0042] The reagents and raw materials used in the present invention are commercially available.
[0043] The positive and progressive effects of the present invention are:
[0044] (1) In the preparation method of the present invention, the distillation of acetic anhydride and acetic acid is effectively avoided. In the first stage, acetic anhydride is added in an amount less than the reaction equivalent to ensure that acetic anhydride is fully converted into acetic acid. The purity of the recovered acetic acid can reach more than 99 wt %, or even more than 99.5 wt %;
[0045] (2) In the preparation method of the present invention, an excess of acetic anhydride is added in the second stage to ensure that the raw material is fully converted into acetic ester. The purity of the recovered acetic anhydride can be greater than 80wt%, or even greater than 85wt%, and can be directly used in the first stage of the next esterification reaction;
[0046] (3) In the preparation method of the present invention, acetic anhydride is fully utilized, that is, the total amount of acetic anhydride used is less, and there is no distillation operation in the whole process, only ordinary distillation is required, the equipment investment is small, the unit consumption is low, and the energy consumption is low. DETAILED DESCRIPTION
[0047] The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples. The experimental methods in the following examples without specifying specific conditions are carried out according to conventional methods and conditions, or selected according to the product specifications.
[0048] In the following examples and comparative examples
[0049] Purity means: mass of tocopherol acetate / total mass of tocopherol acetate and organic impurities×100%.
[0050] The content refers to the mass of tocopherol acetate / the total mass of tocopherol acetate, organic impurities, inorganic impurities (such as metal salt cation impurities, inorganic anion impurities) and water×100%.
[0051] The yield was calculated by actual yield / theoretical yield × 100%.
[0052] The purity of acetic anhydride / acetic acid in the recovered liquid is determined by gas chromatography. The acetic acid in the recovered liquid in the first stage consists of two parts, one of which is 90% of the acetic acid contained in the acetic anhydride itself, and the rest is acetic acid generated by the reaction.
[0053] The content and purity of tocopherol acetate in the product are determined by liquid chromatography.
[0054] Example 1
[0055] A method for preparing tocopherol acetate, the reaction formula of which is as follows:
[0056]
[0057] The following steps are involved:
[0058] a. Add 1000 g (2.32 mol, 1.0 eq) of tocopherol, 223 g of 90% acetic anhydride recovery solution (containing 201 g, 1.97 mol, 0.85 eq) and 10 g (1 wt %) of sodium acetate, heat to 110° C., and react at 110° C. for 3 h. At this time, the concentration of acetic anhydride in the reaction system is less than 0.5 wt % (detected by gas phase).
[0059] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. The acetic acid was recovered until no liquid was discharged. A total of 140 g of acetic acid was recovered with a purity of 99.9 wt %, containing 0.1 wt % of acetic anhydride (detected by gas phase).
[0060] b. Add 237 g (2.32 mol, 1.0 eq) of acetic anhydride to the reaction system and continue the reaction at 110° C. for 3 h. At this time, the tocopherol content in the reaction system is less than 0.5 wt % (detected by gas phase).
[0061] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. Acetic anhydride and acetic acid were recovered until no liquid was discharged. 222 g of a mixed solution of acetic anhydride and acetic acid was recovered. The purity of the recovered liquid acetic anhydride was 90.6wt%, and that of acetic acid was 9.4wt% (detected by gas phase).
[0062] The remaining material was added with 500 mL of n-heptane, and then washed three times with 100 mL of water, and the n-heptane was recovered to obtain tocopherol acetate with a purity of 98.7 wt %, a content of 97.2 wt %, and a yield of 99.2%.
[0063] Example 2
[0064] A method for preparing tocopherol acetate, the reaction formula of which is as follows:
[0065]
[0066] The following steps are involved:
[0067] a. Add 1000 g (2.32 mol, 1.0 eq) of tocopherol, 223 g of 90% acetic anhydride recovery solution (containing 201 g, 1.97 mol, 0.85 eq) and 10 g (1 wt %) of sodium acetate, heat to 110° C., and react at 110° C. for 3 h. At this time, the concentration of acetic anhydride in the reaction system is less than 0.5 wt % (detected by gas phase).
[0068] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. The acetic acid was recovered until no liquid was discharged. A total of 139 g of acetic acid was recovered with a purity of 99.9 wt %, containing 0.1 wt % of acetic anhydride (detected by gas phase).
[0069] b. Add 213 g (2.09 mol, 0.9 eq) of acetic anhydride to the reaction system and continue the reaction at 110° C. for 3 h. At this time, the tocopherol content in the reaction system is less than 0.5 wt % (detected by gas phase).
[0070] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. Acetic anhydride and acetic acid were recovered until no liquid was discharged. 198 g of a mixed solution of acetic anhydride and acetic acid was recovered. The purity of the recovered liquid acetic anhydride was 89.5wt%, and that of acetic acid was 10.5wt% (detected by gas phase).
[0071] Continue to add 500 mL of n-heptane to the remaining material, then wash it three times with 100 mL of water, recover the n-heptane, and obtain tocopherol acetate with a purity of 98.6 wt%, a content of 97.0 wt%, and a yield of 99.1%.
[0072] Example 3
[0073] A method for preparing tocopherol acetate, the reaction formula of which is as follows:
[0074]
[0075] The following steps are involved:
[0076] a. Add 1000 g (2.32 mol, 1.0 eq) of tocopherol, 223 g of 90% acetic anhydride recovery solution (containing 201 g, 1.97 mol, 0.85 eq) and 10 g (1 wt %) of sodium acetate, heat to 90° C., and react at 90° C. for 4 h. At this time, the concentration of acetic anhydride in the reaction system is less than 0.5 wt % (detected by gas phase).
[0077] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. The acetic acid was recovered until no liquid was discharged. A total of 140 g of acetic acid was recovered with a purity of 99.8 wt %, containing 0.2 wt % of acetic anhydride (detected by gas phase).
[0078] b. Add 237 g (2.32 mol, 1.0 eq) of acetic anhydride to the reaction system and continue the reaction at 90° C. for 4 h. At this time, the tocopherol content in the reaction system is less than 0.5 wt % (detected by gas phase).
[0079] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. Acetic anhydride and acetic acid were recovered until no liquid was discharged. 221 g of a mixed solution of acetic anhydride and acetic acid was recovered. The purity of the recovered liquid acetic anhydride was 90.7wt%, and that of acetic acid was 10.3wt% (detected by gas phase).
[0080] Continue to add 500 mL of n-heptane to the remaining material, then wash it three times with 100 mL of water, recover the n-heptane, and obtain tocopherol acetate with a purity of 98.6 wt %, a content of 96.9 wt %, and a yield of 99.0%.
[0081] Example 4
[0082] A method for preparing tocopherol acetate, the reaction formula of which is as follows:
[0083]
[0084] The following steps are involved:
[0085] a. Add 1000 g (2.32 mol, 1.0 eq) of tocopherol, 237 g of 90% acetic anhydride recovery solution (containing 213 g of acetic anhydride, 2.09 mol, 0.9 eq) and 10 g (1 wt %) of sodium acetate, heat to 110° C., and react at 110° C. for 3 h. At this time, the concentration of acetic anhydride in the reaction system is less than 0.5 wt % (detected by gas phase).
[0086] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. The acetic acid was recovered until no liquid was discharged. A total of 149 g of acetic acid was recovered with a purity of 99.7 wt %, containing 0.3 wt % of acetic anhydride (detected by gas phase).
[0087] b. Add 237 g (2.32 mol, 1.0 eq) of acetic anhydride to the reaction system and continue the reaction at 110° C. for 3 h. At this time, the tocopherol content in the reaction system is less than 0.5 wt % (detected by gas phase).
[0088] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. Acetic anhydride and acetic acid were recovered until no liquid was discharged. 227 g of a mixed solution of acetic anhydride and acetic acid was recovered. The purity of the recovered liquid acetic anhydride was 93.9wt%, and that of acetic acid was 6.1wt% (detected by gas phase).
[0089] The remaining material was added with 500 mL of n-heptane, and then washed three times with 100 mL of water, and the n-heptane was recovered to obtain tocopherol acetate with a purity of 98.5 wt %, a content of 97.0 wt %, and a yield of 99.1%.
[0090] Example 5
[0091] A method for preparing tocopherol acetate, the reaction formula of which is as follows:
[0092]
[0093] The following steps are involved:
[0094] a. Add 1000 g (2.32 mol, 1.0 eq) of tocopherol, 250 g of 90% acetic anhydride recovery solution (containing 225 g of acetic anhydride, 2.20 mol, 0.95 eq) and 10 g (1 wt %) of sodium acetate, heat to 110° C., and react at 110° C. for 3 h. At this time, the concentration of acetic anhydride in the reaction system is less than 0.5 wt % (detected by gas phase).
[0095] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. The acetic acid was recovered until no liquid was discharged. A total of 155 g of acetic acid was recovered with a purity of 99.5 wt %, containing 0.5 wt % of acetic anhydride (detected by gas phase).
[0096] b. Add 237 g (2.32 mol, 1.0 eq) of acetic anhydride to the reaction system and continue the reaction at 110° C. for 3 h. At this time, the tocopherol content in the reaction system is less than 0.5 wt % (detected by gas phase).
[0097] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. Acetic anhydride and acetic acid were recovered until no liquid was discharged. 231 g of a mixed solution of acetic anhydride and acetic acid was recovered. The purity of the recovered liquid acetic anhydride was 96.9wt%, and that of acetic acid was 3.1wt% (detected by gas phase).
[0098] Continue to add 500 mL of n-heptane to the remaining material, then wash it three times with 100 mL of water, recover the n-heptane, and obtain tocopherol acetate with a purity of 98.6 wt%, a content of 97.1 wt%, and a yield of 99.0%.
[0099] Example 6
[0100] A method for preparing tocopherol acetate, the reaction formula of which is as follows:
[0101]
[0102] The following steps are involved:
[0103] a. Add 1000 g (2.32 mol, 1.0 eq) of tocopherol, 250 g of 90% acetic anhydride recovery solution (containing 225 g of acetic anhydride, 2.20 mol, 0.95 eq) and 10 g (1 wt %) of sodium acetate, heat to 110° C., and react at 110° C. for 3 h. At this time, the concentration of acetic anhydride in the reaction system is less than 0.5 wt % (detected by gas phase).
[0104] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. The acetic acid was recovered until no liquid was discharged. A total of 153 g of acetic acid was recovered with a purity of 99.5 wt %, containing 0.5 wt % of acetic anhydride (detected by gas phase).
[0105] b. Add 119 g (1.16 mol, 0.5 eq) of acetic anhydride to the reaction system and continue the reaction at 110° C. for 3 h. At this time, the tocopherol content in the reaction system is less than 0.5 wt % (detected by gas phase).
[0106] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. Acetic anhydride and acetic acid were recovered until no liquid was discharged. 112 g of a mixed solution of acetic anhydride and acetic acid was recovered. The purity of the recovered liquid acetic anhydride was 93.8wt%, and that of acetic acid was 6.2wt% (detected by gas phase).
[0107] Continue to add 500 mL of n-heptane to the remaining material, then wash it three times with 100 mL of water, recover the n-heptane, and obtain tocopherol acetate with a purity of 98.5 wt %, a content of 96.8 wt %, and a yield of 98.8%.
[0108] Example 7
[0109] A method for preparing tocopherol acetate, the reaction formula of which is as follows:
[0110]
[0111] The following steps are involved:
[0112] a. Add 1000 g (2.32 mol, 1.0 eq) of tocopherol, 237 g of 90% acetic anhydride recovery solution (containing 213 g of acetic anhydride, 2.09 mol, 0.9 eq) and 10 g (1 wt %) of sodium acetate, heat to 110° C., and react at 110° C. for 3 h. At this time, the concentration of acetic anhydride in the reaction system is less than 0.5 wt % (detected by gas phase).
[0113] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. The acetic acid was recovered until no liquid was discharged. A total of 148 g of acetic acid was recovered with a purity of 99.8 wt %, containing 0.2 wt % of acetic anhydride (detected by gas phase).
[0114] b. Add 166 g (1.63 mol, 0.7 eq) of acetic anhydride to the reaction system and continue the reaction at 110° C. for 3 h. At this time, the tocopherol content in the reaction system is less than 0.5 wt % (detected by gas phase).
[0115] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. Acetic anhydride and acetic acid were recovered until no liquid was discharged. 156 g of a mixed solution of acetic anhydride and acetic acid was recovered. The purity of the recovered liquid acetic anhydride was 91.0 wt %, and that of acetic acid was 9.0 wt % (detected by gas phase).
[0116] Continue to add 500 mL of n-heptane to the remaining material, then wash it three times with 100 mL of water, recover the n-heptane, and obtain tocopherol acetate with a purity of 98.6 wt %, a content of 96.9 wt %, and a yield of 98.9%.
[0117] Example 8
[0118] A method for preparing tocopherol acetate, the reaction formula of which is as follows:
[0119]
[0120] The following steps are involved:
[0121] a. Add 1000 g (2.32 mol, 1.0 eq) of tocopherol, 223 g of 90% acetic anhydride recovery solution (containing 201 g, 1.97 mol, 0.85 eq) and 10 g (1 wt%) of potassium acetate, heat to 80°C, and react at 80°C for 4 h. At this time, the concentration of acetic anhydride in the reaction system is less than 0.5 wt% (detected by gas phase).
[0122] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. The acetic acid was recovered until no liquid was discharged. A total of 139 g of acetic acid was recovered with a purity of 99.8 wt %, containing 0.2 wt % of acetic anhydride (detected by gas phase).
[0123] b. Add 237 g (2.32 mol, 1.00 eq) of acetic anhydride to the reaction system and continue the reaction at 80° C. for 4 h. At this time, the tocopherol content in the reaction system is less than 0.5 wt % (detected by gas phase).
[0124] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. Acetic anhydride and acetic acid were recovered until no liquid was discharged. 220 g of a mixed solution of acetic anhydride and acetic acid was recovered. The purity of the recovered liquid acetic anhydride was 89.3 wt %, and that of acetic acid was 10.7 wt % (detected by gas phase).
[0125] Continue to add 500 mL of n-heptane to the remaining material, then wash it three times with 100 mL of water, recover the n-heptane, and obtain tocopherol acetate with a purity of 98.5 wt %, a content of 96.8 wt %, and a yield of 99.1%.
[0126] Example 9
[0127] A method for preparing tocopherol acetate, the reaction formula of which is as follows:
[0128]
[0129] The following steps are involved:
[0130] a. Add 1000 g (2.32 mol, 1.0 eq) of tocopherol, 223 g (containing 201 g, 1.97 mol, 0.85 eq) of 90% acetic anhydride recovery liquid and 3 g (0.3 wt%) of zinc bromide, heat to 90°C, and react at 90°C for 3 h. At this time, the concentration of acetic anhydride in the reaction system is less than 0.5 wt% (detected by gas phase).
[0131] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. The acetic acid was recovered until no liquid was discharged. A total of 137 g of acetic acid was recovered with a purity of 99.7 wt %, containing 0.3 wt % of acetic anhydride (detected by gas phase).
[0132] b. Add 237 g (2.32 mol, 1.00 eq) of acetic anhydride to the reaction system and continue the reaction at 80° C. for 3 h. At this time, the tocopherol content in the reaction system is less than 0.5 wt % (detected by gas phase).
[0133] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. Acetic anhydride and acetic acid were recovered until no liquid was discharged. 223 g of a mixed solution of acetic anhydride and acetic acid was recovered. The purity of the recovered liquid acetic anhydride was 89.5wt%, and that of acetic acid was 10.5wt% (detected by gas phase).
[0134] Continue to add 500 mL of n-heptane to the remaining material, then wash it three times with 100 mL of water, recover the n-heptane, and obtain tocopherol acetate with a purity of 98.6 wt %, a content of 96.9 wt %, and a yield of 98.8%.
[0135] Example 10
[0136] A method for preparing tocopherol acetate, the reaction formula of which is as follows:
[0137]
[0138] The following steps are involved:
[0139] a. Add 1000 g (2.32 mol, 1.0 eq) of tocopherol, 223 g (containing 201 g, 1.97 mol, 0.85 eq) of 90% acetic anhydride recovery liquid and 2 g (0.2 wt%) of DMAP, heat to 70° C., and react at 70° C. for 3 h, at which time the concentration of acetic anhydride in the reaction system is less than 0.5 wt% (detected by gas phase).
[0140] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. The acetic acid was recovered until no liquid was discharged. A total of 137 g of acetic acid was recovered with a purity of 99.8 wt %, containing 0.2 wt % of acetic anhydride (detected by gas phase).
[0141] b. Add 237 g (2.32 mol, 1.00 eq) of acetic anhydride to the reaction system and continue the reaction at 70° C. for 3 h. At this time, the tocopherol content in the reaction system is less than 0.5 wt % (detected by gas phase).
[0142] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. Acetic anhydride and acetic acid were recovered until no liquid was discharged. 225 g of a mixed solution of acetic anhydride and acetic acid was recovered. The purity of the recovered liquid acetic anhydride was 89.3wt%, and that of acetic acid was 10.7wt% (detected by gas phase).
[0143] Continue to add 500 mL of n-heptane to the remaining material, then wash it three times with 100 mL of water, recover the n-heptane, and obtain tocopherol acetate with a purity of 98.9 wt%, a content of 97.2 wt%, and a yield of 98.9%.
[0144] Comparative Example 1
[0145] A method for preparing tocopherol acetate comprises the following steps:
[0146] Add 1000 g (2.32 mol, 1.0 eq) of tocopherol, 356 g (3.48 mol, 1.5 eq) of acetic anhydride and 10 g (1 wt%) of sodium acetate; raise the temperature to 90°C and react at 90°C for 6 hours, at which time the concentration of tocopherol in the system is less than 0.5 wt% (detected by gas phase).
[0147] The reaction system was distilled under reduced pressure with a vacuum degree of 2000 Pa and a temperature not exceeding 70° C. Acetic anhydride and acetic acid were recovered until no liquid was discharged. 257 g of a mixed liquid of acetic anhydride and acetic acid was recovered, and the recovered liquid contained 46.0 wt % acetic anhydride and 54.0 wt % acetic acid (detected by gas phase).
[0148] The remaining material was continued to be washed three times with 500 mL of n-heptane and 100 mL of water, and the n-heptane was recovered to obtain tocopherol acetate with a purity of 98.7 wt %, a content of 96.4 wt %, and a yield of 99.0%.
[0149] A distillation recovery device was built to separate acetic anhydride and acetic acid, with a column height of 2 m, a reflux ratio of 4:1, and a vacuum degree of 2000 Pa. 100 g of pre-boiling acetic acid was recovered with a purity of 95.0 wt%, containing 5.0 wt% acetic anhydride; 30 g of cross phase with a purity of 70.1 wt% acetic acid, containing 29.9 wt% acetic anhydride; and the remaining acetic anhydride had a purity of 95.6 wt%.
[0150] The main reaction conditions and product conditions of each embodiment and comparative example are listed in Table 1 below.
[0151] Table 1
[0152]
[0153] In summary, the present invention effectively avoids the distillation of acetic anhydride and acetic acid. In the first stage, less than the equivalent amount of acetic anhydride is added to ensure that the acetic anhydride is fully converted into acetic acid, and the purity of the recovered acetic acid can reach more than 99.5wt%. In the second stage, an excess of acetic anhydride is added to ensure that the raw material is fully converted into acetate, and the purity of the recovered acetic anhydride is greater than 85%, which can be directly applied to the first stage. The present invention makes full use of acetic anhydride, and there is no distillation operation in the whole process, only ordinary distillation is required, the equipment investment is small, the unit consumption is low, and the energy consumption is low.
Claims
1. A method for preparing tocopherol acetate, characterized in that: It includes the following steps: S1. Under the action of a catalyst, reacting a first raw material to obtain a first product; the first raw material comprises tocopherol and acetic anhydride in a molar ratio of 1:x, wherein 0.80≤x≤0.95; S2, separating the acetic acid in the first product to obtain a first crude product; S3, reacting a second raw material; the second raw material includes newly added acetic anhydride and the first crude product; the molar ratio of tocopherol in step S1 to the newly added acetic anhydride in step S3 is 1:y, wherein x+y≥1.
3.
2. The method for preparing tocopherol acetate according to claim 1, characterized in that In step S1, the catalyst is sodium acetate, potassium acetate, zinc bromide or 4-dimethylaminopyridine; And / or, in step S1, the mass of the catalyst is 0.2wt%-1.0wt% of the mass of the tocopherol, for example, 0.2wt%, 0.3wt% or 1.0wt%; And / or, in step S1, the molar ratio of the tocopherol to the acetic anhydride is 1:(0.85-0.90), for example, 1:0.85, 1:0.90 or 1:0.
95.
3. The method for preparing tocopherol acetate according to claim 1, characterized in that: In step S1, the reaction temperature is 60-120°C, preferably 90-110°C, such as 70°C, 80°C, 90°C or 110°C; And / or, in step S1, the reaction time is 3h; And / or, in step S1, the reaction is carried out until the content of acetic anhydride in the reaction system is below 0.5 wt %.
4. The method for preparing tocopherol acetate according to claim 1, characterized in that: In step S1, the first raw material further includes acetic acid, and the mass of the acetic anhydride is more than 80wt% of the sum of the masses of the acetic anhydride and the acetic acid, preferably more than 85wt%, for example, 90wt%.
5. The method for preparing tocopherol acetate according to claim 4, characterized in that: The acetic acid and the acetic anhydride are added in the form of a mixture; the mixture is preferably obtained from the previous reaction step S3.
6. The method for preparing tocopherol acetate according to claim 1, characterized in that: In step S2, the separation method is distillation, preferably reduced pressure distillation; And / or, in step S2, the vacuum degree of the distillation is 2000 Pa; and / or, in step S2, the distillation temperature does not exceed 70° C.; And / or, in step S2, the separation is to completely separate the acetic acid.
7. The method for preparing tocopherol acetate according to claim 1, characterized in that: In step S3, the reaction temperature is 60-120°C, preferably 90-110°C, such as 70°C, 80°C, 90°C or 110°C; And / or, in step S3, the reaction time is 3h; And / or, in step S3, the reaction is carried out until the content of tocopherol in the reaction system is below 0.5wt%; And / or, the molar ratio of the tocopherol in step S1 to the acetic anhydride newly added in step S3 is 1:(0.5-1.0), preferably 1:(0.9-1.0), such as 1:0.5 or 1:0.
7.
8. The method for preparing tocopherol acetate according to claim 1, characterized in that: x and y satisfy at least one of the following conditions ①-④: ①x+y≥1.45, for example, x+y=1.45, 1.55, 1.60, 1.75, 1.85, 1.90 or 1.95; ②x+0.2y≥1; ③x+0.15y≥1; ④x+y≤1.
95.
9. The method for preparing tocopherol acetate according to claim 1, characterized in that: In step S3, after the reaction, distillation is further performed until no acetic anhydride or acetic acid is distilled out to obtain a second crude product; the distillation method is preferably reduced pressure distillation; the vacuum degree of the distillation is preferably 2000 Pa; the distillation temperature is preferably not more than 70°C.
10. The method for preparing tocopherol acetate according to claim 9, characterized in that: The second crude product is further purified to obtain tocopherol acetate; the purification step preferably includes: adding n-heptane and then washing with water; the amount of n-heptane to the tocopherol in step S1 is preferably 500mL:1000g; the amount of water used in the water washing is preferably 100mL:1000g compared to the amount of tocopherol in step S1; the number of water washings is preferably three times.