CN115745938B - Method for continuously preparing vitamin E acetate - Google Patents
Method for continuously preparing vitamin E acetate Download PDFInfo
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- CN115745938B CN115745938B CN202211423075.1A CN202211423075A CN115745938B CN 115745938 B CN115745938 B CN 115745938B CN 202211423075 A CN202211423075 A CN 202211423075A CN 115745938 B CN115745938 B CN 115745938B
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- 238000000034 method Methods 0.000 title claims abstract description 38
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 title claims abstract description 36
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 229940042585 tocopherol acetate Drugs 0.000 title claims abstract description 35
- 239000004576 sand Substances 0.000 claims abstract description 51
- 238000006243 chemical reaction Methods 0.000 claims abstract description 48
- KEVYVLWNCKMXJX-ZCNNSNEGSA-N Isophytol Natural products CC(C)CCC[C@H](C)CCC[C@@H](C)CCC[C@@](C)(O)C=C KEVYVLWNCKMXJX-ZCNNSNEGSA-N 0.000 claims abstract description 45
- -1 trimethylhydroquinone diester Chemical class 0.000 claims abstract description 45
- 239000000463 material Substances 0.000 claims abstract description 24
- 230000008569 process Effects 0.000 claims abstract description 16
- 239000007810 chemical reaction solvent Substances 0.000 claims abstract description 11
- 239000012433 hydrogen halide Substances 0.000 claims abstract description 10
- 229910000039 hydrogen halide Inorganic materials 0.000 claims abstract description 10
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 9
- 239000011701 zinc Substances 0.000 claims abstract description 9
- 239000002245 particle Substances 0.000 claims description 30
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical group [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 24
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical group CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 23
- 239000012295 chemical reaction liquid Substances 0.000 claims description 23
- 239000011592 zinc chloride Substances 0.000 claims description 12
- 235000005074 zinc chloride Nutrition 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 4
- 239000000243 solution Substances 0.000 claims description 3
- 150000001335 aliphatic alkanes Chemical group 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 8
- 238000010924 continuous production Methods 0.000 abstract description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 47
- 239000000047 product Substances 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 16
- 208000012839 conversion disease Diseases 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- 239000011259 mixed solution Substances 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 9
- 239000007795 chemical reaction product Substances 0.000 description 9
- 239000002994 raw material Substances 0.000 description 9
- 238000001514 detection method Methods 0.000 description 8
- 229930003427 Vitamin E Natural products 0.000 description 7
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 7
- 238000000227 grinding Methods 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 238000010008 shearing Methods 0.000 description 7
- 229940046009 vitamin E Drugs 0.000 description 7
- 239000011709 vitamin E Substances 0.000 description 7
- 235000019165 vitamin E Nutrition 0.000 description 7
- AUFZRCJENRSRLY-UHFFFAOYSA-N 2,3,5-trimethylhydroquinone Chemical compound CC1=CC(O)=C(C)C(C)=C1O AUFZRCJENRSRLY-UHFFFAOYSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000002699 waste material Substances 0.000 description 3
- OXEURVFAJQZVRZ-UHFFFAOYSA-N CC1C(C)=C(O)C=C(C)C1(O)CC(O)=O Chemical compound CC1C(C)=C(O)C=C(C)C1(O)CC(O)=O OXEURVFAJQZVRZ-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000005265 energy consumption Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 229930003799 tocopherol Natural products 0.000 description 2
- 229960001295 tocopherol Drugs 0.000 description 2
- 239000011732 tocopherol Substances 0.000 description 2
- 235000010384 tocopherol Nutrition 0.000 description 2
- 208000009084 Cold Injury Diseases 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 208000007466 Male Infertility Diseases 0.000 description 1
- 206010000210 abortion Diseases 0.000 description 1
- 231100000176 abortion Toxicity 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 238000012824 chemical production Methods 0.000 description 1
- 230000002595 cold damage Effects 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 239000003163 gonadal steroid hormone Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000000413 hydrolysate Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910001507 metal halide Inorganic materials 0.000 description 1
- 150000005309 metal halides Chemical class 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 206010034754 petechiae Diseases 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 230000019100 sperm motility Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000002640 tocopherol group Chemical group 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for continuously preparing vitamin E acetate, which has the advantages of simple preparation process, short process flow, high-efficiency continuous production, high conversion rate and high selectivity. The invention provides a method for continuously preparing vitamin E acetate, which comprises the steps of continuously feeding a first material and a second material into a sand mill for reaction to generate the vitamin E acetate; wherein the first material comprises a pre-mixed reaction solvent, trimethylhydroquinone diester, zinc halide and aqueous hydrogen halide solution, and the second material comprises isophytol.
Description
Technical Field
The invention relates to a preparation technology of vitamin E acetate, in particular to a method for continuously preparing vitamin E acetate.
Background
Vitamin E (Vitamin E) is a fat-soluble Vitamin, and its hydrolysate is tocopherol, which is one of the most important antioxidants. Tocopherol can promote sex hormone secretion, so that the sperm motility and quantity of men are increased; can increase female estrogen concentration, improve fertility, prevent abortion, and can be used for preventing and treating male infertility, burn, cold injury, capillary hemorrhage, climacteric syndrome, and skin care. The vitamin E acetate has wide application prospect and market value in the fields of medicine, food, cosmetics, feed and the like.
German laid-open patent document DE2000111402 discloses the production of vitamin E acetate by condensation of trimethylhydroquinone diester with isophytol in a polar solvent and water mixture using zinc halide (Lewis acid) and aqueous protonic acid as catalysts. The method fully utilizes the polar solvent to dissolve the catalyst, thereby being convenient for later recovery and application.
EP1583753 (A1) provides a process for the production of alpha-tocopheryl acetate using 2,3, 6-trimethylhydroquinone-1-acetate with a plant alcohol or isophytol or (isophytol) derivative in the presence of a catalyst of the formula Mn +(RlSO3-) n in an aprotic organic solvent. However, the reaction product is a mixture containing vitamin E acetate, vitamin E and the like, and the vitamin E acetate product without vitamin E can be obtained only when a large amount of one raw material is excessive, so that the waste of the raw material is caused, the post-treatment process is increased, and the preparation process of the catalyst used in the process is very complex.
Chinese patent publication CN103396392A provides a method for preparing vitamin E by reacting 2,3, 5-trimethylhydroquinone with isophytol under the condition of using magnesium oxide loaded silicon dioxide as a catalyst. However, the vitamin E product obtained therefrom requires conversion to more stable vitamin E acetate for more convenient storage. In addition, in the preparation process, two raw materials 2,3, 5-trimethylhydroquinone and isophytol are simultaneously added into a reaction system at one time, so that the risk of converting isophytol into other impurities is increased.
EP603695 provides the synthesis of vitamin E by condensation of trimethylhydroquinone and isophytol in a liquid or supercritical carbon dioxide system using an acidic catalyst, hydrochloric acid, zinc chloride and an ion exchanger as catalysts. The process is relatively complex.
In European publication EP01104141.5, a bioesterase is used to convert trimethylhydroquinone diethyl ester into trimethylhydroquinone-4-acetate, followed by purification and then condensation to give vitamin E acetate. However, it is known that the biological esterase has higher difficulty in realizing large-scale industrial production in fine chemical production, and the enzymolysis process has strict requirements, so that the process route is more complex, and the economical efficiency is reduced.
The chinese patent publication CN201610934587.2 provides a method for preparing vitamin E acetate, in which hydrogen halide gas is introduced as a catalyst, metal halides and metal simple substances are loaded on a molecular sieve as a cocatalyst and a stabilizer, and Vitamin E Acetate (VEA) is prepared by reacting 2,3, 5-trimethylhydroquinone diester (TMHQ-DA) with Isophytol (IPL). The process has the advantages of high catalyst activity, small equipment corrosion, capability of directly generating vitamin E acetate by one step by raw materials, good product stability and easy realization of industrialized amplified production. However, in the reaction process of each batch, hydrogen halide gas needs to be consumed, the unit consumption of materials is increased, and the economical efficiency needs to be improved.
The prior art method for preparing vitamin E acetate has the problems of complex process route, multi-step reaction to obtain the final product vitamin E acetate, large volume of required reaction equipment, difficulty in realizing continuous preparation and the like. Therefore, a new method for preparing vitamin E acetate is needed to solve the technical problems.
Disclosure of Invention
In view of the above, the invention provides a method for continuously preparing vitamin E acetate, which has simple preparation process and short process flow, can continuously produce with high efficiency, and can prepare vitamin E acetate with high conversion rate and high selectivity.
The invention provides the following technical scheme for achieving the purpose:
the invention provides a method for continuously preparing vitamin E acetate, which comprises the steps of continuously feeding a first material and a second material into a sand mill for reaction to generate the vitamin E acetate;
Wherein the first material comprises a pre-mixed reaction solvent, trimethylhydroquinone diester, zinc halide and aqueous hydrogen halide solution, and the second material comprises isophytol.
In the method, four materials of a reaction solvent, trimethylhydroquinone diester, zinc halide and hydrogen halide are mixed uniformly in advance, and the obtained first material is a liquid-liquid two-phase system; the inventor finds that the four materials are mixed uniformly in advance and then are continuously added into a sand mill to react with isophytol, so that a target product can be efficiently obtained with a simple process flow, and the reaction yield is improved.
In a preferred embodiment, the particle size D90 of the first material does not exceed 1 μm, preferably 0.1-1 μm, e.g. 0.1 μm, 0.2 μm, 0.3 μm, 0.4 μm, 0.5 μm, 0.6 μm, 0.7 μm, 0.8 μm, 0.9 μm, 1.0 μm, etc., more preferably 0.5-1 μm; and the particle diameter D90 of the reaction liquid in the sand mill is not more than 1. Mu.m, preferably 0.1 to 1. Mu.m, for example, 0.1. Mu.m, 0.2. Mu.m, 0.3. Mu.m, 0.4. Mu.m, 0.5. Mu.m, 0.6. Mu.m, 0.7. Mu.m, 0.8. Mu.m, 0.9. Mu.m, 1.0. Mu.m, etc., more preferably 0.5 to 1. Mu.m. The inventor finds that the particle diameter D90 of the first material is controlled to be not more than 1 mu m, and the particle diameter D90 of the reaction liquid in the sand mill is controlled to be not more than 1 mu m, so that the target product can be obtained with higher yield and higher selectivity; preferably, the particle diameter is controlled to be 0.1-1 μm, more preferably 0.5-1 μm, so that not only can the better selectivity and reaction conversion be obtained, but also the production efficiency is high, and the energy consumption is reduced.
In a preferred embodiment, the first material and the second material are simultaneously and continuously fed into the sand mill, and by simultaneous feeding, the uniformity of the reaction can be ensured, and the waste of raw materials or the increase of impurity content caused by the early addition of a single raw material can be avoided; the inventor discovers that if the two materials are fed in sequence, the waste of raw materials, the loss of products and the like can be caused.
In some embodiments, the reaction solvent is a non-polar solvent, preferably an alkane solvent, such as n-hexane, n-heptane, solvent oil, and the like, more preferably heptane.
In a preferred embodiment, the zinc halide is zinc chloride and the hydrogen halide is HCl and/or HBr.
In a preferred embodiment, the conditions under which the reaction is carried out in the sand mill include: the reaction temperature is controlled to be 60-80 ℃, the residence time of the reaction liquid is not more than 1h, and the method provided by the invention has the advantages that the residence time of the reaction liquid in a sand mill is short, and the target product with high conversion rate and high selectivity can be obtained in a short reaction time. Preferably, in the sand mill, the residence time of the reaction liquid is 20min-60min (such as 20min, 30min, 40min, 50min, 60min and the like), and the better residence time is adopted, so that the production efficiency, the reaction conversion rate and the selectivity are both high.
In a preferred embodiment, the molar ratio of the trimethylhydroquinone diester, the zinc halide and the hydrogen halide is 1:0.2-0.5:0.12-0.3.
In a preferred embodiment, the molar ratio of isophytol to trimethylhydroquinone diester is from 1 to 1.05:1. In the method, the two raw materials can be used for preparing the target product with high efficiency, high conversion rate and high selectivity without any large excess, and the method has higher reaction economy.
In preferred embodiments, the mass ratio of the reaction solvent to the trimethylhydroquinone diester is from 0.5 to 5:1, e.g., 0.5:1, 0.8:1, 1:1, 1.5:1, 2:1, 3:1, 4:1, 5:1, etc.; preferably 0.8-1.5:1, the inventors found that the use of the preferred amount of the reaction solvent is advantageous in terms of achieving excellent productivity, reaction conversion and product selectivity.
In a preferred embodiment, the pre-mixing is performed at a temperature of 60 ℃ to 80 ℃.
The technical scheme provided by the invention has the following beneficial effects:
The preparation method provided by the invention has the advantages of simple process and short flow, can obtain higher reaction yield in shorter reaction time, and is beneficial to reducing production cost and realizing industrial production; by adopting the preparation method provided by the invention, the vitamin E acetate can be prepared with high conversion rate and high selectivity. The method of the invention has the advantages of small volume of the reaction equipment, continuous production and high production efficiency.
Detailed Description
In order that the invention may be readily understood, a further description of the invention will be provided with reference to the following examples. It should be understood that the following examples are only for better understanding of the present invention and are not meant to limit the present invention to the following examples.
Where specific experimental steps or conditions are not noted in the examples, they may be performed according to the operations or conditions of the corresponding conventional experimental steps in the art. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
Some of the reagent specifications and sources in the examples and comparative examples:
1. Anhydrous zinc chloride: > 98%, alatine;
2. trimethylhydroquinone diester: 99.5%, wanhua chemistry;
3. isophytol: 99%, wanhua chemistry;
4. Sand mill: guangzhou Langmuir;
other raw materials are commercially available common reagents unless otherwise specified.
The reaction product detection method comprises the following steps: the gas chromatograph is Agilent 7820A, capillary column (DB-5, 30m×0.25mm×0.25 μm), second order temperature programming, initial temperature 100deg.C, holding for 2 min, and heating to 130deg.C at a rate of 5deg.C/min; then the temperature is raised to 280 ℃ at the speed of 15 ℃/min and the temperature is kept for 22 minutes. Carrier gas high purity N 2, split ratio 20:1. the sample injection temperature is 290 ℃, the detector is FID, the detector temperature is 300 ℃, and the sample injection amount is 0.2 mu L.
The particle diameter D90 is detected by a tester: bettersize2600 (dandongbaite).
Example 1
236G of trimethylhydroquinone diester (molecular weight 236), 27.2g of anhydrous zinc chloride, 12g of concentrated hydrochloric acid (concentration 36.5 wt%) and 188.8g of heptane are weighed and added into a reaction kettle, the temperature is raised to 60 ℃, and the components are mixed under shearing, so that the particle size D90 of the obtained mixed solution reaches 0.8 mu m;
continuously feeding the mixed solution and 296g of isophytol into a sand mill at the same time, wherein the feeding flow rate of the mixed solution and 296g of isophytol is based on the fact that the molar ratio of isophytol to trimethylhydroquinone diester in the feeding is consistent with the corresponding molar ratio in the total dosage of the isophytol and trimethylhydroquinone diester; the reaction temperature in the sand mill is controlled to be 60 ℃, the reaction is carried out in the sand mill while grinding, the particle diameter D90 of the reaction liquid in the sand mill is 0.6 mu m, and the residence time of the reaction liquid is 30min; the reaction product was continuously output from the sand mill. The reaction conversion rate is 99.6% and the product selectivity of vitamin E acetate is 97.2% by detection.
Example 2
236G of trimethylhydroquinone diester (molecular weight 236), 68g of anhydrous zinc chloride, 30g of concentrated hydrochloric acid (concentration 36.5 wt%) and 354g of heptane are weighed and added into a reaction kettle, the temperature is raised to 60 ℃, the components are mixed under shearing, and the particle size D90 of the obtained mixed solution reaches 0.6 mu m;
Continuously feeding the mixture and 310.8g of isophytol into a sand mill at the same time, wherein the feeding flow rates of the mixture and the isophytol are such that the molar ratio of the isophytol to the trimethylhydroquinone diester in the feeding is consistent with the corresponding molar ratio in the total dosage of the isophytol and the trimethylhydroquinone diester; the reaction temperature in the sand mill was controlled to 60 ℃, the reaction was carried out while grinding in the sand mill, the particle diameter D90 of the reaction liquid in the sand mill was set to 0.8. Mu.m, the residence time of the reaction liquid was 50 minutes, and the reaction product was continuously discharged from the sand mill. The reaction conversion rate is 99.7% and the product selectivity of vitamin E acetate is 97.8% by detection.
Example 3
236G of trimethylhydroquinone diester (molecular weight 236), 40.8g of anhydrous zinc chloride, 18g of concentrated hydrochloric acid (concentration 36.5 wt%) and 260g of heptane are weighed and added into a reaction kettle, the temperature is raised to 60 ℃, and the components are mixed under shearing, so that the particle size D90 of the obtained mixed solution reaches 0.9 mu m;
Continuously feeding the mixture and 301.9g of isophytol into a sand mill at the same time, wherein the feeding flow rates of the mixture and the isophytol are such that the molar ratio of the isophytol to the trimethylhydroquinone diester in the feed is consistent with the corresponding molar ratio in the total dosage of the isophytol and the trimethylhydroquinone diester; the reaction temperature in the sand mill is controlled to be 70 ℃, the reaction is carried out in the sand mill while grinding, the particle diameter D90 of the reaction liquid in the sand mill is 0.8 mu m, and the residence time of the reaction liquid is 20min; the reaction product was continuously output from the sand mill. The reaction conversion rate is 99.5% and the product selectivity of vitamin E acetate is 97.6% through detection.
Comparative example 1
236G of trimethylhydroquinone diester, 40.8g of anhydrous zinc chloride, 18g of concentrated hydrochloric acid (with the concentration of 36.5 wt%) and 260g of heptane are weighed into a reaction bottle, the temperature is raised to 70 ℃, then isophytol (310 g) is added dropwise for 5h, and after the dropwise addition is completed, the reaction is continued under heat preservation for 3h. The reaction conversion was 97.5% and the vitamin E acetate product selectivity was 92.6% as measured.
Comparative example 2
236G of trimethylhydroquinone diester (molecular weight 236), 40.8g of anhydrous zinc chloride, 18g of concentrated hydrochloric acid (concentration 36.5 wt%) and 260g of heptane are weighed and added into a reaction kettle, the temperature is raised to 60 ℃, and the components are mixed under shearing, so that the particle size D90 of the obtained mixed solution reaches 2.9 mu m;
Continuously feeding the mixture and 301.9g of isophytol into a sand mill at the same time, wherein the feeding flow rates of the mixture and the isophytol are such that the molar ratio of the isophytol to the trimethylhydroquinone diester in the feed is consistent with the corresponding molar ratio in the total dosage of the isophytol and the trimethylhydroquinone diester; the reaction temperature in the sand mill is controlled to be 70 ℃, the reaction is carried out in the sand mill while grinding, the particle diameter D90 of the reaction liquid in the sand mill is 0.8 mu m, and the residence time of the reaction liquid is 20min; the reaction product was continuously output from the sand mill. The reaction conversion rate is 98.5% and the product selectivity of vitamin E acetate is 96.6% through detection.
The difference from example 3 is that the particle diameter of the mixed solution is not controlled to 1 μm or less, and as a result, both the reaction conversion and the product selectivity are lowered.
Comparative example 3
236G of trimethylhydroquinone diester (molecular weight 236), 40.8g of anhydrous zinc chloride, 18g of concentrated hydrochloric acid (concentration 36.5 wt%) and 260g of heptane are weighed and added into a reaction kettle, the temperature is raised to 60 ℃, and the components are mixed under shearing, so that the particle size D90 of the obtained mixed solution reaches 0.9 mu m;
Continuously feeding the mixture and 301.9g of isophytol into a sand mill at the same time, wherein the feeding flow rates of the mixture and the isophytol are such that the molar ratio of the isophytol to the trimethylhydroquinone diester in the feed is consistent with the corresponding molar ratio in the total dosage of the isophytol and the trimethylhydroquinone diester; the reaction temperature in the sand mill is controlled to be 70 ℃, the reaction is carried out in the sand mill while grinding, the particle diameter D90 of the reaction liquid in the sand mill is 1.8 mu m, and the residence time of the reaction liquid is 15min; the reaction product was continuously output from the sand mill. The detection shows that the reaction conversion rate is 98.0%, and the product selectivity of the vitamin E acetate is 95.6%.
Example 4
236G of trimethylhydroquinone diester (molecular weight 236), 40.8g of anhydrous zinc chloride, 18g of concentrated hydrochloric acid (concentration 36.5 wt%) and 260g of heptane are weighed and added into a reaction kettle, the temperature is raised to 60 ℃, and the components are mixed under shearing, so that the particle size D90 of the obtained mixed solution reaches 0.9 mu m;
Continuously feeding the mixture and 301.9g of isophytol into a sand mill at the same time, wherein the feeding flow rates of the mixture and the isophytol are such that the molar ratio of the isophytol to the trimethylhydroquinone diester in the feed is consistent with the corresponding molar ratio in the total dosage of the isophytol and the trimethylhydroquinone diester; the reaction temperature in the sand mill is controlled to be 70 ℃, the reaction is carried out in the sand mill while grinding, the particle diameter D90 of the reaction liquid in the sand mill is 0.3 mu m, and the retention time of the reaction liquid is 80min; the reaction product was continuously output from the sand mill. The reaction conversion rate is 99.6% and the product selectivity of vitamin E acetate is 97.3% through detection.
As can be seen from a comparison of this example 4 and example 3, the reduction of the particle size of the reaction liquid to a lower particle size does not bring about a more remarkable improvement in the reaction conversion and the product selectivity than the control to 0.5 to 1. Mu.m, but rather, the sand mill is operated with higher energy consumption and longer reaction residence time required for obtaining a lower particle size.
Example 5
236G of trimethylhydroquinone diester (molecular weight 236), 68g of anhydrous zinc chloride, 30g of concentrated hydrochloric acid (concentration 36.5 wt%) and 500g of heptane are weighed and added into a reaction kettle, the temperature is raised to 60 ℃, the components are mixed under shearing, and the particle size D90 of the obtained mixed solution reaches 0.6 mu m;
continuously feeding the mixture and 310.8g of isophytol into a sand mill at the same time, wherein the feeding flow rates of the mixture and the isophytol are such that the molar ratio of the isophytol to the trimethylhydroquinone diester in the feeding is consistent with the corresponding molar ratio in the total dosage of the isophytol and the trimethylhydroquinone diester; the reaction temperature in the sand mill was controlled to 60 ℃, the reaction was carried out while grinding in the sand mill, the particle diameter D90 of the reaction liquid in the sand mill was set to 0.8. Mu.m, the residence time of the reaction liquid was 60 minutes, and the reaction product was continuously discharged from the sand mill. The reaction conversion rate is 99.2% and the product selectivity of vitamin E acetate is 95.8% through detection.
From the experimental results of example 5 and example 2, it can be seen that the mass ratio of the reaction solvent to trimethylhydroquinone diester is preferably controlled to be 0.8 to 1.5:1, higher reaction conversions and product selectivities can be achieved at relatively shorter residence times under substantially similar reaction conditions than higher solvent dosages.
It will be readily appreciated that the above embodiments are merely examples given for clarity of illustration and are not meant to limit the invention thereto. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. While still being apparent from variations or modifications that may be made by those skilled in the art are within the scope of the invention.
Claims (9)
1. A method for continuously preparing vitamin E acetate, characterized in that a first material and a second material are simultaneously and continuously fed into a sand mill for reaction to generate the vitamin E acetate;
Wherein the first material is a pre-mixed reaction solvent, trimethylhydroquinone diester, zinc halide and hydrogen halide aqueous solution, and the second material is isophytol;
The particle diameter D90 of the first material is not more than 1 mu m, and the particle diameter D90 of the reaction liquid in the sand mill is not more than 1 mu m; the mass ratio of the reaction solvent to the trimethylhydroquinone diester is 0.8-1.5:1, the reaction solvent is an alkane solvent;
The conditions under which the reaction is carried out in the sand mill include: the reaction temperature is controlled to be 60-80 ℃, and the residence time of the reaction solution is not more than 1h.
2. The method according to claim 1, wherein the first material has a particle size D90 of 0.1-1 μm; and the particle diameter D90 of the reaction liquid in the sand mill is 0.1-1 mu m.
3. The method according to claim 2, wherein the first material has a particle diameter D90 of 0.5 to 1 μm and the reaction liquid in the sand mill has a particle diameter D90 of 0.5 to 1 μm.
4. A process according to any one of claims 1 to 3, wherein the reaction solvent is heptane.
5. A process according to any one of claims 1 to 3, characterized in that the zinc halide is zinc chloride and the hydrogen halide is HCl and/or HBr.
6. A method according to any one of claims 1-3, characterized in that the residence time of the reaction solution is 20min-60min.
7. A process according to any one of claims 1 to 3, wherein the molar ratio of trimethylhydroquinone diester, zinc halide and hydrogen halide is 1:0.2-0.5:0.12-0.3.
8. A process according to any one of claims 1 to 3, characterized in that the molar ratio of isophytol to trimethylhydroquinone diester is 1-1.05:1.
9. A method according to any one of claims 1-3, wherein the pre-mixing is performed at 60-80 ℃.
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