CN112457229A - Preparation method of vitamin A acetate - Google Patents
Preparation method of vitamin A acetate Download PDFInfo
- Publication number
- CN112457229A CN112457229A CN202011374517.9A CN202011374517A CN112457229A CN 112457229 A CN112457229 A CN 112457229A CN 202011374517 A CN202011374517 A CN 202011374517A CN 112457229 A CN112457229 A CN 112457229A
- Authority
- CN
- China
- Prior art keywords
- reaction
- acid
- formula
- temperature
- carried out
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229960000342 retinol acetate Drugs 0.000 title claims abstract description 26
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 title claims abstract description 26
- 235000019173 retinyl acetate Nutrition 0.000 title claims abstract description 26
- 239000011770 retinyl acetate Substances 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 25
- 238000006243 chemical reaction Methods 0.000 claims description 57
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 35
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 22
- 150000001875 compounds Chemical class 0.000 claims description 22
- 239000002904 solvent Substances 0.000 claims description 22
- PSQYTAPXSHCGMF-BQYQJAHWSA-N β-ionone Chemical compound CC(=O)\C=C\C1=C(C)CCCC1(C)C PSQYTAPXSHCGMF-BQYQJAHWSA-N 0.000 claims description 22
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N pentanal Chemical compound CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 claims description 18
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 12
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 12
- SFEOKXHPFMOVRM-UHFFFAOYSA-N (+)-(S)-gamma-ionone Natural products CC(=O)C=CC1C(=C)CCCC1(C)C SFEOKXHPFMOVRM-UHFFFAOYSA-N 0.000 claims description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
- BBMCTIGTTCKYKF-UHFFFAOYSA-N 1-heptanol Chemical compound CCCCCCCO BBMCTIGTTCKYKF-UHFFFAOYSA-N 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 238000003747 Grignard reaction Methods 0.000 claims description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- 239000002994 raw material Substances 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 238000007239 Wittig reaction Methods 0.000 claims description 8
- 230000035484 reaction time Effects 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 239000003377 acid catalyst Substances 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- RZXHPPIPSKOIDJ-UHFFFAOYSA-N P.[C].[C].[C].[C].[C].[C].[C] Chemical compound P.[C].[C].[C].[C].[C].[C].[C] RZXHPPIPSKOIDJ-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 238000011065 in-situ storage Methods 0.000 claims description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 3
- 239000011777 magnesium Substances 0.000 claims description 3
- 229910052749 magnesium Inorganic materials 0.000 claims description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 23
- 238000003756 stirring Methods 0.000 description 10
- 238000000926 separation method Methods 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 8
- 238000004817 gas chromatography Methods 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- 239000007788 liquid Substances 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- FXHGMKSSBGDXIY-UHFFFAOYSA-N heptanal Chemical compound CCCCCCC=O FXHGMKSSBGDXIY-UHFFFAOYSA-N 0.000 description 6
- 239000012295 chemical reaction liquid Substances 0.000 description 5
- 238000004321 preservation Methods 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000007791 liquid phase Substances 0.000 description 4
- 238000000967 suction filtration Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 238000004537 pulping Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- -1 vinyl ionol Chemical compound 0.000 description 3
- 229920002554 vinyl polymer Polymers 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000010812 external standard method Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 2
- LPDDKAJRWGPGSI-UHFFFAOYSA-N (3-methyl-4-oxobut-2-enyl) acetate Chemical compound CC(=O)OCC=C(C)C=O LPDDKAJRWGPGSI-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- GAWAYYRQGQZKCR-UHFFFAOYSA-N 2-chloropropionic acid Chemical compound CC(Cl)C(O)=O GAWAYYRQGQZKCR-UHFFFAOYSA-N 0.000 description 1
- QZIURHXSYCDODL-UHFFFAOYSA-N C(C)(=O)OCC=C(C=O)C.C(CCCC)=O Chemical compound C(C)(=O)OCC=C(C=O)C.C(CCCC)=O QZIURHXSYCDODL-UHFFFAOYSA-N 0.000 description 1
- 208000035240 Disease Resistance Diseases 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 208000010011 Vitamin A Deficiency Diseases 0.000 description 1
- LPDDKAJRWGPGSI-UTCJRWHESA-N [(z)-3-methyl-4-oxobut-2-enyl] acetate Chemical compound CC(=O)OC\C=C(\C)C=O LPDDKAJRWGPGSI-UTCJRWHESA-N 0.000 description 1
- VUBFDPHDHBTRIR-UHFFFAOYSA-N [Br].CCO Chemical compound [Br].CCO VUBFDPHDHBTRIR-UHFFFAOYSA-N 0.000 description 1
- PPHBKSRTKMLMMO-UHFFFAOYSA-M [Cl-].[Mg+]C=C.C1CCOC1 Chemical compound [Cl-].[Mg+]C=C.C1CCOC1 PPHBKSRTKMLMMO-UHFFFAOYSA-M 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- DUEPRVBVGDRKAG-UHFFFAOYSA-N carbofuran Chemical compound CNC(=O)OC1=CC=CC2=C1OC(C)(C)C2 DUEPRVBVGDRKAG-UHFFFAOYSA-N 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 description 1
- 239000002910 solid waste Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 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
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
- C07C403/06—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms
- C07C403/12—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms by esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/48—Preparation of compounds having groups
- C07C41/50—Preparation of compounds having groups by reactions producing groups
- C07C41/56—Preparation of compounds having groups by reactions producing groups by condensation of aldehydes, paraformaldehyde, or ketones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
- C07C67/293—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/54—Quaternary phosphonium compounds
- C07F9/5442—Aromatic phosphonium compounds (P-C aromatic linkage)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a preparation method of vitamin A acetate, which comprises the following steps: the process provides a synthesis route of the vitamin A acetate C13+ C7, improves the yield of the vitamin A acetate, reduces the process cost and is more beneficial to industrial production.
Description
Technical Field
The invention relates to a preparation method of vitamin A acetate, and particularly relates to a method for preparing vitamin A acetate by utilizing a Wittig reaction.
Background
Vitamin A acetate is an important nutritional chemical, has effects of promoting growth and development of human body, and enhancing disease resistance.
The vitamin A acetate is used for treating vitamin A deficiency, and the vitamin is fat soluble, is an essential factor for regulating the growth and health of epithelial tissue cells, thins the surface of rough and aged skin, promotes the normalization of cell metabolism, and has obvious wrinkle removing effect. At present, vitamin A acetate is widely applied to industries such as medicine, food additives, feed additives, cosmetics and the like, and the preparation and synthesis of the vitamin A acetate are concerned all the time.
At present, two technical routes are mainly adopted for industrially synthesizing the vitamin A acetic acid vinegar. One is route C14+ C6:
and a second route: c15+ C5 route
The two routes have defects, more than 50 raw materials are needed in the C14+ C6 route, the reaction steps are long, the fixed investment is large, the intermittent series reaction is adopted, the production control is not easy, in addition, the production of the double Grignard reagent has a safety problem, and the safety risk is large during the industrial amplification. The price of triphenylphosphine used as a raw material in the route of C15+ C5 is high, and a large amount of triphenylphosphine oxide as a reaction byproduct is solid waste and is difficult to treat; in addition, VA produced by the route contains a large amount of cis-isomer, so that the utilization value is reduced.
Patent CN110143874A reports that strong base is used for catalyzing the reaction of beta-ionone and 2-chloropropionate, then selective hydrogenation is carried out to prepare VA, triphenylphosphine oxide is well avoided, but strong base is used in the reaction process, a side reaction of condensation of raw materials exists, the reaction selectivity is poor, and the cost is high.
In order to overcome the defects of the existing production processes, a new process with high yield and cost advantage needs to be found.
Disclosure of Invention
The invention aims to provide a preparation method of vitamin A acetate, aiming at the defects in the prior art, and the preparation method has the advantages of high yield, economy, environmental protection and the like.
In order to achieve the above purpose, the technical scheme of the invention is as follows:
a preparation method of vitamin A acetate comprises the following steps:
1) bromoethanol reacts with acetone to produce a ketal compound of formula i:
2) the ketal compound shown in the formula I and five-carbon aldehyde (4-acetoxyl-2-methyl-2-butenal) shown in the formula II and magnesium powder are subjected to in-situ Grignard reaction and then subjected to acidolysis reaction to generate heptacarbon alcohol shown in the formula III:
3) reacting heptacarbon alcohol shown in a formula III with triphenyl phosphine and hydrochloric acid to generate heptacarbon phosphine salt shown in a formula IV:
4) the heptacarbon phosphine salt shown in the formula IV and beta-ionone are subjected to a Wittig reaction to obtain vitamin A acetate:
in step 1) of the present invention, the molar ratio of bromoethanol to acetone is 2-10:1, preferably 3-5: 1.
In step 1) of the invention, the reaction is carried out under the action of an acid catalyst, wherein the acid catalyst is selected from one or more of concentrated sulfuric acid, hydrogen chloride, methanesulfonic acid, p-toluenesulfonic acid and the like, and preferably more than 98 wt% of concentrated sulfuric acid and/or p-toluenesulfonic acid;
preferably, the acid catalyst is used in an amount of 0.1 to 1% by mole based on the acetone.
In the step 1) of the invention, the reaction temperature is-20-60 ℃, preferably 30-50 ℃, and the reaction time is 2-10 h.
In the step 1), after the reaction is finished, conventional post-treatment processes such as separation and purification are also included, and the purification is preferably carried out by adopting a rectification method, wherein the preferred rectification conditions are that the rectification temperature is 50-120 ℃, and the pressure is 2-20 KPaA.
In step 2) of the present invention, the molar ratio of the ketal compound represented by formula i to the pentanal (4-acetoxy-2-methyl-2-butenal) represented by formula ii is 1:1.8-2.2:1.8-2.2, preferably 1: 1.9-2.1: 1.9-2.1;
the ketal compound shown in the formula I and the pentanal shown in the formula II can be simultaneously dripped into a reaction system, or the pentanal can be firstly added for laying the bottom, and then the ketal compound is dripped; preferably, a method of firstly adding penta-carbon aldehyde to pave the bottom and then dripping a ketal compound is adopted; the dropping time of the ketal compound and the pentanal is preferably 1-5h, and the dropping time of the raw materials is not included in the Grignard reaction time.
In step 2) of the present invention, the grignard reaction is preferably performed in a solvent environment, and the solvent is selected from one or more of tetrahydrofuran, toluene and anhydrous diethyl ether, and is preferably tetrahydrofuran;
preferably, the solvent is used in an amount of 0.5 to 5 times the amount of the ketal compound and is added to the system simultaneously with the ketal compound.
In the step 2), the temperature of the Grignard reaction is 20-80 ℃, and the preferable temperature is 40-60 ℃; the time is 2-10h, preferably 3-5 h.
In the step 2) of the invention, the acidolysis reaction is carried out by adding the reaction solution into the acid solution for reaction after the completion of the in-situ Grignard reaction, preferably by continuous feeding such as dropwise addition, wherein the feeding time is 0.5-5h, and the raw material dropwise addition time is included in the acidolysis reaction time.
In the step 2), the acidolysis reaction is carried out by using one or more acids selected from sulfuric acid, hydrochloric acid and phosphoric acid;
the acid is preferably an acid aqueous solution with the concentration of 15-25 wt%;
preferably, the amount of the acid is 1 to 10 times, preferably 5 to 8 times, the amount of the ketal compound.
In the step 2), the acidolysis reaction is carried out at the temperature of 15-35 ℃, preferably at the temperature of 20-25 ℃ for 0.5-5 h;
after the acidolysis reaction is finished, the conventional post-treatment modes such as liquid separation, water washing, solvent removal under reduced pressure and the like are also included, and the specific method has no special requirement.
In step 3) of the invention, the molar ratio of the heptanol represented by formula III to the triphenylphosphine and hydrochloric acid (calculated as HCl) is 1: 1-1.2: 1-1.2;
preferably, the hydrochloric acid concentration is 33-36 wt%; the hydrochloric acid is preferably fed continuously, such as dropwise, for 1-4h, and the dropwise feeding time of the raw materials is not included in the reaction time.
In step 3) of the present invention, the reaction is preferably performed in a solvent environment, and the solvent is selected from one or more of methanol, ethanol, isopropanol and the like, preferably methanol;
preferably, the amount of the solvent is 2 to 10 times, preferably 4 to 6 times, the mass of the heptanol.
In the step 3), the reaction is carried out at the temperature of 30-70 ℃, preferably at the temperature of 40-60 ℃ for 2-8 hours, preferably for 3-5 hours;
after the reaction is finished, the post-treatment processes of solvent removal, pulping and the like are also included, the preferable method is pulping purification after solvent removal, in some examples, the pulping purification adopts a method of adding n-hexane, keeping the temperature at 60-65 ℃, stirring for 1-2h, and then carrying out suction filtration.
In step 4) of the present invention, the molar ratio of the heptacarbocosphine salt represented by formula IV to the beta-ionone is 0.9-1.1:1, preferably 1.0-1.05: 1.
In the step 4), the Wittig reaction is carried out under an alkaline condition, wherein the alkali is one or more selected from sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide, and preferably sodium carbonate and/or potassium carbonate;
the alkali is preferably alkali aqueous solution with the concentration of 8-15 wt%;
preferably, the molar ratio of the base to the heptaphosphine salt is from 0.5 to 5:1, preferably from 1 to 2:1.
In the step 4), the Wittig reaction is carried out at the temperature of 30-70 ℃, preferably at the temperature of 40-60 ℃ for 2-8 hours, preferably for 3-5 hours;
after the Wittig reaction is finished, the method further comprises the conventional treatment modes of extraction liquid separation, water washing, solvent removal and the like, wherein the extraction liquid separation is carried out, and the extraction liquid is selected from normal hexane, normal heptane and the like.
Compared with the prior art, the invention has the advantages that:
the invention provides a brand new synthesis route of vitamin A acetate C13+ C7, the yield of the vitamin A acetate is improved to 90% (calculated by beta-ionone), the yield is improved by 5-10% compared with the yield of the prior art, the content of all-trans VA reaches more than 85%, convenience is provided for subsequent separation and purification, and the invention has the advantages of high yield, economy, environmental protection and the like, and is more beneficial to industrial production.
Detailed Description
The technical solution of the present invention is further illustrated by the following specific examples.
Some of the reagent specifications and sources in the examples and comparative examples:
1. beta-ionone: more than 99 percent, and carbofuran;
2. bromine ethanol: greater than 98%, alatin;
3. five-carbon aldehyde: the 4-acetoxy-2-methyl-2-butenal is prepared by the method of patent CN108707076A example 1, and the purity is more than 99 percent.
Other raw materials are commercially available ordinary reagents unless otherwise specified.
Gas Chromatography (GC): model Agilent WAX 1701.42249; the carrier gas is high-purity nitrogen; the sample injection mode is an automatic sample injector; the nitrogen flow is 64.5 ml/min; the temperature of the vaporization chamber is 280 ℃; split-flow sample injection is carried out, and the split-flow ratio is 1: 40; the sample injection amount is 0.2 mul; the column flow rate was 1.5 ml/min; the column temperature is first-order temperature programming, the initial temperature is 100 ℃, the temperature is kept for 2 minutes, then the temperature is raised to 230 ℃ at the speed of 15 ℃/min, and the temperature is kept for 15 minutes; the total running time is 25.67 min; the temperature of the detector is 300 ℃; and (4) selecting an external standard method for quantification for quantitative analysis.
High Performance Liquid Chromatography (HPLC): shimadzu LC-20A with SIL-20A autosampler, CTO-10ASvp column oven, SPD-M20A detector, or an instrument with the same performance. Liquid chromatography conditions: the sample injection amount is 1 mu L, the UV detection wavelength is 328nm, and the column oven: 40 ℃, flow rate: 0.4 ml/min. And (4) selecting an external standard method for quantification for quantitative analysis.
Nuclear magnetic analysis (NMR): model Bruke Fourier 300, with CDCl3 as solvent, was qualitatively analyzed by 1H NMR.
Example 1
Adding 1249g (10mol) of bromoethanol and 290g (5mol) of acetone into a 3L three-neck flask, heating to 40 ℃, adding 1g (0.01mol) of concentrated sulfuric acid, carrying out heat preservation reaction for 6h, wherein the conversion per pass of the acetone is 26%, rectifying and separating the reaction solution, the temperature is 80 ℃, the pressure is 10KPaA, the number of tower plates is 50, and the reflux ratio is 10:1, 316.5g (1.1mol) of ketal compound is obtained with a GC purity of 99.8%. The ketal compounds were characterized by nuclear magnetic analysis, 1H NMR (300MHz, CDCl 3): δ 3.96(t, JH-H6.3 Hz,4H),3.69(t, JH-H6.3 Hz,4H),1.25(s, 6H).
Adding 298.2g (2.1mol) of pentanal, 500g of tetrahydrofuran and 49.9g (2.08mol) of magnesium powder into a 3L three-neck flask, heating to 60 ℃, slowly dropwise adding mixed solution of 289.9g (1mol) of ketal compound and 300g of tetrahydrofuran into the three-neck flask, wherein the dropwise adding time is 4 hours, the reaction temperature in the dropwise adding process is not more than 65 ℃, continuing to react for 3 hours at 65 ℃ after the dropwise adding is finished, slowly adding the reaction solution into a 5L three-neck flask containing 2000g of 20 wt% hydrochloric acid, completely dropwise adding for 2 hours, keeping the temperature and stirring for 1 hour at 20 ℃ after the dropwise adding is finished, separating the solution, washing the organic phase twice with water, and removing the solvent to obtain 330g of heptanal, wherein the GC purity is 98%, and the yield is 95.1%. Heptacarbon alcohols were characterized by nuclear magnetic analysis, 1H NMR (300MHz, DMSO): δ is 5.89-6.11(m, 3H), 4.62(d, 2H), 4.21(d, 2H),3.88(S,1H, hydroxyhydro), 2.32(S, 3H), 2.16(S, 3H).
Weighing 170g (1mol) of heptanol, 288.2g (1.1mol) of triphenylphosphine and 1000g of methanol in a 3L three-necked bottle, heating to 50 ℃, clarifying the system, slowly adding 105g (1mol) of 35% concentrated hydrochloric acid into the system, dropwise adding completely for about 2h, continuing to perform heat preservation reaction for 2h after dropwise adding completely, removing the methanol, adding 1000g of n-hexane into the reaction bottle, stirring for 2h at 60 ℃, and performing suction filtration to obtain 406.8g of heptaphosphine salt, wherein the HPLC content is as follows: 99.6% and yield 90.2%. Heptac phosphine salt was characterized by nuclear magnetic analysis, 1H NMR (300MHz, DMSO): δ 7.31-7.81(m, 15H), 5.22-5.36(m, 5H), 2.36-2.46(m, 5H),2.26(S, 3H).
405.8g (0.9mol) of heptaphosphine salt, 192g (1mol) of beta-ionone and 2000g of 10 wt% (1.88mol) of sodium carbonate aqueous solution are weighed in a 3L three-necked bottle, heated to 60 ℃, kept warm and stirred for 5 hours, 1000g of n-hexane is added into reaction liquid, liquid separation is carried out, organic phase is washed twice, and then the n-hexane is removed to obtain 331g of crude vitamin A acetate oil. Liquid phase analysis was performed to obtain 89% vitamin a acetate (all-trans VA 88%) in 89.8% yield.
Example 2
2498g (20mol) of bromoethanol and 290g (5mol) of acetone are added into a 3L three-neck flask, the temperature is raised to 50 ℃, 0.86g (0.005mol) of p-toluenesulfonic acid is added, the reaction is kept for 4 hours, the conversion per pass of the acetone is 36 percent, the reaction liquid is rectified and separated, the temperature is 120 ℃, the pressure is 15KPaA, the number of tower plates is 50, and the reflux ratio is 10:1, 434.8g (1.5mol) of ketal compound 1 was obtained with a GC purity of 99.8%.
Adding 269.8g (1.9mol) of pentanal, 500g of tetrahydrofuran and 45.5g (1.9mol) of magnesium chips into a 3L three-neck flask, heating to 50 ℃, slowly dropwise adding mixed solution of 289.9g (1mol) of ketal compound and 300g of tetrahydrofuran into the three-neck flask, wherein the dropwise adding time is 5 hours, the reaction temperature in the dropwise adding process is not more than 65 ℃, continuously reacting for 2 hours at 60 ℃ after the dropwise adding is finished, slowly adding the reaction solution into the 5L three-neck flask filled with 2000g of 15 wt% sulfuric acid, completely dropwise adding for 2 hours, keeping the temperature and stirring for 1 hour at 25 ℃ after the dropwise adding is finished, separating the solution, washing the organic phase twice with water, and removing the solvent to obtain 320g of heptanal, wherein the GC purity is 98%, and the yield is 92.2%.
Weighing 170g (1mol) of heptacarbonate, 275.1g (1.05mol) of triphenylphosphine and 1000g of methanol in a 3L three-necked bottle, heating to 50 ℃, clarifying the system, slowly adding 120g (1.08mol) of 33% concentrated hydrochloric acid into the system, completely dropwise adding for about 1h, continuing to perform heat preservation reaction for 5h after complete dropwise adding, removing methanol, adding 1000g of n-hexane into a reaction bottle, stirring for 2h at 60 ℃, and performing suction filtration to obtain 406.8g of heptacarbonate, wherein the HPLC content: 99.6% and yield 90.2%.
472.5g (1.05mol) of heptaphosphine salt, 192g (1mol) of beta-ionone and 700g of 10 wt% (0.5mol) potassium carbonate aqueous solution are weighed in a 3L three-necked bottle, heated to 60 ℃, kept warm and stirred for 5 hours, 1000g of n-hexane is added into reaction liquid, liquid separation is carried out, an organic phase is washed twice, and then the n-hexane is removed to obtain 336g of crude vitamin A acetate oil. Liquid phase analysis was performed with a vitamin a acetate content of 86% (all-trans VA content of 90%) and a yield of 88.1%.
Example 3
Adding 6245g (50mol) of bromoethanol and 290g (5mol) of acetone into a 3L three-necked bottle, heating to 50 ℃, adding 1.72g (0.01mol) of p-toluenesulfonic acid, carrying out heat preservation reaction for 4h, carrying out rectification separation on the reaction liquid, wherein the temperature is 50 ℃, the pressure is 2KPaA, the number of plates is 50, and the reflux ratio is 10: 463.8g (1.6mol) of ketal compound are obtained with a GC purity of 99.7%.
Adding 255.6g (1.8mol) of pentanal, 1000g of tetrahydrofuran and 43.2g (1.8mol) of magnesium chips into a 3L three-neck flask, heating to 40 ℃, slowly dropwise adding a mixed solution of 289.9g (1mol) of ketal compound and 300g of tetrahydrofuran into the three-neck flask for 2h, wherein the reaction temperature in the dropwise adding process is not more than 65 ℃, continuously reacting for 5h at 50 ℃ after the dropwise adding is finished, slowly adding the reaction solution into a 5L three-neck flask containing 2000g of 25 wt% hydrochloric acid, completely dropwise adding for 2h, keeping the temperature and stirring for 1h at 25 ℃ after the dropwise adding is finished, separating, washing the organic phase with water twice, and removing the solvent to obtain 330g of heptanal, wherein the GC purity is 98%, and the yield is 95.1%.
Weighing 170g (1mol) of heptacarbonate, 314.1g (1.2mol) of triphenylphosphine and 1700g of methanol in a 3L three-necked bottle, heating to 70 ℃, clarifying the system, slowly adding 120g (1.18mol) of 36% concentrated hydrochloric acid into the system, completely dripping for about 2h, continuing to perform heat preservation reaction for 3h after the dripping is complete, removing methanol, adding 1000g of n-hexane into a reaction bottle, stirring for 2h at 60 ℃, and performing suction filtration to obtain 419.8g of heptacarbonate, wherein the HPLC content: 99.6% and a yield of 93.1%.
473.4g (1.05mol) of heptaphosphine salt, 192g (1mol) of beta-ionone and 2760g of 10 wt% (2mol) of potassium carbonate aqueous solution are weighed in a 3L three-necked bottle, heated to 40 ℃, kept warm and stirred for 8 hours, 1000g of n-hexane is added into reaction liquid, liquid separation is carried out, organic phase is washed twice, and then the n-hexane is removed to obtain 346g of crude vitamin A acetate oil. Liquid phase analysis was performed with a vitamin a acetate content of 89% (all-trans VA content of 89%) and a yield of 93.8%.
Comparative example 1
Adding 1.2L vinyl magnesium chloride tetrahydrofuran solution (2mol/L, 2.4mol) into a 4L three-necked flask, stirring, cooling to 0 ℃, and dropwise adding 401g beta-ionone (2mol) at a temperature of not more than 10 ℃. After the dropwise addition, the reaction is continued for 2 hours at the temperature of 5-10 ℃. After the reaction, 1L of toluene was added to the three-necked flask, and the tetrahydrofuran was replaced by rectification under reduced pressure. After the replacement, the toluene solution was cooled to 10 ℃ and 1L of water was added, the temperature being controlled not to exceed 20 ℃. After the addition, the stirring is stopped, and the phase separation is carried out by standing. And removing the organic phase by using a solvent to obtain a crude product of the vinyl ionol. The crude product was distilled at 200Pa (absolute pressure) at 130 ℃ to give 422g of vinyl ionol product, 94% content and 90% yield.
288g of triphenylphosphine (1.1mol) and 2L of methanol were added to a 4L three-necked flask, 118g of hydrochloric acid (37%, 1.2mol) were added dropwise with stirring, and after the dropwise addition, the temperature was raised to 50 ℃. 234g of vinyl ionol (1.0mol) were added dropwise to a three-necked flask, and after completion of the addition, the reaction was maintained at 50 ℃ for 2 hours. After the reaction, the reaction solution is brought to 0 ℃, 153g of pentanal (1.0mol) is added, the mixture is stirred uniformly, 300ml of prepared sodium methoxide methanol solution (5mol/L, 1.5mol) is added dropwise, and the temperature is controlled not to exceed 5 ℃. After the dropwise addition, keeping the temperature of 0-5 ℃ for reaction for 1 h. After the reaction, the reaction solution was transferred to an extraction vessel and extracted with 3X 1.5L of n-hexane, and the extracts were combined and the solvent was removed to obtain 308g of crude vitamin A acetate oil. Liquid phase analysis was performed with a vitamin a acetate content of 80% (all-trans VA content of 60%) and a yield of 75%.
Claims (10)
1. A preparation method of vitamin A acetate comprises the following steps:
1) bromoethanol reacts with acetone to produce a ketal compound of formula i:
2) the ketal compound shown in the formula I and the five-carbon aldehyde and magnesium powder shown in the formula II are subjected to in-situ Grignard reaction and then subjected to acidolysis reaction to generate heptacarbon alcohol shown in the formula III:
3) reacting heptacarbon alcohol shown in a formula III with triphenyl phosphine and hydrochloric acid to generate heptacarbon phosphine salt shown in a formula IV:
4) the heptacarbon phosphine salt shown in the formula IV and beta-ionone are subjected to a Wittig reaction to obtain vitamin A acetate:
2. the method of claim 1, wherein: in the step 1), the molar ratio of the bromoethanol to the acetone is 2-10:1, preferably 3-5: 1;
the reaction is carried out under the action of an acid catalyst, wherein the acid catalyst is one or more of concentrated sulfuric acid, hydrogen chloride, methanesulfonic acid, p-toluenesulfonic acid and the like, and the concentrated sulfuric acid with the concentration of more than 98 wt% and/or the p-toluenesulfonic acid are preferred;
preferably, the acid catalyst is used in an amount of 0.1 to 1% by mole based on the acetone.
3. The method according to claim 1 or 2, characterized in that: in the step 1), the reaction temperature is-20-60 ℃, preferably 30-50 ℃ and the reaction time is 2-10 h.
4. A method according to any one of claims 1-3, characterized in that: in the step 2), the molar ratio of the ketal compound shown in the formula I to the pentanal shown in the formula II and the magnesium is 1:1.8-2.2:1.8-2.2, preferably 1: 1.9-2.1: 1.9-2.1;
preferably, the ketal compound shown in the formula I and the pentanal shown in the formula II are dripped into the reaction system, the dripping time is preferably 1-5h, and the dripping time of the raw materials is not included in the Grignard reaction time.
5. The method according to any one of claims 1-4, wherein: in the step 2), the grignard reaction is carried out in a solvent environment, wherein the solvent is one or more selected from tetrahydrofuran, toluene and anhydrous ether, and tetrahydrofuran is preferred;
preferably, the amount of the solvent is 0.5 to 5 times the amount of the ketal compound;
the Grignard reaction is carried out at the temperature of 20-80 ℃, and the preferred temperature is 40-60 ℃; the time is 2-10h, preferably 3-5 h.
6. The method according to any one of claims 1 to 5, wherein: in the step 2), the acidolysis reaction is to add the reaction solution into the acid solution for reaction after the in-situ Grignard reaction is finished;
preferably, a continuous feeding mode is adopted, the feeding time is 0.5-5h, and the dropping time of the raw materials is contained in the acidolysis reaction time;
in the acidolysis reaction, the adopted acid is one or more selected from sulfuric acid, hydrochloric acid and phosphoric acid, and preferably an acid aqueous solution with the concentration of 15-25 wt%;
preferably, the amount of the acid is 1 to 10 times, preferably 5 to 8 times, the amount of the ketal compound;
the acidolysis reaction is carried out at the temperature of 15-35 ℃, preferably at the temperature of 20-25 ℃ for 0.5-5 h.
7. The method according to any one of claims 1-6, wherein: in the step 3), the molar ratio of the heptanol shown in the formula III to the triphenyl phosphine and the hydrochloric acid is 1: 1-1.2: 1-1.2;
preferably, the hydrochloric acid concentration is 33-36 wt%; the hydrochloric acid is preferably fed continuously, such as dropwise, the feeding time is 1-4h, and the dropwise feeding time of the raw materials is not included in the reaction time;
the reaction is carried out in a solvent environment, the solvent is selected from one or more of methanol, ethanol, isopropanol and the like, and methanol is preferred;
preferably, the amount of the solvent is 2 to 10 times, preferably 4 to 6 times, the mass of the heptanol.
8. The method according to any one of claims 1 to 7, wherein: in the step 3), the reaction is carried out at the temperature of 30-70 ℃, preferably 40-60 ℃ for 2-8 hours, preferably 3-5 hours.
9. The method according to any one of claims 1-8, wherein: in the step 4), the molar ratio of the heptacarbochosphine salt shown in the formula IV to the beta-ionone is 0.9-1.1:1, preferably 1.0-1.05: 1;
the Wittig reaction is carried out under alkaline conditions, the alkali is selected from one or more of sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide, and sodium carbonate and/or potassium carbonate are/is preferred;
preferably, the alkali adopts alkali water solution with the concentration of 8-15 wt%;
preferably, the molar ratio of the base to the heptaphosphine salt is from 0.5 to 5:1, preferably from 1 to 2:1.
10. The method according to any one of claims 1-9, wherein: in the step 4), the Wittig reaction is carried out at the temperature of 30-70 ℃, preferably 40-60 ℃ for 2-8h, preferably 3-5 h.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011374517.9A CN112457229B (en) | 2020-11-30 | 2020-11-30 | Preparation method of vitamin A acetate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011374517.9A CN112457229B (en) | 2020-11-30 | 2020-11-30 | Preparation method of vitamin A acetate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112457229A true CN112457229A (en) | 2021-03-09 |
| CN112457229B CN112457229B (en) | 2022-11-08 |
Family
ID=74804986
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011374517.9A Active CN112457229B (en) | 2020-11-30 | 2020-11-30 | Preparation method of vitamin A acetate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112457229B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112961088A (en) * | 2021-03-29 | 2021-06-15 | 万华化学集团股份有限公司 | Preparation method of vitamin A acetate |
| WO2023108327A1 (en) * | 2021-12-13 | 2023-06-22 | 万华化学集团股份有限公司 | Preparation method for light-colored vitamin a |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110143874A (en) * | 2019-05-17 | 2019-08-20 | 万华化学集团股份有限公司 | A kind of preparation method of retinyl acetate |
| CN110903190A (en) * | 2019-12-09 | 2020-03-24 | 万华化学集团股份有限公司 | Preparation method of vitamin A and vitamin A ester |
| CN111484524A (en) * | 2019-01-25 | 2020-08-04 | 新发药业有限公司 | Vitamin A acetate intermediate C15 and preparation method of vitamin A acetate |
| CN111484525A (en) * | 2019-01-25 | 2020-08-04 | 新发药业有限公司 | Vitamin A ester intermediate C15 and preparation method of vitamin A ester |
| CN111484400A (en) * | 2019-01-25 | 2020-08-04 | 新发药业有限公司 | Preparation method of 2-methyl-4- (2,6, 6-trimethylcyclohexene-1-yl) -2-butenal |
-
2020
- 2020-11-30 CN CN202011374517.9A patent/CN112457229B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111484524A (en) * | 2019-01-25 | 2020-08-04 | 新发药业有限公司 | Vitamin A acetate intermediate C15 and preparation method of vitamin A acetate |
| CN111484525A (en) * | 2019-01-25 | 2020-08-04 | 新发药业有限公司 | Vitamin A ester intermediate C15 and preparation method of vitamin A ester |
| CN111484400A (en) * | 2019-01-25 | 2020-08-04 | 新发药业有限公司 | Preparation method of 2-methyl-4- (2,6, 6-trimethylcyclohexene-1-yl) -2-butenal |
| CN110143874A (en) * | 2019-05-17 | 2019-08-20 | 万华化学集团股份有限公司 | A kind of preparation method of retinyl acetate |
| CN110903190A (en) * | 2019-12-09 | 2020-03-24 | 万华化学集团股份有限公司 | Preparation method of vitamin A and vitamin A ester |
Non-Patent Citations (3)
| Title |
|---|
| BERGEN.H.ROBERT等: "Synthesis of tri-, tetra-, and pentadeuterated forms of vitamin A", 《JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS》 * |
| NESNAS,NASRI等: "Synthesis of biotinylated retinoids for cross-linking and isolation of retinol binding proteins", 《TETRAHEDRON》 * |
| 吕国锋等: "合成维生素A醋酸酯新工艺的研究", 《浙江工业大学学报》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112961088A (en) * | 2021-03-29 | 2021-06-15 | 万华化学集团股份有限公司 | Preparation method of vitamin A acetate |
| CN112961088B (en) * | 2021-03-29 | 2023-03-03 | 万华化学集团股份有限公司 | Preparation method of vitamin A acetate |
| WO2023108327A1 (en) * | 2021-12-13 | 2023-06-22 | 万华化学集团股份有限公司 | Preparation method for light-colored vitamin a |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112457229B (en) | 2022-11-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112457229B (en) | Preparation method of vitamin A acetate | |
| CN110143874B (en) | Preparation method of vitamin A acetate | |
| CN110903190B (en) | Preparation method of vitamin A and vitamin A ester | |
| CN111393275B (en) | Method for synthesizing intermediate farnesyl acetone and method for synthesizing plant alcohol, isophytol and geranylgeraniol by using same | |
| CN111484400B (en) | Preparation method of 2-methyl-4- (2,6, 6-trimethylcyclohexene-1-yl) -2-butenal | |
| CN108707076A (en) | A kind of preparation method of 4- acetoxyl-2-methyl-2-butylenoic aldehydes | |
| CN110467519A (en) | A kind of Ethynylation process | |
| CN111138261B (en) | Method for preparing beta-ionone by cyclization | |
| CN111484525A (en) | Vitamin A ester intermediate C15 and preparation method of vitamin A ester | |
| CN106986900B (en) | A kind of preparation method of N- alkyl glucose imines | |
| CN111187146B (en) | Process for producing 2-methyl-3-buten-2-ol | |
| CN113896634B (en) | Preparation method of 3-methoxy methyl acrylate | |
| CN110028466B (en) | Method for producing dimorpholinyl diethyl ether | |
| CN112961088B (en) | Preparation method of vitamin A acetate | |
| CN103396304B (en) | Nervonic acid chemosynthesis method | |
| CN114805066B (en) | Preparation method of apoester key intermediate C10 aldehyde ester | |
| CN115246806B (en) | New preparation method of vitamin E | |
| CN111484510B (en) | Preparation method of (2, 6-trimethyl-1-cyclohexenyl) aldehyde | |
| CN115819227B (en) | Synthesis method of 1-hepten-3-yl isobutyrate | |
| CN115322084B (en) | Method for improving acetone utilization rate in pseudo ionone production process | |
| CN102675087B (en) | Preparation method of novel alpha-ketovaline calcium | |
| KR100624236B1 (en) | One-Step Synthetic Methods for Cinnamaldehyde Derivatives | |
| CN118359524A (en) | Preparation method of cilastatin sodium | |
| CN117624108A (en) | Method for efficiently synthesizing apple ester compound | |
| CN1070194A (en) | Process for synthesizing methamidophos |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |