CN105218494B - The preparation method of vitamin C fat acid diester - Google Patents
The preparation method of vitamin C fat acid diester Download PDFInfo
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- CN105218494B CN105218494B CN201510785644.0A CN201510785644A CN105218494B CN 105218494 B CN105218494 B CN 105218494B CN 201510785644 A CN201510785644 A CN 201510785644A CN 105218494 B CN105218494 B CN 105218494B
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- vitamin
- fat
- acid diester
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- fat acid
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 title claims abstract description 151
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 title claims abstract description 77
- 229930003268 Vitamin C Natural products 0.000 title claims abstract description 77
- 235000019154 vitamin C Nutrition 0.000 title claims abstract description 77
- 239000011718 vitamin C Substances 0.000 title claims abstract description 77
- 239000002253 acid Substances 0.000 title claims abstract description 48
- 150000005690 diesters Chemical class 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 57
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 51
- 150000002148 esters Chemical class 0.000 claims abstract description 26
- 239000000047 product Substances 0.000 claims abstract description 21
- 150000001263 acyl chlorides Chemical class 0.000 claims abstract description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000012043 crude product Substances 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 12
- 239000012230 colorless oil Substances 0.000 claims abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 8
- 239000003444 phase transfer catalyst Substances 0.000 claims abstract description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 5
- 239000003921 oil Substances 0.000 claims abstract description 5
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 claims abstract description 4
- -1 vitamin C fatty acid diesters Chemical class 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 150000002190 fatty acyls Chemical group 0.000 claims description 6
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims description 6
- 239000011230 binding agent Substances 0.000 claims description 5
- 235000019270 ammonium chloride Nutrition 0.000 claims description 4
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 4
- 229930195729 fatty acid Natural products 0.000 claims description 4
- 239000000194 fatty acid Substances 0.000 claims description 4
- SWLVFNYSXGMGBS-UHFFFAOYSA-N ammonium bromide Chemical compound [NH4+].[Br-] SWLVFNYSXGMGBS-UHFFFAOYSA-N 0.000 claims description 3
- UUZYBYIOAZTMGC-UHFFFAOYSA-M benzyl(trimethyl)azanium;bromide Chemical compound [Br-].C[N+](C)(C)CC1=CC=CC=C1 UUZYBYIOAZTMGC-UHFFFAOYSA-M 0.000 claims description 3
- KXHPPCXNWTUNSB-UHFFFAOYSA-M benzyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC1=CC=CC=C1 KXHPPCXNWTUNSB-UHFFFAOYSA-M 0.000 claims description 3
- 230000033228 biological regulation Effects 0.000 claims description 3
- JPWGUOFOCAZONZ-UHFFFAOYSA-N heptan-1-amine;hydrobromide Chemical class Br.CCCCCCCN JPWGUOFOCAZONZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- HWCKGOZZJDHMNC-UHFFFAOYSA-M tetraethylammonium bromide Chemical group [Br-].CC[N+](CC)(CC)CC HWCKGOZZJDHMNC-UHFFFAOYSA-M 0.000 claims description 3
- SRUKOJDGOUUFRB-UHFFFAOYSA-N heptylazanium;chloride Chemical class Cl.CCCCCCCN SRUKOJDGOUUFRB-UHFFFAOYSA-N 0.000 claims description 2
- QBVXKDJEZKEASM-UHFFFAOYSA-M tetraoctylammonium bromide Chemical compound [Br-].CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)CCCCCCCC QBVXKDJEZKEASM-UHFFFAOYSA-M 0.000 claims description 2
- XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 230000003647 oxidation Effects 0.000 abstract description 6
- 238000007254 oxidation reaction Methods 0.000 abstract description 6
- 239000012046 mixed solvent Substances 0.000 abstract description 3
- 235000000069 L-ascorbic acid Nutrition 0.000 abstract 1
- 239000002211 L-ascorbic acid Substances 0.000 abstract 1
- 229960005070 ascorbic acid Drugs 0.000 abstract 1
- 238000001816 cooling Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 238000007792 addition Methods 0.000 description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 238000003672 processing method Methods 0.000 description 5
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 4
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
- 229910014033 C-OH Inorganic materials 0.000 description 3
- 229910014570 C—OH Inorganic materials 0.000 description 3
- 238000013329 compounding Methods 0.000 description 3
- 238000004945 emulsification Methods 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- XQSBLCWFZRTIEO-UHFFFAOYSA-N hexadecan-1-amine;hydrobromide Chemical class [Br-].CCCCCCCCCCCCCCCC[NH3+] XQSBLCWFZRTIEO-UHFFFAOYSA-N 0.000 description 2
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 2
- REEZZSHJLXOIHL-UHFFFAOYSA-N octanoyl chloride Chemical compound CCCCCCCC(Cl)=O REEZZSHJLXOIHL-UHFFFAOYSA-N 0.000 description 2
- 238000003408 phase transfer catalysis Methods 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000007711 solidification Methods 0.000 description 2
- 230000008023 solidification Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- YMBCJWGVCUEGHA-UHFFFAOYSA-M tetraethylammonium chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC YMBCJWGVCUEGHA-UHFFFAOYSA-M 0.000 description 2
- VMKOFRJSULQZRM-UHFFFAOYSA-N 1-bromooctane Chemical class CCCCCCCCBr VMKOFRJSULQZRM-UHFFFAOYSA-N 0.000 description 1
- CLWAXFZCVYJLLM-UHFFFAOYSA-N 1-chlorohexadecane Chemical class CCCCCCCCCCCCCCCCCl CLWAXFZCVYJLLM-UHFFFAOYSA-N 0.000 description 1
- MHPUGCYGQWGLJL-UHFFFAOYSA-N 5-methyl-hexanoic acid Chemical compound CC(C)CCCC(O)=O MHPUGCYGQWGLJL-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 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
- 239000000490 cosmetic additive Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 150000004668 long chain fatty acids Chemical class 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229940097411 palm acid Drugs 0.000 description 1
- 238000005502 peroxidation Methods 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 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
- 229940088594 vitamin Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/62—Three oxygen atoms, e.g. ascorbic acid
Abstract
The preparation method of vitamin C fat acid diester, is related to a kind of L ascorbic acid dibasic acid esters and preparation method thereof.The present invention is the problem weak in order to improve vitamin C monoesters hardly possible compatibility, four ester oxidation resistances.The structural formula of vitamin C fat acid diester is as follows.Method：One：After vitamin C is mixed with ethyl acetate, add pyridine, phase transfer catalyst is added, then to fat acyl chloride is added dropwise in reaction system, rate of addition is maintained, after dropwise addition fat acyl chloride is finished, continue to react, separate water layer, oil reservoir is washed again, ethyl acetate is steamed, colorless oil vitamin C dibasic acid esters crude product is obtained；Two：Vitamin C dibasic acid esters crude product methyl alcohol water mixed solvent is dissolved, cooling, separate methanol layer, gas producing formation removes methyl alcohol and ethyl acetate, obtains sterling, as vitamin C fat acid diester.The compatibility and oxidation resistance of vitamin C fat acid diester of the present invention are remarkably reinforced, and improve the purity of product.The present invention is due to preparing vitamin C fat acid diester.
Description
Technical field
The present invention relates to a kind of L-AA dibasic acid esters and preparation method thereof.
Background technology
Vitamin C can control the peroxidation of free radical, pair aging relevant with free radical, tumour, angiocarpy etc.
Disease has prevention effect.But, the defect of fat-soluble difference and oxidizable denaturation limits it in liposome and in cosmetics
Using.Compared with vitamin C, the solubility and compatibility of vitamin C ester make moderate progress, be a class have concurrently antitumor, anti-aging,
Antibiooxidation, the safe new food additive and cosmetic additive agent of removing various functional characteristics such as interior free yl.
At present, existing vitamin C ester mainly has two kinds, is respectively vitamin C monoesters and the ester of vitamin C four.Vitamin C
Monoesters makes its fat-soluble not high because also containing three hydroxyls in core molecule, easily occurs difficult emulsification, difficult compatibility during compounding and lacks
Point, meanwhile, can produce flocculent deposit or caking youngster's phenomenon because crystal is separated out after a period of time is placed after compounding；The ester of vitamin C four
It is fat-soluble significantly improve, easily emulsification but due to four presence of long alkyl chain, makes its active ingredient parent nucleus i.e. ascorbic
Relative amount is reduced, and causes its oxidation resistance substantially to reduce.
The synthetic method of vitamin C dibasic acid esters has no document report at present.The synthetic method of vitamin C monoesters has biological enzyme
With two kinds of chemical method, wherein enzyme process is only limitted to the primary hydroxyl higher of activity in Vc molecule esterification occurs, and remaining in molecule
Secondary hydroxyl and phenolic hydroxyl group can not be esterified.Chemical method has：(1) ester-interchange method is that vitamin C is prepared into vitamin C methyl esters,
Then there is ester exchange reaction with LCFA again, the method has that step is more, the reaction time is long, the low shortcoming of yield；(2)
Sulfuric acid process is to make solvent with the concentrated sulfuric acid that concentration is 98%, and the resistance to corrosion requirement to equipment is high, meanwhile, the yield of crude product
Only 80% or so；(3) chloride method is to make catalyst with vitamin C and acyl chlorides as raw material, with HCl gases, it is clear that HCl gases
Corrosivity is strong, pollutes environment.Patent CN03129677 does molten with acyl chlorides and vitamin C as raw material with mixed solvents such as water-acetonitriles
Matchmaker, organic or inorganic alkali does acid binding agent, has prepared ascorbic four ester, and the method is to improve vitamin C in organic solvent
Solubility, solvent is done with mixed solvents such as water-acetonitriles, inevitably hydrolyze acyl chlorides, so acyl chlorides is excessively more,
Yield only has 45~75%.The reaction time of above-mentioned all preparation methods is all more than 24 hours.In sum, with reference to existing
The synthetic method of monoesters or four esters, simply changes the parameters such as ratio, the reaction temperature of raw material, it is impossible to expeditiously prepare height
The vitamin C dibasic acid esters of yield, high-purity.
The content of the invention
The present invention is the phenomenon weak in order to improve vitamin C monoesters hardly possible compatibility, four ester oxidation resistances, from molecular structure angle
Degree is started with, and primary hydroxyl in vitamin C molecules and secondary hydroxyl are esterified, and is remarkably reinforced the compatibility ability of such product.It is real
Test result to show, when synthesized vitamin C dibasic acid esters with vitamin C palm acid monoester identical formula by being compounded, place
1 year, caking metachromatism is had no, show that its compatibility and oxidation resistance are remarkably reinforced.
The structural formula of vitamin C fat acid diester of the present invention is：
Wherein R for carbon number be 6~17 linear alkyl chain or carbon number be 6~17 branched alkyl chain.
The preparation method of said vitamin C fatty acid diesters, is carried out according to the following steps：
Step one：After vitamin C is mixed with ethyl acetate, add pyridine to do acid binding agent, add phase transfer catalyst,
Then to fat acyl chloride is added dropwise in reaction system, system starts heat release, maintains rate of addition, system temperature is maintained at 45~50
DEG C, be added dropwise after fat acyl chloride finishes, continue to react 0.5~1h, additions mass concentration is 10~20% dilute sulfuric acids, adjust pH value to
5~7, water layer is separated, oil reservoir is washed 2~3 times again, steams ethyl acetate, obtains colorless oil vitamin C dibasic acid esters crude product；
Step 2：Vitamin C dibasic acid esters crude product Methanol+Water is dissolved, -5~5 DEG C, product solidification are cooled to
In solution bottom, methanol layer is separated, gas producing formation removes Trace Methanol and ethyl acetate, obtains through high vacuum (5~30Pa vacuums)
Sterling, as vitamin C fat acid diester.
Phase transfer catalyst is tetraethylammonium bromide, TBAB, four heptyl ammonium bromides, four n-octyl bromides in step one
Change ammonium, four cetyl ammonium bromides, benzyltrimethylammonium bromide, etamon chloride, tetrabutylammonium chloride, four heptyl chlorinations
Ammonium, four octyl group ammonium chlorides, four cetyl chloride ammoniums or benzyltrimethylammonium chloride.
In step one fat acyl chloride be the carbon number such as stearic acid, palmitic acid, laurate be C7~18 straight chain fatty acyl chlorides or
The carbon numbers such as person's isostearic acid, different hexadecylic acid, different n-nonanoic acid, isooctyl acid, isoamyl acetic acid are the Branched fatty acyl chlorides of C7~18.
Beneficial effects of the present invention are as follows：
1st, the present invention starts with from molecular structure angle, and primary hydroxyl in vitamin C molecules and secondary hydroxyl are esterified, due to
In molecule again introduce two long alkyl chains, make its it is fat-soluble be remarkably reinforced, result of study shows, such product can dissolve well
In edible oil, compared with vitamin C monoesters, it is long placed in without flocculent deposit.Meanwhile, synthesized vitamin C dibasic acid esters is pressed and given birth to dimension
When plain C palms acid monoester identical formula carries out emulsification compounding, place 1 year, have no caking metachromatism, show its compatibility
It is remarkably reinforced with oxidation resistance.
2nd, to improve the existing vitamin C shortcoming that solubility is low in organic solvent, reaction speed is slow, the present invention selects season
Ammonium salt cooks phase transfer catalyst, can be effectively increased vitamin C solubility in organic solvent, esterification reaction rate is substantially carried
It is high.According to said method, the volume of organic solvent is only 1~5 times of vitamin C quality, and reaction can be rapidly completed.
3rd, product is refined using Methanol+Water, effectively increases the purity of product.The inventive method is tieed up
Up to 95%~98%, its purity of high performance liquid chromatography detection is 98%~99% to the high income of raw element C fatty acid diesters.
Brief description of the drawings
Fig. 1 is product prepared by embodiment 11H H NMR spectroscopies；
Fig. 2 is product prepared by embodiment 113C H NMR spectroscopies；
Fig. 3 is the IR spectrums of product prepared by embodiment 1；
Fig. 4 is product prepared by embodiment 51H H NMR spectroscopies；
Fig. 5 is product prepared by embodiment 513C H NMR spectroscopies；
Fig. 6 is the IR spectrums of product prepared by embodiment 5；
Fig. 7 is product prepared by embodiment 61H H NMR spectroscopies；
Fig. 8 is product prepared by embodiment 613C H NMR spectroscopies；
Fig. 9 is the IR spectrums of product prepared by embodiment 6.
Specific embodiment
Technical solution of the present invention is not limited to act specific embodiment set forth below, also including between each specific embodiment
Any combination.
Specific embodiment one：The structural formula of present embodiment vitamin C fat acid diester is：
Wherein R for carbon number be 6~17 linear alkyl chain or carbon number be 6~17 branched alkyl chain.
Specific embodiment two：The preparation method of present embodiment vitamin C fat acid diester, is carried out according to the following steps：
Step one：After vitamin C is mixed with ethyl acetate, add pyridine to do acid binding agent, add phase transfer catalyst,
Then to fat acyl chloride is added dropwise in reaction system, system starts heat release, maintains rate of addition, system temperature is maintained at 45~50
DEG C, after dropwise addition fat acyl chloride is finished, continuing to react 0.5~1h, regulation pH value separates water layer to 5~7, and oil reservoir washes 2~3 again
It is secondary, ethyl acetate is steamed, obtain colorless oil vitamin C dibasic acid esters crude product；
Step 2：Vitamin C dibasic acid esters crude product Methanol+Water is dissolved, -5~5 DEG C, product solidification are cooled to
In solution bottom, methanol layer is separated, gas producing formation removes methyl alcohol and ethyl acetate under 5~30Pa vacuums, obtains sterling, as ties up
Raw element C fatty acid diesters.
Specific embodiment three：Present embodiment from unlike specific embodiment two：Ascorbic matter in step one
Amount is 1g with the volume ratio of ethyl acetate:(1.0~3.0) mL.Other are identical with specific embodiment two.
Specific embodiment four：Present embodiment from unlike specific embodiment two：Pyridine is dimension life in step one
2.0~2.05 times of plain C molal weights.Other are identical with specific embodiment two.
Specific embodiment five：Present embodiment from unlike specific embodiment two：Phase transfer catalysis (PTC) in step one
Agent is tetraethylammonium bromide, TBAB, four heptyl ammonium bromides, ammonium bromide and tetraoctyl ammonium bromide, four cetyl ammonium bromides, benzyl
Trimethylammonium bromide, etamon chloride, tetrabutylammonium chloride, four heptyl ammonium chlorides, four octyl group ammonium chlorides, four Cetyl Chlorides
Change ammonium or benzyltrimethylammonium chloride.Other are identical with specific embodiment two.
Specific embodiment six：Present embodiment from unlike specific embodiment two：Phase transfer catalysis (PTC) in step one
The quality of agent is the 1%~5% of vitamin C quality.Other are identical with specific embodiment two.
Specific embodiment seven：Present embodiment from unlike specific embodiment two：Fat acyl chloride is in step one
Carbon number be C7~18 straight chain fatty acyl chlorides or carbon number be C7~18 Branched fatty acyl chlorides.Other and specific embodiment two
It is identical.
Specific embodiment eight：Present embodiment from unlike specific embodiment two：Fat acyl chloride in step one
Consumption is 1.8~2.3 times of vitamin C mole.Other are identical with specific embodiment two.
Specific embodiment nine：Present embodiment from unlike specific embodiment two：The mixing of step 2 methanol-water is molten
Methyl alcohol and the volume ratio of water are 10 in agent:(0.5~1).Other are identical with specific embodiment two.
Specific embodiment ten：Present embodiment from unlike specific embodiment two：Vitamin C dibasic acid esters in step 2
Crude product is 1g with the amount ratio of Methanol+Water:(1~1.2) mL.Other are identical with specific embodiment two.
For checking beneficial effects of the present invention carry out tests below：
Embodiment 1：
The preparation method of the present embodiment vitamin C fat acid diester, is carried out according to the following steps：
Step one：After 17.6g (0.1mol) vitamin Cs are mixed with 40ml ethyl acetate, pyridine 16g is added
(0.202mol) does acid binding agent, adds TBAB 0.53g (3%) and cooks phase transfer catalyst, is dripped in reaction system
Plus different caprylyl chloride 32.5g (0.2mol), system starts heat release, maintains rate of addition, system temperature is maintained at 50 DEG C.It is added dropwise different
After caprylyl chloride is finished, continue to react 0.5h, thin-layer chromatography detection, vitamin C is completely converted into vitamin C dibasic acid esters, adds quality
Concentration is 15% dilute sulfuric acid, and regulation pH value separates water layer to 6, and oil reservoir is washed 3 times again, steams ethyl acetate, obtains colorless oil dimension
The raw double isooctyl acid esters crude product 42.4g of element C.
Step 2：With 46mL methanol-waters, (methyl alcohol is 10 with the volume ratio of water to crude product:1) dissolve, be cooled to 0 DEG C, product coagulates
Solution bottom is fixed in, methanol layer is poured out, gas producing formation removes Trace Methanol and ethyl acetate, obtains 41.9g sterlings through high vacuum.
The structural formula of the double isooctyl acid esters of vitamin C manufactured in the present embodiment is：
The yield of the present embodiment is 97.9%.HPLC (C18 posts；Detection wavelength UV=250nm；Mobile phase：100% isopropyl
Alcohol；Flow velocity：0.4ml/min)：Retention time 7.09min, purity is 98.4%.
1H NMR (300MHz, CDCl3, unit:Ppm) (as shown in Figure 1)：δ 10.05 (s, 2H, C=C-OH)；4.90-
4.26(m,4H,O-CH2-H)；2.64~2.34 (m, 2H, CH)；1.33~0.90 (m, 28H, CH2,CH3).
13C NMR (75MHz, CDCl3) (as shown in Figure 2) δ 177.11,176.62,166.12,155.18,115.40,
75.20,69.62,68.25,64.69,47.16,46.83,31.59,31.35,29.55,25.35,25.22,22.57,
22.49,13.88,13.81,11.77,11.59.
IR (KBr coating methods) is as shown in Figure 3：3425,2960,2933,2873,2855,1768,1740,1681,1460,
1383,1262,1170,1131,1049cm-1.
Embodiment 2：
The all experiment conditions of the present embodiment and processing method are same as Example 1, simply the addition of TBAB
It is changed to 0.88g (5%).It is final to obtain colorless oil 42.2g, yield 98.5%.High performance liquid chromatography detection result product purity
98.8%.
Embodiment 3：
The all experiment conditions of the present embodiment and processing method are same as Example 1, and simply to be changed to four pungent for TBAB
Base ammonium bromide, addition is changed to 0.7g (4%).It is final to obtain colorless oil 42.3g, yield 98.8%.High performance liquid chromatography is examined
Survey result product purity 98.3%.
Embodiment 4：
The all experiment conditions of the present embodiment and processing method are same as Example 1, and simply TBAB is changed to tetrem
Ammonium chloride, addition is changed to 0.7g (4%).It is final to obtain colorless oil 42.5g, yield 99.3%.High performance liquid chromatography is examined
Survey result product purity 98.7%.
Embodiment 5：
The all experiment conditions of the present embodiment and processing method are same as Example 1, and isooctyl acyl chlorides simply is changed into different nonyl
Ester acyl chlorides, addition is changed to 35.3g (0.20mol).It is final to obtain the double different nonyl resin acid ester 45.2g of colorless oil vitamin C, yield
99.1%.
The structural formula of the double different nonyl resin acid esters of vitamin C manufactured in the present embodiment is：
HPLC (C18 posts；Detection wavelength UV=250nm；Mobile phase:100% isopropanol；Flow velocity：0.4ml/min)：Retain
Time 7.15min, purity 98.7%.
1H NMR (300MHz, CDCl3, unit:Ppm) (as shown in Figure 4):δ 9.85 (s, 2H, C=C-OH)；4.83-
4.24(m,4H,O-CH2-H)；2.41~2.09 (m, 6H, CH2)；1.26~0.91 (m, 28H, CH2,CH3).
13C NMR (75MHz, CDCl3)) (as shown in Figure 5) δ 173.51,173.32,166.31,155.47,115.29,
75.33,69.38,68.09,64.49,50.52,50.32,43.65,43.08,41.84,31.04,29.93,29.85,
26.98,22.61,22.57.
IR:(KBr films, cm-1) (as shown in Figure 6):3439,2956,2869,1750,1680,1467,1364,1140,
1076.
Embodiment 6：
The all experiment conditions of the present embodiment and processing method are same as Example 1, are simply changed to different monooctyl ester acyl chlorides different hard
Acyl chlorides, addition is changed to 60.6g (0.20mol).It is final to obtain the double isostearate 69.8g of colorless oil vitamin C, yield
98.5%.
The structural formula that the present embodiment prepares the double isostearates of vitamin C is：
HPLC (C18 posts；Detection wavelength UV=250nm；Mobile phase:100% isopropanol；Flow velocity：0.4ml/min)：Retain
Time 8.31min, purity：99.3%.
1H NMR (300MHz, CDCl3, unit:Ppm) (as shown in Figure 7):δ 9.96 (s, 2H, C=C-OH)；4.84-
4.24(m,4H,O-CH2-H)；2.62~2.36 (dt, 4H, 2CH2)；1.72~0.84 (m, 66H, CH2,CH3).
13C NMR (75MHz, CDCl3) (as shown in Figure 8) δ 174.27,174.02,166.33,155.37,115.33,
75.37,68.08,64.59,37.09,34.08,33.77,32.75,32.47,32.25,31.92,30.02,29.66,
29.35,29.12,27.08,24.63,24.58,23.04,22.68,22.13,19.70,14.10.
IR (KBr coating methods) is as shown in Figure 9：3472,2958,2923,2852,1741,1719,1681,1631,1464,
1321,1157cm-1。
Claims (9)
1. the preparation method of vitamin C fat acid diester, it is characterised in that the method is carried out according to the following steps：
Step one：After vitamin C is mixed with ethyl acetate, add pyridine to do acid binding agent, add phase transfer catalyst, then
To fat acyl chloride is added dropwise in reaction system, system starts heat release, maintains rate of addition, system temperature is maintained at 45~50 DEG C,
After dropwise addition fat acyl chloride is finished, continue to react 0.5~1h, regulation pH value separates water layer to 5~7, and oil reservoir is washed 2~3 times again,
Ethyl acetate is steamed, colorless oil vitamin C dibasic acid esters crude product is obtained；
Step 2：Vitamin C dibasic acid esters crude product Methanol+Water is dissolved, -5~5 DEG C are cooled to, product freezes solidly on molten
Liquid bottom, separates methanol layer, and gas producing formation removes methyl alcohol and ethyl acetate under 5~30Pa vacuums, obtains sterling, as vitamin
C fatty acid diesters；
The structural formula of the vitamin C fat acid diester is：
Wherein R for carbon number be 6~17 linear alkyl chain or carbon number be 6~17 branched alkyl chain.
2. the preparation method of vitamin C fat acid diester according to claim 1, it is characterised in that vitamin C in step one
The volume ratio of quality and ethyl acetate be 1g:(1.0~3.0) mL.
3. the preparation method of vitamin C fat acid diester according to claim 1, it is characterised in that pyridine is dimension in step one
2.0~2.05 times of raw element C moles.
4. the preparation method of vitamin C fat acid diester according to claim 1, it is characterised in that phase transfer is urged in step one
Agent is tetraethylammonium bromide, TBAB, four heptyl ammonium bromides, ammonium bromide and tetraoctyl ammonium bromide, benzyltrimethylammonium bromide, four
Ethyl ammonium chloride, tetrabutylammonium chloride, four heptyl ammonium chlorides, four octyl group ammonium chlorides or benzyltrimethylammonium chloride.
5. the preparation method of vitamin C fat acid diester according to claim 1, it is characterised in that phase transfer is urged in step one
The quality of agent is the 1%~5% of vitamin C quality.
6. the preparation method of vitamin C fat acid diester according to claim 1, it is characterised in that fat acyl chloride in step one
For straight chain fatty acyl chlorides or carbon number that carbon number is C7~18 are the Branched fatty acyl chlorides of C7~18.
7. the preparation method of vitamin C fat acid diester according to claim 1, it is characterised in that fat acyl chloride in step one
Consumption be 1.8~2.3 times of vitamin C mole.
8. the preparation method of vitamin C fat acid diester according to claim 1, it is characterised in that step 2 methanol-water is mixed
Methyl alcohol and the volume ratio of water are 10 in bonding solvent:(0.5~1).
9. the preparation method of vitamin C fat acid diester according to claim 1, it is characterised in that vitamin C in step 2
Dibasic acid esters crude product is 1g with the amount ratio of Methanol+Water:(1~1.2) mL.
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| Oxidation of Lipids. XIV. Inhibition of Oxidation of Methyl Linoleate by Fatty Acid Esters of L-Ascorbic Acid;M Takahashi, et al.;《Bull. Chem. Soc. Jpn.》;19861031;第59卷(第10期);第3179 * |
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Denomination of invention: Preparation method of vitamin C fatty acid diesters Effective date of registration: 20231113 Granted publication date: 20170531 Pledgee: Tonghua Branch of China Construction Bank Corp. Pledgor: Dongfanghong American ginseng Pharmaceutical (Tonghua) Co.,Ltd. Registration number: Y2023220000124 |