CN1045004C - Process for producing carotene compounds - Google Patents
Process for producing carotene compounds Download PDFInfo
- Publication number
- CN1045004C CN1045004C CN95102991A CN95102991A CN1045004C CN 1045004 C CN1045004 C CN 1045004C CN 95102991 A CN95102991 A CN 95102991A CN 95102991 A CN95102991 A CN 95102991A CN 1045004 C CN1045004 C CN 1045004C
- Authority
- CN
- China
- Prior art keywords
- compound
- phosphine
- alkali metal
- palladium
- reaction
- 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.)
- Expired - Fee Related
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- 238000000034 method Methods 0.000 title claims abstract description 53
- -1 carotene compounds Chemical class 0.000 title claims abstract description 30
- UPYKUZBSLRQECL-UKMVMLAPSA-N Lycopene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1C(=C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=C)CCCC2(C)C UPYKUZBSLRQECL-UKMVMLAPSA-N 0.000 title abstract description 14
- 235000005473 carotenes Nutrition 0.000 title abstract description 14
- NCYCYZXNIZJOKI-UHFFFAOYSA-N vitamin A aldehyde Natural products O=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-UHFFFAOYSA-N 0.000 title abstract description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 49
- 150000001875 compounds Chemical class 0.000 claims description 40
- XYFCBTPGUUZFHI-UHFFFAOYSA-N phosphine group Chemical group P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 27
- 229910052799 carbon Inorganic materials 0.000 claims description 25
- 229910052763 palladium Inorganic materials 0.000 claims description 25
- 125000004432 carbon atom Chemical group C* 0.000 claims description 23
- 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 17
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 15
- 239000003513 alkali Substances 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 229910052744 lithium Inorganic materials 0.000 claims description 9
- 229910052783 alkali metal Inorganic materials 0.000 claims description 8
- 238000005869 desulfonation reaction Methods 0.000 claims description 8
- ZOUWOGOTHLRRLS-UHFFFAOYSA-N palladium;phosphane Chemical group P.[Pd] ZOUWOGOTHLRRLS-UHFFFAOYSA-N 0.000 claims description 8
- 150000001339 alkali metal compounds Chemical class 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 4
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 4
- 150000001340 alkali metals Chemical group 0.000 claims description 4
- 230000006326 desulfonation Effects 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 22
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 239000002778 food additive Substances 0.000 abstract 1
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
- 239000002904 solvent Substances 0.000 description 26
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical group CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
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- 239000000243 solution Substances 0.000 description 16
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 9
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
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- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
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- 125000004423 acyloxy group Chemical group 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical class CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
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- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
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- 229910052760 oxygen Inorganic materials 0.000 description 3
- TZMFJUDUGYTVRY-UHFFFAOYSA-N pentane-2,3-dione Chemical compound CCC(=O)C(C)=O TZMFJUDUGYTVRY-UHFFFAOYSA-N 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
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- 229930195734 saturated hydrocarbon Natural products 0.000 description 3
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 3
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- OWLPCALGCHDBCN-UHFFFAOYSA-N 4,4,4-trifluoro-1-(furan-2-yl)butane-1,3-dione Chemical compound FC(F)(F)C(=O)CC(=O)C1=CC=CO1 OWLPCALGCHDBCN-UHFFFAOYSA-N 0.000 description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
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- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
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- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
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- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
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- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
- GPNDARIEYHPYAY-UHFFFAOYSA-N palladium(ii) nitrate Chemical compound [Pd+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O GPNDARIEYHPYAY-UHFFFAOYSA-N 0.000 description 2
- 125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
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- 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
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- 150000003818 basic metals Chemical group 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
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- 125000002592 cumenyl group Chemical group C1(=C(C=CC=C1)*)C(C)C 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- UKPXULFIISGBHG-UHFFFAOYSA-N cyclopropene Chemical compound [CH]1C=C1 UKPXULFIISGBHG-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 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
- QAMFBRUWYYMMGJ-UHFFFAOYSA-N hexafluoroacetylacetone Chemical compound FC(F)(F)C(=O)CC(=O)C(F)(F)F QAMFBRUWYYMMGJ-UHFFFAOYSA-N 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 235000012204 lemonade/lime carbonate Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 229960001708 magnesium carbonate Drugs 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- LGRLWUINFJPLSH-UHFFFAOYSA-N methanide Chemical compound [CH3-] LGRLWUINFJPLSH-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- RFLFDJSIZCCYIP-UHFFFAOYSA-L palladium(2+);sulfate Chemical compound [Pd+2].[O-]S([O-])(=O)=O RFLFDJSIZCCYIP-UHFFFAOYSA-L 0.000 description 1
- INIOZDBICVTGEO-UHFFFAOYSA-L palladium(ii) bromide Chemical compound Br[Pd]Br INIOZDBICVTGEO-UHFFFAOYSA-L 0.000 description 1
- 238000005502 peroxidation Methods 0.000 description 1
- 150000004714 phosphonium salts Chemical class 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- WWDMJSSVVPXVSV-YCNIQYBTSA-N retinyl ester Chemical compound CC1CCCC(C)(C)C1\C=C\C(\C)=C\C=C\C(\C)=C\C(O)=O WWDMJSSVVPXVSV-YCNIQYBTSA-N 0.000 description 1
- 229940108325 retinyl palmitate Drugs 0.000 description 1
- 235000019172 retinyl palmitate Nutrition 0.000 description 1
- 239000011769 retinyl palmitate Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- QBIHEHITTANFEO-UHFFFAOYSA-N sodium;tetrahydrate Chemical compound O.O.O.O.[Na] QBIHEHITTANFEO-UHFFFAOYSA-N 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 0.000 description 1
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
- 238000002371 ultraviolet--visible spectrum Methods 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 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
- 125000005023 xylyl group Chemical group 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a process for preparing a carotene compound. According to the process of the invention, a carotene compound useful as a food additive, etc., can be prepared in high purity and yield. Additionaly, the preparing a carotene compound of the inventon has a short procedure, geniality reaction condition and is easy to be operated.
Description
The present invention relates to can be used as the new preparation process of the carotene compounds of usefulness such as foodstuff additive.
Importance of the present invention has been to provide the industrial production technology of a kind of economy of carotene compounds.
Known with regard to the preparation of carotene compounds have a following method:
(A) make the method (as the preparation of β-Hu Luobusu) of peroxidation Yu phosphonium salt
Ra: aromatic moieties; Xa
(1): inorganic or organic acid residue (United States Patent (USP) 4105855);
(B) method that retinyl-sulfone and retinyl ester are reacted
Ret=retinyl-or similar group; Rb=alkyl or similar group; Inorganic or the organic acid residue that Xb=can obtain after removing acidic hydrogen (United States Patent (USP) 40383223).
About the method for above-mentioned production carotene compounds, method (A) not only needs monovalent or more triphenyl phosphine to synthesize carotenoid initial compounds (as vitamin A), and needs to use dangerous superoxide; Method (B) is for may not be satisfactory in industrial enforcement, because starting raw material retinyl-halogen instability, the yield of purpose carotene compounds is low.So, still need and set up the industrialization carotene compounds production method that a kind of production sequence is short, reaction conditions is gentle and be convenient to operate.
The invention provides:
(1) a kind of method for preparing logical formula III compound:
R wherein
1And R
2Represent hydrogen, hydroxyl or oxygen independently of one another; This method comprises: in the presence of alkali and palladium complex, make the reaction of logical formula I compound and logical formula II compound, and make products therefrom carry out the desulfonation reaction;
R wherein
1And R
2This represents hydrogen, hydroxyl or oxygen independently; R represents hydrocarbon residue;
R wherein
1And R
2Represent hydrogen, hydroxyl or oxygen independently of one another; X represents acyloxy or formula-SO
2-R " group, wherein R " represents hydrocarbon residue;
(2) according to the method for above-mentioned (1), R wherein
1And R
2Represent hydrogen independently of one another;
(3) according to the method for above-mentioned (1), wherein X represents the group of Shi-O-CO-R ', and wherein R ' represents hydrocarbon residue;
(4) according to the method for above-mentioned (1), wherein said alkali is alkali metal compound;
(5) according to the method for above-mentioned (4), wherein said alkali metal compound is selected from alkali metal hydrocarbonate, alkaline carbonate, alkali metal hydroxide, lithium aryl, lithium alkylide and alkali metal alkoxide;
(6) according to the method for above-mentioned (1), wherein said alkali is about 1-3 equivalent with respect to the ratio of compound (I);
(7) side according to above-mentioned (1) goes, and wherein said palladium complex is tertiary phosphine-palladium complex;
(8) according to the method for above-mentioned (7), wherein said tertiary phosphine is selected from trialkyl phosphine, triaryl phosphine and tri-alkoxy phosphine;
(9) according to the method for above-mentioned (7), wherein said tertiary phosphine-palladium complex is four (triphenyl phosphine) palladium;
(10) according to the method for above-mentioned (1), wherein said palladium complex is about 0.01-0.1 equivalent with respect to the ratio of compound (II).
About logical formula I, the hydrocarbon residue of R representative is the hydrocarbon residue that contains 1-20 carbon atom.This class hydrocarbon residue can be enumerated alkyl, cycloalkyl, thiazolinyl, alkynyl, cycloalkenyl group, aryl and aralkyl.
Alkyl is the alkyl of 1-15 carbon atom, therefore comprises methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, sec-butyl, the tertiary butyl, amyl group, hexyl, heptyl, octyl group, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl etc.
Cycloalkyl is the cycloalkyl of 3-8 carbon atom, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.
Thiazolinyl is the thiazolinyl of 2-10 carbon atom, for example vinyl, allyl group, 2-methacrylic, crotyl, 3-butenyl, 3-octenyl etc.
Alkynyl is the alkynyl of 2-10 carbon atom, for example ethynyl 2-propynyl, 3-hexin base etc.
Cycloalkenyl group is the cycloalkenyl group of 3-10 carbon atom, for example cyclopropenyl radical, cyclopentenyl, cyclohexenyl etc.
Aryl is the aryl of 6-14 carbon atom, for example phenyl, naphthyl etc.
Aralkyl is the aralkyl of 7-16 carbon atom, for example benzyl, styroyl etc.
Above-mentioned cycloalkyl, cycloalkenyl group, aryl and aralkyl can be chosen wantonly by alkyl respectively and further replace.Comprise the alkyl of 1-6 carbon atom, for example methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, sec-butyl, the tertiary butyl, amyl group, hexyl etc. as substituent alkyl.
R be preferably 1-15 carbon atom alkyl, can choose the aryl of 6-14 the carbon atom that is replaced by the alkyl of 1-6 carbon atom wantonly, maybe can choose wantonly by the aralkyl of 7-16 carbon atom of the alkyl of 1-6 carbon atom replacement.
More preferably, R is the aryl that can choose 6-14 the carbon atom that is replaced by the alkyl of 1-6 carbon atom wantonly.The number of the alkyl of substituted aryl is preferably 1-3.
More preferably, R is by the phenyl of the alkyl of 1-6 carbon atom replacement, as phenyl, o-tolyl, a tolyl, p-methylphenyl, cumenyl, xylyl etc.
R
1And R
2Respectively do for oneself hydrogen, R is the logical formula I compound of phenyl or p-methylphenyl, is specially adapted to preparation method of the present invention.
About logical formula II, X can be: for example the acyloxy of any same form representative :-O-CO-R ' in the following formula ,-O-SO-R ' or-O-SO
2-R ', wherein R ' represents hydrocarbon residue; Or formula-SO
2-R " group, wherein R " represents hydrocarbon residue.
Hydrocarbon residue R ' and R " can be with R in the identical hydrocarbon residue mentioned.
R ' and R " be preferably separately 1-15 carbon atom base, can choose the aryl of 6-14 the carbon atom that is replaced by the alkyl of 1-6 carbon atom wantonly, maybe can choose wantonly by the aralkyl of 7-16 carbon atom of the alkyl of 1-6 carbon atom replacement.
R ' and R " are preferably the alkyl of 1-15 carbon atom separately.
R ' and R " particularly preferred example be methyl and pentadecyl.
X is preferably the group of formula-O-CO-R ', and wherein R ' represents hydrocarbon residue.
More preferably, X is acetoxyl group or palm acyloxy.
R
1And R
2Respectively do for oneself hydrogen, X is that the logical formula II compound of acetoxyl group or palm acyloxy is retinyl acetate or Vitamin A Palmitate 1.7 M.I.U/Gram.These two compounds are comparatively stable to light, heat and moisture, therefore use these two compound particularly advantageouies in preparation method of the present invention.
Be used for preferred bases of the present invention and comprise alkali metal compound, alkaline earth metal compound, organic bases and organic zinc compound.More preferably, described alkali is alkali metal compound.
Alkali metal compound comprises: alkali metal hydrocarbonate, as sodium bicarbonate, saleratus etc.; Alkaline carbonate is as yellow soda ash, salt of wormwood etc.; Alkali metal hydroxide is as sodium hydroxide, potassium hydroxide etc.; Alkalimetal hydride is as sodium hydride, potassium hydride KH etc.; Alkali metal alkoxide is as sodium methylate, sodium ethylate, butanols potassium etc.; Lithium aryl is as phenyl lithium etc.; Lithium alkylide is as butyllithium etc.
Alkaline earth metal compound comprises alkaline earth metal carbonate, as lime carbonate, magnesiumcarbonate etc.; Alkaline earth metal hydroxides is as calcium hydroxide, magnesium hydroxide etc.
Organic bases comprises: trialkylamine, as triethylamine, Tributylamine etc.; Aromatic uncle amine, as N, accelerine, pyridine, lutidine, collidine, 4-(dimethylamino) pyridine etc.; 1,8-diazabicyclo [5.4.0] undecylene-7 (DBU) etc.
Organic zinc compound comprises diaryl zine, as phenylbenzene zinc etc.; Dialkyl group zinc is as zinc methide etc.
The particularly preferred example of described alkali has: alkali metal hydrocarbonate, as sodium bicarbonate, saleratus etc.; Alkaline carbonate is as yellow soda ash, salt of wormwood etc.; Alkali metal hydroxide is as sodium hydroxide, potassium hydroxide etc.; Lithium aryl is as phenyl lithium etc.; Lithium alkylide is as butyllithium etc.; Alkali metal alkoxide is as sodium methylate, sodium ethylate, butanols potassium etc.
Described alkali is about the 1-5 equivalent with respect to the ratio of compound (I), preferably is about the 1-3 equivalent.
Palladium complex comprises tertiary phosphine-palladium complex, copper-palladium complex etc.Preferred palladium complex is tertiary phosphine-palladium complex.
Tertiary phosphine comprises trialkyl phosphine, as trimethyl-phosphine, triethyl phosphine etc.; Triaryl phosphine is as triphenylphosphine etc.; The tri-alkoxy phosphine is as trimethoxy phosphine, triethoxy phosphine etc.
Described ketone is the ketone compound that can cooperate with palladium, therefore comprises acetone derivatives, as dibenzalacetone, methyl ethyl diketone, trifluoroacetylacetone, hexafluoroacetylacetone, benzoyltrifluoroacetone, furoyltrifluoroacetone(FTA, etc.; Diphenylpropane-1,3-dione(DPPO) etc.
Can mention four (triphenyl phosphine) palladium, four (triethoxy phosphine) palladium, two [1,2-two (diphenyl phosphine) ethane] palladium, two [1,1 '-two (diphenyl phosphine) ferrocene] palladium, two (triphenyl phosphine) dichloro palladium etc. in described tertiary phosphine-palladium complex.
Can mention two (methyl ethyl diketone) palladium, three (dibenzalacetone) (triphenyl phosphine) two palladiums, three (tribenzal methyl ethyl diketone) (triphenyl phosphines), two palladiums etc. in described ketone-palladium complex.
Palladium complex is about the 0.001-1 equivalent with respect to the ratio of compound (II), preferably about 0.01-0.1 equivalent.
Palladium complex can prepare by making palladium compound and above-mentioned phosphine or reactive ketone.
Operable palladium compound comprises the halogenation palladium, as Palladous chloride, palladium bromide etc.; The organic acid salt of palladium is as acid chloride etc.; The inorganic acid salt of palladium is as Palladous nitrate, palladous sulfate etc.
Every mole of described palladium compound uses described phosphine of about 1-6 mole or ketone when carrying out this reaction, and the about 1-3 mole of preferred use uses about 1-1.2 mole better effects if.This is reflected in the solvent of disturbance reponse not and carries out.
The solvent of above-mentioned not disturbance reponse can be with the reaction of compound (I) and compound (II) in the employed solvent species solvent of class mutually.
The used quantity of solvent of every gram palladium compound is generally about 10-500 milliliter, preferably about 20-100 milliliter.
Temperature of reaction is generally-80 ℃ to+200 ℃ approximately, preferred about 40 ℃ to 150 ℃.
Reaction times was generally about 0.5-5 hour.
The palladium complex that is generated can for example be used redistribution procedure, method of enrichment, solvent extration, fractionating process, crystallization process, recrystallization method, chromatography etc. with known method separation and purification from reaction mixture itself.When implementing the inventive method, can use isolating in advance palladium complex, also can in the reaction mixture that contains compound (I) and/or compound (II), prepare palladium complex.
In addition, be to improve the stability of palladium complex, the phosphine or the ketone that are used to prepare palladium complex can excessively add, and also can use these reactants with suitable combination.Its add-on is about the 1-3 equivalent with respect to palladium complex in this case.
In the methods of the invention, reaction was undertaken by the following the first step and second step.
(1) the first step
(2) second steps
The reaction of the inventive method the first step, i.e. the reaction of compound (I) and compound (II) is carried out in the solvent of disturbance reponse not.
Do not disturb the solvent of above-mentioned reaction to comprise: various ethers, as ether, diox, tetrahydrofuran (THF) etc.; Amides is as dimethyl formamide, N,N-DIMETHYLACETAMIDE, hexamethylphosphoramide etc.; The sulfoxide class is as methyl-sulphoxide etc.; The cyclic amide class is as N-Methyl pyrrolidone etc.; Aromatic hydrocarbons is as benzene,toluene,xylene etc.; Saturated hydrocarbons is as hexane, heptane, hexanaphthene etc.Can be with suitable two or more above-mentioned solvents that are used in combination.Solvent phase is about 0.2-50 milliliter for the amount of whenever digesting compound (I), preferably about 5-20 milliliter.
When carrying out this reaction, every mole compound (I) uses about 1-6 mole compound (II), preferably about 1-3 mole.
Temperature of reaction is generally-80 ℃ to+60 ℃ approximately, preferred-40 ℃ to+40 ℃ approximately.
Reaction times was generally about 1-24 hour.
This reaction is preferably carried out in inert gas atmosphere (as nitrogen, helium etc.).
The reaction in second step of the inventive method, i.e. desulfonation reaction is undertaken by the sulfone that is generated by compound (I) and compound (II) reaction is contacted with alkali.
Operable alkali comprises above-mentioned alkali.The ratio of alkali is also identical with above-mentioned ratio.
This is reflected in the solvent of disturbance reponse not and carries out.
The solvent of disturbance reponse does not comprise various ethers, as ether, diox, tetrahydrofuran (THF) etc.; Alcohols is as methyl alcohol, ethanol, n-propyl alcohol, Virahol etc.; Aromatic hydrocarbons is as benzene,toluene,xylene etc.; Saturated hydrocarbons is as hexane, heptane, hexanaphthene etc.These solvents can use with the appropriate combination of two or more solvents.
Temperature of reaction is generally about 0 to 40 ℃.
Reaction times was generally about 1-24 hour.
Above-mentioned desulfonation reaction can be carried out after the sulfone of isolating compound (I) and compound (II) reaction generation, also can not separate sulfone from reaction mixture and promptly carry out the desulfonation reaction.
Promptly do not carry out the desulfonation reaction if do not separate sulfone in advance from reaction mixture, then this desulfonation reaction is undertaken by add the normal described alkali of about 1-3 in reaction mixture.Temperature of reaction and time are also same as described above in this case.
The carotene compound that the inventive method makes can for example be used distribution, method of enrichment, solvent extration, fractionating process, crystallization process, recrystallization method, chromatography etc. with known method separation and purification from reaction mixture itself again.
Initial compounds (I) can prepare with the open described method of S-48-4453 of Japan's special permission or similar with it any method.For example, compound (I) can be by making general formula R SO
2The reaction of the basic metal-sulfinate of M and compound (II) prepares that (wherein R represents hydrocarbon residue; M represents basic metal, for example lithium, potassium, sodium etc.).
This is reflected in the solvent of disturbance reponse not and carries out.
The solvent of above-mentioned not disturbance reponse comprises various alcohols, as methyl alcohol, ethanol, n-propyl alcohol, Virahol etc.; Ethers is as ether, diox, tetrahydrofuran (THF) etc.; Ketone is as acetone, methylethylketone etc.; Nitrile is as acetonitrile etc.; Amides is as dimethyl formamide, N,N-DIMETHYLACETAMIDE, hexamethylphosphoramide etc.; The sulfoxide class is as methyl-sulphoxide etc.; The ester class is as ethyl acetate etc.; The cyclic amide class is as N-Methyl pyrrolidone etc.; Aromatic hydrocarbons is as benzene,toluene,xylene etc.; Halogenated hydrocarbon is as methylene dichloride, chloroform etc.; Saturated hydrocarbons is as hexane, heptane, hexanaphthene etc.; And other solvents.These solvents can use with the appropriate combination of two or more solvents.Whenever the quantity of solvent of digesting compound (II) is generally about 0.2-100 milliliter, preferably about 5-50 milliliter.
When carrying out this reaction, every mole compound (II) uses the described basic metal-sulfinate of about 1-6 mole, preferably about 1-3 mole.
Temperature of reaction is generally-80 ℃ to+60 ℃ approximately, preferred-40 ℃ to+40 ℃ approximately.
Reaction times was generally about 1-24 hour.
The compound that is generated (I) can for example be used distribution, method of enrichment, solvent extration, fractionating process, crystallization process, recrystallization method, chromatography etc. with known method separation and purification from reaction mixture itself again.
Contain compound (I) and be used to prepare the reaction mixture of the compound (II) of compound (I), can be directly use as the starting raw material of the inventive method.
Initial compounds (II) can prepare with known method itself.For example, it can prepare with technology (Pure and Appl.Chem.51:447-462,871-886,1979) or the similar with it any preparation method described in the document.
Following reference example and embodiment are used for describing in more detail the present invention, and never should think to limit the scope of the invention.The implication of used abbreviation is as follows among reference example and the embodiment: Ac: ethanoyl.
Used post stationary phase silica gel is the Kieselgel 60 of Merck company among reference example and the embodiment.The volume ratio of each solvent of numeral in the bracket of solvent mixture back.
Reference example 1
The preparation of retinyl-p-methylphenyl sulfone
Retinyl acetate retinyl-p-methylphenyl sulfone
In 200ml ethanol, dissolve 6.57g (20mmol) retinyl acetate and 5.05g (20.2mmol) paratoluenesulfonic acid sodium salt tetrahydrate, this solution was refluxed 10 hours.Reaction mixture and being poured in the 200ml frozen water then.With this mixture of 200ml extracted with diethyl ether 3 times, extraction liquid is used anhydrous sodium sulfate drying after merging.Steam solvent, resistates carries out silica gel column chromatography with ethyl acetate-hexane (1: 4).Concentrate purpose fraction and crystallization, obtain 7.81g retinyl-p-methylphenyl sulfone (is 92% by the retinyl acetate rate of collecting) (light yellow crystallization).The NMR spectrum of this retinyl-p-methylphenyl sulfone is as follows:
1H-NMR, δ: 0.8-2.1 (m, 21H), 2.4 (m, 3H), 3.9 (d, 2H), 5.2-5.5 (t, 1H), 5.8-6.7 (m, 5H), 7.3-7.7 (m, 4H).
Embodiment 1
(1) 15-p-toluenesulfonyl-15,15 '-preparation of dihydro-β-Hu Luobusu (hereinafter referred to as the C sulfone)
Retinyl-p-methylphenyl sulfone
15-p-toluenesulfonyl-15,15 '-dihydro-β-Hu Luobusu
In the 20ml tetrahydrofuran (THF), dissolve 4.25g (10mmol) retinyl-p-methylphenyl sulfone, under nitrogen gas stream, solution is maintained-78 ℃, add the hexane that 6.88ml is dissolved with the 11mmol n-Butyl Lithium, obtain a kind of solution (being called solution A) with 15 fens clock times.On the other hand, 3.94g (12mmol) retinyl acetate and 0.33g (1.2mmol) triphenyl phosphine are dissolved in the 20ml tetrahydrofuran (THF), under room temperature (20 ℃), in nitrogen gas stream, add 0.14g (0.6mmol) acid chloride powder then, mixture was stirred 1 hour, obtain a kind of solution (being called solution B).Solution A is added in the solution B, and mixture stirred 4 hours down in room temperature (20 ℃), with the dilution of 100ml frozen water, used 100ml chloroform extraction 3 times then.Organic layer merges the back and uses anhydrous sodium sulfate drying, steams solvent.Resistates carries out silica gel column chromatography with ethyl acetate-hexane (1: 20), obtains 5.51g purpose C
40Sulfone (is 79.6% by the retinyl-p-methylphenyl sulfone rate of collecting).This C
40The NMR spectrum of sulfone is as follows:
1H-NMR (CDCl
3), δ: 0.8-2.0 (m, 42H), 2.3-2.5 (m, 3H), 3.7 (m, 1H), 5.1-6.8 (m, 14H), 7.2-7.9 (m, 4H).
(2) pass through C
40The sulfone desulfonation prepares β-Hu Luobusu
C
40Sulfone
β-Hu Luobusu
In 20ml ethanol, dissolve 3.47g (5mmol) C
40Sulfone adds the finely divided potassium hydroxide of 0.88g (15mmol) then, and this mixture was refluxed in nitrogen gas stream 5 hours.Make the reaction mixture cooling then, pour in the 50ml frozen water, use 100ml extracted with diethyl ether 3 times.Organic layer merges the back and uses anhydrous sodium sulfate drying, steams ether.Resistates is dissolved in a small amount of methylene dichloride, uses methanol crystallization, and the β-Hu Luobusu that obtains 2.20g red crystals shape (is pressed C
40The sulfone rate of collecting is 82%).The physical constant of this β-Hu Luobusu is as follows:
1H-NMR (CDCl
3), δ: 1.1-1.2 (m, 42H), 6.2-7.8 (m, 14H) ultraviolet-visible spectrum (CHCl
3), λ
Max: 281,463,489nm fusing point: 175-180 ℃.
Embodiment 2
Separation of C in advance not
40Sulfone prepares β-Hu Luobusu
Retinyl acetate retinyl-p-methylphenyl sulfone
β-Hu Luobusu
In the 40ml tetrahydrofuran (THF), dissolve 3.94g (12mmol) retinyl acetate, 4.25g (10mmol) retinyl-p-methylphenyl sulfone and 0.33g (1.2mmol) triphenyl phosphine.Under room temperature (20 ℃), in nitrogen gas stream, add 0.14g (0.6mmol) acid chloride powder then, mixture was stirred 1 hour.In this solution, add 1.12g (10mmol) potassium tert.-butoxide powder with 4 hours times, and then add 2.24g (20mmol) potassium tert.-butoxide, this mixture was stirred 5 hours.This reaction mixture is poured in the 100ml frozen water, used 100ml extracted with diethyl ether 3 times.Ether layer merges the back and uses anhydrous sodium sulfate drying, steams solvent.Resistates is dissolved in a small amount of methylene dichloride, uses methanol crystallization, obtains 3.59g red crystals shape β-Hu Luobusu (is 67% by the retinyl acetate rate of collecting).
Comparative example 1
In the 20ml tetrahydrofuran (THF), dissolve 4.25g (10mmol) retinyl-p-methylphenyl sulfone.Under-20 ℃, in nitrogen gas stream, add 1.12g (10mmol) n-Butyl Lithium, and under said temperature, mixture was stirred 30 minutes to this solution.In gained solution, add the solution of 3.94g (12mmol) retinyl acetate in the 10ml tetrahydrofuran (THF), this mixture was stirred 3 hours under 20 ℃ temperature.Aforesaid operations does not obtain C
40Sulfone.
Comparative example 2
Dissolve 4.25g (10mmol) retinyl-p-methylphenyl sulfone in the 20ml tetrahydrofuran (THF), solution is maintained-78 ℃ in nitrogen gas stream, the hexane with 15 minutes times adding 6.88ml is dissolved with the 11mmol n-Butyl Lithium obtains a kind of solution.Solution stirring after 10 minutes, is dripped the solution of 3.94g (12mmol) retinyl acetate in the 20ml tetrahydrofuran (THF) under uniform temp, this mixture was stirred 1 hour.Aforesaid operations does not obtain C
40Sulfone.In addition, even do not obtain C after 4 hours at the reaction mixture restir yet
40Sulfone.
According to method of the present invention, can prepare the carotene compounds that can be used as uses such as foodstuff additive with high purity and good yield.In addition, prepare that the carotene compounds program is short, reaction conditions is gentle, be convenient to operation by the inventive method.
Claims (5)
1. one kind prepares the method for leading to the formula III compound:
R wherein
1And R
2Represent hydrogen independently of one another; This method comprises two steps, in the first step, logical formula I compound and logical formula II compound is reacted in the presence of tertiary phosphine-palladium complex,
R wherein
1And R
2Represent hydrogen independently of one another; The phenyl that the R representative is replaced by the alkyl of 1-6 carbon atom;
R wherein
1And R
2Represent hydrogen independently of one another; X represents the group of Shi-O-CO-R ', and wherein R ' represents hydrocarbon residue,
In second step, in the presence of the alkali metal compound that is selected from alkali metal hydrocarbonate, alkaline carbonate, alkali metal hydroxide, lithium aryl, lithium alkylide and alkali metal alkoxide, the first step products therefrom is carried out desulfonation and react.
2. according to the process of claim 1 wherein that the ratio of described alkali with respect to compound (I) is the 1-3 equivalent.
3. according to the process of claim 1 wherein that described tertiary phosphine is selected from trialkyl phosphine, triaryl phosphine and tri-alkoxy phosphine.
4. according to the process of claim 1 wherein that described tertiary phosphine-palladium complex is four (triphenyl phosphine) palladium.
5. according to the process of claim 1 wherein that the ratio of described tertiary phosphine-palladium complex with respect to compound (II) is the 0.01-0.1 equivalent.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP056173/94 | 1994-03-25 | ||
| JP5617394 | 1994-03-25 |
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| Publication Number | Publication Date |
|---|---|
| CN1114309A CN1114309A (en) | 1996-01-03 |
| CN1045004C true CN1045004C (en) | 1999-09-08 |
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ID=13019718
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|---|---|---|---|
| CN95102991A Expired - Fee Related CN1045004C (en) | 1994-03-25 | 1995-03-25 | Process for producing carotene compounds |
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| CN114426508B (en) * | 2022-02-09 | 2022-11-08 | 万华化学集团股份有限公司 | Preparation method of beta-carotene intermediate polyene thioether |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2945069A (en) * | 1958-01-31 | 1960-07-12 | Eastman Kodak Co | Synthesis of beta-carotene |
| US3803252A (en) * | 1971-05-19 | 1974-04-09 | Rhone Poulenc Sa | Process for the preparation of carotenoid compounds |
| EP0455119A2 (en) * | 1990-05-03 | 1991-11-06 | BASF Aktiengesellschaft | Process for the preparation of canthaxanthin and astaxanthin |
-
1995
- 1995-03-25 CN CN95102991A patent/CN1045004C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2945069A (en) * | 1958-01-31 | 1960-07-12 | Eastman Kodak Co | Synthesis of beta-carotene |
| US3803252A (en) * | 1971-05-19 | 1974-04-09 | Rhone Poulenc Sa | Process for the preparation of carotenoid compounds |
| EP0455119A2 (en) * | 1990-05-03 | 1991-11-06 | BASF Aktiengesellschaft | Process for the preparation of canthaxanthin and astaxanthin |
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| CN1114309A (en) | 1996-01-03 |
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