CN106083507A - A kind of preparation method of lycopene - Google Patents
A kind of preparation method of lycopene Download PDFInfo
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- CN106083507A CN106083507A CN201610383792.4A CN201610383792A CN106083507A CN 106083507 A CN106083507 A CN 106083507A CN 201610383792 A CN201610383792 A CN 201610383792A CN 106083507 A CN106083507 A CN 106083507A
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- 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 claims abstract description 33
- OAIJSZIZWZSQBC-GYZMGTAESA-N lycopene Chemical compound CC(C)=CCC\C(C)=C\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C=C(/C)CCC=C(C)C OAIJSZIZWZSQBC-GYZMGTAESA-N 0.000 title claims abstract description 33
- 235000012661 lycopene Nutrition 0.000 title claims abstract description 33
- 239000001751 lycopene Substances 0.000 title claims abstract description 33
- JEVVKJMRZMXFBT-XWDZUXABSA-N Lycophyll Natural products OC/C(=C/CC/C(=C\C=C\C(=C/C=C/C(=C\C=C\C=C(/C=C/C=C(\C=C\C=C(/CC/C=C(/CO)\C)\C)/C)\C)/C)\C)/C)/C JEVVKJMRZMXFBT-XWDZUXABSA-N 0.000 title claims abstract description 32
- 229960004999 lycopene Drugs 0.000 title claims abstract description 32
- ZCIHMQAPACOQHT-ZGMPDRQDSA-N trans-isorenieratene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/c1c(C)ccc(C)c1C)C=CC=C(/C)C=Cc2c(C)ccc(C)c2C ZCIHMQAPACOQHT-ZGMPDRQDSA-N 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- MBKDYNNUVRNNRF-UHFFFAOYSA-N medronic acid Chemical compound OP(O)(=O)CP(O)(O)=O MBKDYNNUVRNNRF-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229940058213 medronate Drugs 0.000 claims abstract description 12
- 238000006482 condensation reaction Methods 0.000 claims abstract description 11
- HNZUNIKWNYHEJJ-UHFFFAOYSA-N geranyl acetone Natural products CC(C)=CCCC(C)=CCCC(C)=O HNZUNIKWNYHEJJ-UHFFFAOYSA-N 0.000 claims abstract description 11
- JXJIQCXXJGRKRJ-KOOBJXAQSA-N pseudoionone Chemical compound CC(C)=CCC\C(C)=C\C=C\C(C)=O JXJIQCXXJGRKRJ-KOOBJXAQSA-N 0.000 claims abstract description 11
- QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 claims abstract description 8
- 230000007062 hydrolysis Effects 0.000 claims abstract description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 6
- 239000002253 acid Substances 0.000 claims abstract description 4
- 238000006114 decarboxylation reaction Methods 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 49
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 20
- 239000003513 alkali Substances 0.000 claims description 20
- -1 carbon phosphate ester Chemical class 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical group [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 12
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 10
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 claims description 9
- 239000002585 base Substances 0.000 claims description 9
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 8
- 150000001298 alcohols Chemical class 0.000 claims description 8
- 229910052744 lithium Inorganic materials 0.000 claims description 8
- 229910052783 alkali metal Inorganic materials 0.000 claims description 7
- 239000000010 aprotic solvent Substances 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 6
- 239000011261 inert gas Substances 0.000 claims description 6
- 150000002924 oxiranes Chemical class 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 3
- IHTFTOGFXXXQBO-UHFFFAOYSA-B [C+4].[C+4].[C+4].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O Chemical class [C+4].[C+4].[C+4].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O IHTFTOGFXXXQBO-UHFFFAOYSA-B 0.000 claims description 3
- 229910000102 alkali metal hydride Inorganic materials 0.000 claims description 3
- 150000008046 alkali metal hydrides Chemical class 0.000 claims description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical group [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 2
- 239000012312 sodium hydride Substances 0.000 claims description 2
- 230000005945 translocation Effects 0.000 claims description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims 2
- 239000010931 gold Substances 0.000 claims 2
- 229910052737 gold Inorganic materials 0.000 claims 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims 1
- 150000004678 hydrides Chemical class 0.000 claims 1
- 150000002576 ketones Chemical class 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- DISPOJHKKXSCLS-UHFFFAOYSA-N n-diaminophosphorylmethanamine Chemical compound CNP(N)(N)=O DISPOJHKKXSCLS-UHFFFAOYSA-N 0.000 claims 1
- 239000011574 phosphorus Substances 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- TVACALAUIQMRDF-UHFFFAOYSA-N dodecyl dihydrogen phosphate Chemical compound CCCCCCCCCCCCOP(O)(O)=O TVACALAUIQMRDF-UHFFFAOYSA-N 0.000 abstract description 19
- 239000002994 raw material Substances 0.000 abstract description 5
- RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 150000001299 aldehydes Chemical class 0.000 abstract 2
- 150000002118 epoxides Chemical class 0.000 abstract 2
- 150000005672 tetraenes Chemical class 0.000 abstract 2
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 abstract 1
- CGMDPTNRMYIZTM-UHFFFAOYSA-N Sarohornene Natural products CC=CC=CC=CC CGMDPTNRMYIZTM-UHFFFAOYSA-N 0.000 abstract 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 238000000034 method Methods 0.000 description 11
- 235000002639 sodium chloride Nutrition 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 239000007788 liquid Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- 208000035126 Facies Diseases 0.000 description 6
- 238000013019 agitation Methods 0.000 description 6
- 230000006837 decompression Effects 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 239000007789 gas Substances 0.000 description 6
- 238000012805 post-processing Methods 0.000 description 6
- 238000004886 process control Methods 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- 150000001335 aliphatic alkanes Chemical class 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- 235000014443 Pyrus communis Nutrition 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 239000002027 dichloromethane extract Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 3
- 238000009413 insulation Methods 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 229960002668 sodium chloride Drugs 0.000 description 3
- 238000013517 stratification Methods 0.000 description 3
- 235000011149 sulphuric acid Nutrition 0.000 description 3
- 239000001117 sulphuric acid Substances 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 2
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 235000013373 food additive Nutrition 0.000 description 2
- 239000002778 food additive Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 150000003568 thioethers Chemical class 0.000 description 2
- OAIJSZIZWZSQBC-UHFFFAOYSA-N (7Z,9Z,7'Z,9'Z)-ψ,ψ-carotene Chemical compound CC(C)=CCCC(C)=CC=CC(C)=CC=CC(C)=CC=CC=C(C)C=CC=C(C)C=CC=C(C)CCC=C(C)C OAIJSZIZWZSQBC-UHFFFAOYSA-N 0.000 description 1
- 0 CC(C1*=C1)=[N+]CC=C(C)NC Chemical compound CC(C1*=C1)=[N+]CC=C(C)NC 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- CWXOAQXKPAENDI-UHFFFAOYSA-N sodium methylsulfinylmethylide Chemical compound [Na+].CS([CH2-])=O CWXOAQXKPAENDI-UHFFFAOYSA-N 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
- C07C1/32—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen
- C07C1/34—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen reacting phosphines with aldehydes or ketones, e.g. Wittig reaction
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
- C07C45/57—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom
- C07C45/58—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom in three-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D301/00—Preparation of oxiranes
- C07D301/02—Synthesis of the oxirane ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/48—Compounds containing oxirane rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. ester or nitrile radicals
-
- 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
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4015—Esters of acyclic unsaturated acids
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- 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)
- Cosmetics (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
The invention provides the preparation method of a kind of lycopene, this preparation method includes: in the basic conditions, pseudoionone reacts with methyl chloroacetate and prepares epoxide, then this epoxide hydrolysis decarboxylation in acid condition obtains 2,6,10 trimethyl 3,5,9 hendecane triolefin 1 aldehyde；2,6,10 trimethyl 3,5,9 hendecane triolefin 1 aldehyde and Medronate tetra-ethyl ester carry out condensation reaction and prepare 3,7,11 trimethyl 1,4,6,10 tetraene dodecylphosphoric acid dialkyls；3,7,11 trimethyl Isosorbide-5-Nitraes, there is indexing in 6,10 tetraene dodecylphosphoric acid dialkyls, then with 2,7 dimethyl 2,4,6 sarohornene 1,8 dialdehyde occur Wittig Horner condensation reaction to obtain lycopene.This preparation method raw material is easy to get, synthetic route is short, low cost, it is adaptable to commercial production.
Description
Technical field
The present invention relates to food additive field, be specifically related to the preparation method of a kind of lycopene.
Background technology
Class Hu Luosu that nature exists there are about kind more than 600, but wherein only have six kinds and can be used for commercial production.Lycopene
As a class staple product therein, to removing free radical, anti-aging, suppress tumor, treatment heart disease etc. to have important effect,
And be widely used in medicine, food additive and feed additive.Roche company have developed use triphenylphosphine with
Wittig reacts the synthetic route being characterized, and other synthetic methods in early days also will use triphenylphosphine.Start from Babler
With since the route that C15 phosphate ester (3,7,11-trimethyls-Isosorbide-5-Nitrae, 6,10-tetraene dodecylphosphoric acid dialkyls) is characterized,
Shen Runbo et al. has applied for the complete synthesis route of lycopene being characterized with Wittig-Horner condensation reaction the most in succession.
In the recent period, Shen Runbo et al. reports with compound 3,7,11-in number of patent application is CN201010120583.3
Trimethyl-1,3,6,10-tetraene dodecylphosphoric acid diethylesters prepare the new technology of lycopene (6), this synthesis route
As follows:
This process route is succinct, and easy to operate, yield is higher, has very much industrialization potential.Its key intermediate 2,6,10-tri-
The synthetic method of methyl-2,5,9-hendecane triolefin-1-aldehyde (3) mainly has following two.
The first, Michael et al. reports to react with sulfonium salt with pseudoionone at US4000131 and obtains epoxidation
Thing, then catalysis open loop obtains 2,6,10-trimethyl-3,5,9-hendecane triolefin-1-aldehyde, then prepares through base-catalysed rearrangement
2,6,10-trimethyl-2,5,9-hendecane triolefin-1-aldehyde (3).But the method to be used the iodomethane of costliness, has pollution
Diyl thioether and dangerous highly basic DMSO sodium salt, it is more difficult to be applied to commercial production.
It two is, Shen Runbo et al. Chinese Patent Application No. 201010189861.0 " intermediate of lycopene and
The preparation method of intermediate " in report with C14 acetal (2,6,10-trimethyl-3,5,9-hendecane triolefin-1-acetal) for pass
The new technique for synthesizing of the lycopene (6) of key intermediate, its synthesis route is as follows:
Though the method relatively has an industrialization potential, but its raw material 4-methyl-5 used, 5-dialkoxy-1-amylene-1-
Phosphate dialkyl ester (7) source difficulty, synthesis difficulty is the biggest, it is more difficult to is applied to industrialized production, what is particularly worth mentioning is that
The mixture that C14 acetal (8) is four kinds of cis-trans-isomers prepared by the method.
Summary of the invention
In order to overcome the deficiencies in the prior art, first purpose of the present invention is to provide the preparation side of a kind of lycopene
Method, the method has the simple advantage of process route, and raw material is easy to get, the feature of low cost.
1, the preparation method of a kind of lycopene, comprises the steps:
1) under inert gas shielding, the pseudoionone of formula (1) is carried out in the presence of a base with methyl chloroacetate
Reaching gloomy reaction and prepare the epoxide of formula (2), described epoxide is methyl-3-(4,8-dimethyl-1,3,7-nonyls three
Alkene-1-base)-3-methyl oxirane-2-carboxylate methyl ester, the epoxide hydrolysis decarboxylation in acid condition of this formula (2) obtains
2,6,10-trimethyl-3 of formula (3), 5,9-hendecane triolefin-1-aldehyde, reaction equation is as follows:
2) under inert gas shielding, 2,6,10-trimethyl-3 of formula (3), 5,9-hendecane triolefin-1-aldehyde and methylene
Diphosphonic acid tetraalkyl ester and alkali carry out Wittig-Horner condensation reaction in ether solvent or aprotic solvent and prepare formula
(4) Isosorbide-5-Nitrae, 6,10-tetra-double bond 15 carbon phosphate esters, reaction equation is as follows:
3) under inert gas shielding, in ether solvent or dipolar aprotic solvent in the presence of a base, described formula (4)
1,4,6,10-tetra-double bond 15 carbon phosphate ester carries out resetting translocation reaction under the conditions of temperature-30～0 DEG C；
4) resetting indexing complete, add the 2 of formula (5), 7-dimethyl-2,4,6-sarohornene-1,8-dialdehyde, in alkali existence
Under, in ether solvent or dipolar aprotic solvent, under the conditions of temperature-30～0 DEG C, carry out Wittig-Horner condensation reaction
Being prepared into the lycopene of formula (6), reaction equation is as follows:
Preferably, described in described formula (4), R is the one in methyl, ethyl, isopropyl.
Preferably, step 1) described in the consumption of pseudoionone and the consumption mol ratio of described alkali be 1:(4.0～
4.5), the consumption of described pseudoionone is 1:(2.0～2.5 with the mol ratio of the consumption of methyl chloroacetate).
Preferably, step 2) described in 2,6,10-trimethyl-3 of formula (3), the consumption of 5,9-hendecane triolefin-1-aldehyde with
The mol ratio of the consumption of described alkali is 1:(1.0～1.5), 2,6,10-trimethyl-3 of described formula (3), 5,9-hendecane triolefins-
The consumption of 1-aldehyde is 1:(1.0～1.3 with the mol ratio of the consumption of Medronate tetra-ethyl ester).
Preferably, step 1) described alkali is alkali metal hydride or the alkali metal salt of alcohols or lithium alkylide, wherein: alkali metal
Hydride is sodium hydride or hydrofining；The alkali metal salt of alcohols is the one in Feldalat NM or sodium tert-butoxide or potassium tert-butoxide；Alkane
Base lithium is butyl lithium.
Preferably, step 1) described in the gloomy reaction that reaches carry out under the conditions of-10～0 DEG C；Step 2) described Wittig-
Horner condensation reaction is carried out under the conditions of 10～20 DEG C.
Preferably, in step 2) in concretely comprise the following steps: described Medronate tetra-ethyl ester and alkali reaction generate corresponding
Carbanion, then add 2,6,10-trimethyl-3 of described formula (3), 5,9-hendecane triolefin-1-aldehyde are carried out
Wittig-Horner condensation reaction；Or by described Medronate tetraalkyl ester and described formula (3) 2,6,10-front three
It is added dropwise in alkali after the mixing of base-3,5,9-hendecane triolefin-1-aldehyde.
Preferably, in step 3) described in the Isosorbide-5-Nitrae of formula (4), the consumption of 6,10-tetra-double bond 15 carbon phosphate esters and described alkali
The mol ratio of consumption be 1:1.0-1.5；The consumption of the 1,4,6,10-tetra-double bond 15 carbon phosphate ester of described formula (4) is with described
The mol ratio of the consumption of ten carbon dialdehydes of formula (5) is 1:0.4-0.5.
Preferably, in step 3) described in the alkali metal salt that alkali is alcohols or lithium alkylide, wherein, the alkali metal salt of alcohols
For the one in Sodium ethylate, sodium tert-butoxide, potassium tert-butoxide；Lithium alkylide is butyl lithium.
Preferably, described ether solvent is the one in ether, oxolane, glycol dimethyl ether, described non-matter
Sub-solvent is the one in dimethylformamide, dimethyl sulfoxide, HMPA.
Compared to existing technology, the beneficial effects of the present invention is:
1, the present invention only needs four-step reaction can generate the tomato red of target product formula (6) with pseudoionone for raw material
Element, has the simple advantage of process route, and raw material is easy to get, low cost, great industrial value.
2, in the present invention and do not contain the expensive iodomethane that prior art is conventional, there is the diyl thioether of pollution and dangerous
Highly basic DMSO sodium salts etc., have safe and environment-friendly advantage.
Detailed description of the invention
Below, in conjunction with detailed description of the invention, the present invention is described further:
Embodiment 1
(1) preparation of 2,6,10-trimethyl-3,5,9-hendecane triolefin-1-aldehyde
Under nitrogen protection, toward 19.62g (0.1mol, content 98%) pseudoionone in tri-mouthfuls of reaction bulbs of 500mL and
21.93g methyl chloroacetate (0.2mol), mechanical agitation, cryosel bath cooling is added dropwise to 72mL 30% under conditions of keeping 0-10 DEG C
Methanol solution of sodium methylate, about 30min drip off.Continue, at-10 DEG C of stirring reaction 2.0h, to add 100mL pure water afterwards, be heated to
Interior temperature about 30 DEG C, drips 133.2g 10% aqueous sulfuric acid, neutralizes and controls pH about 4.5, controls temperature during dropping
Degree, less than 35 DEG C, drips complete continuation and reacts 30min between 40-45 DEG C.Hydrolyze complete, in reaction system, add 50mL
Dichloromethane, is transferred to separatory funnel, refines and separates organic layer, and water layer 50mL dichloromethane extracts 2 times, merges organic layer and uses
50mL pure water washs, and organic facies 50g Matrii Sulfas Exsiccatus is dried, and then 50 DEG C of decompressions are distilled off dichloromethane, and decompressing and extracting is extremely
0mbar, obtains light brown liquid, gas phase analysis product content 94.59%, and yield is 73.52%.
(2) preparation of 3,7,11-trimethyl-1,4,6,10-tetraene dodecylphosphoric acid diethylester
The generation of Medronate tetra-ethyl ester carbanion: under nitrogen protection, equipped with airway, thermometer and machinery
In the 250mL there-necked flask of agitator, add 3.28g (purity 99.0%, 0.06mol) Feldalat NM and the stirring cooling of 20mL ether
To 19 DEG C, being slowly added dropwise 18g (purity 95.84%, 0.06mol) Medronate tetra-ethyl ester, in dropping process control, temperature is not
More than 35 DEG C, used time 15min.Drip and finish, continue at room temperature reaction 1.0h.
Above-mentioned system cools to 18 DEG C, dropping 13.1g (purity 94.59%, 0.06mol) 2,6,10-trimethyl-3, and 5,9-
Hendecane triolefin-1-aldehyde, in dropping process control, temperature must not exceed 35 DEG C, used time 15min.Drip and finish, continue 10 DEG C of reactions
2.0h。
Hydrolysis: after above-mentioned reaction completes, molten to reaction system dropping 0.51g (purity 98%, 0.005mol) sulphuric acid
It is made into the aqueous solution of 2.5% in 20g water, is between 6-7 to system pH value, drip and finish stirring 5min, carry out post processing.
Post processing: reactant liquor is proceeded in 500mL pear shape separatory funnel, stratification, separate organic layer, water layer 10*
2mL hexamethylene extracts, and organic layer washs with 50mL 5% saline after merging, and organic facies directly separates and proceeds in 250mL alembic,
60 DEG C of concentrating under reduced pressure eliminate solvent, drain and obtain concentrate, for brown oil liquid.
Gas chromatographic analysis: 3,7,11-trimethyl-1,4,6,10-tetraene dodecylphosphoric acid diethylester=93.19%
(containing multiple cis-trans-isomers).
3,7,11-trimethyl-1,4,6,10-tetraene dodecylphosphoric acid diethylester is to 2,6,10-trimethyl-3,5,9-ten
The yield of one alkane triolefin-1-aldehyde is: 92.39%.
(3) lycopene is prepared by 3,7,11-trimethyl-1,4,6,10-tetraene dodecylphosphoric acid diethylester
Under nitrogen protection, in tri-mouthfuls of reaction bulbs of 500mL, add 7.38g (step (2) prepares), 0.02mol) 3,7,
11-trimethyl-1,4,6,10-tetraene dodecylphosphoric acid diethylester and the glycol dimethyl ether of 50mL and solutions of dimethyl phosphoryl triamine
Mixed liquor, under mechanical agitation, cryosel is bathed and is added 0.02mol sodium tert-butoxide at-5-0 DEG C, insulated and stirred reaction 2.0h
After completion of the reaction in-20～0 DEG C be added dropwise to 20mL dissolved with 1.31g (0.008mol) formula (5) 2,7-dimethyl-2,
4,6-sarohornene-1, the oxolane of 8-dialdehyde and the mixed liquor of dimethyl sulfoxide, oxolane and diformazan in described mixed liquor
The volume ratio of base sulfoxide is 5:1；About 30min drips off, and continues insulation reaction 1.0h.
React complete, in reaction mixture, add 50mL pure water, stir 5 minutes, be transferred to separatory funnel, stand and divide
Going out organic layer, water layer respectively extracts 2 times with 50mL oxolane, merges organic layer 50mL1% sodium-chloride water solution and washs, organic
Decompression is distilled off solvent mutually, obtains lycopene crude product.
Embodiment 2
(1) preparation of 2,6,10-trimethyl-3,5,9-hendecane triolefin-1-aldehyde
Under nitrogen protection, toward 19.62g (0.1mol, content 98%) pseudoionone in tri-mouthfuls of reaction bulbs of 500mL and
0.23mol methyl chloroacetate, mechanical agitation, cryosel bath cooling is added dropwise to 115mL 30% hydrofining under conditions of keeping 0-10 DEG C
Methanol solution, about 30min drip off.Continue, at-5 DEG C of stirring reaction 2.0h, to add 100mL pure water afterwards, be heated to interior temperature 30
About DEG C, drip 133.2g 10% aqueous sulfuric acid, neutralize and control pH about 4.5, control temperature during dropping and do not surpass
Cross 35 DEG C, drip complete continuation between 40-45 DEG C, react 30min.Hydrolyze complete, in reaction system, add 50mL dichloromethane
Alkane, is transferred to separatory funnel, refines and separates organic layer, and water layer 50mL dichloromethane extracts 2 times, merges organic layer 50mL pure
Water purification wash, organic facies 50g Matrii Sulfas Exsiccatus is dried, and then 50 DEG C of decompressions are distilled off dichloromethane, decompressing and extracting to 0mbar,
Obtaining light brown liquid, gas phase analysis product content 95.54%, yield is 74.72%.
(2) preparation of 3,7,11-trimethyl-1,4,6,10-tetraene dodecylphosphoric acid diethylester
The generation of Medronate tetra-ethyl ester carbanion: under nitrogen protection, equipped with airway, thermometer and machinery
In the 250mL there-necked flask of agitator, add 3.28g (purity 99.0%, 0.06mol) Feldalat NM and 20mL sub-without dimethyl
Sulfone, stirring cools to 19 DEG C, is slowly added dropwise 0.06mol Medronate tetra-ethyl ester, and in dropping process control, temperature is less than 35
DEG C, used time 15min.Drip and finish, continue at room temperature reaction 1.0h.
Above-mentioned system cools to 18 DEG C, dropping 10.91g (purity 94.59%, 0.05mol) 2,6,10-trimethyl-3, and 5,
9-hendecane triolefin-1-aldehyde, in dropping process control, temperature must not exceed 35 DEG C, used time 15min.Drip and finish, continue 15 DEG C of reactions
2.0h。
Hydrolysis: after above-mentioned reaction completes, molten to reaction system dropping 0.51g (purity 98%, 0.005mol) sulphuric acid
It is made into the aqueous solution of 2.5% in 20g water, is between 6-7 to system pH value, drip and finish stirring 5min, carry out post processing.
Post processing: reactant liquor is proceeded in 500mL pear shape separatory funnel, stratification, separate organic layer, water layer 10*
2mL hexamethylene extracts, and organic layer washs with 50mL 5% saline after merging, and organic facies directly separates and proceeds in 250mL alembic,
60 DEG C of concentrating under reduced pressure eliminate solvent, drain and obtain concentrate, for brown oil liquid.
Gas chromatographic analysis: 3,7,11-trimethyl-1,4,6,10-tetraene dodecylphosphoric acid diethylester=94.23%
(containing multiple cis-trans-isomers).
3,7,11-trimethyl-1,4,6,10-tetraene dodecylphosphoric acid diethylester is to 2,6,10-trimethyl-3,5,9-ten
The yield of one alkane triolefin-1-aldehyde is: 95.01%.
(3) lycopene is prepared by 3,7,11-trimethyl-1,4,6,10-tetraene dodecylphosphoric acid diethylester
Under nitrogen protection, in tri-mouthfuls of reaction bulbs of 500mL, add 7.38g (step (2 prepare), 0.02mol) 3,7,
11-trimethyl-1,4,6,10-tetraene dodecylphosphoric acid diethylester and the oxolane of 50mL and the mixing of dimethyl sulfoxide
Liquid, under mechanical agitation, cryosel adds 0.026mol butyl lithium, insulated and stirred reaction 2.0h at bathing-5-0 DEG C
After completion of the reaction in-20-0 DEG C be added dropwise to 20mL dissolved with 0.009mol formula (5) 2,7-dimethyl-2,4,6-pungent three
Alkene-1, the oxolane of 8-dialdehyde and the mixed liquor of dimethyl sulfoxide, oxolane and dimethyl sulfoxide in described mixed liquor
Volume ratio is 5:1；About 30min drips off, and continues insulation reaction 1.0h.
React complete, in reaction mixture, add 50mL pure water, stir 5 minutes, be transferred to separatory funnel, stand and divide
Going out organic layer, water layer respectively extracts 2 times with 50mL oxolane, merges organic layer 50mL1% sodium-chloride water solution and washs, organic
Decompression is distilled off solvent mutually, obtains lycopene crude product.
Embodiment 3
(1) preparation of 2,6,10-trimethyl-3,5,9-hendecane triolefin-1-aldehyde
Under nitrogen protection, toward 19.62g (0.1mol, content 98%) pseudoionone in tri-mouthfuls of reaction bulbs of 500mL and
0.25mol methyl chloroacetate, mechanical agitation, cryosel bath cooling is added dropwise to 192mL 30% butyl lithium under conditions of keeping 0-10 DEG C
Methanol solution, about 30min drip off.Continue, at 0 DEG C of stirring reaction 2.0h, to add 100mL pure water afterwards, be heated to interior temperature 30 DEG C
Left and right, drips 133.2g 10% aqueous sulfuric acid, neutralizes and controls pH about 4.5, controls temperature and be less than during dropping
35 DEG C, drip complete continuation between 40-45 DEG C, react 30min.Hydrolyze complete, in reaction system, add 50mL dichloromethane
Alkane, is transferred to separatory funnel, refines and separates organic layer, and water layer 50mL dichloromethane extracts 2 times, merges organic layer 50mL pure
Water purification wash, organic facies 50g Matrii Sulfas Exsiccatus is dried, and then 50 DEG C of decompressions are distilled off dichloromethane, decompressing and extracting to 0mbar,
Obtaining light brown liquid, gas phase analysis product content 92.12%, yield is 71.73%.
(2) preparation of 3,7,11-trimethyl-1,4,6,10-tetraene dodecylphosphoric acid diethylester
The generation of Medronate tetra-ethyl ester carbanion: under nitrogen protection, equipped with airway, thermometer and machinery
In the 250mL there-necked flask of agitator, adding 0.075mol Feldalat NM and 20mL dimethylformamide, stirring cools to 19 DEG C,
Being slowly added dropwise 0.065mol Medronate tetra-ethyl ester, in dropping process control, temperature is less than 35 DEG C, used time 15min.Drip and finish,
Continue at room temperature reaction 1.0h.
Above-mentioned system cools to 18 DEG C, dropping 10.91g (purity 94.59%, 0.05mol) 2,6,10-trimethyl-3, and 5,
9-hendecane triolefin-1-aldehyde, in dropping process control, temperature must not exceed 35 DEG C, used time 15min.Drip and finish, continue 20 DEG C of reactions
2.0h。
Hydrolysis: after above-mentioned reaction completes, molten to reaction system dropping 0.51g (purity 98%, 0.005mol) sulphuric acid
It is made into the aqueous solution of 2.5% in 20g water, is between 6-7 to system pH value, drip and finish stirring 5min, carry out post processing.
Post processing: reactant liquor is proceeded in 500mL pear shape separatory funnel, stratification, separate organic layer, water layer 10*
2mL hexamethylene extracts, and organic layer washs with 50mL 5% saline after merging, and organic facies directly separates and proceeds in 250mL alembic,
60 DEG C of concentrating under reduced pressure eliminate solvent, drain and obtain concentrate, for brown oil liquid.
Gas chromatographic analysis: 3,7,11-trimethyl-1,4,6,10-tetraene dodecylphosphoric acid diethylester=91.75%
(containing multiple cis-trans-isomers).
3,7,11-trimethyl-1,4,6,10-tetraene dodecylphosphoric acid diethylester is to 2,6,10-trimethyl-3,5,9-ten
The yield of one alkane triolefin-1-aldehyde is: 91.24%.
(3) lycopene is prepared by 3,7,11-trimethyl-1,4,6,10-tetraene dodecylphosphoric acid diethylester
Under nitrogen protection, in tri-mouthfuls of reaction bulbs of 500mL, add 7.38g (step (2 prepare), 0.02mol) 3,7,
11-trimethyl-Isosorbide-5-Nitrae, 6,10-tetraene dodecylphosphoric acid diethylesters and the ether of 50mL and the mixed liquor of dimethylformamide,
Under mechanical agitation, cryosel adds 0.03mol Sodium ethylate, insulated and stirred reaction 2.0h at bathing-5-0 DEG C
After completion of the reaction in-20-0 DEG C be added dropwise to 20mL dissolved with 0.01mol formula (5) 2,7-dimethyl-2,4,6-pungent three
Alkene-1, the oxolane of 8-dialdehyde and the mixed liquor of dimethyl sulfoxide, oxolane and dimethyl sulfoxide in described mixed liquor
Volume ratio is 5:1；About 30min drips off, and continues insulation reaction 1.0h.
React complete, in reaction mixture, add 50mL pure water, stir 5 minutes, be transferred to separatory funnel, stand and divide
Going out organic layer, water layer respectively extracts 2 times with 50mL oxolane, merges organic layer 50mL1% sodium-chloride water solution and washs, organic
Decompression is distilled off solvent mutually, obtains lycopene crude product.
Embodiment 4～6 and the Feldalat NM differed only in the alkali alternative embodiment 1 used in table 1 of embodiment 1, in table 1
" reaction temperature " alternative embodiment 1 in " after completion of the reaction in-20～0 DEG C be added dropwise to 20mL dissolved with 1.31g
(0.008mol) oxolane of formula (5) 2,7-dimethyl-2,4,6-sarohornene-1,8-dialdehyde and the mixing of dimethyl sulfoxide
Liquid " in temperature.
Table 1
Checking embodiment 1
Lycopene synthesized by Example 1～6 method, obtains crystal with 20mL dichloromethane recrystallization, then with high
Effect liquid phase chromatogram method is to the content of lycopene in crystal and the mensuration of yield, and result is as shown in table 2, concrete detection equipment and
Its parameter is as follows:
Chromatographic column: Shimadzu VP-ODS C18 post, 150L × 4.6
Flowing phase: methanol: dichloromethane=3:1
Flow velocity: 1.0mL/min
Column temperature: 30 ± 5 DEG C
Detection wavelength: 472nm
Acquisition time: 12min
All-trans lycopene goes out peak in 8.7min under this testing conditions, and sample appearance time and wavelength are all and standard substance
It is consistent.Crystalline melting point is 176-180 DEG C, is consistent with standard substance.
For a person skilled in the art, can technical scheme as described above and design, make other each
Plant corresponding change and deformation, and all these changes and deforms the protection model that all should belong to the claims in the present invention
Within enclosing.
Claims (10)
1. the preparation method of a lycopene, it is characterised in that comprise the steps:
1) under inert gas shielding, the pseudoionone of formula (1) carries out reaching gloomy in the presence of a base with methyl chloroacetate
Reaction prepares the epoxide of formula (2), and described epoxide is methyl-3-(4,8-dimethyl-1,3,7-nonyl triolefin-1-
Base)-3-methyl oxirane-2-carboxylate methyl ester, the epoxide hydrolysis decarboxylation in acid condition of this formula (2) obtains formula (3)
2,6,10-trimethyl-3,5,9-hendecane triolefin-1-aldehyde, reaction equation is as follows:
2) under inert gas shielding, 2,6,10-trimethyl-3 of formula (3), 5,9-hendecane triolefin-1-aldehyde, methylene two phosphorus
Acid tetraalkyl ester and alkali carry out Wittig-Horner condensation reaction in ether solvent or aprotic solvent and prepare formula (4)
Isosorbide-5-Nitrae, 6,10-tetra-double bond 15 carbon phosphate esters, reaction equation is as follows:
3) under inert gas shielding, in ether solvent or dipolar aprotic solvent in the presence of a base, the Isosorbide-5-Nitrae of described formula (4),
6,10-tetra-double bond 15 carbon phosphate ester carries out resetting translocation reaction under the conditions of temperature-30～0 DEG C；
4) indexing is reset complete, the 2 of addition formula (5), 7-dimethyl-2,4,6-sarohornene-1,8-dialdehyde, in the presence of a base,
Ether solvent or dipolar aprotic solvent carry out Wittig-Horner condensation reaction under the conditions of temperature-30～0 DEG C be prepared into
The lycopene of formula (6), reaction equation is as follows:
The preparation method of a kind of lycopene the most according to claim 1, it is characterised in that: described in described formula (4), R is
One in methyl, ethyl, isopropyl.
The preparation method of a kind of lycopene the most according to claim 1, it is characterised in that: step 1) described in false purple sieve
The blue consumption of ketone is 1:(4.0～4.5 with the consumption mol ratio of described alkali), the consumption of described pseudoionone and methyl chloroacetate
The mol ratio of consumption be 1:(2.0～2.5).
The preparation method of a kind of lycopene the most according to claim 1, it is characterised in that: step 2) described in formula (3)
The mol ratio of consumption of consumption and described alkali of 2,6,10-trimethyl-3,5,9-hendecane triolefin-1-aldehyde be 1:(1.0～
1.5), 2,6,10-trimethyl-3 of described formula (3), the consumption of 5,9-hendecane triolefin-1-aldehyde and Medronate tetra-ethyl ester
The mol ratio of consumption be 1:(1.0～1.3).
The preparation method of a kind of lycopene the most according to claim 1, it is characterised in that: step 1) described alkali be alkali gold
Belong to hydride or the alkali metal salt of alcohols or lithium alkylide, wherein: alkali metal hydride is sodium hydride or hydrofining；The alkali gold of alcohols
Belonging to salt is the one in Feldalat NM or sodium tert-butoxide or potassium tert-butoxide；Lithium alkylide is butyl lithium.
The preparation method of a kind of lycopene the most according to claim 1, it is characterised in that: step 1) described in reach gloomy instead
Should carry out under the conditions of-10～0 DEG C；Step 2) described Wittig-Horner condensation reaction carries out under the conditions of 10～20 DEG C.
7. according to the preparation method of a kind of lycopene described in claim 1, it is characterised in that: in step 2) in concrete steps
For: described Medronate tetra-ethyl ester generates corresponding carbanion with alkali reaction, then adds the 2 of described formula (3),
6,10-trimethyl-3,5,9-hendecane triolefin-1-aldehyde carries out Wittig-Horner condensation reaction；Or by described methylene
Diphosphonic acid tetraalkyl ester is added dropwise in alkali after mixing with described formula (3) 2,6,10-trimethyl-3,5,9-hendecane triolefin-1-aldehyde.
The preparation method of a kind of lycopene the most according to claim 1, it is characterised in that: in step 3) described in formula
(4) consumption of 1,4,6,10-tetra-double bond 15 carbon phosphate ester is 1:1.0-1.5 with the mol ratio of the consumption of described alkali；Described
The consumption of the 1,4,6,10-tetra-double bond 15 carbon phosphate ester of formula (4) with the mol ratio of the consumption of ten carbon dialdehydes of described formula (5) is
1:0.4-0.5。
The preparation method of a kind of lycopene the most according to claim 1, it is characterised in that: in step 3) described in alkali
For alkali metal salt or the lithium alkylide of alcohols, wherein, the alkali metal salt of alcohols is in Sodium ethylate, sodium tert-butoxide, potassium tert-butoxide
Kind；Lithium alkylide is butyl lithium.
10. according to the preparation method of a kind of lycopene described in claim 1, it is characterised in that: described ether solvent is second
One in ether, oxolane, glycol dimethyl ether, described aprotic solvent be dimethylformamide, dimethyl sulfoxide, six
One in methyl phosphoric triamide.
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| CN107641091A (en) * | 2017-07-31 | 2018-01-30 | 肇庆巨元生化有限公司 | A kind of preparation method of the carrot aldehyde of β Apos 12 ' |
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| US4000131A (en) * | 1974-05-10 | 1976-12-28 | Hoffmann-La Roche Inc. | Process for preparing epoxide-cyclohexyl compound and resultant compound |
| CN102140117A (en) * | 2010-02-02 | 2011-08-03 | 绍兴文理学院 | 1, 4, 6, 10-tetra-double bond pentadec-carbon phosphonate, preparation method thereof and method for preparing lycopene |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4000131A (en) * | 1974-05-10 | 1976-12-28 | Hoffmann-La Roche Inc. | Process for preparing epoxide-cyclohexyl compound and resultant compound |
| CN102140117A (en) * | 2010-02-02 | 2011-08-03 | 绍兴文理学院 | 1, 4, 6, 10-tetra-double bond pentadec-carbon phosphonate, preparation method thereof and method for preparing lycopene |
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|---|---|---|---|---|
| CN107641091A (en) * | 2017-07-31 | 2018-01-30 | 肇庆巨元生化有限公司 | A kind of preparation method of the carrot aldehyde of β Apos 12 ' |
| CN107641091B (en) * | 2017-07-31 | 2019-05-17 | 肇庆巨元生化有限公司 | A kind of preparation method of β-apo- -12 '-carrot aldehyde |
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