CN111592439A - Method for synthesizing lycopene - Google Patents
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- CN111592439A CN111592439A CN202010578182.6A CN202010578182A CN111592439A CN 111592439 A CN111592439 A CN 111592439A CN 202010578182 A CN202010578182 A CN 202010578182A CN 111592439 A CN111592439 A CN 111592439A
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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 71
- 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 71
- 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 71
- 229960004999 lycopene Drugs 0.000 title claims abstract description 71
- 235000012661 lycopene Nutrition 0.000 title claims abstract description 71
- 239000001751 lycopene Substances 0.000 title claims abstract description 71
- 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 71
- 238000000034 method Methods 0.000 title claims abstract description 24
- 230000002194 synthesizing effect Effects 0.000 title claims description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 84
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 claims abstract description 26
- XEGOZCWNWANQIU-UHFFFAOYSA-N 2,6,10-trimethylundeca-2,5,9-trienal Chemical compound CC(C)=CCCC(C)=CCC=C(C)C=O XEGOZCWNWANQIU-UHFFFAOYSA-N 0.000 claims abstract description 21
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 claims abstract description 15
- -1 dodecyl diethyl phosphonate Chemical compound 0.000 claims abstract description 15
- HNZUNIKWNYHEJJ-UHFFFAOYSA-N geranyl acetone Natural products CC(C)=CCCC(C)=CCCC(C)=O HNZUNIKWNYHEJJ-UHFFFAOYSA-N 0.000 claims abstract description 15
- 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 15
- AYODHZHFDRRQEZ-XLKYRCCQSA-N (2e,4e,6e)-2,7-dimethylocta-2,4,6-trienedial Chemical compound O=CC(/C)=C/C=C/C=C(\C)C=O AYODHZHFDRRQEZ-XLKYRCCQSA-N 0.000 claims abstract description 13
- PJGJQVRXEUVAFT-UHFFFAOYSA-N chloroiodomethane Chemical compound ClCI PJGJQVRXEUVAFT-UHFFFAOYSA-N 0.000 claims abstract description 13
- JJNUJWMGIWJSLT-UHFFFAOYSA-N lithium trimethylsilanide Chemical compound [Li+].C[Si-](C)C JJNUJWMGIWJSLT-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 13
- 239000012043 crude product Substances 0.000 claims abstract description 12
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 10
- XDVMALRBCQSYLB-UHFFFAOYSA-N diethoxyphosphoryloxymethyl diethyl phosphate Chemical compound P(=O)(OCC)(OCC)OCOP(=O)(OCC)OCC XDVMALRBCQSYLB-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000002994 raw material Substances 0.000 claims abstract description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 50
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 50
- 239000002904 solvent Substances 0.000 claims description 38
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 25
- 239000003054 catalyst Substances 0.000 claims description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- 230000035484 reaction time Effects 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- 238000010992 reflux Methods 0.000 claims description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 12
- 239000011259 mixed solution Substances 0.000 claims description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 11
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 11
- 239000000047 product Substances 0.000 claims description 11
- 239000012312 sodium hydride Substances 0.000 claims description 11
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 11
- 238000001308 synthesis method Methods 0.000 claims description 9
- 238000010438 heat treatment Methods 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 230000009471 action Effects 0.000 claims description 6
- 238000001953 recrystallisation Methods 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 238000009833 condensation Methods 0.000 claims description 4
- 230000005494 condensation Effects 0.000 claims description 4
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000003208 petroleum Substances 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 230000008569 process Effects 0.000 abstract description 4
- 239000006227 byproduct Substances 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 23
- 238000003756 stirring Methods 0.000 description 22
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 238000004809 thin layer chromatography Methods 0.000 description 12
- 238000004566 IR spectroscopy Methods 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 239000012467 final product Substances 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 238000004896 high resolution mass spectrometry Methods 0.000 description 5
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- XILIYVSXLSWUAI-UHFFFAOYSA-N 2-(diethylamino)ethyl n'-phenylcarbamimidothioate;dihydrobromide Chemical compound Br.Br.CCN(CC)CCSC(N)=NC1=CC=CC=C1 XILIYVSXLSWUAI-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 239000000576 food coloring agent Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 2
- AYODHZHFDRRQEZ-UHFFFAOYSA-N 2,7-dimethylocta-2,4,6-trienedial Chemical compound O=CC(C)=CC=CC=C(C)C=O AYODHZHFDRRQEZ-UHFFFAOYSA-N 0.000 description 2
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 238000007239 Wittig reaction Methods 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000001177 diphosphate Substances 0.000 description 2
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 2
- 235000011180 diphosphates Nutrition 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 235000013373 food additive Nutrition 0.000 description 2
- 239000002778 food additive Substances 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
- MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 235000021466 carotenoid Nutrition 0.000 description 1
- 150000001747 carotenoids Chemical class 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 235000015140 cultured milk Nutrition 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07C45/41—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by hydrogenolysis or reduction of carboxylic groups or functional derivatives thereof
-
- 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
- C07C7/00—Purification; Separation; Use of additives
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Analytical Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Water Supply & Treatment (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for preparing lycopene. The method comprises the following steps: preparing 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde by using pseudo ionone, chloroiodomethane, lithium bromide and trimethyl silyl lithium as raw materials; reacting the diethyl ester with tetraethyl methylene diphosphate to obtain 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate; reacting 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate with 2, 7-dimethyl-2, 4, 6-octatrienedial to obtain a lycopene crude product. The invention solves the problem that byproducts are not easy to separate in the synthesis of the lycopene at present, prepares the intermediate of the synthesis process of the lycopene by a brand new method, synthesizes the lycopene by three-step reaction, has simple synthesis process, convenient operation, green and environment-friendly production process, relatively low cost and easy realization of industrialization.
Description
Technical Field
The invention belongs to the field of food additives, and particularly relates to a synthesis method of a food colorant lycopene.
Background
Lycopene is a natural and safe food colorant, and is a nutrient enhancer with excellent performance. Lycopene not only has bright color and strong tinting strength, but also has excellent physiological function. With the continuous exploration on the physiological activity of lycopene, the application prospect of lycopene in the fields of food, medicine, cosmetics and the like is wider and wider. It is also becoming more and more important how to efficiently and inexpensively prepare lycopene.
At present, there are three main ways of producing lycopene: chemical synthesisMethods, natural extraction methods and microbial fermentation methods. The natural extraction method has high cost and low yield. The intermediate product of the microbial fermentation method during production can affect the separation purity of lycopene, and the related technology needs to be further mature. The chemical synthesis of lycopene has the characteristics of high yield and low cost, and has higher economic benefit. And the chemically synthesized lycopene can be used as a food colorant to be added into various foods (modified milk, flavored fermented milk, candies, instant grains, baked foods, solid soup bases, semi-solid compound seasonings, beverages and jellies) specified in the GB 2760-2014 food safety national standard food additive use standard. At present, the chemical synthesis route of lycopene used in industry uses pseudoionone as raw material and carries out nucleophilic addition, selective hydrogenation and SN1Substitution salifying reaction to generate triphenyl (3,7, 11-trimethyl-2, 4,6, 10-tetraene dodecyl) -phosphine bromide, and finally carrying out Wittig reaction with 2, 7-dimethyl-2, 4, 6-octatriene-1, 8-dialdehyde to obtain the lycopene. Triphenylphosphine oxide which is not easy to separate and recover is generated in the process of synthesizing the lycopene by the Wittig method, and a byproduct phosphonate is easy to dissolve in water and separate when the lycopene is synthesized by the Wittig-Horner method. The invention provides a synthesis method of lycopene, aiming at meeting the higher development requirements of the food industry in the future and enabling people to obtain cheaper green and safe lycopene, and under the background of a feasible scheme that the industry needs easy industrialization, relatively cheap production cost and considerable yield of final products.
Disclosure of Invention
In order to overcome the disadvantages and shortcomings of the prior art, the invention aims to provide a preparation method of lycopene.
The purpose of the invention is realized by the following scheme:
lycopene of formula C40H56The relative molecular weight is 536.85, the deep red needle crystal is dissolved in chloroform, benzene and grease, is insoluble in water, is unstable to light and oxygen, and turns brown when meeting iron.
The structural formula of the lycopene is as follows:
the synthesis method of the lycopene comprises a preparation method of alpha-substituted-alpha, beta-unsaturated aldehyde and a Wittig-Horner reaction, and specifically comprises the following steps:
(1) pseudo ionone (compound I), chloroiodomethane, lithium bromide and trimethyl silyl lithium are used as raw materials, tetrahydrofuran or/and toluene are used as solvents, low-temperature reaction is carried out, and then temperature rise reaction is carried out, so that 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde (compound II) is obtained;
(2) tetraethyl methylene diphosphate (compound III) reacts with 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde (compound II) in a solvent under the action of an alkaline catalyst to obtain 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate (compound IV);
(3) reacting diethyl 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl phosphonate (compound IV) with 2, 7-dimethyl-2, 4, 6-octatrienedial (compound V) in a solvent under the action of an alkaline catalyst, recrystallizing a product after reaction to obtain a lycopene crude product, heating the lycopene crude product in ethanol, and carrying out condensation reflux reaction to obtain the lycopene (compound VI).
The molar ratio of the pseudo ionone, the chloroiodomethane, the lithium bromide and the trimethyl silyllithium in the step (1) is 1: 1: 1: 1-1: 4: 4: 4, preferably 1: 3: 3: 3; the temperature of the low-temperature reaction in the step (1) is-80 ℃ to-30 ℃, and is preferably-78 ℃; the low-temperature reaction time in the step (1) is 0.5-4 h, preferably 1 h; the temperature of the temperature-raising reaction in the step (1) is 0-35 ℃, and is preferably 25 ℃; the reaction time for raising the temperature in the step (1) is 6-18 h, preferably 12 h; to avoid too violent reaction, it is preferable to add trimethylsilyllithium to the pseudoionone, chloroiodomethane and lithium bromide at a rate of 0.5 mL/min.
The alkaline catalyst in the step (2) is at least one of sodium hydride, sodium ethoxide and potassium tert-butoxide, preferably sodium hydride; the molar ratio of the 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde, the tetraethyl methylene diphosphate and the basic catalyst in the step (2) is 1: 0.8: 0.8-1: 3: 3, preferably 1: 1.2: 1.2; the reaction time in the step (2) is 0.5-8 h, preferably 2 h; the reaction temperature in the step (2) is 0-55 ℃, and preferably 35 ℃; for good catalytic effect, the tetraethyl methylene diphosphate is preferably added to the solvent containing the basic catalyst at a rate of 1mL/min, and then 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde is added at a rate of 1 mL/min; in order to avoid the reaction from being too violent, the temperature of the reaction system is preferably controlled to be 0 ℃ when the reagent is added; the solvent in the step (2) is at least one of toluene, tetrahydrofuran and N, N-dimethylformamide, and is preferably toluene.
The alkaline catalyst in the step (3) is at least one of sodium hydride, sodium ethoxide and potassium tert-butoxide, preferably potassium tert-butoxide; the molar ratio of the 2, 7-dimethyl-2, 4, 6-octatrienedial, the 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate and the alkaline catalyst in the step (3) is 1: 0.8: 0.8-1: 5: 5, preferably 1: 2.2: 2.6; the reaction time in the step (3) is 0.5-8 h, preferably 3 h; the reaction temperature in the step (3) is 0-55 ℃, and preferably 30 ℃; in order to achieve good catalytic effect, preferably 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate is added into solvent containing alkaline catalyst at the speed of 1mL/min, and then 2, 7-dimethyl-2, 4, 6-octatrienedial is added at the speed of 1 mL/min; in order to avoid too violent reaction, the temperature of the reaction system is preferably controlled to be-30 ℃ when the reagent is added; the solvent in the step (3) is at least one of toluene, tetrahydrofuran and dimethyl sulfoxide, and is preferably a mixed solution of tetrahydrofuran and dimethyl sulfoxide with a volume ratio of 8: 1; the recrystallization solvent in the step (3) is one of dichloromethane, chloroform and petroleum ether, and dichloromethane is preferred.
The reflux reaction time in the step (3) is 0.5-4 h, preferably 1 h; the temperature of the reflux reaction in the step (4) is 50 ℃ to 100 ℃, and preferably 75 ℃.
Preferably, the synthesis method comprises the following steps:
(1) pseudo ionone, chloroiodomethane, lithium bromide and trimethyl silyl lithium are used as raw materials, tetrahydrofuran is used as a solvent, the raw materials are firstly reacted for 1 hour at minus 78 ℃, and then the temperature is raised to 25 ℃ for 12 hours to obtain 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde;
(2) tetraethyl methylene diphosphate reacts with 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde in a solvent under the action of an alkaline catalyst sodium hydride at the temperature of 35 ℃ for 2 hours to obtain 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate;
(3) reacting 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate with 2, 7-dimethyl-2, 4, 6-octatrienedial in a solvent at 30 ℃ for 3h under the condition of a basic catalyst of potassium tert-butoxide, recrystallizing the reacted product to obtain a lycopene crude product, and heating the lycopene crude product in ethanol and carrying out condensation reflux reaction to obtain the lycopene.
The synthetic route of the method is preferably as follows:
in the present invention, the temperature and pressure are not specified, and both are carried out at room temperature and atmospheric pressure.
The invention designs a total synthetic route by synthesis and inverse synthetic analysis, and based on the organic synthesis theory, by constructing multistep reactions, such as preparation of alpha-substituted-alpha, beta-unsaturated aldehyde, Wittig-Horner reaction and the like, searching for proper synthetic reaction conditions, such as reactant molar ratio, temperature, reaction time, solvent and the like, lycopene is finally synthesized, and the structure of a final product is identified by infrared spectroscopy (IR), High Resolution Mass Spectrometry (HRMS) and Nuclear Magnetic Resonance (NMR), and the result is determined to be a target final product.
Compared with the prior art, the invention has the following advantages and beneficial effects:
1. the invention adopts a brand new technical route and technical means to synthesize the intermediate product 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde.
2. The invention adopts a synthesis route characterized by the Wittig-Horner reaction, avoids the problem that byproducts are not easy to separate caused by the Wittig reaction in the prior art, and is a key step for green synthesis of lycopene.
3. The lycopene is synthesized by 3 steps of reaction, compared with the existing lycopene synthesis process, the method has the advantages of short reaction steps, considerable reaction yield and certain industrialization potential.
4. The synthetic method has the advantages that the raw materials are cheap and easy to obtain, the pseudo ionone and the 2, 7-dimethyl-2, 4, 6-octatriene-1, 8-dialdehyde used in the reaction are chemical intermediates commonly applied to the industrial production of the carotenoid, the raw material sources are wide, the production cost is relatively low, and the industrialization is easy to realize.
Detailed Description
The present invention will be described in further detail with reference to examples, but the embodiments of the present invention are not limited thereto.
The reagents used in the examples are commercially available without specific reference.
In the examples, the room temperature or the normal temperature is 25 ℃.
Example 1
A synthesis method of lycopene comprises the following steps:
(1) after a 200mL round-bottom flask was placed at-78 ℃ and stirred, pseudoionone (1.92g,10.00mmol), tetrahydrofuran (10mL), iodochloromethane (2.2mL,30.00mmol), and lithium bromide (1.5mol/L tetrahydrofuran solution) (20mL,30.00mmol) were added in this order, trimethylsilyllithium (1mol/L n-pentane solution) (30mL,30.00mmol) was added to the reaction solution at a rate of 0.5mL/min, and after 1 hour of reaction, the reaction was allowed to stir vigorously and was allowed to warm at 25 ℃ for a further 12 hours, followed by Thin Layer Chromatography (TLC). After the reaction is finished, 20mL of saturated ammonium chloride solution is added and stirring is continued for 15min, the organic layer is washed by water (20mL) and saturated saline solution (20mL), dried by anhydrous sodium sulfate, filtered, the solvent is removed under reduced pressure, and the organic layer is purified by column chromatography to obtain yellow liquid 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde (1.53g,7.43mmol) with the yield of 74.3%;
(2) to a 200mL round-bottom flask were added sodium hydride (0.35g,8.92mmol), and toluene (20mL) in that order. The flask was placed at 0 deg.C and stirred, the compound tetraethylmethylene diphosphate (2.57g,8.92mmol) was dissolved in toluene (20mL) and added to the flask at 1mL/min and after addition stirring was continued for 0.5 h. Then 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde (1.53g,7.43mmol) was dissolved in toluene (20mL) and added to the reaction flask at a rate of 1mL/min, after the addition was completed, the reaction was continued with stirring for 0.5h, then the temperature was raised to 35 ℃ and the reaction was continued for 2h, monitored by thin layer chromatography. After the reaction was completed, water (20mL) was added to the reaction solution and stirring was continued for 10min, and then the organic layer was washed twice with a saturated sodium chloride solution (30mL), dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure, and further purified by column chromatography to obtain diethyl 3,7, 11-trimethyl-1, 4,6, 10-tetraene-dodecylphosphonate (2.15g,6.32mmol), with a yield of 85.1%.
(3) To a 100mL round-bottomed flask were sequentially added 9mL of a mixed solution of potassium tert-butoxide (7.6mL,7.58mmol) and tetrahydrofuran and dimethylsulfoxide in a volume ratio of 8: 1. The reaction flask is placed at minus 30 ℃ and stirred, diethyl 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl phosphonate (2.15g,6.32mmol) is dissolved in 9mL of mixed solution of tetrahydrofuran and dimethyl sulfoxide with the volume ratio of 8:1 and added into the reaction flask at the speed of 1mL/min, and after the addition is finished, the stirring reaction is continued for 0.5 h. Dissolving 2, 7-dimethyl-2, 4, 6-octatrienedial (0.47g,2.87mmol) in 9mL of mixed solution of tetrahydrofuran and dimethyl sulfoxide with the volume ratio of 8:1, adding the solution into a reaction bottle at the speed of 1mL/min, continuing to stir for reaction for 0.5h after the addition is finished, then heating to 30 ℃ and continuing to react for 3h, and monitoring by thin-layer chromatography. After completion of the reaction, chloroform (20mL) and a saturated sodium chloride solution (30mL) were added and the mixture was washed twice, and the organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain a crude product, which was recrystallized from methylene chloride. Adding the crude lycopene product obtained by recrystallization into a 50mL round-bottom flask, dissolving the crude lycopene product in ethanol, placing the reaction flask at 75 ℃, condensing and refluxing, stirring for 1h, and evaporating the solvent to dryness under reduced pressure to obtain lycopene (0.90g,1.68mmol) with the yield of 58.5%.
The compound prepared in example 1 is lycopene, whose characterization data are shown below:
1H NMR(600MHz,CDCl3),：6.60～6.51(m,4H),6.42(dd,J＝15.1,11.0Hz,2H),6.28(d,J＝14.9Hz,2H),6.21～6.15(m,4H),6.11(d,J＝11.5Hz,2H),5.91～5.85(m,2H),5.04(tq,J＝5.4,1.6Hz,2H),2.09～2.00(m,8H),1.90(s,12H),1.75(s,6H),1.62(s,6H),1.55(s,6H)；
13C NMR(151MHz,CDCl3),：138.49,136.33,135.53,135.15,134.38,131.62,130.73,130.53,129.05,124.70,124.13,123.78,122.93,39.22,25.67,24.68,16.69,15.95,11.89,11.78；
DEPT 135：136.33,134.38,131.62,130.53,129.05,124.70,124.13,123.78,122.92,39.22(D),25.67(D),24.68,16.69,15.95,11.89,11.78；
IR(KBr,cm-1)3033,2971,2912,2852,1628,1552,1440,1376,955；
HRMS(ESI)[M+H+]calculated for C40H56：536.4377,founded：536.4362。
the final product was structurally characterized by infrared spectroscopy (IR), Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR), which confirmed that lycopene was indeed synthesized in this example.
Example 2
A synthesis method of lycopene comprises the following steps:
(1) after a 200mL round-bottom flask was placed at-80 ℃ and stirred, pseudoionone (1.92g,10.00mmol), tetrahydrofuran (10mL), iodochloromethane (0.8mL,10.00mmol), and lithium bromide (1.5mol/L tetrahydrofuran solution) (6.7mL,10.00mmol) were added in this order, trimethylsilyllithium (1mol/L n-pentane solution) (10mL,10.00mmol) was added to the reaction solution at a rate of 0.5mL/min, and after stirring vigorously for 0.5h, the reaction was continued at 0 ℃ for 6h, followed by Thin Layer Chromatography (TLC). After the reaction is finished, 20mL of saturated ammonium chloride solution is added and stirring is continued for 15min, the organic layer is washed by water (20mL) and saturated saline solution (20mL), dried by anhydrous sodium sulfate, filtered, the solvent is removed under reduced pressure, and column chromatography purification is carried out to obtain yellow liquid 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde (1.44g,6.99mmol) with the yield of 69.9%;
(2) to a 200mL round bottom flask were added sodium hydride (0.14g,5.6mmol), and toluene (20mL) in that order. The flask was placed at 0 deg.C and stirred, the compound tetraethylmethylene diphosphate (1.61g,5.6mmol) was dissolved in toluene (20mL) and added to the flask at 1mL/min and after addition stirring was continued for 0.5 h. Then 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde (1.44g,6.99mmol) was dissolved in toluene (20mL) and added to the reaction flask at a rate of 1mL/min, after which the reaction was stirred for 0.5h and then at 0 ℃ for 0.5h, monitored by thin layer chromatography. After the reaction was completed, water (20mL) was added to the reaction solution and stirring was continued for 10min, and then the organic layer was washed twice with a saturated sodium chloride solution (30mL), dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure, and further purified by column chromatography to obtain diethyl 3,7, 11-trimethyl-1, 4,6, 10-tetraene-dodecylphosphonate (1.83g,5.38mmol), yield 76.9%.
(3) To a 100mL round-bottomed flask were sequentially added 9mL of a mixed solution of potassium tert-butoxide (6.4mL,6.32mmol) and tetrahydrofuran and dimethylsulfoxide in a volume ratio of 8: 1. The reaction flask is placed at minus 30 ℃ and stirred, diethyl 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl phosphonate (2.15g,6.32mmol) is dissolved in 9mL of mixed solution of tetrahydrofuran and dimethyl sulfoxide with the volume ratio of 8:1 and added into the reaction flask at the speed of 1mL/min, and after the addition is finished, the stirring reaction is continued for 0.5 h. Dissolving 2, 7-dimethyl-2, 4, 6-octatrienedial (1.29g,7.9mmol) in 9mL of mixed solution of tetrahydrofuran and dimethyl sulfoxide with the volume ratio of 8:1, adding the solution into a reaction bottle at the speed of 1mL/min, continuing stirring and reacting for 0.5h after the addition is finished, then heating to 0 ℃ and continuing to react for 0.5h, and monitoring by thin-layer chromatography. After completion of the reaction, chloroform (20mL) and a saturated sodium chloride solution (30mL) were added and the mixture was washed twice, and the organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain a crude product, which was recrystallized from methylene chloride. Adding the crude lycopene product obtained by recrystallization into a 50mL round-bottom flask, dissolving the crude lycopene product in ethanol, placing the reaction flask at 50 ℃, condensing and refluxing, stirring for 0.5h, and evaporating the solvent to dryness under reduced pressure to obtain lycopene (0.75g,1.4mmol) with the yield of 17.8%.
The compound prepared in example 2 was lycopene, whose characterization data are shown below:
1H NMR(600MHz,CDCl3),：6.60～6.51(m,4H),6.42(dd,J＝15.1,11.0Hz,2H),6.28(d,J＝14.9Hz,2H),6.21～6.15(m,4H),6.11(d,J＝11.5Hz,2H),5.91～5.85(m,2H),5.04(tq,J＝5.4,1.6Hz,2H),2.09～2.00(m,8H),1.90(s,12H),1.75(s,6H),1.62(s,6H),1.55(s,6H)；
13C NMR(151MHz,CDCl3),：138.49,136.33,135.53,135.15,134.38,131.62,130.73,130.53,129.05,124.70,124.13,123.78,122.93,39.22,25.67,24.68,16.69,15.95,11.89,11.78；
DEPT 135：136.33,134.38,131.62,130.53,129.05,124.70,124.13,123.78,122.92,39.22(D),25.67(D),24.68,16.69,15.95,11.89,11.78；
IR(KBr,cm-1)3033,2971,2912,2852,1628,1552,1440,1376,955；
HRMS(ESI)[M+H+]calculated for C40H56：536.4377,founded：536.4362。
the final product was structurally characterized by infrared spectroscopy (IR), Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR), which confirmed that lycopene was indeed synthesized in this example.
Example 3
A synthesis method of lycopene comprises the following steps:
(1) after a 200mL round-bottom flask was placed at-30 ℃ and stirred, pseudoionone (1.92g,10.00mmol), tetrahydrofuran (10mL), iodochloromethane (2.9mL,40.00mmol), and lithium bromide (1.5mol/L tetrahydrofuran solution) (26.6mL,40.00mmol) were added in this order, trimethylsilyllithium (1mol/L n-pentane solution) (40mL,40.00mmol) was added to the reaction solution at a rate of 0.5mL/min, and after vigorous stirring for 4 hours, the reaction was continued at 35 ℃ for 18 hours, followed by Thin Layer Chromatography (TLC). After the reaction is finished, 20mL of saturated ammonium chloride solution is added and stirring is continued for 15min, the organic layer is washed by water (20mL) and saturated saline solution (20mL), dried by anhydrous sodium sulfate, filtered, the solvent is removed under reduced pressure, and column chromatography purification is carried out to obtain yellow liquid 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde (1.49g,7.23mmol) with the yield of 72.3%;
(2) to a 200mL round-bottom flask were added sodium hydride (0.52g,21.7mmol), and toluene (20mL) in that order. The flask was placed at 0 deg.C and stirred, the compound tetraethyl methylene diphosphate (6.25g,21.7mmol) was dissolved in toluene (20mL) and added to the flask at 1mL/min and after addition stirring was continued for 0.5 h. Then 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde (1.49g,7.23mmol) was dissolved in toluene (20mL) and added to the reaction flask at a rate of 1mL/min, after the addition was completed, the reaction was stirred for 0.5h, then the temperature was raised to 55 ℃ and the reaction was continued for 8h, monitored by thin layer chromatography. After the reaction was completed, water (20mL) was added to the reaction solution and stirring was continued for 10min, and then the organic layer was washed twice with a saturated sodium chloride solution (30mL), dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure, and further purified by column chromatography to obtain diethyl 3,7, 11-trimethyl-1, 4,6, 10-tetraene-dodecylphosphonate (2.03g,5.97mmol), yield 81.6%.
(3) To a 100mL round-bottomed flask were sequentially added 9mL of a mixed solution of potassium tert-butoxide (6.0mL,5.97mmol) and tetrahydrofuran and dimethylsulfoxide in a volume ratio of 8: 1. The reaction flask is placed at minus 30 ℃ and stirred, diethyl 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl phosphonate (2.03g,5.97mmol) is dissolved in 9mL of mixed solution of tetrahydrofuran and dimethyl sulfoxide with the volume ratio of 8:1 and added into the reaction flask at the speed of 1mL/min, and after the addition is finished, the stirring reaction is continued for 0.5 h. Dissolving 2, 7-dimethyl-2, 4, 6-octatrienedial (0.20g,1.20mmol) in 9mL of mixed solution of tetrahydrofuran and dimethyl sulfoxide with the volume ratio of 8:1, adding the mixed solution into a reaction bottle at the speed of 1mL/min, continuing stirring and reacting for 0.5h after the addition is finished, then heating to 55 ℃ and continuing to react for 8h, and monitoring by thin-layer chromatography. After completion of the reaction, chloroform (20mL) and a saturated sodium chloride solution (30mL) were added and the mixture was washed twice, and the organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain a crude product, which was recrystallized from methylene chloride. Adding the crude lycopene product obtained by recrystallization into a 50mL round-bottom flask, dissolving the crude lycopene product in ethanol, placing the reaction flask at 75 ℃, condensing and refluxing, stirring for 1h, and evaporating the solvent under reduced pressure to dryness to obtain lycopene (0.38g,0.70mmol) with the yield of 58.3%.
The compound prepared in example 3 was lycopene, whose characterization data are shown below:
1H NMR(600MHz,CDCl3),：6.60～6.51(m,4H),6.42(dd,J＝15.1,11.0Hz,2H),6.28(d,J＝14.9Hz,2H),6.21～6.15(m,4H),6.11(d,J＝11.5Hz,2H),5.91～5.85(m,2H),5.04(tq,J＝5.4,1.6Hz,2H),2.09～2.00(m,8H),1.90(s,12H),1.75(s,6H),1.62(s,6H),1.55(s,6H)；
13C NMR(151MHz,CDCl3),：138.49,136.33,135.53,135.15,134.38,131.62,130.73,130.53,129.05,124.70,124.13,123.78,122.93,39.22,25.67,24.68,16.69,15.95,11.89,11.78；
DEPT 135：136.33,134.38,131.62,130.53,129.05,124.70,124.13,123.78,122.92,39.22(D),25.67(D),24.68,16.69,15.95,11.89,11.78；
IR(KBr,cm-1)3033,2971,2912,2852,1628,1552,1440,1376,955；
HRMS(ESI)[M+H+]calculated for C40H56：536.4377,founded：536.4362。
the final product was structurally characterized by infrared spectroscopy (IR), Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR), which confirmed that lycopene was indeed synthesized in this example.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (10)
1. A synthesis method of lycopene is characterized by comprising the following steps:
(1) pseudo ionone, chloroiodomethane, lithium bromide and trimethyl silyl lithium are taken as raw materials, tetrahydrofuran or/and toluene are taken as solvents, low-temperature reaction is carried out, and then high-temperature reaction is carried out, so as to obtain 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde;
(2) tetraethyl methylene diphosphate reacts with 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde in a solvent under the action of an alkaline catalyst to obtain 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate;
(3) reacting 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate with 2, 7-dimethyl-2, 4, 6-octatrienedial in a solvent under the action of an alkaline catalyst, recrystallizing a product after reaction to obtain a lycopene crude product, and heating the lycopene crude product in ethanol and carrying out condensation reflux reaction to obtain the lycopene.
2. A method of synthesizing lycopene according to claim 1, wherein in the step (1):
the molar ratio of the pseudo ionone, the chloroiodomethane, the lithium bromide and the trimethyl silyl lithium is 1: 1: 1: 1-1: 4: 4: 4;
the temperature of the low-temperature reaction is-80 ℃ to-30 ℃;
the low-temperature reaction time is 0.5-4 h;
the temperature of the temperature raising reaction is 0-35 ℃;
the reaction time for raising the temperature is 6-18 h.
3. A method of synthesizing lycopene according to claim 1, wherein in the step (1):
the molar ratio of the pseudo ionone, the chloroiodomethane, the lithium bromide and the trimethyl silyl lithium is 1: 3: 3: 3;
the temperature of the low-temperature reaction is-78 ℃;
the time of the low-temperature reaction is 1 h;
the temperature of the reaction at the elevated temperature is 25 ℃;
the reaction time is 12 hours when the temperature is increased;
trimethyl silyllithium is added into pseudo ionone, chloroiodomethane and lithium bromide at the speed of 0.5mL/min for reaction.
4. A method of synthesizing lycopene according to claim 1, wherein in the step (2):
the alkaline catalyst is at least one of sodium hydride, sodium ethoxide and potassium tert-butoxide;
the mole ratio of the 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde, tetraethyl methylene diphosphate and alkaline catalyst is 1: 0.8: 0.8-1: 3: 3;
the reaction time is 0.5-8 h;
the reaction temperature is 0-55 ℃;
the solvent is at least one of toluene, tetrahydrofuran and N, N-dimethylformamide.
5. A method of synthesizing lycopene according to claim 1, wherein in the step (2):
the alkaline catalyst is sodium hydride;
the mole ratio of the 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde, tetraethyl methylene diphosphate and alkaline catalyst is 1: 1.2: 1.2;
the reaction time is 2 hours;
the reaction temperature is 35 ℃;
the tetraethyl methylene diphosphate is added to a solvent containing a basic catalyst at a rate of 1mL/min, followed by addition of 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde at a rate of 1 mL/min; controlling the temperature of the reaction system to be 0 ℃ when adding the reagent;
the solvent is toluene.
6. A method of synthesizing lycopene according to claim 1, wherein in the step (3):
the alkaline catalyst is at least one of sodium hydride, sodium ethoxide and potassium tert-butoxide;
the molar ratio of the 2, 7-dimethyl-2, 4, 6-octatrienedial to the 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate to the alkaline catalyst is 1: 0.8: 0.8-1: 5: 5;
the reaction time is 0.5-8 h;
the reaction temperature is 0-55 ℃;
the solvent is at least one of toluene, tetrahydrofuran and dimethyl sulfoxide;
the recrystallization solvent is one of dichloromethane, chloroform and petroleum ether.
7. A method of synthesizing lycopene according to claim 1, wherein in the step (3):
the alkaline catalyst is potassium tert-butoxide;
the molar ratio of the 2, 7-dimethyl-2, 4, 6-octatrienedial to the 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate to the alkaline catalyst is 1: 2.2: 2.6;
the reaction time is 3 hours;
the reaction temperature is 30 ℃;
adding the 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate into a solvent containing a basic catalyst at the speed of 1mL/min, and then adding 2, 7-dimethyl-2, 4, 6-octatrienedial at the speed of 1 mL/min; controlling the temperature of a reaction system to be-30 ℃ when adding a reagent;
the solvent is a mixed solution of tetrahydrofuran and dimethyl sulfoxide with the volume ratio of 8: 1;
the recrystallization solvent is dichloromethane.
8. A method of synthesis of lycopene according to claim 1, characterized in that:
the reflux reaction time in the step (3) is 0.5-4 h, and the reflux reaction temperature is 50-100 ℃.
9. A method of synthesis of lycopene according to claim 1, characterized in that:
the reflux reaction time in the step (3) is 1 h; the temperature of the reflux reaction was 75 ℃.
10. A method of synthesis of lycopene according to claim 1, characterized by comprising the following steps:
(1) pseudo ionone, chloroiodomethane, lithium bromide and trimethyl silyl lithium are used as raw materials, tetrahydrofuran is used as a solvent, the raw materials are firstly reacted for 1 hour at minus 78 ℃, and then the temperature is raised to 25 ℃ for 12 hours to obtain 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde;
(2) tetraethyl methylene diphosphate reacts with 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde in a solvent under the action of an alkaline catalyst sodium hydride at the temperature of 35 ℃ for 2 hours to obtain 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate;
(3) reacting 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate with 2, 7-dimethyl-2, 4, 6-octatrienedial in a solvent at 30 ℃ for 3h under the condition of a basic catalyst of potassium tert-butoxide, recrystallizing the reacted product to obtain a lycopene crude product, and heating the lycopene crude product in ethanol and carrying out condensation reflux reaction to obtain the lycopene.
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