CN105295007B - One kind conjugation water-soluble polymer tracer material and preparation method thereof - Google Patents
One kind conjugation water-soluble polymer tracer material and preparation method thereof Download PDFInfo
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- 239000000463 material Substances 0.000 title claims abstract description 20
- 239000000700 radioactive tracer Substances 0.000 title claims abstract description 13
- 230000021615 conjugation Effects 0.000 title claims description 7
- 229920003169 water-soluble polymer Polymers 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 86
- 238000006243 chemical reaction Methods 0.000 claims description 53
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 40
- 229910052757 nitrogen Inorganic materials 0.000 claims description 40
- 239000000243 solution Substances 0.000 claims description 38
- 239000012043 crude product Substances 0.000 claims description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- 150000001875 compounds Chemical class 0.000 claims description 22
- 239000007787 solid Substances 0.000 claims description 21
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 20
- 239000012044 organic layer Substances 0.000 claims description 20
- 239000003208 petroleum Substances 0.000 claims description 20
- 239000003054 catalyst Substances 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- 238000006116 polymerization reaction Methods 0.000 claims description 16
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 15
- 238000000967 suction filtration Methods 0.000 claims description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 14
- 238000001035 drying Methods 0.000 claims description 14
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 12
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical class COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 12
- 238000004140 cleaning Methods 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- 239000000741 silica gel Substances 0.000 claims description 12
- 229910002027 silica gel Inorganic materials 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- 238000007789 sealing Methods 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 229940125904 compound 1 Drugs 0.000 claims description 9
- 229940125782 compound 2 Drugs 0.000 claims description 9
- 229940126214 compound 3 Drugs 0.000 claims description 9
- 229940125898 compound 5 Drugs 0.000 claims description 9
- 239000000376 reactant Substances 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 8
- 229920000642 polymer Polymers 0.000 claims description 8
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 238000001556 precipitation Methods 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- 238000010898 silica gel chromatography Methods 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 8
- SGRHVVLXEBNBDV-UHFFFAOYSA-N 1,6-dibromohexane Chemical class BrCCCCCCBr SGRHVVLXEBNBDV-UHFFFAOYSA-N 0.000 claims description 7
- -1 bromo- 1- propyl Chemical group 0.000 claims description 7
- 239000012265 solid product Substances 0.000 claims description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 230000006837 decompression Effects 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 239000011780 sodium chloride Substances 0.000 claims description 5
- 235000002639 sodium chloride Nutrition 0.000 claims description 5
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 5
- ZZPNDIHOQDQVNU-UHFFFAOYSA-N 2-hydroxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound CC1(C)OB(O)OC1(C)C ZZPNDIHOQDQVNU-UHFFFAOYSA-N 0.000 claims description 4
- GHPHCDZRWUIBCE-UHFFFAOYSA-N 3-bromo-2-methylpropanoyl bromide Chemical class BrCC(C)C(Br)=O GHPHCDZRWUIBCE-UHFFFAOYSA-N 0.000 claims description 4
- 206010013786 Dry skin Diseases 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 229910052593 corundum Inorganic materials 0.000 claims description 4
- 239000013078 crystal Substances 0.000 claims description 4
- 230000001351 cycling effect Effects 0.000 claims description 4
- 238000006392 deoxygenation reaction Methods 0.000 claims description 4
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 claims description 4
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N n-propyl alcohol Natural products CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- 230000007935 neutral effect Effects 0.000 claims description 4
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 4
- 235000011056 potassium acetate Nutrition 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 230000003252 repetitive effect Effects 0.000 claims description 4
- 238000004062 sedimentation Methods 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 229910001845 yogo sapphire Inorganic materials 0.000 claims description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 3
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 3
- 235000011089 carbon dioxide Nutrition 0.000 claims description 3
- 230000008014 freezing Effects 0.000 claims description 3
- 238000007710 freezing Methods 0.000 claims description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 3
- QATBRNFTOCXULG-UHFFFAOYSA-N n'-[2-(methylamino)ethyl]ethane-1,2-diamine Chemical compound CNCCNCCN QATBRNFTOCXULG-UHFFFAOYSA-N 0.000 claims description 3
- 238000005292 vacuum distillation Methods 0.000 claims description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims 2
- LCPVQAHEFVXVKT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)pyridin-3-amine Chemical compound NC1=CC=CN=C1OC1=CC=C(F)C=C1F LCPVQAHEFVXVKT-UHFFFAOYSA-N 0.000 claims 1
- OKUSWAGOKUGEDX-UHFFFAOYSA-N C(CCC)Br(CCCC)(CCCC)CCCC Chemical compound C(CCC)Br(CCCC)(CCCC)CCCC OKUSWAGOKUGEDX-UHFFFAOYSA-N 0.000 claims 1
- 150000002220 fluorenes Chemical class 0.000 claims 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 claims 1
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 claims 1
- RKHXQBLJXBGEKF-UHFFFAOYSA-M tetrabutylphosphanium;bromide Chemical compound [Br-].CCCC[P+](CCCC)(CCCC)CCCC RKHXQBLJXBGEKF-UHFFFAOYSA-M 0.000 claims 1
- 229920000547 conjugated polymer Polymers 0.000 abstract description 13
- 229920002098 polyfluorene Polymers 0.000 abstract description 4
- 238000010521 absorption reaction Methods 0.000 abstract 1
- 238000012377 drug delivery Methods 0.000 abstract 1
- 238000011084 recovery Methods 0.000 abstract 1
- 210000004881 tumor cell Anatomy 0.000 abstract 1
- SWLVFNYSXGMGBS-UHFFFAOYSA-N ammonium bromide Chemical compound [NH4+].[Br-] SWLVFNYSXGMGBS-UHFFFAOYSA-N 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 4
- 102100022365 NAD(P)H dehydrogenase [quinone] 1 Human genes 0.000 description 3
- 108010066657 azoreductase Proteins 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 239000004411 aluminium Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 238000003809 water extraction Methods 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 238000012644 addition polymerization Methods 0.000 description 1
- 238000004176 ammonification Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 229920000867 polyelectrolyte Polymers 0.000 description 1
- LUMVCLJFHCTMCV-UHFFFAOYSA-M potassium;hydroxide;hydrate Chemical compound O.[OH-].[K+] LUMVCLJFHCTMCV-UHFFFAOYSA-M 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000011540 sensing material Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
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- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a kind of soluble conjugated polymer tracer molecule, the material has following molecular structural formula：
Description
Technical field
The invention belongs to soluble conjugated polymer bio-sensing field, and in particular to using main chain as polyfluorene structure, side chain
The synthesis of water-soluble polymer with azo quasi-molecule and season ammonification group.
Background technology
Conductive conjugated polymer due to excellent light, electrical property and by organic electronics, biological electronics etc. lead
Domain researcher earnestly pays close attention to.Soluble conjugated polymer can be used for chemistry/life as high sensitivity fluorescence probe and sensing material
The fields such as thing sensing, biomedical imaging, medical diagnosis on disease and treatment.Soluble conjugated polymer is poly- as the special conjugation of a class
Compound is primarily referred to as the conjugated polymer that side chain contains ionic functional group or non-ionic water-soluble functional group, and it is common by tradition
The water soluble nature of the excellent photoelectric property of conjugated polymer and polyelectrolyte is combined, and it is advantageously applied to DNA, albumen
The detection of the biomolecule such as matter.
The content of the invention
Technical problem：It is an object of the invention to a kind of soluble conjugated polymer tracer material and preparation method thereof.This
Prepared material has the characteristic for absorbing main chain polyfluorene structure blue light, the spy in colon cancer tumours cell is run into invention
Determine in the case of azo reductase, azo molecules fracture, blue light recovers, and reaches the purpose of detection cancer cell.
Technical scheme：The soluble conjugated polymer tracer material of the present invention has following molecular structure：
Wherein, n is the degree of polymerization, and n is 8-12；
The 5 of side chain are the degree of polymerization of azo quasi-molecule, represent that a side chain is connected to 5 azo molecules.
The main chain of the material is made up of polyfluorene.
The side chain of the material is the molecular structure of azo.
The preparation method of soluble conjugated polymer tracer material of the present invention is：
This method is comprised the following steps that：
Compound 1：2,7- dibromo fluorenes, the positive tetrabutyl are added in two mouthfuls of round-bottomed flasks with reflux condensing tube and magneton
Ammonium bromide and 1,6- dibromo-hexanes；Finish and vacuumize the sealing of whole reaction system, be then charged with nitrogen, holding was entirely reacted
Journey is carried out in nitrogen atmosphere；The KOH aqueous solution of addition 50%, 4-5h is reacted under 90 DEG C of environment, reactant mixture is cooled down
To room temperature；Reactant mixture is neutralized to after neutrality with hydrochloric acid solution, extracted with dichloromethane, extract is dry with anhydrous sodium sulfate
It is dry；Filtering, with Rotary Evaporators depressurize precipitation, excessive 1,6-dibromo-hexane is removed with vacuum distillation；Solid crude product is mixed
Upper silica gel is using petroleum ether as cleaning solution, and residue is recrystallized to give white crystal with ethanol/methylene after decompression precipitation；
Compound 2：2,7- dibromos fluorenes and positive four fourth are added in two mouthfuls of round-bottomed flasks with reflux condensing tube and magneton
Base ammonium bromide, finishes and vacuumizes the sealing of whole reaction system, be then charged with nitrogen, keeps whole course of reaction in nitrogen atmosphere
It is middle to carry out；Solvent DMF is injected with syringe, fully after dissolving, sodium hydroxide solution, stirring are injected with syringe
30min；Place a device into and the bromo- 1- propyl alcohol of 3- is slowly added under 90 DEG C of environment, react 24 hours；Saturated common salt is used after completion of the reaction
Water and dichloromethane are extracted three times, are merged organic layer, are then dried, mix solid crude product with anhydrous sodium sulfate after suction filtration
Upper silica gel is with petroleum ether and ethyl acetate 4:1 is cleaning solution, is purified using silica gel chromatography, then organic layer is dried,
It is concentrated to give white solid product；
Compound 3：Compound 1, connection boric acid pinacol ester and potassium acetate are added in two mouthfuls of round-bottomed flasks with magneton,
And add catalyst 1, double (diphenylphosphine) ferrocene of 1'-] palladium chloride dichloromethane complex, finish whole reaction system
Sealing lucifuge is simultaneously vacuumized, and is then charged with nitrogen, keeps whole course of reaction to be carried out in nitrogen atmosphere；Place a device into 90 DEG C
Under environment, solvent DMF is injected with syringe, is reacted 24 hours；After completion of the reaction by crude product dichloromethane
Dissolving, by alumina column, removes catalyst；Extracted three times with saturated aqueous common salt and dichloromethane, merge organic layer, Ran Houyong
Anhydrous sodium sulfate is dried, and solid crude product is mixed into upper silica gel with petroleum ether and ethyl acetate 10 after suction filtration:1 is cleaning solution,
Purified using silica gel chromatography, then organic layer is dried, white solid product is concentrated to give；
Compound 4：In the polymerization pipe with magneton, compound 2 and compound 3, positive TBAB are added, and urge
Agent tetrakis triphenylphosphine palladium, finishes and whole reaction system is sealed into lucifuge and vacuumized, be then charged with nitrogen, keeps whole anti-
Process is answered to be carried out in nitrogen atmosphere；By toluene solution, solution of potassium carbonate deoxygenation processing, after extract two kinds of solution with syringe and add
In polymerization pipe, place a device under 90 DEG C of environment, react 4 days；Crude product tetrahydrofuran is dissolved after completion of the reaction, passes through oxygen
Change aluminium post, remove catalyst；Settled after being spin-dried in petroleum ether, post-consumer polymer suction filtration, drying will be settled in beaker；
Compound 5：In the single necked round bottom flask with magneton, compound 4 is added, finishes and seals whole reaction system
And vacuumize, nitrogen is then charged with, keeps whole course of reaction to be carried out in nitrogen atmosphere；Add anhydrous methylene chloride and three second
Amine, after the bromo- 2- methyl propionyl bromides of 2- are added dropwise；Place a device under 0 DEG C of environment, react 2 hours；To slightly it produce after completion of the reaction
Thing dichloromethane and water extraction；Merge organic layer, be then dried, be spin-dried for after suction filtration with anhydrous sodium sulfate, in beaker
Settled with petroleum ether, by sedimentation post-consumer polymer drying；
Compound 6：In the polymerization pipe with magneton, compound 5 is added, methyl phenyl ethers anisole, CuBr, dry ice freezing is vacuumized,
Logical nitrogen, ethanol thaws, such repetitive cycling three times；Add micro N, N, N, N, N- five methyl diethylentriamines, at 100 DEG C
Reaction 24 hours, the crude product that reaction terminates removes catalyst by neutral alundum (Al2O3), concentrates, and is 4/1V/ in methanol/water
Settled three times in V mixed liquors, the lower 40 DEG C of dryings of vacuum, you can obtain faint yellow solid；
Compound 7：In the single necked round bottom flask with magneton, compound 6 is added, tetrahydrofuran is added, at -78 DEG C
Under, slowly instill after trimethylamine, 30min, solution temperature is warmed to room temperature, after 24h, steam solvent, obtain faint yellow solid.
Beneficial effect：The present invention synthesizes a kind of soluble conjugated polymer tracer molecule by a kind of efficient method.Will
Material is dissolved in dichloromethane solution, before azo reductase is added, and no blue light is irradiated under 365nm laser, adds azo
After reductase, blue light is had under the irradiation of 365nm laser, this property can effectively detect the colon with azo reductase
Cancer cell, plays the applications well effect of cancer cell early detection.
Embodiment
A kind of soluble conjugated polymer tracer material structure of the present invention is as follows：
Wherein, n is the degree of polymerization, and n is 8-12；
The 5 of side chain are the degree of polymerization of azo quasi-molecule, represent that a side chain is connected to 5 azo molecules.
The soluble conjugated polymer tracer material preparation method of the present invention is as follows：
Compound 1：2,7- dibromo fluorenes, the positive tetrabutyl are added in two mouthfuls of round-bottomed flasks with reflux condensing tube and magneton
Ammonium bromide and 1,6- dibromo-hexanes；Finish and vacuumize the sealing of whole reaction system, be then charged with nitrogen, holding was entirely reacted
Journey is carried out in nitrogen atmosphere；The KOH aqueous solution of addition 50%, 4-5h is reacted under 90 DEG C of environment, reactant mixture is cooled down
To room temperature；Reactant mixture is neutralized to after neutrality with hydrochloric acid solution, extracted with dichloromethane, extract is dry with anhydrous sodium sulfate
It is dry；Filtering, with Rotary Evaporators depressurize precipitation, excessive 1,6-dibromo-hexane is removed with vacuum distillation；Solid crude product is mixed
Upper silica gel is using petroleum ether as cleaning solution, and residue is recrystallized to give white crystal with ethanol/methylene after decompression precipitation；
Compound 2：2,7- dibromos fluorenes and positive four fourth are added in two mouthfuls of round-bottomed flasks with reflux condensing tube and magneton
Base ammonium bromide, finishes and vacuumizes the sealing of whole reaction system, be then charged with nitrogen, keeps whole course of reaction in nitrogen atmosphere
It is middle to carry out；Solvent DMF is injected with syringe, fully after dissolving, sodium hydroxide solution, stirring are injected with syringe
30min；Place a device into and the bromo- 1- propyl alcohol of 3- is slowly added under 90 DEG C of environment, react 24 hours；Saturated common salt is used after completion of the reaction
Water and dichloromethane are extracted three times, are merged organic layer, are then dried, mix solid crude product with anhydrous sodium sulfate after suction filtration
Upper silica gel is with petroleum ether and ethyl acetate 4:1 is cleaning solution, is purified using silica gel chromatography, then organic layer is dried,
It is concentrated to give white solid product；
Compound 3：Compound 1, connection boric acid pinacol ester and potassium acetate are added in two mouthfuls of round-bottomed flasks with magneton,
And add catalyst 1, double (diphenylphosphine) ferrocene of 1'-] palladium chloride dichloromethane complex, finish whole reaction system
Sealing lucifuge is simultaneously vacuumized, and is then charged with nitrogen, keeps whole course of reaction to be carried out in nitrogen atmosphere；Place a device into 90 DEG C
Under environment, solvent DMF is injected with syringe, is reacted 24 hours；After completion of the reaction by crude product dichloromethane
Dissolving, by alumina column, removes catalyst；Extracted three times with saturated aqueous common salt and dichloromethane, merge organic layer, Ran Houyong
Anhydrous sodium sulfate is dried, and solid crude product is mixed into upper silica gel with petroleum ether and ethyl acetate 10 after suction filtration:1 is cleaning solution,
Purified using silica gel chromatography, then organic layer is dried, white solid product is concentrated to give；
Compound 4：In the polymerization pipe with magneton, compound 2 and compound 3, positive TBAB are added, and urge
Agent tetrakis triphenylphosphine palladium, finishes and whole reaction system is sealed into lucifuge and vacuumized, be then charged with nitrogen, keeps whole anti-
Process is answered to be carried out in nitrogen atmosphere；By toluene solution, solution of potassium carbonate deoxygenation processing, after extract two kinds of solution with syringe and add
In polymerization pipe, place a device under 90 DEG C of environment, react 4 days；Crude product tetrahydrofuran is dissolved after completion of the reaction, passes through oxygen
Change aluminium post, remove catalyst；Settled after being spin-dried in petroleum ether, post-consumer polymer suction filtration, drying will be settled in beaker；
Compound 5：In the single necked round bottom flask with magneton, compound 4 is added, finishes and seals whole reaction system
And vacuumize, nitrogen is then charged with, keeps whole course of reaction to be carried out in nitrogen atmosphere；Add anhydrous methylene chloride and three second
Amine, after the bromo- 2- methyl propionyl bromides of 2- are added dropwise；Place a device under 0 DEG C of environment, react 2 hours；To slightly it produce after completion of the reaction
Thing dichloromethane and water extraction；Merge organic layer, be then dried, be spin-dried for after suction filtration with anhydrous sodium sulfate, in beaker
Settled with petroleum ether, by sedimentation post-consumer polymer drying；
Compound 6：In the polymerization pipe with magneton, compound 5 is added, methyl phenyl ethers anisole, CuBr, dry ice freezing is vacuumized,
Logical nitrogen, ethanol thaws, such repetitive cycling three times；Add micro N, N, N, N, N- five methyl diethylentriamines, at 100 DEG C
Reaction 24 hours, the crude product that reaction terminates removes catalyst by neutral alundum (Al2O3), concentrates, and is 4 in first alcohol and water：1
Settled three times in mixed liquor, the lower 40 DEG C of dryings of vacuum, you can obtain faint yellow solid；
Compound 7：In the single necked round bottom flask with magneton, compound 6 is added, tetrahydrofuran is added, at -78 DEG C
Under, slowly instill after trimethylamine, 30min, solution temperature is warmed to room temperature, after 24h, steam solvent, obtain faint yellow solid.
For a better understanding of the present invention, the technical side of the present invention is further illustrated below by embodiment
Case：
Compound 1：2,7- dibromo fluorenes 9.72g are added in two mouthfuls of round-bottomed flasks with reflux condensing tube and magneton, just
TBAB 2g and 1,6- dibromo-hexane 12ml；Finish and vacuumize the sealing of whole reaction system, be then charged with nitrogen, protect
Whole course of reaction is held to carry out in nitrogen atmosphere；Add 50% KOH aqueous solution 100ml, under 90 DEG C of environment react 4-
5h, room temperature is cooled to by reactant mixture；Reactant mixture is neutralized to after neutrality with hydrochloric acid solution, extracted with dichloromethane,
Extract anhydrous sodium sulfate drying；Filtering, precipitation, excessive 1, the decompression steaming of 6-dibromo-hexane are depressurized with Rotary Evaporators
Distillation is gone；Solid crude product is mixed into upper silica gel using petroleum ether as cleaning solution, residue methanol and dichloromethane after decompression precipitation
It is recrystallized to give white crystal, i.e. compound 1, common 16.5g (yield 85%)；
Compound 2：2,7- dibromo fluorenes 9.72g and just are added in two mouthfuls of round-bottomed flasks with reflux condensing tube and magneton
TBAB 3g, finishes and vacuumizes the sealing of whole reaction system, be then charged with nitrogen, keeps whole course of reaction in nitrogen
Atmosphere encloses middle progress；Solvent DMF is injected with syringe, fully after dissolving, 50% KOH water is injected with syringe
Solution 100ml, stirs 30min；Place a device into and the bromo- 1- propyl alcohol 8ml of 3- are slowly added under 90 DEG C of environment, react 24 hours；Instead
Extracted three times with saturated aqueous common salt and dichloromethane after should finishing, merge organic layer, be then dried, taken out with anhydrous sodium sulfate
Solid crude product is mixed into upper silica gel with petroleum ether and ethyl acetate 4 after filter:1 is cleaning solution, is purified using silica gel chromatography,
Then organic layer dried, be concentrated to give white solid product, i.e. compound 2, common 9.5g (yield 72%)；
Compound 3：Compound 1 common 6.5g, connection boric acid pinacol ester 10g are added in two mouthfuls of round-bottomed flasks with magneton
With potassium acetate 3g, and catalyst 1 is added, double (diphenylphosphine) ferrocene of 1'-] palladium chloride dichloromethane complex 150mg, plus
Finish and whole reaction system is sealed into lucifuge and vacuumized, be then charged with nitrogen, keep whole course of reaction to enter in nitrogen atmosphere
OK；Place a device under 90 DEG C of environment, solvent DMF 60ml is injected with syringe, react 24 hours；React
Crude product dichloromethane is dissolved after finishing, by alumina column, catalyst is removed；Extracted with saturated aqueous common salt and dichloromethane
Three times, merge organic layer, be then dried with anhydrous sodium sulfate, after suction filtration by solid crude product mix upper silica gel with petroleum ether and
Ethyl acetate 10:1 is cleaning solution, is purified using silica gel chromatography, and then organic layer is dried, white solid is concentrated to give
Product, i.e. compound 3, common 4.68g (yield 63%)；
Compound 4：In the polymerization pipe with magneton, the common 0.88g of compound 2, the common 1.48g of compound 3, positive four fourth are added
Base ammonium bromide 2g, and catalyst tetrakis triphenylphosphine palladium 150mg, finish and whole reaction system are sealed into lucifuge and vacuumized, so
After be filled with nitrogen, keep whole course of reaction to be carried out in nitrogen atmosphere；By toluene solution, solution of potassium carbonate deoxygenation is handled, after
Extracted with syringe in two kinds of solution each 10ml, 3ml addition polymerization pipes, place a device under 90 DEG C of environment, react 4 days；React
Crude product tetrahydrofuran is dissolved after finishing, by alumina column, catalyst is removed；Settle, will be burnt in petroleum ether after being spin-dried for
Post-consumer polymer suction filtration is settled in cup, drying obtains the common 1g (yield 62%) of compound 4；
Compound 5：In the single necked round bottom flask with magneton, the common 0.8g of compound 4 is added, is finished whole reactant
System seals and vacuumized, and is then charged with nitrogen, keeps whole course of reaction to be carried out in nitrogen atmosphere；Add anhydrous methylene chloride
10ml, triethylamine 5ml, after the bromo- 2- methyl propionyl bromide 3ml of 2- are added dropwise；Place a device under 0 DEG C of environment, react 2 hours；
Crude product dichloromethane and water are extracted after completion of the reaction；Merge organic layer, be then dried with anhydrous sodium sulfate, suction filtration
After be spin-dried for, settled in beaker with petroleum ether, will sedimentation post-consumer polymer drying, obtain the common 0.6g (yield 54%) of compound 5；
Compound 6：In the polymerization pipe with magneton, compound 5 common 0.3g, methyl phenyl ethers anisole 3ml, CuBr30mg are added, is done
Shaft ice frozen, is vacuumized, and leads to nitrogen, and ethanol thaws, such repetitive cycling three times；Add micro N, N, N, N, the sub- second of N- pentamethyls two
Base triamine, reacts 24 hours at 100 DEG C, and the crude product that reaction terminates removes catalyst by neutral alundum (Al2O3), concentrates,
First alcohol and water is 4：Settled three times in 1 mixed liquor, the lower 40 DEG C of dryings of vacuum, you can obtain faint yellow solid, yield is 67%；
Compound 7：In the single necked round bottom flask with magneton, compound 6 is added, tetrahydrofuran is added, at -78 DEG C
Under, slowly instill after trimethylamine, 30min, solution temperature is warmed to room temperature, after 24h, steam solvent, obtain faint yellow solid, yield
For 71%.
Claims (4)
1. one kind conjugation water-soluble polymer tracer material, it is characterised in that the material has following molecular structural formula：
Wherein, n is the degree of polymerization, and n is 8-12；
The 5 of side chain are the degree of polymerization of azo quasi-molecule, represent that a side chain is connected to 5 azo molecules.
2. conjugation water-soluble polymer tracer material according to claim 1, it is characterised in that the main chain of the material is by gathering
Fluorenes is constituted.
3. conjugation water-soluble polymer tracer material according to claim 1, it is characterised in that the molecular side chain of the material
For the molecular structure of azo.
4. a kind of preparation method of conjugation water-soluble polymer tracer material as claimed in claim 1, it is characterised in that the party
Method comprises the following steps：
Compound 1：2,7- dibromo fluorenes, positive tetrabutyl phosphonium bromide are added in two mouthfuls of round-bottomed flasks with reflux condensing tube and magneton
Ammonium and 1,6- dibromo-hexanes；Finish and vacuumize the sealing of whole reaction system, be then charged with nitrogen, keep whole course of reaction to exist
Carried out in nitrogen atmosphere；The KOH aqueous solution of addition 50%, 4-5h is reacted under 90 DEG C of environment, reactant mixture is cooled into room
Temperature；Reactant mixture is neutralized to after neutrality with hydrochloric acid solution, extracted with dichloromethane, extract anhydrous sodium sulfate drying；
Filtering, with Rotary Evaporators depressurize precipitation, excessive 1,6-dibromo-hexane is removed with vacuum distillation；Solid crude product is mixed
Silica gel is using petroleum ether as cleaning solution, and residue is recrystallized to give white crystal with ethanol/methylene after decompression precipitation；
Compound 2：Compound 1, connection boric acid pinacol ester and potassium acetate are added in two mouthfuls of round-bottomed flasks with magneton, and is added
Enter catalyst [1,1'- double (diphenylphosphine) ferrocene] palladium chloride dichloromethane complex, finish whole reaction system is close
Envelope lucifuge is simultaneously vacuumized, and is then charged with nitrogen, keeps whole course of reaction to be carried out in nitrogen atmosphere；Place a device into 90 DEG C of rings
Under border, solvent DMF is injected with syringe, is reacted 24 hours；It is after completion of the reaction that crude product is molten with dichloromethane
Solution, by alumina column, removes catalyst；Extracted three times with saturated aqueous common salt and dichloromethane, merge organic layer, then with nothing
Aqueous sodium persulfate is dried, and solid crude product is mixed into upper silica gel with petroleum ether and ethyl acetate 10 after suction filtration:1 is cleaning solution, profit
Purified with silica gel chromatography, then organic layer is dried, white solid product is concentrated to give；
Compound 3：2,7- dibromos fluorenes and positive tetrabutyl bromine are added in two mouthfuls of round-bottomed flasks with reflux condensing tube and magneton
Change ammonium, finish and vacuumize the sealing of whole reaction system, be then charged with nitrogen, keep whole course of reaction to enter in nitrogen atmosphere
OK；Solvent DMF is injected with syringe, fully after dissolving, sodium hydroxide solution, stirring are injected with syringe
30min；Place a device into and the bromo- 1- propyl alcohol of 3- is slowly added under 90 DEG C of environment, react 24 hours；Saturated common salt is used after completion of the reaction
Water and dichloromethane are extracted three times, are merged organic layer, are then dried, mix solid crude product with anhydrous sodium sulfate after suction filtration
Upper silica gel is with petroleum ether and ethyl acetate 4:1 is cleaning solution, is purified using silica gel chromatography, then organic layer is dried,
It is concentrated to give white solid product；
Compound 4：In the polymerization pipe with magneton, compound 2 and compound 3, positive TBAB, and catalyst are added
Tetrakis triphenylphosphine palladium, is finished and whole reaction system is sealed into lucifuge and vacuumized, and is then charged with nitrogen, and holding was entirely reacted
Journey is carried out in nitrogen atmosphere；By toluene solution, solution of potassium carbonate deoxygenation processing, after extracted two kinds of solution with syringe and added and polymerize
Guan Zhong, is placed a device under 90 DEG C of environment, is reacted 4 days；Crude product tetrahydrofuran is dissolved after completion of the reaction, passes through aluminum oxide
Post, removes catalyst；Settled after being spin-dried in petroleum ether, post-consumer polymer suction filtration, drying will be settled in beaker；
Compound 5：In the single necked round bottom flask with magneton, compound 4 is added, finishes and whole reaction system is sealed and taken out
Vacuum, is then charged with nitrogen, keeps whole course of reaction to be carried out in nitrogen atmosphere；Anhydrous methylene chloride and triethylamine are added,
After the bromo- 2- methyl propionyl bromides of 2- are added dropwise；Place a device under 0 DEG C of environment, react 2 hours；After completion of the reaction by crude product
Extracted with dichloromethane and water；Merge organic layer, be then dried, be spin-dried for after suction filtration with anhydrous sodium sulfate, used in beaker
Petroleum ether is settled, by sedimentation post-consumer polymer drying；
Compound 6：In the polymerization pipe with magneton, compound 5, methyl phenyl ethers anisole, 4- methacryls amido -2 ', 3- bis- are added
Methyl- benzene, CuBr, dry ice freezing is vacuumized, and leads to nitrogen, and ethanol thaws, such repetitive cycling three times；Micro N, N are added,
N, N, N- five methyl diethylentriamine, react 24 hours at 100 DEG C, and the crude product that reaction terminates is by neutral alundum (Al2O3)
Catalyst is removed, is concentrated, is settled three times in methanol/water is 4/1V/V mixed liquors, the lower 40 DEG C of dryings of vacuum, you can obtain yellowish
Color solid；
Compound 7：In the single necked round bottom flask with magneton, compound 6 is added, tetrahydrofuran is added, at -78 DEG C, slowly
Slow to instill after trimethylamine, 30min, solution temperature is warmed to room temperature, after 24h, steams solvent, obtains faint yellow solid.
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