CN113234097A - tBu-azaBODIPY photo-thermal dye and preparation method thereof - Google Patents
tBu-azaBODIPY photo-thermal dye and preparation method thereof Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 238000006243 chemical reaction Methods 0.000 claims abstract description 39
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 61
- 150000001875 compounds Chemical class 0.000 claims description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
- 239000007787 solid Substances 0.000 claims description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- 238000001914 filtration Methods 0.000 claims description 10
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 9
- FJJYHTVHBVXEEQ-UHFFFAOYSA-N 2,2-dimethylpropanal Chemical compound CC(C)(C)C=O FJJYHTVHBVXEEQ-UHFFFAOYSA-N 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 7
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 6
- 239000005695 Ammonium acetate Substances 0.000 claims description 6
- 229940043376 ammonium acetate Drugs 0.000 claims description 6
- 235000019257 ammonium acetate Nutrition 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 239000011259 mixed solution Substances 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 238000000967 suction filtration Methods 0.000 claims description 6
- 239000012043 crude product Substances 0.000 claims description 5
- 239000012153 distilled water Substances 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 5
- 239000012074 organic phase Substances 0.000 claims description 5
- 238000002390 rotary evaporation Methods 0.000 claims description 5
- 239000000243 solution Substances 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 4
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 4
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 4
- 101001018064 Homo sapiens Lysosomal-trafficking regulator Proteins 0.000 claims description 3
- 102100033472 Lysosomal-trafficking regulator Human genes 0.000 claims description 3
- 235000010703 Modiola caroliniana Nutrition 0.000 claims description 3
- 244000038561 Modiola caroliniana Species 0.000 claims description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000010791 quenching Methods 0.000 claims description 2
- 230000000171 quenching effect Effects 0.000 claims description 2
- 239000000975 dye Substances 0.000 abstract description 45
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 abstract description 7
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 abstract description 5
- 238000011160 research Methods 0.000 abstract description 5
- 239000000463 material Substances 0.000 abstract description 4
- 241000425347 Phyla <beetle> Species 0.000 abstract description 3
- 238000011161 development Methods 0.000 abstract description 3
- 230000003595 spectral effect Effects 0.000 abstract description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 230000007704 transition Effects 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 238000002189 fluorescence spectrum Methods 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- OVTCUIZCVUGJHS-UHFFFAOYSA-N dipyrrin Chemical compound C=1C=CNC=1C=C1C=CC=N1 OVTCUIZCVUGJHS-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000002096 quantum dot Substances 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000007669 thermal treatment Methods 0.000 description 1
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/022—Boron compounds without C-boron linkages
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B57/00—Other synthetic dyes of known constitution
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Abstract
A tBu-azaBODIPY photo-thermal dye and a preparation method thereof relate to a photo-thermal dye and a preparation method thereof, and the general formula of the dye is shown as formula I:
Description
Technical Field
The invention relates to a photothermal dye and a preparation method thereof, in particular to a tBu-azaBODIPY photothermal dye and a preparation method thereof.
Background
Among the numerous dyes, azafluorodipyrromethene (BF)2Azadipyrromethene, azaBODIPY for short) dyes have been used in recent yearsThe absorption and emission wavelengths of the novel near-infrared fluorescent dye are positioned in a visible-near infrared region, and the novel near-infrared fluorescent dye is easy to regulate and control and is widely researched. The quantum dot has the characteristics of narrow half-peak width, high quantum yield, large molar extinction coefficient and the like, has wide application prospect in the fields of biology, medicine, materials and the like, and has become a hotspot of research in recent years. However, the modification of the molecule is difficult, and the molecular structure is single.
In recent years, azafluorodipyrromethene has been extensively developed, and systematic studies by O' shear group, Jiano group and Jiang group have been carried out ((R))Chem. Soc. Rev., 2016, 45, 3846-3864). However, the 1, 7-positions in the parent nucleus structure of azaBODIPY are all aryl substituted (Chem. Soc. Rev., 2020, 49, 7533-7567)。
To date, there has been no report on the structure of 1, 7-tert-butyl substituted azafluorodipyrromethene.
Disclosure of Invention
The invention aims to provide a tBu-azaBODIPY photothermal dye and a preparation method thereof, and the invention develops a novel 1, 7-tert-butyl substituted dye tBu--azaBODIPY. The tBu-azaBODIPY dye is further applied to the development of biological and material research, provides a novel dye and enriches the phyla of dye families. As a novel tBu-azaBODIPY dye, the non-radiative transition is beneficial to photothermal conversion, and the photothermal conversion and singlet oxygen generation are higher in efficiency, good in water solubility and good in stability than those of the traditional Ar-azaBODIPY dye in addition to the advantages of the spectral performance of the classical traditional Ar-azaBODIPY dye and the like.
The purpose of the invention is realized by the following technical scheme:
a tBu-azaBODIPY photothermal dye, which has a general formula shown in formula I:
in formula I, Ar is selected from Ar1、Ar2、Ar3、Ar4、Ar5、Ar6、Ar7、Ar8、Ar9And Ar10An aryl group;
a preparation method of tBu-azaBODIPY photo-thermal dye comprises the following preparation steps:
(1) compound M3: adding arylethanone M2 and potassium hydroxide into a single-neck round-bottom flask, adding an ethanol/water solution into the system, adding trimethylacetaldehyde M1, and stirring at room temperature for 24 hours; after the reaction is finished, filtering, and recrystallizing the obtained solid by using ethanol to obtain a light white solid compound M3;
ar in M2 is selected from Ar1-Ar10A group; ar in M3 is selected from Ar1-Ar10A group;
(2) compound M4: adding a compound M3 into a reaction bottle, adding dry methanol to dissolve the compound, adding nitromethane and triethylamine into the system, and heating and refluxing for 6 hours; after the reaction is finished, cooling and standing the reaction system to room temperature, acidifying the reaction system to weak acidity by using hydrochloric acid, extracting the reaction system by using dichloromethane/distilled water, drying an organic phase by using anhydrous MgSO4, filtering out solids, and removing the solvent from the filtrate by using a rotary evaporator through rotary evaporation to obtain a crude product; recrystallizing with dichloromethane and anhydrous ether, filtering, and washing with cold ether to obtain white solid compound M4;
ar in M4 is selected from Ar1-Ar10A group;
(3) compound M5: the compound M4 and ammonium acetate were added to a reaction flask, and ethanol was added to dissolve it, followed by heating and refluxing for 48 hours. Cooling the system to room temperature, performing suction filtration, and washing with ethanol to obtain mauve solid compound M5;
ar in M5 is selected from Ar1-Ar10A group;
(4) dissolving the solid M5 obtained in the step (3) in dichloromethane, then adding triethylamine, and reacting for 0.5 h; finally, adding boron trifluoride diethyl etherate to react for 3 hours; and quenching the reaction mixed solution by using ice, extracting by using dichloromethane, distilling under reduced pressure, purifying the residue by using a silica gel column, wherein a developing agent is dichloromethane/n-hexane, and obtaining a dark blue solid I.
The invention has the advantages and effects that:
1. the invention introduces a novel strategic design, and develops a novel 1, 7-tertiary butyl substituted dye tBu--azaBODIPY. The tBu-azaBODIPY dye is further applied to the development of biological and material research, provides a novel dye and enriches the phyla of dye families. As a novel tBu-azaBODIPY dye, the non-radiative transition is beneficial to photothermal conversion, and the photothermal conversion and singlet oxygen generation are higher in efficiency, good in water solubility and good in stability than those of the traditional Ar-azaBODIPY dye in addition to the advantages of the spectral performance of the classical traditional Ar-azaBODIPY dye and the like.
2. The dye has high photo-thermal conversion efficiency and can be applied to the field of photo-thermal treatment. Meanwhile, the dye has excellent water solubility, high singlet oxygen generation efficiency and cell membrane permeability, and can be applied to research on tumor photothermal-photodynamic therapy.
3. The tBu-azaBODIPY photothermal dye has the following characteristics:
the compound is mainly characterized in that the 1, 7-tert-butyl substituted aza-fluoro-boron dipyrromethene azaBODIPY dye structure is a breakthrough of the traditional classical Ar-azaBODIPY structure.
The compound of the invention has non-radiative transition, which is beneficial to photo-thermal conversion, and has high photo-thermal conversion and singlet oxygen generation efficiency, good water solubility and good stability.
The compound of the invention has the advantages of easily obtained raw materials, novel structure, easy preparation and easy industrialization, and can obtain the target compound through 4 steps of reaction.
Drawings
FIG. 1 is a structural formula I-1 of the novel photothermal dye of the present invention;
FIG. 2 is a hydrogen spectrum of structural formula I-1 of the novel photothermal dye of the present invention;
FIG. 3 is a carbon spectrum of structural formula I-1 of the novel photothermal dye of the present invention;
FIG. 4 shows the absorption spectrum of structural formula I-1 of the novel photothermal dye of the present invention: (λ abs = 620 nm in CH2Cl2);
FIG. 5 shows fluorescence spectra of structural formula I-1 of the novel photothermal dye of the present invention: (λ em = 650 nm in CH2Cl2);
FIG. 6 shows the photothermal dye I-1 in CH according to the present invention2Cl2Color in solution;
FIG. 7 is a crystal structure of the novel photothermal dye I-2 of the present invention;
FIG. 8 is a comparative photo-thermal conversion plot of the novel photo-thermal dyes of the present invention I-2, I-3 and the conventional aza-BODIPY.
Detailed Description
The present invention will be described in detail with reference to the embodiments shown in the drawings.
Unless otherwise indicated, the terms used herein have the following meanings.
Wherein, in the general formula I of the invention, Ar is selected from the Ar1-Ar10The radical, preferably Ph.
The invention provides a method for preparing the photothermal dye, which comprises the steps of firstly preparing M3, secondly preparing M4, then preparing a precursor M5, and finally complexing boron trifluoride diethyl etherate to obtain the novel 1, 7-tert-butyl substituted tBu-aza BODIPY. The specific embodiment is as follows:
(1) compound M3: arylethanone M2 and potassium hydroxide were added to a single-neck round-bottom flask, and an ethanol/water solution was added to the system, followed by trimethylacetaldehyde M1, followed by stirring at room temperature overnight. In the reaction process, a product is precipitated from the mixed solution, after the reaction is finished, the product is filtered, and the solid obtained by filtering is recrystallized by ethanol to obtain a light white solid compound M3;
the reaction time is 3-24 hours. The molar ratio of the corresponding aldehyde to the corresponding ketone charged was 1.2: 1.
(2) Compound M4: adding the compound M3 into a reaction bottle, adding dry methanol to dissolve the compound, adding nitromethane and diethylamine into the system, and heating and refluxing for 6 h. After the reaction is finished, cooling and standing the reaction system to room temperature, acidifying with hydrochloric acid to weak acidity, extracting the mixed solution with dichloromethane/distilled water, drying the organic phase with anhydrous MgSO4, filtering to remove solids, removing the solvent from the filtrate by rotary evaporation with a rotary evaporator to obtain a crude product, recrystallizing with dichloromethane and anhydrous ether, performing suction filtration, and washing with cold ether to obtain a white solid compound M4;
in a preferred embodiment, the reaction temperature is 80 ℃. The reaction time is 4-8 hours.
(3) Compound M5: adding the compound M4 and ammonium acetate into a reaction bottle, adding ethanol for dissolving, heating and refluxing for 24 h, cooling the system to room temperature, performing suction filtration, and washing with ethanol to obtain a mauve solid compound M5.
The molar ratio of M4 to ammonium acetate fed was 1: 20. It is important to emphasize that the ammonium acetate must be in excess or not reacted.
(4) The solid M5 obtained in step (3) was dissolved in dichloromethane, and triethylamine was added thereto to react for half an hour. Finally, boron trifluoride ethyl ether was added to the reaction mixture to react for 3 hours. The mixture was quenched with ice. Extracting with dichloromethane, distilling under reduced pressure, and purifying the residue with silica gel column to obtain solid I of black blue.
For the above compounds of the invention, NMR spectra were taken including1H, 13C NMR nuclear magnetic spectrum, absorption spectrum, fluorescence spectrum, mass spectrum, etc.
Example 1
Preparation of novel 1, 7-tert-butyl substituted tBu-aza-BODIPY photothermal dye I-1
(1) And (3) synthesizing 1, 7-tert-butyl substituted tBu-azaBODIPY photothermal dye I-1.
(2) Compound M3-1: acetophenone M2-1 (1.00 g, 8.3 mmol) and potassium hydroxide (0.93 g, 16.6 mmol) were added to a single-neck round-bottom flask, an ethanol/water solution (85: 15= v/v, 100 mL) was added to the system, and trimethylacetaldehyde M1-1 (1.43 g, 16.6 mmol) was added thereto, and stirred at room temperature for 24 hours, during which the product precipitated from the mixed solution, after completion of the reaction, the mixed solution was filtered, and the resulting solid was filtered and recrystallized from ethanol to give compound M3-1 (1.02 mg, 65%) as a pale white solid.
(3) Compound M4-1: compound M3-1 (1.02 g, 5.4 mmol) was weighed into a reaction flask, 100 mL of dry methanol was added to dissolve it, nitromethane (659.2 mg, 10.8 mmol) and triethylamine (2.19 g, 21.6 mmol) were added to the system, and the mixture was refluxed for 24 hours. After the reaction was completed, the reaction system was cooled and allowed to stand at room temperature, acidified to weak acidity with 1 mol/L hydrochloric acid, the mixture was extracted with dichloromethane/distilled water, the organic phase was dried over anhydrous MgSO4, the solid was filtered off by filtration, the filtrate was subjected to rotary evaporation with a rotary evaporator to remove most of the solvent to give a crude product, which was recrystallized with dichloromethane and anhydrous ether, subjected to suction filtration and washed with cold ether to give compound M4-1 (783 mg, 58%) as a white solid.
(4) Compound M4-1 (783 mg, 3.14 mmol) and ammonium acetate (4.8 g, 62.8 mmol) were weighed into a reaction flask, 60 mL of evaporated ethanol was added to dissolve, heated under reflux for 48 h, after the starting materials had reacted completely, the system was cooled to room temperature, filtered under suction, and washed with cold ethanol to give a magenta solid compound M5-1 (0.20 g, 31%).
(5) Compound I-1 Compound M5-1 (0.20 g, 0.49 mmol) was weighed into a reaction flask, vacuum-pumped, nitrogen-replaced, 50 mL of methylene chloride was added as a solvent, triethylamine (98.8 mg, 0.98 mmol) was added thereto and stirred for 30 min, boron trifluoride diethyl etherate (277.2 mg, 1.95 mmol) was added thereto and stirred for 12 h. Extracting the mixture with dichloromethane/distilled water, and extracting the organic phase with anhydrous MgSO4Drying, filtration to remove the solid, rotary evaporation of the filtrate with a rotary evaporator to remove most of the solvent to give the crude product, recrystallization with dichloromethane and anhydrous ether, suction filtration, and washing with cold ether to give a blue-green solid (134.5 mg, 60.2%).1H NMR (500 MHz, CDCl3):δ(ppm) 7.46 (d, 3J = 7.5 Hz, 4H), 7.35 (t, 3J = 7.5 Hz, 4H), 7.19 (t, 3J = 7.5 Hz, 2H), 6.65 (s, 2H), 1.31 (s, 18H)。 13C NMR (125 MHz, CDCl3): δ 137.5, 133.1, 131.9, 128.9, 126.1, 123.7, 113.9, 104.2, 31.8, 30.7. HRMS (ESI) m/z calcd for C28H30BF2N3Na+ (M+Na)+ 480.23931, found 480.23944.
The foregoing is a more detailed description of the invention in connection with specific preferred embodiments and it is not intended that the invention be limited to the specific details set forth herein. For those skilled in the art to which the invention pertains, a number of simple deductions and substitutions can be made on the premise of the core concept of the invention, and all should be considered as belonging to the protection scope of the invention. As a person of ordinary skill in the art to which the invention pertains, numerous and simple inferences can be made based on the present invention to find other applications of the compounds of the present invention, which are considered to fall within the scope of the present invention.
Claims (2)
2. a preparation method of tBu-azaBODIPY photo-thermal dye is characterized by comprising the following preparation steps:
(1) compound M3: adding arylethanone M2 and potassium hydroxide into a single-neck round-bottom flask, adding an ethanol/water solution into the system, adding trimethylacetaldehyde M1, and stirring at room temperature for 24 hours; after the reaction is finished, filtering, and recrystallizing the obtained solid by using ethanol to obtain a light white solid compound M3;
ar in M2 is selected from Ar1-Ar10A group; ar in M3 is selected from Ar1-Ar10A group;
(2) compound M4: adding a compound M3 into a reaction bottle, adding dry methanol to dissolve the compound, adding nitromethane and triethylamine into the system, and heating and refluxing for 6 hours; after the reaction is finished, cooling and standing the reaction system to room temperature, acidifying the reaction system to weak acidity by using hydrochloric acid, extracting the reaction system by using dichloromethane/distilled water, drying an organic phase by using anhydrous MgSO4, filtering out solids, and removing the solvent from the filtrate by using a rotary evaporator through rotary evaporation to obtain a crude product; recrystallizing with dichloromethane and anhydrous ether, filtering, and washing with cold ether to obtain white solid compound M4;
ar in M4 is selected from Ar1-Ar10A group;
(3) compound M5: adding the compound M4 and ammonium acetate into a reaction bottle, adding ethanol for dissolving, and heating and refluxing for 48 h;
cooling the system to room temperature, performing suction filtration, and washing with ethanol to obtain mauve solid compound M5;
ar in M5 is selected from Ar1-Ar10A group;
(4) dissolving the solid M5 obtained in the step (3) in dichloromethane, then adding triethylamine, and reacting for 0.5 h; finally, adding boron trifluoride diethyl etherate to react for 3 hours; and quenching the reaction mixed solution by using ice, extracting by using dichloromethane, distilling under reduced pressure, purifying the residue by using a silica gel column, wherein a developing agent is dichloromethane/n-hexane, and obtaining a dark blue solid I.
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CN116813654B (en) * | 2023-08-25 | 2023-12-01 | 苏州纳微生命科技有限公司 | Fluorescent dye, magnetic fluorescent coding microsphere, and preparation method and application thereof |
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