CN113429421A - Preparation method of organic small-molecule fluorescent probe - Google Patents
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Abstract
The invention discloses a preparation method of an organic small-molecule fluorescent probe, which constructs and prepares a fluorescent probe small molecule with a novel structure by utilizing an organic total synthesis method, and belongs to the fields of chemical sensing technology and fluorescence imaging. Compared with the existing fluorescent probe with a more researched benzo-dithiadiazole structure, the organic small-molecule fluorescent probe has the advantages of simple synthetic method, easy modification, stable structure, high fluorescence quantum yield and the like.
Description
Technical Field
The invention provides a preparation method of a novel near-infrared two-region fluorescent micromolecule, and relates to the fields of a fluorescent probe detection technology, a fluorescent imaging technology and the like.
Technical Field
Fluorescence microscopy is one of the most widely used techniques in current optical imaging, and near-infrared fluorescence living body imaging, which is also fluorescence imaging, is also receiving more and more attention in the biomedical field. Traditional fluorescence imaging is mainly focused in a near infrared region (NIR-I), the fluorescence emission wavelength range is 650-950 nm, the wavelength is short (<1000nm), the photon penetration depth is poor, and the traditional fluorescence imaging becomes a main obstacle for the application of biomedical fluorescence imaging of living bodies. Compared with visible light and NIR-I light, fluorescence imaging with the wavelength of 1000-1700 nm, namely near infrared two-region (NIR-II), can penetrate deeper biological tissues and scatter less light in the wavelength window. Due to the advantages of deeper biological tissue penetration (about 5-20 mm), reduced background autofluorescence and improved signal-to-noise ratio of NIR-II light, fluorescence imaging emerging in the NIR-II region is receiving more and more attention. The probes in NIR-II fluorescence imaging are mainly of the following classes: rare earth elements, nano materials, carbon nanotubes, quantum dots, organic molecular polymers and organic small molecular compounds.
Generally, organic near-infrared two-region fluorescent small molecules are mainly divided into three types, the first type is the near-infrared two-region fluorescent small molecules taking a benzodithiadiazole structure as a main body, the fluorescence quantum yield of the probe is high, the synthesis steps of the probe are complex, and a tin reagent with high toxicity is required for synthesis. The second type is near-infrared two-region fluorescent micromolecule taking polymethyl as a main body, mainly replaces electron-donating groups by extending near-infrared one-region cyanine dye probes, but has poor stability, is easy to decompose under illumination and has low quantum yield. The third type is to research cyanine dye, which has fluorescence tailing at 1000-1200nm, and has extremely low fluorescence quantum yield and high requirement on a test instrument.
Therefore, the near-infrared two-region fluorescent micromolecules which are high in fluorescence quantum yield, simple in synthesis process, stable in chemical structure, safe to human bodies and easy to modify are prepared, so that a near-infrared two-region fluorescent micromolecule library is further expanded, the defects of other near-infrared two-region fluorescent micromolecules in actual use are overcome, and the near-infrared two-region fluorescent micromolecules have high scientific research and clinical application values.
Disclosure of Invention
The invention provides a preparation method of a near-infrared two-region fluorescent micromolecule, and the fluorescent micromolecule prepared by the method has the advantages of high fluorescent quantum yield, simple synthesis process, stable chemical structure, safety to human bodies and easiness in modification.
In order to realize the purpose of the invention, the specific technical scheme is as follows:
a near-infrared two-region fluorescent small molecule F1 has a structure as follows:
the invention is provided with
As an electron acceptor, with
Is a pi bridge, to
For electron donor, the final construction constructed near-infrared two-zone probe:
A preparation method of an organic small molecule fluorescent probe mainly uses naphthalimide as a strong electron acceptor, uses dioxythiophene as a pi bridge to increase the stability of a fluorescent small molecule chemical structure, and uses an N, N-dimethyl styrene structure as an electron donor to construct a near-infrared two-region fluorescent small molecule with a D-pi-A system structure. The organic small-molecule fluorescent probe has the advantages of simple synthesis, stable chemical structure, easy modification, high fluorescence quantum yield and the like, and has great development potential in the fields of tumor surgical navigation imaging and medical cell marking. The method comprises the following process steps:
A. synthesis of intermediate 1
Adding N, N-dimethylformamide, 1, 8-naphthalimide and a catalyst I into a reaction kettle with stirring, heating to 105-125 ℃ under stirring, dropwise adding weighed 1, 3-dibromopropane under the protection of nitrogen, reacting for 3-6 hours under heat preservation, extracting with ethyl acetate for several times, washing the extract with saturated saline solution, adding Na2SO4Drying water, distilling off solvent and other low-boiling organic components under reduced pressure to obtain a crude product I, and separating the crude product I by a silica gel column, wherein an eluent is a mixed solution of petroleum ether and ethyl acetate to obtain an intermediate I M1 product.
B. Synthesis of intermediate bis M2
Dissolving the intermediate I M1 in ultra-dry tetrahydrofuran, heating to 45-55 ℃ in nitrogen atmosphere, then dropwise adding a methyl magnesium chloride solution, after dropwise adding, heating to 60-66 ℃, refluxing and stirring for reaction for 1-3 h, cooling the mixture to room temperature, slowly dropwise adding a diluted fluoboric acid solution, controlling the reaction speed, after the reaction is finished, filtering and drying to obtain an intermediate II M2 product.
C. Synthesis of intermediate tri M3
Adding 5-bromo-2- (3, 4-vinyldioxythiophene) formaldehyde into a xylene solution, carrying out reflux until the water content in the solution is 50-200 ppm to obtain a xylene solution of thiophenal, adding (formylmethylene) triphenylphosphine into the xylene solution, carrying out reflux until the water content in the solution is 50-200 ppm, dropwise adding the obtained solution into the xylene solution of thiophenal, and carrying out reflux reaction for 6-10 hours. And (3) evaporating the solvent under reduced pressure to obtain a second crude product, purifying the second crude product on a silica gel column by using a petroleum ether/dichloromethane mixture as an eluent to obtain a white powdery dioxythiophene intermediate product, namely the product of the tri M3.
D. Synthesis of intermediate TetraM 4
Adding a second catalyst into N, N-dimethylformamide, sequentially adding metered 4-vinyl-N, N-dimethylaniline and an intermediate III 3 under stirring, heating the mixed solution to 105-135 ℃, reacting for 20-30 hours under the protection of nitrogen gas under stirring, extracting the reaction solution with water and dichloromethane after the reaction is finished, separating the phases, and adding Na into the combined organic phase2SO4Drying and evaporation of the solvent under reduced pressure and purification of the residue by column chromatography with dichloromethane as eluent gave the intermediate tetrakis M4 product.
E. Synthesis of organic small-molecule fluorescent probe F1
And mixing the weighed intermediate II M2 and intermediate IV M4 in ethanol, adding a catalyst III, stirring for 4-12 hours under the protection of nitrogen, decompressing and evaporating the solvent after the reaction is finished, purifying the residue by column chromatography, and taking a mixed solution of dichloromethane and methanol as an eluent to obtain a final product, namely the organic small-molecule fluorescent probe F1.
Preferably, in the step A, the reaction temperature after the 1, 3-dibromopropane is dripped under the protection of nitrogen is 115-125 ℃.
Preferably, in step a, the first catalyst is one or a mixture of two or more of methylamine, dimethylamine, trimethylamine, triethylamine, lithium carbonate, potassium carbonate and the like.
Preferably, in step a, the first catalyst is a mixture of potassium carbonate and triethylamine.
Preferably, in the step C, 5-bromo-2- (3, 4-vinyldioxythiophene) formaldehyde is added into the xylene solution, and water is brought into the xylene solution by refluxing until the water content in the xylene solution is 50-80 ppm. Adding (formylmethylene) triphenylphosphine into a xylene solution, and carrying out reflux to bring water until the water content in the solution is 50-80 ppm.
Preferably, the mixed solution in the step D is heated to 115-135 ℃.
Preferably, in step D, the catalyst two is one or a mixture of two or more of triphenylphosphine, triethylamine, 3, 5-dimethylpyridine, potassium carbonate and lithium carbonate.
Preferably, in step D, the catalyst two is a mixture of triphenylphosphine and potassium carbonate.
Preferably, in step E, the catalyst iii is one or a mixture of two or more of anhydrous lithium hydroxide, lithium carbonate, potassium carbonate, and the like.
Preferably, in step E, the catalyst three is anhydrous lithium hydroxide.
The invention has the following beneficial technical effects:
1. the fluorescent small molecule can be used as a probe for NIR-II area fluorescence imaging.
2. In the structure of the organic small-molecule fluorescent probe, bromopropyl is connected as an electron donor, so that the molecular steric hindrance effect is effectively reduced, and the probe is easy to further modify.
3. The preparation method of the invention greatly simplifies the process synthesis process of the organic small-molecule fluorescent probe, shortens the preparation time of the product and improves the yield of the product.
4. The fluorescent probe is safe to human bodies, and the fluorescence quantum yield of the fluorescent probe is high.
5. In the invention, effective catalysts are used in the key steps, so that the reaction temperature is greatly reduced, the reaction time is shortened, the product yield is improved, and the energy consumption and the raw material consumption are greatly saved.
6. The near-infrared two-region fluorescent micromolecule is prepared by an organic total synthesis method, has the advantages of simple synthesis steps, easy modification, stable chemical structure, high fluorescence quantum yield and the like, and has great development potential in the fields of tumor surgical navigation imaging and medical cell marking.
Description of the drawings:
FIG. 1 is a graph of the wavelength absorption performance of the organic small molecule fluorescent probe of the present invention.
FIG. 2 is a graph of the wavelength intensity performance of the organic small molecule fluorescent probe of the present invention.
Detailed Description
In order to make the technical solutions of the present invention better understood by those skilled in the art, the present invention will be further described in detail with reference to the drawings and the detailed description of the present specification.
Example 1
A preparation method of an organic small molecule fluorescent probe comprises the following steps:
A. synthesis of intermediate 1
Adding N, N-dimethylformamide, 1, 8-naphthalimide (100.0g,0.59mol) and potassium carbonate (10g) into a reaction kettle with stirring, heating to 115 ℃ under stirring, dropwise adding weighed 1, 3-dibromopropane (240g, 1.18mol) under the protection of nitrogen, reacting for 3.5 hours under heat preservation, extracting with ethyl acetate (1000ml) twice, washing the extract with saturated saline solution, adding Na2SO4Drying water, distilling off solvent and other low-boiling organic components under reduced pressure to obtain a crude product I, and separating the crude product I by a silica gel column, wherein an eluent is petroleum ether: a mixture of ethyl acetate (1: 10) gave 157.0g (98.4%) of intermediate one M1 product in 90.1% yield.
B. Synthesis of intermediate bis M2
Dissolving the intermediate I1 (120.0g,0.41mol) in ultra-dry tetrahydrofuran, heating to 48 ℃ in nitrogen atmosphere, then dropwise adding a methyl magnesium chloride solution, heating to 66 ℃, refluxing and stirring for reaction for 2 hours, cooling the mixture to room temperature, slowly dropwise adding a diluted 10 mass percent fluoboric acid solution, controlling the reaction speed, filtering and drying after the reaction is finished, and obtaining 140g (98.2%) of the intermediate II 2 product with the yield of 91.5%.
C. Synthesis of intermediate tri M3
Adding 5-bromo-2- (3, 4-vinyldioxythiophene) formaldehyde (100.0g, 0.40mol) into a xylene solution, refluxing to bring water to the water content of 80ppm in the solution to obtain the xylene solution of thiophenal, adding (formyl methylene) triphenylphosphine (100g, 0.52mol) into the xylene solution, refluxing to bring water to the water content of 80ppm in the solution, dropwise adding the obtained solution into the xylene solution of thiophenal, and refluxing for 6-10 hours. Evaporation of the solvent under reduced pressure gave crude product two which was purified on a silica gel column using a mixture of petroleum ether/dichloromethane (2:1, v/v) as eluent to give 99.0g (95.2%) of the intermediate TriM 3 as a white powder in 85% yield.
D. Synthesis of intermediate TetraM 4
To N, N-dimethylformamide was added triphenylphosphine (10.5g), K2CO3(12.0g), metered amounts of 4-vinyl-N, N-dimethylaniline (120g, 0.82mol) and intermediate Tris 3(80g, 0.28mol) were added successively with stirring, and the mixture was heated to 118 deg.CStirring and reacting for 25 hours under the protection of nitrogen, extracting the reaction solution with water and dichloromethane after the reaction is finished, separating the phases, and combining the organic phases with Na2SO4Drying and evaporation of the solvent under reduced pressure gave 54.0g (96.1%) of intermediate tetram 4 product in 53.9% yield as a residue which was purified by column chromatography with dichloromethane as eluent.
E. Synthesis of organic small-molecule fluorescent probe F1
The weighed intermediate di M2(100g,0.27mol) and intermediate tetra M4(50g,0.14mol) are mixed in ethanol, anhydrous lithium hydroxide (120mg) is added, stirring is carried out for 4-12 hours under the protection of nitrogen, after the reaction is finished, the solvent is evaporated under reduced pressure, the residue is purified by column chromatography, and a mixed solution of dichloromethane and methanol is used as an eluent, so that 81.3g (96.3%) of the final product, namely the organic small molecule fluorescent probe F1 is obtained, and the yield is 81.2%.
As shown in FIG. 1, the fluorescence of the small organic molecule fluorescent probe F1 obtained in this example has an absorbance of 0.45 at a wavelength of 900nm, and the absorbance reaches a maximum. As shown in fig. 2, when the wavelength is 1100nm, the light intensity is 4000 and the light intensity reaches a maximum value.
Example 2
Based on embodiment 1, a method for preparing an organic small molecule fluorescent probe comprises the following steps:
A. synthesis of intermediate M1
Adding N, N-dimethylformamide, 1, 8-naphthalimide (100.0g,0.59mol) and potassium carbonate (10g) into a reaction kettle with stirring, heating to 118 ℃ under stirring, dropwise adding weighed 1, 3-dibromopropane (240g, 1.18mol) under the protection of nitrogen, reacting for 3.5 hours under heat preservation, extracting twice with ethyl acetate (1000ml), extractingThe solution was washed with saturated brine and Na was added2SO4Drying water, distilling off solvent and other low-boiling organic components under reduced pressure, and separating the crude product with silica gel column, wherein the eluent is petroleum ether: a mixture of ethyl acetate (1: 10) gave intermediate M1 product 158.5g (98.2%) in 90.9% yield.
Example 3
Based on embodiment 1, a method for preparing an organic small molecule fluorescent probe comprises the following steps:
A. synthesis of intermediate M1
Adding N, N-dimethylformamide, 1, 8-naphthalimide (100.0g,0.59mol) and potassium carbonate (10g) into a reaction kettle with stirring, heating to 120 ℃ under stirring, dropwise adding weighed 1, 3-dibromopropane (240g, 1.18mol) under the protection of nitrogen, reacting for 3.5 hours under heat preservation, extracting with ethyl acetate (1000ml) twice, washing the extract with saturated saline solution, adding Na2SO4Drying water, distilling off solvent and other low-boiling organic components under reduced pressure, and separating the crude product with silica gel column, wherein the eluent is petroleum ether: a mixture of ethyl acetate (1: 10) gave 157.2g (98.7%) of intermediate M1 product in 90.6% yield.
Example 4
Based on embodiment 2, a method for preparing an organic small molecule fluorescent probe comprises the following steps:
A. synthesis of intermediate M1
Adding N, N-dimethylformamide, 1, 8-naphthalimide (100.0g,0.59mol), potassium carbonate (10g) and triethylamine to a reaction kettle (2g) with stirring, heating to 118 ℃ under stirring, dropwise adding weighed 1, 3-dibromopropane (240g, 1.18mol) under the protection of nitrogen, reacting for 3.5 hours under heat preservation, extracting twice with ethyl acetate (1000ml), washing the extract with saturated saline solution, adding Na2SO4Drying water, distilling off solvent and other low-boiling organic components under reduced pressure, and separating the crude product with silica gel column, wherein the eluent is petroleum ether: a mixture of ethyl acetate (1: 10) gave 160.8g (98.1%) of intermediate one M1 product in 92.1% yield.
Example 5
Based on embodiment 1, a method for preparing an organic small molecule fluorescent probe comprises the following steps:
C. synthesis of intermediate tri M3
Adding 5-bromo-2- (3, 4-vinyldioxythiophene) formaldehyde (100.0g, 0.40mol) into a xylene solution, refluxing to bring water to the water content of 50ppm in the solution to obtain the xylene solution of thiophenal, adding (formyl methylene) triphenylphosphine (100g, 0.52mol) into the xylene solution, refluxing to bring water to the water content of 50ppm in the solution, dropwise adding the obtained solution into the xylene solution of thiophenal, and refluxing for 6-10 hours. The solvent was evaporated under reduced pressure and the crude product was purified on silica gel column using petroleum ether/dichloromethane (2:1, v/v) mixture as eluent to give 98.8g (95.7%) of the intermediate tri M3 product as a white powder in 85.5% yield.
Example 6
Based on embodiment 1, a method for preparing an organic small molecule fluorescent probe comprises the following steps:
D. synthesis of intermediate TetraM 4
To N, N-dimethylformamide was added triphenylphosphine (10.5g), K2CO3(12.0g) to which were added, with stirring, metered amounts of 4-vinyl-N, N-dimethylaniline (120g, 0.82mol) and intermediate Tris 3(80g, 0.28mol) in that order, the mixture was heated to 120 ℃ and reacted with stirring under nitrogen protection for 25 hours, after completion of the reaction, the reaction solution was extracted with water and dichloromethane, the phases were separated and the combined organic phases were freed from Na2SO4Drying and evaporation of the solvent under reduced pressure gave 54.7g (96.5%) of intermediate tetram 4 product in 54.8% yield by column chromatography with dichloromethane as eluent.
Example 7
Based on embodiment 1, a method for preparing an organic small molecule fluorescent probe comprises the following steps:
D. synthesis of intermediate TetraM 4
To N, N-dimethylformamide was added triphenylphosphine (10.5g), K2CO3(12.0g) 4-ethylene was added in metered amounts in succession with stirringo-N, N-dimethylaniline (120g, 0.82mol) and intermediate Tris 3(80g, 0.28mol), then heating the mixed solution to 130 ℃ and stirring under nitrogen protection for 25 hours, after the reaction is finished, extracting the reaction solution with water and dichloromethane, separating the phases, and combining the organic phases with Na2SO4Drying and evaporation of the solvent under reduced pressure gave 54.2g (96.0%) of intermediate tetram 4 product in 54.0% yield by column chromatography with dichloromethane as eluent.
Example 7
Based on embodiment 1, a method for preparing an organic small molecule fluorescent probe comprises the following steps:
D. synthesis of intermediate TetraM 4
Triphenylphosphine (20.5g) was added to N, N-dimethylformamide, and metered amounts of 4-vinyl-N, N-dimethylaniline (120g, 0.82mol) and intermediate Tris 3(80g, 0.28mol) were added successively with stirring, and then the mixed solution was heated to 130 ℃ and stirred under nitrogen protection for 25 hours, after the reaction was completed, the reaction solution was extracted with water and dichloromethane, the phases were separated, and the combined organic phases were extracted with Na2SO4Drying and evaporation of the solvent under reduced pressure gave 54.0g (96.3%) of intermediate tetram 4 product in 54.0% yield by column chromatography with dichloromethane as eluent.
Example 8
Based on embodiment 1, a method for preparing an organic small molecule fluorescent probe comprises the following steps:
E. synthesis of organic small-molecule fluorescent probe F1
The weighed intermediate di M2(100g,0.27mol) and intermediate tetra M4(50g,0.14mol) were mixed in ethanol, anhydrous lithium hydroxide (100mg) and lithium carbonate (100mg) were added, the mixture was stirred under nitrogen for 4 to 12 hours, after the reaction was completed, the solvent was evaporated under reduced pressure, the residue was purified by column chromatography, and a mixture of dichloromethane and methanol was used as an eluent, to obtain 80.0g (96.1%) of the final product, organic small molecule fluorescent probe F1, with a yield of 79.7%.
Compared with the existing near-infrared two-region fluorescent probe with a frequently-researched benzodithiadiazole structure, the organic small-molecule fluorescent probe has the advantages of simple synthesis method, easiness in modification, stable structure, high fluorescence quantum yield and the like, is expected to be further modified, develops a novel near-infrared two-region probe with more excellent water solubility and optical property, and provides a novel probe family for the research of the near-infrared two-region probe in the fields of tumor surgery navigation imaging and medical cell marking.
The above description is only of the preferred embodiments of the present invention, and it should be noted that: it will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the principles of the invention and these are intended to be within the scope of the invention.
Claims (10)
1. A preparation method of an organic small molecule fluorescent probe is characterized by comprising the following steps: the method comprises the following steps:
A. synthesis of intermediate M1
Adding N, N-dimethylformamide, 1, 8-naphthalimide and a catalyst I into a reaction kettle with stirring, heating to 105-125 ℃ under stirring, dropwise adding 1, 3-dibromopropane under the protection of nitrogen, reacting for 3-6 hours under heat preservation, extracting with ethyl acetate for several times, washing the extract with saturated saline water, adding Na2SO4Drying water, distilling under reduced pressure to obtain a first crude product, performing silica gel column separation on the first crude product, wherein an eluent is a mixed solution of petroleum ether and ethyl acetate to obtain an intermediate M1;
B. synthesis of intermediate bis M2
Dissolving the intermediate I M1 in ultra-dry tetrahydrofuran, heating to 45-55 ℃ in a nitrogen atmosphere, then dropwise adding a methyl magnesium chloride solution, after dropwise adding, heating to 60-66 ℃, refluxing and stirring for reaction for 1-3 hours, cooling the mixture to room temperature, dropwise adding a diluted fluoboric acid solution, controlling the reaction speed, after the reaction is finished, filtering and drying to obtain an intermediate II M2;
C. synthesis of intermediate tri M3
Adding 5-bromo-2- (3, 4-vinyldioxythiophene) formaldehyde into a xylene solution, carrying out reflux to bring water to the water content of the solution of 50-200 ppm to obtain a xylene solution of thiophenal, (formyl methylene) triphenylphosphine is added into the xylene solution, carrying out reflux to bring water to the water content of the solution of 50-200 ppm, dropwise adding the obtained solution into the xylene solution of thiophenal, and carrying out reflux reaction for 6-10 hours; evaporating the solvent under reduced pressure to obtain a second crude product, purifying the second crude product on a silica gel column, and using a petroleum ether/dichloromethane mixture as an eluent to obtain a white powdery dioxythiophene intermediate tri M3;
D. synthesis of intermediate TetraM 4
Adding a second catalyst into N, N-dimethylformamide, sequentially adding 4-vinyl-N, N-dimethylaniline and an intermediate III M3 under stirring, heating the mixed solution to 105-135 ℃, reacting for 20-30 hours under the protection of nitrogen gas under stirring, extracting the reaction solution with water and dichloromethane after the reaction is finished, separating the phases, and adding Na into the combined organic phase2SO4Drying and evaporating the solvent under reduced pressure and purifying the residue by column chromatography with dichloromethane as eluent to give intermediate tetra M4;
E. synthesis of organic small-molecule fluorescent probe F1
Mixing the intermediate II 2 and the intermediate IV 4 in ethanol, adding a catalyst III, stirring for 4-12 hours under the protection of nitrogen, evaporating the solvent under reduced pressure after the reaction is finished, purifying the residue by column chromatography, and taking the mixed solution of dichloromethane and methanol as an eluent to obtain an organic small-molecule fluorescent probe F1:
2. the method for preparing the organic small molecule fluorescent probe according to claim 1, wherein the method comprises the following steps: in the step A, the reaction temperature after 1, 3-dibromopropane is dripped under the protection of nitrogen is 115-125 ℃.
3. The method for preparing the organic small molecule fluorescent probe according to claim 1, wherein the method comprises the following steps: in the step A, the catalyst I is one or a mixture of more than two of methylamine, dimethylamine, trimethylamine, triethylamine, lithium carbonate, potassium carbonate and the like.
4. The method for preparing the organic small molecule fluorescent probe according to claim 1, wherein the method comprises the following steps: in step a, the first catalyst is a mixture of potassium carbonate and triethylamine.
5. The method for preparing the organic small molecule fluorescent probe according to claim 1, wherein the method comprises the following steps: in the step C, adding 5-bromo-2- (3, 4-vinyl dioxythiophene) formaldehyde into a xylene solution, and carrying out reflux to bring water until the water content in the solution is 50-80 ppm; adding (formylmethylene) triphenylphosphine into a xylene solution, and carrying out reflux to bring water until the water content in the solution is 50-80 ppm.
6. The method for preparing the organic small molecule fluorescent probe according to claim 1, wherein the method comprises the following steps: and D, heating the mixed solution to 115-135 ℃.
7. The method for preparing the organic small molecule fluorescent probe according to claim 1, wherein the method comprises the following steps: in the step D, the catalyst II is one or a mixture of more than two of triphenylphosphine, triethylamine, 3, 5-dimethylpyridine, potassium carbonate and lithium carbonate.
8. The method for preparing the organic small molecule fluorescent probe according to claim 1, wherein the method comprises the following steps: in step D, the second catalyst is a mixture of triphenylphosphine and potassium carbonate.
9. The method for preparing the organic small molecule fluorescent probe according to claim 1, wherein the method comprises the following steps: in the step E, the catalyst III is one or a mixture of more than two of anhydrous lithium hydroxide, lithium carbonate, potassium carbonate and the like.
10. The method for preparing the organic small molecule fluorescent probe according to claim 1, wherein the method comprises the following steps: in step E, the catalyst three is anhydrous lithium hydroxide.
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| CN114539232A (en) * | 2022-01-26 | 2022-05-27 | 深圳大学 | pH reversible activation near-infrared two-region aggregation-induced emission I type photosensitizer and application thereof |
| CN114634499A (en) * | 2022-02-14 | 2022-06-17 | 深圳大学 | Aggregation-induced emission material and preparation method and application thereof |
| WO2023010925A1 (en) * | 2021-08-03 | 2023-02-09 | 南京诺源医疗器械有限公司 | Method for preparing second near-infrared region fluorescent micromolecules |
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| CN111334066A (en) * | 2018-12-18 | 2020-06-26 | 中国科学院大连化学物理研究所 | 640nm excited near-infrared fluorescent dye and preparation method thereof |
| CN111961040A (en) * | 2020-09-03 | 2020-11-20 | 山东大学 | Carbazolyl-based organic diheterocyclic near-infrared fluorescent probe and preparation method and application thereof |
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| CN111334066A (en) * | 2018-12-18 | 2020-06-26 | 中国科学院大连化学物理研究所 | 640nm excited near-infrared fluorescent dye and preparation method thereof |
| CN111961040A (en) * | 2020-09-03 | 2020-11-20 | 山东大学 | Carbazolyl-based organic diheterocyclic near-infrared fluorescent probe and preparation method and application thereof |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2023010925A1 (en) * | 2021-08-03 | 2023-02-09 | 南京诺源医疗器械有限公司 | Method for preparing second near-infrared region fluorescent micromolecules |
| CN114539232A (en) * | 2022-01-26 | 2022-05-27 | 深圳大学 | pH reversible activation near-infrared two-region aggregation-induced emission I type photosensitizer and application thereof |
| CN114539232B (en) * | 2022-01-26 | 2023-04-28 | 深圳大学 | PH reversible activated near infrared two-region aggregation-induced emission type I photosensitizer and application thereof |
| CN114634499A (en) * | 2022-02-14 | 2022-06-17 | 深圳大学 | Aggregation-induced emission material and preparation method and application thereof |
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