Organic small-molecule fluorescent dye with asymmetric structure and synthesis method of organic small-molecule fluorescent dye
By designing asymmetric organic small molecule fluorescent dyes, the problem of insufficient emission wavelength of zeatan dyes has been solved, enabling their application in biomedical imaging. A simple and efficient synthesis method has also been provided, improving the purity and yield of the dyes.
Patent Information
- Application Number
- CN202511510165.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-22
- Publication Date
- 2026-01-16
AI Technical Summary
Existing zeatane dyes mostly emit wavelengths below 800 nm, limiting their application in biological fields such as in vivo imaging. Furthermore, their synthesis is complex, and their purity and yield are difficult to control.
Asymmetric organic small molecule fluorescent dyes were designed, and dyes with larger conjugated systems were prepared through synthetic routes including amination, alkylation, aldehydeation, coupling, lithium-aldehyde reaction, intramolecular dehydration and oxidation, providing more modification sites.
The fluorescence emission wavelength exceeds 800 nm, exhibiting excellent fluorescence performance. The dye is widely used in the field of biomedical imaging. The synthesis method is simple to operate, the product has high purity, and the yield is stable.
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Figure CN121342837A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the biomedical technology field, and in particular to a kind of organic small molecule fluorescent dye of asymmetric structure and synthesis method thereof. BACKGROUND
[0002] In recent years, due to the strong tissue penetration, weak tissue scattering, low tissue absorption and other advantages, the near-infrared organic small molecule fluorescent dye with emission wavelength exceeding 800 nm has been widely concerned in the field of biomedical imaging, especially showing important application value in vivo imaging and surgical navigation. Therefore, it is an urgent need to develop the near-infrared organic small molecule fluorescent dye with emission wavelength exceeding 800 nm.
[0003] Among the numerous fluorescent dye nuclei, xanthene dyes are widely used due to their high molar extinction coefficient, high fluorescence quantum yield, good stability and easy modification. However, the currently reported xanthene dyes have an emission wavelength mostly less than 800 nm, although they have high brightness, but still have certain limitations in biological applications such as in vivo imaging, so it is particularly urgent to develop xanthene dyes with emission wavelength exceeding 800 nm. At present, the synthesis of long-wavelength xanthene dyes still faces problems such as complex operation, difficult control of purity and yield, etc. Therefore, it is urgent to develop a simple and stable synthetic method. SUMMARY
[0004] The technical problem to be solved by the present application is to provide a kind of organic small molecule fluorescent dye of asymmetric structure and synthesis method thereof, the organic small molecule fluorescent dye has a larger conjugated system, the design of asymmetric structure makes it have more modification sites, which can meet the targeting demand of complex biological system;The synthesis method has the advantages of mild reaction condition, high product purity and stable yield.
[0005] To solve the above technical problems, the present application first discloses a kind of organic small molecule fluorescent dye of asymmetric structure, the organic small molecule fluorescent dye of asymmetric structure has the structure general formula of formula 1 or formula 1-1:
[0006]
[0007] Wherein, R1, R2 are each independently selected from cycloalkyl or alkyl, the alkyl contains 1-6 carbon atoms, and the cycloalkyl contains 3-6 carbon atoms;R3, R4 are each independently selected from one of cycloalkyl, alkyl, ether bond, halogen, alkoxy, carboxyl, sulfonate, the cycloalkyl contains 3-6 carbon atoms, and the alkyl and alkoxy both contain 1-2 carbon atoms;R5 is methyl.
[0008] The application further discloses a synthesis method of the asymmetric structure organic small-molecule fluorescent dye.
[0009]
[0010] (I)
[0011]
[0012] (II)
[0013] comprising the following steps:
[0014] S1: aminoalkylation of 7-bromo-2-hydroxynaphthalene and sodium pyrosulfite in ammonia water to obtain a compound shown in formula 2.
[0015] S2: alkylation of the compound shown in formula 2 prepared in S1 with an alkylating agent in a solvent to obtain a compound shown in formula 3, wherein the solvent is N, N-dimethylformamide.
[0016] S3: aldehyde group reaction of the compound shown in formula 3 prepared in S2 with a formylating agent (Vilsmeier-haack reagent) in a solvent to obtain a compound shown in formula 4, wherein the solvent is 1,2-dichloroethane.
[0017] S4: coupling reaction of the compound shown in formula 4 prepared in S3, a coupling reagent and a catalyst in a solvent to obtain a compound shown in formula 5, wherein the solvent is anhydrous N, N-dimethylformamide.
[0018] S5: lithium aldehyde reaction of the compound shown in formula 5 prepared in S4 with a nucleophile in a solvent to obtain a compound shown in formula 6, wherein the solvent is anhydrous tetrahydrofuran.
[0019] S6: intramolecular dehydration reaction of the compound shown in formula 6 prepared in S5 with an acid catalyst in a solvent to obtain a compound shown in formula 7, wherein the solvent is dichloromethane.
[0020] S7: oxidation reaction of the compound shown in formula 7 prepared in S6 with an oxidizing agent in a solvent to obtain the asymmetric structure organic small-molecule fluorescent dye shown in formula 1, wherein the solvent is dichloromethane.
[0021] Further, the molar ratio of 7-bromo-2-hydroxynaphthalene, sodium pyrosulfite and ammonia (ammonia in ammonia water) in S1 is 1:1.2:4-5, the temperature of the aminoalkylation reaction is 150-155 DEG C, and the time is 40-48 h.
[0022] Further, the alkylating agent in S2 is a halogenated alkyl compound, the molar ratio of the compound of formula 2 to the alkylating agent is 1:1.2-1.5, the temperature of the alkylating reaction is 160℃, and the reaction time is 24h.
[0023] Further, the formylating agent in S3 is prepared from phosphorus oxychloride and N,N-dimethylformamide, the molar ratio of the compound of formula 3 to the formylating agent is 1:4-6, the temperature of the aldehyde group reaction is 90-95℃, and the reaction time is 3-4.5h.
[0024] Further, the coupling agent in S4 is 7-diethylamino-2-naphthol or 7-methoxy-2-naphthol, the catalyst is cesium carbonate and cuprous iodide, the molar ratio of the compound of formula 4, cesium carbonate, coupling agent, cuprous iodide is 1:1.2:1.2-1.5:0.2-0.3; the coupling agent used in the coupling reaction in reaction formula (I) is 7-diethylamino-2-naphthol, the temperature of the coupling reaction is 145℃, and the reaction time is 48-55h; the coupling agent used in the coupling reaction in reaction formula (II) is 7-methoxy-2-naphthol, the temperature of the coupling reaction is 145℃, and the reaction time is 40-48h.
[0025] Further, the nucleophile in S5 is a phenyl Grignard reagent, the molar ratio of the compound of formula 5 to the nucleophile is 1:3.5, the compound of formula 5 is dissolved in anhydrous tetrahydrofuran and cooled at-78℃, the nucleophile is added, and the lithium aldehyde reaction is carried out at room temperature, and the reaction time is 4-5h.
[0026] Further, the acid catalyst in S6 is a protonic acid or a Lewis acid, the mass-volume ratio of the compound of formula 6 to the acid catalyst is 1g:2mL, the intramolecular dehydration reaction is carried out at room temperature, and the reaction time is 2-3h.
[0027] Further, the protonic acid is methylsulfonic acid.
[0028] Further, the mass ratio of the oxidizing agent to the compound of formula 7 in S7 is 1:10, the oxidizing agent is generally tetrachlorobenzoquinone, the oxidation reaction is carried out at room temperature, and the reaction time is 2-3h.
[0029] The present application has the following beneficial effects:
[0030] (1) The asymmetric structure organic small molecule fluorescent dye provided by the present application has a large conjugated system, which has excellent fluorescence emission performance (820-870nm) in the near-infrared region, and has a wide application prospect in the field of biomedical imaging.
[0031] (2) The asymmetric structure organic small molecule fluorescent dye provided by the application has more modification sites, and by introducing different functional groups, the dye molecules are further functionalized, and the application range of the dye molecules in the biomedical field is expanded.
[0032] (3) The synthetic method provided by the application has the advantages of mild reaction conditions, simple operation, high product purity and stable yield. BRIEF DESCRIPTION OF DRAWINGS
[0033] Figure 1 is an emission spectrum of the asymmetric structure organic small molecule fluorescent dye prepared in Example 1 in DCM (the abscissa represents wavelength, the left ordinate represents normalized absorbance, and the right ordinate represents normalized emission);
[0034] Figure 2 is an emission spectrum of the asymmetric structure organic small molecule fluorescent dye prepared in Example 1 in DMSO (the abscissa represents wavelength, the left ordinate represents normalized absorbance, and the right ordinate represents normalized emission);
[0035] Figure 3 is an emission spectrum of the asymmetric structure organic small molecule fluorescent dye prepared in Example 1 in MeOH (the abscissa represents wavelength, the left ordinate represents normalized absorbance, and the right ordinate represents normalized emission);
[0036] Figure 4 is an emission spectrum of the asymmetric structure organic small molecule fluorescent dye prepared in Example 1 in THF (the abscissa represents wavelength, the left ordinate represents normalized absorbance, and the right ordinate represents normalized emission);
[0037] Figure 5 is an emission spectrum of the asymmetric structure organic small molecule fluorescent dye prepared in Example 1 in TCM (the abscissa represents wavelength, the left ordinate represents normalized absorbance, and the right ordinate represents normalized emission);
[0038] Figure 6 is the response ability of the asymmetric structure organic small molecule fluorescent dye prepared in Example 1 to tetrachlorobenzoquinone (the abscissa represents wavelength, and the ordinate represents normalized absorbance). DETAILED DESCRIPTION
[0039] The technical solutions in the embodiments of the application will be clearly and completely described below with reference to the embodiments of the application. Obviously, the described embodiments are only part of the embodiments of the application, rather than all the embodiments of the application. Based on the embodiments in the application, all other embodiments obtained by those skilled in the art without creative labor fall within the protection scope of the application.
[0040] Example 1
[0041] The synthetic route for the first type of asymmetric organic small molecule fluorescent dye provided in this embodiment is as follows:
[0042]
[0043] Specifically, the following steps are included:
[0044] Step 1: Synthesize the compound shown in Formula 2
[0045] Weigh 40.0 g (179 mmol) of 7-bromo-2-hydroxynaphthalene and 40.9 g (215 mmol) of sodium metabisulfite into a 350 mL pressure-resistant flask. Add 80 mL of water to the pressure-resistant flask to dissolve the reactants completely. Separately, add 35 mL (900 mmol) of ammonia solution to the pressure-resistant flask. Place the reaction system in an oil bath at 155 °C and heat for approximately 48 h until the reactants have reacted completely. Then, cool the reaction system to room temperature, filter, and dry to obtain 38 g of the compound shown in Formula 2 (yield 95%).
[0046] The nuclear magnetic resonance hydrogen spectrum of the compound shown in Formula 2 ( 1 H NMR and carbon spectroscopy 13 The specific data for C NMR are as follows:
[0047] 1 H NMR (400 MHz, Chloroform-d) δ 7.73 (s, 1H), 7.60 (d, J = 8.7 Hz,1H), 7.53 (d, J = 8.6 Hz, 1H), 7.27 (dd, J = 8.6, 1.8 Hz, 1H), 6.92 (dd, J =8.7, 2.2 Hz, 1H), 6.85 (d, J = 1.9 Hz, 1H), 3.89 (s, 2H). 13 C NMR (151 MHz, CDCl3) δ 145.22, 136.36, 129.55, 129.41, 127.89, 126.44, 125.87, 120.73, 118.66, 107.57.
[0048] Step 2: Synthesize the compound shown in Formula 3
[0049] Take 10 g (45 mmol) of the compound of formula 2 prepared in step 1 into a 250 mL round-bottom flask, and add 10 mL of N,N-dimethylformamide to the round-bottom flask to completely dissolve the reactants. Then, add 6.7 mL (68 mmol) of 1-bromo-3-chloropropane to the round-bottom flask. Place the reaction system in an oil bath at 160 ℃, heat to reflux, and magnetically stir the reaction for 24 h. After the reaction is completed, reduce the reaction system to room temperature, extract with dichloromethane, concentrate, and finally separate and purify by column chromatography elution with ethyl acetate and petroleum ether in a volume ratio of 1:15 to obtain 8 g of the compound of formula 3 (yield 59%).
[0050] The specific data of the1H nuclear magnetic resonance spectrum (H NMR) and the13C nuclear magnetic resonance spectrum (C NMR) of the compound of formula 3 are as follows: 1 13
[0051] 1 H NMR (400 MHz, Chloroform-d) δ 7.79 (d, J = 1.9 Hz, 1H), 7.40 (d, J= 8.5 Hz, 1H), 7.23 (s, 1H), 7.18 (dd, J = 8.5, 1.9 Hz, 1H), 3.22 (q, J = 5.6Hz, 5H), 2.97 (t, J = 6.7 Hz, 2H), 2.92-2.88 (m, 2H), 2.14-2.06 (m, 2H),2.05-1.97 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 142.09, 133.53, 129.13, 125.71,125.39, 124.93, 124.18, 123.46, 119.71, 110.15, 50.50, 49.86, 28.69, 23.40,22.00, 21.67。
[0052] Step 3: Synthesis of the compound of formula 4
[0053] Take 1 g (3.31 mmol) of the compound of formula 3 prepared in step 2 into a 100 mL round-bottom flask, add 10 mL of 1,2-dichloroethane to the round-bottom flask to completely dissolve the reactants, and then add 1.84 g (19.85 mmol) of Vilsmeier-haack reagent. React at 90 ℃ for 3 h. After the reaction is completed, add saturated sodium carbonate solution to quench, and finally separate and purify by column chromatography elution with ethyl acetate and petroleum ether in a volume ratio of 1:10 to obtain 0.4 g of the compound of formula 4 (yield 36%).
[0054] The Vilsmeier-haack reagent was prepared by the following method:
[0055] Measure 8.32 mL (107.62 mmol) N,N-dimethylformamide in a 50 mL round bottom flask. After cooling to 0 °C, add 10 mL (107.62 mmol) phosphorus oxychloride dropwise, mix and stir for 30 min to obtain 9.96 g (107.62 mmol) Vilsmeier-haack reagent.
[0056] The specific data of the hydrogen spectrum (H NMR) and carbon spectrum (C NMR) of the compound shown in formula 4 are as follows: 1 H NMR) and carbon spectrum (C NMR) of the compound shown in formula 4 are as follows: 13
[0057] 1 H NMR (400 MHz, Chloroform-d) δ 10.31 (s, 1H), 8.13 (s, 1H), 7.78(s, 1H), 7.32 (s, 1H), 3.31 (dt, J = 9.3, 5.7 Hz, 5H), 2.94 (t, J = 6.6 Hz,2H), 2.91-2.85 (m, 2H), 2.13-2.04 (m, 3H), 2.04-1.95 (m, 2H). 13 C NMR (101 MHz,CDCl3) δ 191.78, 144.58, 136.32, 131.51, 127.77, 126.55, 125.50, 125.02,124.09, 121.28, 109.15, 50.50, 49. 72 , 28.68, 23.17, 21.45, 21.11。
[0058] Step 4: synthesis of the compound shown in formula 5
[0059] Weigh 1 g (3.03 mmol) of the compound of formula 4 prepared in step 3, 1.18 g (3.63 mmol) of cesium carbonate, and 0.68 g (3.63 mmol) of 7-diethylamino-2-naphthol into a Schlenk flask. Under nitrogen protection, add 30 mL of anhydrous N,N-dimethylformamide and 0.17 g (908.47 μmol) of cuprous iodide, and react at 145 °C for 48 h. After the reaction is complete, cool to room temperature, filter using a Buchner funnel (lined with an appropriate amount of diatomaceous earth for filtration), extract with dichloromethane, concentrate, and finally elute by column chromatography with ethyl acetate and petroleum ether in a volume ratio of 1:10 to obtain 0.5 g of the compound of formula 5 (yield 35%).
[0060] The 7-diethylamino-2-naphthol was prepared by the following method:
[0061] 10 g (62.43 mmol) of 2,7-dihydroxynaphthalene, 11.87 g (62.43 mmol) of sodium metabisulfite, 14.85 mL (143.60 mmol) of diethylamine, and 50 mL of water were weighed into a pressure-resistant flask and reacted at 130 °C for 2 h, followed by heating to 150 °C and reacting for 48 h. After the reaction was completed, the mixture was cooled to room temperature, filtered using a Buchner funnel, extracted with dichloromethane, concentrated, and finally eluted by column chromatography with ethyl acetate and petroleum ether in a volume ratio of 1:30 to obtain 7 g of 7-diethylamino-2-naphthol (yield 70%).
[0062] The nuclear magnetic resonance hydrogen spectrum of the compound shown in Formula 5 ( 1 H NMR and carbon spectroscopy 13 The specific data for C NMR are as follows:
[0063]
[0064] Step 5: Synthesize the compound shown in Formula 6
[0065] 100 mg (215.23 μol) of the compound of formula 5 prepared in step 4 was weighed into a dried Slack reactor. Under nitrogen protection, 2 mL of anhydrous tetrahydrofuran was added to the reactor to completely dissolve the reactant. The reactor was then cooled at -78 °C for 0.5 h. After cooling, 124.51 μL (645.70 μol) of o-tolyl magnesium bromide solution was added directly, and the reaction system was then transferred to room temperature and stirred for 5 h. After the reaction was completed, the organic layer was extracted with ethyl acetate, concentrated, and finally separated by column chromatography using ethyl acetate and petroleum ether in a volume ratio of 1:8 to obtain 80 mg of the compound of formula 6 (yield 67%).
[0066] The mass spectrum of the compound shown in formula 6 is as follows: HRMS (ESI) m / z C 38 H 40 N2O2 [M] + 557.3168; Found 557.3169.
[0067] Step 6: Synthesis of the compound shown in formula 7
[0068] Take 100 mg of the compound shown in formula 6 prepared in step 5 into a 50 mL round-bottom flask, add an appropriate amount of dichloromethane to completely dissolve the reactants, and then add 0.2 mL of methyl sulfonic acid dropwise at room temperature and stir for 2 h. TLC point plate to the complete reaction of the raw material, then add sodium bicarbonate aqueous solution to neutralize the reaction system to pH = 7, extract with dichloromethane to obtain the organic phase, concentrate, and finally elute and separate by column chromatography with ethyl acetate and petroleum ether in a volume ratio of 1:10 to obtain 62 mg of the compound shown in formula 7 (yield 62 %).
[0069] The specific data of the nuclear magnetic resonance hydrogen spectrum (1H NMR) and carbon spectrum (13C NMR) of the compound shown in formula 7 are as follows:
[0070]
[0071] Step 7: Synthesis of an asymmetric structure of an organic small molecule fluorescent dye
[0072] Take 100 mg of the compound shown in formula 7 prepared in step 6 into a 50 mL round-bottom flask, add 2 mL of dichloromethane to the round-bottom flask to completely dissolve the reactants, then add 10 mg of chloranil, and stir at room temperature for 3 h; after the reaction is completed, extract the reaction system with dichloromethane, and finally elute and separate by column chromatography with methanol and dichloromethane in a volume ratio of 1:10 to obtain 30 mg of the asymmetric structure of the organic small molecule fluorescent dye shown in formula 1 (yield 30 %).
[0073] The specific data of the nuclear magnetic resonance hydrogen spectrum (1H NMR) and carbon spectrum (13C NMR) of the asymmetric structure of the organic small molecule fluorescent dye shown in formula 1 are as follows: 1 H NMR) and carbon spectrum (13C NMR) of the asymmetric structure of the organic small molecule fluorescent dye shown in formula 1 are as follows: 13 CNMR) of the asymmetric structure of the organic small molecule fluorescent dye shown in formula 1 are as follows:
[0074] 1H NMR (400 MHz, CDC13) δ 8.21 (d, J = 8.6 Hz, 1H), 7.79 (d, J = 9.1 Hz, 1H), 7.70-7.56 (m, 5H), 7.40 (d, J = 8.6 Hz, 1H), 7.26 (s, 1H), 7.00 (dd, J = 9.1, 2.5 Hz, 1H), 6.84 (d, J = 2.4 Hz, 1H), 3.63 (q, J = 6.0 Hz, 5H), 3.05 (dt, J = 10.6, 5.3 Hz, 6H), 2.90 (d, J = 6.4 Hz, 2H), 2.24-2.14 (m, 4H), 2.06 (d, J = 9.8 Hz, 3H), 1.01 (t, J = 7.1 Hz, 6H). 13 C NMR (101 MHz, CDC13) δ 160.01, 159.59, 150.22, 149.90, 149.21, 143.93, 138.56, 136.57, 135.13, 133.53, 133.47, 131.92, 131.00, 130.31, 129.76, 128.79, 128.09, 127.67, 127.55, 122.60, 120.24, 116.38, 113.86, 111.15, 109.81, 106.43, 102.84, 51.81, 50.95, 44.58, 29.68, 28.34, 22.97, 20.86, 20.35, 19.85, 12.80.
[0075] See Figure 1 It can be seen that the organic small molecule fluorescent dye has a fluorescence emission wavelength of 882 nm and an absorption wavelength of 842 nm in DCM.
[0076] See Figure 2 It can be seen that the organic small molecule fluorescent dye has a fluorescence emission wavelength of 892 nm and an absorption wavelength of 845 nm in DMSO.
[0077] See Figure 3 It can be seen that the organic small molecule fluorescent dye has a fluorescence emission wavelength of 875 nm and an absorption wavelength of 842 nm in MeOH.
[0078] See Figure 4It can be seen that the organic small molecule fluorescent dye has a fluorescence emission wavelength of 864 nm and an absorption wavelength of 838 nm in THF.
[0079] Referring to Figure 5 It can be seen that the organic small molecule fluorescent dye has a fluorescence emission wavelength of 862 nm and an absorption wavelength of 842 nm in TCM.
[0080] Figure 6 The response of the asymmetrically structured organic small molecule fluorescent dye prepared in Example 1 to the oxidant 4-chloranil is illustrated. It is illustrated that the asymmetrically structured organic small molecule fluorescent dye provided in the present application exhibits strong fluorescence emission and absorption characteristics in different solvents, and the organic small molecule provided in the present application can respond well to the oxidant.
[0081] Example 2
[0082] Another type of asymmetrically structured organic small molecule fluorescent dye is provided in the present embodiment, and the synthetic route thereof is shown as follows:
[0083]
[0084] The method comprises the following steps:
[0085] The synthesis methods of steps 1 to 3 are the same as those of Example 1.
[0086] Step 4: Synthesis of the compound shown in formula 5
[0087] 1 g (3.03 mmol) of the compound shown in formula 4, 1.18 g (3.63 mmol) of cesium carbonate, and 0.63 g (3.63 mmol) of 7-methoxy 2-naphthol were weighed into a 100 mL two-necked flask. Under the protection of nitrogen, 15 mL of anhydrous N, N-dimethylformamide and 0.17 g (908.47 umol) of cuprous iodide were added, and the mixture was reacted at 145 °C for 48 h. After the reaction was completed, the mixture was cooled to room temperature, filtered under suction using a Buchner funnel (with an appropriate amount of diatomaceous earth to assist filtration), extracted with dichloromethane, concentrated, and finally separated and purified by column chromatography using ethyl acetate and petroleum ether in a volume ratio of 1:8 to obtain 0.65 g of the compound shown in formula 5 (yield 50%).
[0088] Step 5: Synthesis of the compound shown in formula 6
[0089] Take 100 mg (236.12 umol) of the compound represented by formula 5 prepared in step 4 into a dried Schlenk reactor, and add 2 mL of anhydrous tetrahydrofuran into the reactor to completely dissolve the reactants. Cool the reactor in a low-temperature reactor at -78 ℃ for 0.5 h, and then directly add 159.84 uL (826.42 umol) of o-tolyl magnesium bromide solution. Then, transfer the reaction system to room temperature and stir for 5 h. After the reaction is completed, extract the organic layer with ethyl acetate, concentrate, and finally separate and purify 62 mg of the compound represented by formula 6 by column chromatography elution with ethyl acetate and petroleum ether at a volume ratio of 1:8 (yield 51 %).
[0090] Step 6: Synthesis of the compound represented by formula 7
[0091] Take 100 mg of the compound represented by formula 6 prepared in step 5 into a 50 mL round-bottom flask, add an appropriate amount of dichloromethane to completely dissolve the reactants, and then add 0.2 mL of methyl sulfonic acid dropwise at room temperature and stir for 2 h. TLC point plate until the raw material is completely reacted, and then add sodium bicarbonate aqueous solution to neutralize the reaction system to pH = 7. Extract the organic phase with dichloromethane, concentrate, and finally separate and purify 45 mg of the compound represented by formula 7 by column chromatography elution with ethyl acetate and petroleum ether at a volume ratio of 1:10 (yield 45 %).
[0092] Step 7: Synthesis of an asymmetric organic small-molecule fluorescent dye
[0093] Take 100 mg of the compound represented by formula 7 prepared in step 6 into a 50 mL round-bottom flask, add 2 mL of dichloromethane to completely dissolve the reactants, and then add 10 mg of chloranil. Stir at room temperature for 2 h, and then extract the reaction system with dichloromethane. Finally, separate and purify 10 mg of the asymmetric organic small-molecule fluorescent dye represented by formula 1-1 by column chromatography elution with methanol and dichloromethane at a volume ratio of 1:10 (yield 10 %).
[0094] In this embodiment, the end group of the organic small-molecule fluorescent dye is modified to a methoxy group. By this method, the absorption and emission wavelength of the organic small-molecule fluorescent dye can be changed, and its performance can be regulated.
[0095] The above merely describes preferred embodiments of the present application, and is not intended to limit the present application in any form or in essence. It should be noted that those skilled in the art can make some improvements and supplements without departing from the method of the present application, and these improvements and supplements should also be considered as the protection scope of the present application. For those skilled in the art, some slight changes, modifications and equivalent changes made by using the disclosed technical content without departing from the spirit and scope of the present application are equivalent embodiments of the present application; meanwhile, any equivalent changes, modifications and evolution made according to the essential technology of the present application to the above embodiments are still within the scope of the technical solutions of the present application.
Claims
1. A class of small organic fluorescent dyes of non-symmetrical structure, characterized in that, The asymmetric structure of the organic small molecule fluorescent dye has a structural general formula of formula 1 or formula 1-1: Wherein, R1, R2 are each independently selected from cycloalkyl or alkyl, the alkyl contains 1-6 carbon atoms, and the cycloalkyl contains 3-6 carbon atoms; R3, R4 are each independently selected from one of cycloalkyl, alkyl, ether bond, halogen, alkoxy, carboxyl, sulfonate, the cycloalkyl contains 3-6 carbon atoms, and the alkyl and alkoxy each contain 1-2 carbon atoms; R5 is methyl.
2. A method of synthesizing an organic small-molecule fluorescent dye of asymmetric structure as claimed in claim 1, characterized by, The synthesis route of formula 1 is shown in reaction formula (I), and the synthesis route of formula 1-1 is shown in reaction formula (II): （I） (II) Comprising the following steps: S1: 7-bromo-2-hydroxynaphthalene is subjected to amination reaction with sodium pyrosulfite in ammonia water to obtain a compound shown in formula 2; S2: the compound shown in formula 2 prepared in S1 is subjected to alkylation reaction with an alkylating agent in a solvent to obtain a compound shown in formula 3, and the solvent is N,N-dimethylformamide; S3: the compound shown in formula 3 prepared in S2 is subjected to aldehyde group reaction with a formylating agent in a solvent to obtain a compound shown in formula 4, and the solvent is 1,2-dichloroethane; S4: the compound shown in formula 4 prepared in S3, a coupling agent and a catalyst are subjected to coupling reaction in a solvent to obtain a compound shown in formula 5, and the solvent is anhydrous N,N-dimethylformamide; S5: the compound shown in formula 5 prepared in S4 is subjected to lithium aldehyde reaction with a nucleophile in a solvent to obtain a compound shown in formula 6, and the solvent is anhydrous tetrahydrofuran; S6: the compound shown in formula 6 prepared in S5 is subjected to intramolecular dehydration reaction with an acid catalyst in a solvent to obtain a compound shown in formula 7, and the solvent is dichloromethane; S7: the compound shown in formula 7 prepared in S6 is subjected to oxidation reaction with an oxidizing agent in a solvent to obtain the asymmetric structure of the organic small molecule fluorescent dye shown in formula 1, and the solvent is dichloromethane.
3. The method of synthesis of claim 2, wherein, The molar ratio of 7-bromo-2-hydroxynaphthalene, sodium pyrosulfite and ammonia in S1 is 1:1.2:4-5.
4. The method of synthesis of claim 2, wherein, The alkylating agent in S2 is a halogenated alkyl compound, and the molar ratio of the compound shown in formula 2 to the alkylating agent is 1:1.2-1.
5.
5. The method of synthesis of claim 2, wherein, The formylating agent in S3 is prepared from phosphorus oxychloride and N,N-dimethylformamide, and the molar ratio of the compound shown in formula 3 to the formylating agent is 1:4-6.
6. The method of synthesis of claim 2, wherein, The coupling agent in S4 is 7-diethylamino-2-naphthol or 7-methoxy-2-naphthalene, and the catalyst is cesium carbonate and cuprous iodide, and the molar ratio of the compound shown in formula 4, cesium carbonate, the coupling agent, cuprous iodide is 1:1.2:1.2-1.5:0.2-0.
3.
7. The method of synthesis of claim 2, wherein, The nucleophile in S5 is a phenyl Grignard reagent, and the molar ratio of the compound shown in formula 5 to the nucleophile is 1:3.
5.
8. The method of synthesis of claim 2, wherein, The acid catalyst in S6 is a protonic acid or a Lewis acid, and the mass-volume ratio of the compound shown in formula 6 to the acid catalyst is 1g:2mL.
9. The method of synthesis of claim 8, wherein, The protonic acid is methylsulfonic acid.
10. The method of synthesis of claim 2, wherein, The mass ratio of the oxidizing agent to the compound shown in formula 7 in S7 is 1:10.