Synthesis and Application of Benzo[1,2-c:4,5-c`]bis([1,2,5]thiadiazole) Dyes

Abstract

The present invention discloses a method for preparing a class of benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) near-infrared zone II organic dyes and their application, belonging to the fields of fine chemicals and organic dye synthesis. The organic dye of the present invention is an electron donor-acceptor-donor (D-A-D) type organic dye based on an acceptor unit benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole), wherein the electron donor is a triphenylamine-thieno ring derivative unit, and the electron donating ability is enhanced by expanding the planar conjugation of the electron donor to promote the red shift of the ultraviolet absorption and fluorescence emission spectrum of the dye, thereby obtaining a near-infrared zone II fluorescent dye with long-wave absorption. The fluorescence emission spectra of the two classes of benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) organic dyes of the present invention are both located in the near-infrared zone II (1000-1700nm), and therefore have great application potential in the field of near-infrared zone II fluorescence imaging.

Description

Technical Field

[0001] The invention belongs to the technical field of fine chemicals and organic dye synthesis, and specifically relates to the synthesis and application of a benzo[1,2-c4,5-c']bis([1,2,5]thiadiazole) type near-infrared second-zone fluorescent dye. Background Art

[0002] Understanding the distribution of biomolecules in real time at the microscopic level has profound implications for the early diagnosis and treatment of tissue and organ diseases. Among various imaging techniques, fluorescence imaging offers the advantages of high sensitivity, rapidity, and real-time monitoring. Because biological tissues exhibit strong background fluorescence in the visible light region, tissue light scattering results in a low imaging signal-to-noise ratio, making visible light difficult to penetrate biological tissues. Fluorescence imaging based on near-infrared light (750–1700 nm) can avoid these issues. In particular, near-infrared region II (1000–1700 nm), where biological autofluorescence is weak, allows for the acquisition of high signal-to-noise ratio signals. Furthermore, this region has greater penetration into biological tissues, facilitating deep-tissue fluorescence imaging. Therefore, near-infrared region II fluorescence imaging can simultaneously benefit from reduced tissue autofluorescence and photon scattering, resulting in better spatial resolution and contrast than visible light or near-infrared region I (750–1000 nm) fluorescence imaging.

[0003] A wide variety of near-infrared (NIR) II fluorescent materials have been developed, including carbon nanotubes, quantum dots, rare earth nanoparticles, and organic dyes. However, inorganic materials contain heavy metal ions and are not easily degradable, resulting in high biotoxicity. Organic dyes, due to their excellent biosafety and structural modifiability, have attracted widespread attention. However, most existing NIR II organic fluorescent dyes have a maximum absorption wavelength in the NIR I region or the visible region (<900 nm), resulting in low signal-to-noise ratios and weak tissue penetration of the excitation light. Therefore, designing organic nanoparticles that combine high biocompatibility, high signal-to-noise ratio, and high imaging depth would have greater potential for fluorescence imaging applications. To address the challenges of current NIR II organic dyes and based on our experience in organic dye design, we propose a coplanar design of DAD-type fluorescent molecules to enhance the conjugation effect of the fluorescent molecules and promote electron delocalization, resulting in a red-shifted absorption and emission spectrum. This results in fluorescent dyes with long-wavelength absorption, even in the NIR II region. Based on this design concept, a triarylamine with a strong electron-donating unit and a thiophene derivative were covalently linked to form a planar conjugated electron donor. In the DAD fluorescent molecule, the introduction of the thiophene unit reduces the steric repulsion between the electron donor and acceptor monomers, thereby achieving a coplanar π-conjugated structure throughout the molecule.

[0004] Benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) is an excellent electron acceptor with typical quinone-type characteristics, which can enhance electron delocalization and reduce the band gap. The introduction of planar conjugated rigid donor units at both ends of benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) promotes intramolecular charge transfer, further reducing the band gap energy, enhancing the brightness of the fluorophore, and red-shifting the ultraviolet absorption and fluorescence emission bands to the near-infrared region (Chem. Mater. 2008, 20, 6208-6216; Acc. Mater. Res. 2021, 2, 170-183). Therefore, based on the benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) receptor unit, a near-infrared second-zone organic fluorescent dye with long-wavelength absorption was synthesized, which can be used as a contrast agent in the field of near-infrared second-zone fluorescence imaging of tissues and organs such as blood vessels, rheumatoid arthritis, tumors, and liver function. Summary of the Invention

[0005] To address the shortcomings of the existing technology, the present invention aims to provide the synthesis and application of benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) dyes. Using triphenylamine-thieno ring derivative planar units and benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) as electron donors and electron donors, respectively, the present invention reduces the inter-unit steric repulsion effect and induces a planar molecular conformation, resulting in a near-infrared region II fluorescent dye with a maximum absorption wavelength greater than 900 nm. This fluorescent dye can be used as a near-infrared region II fluorescent imaging contrast agent to improve the imaging sensitivity and resolution of tissues and organs such as blood vessels, rheumatoid arthritis, tumors, and liver function.

[0006] The purpose of the present invention can be achieved through the following technical solutions:

[0007] A method for synthesizing a class of benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) organic dyes, the synthetic route of which is as follows:

[0008]

[0009] Wherein R1 is H, methyl, ethyl and methoxy, and R2 is a straight chain or branched alkyl-C n H 2n+1 , n≤8, or a straight-chain or branched alkyl substituted phenyl group with less than 8 carbon atoms -Ph-C n H 2n+1 ,n≤8.

[0010] The synthetic route of the compound of formula (I) of the present invention is as follows:

[0011]

[0012] The present invention provides a method for preparing the above-mentioned benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) organic dye, comprising the following steps:

[0013] Step 1: Under inert gas atmosphere, weak base, tetrakis(triphenylphosphine)palladium catalysis and light protection, 4-(dimethylphenylamino)phenylboronic acid pinacol ester and 2-bromothiophene-3-carboxylic acid methyl ester undergo Suzuki coupling reaction to obtain compound 1;

[0014] Step 2: After reacting n-butyl bromobenzene and n-butyl lithium under anhydrous and oxygen-free conditions and inert gas protection at -70°C, compound 1 is added to the reaction system, followed by simple treatment; Step 3: The reaction system is dissolved in acetic acid solvent, and then catalytically dehydrated with concentrated sulfuric acid to obtain compound 2;

[0015] Step 4: In an anhydrous and oxygen-free, inert gas atmosphere at -30°C, n-butyl lithium and compound 2 undergo a substitution reaction, followed by the addition of isopropyl pinacol ester, followed by simple treatment;

[0016] Step 5: Under the protection of inert gas, weak base, tetrakis(triphenylphosphine)palladium catalysis and light protection, the crude product of the reaction system and 4,7-dibromobenzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) (BBT) are subjected to Suzuki coupling reaction to obtain the final product (I).

[0017] Furthermore, in step 1, the molar ratio of methyl 2-bromothiophene-3-carboxylate and 4-(xylylamino)phenylboronic acid pinacol ester is 1:1.5; the molar ratio of methyl 2-bromothiophene-3-carboxylate and tetrakis(triphenylphosphine)palladium is 1:0.05; the molar ratio of methyl 2-bromothiophene-3-carboxylate and K2CO3 / KF solution is 1:2; the solvents THF and Tol are 20 mL each; the Suzuki reaction temperature is 90°C, and the reaction time is 24 h.

[0018] Furthermore, in step 2, the molar ratio of n-butyl lithium and n-butyl bromobenzene is 4.2:4, the reaction temperature is -70°C, and the reaction time is 1 hour; the molar ratio of compound 1 and n-butyl bromobenzene is 1:4, the reaction temperature is room temperature, and the reaction time is 12 hours; in step 3, 1 to 2 drops of trifluoromethanesulfonic acid are used to catalyze the dehydration ring, the reaction temperature is 120°C, and the reaction time is 20-30 minutes.

[0019] Furthermore, in step 4, the molar ratio of compound 2 and n-butyl lithium is 1:1.5, the reaction temperature is -30°C, and the reaction time is 2 hours; in step 5, the crude product from the reaction in step 4, the molar ratio of benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) and tetrakis(triphenylphosphine)palladium is 1:0.2; the reaction temperature is 90°C, and the reaction time is 24 hours.

[0020] The synthetic route of the compound of formula (II) of the present invention is as follows:

[0021]

[0022] The present invention provides a method for preparing the above-mentioned benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) organic dye, comprising the following steps:

[0023] Step 6: Under inert gas protection, weak base, tetrakis(triphenylphosphine)palladium catalysis and light protection, thiophene-2-boronic acid and diethyl 2,5-dibromoterephthalate undergo Suzuki coupling reaction to obtain compound 3;

[0024] Step 7: Under inert gas protection, weak base, tetrakis(triphenylphosphine)palladium catalysis and light protection, compound 3 and 4-(ditolylamino)benzopinacol borate undergo Suzuki coupling reaction to obtain compound 4;

[0025] Step 8: In anhydrous and oxygen-free environment, under inert gas protection and at -70°C, n-butyl bromobenzene and n-butyl lithium undergo a substitution reaction, and then compound 4 is added to the reaction system, followed by simple treatment; Step 9: The reaction system is catalytically dehydrated with boron trifluoride etherate to obtain compound 5;

[0026] Step 10: In anhydrous and oxygen-free, inert gas atmosphere at -30°C, n-butyl lithium and compound 5 undergo substitution reaction, and then isopropyl pinacol ester is added, followed by simple treatment; Step 11: In an inert gas atmosphere, weak base, tetrakis(triphenylphosphine)palladium catalysis and light-proof conditions, the crude product of the reaction system and 4,7-dibromobenzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) (BBT) undergo Suzuki coupling reaction to obtain the final product (II).

[0027] Furthermore, in step 6, the molar ratio of diethyl 2,5-dibromoterephthalate to thiophenol-2-boric acid is 1:2; the molar ratio of diethyl 2,5-dibromoterephthalate to tetrakis(triphenylphosphine)palladium is 1:0.05; the Suzuki reaction temperature is 90° C., and the reaction time is 24 h.

[0028] Furthermore, in step 7, the molar ratio of 4-(dimethylphenylamino)benzopinacol borate to compound 3 is 1:1.5; the molar ratio of compound 3 to tetrakis(triphenylphosphine)palladium is 1:0.05; the Suzuki reaction temperature is 90°C, and the reaction time is 24h.

[0029] Furthermore, in step 8, the molar ratio of n-butyl lithium and n-butyl bromobenzene is 1:1.02, the reaction temperature is -70°C, and the reaction time is 1 hour; the molar ratio of compound 4 and n-butyl bromobenzene is 1:6, the reaction temperature is room temperature, and the reaction time is 12 hours; in step 9, the molar ratio of compound 4 and boron trifluoride ether is 1:0.9, the reaction temperature is room temperature, and the reaction time is 20-30 minutes.

[0030] Furthermore, in step 10, the molar ratio of compound 5 and n-butyl lithium is 1:1.2, the reaction temperature is -30°C, and the reaction time is 1 hour; through simple treatment, in step 11, the crude product of step 10 is used; the molar ratio of 4,7-dibromobenzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) and tetrakis(triphenylphosphine)palladium is 1:0.2; the reaction temperature is 90°C, and the reaction time is 24 hours.

[0031] Beneficial effects of the present invention:

[0032] The benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) organic dye compounds (I) and (II) proposed in the present invention are synthesized for the first time. Compound (I) has an ultraviolet absorption wavelength of up to 984 nm and a fluorescence emission wavelength of up to 1307 nm, while compound (II) has an ultraviolet absorption wavelength of up to 961 nm and an emission wavelength of up to 1246 nm. Therefore, the benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) organic dye compounds (I) and (II) synthesized in the present invention can be used as contrast agents for near-infrared second-region bioluminescent imaging and therapy. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0034] Figure 1 is a UV-visible absorption spectrum of Example 1 of the present invention tested in dichloromethane;

[0035] Figure 2 is a UV-visible absorption spectrum of Example 2 of the present invention tested in dichloromethane;

[0036] Figure 3 is a fluorescence emission spectrum of Example 1 of the present invention tested in dichloromethane;

[0037] Figure 4 is a fluorescence emission spectrum of Example 2 of the present invention tested in dichloromethane;

[0038] Figure 5 This is a near-infrared second-zone fluorescence imaging image of nanoparticles of different concentrations prepared in Example 1 of the present invention;

[0039] Figure 6 This is a near-infrared second-zone fluorescence imaging image of nanoparticles of different concentrations prepared in Example 2 of the present invention. DETAILED DESCRIPTION

[0040] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0041] Example 1

[0042] 1. The benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) organic dye synthesized in this embodiment has the following structure:

[0043]

[0044] The specific synthesis steps are as follows:

[0045] 1.1 Synthesis of Compound 1

[0046]

[0047] 4-(Dimethylphenylamino)benzopinacol borate (2.5 g, 6.3 mmol), methyl 2-bromothiophene-3-carboxylate (0.92 g, 4.2 mmol), tetrakis(triphenylphosphine)palladium (240 mg, 0.2 mmol), deoxygenated KCO / KF aqueous solution (2 M, 4.2 mL), and deoxygenated THF / Tol (V / V = 20 mL / 20 mL) were added to a 150 mL two-necked flask. The system was protected by nitrogen and placed in a 90°C oil bath in the dark for 24 h. The reaction progress was monitored by thin-layer chromatography. After completion, the product was extracted with DCM. The resulting organic phase was dried over anhydrous magnesium sulfate and filtered. After vacuum distillation, it was separated by silica gel chromatography to yield compound 1 (1.3 g, 3.14 mmol). 1HNMR(400MHz,Chloroform-d)δ7.52–7.43(m,1H),7.36–7.29(m,2H),7.20–7 .14(m,1H),7.12–7.02(m,8H),7.02–6.94(m,2H),3.76(s,3H),2.33(s,6H). 13 CNMR(100MHz,Chloroform-d)δ164.53,152.35,149.09,145.30,133.57,130 .83,130.44,130.40,127.08,125.71,125.65,123.63,120.83,51.54,20.70.

[0048] 1.2 Synthesis of Compound 2

[0049]

[0050] Under nitrogen protection, at -70°C, n-butyllithium (1.6M, 8.3mL, 13.2mmol) was added dropwise to a mixture of n-butylbromobenzene (2.68g, 12.6mmol) and dry THF (10mL) and the reaction was maintained for 1h. The system was then transferred to room temperature, and a solution of compound 1 (1.3g, 3.1mmol) in dry THF (10mL) was added by injection and the reaction was maintained for 12h. The system was then subjected to reduced pressure distillation and silica gel column chromatography. The column chromatography eluate was dissolved with an appropriate amount of glacial acetic acid, and two drops of trifluoromethanesulfonic acid were added at 120°C for 25min. The reaction progress was monitored by thin-layer chromatography. Water was then added to quench the reaction, and the organic phase was separated by a separatory funnel, dried over anhydrous magnesium sulfate, and separated by silica gel column chromatography to obtain compound 2 (0.74g, 1.15mmol) with a reaction yield of 37%. 1 HNMR(400MHz,Chloroform-d)δ7.29(d,J=0.6Hz,0H),7.24–7.18(m,2H),7.15(d,J=2.1Hz,1H),7.09–7.03(m,5H),7.01–6.97(m,8H),6.9 7–6.91(m,5H),6.89–6.84(m,1H),2.59–2.51(m,4H),2.29(s,6H),1.59–1.53(m,4H),1.34(q,J=14.7,7.4Hz,4H),0.92(t,J=7.3Hz,6H). 13CNMR(100MHz,Chloroform-d)δ155.63,155.44,146.56,145.86,142.56,141.55,141.43,132.53,131.72,130.1 3,128.55,128.21,127.02,124.50,123.59,122.43,122.12,119.91,62.89,35.11,33.47,22.28,20.64,13.79.

[0051] 1.3 Synthesis of Compound (I)

[0052]

[0053] Under nitrogen protection, n-butyl lithium (1.6 M, 0.82 mL, 1.3 mmol) was added dropwise to a solution of compound 2 (0.55 g, 0.87 mmol) in dry THF (15 mL) at -30°C. The reaction was maintained for 2 h, and then isopropyl pinacol borate (0.53 mL, 2.6 mmol) was injected at low temperature. The system was then transferred to room temperature and the reaction was maintained for 24 h. The solvent was then dried, and 4,7-dibromobenzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) (BBT) (150 mg, 0.43 mmol), tetrakis(triphenylphosphine)palladium (98 mg, 85 μmol), deoxygenated K2CO3 / KF aqueous solution (2 M, 0.85 mL) and deoxygenated THF / Tol (V / V = 20 mL / 20 mL) were added and placed in a 90°C oil bath in the dark for 24 h. The reaction process was monitored by thin-layer chromatography. After the reaction was complete, the reaction system was extracted with DCM, and the organic phase was dried over anhydrous magnesium sulfate. Finally, it was purified by vacuum distillation and silica gel column chromatography to obtain a black solid compound (I) (130 mg). The reaction yield was 21%. 1 HNMR(400MHz,Chloroform-d)δ7.32–7.17(m,10H),7.10–6.92(m,30H),2.56(t,J=5.4Hz ,8H),2.47–1.94(m,12H),1.60–1.49(m,4H),1.39–1.23(m,12H),0.89(t,J=7.3Hz,12H). 13CNMR(100MHz,Chloroform-d)δ157.13,150.79,148.07,145.99,145.96,145.93,143.02,142.79,142.19,141.63,133.47,130.82,130.6 7,129.91,129.35,129.26,128.93,125.89,125.37,122.71,121.63,121.57,121.51,121.49,63.74,35.57,33.96,22.68,21.10,14.15.

[0054] Example 2

[0055] 2. The benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) organic dye synthesized in this example has the following structure:

[0056]

[0057] The specific synthesis steps are as follows

[0058] 2.1 Synthesis of Compound 3

[0059]

[0060] Diethyl 2,5-dibromoterephthalate (2 g, 13 mmol), thiophene-2-boronic acid (3.4 g, 26 mmol), tetrakis(triphenylphosphine)palladium (760 mg, 6.5 mmol), a deoxygenated K2CO3 / KF aqueous solution (2 M, 13 mL), and deoxygenated THF / Tol (V / V = 20 mL / 20 mL) were added to a 150 mL two-necked flask. The system was protected by nitrogen and placed in a 90°C oil bath in the dark for 24 hours. The reaction progress was monitored by thin-layer chromatography. After completion, the mixture was extracted with dichloromethane (DCM). The resulting organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was added to silica gel for column chromatography to yield compound 3 (3.8 g, 9.9 mol). The yield was 76.2%. 1 HNMR(400MHz,Chloroform-d)δ7.97(s,1H),7.84(s,1H),7.38(dd,J=4.3,2.1Hz,1H),7.07–7.03( m,2H),4.41(q,J=7.2Hz,2H),4.20(q,J=7.1Hz,2H),1.40(t,J=7.2Hz,3H),1.15(t,J=7.2Hz,3H). 13CNMR(100MHz,Chloroform-d)δ167.49,166.20,140.60,136.10,135.69,135.29 ,134.23,134.06,128.14,127.87,127.40,121.28,62.51,62.26,14.33,13.92.

[0061] 2.2 Synthesis of Compound 4

[0062]

[0063] Compound 3 (2.2 g, 5.5 mmol), 4-(dimethylphenylamino)benzopinacol borate (1.4 g, 3.6 mmol), tetrakis(triphenylphosphine)palladium (210 mg, 0.18 mmol), deoxygenated KCO / KF (2 M, 3.6 mL), and deoxygenated THF / Tol (V / V = 20 mL / 20 mL) were added to a 150 mL two-necked flask. The system was protected by nitrogen and placed in a 90°C oil bath in the dark for 24 h. The reaction was monitored by thin-layer chromatography. After completion, the product was extracted with DCM, and the organic phase was dried over anhydrous magnesium sulfate and filtered. Finally, it was separated by silica gel column chromatography to obtain compound 4 (1.5 g, 2.6 mmol) in a 70% yield. 1 HNMR(400MHz,Chloroform-d)δ7.85(s,1H),7.73(s,1H),7.37(dd,J=4.8,1.6Hz,1H),7.21–7 .15(m,2H),7.12–6.99(m,12H),4.20(q,J=12.1,7.2Hz,4H),2.33(s,6H),1.19–1.09(m,6H). 13 CNMR(100MHz,Chloroform-d)δ168.85,168.67,148.49,145.57,141.60,141.30,134.59,133.71,133.29,132.89 ,132.79,132.60,131.74,130.37,129.50,127.68,127.16,126.62,125.25,122.10,61.60,61.43,20.69,13.63.

[0064] 2.3 Synthesis of Compound 5

[0065]

[0066] Under nitrogen protection, at -70 ° C, n-butyl lithium (1.6 M, 9.8 mL, 15.6 mmol) was added dropwise to a mixture of n-butyl bromobenzene (3.4 g, 16 mmol) and dry THF (10 mL) and the reaction was maintained for 2 h. The system was then transferred to room temperature, and a solution of compound 4 (1.5 g, 2.6 mmol) in dry THF (10 mL) was added by injection and the reaction was maintained for 12 h. The system was then subjected to reduced pressure distillation and silica gel column chromatography. The column chromatography eluting material was dissolved in an appropriate amount of DCM, and boron trifluoride etherate (0.3 mL) was added at room temperature to react for 25 min. Water was then added to quench the reaction, and the organic phase was separated by a separatory funnel and dried over anhydrous magnesium sulfate. Finally, silica gel column chromatography was performed to obtain compound 5 (1.1 g, 1.1 mmol) with a reaction yield of 48%. 1 HNMR(400MHz,Chloroform-d)δ7.59(s,1H),7.44(d,J=8.3Hz,1H),7.39(d,J=0.7Hz,1H),7.22(d,J=1.3Hz,1H),7.18–7.11(m,3H),7.1 0–6.97(m,16H),6.97–6.86(m,8H),2.56(dd,J=7.7,3.8Hz,8H),2.29(s,8H),1.60–1.52(m,6H),1.37–1.32(m,8H),0.96–0.87(m,12H). 13 CNMR(100MHz,Chloroform-d)δ156.77,154.37,154.06,151.72,148.28,146.17,144 .07,143.13,142.31,142.11,141.89,138.75,136.96,134.97,132.93,130.51,129.0 6,129.00,128.93,128.72,128.18,124.90,123.88,123.05,121.77,120.98,118.22,117.91,65.03,63.01,35.55,35.52,33.87,22.73,22.71,21.04,14.22,14.20,1.18.

[0067] 2.4 Synthesis of compound (II)

[0068]

[0069] Under nitrogen protection, n-butyllithium (1.6 M, 0.97 mL, 1.2 mmol) was added dropwise to a solution of compound 5 (1 g, 1 mmol) in dry THF (15 mL) at -30°C. The reaction was maintained for 2 h. Isopropyl pinacol borate (0.64 mL, 3 mmol) was then added at low temperature. The system was then transferred to room temperature and the reaction was maintained for 20 h. The reaction system was then briefly handled, the solvent was spin-dried, and 4,7-dibromobenzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) (BBT) (150 mg, 4.3 mmol), tetrakis(triphenylphosphine)palladium (98 mg, 0.9 mmol), deoxygenated K2CO3 / KF aqueous solution (2 M, 0.9 mL), and deoxygenated THF / Tol (V / V = 20 mL:20 mL) were added. The mixture was then placed in an oil bath at 90°C in the dark for 24 h. The reaction process was monitored by thin-layer chromatography. After the reaction was complete, the reaction system was extracted with DCM, and the organic phase was dried over anhydrous magnesium sulfate. Finally, it was purified by reduced pressure distillation and silica gel column chromatography to obtain a black solid compound (II) (50 mg). 1 HNMR(400MHz,Chloroform-d)δ8.88(s,2H),7.62(d,J=20.9Hz,4H),7.53–7.44(m,2H),7.46–7.28(m,8H),7.32–7 .12(m,12H),7.12–6.90(m,32H),2.59–2.53(m,16H),2.37–2.23(m,12H),1.63–1.50(m,16H),1.47–0.73(m,40H). 13 CNMR(100MHz,Chloroform-d)δ158.14,154.89,154.12,152.01,148.43,145.96,143.86, 142.96,142.18,141.94,141.77,139.84,136.88,134.69,132.90,132.76,130.39,130.34 ,129.17,128.85,128.79,128.76,128.55,124.84,124.73,122.88,121.51,121.09,118.85,118.03,64.92,63.36,35.44,35.40,33.79,33.75,29.84,22.58,22.52,20.90,14.10.

[0070] 3. The compounds (I) and (II) synthesized in the above examples were subjected to UV-visible absorption spectrum test.

[0071] The UV-visible absorption spectra of compound (I) and compound (II) are shown as follows: Figure 1 and Figure 2 The measured data are summarized in Table 1.

[0072] Solvent: dichloromethane Temperature: room temperature

[0073] dye Maximum UV-visible absorption wavelength (nm) Compound I 984 Compound II 961

[0074] Table 1

[0075] from Figure 1 and Figure 2 As can be seen, compounds (I) and (II) have only one absorption peak in the NIR II region, which is caused by charge transfer within the compound molecules; the maximum absorption wavelengths of compounds (I) and (II) are 984 nm and 961 nm, respectively. This indicates that compounds (I) and (II) have good absorption capabilities in the NIR II region and have potential applications in the field of NIR II fluorescence imaging.

[0076] The fluorescence emission spectra of compound (I) and compound (II) synthesized in the above examples were tested. The fluorescence emission spectra of compound (I) and compound (II) were as follows: Figure 3 and Figure 4 The measured data are summarized in Table 2.

[0077] Solvent: dichloromethane Temperature: room temperature

[0078] dye Maximum fluorescence emission wavelength (nm) Compound I 1307 Compound II 1246

[0079] Table 2

[0080] The maximum fluorescence emission wavelengths of compound (I) and compound (II) are 1307 nm and 1246 nm, respectively, which indicates that compound (I) and compound (II) have good near-infrared second region light emission capabilities.

[0081] The compounds (I) and (II) synthesized in the above examples were subjected to near-infrared second-zone fluorescence imaging tests. The near-infrared second-zone fluorescence imaging tests of the nanoparticles with different doping concentrations prepared from the compounds (I) and (II) were as follows: Figure 5 and Figure 6 As shown, this indicates that compound (I) and compound (II) have good near-infrared second-region fluorescence imaging capabilities.

[0082] Solvent: water; Dispersant: DSPE-mPEG2000; Excitation wavelength: 980 nm

[0083] Throughout this specification, references to terms such as "one embodiment," "example," or "specific example" indicate that the specific features, structures, materials, or characteristics described in conjunction with that embodiment or example are included in at least one embodiment or example of the present invention. In this specification, schematic representations of these terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

[0084] The basic principles, main features, and advantages of the present invention are shown and described above. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The above embodiments and descriptions are merely illustrative of the principles of the present invention. Various changes and modifications may be made to the present invention without departing from the spirit and scope of the present invention, and such changes and modifications fall within the scope of the invention as claimed.

Claims

1. A fluorescent dye, characterized in that The structural formula is: Wherein, R1 is H, methyl, ethyl or methoxy; R2 is a straight or branched alkyl-C n H 2n+1 , n<8, or a straight-chain or branched alkyl substituted phenyl group with less than 8 carbon atoms -Ph-C n H 2n+1 ,n<8.

2. A synthetic route for a fluorescent dye, characterized in that: The details are as follows: Wherein R1 is H, methyl, ethyl or methoxy; R2 is a straight or branched alkyl-C n H 2n+1 , n<8, or a straight-chain or branched alkyl substituted phenyl group with less than 8 carbon atoms -Ph-C n H 2n+1 ,n<8; R2-M is an organometallic compound containing R2.

3. The synthetic route of a fluorescent dye according to claim 2, characterized in that: The palladium catalyst used in the synthesis process is tetrakis(triphenylphosphine)palladium, palladium acetate / triphenylphosphine or tris(dibenzylideneacetone)dipalladium, and the amount thereof is 0.05-0.2 equivalent of the borate derivative.

4. The synthetic route of a fluorescent dye according to claim 2, characterized in that: The R2-M is an organic magnesium reagent or an organic lithium reagent, and its usage is 3 to 8 equivalents of the ester derivative.

5. The synthetic route of a fluorescent dye according to claim 2, characterized in that: The Lewis acid catalyst used in the synthesis process is sulfuric acid, methanesulfonic acid or boron trifluoride etherate, and the amount thereof is 0.1 to 1 equivalent of the ester derivative.

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