A boron difluoride complex containing non-alternating conjugated ligand, its preparation method and application

Abstract

This invention discloses a boron difluoride complex containing non-alternating conjugated ligands, its preparation method, and its applications. The boron difluoride complex is a compound of formula (I) or a salt thereof; wherein R is C 1～4 Alkyl, halogen, cyano, pinacol borate ester, formaldehyde, nitro, phenyl, C 1～4 Alkoxycarbonyl, C 1～4 Alkyloxy, C 1～3 One or more alkoxy groups. The fluorescent dye has a simple synthesis process, mild reaction conditions, low synthesis cost, high yield, and low toxicity, making it suitable for large-scale industrial production.

Description

Technical Field

[0001] This invention belongs to the field of preparation technology of long-wavelength absorption BF2 complexes, specifically relating to the preparation method and photophysical properties of BF2 complexes with 1-azaazine (non-alternating conjugation) as ligand. Background Technology

[0002] Bodifluoride (BODIPY) dyes have attracted widespread attention in chemistry, materials science, and life sciences due to their ease of synthesis and functionalization, excellent and tunable photophysical properties, and good photochemical stability. However, traditional BODIPY molecules possess a symmetrical rigid conjugated backbone, and the excited equilibrium structure formed after photoexcitation is similar to the ground state structure. Therefore, these dyes typically have a small Stokes shift, resulting in significant overlap between absorption and emission spectra. This presents several challenges for practical applications, such as fluorescence reabsorption by surrounding molecules leading to fluorescence self-quenching, and interference between excitation light and dye-generated fluorescence, thus reducing detection sensitivity and imaging contrast. In recent years, to overcome the drawback of the small Stokes shift in traditional BODIPY dyes, their analogues—boron difluoride compounds—have gradually become a research hotspot. While the UV absorption values ​​of traditional phenolic backbone-containing BF2 complexes are mostly below 400 nm, the compound G of this invention achieves a UV absorption value of 479 nm.

[0003] Boron difluoride compounds are formed by the chelation of boron difluoride groups (BF2) with bidentate ligands. Based on the coordinating atoms, they can be mainly classified into three categories: N,N-, N,O-, and O,O- bidentate. Similar to traditional bodies, boron difluoride compounds, due to the coordination effect of the BF2 groups, are a class of strongly luminescent fluorescent molecules with long fluorescence lifetimes and high fluorescence quantum yields. Due to the asymmetry of the ligand structure, the shapes of the ground state and excited state energy curves of boron difluoride compounds differ significantly. Therefore, the geometric configuration at the excitation equilibrium state changes significantly compared to the ground state, exhibiting a large Stokes shift. However, currently reported boron difluoride compounds typically have short absorption wavelengths, which is a key issue limiting their application in many fields. Compared to visible light dyes, near-infrared dyes have advantages such as strong cell penetration, strong photothermal properties, and low interference and toxicity to biological tissues, showing great application value in cell analysis and detection, biomolecular labeling, and photothermal / photodynamic therapy. Therefore, the design and research of novel boron difluoride dyes with near-infrared absorption characteristics have received much attention and have significant academic research and practical application value. Summary of the Invention

[0004] One of the objectives of this invention is to provide a compound of formula (I) or a salt thereof.

[0005]

[0006] Where R is C 1～4 Alkyl, halogen, cyano, pinacol borate ester, formaldehyde, nitro, phenyl, C 1～4 Alkoxycarbonyl, C 1～4 Alkyloxy, C 1～3 One or more of the alkoxy groups.

[0007] A second objective of this invention is to provide a compound of formula (II) or a salt thereof.

[0008]

[0009] Where R is C 1～4 Alkyl, halogen, cyano, pinacol borate ester, formaldehyde, nitro, phenyl, C 1～4 Alkoxycarbonyl, C 1～4 Alkyloxy, C 1～3 One or more of the alkoxy groups.

[0010] X is S,O,SO 2， Alkylene, -NH-, sulfinyl, sulfonyl.

[0011] A third objective of this invention is to provide a compound of formula (Ⅲ) or a salt thereof.

[0012]

[0013] Where R is C 1～4 Alkyl, halogen, cyano, pinacol borate ester, formaldehyde, nitro, phenyl, C 1～4 Alkoxycarbonyl, C 1～4 Alkyloxy, C 1～3 One or more of the alkoxy groups.

[0014] A fourth objective of this invention is to provide a compound of formula (Ⅳ) or a salt thereof.

[0015]

[0016] Ar represents aromatic groups such as benzene, indole, and benzofuran.

[0017] The foregoing and other aspects of the invention are now described in detail with reference to the description and methods provided herein. It should be understood that the invention may be embodied in various forms and should not be construed as limited to the embodiments mentioned herein. Rather, these embodiments are provided to make this disclosure sufficient and complete and to fully convey the scope of the invention to those skilled in the art.

[0018] The terminology used in the description of this invention is for the purpose of describing particular embodiments only and is not intended to limit the invention. As used in the description of embodiments of the invention and the appended claims, the singular forms “a,” “an,” and “the” are intended to include the plural forms unless explicitly stated otherwise in the context. Furthermore, as used herein, “and / or” refers to and includes any and all possible combinations of one or more of the associated listed items. It will be further understood that, when used in this specification, the terms “comprising” and / or “including” specify the presence of the stated features, integers, steps, operations, elements, and / or ingredients, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, ingredients, and / or groups thereof.

[0019] Generally, the nomenclature used herein and the laboratory procedures described herein in organic chemistry, medicinal chemistry, and biology are well-known and commonly used in the art. Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which they belong. Where multiple definitions exist for the terms used herein, those in this section shall prevail unless otherwise stated.

[0020] A. Definition

[0021] As used herein, "alkyl" refers to a monovalent saturated hydrocarbon chain having a specified number of carbon atoms. For example, C 1-4 Alkyl refers to an alkyl group having 1 to 4 carbon atoms. Alkyl groups can be straight-chain or branched. In some embodiments, branched alkyl groups may have one, two, or three branches. Exemplary alkyl groups include, but are not limited to, methyl, ethyl, and propyl (n-propyl and isopropyl), and butyl (n-butyl, isobutyl, sec-butyl, and tert-butyl).

[0022] As used in this article, "alkoxy" refers to the -O-alkyl group. For example, C 1-6 Alkyl groups contain 1-6 carbon atoms. (C) 1-3 Alkoxy groups contain 1 to 3 carbon atoms. Exemplary alkoxy groups include, but are not limited to, methoxy, ethoxy, and propoxy.

[0023] As used in this article, "halogen" refers to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I). "Halogen" refers to a halogen group: fluorine (-F), chlorine (-Cl), bromine (-Br), or iodine (-I).

[0024] As described herein, "ester group" refers to the -OCO-alkyl group. For example, formate group, acetate group.

[0025] As described in this article, "amino" refers to -N-alkyl. For example, dimethylamino, diethylamino.

[0026] As used herein, reference to "substituted" in a group means that one or more hydrogen atoms bonded to a member atom (e.g., a carbon atom) in the group are replaced by a substituent selected from groups of substituents as defined. It should be understood that the term "substituted" includes the implicit requirement that such substitution occurs according to the permissible valence of the substituted atom and the substituent, and that the substitution forms a stable compound (i.e., a compound that does not spontaneously transform, for example, through rearrangement, cyclization, or elimination, and is sufficiently stable to be separated from the reaction mixture). When a group is referred to as potentially containing one or more substituents, one or more (as desired) member atoms in the group may be substituted. Furthermore, a single member atom in a group may be substituted by more than one substituent, provided that such substitution conforms to the permissible valence of that atom.

[0027] As described herein, "optionally substituted" means that a particular group may be unsubstituted or may be substituted as further defined.

[0028] As used herein, a “pharmaceutically acceptable salt” is a salt that retains the desired biological activity of the target compound and exhibits minimal undesirable toxicological effects. These pharmaceutically acceptable salts can be prepared in situ during the final isolation and purification of the compound or by reacting the purified compound, in its free acid or free base form, separately with a suitable base or acid.

[0029] The fifth objective of this invention is to disclose a method for preparing the aforementioned boron difluoride-containing small organic molecules, comprising the following steps:

[0030] 1) The compound cycloheptatrienolone was dissolved in a pre-dried toluene solution, thionyl chloride was added, and the mixture was heated under reflux for 5 hours. The solvent was removed from the reaction solution under reduced pressure, and the solution was purified by silica gel chromatography to obtain a yellow-brown solid, namely compound A.

[0031] 2) Dissolve compound A in anhydrous ethanol, add ammonia water, heat under reflux for 5 hours, remove the solvent from the reaction solution under reduced pressure to obtain crude product, dissolve in ethanol, add pre-prepared hydrochloric acid aqueous solution, heat under reflux for 1 hour, add saturated sodium bicarbonate solution until no bubbles are generated, remove the solvent from the reaction solution under reduced pressure, and separate and purify by silica gel chromatography to obtain black solid, which is compound B.

[0032] 3) Under nitrogen protection, compound B was dissolved in diketene and heated under reflux for 4 hours. The solvent was removed from the reaction solution under reduced pressure, and the solution was purified by silica gel chromatography to obtain a white solid, namely compound C.

[0033] 4) Under nitrogen protection, compound C was dissolved in anhydrous ethanol, sodium ethoxide was added, and the mixture was heated under reflux for 2 hours. The solvent was removed from the reaction solution under reduced pressure, and the residue was dissolved in water. Hydrochloric acid aqueous solution was added, and a yellow solid, compound D, was precipitated under reduced pressure.

[0034] 5) Dissolve compound D in aqueous hydrobromic acid solution, heat under reflux for 2 hours, add saturated sodium bicarbonate solution dropwise until no bubbles are produced, remove solvent under reduced pressure to obtain orange solid, i.e., compound E.

[0035] 6) Compound E was dissolved in ultradry 1,2-dichloroethane, phosphorus tribromooxyphosphate was added, and the mixture was heated under reflux for 12 h. The solvent was removed from the reaction solution under reduced pressure, and the solution was purified by silica gel chromatography to obtain a brown solid, namely compound F.

[0036] 7) Under nitrogen protection, compound 1-bromo-3,6-di-tert-butyl-9H-carbazole was dissolved in triethylamine, and palladium dichloride, pinacol borane, and 1,4-dioxane were added. The mixture was heated under reflux for 3 hours, and the solvent was removed from the reaction solution under reduced pressure. The solution was then purified by silica gel chromatography to obtain a white solid, namely compound G.

[0037] 8) Dissolve compounds F and G in ethanol, add tetra(triphenylphosphine)palladium, anhydrous potassium carbonate, pre-deoxygenated toluene solution, and water, heat under reflux for 6 h, remove the solvent under reduced pressure, and purify by silica gel chromatography to obtain a red solid, namely compound H.

[0038] 9) Under nitrogen protection, compound H was dissolved in ultradry 1,2-dichloroethane, and N,N-diisopropylethylamine and boron trifluoride diethyl ether solution were added. The mixture was heated under reflux for 30 minutes, and the solvent was removed under reduced pressure. The solution was then purified by silica gel chromatography to obtain a purple solid, which is compound I.

[0039] Preferably, in step 1), the silica gel column chromatography separation conditions are ethyl acetate: petroleum ether = 3:7.

[0040] Preferably, in step 2), the silica gel column chromatography separation conditions are ethyl acetate: petroleum ether = 5:7.

[0041] Preferably, in step 3), the silica gel column chromatography separation conditions are ethyl acetate: petroleum ether = 1:1.

[0042] Preferably, in step 4), the molar ratio of compound C to sodium ethoxide is 1:3.

[0043] Preferably, in step 6), the molar ratio of compound E to phosphorus tribromooxy is 1:1.

[0044] Preferably, in step 6), the silica gel column chromatography separation conditions are dichloromethane:triethylamine = 10:1.

[0045] Preferably, in step 7), the molar ratio of compound F, palladium dichloride of bis(triphenylphosphine) and pinacol borane is 1:0.1:5.

[0046] Preferably, in step 7), the silica gel column chromatography separation conditions are dichloromethane: petroleum ether = 1:4.

[0047] Preferably, in step 8), the silica gel column chromatography separation conditions are ethyl acetate: petroleum ether = 1:1.

[0048] Preferably, in step 9), the silica gel column chromatography separation conditions are dichloromethane:triethylamine = 20:1.

[0049] Preferably, step 1) involves dissolving the compound cycloheptatrienolone in a pre-dried toluene solution, adding thionyl chloride, heating under reflux at 110°C for 5 hours, cooling the resulting mixture to room temperature, preparing a saturated sodium bicarbonate aqueous solution, adding it dropwise to the reaction solution until no bubbles are generated, extracting with ethyl acetate, drying the organic phase with anhydrous Na2SO4, filtering, removing the solvent under reduced pressure, and separating and purifying by silica gel chromatography to obtain a yellow-brown solid, namely compound A.

[0050] Preferably, step 2) involves dissolving compound B in anhydrous ethanol, adding ammonia, heating at 60°C under reflux for 5 hours, allowing to cool to room temperature, extracting with ethyl acetate, drying with anhydrous Na₂SO₄, filtering, removing the solvent under reduced pressure, and obtaining the crude product by column chromatography. The crude product is then dissolved in ethanol, refluxed at 60°C for 1 hour with a pre-prepared hydrochloric acid aqueous solution, allowed to cool to room temperature, and saturated sodium bicarbonate solution is added until no bubbles are generated. The product is extracted with dichloromethane, dried with anhydrous Na₂SO₄, filtered, and evaporated under reduced pressure. The resulting black solid, compound B, is then purified by silica gel column chromatography.

[0051] Preferably, step 3) involves dissolving compound B in diketene under nitrogen protection, heating and refluxing at 69°C for 6 hours, allowing it to cool to room temperature, extracting with dichloromethane, drying the organic phase with anhydrous Na2SO4, filtering, removing the organic phase under reduced pressure, and separating and purifying by silica gel chromatography to obtain a pale yellow solid, namely compound C.

[0052] Preferably, step 4) involves dissolving compound C in anhydrous ethanol, adding sodium ethoxide, heating under reflux at 78°C for 2 hours, allowing to cool to room temperature, extracting with dichloromethane, drying the organic phase with anhydrous Na2SO4, filtering, concentrating under reduced pressure, dissolving the residue in water, adding hydrochloric acid aqueous solution, and precipitating a yellow solid under reduced pressure, which is compound D.

[0053] Preferably, step 5) involves dissolving compound D in an aqueous hydrobromic acid solution, heating it under reflux at 100°C for 2 hours, allowing it to cool to room temperature, adding saturated sodium bicarbonate solution dropwise until no more bubbles are generated, extracting with ethyl acetate, drying the organic phase with anhydrous Na2SO4, filtering, concentrating under reduced pressure, and purifying by silica gel chromatography to obtain an orange solid, namely compound E.

[0054] Preferably, step 6) involves dissolving compound E in ultradry 1,2-dichloroethane, adding phosphorus tribromooxy, heating under reflux at 101°C for 12 hours, allowing to cool to room temperature, and adding saturated sodium bicarbonate dropwise until no more bubbles are produced. The mixture is then extracted with dichloromethane, dried over anhydrous Na₂SO₄, filtered, and the organic phase is removed under reduced pressure. The resulting product is purified by silica gel chromatography to obtain an orange solid, compound F.

[0055] Preferably, step 7) involves dissolving compound 1-bromo-3,6-di-tert-butyl-9H-carbazole in triethylamine under nitrogen protection, adding palladium dichloride, pinacol borane, and 1,4-dioxane, heating under reflux at 101°C for 3 hours, allowing to cool to room temperature, extracting with dichloromethane, drying the organic phase with anhydrous Na2SO4, filtering, removing the organic phase under reduced pressure, and purifying by silica gel chromatography to obtain a white solid, namely compound G.

[0056] Preferably, step 8) involves dissolving compounds F and G in ethanol under nitrogen protection, adding tetra(triphenylphosphine)palladium, anhydrous potassium carbonate, pre-deoxygenated toluene solution, and water, heating at 100°C under reflux for 6 hours, allowing to cool to room temperature, separating the product spots through a silica gel thin-layer plate, scraping off the product, dissolving it in dichloromethane, filtering, and concentrating under reduced pressure to remove the organic phase, yielding a red solid, namely compound H.

[0057] Preferably, step 9) involves dissolving compound H in ultra-dry 1,2-dichloroethane under nitrogen protection, adding N,N-diisopropylethylamine and boron trifluoride diethyl ether solution, heating under reflux at 69°C for 30 minutes, allowing to cool to room temperature, adding saturated sodium bicarbonate aqueous solution dropwise until no bubbles are generated, extracting with dichloromethane, drying the organic phase with anhydrous Na2SO4, filtering, removing the organic phase under reduced pressure, and separating and purifying by silica gel chromatography to obtain a purple solid, namely compound I.

[0058] Compared with the prior art, the present invention has the following significant advantages:

[0059] (1) The fluorescent compound of the present invention has a high oxygen quantum yield and low biotoxicity. The BODIPY fluorescent molecule has the advantages of structural stability, non-degradability, stable luminescence, and low toxicity, making it a good choice as a dye. The material itself has stronger anti-interference ability and is not easily interfered with in the in vivo microenvironment. In addition, the material also has the advantages of being non-toxic, biocompatible, and having a targeted intervention effect on tumor tissue, and has considerable application prospects.

[0060] (2) The synthesis process of the fluorescent dye is simple, the reaction conditions are mild, the synthesis cost is low, the yield is high, and the molecule itself has low toxicity, making it suitable for large-scale industrial production. Attached Figure Description

[0061] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the accompanying drawings used in the description of the specific embodiments or the prior art will be briefly introduced below.

[0062] Figure 1 For compound A 1 H NMR spectrum.

[0063] Figure 2 For compound B 1 H NMR spectrum.

[0064] Figure 3 For compound C 1 H NMR spectrum.

[0065] Figure 4 For compound D 1 H NMR spectrum.

[0066] Figure 5 For compound E 1 H NMR spectrum.

[0067] Figure 6 For compound F 1 H NMR spectrum.

[0068] Figure 7 For compound H 1 H NMR spectrum.

[0069] Figure 8 For compound I 1 H NMR spectrum.

[0070] Figure 9 For compound I 1 B NMR spectrum.

[0071] Figure 10 For compound I 1 F NMR spectrum.

[0072] Figure 11 This is the fluorescence emission spectrum of compound I. Detailed Implementation

[0073] To enable those skilled in the art to better understand the technical means and creative features of this invention, the technical solutions in the embodiments of this invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are merely some, not all, of the embodiments of this invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort should fall within the scope of protection of this invention.

[0074] The present invention will now be described in further detail with reference to the accompanying drawings.

[0075] Example 1

[0076] Step 1:

[0077]

[0078] The compound cycloheptatrienolone (2 g, 0.0164 mol) was dissolved in pre-dried toluene (50 mL), and thionyl chloride (1.8 mL) was added. The mixture was heated under reflux at 110 °C for 5 h. The resulting mixture was cooled to room temperature, and a saturated sodium bicarbonate aqueous solution was prepared and added dropwise to the reaction solution until no bubbles were produced. The mixture was extracted with ethyl acetate, and the organic phase was dried over anhydrous Na2SO4. After filtration and removal of the solvent under reduced pressure, the mixture was purified by silica gel chromatography to obtain 1.4 g of a yellow solid, namely compound A, with a yield of 60.82%. 1 H NMR (500MHz, CDCl3) δ7.70 (d, J = 9.4Hz, 1H), 7.19–7.07 (m, 2H), 7.04–6.97 (m, 1H), 6.86 (t, J = 10.1Hz, 1H) ppm.

[0079] Step 2

[0080]

[0081] Compound A (3 g, 0.0213 mol) was dissolved in anhydrous ethanol (120 mL), and ammonia (150 mL) was added. The mixture was heated under reflux at 60 °C for 5 h, allowed to stand and cool to room temperature, extracted with ethyl acetate, dried over anhydrous Na₂SO₄, filtered and concentrated under vacuum, and the organic phase reaction solution was evaporated to dryness under reduced pressure. The solvent was removed under reduced pressure, and the mixture was purified by silica gel column chromatography to obtain 1.84 g of black solid, which is compound B, with a yield of 71.5%. 1 H NMR (500MHz, CDCl3) δ7.34–7.27(m,1H),7.23(d,J=11.5Hz,1H),7.15(t,J=10.1Hz,1H),6.86(d,J=10.1Hz,1H),6.75(t,J=9.4Hz,1H)ppm.

[0082] Step 3

[0083]

[0084] Under nitrogen protection, compound B (2 g, 0.0165 mol) was dissolved in diketene (10 mL), heated to reflux at 69 °C for 6 h, allowed to cool to room temperature, extracted with dichloromethane, dried the organic phase with anhydrous Na2SO4, filtered, removed the organic phase under reduced pressure, and purified by silica gel chromatography to obtain 2.03 g of pale yellow solid, namely compound C, with a yield of 65.05%. 1 H NMR (500MHz, CDCl3) δ10.03(s,1H),8.98(dd,J=12.4,10.0Hz,1H),7.44–7.31(m,3H),7.04(qd,J=9.6,8.0,4.6Hz,1H),3.66(s,2H),2.33(s,3H)ppm.

[0085] Step 4

[0086]

[0087] Compound C (1 g, 4.52 mmol) was dissolved in anhydrous ethanol (50 mL), and sodium ethoxide (1.183 g, 17.39 mmol) was added. The mixture was heated under reflux at 78 °C for 2 h, allowed to stand and cool to room temperature, and then extracted with dichloromethane. The organic phase was dried over anhydrous Na₂SO₄, filtered, concentrated under reduced pressure, and evaporated to dryness. The residue was dissolved in water, and hydrochloric acid aqueous solution was added. A yellow solid of 650 mg, namely compound D, was precipitated under reduced pressure, with a yield of 76.8%. 1 H NMR (500MHz, CDCl3) δ11.88(s,1H),9.56(d,J=10.9Hz,1H),7.93(d,J=9.5Hz,1H),7 .79(t,J=10.1Hz,1H),7.72(t,J=9.8Hz,1H),7.58(t,J=9.7Hz,1H),2.75(s,3H)ppm.

[0088] Step 5

[0089]

[0090] Compound D (1 g, 5.34 mmol) was dissolved in 20 mL of hydrobromic acid aqueous solution, heated to reflux at 100 °C for 2 h, allowed to cool to room temperature, and saturated sodium bicarbonate aqueous solution was added dropwise until no bubbles were produced. The mixture was extracted with ethyl acetate, dried over anhydrous Na₂SO₄, filtered, concentrated under reduced pressure, and evaporated to dryness. The solution was then purified by silica gel column chromatography to give 0.6 g of orange solid, which is compound E, with a yield of 77.37%. 1H NMR (500MHz, CDCl3) δ11.26 (s, 1H), 7.58 (d, J = 11.0Hz, 1H), 7.24 (d, J = 8.7Hz, 1H), 7.15 (dt, J = 13.7, 10.5Hz, 2H), 7.00 (t, J = 9.7Hz, 1H) ppm.

[0091] Step 6

[0092]

[0093] Compound E (1 g, 4.829 mmol) was dissolved in ultradry 1,2-dichloroethane (100 mL), and phosphorus tribromooxygenase (2.38 g, 4.429 mmol) was added. The mixture was heated under reflux at 101 °C for 12 h, allowed to cool to room temperature, and saturated sodium bicarbonate was added dropwise until no more bubbles were produced. The mixture was extracted with dichloromethane, and the organic phase was dried over anhydrous Na₂SO₄. After filtration and removal of the organic phase under reduced pressure, the mixture was purified by silica gel column chromatography to give 750 mg of an orange solid, which is compound F, with a yield of 74.46%. 1 H NMR (500MHz, CDCl3) δ8.63(d,J=9.8Hz,1H),8.49(d,J=10.0Hz,1H),7.91(d,J= 9.8Hz,1H),7.79(t,J=9.9Hz,1H),7.69(t,J=9.8Hz,1H),7.41–7.34(m,1H)ppm.

[0094] Step 7

[0095]

[0096] Under nitrogen protection, compound 1-bromo-3,6-di-tert-butyl-9H-carbazole (358 mg, 1.0 mmol) was dissolved in triethylamine (1.49 ml), and palladium dichloride dichloride (70.2 mg, 0.1 mmol), pinacol borane (0.8 ml, 5 mmol), and 1,4-dioxane (4 ml) were added. The mixture was heated to reflux at 101 °C for 3 h, allowed to stand and cool to room temperature, extracted with dichloromethane, dried over anhydrous Na2SO4, filtered, and the organic phase was removed under reduced pressure. The mixture was purified by silica gel column chromatography to give 345 mg of white solid, compound G, with a yield of 85%. 1 H NMR (400MHz, CDCl3) δ8.96 (s, 1H), 8.22 (d, J = 2.0Hz, 1H), 8.08 (d, J = 1.6Hz, 1H), 7.89 (d, J=2.0Hz,1H),7.47(dd,J=8.5,1.9Hz,1H),7.40(d,J=8.5Hz,1H),1.50-1.41(m,30H)ppm.

[0097] Step 8

[0098]

[0099] Under nitrogen protection, compounds F (208 mg, 1 mmol) and G (405 mg, 1 mmol) were dissolved in ethanol (0.3 mL). Tetra(triphenylphosphine)palladium, anhydrous potassium carbonate, pre-deoxygenated toluene solution, and water were added. The mixture was heated to reflux at 100 °C for 6 h, allowed to stand and cool to room temperature, and the product spots were separated by silica gel thin-layer chromatography. The product was scraped off, dissolved in dichloromethane, filtered, and concentrated under reduced pressure to remove the organic phase, yielding 296 mg of red solid, namely compound H, with a yield of 73%. 1 H NMR(500MHz, CDCl3)δ11.54(s,1H),8.83–8.63(m,1H),8.48(d,J=9.9Hz,1H),8.33–8.01( m,3H),7.95(s,1H),7.70(t,J=4.8Hz,2H),7.64–7.39(m,3H),1.54(d,J=36.4Hz,18H)ppm.

[0100] Step 9

[0101]

[0102] Under nitrogen protection, compound H (300 mg, 0.66 mmol) was dissolved in ultradry 1,2-dichloroethane (5 mL). N,N-diisopropylethylamine (4.6 mL, 26.41 mmol) and boron trifluoride diethyl ether solution (8.4 mL, 31.692 mmol) were added. The mixture was heated to reflux at 69 °C for 30 minutes, allowed to cool to room temperature, and saturated sodium bicarbonate aqueous solution was added dropwise until no more bubbles were produced. The mixture was extracted with dichloromethane, and the organic phase was dried over anhydrous Na₂SO₄. After filtration and removal of the organic phase under reduced pressure, the mixture was purified by silica gel column chromatography to obtain 280 mg of a purple solid, compound I. The fluorescence emission spectrum of compound I was measured and the results are shown in [Figure number missing]. Figure 11 The yield was 83.5%. 1 H NMR (500MHz, CDCl3) δ9.50–9.44(m,1H),8.55(d,J=10.2Hz,1H),8.32(d,J=1.7Hz,1H),8.13(d,J=2.0Hz,1H),8.04–7.95( m,3H),7.91(d,J=8.5Hz,1H),7.83(t,J=9.4Hz,1H),7.77(s,1H),7.62(dd,J=8.5,2.0Hz,1H),1.51(d,J=27.3Hz,18H)ppm.

Claims

1. A boron difluoride complex containing non-alternating conjugated ligands, characterized in that, It is a compound of formula (Ⅲ) or a salt thereof; ； Where R is C 1~4 Alkyl, halogen, cyano, pinacol borate ester, formaldehyde, nitro, phenyl, C 1~4 Alkoxycarbonyl, C 1~4 Alkyloxy, C 1~3 One or more of the alkoxy groups.

2. The boron difluoride complex containing non-alternating conjugated ligands according to claim 1, characterized in that, The specific compounds are as follows: 。 3. A method for preparing the boron difluoride composite as described in claim 2, characterized in that, Includes the following steps: 1) The compound cycloheptatrienolone was dissolved in toluene, thionyl chloride was added to it, and the mixture was heated under reflux to carry out a halogenation reaction to obtain compound A; ； 2) Compound A was dissolved in anhydrous ethanol, ammonia was added, and the mixture was heated under reflux to carry out an ammoniation reaction to obtain compound B; ； 3) Compound B was dissolved in diketene under nitrogen protection and heated under reflux to give compound C; ； 4) Under nitrogen protection, compound C was dissolved in anhydrous ethanol, sodium ethoxide was added, and the mixture was heated under reflux to give compound D. ； 5) Compound D was dissolved in an aqueous solution of hydrobromic acid and heated under reflux to give compound E; ； 6) Compound E was dissolved in 1,2-dichloroethane, phosphorus tribromooxyphosphate was added, and the mixture was heated under reflux to give compound F; ； 7) Under nitrogen protection, compound 1-bromo-3,6-di-tert-butyl-9H-carbazole was dissolved in triethylamine, and palladium dichloride, pinacol borane, and 1,4-dioxane were added to the solution. The mixture was heated under reflux to give compound G. ； 8) Dissolve compounds F and G in ethanol, add tetrakis(triphenylphosphine)palladium, anhydrous potassium carbonate, toluene and water, and heat under reflux to give compound H; ； 9) Under nitrogen protection, compound H was dissolved in ultra-dry 1,2-dichloroethane, and N,N-diisopropylethylamine and boron trifluoride diethyl ether solution were added to it. The mixture was heated under reflux to obtain the boron difluoride complex. 。 4. The use of the boron difluoride complex as described in any one of claims 1 to 2 in the preparation of fluorescent dyes.

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