Boron difluoride compound containing non-alternating conjugated ligand as well as preparation method and application of boron difluoride compound

Abstract

The invention discloses a boron difluoride compound containing a non-alternating conjugated ligand as well as a preparation method and application of the boron difluoride compound. The boron difluoride compound is a compound shown in a formula (I) or a salt of the compound. Wherein R is one or more of C1-4 alkyl groups, halogen, cyano groups, boronic acid pinacol ester groups, formaldehyde groups, nitryl groups, phenyl groups, C1-4 alkoxycarbonyl groups, C1-4 alkylacyloxy groups and C1-3 alkoxy groups. The fluorescent dye is simple in synthesis process, mild in reaction condition, low in synthesis cost, relatively high in yield, low in molecular toxicity and suitable for industrial mass production. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the technical field of preparation of long-wavelength absorbing BF2 complexes, and specifically relates to a preparation method and photophysical properties of a BF2 complex using 1-azaazulene (non-alternating conjugation) as a ligand. Background Art

[0002] Boron dipyrromethene (BODIPY) dyes have attracted extensive attention in related fields such as chemistry, materials science, and life sciences due to their advantages such as easy synthesis and functional modification, excellent and adjustable photophysical properties, and good light and chemical stability. However, traditional BODIPY molecules have a symmetrical rigid conjugated skeleton, and the excited equilibrium state structure formed after the molecule is excited by light is similar to the ground state structure. Therefore, this type of dye usually has a small Stokes shift, and the absorption spectrum and emission spectrum have a large cross-overlap. This will bring a series of problems to practical applications, such as: the generated fluorescence is reabsorbed by the surrounding molecules, resulting in fluorescence self-quenching; the excitation light and the fluorescence generated by the dye interfere with each other, so the detection sensitivity and imaging contrast are reduced. In recent years, in order to overcome the disadvantage of the small Stokes shift of traditional BODIPY dyes, its analogs-boron difluoride compounds have gradually become one of the research hotspots. The ultraviolet absorption value of traditional BF2 complexes containing phenolic skeletons is mostly below 400 nanometers, and the ultraviolet absorption value of compound G of the present invention reaches 479 nanometers.

[0003] Boron difluoride compounds are formed by the chelation of boron difluoride groups (BF2) and bidentate ligands. According to the coordinated atoms, they can be mainly divided into three categories: N,N-, N,O- and O,O-bidentate. Similar to traditional BODIPY, boron difluoride compounds are a class of strong luminescent fluorescent molecules with long fluorescence lifetime and high fluorescence quantum yield due to the coordination effect of the BF2 group. Due to the asymmetry of the ligand structure, there is a big difference in the shape of the potential energy curve between the ground state and the excited state of boron difluoride compounds. Therefore, the geometric configuration when reaching the excited equilibrium state will change significantly compared with the ground state, which is manifested as a large Stokes shift. However, the boron difluoride compounds reported so far usually have the characteristics of short absorption wavelength, which has become a key problem limiting their application in many fields. Compared with dyes in the visible light region, near-infrared dyes have the characteristics of strong cell penetration, strong photothermal properties, low interference and toxicity to biological tissues, etc., and have shown great application value in the fields of cell analysis and detection, biomolecule labeling, photothermal / photodynamic therapy, etc. Therefore, the design and research of new boron difluoride dyes with near-infrared absorption characteristics have received much attention and have important academic research and practical application value. Summary of the invention

[0004] One of the objects of the present invention is to provide a compound of formula (I) or a salt thereof

[0005]

[0006] Where R is C 1～4 Alkyl, halogen, cyano, boric acid pinacol ester, formaldehyde, nitro, phenyl, C 1～4 Alkoxycarbonyl, C 1～4 Alkanoyloxy, C 1～3 One or more alkoxy groups.

[0007] The second object of the present invention is to provide a compound of formula (II) or a salt thereof

[0008]

[0009] Where R is C 1～4 Alkyl, halogen, cyano, boric acid pinacol ester, formaldehyde, nitro, phenyl, C 1～4 Alkoxycarbonyl, C 1～4 Alkanoyloxy, C 1～3 One or more alkoxy groups.

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

[0011] The third object of the present invention is to provide a compound of formula (III) or a salt thereof

[0012]

[0013] Where R is C 1～4 Alkyl, halogen, cyano, boric acid pinacol ester, formaldehyde, nitro, phenyl, C 1～4 Alkoxycarbonyl, C 1～4 Alkanoyloxy, C 1～3 One or more alkoxy groups.

[0014] The fourth object of the present invention is to provide a compound of formula (IV) or a salt thereof

[0015]

[0016] Wherein, Ar is an aromatic group such as benzene, indole, benzofuran, etc.

[0017] The foregoing and other aspects of the present invention are now described in detail with respect to the description and methods provided herein. It should be understood that the present invention can be embodied in different forms and should not be construed as being limited to the embodiments mentioned herein. On the contrary, these embodiments are provided to make this disclosure fully and completely and to fully convey the scope of the present invention to those skilled in the art.

[0018] The terms used in the description of the present invention herein are only for describing specific embodiments and are not intended to limit the present invention. As used in the description of the embodiments of the present invention and the appended claims, the singular forms of "one", "an" and "the" are intended to include plural forms unless otherwise explicitly mentioned in the context. In addition, as used herein, "and / or" refers to and includes any and all possible combinations of one or more related listed items. It will be further understood that when used in this specification, the terms "comprising" and / or "including" specify the presence of the features, integers, steps, operations, elements and / or components, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components and / or their groups.

[0019] Generally, the nomenclature used herein and the laboratory procedures in organic chemistry, medicinal chemistry, and biology described herein are well known and commonly used in the art. Unless otherwise mentioned, all technical and scientific terms used herein have the same meanings as those commonly understood by those of ordinary skill in the art to which the art belongs. In the case where there are multiple definitions for terms used herein, those in this section shall prevail unless otherwise mentioned.

[0020] A. Definition

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

[0022] As used herein, "alkoxy" refers to the group -O-alkyl. For example, C 1-6 Alkoxy groups contain 1 to 6 carbon atoms. 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 herein, "halogen" refers to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I). "Halo" refers to the halogen radical: fluorine (-F), chlorine (-Cl), bromine (-Br), or iodine (-I).

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

[0025] As used herein, "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 attached to a member atom (e.g., a carbon atom) in the group are replaced by a substituent selected from the group of defined substituents. It should be understood that the term "substituted" includes an implicit provision that such substitution is in accordance with the valence allowed by the substituted atom and the substituent and that the substitution forms a stable compound (i.e., a compound that does not spontaneously undergo transformation, such as by rearrangement, cyclization or elimination, and which is sufficiently stable to be separated from the reaction mixture). When it is mentioned that a group may contain one or more substituents, one or more (as required) member atoms in the group may be substituted. In addition, a single member atom in a group may be substituted by more than one substituent, as long as such substitution complies with the valence allowed by the atom.

[0027] As used herein, "optionally substituted" means that the specified group may be unsubstituted, or may be substituted as further defined.

[0028] As used herein, "pharmaceutically acceptable salts" refer to salts that retain the desired biological activity of the target compound and exhibit minimal undesirable toxicological effects. These pharmaceutically acceptable salts can be prepared in situ during the final isolation and purification of the compound or by separately reacting the purified compound in its free acid or free base form with a suitable base or acid, respectively.

[0029] The fifth object of the present invention is to disclose a method for preparing the above-mentioned organic small molecules containing boron difluoride, comprising the following steps:

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

[0031] 2) Compound A was dissolved in anhydrous ethanol, and aqueous ammonia was added thereto, and the mixture was heated under reflux for 5 h. The reaction solution was decompressed and the solvent was removed to obtain a crude product. The crude product was dissolved in ethanol, and a pre-prepared aqueous hydrochloric acid solution was added and heated under reflux for 1 h. A saturated sodium bicarbonate solution was added until no bubbles were generated. The reaction solution was decompressed and the solvent was removed. The product was separated and purified by silica gel chromatography to obtain a black solid, namely compound B.

[0032] 3) Compound B was dissolved in diethylene ketone under nitrogen protection, heated under reflux for 4 h, the reaction solution was decompressed to remove the solvent, and the reaction solution was separated and purified by silica gel chromatography to obtain a white solid, namely compound C.

[0033] 4) Compound C was dissolved in anhydrous ethanol under nitrogen protection, sodium ethoxide was added thereto, and the mixture was heated under reflux for 2 h. The solvent was removed from the reaction solution under reduced pressure, and the residue was dissolved in water and aqueous hydrochloric acid was added thereto. A yellow solid was precipitated under reduced pressure, i.e., compound D.

[0034] 5) Compound D was dissolved in aqueous hydrobromic acid, heated under reflux for 2 h, saturated aqueous sodium bicarbonate solution was added dropwise until no bubbles were generated, and the solvent was removed under reduced pressure to obtain an orange solid, i.e., Compound E.

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

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

[0037] 8) Compounds F and G were dissolved in ethanol, and tetrakis(triphenylphosphine)palladium, anhydrous potassium carbonate, a pre-deoxygenated toluene solution, and water were added thereto. The mixture was heated to reflux for 6 h. The solvent was removed from the reaction solution under reduced pressure, and the reaction solution was separated and purified by silica gel chromatography to obtain a red solid, namely compound H.

[0038] 9) Under nitrogen protection, compound H was dissolved in ultra-dry 1,2-dichloroethane, N,N-diisopropylethylamine and boron trifluoride ether solution were added thereto, and the mixture was heated to reflux for 30 minutes. The solvent was removed from the reaction solution under reduced pressure, and a purple solid was obtained by separation and purification on a silica gel chromatography column, namely 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 oxybromide is 1:1.

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

[0045] Preferably, in step 7), the molar ratio of compound F to bistriphenylphosphine palladium dichloride 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 condition is dichloromethane:triethylamine=20:1.

[0049] Preferably, the specific process of step 1) is to dissolve the compound tropolone in a pre-dried toluene solution, add thionyl chloride thereto, heat and reflux at 110° C. for 5 h, cool the resulting mixture to room temperature, prepare a saturated sodium bicarbonate aqueous solution, add it dropwise to the reaction solution until no bubbles are generated, extract with ethyl acetate, dry the organic phase with anhydrous Na2SO4, filter, remove the solvent under reduced pressure, and separate and purify it through a silica gel chromatography column to obtain a yellow-brown solid, i.e., compound A.

[0050] Preferably, the specific process of step 2) is to dissolve compound B in anhydrous ethanol, add aqueous ammonia thereto, heat under reflux at 60°C for 5h, stand and cool to room temperature, extract with ethyl acetate, then dry with anhydrous Na2SO4, filter, remove the solvent under reduced pressure, and analyze by column chromatography to obtain a crude product, dissolve it in ethanol, add a pre-prepared aqueous hydrochloric acid solution, heat under reflux at 60°C for 1h, stand and cool to room temperature, add a saturated sodium bicarbonate solution until no bubbles are generated, extract with dichloromethane, dry the organic phase with anhydrous Na2SO4, filter, decompress the organic phase and purify it by silica gel chromatography to obtain a black solid, namely compound B.

[0051] Preferably, the specific process of step 3) is to dissolve compound B in diethylene ketone under nitrogen protection, heat and reflux at 69° C. for 6 h, let stand and cool to room temperature, extract with dichloromethane, dry the organic phase with anhydrous Na2SO4, filter, remove the organic phase under reduced pressure, and separate and purify by silica gel chromatography to obtain a light yellow solid, i.e., compound C.

[0052] Preferably, the specific process of step 4) is to dissolve compound C in anhydrous ethanol, add sodium ethoxide thereto, heat under reflux at 78°C for 2h, stand and cool to room temperature, extract with dichloromethane, dry the organic phase with anhydrous Na2SO4, filter, concentrate under reduced pressure and spin dry, dissolve the residue in water and add aqueous hydrochloric acid solution, and precipitate a yellow solid under reduced pressure, i.e., compound D.

[0053] Preferably, the specific process of step 5) is to dissolve compound D in an aqueous hydrobromic acid solution, heat under reflux at 100° C. for 2 h, stand and cool to room temperature, add saturated aqueous sodium bicarbonate solution dropwise until no bubbles are generated, extract with ethyl acetate, dry the organic phase with anhydrous Na2SO4, filter, concentrate under reduced pressure and spin dry, and separate and purify by silica gel chromatography to obtain an orange solid, i.e., compound E.

[0054] Preferably, the specific process of step 6) is to dissolve compound E in ultra-dry 1,2-dichloroethane, add phosphorus oxybromide thereto, heat and reflux at 101°C for 12h, cool to room temperature, and drop saturated sodium bicarbonate until no bubbles are generated. Extract with dichloromethane, dry the organic phase with anhydrous Na2SO4, filter, remove the organic phase under reduced pressure, and separate and purify by silica gel chromatography to obtain an orange solid, namely compound F.

[0055] Preferably, the specific process of step 7) is to dissolve the compound 1-bromo-3,6-di-tert-butyl-9H-carbazole in triethylamine under nitrogen protection, add bistriphenylphosphine palladium dichloride, pinacol borane, and 1,4-dioxane thereto, heat and reflux at 101° C. for 3 h, let stand and cool to room temperature, extract with dichloromethane, dry the organic phase with anhydrous Na2SO4, filter, remove the organic phase under reduced pressure, and separate and purify by silica gel chromatography to obtain a white solid, i.e., compound G.

[0056] Preferably, the specific process of step 8) is to dissolve compounds F and G in ethanol under nitrogen protection, add tetrakis(triphenylphosphine)palladium, anhydrous potassium carbonate, a toluene solution deoxygenated in advance, and water, heat and reflux at 100°C for 6h, cool to room temperature, separate the product spots by silica gel thin layer plate, scrape the product, dissolve it with dichloromethane, filter, and concentrate under reduced pressure to remove the organic phase to obtain a red solid, i.e., compound H.

[0057] Preferably, the specific process of step 9) is to dissolve compound H in ultra-dry 1,2-dichloroethane under nitrogen protection, add N,N-diisopropylethylamine and boron trifluoride ether solution thereto, heat and reflux at 69° C. for 30 minutes, cool to room temperature, add saturated sodium bicarbonate aqueous solution dropwise until no bubbles are generated, extract with dichloromethane, dry the organic phase with anhydrous Na2SO4, filter, remove the organic phase under reduced pressure, and separate and purify by silica gel chromatography to obtain a purple solid, i.e., 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 high oxygen quantum yield and weak biological dark toxicity. The BODIPY fluorescent molecule has the advantages of stable structure, non-degradable molecules, stable luminescence, low toxicity, etc., and is a good choice as a dye. The material itself has stronger anti-interference ability and is not easily disturbed in the microenvironment in the body; in addition, the material also has the advantages of non-toxicity, good biocompatibility, targeted intervention effect on tumor tissue, etc., 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, which is suitable for large-scale industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0061] In order to more clearly illustrate the specific implementation of the present invention or the technical solution in the prior art, the drawings required for use in the specific implementation or the description of the prior art are 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] Fig. 9 For compound I 1 B NMR spectrum.

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

[0072] Fig.11 is the fluorescence emission spectrum of compound I. DETAILED DESCRIPTION

[0073] In order to make the technical means and creative features implemented by the present invention better understood by those skilled in the art, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the accompanying drawings of the present invention. Obviously, the described embodiments are only embodiments of a part of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in the field without creative work should fall within the scope of protection of the present invention.

[0074] The present invention is further described in detail below with reference to the accompanying drawings.

[0075] Example 1

[0076] Step 1:

[0077]

[0078] The compound tropone (2 g, 0.0164 mol) was dissolved in pre-dried toluene (50 mL), to which thionyl chloride (1.8 mL) was added, and the mixture was heated to reflux at 110° C. for 5 h. The resulting mixture was cooled to room temperature, and a saturated aqueous sodium bicarbonate solution was prepared and added dropwise to the reaction solution until no bubbles were generated. The mixture was extracted with ethyl acetate, and the organic phase was dried over anhydrous Na2SO4, filtered, and the solvent was removed under reduced pressure. The mixture was separated and purified by silica gel chromatography to obtain 1.4 g of a yellow solid, i.e., 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 aqueous ammonia (150 mL) was added thereto. The mixture was heated to reflux at 60°C for 5 h, allowed to stand and cool to room temperature, extracted with ethyl acetate, and then dried over anhydrous Na2SO4, filtered and concentrated in vacuo, the organic phase reaction liquid was dried under reduced pressure, the solvent was removed under reduced pressure, and separated and purified by silica gel chromatography to obtain 1.84 g of black solid, i.e., 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 diethylene ketone (10 mL), heated to reflux at 69°C for 6 h, allowed to stand and cool to room temperature, extracted with dichloromethane, the organic phase was dried over anhydrous Na2SO4, filtered, and the organic phase was removed under reduced pressure. The product was separated and purified by silica gel chromatography to obtain 2.03 g of a light yellow solid, i.e., 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 thereto. The mixture was heated to reflux at 78°C for 2 h, and allowed to stand and cool to room temperature. The mixture was extracted with dichloromethane, and the organic phase was dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and dried by rotation. The residue was dissolved in water and aqueous hydrochloric acid was added. 650 mg of a yellow solid was precipitated under reduced pressure, i.e., compound D. The yield was 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 aqueous hydrobromic acid solution (20 mL), heated under reflux at 100°C for 2 h, allowed to stand and cool to room temperature, and then saturated aqueous sodium bicarbonate solution was added dropwise until no bubbles were generated. The mixture was extracted with ethyl acetate, and the organic phase was dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and dried by spin drying. The mixture was separated and purified by silica gel chromatography to obtain 0.6 g of an orange solid, i.e., 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 ultra-dry 1,2-dichloroethane (100 ml), phosphorus oxybromide (2.38 g, 4.429 mmol) was added, and the mixture was heated to reflux at 101°C for 12 h, cooled to room temperature, and saturated sodium bicarbonate was added dropwise until no bubbles were generated. The mixture was extracted with dichloromethane, and the organic phase was dried over anhydrous Na2SO4, filtered, and the organic phase was removed under reduced pressure. The mixture was separated and purified by silica gel chromatography to obtain 750 mg of an orange solid, i.e., 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 bistriphenylphosphine palladium dichloride (70.2 mg, 0.1 mmol), pinacol borane (0.8 ml, 5 mmol), 1,4-dioxane (4 ml) were added thereto. The mixture was heated to reflux at 101°C for 3 h, allowed to stand and cool to room temperature, extracted with dichloromethane, and the organic phase was dried over anhydrous Na2SO4, filtered, and the organic phase was removed under reduced pressure. The mixture was separated and purified by silica gel chromatography to obtain 345 mg of a white solid, i.e., 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, compound F (208 mg, 1 mmol) and G (405 mg, 1 mmol) were dissolved in ethanol (0.3 mL), and tetrakis(triphenylphosphine)palladium, anhydrous potassium carbonate, a pre-deoxygenated toluene solution, and water were added thereto. The mixture was heated to reflux at 100°C for 6 h, and allowed to stand and cool to room temperature. The product spots were separated by silica gel thin layer plate, the product was scraped off, dissolved with dichloromethane, filtered, and concentrated under reduced pressure to remove the organic phase to obtain 296 mg of a red solid, i.e., 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 ultra-dry 1,2-dichloroethane (5 ml), N,N-diisopropylethylamine (4.6 ml, 26.41 mmol) and boron trifluoride ether solution (8.4 ml, 31.692 mmol) were added thereto, heated to reflux at 69°C for 30 minutes, allowed to stand and cool to room temperature, saturated sodium bicarbonate aqueous solution was added dropwise until no bubbles were generated, extracted with dichloromethane, the organic phase was dried over anhydrous Na2SO4, filtered, the organic phase was removed under reduced pressure, and separated and purified by silica gel chromatography to obtain 280 mg of a purple solid, namely compound I. The fluorescence emission spectrum of compound I was measured, and the results are shown in FIG. Fig.11 , with a yield of 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: is a compound of formula (I) or a salt thereof; Where R is C 1～4 Alkyl, halogen, cyano, boric acid pinacol ester, formaldehyde, nitro, phenyl, C 1～4 Alkoxycarbonyl, C 1～4 Alkanoyloxy, C 1～3 One or more alkoxy groups.

2. A boron difluoride complex containing non-alternating conjugated ligands, characterized in that: A compound of formula (II) or a salt thereof; Where R is C 1～4 Alkyl, halogen, cyano, boric acid pinacol ester, formaldehyde, nitro, phenyl, C 1～4 Alkoxycarbonyl, C 1～4 Alkanoyloxy, C 1～3 One or more alkoxy groups; X is S,O,SO 2， Alkylene, -NH-, sulfinyl or sulfonyl.

3. A boron difluoride complex containing non-alternating conjugated ligands, characterized in that: is a compound of formula (IV) or a salt thereof; Wherein, Ar is phenyl, indolyl or benzofuranyl.

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

5. The boron difluoride complex containing non-alternating conjugated ligands according to claim 4, characterized in that: The following specific compounds:

6. A method for preparing the boron difluoride complex as claimed in claim 5, characterized in that: The following steps are involved: 1) dissolving the compound tropolone in toluene, adding thionyl chloride thereto, heating under reflux to carry out halogenation reaction, and obtaining compound A; 2) dissolving compound A in anhydrous ethanol, adding aqueous ammonia, heating under reflux to carry out an amination reaction, and obtaining compound B; 3) Dissolving compound B in diethylene ketone under nitrogen protection, heating under reflux to react, to obtain compound C; 4) Dissolving compound C in anhydrous ethanol under nitrogen protection, adding sodium ethoxide thereto, heating under reflux to react, and obtaining compound D; 5) dissolving compound D in aqueous hydrobromic acid solution, heating under reflux to react, to obtain compound E; 6) dissolving compound E in 1,2-dichloroethane, adding phosphorus oxybromide thereto, heating under reflux to react, and obtaining compound F; 7) Dissolving the compound 1-bromo-3,6-di-tert-butyl-9H-carbazole in triethylamine under nitrogen protection, adding bistriphenylphosphine palladium dichloride, pinacol borane, and 1,4-dioxane thereto, and heating under reflux to react to obtain compound G; 8) Compounds F and G are dissolved in ethanol, tetrakis(triphenylphosphine)palladium, anhydrous potassium carbonate, toluene and water are added thereto, and the mixture is heated under reflux to react, thereby obtaining compound H; 9) Under nitrogen protection, compound H is dissolved in ultra-dry 1,2-dichloroethane, N,N-diisopropylethylamine and boron trifluoride ether solution are added thereto, and the mixture is heated under reflux to react, thereby obtaining the boron difluoride complex; 7. Use of the boron difluoride complex according to any one of claims 1 to 5 in the preparation of fluorescent dyes.

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