Aldehyde-group-oriented bi (hetero) aromatic compound as well as synthesis method and application thereof

Abstract

The synthesis method comprises the following steps: by taking an aldehyde group as a guiding group, taking a (hetero) aryl aldehyde compound and a (hetero) aromatic compound as reaction substrates and taking an iridium compound as a catalyst, carrying out reaction on the aldehyde group and the (hetero) aromatic compound under the synergistic effect of an oxidizing agent, an additive, a solvent, temperature and time, so as to obtain the (hetero) aromatic compound. Through a C-H / C-H oxidative coupling mode, the ortho-position aldehyde group substituted di (hetero) aromatic compound is efficiently prepared, and the technical problems that the aldehyde group coordination capacity is weak, side reactions are prone to occurring and the like are solved. Meanwhile, the bis (hetero) aromatic hydrocarbon compound and the derivative thereof can be used as a multicolor fluorescent probe with excellent performance, specific marking and high-resolution imaging of lipid droplets in living cells and mouse fatty liver are realized, and a new tool is provided for diagnosis of metabolic diseases.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology, specifically relating to an aldehyde-directed bi(hetero)aromatic compound, its synthesis method, and its application. Background Technology

[0002] Ortho-aldehyde substituted bi(hetero)aromatic hydrocarbons and their derivatives represent a valuable class of skeletal structures with significant applications, widely found in natural products, pharmaceutical molecules, and functional materials. For example, salvinal, containing the 3-aldehyde-2-arylbenzofuran skeleton, is a naturally occurring product with remarkable biological activity; raloxifene, a clinical drug used to treat postmenopausal osteoporosis in women, also contains this skeletal structure. In the field of functional materials, the polymer PCPDTBT based on this skeleton can be used for photoimaging and photothermal therapy, and the energy conversion efficiency of the organic solar cell material BT-CIC, also based on this skeleton, can reach 11.2% ± 0.4%.

[0003] Currently, methods for preparing ortho-aldehyde-substituted bi(hetero)aromatics mainly include intermolecular or intramolecular cyclization reactions, traditional Suzuki cross-coupling reactions, and transition metal-catalyzed ortho-CH(hetero)arylation reactions (CH / CX type). However, these methods generally suffer from drawbacks such as numerous synthetic steps, complex purification processes, difficulty in obtaining precursors, and low atom economy, making it difficult to achieve rapid synthesis of structurally diverse ortho-aldehyde-substituted bi(hetero)aromatics. In recent years, the transient directing group (TDG) strategy has become increasingly mature in the field of CH bond activation, effectively solving the technical pain point of requiring additional installation and removal of traditional static directing groups. This strategy promotes cyclometalation and CH functionalization by adding amines to the reaction system, which condense with aldehydes to form in-situ reversible imine intermediates as temporary directing groups. However, the above methods have technical bottlenecks. The amino group is sometimes difficult to completely remove, easily leading to nitrogen atom residues, which restricts the subsequent application of the product. Directly using the aldehyde group as a directing group to activate the CH bond has higher atom economy and avoids the steps of installing and removing exogenous directing groups. However, this technical route still faces key challenges that urgently need to be addressed. For example, compared to ketones, esters, and amides, aldehydes have weaker metal coordination ability, limiting their use in coordination-assisted CH bond functionalization reactions. Furthermore, aldehydes are easily oxidized by oxidants, leading to side reactions such as dealdehydeing, acidification, and carbonylation. Therefore, developing an efficient and universal method for the synthesis of aldehyde-directed bi(hetero)aromatic compounds has significant academic value and application prospects. Summary of the Invention

[0004] To address the aforementioned shortcomings, this invention discloses an aldehyde-directed bi(hetero)aromatic compound, its synthesis method, and its applications. This method uses an aldehyde group as the directing group and efficiently prepares ortho-aldehyde-substituted bi(hetero)aromatic compounds through iridium-catalyzed CH / CH oxidative cross-coupling. The obtained bi(hetero)aromatic compounds and their derivatives can be used as multicolor fluorescent probes in lipid droplet imaging, providing a new tool for the diagnosis of metabolic diseases.

[0005] This invention is achieved using the following technical solution:

[0006] An aldehyde-directed bi(hetero)aromatic compound, which is an ortho-aldehyde-substituted bi(hetero)aromatic compound and has the following general structural formula: Ar 1 It is one of benzothiophene, benzofuran, thiophene and its derivatives, wherein the substituents of the derivatives are taken from one or more of methyl, methoxy, phenyl, triphenylamino, ester, cyano, cyclohexyl, bromine, chlorine and fluorine atoms; Ar 2 It is one of thiophene, benzothiophene, furan, indole, pyrrole, benzene and its derivatives, and the substituent of the derivative is taken from one or more of methyl, methoxy, phenyl, trimethylsilyl, n-butyl, p-toluenesulfonyl, bromine atom, fluorine atom, and chlorine atom.

[0007] The method for synthesizing aldehyde-directed bi(hetero)aromatic compounds involves using a (hetero)aromatic aldehyde compound and a (hetero)aromatic compound as reaction substrates, adding an iridium compound, an oxidizing agent, an additive, and a solvent to undergo a CH / CH oxidative coupling reaction to generate ortho-aldehyde-substituted bi(hetero)aromatic compounds; the (hetero)aromatic aldehyde compounds have the following general structural formula:

[0008] Ar 1 It is one of benzothiophene, benzofuran, thiophene and its derivatives, wherein the substituents of the derivatives are taken from one or more of methyl, methoxy, phenyl, triphenylamino, ester, cyano, cyclohexyl, bromine atom, chlorine atom, and fluorine atom;

[0009] The (hetero)aromatic compounds have the following general structural formula:

[0010] Ar 2 It is one of thiophene, benzothiophene, furan, indole, pyrrole, benzene and its derivatives, and the substituent of the derivative is taken from one or more of methyl, methoxy, phenyl, trimethylsilyl, n-butyl, p-toluenesulfonyl, bromine atom, fluorine atom, and chlorine atom.

[0011] The general reaction formula for the CH / CH oxidative coupling reaction is as follows:

[0012] .

[0013] Furthermore, the iridium compound is one of [Cp*IrCl2]2, [Ir(cod)2]OTf, [Ir(OMe)(1,5-cod)]2, IrCl3, and [Ir(cod)Cl]2; the amount of the iridium compound is 2.5-10% of the molar amount of the heteroaryl aldehyde compound; the oxidant is one or more of silver acetate, silver carbonate, copper oxide, copper isooctanoate, pentafluoroiodobenzene, and hexabromobenzene, and the molar ratio of the oxidant to the heteroaryl aldehyde compound is (1-3):1; the solvent is one of 1,2-dichloroethane, dichloromethane, 3,4-dichlorotoluene, toluene, and tert-butanol.

[0014] Furthermore, when the iridium compound is [Cp*IrCl2]2 and its amount is 5.0% of the molar amount of the (hetero)aryl aldehyde compound, when Ar 2 When the oxidant is thiophene, benzothiophene, furan, indole, pyrrole and their derivatives, the oxidant is silver acetate and the molar ratio of the oxidant to the (hetero)aryl aldehyde compound is 3:1; when Ar 2 When the oxidant is benzene or its derivatives, the oxidant is copper isooctanoate and pentafluoroiodobenzene, and the molar ratio of copper isooctanoate to (hetero)aryl aldehyde is 1:1, and the molar ratio of pentafluoroiodobenzene to (hetero)aryl aldehyde is 2:1.

[0015] Furthermore, the additives include acidic additives and basic additives, wherein the acidic additive is one of acetic acid, acetic anhydride, and trifluoroacetic acid, and the basic additive is one of sodium trimethylacetate hydrate, potassium acetate, and cesium neopentanoate; the molar ratio of the acidic additive to the (hetero)aryl aldehyde compound is (1-3):1, and the molar ratio of the basic additive to the (hetero)aryl aldehyde compound is (1-3):1.

[0016] Furthermore, when Ar 1 When the compounds are thiophene and their derivatives, no acidic additives are required, and the basic additive is potassium acetate, with a molar ratio of basic additive to (hetero)aryl aldehyde compound of 2:1; when Ar 2 When the compounds are thiophene, benzothiophene, furan, indole, pyrrole, and their derivatives, the acidic additive is acetic acid and the molar ratio of the acidic additive to the (hetero)aryl aldehyde compound is 1:1; the alkaline washing additive is sodium trimethylacetate hydrate and the molar ratio of the alkaline additive to the (hetero)aryl aldehyde compound is 1:1; when Ar 2 When the compound is benzene or its derivatives, no basic additive is required, and the acidic additive is acetic anhydride. The molar ratio of the acidic additive to the (hetero)aryl aldehyde compound is 1:1.

[0017] Furthermore, the reaction temperature of the CH / CH oxidative coupling reaction is 80–150 °C, and the reaction time is 12–48 hours.

[0018] Furthermore, using 5-phenylbenzothiophene-3-carboxaldehyde and 2-phenylthiophene as reaction substrates, [Cp*IrCl2]2, oxidant, additives, and solvent were added and reacted at 100°C for 24 hours under an argon atmosphere to generate ortho-aldehyde-substituted bi(hetero)aromatic compounds. During the reaction, compounds with the following structural formula were generated. Circular iridium metal intermediates.

[0019] The application of the aldehyde-directed bi(hetero)aromatic compounds involves using them as fluorescent probes for specific labeling and high-resolution imaging of lipid droplets in live cells and mouse fatty livers; or modifying the aldehyde-directed bi(hetero)aromatic compounds through Suzuki cross-coupling, oxidation, and intramolecular Friedel-Crafts cyclization reactions to obtain derivatives of the bi(hetero)aromatic compounds, including bi(hetero)aromatic compounds containing triphenylamine groups and polycyclic heteroaromatic compounds, and then using these derivatives as fluorescent probes for specific labeling and high-resolution imaging of lipid droplets in live cells and mouse fatty livers.

[0020] Compared with existing technologies, this technical solution has the following advantages:

[0021] 1. This invention achieves aldehyde-directed iridium-catalyzed CH / CH oxidative cross-coupling of (hetero)aryl aldehydes and (hetero)aromatics. By rationally selecting catalysts, oxidants, additives, and solvents, it effectively solves the technical problems of weak aldehyde coordination ability and numerous side reactions. The reaction conditions of this invention are mild, and the substrate applicability is wide. It can effectively tolerate a variety of electron-donating groups (methyl, methoxy, phenyl, triphenylamino, n-butyl) and electron-withdrawing groups (ester, cyano). Crucially, sensitive halogen functional groups such as fluorine, chlorine, and bromine can also maintain structural integrity during the reaction, reserving active sites for subsequent synthetic modifications of the target compound, greatly improving the flexibility and convenience of synthesis.

[0022] 2. The method of this invention can efficiently prepare structurally diverse ortho-aldehyde substituted bi(hetero)aromatic compounds and successfully achieve gram-scale synthesis, which has good potential for industrial application and lays a solid foundation for the large-scale production of such compounds and their subsequent practical application as fluorescent probes.

[0023] 3. This invention further modifies the structure of ortho-aldehyde-substituted bi(hetero)aromatic compounds, such as introducing triphenylamine (TPA) as an electron-donating group to construct a donor-acceptor π-conjugated system, or further expanding the π-conjugated system through oxidation and intramolecular Friedel-Crafts cyclization reactions, ultimately obtaining multicolor fluorescent probes with emission wavelengths in the range of 468-564 nm, achieving cyan, green, and yellow fluorescence emission. When applied to lipid droplet imaging, the above multicolor fluorescent probes exhibit excellent comprehensive performance: good biocompatibility (extremely low cytotoxicity in the 0-20 μM concentration range, with cell viability exceeding 85%); good resistance to photobleaching (retaining more than 80% of the initial fluorescence intensity after 10 minutes of continuous scanning); and high targeting specificity (Pearson correlation coefficient with lipid droplets ≥0.88). Excellent imaging effects were observed in both live cell (HepG2 cells) and diet-induced fatty liver mouse models, clearly demonstrating the distribution, quantity, and size characteristics of lipid droplets, providing reliable imaging evidence and technical support for the early diagnosis of metabolic diseases such as fatty liver. Attached Figure Description

[0024] Figure 1 These are the absorbable spectra of compounds I, II, and III described in Experimental Example 1, where 3m represents compound I, 8 represents compound II, and 12 represents compound III.

[0025] Figure 2 These are the photoluminescence spectra of compounds I, II, and III described in Experimental Example 1, where 3m represents compound I, 8 represents compound II, and 12 represents compound III.

[0026] Figure 3 This is a schematic diagram of the cytotoxicity test results of the probe described in Experiment Example 2, where 3m represents compound I, 8 represents compound II, and 12 represents compound III.

[0027] Figure 4 The image is a confocal fluorescence image of the probe-stained cells described in Experiment Example 3, where 3m represents compound I, 8 represents compound II, and 12 represents compound III.

[0028] Figure 5 This is a schematic diagram of the photostability test results of the probe described in Experiment Example 3, where 3m represents compound I, 8 represents compound II, and 12 represents compound III.

[0029] Figure 6 This is a schematic diagram of the results of the co-staining experiment of the probe and commercial dye described in Experiment Example 4, where 3m represents compound I, 8 represents compound II, and 12 represents compound III.

[0030] Figure 7This is a slice analysis of the liver tissue of mice in the diet-induced fatty liver mouse model described in Experiment Example 5.

[0031] Figure 8 This is a confocal fluorescence image of the liver tissue of a mouse model of diet-induced fatty liver obtained after probe staining in Experiment Example 5. Detailed Implementation

[0032] The following examples further illustrate the present invention, but are not intended to limit the invention. Specific experimental conditions and methods not specified in the following examples are generally conventional methods well known to those skilled in the art, including conventional reactions carried out under magnetic stirring, argon, or air conditions; and catalytic reactions carried out under magnetic stirring, argon protection, and in 10 mL or 25 mL Schlenk tubes. Unless otherwise stated, all reagents and anhydrous solvents are from commercial suppliers (BidePharmatech, Aladdin, Energy Chemical, Adamas-beta, and Beijing InnoChem) and require no further purification before use. 3,4-Dichlorotoluene was purified and dried according to standard methods before use; 5-methoxybenzothiophene-3-carboxaldehyde (J. Med. Chem. 2015, 58, 2378–2389.), 5-phenylthiophene-3-carboxaldehyde (J. Am. Chem. Soc. 2018, 140, 6432–6440.) and 4,5,6,7-tetrahydrobenzothiophene-3-carboxaldehyde [(a) Nat. Chem. 2024, 16,817–826. (b) Chem. Heterocycl. Compd. 2015, 50, 1748–1755.] were prepared by conventional methods; other (hetero)aryl aldehyde reaction substrates were prepared by conventional methods (Asian J. Org. Chem. 2025, 14, e202500159). Nuclear magnetic resonance (NMR) spectra were recorded using a Bruker DPX 400 (400 MHz) or Bruker DPX 500 (500 MHz) instrument. 1 Chemical shift reference tetramethylsilane signal (TMS: δ0ppm) by 1H NMR (400 or 600 MHz). 13Chemical shifts were determined by C NMR (100 or 150 MHz) using CDCl3 as an internal standard (CDCl3: δ 77.0 ppm). High-resolution mass spectrometry (HRMS) data were recorded on an Agilent Technologies 6224 TOF LC / MS under electrospray ionization (ESI) conditions. X-ray single-crystal diffraction data were collected using a Bruker D8 VENTURE. Absorption spectra were measured using a PerkinElmer LAMBDA 1050+ UV-Vis spectrophotometer. Emission spectra were measured using a HITACHI F-4700 spectrometer. Confocal imaging was performed using a Leica STELLARIS 5 confocal fluorescence microscope.

[0033] Example 1: The structural formula is as follows The synthesis of 2-(5-methylthiophene-2-yl)benzothiophene-3-carboxaldehyde was performed as follows: Benzothiophene-3-carboxaldehyde (0.2 mmol), 2-methylthiophene (0.6 mmol, 3.0 equivalent), [Cp*IrCl2]2 (5.0 mol%), silver acetate (0.6 mmol, 3.0 equivalent), acetic acid (0.2 mmol, 1.0 equivalent), sodium trimethylacetate hydrate (0.2 mmol, 1.0 equivalent), and 1,2-dichloroethane (0.5 mL) were added sequentially to a 10 mL Schlenk tube. The tube was then sealed, and the reaction was carried out at 100 °C for 24 hours under an argon atmosphere. After the reaction was completed, the solvent was evaporated under reduced pressure, and the product was purified by column chromatography to obtain 35.1 mg of a yellow solid, with a yield of 68%. Further analysis revealed… 1 H NMR (500 MHz, CDCl3): δ = 10.32 (s, 1H), 8.71 (d, J = 8.0 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.47 (t, J = 7.8 Hz, 1H), 7.39 (t, J = 7.5 Hz, 1H), 7.18 (d, J = 3.0 Hz, 1H), 6.83 (s, 1H), 2.54 (s, 3H) ppm, 13 C10 NMR (125 MHz, CDCl3): δ = 186.3, 152.7, 145.2, 137.5, 137.3, 130.7, 130.1, 129.4, 126.8, 126.2, 125.9, 125.0, 121.4, 15.4 ppm, HRMS (ESI) precise mass calculation C10 14 H 10 OS2 [M+H] +: 259.0246, measured value: 259.0249.

[0034] Example 2: The structural formula is as follows 2-(5-methylthiophene-2-yl)benzofuran-3-carboxaldehyde was synthesized using the same method as described in Example 1, except that the reaction substrates were benzofuran-3-carboxaldehyde and 2-methylthiophene. The product yielded 24.2 mg of a yellow solid, with a yield of 50%. Further analysis revealed… 1 H NMR (500 MHz, CDCl3): δ =10.50 (s, 1H), 8.21 – 8.17 (m, 1H), 7.65 (d, J = 3.5 Hz, 1H), 7.51 –7.47 (m,1H), 7.37 – 7.33 (m, 2H), 6.89 (d, J = 2.5 Hz, 1H), 2.59 (s, 3H) ppm, 13 C10 NMR (125 MHz, CDCl3): δ = 185.3, 159.1, 153.5, 146.2, 130.7, 127.8, 126.9, 125.8, 125.6, 124.8, 122.1, 115.6, 110.9, 15.5 ppm, HRMS (ESI) accurate mass calculation C10 14 H 10 O2S [M+H] + : 243.0475, measured value: 243.0482.

[0035] Example 3: The structural formula is as follows The synthesis of 5-methyl-2-(5-methylthiophen-2-yl)benzothiophene-3-carboxaldehyde was performed using the same method as described in Example 1, except that the reaction substrates were 5-methylbenzothiophene-3-carboxaldehyde and 2-methylthiophene. The product yielded 41.9 mg of a yellow solid, with a yield of 77%. Further analysis revealed… 1 H NMR (400 MHz, CDCl3): δ = 10.31 (s, 1H), 8.54 (s, 1H), 7.64 (d, J = 8.4 Hz, 1H), 7.24 (d, J = 8.7 Hz, 1H), 7.17 (s, 1H), 6.84 (s, 1H), 2.55 (s, 3H), 2.49 (s, 3H) ppm, 13C10 NMR (100 MHz, CDCl3): δ = 186.4, 153.0, 145.0, 137.5, 136.4, 134.7, 130.6, 130.4, 129.3, 127.5, 126.7, 124.9, 121.0, 21.6, 15.5 ppm, HRMS (ESI) precise mass calculation C10 15 H 12 OS2 [M+H] + : 273.0403, measured value: 273.0407.

[0036] Example 4: The structural formula is as follows The synthesis of 5-methoxy-2-(5-methylthiophen-2-yl)benzothiophene-3-carboxaldehyde was performed using the same method as described in Example 1, except that the reaction substrates were 5-methoxybenzothiophene-3-carboxaldehyde and 2-methylthiophene. The product yielded 35.1 mg of an orange-yellow solid, with a yield of 61%. Further analysis revealed… 1 HNMR (400 MHz, CDCl3): δ = 10.31 (s, 1H), 8.25 (s, 1H), 7.63 (d, J = 8.8 Hz,1H), 7.17 (s, 1H), 7.05 (d, J = 8.8 Hz, 1H), 6.84 (s, 1H), 3.92 (s, 3H), 2.56 (s, 3H) ppm, 13 C10 NMR (100 MHz, CDCl3): δ = 186.4, 159.0, 153.8, 145.0, 138.6, 130.5, 130.3, 129.8, 129.3, 126.8, 122.0, 116.5, 106.6, 55.6, 15.5 ppm, HRMS (ESI) accurate mass calculation C10 15 H 12 O2S2 [M+H] + : 289.0352, measured value: 289.0348.

[0037] Example 5: The structural formula is as follows 2-(5-methylthiophene-2-yl)-5-phenylbenzothiophene-3-carboxaldehyde was synthesized using the same method as described in Example 1, except that the reaction substrates were 5-phenylbenzothiophene-3-carboxaldehyde and 2-methylthiophene. The product yielded 46.8 mg of a yellow solid, with a yield of 70%. Further analysis revealed… 1H NMR (400 MHz, CDCl3): δ = 10.35 (s, 1H), 8.97 (s, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.72 – 7.63 (m, 3H), 7.50 – 7.43 (m, 2H), 7.40 – 7.33 (m, 1H), 7.19 (s, 1H), 6.84 (s, 1H), 2.55 (s, 3H) ppm, 13 C10 NMR (100 MHz, CDCl3): δ = 186.3, 153.4, 145.3, 140.8, 139.7, 138.0, 136.5, 130.8, 130.2, 129.5, 128.8, 127.5, 127.4, 126.8, 125.4, 123.3, 121.6, 15.5 ppm. HRMS (ESI) accurate mass calculation C10 20 H 14 OS2 [M+H] + : 335.0559, measured value: 335.0555.

[0038] Example 6: The structural formula is as follows The synthesis of 5-(4-(diphenylamine)phenyl)-2-(5-methylthiophene-2-yl)benzothiophene-3-carboxaldehyde was performed using the same method as described in Example 1, except that the reaction substrates were 5-(4-(diphenylamine)phenyl)benzothiophene-3-carboxaldehyde and 2-methylthiophene. The product yielded 50.1 mg of a yellow solid, with a yield of 50%. Further analysis revealed… 1 H NMR (400 MHz, CDCl3): δ = 10.35 (s, 1H), 8.94 (s, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.57 (d, J = 8.0 Hz, 2H), 7.28 (t, J = 7.6 Hz, 4H), 7.20 (s, 1H), 7.18 – 7.12 (m, 6H), 7.04 (t, J = 7.2Hz, 2H), 6.85 (s, 1H), 2.57 (s, 3H) ppm, 13C10 NMR (100 MHz, CDCl3): δ = 186.3, 153.3, 147.6, 147.3, 145.2, 139.3, 138.0, 136.1, 134.8, 130.8, 130.3, 129.5, 129.3, 128.2, 126.8, 125.0, 124.4, 123.9, 122.9, 122.8, 121.6, 15.5 ppm. HRMS (ESI) accurate mass calculation of C10. 32 H 23 NOS2 [M+H] + : 502.1294, measured value: 502.1296.

[0039] Example 7: The structural formula is as follows The methyl 3-aldehyde-2-(5-methylthiophen-2-yl)benzothiophene-5-carboxylate was synthesized using the same method as described in Example 1, except that the reaction substrates were methyl 3-aldehyde-benzothiophene-5-carboxylate and 2-methylthiophene. The product yielded 40.5 mg of a pale yellow solid, with a yield of 64%. Further analysis revealed… 1 H NMR (400 MHz, CDCl3): δ = 10.36 (s, 1H), 9.36 (s, 1H), 8.09 (d, J = 8.4Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.24 (s, 1H), 6.88 (s, 1H), 3.98 (s, 3H), 2.58 (s, 3H) ppm, 13 C10 NMR (100 MHz, CDCl3): δ = 186.0, 167.1, 153.6, 145.8, 141.7, 137.2, 131.1, 129.7, 129.3, 128.4, 127.0, 126.58, 126.56, 121.4, 52.3, 15.5 ppm. HRMS (ESI) precise mass calculation of C10. 16 H 12 O3S2 [M+H] + : 317.0301, measured value: 317.0302.

[0040] Example 8: The structural formula is as follows The synthesis of 5-bromo-2-(5-methylthiophen-2-yl)benzothiophene-3-carboxaldehyde was performed using the same method as described in Example 1, except that the reaction substrates were 5-bromobenzothiophene-3-carboxaldehyde and 2-methylthiophene. The product yielded 47.7 mg of a yellow solid, with a yield of 71%. Further analysis revealed… 1 H NMR (500 MHz, CDCl3): δ = 10.30 (s, 1H), 8.91 (d, J = 2.0 Hz, 1H), 7.63 (d, J = 8.5 Hz, 1H), 7.51 (dd, J = 8.5, 2.0 Hz, 1H), 7.21 (d, J = 3.5 Hz, 1H), 6.87 (d, J = 3.5Hz, 1H), 2.58 (s, 3H) ppm, 13 C10 NMR (125 MHz, CDCl3): δ = 186.0, 153.9, 145.8, 138.8, 136.0, 131.1, 129.6, 129.0, 128.5, 127.7, 127.0, 122.6, 120.7, 15.5 ppm; HRMS (ESI) accurate mass calculation C10 14 H9 79 BrOS2 [M+H] + Measured value: 336.9351; Actual value: 336.9362; Precise mass calculation C 14 H9 81 BrOS2 [M+H] + : 338.9331, measured value: 338.9341.

[0041] Example 9: The structural formula is as follows The synthesis of 6-fluoro-2-(5-methylthiophen-2-yl)benzothiophene-3-carboxaldehyde was performed using the same method as described in Example 1, except that the reaction substrates were 6-fluorobenzothiophene-3-carboxaldehyde and 2-methylthiophene. The product yielded 43.6 mg of a yellow solid, with a yield of 79%. Further analysis revealed… 1 H NMR (400 MHz, CDCl3): δ = 10.30 (s, 1H), 8.69 (s, 1H), 7.45 (d, J = 8.4 Hz, 1H), 7.28 – 7.15(m, 2H), 6.85 (s, 1H), 2.57 (s, 3H) ppm, 13 C NMR (100 MHz, CDCl3): δ = 186.1,161.1 (d, J C-F= 245.9 Hz), 152.4, 145.4, 138.5 (d, J C-F = 9.8 Hz), 133.8,130.8, 129.8, 128.9, 126.8, 126.4 (d, J C-F = 8.7 Hz), 115.0 (d, J C-F = 23.2Hz), 107.7 (d, J C-F = 25.5 Hz), 15.5 ppm, 19 F NMR (471 MHz, CDCl3): δ = -114.30 ppm, HRMS (ESI) accurate mass calculation C 14 H9FOS2 [M+H] + : 277.0152, measured value: 277.0153.

[0042] Example 10: The structural formula is as follows The synthesis of 7-chloro-2-(5-methylthiophen-2-yl)benzothiophene-3-carboxaldehyde was performed using the same method as described in Example 1, except that the reaction substrates were 7-chlorobenzothiophene-3-carboxaldehyde and 2-methylthiophene. The product yielded 50.2 mg of a pale yellow solid, with a yield of 86%. Further analysis revealed… 1 H NMR (400MHz, CDCl3): δ = 10.32 (s, 1H), 8.62 (d, J = 9.0 Hz, 1H), 7.46 – 7.38 (m, 2H), 7.23 (s, 1H), 6.87 (s, 1H), 2.58 (s, 3H) ppm, 13 C10 NMR (100 MHz, CDCl3): δ = 186.3, 153.2, 145.8, 138.6, 136.8, 131.1, 129.8, 129.7, 127.7, 127.0, 126.8, 125.5, 123.4, 15.5 ppm. HRMS (ESI) precise mass calculation of C10. 14 H9 35 ClOS2 [M+H] + Measured value: 292.9857; Actual value: 292.9855; Precise mass calculation C 14 H9 37 ClOS2 [M+H] + : 294.9827, measured value: 294.9835.

[0043] Example 11: The structural formula is as follows 2-(5-bromothiophene-2-yl)benzothiophene-3-carboxaldehyde was synthesized using the same method as described in Example 1, except that the reaction substrates were benzothiophene-3-carboxaldehyde and 2-bromothiophene. The product yielded 32.2 mg of a yellow solid, with a yield of 50%. Further analysis revealed… 1 H NMR (500 MHz, CDCl3): δ =10.31 (s, 1H), 8.73 (d, J = 8.0 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.52 (t, J= 7.3 Hz, 1H), 7.46 (t, J = 7.5 Hz, 1H), 7.17 (q, J = 3.8 Hz, 2H) ppm, 13 C10 NMR (125 MHz, CDCl3): δ = 185.6, 150.3, 137.7, 137.0, 133.9, 131.2, 130.6, 130.2, 126.5, 126.3, 125.1, 121.5, 116.9 ppm, HRMS (ESI) accurate mass calculation C10 13 H7 79 BrOS2 [M+H] + Measured value: 322.9195; Actual value: 322.9196; Precise mass calculation C 13 H7 81 BrOS2 [M+H] + : 324.9174, measured value: 324.9176.

[0044] Example 12: The structural formula is as follows The synthesis of 2-(5-chlorothiophene-2-yl)-6-fluorobenzothiophene-3-carboxaldehyde was performed using the same method as described in Example 1, except that the reaction substrates were 6-fluorobenzothiophene-3-carboxaldehyde and 2-chlorothiophene. The product yielded 24.9 mg of a pale yellow solid, with a yield of 42%. Further analysis revealed… 1 H NMR (400 MHz, CDCl3): δ = 10.26 (s, 1H), 8.70 (s, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.24 (d, J= 11.3 Hz, 1H), 7.17 (s, 1H), 7.03 (s, 1H) ppm, 13 C NMR (125 MHz, CDCl3): δ =185.5, 161.2 (d, J C-F = 246.8 Hz), 150.2 (d, JC-F = 3.4 Hz), 138.7 (d, J C-F =10.1 Hz), 134.7, 133.4, 130.6, 129.9, 129.7, 127.6, 126.6 (d, J C-F = 8.5 Hz), 115.4 (d, J C-F = 23.1 Hz), 107.9 (d, J C-F = 25.6 Hz) ppm, 19 F NMR (471 MHz, CDCl3): δ = -113.47 ppm. HRMS (ESI) precise mass calculation C 13 H6 35 ClFOS2 [M+H] + Measured value: 296.9606; Accurate mass calculation C 13 H6 37 ClFOS2 [M+H] + : 298.9576, measured value: 298.9578.

[0045] Example 13: The structural formula is as follows The synthesis of 5-phenyl-2-(5-phenylthiophen-2-yl)benzothiophene-3-carboxaldehyde was performed using the same method as described in Example 1, except that the reaction substrates were 5-phenylbenzothiophene-3-carboxaldehyde and 2-phenylthiophene. The product yielded 47.5 mg of a yellow solid, with a yield of 60%. Further analysis revealed… 1 H NMR (500 MHz, CDCl3): δ = 10.44 (s, 1H), 9.00 (s, 1H), 7.85 (d, J = 8.5 Hz, 1H), 7.71 (d, J = 7.5 Hz, 2H), 7.68 (dd, J = 8.5, 1.0 Hz, 1H), 7.65 (d, J = 7.5Hz, 2H), 7.48 (t, J = 7.8 Hz, 2H), 7.43 (t, J = 7.5 Hz, 2H), 7.40 – 7.35 (m,4H) ppm, 13C10 NMR (125 MHz, CDCl3): δ = 186.1, 152.6, 149.1, 140.8, 139.8, 138.0, 136.6, 133.1, 131.6, 131.5, 129.9, 129.1, 128.8, 128.6, 127.51, 127.46, 126.0, 125.6, 124.2, 123.4, 121.7 ppm. HRMS (ESI) accurate mass calculation C10 25 H 16 OS2 [M+H] + : 397.0716, measured value: 397.0715.

[0046] Example 14: The structural formula is as follows The synthesis of 7-chloro-2-(5-methylfuran-2-yl)benzothiophene-3-carboxaldehyde was performed using the same method as described in Example 1, except that the reaction substrates were 7-chlorobenzothiophene-3-carboxaldehyde and 2-methylfuran. The product yielded 41.4 mg of a pale yellow solid, with a yield of 75%. Further analysis revealed… 1 H NMR (500MHz, CDCl3): δ = 10.58 (s, 1H), 8.59 (d, J = 8.0 Hz, 1H), 7.43 – 7.36 (m, 2H), 6.90 (d, J = 3.0 Hz, 1H), 6.23 (d, J = 3.0 Hz, 1H), 2.44 (s, 3H) ppm, 13 C10 NMR (125 MHz, CDCl3): δ = 186.9, 156.6, 147.1, 145.1, 138.6, 136.3, 128.2, 127.6, 126.9, 125.3, 123.5, 115.8, 109.3, 14.0 ppm, HRMS (ESI) accurate mass calculation C10 14 H9 35 ClO2S[M+H] + Measured value: 277.0085; Precise mass calculation C 14 H9 37 ClO2S [M+H] + : 279.0056, measured value: 279.0049.

[0047] Example 15: The structural formula is as follows 7-Chloro-2-(5-(trimethylsilyl)thiophen-2-yl)benzothiophene-3-carboxaldehyde was synthesized using the same method as described in Example 1, except that the reaction substrates were 7-chlorobenzothiophene-3-carboxaldehyde and trimethyl(thiophene-2-yl)silane. The product yielded 35 mg of a yellow solid, with a yield of 50%. Further analysis revealed… 1 H NMR (400 MHz, CDCl3): δ = 10.36 (s, 1H), 8.64 (d, J = 7.2 Hz, 1H), 7.49 –7.39 (m, 3H), 7.31 (s, 1H), 0.39 (s, 9H) ppm, 13 C10 NMR (100 MHz, CDCl3): δ = 186.4, 152.8, 147.2, 138.6, 137.0, 136.8, 135.1, 131.9, 130.0, 127.7, 126.8, 125.6, 123.5, -0.21 ppm, HRMS (ESI) accurate mass calculation C10 16 H 15 35 ClOS2Si [M+H] + Measured value: 351.0095; Actual value: 351.0091; Precise mass calculation C 16 H 15 37 ClOS2Si [M+H] + : 353.0066, measured value: 353.0069.

[0048] Example 16: The structural formula is as follows 2-(4-methylthiophene-2-yl)benzothiophene-3-carboxaldehyde was synthesized using the same method as described in Example 1, except that the reaction substrates were benzothiophene-3-carboxaldehyde and 3-methylthiophene. The product yielded 26.8 mg of a yellow solid, with a yield of 52%. Further analysis revealed… 1 H NMR (500 MHz, CDCl3): δ =10.34 (s, 1H), 8.74 (d, J = 8.0 Hz, 1H), 7.79 (d, J = 7.5 Hz, 1H), 7.49 (t, J= 7.3 Hz, 1H), 7.42 (t, J = 7.3 Hz, 1H), 7.20 (s, 1H), 7.15 (s, 1H), 2.34 (s,3H) ppm, 13C10 NMR (125 MHz, CDCl3): δ = 186.4, 152.5, 139.2, 137.7, 137.3, 132.7, 132.3, 129.9, 126.3, 126.0, 125.3, 125.1, 121.5, 15.7 ppm, HRMS (ESI) precise mass calculation C10 14 H 10 OS2 [M+H] + : 259.0246, measured value: 259.0245.

[0049] Example 17: The structural formula is as follows The synthesis of 2-(5-bromo-4-n-butylthiophene-2-yl)-7-chlorobenzothiophene-3-carboxaldehyde was performed using the same method as described in Example 1, except that the reaction substrates were 7-chlorobenzothiophene-3-carboxaldehyde and 2-bromo-3-n-butylthiophene. The product yielded 61.8 mg of a yellow solid, with a yield of 75%. Further analysis revealed… 1 HNMR (400 MHz, CDCl3): δ = 10.30 (s, 1H), 8.61 (d, J = 7.2 Hz, 1H), 7.48 – 7.40(m, 2H), 7.12 (s, 1H), 2.63 (t, J = 7.6 Hz, 2H), 1.63 (t, J = 6.8 Hz, 2H),1.46 – 1.37 (m, 2H), 0.97 (t, J = 7.4 Hz, 3H) ppm, 13 C10 NMR (100 MHz, CDCl3): δ = 185.8, 151.6, 143.9, 138.4, 137.0, 131.6, 131.5, 130.4, 127.9, 126.9, 125.8, 123.5, 114.4, 31.8, 29.3, 22.3, 13.9 ppm. HRMS (ESI) precise mass calculation of C10. 17 H 14 BrClOS2[M+H] + : 412.9431, measured value: 412.9430.

[0050] Example 18: The structural formula is as follows 5-Bromo-2-(4,5-dimethylthiophen-2-yl)benzothiophene-3-carboxaldehyde was synthesized using the same method as described in Example 1, except that the reaction substrates were 5-bromobenzothiophene-3-carboxaldehyde and 2,3-dimethylthiophene. The product yielded 49 mg of a yellow solid, with a yield of 70%. Further analysis revealed that…1 H NMR (400 MHz, CDCl3): δ = 10.29 (s, 1H), 8.88 (s, 1H), 7.60 (d, J = 8.4 Hz, 1H), 7.48 (d, J = 8.8 Hz, 1H), 7.09 (s, 1H), 2.41 (s, 3H), 2.19 (s, 3H) ppm, 13 C10 NMR (100 MHz, CDCl3): δ = 186.0, 154.2, 139.3, 138.9, 135.9, 135.2, 133.8, 128.9, 128.2, 127.6, 127.1, 122.6, 120.7, 13.6, 13.4 ppm. HRMS (ESI) precise mass calculation of C10. 15 H 11 79 BrOS2 [M+H] + Measured value: 350.9508; Actual value: 350.9505; Precise mass calculation C 15 H 11 81 BrOS2 [M+H] + : 352.9487, measured value: 352.9485.

[0051] Example 19: The structural formula is as follows The synthesis of 5-phenyl-[2,2'-bibenzothiophene]-3-carboxaldehyde was performed using the same method as described in Example 1, except that the reaction substrates were 5-phenylbenzothiophene-3-carboxaldehyde and benzothiophene. The product yielded 32.6 mg of a pale yellow solid, with a yield of 44%. Further analysis revealed… 1 H NMR (500 MHz, CDCl3): δ = 10.46 (s, 1H), 9.03 (s, 1H), 7.89 (d, J = 8.5 Hz, 3H), 7.72 (d, J= 8.0 Hz, 3H), 7.63 (s, 1H), 7.49 (t, J = 7.5 Hz, 2H), 7.47 – 7.44 (m, 2H), 7.39 (t, J = 7.3 Hz, 1H) ppm, 13C10 NMR (125 MHz, CDCl3): δ = 186.3, 152.5, 141.2, 140.7, 140.0, 139.5, 137.8, 137.3, 132.4, 131.0, 128.9, 127.5, 126.0, 125.8, 125.3, 124.6, 123.6, 122.2, 121.8 ppm. HRMS (ESI) precise mass calculation of C10. 23 H 14 OS2 [M+H] + : 371.0559, measured value: 371.0562.

[0052] Example 20: The structural formula is as follows 2-(1-methyl-1H-indol-3-yl)benzothiophene-3-carboxaldehyde was synthesized using the same method as described in Example 1, except that the reaction substrates were benzothiophene-3-carboxaldehyde and 1-methyl-1H-indol. The product yielded 24.5 mg of a red solid, with a yield of 42%. Further analysis revealed… 1 H NMR (400 MHz, CDCl3): δ = 10.18 (s, 1H), 8.77 (d, J = 8.0 Hz, 1H), 7.95 (d, J = 7.6 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.50 (t, J = 7.6 Hz, 1H), 7.46 – 7.34 (m, 4H), 7.29(d, J = 7.6 Hz, 1H), 3.91 (s, 3H) ppm, 13 C10 NMR (100 MHz, CDCl3): δ = 186.8, 154.8, 137.8, 137.3, 137.2, 131.0, 129.2, 127.0, 126.0, 125.3, 124.6, 123.4, 121.5, 121.4, 119.8, 110.0, 106.9, 33.3 ppm. HRMS (ESI) precise mass calculation of C10. 18 H 13 NOS[M+H] + : 292.0791, measured value: 292.0799.

[0053] Example 21: The structural formula is as follows 2-(1-p-toluenesulfonyl-1H-indole-3-yl)benzothiophene-3-carboxaldehyde was synthesized using the same method as described in Example 1, except that the reaction substrates were benzothiophene-3-carboxaldehyde and 1-p-toluenesulfonyl-1H-indole. The product yielded 51.7 mg of a dark red solid, with a yield of 60%. Further analysis revealed… 1 H NMR (400 MHz, CDCl3): δ = 10.07 (s, 1H), 8.79 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 8.0Hz, 1H), 7.87 (s, 4H), 7.75 (d, J = 7.6Hz, 1H), 7.54 (t, J = 7.5Hz, 1H), 7.50 – 7.41 (m, 2H), 7.33(dd, J = 21.4, 7.8 Hz, 3H), 2.38 (s, 3H)ppm, 13 C10 NMR (100 MHz, CDCl3): δ = 185.8, 150.5, 145.8, 138.3, 136.8, 134.9, 134.7, 131.4, 130.2, 129.4, 127.1, 127.0, 126.4, 126.00, 125.97, 125.1, 124.3, 121.7, 120.3, 113.8, 113.5, 21.7 ppm. HRMS (ESI) precise mass calculation of C10. 24 H 17 NO3S2[M+H] + : 432.0723, measured value: 432.0719.

[0054] Example 22: The structural formula is as follows The methyl 5-(7-chloro-3-aldehyde benzothiophene-2-yl)-1-methyl-1H-pyrrole-2-carboxylate was synthesized using the same method as described in Example 1, except that the reaction substrates were 7-chlorobenzothiophene-3-carboxaldehyde and methyl 1-methyl-1H-pyrrole-2-carboxylate. The product yielded 34.6 mg of a white solid, with a yield of 52%. Further analysis revealed… 1 H NMR (400 MHz, CDCl3): δ = 10.24 (s, 1H), 8.57 (d, J = 7.6Hz, 1H), 7.45 – 7.35 (m, 2H), 7.20 (d, J = 9.2 Hz, 2H), 4.03 (s, 3H), 3.88(s, 3H) ppm, 13C10 NMR (100 MHz, CDCl3): δ = 186.1, 161.1, 154.7, 138.7, 136.3, 129.6, 129.1, 127.5, 126.9, 125.0, 124.3, 122.9, 118.5, 114.0, 51.5, 37.3 ppm. HRMS (ESI) precise mass calculation of C10 NMR. 16 H 12 35 ClNO3S [M+H] + Measured value: 334.0300; Actual value: 334.0298; Precise mass calculation C 16 H 12 37 ClNO3S [M+H] + : 336.0270, measured value: 336.0275.

[0055] Example 23: The structural formula is as follows The synthesis of 5-bromo-4',5'-dimethyl-[2,2'-bithiophene]-3-carboxaldehyde was performed as follows: 5-bromothiophene-3-carboxaldehyde (0.1 mmol), 2,3-dimethylthiophene (0.3 mmol, 3.0 equivalent), [Cp*IrCl2]2 (5.0 mol%), silver acetate (0.2 mmol, 2.0 equivalent), potassium acetate (0.2 mmol, 2.0 equivalent), and dichloromethane (0.5 mL) were added sequentially to a 10 mL Schlenk tube. The tube was then sealed, and the reaction was carried out at 100 °C for 24 hours under an argon atmosphere. After the reaction was complete, the solvent was evaporated under reduced pressure, and the product was purified by column chromatography to obtain 10.5 mg of a yellow solid, with a yield of 35%. Analysis showed that… 1 H NMR (500 MHz, CDCl3): δ = 9.96 (s, 1H), 7.43 (s, 1H), 6.95 (s, 1H), 2.38 (s, 3H), 2.17 (s, 3H) ppm, 13 C10 NMR (125 MHz, CDCl3): δ = 184.1, 149.7, 137.8, 136.8, 134.9, 132.4, 129.2, 126.0, 111.8, 13.5, 13.2 ppm; HRMS (ESI) accurate mass calculation C10 11 H9 79 BrOS2 [M+H] + Measured value: 300.9351; Actual value: 300.9356; Precise mass calculation C 11 H9 81BrOS2 [M+H] + 302.9331, measured value: 302.9333.

[0056] Example 24: The structural formula is as follows The synthesis of 3-aldehyde-4',5'-dimethyl-[2,2'-bithiophene]-5-methylcyano was performed using the same method as described in Example 23, except that the reaction substrates were 4-aldehyde-thiophene-2-methylcyano and 2,3-dimethylthiophene. The product yielded 11.1 mg of a yellow solid, with a yield of 45%. Further analysis revealed… 1 H NMR (500MHz, CDCl3): δ = 10.08 (s, 1H), 7.94 (s, 1H), 7.12 (s, 1H), 2.42 (s, 3H), 2.20 (s, 3H) ppm, 13 C10 NMR (125 MHz, CDCl3): δ = 183.9, 152.8, 139.9, 137.6, 135.6, 135.3, 133.6, 125.2, 113.0, 107.8, 13.5, 13.4 ppm, HRMS (ESI) accurate mass calculation C10 12 H9NOS2 [M+H] + : 248.0199, measured value: 248.0198.

[0057] Example 25: The structural formula is as follows The synthesis of 4',5'-dimethyl-5-phenyl-[2,2'-bithiophene]-3-carboxaldehyde was performed using the same method as described in Example 23, except that the reaction substrates were 5-phenylthiophene-3-carboxaldehyde and 2,3-2,3-dimethylthiophene. The product yielded 10.1 mg of a yellow solid, with a yield of 34%. Further analysis revealed… 1 H NMR (500 MHz, CDCl3): δ = 10.11 (s, 1H), 7.67 (s, 1H), 7.59 (d, J = 7.5 Hz, 2H), 7.40 (t, J = 7.5 Hz, 2H), 7.33 (t, J = 7.5 Hz, 1H), 7.01 (s, 1H), 2.39 (s,3H), 2.18 (s, 3H) ppm, 13C10 NMR (125 MHz, CDCl3): δ = 185.5, 147.6, 142.6, 137.23, 137.20, 134.8, 132.8, 132.0, 129.0, 128.3, 127.4, 125.8, 121.9, 13.6, 13.2 ppm. HRMS (ESI) precise mass calculation of C10. 17 H 14 OS2 [M+H] + : 299.0559, measured value: 299.0553.

[0058] Example 26: The structural formula is as follows 2-(4,5-dimethylthiophene-2-yl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxaldehyde was synthesized using the same method as described in Example 23, except that the reaction substrates were 4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxaldehyde and 2,3-dimethylthiophene. The product yielded 8.8 mg of a yellow solid, with a yield of 32%. Further analysis revealed… 1 H NMR (500 MHz, CDCl3): δ = 10.08 (s, 1H), 6.87 (s, 1H), 2.90 (t,J = 6.0 Hz, 2H), 2.72 (t, J = 6.0 Hz, 2H), 2.37 (s, 3H), 2.15 (s, 3H), 1.85 –1.76 (m, 4H) ppm, 13 C10 NMR (125 MHz, CDCl3): δ = 186.9, 147.5, 136.4, 136.3, 135.5, 134.4, 134.3, 131.8, 128.2, 25.9, 24.8, 22.8, 22.2, 13.6, 13.1 ppm, HRMS (ESI) accurate mass calculation C10 15 H 16 OS2 [M+H] + : 277.0716, measured value: 277.0710.

[0059] Example 27: The structural formula is as follows The synthesis of 4,4',5'-trimethyl-[2,2'-bithiophene]-3-carboxaldehyde was performed using the same method as described in Example 23, except that the reaction substrates were 4-methylthiophene-3-carboxaldehyde and 2,3-dimethylthiophene. The product yielded 5.2 mg of a yellow solid, with a yield of 22%. Further analysis revealed… 1H NMR (500 MHz, CDCl3): δ = 10.14 (s, 1H), 6.91 (s, 1H), 6.78 (s, 1H), 2.47 (s, 3H), 2.38 (s,3H), 2.16 (s, 3H) ppm, 13 C10 NMR (125 MHz, CDCl3): δ = 187.1, 150.6, 139.5, 136.8, 134.5, 134.4, 132.2, 127.9, 120.5, 16.7, 13.6, 13.2 ppm, HRMS (ESI) accurate mass calculation C10 12 H 12 OS2 [M+H] + : 237.0403, measured value: 237.0412.

[0060] Example 28: The structural formula is as follows The synthesis of 2-phenylbenzothiophene-3-carboxaldehyde was as follows: Benzothiophene-3-carboxaldehyde (0.2 mmol), benzene (2.0 mL), [Cp*IrCl2]2 (5.0 mol%), pentafluoroiodobenzene (0.4 mmol, 2.0 equivalent), copper diethylhexanoate (0.2 mmol, 1.0 equivalent), acetic anhydride (0.2 mmol, 1.0 equivalent), and 3,4-dichlorotoluene (3.0 mL) were added sequentially to a 25 mL Schlenk tube. The tube was then sealed, and the reaction was carried out at 150 °C for 48 hours under an argon atmosphere. After the reaction was completed, the solvent was evaporated under reduced pressure, and the product was purified by column chromatography to obtain 33.8 mg of a white solid, with a yield of 71%. Further analysis revealed that… 1 H NMR (500 MHz, CDCl3): δ = 10.05 (s, 1H), 8.79 (d, J =8.0 Hz, 1H), 7.85 (d, J = 7.5 Hz, 1H), 7.59 (s, 2H), 7.52 (s, 4H), 7.45 (t, J= 7.0 Hz, 1H) ppm, 13 C10 NMR (125 MHz, CDCl3): δ = 186.8, 160.8, 137.9, 137.0, 131.5, 130.5, 130.1, 130.0, 128.9, 126.3, 125.8, 125.1, 121.6 ppm. HRMS (ESI) precise mass calculation of C10 NMR... 15 H 10 OS [M+H] + : 239.0526, measured value: 239.0528.

[0061] Example 29: The structural formula is as follows The synthesis of 5-methyl-2-phenylbenzothiophene-3-carboxaldehyde was performed using the same method as described in Example 28, except that the reaction substrates were 5-methylbenzothiophene-3-carboxaldehyde and benzene. The product yielded 31.8 mg of a yellow solid, with a yield of 63%. Further analysis revealed… 1 H NMR (400 MHz, CDCl3): δ =10.04 (s, 1H), 8.61 (s, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.57 (s, 2H), 7.51 (s,3H), 7.27 (d, J = 8.4 Hz, 1H), 2.52 (s, 3H) ppm, 13 C10 NMR (100 MHz, CDCl3): δ = 186.9, 161.0, 137.3, 136.4, 135.1, 131.7, 130.5, 129.93, 129.85, 128.8, 127.5, 125.0, 121.2, 21.6 ppm, HRMS (ESI) precise mass calculation C10 16 H 12 OS [M+H] + : 253.0682, measured value: 253.0680.

[0062] Example 30: The structural formula is as follows 5-Methoxy-2-phenylbenzothiophene-3-carboxaldehyde was synthesized using the same method as described in Example 28, except that the reaction substrates were 5-methoxybenzothiophene-3-carboxaldehyde and benzene. The product yielded 27.3 mg of a yellow solid, with a yield of 51%. Further analysis revealed… 1 H NMR (400 MHz, CDCl3): δ =10.04 (s, 1H), 8.31 (s, 1H), 7.70 (d, J = 8.8 Hz, 1H), 7.58 (s, 2H), 7.52 (s,3H), 7.09 (d, J = 8.8 Hz, 1H), 3.94 (s, 3H) ppm, 13 C10 NMR (100 MHz, CDCl3): δ = 186.9, 161.9, 159.0, 138.3, 131.7, 130.5, 130.2, 130.0, 129.8, 128.9, 122.2, 116.5, 106.6, 55.6 ppm. HRMS (ESI) precise mass calculation of C10.16 H 12 O2S [M+H] + : 269.0631, measured value: 269.0633.

[0063] Example 31: The structural formula is as follows 2,5-Diphenylbenzothiophene-3-carboxaldehyde was synthesized using the same method as described in Example 28, except that the reaction substrates were 5-phenylbenzothiophene-3-carboxaldehyde and benzene. The product yielded 40.8 mg of a yellow solid, with a yield of 65%. Further analysis revealed… 1 H NMR (400 MHz, CDCl3): δ = 10.09(s, 1H), 9.04 (s, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.71 (t, J = 7.4 Hz, 3H),7.64 – 7.59 (m, 2H), 7.54 (s, 3H), 7.48 (t, J = 7.4 Hz, 2H), 7.38 (t, J = 7.2Hz, 1H) ppm, 13 C10 NMR (100 MHz, CDCl3): δ = 186.8, 161.4, 140.9, 139.8, 137.7, 136.9, 131.6, 130.6, 130.2, 130.1, 128.9, 128.8, 127.6, 127.4, 125.3, 123.5, 121.8 ppm. HRMS (ESI) precise mass calculation of C10. 21 H 14 OS [M+H] + : 315.0839, measured value: 315.0838.

[0064] Example 32: The structural formula is as follows The synthesis of 5-bromo-2-phenylbenzothiophene-3-carboxaldehyde was performed using the same method as described in Example 28, except that the reaction substrates were 5-bromobenzothiophene-3-carboxaldehyde and benzene. The product yielded 44.2 mg of a yellow solid, with a yield of 70%. Further analysis revealed… 1 H NMR (500 MHz, CDCl3): δ = 10.01 (s,1H), 8.96 (d, J = 2.0 Hz, 1H), 7.70 (d, J = 8.5 Hz, 1H), 7.60 – 7.57 (m, 2H),7.56 – 7.53 (m, 4H) ppm, 13C10 NMR (125 MHz, CDCl3): δ = 186.4, 161.9, 138.5, 136.4, 131.0, 130.5, 130.3, 129.2, 129.00, 128.97, 127.8, 122.8, 120.7 ppm, HRMS (ESI) accurate mass calculation C10 15 H9 79 BrOS [M+H] + Measured value: 316.9631; Actual value: 316.9628; Precise mass calculation C 15 H9 81 BrOS [M+H] + : 318.9610, measured value: 318.9611.

[0065] Example 33: The structural formula is as follows The methyl 3-aldehyde-2-phenylbenzothiophene-5-carboxylate was synthesized using the same method as described in Example 28, except that the reaction substrates were methyl 3-aldehyde-benzothiophene-5-carboxylate and benzene. The product yielded 38.5 mg of a white solid, with a yield of 65%. Further analysis revealed… 1 H NMR (400 MHz, CDCl3): δ = 10.07 (s, 1H), 9.41 (s, 1H), 8.11 (d, J = 8.4 Hz, 1H), 7.88 (d, J= 8.4 Hz, 1H), 7.59 (s, 2H), 7.55 (s, 3H), 3.98 (s, 3H) ppm, 13 C10 NMR (100 MHz, CDCl3): δ = 186.4, 167.1, 161.5, 142.1, 136.9, 131.0, 130.5, 130.3, 130.1, 129.0, 128.4, 126.7, 126.5, 121.6, 52.3 ppm. HRMS (ESI) accurate mass calculation of C10 NMR. 17 H 12 O3S [M+H] + : 297.0580, measured value: 297.0585.

[0066] Example 34: The structural formula is as follows The synthesis of 6-fluoro-2-phenylbenzothiophene-3-carboxaldehyde was performed using the same method as described in Example 28, except that the reaction substrates were 6-fluorobenzothiophene-3-carboxaldehyde and benzene. The product yielded 30.7 mg of a white solid, with a yield of 60%. Further analysis revealed… 1H NMR (400 MHz, CDCl3): δ = 10.02 (s,1H), 8.75 (t, J = 5.8 Hz, 1H), 7.57 (s, 2H), 7.53 (s, 4H), 7.26 (t, J = 8.8Hz, 1H) ppm, 13 C NMR (125 MHz, CDCl3): δ = 186.6, 161.0 (d, J C-F = 245.5 Hz), 160.4 (d, J C-F = 2.8 Hz), 138.9 (d, J C-F = 10.0 Hz), 133.5, 131.2, 130.5,130.2, 129.5, 129.0, 126.5 (d, J C-F = 8.9 Hz), 115.1 (d, J C-F = 23.0 Hz), 107.9 (d, J C-F = 25.5 Hz) ppm, 19 F NMR (565 MHz, CDCl3): δ = -114.59 ppm, HRMS (ESI) accurate mass calculation C 15 H9FOS [M+H] + : 257.0431, measured value: 257.0429.

[0067] Example 35: The structural formula is as follows The synthesis of 7-chloro-2-phenylbenzothiophene-3-carboxaldehyde was performed using the same method as described in Example 28, except that the reaction substrates were 7-chlorobenzothiophene-3-carboxaldehyde and benzene. The product yielded 34.8 mg of a white solid, with a yield of 64%. Further analysis revealed… 1 H NMR (400 MHz, CDCl3): δ = 10.04 (s,1H), 8.68 (d, J = 7.6 Hz, 1H), 7.60 (s, 2H), 7.54 (s, 3H), 7.50 – 7.41 (m,2H) ppm, 13 C10 NMR (100 MHz, CDCl3): δ = 186.7, 161.2, 138.3, 137.3, 131.1, 130.53, 130.46, 130.3, 129.0, 127.7, 127.0, 125.4, 123.5 ppm, HRMS (ESI) accurate mass calculation C10 15 H935 ClOS [M+H] + Measured value: 273.0136; Actual value: 273.0141; Precise mass calculation C 15 H9 37 ClOS [M+H] + : 275.0106, measured value: 275.0105.

[0068] Example 36: The structural formula is as follows 2-Phenylenol-3-carboxaldehyde was synthesized using the same method as described in Example 28, except that the reaction substrates were benzofuran-3-carboxaldehyde and benzene. The product yielded 33.8 mg of a pale yellow solid, with a yield of 76%. Further analysis revealed… 1 H NMR (500 MHz, CDCl3): δ = 10.35 (s, 1H), 8.29(d, J = 7.0 Hz, 1H), 7.88 – 7.85 (m, 2H), 7.59 – 7.55 (m, 4H), 7.42 – 7.38(m, 2H) ppm, 13 C10 NMR (125 MHz, CDCl3): δ = 186.7, 165.4, 154.0, 131.1, 129.1, 128.6, 126.0, 125.4, 124.8, 122.7, 117.5, 111.1 ppm, HRMS (ESI) accurate mass calculation C10 15 H 10 O2 [M+H] + : 223.0754, measured value: 223.0759.

[0069] Example 37: The structural formula is as follows 2-(4-Tolyl)benzofuran-3-carboxaldehyde and its structural formula are 2-(3-Tolyl)benzofuran-3-carboxaldehyde was synthesized using the same method as described in Example 28, except that the reaction substrates were benzofuran-3-carboxaldehyde and toluene. The product yielded 33.5 mg of a pale yellow solid, with a yield of 71%. NMR analysis determined the meta / para isomer ratio to be meta / para = 1.1:1. 1H NMR (500 MHz, CDCl3): δ = 10.34 (d, J = 3.0 Hz, 1.00H), 8.30 – 8.25 (m, 1.00H), 7.76 (d, J = 8.0 Hz, 1.00H), 7.68 – 7.64 (m, 1.04H), 7.55 (t, J = 6.0Hz, 1.03H), 7.45 (t, J = 7.5 Hz, 0.58H), 7.41 – 7.35 (m, 3.62H), 2.47 (d, J =5.5 Hz, 3.00H) ppm, 13 C10 NMR (100 MHz, CDCl3): δ = 186.8, 186.7, 165.7, 153.93, 153.86, 141.7, 139.0, 131.9, 129.9, 129.6, 129.0, 128.5, 126.4, 125.9, 125.8, 125.7, 125.5, 125.4, 124.8, 124.7, 122.7, 122.6, 117.4, 117.1, 111.09, 111.05, 21.6, 21.4 ppm. HRMS (ESI) precise mass calculation of C10. 16 H 12 O2 [M+H] + : 237.0911, measured value: 237.0915.

[0070] Example 38: The structural formula is as follows 2-(4-chlorophenyl)benzo[b]furan-3-carboxaldehyde and its structural formula are 2-(3-chlorophenyl)benzofuran-3-carboxaldehyde was synthesized using the same method as described in Example 28, except that the reaction substrates were benzofuran-3-carboxaldehyde and chlorobenzene. The product yielded 31.7 mg of a pale yellow solid, with a yield of 62%. NMR analysis determined that the ratio of its para to meta isomers was para / meta = 1.1:1. 1 H NMR (400 MHz, CDCl3): δ = 10.35 (d, J = 8.8 Hz, 0.98H), 8.27 (s, 1.00H), 7.87 (s, 0.48H), 7.82 (d, J = 8.0 Hz, 1.05H), 7.75 (d, J = 5.6 Hz, 0.52H),7.59 – 7.49 (m, 3.00H), 7.41 (s, 2.02H) ppm, 13C10 NMR (125 MHz, CDCl3): δ = 186.13, 186.12, 163.7, 163.2, 154.0, 153.9, 137.5, 135.3, 131.1, 130.4, 130.2, 129.5, 128.8, 127.2, 127.0, 126.4, 126.3, 125.3, 125.2, 125.02, 124.96, 122.8, 122.6, 118.0, 117.6, 111.22, 111.16 ppm. HRMS (ESI) precise mass calculation of C10. 15 H9 35 ClO2 [M+H] + : 257.0364, Measured value: 257.0366; C 15 H9 37 ClO2 [M+H] + : 259.0335, measured value: 259.0337.

[0071] Example 39: The structural formula is as follows 2-(3,4-xylyl)benzofuran-3-carboxaldehyde was synthesized using the same method as described in Example 28, except that the reaction substrates were benzofuran-3-carboxaldehyde and o-xylene. The product yielded 31.5 mg of a pale yellow solid, with a yield of 63%. Further analysis revealed… 1 H NMR (500 MHz, CDCl3): δ =10.34 (s, 1H), 8.29 – 8.24 (m, 1H), 7.63 (s, 1H), 7.59 (d, J = 7.5 Hz, 1H), 7.54 (d, J = 6.5 Hz, 1H), 7.40 – 7.36 (m, 2H), 7.32 (d, J = 7.5 Hz, 1H), 2.37 (d, J = 4.5 Hz, 6H) ppm, 13 C10 NMR (125 MHz, CDCl3): δ = 186.9, 166.0, 153.9, 140.5, 137.7, 130.4, 130.1, 126.7, 126.1, 125.8, 125.5, 124.7, 122.6, 117.1, 111.0, 19.9, 19.8 ppm. HRMS (ESI) accurate mass calculation C10. 17 H 14 O2 [M+H] + : 251.1067, measured value: 251.1066.

[0072] Example 40: The structural formula is as follows 2-(3,4-dichlorotoluyl)benzofuran-3-carboxaldehyde was synthesized using the same method as described in Example 28, except that the reaction substrates were benzofuran-3-carboxaldehyde and 1,2-dichlorobenzene. The product yielded 32.5 mg of a pale yellow solid, with a yield of 56%. Further analysis revealed… 1 H NMR (500 MHz, CDCl3): δ= 10.35 (s, 1H), 8.25 (d, J = 7.5 Hz, 1H), 7.99 (d, J = 1.5 Hz, 1H), 7.72(dd, J = 8.3, 1.8 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.56 (d, J = 8.0 Hz,1H), 7.46 – 7.38 (m, 2H) ppm, 13 C10 NMR (125 MHz, CDCl3): δ = 185.6, 161.7, 154.0, 135.6, 133.7, 131.2, 130.4, 128.4, 127.9, 126.6, 125.2, 125.1, 122.7, 118.0, 111.2 ppm. HRMS (ESI) precise mass calculation of C10. 15 H8Cl2O2 [M+H] + : 290.9975, measured value: 290.9970.

[0073] Example 41: The structural formula is as follows 2-(3,5-xylyl)benzofuran-3-carboxaldehyde was synthesized using the same method as described in Example 28, except that the reaction substrates were benzofuran-3-carboxaldehyde and m-xylene. The product yielded 26.5 mg of a pale yellow solid, with a yield of 53%. Further analysis revealed… 1 H NMR (400 MHz, CDCl3): δ =10.34 (s, 1H), 8.27 (d, J = 6.4 Hz, 1H), 7.55 (d, J = 6.4 Hz, 1H), 7.47 (s,2H), 7.42 – 7.36 (m, 2H), 7.21 (s, 1H), 2.43 (s, 6H) ppm, 13C10 NMR (100 MHz, CDCl3): δ = 187.0, 166.1, 153.9, 138.9, 132.9, 128.4, 127.0, 125.9, 125.4, 124.8, 122.7, 117.3, 111.1, 21.3 ppm, HRMS (ESI) accurate mass calculation C10 17 H 14 O2 [M+H] + : 251.1067, measured value: 251.1070.

[0074] Example 42: The structural formula is as follows 2-(3-chloro-5-methylphenyl)benzofuran-3-carboxaldehyde was synthesized using the same method as described in Example 28, except that the reaction substrates were benzofuran-3-carboxaldehyde and 1-chloro-3-methylbenzene. The product yielded 24.8 mg of a pale yellow solid, with a yield of 46%. Further analysis revealed… 1 H NMR (400 MHz, CDCl3): δ = 10.35 (s, 1H), 8.27 (d, J = 6.8 Hz, 1H), 7.67 (s, 1H), 7.56 (d, J= 8.4 Hz, 2H), 7.45 – 7.35 (m, 3H), 2.46 (s, 3H) ppm, 13 C10 NMR (100 MHz, CDCl3): δ = 186.2, 163.6, 154.0, 140.9, 135.0, 131.7, 130.0, 127.9, 126.3, 126.0, 125.2, 125.0, 122.8, 117.9, 111.2, 21.3 ppm. HRMS (ESI) precise mass calculation C10 16 H 11 35 ClO2[M+H] + Measured value: 271.0521; Actual value: 271.0527; Precise mass calculation C 16 H 11 37 ClO2 [M+H] + : 273.0491, Measured value: 273.0491.

[0075] Example 43: The structural formula is as follows 2-(4-methoxy-3,5-dimethylphenyl)benzofuran-3-carboxaldehyde was synthesized using the same method as described in Example 28, except that the reaction substrates were benzofuran-3-carboxaldehyde and 2-methoxy-1,3-dimethylbenzene. The product yielded 29.1 mg of a pale yellow solid, with a yield of 52%. Further analysis revealed… 1 HNMR (400 MHz, CDCl3): δ = 10.33 (s, 1H), 8.26 (d, J = 4.3 Hz, 1H), 7.52 (s,3H), 7.38 (d, J = 3.6 Hz, 2H), 3.81 (s, 3H), 2.39 (s, 6H) ppm, 13 C10 NMR (100MHz, CDCl3): δ = 186.9, 165.7, 159.7, 153.8, 132.1, 129.8, 125.8, 125.5, 124.7, 124.0, 122.6, 117.0, 111.0, 59.8, 16.3 ppm, HRMS (ESI) accurate mass calculation C10 18 H 16 O3 [M+H] + : 281.1173, Measured value: 281.1173.

[0076] Example 44: Gram-scale reaction of 2-(5-methylthiophene-2-yl)benzothiophene-3-carboxaldehyde as described in Example 1: Benzothiophene-3-carboxaldehyde (8.0 mmol), 2-methylthiophene (24 mmol, 3.0 equivalent), [Cp*IrCl2]2 (5.0 mol%), silver acetate (24 mmol, 3.0 equivalent), acetic acid (8.0 mmol, 1.0 equivalent), sodium trimethylacetate hydrate (8.0 mmol, 1.0 equ equivalent), and 1,2-dichloroethane (20 mL) were added sequentially to a 100 mL Schlenk tube. The tube was then sealed, and the reaction was carried out at 100 °C for 24 hours under an argon atmosphere. After the reaction was completed, the solvent was evaporated under reduced pressure, and the product was purified by column chromatography to obtain 1428.1 mg of a yellow solid, with a yield of 69%. The results of this reaction indicate that the method described in this invention has good potential for industrial scale-up applications.

[0077] Example 45: The structural formula is as follows The synthesis method of the cycloiridium metal intermediate is as follows: [Cp*IrCl2]2 (0.05 mmol), 5-phenylbenzothiophene-3-carboxaldehyde (0.25 mmol, 5.0 equivalent), sodium acetate (0.5 mmol, 10 equivalent), and 1,2-dichloroethane (0.5 mL) were added sequentially to a 10 mL Schlenk tube. The tube was then sealed, and the reaction was carried out at 80 °C for 24 hours under an argon atmosphere. After the reaction was completed, the solvent was evaporated under reduced pressure, and the product was purified by column chromatography to obtain 36 mg of a yellow solid, with a yield of 60%. Analysis showed that... 1 H NMR (500 MHz, CDCl3): δ = 9.25(s, 1H), 8.08 (d, J = 1.0 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 7.5Hz, 2H), 7.49 – 7.42 (m, 3H), 7.37 (t, J = 7.3 Hz, 1H), 1.83 (s, 15H) ppm, 13 CNMR (125 MHz, CDCl3): δ = 208.9, 190.0, 145.8, 143.5, 141.2, 139.2, 137.2, 128.8, 127.4, 127.3, 122.9, 122.3, 118.4, 89.9, 9.48 ppm, HRMS (ESI) accurate mass calculation C 25 H 24 ClIrOS [M-Cl] + Measured value: 565.1172, actual value: 565.1168. Characterization revealed the presence of the oxygen-coordinated cycloiridium metal intermediate described in this embodiment during the reactions in Examples 13, 19, and 31. This provides crucial evidence for the catalytic cycle of the CH / CH oxidative coupling reaction described in this invention, confirming the rationality of the reaction pathway.

[0078] X-ray diffraction of single crystals of cycloiridium metal intermediates were obtained from 1,2-dichloroethane-n-hexane solution. The X-ray single crystal structure data are stored at the Cambridge Crystallographic Data Center (CCDC 2503533). The diffraction data were collected using Ga-Kα radiation (λ = 1.34138 Å) and Bruker D8 VENTURE. Detailed information is shown in Table 1.

[0079] Table 1. Analytical information on iridium cyclometallic intermediates

[0080]

[0081] Example 46: The synthesis of the triphenylamine-modified compound 2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)benzothiophen-3-carboxaldehyde was performed as follows: 2-(5-bromothiophen-2-yl)benzothiophen-3-carboxaldehyde (0.6 mmol), triphenylamine 4-boronic acid 7 (1.2 mmol, 2.0 equivalent), Pd(PPh3)4 (5.0 mol%), toluene (5.0 mL), ethanol (3.0 mL), and 2.0 M sodium carbonate solution (3.0 mL) were added sequentially to a 100 mL Schlenk tube. The tube was then sealed, and the reaction was carried out at 130 °C for 12 hours under an argon atmosphere. After the reaction was complete, the product was extracted with ethyl acetate, the solvent was evaporated under reduced pressure, and the product was purified by column chromatography to obtain 277.7 mg of an orange-yellow solid, with a yield of 95%. The product was analyzed... 1 H NMR (500 MHz, CDCl3): δ = 10.42 (s,1H), 8.74 (d, J = 8.0 Hz, 1H), 7.80 (d, J = 7.5 Hz, 1H), 7.52 – 7.47 (m, 3H),7.43 (t, J = 7.0 Hz, 1H), 7.35 (d, J = 4.0 Hz, 1H), 7.31 – 7.27 (m, 5H), 7.15(s, 2H), 7.13 (s, 2H), 7.10 – 7.05 (m, 4H) ppm, 13 C10 NMR (125 MHz, CDCl3): δ = 186.2, 152.3, 149.2, 148.3, 147.1, 137.5, 137.4, 131.6, 130.5, 129.6, 129.4, 126.7, 126.6, 126.4, 126.0, 125.1, 124.9, 123.5, 123.2, 123.0, 121.5 ppm. HRMS (ESI) precise mass calculation of C10. 31 H 21 NOS2 [M+H] + : 488.1138, measured value: 488.1129.

[0082] The reaction formula for the synthesis is:

[0083] .

[0084] Example 47: The structural formula is as follows The synthesis method of polycyclic aromatic hydrocarbon compound A is as follows: First, 2-(5-methylthiophene-2-yl)benzothiophene-3-carboxaldehyde (1.0 mmol) was added to a 50 mL round-bottom flask and completely dissolved in 10 mL of 1,4-dioxane:water (7:3; v / v). Then, sodium chlorite (1.5 mmol, 1.5 eq equivalent) and aminosulfonic acid (5.0 mmol, 5.0 eq equivalent) were added sequentially. After reacting for 5 hours at room temperature, the reaction was quenched with 10% sodium bicarbonate solution. The product was extracted with ethyl acetate, the solvent was evaporated under reduced pressure, and the product was purified by column chromatography to obtain the product with the following structural formula: 197.3 mg of a yellow solid of 2-(5-methylthiophen-2-yl)benzothiophen-3-carboxylic acid was obtained in 72% yield. Subsequently, oxalyl chloride (0.25 mmol, 2.5 equivalents) and two drops of N,N-dimethylformamide were slowly added dropwise to 2.0 mL of anhydrous dichloromethane solution containing 2-(5-methylthiophen-2-yl)benzothiophen-3-carboxylic acid at 0 °C. The reaction tube was sealed and the reaction was carried out at room temperature under an argon atmosphere for 6.0 h. After the reaction was completed, the solvent was evaporated under reduced pressure to obtain the acyl chloride intermediate.

[0085] Then, 1.0 mL of anhydrous dichloromethane was added, and aluminum trichloride (0.4 mmol, 4.0 equivalent) was stirred and dissolved. The system was then cooled to -20 °C. Under an argon atmosphere, 1.0 mL of a pre-prepared anhydrous dichloromethane solution of the acyl chloride intermediate was slowly added dropwise to the above system. After the addition was complete, the reaction was stirred overnight at -20 °C. Subsequently, 2.0 mL of water was added to the reaction flask at -20 °C, and stirring was continued for 5.0 min. The reaction mixture was dissolved in dichloromethane and extracted with ammonium chloride and sodium bicarbonate solution. The solvent was then evaporated under reduced pressure, and the product was purified by column chromatography to obtain 7.7 mg of a dark green solid polycyclic aromatic hydrocarbon compound, with a yield of 30%. Analysis showed that... 1 H NMR (500 MHz, CDCl3): δ = 7.94 (d, J = 8.0 Hz,1H), 7.70 (d, J = 8.0 Hz, 1H), 7.37 (t, J = 7.8 Hz, 1H), 7.21 (t, J = 7.8 Hz,1H), 6.70 (d, J = 1.0 Hz, 1H), 2.46 (s, 3H) ppm, 13 C10 NMR (125 MHz, CDCl3): δ = 183.6, 153.4, 145.3, 144.4, 143.0, 132.7, 132.6, 126.6, 124.0, 123.3, 121.7, 119.7, 15.8 ppm. HRMS (ESI) precise mass calculation of C10.14 H8OS2 [M+H] + : 257.0090, measured value: 257.0078.

[0086] The reaction formula for the synthesis is as follows:

[0087] .

[0088] Example 48: The structural formula is as follows Synthesis of polycyclic aromatic hydrocarbon compound B: First, 2-phenylbenzothiophene-3-carboxaldehyde (1.0 mmol) was added to a 50 mL round-bottom flask and completely dissolved in 10 mL of 1,4-dioxane:water (7:3; v / v) solution. Then, sodium chlorite (1.5 mmol, 1.5 equivalent) and aminosulfonic acid (5.0 mmol, 5.0 equivalent) were added sequentially. After reacting for 5 hours at room temperature, the reaction was quenched with 10% sodium bicarbonate solution. The product was extracted with ethyl acetate, the solvent was evaporated under reduced pressure, and the product was purified by column chromatography to obtain the product with the following structural formula: 188 mg of a yellow solid of 2-phenylbenzothiophene-3-carboxaldehyde was obtained, with a yield of 74%. Subsequently, thionyl chloride (0.4 mmol, 4.0 equivalent) and two drops of N,N-dimethylformamide were slowly added dropwise to 4.0 mL of anhydrous 1,2-dichloroethane solution containing dissolved 2-phenylbenzothiophene-3-carboxaldehyde. The reaction tube was sealed, and the reaction was carried out at 100 °C for 1.0 h. After the reaction was complete, the solvent was evaporated under reduced pressure to obtain the acyl chloride intermediate.

[0089] Then, 2.0 mL of anhydrous dichloromethane was taken, and aluminum trichloride (0.2 mmol, 2.0 equivalent) was added. Next, a pre-prepared 2.0 mL solution of anhydrous dichloromethane containing the acyl chloride intermediate was slowly added dropwise to the above system. The reaction tube was sealed, and the reaction was carried out at 60 °C for 5.0 hours. After the reaction was completed, the reaction mixture was dissolved in dichloromethane and extracted with ammonium chloride and sodium bicarbonate solution. The solvent was then evaporated under reduced pressure, and the product was purified by column chromatography to obtain 11.8 mg of an orange-yellow solid of a polycyclic aromatic hydrocarbon, with a yield of 50%. Analysis showed that… 1 H NMR (500 MHz, CDCl3): δ = 8.08 (d, J = 8.0 Hz,1H), 7.74 (d, J = 8.2 Hz, 1H), 7.45 – 7.37 (m, 2H), 7.33 – 7.26 (m, 2H), 7.20(t, J = 7.3 Hz, 1H), 7.13 (d, J = 7.5 Hz, 1H) ppm, 13C10 NMR (125 MHz, CDCl3): δ = 187.1, 162.1, 143.9, 138.5, 136.7, 134.7, 133.5, 132.3, 129.4, 126.5, 125.2, 123.4, 123.0, 122.8, 120.1 ppm, HRMS (ESI) precise mass calculation C10 15 H8OS [M+H] + : 237.0369, measured value: 237.0366.

[0090] The reaction formula for the synthesis is as follows:

[0091] .

[0092] Experimental Example 1: 5-phenyl-2-(5-phenylthiophen-2-yl)benzothiophen-3-carboxaldehyde prepared in Example 13 is designated as Compound I; 2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)benzothiophen-3-carboxaldehyde prepared in Example 46 is designated as Compound II; and the polycyclic aromatic hydrocarbon compound B prepared in Example 48 is designated as Compound III.

[0093] By UV-Vis absorption spectroscopy (see...) Figure 1 ) and photoluminescence spectrum (see Figure 2 A systematic analysis of the optical properties of compounds I, II, and III was conducted; among them, the maximum absorption wavelength (λ) of compound I in toluene solution was analyzed. abs The wavelength is 371 nm, corresponding to the center wavelength of the emission peak (λ). em Compound II exhibits a redshift in both absorption and emission peaks, with maximum absorption and emission wavelengths of 415 nm and 534 nm, respectively, resulting in green fluorescence. Compound III displays a unique absorption spectrum, showing a double-peak split at 321 nm and 345 nm, along with a low-energy absorption band at 435 nm. This is attributed to its unique polycyclic conjugated structure. The emission wavelength of this compound undergoes a significant redshift (λ). em =564nm), which corresponds to the yellow fluorescence.

[0094] Example 2: Lipid droplets (LDs), as a type of dynamic organelle, are closely related to the development of various metabolic diseases such as obesity, fatty liver, and diabetes due to dysregulation of their regulation. Therefore, specific labeling of intracellular lipid droplets and accurate imaging have become one of the effective strategies for the early diagnosis of related diseases. Fluorescent probes containing aldehyde or carbonyl groups have shown unique advantages in the field of lipid droplet-specific bioimaging due to their good compatibility with the lipophilic microenvironment inside lipid droplets.

[0095] Cytotoxicity test of fluorescent probes: Compounds I, II, and III described in Example 1 were used as fluorescent probes. Before live-cell lipid droplet imaging experiments, their cytotoxicity was assessed using the MTT assay. HepG2 cells were seeded in 96-well plates (3000-4000 cells per well). After overnight culture, the original culture medium was discarded and replaced with fresh culture medium containing the target probes (compounds I, II, and III). The concentration gradient of the probes was set at 0-20 μmol / L. The cells were cultured for another 24 hours in the dark. After culture, 20 μL of MTT solution was added to each well. After 4.0 hours of incubation, the optical density (OD) value of each well at 490 nm was measured using a microplate reader. The results showed that the cell viability of the three probes was higher than 85% within the concentration range of 0-20 μmol / L, indicating good biocompatibility (see [link to article]). Figure 3 ).

[0096] Experimental Example 3: Imaging of lipid droplets in live cells using fluorescent probes: HepG2 cells were imaged using a 2.0 × 10⁻⁶ probe. 4 Cells were seeded at a density of 1 cell / dish in 35 mm glass culture dishes and cultured overnight. The original culture medium was discarded and replaced with fresh medium containing oleic acid (OA, 500 μmol / L) and palmitic acid (PA, 250 μmol / L), and incubated for another 24 h. After incubation, the culture medium was discarded, and the cells were washed three times with phosphate-buffered saline (PBS). Subsequently, fresh medium containing the target probes (compounds I, II, and III described in Example 1, at a concentration of 10 μmol / L) was added to the culture dishes, and the cells were incubated at 37°C for 1.0 h. Finally, the cells were washed three times with PBS, and imaging was performed using a laser confocal scanning microscope (CLSM). The experimental results are as follows: Figure 4 As shown, probe compound I emits cyan fluorescence, probe compound II emits green fluorescence, and compound III emits yellow fluorescence. All three probes can clearly label lipid droplets accumulated in cells. In addition, these probes exhibit strong resistance to photobleaching. After 10 minutes of continuous scanning with a laser at 10% power, a scan rate of 5.0 s / frame, and a wavelength of 405 nm, the cells still retained 80% of the initial fluorescence (see...). Figure 5 ).

[0097] Experiment Example 4: Building upon Experiment Example 3, to further verify the specificity of intracellular lipid droplet probes, a co-staining experiment was conducted using the known lipid droplet dye TNBD and the commercially available dye LipiD-Blue. In OA / PA-treated HepG2 cells, the cyan fluorescence of probe compound I significantly overlapped with the red emission signal of TNBD, while almost no signal was observed in control cells. Quantitative analysis showed a Pearson correlation coefficient (Rr) of 0.92, confirming its high specificity for lipid droplets. Similarly, the green fluorescence signal generated by probe compound II and the yellow fluorescence signal generated by probe compound III highly matched the blue emission signal of LipiD-Blue, with corresponding Rr values ​​of 0.93 and 0.88, respectively, further demonstrating that all three possess reliable lipid droplet targeting capabilities (see [link to experiment example]). Figure 6 ).

[0098] Experiment 5: Based on the cell experiment results obtained in Experiments 2-4, probe compound III was further applied to a diet-induced fatty liver mouse model under pathologically relevant conditions. Histological analysis showed that the liver tissue of the model group mice exhibited obvious pathological features, including abnormal tissue morphology and a large accumulation of lipid droplets (see...). Figure 7 After staining with probe compound III, lipid droplets were clearly visible in the fatty liver tissue. Compared with the liver tissue of normally fed mice, the number and size of lipid droplets were significantly increased (see [link to original text]). Figure 8 The above results indicate that probe compound III has the potential to be used as a biological probe for the diagnosis of fatty liver and related metabolic disorders.

[0099] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. An aldehyde-directed bi(hetero)aromatic compound, characterized in that: The aldehyde-directed bi(hetero)aromatic compounds are ortho-aldehyde-substituted bi(hetero)aromatic compounds and have the following general structural formula: Ar 1 It is one of benzothiophene, benzofuran, thiophene and its derivatives, wherein the substituents of the derivatives are taken from one or more of methyl, methoxy, phenyl, triphenylamino, ester, cyano, cyclohexyl, bromine, chlorine and fluorine atoms; Ar 2 It is one of thiophene, benzothiophene, furan, indole, pyrrole, benzene and its derivatives, and the substituent of the derivative is taken from one or more of methyl, methoxy, phenyl, trimethylsilyl, n-butyl, p-toluenesulfonyl, bromine atom, fluorine atom, and chlorine atom.

2. The method for synthesizing aldehyde-directed bi(hetero)aromatic compounds as described in claim 1, characterized in that: The synthetic method uses (hetero)aryl aldehydes and (hetero)aryl compounds as reaction substrates, adds iridium compounds, oxidants, additives, and solvents to undergo a CH / CH oxidative coupling reaction to generate ortho-aldehyde-substituted bi(hetero)aryl compounds; the (hetero)aryl aldehyde compounds have the following general structural formula: Ar 1 It is one of benzothiophene, benzofuran, thiophene and its derivatives, wherein the substituents of the derivatives are taken from one or more of methyl, methoxy, phenyl, triphenylamino, ester, cyano, cyclohexyl, bromine atom, chlorine atom, and fluorine atom; The (hetero)aromatic compounds have the following general structural formula: Ar 2 It is one of thiophene, benzothiophene, furan, indole, pyrrole, benzene and its derivatives, and the substituent of the derivative is taken from one or more of methyl, methoxy, phenyl, trimethylsilyl, n-butyl, p-toluenesulfonyl, bromine atom, fluorine atom, and chlorine atom.

3. The synthesis method according to claim 2, characterized in that: The iridium compound is one of [Cp*IrCl2]2, [Ir(cod)2]OTf, [Ir(OMe)(1,5-cod)]2, IrCl3, and [Ir(cod)Cl]2; the amount of the iridium compound is 2.5-10% of the molar amount of the heteroaryl aldehyde compound; the oxidant is one or more of silver acetate, silver carbonate, copper oxide, copper isooctanoate, pentafluoroiodobenzene, and hexabromobenzene, and the molar ratio of the oxidant to the heteroaryl aldehyde compound is (1-3):1; the solvent is one of 1,2-dichloroethane, dichloromethane, 3,4-dichlorotoluene, toluene, and tert-butanol.

4. The synthesis method according to claim 3, characterized in that: When the iridium compound is [Cp*IrCl2]2 and its amount is 5.0% of the molar amount of the (hetero)aryl aldehyde compound, when Ar 2 When the oxidant is thiophene, benzothiophene, furan, indole, pyrrole and their derivatives, the oxidant is silver acetate and the molar ratio of the oxidant to the (hetero)aryl aldehyde compound is 3:1; when Ar 2 When the oxidant is benzene or its derivatives, the oxidant is copper isooctanoate and pentafluoroiodobenzene, and the molar ratio of copper isooctanoate to (hetero)aryl aldehyde is 1:1, and the molar ratio of pentafluoroiodobenzene to (hetero)aryl aldehyde is 2:

1.

5. The synthesis method according to claim 2 or 3, characterized in that: The additives include acidic additives and basic additives, wherein the acidic additive is one of acetic acid, acetic anhydride, and trifluoroacetic acid, and the basic additive is one of sodium trimethylacetate hydrate, potassium acetate, and cesium neopentanoate; the molar ratio of the acidic additive to the (hetero)aryl aldehyde compound is (1-3):1, and the molar ratio of the basic additive to the (hetero)aryl aldehyde compound is (1-3):

1.

6. The synthesis method according to claim 5, characterized in that: When Ar 1 When the compounds are thiophene and their derivatives, no acidic additives are required, and the basic additive is potassium acetate, with a molar ratio of basic additive to (hetero)aryl aldehyde compound of 2:1; when Ar 2 When the compounds are thiophene, benzothiophene, furan, indole, pyrrole, and their derivatives, the acidic additive is acetic acid and the molar ratio of the acidic additive to the (hetero)aryl aldehyde compound is 1:1; the alkaline washing additive is sodium trimethylacetate hydrate and the molar ratio of the alkaline additive to the (hetero)aryl aldehyde compound is 1:1; when Ar 2 When the compound is benzene or its derivatives, no basic additive is required, and the acidic additive is acetic anhydride. The molar ratio of the acidic additive to the (hetero)aryl aldehyde compound is 1:

1.

7. The synthesis method according to claim 5, characterized in that: The reaction temperature for the CH / CH oxidative coupling reaction is 80–150 °C, and the reaction time is 12–48 hours.

8. The synthesis method according to claim 7, characterized in that: Using 5-phenylbenzothiophene-3-carboxaldehyde and 2-phenylthiophene as substrates, [Cp*IrCl2]2, oxidant, additives, and solvent were added and reacted at 100°C for 24 hours under an argon atmosphere to generate ortho-aldehyde-substituted bi(hetero)aromatic compounds. During the reaction, compounds with the following structural formula were generated. Circular iridium metal intermediates.

9. The application of the aldehyde-directed bi(hetero)aromatic compound as described in claim 1, characterized in that: The aldehyde-directed bi(hetero)aromatic compounds are used as fluorescent probes for specific labeling and high-resolution imaging of lipid droplets in live cells and mouse fatty livers; or the aldehyde-directed bi(hetero)aromatic compounds are modified by Suzuki cross-coupling reaction, oxidation reaction and intramolecular Friedel-Crafts cyclization reaction to obtain derivatives of the bi(hetero)aromatic compounds, including bi(hetero)aromatic compounds containing triphenylamine groups and polycyclic heteroaromatic compounds, and then the derivatives of the bi(hetero)aromatic compounds are used as fluorescent probes for specific labeling and high-resolution imaging of lipid droplets in live cells and mouse fatty livers.

10. Derivatives of the bi(hetero)aromatic compounds obtained in the application as described in claim 9.

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