A method for synthesizing a biphenyl compound and derivatives thereof

Abstract

This invention discloses a method for synthesizing biphenyl compounds and their derivatives, comprising the following steps: under blue light irradiation and in an inert atmosphere, an aryl halogen compound reacts with a base in solvent A, and then the reaction mixture is separated to obtain the biphenyl compounds and their derivatives. The technical solution of this invention has the following significant advantages: without the need for additional photocatalysts, the synthesis of biphenyl compounds and their derivatives can be achieved solely through photoinduction. Compared with existing technologies, the method for synthesizing biphenyl compounds and their derivatives described in this invention has the following characteristics: wide availability of raw materials, simple operation process, mild reaction conditions, economic efficiency, and environmental friendliness.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a method for synthesizing biphenyl compounds and their derivatives. Background Technology

[0002] Biphenyl structures are widely found in chemistry and nature, and are important components of many drugs, pesticides, ligands, and natural products. Traditional bioaromatic synthesis mainly relies on transition metal-catalyzed cross-coupling reactions, such as Suzuki coupling and Heck coupling. While these methods are efficient, they suffer from problems such as demanding reaction conditions and limited substrate applicability in certain cases (Angew. Chem. Int. Ed., 2012, 51, 5062).

[0003] In recent years, radical arylation methods have attracted attention due to their mild reaction conditions and adaptability to complex substrates. However, existing radical arylation methods typically require stoichiometric reducing agents (such as tributyltin hydride), limiting their widespread application (J. Am. Chem. Soc., 1959, 1563). Furthermore, while radical Smiles rearrangements have been widely used in intermolecular radical cascade reactions, their application in biogenic aromatics synthesis remains relatively limited, especially in the synthesis of biogenic aromatics under radical mechanisms, where related research is scarce (Chem. Sci., 2020, 11, 12822).

[0004] In radical arylation reactions, the generation of aryl radicals is a crucial step. While aryl halides are ideal radical precursors, their direct single-electron transfer (SET) reduction is thermodynamically infeasible in most common photocatalytic systems (Chem. Rev., 2022, 122, 2292). Furthermore, the orthogonal addition pathway commonly found in radical arylation reactions often competes with the desired ipso-arylation pathway, leading to reduced reaction selectivity (Angew. Chem. Int. Ed., 2016, 55, 2450). Therefore, developing a photocatalytic method capable of efficiently generating aryl radicals under mild conditions and selectively achieving ipso-arylation is of great significance for the synthesis of biogenic aromatics (Angew. Chem. Int. Ed. 2024, e202407979). Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention proposes an innovative method for synthesizing biphenyls and their derivatives. This method creatively utilizes weak halogen bond interactions to achieve the efficient synthesis of biphenyl compounds and their derivatives solely through photoinduction, without the need for additional photocatalysts. This technological breakthrough opens up a simple, efficient, economical, and environmentally friendly new route for the synthesis of biphenyl compounds.

[0006] A method for synthesizing biphenyl compounds and their derivatives, characterized by comprising the following steps: Under blue light irradiation and in an inert atmosphere, aryl halogen compounds react with a base in solvent A, and then the reaction mixture is separated to obtain biphenyl compounds and their derivatives.

[0007] Preferably, the aryl halogen compound has the structure of any one of formulas V to VIII: In Equation V, R 1 It represents at least one electron-withdrawing group such as ester, cyano, trifluoromethyl, acyl, halogen, or alkyl substituent; R 2 It represents at least one electron-withdrawing group, such as ester, cyano, trifluoromethyl, acyl, or halogen group; In Equation VI, R 3 It represents at least one electron-withdrawing group such as ester group, cyano group, trifluoromethyl group, acyl group, halogen group or electron-donating group such as methyl group, methoxy group; R 4 It represents at least one electron-withdrawing group such as ester group, cyano group, trifluoromethyl group, acyl group, halogen group or electron-donating group such as methyl group, methoxy group; In formulas V, VI, VII or VIII, X represents at least one of bromine or iodine atoms, and PG represents at least one of methyl, ethyl, propyl or phenyl. The structure of the biphenyl compound and its derivatives is any one of Formulas I to IV: In Equation I, R 1 R represents at least one electron-withdrawing group such as ester, cyano, trifluoromethyl, acyl, halogen, or alkyl substituent; 2 It represents at least one electron-withdrawing group, such as ester, cyano, trifluoromethyl, acyl, or halogen group; In formula II, R 3 R represents at least one electron-withdrawing group such as ester, cyano, trifluoromethyl, acyl, halogen group, or electron-donating group such as methyl, methoxy; 4It represents at least one electron-withdrawing group, such as ester, cyano, trifluoromethyl, acyl, halogen group, or electron-donating group, such as methyl or methoxy. In Formula III or Formula IV, PG represents at least one of methyl, ethyl, propyl, or phenyl.

[0008] Preferably, the compound represented by Formula I is any one of the compounds represented by Formula I-1 to Formula I-4: Preferably, the compound represented by Formula II is any one of the compounds represented by Formula II-1 to Formula II-8: Preferably, the compound represented by formula III is formula III-1; the compound represented by formula IV is formula IV-1 or IV-2. Preferably, the molar ratio of the aryl halogen compound to the base is 1:2 to 5.

[0009] Preferably, the concentration of the aryl halogen compound in the solvent is 0.1-1.0 mol / L.

[0010] Preferably, the base is any one of N,N,N',N'-tetramethylethylenediamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, triethylamine, N,N-diisopropylethylamine, and ethylenediamine.

[0011] Preferably, solvent A is any one of acetonitrile, diethyl ether, tetrahydrofuran, toluene, dichloromethane, chloroform, N-methylpyrrolidone, dimethylformamide, or dimethylacetamide.

[0012] Preferably, the wavelength of the blue light is 460 nanometers; the blue light is provided by a blue light-emitting diode with a power of 100W.

[0013] Preferably, the reaction temperature range is 55°C to 65°C; the reaction time is 10 hours to 24 hours.

[0014] Preferably, the separation method involves distilling the reaction mixture under reduced pressure, followed by separation by silica gel chromatography and then distilling under reduced pressure again. The stationary phase of the silica gel chromatography is silica, and the mobile phase is a mixed solvent composed of petroleum ether and ethyl acetate in a volume ratio of 10:1 to 2:1.

[0015] Compared with the prior art, the technical solution of the present invention has the following significant advantages: This invention provides the first method for synthesizing perfluoroalkane compounds and their derivatives solely through photoinduction without the need for additional photocatalysts. Compared to existing technologies, the method for synthesizing perfluoroalkane compounds and their derivatives described in this invention has the following advantages: wide availability of raw materials, simple operation process, mild reaction conditions, high cost-effectiveness, and environmental friendliness. Attached Figure Description

[0016] Figure 1 This is a synthetic route diagram of biphenyl compounds and their derivatives in a specific embodiment of the present invention. Detailed Implementation

[0017] Exemplary embodiments of the present invention will now be specifically given; however, it should be understood that the present disclosure may be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art.

[0018] Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Nuclear magnetic resonance (NMR) measurements were performed using a NJE NMR spectrometer. Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0019] The synthetic route for the biphenyl compounds and their derivatives of this invention is as follows: Example 1 The compound shown in formula I-1 according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula I-1. The specific steps are as follows: The pre-dried reaction tube was cooled to room temperature under vacuum, and under nitrogen protection, the compound shown in Formula V-1 (0.2 mmol) and N,N,N',N'-tetramethylethylenediamine (0.6 mmol) were added. Acetonitrile (2 mL) was added to the reaction tube via syringe. The mixture was stirred overnight (12 h) at 60°C on a 100W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2; mobile phase: a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1; the product was obtained by vacuum distillation after collection) to give the compound shown in Formula I-1.

[0020] The structural verification experimental data are as follows: White solid (33 mg, 0.110 mmol, 55%). 1H NMR (400 MHz, Chloroform- d )δ7.89 – 7.83 (m, 1H), 7.60 (t, J = 7.69 Hz, 1H), 7.54 – 7.43 (m, 2H), 7.39 –7.34 (m, 1H), 7.28 – 7.19 (m, 1H), 7.08 – 7.01 (m, 1H), 6.35 – 6.21 (m, 1H), 3.78 (s, 3H), 2.57 (d, J = 7.19 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 169.1,168.9, 140.7, 140.4, 132.0, 130.8, 129.7, 129.6, 129.5, 129.0, 129.0, 128.3,128.1,128.0, 52.8, 26.5. The obtained compound was verified to be the compound shown in Formula I-1.

[0021] Example 2 The compound shown in formula I-2 is synthesized according to Figure 1 The synthetic route diagram shown below illustrates the synthesis of the compound represented by formula I-2. The specific steps are as follows: The pre-dried reaction tube was cooled to room temperature under vacuum, and under nitrogen protection, the compound shown in Formula V-2 (0.2 mmol) and N,N,N',N'-tetramethylethylenediamine (0.6 mmol) were added. Acetonitrile (2 mL) was added to the reaction tube via syringe. The mixture was stirred overnight (12 h) at 60°C on a 100W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2; mobile phase: a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1; the product was obtained by vacuum distillation after collection) to give the compound shown in Formula I-2. The structural verification experimental data are as follows: White solid (36 mg, 0.10 3mmol, 51%). 1H NMR(400 MHz, CDCl3) δ 7.87 –7.83 (m, 1H), 7.79 (d, J = 1.89 Hz, 1H), 7.53 – 7.41 (m, 3H), 7.24 – 7.20 (m,1H), 6.91 (s, 1H), 6.29 (s, 1H), 3.76 (s, 3H), 2.57 (d, J = 5.43 Hz, 3H). 13 CNMR(101 MHz, CDCl3) δ 169.0, 168.5, 140.5, 138.0, 137.8, 132.5, 131.9, 131.1,130.8, 130.7, 130.2,129.6, 128.2, 121.9, 52.7, 26.5. The obtained compound was verified to be the compound shown in Formula I-2.

[0022] Example 3 The compound shown in formula I-3 is synthesized according to Figure 1 The synthetic route diagram shown below synthesizes the compound represented by formula I-3. The specific steps are as follows: The pre-dried reaction tube was cooled to room temperature under vacuum, and under nitrogen protection, the compound shown in Formula V-3 (0.2 mmol) and N,N,N',N'-tetramethylethylenediamine (0.6 mmol) were added. Acetonitrile (2 mL) was added to the reaction tube via syringe. The mixture was stirred overnight (12 h) at 60°C on a 100W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2; mobile phase: a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1; the product was obtained by vacuum distillation after collection) to give the compound shown in Formula I-3.

[0023] The structural verification experimental data are as follows: White solid (42 mg, 0.22 mmol, 61%). 1H NMR (400 MHz, CDCl3) δ 7.87 (dd,J = 7.68, 1.49 Hz, 1H), 7.53 (s, 2H), 7.50 (dd, J = 7.30, 1.44 Hz, 1H), 7.47– 7.42 (m, 1H), 7.24 – 7.20(m, 2H), 6.30 (s, 1H), 3.78 (s, 3H), 2.57 (d, J =4.90 Hz, 3H). 13 C NMR(101 MHz, CDCl3) δ 169.1, 168.9, 140.8, 140.2, 135.2,132.0, 131.9, 131.0, 130.8, 130.1, 129.7,129.7, 128.3, 123.5, 52.8, 26.5. Verification confirmed that the obtained compound is the compound shown in Formula I-3.

[0024] Example 4 The compound shown in formula I-4 according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula I-4. The specific steps are as follows: The pre-dried reaction tube was cooled to room temperature under vacuum, and under nitrogen protection, the compound shown in Formula V-4 (0.2 mmol) and N,N,N',N'-tetramethylethylenediamine (0.6 mmol) were added. Acetonitrile (2 mL) was added to the reaction tube via syringe. The mixture was stirred overnight (12 h) at 60°C on a 100W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2; mobile phase: a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1; the product was obtained by vacuum distillation after collection) to give the compound shown in Formula I-4.

[0025] The structural verification experimental data are as follows: White solid (24 mg, 0.106 mmol, 42% yield). 1H NMR(400 MHz, CDCl3) δ7.92 – 7.70 (m, 1H), 7.65 – 7.45 (m, 1H), 7.41 – 7.39 (m, 1H), 7.29 – 7.22(m, 2H), 7.14– 7.00(m, 1H), 6.96 (d, J = 8.4 Hz, 1H), 5.53 (s, 1H), 3.76 (s,3H), 2.76 (s, 3H), 2.68 (d, J = 4.8 Hz, 3H). 13 C NMR(101 MHz, CDCl3) δ 170.2,156.4, 136.4, 135.5, 131.1, 130.7, 130.2, 129.8, 129.2, 128.1, 127.4, 121.2,110.5, 55.2, 26.2. The obtained compound was verified to be the compound shown in Formula I-4.

[0026] Example 5 The compound shown in Formula II-1 according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula II-1. The specific steps are as follows: The pre-dried reaction tube was cooled to room temperature under vacuum, and under nitrogen protection, the compound shown in Formula VI-1 (0.2 mmol) and N,N,N',N'-tetramethylethylenediamine (0.6 mmol) were added. Acetonitrile (2 mL) was added to the reaction tube via syringe. The mixture was stirred overnight (12 h) at 60°C on a 100W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2; mobile phase: a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1; the product was obtained by vacuum distillation after collection) to give the compound shown in Formula II-1.

[0027] The structural verification experimental data are as follows: yellow solid (20 mg, 0.0870 mmol, 43%). 1H NMR(400 MHz, CDCl3) δ 7.82 –7.66(m, 1H), 7.55 – 7.42 (m, 2H), 7.41 – 7.34 (m, 3H), 7.25 – 7.20 (m, 1H),7.19 – 7.10 (m, 1H), 5.55 (s, 1H), 2.78 (d, J= 4.9 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 169.7, 159.5 (d, J = 246.5 Hz), 136.7, 133.6, 131.4 (d, J = 3.3 Hz), 131.2, 130.2, 129.9 (d, J = 8.0 Hz), 128.4, 128.1, 127.7, 124.5(d, J = 3.8Hz), 115.8 (d, J = 22.4 Hz), 26.7. The obtained compound was verified to be the compound shown in Formula II-1.

[0028] Example 6 The compound shown in formula II-2 is synthesized according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula II-2. The specific steps are as follows: The pre-dried reaction tube was cooled to room temperature under vacuum, and under nitrogen protection, the compound shown in Formula VI-2 (0.2 mmol) and N,N,N',N'-tetramethylethylenediamine (0.6 mmol) were added. Acetonitrile (2 mL) was added to the reaction tube via syringe. The mixture was stirred overnight (12 h) at 60°C on a 100W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2; mobile phase: a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1; the product was obtained by vacuum distillation after collection) to give the compound shown in Formula II-2.

[0029] The structural verification experimental data are as follows: yellow solid (30 mg, 0.122mg, 61%) 1H NMR(400 MHz, CDCl3) δ 7.76 – 7.71(m, 1H), 7.51 – 7.42 (m, 3H), 7.34 – 7.30 (m, 3H), 7.29 – 7.26 (m, 1H), 5.39(s, 1H), 2.69 (d, J = 4.8 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 169.4, 139.4, 137.0, 136.2, 132.9, 131.3, 130.9, 130.0, 129.7, 129.4, 128.4, 128.4, 127.1, 26.8. (Equation II-2 is consistent with literature reports. Thomas Sephton, Jonathan M. Large, Louise S. Natrajan, Sam Butterworth, and Michael F., Angew. Chem. Int. Ed . 2024,e202407979) The obtained compound was verified to be the compound shown in Formula II-2.

[0030] Example 7 The compound shown in formula II-3 according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula II-3. The specific steps are as follows: The pre-dried reaction tube was cooled to room temperature under vacuum, and under nitrogen protection, the compound shown in Formula VI-3 (0.2 mmol) and N,N,N',N'-tetramethylethylenediamine (0.6 mmol) were added. Acetonitrile (2 mL) was added to the reaction tube via syringe. The mixture was stirred overnight (12 h) at 60°C on a 100W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2; mobile phase: a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1; the product was obtained by vacuum distillation after collection) to give the compound shown in Formula II-3.

[0031] The structural verification experimental data are as follows: white solid (30mg, 0.103mmol, 51%). 1H NMR(400 MHz, CDCl3) δ 7.74 –7.69 (m, 1H), 7.68- 7.55 (m, 1H), 7.54 – 7.41 (m, 2H), 7.40 – 7.35 (m, 1H),7.33 – 7.28 (m, 1H), 7.27 – 7.18 (m, 2H), 5.46 (s, 1H), 2.71 (d, J= 4.8 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 169.4, 141.5, 138.8, 136.1, 132.8, 131.3, 130.9, 130.1, 129.7, 128.5, 128.5, 127.8, 123.2, 26.9. (Equation II-3 is consistent with literature reports. Thomas Sephton, Jonathan M. Large, Louise S. Natrajan, Sam Butterworth, and Michael F. , Angew. Chem. Int. Ed . 2024, e202407979) The obtained compound was verified to be the compound shown in Formula II-3.

[0032] Example 8 The compound shown in formula II-4 according to Figure 1 The synthetic route diagram shown below synthesizes the compound represented by formula II-4. The specific steps of VI-4 are as follows: The pre-dried reaction tube was cooled to room temperature under vacuum, and under nitrogen protection, the compound shown in Formula VI-4 (0.2 mmol) and N,N,N',N'-tetramethylethylenediamine (0.6 mmol) were added. Acetonitrile (2 mL) was added to the reaction tube via syringe. The mixture was stirred overnight (12 h) at 60°C on a 100W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2; mobile phase: a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1; the product was obtained by vacuum distillation after collection) to give the compound shown in Formula II-4.

[0033] The structural verification experimental data are as follows: White solid (25 mg, 0.106 mmol, 53% yield). 1H NMR(400 MHz, CDCl3) δ7.81 – 7.70 (m, 1H), 7.57 – 7.45 (m, 1H), 7.42 – 7.35 (m, 2H), 7.31 – 7.22(m, 2H), 7.14 – 7.00 (m, 1H), 6.96 (d, J = 8.4 Hz,1H), 5.52 (s, 1H), 3.77 (s,3H), 2.68 (d, J = 4.8 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 170.1, 156.5, 136.4, 135.9, 131.1, 130.9, 130.3, 129.8, 129.4, 128.5, 127.9, 121.2, 110.9, 55.7, 26.7. (Equation II-4 is consistent with literature reports. Thomas Sephton, Jonathan M. Large, Louise S. Natrajan, Sam Butterworth, and Michael F. , Angew. Chem. Int. Ed . 2024,e202407979) The obtained compound was verified to be the compound shown in Formula II-4.

[0034] Example 9 Synthetic compound shown in formula II-5 according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula II-5. The specific steps are as follows: The pre-dried reaction tube was cooled to room temperature under vacuum, and under nitrogen protection, the compound shown in Formula VI-5 (0.2 mmol) and N,N,N',N'-tetramethylethylenediamine (0.6 mmol) were added. Acetonitrile (2 mL) was added to the reaction tube via syringe. The mixture was stirred overnight (12 h) at 60°C on a 100W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2; mobile phase: a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1; the product was obtained by vacuum distillation after collection) to give the compound shown in Formula II-5.

[0035] The structural verification experimental data are as follows: White solid (33 mg, 0.124 mmol, 62% yield). 1H NMR(400 MHz, CDCl3) δ7.88 – 7.84 (m, 1H), 7.69 – 7.62 (m, 1H), 7.60 – 7.46 (m, 1H), 7.44 – 7.33(m, 3H), 7.30 – 7.26 (m, 1H), 7.09 – 7.00(m, 1H), 6.28 (s, 1H), 3.74 (s, 3H), 2.58 (d, J = 5.0 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 170.4, 169.3, 141.5, 138.8, 136., 1431.7, 130.9, 130.5, 129.6, 129.5, 129.2, 128.3, 127.8, 127.7, 52.5, 26.4. (Equation II-5 is consistent with literature reports. Thomas Sephton, Jonathan M. Large, Louise S. Natrajan, Sam Butterworth, and Michael F. , Angew. Chem. Int. Ed . 2024,e202407979) The obtained compound was verified to be the compound shown in Formula II-5.

[0036] Example 10 The compound shown in Formula II-6 according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula II-6. The specific steps are as follows: The pre-dried reaction tube was cooled to room temperature under vacuum, and under nitrogen protection, the compound shown in Formula VI-6 (0.2 mmol) and N,N,N',N'-tetramethylethylenediamine (0.6 mmol) were added. Acetonitrile (2 mL) was added to the reaction tube via syringe. The mixture was stirred overnight (12 h) at 60°C on a 100W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2; mobile phase: a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1; the product was obtained by vacuum distillation after collection) to give the compound shown in Formula II-6.

[0037] The structural verification experimental data are as follows: White solid (21 mg, 0.086 mmol, 43% yield). 1H NMR (400 MHz, CDCl3): δ7.80−7.60 (m, 1H), 7.59−7.46 (m, 1H), 7.45−7.38 (m, 2H), 7.37 – 7.30 (m, 4H), 5.35 (s, 1H), 2.76 (d, J = 4.9 Hz, 3H)ppm. 13 C NMR (101 MHz, CDCl3): δ 170.3,162.7, 138.4, 138.1, 135.8,133.7, 130.2, 130.1, 129.9, 128.8, 128.7, 127.9,26.8 Upon verification, the obtained compound is the compound shown in Formula II-6.

[0038] Example 11 The compound shown in Formula II-7 according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula II-7. The specific steps are as follows: The pre-dried reaction tube was cooled to room temperature under vacuum, and under nitrogen protection, the compound shown in Formula VI-7 (0.2 mmol) and N,N,N',N'-tetramethylethylenediamine (0.6 mmol) were added. Acetonitrile (2 mL) was added to the reaction tube via syringe. The mixture was stirred overnight (12 h) at 60°C on a 100W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2; mobile phase: a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1; the product was obtained by vacuum distillation after collection) to give the compound shown in Formula II-7.

[0039] The structural verification experimental data are as follows: White solid (23 mg, 0.078 mmol, 39% yield). 1 H NMR (400 MHz, CDCl3): δ7.82−7.61 (m, 1H), 7.58−7.42 (m, 1H), 7.41−7.36 (m, 2H), 7.35 – 7.21 (m, 4H), 5.39 (s, 1H), 2.70 (d, J = 4.9 Hz, 3H)ppm. 13C NMR (101 MHz, CDCl3): δ 170.7,162.4, 138.3, 138.0, 135.6,133.6, 130.2, 130.2, 129.8, 128.7, 128.6, 127.8,26.7 Upon verification, the obtained compound is the compound shown in Formula II-7.

[0040] Example 12 The compound shown in formula II-8 according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula II-8. The specific steps are as follows: The pre-dried reaction tube was cooled to room temperature under vacuum, and under nitrogen protection, the compound shown in Formula VI-8 (0.2 mmol) and N,N,N',N'-tetramethylethylenediamine (0.6 mmol) were added. Acetonitrile (2 mL) was added to the reaction tube via syringe. The mixture was stirred overnight (12 h) at 60°C on a 100W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2; mobile phase: a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1; the product was obtained by vacuum distillation after collection) to give the compound shown in Formula II-8.

[0041] The structural verification experimental data are as follows: White solid (25 mg, 0.108 mmol, 54% yield). 1 H NMR (400 MHz, CDCl3): δ7.89 – 7.30 (m, 8H), 5.58 (s, 1H), 2.76 (d, J = 4.9 Hz, 3H). 13 C NMR (125 MHz, CDCl3,) δ: 170.8, 143.4, 136.3, 135.2, 133.3, 132.6, 131.2, 130.5, 129.4,129.4, 128.8,127.6, 26.7; The obtained compound was verified to be the compound shown in Formula II-8.

[0042] Example 13 The compound shown in Formula III-1 according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula III-1. The specific steps are as follows: The pre-dried reaction tube was cooled to room temperature under vacuum, and under nitrogen protection, the compound shown in Formula VII-1 (0.2 mmol) and N,N,N',N'-tetramethylethylenediamine (0.6 mmol) were added. Acetonitrile (2 mL) was added to the reaction tube via syringe. The mixture was stirred overnight (12 h) at 60°C on a 100W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2; mobile phase: a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1; the product was obtained by vacuum distillation after collection) to give the compound shown in Formula III-1.

[0043] The structural verification experimental data are as follows: white solid (26 mg, 0.098 mmol, 29%). 1 H NMR(400 MHz, CDCl3) δ 7.99 –7.80 (m, 3H), 7.77 – 7.60 (m, 1H), 7.59 – 7.46 (m, 4H), 7.45 – 7.40 (m, 2H),7.39 – 7.30 (m, 1H), 5.13 (s, 1H), 2.35 (d, J= 4.9 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 169.4, 138.4, 137.7, 136.5, 133.8, 131.9, 131.6, 130.4, 129.5, 128.4, 128.6, 128.1, 127.1, 126.8, 126.5, 125.5, 125.6, 26.7. (Equation III-1 is consistent with literature reports. Thomas Sephton, Jonathan M. Large, Louise S. Natrajan, Sam Butterworth, and Michael F. , Angew. Chem. Int. Ed . 2024, e202407979) The obtained compound was verified to be the compound shown in Formula III-1.

[0044] Example 14 Synthetic compound shown in formula IV-1 according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by Formula IV-1. The specific steps are as follows: The pre-dried reaction tube was cooled to room temperature under vacuum, and under nitrogen protection, the compound shown in Formula VIII-1 (0.2 mmol) and N,N,N',N'-tetramethylethylenediamine (0.6 mmol) were added. Acetonitrile (2 mL) was added to the reaction tube via a syringe. The mixture was stirred overnight (12 h) at 60°C on a 100 W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2; mobile phase: a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1; the product was obtained by vacuum distillation after collection) to give the compound shown in Formula IV-1.

[0045] The structural verification experimental data are as follows: white solid (27 mg, 0.130 mmol, 65%). 1 H NMR(400 MHz, CDCl3): δ 7.66(d, J = 8.1 Hz, 1H), 7.50 −7.44(m, 1H), 7.43−7.38 (m, 5H), 7.37−7.33(m, 2H),5.31 (s, 1H), 2.67 (d, J = 4.9 Hz, 3H). 13 C NMR (101 MHz, CDCl3): δ170.2, 140.0,139.2, 135.5, 130.1, 130.0, 128.6, 128.53, 128.51, 127.6,127.4, 26.6. The obtained compound was verified to be the compound shown in Formula IV-1.

[0046] Example 15 The compound shown in formula IV-2 according to Figure 1 The synthetic route diagram shown illustrates the synthesis of the compound represented by formula IV-2. The specific steps are as follows: The pre-dried reaction tube was cooled to room temperature under vacuum, and under nitrogen protection, the compound shown in Formula VIII-2 (0.2 mmol) and N,N,N',N'-tetramethylethylenediamine (0.6 mmol) were added. Acetonitrile (2 mL) was added to the reaction tube via syringe. The mixture was stirred overnight (12 h) at 60°C on a 100W blue LED (460 nm) lamp. The reaction mixture was then subjected to vacuum distillation and silica gel chromatography (stationary phase: SiO2; mobile phase: a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1; the product was obtained by vacuum distillation after collection) to give the compound shown in Formula IV-2.

[0047] The structural verification experimental data are as follows: as a wihte solid (34 mg, 0.100 mmol, 50%). 1 H NMR (400 MHz, Chloroform-d) δ 8.49 (dd, J = 8.05, 1.46 Hz, 1H), 8.22 – 8.17 (m, 2H), 7.81 (ddd, J = 8.35, 7.31, 1.48 Hz, 1H), 7.68 – 7.59 (m, 1H), 7.42 (dd, J = 8.87,2.30 Hz, 1H), 7.08 (d, J = 8.76 Hz, 1H), 3.31 (s, 3H), 2.89 (s, 3H). 13 C NMR(101 MHz, Chloroform-d) δ 159.2, 153.0, 133.7,133.1, 133.0, 129.9, 129.3,129.1, 128.9, 125.2, 123.4, 122.2, 120.4, 116.8, 37.7, 36.9. The obtained compound was verified to be the compound shown in Formula IV-2.

[0048] The present invention has been described in detail above. For those skilled in the art, the invention can be practiced in a wide range of ways with equivalent parameters, concentrations, and conditions without departing from its spirit and scope, and without requiring unnecessary experiments. Although specific embodiments have been given, it should be understood that further modifications can be made to the invention. In summary, according to the principles of the invention, this application is intended to include any changes, uses, or improvements to the invention, including changes made using conventional techniques known in the art that depart from the scope disclosed herein. Some of the essential features can be applied within the scope of the following appended claims.

Claims

1. A method for synthesizing biphenyl compounds and their derivatives, characterized in that, Includes the following steps: Under blue light irradiation and in an inert atmosphere, aryl halogen compounds react with a base in solvent A, and then the reaction mixture is separated to obtain biphenyl compounds and their derivatives.

2. The method for synthesizing biphenyl compounds and their derivatives as described in claim 1, characterized in that, The aryl halogen compound has the structure of any one of formulas V to VIII: In Equation V, R 1 It represents at least one electron-withdrawing group such as ester, cyano, trifluoromethyl, acyl, halogen, or alkyl substituent; R 2 It represents at least one electron-withdrawing group, such as ester, cyano, trifluoromethyl, acyl, or halogen group; In Equation VI, R 3 It represents at least one electron-withdrawing group such as ester group, cyano group, trifluoromethyl group, acyl group, halogen group or electron-donating group such as methyl group, methoxy group; R 4 It represents at least one electron-withdrawing group such as ester group, cyano group, trifluoromethyl group, acyl group, halogen group or electron-donating group such as methyl group, methoxy group; In formulas V, VI, VII or VIII, X represents at least one of bromine or iodine atoms, and PG represents at least one of methyl, ethyl, propyl or phenyl. The structure of the biphenyl compound and its derivatives is any one of Formulas I to IV: In Equation I, R 1 It represents at least one electron-withdrawing group such as ester, cyano, trifluoromethyl, acyl, halogen, or alkyl substituent; R 2 It represents at least one electron-withdrawing group, such as ester, cyano, trifluoromethyl, acyl, or halogen group; In formula II, R 3 It represents at least one electron-withdrawing group such as ester group, cyano group, trifluoromethyl group, acyl group, halogen group or electron-donating group such as methyl group, methoxy group; R 4 It represents at least one electron-withdrawing group, such as ester, cyano, trifluoromethyl, acyl, halogen group, or electron-donating group, such as methyl or methoxy. In Formula III or Formula IV, PG represents at least one of methyl, ethyl, propyl, or phenyl.

3. The method for synthesizing biphenyl compounds and their derivatives as described in claim 1, characterized in that, The molar ratio of the aryl halogen compound to the base is 1:2~5.

4. The method for synthesizing biphenyl compounds and their derivatives as described in claim 1, characterized in that, The concentration of the aryl halogen compound in the solvent is 0.1-1.0 mol / L.

5. The method for synthesizing biphenyl compounds and their derivatives as described in claim 1, characterized in that, The base is any one of N,N,N',N'-tetramethylethylenediamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, triethylamine, N,N-diisopropylethylamine, and ethylenediamine.

6. The method for synthesizing biphenyl compounds and their derivatives as described in claim 1, characterized in that, Solvent A is any one of acetonitrile, diethyl ether, tetrahydrofuran, toluene, dichloromethane, chloroform, N-methylpyrrolidone, dimethylformamide, or dimethylacetamide.

7. The method for synthesizing biphenyl compounds and their derivatives as described in claim 1, characterized in that, The wavelength of the blue light is 460 nanometers; the blue light is provided by a blue light-emitting diode with a power of 100W.

8. The method for synthesizing biphenyl compounds and their derivatives as described in claim 1, characterized in that, The reaction temperature range is 55°C to 65°C; the reaction time is 10 hours to 24 hours.

9. The method for synthesizing biphenyl compounds and their derivatives as described in claim 1, characterized in that, The separation method involves distilling the reaction mixture under reduced pressure, followed by separation by silica gel chromatography and then distilling under reduced pressure again. The stationary phase of the silica gel chromatography is silica, and the mobile phase is a mixed solvent composed of petroleum ether and ethyl acetate in a volume ratio of 10:1 to 2:1.

Images