Method for preparing asymmetric diaryl hydrocarbon compound through coupling of Suzuki-Miyaura catalyzed by Pd in water phase

Abstract

The method comprises the following steps: adding ligands PEG-PyTA and K2PdCl4 into a water / ethanol mixed solvent, stirring and uniformly mixing at room temperature under the protection of inert gas, then adding aryl bromide (I), arylboronic acid (II) and an alkaline substance, stirring and reacting at 50 DEG C for 4-12 hours, and then carrying out post-treatment on the reaction liquid to obtain the asymmetric diaryl hydrocarbon compound. The asymmetric diaryl hydrocarbon compound (III) is obtained; the method is small in catalyst dosage, short in reaction time and wide in substrate application range, the product can be extracted and separated through a common organic solvent, the catalyst is left in a water phase, and repeated use is achieved; the method disclosed by the invention is green, economical and low in three-waste amount, and has a wide application prospect; .

Description

Technical Field

[0001] This invention relates to the preparation of asymmetric diaryl hydrocarbons, specifically to a method for preparing asymmetric diaryl hydrocarbons by Pd-catalyzed Suzuki-Miyaura coupling in an aqueous phase. Background Technology

[0002] Asymmetric diaromatics are an important class of organic compounds with wide applications in pharmaceuticals, pesticides, and materials. The Suzuki-Miyaura coupling reaction (Pd-catalyzed cross-coupling of aryl halides with arylboronic acids or esters) is one of the most important methods for synthesizing these compounds. This method generally requires the assistance of ligands. By complexing with metallic Pd, the ligands can not only modulate the catalytic activity of Pd but also stabilize it, preventing it from polymerizing into Pd black and losing its activity, thereby reducing the amount of Pd used and lowering production costs.

[0003] Initially, ligands used in the Suzuki-Miyaura coupling reaction were primarily phosphorus-containing organic compounds. These phosphorus-containing organic compounds were mostly highly toxic, sensitive to oxygen, thermally unstable, and cumbersome to handle. Therefore, in the last decade or so, academia and industry have focused on developing phosphorus-free ligands for the Suzuki-Miyaura coupling reaction, such as carbene-containing ligands. N Or organic compounds containing oxygen, etc.

[0004] In 2013, Didier Astruc's research group reported a novel structure containing... N Organic compound: 4-(2'-pyridyl)-1,2,3-triazole (PyTA) (Adv Synth Catal, 2003, 355, 129-142). PyTA has good electron-rich properties and can be used as... N , NA bidentate ligand coordinates with Pd(OAc)₂ to form a PyTA-Pd(OAc)₂ complex. This complex exhibits good catalytic activity in the Suzuki-Miyaura coupling reaction. Using 4-methoxyiodobenzene and phenylboronic acid as substrates, 0.5 mmol% PyTA-Pd(OAc)₂ as catalyst, ethanol / water (1.5:1.0, v / v) as reaction medium, and 3.0 equivalents of K₂CO₃ as base, the reaction was carried out at room temperature for 48 h. The yield of the coupling product 4-methoxy-1,1'-biphenyl was 77%, and the total oxygen ionization (TON) was 154. Increasing the reaction temperature to 50 °C increased the yield to 88% and the TON to 176. The reactivity of 4-methoxybromobenzene was slightly lower than that of 4-methoxyiodobenzene, but similar results could be obtained by increasing the temperature to 80 °C or extending the reaction time to 96 h. The authors also attempted to catalyze the coupling reaction of the active chlorinated compound 4-nitrochlorobenzene with phenylboronic acid using PyTA-Pd(OAc)2, but the results were unsatisfactory. Furthermore, they prepared a corresponding heterogeneous catalyst by loading PyTA-Pd(OAc)2 onto a dendritic macromolecular material and applied it to the same coupling reaction. Not only was the catalyst and product separation simple, but the catalytic activity was also slightly improved, with a maximum TON of 194. However, the recovered heterogeneous catalyst was not reused.

[0005] PyTA, as a novel structure N , N - Bidentate ligands have shown promising application prospects in Pd-catalyzed Suzuki-Miyaura coupling reactions. However, there are still some limitations to their direct application, mainly: (1) The preparation cost of PyTA is high, and separation under homogeneous reaction conditions is difficult, resulting in the inability to reuse it; although PyTA can be easily separated by loading it onto dendritic macromolecules, the reusability of the recovered catalyst needs to be verified; (2) Although the amount of catalyst Pd used in the method is relatively small (0.5 mmol%) and the reaction temperature is low (50-80℃), the reaction time is long, generally requiring 48-96 hours, and the reaction efficiency is low, i.e., TOF = 2-4 h. -1 (3) So far, only three PyTA-catalyzed Suzuki-Miyaura coupling reactions have been reported, and the universality of the reactions needs to be further investigated.

[0006] Summary of the Invention

[0007] The purpose of this invention is to provide a novel method for preparing asymmetric diaryl hydrocarbon compounds via the Suzuki-Miyaura coupling reaction.

[0008] This invention utilizes polyethylene glycol (PEG)-functionalized pyridine-triazole (PyTA) as a water-soluble ligand, K₂PdCl₄ as the Pd source, ethanol / water as the reaction medium, and aryl bromides and arylboronic acids as raw materials to prepare asymmetric diaromatic compounds. This method is green, economical, and produces minimal waste, showing broad application prospects.

[0009] The technical solution of the present invention is as follows: A method for preparing an asymmetric diaryl hydrocarbon compound, comprising: The ligand PEG-PyTA and K2PdCl4 (Pd source) were added to a water / ethanol mixed solvent and stirred at room temperature for 30 min under inert gas protection. Then, aryl bromide (I), arylboronic acid (II) and basic substances were added and the reaction was stirred at 50 °C for 4-12 h. After post-treatment, the reaction solution was used to obtain asymmetric diaryl hydrocarbon compound (III). The preferred molar ratio of aryl bromide (I) to arylboronic acid (II) is 1:1.2; The preferred molar ratio of ligand PEG-PyTA, K2PdCl4, and aryl bromide (I) is 0.06:0.1:100; ligand PEG-PyTA and K2PdCl4 can each be added in aqueous solution form. The preferred alkaline substance is KOH, and the molar ratio of aryl bromide (I) to KOH is 1:3; In the preferred water / ethanol mixed solvent, the volume ratio of water to ethanol is 9:1; Specific post-processing method: After the reaction is completed, the temperature is lowered to room temperature, and the reaction solution is extracted with methyl tert-butyl ether (the remaining aqueous phase containing the catalyst is reserved for reuse). The extract is dried with anhydrous sodium sulfate and concentrated under reduced pressure to recover methyl tert-butyl ether, to obtain crude product. The crude product is purified by column chromatography to obtain asymmetric diaryl hydrocarbon compound (III). In the above method, PEG-PyTA and its complex with K2PdCl4, PEG-PyTA-PdCl2, are both soluble in the reaction medium, while the asymmetric diaryl hydrocarbons of the product are insoluble in the system. Therefore, after the reaction is completed, the product can be separated by extraction with a common organic solvent, while the catalyst remains in the aqueous phase, allowing for multiple reuses. The reaction formula is as follows:

[0010] In equations (I), (II), and (III), R 1 One or more substituents on the benzene ring, each substituent being independently selected from: H, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, aldehyde, C1-C3 alkyl acyl, cyano, nitro, hydroxy or amino, or R 1Together with the benzene ring, it forms a naphthyl group; R 2 One or more substituents on the benzene ring, each substituent being independently selected from: H, C1-C5 alkyl, C1-C3 alkoxy, halogen or trifluoromethyl, or R 2 It forms a naphthyl group together with the benzene ring.

[0011] In this invention, the structural formula of the ligand PEG-PyTA (polyethylene glycol-functionalized pyridine-triazole) is as follows: n=21~112 PEG-PyTA was prepared in-house, and the preparation method can be found in our previous report (Catalysis Communication, 2017, 101, 5-9).

[0012] The specific preparation method of PEG-PyTA is as follows: (1) Dissolve PEG and methanesulfonyl chloride in dichloromethane, cool to 0~5 ℃, add pyridine dropwise, and continue stirring the reaction at room temperature for 12 h after the addition is complete. After the reaction is complete, pour the reaction solution into ice water to stop the reaction, separate the organic layer, wash the organic layer with 5% HCl aqueous solution and saturated brine in sequence, dry it with anhydrous Na2SO4, filter to remove the desiccant, concentrate and recover dichloromethane under normal pressure, add methyl tert-butyl ether to the residue, precipitate a white solid, filter, and dry under vacuum at 40 ℃ to obtain methanesulfonated PEG, denoted as: PEG-OMs; PEG has an average molecular weight between 1,000 and 5,000 and can be commercially obtained through conventional channels. The molar ratio of PEG, methanesulfonyl chloride, and pyridine is 1:2.0~4.0:2.0~4.0; (2) Dissolve the PEG-OMs and NaN3 obtained in step (1) in DMF, heat to 60~65 ℃ and stir for 12 h. After the reaction is complete, concentrate under reduced pressure to recover DMF. Dissolve the residue in water, add dichloromethane for extraction, dry the extract with Na2SO4, filter to remove the desiccant, concentrate under normal pressure to recover dichloromethane, add methyl tert-butyl ether to the residue, precipitate a white solid, filter, and dry under vacuum at 40℃ to obtain PEG with azido-substituted group, denoted as: PEG-N3; The molar ratio of PEG-OMs to NaN3 is 1:2.0~4.0; (3) Dissolve the PEG-N3, 2-acetylenypyridine, copper sulfate and sodium ascorbate obtained in step (2) in methanol / water (1:1, v / v), heat to 40~45 ℃ and stir for 24 h. After the reaction is complete, concentrate under reduced pressure to recover methanol. Add dichloromethane to the residue for extraction. Wash the extract with 5% ammonia water and saturated brine in sequence, then dry with anhydrous Na2SO4. Filter to remove the desiccant, concentrate under normal pressure to recover dichloromethane, add methyl tert-butyl ether to the residue, precipitate a white solid, filter, and dry under vacuum at 40 ℃ to obtain PEG-PyTA. The molar ratio of PEG-N3, 2-acetylenepyridine, copper sulfate, and sodium ascorbate is 1:2.0~4.0:0.01~0.05:0.01~0.05; Synthetic route of PEG-PyTA (taking PEG-2000 as a starting material as an example):

[0013] Compared with the prior art, the beneficial effects of the present invention are mainly reflected in: (1) This invention uses self-made water-soluble PEG-PyTA as ligand, water-soluble K2PdCl4 as Pd source, KOH as base, and water / ethanol (9:1, v / v) as reaction medium to prepare a series of asymmetric diaromatic compounds via Suzuki-Miyaura coupling method. The developed catalytic method is green, economical, and produces little waste.

[0014] (2) The catalytic efficiency used in this invention is high, with PEG-PyTA at 0.06 mol% and K2PdCl4 at 0.1 mol%, achieving a maximum TON of 980 and a maximum TOF of 245 h. -1 These figures are 5 times and 100 times that of non-PEG functionalized PyTA-Pd(OAc)2, respectively.

[0015] (3) In this invention, water is used as the main reaction medium. The product is insoluble in water, while PEG-PyTA is soluble in water. The product and catalyst can be separated by simple organic solvent extraction, and the post-processing is simple. PEG-PyTA is dissolved in the aqueous phase. After adding K2PdCl4 and KOH, the aqueous phase can be reused more than 5 times and still retains considerable catalytic activity, which greatly reduces the amount of waste.

[0016] (4) The method of the present invention has strong functional group compatibility and a wide range of applicable substrates. Attached Figure Description

[0017] Figure 1 PEG-PyTA 1 H NMR spectrum (500 MHz).

[0018] Figure 2 PEG-PyTA13 C NMR spectrum (125 MHz).

[0019] Figure 3 Mass spectrum of PEG-PyTA (MALDI-TOF-MS). Detailed Implementation

[0020] The present invention is further described below through specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0021] The PEG-PyTA used in the following examples was prepared in-house, and the preparation process is as follows: Weigh commercially available PEG-2000 (30 mmol, 60.0 g) into a 500 mL four-necked flask, add 300 mL of dichloromethane, and stir to dissolve. Add methanesulfonyl chloride (90 mmol, 10.3 g), and cool to 0-5 °C. o C, add pyridine (90 mmol, 7.1 g) dropwise over 30 min. After the addition is complete, stir at room temperature for 12 h. Once the reaction is complete, pour the reaction mixture into 200 mL of ice water, separate the organic phase, and wash successively with 200 mL of 5% hydrochloric acid aqueous solution and 200 mL of saturated brine, then dry with anhydrous sodium sulfate. Filter to remove the desiccant, and recover dichloromethane under normal pressure. Add the residue dropwise to 200 mL of methyl tert-butyl ether, precipitating a large amount of white solid. Filter, and at 40 °C... o Vacuum drying at C yielded 60.2 g of methanesulfonated PEG (PEG-OMs). Yield: 93%; Melting point: 50.2 °C. o C; 1 H NMR (500 MHz, CDCl3): d =4.38-4.36 (m, 2H), 3.77-3.75 (m, 2H), 3.67-3.59 (m, 108H, CH2 of PEG chain), 3.08 (s, 3H) ppm; 13 C NMR (125 MHz, CDCl3): d =70.6-70.5 (C ofPEG chain), 69.2, 68.9, 37.7 ppm.

[0022] Weigh the prepared PEG-OMs (10 mmol, 21.6 g) and NaN3 (30 mmol, 2.6 g) into a 500 mL reaction flask, add 120 mL of DMF, and heat to 65°C. oDissolve at C. Stir the reaction at this temperature for 12 h. After the reaction is complete, cool to room temperature, filter, and concentrate the filtrate under reduced pressure to recover DMF. Dissolve the concentrated residue successively in 120 mL of dichloromethane, wash with 100 mL of saturated brine, and dry with anhydrous sodium sulfate. Filter to remove the desiccant, recover dichloromethane under normal pressure, and add the residue dropwise to 100 mL of methyl tert-butyl ether, precipitating a large amount of white solid. Filter, and 40... o Vacuum drying at C yielded 19.2 g of azide-substituted PEG (PEG-N3). Yield: 92%; Melting point: 51.5 °C. o C; 1 H NMR (500 MHz, CDCl3): d =3.62 (m, 99H, CH2 of PEGchain), 3.37 (t, J =5Hz, 3H)ppm; 13 C NMR (25 MHz, CDCl3): d =70.6-70.5 (C of PEG chain), 69.3, 9.0, 37.7 ppm.

[0023] Weigh PEG-N3 (10 mmol, 20.8 g), 2-ethynylpyridine (30 mmol, 3.1 g), and copper sulfate (0.3 mmol, 0.05 g) into a 250 mL single-necked flask and dissolve in 80 mL of methanol / water (1:1, v / v). Under nitrogen protection, add sodium ascorbate (0.3 mmol, 0.06 g). Heat to 45°C. o At temperature C, the reaction was carried out for 24 hours. After the reaction was complete, the reaction solution was concentrated to recover methanol. The residue was dissolved in 100 mL of dichloromethane, washed successively with 100 mL of 5% ammonia water, 100 mL of saturated brine, and dried over anhydrous sodium sulfate. The desiccant was removed by filtration, and dichloromethane was recovered under normal pressure. The residue was added dropwise to 100 mL of methyl tert-butyl ether, precipitating a large amount of white solid. The mixture was then filtered and dried at 40 °C. o Vacuum drying at C yielded 21.3 g of PyTA-functionalized PEG (PEG-PyTA). Yield: 93%; Melting point: 48.5 °C. o C. 1 H NMR (500 MHz, MeOD): d =8.61 (s, 1H), 8.53 (s, 1H), 8.10 (d, J =7.8 Hz, 1H), 7.96-7.92 (m, 1H), 7.39 (t, J =6.0 Hz, 1H), 4.69 (t, J =5.0 Hz, 2H), 3.98 (t,J =5.0 Hz, 2H), 3.67-3.58 (m, 132H, CH2 of PEG chain) ppm; 13 C NMR (125 MHz, CDCl3): d =149.1, 147.7, 137.5, 123.7, 123.0, 120.0, 70.1 (C of PEG chain), 50.3, 68.9 ppm.

[0024] Replacing PEG-2000 with PEG-1000, PEG-3000, PEG-4000, and PEG-5000, the corresponding PEG-PyTA can be prepared using the same method, with overall yields of 75%, 78%, 82%, and 85% for the three-step reaction, respectively.

[0025] Example 1: Preparation of 4-methyl-1,1'-biphenyl

[0026] Weigh 1.38 g (6 × 10⁶ ml) of a 1.0% PEG-PyTA aqueous solution into a 15 mL single-necked reaction tube. -3 mmol) and a 0.5% K2PdCl4 aqueous solution (0.65 g, 1×10 mmol) -2 Dissolve 10 mmol of bromobenzene in 8 mL of water / ethanol (9:1, v / v) and stir for 30 min at room temperature under nitrogen protection. Then add bromobenzene (1.55 g, 10 mmol), p-methylphenylboronic acid (1.65 g, 12 mmol), and KOH (1.68 g, 30 mmol) sequentially. Place the reaction tube in a container preheated to 50°C. o The reaction was carried out in a water bath at C with stirring for 4 h. After the reaction was completed, the mixture was cooled to room temperature, and 5 mL of methyl tert-butyl ether was added. The mixture was extracted 2-3 times to ensure complete extraction of the product. The remaining aqueous phase containing the catalyst was reserved for reuse. The extracts were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to recover methyl tert-butyl ether. The crude product was purified by column chromatography (using petroleum ether / ethyl acetate at a volume ratio of 20:1) to give 1.63 g of 4-methyl-1,1'-biphenyl, with a yield of 97%. The product was a white solid with a melting point of 47.5°C. o C.

[0027] Examples 2-24

[0028] Diaryl aromatic compounds were prepared using different aryl bromides and arylboronic acids. The experimental procedures were the same as in Example 1, and the results are shown in Table 1.

[0029] Table 1. Preparation of diaromatic compounds from different aryl bromides and arylboronic acids

[0030] Example 25 Preparation of 4-methyl-1,1'-biphenyl by using a catalyst

[0031] After the first reaction, the product was extracted with methyl tert-butyl ether, while the ligand PEG-PyTA and the reaction medium water remained in the reaction tube. 0.5% K₂PdCl₄ aqueous solution (0.65 g, 1×10⁻⁶) was then added. -2 Under nitrogen protection, the mixture was stirred at room temperature for 30 min. Then, bromobenzene (1.55 g, 10 mmol), p-methylphenylboronic acid (1.65 g, 12 mmol), and KOH (1.68 g, 30 mmol) were added sequentially. The reaction was heated to 50 °C, and the specific reaction time and post-treatment procedures were the same as in Example 1. 1.60 g of 4-methyl-1,1'-biphenyl was obtained, with a yield of 95%. The aqueous phase was reused four times consecutively, with yields of 96%, 93%, 92%, and 90%, respectively.

[0032] Characterization data of the product: 4-Methyl-1,1'-Biphenyl (Example 1) White solid, melting point: 47.5°C o C; 1 H NMR (500 MHz, CDCl3): δ=7.64-7.61 (m, 2H), 7.55-7.53 (m, 2H), 7.48-7.45 (m, 2H), 7.38-7.35 (m, 1H), 7.29 (d, J =8.0 Hz, 2H), 2.44 (s, 3H) ppm; 13 CNMR (125 MHz, CDCl3): δ=141.2, 138.4, 137.0, 129.5, 128.7, 127.0, 126.9, 21.1 ppm.

[0033] 4,4'-Dimethyl-1,1'-Biphenyl (Example 2)

[0034] White solid, melting point: 121.9°C o C; 1 H NMR (500 MHz, CDCl3): δ=7.51-7.49 (m, 4H), 7.26 (d, J =7.9 Hz, 4H), 2.41 (s, 6H) ppm; 13 C NMR (125 MHz, CDCl3): δ=138.3, 136.7, 129.4, 126.8, 21.1 ppm.

[0035] 2,4'-Dimethyl-1,1'-Biphenyl (Example 3)

[0036] Pale yellow liquid; 1 H NMR (500 MHz, CDCl3): δ=7.35-7.27 (m, 8H), 2.49 (s, 3H), 2.36 (s, 3H) ppm; 13 C NMR (125 MHz, CDCl3): δ=141.9, 139.0, 136.3, 135.4, 130.3, 129.9, 129.1, 128.8, 127.1, 125.7, 21.2, 20.5 ppm.

[0037] 2,6,4'-Trimethyl-1,1'-Biphenyl (Example 4)

[0038] White solid, melting point: 36.5°C o C; 1 H NMR (500 MHz, CDCl3): δ=7.29 (d, J =7.8 Hz, 2H), 7.23-7.20 (m, 1H), 7.16 (d, J =7.5 Hz, 2H), 7.10 (d, J =8.0 Hz, 2H), 2.47 (s, 3H), 2.11 (s, 6H) ppm; 13 C NMR (125 MHz, CDCl3): δ=141.9, 138.0, 136.2, 136.1, 129.1, 128.9, 127.2, 126.9, 21.2, 20.9 ppm.

[0039] 4-(4'-Methylphenyl)anisole (Example 5)

[0040] White solid, melting point: 110.3°C o C; 1 H NMR (500 MHz, CDCl3): δ=7.55-7.51 (m, 2H), 7.48-7.46 (m, 2H), 7.24 (d, J =7.9 Hz, 2H), 7.00-6.97 (m, 2H), 3.87 (s, 3H), 2.40 (s, 3H) ppm; 13 CNMR (125 MHz, CDCl3): δ=159.0, 138.0, 136.4, 133.8, 129.4, 128.0, 126.6, 114.2, 55.4, 21.1 ppm.

[0041] 4-Methyl-4'-trifluoromethyl-1,1'-biphenyl (Example 6)

[0042] White solid, melting point: 135.5°C o C; 1 H NMR (500 MHz, CDCl3): δ=7.70 (s, 4H), 7.51-7.53 (m, 2H), 7.30 (d, J =7.9 Hz, 2H), 2.43 (s, 3H) ppm; 13 C NMR (125 MHz, CDCl3): δ=144.7, 138.2, 136.9, 129.7, 129.1 (q, J= 32.3 Hz), 127.2, 127.1, 125.6 (q, J =3.8 Hz), 124.4 (q, J =270.1Hz), 21.2 ppm.

[0043] 4-(4'-Methylphenyl)benzaldehyde (Example 7)

[0044] White solid, melting point: 104.2°C o C; 1 H NMR (500 MHz, CDCl3): δ=10.06 (s, 1H), 7.96-7.95 (m, 2H), 7.77-7.75 (m, 2H), 7.57-7.55 (m, 2H), 7.31 (d, J =7.9 Hz, 2H), 2.44 (s, 3H) ppm; 13 C NMR (125 MHz, CDCl3): δ=191.9, 147.2, 138.6, 136.8, 135.0, 130.3, 129.8, 127.4, 127.2, 21.2ppm.

[0045] 4-(4'-Methylphenyl)acetophenone (Example 8)

[0046] White solid, melting point: 120.0°C o C; 1 H NMR (500 MHz, CDCl3): δ=8.05-8.03 (m, 2H), 7.78-7.70 (m, 2H), 7.55 (d, J =8.1 Hz, 2H), 7.30 (d, J =8.0 Hz, 2H), 2.65 (s, 3H), 2.43 (s, H) ppm; 13C NMR (125 MHz, CDCl3): δ=197.8, 145.7, 138.3, 137.0, 135.6, 129.7, 128.9, 127.1, 127.0, 26.7, 21.2 ppm.

[0047] 4-(4'-Methylphenyl)benzonitrile (Example 9)

[0048] White solid, melting point: 109.4°C o C; 1 H NMR (500 MHz, CDCl3): δ=7.73-7.72 (m, 2H), 7.69-7.67 (m, 2H), 7.52-7.50 (m, 2H), 7.30 (d, J =7.9 Hz, 2H), 2.43 (s, 3H) ppm; 13 C NMR (125MHz, CDCl3): δ=145.6, 138.8, 136.3, 132.6, 129.8, 127.5, 127.1, 119.0, 110.6, 21.2 ppm.

[0049] 4-Methyl-4'-nitrobiphenyl (Example 10)

[0050] Bright yellow solid, melting point: 139.5°C o C; 1 H NMR (500 MHz, CDCl3): δ=8.29-8.31 (m, 2H), 7.72-7.75 (m, 2H), 7.54-7.56 (m, 2H), 7.32 (d, J =8.1 Hz, 2H), 2.44 (s, 3H) ppm; 13 C NMR (125MHz, CDCl3): δ=146.9, 139.1, 135.9, 133.1, 129.9, 127.5, 127.2, 124.1, 21.2 ppm.

[0051] 4-(4'-Methylphenyl)phenol (Example 11)

[0052] White solid, melting point: 153.0°C o C; 1 H NMR (500 MHz, CDCl3): δ=7.49-7.45 (m, 4H), 7.24 (d, J =8.0 Hz, 2H), 6.93-6.90 (m, 2H), 4.80 (s, 1H), 2.40 (s, 3H) ppm; 13C NMR (125 MHz, CDCl3): δ=154.8, 137.9, 136.4, 134.0, 129.5, 128.2, 126.6, 115.6, 21.1 ppm.

[0053] 4-(4'-Methylphenyl)aniline (Example 12)

[0054] Bright yellow solid, melting point: 99.1°C. o C; 1 H NMR (500 MHz, CDCl3): δ=7.47-7.41 (m, 4H), 7.23 (d, J =7.9 Hz, 2H), 6.79-6.76 (m, 2H), 3.72 (s, 2H), 2.40 (s, 3H) ppm; 13 C NMR (125 MHz, CDCl3): δ=145.6, 138.3, 135.9, 131.6, 129.4, 127.8, 126.3, 115.4, 21.0 ppm.

[0055] 2-(4-Methylphenyl)naphthalene (Example 13)

[0056] White solid, melting point: 97.1°C o C; 1 H NMR (500 MHz, CDCl3): δ=8.05 (s, 1H), 7.94-7.88 (m, 2H), 7.78-7.76 (m, 2H), 7.66-7.65 (m, 2H), 7.54-7.48 (m, 2H), 7.33 (d, J =7.9 Hz, 2H), 2.45 (s, 3H) ppm; 13 C NMR (125 MHz, CDCl3): δ=138.5, 138.2, 137.2, 133.7, 132.5, 129.6, 128.3, 128.1, 127.6, 127.3, 126.2, 125.8, 125.6, 125.4, 21.2 ppm.

[0057] 1,1'-Biphenyl (Example 14)

[0058] White solid, melting point: 69.9°C o C; 1 H NMR (500 MHz, CDCl3): δ=7.63-7.61 (m, 4H), 7.48-7.45 (m, 4H), 7.39-7.35 (m, 2H) ppm; 13C NMR (125 MHz, CDCl3): δ=141.2, 128.8, 127.3, 127.2 ppm.

[0059] 3-Methyl-1,1'-biphenyl (Example 15)

[0060] Pale yellow liquid; 1 H NMR (500 MHz, CDCl3): δ=7.68-7.66 (m, 2H), 7.53-7.47 (m, 4H), 7.43-7.40 (m, 2H), 7.25 (d, J =7.5 Hz, 1H), 2.50 (s, 3H) ppm; 13 C NMR (125 MHz, CDCl3): δ =141.4, 141.2, 138.3, 128.8, 128.7, 128.1, 128.0, 127.3, 127.2, 124.3, 21.5 ppm.

[0061] 2-Methyl-1,1'-biphenyl (Example 16)

[0062] Pale yellow liquid; 1 H NMR (500 MHz, CDCl3): δ=7.46-7.43 (m, 2H), 7.39-7.35 (m, 3H), 7.31-7.26 (m, 4H), 2.31 (s, 3H) ppm; 13 C NMR (125 MHz, CDCl3): δ=142.1, 142.0, 135.4, 130.3, 129.8, 129.2, 128.1, 127.2, 126.8, 125.8, 20.5 ppm.

[0063] 4-Methoxy-1,1'-Biphenyl (Example 17)

[0064] White solid, melting point: 86.3°C o C; 1 H NMR (500 MHz, CDCl3): δ=7.58-7.54 (m, 4H), 7.45-7.42 (m, 2H), 7.34-7.31 (m, 1H), 7.02-6.99 (m, 2H), 3.87 (s, 3H) ppm; 13 C NMR (125 MHz, CDCl3): δ=159.2, 140.9, 133.8, 128.7, 128.2, 126.8, 126.7, 114.2, 55.4 ppm.

[0065] 3-Methoxy-1,1'-Biphenyl (Example 18)

[0066] Pale yellow liquid; 1 H NMR (500 MHz, CDCl3): δ=7.64-7.62 (m, 2H), 7.49-7.46 (m, 2H), 7.41-7.37 (m, 2H), 7.24-7.22 (m, 1H), 7.17 (t, J =2.1 Hz, 1H), 6.93-6.95 (m, 1H), 3.90 (s, 3H) ppm; 13 C NMR (125 MHz, CDCl3): δ=160.0, 142.8, 141.1, 129.7, 128.7, 127.4, 127.2, 119.7, 112.9, 112.7, 55.3 ppm.

[0067] 2-Methoxy-1,1'-Biphenyl (Example 19)

[0068] White solid, melting point: 84.2°C o C; 1 H NMR (500 MHz, CDCl3): δ=7.59-7.56 (m, 2H), 7.47-7.44 (m, 2H), 7.38-7.35 (m, 3H), 7.09-7.06 (m, 1H), 7.04-7.02 (m, 1H), 3.85 (s, 3H) ppm; 13 C NMR (125 MHz, CDCl3): δ=156.5, 138.6, 130.9, 130.7, 129.5, 128.6, 128.0, 126.9, 120.8, 111.2, 55.6 ppm.

[0069] 4-Fluoro-1,1'-Biphenyl (Example 20)

[0070] White solid, melting point: 75.5°C o C; 1 H NMR (500 MHz, CDCl3): δ=7.58-7.55 (m, 4H), 7.45 (t, J =7.7 Hz, 2H), 7.36 (t, J =7.4 Hz, 1H), 7.17-7.13 (m, 2H) ppm; 13 C NMR (125 MHz, CDCl3): δ=162.5 (d, J =244.8Hz), 140.3, 137.4, 128.8, 128.7 (d, J=7.7 Hz), 127.3, 127.0, 115.6 (d, J =21.4 Hz) ppm.

[0071] 4-Chloro-1,1'-Biphenyl (Example 21)

[0072] White solid, melting point: 77.5°C o C; 1 H NMR (500 MHz, CDCl3): δ=7.58-7.53 (m, 4H), 7.48-7.41 (m, 4H), 7.40-7.36 (m, 1H) ppm; 13 C NMR (125 MHz, CDCl3): δ=140.0, 139.7, 133.4, 128.9, 128.9, 128.4, 127.6, 127.0 ppm.

[0073] 4-Trifluoromethyl-1,1'-Biphenyl (Example 22)

[0074] White solid, melting point: 68.4°C o C; 1 H NMR (500 MHz, CDCl3): δ=7.72 (s, 4H), 7.63-7.61 (m, 2H), 7.51-7.48 (m, 2H), 7.45-7.41 (m, 1H) ppm; 13 C NMR (125 MHz, CDCl3): δ=144.8, 139.8, 129.7, 129.3 (q, J =32.5 Hz), 129.0, 128.2, 127.4, 127.3, 125.7 (q, J =3.8 Hz), 124.3 (q, J =270.2 Hz) ppm.

[0075] 4-tert-butyl-1,1'-biphenyl (Example 23)

[0076] Pale yellow solid, melting point: 50.5°C. o C; 1 H NMR (500 MHz, CDCl3): δ=7.62-7.60 (m, 2H), 7.57-7.55 (m, 2H), 7.50-7.48 (m, 2H), 7.46-7.43 (m, 2H), 7.36-7.33 (m, 1H), 1.39 (s, 9H) ppm; 13CNMR (125 MHz, CDCl3): δ=150.3, 141.1, 138.3, 128.7, 127.1, 127.0, 126.8, 125.7, 34.5, 31.4 ppm.

[0077] 1-Phenylanthide (Example 24)

[0078] Pale yellow liquid; 1 H NMR (500 MHz, CDCl3): δ=7.98-7.96 (m, 2H), 7.92 (d, J =8.1 Hz, 1H), 7.60-7.53 (m, 6H), 7.50-7.47 (m, 3H) ppm; 13 C NMR (125 MHz, CDCl3): δ=140.8, 140.3, 133.8, 131.7, 130.1, 128.3, 127.6, 127.2, 126.9, 126.1, 126.0, 125.9, 125.8, 125.4ppm.

Claims

1. A method for preparing an asymmetric diaryl hydrocarbon compound, characterized in that, include: The ligands PEG-PyTA and K2PdCl4 were added to a water / ethanol mixed solvent and stirred at room temperature under inert gas protection. Then, aryl bromide (I), arylboronic acid (II), and basic substances were added and stirred at 50 °C for 4-12 h. After post-treatment, the reaction solution was used to obtain asymmetric diaryl hydrocarbon compound (III). The structural formula of the ligand PEG-PyTA is as follows: n=21~112 The reaction formula is as follows: In equations (I), (II), and (III), R 1 One or more substituents on the benzene ring, each substituent being independently selected from: H, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, aldehyde, C1-C3 alkyl acyl, cyano, nitro, hydroxy or amino, or R 1 Together with the benzene ring, it forms a naphthyl group; R 2 One or more substituents on the benzene ring, each substituent being independently selected from: H, C1-C5 alkyl, C1-C3 alkoxy, halogen or trifluoromethyl, or R 2 It forms a naphthyl group together with the benzene ring.

2. The method for preparing the asymmetric diaryl hydrocarbon compound as described in claim 1, characterized in that, The molar ratio of aryl bromide (I) and arylboronic acid (II) is 1:1.

2.

3. The method for preparing the asymmetric diaryl hydrocarbon compound as described in claim 1, characterized in that, The molar ratio of ligand PEG-PyTA, K2PdCl4, and aryl bromide (I) is 0.06:0.1:

100.

4. The method for preparing the asymmetric diaryl hydrocarbon compound as described in claim 1, characterized in that, The alkaline substance is KOH, and the molar ratio of aryl bromide (I) to KOH is 1:

3.

5. The method for preparing the asymmetric diaryl hydrocarbon compound as described in claim 1, characterized in that, In the water / ethanol mixed solvent, the volume ratio of water to ethanol is 9:

1.

6. The method for preparing the asymmetric diaryl hydrocarbon compound as described in claim 1, characterized in that, Post-processing method: After the reaction was completed, the mixture was cooled to room temperature and extracted with methyl tert-butyl ether. The extract was dried with anhydrous sodium sulfate and concentrated under reduced pressure to recover the methyl tert-butyl ether, yielding a crude product. The crude product was purified by column chromatography to obtain an asymmetric diaryl hydrocarbon compound (III).

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