A method for synthesizing 3-arylquinoline compounds by nickel catalysis

Abstract

The invention discloses a method for synthesizing 3-arylquinoline compounds by nickel catalysis, using quinoline, n-heptyl Grignard reagent, and iodobenzene as raw materials, and realizing the synthesis of 3-arylquinoline compounds by nickel metal catalysis under a nitrogen environment. The method has the advantages of a wide substrate range, mild reaction conditions, a high yield of the target product, simple reaction operation, and low reaction pollution, and it has certain feasibility for industrial large-scale production.

Description

Technical Field

[0001] The invention relates to a method for synthesizing 3-arylquinoline compounds by nickel catalysis, and belongs to the field of organic chemistry and chemical industry. Background Art

[0002] Substituted nitrogen heterocycles with quinoline as the structural center are widely present in synthetic drugs and natural products. They are an important pharmacophore and are commonly found in many biologically active molecules. They play an irreplaceable role in the treatment of diseases, such as anti-malarial, anti-tuberculosis, and cancer treatment.

[0003] In recent years, with the surge in resource investment in the biopharmaceutical and new energy industries, related industries have placed higher demands on the large-scale and efficient synthesis of bioactive compounds and new functional molecules. Traditional synthesis methods for substituted nitrogen heterocyclic compounds can no longer meet the requirements of high efficiency and environmental protection. In recent years, transition metal-catalyzed C-H bond activation and functionalization have provided new ideas and methods for the convenient and efficient synthesis of nitrogen-containing heterocyclic compounds. However, many problems still need to be solved, such as the formation of more byproducts due to excessively high reaction temperatures and the increased production costs caused by the use of precious metal catalysts. Therefore, the development of a mild, rapid, and inexpensive metal-catalyzed nitrogen heterocyclic arylation method is of great significance in the field of organic synthesis.

[0004] Currently reported methods for synthesizing substituted quinolines include palladium-catalyzed reaction of quinoline without a directing group with iodobenzene to achieve arylation at the 3-position, and reaction of quinoline with phenylboronic acid via the introduction of a directing group onto the N atom of quinoline. However, these methods for synthesizing 3-arylquinolines suffer from the requirements of expensive transition metals and toxic ligands, high reaction temperatures, and prolonged reaction times. Therefore, the development of a green and facile method for synthesizing 3-arylquinolines is crucial. Summary of the Invention

[0005] To address the shortcomings of existing synthesis methods, we have developed a method for the synthesis of 3-arylquinoline compounds. This method uses quinoline, n-heptyl Grignard reagent, and iodobenzene as raw materials and is catalyzed by nickel metal under a nitrogen atmosphere to achieve the synthesis of 3-arylquinoline compounds.

[0006] In order to achieve the above-mentioned object of the invention, the present invention proposes the following technical solutions:

[0007]

[0008] This scheme uses quinoline I, Grignard reagent II and iodobenzene III as raw materials, and carries out a two-step electrophilic addition and reductive elimination reaction catalyzed by nickel under a nitrogen environment to obtain an aryl quinoline compound IV.

[0009] As a preferred embodiment, the quinoline compound I has a structure shown in Formula 1:

[0010]

[0011] Wherein, R is various aliphatic hydrocarbon groups or halogen atoms.

[0012] As a preferred solution, the n-heptyl Grignard reagent II has a structure shown in Formula 2:

[0013]

[0014] As a preferred embodiment, the iodobenzene III has a structure shown in Formula 3:

[0015]

[0016] Wherein, R' is an aliphatic hydrocarbon group or various halogen atom substituents.

[0017] As a preferred embodiment, the 3-arylquinoline compound IV has a structure shown in Formula 4:

[0018]

[0019] Wherein, R and R' are aliphatic hydrocarbon groups or various halogen atom substituents.

[0020] As a preferred solution, the molar amount of the n-heptyl Grignard reagent is 1.5 times the molar amount of quinoline. Increasing or decreasing the ratio of the Grignard reagent significantly reduces the yield of the target product. When the ratio is 1.5 times, the reaction yield is optimal.

[0021] As a preferred embodiment, the molar amount of iodobenzene is 1 to 2 times the molar amount of quinoline. Increasing the proportion of iodobenzene significantly improves the yield of the target product. When the added amount reaches or exceeds 2 times that of quinoline, the yield of the target product of the reaction does not significantly increase.

[0022] As a preferred solution, the solvent used in the reaction is diethylene glycol dimethyl ether.

[0023] The specific reaction mechanism of the two-step electrophilic addition and reductive elimination between quinoline, an n-heptyl Grignard reagent, and iodobenzene of the present invention is as follows: Initially, Ni(COD)2 is reduced by the Grignard reagent to a zero-valent nickel compound, which then coordinates with quinoline to form intermediate A. The n-heptyl Grignard reagent then undergoes nucleophilic addition to intermediate A to form intermediate B. Iodobenzene then electrophilically attacks intermediate B, followed by reductive elimination to yield the target product.

[0024] Compared with the prior art, the technical solution of the present invention has the following advantages:

[0025] First, this method does not require noble metals and toxic ligands;

[0026] Second, this method is a one-pot, two-step process with high atom utilization and selectivity;

[0027] Third, the method has a high yield of 78% and is tolerant to a variety of functional groups;

[0028] Fourth, this method is simple, mild, green, and can effectively synthesize 3-arylquinoline compounds;

[0029] Fifth, this method has certain feasibility for industrial large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 The nickel-catalyzed method for synthesizing 3-phenylquinoline is proposed; Figure 2 is the H NMR spectrum of 3-phenylquinoline; Figure 3 This is the carbon NMR spectrum of 3-phenylquinoline. DETAILED DESCRIPTION

[0031] To make the above-mentioned features, advantages, and purposes of the present invention more clearly understood, the present invention is described in detail below in conjunction with specific embodiments. The above description sets forth many specific details to facilitate a full understanding of the present invention. However, the present invention can be implemented in many other ways than those described herein, and those skilled in the art can make similar modifications without violating the scope of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0032] Unless otherwise specified, the reaction raw materials and catalysts involved in the following examples are conventional commercially available reagents on the market.

[0033] Condition optimization experiment: Taking the synthesis of 3-phenylquinoline from quinoline, n-heptylmagnesium bromide, and iodobenzene as an example, the optimal reaction conditions were obtained by optimizing the reactant ratio, catalyst selection, solvent selection, reaction time, and reaction temperature. The reaction yield was monitored by gas chromatography. The specific reaction under the optimal reaction conditions is as follows:

[0034] In a glove box, quinoline (25.8 mg, 0.2 mmol) and bis(1,5-cyclooctadiene)nickel (5.5 mg, 10 mol%) were weighed into a 10 mL reaction tube equipped with a magnetic stir bar, and 2 mL of diethylene glycol dimethyl ether was added. The tube was sealed with a Teflon-lined screw cap and removed from the glove box. Under nitrogen, n-heptylmagnesium bromide (0.6 mL, 1.0 M in tetrahydrofuran) was added dropwise via syringe. The reaction was stirred at 30°C for 20 minutes. Iodobenzene (0.4 mmol) was then added to the tube under nitrogen, and the reaction was stirred at 30°C for 3 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride (2 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (3 × 3 mL). The combined layers were dried over anhydrous sodium sulfate, and then an excess of 1,2-dichloro-4,5-dicyanobenzoquinone (0.3 mmol, 68.1 mg) was added. The solvent was evaporated under vacuum, and the target product 3-phenylquinoline was obtained by column chromatography using a solvent mixture of petroleum ether and ethyl acetate as a white solid with a yield of 78%.

[0035]

[0036]

[0037] As can be seen from Experimental Groups 1 to 7 in the table above, the nickel catalyst and its dosage significantly affect the yield of the target product. The reaction proceeded smoothly under various nickel catalysts, with the highest yield of the target product achieved under bis(1,5-cyclooctadiene) nickel catalysis. In the absence of a nickel catalyst, almost no target product was obtained. The highest yield of the target product was achieved when the nickel catalyst dosage was 10%.

[0038] As can be seen from Experimental Groups 1 and 8-10 in the table above, the reaction proceeded smoothly in most organic solvents. The highest yield was achieved using diethylene glycol dimethyl ether as the reaction solvent. However, the reaction proceeded smoothly but with lower yields when using tetrahydrofuran and cyclopentyl methyl ether as solvents. And when using 1,4-dioxane as the solvent, almost no target product was obtained. Diethylene glycol dimethyl ether was the optimal reaction solvent for this reaction.

[0039] As can be seen from Experimental Groups 1 and 11-16 in the table above, reaction temperature affects the yield of the target product. In the first step, increasing the temperature decreases the yield, with the highest yield occurring at 30°C. In the second step, increasing the temperature decreases the yield, with the highest yield occurring at 30°C. The yield of the target product is highest when the first and second steps are at 30°C.

[0040] As can be seen from Experimental Groups 1 and 17-25 in the table above, reaction time affects the yield of the target product. In the first step, increasing the reaction time decreases the yield, with the highest yield occurring at 20 minutes. In the second step, increasing the reaction time increases the yield, reaching its highest at 3 hours. Further increases in reaction time decrease the yield. The highest yield of the target product was achieved with a 20-minute reaction in the first step and a 3-hour reaction in the second step.

[0041] The present invention will be further described below with reference to specific Preparation Examples 1 to 8:

[0042] Preparation Example 1

[0043] In a glove box, quinoline (25.8 mg, 0.2 mmol) and bis(1,5-cyclooctadiene)nickel (5.5 mg, 10 mol%) were weighed into a 10 mL reaction tube equipped with a magnetic stir bar, and 2 mL of diethylene glycol dimethyl ether was added. The tube was sealed with a Teflon-lined screw cap and removed from the glove box. Under nitrogen, n-heptylmagnesium bromide (0.6 mL, 1.0 M in tetrahydrofuran) was added dropwise via syringe. The reaction was stirred at 30°C for 20 minutes. Iodobenzene (0.4 mmol) was then added to the tube under nitrogen, and the reaction was stirred at 30°C for 3 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride (2 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (3 × 3 mL). The combined layers were dried over anhydrous sodium sulfate, and then an excess of 1,2-dichloro-4,5-dicyanobenzoquinone (0.3 mmol, 68.1 mg) was added. The solvent was evaporated under vacuum, and the target product 3-phenylquinoline was obtained by column chromatography using a solvent mixture of petroleum ether and ethyl acetate as a white solid with a yield of 78%.

[0044] 1 H NMR (400MHz, CDCl3) δ9.18(d,1H),8.28(d,1H),8.14(d,1H),7.87(m,1H),7.71(m,3H),7.60-7.50(m,3H),7.45-7.40(m,1H).

[0045] 13 C NMR (101MHz, CDCl3) δ149.9,147.3,137.8,133.8,133.2,129.3,129.2,129.1,128.1,128.0,128.0,127.4,126.9.

[0046] Preparation Example 2

[0047] In a glove box, quinoline (25.8 mg, 0.2 mmol) and bis(1,5-cyclooctadiene)nickel (5.5 mg, 10 mol%) were weighed into a 10 mL reaction tube equipped with a magnetic stir bar, and 2 mL of diethylene glycol dimethyl ether was added. The tube was sealed with a Teflon-lined screw cap and removed from the glove box. Under nitrogen, n-heptylmagnesium bromide (0.6 mL, 1.0 M in tetrahydrofuran) was added dropwise via syringe. The reaction was stirred at 30°C for 20 minutes. 2-Methyliodobenzene (0.4 mmol) was then added to the tube under nitrogen, and the reaction was stirred at 30°C for 3 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride (2 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (3 × 3 mL). The combined layers were dried over anhydrous sodium sulfate, and then an excess of 1,2-dichloro-4,5-dicyanobenzoquinone (0.3 mmol, 68.1 mg) was added. The solvent was evaporated under vacuum, and the product was separated by column chromatography using a solvent mixture of petroleum ether and ethyl acetate to obtain the target product 3-(o-methylphenyl)quinoline as a white solid with a yield of 70%.

[0048] 1 H NMR (400MHz, CDCl3) δ8.93(d,J=2.2Hz,1H),8.16(d,J=8.5Hz,1H),8.08(d,J=2.1Hz, 1H),7.84(d,J=8.1Hz,1H),7.73(m,1H),7.57(m,1H),7.39-7.27(m,4H),2.32(s,3H).

[0049] 13 C NMR (101MHz, CDCl3) δ151.38,146.90,138.02,135.75,135.26,134.74,130. 56,130.11,129.30,129.18,128.11,127.79,127.67,126.82,126.10,20.40.

[0050] Preparation Example 3

[0051] In a glove box, quinoline (25.8 mg, 0.2 mmol) and bis(1,5-cyclooctadiene)nickel (5.5 mg, 10 mol%) were weighed into a 10 mL reaction tube equipped with a magnetic stir bar, and 2 mL of diethylene glycol dimethyl ether was added. The tube was sealed with a Teflon-lined screw cap and removed from the glove box. n-Heptylmagnesium bromide (0.6 mL, 1.0 M in tetrahydrofuran) was added dropwise via syringe under nitrogen. The reaction was stirred at 30°C for 20 minutes. 3-Methyliodobenzene (0.4 mmol) was then added to the tube under nitrogen, and the reaction was stirred at 30°C for 3 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride (2 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (3 × 3 mL). The combined layers were dried over anhydrous sodium sulfate, and then an excess of 1,2-dichloro-4,5-dicyanobenzoquinone (0.3 mmol, 68.1 mg) was added. The solvent was evaporated under vacuum, and the product was separated by column chromatography using a solvent mixture of petroleum ether and ethyl acetate to obtain the target product 3-(m-methylphenyl)quinoline as a white solid with a yield of 75%.

[0052] 1 H NMR (400MHz, CDCl3) δ9.17(d,J=2.3Hz,1H),8.27(d,J=2.2Hz,1H),8.14(d,J=8.4Hz,1H),7.86(d,J=8. 2Hz,1H),7.74-7.67(m,1H),7.60-7.48(m,3H),7.40(t,J=7.8Hz,1H),7.27-7.21(m,1H),2.46(s,3H).

[0053] 13 C NMR (101MHz, CDCl3) δ149.95,147.24,138.81,137.78,133.91,133.12,129. 25,129.15,129.02,128.81,128.10,127.99,127.93,126.90,124.48,21.52.

[0054] Preparation Example 4

[0055] In a glove box, quinoline (25.8 mg, 0.2 mmol) and bis(1,5-cyclooctadiene)nickel (5.5 mg, 10 mol%) were weighed into a 10 mL reaction tube equipped with a magnetic stir bar, and 2 mL of diethylene glycol dimethyl ether was added. The tube was sealed with a Teflon-lined screw cap and removed from the glove box. n-Heptylmagnesium bromide (0.6 mL, 1.0 M in tetrahydrofuran) was added dropwise via syringe under nitrogen. The reaction was stirred at 30°C for 20 minutes. 4-Methyliodobenzene (0.4 mmol) was then added to the tube under nitrogen, and the reaction was stirred at 30°C for 3 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride (2 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (3 × 3 mL). The combined layers were dried over anhydrous sodium sulfate, and then an excess of 1,2-dichloro-4,5-dicyanobenzoquinone (0.3 mmol, 68.1 mg) was added. The solvent was evaporated under vacuum, and the product was separated by column chromatography using a solvent mixture of petroleum ether and ethyl acetate to obtain the target product 3-(p-methylphenyl)quinoline as a white solid with a yield of 79%.

[0056] 1 H NMR (400MHz, CDCl3) δ9.17(d,J=2.3Hz,1H),8.26(d,J=2.2Hz,1H),8.13(d,J=8.4Hz,1H), 7.85(d,J=7.8Hz,1H),7.70(m,1H),7.62-7.52(m,3H),7.32(d,J=7.9Hz,2H),2.42(s,3H).

[0057] 13 C NMR (101MHz, CDCl3) δ149.87,147.14,137.99,134.88,133.70,132.74,129.84,129.13,128.02,127.88,127.17,126.87,21.13.

[0058] Preparation Example 5

[0059] In a glove box, quinoline (25.8 mg, 0.2 mmol) and bis(1,5-cyclooctadiene)nickel (5.5 mg, 10 mol%) were weighed into a 10 mL reaction tube equipped with a magnetic stir bar. 2 mL of diethylene glycol dimethyl ether was added. The tube was sealed with a Teflon-lined screw cap and removed from the glove box. n-Heptylmagnesium bromide (0.6 mL, 1.0 M in tetrahydrofuran) was added dropwise via syringe under nitrogen. The reaction was stirred at 30°C for 20 minutes. 4-Fluoroiodobenzene (0.4 mmol) was then added to the tube under nitrogen, and the reaction was stirred at 30°C for 3 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride (2 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (3 × 3 mL). The combined layers were dried over anhydrous sodium sulfate, followed by the addition of an excess of 1,2-dichloro-4,5-dicyanobenzoquinone (0.3 mmol, 68.1 mg). The solvent was evaporated under vacuum, and the product was separated by column chromatography using a solvent mixture of petroleum ether and ethyl acetate to obtain the target product 3-(4-fluorophenyl)quinoline as a white solid with a yield of 70%.

[0060] 1 H NMR (400MHz, CDCl3) δ9.16 (s, 1H), 8.28 (d, J = 2.2Hz, 1H), 8.17 (d, J = 8.4Hz, 1 H),7.90(d,J=8.8Hz,1H),7.78-7.67(m,3H),7.61(m,1H),7.28-7.21(m,2H).

[0061] 19 FNMR (376MHz,CDCl3)δ-114.08.

[0062] 13 C NMR (101MHz, CDCl3) δ164.15,149.63,147.25,134.00,133.97,133.08,129.46,129.20,129.11,129.03,127.92,127.11,116.27,116.05.

[0063] Preparation Example 6

[0064] In a glove box, quinoline (25.8 mg, 0.2 mmol) and bis(1,5-cyclooctadiene)nickel (5.5 mg, 10 mol%) were weighed into a 10 mL reaction tube equipped with a magnetic stir bar, and 2 mL of diethylene glycol dimethyl ether was added. The tube was sealed with a Teflon-lined screw cap and removed from the glove box. Under nitrogen, n-heptylmagnesium bromide (0.6 mL, 1.0 M in tetrahydrofuran) was added dropwise via syringe. The reaction was stirred at 30°C for 20 minutes. 4-Chloroiodobenzene (0.4 mmol) was then added to the tube under nitrogen, and the reaction was stirred at 30°C for 3 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride (2 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (3 × 3 mL). The combined layers were dried over anhydrous sodium sulfate, and then an excess of 1,2-dichloro-4,5-dicyanobenzoquinone (0.3 mmol, 68.1 mg) was added. The solvent was evaporated under vacuum, and the product was separated by column chromatography using a solvent mixture of petroleum ether and ethyl acetate to obtain the target product 3-(4-chlorophenyl)quinoline as a white solid with a yield of 75%.

[0065] 1 H NMR (400MHz, CDCl3) δ9.16(d,J=2.3Hz,1H),8.29(d,J=2.2Hz,1H),8.17(d,J=8.5 Hz,1H),7.90(d,J=7.8Hz,1H),7.76(m,1H),7.70-7.58(m,3H),7.55-7.49(m,2H).

[0066] 13 C NMR (101MHz, CDCl3) δ149.45,147.38,136.28,134.36,133.17,132.61,129.61,129.35,129.21,128.60,127.96,127.86,127.16.

[0067] Preparation Example 7

[0068] In a glove box, quinoline (25.8 mg, 0.2 mmol) and bis(1,5-cyclooctadiene)nickel (5.5 mg, 10 mol%) were weighed into a 10 mL reaction tube equipped with a magnetic stir bar, and 2 mL of diethylene glycol dimethyl ether was added. The tube was sealed with a Teflon-lined screw cap and removed from the glove box. n-Heptylmagnesium bromide (0.6 mL, 1.0 M in tetrahydrofuran) was added dropwise via syringe under nitrogen. The reaction was stirred at 30°C for 20 minutes. 4-Bromoiodobenzene (0.4 mmol) was then added to the tube under nitrogen, and the reaction was stirred at 30°C for 3 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride (2 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (3 × 3 mL). The combined layers were dried over anhydrous sodium sulfate, and then an excess of 1,2-dichloro-4,5-dicyanobenzoquinone (0.3 mmol, 68.1 mg) was added. The solvent was evaporated under vacuum, and the product was separated by column chromatography using a solvent mixture of petroleum ether and ethyl acetate to obtain the target product 3-(4-bromophenyl)quinoline as a white solid with a yield of 75%.

[0069] 1 H NMR (400MHz, CDCl3) δ9.16(d,J=2.3Hz,1H),8.29(d,J=2.2Hz,1H),8.17(d,J=8.5 Hz,1H),7.90(d,J=7.8Hz,1H),7.76(m,1H),7.70-7.58(m,3H),7.55-7.49(m,2H).

[0070] 13 C NMR (101MHz, CDCl3) δ149.45,147.38,136.28,134.36,133.17,132.61,129.61,129.35,129.21,128.60,127.96,127.86,127.16.

[0071] Preparation Example 8

[0072] In a glove box, quinoline (25.8 mg, 0.2 mmol) and bis(1,5-cyclooctadiene)nickel (5.5 mg, 10 mol%) were weighed into a 10 mL reaction tube equipped with a magnetic stir bar, and 2 mL of diethylene glycol dimethyl ether was added. The tube was sealed with a Teflon-lined screw cap and removed from the glove box. Under nitrogen, n-heptylmagnesium bromide (0.6 mL, 1.0 M in tetrahydrofuran) was added dropwise via syringe. The reaction was stirred at 30°C for 20 minutes. 4-Iodoiodobenzene (0.4 mmol) was then added to the tube under nitrogen, and the reaction was stirred at 30°C for 3 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride (2 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (3 × 3 mL). The combined layers were dried over anhydrous sodium sulfate, and then an excess of 1,2-dichloro-4,5-dicyanobenzoquinone (0.3 mmol, 68.1 mg) was added. The solvent was evaporated under vacuum, and the product was separated by column chromatography using a solvent mixture of petroleum ether and ethyl acetate to obtain the target product 3-(4-iodophenyl)quinoline as a white solid with a yield of 72%.

[0073] 1 H NMR (400MHz, CDCl3) δ9.15(d,J=2.3Hz,1H),8.29(d,J=2.1Hz,1H),8.16(d,J =8.5Hz,1H),7.93-7.85(m,3H),7.76(m,1H),7.61(m,1H),7.49-7.43(m,2H).

[0074] 13 C NMR (101MHz, CDCl3) δ149.33,147.44,138.26,137.33,133.11,132.69,129.64,129.23,129.11,127.97,127.85,127.17,94.09.

[0075] Preparation Example 9

[0076] In a glove box, quinoline (25.8 mg, 0.2 mmol) and bis(1,5-cyclooctadiene)nickel (5.5 mg, 10 mol%) were weighed into a 10 mL reaction tube equipped with a magnetic stir bar, and 2 mL of diethylene glycol dimethyl ether was added. The tube was sealed with a Teflon-lined screw cap and removed from the glove box. Under nitrogen, n-heptylmagnesium bromide (0.6 mL, 1.0 M in tetrahydrofuran) was added dropwise via syringe. The reaction was stirred at 30°C for 20 minutes. 1-Iodonaphthalene (0.4 mmol) was then added to the tube under nitrogen, and the reaction was stirred at 30°C for 3 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride (2 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (3 × 3 mL). The combined layers were dried over anhydrous sodium sulfate, and then an excess of 1,2-dichloro-4,5-dicyanobenzoquinone (0.3 mmol, 68.1 mg) was added. The solvent was evaporated under vacuum, and the product was separated by column chromatography using a solvent mixture of petroleum ether and ethyl acetate to obtain the target product 3-(naphthalen-1-yl)quinoline as a white solid with a yield of 69%.

[0077] 1 H NMR (400MHz, CDCl3) δ9.11 (d, J = 2.2Hz, 1H), 8.28-8.22 (m, 2H), 7.96 (m, 2H), 7.9 0-7.86(m,2H),7.79(m,1H),7.64-7.57(m,2H),7.57-7.51(m,2H),7.47(m,1H).

[0078] 13 C NMR (101MHz, CDCl3) δ151.83,147.19,136.20,136.13,133.71,133.57,131.53,129.44,1 29.21,128.47,128.39,127.80,127.70,127.67,126.90,126.50,126.01,125.32,125.22. Preparation Example 10

[0079] In a glove box, 6-methylquinoline (28.6 mg, 0.2 mmol) and bis(1,5-cyclooctadiene)nickel (5.5 mg, 10 mol%) were weighed into a 10 mL reaction tube equipped with a magnetic stir bar. 2 mL of diethylene glycol dimethyl ether was added. The tube was sealed with a Teflon-lined screw cap and removed from the glove box. n-Heptylmagnesium bromide (0.6 mL, 1.0 M in tetrahydrofuran) was added dropwise via syringe under nitrogen. The reaction was stirred at 30°C for 20 minutes. Iodobenzene (0.4 mmol) was then added to the tube under nitrogen, and the reaction was stirred at 30°C for 3 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride (2 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (3 × 3 mL). The combined layers were dried over anhydrous sodium sulfate, and then an excess of 1,2-dichloro-4,5-dicyanobenzoquinone (0.3 mmol, 68.1 mg) was added. The solvent was evaporated under vacuum, and the product was separated by column chromatography using a solvent mixture of petroleum ether and ethyl acetate to obtain the target product 6-methyl-3-phenylquinoline as a white solid with a yield of 79%.

[0080] 1 H NMR (400MHz, CDCl3) δ9.14(d,J=2.1Hz,1H),8.23(d,J=2.1Hz,1H),8.06(d,J=8.6Hz,1 H),7.77-7.70(m,2H),7.65(s,1H),7.60-7.51(m,3H),7.49-7.43(m,1H),2.58(s,3H).

[0081] 13 C NMR (101MHz, CDCl3) δ148.96,145.89,138.00,136.86,133.76,132.59,131.68,129.10,128.79,128.02,127.97,127.36,126.76,21.61.

[0082] Preparation Example 11

[0083] In a glove box, 7,8-benzoquinoline (36.0 mg, 0.2 mmol) and bis(1,5-cyclooctadiene)nickel (5.5 mg, 10 mol%) were weighed into a 10 mL reaction tube equipped with a magnetic stir bar. 2 mL of diethylene glycol dimethyl ether was added. The tube was sealed with a Teflon-lined screw cap and removed from the glove box. n-Heptylmagnesium bromide (0.6 mL, 1.0 M in tetrahydrofuran) was added dropwise via syringe under nitrogen. The reaction was stirred at 30°C for 20 minutes. Iodobenzene (0.4 mmol) was then added to the tube under nitrogen, and the reaction was stirred at 30°C for 3 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride (2 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (3 × 3 mL). The combined layers were dried over anhydrous sodium sulfate, and then an excess of 1,2-dichloro-4,5-dicyanobenzoquinone (0.3 mmol, 68.1 mg) was added. The solvent was evaporated under vacuum, and the target product, 3-phenylbenzo[h]quinoline, was obtained by column chromatography using a solvent mixture of petroleum ether and ethyl acetate as a white solid with a yield of 64%.

[0084] 1 H NMR (400MHz, CDCl3) δ9.33-9.23(m,2H),8.32(d,J=2.3Hz,1H),7.94-7.87(m, 1H),7.84(d,J=8.8Hz,1H),7.78-7.70(m,5H),7.54(m,2H),7.47-7.41(m,1H).

[0085] 13 C NMR (101MHz, CDCl3) δ147.88,145.51,137.92,134.54,133.57,133.33,131.31,1 29.17,128.19,128.15,128.05,127.86,127.38,127.19,126.19,125.46,124.29.

[0086] The above-described embodiments merely illustrate several implementations of the present invention. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the appended claims.

Claims

1. A method for synthesizing 3-arylquinoline compounds using nickel catalysis, characterized in that: The synthesis method of 3-arylquinoline compound IV is as follows: Using quinoline I, n-heptyl Grignard reagent II and iodobenzene III as raw materials, a two-step electrophilic addition and reductive elimination reaction is carried out under a nitrogen environment using nickel as a catalyst to obtain a 3-arylquinoline compound IV; R is an aliphatic hydrocarbon group or a halogen atom; R' is an aliphatic hydrocarbon group or a halogen atom.

2. The method for synthesizing 3-arylquinoline compounds using nickel catalysis according to claim 1, wherein: The molar amount of the n-heptyl Grignard reagent is 1.5 times the molar amount of quinoline; The molar amount of the iodobenzene is 1 to 2 times the molar amount of quinoline.

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