Asymmetric diaryl ketone compound and synthesis method thereof

Abstract

According to the method, aryl anhydride and aryl bromide are used as main raw materials, N, N-dimethylacetamide is used as a solvent, 5mol% of bis (triphenylphosphine) palladium dichloride and 5mol% of ethylene glycol dimethyl ether nickel bromide are used as catalysts, 10mol% of 2-(dicyclohexylphosphine) 3, 3 '-dicyclohexylphosphine is used as a catalyst, and the asymmetric diaryl ketone compound is prepared through a one-step reaction. The method comprises the following steps: by taking 2, 6-dimethoxy-2 ', 4', 6 '-triisopropyl-1, 1'-biphenyl and 5mol% alpha, alpha, alpha-terpyridyl as ligands, one equivalent of sodium sulfate as an additive and two equivalent of zinc powder as a reducing agent, putting the materials into a reaction container in a nitrogen atmosphere, heating to 40 DEG C, and reacting for 12 hours to obtain the asymmetric diaryl ketone compound I with high yield. The method has the advantages of simplicity and convenience in operation, mild reaction conditions, high yield, few additives, high selectivity and the like, and has certain feasibility for realizing industrial production.

Description

[Technical field]

[0001] The invention belongs to the field of organic synthesis catalyzed by transition metal palladium, and specifically relates to an asymmetric diaryl ketone compound and a synthesis method thereof. [Background technology]

[0002] Bis-aryl ketone compounds are widely found in natural products, pesticides, medicines and functional materials, and are an important class of chemical reaction intermediates. For example, hydroxybenzophenone compounds (Phenstatin) extracted from African red willow are anti-tumor drugs that bind to intracellular tubulin and have a strong inhibitory effect on the growth of tumor cells (Pettit G R., et al. J. Med. Chem., 1998, 41, 1688-1695); Fenofibrate is a drug that can reduce the levels of triglycerides, cholesterol, and low-density lipoprotein, and is clinically used to treat hypercholesterolemia and severe hypertriglyceridemia (Gong Y., et al. EBioMedicine., 2016, 13, 201-211).

[0003] The most widely used methods for synthesizing diaryl ketones are as follows: 1. Carbonylation of aryl metal compounds or aryl halides mediated by metal carbonyl compounds or CO. Metal carbonyl compounds are usually chemically toxic and have poor stability. They are prone to spontaneous combustion when exposed to oxygen or oxidants. CO as a carbonyl source usually requires high temperature and high pressure conditions, and can only synthesize symmetrical diaryl ketones (Sally NF, et al. Synthesis., 1973, 3, 160–161; Rhee I., et al. Synthesis., 1977, 11, 776–777; Beletskaya IP., et al. J Organomet Chem., 1983, 250, 551–564). 2. Synthesis of diaryl ketones by activation of aromatic hydrocarbon CH bonds. This strategy requires special directing groups (such as pyridine, acetanilide, etc.) to activate CH to achieve acylation of aromatic molecules. Since specific reaction substrates are required, the functional group tolerance is weak, the substrate range is narrow, and the atom economy is poor (Guin S K., et al. Org. Lett., 2012, 14, 5294-5297; Wu Y., et al. Chem. Commun., 2013, 49, 689-691). 3. Acylation reaction of highly active carboxylic acid derivatives with aromatics. Highly active carboxylic acid derivatives (such as amides, acyl chlorides, peroxides, etc.) generally require special preparation and have strong toxicity, which reduces the step economy of the reaction (Haddach M., et al. Tetrahedron Lett., 1999, 40, 3109-3112; Wang D., et al. Org. Lett., 2003, 5, 4645-4648). 4. Synthesis of aromatic ketone compounds by reductive cross-coupling between electrophiles. In recent years, transition metal-catalyzed reductive coupling reactions have attracted much attention due to their mild reaction conditions, good step economy, and high functional group tolerance (Wu F., et al. Org. Lett., 2012, 14, 3044-3047; Jia X., Chem. Commun., 2015, 51, 10302-10305). However, due to the lack of selectivity between electrophiles, a portion of self-coupling by-products will be generated while generating cross-coupling products, which reduces atom economy to a certain extent. At present, there is still a lack of a method for preparing asymmetric biaryl ketone compounds with wide substrate applicability, high atom economy, high selectivity and industrial application value under mild reaction conditions.

[0004] Aryl anhydrides have the special property of being both electrophilic and nucleophilic, and can be obtained from abundant aromatic carboxylic acids. Aryl halides have the advantages of being cheap, low toxicity, high stability, and storage resistance. Therefore, this patent discloses a method for synthesizing asymmetric aromatic ketone compounds by palladium / nickel bimetallic catalysis with aromatic anhydrides and aromatic halides as reaction substrates. This method has the advantages of mild reaction conditions, high atom economy, wide application range of substrates, high product yield, and has certain potential industrial application value. At present, there are no public documents or patents at home and abroad on the synthesis of asymmetric diaryl ketone compounds by palladium / nickel catalysis of aromatic anhydrides and aromatic bromides. [Summary of the invention]

[0005] The object of the present invention is to provide a method for efficiently synthesizing asymmetric diaryl ketone compounds using palladium and nickel as catalysts and aromatic anhydrides and aromatic bromides as raw materials. The method has the advantages of simple operation, mild reaction conditions, high yield, less additives, etc., and has certain feasibility for realizing its industrial production.

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

[0007] The palladium catalyst is bis(triphenylphosphine)palladium dichloride, and the nickel catalyst is ethylene glycol dimethyl ether nickel bromide.

[0008] The solvent is N,N-dimethylacetamide.

[0009] An asymmetric bicyclic ketone compound and a synthesis method thereof, wherein the asymmetric bicyclic ketone compound I has the following general structural formula:

[0010]

[0011] wherein Ar 1 Ar is phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-cyclohexylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 2-methoxyphenyl, 4-phenoxyphenyl, 4-acetoxyphenyl, 4-phenylphenyl, 3-phenylphenyl, 4-methyl-2-phenylphenyl, 2-naphthyl, 1-adamantyl, 2-thienyl. 2 It is 4-phenylphenyl, 3-phenylphenyl, 4-methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-aminophenyl, 4-acetylphenyl, 4-cyanophenyl, 4-chlorophenyl, 4-fluorophenyl, 4-trifluoromethoxyphenyl, 4-trifluoromethylphenyl, 2-naphthyl, 4-(4-bromophenyl)pyridine, 7-quinoline, 5-benzofuran, 2-thienyl, 2-fluorenyl, and 3,4-dioxyphenyl.

[0012] The synthesis method of compound I is characterized by using aromatic anhydride II and aromatic bromide III as raw materials, N,N-dimethylacetamide as solvent, bis(triphenylphosphine)palladium dichloride and ethylene glycol dimethyl ether nickel bromide as catalysts, 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl and α,α,α-terpyridine as ligands, sodium sulfate as additive, zinc powder as reducing agent, and reacting at 40°C for 12 hours to obtain asymmetric diaryl ketone compound I in high yield.

[0013] In the above-mentioned synthesis method, the structural formulas of the raw materials aryl anhydride ⅠⅠ and aryl bromide Ⅲ are as follows:

[0014]

[0015] wherein Ar 1 Ar is phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-cyclohexylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 2-methoxyphenyl, 4-phenoxyphenyl, 4-acetoxyphenyl, 4-phenylphenyl, 3-phenylphenyl, 4-methyl-2-phenylphenyl, 2-naphthyl, 1-adamantyl, 2-thienyl. 2 It is 4-phenylphenyl, 3-phenylphenyl, 4-methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-aminophenyl, 4-acetylphenyl, 4-cyanophenyl, 4-chlorophenyl, 4-fluorophenyl, 4-trifluoromethoxyphenyl, 4-trifluoromethylphenyl, 2-naphthyl, 4-(4-bromophenyl)pyridine, 7-quinoline, 5-benzofuran, 2-thienyl, 2-fluorene, and 3,4-dioxyphenyl.

[0016] The synthesis method of the asymmetric diaryl ketone compound provided by the present invention is a green and efficient synthesis route, and has the advantages of high yield of target product, less additives, mild reaction conditions, simple reaction operation and high selectivity.

Brief Description of the Drawings

[0017] Attached Figure 1 Shown is a route map for preparing asymmetric diaryl ketone compounds provided by the present invention. [Specific implementation method]

[0018] The present invention provides a method for synthesizing an asymmetric diaryl ketone compound, as shown in the attached figure: aryl anhydride and aryl bromide are used as raw materials, N,N-dimethylacetamide is used as solvent, 5 mol% of bis(triphenylphosphine)palladium dichloride and 5 mol% of ethylene glycol dimethyl ether nickel bromide are used as catalysts, 10 mol% of 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl and 5 mol% of α,α,α-terpyridine are used as ligands, one equivalent of sodium sulfate is used as an additive, and two equivalents of zinc powder are used as a reducing agent. The mixture is placed in a reaction container under a nitrogen atmosphere, heated to 40°C, reacted for 12 hours, and after the reaction is completed, separated and purified by column chromatography to obtain the corresponding target product.

[0019] The present invention will be further described below in conjunction with specific preparation examples:

[0020] Preparation Example 1

[0021] Benzoic anhydride 0.2mmol, 4-bromobiphenyl 0.4mmol, bis(triphenylphosphine)palladium dichloride (5mol%, 0.01mmol), ethylene glycol dimethyl ether nickel bromide (5mol%, 0.01mmol), 2-(dicyclohexylphosphine) 3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10mol%, 0.02mmol), α,α,α-terpyridine (5mol%, 0.01mmol), sodium sulfate (1equiv, 0.2mmol), zinc powder (2equiv, 0.4mmol), N,N-dimethylacetamide (0.5mL) were added to a 25mL tubular reactor, and heated to 40°C for 12h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 93%. 1 H NMR (400MHz, CDCl3) δ7.97(d,J=8.0Hz,2H),7.91(d,J=8.0Hz,2H),7.78(d,J =8.0Hz,2H),7.75–7.65(m,3H),7.57(q,J=8.0Hz,4H),7.48(t,J=8.0Hz,1H). 13 C NMR (100MHz, CDCl3) δ196.4,145.3,140.0,137.8,136.3,132.4,130.8,130.0,129.0,128.3,128.2,127.3,127.0.

[0022] Preparation Example 2

[0023] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.4 mmol of 3-bromobiphenyl, bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added, and the mixture was heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 73%. 1 H NMR (400MHz, CDCl3) δ8.09 (s, 1H), 7.96–7.78 (m, 4H), 7.69–7.58 (m, 4H), 7.57–7.48 (m, 4H), 7.42 (t, J = 8.0Hz, 1H). 13 C NMR (100MHz, CDCl3) δ196.7,141.5,140.2,138.2,137.6,132.6,131.1,130.2,129.0,128.8,128.7,128.4,127.9,127.3.

[0024] Preparation Example 3

[0025] Benzoic anhydride 0.2mmol, 4-methylbromobenzene 0.4mmol, bis(triphenylphosphine)palladium dichloride (5mol%, 0.01mmol), ethylene glycol dimethyl ether nickel bromide (5mol%, 0.01mmol), 2-(dicyclohexylphosphine) 3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10mol%, 0.02mmol), α,α,α-terpyridine (5mol%, 0.01mmol), sodium sulfate (1equiv, 0.2mmol), zinc powder (2equiv, 0.4mmol), N,N-dimethylacetamide (0.5mL) were added to a 25mL tubular reactor, and heated to 40°C for 12h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 50%. 1 H NMR (400MHz, CDCl3) δ7.83(t,J=8.0Hz,2H),7.76(d,J=8.0Hz,2H),7.61(t,J=8.0Hz,1H),7.51(dd,J=8.0,4.0Hz,2H),7.31(d,J=8.0Hz,2H),2.47(s,3H).13 C NMR (100MHz, CDCl3) δ196.5,143.3,138.0,134.9,132.2,130.3,130.0,129.0,128.2,21.7.

[0026] Preparation Example 4

[0027] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.4 mmol of 4-methylformyl bromobenzene, bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added, and the mixture was heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 79%. 1 H NMR (400MHz, CDCl3) δ8.18(d,J=8.4Hz,2H),7.85(dd,J=14.8,7.8Hz,4H),7.64(dd,J=10.6,4.4Hz,1H),7.53(t,J=7.6Hz,2H),3.99(s,3H). 13 C NMR (100MHz, CDCl3) δ196.1,166.3,141.3,137.0,133.2,133.0,130.3,129.8,129.5,128.5,127.3,52.5.

[0028] Preparation Example 5

[0029] Benzoic anhydride 0.2mmol, 3-methoxybromobenzene 0.4mmol, bis(triphenylphosphine)palladium dichloride (5mol%, 0.01mmol), ethylene glycol dimethyl ether nickel bromide (5mol%, 0.01mmol), 2-(dicyclohexylphosphine) 3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10mol%, 0.02mmol), α,α,α-terpyridine (5mol%, 0.01mmol), sodium sulfate (1equiv, 0.2mmol), zinc powder (2equiv, 0.4mmol), N,N-dimethylacetamide (0.5mL) were added to a 25mL tubular reactor, and heated to 40°C for 12h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 66%. 1 H NMR (400MHz, CDCl3) δ7.84(d,J=7.0Hz,2H),7.62(t,J=7.4Hz,1H),7.51(t,J=7.6Hz,2H),7.45–7.31(m,3H),7.16(d,J=8.0Hz,1H),3.89(s,3H). 13 C NMR (100MHz, CDCl3) δ196.5,159.6,132.4,130.1,129.2,128.3,122.9,118.9,114.4,55.5.

[0030] Preparation Example 6

[0031] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.4 mmol of 4-aminobromobenzene, bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added, and the mixture was heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 29%. 1 H NMR (400MHz, CDCl3) δ7.76(d,J=8.4Hz,4H),7.58(t,J=7.4Hz,1H),7.49(t,J=7.5Hz,2H),6.73(d,J=8.6Hz,2H),3.91(s,2H). 13C NMR (100MHz, CDCl3) δ195.5,150.7,138.9,133.0,131.5,129.6,128.1,127.6,113.9.

[0032] Preparation Example 7

[0033] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.4 mmol of 4-acetyl bromobenzene, bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added, and the mixture was heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 76%. 1 H NMR (400MHz, CDCl3) δ8.09(d,J=8.0Hz,2H),7.90(d,J=8.0Hz,2H),7.84(d,J=8.0Hz,2H),7.66(t,J=8.0Hz,1H),7.54(t,J=8.0Hz,2H),2.71(s,3H). 13 C NMR (100MHz, CDCl3) δ197.6,196.0,141.4,139.6,137.0,133.0,130.1,130.1,128.5,128.2,26.9.

[0034] Preparation Example 8

[0035] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.4 mmol of 4-cyanobenzene, bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added, and the mixture was heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 65%. 1 H NMR (400MHz, CDCl3) δ7.91(d,J=8.0Hz,2H),7.84–7.81(m,4H),7.68(t,J=8.0Hz,1H),7.55(t,J=8.0Hz,2H). 13 C NMR (100MHz, CDCl3) δ195.1,141.3,136.4,133.4,132.2,130.3,130.1,128.7,118.1,115.7.

[0036] Preparation Example 9

[0037] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.4 mmol of 4-chlorobromobenzene, bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added, and the mixture was heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 60%. 1 H NMR (400MHz, CDCl3) δ7.87–7.72(m,4H),7.64(t,J=7.4Hz,1H),7.55–7.48(m,4H). 13 C NMR (100MHz, CDCl3) δ195.6,138.9,137.3,135.9,132.7,131.5,130.0,128.7,128.5.

[0038] Preparation Example 10

[0039] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.4 mmol of 4-fluorobromobenzene, bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added, and the mixture was heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 56%. 1 H NMR (400MHz, CDCl3) δ7.88(dd,J=8.6,5.6Hz,2H),7.80(d,J=7.4Hz,2H),7.63(t,J=7.4Hz,1H),7.52(t,J=7.6Hz,2H),7.19(t,J=8.6Hz,2H). 13 C NMR (100MHz, CDCl3) δ195.3,166.7,164.2,137.5,133.0–132.4(m),130.0,128.4,115.6,115.4.

[0040] Preparation Example 11

[0041] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.4 mmol of 4-trifluoromethoxy bromobenzene, bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added, and the mixture was heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 86%. 1H NMR (400MHz, CDCl3) δ7.91(d,J=8.0Hz,2H),7.84(d,J=8.0Hz,2H),7.66(t,J=8.0Hz,1H),7.55(t,J=8.0Hz,2H),7.37(d,J=8.0Hz,2H). 13 C NMR (100MHz, CDCl3) δ195.2,152.2,137.2,135.9,132.8,132.0,130.0,128.5,120.3.119.9(d,J C-F =257Hz).

[0042] Preparation Example 12

[0043] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.4 mmol of 4-trifluoromethyl bromobenzene, bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added, and the mixture was heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 76%. 1 H NMR (400MHz, CDCl3) δ7.93(d,J=8.0Hz,1H),7.84(d,J=8.0Hz,H),7.79(d,J=8.0Hz,2H),7.67(t,J=8.0Hz,1H),7.55(t,J=8.0Hz,2H).

[0044] Preparation Example 13

[0045] Benzoic anhydride (0.2mmol), 2-naphthyl bromide (0.4mmol), bis(triphenylphosphine)palladium dichloride (5mol%, 0.01mmol), ethylene glycol dimethyl ether nickel bromide (5mol%, 0.01mmol), 2-(dicyclohexylphosphine) 3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10mol%, 0.02mmol), α,α,α-terpyridine (5mol%, 0.01mmol), sodium sulfate (1equiv, 0.2mmol), zinc powder (2equiv, 0.4mmol), N,N-dimethylacetamide (0.5mL) were added to a 25mL tubular reactor, and heated to 40°C for 12h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 77%. 1 H NMR (CDCl3, 400MHz) δ8.29 (s, 1H), 8.00–7.91 (m, 6H), 7.69–7.62m, 2H), 7.60–7.55 (m, 3H). 13 C NMR (CDCl3, 100MHz) δ196.8,138.0,135.3,134.9,132.7,132.4,132.3,131.9,129.5,128.6,128.4,128.4,127.9,126.9,125.8.

[0046] Preparation Example 14

[0047] Benzoic anhydride (0.2 mmol), 4-(4-bromophenyl)pyridine (0.4 mmol), bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor, and heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 64%. 1H NMR (400MHz, CDCl3) δ8.75(d,J=8.0Hz,1H),8.13(d,J=8.0Hz,2H),7.93(d,J=8.0Hz,2H),7 .88–7.78(m,4H),7.62(t,J=8.0Hz,1H),7.51(t,J=8.0Hz,2H),7.31(dd,J=8.0,4.0Hz,1H). 13 C NMR (100MHz, CDCl3) δ196.4, 156.2, 149.9, 143.0, 137.7 (d, J = 8.0Hz), 137.0, 132.5, 130.6, 130.1, 128.4, 126.8, 122.9, 121.1.

[0048] Preparation Example 15

[0049] Benzoic anhydride (0.2 mmol), 7-bromoquinoline (0.4 mmol), bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor, and heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 64%. 1 H NMR (400MHz, CDCl3) δ9.04 (dd, J=4.0, 2.0Hz, 1H), 8.52 (s, 1H), 8.29 (d, J=8.0Hz, 1H), 8.10 (dd, J=8. 0,2.0Hz,1H),8.00(d,J=8.0Hz,1H),7.93(d,J=8.0Hz,2H),7.67(t,J=8.0Hz,1H),7.59–7.53(m,3H). 13 C NMR (100MHz, CDCl3) δ196.3,151.4,147.2,138.2,137.3,136.1,132.8,130.4,130.2,128.5,128.4,126.5,122.9.

[0050] Preparation Example 16

[0051] Benzoic anhydride (0.2 mmol), 5-bromobenzofuran (0.4 mmol), bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor, and heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 71%. 1 H NMR (400MHz, CDCl3) δ8.19(d,J=2.8Hz,1H),7.91(dd,J=8.2,4.0Hz,1H),7.85–7.68(m,3H),7.59–7.30(m,5H). 13 C NMR (100MHz, CDCl3) δ196.8,143.8,139.1,138.1,134.0,132.3,130.1,128.3,127.9,126.3,125.5,124.6,122.5.

[0052] Preparation Example 17

[0053] Benzoic anhydride (0.2 mmol), 2-bromofuran (0.4 mmol), bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor, and heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 54%. 1H NMR (400MHz, CDCl3) δ7.88 (dd, J=8.0, 4.0Hz, 1H), 7.74 (dd, J=8.0, 4.0Hz, 1H), 7.67 (dd, J=8.0,4.0Hz,1H),7.65–7.57(m,1H),7.51(t,J=8.0Hz,1H),7.18(dd,J=8.0,4.0Hz,1H). 13 C NMR (100MHz, CDCl3) δ188.3,143.7,138.2,134.9,134.3,132.3,129.2,128.5,128.0.

[0054] Preparation Example 18

[0055] Benzoic anhydride (0.2 mmol), 2-bromofluorene (0.4 mmol), bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor, and heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 57%. 1 H NMR (400MHz, CDCl3) δ8.07(s,1H),7.89(q,J=8.0Hz,5H),7.65(t,J=8.0Hz,2H),7.55(t,J=8.0Hz,2H),7.49–7.39(m,2H),4.01(s,2H). 13 C NMR (100MHz, CDCl3) δ196.8,146.0,144.5,143.1,140.6,138.2,135.9,13 2.2,130.0,129.7,128.3,128.0,127.1,126.9,125.3,120.9,119.5,37.0.

[0056] Preparation Example 19

[0057] Benzoic anhydride (0.2 mmol), 3,4-dioxybromobenzene (0.4 mmol), bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor, and heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 40%. 1 H NMR (400MHz, CDCl3) δ7.78(d,J=7.0Hz,1H),7.60(t,J=7.4Hz,1H),7.50(t,J=7.5Hz,2H),7.41(d,J=7.7Hz,2H),6.90(d,J=8.0Hz,1H),6.10(s,2H). 13 CNMR (100MHz, CDCl3) δ195.2, 151.5, 148.0, 138.2, 132.0 (d, J = 7.9Hz), 129.7, 128.2, 126.9, 109.9, 107.7, 101.9.

[0058] Preparation Example 20

[0059] To a 25 mL tubular reactor, p-toluic anhydride (0.2 mmol), 4-bromobiphenyl (0.4 mmol), bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added, and the mixture was heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 82%. 1H NMR (400MHz, CDCl3) δ7.92(d,J=8.0Hz,2H),7.80(d,J=8.0Hz,2H),7.74(d,J=8.0Hz,2H),7.69(d ,J=8.0Hz,2H),7.52(t,J=8.0Hz,2H),7.44(t,J=8.0Hz,1H),7.34(d,J=8.0Hz,2H),2.49(s,3H). 13 C NMR (100MHz, CDCl3) δ196.2, 145.0, 143.2, 140.1, 136.6, 135.1, 130.6, 130.3, 129.0 (d, J = 5.4Hz), 128.2, 127.3, 126.9, 21.7.

[0060] Preparation Example 21

[0061] To a 25 mL tubular reactor, m-toluic anhydride (0.2 mmol), 4-bromobiphenyl (0.4 mmol), bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added, and the mixture was heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 72%. 1 H NMR (400MHz, CDCl3) δ7.92(d,J=8.2Hz,2H),7.73(d,J=8.2Hz,2H),7.69(d,J=7.2Hz ,3H),7.64(d,J=7.2Hz,1H),7.51(t,J=7.6Hz,2H),7.47–7.38(m,3H),2.47(s,3H). 13 C NMR (100MHz, CDCl3) δ196.6,145.2,140.0,138.2,137.8,136.4,133.2,130.7,130.4,129.0,128.2,128.1,127.3,127.0,21.4

[0062] Preparation Example 22

[0063] To a 25 mL tubular reactor, o-methylbenzoic anhydride (0.2 mmol), 4-bromobiphenyl (0.4 mmol), bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added, and the mixture was heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 86%. 1 H NMR (400MHz, CDCl3) δ7.81 (d, J=8.4Hz, 2H), 7.58 (dd, J=17.2, 8.0Hz, 4H), 7.40 (t, J=7.4Hz, 2H),7.33(t,J=7.0Hz,2H),7.28(d,J=6.8Hz,1H),7.22(dd,J=12.0,7.6Hz,2H),2.29(s,3H). 13 C NMR (100MHz, CDCl3) δ198.3,145.9,139.9,138.7,136.7,136.4,131.0,130.8,130.3,129.0,128.4,128.3,127.3,127.2,125.3,20.0.

[0064] Preparation Example 23

[0065] To a 25 mL tubular reactor, p-cyclohexylbenzoic anhydride (0.2 mmol), 4-bromobiphenyl (0.4 mmol), bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added, and the mixture was heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 96%. 1H NMR (400MHz, CDCl3) δ7.82(d,J=8.2Hz,2H),7.71(d,J=8.0Hz,2H),7.63(d,J=8.2Hz,2H),7.58(d,J=7.4Hz,2H),7.41(t,J=7.6Hz,2H),7.33(t,J=7.4H z,1H),7.26(d,J=8.0Hz,2H),2.53(t,J=9.8Hz,1H),1.83(t,J=13.8Hz,4H) ,1.71(d,J=12.6Hz,1H),1.37(dd,J=22.4,11.8Hz,4H),1.23–1.18(m,1H). 13 C NMR (100MHz, CDCl3) δ196.1, 153.1, 145.0, 140.1, 136.7, 135.4, 130.7, 130.4, 129.0, 128.1, 127.3, 126.9 (d, J = 8.8Hz), 44.8, 34.2, 26.8, 26.1.

[0066] Preparation Example 24

[0067] To a 25 mL tubular reactor, p-tert-butylbenzoic anhydride (0.2 mmol), 4-bromobiphenyl (0.4 mmol), bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added, and the mixture was heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 79%. 1 H NMR (400MHz, CDCl3) δ7.95 (d, J = 8.0 Hz, 2H), 7.85 (d, J = 8.0 Hz, 2H), 7.75 (d, J = 8. 0Hz,2H),7.71(d,J=8.0Hz,2H),7.55(m,4H),7.46(t,J=8.0Hz,1H),1.43(s,9H). 13C NMR (100MHz, CDCl3) δ196.1,156.2,145.0,140.1,136.6,135.0,130.7,130.1,129.0,128.2,127.4,127.0,125.3,35.2,31.2.

[0068] Preparation Example 25

[0069] To a 25 mL tubular reactor, p-methoxybenzoic anhydride (0.2 mmol), 4-bromobiphenyl (0.4 mmol), bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added, and the mixture was heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 72%. 1 H NMR (400MHz, CDCl3) δ7.91(d,J=12.0Hz,2H),7.80(d,J=8.0Hz,2H),7.74(d,J=8.0Hz,2H),7.69( d,J=8.0Hz,2H),7.52(t,J=8.0Hz,2H),7.44(t,J=8.0Hz,1H),7.34(d,J=8.0Hz,2H),2.49(s,3H). 13 C NMR (100MHz, CDCl3) δ196.2,145.1,143.2,140.1,136.7,135.1,130.6,130.3,129.1,129.0,128.2,127.3,127.1,127.0,21.7.

[0070] Preparation Example 26

[0071] To a 25 mL tubular reactor, o-anisylbenzoic anhydride (0.2 mmol), 4-bromobiphenyl (0.4 mmol), bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added, and the mixture was heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 98%. 1 H NMR (400MHz, CDCl3) δ7.82(d,J=8.2Hz,2H),7.57(t,J=8.0Hz,4H),7.39(t,J=7.4Hz ,3H),7.36–7.26(m,2H),6.98(t,J=7.6Hz,1H),6.94(d,J=8.4Hz,1H),3.67(s,3H). 13 C NMR (100MHz, CDCl3) δ196.1,157.3,145.6,140.1,136.5,131.9,130.5,129.6,129.0(s),128.9,128.2,127.3,126.9,120.6,111.5,55.7.

[0072] Preparation Example 27

[0073] Phenoxybenzoic anhydride (0.2 mmol), 4-bromobiphenyl (0.4 mmol), bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor, and heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 90%. 1H NMR (400MHz, CDCl3) δ7.70–7.63(m,2H),7.54–7.27(m,11H),7.22(dd,J=8.2,1.4Hz,2H),7.16–7.07(m,3H). 13 C NMR (100MHz, CDCl3) δ198.4,145.4,141.2,140.2,139.9,139.1,136.1,130.6,130 .3(d,J=22.1Hz),129.1,128.9,128.8,128.3,128.2,127.3(t,J=15.1Hz),126.8.

[0074] Preparation Example 28

[0075] To a 25 mL tubular reactor, add p-acetoxybenzoic anhydride (0.2 mmol), 4-bromobiphenyl (0.4 mmol), bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL), and heat to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 58%. 1 H NMR (400MHz, CDCl3) δ7.82(d,J=8.4Hz,3H),7.76(dd,J=11.2,8.4Hz,1H),7.64(d,J=8.0Hz,2H),7.5 8(d,J=7.4Hz,2H),7.42(t,J=7.6Hz,2H),7.34(t,J=7.4Hz,1H),7.17(d,J=8.6Hz,2H),2.28(s,3H). 13 C NMR (101MHz, CDCl3) δ195.3, 169.0, 153.9, 145.4, 140.0, 135.7 (d, J = 88.1Hz), 131.7, 130.7, 129.0, 128.3, 127.4, 127.1, 121.6, 115.3, 21.2.

[0076] Preparation Example 29

[0077] To a 25 mL tubular reactor, p-phenylbenzoic anhydride (0.2 mmol), 4-bromobiphenyl (0.4 mmol), bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added, and the mixture was heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 53%. 1 H NMR (400MHz, CDCl3) δ8.00(d,J=8.6Hz,4H),7.33(t,J=7.8Hz,4H),7.14(t,J=7.4Hz,2H),7.01(d,J=8.0Hz,4H),6.94(d,J=8.6Hz,4H). 13 C NMR (100MHz, CDCl3) δ171.5,162.7,155.4,132.5,130.1,124.7,123.4,120.3,117.2.

[0078] Preparation Example 30

[0079] 3-phenylbenzoic anhydride (0.2mmol), 4-bromobiphenyl (0.4mmol), bis(triphenylphosphine)palladium dichloride (5mol%, 0.01mmol), ethylene glycol dimethyl ether nickel bromide (5mol%, 0.01mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10mol%, 0.02mmol), α,α,α-terpyridine (5mol%, 0.01mmol), sodium sulfate (1equiv, 0.2mmol), zinc powder (2equiv, 0.4mmol), N,N-dimethylacetamide (0.5mL) were added to a 25mL tubular reactor, and heated to 40°C for 12h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 68%. 1H NMR (400MHz, CDCl3) δ7.99(s,1H),7.87(dd,J=8.4,1.4Hz,2H),7.75(t,J=9.0Hz,2H),7.65(dd,J=8.4,1.4Hz, 2H),7.58(t,J=8.4Hz,4H),7.51(t,J=7.8Hz,1H),7.45–7.37(m,4H),7.34–7.30(m,1H),7.19(d,J=1.4Hz,1H). 13 C NMR (100MHz, CDCl3) δ196.4,145.4,141.4,140.2,140.0,138.4,136.2,131.1, 130.8,129.1,129.0,129.0,128.8,128.6,128.2,127.8,127.3,127.3,127.1.

[0080] Preparation Example 31

[0081] 4'-methylbiphenyl-2-anhydride (0.2mmol), 4-bromobiphenyl (0.4mmol), bis(triphenylphosphine)palladium dichloride (5mol%, 0.01mmol), ethylene glycol dimethyl ether nickel bromide (5mol%, 0.01mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10mol%, 0.02mmol), α,α,α-terpyridine (5mol%, 0.01mmol), sodium sulfate (1equiv, 0.2mmol), zinc powder (2equiv, 0.4mmol), N,N-dimethylacetamide (0.5mL) were added to a 25mL tubular reactor, and heated to 40°C for 12h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 95%. 1 H NMR(400MHz, CDCl3)δ7.80(d,J=8.0Hz,2H),7.64–7.53(m,7H),7.49(t,J=8.0Hz,3H ),7.42(t,J=8.0Hz,1H),7.24(d,J=8.0Hz,2H),7.07(d,J=8.0Hz,2H),2.29(s,3H). 13 C NMR (100MHz, CDCl3) δ198.4,145.4,141.2,139.9,139.0,137.3,137.1,136.2 ,130.6,130.3,130.1,129.1,128.9,128.8,128.7,128.2,127.3,126.8,21.1.

[0082] Preparation Example 32

[0083] 2-naphthoic anhydride (0.2mmol), 4-bromobiphenyl (0.4mmol), bis(triphenylphosphine)palladium dichloride (5mol%, 0.01mmol), ethylene glycol dimethyl ether nickel bromide (5mol%, 0.01mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10mol%, 0.02mmol), α,α,α-terpyridine (5mol%, 0.01mmol), sodium sulfate (1equiv, 0.2mmol), zinc powder (2equiv, 0.4mmol), N,N-dimethylacetamide (0.5mL) were added to a 25mL tubular reactor, and heated to 40°C for 12h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 46%. 1 H NMR (400MHz, CDCl3) δ8.35 (s, 1H), 8.04–7.94 (m, 6H), 7.78 (d, J = 8.0Hz, 2H), 7.72 (d,J=8.0Hz,2H),7.69–7.58(m,2H),7.53(t,J=8.0Hz,2H),7.46(t,J=8.0Hz,1H). 13 C NMR (100MHz, CDCl3) δ196.4,145.2,140.0,136.6,135.3,135.0,132.3,131 .8,130.8,129.5,129.0,128.4,128.2,127.9,127.4,127.1,126.9,125.8.

[0084] Preparation Example 33

[0085] 1-adamantanic anhydride (0.2 mmol), 4-bromobiphenyl (0.4 mmol), bis(triphenylphosphine)palladium dichloride (5 mol%, 0.01 mmol), ethylene glycol dimethyl ether nickel bromide (5 mol%, 0.01 mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10 mol%, 0.02 mmol), α,α,α-terpyridine (5 mol%, 0.01 mmol), sodium sulfate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor, and the mixture was heated to 40° C. for 12 h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 50%.1 H NMR (400MHz, CDCl3) δ7.74(d,J=8.0Hz,2H),7.66(d,J=8.0Hz,4H),7.51(t,J=8 .0Hz,2H),7.43(t,J=8.0Hz,1H),2.12(t,J=8.0Hz,9H),1.83(t,J=8.0Hz,6H). 13 C NMR (100MHz, CDCl3) δ209.4,143.2,140.2,138.0,128.9,128.1,127.9,127.2,126.7,47.0,39.2,36.6,28.2.

[0086] Preparation Example 34

[0087] 2-Thiophene anhydride (0.2mmol), 4-bromobiphenyl (0.4mmol), bis(triphenylphosphine)palladium dichloride (5mol%, 0.01mmol), ethylene glycol dimethyl ether nickel bromide (5mol%, 0.01mmol), 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (10mol%, 0.02mmol), α,α,α-terpyridine (5mol%, 0.01mmol), sodium sulfate (1equiv, 0.2mmol), zinc powder (2equiv, 0.4mmol), N,N-dimethylacetamide (0.5mL) were added to a 25mL tubular reactor, and heated to 40°C for 12h under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 50%. 1 H NMR(400MHz, CDCl3)δ7.90(d,J=8.4Hz,2H),7.71–7.63(m,4H),7.61–7.56(m ,2H),7.42(t,J=7.4Hz,2H),7.37–7.32(m,1H),7.12(dd,J=5.0,3.8Hz,1H). 13 CNMR (100MHz, CDCl3) δ187.8,145.2,143.7,140.0,136.8,134.7,134.2,130.7,129.9,129.0,128.2,128.0,127.2,127.0

[0088] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention should be based on the attached claims.

Claims

1. An asymmetric diaryl ketone compound and a synthesis method thereof, wherein the palladium catalyst is bis(triphenylphosphine)palladium dichloride and the nickel catalyst is ethylene glycol dimethyl ether nickel bromide.

2. The solvent is N,N-dimethylacetamide.

3. The general structural formula of the asymmetric diaryl ketone compound I is as follows:

4. Wherein the Ar 1 Ar is phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-cyclohexylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 2-methoxyphenyl, 4-phenoxyphenyl, 4-acetoxyphenyl, 4-phenylphenyl, 3-phenylphenyl, 4-methyl-2-phenylphenyl, 2-naphthyl, 1-adamantyl, 2-thienyl. 2 It is 4-phenylphenyl, 3-phenylphenyl, 4-methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-aminophenyl, 4-acetylphenyl, 4-cyanophenyl, 4-chlorophenyl, 4-fluorophenyl, 4-trifluoromethoxyphenyl, 4-trifluoromethylphenyl, 2-naphthyl, 4-(4-bromophenyl)pyridine, 7-quinoline, 5-benzofuran, 2-thienyl, 2-fluorenyl, and 3,4-dioxyphenyl.

5. The synthesis method according to claim 1, characterized in that With aromatic anhydride II and aromatic bromide III as raw materials, N,N-dimethylacetamide as solvent, bis(triphenylphosphine)palladium dichloride and ethylene glycol dimethyl ether nickel bromide as catalysts, 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl and α,α,α-terpyridine as ligands, sodium sulfate as additive, zinc powder as reducing agent, the reaction is effectively carried out at 40°C for 12 hours to obtain asymmetric biaryl ketone compound I in high yield. In the above synthesis method, the structural formulas of the raw materials aryl anhydride II and aryl bromide III are as follows: wherein Ar 1 Ar is phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-cyclohexylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 2-methoxyphenyl, 4-phenoxyphenyl, 4-acetoxyphenyl, 4-phenylphenyl, 3-phenylphenyl, 4-methyl-2-phenylphenyl, 2-naphthyl, 1-adamantyl, 2-thienyl. 2 It is 4-phenylphenyl, 3-phenylphenyl, 4-methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-aminophenyl, 4-acetylphenyl, 4-cyanophenyl, 4-chlorophenyl, 4-fluorophenyl, 4-trifluoromethoxyphenyl, 4-trifluoromethylphenyl, 2-naphthyl, 4-(4-bromophenyl)pyridine, 7-quinoline, 5-benzofuran, 2-thienyl, 2-fluorenyl, and 3,4-dioxyphenyl.

6. The synthesis method according to claim 1, characterized in that With aromatic anhydride and aromatic bromide as raw materials, N,N-dimethylacetamide as solvent, 5 mol% bis(triphenylphosphine)palladium dichloride and 5 mol% ethylene glycol dimethyl ether nickel bromide as catalysts, 10 mol% 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl and 5 mol% α,α,α-terpyridine as ligands, one equivalent of sodium sulfate as additive, two equivalents of zinc powder as reducing agent, placed in a reaction vessel under a nitrogen atmosphere, heated to 40°C, and reacted for 12 hours.

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