An asymmetric bis-aryl ketone compound and a method for synthesizing the same

Abstract

The application discloses an asymmetric bis-aryl ketone compound and a synthesis method thereof. The method uses aryl anhydride and aryl bromide as main raw materials, N,N dimethylacetamide as a solvent, 5mol% of bis(triphenylphosphine)palladium dichloride and 5mol% of ethylene glycol dimethyl ether nickel bromide as catalysts, 10mol% of 2-(dicyclohexylphosphine) 3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl and 5mol% of alpha,alpha,alpha-tripyridine as ligands, one equivalent of sodium sulfate as an additive, two equivalents of zinc powder as a reducing agent, is placed into a reaction container under a nitrogen atmosphere, heated to 40 DEG C, and reacted for 12 hours to obtain the asymmetric bis-aryl ketone compound I with high yield. The method has the advantages of simple operation, mild reaction condition, high yield, few additives, high selectivity and the like, and has certain feasibility for realizing industrial production.

Description

[Technical Field]

[0001] This invention belongs to the field of transition metal palladium-catalyzed organic synthesis, and specifically relates to an asymmetric diaryl ketone compound and its synthesis method. [Background Technology]

[0002] Biaryl ketones are widely found in natural products, pesticides, pharmaceuticals, and functional materials, and are an important class of chemical reaction intermediates. For example, phenylbenzophenone (Phenstatin), extracted from African tamarisk, is an antitumor drug that binds to intracellular tubulin and has 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 lower triglyceride, cholesterol, and low-density lipoprotein levels, 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 reactions of aryl metal compounds or aryl halides mediated by carbonyl metal compounds or CO. Carbonyl metal compounds are usually chemically toxic and have poor stability, easily igniting upon contact with oxygen or oxidants. Using 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 OrganometChem., 1983, 250, 551–564). 2. Synthesis of diaryl ketones through activation of aromatic CH bonds. This strategy requires specific directing groups (such as pyridine, acetanilide, etc.) to activate CH to achieve acylation of aromatic molecules. Due to the need for specific reaction substrates, it suffers from weak functional group tolerance, a narrow substrate range, and poor atom economy (Guin S K., et al. Org. Lett., 2012, 14, 5294–5297; Wu Y., et al. Chem. Commun., 2013, 49, 689–691). 3. Acylation reactions of highly reactive carboxylic acid derivatives with aromatics. Highly reactive carboxylic acid derivatives (such as amides, acyl chlorides, peroxides, etc.) generally require special preparation and exhibit strong toxicity, reducing 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 aryl ketones via reductive cross-coupling between electrophiles. In recent years, transition metal-catalyzed reductive coupling reactions have attracted considerable 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, some self-coupling byproducts are generated along with the cross-coupling products, which reduces atom economy to some extent. Currently, a method for preparing asymmetric diaryl ketones with broad substrate applicability, high atom economy, high selectivity, and industrial application value under mild reaction conditions is still lacking.

[0004] Aryl anhydrides possess the unique property of acting as both electrophiles and nucleophiles, and can be obtained from abundant aryl carboxylic acids. Furthermore, aryl halides offer advantages such as low cost, low toxicity, high stability, and good storage resistance. Therefore, this patent discloses a method for synthesizing asymmetric aryl ketones using palladium / nickel bimetallic catalysis with aryl anhydrides and aryl halides as reaction substrates. This method offers advantages such as mild reaction conditions, high atom economy, a wide range of applicable substrates, and high product yield, demonstrating potential industrial application value. Currently, there are no published documents or patents domestically or internationally regarding the synthesis of asymmetric diaryl ketones from aryl anhydrides and aryl bromides using palladium / nickel catalysis. [Summary of the Invention]

[0005] The purpose of this invention is to provide a method for the efficient synthesis of asymmetric diaryl ketone compounds using palladium and nickel as catalysts and aryl anhydrides and aryl bromides as raw materials. This method has advantages such as simple operation, mild reaction conditions, high yield, and few additives, making it feasible for industrial production.

[0006] To achieve the above-mentioned objectives, the present invention proposes the following technical solution:

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

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

[0009] An asymmetric dimethyl ketone compound and its synthetic method, wherein the general structural formula of asymmetric dimethyl ketone compound I is as follows:

[0010]

[0011] The Ar 1 The derivatives are phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-cyclohexanephenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 2-methoxyphenyl, 4-phenoxyphenyl, 4-acetoxyphenyl, 4-phenylphenyl, 3-phenylphenyl, 4-methyl-2-phenylphenyl, 2-naphthyl, 1-adamantyl, and 2-thiophene. 2 It is 4-phenylphenyl, 3-phenylphenyl, 4-methylphenyl, 4-methyl ester phenyl, 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 method for synthesizing compound I is characterized by using aryl anhydride II and aryl 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, and zinc powder as reducing agent. The reaction is carried out effectively at 40°C for 12 hours to obtain asymmetric diaryl ketone compound I in high yield.

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

[0014]

[0015] The Ar 1 The derivatives are phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-cyclohexanephenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 2-methoxyphenyl, 4-phenoxyphenyl, 4-acetoxyphenyl, 4-phenylphenyl, 3-phenylphenyl, 4-methyl-2-phenylphenyl, 2-naphthyl, 1-adamantyl, and 2-thiophene. 2 It is 4-phenylphenyl, 3-phenylphenyl, 4-methylphenyl, 4-methyl ester phenyl, 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, 3,4-dioxyphenyl.

[0016] The method for synthesizing asymmetric diaryl ketone compounds provided by this invention is a green and efficient synthetic route. Its advantages include: high yield of target product, few additives, mild reaction conditions, simple reaction operation, and high selectivity. [Attached Image Description]

[0017] The attached figure shows a route diagram for preparing asymmetric bisaryl ketone compounds provided by the present invention.

Detailed Implementation Methods

[0018] The present invention provides a method for synthesizing asymmetric diaryl ketone compounds, as shown in the attached figures: aryl anhydrides and aryl bromides are used as raw materials, N,N-dimethylacetamide is used as a solvent, 5 mol% bis(triphenylphosphine)palladium dichloride and 5 mol% ethylene glycol dimethyl ether nickel bromide are used as catalysts, 10 mol% 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl and 5 mol% 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. Under a nitrogen atmosphere, the mixture is placed in a reaction vessel, heated to 40°C, and reacted for 12 hours. After the reaction is completed, the target product is obtained by column chromatography separation and purification.

[0019] The invention will be further illustrated below with specific preparation examples:

[0020] Preparation Example 1

[0021] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.4 mmol of 4-bromobiphenyl, 5 mol% (0.01 mmol) of bis(triphenylphosphine)palladium dichloride, 5 mol% (0.01 mmol) of ethylene glycol dimethyl ether nickel bromide, 10 mol% (0.02 mmol) of 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl, 5 mol% (0.01 mmol) of α,α,α-terpyridine, 1 equiv (0.2 mmol) of sodium sulfate, 2 equiv (0.4 mmol) of zinc powder, and 0.5 mL of N,N-dimethylacetamide were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 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, 5 mol% (0.01 mmol) of bis(triphenylphosphine)palladium dichloride, 5 mol% (0.01 mmol) of ethylene glycol dimethyl ether nickel bromide, 10 mol% (0.02 mmol) of 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl, 5 mol% (0.01 mmol) of α,α,α-terpyridine, 1 equiv (0.2 mmol) of sodium sulfate, 2 equiv (0.4 mmol) of zinc powder, and 0.5 mL of N,N-dimethylacetamide were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 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] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.4 mmol of 4-methylbromobenzene, 5 mol% (0.01 mmol) of bis(triphenylphosphine)palladium dichloride, 5 mol% (0.01 mmol) of ethylene glycol dimethyl ether nickel bromide, 10 mol% (0.02 mmol) of 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl, 5 mol% (0.01 mmol) of α,α,α-terpyridine, 1 equiv (0.2 mmol) of sodium sulfate, 2 equiv (0.4 mmol) of zinc powder, and 0.5 mL of N,N-dimethylacetamide were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 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). 13C 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 methyl 4-carboxybromobenzene, 5 mol% (0.01 mmol) of bis(triphenylphosphine)palladium dichloride, 5 mol% (0.01 mmol) of ethylene glycol dimethyl ether nickel bromide, 10 mol% (0.02 mmol) of 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl, 5 mol% (0.01 mmol) of α,α,α-terpyridine, 1 equiv (0.2 mmol) of sodium sulfate, 2 equiv (0.4 mmol) of zinc powder, and 0.5 mL of N,N-dimethylacetamide were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 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] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.4 mmol of 3-methoxybromobenzene, 5 mol% (0.01 mmol) of bis(triphenylphosphine)palladium dichloride, 5 mol% (0.01 mmol) of ethylene glycol dimethyl ether nickel bromide, 10 mol% (0.02 mmol) of 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl, 5 mol% (0.01 mmol) of α,α,α-terpyridine, 1 equiv (0.2 mmol) of sodium sulfate, 2 equiv (0.4 mmol) of zinc powder, and 0.5 mL of N,N-dimethylacetamide were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 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, 5 mol% (0.01 mmol) of bis(triphenylphosphine)palladium dichloride, 5 mol% (0.01 mmol) of ethylene glycol dimethyl ether nickel bromide, 10 mol% (0.02 mmol) of 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl, 5 mol% (0.01 mmol) of α,α,α-terpyridine, 1 equiv (0.2 mmol) of sodium sulfate, 2 equiv (0.4 mmol) of zinc powder, and 0.5 mL of N,N-dimethylacetamide were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 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). 13 CNMR (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-acetylbromobenzene, 5 mol% (0.01 mmol) of bis(triphenylphosphine)palladium dichloride, 5 mol% (0.01 mmol) of ethylene glycol dimethyl ether nickel bromide, 10 mol% (0.02 mmol) of 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl, 5 mol% (0.01 mmol) of α,α,α-terpyridine, 1 equiv (0.2 mmol) of sodium sulfate, 2 equiv (0.4 mmol) of zinc powder, and 0.5 mL of N,N-dimethylacetamide were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 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-cyanobromobenzene, 5 mol% (0.01 mmol) of bis(triphenylphosphine)palladium dichloride, 5 mol% (0.01 mmol) of ethylene glycol dimethyl ether nickel bromide, 10 mol% (0.02 mmol) of 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl, 5 mol% (0.01 mmol) of α,α,α-terpyridine, 1 equiv (0.2 mmol) of sodium sulfate, 2 equiv (0.4 mmol) of zinc powder, and 0.5 mL of N,N-dimethylacetamide were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 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). 13C 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, 5 mol% (0.01 mmol) of bis(triphenylphosphine)palladium dichloride, 5 mol% (0.01 mmol) of ethylene glycol dimethyl ether nickel bromide, 10 mol% (0.02 mmol) of 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl, 5 mol% (0.01 mmol) of α,α,α-terpyridine, 1 equiv (0.2 mmol) of sodium sulfate, 2 equiv (0.4 mmol) of zinc powder, and 0.5 mL of N,N-dimethylacetamide were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 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, 5 mol% (0.01 mmol) of bis(triphenylphosphine)palladium dichloride, 5 mol% (0.01 mmol) of ethylene glycol dimethyl ether nickel bromide, 10 mol% (0.02 mmol) of 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl, 5 mol% (0.01 mmol) of α,α,α-terpyridine, 1 equiv (0.2 mmol) of sodium sulfate, 2 equiv (0.4 mmol) of zinc powder, and 0.5 mL of N,N-dimethylacetamide were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 56%. 1H 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 CNMR(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-trifluoromethoxybromobenzene, 5 mol% (0.01 mmol) of bis(triphenylphosphine)palladium dichloride, 5 mol% (0.01 mmol) of ethylene glycol dimethyl ether nickel bromide, 10 mol% (0.02 mmol) of 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl, 5 mol% (0.01 mmol) of α,α,α-terpyridine, 1 equiv (0.2 mmol) of sodium sulfate, 2 equiv (0.4 mmol) of zinc powder, and 0.5 mL of N,N-dimethylacetamide were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 86%. 1 H 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-trifluoromethylbromobenzene, 5 mol% (0.01 mmol) of bis(triphenylphosphine)palladium dichloride, 5 mol% (0.01 mmol) of ethylene glycol dimethyl ether nickel bromide, 10 mol% (0.02 mmol) of 2-(dicyclohexylphosphine)3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl, 5 mol% (0.01 mmol) of α,α,α-terpyridine, 1 equiv (0.2 mmol) of sodium sulfate, 2 equiv (0.4 mmol) of zinc powder, and 0.5 mL of N,N-dimethylacetamide were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 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 (0.2 mmol), 2-naphthyl bromide (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), and N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor. The reactor was heated to 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 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), and N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor. The reactor was heated to 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 64%. 1 H 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), and N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 64%. 1H 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), and N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 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), and N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 54%. 1 H 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), and N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor. The reactor was heated to 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 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), and N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 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), and N,N-dimethylacetamide (0.5 mL) were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 82%. 1 H 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-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), and N,N-dimethylacetamide (0.5 mL) were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 72%. 1H 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-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), and N,N-dimethylacetamide (0.5 mL) were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 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), and N,N-dimethylacetamide (0.5 mL) were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 96%. 1 H 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), and N,N-dimethylacetamide (0.5 mL) were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 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). 13 C 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), and N,N-dimethylacetamide (0.5 mL) were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 72%. 1H 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] An o-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), and N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor. The reactor was heated to 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 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] To a 25 mL tubular reactor, p-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), and N,N-dimethylacetamide (0.5 mL) were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 90%. 1 H 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, 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), and N,N-dimethylacetamide (0.5 mL) were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 58%. 1H 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 CNMR(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), and N,N-dimethylacetamide (0.5 mL) were added. The reaction was carried out at 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 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-Phenylacetic 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), and N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor. The reactor was heated to 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 68%. 1 H 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 (0.2 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), and N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor. The reactor was heated to 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 95%. 1H 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 (0.2 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), and N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor. The reactor was heated to 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 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-Adamantane 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), and N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor. The reactor was heated to 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 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 (0.2 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), and N,N-dimethylacetamide (0.5 mL) were added to a 25 mL tubular reactor. The reactor was heated to 40 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 50%. 1H 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 embodiments described above are merely illustrative of several implementations of the present invention, and 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 those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. A method for synthesizing an asymmetric diaryl ketone, characterized in that, Using aryl anhydride II and aryl 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, and zinc powder as reducing agent, the asymmetric diaryl ketone compound I can be obtained in high yield by reacting effectively at 40℃ for 12 h. In the above synthetic method, the structural formulas of the starting materials arylic anhydride II, aryl bromide III, and asymmetric diaryl ketone compound I are as follows: The Ar 1 The following are listed: phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-cyclohexanephenyl, 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; Ar 2 It is 4-phenylphenyl, 3-phenylphenyl, 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.

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

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