A biaromatic compound and its synthesis method

Abstract

This invention discloses a class of biaromatic compounds and their synthetic method. The method uses arylic anhydrides and aryl bromides as main raw materials, N,N-dimethylacetamide as a solvent, 10 mol% palladium dibenzylacetone and 10 mol% nickel diethylene glycol dimethyl ether bromide as catalysts, 20 mol% 2-dicyclohexylphospho-2'-methylbiphenyl and 10 mol% 2,6'-dimethyl-2,2'-bipyridine, one equivalent of sodium tetrafluoroborate as an additive, and two equivalents of zinc powder as a reducing agent. Under a nitrogen atmosphere, the mixture is placed in a reaction vessel, heated to 100°C, and reacted for 12 hours to obtain biaromatic compound I in high yield. This method has the advantages of simple operation, mild reaction conditions, high yield, few additives, and high selectivity, making it feasible for industrial production.

Description

[Technical Field]

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

[0002] Biaryrheic compounds are widely found in many natural compounds, pharmaceutical intermediates, agricultural pesticides, and polymer materials. For example, OTBN can be used as a common intermediate in the preparation of sartan drugs (Miller J A., et al. Tetrahedron Lett., 1998, 40, 7275–7278); Losartan is an angiotensin II receptor blocker, clinically used to treat hypertension (Charpentier B., et al. J. Med. Chem., 1995, 38, 4993–5006); Adapalene is used to treat acne vulgaris (Charpentier B., et al. J. Med. Chem., 1995, 38, 4993–5006). Therefore, biaryrheic compounds have broad application prospects.

[0003] Currently, methods for synthesizing biaromatic compounds typically use aryl carboxylic acids, aryl halides, aryl carboxylic acid derivatives, aryl metal compounds, aryl borate esters, or aryl trifluoromethanesulfonic acid as reactants. When aryl carboxylic acids and their derivatives participate in the synthesis of biaromatics, high temperatures and oxidants are often required for oxidative decarboxylation reactions. Excessive oxidizing substrates and oxidants not only increase reaction costs but also reduce the tolerance of reducing substrates. Furthermore, they can lead to oxidative side reactions, limiting the application of carboxylic acid coupling reactions (Gooβen L J., et al. J. Am. Chem. Soc., 2007, 129, 4824–4833; Gooβen L J., et al. Angew. Chem., 2008, 120, 7211–7214; Becht J M., et al. Org. Lett., 2007, 9, 1781–1783). Aryl halides are generally synthesized into biaromatic compounds through electrophilic-nucleophilic coupling reactions with nucleophiles. However, most nucleophiles have disadvantages such as poor stability, sensitivity to air, and difficulty in storage (Ullmann. J. Org. Chem., 1977, 42, 1821-1823; Reeves J T., Org. Lett., 2010, 12, 4388–4391; Minami H., Angew. Chem. Int. Ed., 2015, 54, 4665–4668). Aryl metal compounds are generally synthesized from aryl halides, and arylboronic acids and aryl trifluoromethanesulfonates are also typically obtained by conversion of aryl metal compounds or aryl halides (Kamikawa T., et al. Tetrahedron Lett., 1997, 38, 7087-7090; Littke A F., et al. J. Am. Chem. Soc., 2000, 122, 4020-4028; Reeves E K., et al. J. Org. Chem., 2019, 84, 11799-11812). Currently, a method for preparing biaromatic compounds 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 biaromatic compounds via a palladium / nickel bimetallic catalytic decarbonylation cross-reduction coupling reaction using aryl anhydrides and aryl halides as substrates. This method offers advantages such as mild reaction conditions, high atom economy, a wide range of applicable substrates, and high product yield, demonstrating significant potential for industrial application. Currently, there are no published documents or patents domestically or internationally regarding the palladium / nickel co-catalyzed synthesis of biaromatic compounds from aryl anhydrides and aryl bromides. [Summary of the Invention]

[0005] The purpose of this invention is to provide a novel method for the efficient synthesis of biaromatic 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 palladium dibenzylacetone, and the nickel catalyst is nickel dimethyl ether bromide.

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

[0009] A biaromatic compound and its synthetic method, wherein the general structural formula of biaromatic compound I is as follows:

[0010] Ar 1 -Ar 2

[0011] I

[0012] The Ar 1 Ar is phenyl, 4-methylphenyl, 2-methylphenyl, 4-cyclohexanephenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 2-methoxyphenyl, 4-phenylphenyl, 3-phenylphenyl, 4-methyl-2-phenylphenyl, 2-naphthyl, 4-chlorophenyl, 4-trifluoromethylphenyl. 2The compounds are 4-phenylphenyl, 3-phenylphenyl, 4-methylphenyl, 4-methyl ester phenyl, 3,4-dimethylphenyl, 4-ethyl carboxylate phenyl, 4-acetylphenyl, 4-methoxyphenyl, 3-methoxyphenyl, 2-methoxyphenyl, 4-cyanophenyl, 4-fluorophenyl, 4-trifluoromethoxyphenyl, 4-trifluoromethylphenyl, 2-benzophenone, 7-quinoline, 2-fluorenyl, 2-naphthyl, 1-naphthyl, 4-(4-bromophenyl)pyridine, 5-benzofuran, 5-N-methylindolyl, 3-ethoxypyridine, and 3,4-dioxyphenyl.

[0013] The method for synthesizing compound I is characterized by using arylic anhydride II and aryl bromide III as raw materials, N,N-dimethylacetamide as solvent, palladium dibenzylacetone and nickel diethylene glycol dimethyl ether bromide as catalysts, 2-dicyclohexylphospho-2'-methylbiphenyl and 2,6'-dimethyl-2,2'-bipyridine as ligands, sodium tetrafluoroborate as additive, and zinc powder as reducing agent. The reaction is carried out effectively at 100°C for 12 hours to obtain compound I in high yield.

[0014] In the above synthetic method, the structural formulas of the starting materials aryl anhydride ⅠⅠ and aryl bromide Ⅲ are as follows:

[0015]

[0016] Ar 1 Ar is phenyl, 4-methylphenyl, 2-methylphenyl, 4-cyclohexanephenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 2-methoxyphenyl, 4-phenylphenyl, 3-phenylphenyl, 4-methyl-2-phenylphenyl, 2-naphthyl, 4-chlorophenyl, 4-trifluoromethylphenyl. 2 The compounds are 4-phenylphenyl, 3-phenylphenyl, 4-methylphenyl, 4-methyl ester phenyl, 3,4-dimethylphenyl, 4-ethyl carboxylate phenyl, 4-acetylphenyl, 4-methoxyphenyl, 3-methoxyphenyl, 2-methoxyphenyl, 4-cyanophenyl, 4-fluorophenyl, 4-trifluoromethoxyphenyl, 4-trifluoromethylphenyl, 2-benzophenone, 7-quinoline, 2-fluorenyl, 2-naphthyl, 1-naphthyl, 4-(4-bromophenyl)pyridine, 5-benzofuran, 5-N-methylindolyl, 3-ethoxypyridine, and 3,4-dioxyphenyl.

[0017] The method for synthesizing biaromatic 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]

[0018] Attached Figure Figure 1 The diagram shown is a route diagram for preparing biaromatic compounds provided by the present invention.

Detailed Implementation Methods

[0019] The present invention provides a method for synthesizing biaromatic 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, 10 mol% palladium dibenzylacetone and 10 mol% nickel diethylene glycol dimethyl ether bromide are used as catalysts, 20 mol% 2-dicyclohexylphospho-2'-methylbiphenyl and 10 mol% 2,6'-dimethyl-2,2'-bipyridine are used, one equivalent of sodium tetrafluoroborate is used as an additive, and two equivalents of zinc powder is used as a reducing agent. Under a nitrogen atmosphere, the mixture is placed in a reaction vessel, heated to 100°C, and reacted for 12 hours. After the reaction is completed, the target product is obtained by column chromatography separation and purification.

[0020] The invention will be further illustrated below with specific preparation examples:

[0021] Preparation Example 1

[0022] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 4-bromobiphenyl, and 10 mol% (0.02 mmol) of palladium dibenzylacetone, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reaction was carried out at 100 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 84%. 1 H NMR (400MHz, CDCl3): δ7.68–7.64(m,8H),7.46(t,J=8.0Hz, 4H), 7.36(t,J=8.0Hz 2H). 13 CNMR (100MHz, CDCl3) δ140.8,140.2,128.9,127.5,127.4,127.1.

[0023] Preparation Example 2

[0024] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 3-bromobiphenyl, 10 mol% (0.02 mmol) of palladium dibenzylacetone, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reactor was heated to 100 °C for 12 h under a nitrogen atmosphere. After the reaction, the product was purified by column chromatography with a yield of 90%. 1 H NMR (400MHz, CDCl3) δ7.87 (s, 1H), 7.71 (d, J = 8.0Hz, 4H), 7.63 (d, J = 8.0Hz, 2H), 7.59–7.48 (m, 5H), 7.42 (t, J = 8.0Hz, 2H). 13 C NMR (100MHz, CDCl3) δ141.8,141.2,129.2,128.8,127.4,127.3,126.2,126.2.

[0025] Preparation Example 3

[0026] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of methyl 4-acetate bromobenzene, 10 mol% (0.02 mmol) of dibenzylacetone palladium, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reaction was carried out at 100 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 74%. 1 H NMR (400MHz, CDCl3) δ8.15(d,J=8.0Hz,2H),7.70(d,J=8.0Hz,2H),7.66(d,J=8. 0Hz,2H),7.51(t,J=8.0Hz,2H),7.43(t,J=8.0Hz,1H),7.30(s,1H),3.98(s,3H). 13C NMR (100MHz, CDCl3) δ130.1,128.9,128.2,127.3,127.1,52.2,29.7.

[0027] Preparation Example 4

[0028] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of methyl 4-acetate bromobenzene, 10 mol% (0.02 mmol) of dibenzylacetone palladium, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reaction was carried out at 100 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 74%. 1 H NMR (400MHz, CDCl3) δ7.62(t,J=8.0Hz,4H),7.48(t,J=8.0Hz,2H),7.42–7.36(m,3H),3.76(s,3H),3.72(s,2H). 13 C NMR (100MHz, CDCl3) δ172.1,140.8,140.2,133.0,129.7,128.8,127.4,127.3,127.1,52.2,40.9.

[0029] Preparation Example 5

[0030] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 4-acetylbromobenzene, 10 mol% (0.02 mmol) of palladium dibenzylacetone, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reactor was heated to 100 °C for 12 h under a nitrogen atmosphere. After the reaction, the product was purified by column chromatography, with a yield of 61%. 1H NMR (400MHz, CDCl3) δ8.07(d,J=8.4Hz,2H),7.72(d,J=8.4Hz,2H),7.67(d,J=7.2Hz,2H),7.51(t,J=7.4Hz,2H),7.44(t,J=7.4Hz,1H),2.68(s,3H). 13 C NMR (100MHz, CDCl3) δ197.8,145.8,139.9,135.9,129.0,128.9,128.3,127.3,127.3,26.7.

[0031] Preparation Example 6

[0032] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 4-methoxybromobenzene, 10 mol% (0.02 mmol) of dibenzylacetone palladium, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reaction was carried out at 100 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 34%. 1 H NMR (400MHz, CDCl3) δ7.59 (t, J = 8.0 Hz, 4H), 7.46 (t, J = 8.0 Hz, 2H), 7.35 (t, J = 8.0 Hz, 1H), 7.03 (d, J = 8.0 Hz, 2H), 3.90 (s, 3H). 13 C NMR (100MHz, CDCl3) δ159.2,140.9,133.8,128.8,128.2,126.8,126.7,114.2,55.4.

[0033] Preparation Example 7

[0034] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 3-methoxybromobenzene, 10 mol% (0.02 mmol) of palladium dibenzyl acetone, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reaction was carried out at 100 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 43%. 1 H NMR(400MHz, CDCl3)δ7.64(d,J=8.0Hz,2H),7.48(td,J=8.0,4.0Hz,2H),7.43–7.38(m,2H) ,7.24(d,J=8.0Hz,1H),7.18(d,J=4.0Hz,1H),6.95(d,J=8.0Hz,1H),3.91(d,J=4.0Hz,3H). 13 C NMR (100MHz, CDCl3) δ160.0,142.8,141.1,129.8,128.8,127.5,127.3,119.7,112.9,112.7,55.3.

[0035] Preparation Example 8

[0036] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 2-methoxybromobenzene, 10 mol% (0.02 mmol) of palladium dibenzyl acetone, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reaction was carried out at 100 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 41%. 1 H NMR (400MHz, CDCl3) δ7.46 (d, J = 8.0 Hz, 2H), 7.34 (t, J = 8.0 Hz, 2H), 7.28–7.22 (m, 3H), 6.98–6.90 (m, 2H), 3.74 (s, 3H). 13C NMR (100MHz, CDCl3) δ156.5,138.6,130.9,130.8,129.6,128.6,128.0,126.9,120.9,111.3,55.6,29.7.

[0037] Preparation Example 9

[0038] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 4-cyanobromobenzene, 10 mol% (0.02 mmol) of palladium dibenzyl acetone, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reactor was heated to 100 °C for 12 h under a nitrogen atmosphere. After the reaction, the product was purified by column chromatography, with a yield of 60%. 1 H NMR (400MHz, CDCl3) δ7.74(q,J=8.0Hz,4H),7.63(d,J=8.0Hz,2H),7.52(t,J=8.0Hz,2H),7.46(t,J=8.0Hz,1H). 13 C NMR (100MHz, CDCl3) δ145.7,139.2,132.6,129.1,128.7,127.8,127.3,119.0,110.9.

[0039] Preparation Example 10

[0040] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 4-fluorobromobenzene, 10 mol% (0.02 mmol) of dibenzylacetone palladium, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reaction was carried out at 100 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 62%. 1H NMR (400MHz, CDCl3) δ7.64–7.55(m,4H),7.48(t,J=7.6Hz,2H),7.43–7.37(m,1H),7.17(t,J=8.8Hz,2H). 13 C NMR(100MHz,CDCl3)δ162.5(d,J CF =246.2Hz), 140.3, 137.4 (d, J) CF =3.1Hz), 128.9, 128.7 (d, J) CF =8.0Hz),127.3,127.1,115.6(d,J CF =21.4Hz)

[0041] Preparation Example 11

[0042] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 4-trifluoromethylbromobenzene, 10 mol% (0.02 mmol) of palladium dibenzylacetone, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reactor was heated to 100 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 61%. 1 H NMR (400MHz, CDCl3) δ7.73 (s, 4H), 7.64 (d, J = 7.4Hz, 2H), 7.51 (t, J = 7.4Hz, 2H), 7.44 (t, J = 7.4Hz, 1H).

[0043] Preparation Example 12

[0044] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 2-bromobenzophenone, 10 mol% (0.02 mmol) of palladium dibenzylacetone, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reactor was heated to 100 °C for 12 h under a nitrogen atmosphere. After the reaction, the product was purified by column chromatography, with a yield of 76%. 1 H NMR (400MHz, CDCl3) δ7.69 (d, J=8.0Hz, 2H), 7.63 (td, J=8.0Hz, 4.0Hz, 1H), 7. 58–7.49(m,3H),7.45(t,J=8.0Hz,1H),7.34–7.29(m,4H),7.28–7.12(m,3H). 13 CNMR (100MHz, CDCl3) δ198.9,141.2,140.2,139.0,137.4,132.9,130.4,130.1,130.0,129.1,128.8,128.2,128.1,127.4,127.1.

[0045] Preparation Example 13

[0046] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 7-bromoquinoline, 10 mol% (0.02 mmol) of palladium dibenzylacetone, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reaction was carried out at 100 °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%. 1H NMR (400MHz, CDCl3) δ8.98(d,J=4.0Hz,1H),8.39(s,1H),8.23(d,J=8.0Hz,1H),7.93(d,J=8.0Hz, 1H),7.87(dd,J=8.0,4.0Hz,1H),7.80(d,J=8.0Hz,2H),7.54(t,J=8.0Hz,2H),7.48–7.42(m,2H). 13 C NMR (100MHz, CDCl3) δ150.7,148.3,142.5,140.3,136.1,129.1,128.3,128.0,127.5,126.9,126.4.

[0047] Preparation Example 14

[0048] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 2-bromofluorene, 10 mol% (0.02 mmol) of palladium dibenzylacetone, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reactor was heated to 100 °C for 12 h under a nitrogen atmosphere. After the reaction, the product was purified by column chromatography, with a yield of 74%. 1 H NMR(400MHz, CDCl3)δ7.89(d,J=8.0Hz,1H),7.85(d,J=8.0Hz,1H),7.82,7.71–7.65( m,3H),7.60(d,J=8.0Hz,1H),7.50(t,J=8.0Hz,2H),7.45–7.34(m,3H),4.01(s,2H). 13 C NMR (100MHz, CDCl3) δ143.9,143.5,141.6,141.5,141.0,139.9,128.8,127.2,127.2,126.9,126.8,126.1,125.1,123.9,120.2,120.0,37.1.

[0049] Preparation Example 15

[0050] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 1-bromonaphthalene, 10 mol% (0.02 mmol) of palladium dibenzyl acetone, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reactor was heated to 100 °C for 12 h under a nitrogen atmosphere. After the reaction, the product was purified by column chromatography, with a yield of 52%. 1 H NMR (400MHz, CDCl3) δ8.05 (s, 1H), 7.89 (dt, J = 9.0, 5.2Hz, 3H), 7.75 (dd, J = 13.4, 4.8Hz, 3H), 7.53–7.46 (m, 4H), 7.38 (t, J = 7.4Hz, 1H). 13 C NMR (100MHz, CDCl3) δ141.2,138.6,133.7,132.6,128.9,128.4,128.2,127.7,127.5,127.4,126.3,126.0,125.8,125.6.

[0051] Preparation Example 16

[0052] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 2-bromonaphthalene, 10 mol% (0.02 mmol) of palladium dibenzylacetone, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reactor was heated to 100 °C for 12 h under a nitrogen atmosphere. After the reaction, the product was purified by column chromatography, with a yield of 82%. 1 H NMR (400MHz, CDCl3) δ8.09 (s, 1H), 7.98–7.90 (m, 3H), 7.79 (t, J = 8.0Hz 3H), 7.57–7.50 (m, 4H), 7.43 (t, J = 8.0Hz, 1H). 13C NMR (100MHz, CDCl3) δ141.2,138.6,133.7,132.7,128.9,128.5,128.2,127.7,127.5,127.4,126.3,126.0,125.8,125.6.

[0053] Preparation Example 17

[0054] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 4-(4-bromophenyl)pyridine, 10 mol% (0.02 mmol) of dibenzylacetone palladium, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reaction was carried out at 100 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 51%. 1 H NMR(400MHz, CDCl3)δ8.65(dt,J=8.0,4.0Hz,1H),8.02(dt,J=12.0,4.0Hz,2H),7.74–7.69(m,2H),7.65(dt, J=8.0,4.0Hz,2H),7.59(dt,J=8.0,4.0Hz,2H),7.39(t,J=8.0Hz,2H),7.32–7.28(m,1H),7.20–7.16(m,1H). 13 C NMR (100MHz, CDCl3) δ156.8,149.3,142.0,140.5,137.6,137.4,128.9,127.6,127.6,127.5,127.2,122.3,120.8.

[0055] Preparation Example 18

[0056] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 5-bromobenzofuran, 10 mol% (0.02 mmol) of dibenzylacetone palladium, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reactor was heated to 100 °C for 12 h under a nitrogen atmosphere. After the reaction, the product was purified by column chromatography, with a yield of 47%. 1 H NMR (400MHz, CDCl3) δ8.08(d,J=4.0Hz,1H),7.99(d,J=8.0Hz,1H),7.71(d,J=8.0Hz, 2H),7.64(dd,J=8.0,4.0Hz,1H),7.52(t,J=8.0Hz,3H),7.42(dd,J=12.0,4.0Hz,2H). 13 C NMR (101MHz, CDCl3) δ141.4,140.2,138.8,137.8,128.9,127.5,127.2,127.1,124.1,123.9,122.7,122.0.

[0057] Preparation Example 19

[0058] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 5-bromo-1-methylindole, 10 mol% (0.02 mmol) of dibenzylacetone palladium, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reaction was carried out at 100 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 21%. 1H NMR(400MHz, CDCl3)δ7.77(d,J=1.2Hz,1H),7.62–7.56(m,2H),7.43–7.29(m,4H),7. 23(t,J=7.4Hz,1H),7.01(d,J=3.2Hz,1H),6.47(dd,J=3.2,1.0Hz,1H),3.75(s,3H). 13 C NMR (100MHz, CDCl3) δ142.6,136.3,132.9,129.5,128.9,128.6,127.4,126.3,121.4,119.4,109.4,101.3,33.0,29.7.

[0059] Preparation Example 20

[0060] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 2-bromo-4-ethoxypyridine, and 10 mol% (0.02 mmol) of dibenzylacetone palladium, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 mol% (0.02 mmol) of sodium tetrafluoroborate, 2 equiv (0.2 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reaction was carried out at 100 °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) δ8.42(d,J=4.0Hz,1H),7.82(dd,J=12.0,4.0Hz,1H),7.56(d,J=8.0Hz,2H),7.48(t, J=8.0Hz,2H),7.38(t,J=8.0Hz,1H),6.84(d,J=8.0Hz,1H),4.45(q,J=8.0Hz,2H),1.47(t,J=8.0Hz,3H). 13 C NMR (100MHz, CDCl3) δ163.4,145.0,138.0,137.5,130.0,129.0,127.3,126.7,111.0,61.9,14.7.

[0061] Preparation Example 21

[0062] To a 25 mL tubular reactor, 0.2 mmol of benzoic anhydride, 0.8 mmol of 3,4-dioxybromobenzene, 10 mol% (0.02 mmol) of palladium dibenzylacetone, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added. The reaction was carried out at 100 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 44%. 1 H NMR (400MHz, CDCl3) δ7.55(d,J=7.4Hz,2H),7.44(t,J=7.6Hz,2H),7.35(t,J=7.4Hz,1H),7.13–7.07(m,2H),6.92(d,J=7.8Hz,1H),6.04(s,2H). 13 C NMR (100MHz, CDCl3) δ148.1,147.1,140.9,135.6,128.8,126.9,126.9,120.7,108.6,107.7,101.2.

[0063] Preparation Example 22

[0064] 0.2 mmol of p-toluic anhydride, 0.8 mmol of 4-bromobiphenyl, 10 mol% (0.02 mmol) of palladium dibenzylacetone, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 2-dicyclohexylphospho-2'-methylbiphenyl (20 mol% (0.04 mmol)), 2,6'-dimethyl-2,2'-bipyridine (10 mol% (0.02 mmol)), sodium tetrafluoroborate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), and 1 mL of N,N-dimethylacetamide were added to a 25 mL tubular reactor. The reactor was heated to 100 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 59%. 1 H NMR (400MHz, CDCl3) δ7.73–7.66(m,6H),7.59(d,J=8.0Hz,2H),7.50(t,J=8.0Hz,2H),7.40(t,J=8.0Hz,1H),7.31(d,J=8.0Hz,2H),2.45(s,3H). 13C NMR (100MHz, CDCl3) δ140.8,140.1,139.9,137.9,137.2,129.6,128.8,127.5,127.3,127.1,126.9,21.2.

[0065] Preparation Example 23

[0066] 0.2 mmol of p-tert-butylbenzoic anhydride, 0.8 mmol of 4-bromobiphenyl, and 10 mol% (0.02 mmol) of dibenzylacetone palladium, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 2-dicyclohexylphospho-2'-methylbiphenyl, 20 mol% (0.04 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 10 mol% (0.02 mmol) of sodium tetrafluoroborate, 1 equiv (0.2 mmol) of zinc powder, 2 equiv (0.4 mmol) of zinc, and 1 mL of N,N-dimethylacetamide were added to a 25 mL tubular reactor. The reactor was heated to 100 °C and reacted for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 59%. 1 H NMR (400MHz, CDCl3) δ7.76–7.67(m,6H),7.64(d,J=8.0Hz,2H),7.52(dd,J=16.0,8.0Hz,4H),7.41(t,J=8.0Hz,1H),1.43(s,9H). 13 C NMR (100MHz, CDCl3) δ150.4,140.8,140.0,139.7,137.8,128.8,127.5; 127.4,127.1,127.1,126.7,125.8,34.6,31.4.

[0067] Preparation Example 24

[0068] 0.2 mmol of 4-chlorobenzoic anhydride, 0.8 mmol of 4-bromobiphenyl, and 10 mol% (0.02 mmol) of dibenzylacetone palladium, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 2-dicyclohexylphospho-2'-methylbiphenyl (20 mol% (0.04 mmol)), 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added to a 25 mL tubular reactor. The reactor was heated to 100 °C and reacted for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 66%. 1H NMR (400MHz, CDCl3) δ7.70 (dd, J=16.0, 8.0Hz, 6H), 7.61 (d, J=8.0Hz, 2H), 7.53–7.45 (m, 4H), 7.41 (t, J=8.0Hz, 1H). 13 C NMR (100MHz, CDCl3) δ140.5,140.5,139.2,138.9,133.5,129.0,128.9,128.3,127.6,127.5,127.4,127.1.

[0069] Preparation Example 25

[0070] 0.2 mmol of 4-trifluoromethylbenzoic anhydride, 0.8 mmol of 4-bromobiphenyl, 10 mol% (0.02 mmol) of dibenzylacetone palladium, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added to a 25 mL tubular reactor. The reactor was heated to 100 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography, with a yield of 37%. 1 H NMR (400MHz, CDCl3) δ7.78(d,J=8.0Hz,4H),7.75(d,J=4.0Hz,4H),7.70(d,J=8.0Hz,2H),7.53(t,J=8.0Hz,2H),7.44(t,J=8.0Hz,1H).

[0071] Preparation Example 26

[0072] 0.2 mmol of 4-methylbiphenyl-2-anhydride, 0.8 mmol of 4-bromobiphenyl, and 10 mol% (0.02 mmol) of dibenzylacetone palladium, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.04 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 10 mol% (0.02 mmol) of sodium tetrafluoroborate, 1 equiv (0.2 mmol) of zinc powder, 2 equiv (0.4 mmol) of zinc, and 1 mL of N,N-dimethylacetamide were added to a 25 mL tubular reactor. The reactor was heated to 100 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the product was purified by column chromatography with a yield of 37%.1 H NMR (400MHz, CDCl3) δ7.64(d,J=8.0Hz,1H),7.51(d,J=8.0Hz,1H),7.46(t,J=8.0Hz, 1H),7.36(t,J=8.0Hz,1H),7.26(d,J=8.0Hz,1H),7.09(q,J=8.0Hz,1H),2.35(s,1H). 13 C NMR (100MHz, CDCl3) δ140.7,140.7,140.6,140.1,139.0,138.5,136.2,130.7 ,130.6,130.3,129.8,128.8,128.7,127.5,127.3,127.2,127.0,126.5,21.2.

[0073] Preparation Example 27

[0074] 0.2 mmol of 2-naphthalic anhydride, 0.8 mmol of 4-bromobiphenyl, and 10 mol% (0.02 mmol) of dibenzylacetone palladium, 10 mol% (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 20 mol% (0.04 mmol) of 2-dicyclohexylphospho-2'-methylbiphenyl, 10 mol% (0.02 mmol) of 2,6'-dimethyl-2,2'-bipyridine, 1 equiv (0.2 mmol) of sodium tetrafluoroborate, 2 equiv (0.4 mmol) of zinc powder, and 1 mL of N,N-dimethylacetamide were added to a 25 mL tubular reactor. The reactor was heated to 100 °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%. 1 H NMR (400MHz, CDCl3) δ8.05(d,J=8.0Hz,1H),7.96(dd,J=16.0,8.0Hz,2H),7.77(dd,J=16.0,8.0Hz,4H),7.66–7.48(m,8H),7.44(t,J=8.0Hz,1H). 13 C NMR (100MHz, CDCl3) δ140.88,140.2,139.9,133.8,131.7,130.6,128.9,128.4,127.8,127.4,127.2,127.1,127.0,126.1,126.1,125.9,125.5.

[0075] Preparation Example 28

[0076] 0.2 mmol of 2-methylbenzoic anhydride, 0.8 mmol of 4-bromobiphenyl, palladium dibenzylacetone (10 mol%, 0.02 mmol), nickel diethylene glycol dimethyl ether bromide (10 mol%, 0.02 mmol), 2-dicyclohexylphospho-2'-methylbiphenyl (20 mol%, 0.04 mmol), 2,6'-dimethyl-2,2'-bipyridine (10 mol%, 0.02 mmol), sodium tetrafluoroborate (1 equiv, 0.2 mmol), zinc powder (2 equiv, 0.4 mmol), and N,N-dimethylacetamide (1 mL) were added to a 25 mL tubular reactor. The reactor was heated to 100 °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) δ7.62–7.55(m,4H),7.42–7.36(m,2H),7.36–7.25(m,3H),7.21(d,J=2.8Hz,4H),2.26(s,3H). 13 C NMR (100MHz, CDCl3) δ141.5,141.1,141.1,139.6,135.5,130.4,129.9,129.7,128.9,127.4,127.4,127.1,126.8,125.9,20.6.

[0077] 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 biaromatic compounds, characterized in that, Using arylic anhydride II and aryl bromide III as raw materials, N,N-dimethylacetamide as solvent, dibenzylacetone palladium and ethylene glycol dimethyl ether nickel bromide as catalysts, 2-dicyclohexylphospho-2'-methylbiphenyl and 2,6'-dimethyl-2,2'-bipyridine as ligands, sodium tetrafluoroborate as additive, and zinc powder as reducing agent, the biaromatic compound I can be obtained in high yield by reacting effectively at 100℃ for 12 h. In the above synthetic method, the structural formulas of the starting materials arylic anhydride II, aryl bromide III, and biaryl hydrocarbon compound I are as follows: The Ar 1 The following are listed: phenyl, 4-methylphenyl, 2-methylphenyl, 4-cyclohexanephenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 2-methoxyphenyl, 4-phenylphenyl, 3-phenylphenyl, 4-methyl-2-phenylphenyl, 2-naphthyl, 4-chlorophenyl, 4-trifluoromethylphenyl; Ar 2 The compounds are 4-phenylphenyl, 3-phenylphenyl, 4-methylphenyl, 3,4-dimethylphenyl, 4-ethyl carboxylate phenyl, 4-acetylphenyl, 4-methoxyphenyl, 3-methoxyphenyl, 2-methoxyphenyl, 4-cyanophenyl, 4-fluorophenyl, 4-trifluoromethoxyphenyl, 4-trifluoromethylphenyl, 2-benzophenone, 7-quinoline, 2-fluorenyl, 2-naphthyl, 1-naphthyl, 4-(4-bromophenyl)pyridine, 5-benzofuran, 5-N-methylindolyl, 3-ethoxypyridine, 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 reference, 10 mol% palladium dibenzylacetone and 10 mol% nickel diethylene glycol dimethyl ether bromide were used as catalysts, 20 mol% 2-dicyclohexylphospho-2'-methylbiphenyl and 10 mol% 2,6'-dimethyl-2,2'-bipyridine were used as ligands, one equivalent of sodium tetrafluoroborate 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 100°C, and reacted for 12 hours.

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