Preparation method of biphenyl-2-carboxylic acid compound at room temperature
By using a ruthenium catalyst at room temperature, the efficient synthesis of biphenyl-2-carboxylic acid compounds is achieved under the synergy, solving the problem of high-temperature, high-pressure and precious metal catalysts in the prior art, and achieving low energy consumption, low cost and environmentally friendly synthesis effects.
Patent Information
- Application Number
- CN202411829666.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-12
- Publication Date
- 2025-04-04
AI Technical Summary
The existing synthesis methods of biphenyl-2-carboxylic acid compounds require high temperature and high pressure conditions or the use of harmful additives such as precious metal catalysts and silver salts, resulting in high energy consumption, high cost and environmental pollution, making it difficult to meet the needs of green chemistry and sustainable development.
Using the ruthenium catalyst method at room temperature, the efficient synthesis of biphenyl-2-carboxylic acid compounds is achieved through the synergistic action of aryl carboxylic acid and arylsulfonium trifluoromethanesulfonic acid under the ruthenium catalyst, ligand and base.
It has achieved efficient synthesis of biphenyl-2-carboxylic acid compounds under mild conditions, reducing energy consumption and production costs, avoiding the use of precious metal catalysts and silver salts, and meeting the requirements of green chemistry and sustainable development.
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Abstract
Description
Technical Field
[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for preparing biphenyl-2-carboxylic acid compounds. Background Art
[0002] Biphenyl-2-carboxylic acid compounds have extensive and important applications in the field of chemistry. As key intermediates in organic synthesis, they are widely used in the synthesis and modification of drugs, especially in improving the activity, solubility and bioavailability of drugs, and have important application value. In addition, biphenyl-2-carboxylic acid compounds are also commonly used in the preparation of catalysts and are the basic materials for many important catalytic reactions. As an important component of optoelectronic functional materials in materials science, they are widely used in organic photovoltaic cells, OLEDs (organic light-emitting diodes) and other fields, promoting the development of electronic and energy materials. In addition, biphenyl-2-carboxylic acid compounds also play an important role in the synthesis of chemicals such as pesticides, dyes, and surfactants. Therefore, they have huge industrial application potential and market demand.
[0003] However, the existing synthesis methods of biphenyl-2-carboxylic acid compounds still face many challenges. Traditional synthesis routes usually require high temperature, high pressure conditions or the use of harsh reaction conditions such as strong acids and strong bases, which not only increase the energy consumption and production costs of the reaction, but also may cause side reactions, thereby affecting the purity and yield of the final product. Especially in the synthesis of some multi-functional substrates, the control of reaction conditions becomes particularly complicated, which may lead to the degradation of raw materials or the formation of unnecessary by-products. In addition, most of these traditional methods rely on precious metal catalysts (such as palladium, rhodium, etc.), which are highly efficient but expensive. Although there have been some attempts to simplify the synthesis of biphenyl-2-carboxylic acid compounds through direct ortho-arylation of aromatic carboxylic acids, most of the existing reports rely on precious metal catalysts or require the participation of additives such as silver salts, and the reaction usually needs to be carried out at high temperatures. These methods not only increase costs, but also limit their application in industrial production, and it is difficult to meet the needs of green chemistry and sustainable development.
[0004] Therefore, how to develop a low-energy, efficient, and green synthesis method under mild conditions (such as room temperature) has become a hot topic in current research. In particular, there is still a lot of room for technical improvement in reducing the dependence on precious metal catalysts, reducing harmful additives, and improving the adaptability of reaction substrates. In order to meet the growing market demand and the dual requirements of environmental protection and economic benefits, developing a preparation method for biphenyl-2-carboxylic acid compounds that can both improve synthesis efficiency and reduce production costs has become a problem that needs to be solved in the current field of organic synthesis. Summary of the invention
[0005] In view of the shortcomings of the prior art, the present invention provides a method for preparing biphenyl-2-carboxylic acid compounds at room temperature, which uses a cheap ruthenium catalyst, avoids the use of precious metal catalysts and additives such as silver salts, and solves the problems of high temperature, complex reaction conditions and heavy environmental burden in traditional synthesis methods. The method is not only simple to operate, with mild reaction conditions, but also has high substrate adaptability and reaction yield, meets the requirements of green and sustainable development, and has important academic significance and broad industrial application prospects.
[0006] The object of the present invention is achieved by: a method for preparing biphenyl-2-carboxylic acid compounds at room temperature, the substrate used comprising:
[0007] Compound A, an aryl carboxylic acid, and
[0008] Compound B, arylsulfonium trifluoromethanesulfonate;
[0009] The method comprises the following steps: starting materials including compound A and compound B are used to obtain biphenyl-2-carboxylic acid compounds through the synergistic effect of a ruthenium catalyst, a ligand and a base at room temperature.
[0010] Furthermore, the compound A comprises any one of the following structural formulas:
[0011] .
[0012] Further, the compound B includes any one of the following structural formulas:
[0013]
[0014] Among them, OMe represents methoxy, Ph represents phenyl, Me represents methyl, TT represents thianthrene, and OTf represents trifluoromethanesulfonate.
[0015] Furthermore, the biphenyl-2-carboxylic acid compound includes any one of the following structural formulas:
[0016] .
[0017] Further, the reaction formula is as follows:
[0018] ; Here, Ar represents an aryl group, and TT represents thianthrene.
[0019] Furthermore, the molar ratio of compound A to compound B is 1:1-1:1.5, the molar ratio of compound A to ruthenium catalyst is 1:0.01-1:0.05, the molar ratio of compound A to ligand is 1:0.02-1:0.2, and the molar ratio of compound A to base is 1:1-1:2.
[0020] Furthermore, the ruthenium catalyst includes at least one of p-cymene ruthenium dichloride dimer, p-cymene ruthenium diiodide dimer, and phenyl ruthenium dichloride dimer.
[0021] Furthermore, the ligand includes at least one of triphenylphosphine, tricyclohexylphosphine, tri-n-butylphosphine, and 1,10-phenanthroline.
[0022] Furthermore, the base includes at least one of potassium carbonate, sodium carbonate, potassium bicarbonate, and potassium phosphate; the reaction solvent includes any one of acetone, dichloromethane, tetrahydrofuran, acetonitrile, and N-methylpyrrolidone, the reaction gas atmosphere is argon, the reaction temperature is room temperature, and the reaction time is 12-24 hours.
[0023] In the present invention, under the action of a base, an aromatic carboxylic acid and a cymene dichloride ruthenium dimer undergo deprotonation and metallization to form an intermediate containing a carbon-ruthenium bond, which is then subjected to oxidation addition and reduction elimination with an aromatic sulfonium trifluoromethanesulfonate to obtain a biphenyl-2-carboxylic acid compound; after the method is optimized, the reaction conditions are mild and green, and the method can be carried out at room temperature without the need for additional use of a silver salt additive, thereby achieving efficient synthesis; the method not only has a wide substrate adaptability, but also has an excellent reaction yield, demonstrating the novelty and significant advantages of synthesizing biphenyl-2-carboxylic acid compounds.
[0024] Compared with the prior art, the present invention has the following beneficial effects:
[0025] High efficiency: The present invention uses a cheap ruthenium catalyst to achieve efficient synthesis of biphenyl-2-carboxylic acid compounds at room temperature. Compared with traditional methods, the reaction conditions are mild, which not only improves the reaction efficiency and yield, but also reduces energy consumption and production costs.
[0026] Simplified steps: The trifluoromethanesulfonic acid arylsulfonium salt used is derived from simple aromatic hydrocarbons, and the arylation reaction is completed in one step at room temperature, which simplifies the cumbersome reaction steps in traditional synthesis, avoids the use of harsh conditions such as high temperature and high pressure, and makes the operation process simpler.
[0027] Broad substrate compatibility: This method is applicable to a variety of aryl carboxylic acids and aryl sulfonium salts, and has high substrate adaptability. Different types of aromatic groups and functional groups can be successfully reacted under this reaction condition, expanding the scope of biphenyl-2-carboxylic acid compounds that can be synthesized.
[0028] Reducing side reactions: Compared with the traditional high temperature and high pressure synthesis method, the present invention adopts mild reaction conditions, reduces the occurrence of side reactions, ensures higher product purity and yield, and thus improves the selectivity of the synthesis.
[0029] Green chemistry: This invention avoids the use of precious metal catalysts and harmful additives such as silver salts in the reaction, and adopts cheap and environmentally friendly ruthenium catalysts, which conforms to the principles of green chemistry. The reaction conditions are mild and there are few by-products, which helps to reduce environmental pollution and promote the realization of sustainable development.
[0030] These advantages make the present invention have significant technical advantages in the synthesis of biphenyl-2-carboxylic acid compounds, which can not only improve the synthesis efficiency and reduce the cost, but also meet the requirements of green chemistry, and have broad industrial application prospects and environmentally friendly advantages. DETAILED DESCRIPTION
[0031] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.
[0032] The invention provides a method for preparing biphenyl-2-carboxylic acid compounds at room temperature. The method uses aryl carboxylic acid and trifluoromethanesulfonic acid arylsulfonium salt as starting raw materials, under the conditions of p-cymene ruthenium dichloride dimer as a catalyst, tricyclohexylphosphine as a ligand, potassium carbonate as a base, and N-methylpyrrolidone as a solvent, and realizes direct arylation of ortho-carbon-hydrogen bonds through the synergistic effect of carboxylic acid guidance and trifluoromethanesulfonic acid arylsulfonium salt, thereby efficiently synthesizing biphenyl-2-carboxylic acid compounds.
[0033] Example 1: Preparation of Compound 16
[0034]
[0035] A 10 mL Shrek tube with a branch tube and a magnetic stirrer was selected, and 2-methylbenzoic acid 1 (28.2 mg, 0.20 mmol), trifluoromethanesulfonic acid arylsulfonium salt 11 (113.4 mg, 0.24 mmol), p-cymene dichlororuthenium dimer (3.1 mg, 0.005 mmol), tricyclohexylphosphine (5.6 mg, 0.02 mmol), potassium carbonate (33.1 mg, 0.24 mmol) were added respectively. After replacing argon three times, 4 mL of N-methylpyrrolidone was added under argon atmosphere; then the reaction was carried out at room temperature for 24 hours.
[0036] After the reaction, the solvent was removed by rotary evaporation and then the mixture was purified by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate: methanol, volume ratio = 20:1:0.1) to obtain compound 16 (43.8 mg, 96%).
[0037] The product structure characterization data are as follows:
[0038] 1 H NMR (400 MHz, CDCl 3 ): δ 7.37 – 7.27 (m, 3H), 7.23 – 7.15 (m, 2H), 6.96 – 6.90 (m, 2H), 3.84 (s, 3H), 2.39 (s, 3H) ppm.
[0039] 13 C NMR (101 MHz, CDCl 3 ): δ 170.5, 159.0, 139.6, 135.3, 133.3, 133.1, 129.33, 129.29, 128.7, 127.2, 113.7, 55.2, 19.7 ppm.
[0040] Example 2: Preparation of Compound 17
[0041]
[0042] A 10 mL Shrek tube with a branch tube and a magnetic stirrer was selected, and 2-methoxybenzoic acid 2 (30.6 mg, 0.20 mmol), trifluoromethanesulfonic acid arylsulfonium salt 11 (113.4 mg, 0.24 mmol), p-cymene dichlororuthenium dimer (3.1 mg, 0.005 mmol), tricyclohexylphosphine (5.6 mg, 0.02 mmol), potassium carbonate (33.1 mg, 0.24 mmol) were added respectively. After replacing argon three times, 4 mL of N-methylpyrrolidone was added under argon atmosphere; then the reaction was carried out at room temperature for 24 hours.
[0043] After the reaction, the solvent was removed by rotary evaporation and then the mixture was purified by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate: methanol, volume ratio = 20:1:0.1) to obtain compound 17 (49.1 mg, 95%).
[0044] The product structure characterization data are as follows:
[0045] 1 H NMR (400 MHz, CDCl 3): δ 7.41 – 7.36 (m, 1H), 7.35 – 7.30 (m, 2H), 6.98 – 6.95 (m, 1H), 6.94 – 6.89 (m, 3H), 3.87 (s, 3H), 3.83 (s, 3H) ppm.
[0046] 13 C NMR (101 MHz, CDCl 3 ): δ 168.7, 159.1, 156.4, 140.7, 132.4, 130.4, 129.3, 122.9, 121.9, 113.7, 109.4, 56.0, 55.2 ppm.
[0047] Example 3: Preparation of Compound 18
[0048]
[0049] A 10 mL Shrek tube with a branch tube and a magnetic stirrer was selected, and 2-phenylbenzoic acid 3 (39.8 mg, 0.20 mmol), trifluoromethanesulfonic acid arylsulfonium salt 11 (113.4 mg, 0.24 mmol), p-cymene dichlororuthenium dimer (3.1 mg, 0.005 mmol), tricyclohexylphosphine (5.6 mg, 0.02 mmol), potassium carbonate (33.1 mg, 0.24 mmol) were added respectively. After replacing argon three times, 4 mL of N-methylpyrrolidone was added under argon atmosphere; then the reaction was carried out at room temperature for 24 hours.
[0050] After the reaction, the solvent was removed by rotary evaporation and then the mixture was purified by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate: methanol, volume ratio = 20:1:0.1) to obtain compound 18 (55.9 mg, 92%).
[0051] The product structure characterization data are as follows:
[0052] 1 H NMR (400 MHz, CDCl 3 ): δ 7.53 – 7.48 (m, 1H), 7.46 – 7.40 (m, 4H), 7.40 – 7.34 (m, 5H), 7.00 – 6.94 (m, 2H), 3.85 (s, 3H) ppm.
[0053] 13 C NMR (101 MHz, CDCl3 ): δ 170.0, 159.1, 140.5, 140.2, 139.8, 132.8,132.7, 129.5, 129.3, 128.8, 128.4, 128.3, 128.2, 127.4, 113.7, 55.2 ppm.
[0054] Example 4: Preparation of Compound 19
[0055]
[0056] A 10 mL Shrek tube with a branch tube and a magnetic stirrer was selected, and 2-methoxycarbonylbenzoic acid 4 (38.0 mg, 0.20 mmol), trifluoromethanesulfonic acid arylsulfonium salt 11 (113.4 mg, 0.24 mmol), p-cymene dichlororuthenium dimer (3.1 mg, 0.005 mmol), tricyclohexylphosphine (5.6 mg, 0.02 mmol), potassium carbonate (33.1 mg, 0.24 mmol) were added respectively. After replacing argon three times, 4 mL of N-methylpyrrolidone was added under argon atmosphere; then the reaction was carried out at room temperature for 24 hours.
[0057] After the reaction, the solvent was removed by rotary evaporation and then the mixture was purified by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate: methanol, volume ratio = 20:1:0.1) to obtain compound 19 (29.7 mg, 52%).
[0058] The product structure characterization data are as follows:
[0059] 1 H NMR (400 MHz, CDCl 3 ): δ 8.00 – 7.93 (m, 1H), 7.55 – 7.47 (m, 2H), 7.32 – 7.27 (m, 2H), 6.95 – 6.90 (m, 2H), 3.90 (s, 3H), 3.83 (s, 3H) ppm.
[0060] 13 C NMR (101 MHz, CDCl 3 ): δ 169.4, 166.2, 159.3, 140.2, 134.7, 134.3,131.5, 129.7, 129.0, 128.5, 128.0, 113.7, 55.2, 52.5 ppm.
[0061] Example 4: Preparation of Compound 20
[0062]
[0063] A 10 mL Shrek tube with a branch tube and a magnetic stirrer was selected, and 3-methoxybenzoic acid 5 (31.0 mg, 0.20 mmol), trifluoromethanesulfonic acid arylsulfonium salt 11 (113.4 mg, 0.24 mmol), p-cymene dichlororuthenium dimer (3.1 mg, 0.005 mmol), tricyclohexylphosphine (5.6 mg, 0.02 mmol), potassium carbonate (33.1 mg, 0.24 mmol) were added respectively. After replacing argon three times, 4 mL of N-methylpyrrolidone was added under argon atmosphere; then the reaction was carried out at room temperature for 24 hours.
[0064] After the reaction, the solvent was removed by rotary evaporation and then the mixture was purified by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate: methanol, volume ratio = 20:1:0.1) to obtain compound 20 (40.7 mg, 79%).
[0065] The product structure characterization data are as follows:
[0066] 1 H NMR (400 MHz, CDCl 3 ): δ 7.24 - 7.21 (m, 1H), 7.20 - 7.16 (m, 1H), 7.15 - 7.09 (m, 2H), 6.98 - 6.94 (m, 1H), 6.86 - 6.80 (m, 2H), 3.77 (s, 3H), 3.74 (s, 3H) ppm.
[0067] 13 C NMR (101 MHz, CDCl 3 ): δ 169.1, 158.6, 158.2, 134.5, 133.3, 131.8, 131.5, 129.4, 117.4, 114.2, 113.4, 55.5, 55.2 ppm.
[0068] Example 5: Preparation of Compound 21
[0069]
[0070] A 10 mL Shrek tube with a branch tube and a magnetic stirrer was selected, and 3-phenylbenzoic acid 6 (39.6 mg, 0.20 mmol), trifluoromethanesulfonic acid arylsulfonium salt 11 (113.4 mg, 0.24 mmol), p-cymene dichlororuthenium dimer (3.1 mg, 0.005 mmol), tricyclohexylphosphine (5.6 mg, 0.02 mmol), potassium carbonate (33.1 mg, 0.24 mmol) were added respectively. After replacing argon three times, 4 mL of N-methylpyrrolidone was added under argon atmosphere; then the reaction was carried out at room temperature for 24 hours.
[0071] After the reaction, the solvent was removed by rotary evaporation and then the mixture was purified by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate: methanol, volume ratio = 20:1:0.1) to obtain compound 21 (40.1 mg, 66%).
[0072] The product structure characterization data are as follows:
[0073] 1 H NMR (400 MHz, CDCl 3 ): δ 8.08 – 8.03 (m, 1H), 7.77 – 7.72 (m, 1H), 7.69 – 7.64 (m, 2H), 7.51 – 7.44 (m, 3H), 7.43 – 7.36 (m, 1H), 7.35 – 7.29(m, 2H), 7.01 – 6.95 (m, 2H), 3.87 (s, 3H) ppm.
[0074] 13 C NMR (101 MHz, CDCl 3 ): δ 169.4, 159.0, 140.8, 139.72, 139.71,133.2, 131.20, 131.17, 129.6, 129.4, 128.9, 128.3, 127.7, 127.0, 113.6, 55.2 ppm.
[0075] Example 6: Preparation of Compound 22
[0076]
[0077] A 10 mL Shrek tube with a branch tube and a magnetic stirrer was selected, and 3-bromobenzoic acid 7 (40.2 mg, 0.20 mmol), trifluoromethanesulfonic acid arylsulfonium salt 11 (113.4 mg, 0.24 mmol), p-cymene dichlororuthenium dimer (3.1 mg, 0.005 mmol), tricyclohexylphosphine (5.6 mg, 0.02 mmol), potassium carbonate (33.1 mg, 0.24 mmol) were added respectively. After replacing argon three times, 4 mL of N-methylpyrrolidone was added under argon atmosphere; then the reaction was carried out at room temperature for 24 hours.
[0078] After the reaction, the solvent was removed by rotary evaporation and then the mixture was purified by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate: methanol, volume ratio = 20:1:0.1) to obtain compound 22 (31.2 mg, 66%).
[0079] The product structure characterization data are as follows:
[0080] 1 H NMR (400 MHz, CDCl 3 ): δ 7.97 – 7.87 (m, 1H), 7.68 – 7.54 (m, 1H), 7.25 – 7.18 (m, 3H), 6.97 – 6.90 (m, 2H), 3.84 (s, 3H) ppm.
[0081] 13 C NMR (101 MHz, CDCl 3 ): δ 167.9, 159.2, 140.9, 134.1, 132.5, 132.3, 132.3, 129.3, 120.6, 113.7, 55.3 ppm.
[0082] Example 7: Preparation of Compound 23
[0083]
[0084] A 10 mL Shrek tube with a branch tube and a magnetic stirrer was selected, and 3-acetylbenzoic acid 8 (33.0 mg, 0.20 mmol), trifluoromethanesulfonic acid arylsulfonium salt 11 (113.4 mg, 0.24 mmol), p-cymene dichlororuthenium dimer (3.1 mg, 0.005 mmol), tricyclohexylphosphine (5.6 mg, 0.02 mmol), potassium carbonate (33.1 mg, 0.24 mmol) were added respectively. After replacing argon three times, 4 mL of N-methylpyrrolidone was added under argon atmosphere; then the reaction was carried out at room temperature for 24 hours.
[0085] After the reaction, the solvent was removed by rotary evaporation and then the mixture was purified by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate: methanol, volume ratio = 20:1:0.1) to obtain compound 23 (29.2 mg, 54%).
[0086] The product structure characterization data are as follows:
[0087] 1 H NMR (400 MHz, CDCl 3 ): δ 8.31 – 8.22 (m, 1H), 8.03 – 7.97 (m, 1H), 7.41 – 7.37 (m, 1H), 7.21 – 7.16 (m, 2H), 6.91 – 6.85 (m, 2H), 3.77 (s, 3H), 2.57 (s, 3H) ppm.
[0088] 13 C NMR (101 MHz, CDCl 3 ): δ 196.8, 168.7, 159.5, 146.4, 135.3, 132.3, 131.1, 131.0, 130.5, 130.0, 129.4, 113.7, 55.2, 26.6 ppm.
[0089] Example 8: Preparation of Compound 24
[0090]
[0091] A 10 mL Shrek tube with a branch tube and a magnetic stirrer was selected, and 2-methyl-4-methoxybenzoic acid 9 (33.2 mg, 0.20 mmol), trifluoromethanesulfonic acid arylsulfonium salt 11 (113.4 mg, 0.24 mmol), p-cymene dichlororuthenium dimer (3.1 mg, 0.005 mmol), tricyclohexylphosphine (5.6 mg, 0.02 mmol), potassium carbonate (33.1 mg, 0.24 mmol) were added respectively. After replacing argon three times, 4 mL of N-methylpyrrolidone was added under argon atmosphere; then the reaction was carried out at room temperature for 24 hours.
[0092] After the reaction, the solvent was removed by rotary evaporation and then the mixture was purified by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate: methanol, volume ratio = 20:1:0.1) to obtain compound 24 (47.3 mg, 87%).
[0093] The product structure characterization data are as follows:
[0094] 1 H NMR (400 MHz, CDCl 3 ): δ 7.32 – 7.27 (m, 2H), 6.95 – 6.90 (m, 2H), 6.72 (s, 2H), 3.84 – 3.81 (m, 6H), 2.38 (s, 3H) ppm.
[0095] 13 C NMR (101 MHz, CDCl 3 ): δ 170.4, 159.9, 159., 141.83, 137.7, 133.5, 129.1, 125.8, 114.3, 113.7, 112.5, 55.24, 55.20, 20.1 ppm.
[0096] Example 9: Preparation of Compound 25
[0097]
[0098] A 10 mL Shrek tube with a branch tube and a magnetic stirrer was selected, and 4-chloro-3-methoxybenzoic acid 10 (39.2 mg, 0.20 mmol), trifluoromethanesulfonic acid arylsulfonium salt 11 (113.4 mg, 0.24 mmol), p-cymene dichlororuthenium dimer (3.1 mg, 0.005 mmol), tricyclohexylphosphine (5.6 mg, 0.02 mmol), potassium carbonate (33.1 mg, 0.24 mmol) were added respectively. After replacing argon three times, 4 mL of N-methylpyrrolidone was added under argon atmosphere; then the reaction was carried out at room temperature for 24 hours.
[0099] After the reaction, the solvent was removed by rotary evaporation and then the mixture was purified by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate: methanol, volume ratio = 20:1:0.1) to obtain compound 25 (43.8 mg, 75%).
[0100] The product structure characterization data are as follows:
[0101] 1 H NMR (400 MHz, CDCl 3 ): δ 7.40 – 7.34 (m, 2H), 7.22 – 7.16 (m, 2H), 6.94 – 6.89 (m, 2H), 3.97 (s, 3H), 3.84 (s, 3H) ppm.
[0102] 13 C NMR (101 MHz, CDCl 3 ): δ 168.4, 159.0, 153.7, 135.7, 132.4, 132.2, 129.6, 129.4, 125.6, 113.5, 113.1, 56.4, 55.2 ppm.
[0103] Example 10: Preparation of Compound 26
[0104]
[0105] A 10 mL Shrek tube with a branch tube and a magnetic stirrer was selected, and 2-methylbenzoic acid 1 (28.2 mg, 0.20 mmol), trifluoromethanesulfonic acid arylsulfonium salt 12 (109.6 mg, 0.24 mmol), p-cymene dichlororuthenium dimer (3.1 mg, 0.005 mmol), tricyclohexylphosphine (5.6 mg, 0.02 mmol), potassium carbonate (33.1 mg, 0.24 mmol) were added respectively. After replacing argon three times, 4 mL of N-methylpyrrolidone was added under argon atmosphere; then the reaction was carried out at room temperature for 24 hours.
[0106] After the reaction, the solvent was removed by rotary evaporation and then the mixture was purified by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate: methanol, volume ratio = 20:1:0.1) to obtain compound 26 (41.1 mg, 91%).
[0107] The product structure characterization data are as follows:
[0108] 1 H NMR (400 MHz, CDCl 3 ): δ 7.38 – 7.32 (m, 1H), 7.30 – 7.26 (m, 2H), 7.25 – 7.18 (m, 4H), 2.42- 2.38 (m, 6H) ppm.
[0109] 13 C NMR (101 MHz, CDCl 3 ): δ 170.4, 140.0, 137.9, 137.0, 135.3, 133.1,129.3, 129.0, 128.8, 128.0, 127.2, 21.1, 19.6 ppm.
[0110] Example 11: Preparation of Compound 27
[0111]
[0112] A 10 mL Shrek tube with a branch tube and a magnetic stirrer was selected, and 2-methylbenzoic acid 1 (28.2 mg, 0.20 mmol), trifluoromethanesulfonic acid arylsulfonium salt 13 (118.2 mg, 0.24 mmol), p-cymene dichlororuthenium dimer (3.1 mg, 0.005 mmol), tricyclohexylphosphine (5.6 mg, 0.02 mmol), potassium carbonate (33.1 mg, 0.24 mmol) were added respectively. After replacing argon three times, 4 mL of N-methylpyrrolidone was added under argon atmosphere; then the reaction was carried out at room temperature for 24 hours.
[0113] After the reaction, the solvent was removed by rotary evaporation and then the mixture was purified by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate: methanol, volume ratio = 20:1:0.1) to obtain compound 27 (22.5 mg, 43%).
[0114] The product structure characterization data are as follows:
[0115] 1 H NMR (400 MHz, CDCl 3 ): δ 7.91 – 7.84 (m, 2H), 7.72 – 7.65 (m, 1H), 7.52 – 7.47 (m, 2H), 7.45 – 7.40 (m, 2H), 7.39 – 7.36 (m, 1H), 7.35 – 7.30(m, 1H), 7.28 – 7.24 (m, 1H), 2.49 (s, 3H) ppm.
[0116] 13 C NMR (101 MHz, CDCl 3 ): δ 169.6, 138.7, 138.4, 135.6, 134.4, 133.4,131.9, 129.4, 129.0, 128.4, 128.0, 127.8, 126.6, 126.2, 125.9, 125.7, 124.9,19.9 ppm.
[0117] Example 12: Preparation of Compound 28
[0118]
[0119] A 10 mL Shrek tube with a branch tube and a magnetic stirrer was selected, and 2-methylbenzoic acid 1 (28.2 mg, 0.20 mmol), trifluoromethanesulfonic acid arylsulfonium salt 14 (123.4 mg, 0.24 mmol), p-cymene dichlororuthenium dimer (3.1 mg, 0.005 mmol), tricyclohexylphosphine (5.6 mg, 0.02 mmol), potassium carbonate (33.1 mg, 0.24 mmol) were added respectively. After replacing argon three times, 4 mL of N-methylpyrrolidone was added under argon atmosphere; then the reaction was carried out at room temperature for 24 hours.
[0120] After the reaction, the solvent was removed by rotary evaporation and then the mixture was purified by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate: methanol, volume ratio = 20:1:0.1) to obtain compound 28 (55.6 mg, 98%).
[0121] The product structure characterization data are as follows:
[0122] 1 H NMR (400 MHz, CDCl 3 ): δ 7.37 – 7.33 (m, 1H), 7.25 – 7.19 (m, 2H), 7.19 – 7.16 (m, 2H), 7.15 – 7.11 (m, 1H), 2.42 (s, 3H), 2.31 (s, 6H) ppm.
[0123] 13 C NMR (101 MHz, CDCl 3 ): δ 170.5, 140.0, 138.3, 136.4, 135.6, 135.2, 133.1, 129.5, 129.4, 129.3, 128.7, 127.2, 125.5, 51.7, 19.7, 19.4 ppm.
[0124] Example 13: Preparation of Compound 29
[0125]
[0126] A 10 mL Shrek tube with a branch tube and a magnetic stirrer was selected, and 2-methylbenzoic acid 1 (28.2 mg, 0.20 mmol), trifluoromethanesulfonic acid arylsulfonium salt 15 (119.4 mg, 0.24 mmol), p-cymene dichlororuthenium dimer (3.1 mg, 0.005 mmol), tricyclohexylphosphine (5.6 mg, 0.02 mmol), potassium carbonate (33.1 mg, 0.24 mmol) were added respectively. After replacing argon three times, 4 mL of N-methylpyrrolidone was added under argon atmosphere; then the reaction was carried out at room temperature for 24 hours.
[0127] After the reaction, the solvent was removed by rotary evaporation and then the mixture was purified by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate: methanol, volume ratio = 20:1:0.1) to obtain compound 29 (35.8 mg, 67%).
[0128] The product structure characterization data are as follows:
[0129] 1 H NMR (400 MHz, CDCl 3 ): δ 7.57 – 7.48 (m, 2H), 7.37 – 7.31 (m, 1H), 7.25 – 7.19 (m, 1H), 7.14 – 7.09 (m, 1H), 7.01 – 6.97 (m, 1H), 3.95 (s, 3H), 2.37 (s, 3H) ppm.
[0130] 13 C NMR (101 MHz, CDCl 3 ): δ 69.8, 160.5, 137.3, 135.7, 134.2, 133.6,133.2, 133.0, 129.6, 129.5, 126.9, 116.1, 111.2, 101.7, 56.1, 19.6 ppm.
[0131] The above embodiments are only used to help understand the method and core idea of the present invention. It should be noted that, for those skilled in the art, several improvements and modifications can be made to the present invention without departing from the principles of the present invention, and these improvements and modifications also fall within the scope of protection of the claims of the present invention.
Claims
1. A method for preparing biphenyl-2-carboxylic acid compounds at room temperature, characterized in that: Substrates used include: Compound A, an aryl carboxylic acid, and Compound B, arylsulfonium trifluoromethanesulfonate; The method comprises the following steps: starting materials including compound A and compound B are used to obtain biphenyl-2-carboxylic acid compounds through the synergistic effect of a ruthenium catalyst, a ligand and a base at room temperature.
2. The method for preparing biphenyl-2-carboxylic acid compounds at room temperature according to claim 1, wherein: The compound A includes any of the following structural formulas: 。 3. The method for preparing biphenyl-2-carboxylic acid compounds at room temperature according to claim 1, characterized in that: The compound B includes any of the following structural formulas: Among them, OMe represents methoxy, Ph represents phenyl, Me represents methyl, TT represents thianthrene, and OTf represents trifluoromethanesulfonate.
4. A method for preparing biphenyl-2-carboxylic acid compounds at room temperature according to any one of claims 1 to 3, characterized in that: The biphenyl-2-carboxylic acid compound includes any one of the following structural formulas: 。 5. A method for preparing biphenyl-2-carboxylic acid compounds at room temperature according to any one of claims 1 to 3, characterized in that: The reaction formula is as follows: Here, Ar represents an aryl group, and TT represents thianthrene.
6. A method for preparing biphenyl-2-carboxylic acid compounds at room temperature according to any one of claims 1 to 3, characterized in that: The molar ratio of compound A to compound B is 1:1-1:1.5, the molar ratio of compound A to ruthenium catalyst is 1:0.01-1:0.05, the molar ratio of compound A to ligand is 1:0.02-1:0.2, and the molar ratio of compound A to base is 1:1-1:
2.
7. A method for preparing biphenyl-2-carboxylic acid compounds at room temperature according to any one of claims 1 to 3, characterized in that: The ruthenium catalyst includes at least one of p-cymene ruthenium dichloride dimer, p-cymene ruthenium diiodide dimer, and phenyl ruthenium dichloride dimer.
8. A method for preparing biphenyl-2-carboxylic acid compounds at room temperature according to any one of claims 1 to 3, characterized in that: The ligand includes at least one of triphenylphosphine, tricyclohexylphosphine, tri-n-butylphosphine and 1,10-phenanthroline.
9. A method for preparing biphenyl-2-carboxylic acid compounds at room temperature according to any one of claims 1 to 3, characterized in that: The base includes at least one of potassium carbonate, sodium carbonate, potassium bicarbonate, and potassium phosphate; the reaction solvent includes any one of acetone, dichloromethane, tetrahydrofuran, acetonitrile, and N-methylpyrrolidone; the reaction gas atmosphere is argon, the reaction temperature is room temperature, and the reaction time is 12-24 hours.