A bidentate pyrimidine-based triazolium carbene palladium hydrated 3-pyridine sulfonate compound, its preparation method and application

Abstract

The present invention discloses a bidentate pyrimidinyl triazolium carbene palladium hydrate 3-pyridine sulfonate compound, a preparation method and an application thereof. The structural formula of the compound is I, wherein R1 is hydrogen, alkyl, alkoxy, halogenated hydrocarbon group, halogen or aryl, R2 is alkyl or benzyl, and X is a monovalent anion. The preparation method is as follows: adding the bidentate pyrimidinyl triazolium salt, silver oxide, palladium salt and sodium 3-pyridine sulfonate into an organic solvent, and stirring at 50-90 °C for 6-12 hours. Due to the electrostatic guiding effect between the sulfonate group and the substrate hydroxyl group in the bidentate pyrimidinyl triazolium carbene palladium hydrate 3-pyridine sulfonate compound, the coupling reaction at the meta-position of phenol or benzyl alcohol can be efficiently and selectively catalyzed in the aqueous phase. #imgabs0#

Description

Technical Field

[0001] The present invention relates to a palladium catalyst, and particularly to a bidentate pyrimidinyl triazole carbene palladium hydrated 3-pyridine sulfonate compound, a preparation method thereof, and an application thereof. Background Art

[0002] Phenol (benzyl alcohol) derivatives are commonly present in natural products, drug molecules, and functional materials. The hydroxyl group of phenol (benzyl alcohol) has a strong ortho-para directing effect. Therefore, the meta-aryl substitution products of phenol (benzyl alcohol) are rarely reported. In recent years, the coupling reaction of transition metal-catalyzed haloarenes with arylboronic acids has become one of the most direct and effective methods for synthesizing biaryl compounds. When polyhaloarenes react with arylboronic acids, selectivity problems will be encountered. For example, when 3,4-dichloroarene couples with arylboronic acid, meta- and para-coupled products will be produced (J. Am. Chem. Soc. 2020, 142, 21891-21898). The reaction equation is as follows:

[0003]

[0004] When polyhaloarenes are used as reaction substrates to produce corresponding coupling compounds at different positions, how to control the high selectivity of polyhaloarenes to produce target substituents remains to be solved. Summary of the Invention

[0005] Object of the Invention: The first object of the present invention is to provide a bidentate pyrimidinyl triazole carbene palladium hydrated 3-pyridine sulfonate compound that can efficiently and selectively catalyze the meta-coupling reaction of phenol or benzyl alcohol; the second object of the present invention is to provide a preparation method of the bidentate pyrimidinyl triazole carbene palladium hydrated 3-pyridine sulfonate compound; the third object of the present invention is to provide an application of the bidentate pyrimidinyl triazole carbene palladium hydrated 3-pyridine sulfonate compound in the catalytic meta-coupling reaction of phenol or benzyl alcohol.

[0006] Technical Solution: The bidentate pyrimidinyl triazole carbene palladium hydrated 3-pyridine sulfonate compound described in the present invention has the following structural formula:

[0007]

[0008] Among them, R1 is hydrogen, alkyl, alkoxy, halogenated hydrocarbon group, halogen, or aryl, R2 is alkyl or benzyl, and X is a monovalent anion.

[0009] Preferably, R1 is hydrogen, methyl, ethyl, methoxy, trifluoromethyl, fluoro group, chloro group, bromo group, or phenyl.

[0010] Preferably, R2 is methyl, ethyl, n-propyl, isopropyl, n-butyl, and benzyl.

[0011] Preferably, the monovalent anion X is BF4 - or PF6 - .

[0012] Preferably, the structural formula of the bidentate pyrimidinyltriazolium carbene palladium hydrated 3-pyridinesulfonate compound is as follows:

[0013]

[0014]

[0015] The preparation method of the bidentate pyrimidinyltriazolium carbene palladium hydrated 3-pyridinesulfonate compound of the present invention: Add the bidentate pyrimidinyltriazolium salt, silver oxide, palladium salt and 3-pyridinesulfonate sodium into an organic solvent, stir at 50-90 °C for 6-12 hours, and obtain the bidentate pyrimidinyltriazolium carbene palladium hydrated 3-pyridinesulfonate compound. The synthesis route is as follows:

[0016]

[0017] Among them, the synthesis method of the bidentate pyrimidinyltriazolium salt is:

[0018]

[0019] Among them, R1 is hydrogen, alkyl, alkoxy, halogenated hydrocarbon group, halogen or aryl, R2 is alkyl or benzyl, and X is a monovalent anion. Preferably, R1 is hydrogen, methyl, ethyl, methoxy, trifluoromethyl, fluoro group, chloro group, bromo group or phenyl; R2 is methyl, ethyl, n-propyl, isopropyl, n-butyl and benzyl.

[0020] Preferably, the molar ratio of the bidentate pyrimidinyltriazolium salt, silver oxide, palladium salt and 3-pyridinesulfonate sodium is 1:0.5-1:1-1.2:1-1.1.

[0021] Preferably, the organic solvent is toluene, 1,4-dioxane, tetrahydrofuran, acetone or dichloromethane; the palladium salt is palladium chloride, palladium acetate or palladium tetrafluoroborate.

[0022] The application of the bidentate pyrimidinyltriazolium carbene palladium hydrated 3-pyridinesulfonate compound of the present invention in the meta-coupling reaction of phenol or benzyl alcohol.

[0023] Preferably, the application method is: Add 3,4-dichlorophenol or 3,4-dichlorobenzyl alcohol, arylboronic acid, base and the bidentate pyrimidinyltriazolium carbene palladium hydrated 3-pyridinesulfonate compound into water, react at 80-100 °C for 12-24 hours, after the reaction is completed, cool, extract the reaction solution with dichloromethane three times, and after the extract is concentrated, purified and dried, obtain the product 3-aryl-4-chlorophenol or 3-aryl-4-chlorobenzyl alcohol. The synthesis route is as follows:

[0024]

[0025] Among them, n is 0 or 1, R is hydrogen, methyl, ethyl, methoxy, hydroxy, benzyloxy, trifluoromethyl, mercapto, phenyl, fluoro, cyano, acetyl or methyl formate; Y is carbon or nitrogen.

[0026] Preferably, the molar ratio of the 3,4-dichlorophenol or 3,4-dichlorobenzyl alcohol, arylboronic acid, base and bidentate pyrimidyltriazolylcarbene palladium 3-pyridinesulfonate hydrate compound is 1:1-1.5:1-3:0.005-0.02; the base is potassium carbonate, sodium carbonate, cesium carbonate, sodium phosphate or potassium phosphate.

[0027] Invention mechanism: The bidentate pyrimidyltriazolylcarbene palladium 3-pyridinesulfonate hydrate compound of the present invention is used as a palladium catalyst. A 3-pyridinesulfonate is introduced into the bidentate pyrimidyltriazolylcarbene palladium ring. Through the electrostatic guiding effect between the sulfonate group in the catalyst and the hydroxyl group of the substrate dichlorophenol (benzyl alcohol), the coupling reaction between the meta-position of 3,4-dichlorophenol (benzyl alcohol) and arylboronic acid in the aqueous phase is efficiently and selectively catalyzed to synthesize 3-aryl-4-chlorophenol (benzyl alcohol).

[0028] Beneficial effects: Compared with the prior art, the present invention has the following remarkable advantages: (1) The electrostatic guiding effect between the sulfonate group and the substrate hydroxyl group in the bidentate pyrimidyltriazolylcarbene palladium 3-pyridinesulfonate hydrate compound efficiently and selectively catalyzes the coupling reaction of the meta-position chlorine of phenol (benzyl alcohol) in the aqueous phase; (2) The reaction conditions are mild, the operation is simple, and it is economical and efficient; (3) The bidentate pyrimidyltriazolylcarbene palladium 3-pyridinesulfonate hydrate compound is applied to the coupling reaction of the meta-position chlorine of phenol (benzyl alcohol), with high selectivity, and the solvent is water, avoiding the use of organic solvents, which is green and environmentally friendly. Detailed implementation manners

[0029] The technical solutions of the present invention will be further described below in conjunction with the embodiments.

[0030] Example 1

[0031] (1) Synthesis of bidentate pyrimidyltriazolium salt L1

[0032] S1: Add 1 mmol of triazole, 1.1 mmol of 2-bromopyrimidine, 2 mmol of potassium carbonate and 15 mL of dimethyl sulfoxide to a 50 mL round-bottom flask. After stirring at 100 °C for 12 hours, filter, concentrate, and separate by column chromatography to obtain N-pyrimidine-substituted triazole with a yield of 86%. The synthesis route is as follows:

[0033]

[0034] 1H NMR data:1 1H NMR (400 MHz, CDCl3) δ 9.24 (s, 1H), 8.81 (d, J = 4.8 Hz, 2H), 8.17 (s, 1H), 7.34 (t, J = 4.8 Hz, 1H).

[0035] S2: 1 mmol of N-pyrimidine-substituted triazole, 5 mmol of methyl bromide, 10 mmol of NaBF4 and 20 mL of 1,4-dioxane were added to a 50 mL round-bottom flask and stirred at 100 °C for 24 h. After filtration and drying of the obtained solid, N-methyl bidentate pyrimidinyl triazole tetrafluoroborate was obtained with a yield of 90%. The synthetic route is as follows:

[0036]

[0037] 1H NMR data: 1H NMR data: 1 1H NMR (400 MHz, CD3CN) δ 10.29 (s, 1H), 9.03–8.75 (m, 3H), 7.68 (t, J = 4.9 Hz, 1H), 2.62 (s, 3H).

[0038] (2) Preparation of bidentate pyrimidinyl triazole carbene palladium hydrate 3-pyridine sulfonate compound 1. The synthetic route is as follows:

[0039]

[0040] Under a nitrogen atmosphere, 1 mmol of bidentate pyrimidinyl triazole salt L1, 0.5 mmol of silver oxide, 1 mmol of palladium chloride, 1 mmol of sodium 3-pyridine sulfonate and 20 mL of toluene were added to a 50 mL round-bottom flask. After stirring at 90 °C for 6 h, filtration, concentration and column chromatography separation were carried out to obtain compound 1 with a yield of 80%.

[0041] 1H NMR data: 1 1H NMR (400 MHz, CDCl3) δ 9.28 (s, 1H), 8.62–8.36 (m, 4H), 7.69 (t, J = 5.0 Hz, 1H), 7.56 (s, 1H), 6.63 (t, 1H), 2.50 (s, 3H), 1.92 (s, 2H).

[0042] Example 2

[0043] (1) Synthesis of bidentate pyrimidinyl triazole salt L3

[0044] The synthesis method was the same as that of bidentate pyrimidinyl triazole salt L1 in Example 1;

[0045] (2) Preparation of bidentate pyrimidinyl triazole carbene palladium hydrate 3-pyridine sulfonate compound 3. The synthetic route is as follows:

[0046]

[0047] In a nitrogen atmosphere, 1 mmol of bidentate pyrimidinyltriazolium salt L3, 1 mmol of silver oxide, 1.1 mmol of palladium acetate, 1.1 mmol of sodium 3-pyridinesulfonate and 20 mL of tetrahydrofuran were added to a 50 mL round-bottom flask. After stirring at 60 °C for 12 hours, the mixture was filtered, concentrated, and separated by column chromatography to obtain compound 3 with a yield of 82%.

[0048] 1H NMR data: 1 H NMR(400MHz,CDCl3)δ9.30(s,1H),8.61–8.45(m,2H),8.29(s,1H),8.12(s,1H),7.69(t,1H),7.53(s,1H),2.61(q,2H),1.93(s,2H),1.02(t,3H).

[0049] Example 3

[0050] (1) Synthesis of bidentate pyrimidinyltriazolium salt L5

[0051] The synthesis method was the same as that of bidentate pyrimidinyltriazolium salt L1 in Example 1;

[0052] (2) Preparation of bidentate pyrimidinyltriazolium carbene palladium hydrate 3-pyridinesulfonate compound 5. The synthesis route is as follows:

[0053]

[0054] In a nitrogen atmosphere, 1 mmol of bidentate pyrimidinyltriazolium salt L5, 0.6 mmol of silver oxide, 1.2 mmol of palladium chloride, 1.1 mmol of sodium 3-pyridinesulfonate and 20 mL of 1,4-dioxane were added to a 50 mL round-bottom flask. After stirring at 100 °C for 8 hours, the mixture was filtered, concentrated, and separated by column chromatography to obtain compound 5 with a yield of 78%.

[0055] 1H NMR data: 1 H NMR(400MHz,CDCl3)δ9.28(s,1H),8.62–8.44(m,2H),8.27(s,1H),8.10(s,1H),7.68(t,1H),7.52(s,1H),2.99(m,1H),2.36(s,3H),1.94(s,2H),1.07(d,6H).

[0056] Example 4

[0057] (1) Synthesis of bidentate pyrimidinyltriazolium salt L7

[0058] The synthesis method is the same as that of the bidentate pyrimidinyltriazole salt L1 in Example 1;

[0059] (2) Preparation of bidentate pyrimidinyltriazole carbene palladium hydrate 3-pyridine sulfonate compound 7, the synthetic route is as follows:

[0060]

[0061] Under a nitrogen atmosphere, 1 mmol of bidentate pyrimidinyltriazole salt L7, 0.7 mmol of silver oxide, 1.2 mmol of palladium tetrafluoroborate, 1 mmol of sodium 3-pyridine sulfonate and 20 mL of acetone were added to a 50 mL round-bottom flask. After stirring at 50 °C for 12 hours, it was filtered, concentrated, and separated by column chromatography to obtain compound 7 with a yield of 70%.

[0062] 1H NMR data: 1 H NMR(400MHz,CDCl3)δ9.28(s,1H),8.63–8.43(m,2H),8.26(s,1H),8.10(s,1H),7.67(t,1H),7.53(s,1H),2.98(m,1H),2.60(q,2H),1.96(s,2H),1.25(t,3H),1.07(d,6H).

[0063] Example 5

[0064] (1) Synthesis of bidentate pyrimidinyltriazole salt L 10 synthesis

[0065] The synthesis method is the same as that of the bidentate pyrimidinyltriazole salt L1 in Example 1;

[0066] (2) Preparation of bidentate pyrimidinyltriazole carbene palladium hydrate 3-pyridine sulfonate compound 10, the synthetic route is as follows:

[0067]

[0068] Under a nitrogen atmosphere, 1 mmol of bidentate pyrimidinyltriazole salt L 10 , 0.8 mmol of silver oxide, 1.1 mmol of palladium tetrafluoroborate, 1 mmol of sodium 3-pyridine sulfonate and 20 mL of dichloromethane were added to a 50 mL round-bottom flask. After stirring at 50 °C for 12 hours, it was filtered, concentrated, and separated by column chromatography to obtain compound 10 with a yield of 77%.

[0069] 1H NMR data: 11H NMR (400 MHz, CDCl3) δ 9.29 (s, 1H), 8.72–8.45 (m, 4H), 7.68 (t, 1H), 7.52–7.26 (m, 6H), 2.56 (t, 2H), 1.94 (s, 2H), 1.46 (m, 2H), 0.97 (t, 3H).

[0070] Example 6

[0071] (1) Synthesis of bidentate pyrimidinyltriazolium salt L 12 Synthesis

[0072] The synthesis method is the same as that of bidentate pyrimidinyltriazolium salt L1 in Example 1;

[0073] (2) Preparation of bidentate pyrimidinyltriazolium carbene palladium hydrate 3-pyridinesulfonate compound 12. The synthetic route is as follows:

[0074]

[0075] Under a nitrogen atmosphere, 1 mmol of bidentate pyrimidinyltriazolium salt L 12 , 0.9 mmol of silver oxide, 1.2 mmol of palladium acetate, 1.2 mmol of sodium 3-pyridinesulfonate and 20 mL of toluene were added to a 50 mL round-bottom flask. After stirring at 80 °C for 10 hours, it was filtered, concentrated, and separated by column chromatography to obtain compound 12 with a yield of 85%.

[0076] 1H NMR data: 1 1H NMR (400 MHz, CDCl3) δ 9.29 (s, 1H), 8.60–8.43 (m, 2H), 8.28 (s, 1H), 8.11 (s, 1H), 7.68 (t, 1H), 7.52 (s, 1H), 2.57 (t, 2H), 2.37 (s, 3H), 1.96 (s, 2H), 1.43–1.35 (m, 4H), 0.98 (t, 3H).

[0077] Example 7

[0078] (1) Synthesis of bidentate pyrimidinyltriazolium salt L 16 Synthesis

[0079] The synthesis method is the same as that of bidentate pyrimidinyltriazolium salt L1 in Example 1;

[0080] (2) Preparation of bidentate pyrimidinyltriazolium carbene palladium hydrate 3-pyridinesulfonate compound 16. The synthetic route is as follows:

[0081]

[0082] In a nitrogen atmosphere, 1 mmol of bidentate pyrimidinyl triazole salt L was added to a 50 mL round-bottom flask. 16 , 0.7 mmol silver oxide, 1.1 mmol palladium acetate, 1.1 mmol sodium 3-pyridinesulfonate and 20 mL tetrahydrofuran, stirred at 70°C for 10 hours, filtered, concentrated and separated by column chromatography to obtain compound 16 with a yield of 76%.

[0083] H NMR spectrum data: 1 H NMR(400MHz, CDCl3)δ9.38(s,1H),8.60–8.43(m,2H),8.21(s,1H),8.05(s, 1H),7.68(t,1H),7.52(s,1H),7.05–7.17(m,5H),3.92(s,2H),1.94(s,2H).

[0084] Example 8

[0085] (1) Bis(pyrimidinyl)triazole salt L 18 Synthesis

[0086] The synthesis method is the same as that of Example 1: bidentate pyrimidinyl triazole salt L1;

[0087] (2) Preparation of bidentate pyrimidinyl triazole carbene palladium hydrate 3-pyridine sulfonate compound 18, the synthetic route is as follows:

[0088]

[0089] In a nitrogen atmosphere, 1 mmol of bidentate pyrimidinyl triazole salt L was added to a 50 mL round-bottom flask. 18 , 0.6 mmol silver oxide, 1.1 mmol palladium chloride, 1 mmol 3-pyridine sulfonate compound and 20 mL 1,4-dioxane, stirred at 80 °C for 12 hours, filtered, concentrated and separated by column chromatography to obtain compound 18 with a yield of 76%.

[0090] H NMR spectrum data: 1 H NMR (400MHz, CDCl3) δ9.36(s,1H),8.73–8.45(m,4H),7.67(t,1H),7.55(s,1H),7.50–7.10(m,10H),3.91(s,2H),1.97(s,2H).

[0091] Example 9

[0092] The preparation of 3-(4-methyl)phenyl-4-chlorophenol, the synthetic route is as follows:

[0093]

[0094] Add 0.005 mmol of bidentate pyrimidine-based triazolium carbene palladium(Ⅱ) 3-pyridinesulfonate hydrate compound 1, 1 mmol of 3,4-dichlorophenol, 1.5 mmol of 4-methylphenylboronic acid, 3 mmol of potassium carbonate and water (5 ml) into a flask, and react at 100 °C for 24 hours; after the reaction is completed, cool it down. The reaction solution is extracted with dichloromethane three times, and the combined organic phases are dried with anhydrous MgSO4 for 30 minutes, and then filtered; the filtrate is concentrated, purified by column chromatography and dried to obtain the product 3-(4-methyl)phenyl-4-chlorophenol with a yield of 82%.

[0095] 1H NMR data: 1 H NMR(400 MHz, CDCl3) δ 7.31(t, J = 8.6 Hz, 3H), 7.23(d, J = 8.0 Hz, 2H), 6.81(d, J = 3.0 Hz, 1H), 6.75(dd, J = 8.6, 3.1 Hz, 1H), 5.17(s, 1H), 2.40(s, 3H).

[0096] Example 10

[0097] The preparation of 3-(4-methoxy)phenyl-4-chlorophenol has the following synthetic route:

[0098]

[0099] Add 0.008 mmol of bidentate pyrimidine-based triazolium carbene palladium(Ⅱ) 3-pyridinesulfonate hydrate compound 3, 1 mmol of 3,4-dichlorophenol, 1.3 mmol of 4-methoxyphenylboronic acid, 2 mmol of cesium carbonate and water (5 ml) into a flask, and react at 100 °C for 20 hours; after the reaction is completed, cool it down. The reaction solution is extracted with dichloromethane three times, and the combined organic phases are dried with anhydrous MgSO4 for 30 minutes, and then filtered; the filtrate is concentrated, purified by column chromatography and dried to obtain the product 3-(4-methoxy)phenyl-4-chlorophenol with a yield of 85%.

[0100] 1H NMR data: 1 H NMR(400 MHz, CDCl3) δ 7.38–7.30(m, 2H), 7.19(d, J = 8.4 Hz, 1H), 7.00–6.92(m, 3H), 6.78(dd, J = 8.4, 2.6 Hz, 1H), 5.25(s, 1H), 3.85(s, 3H).

[0101] Example 11

[0102] The preparation of 3-(4-trifluoromethyl)phenyl-4-chlorophenol has the following synthetic route:

[0103]

[0104] Add 0.02 mmol of bidentate pyrimidinyltriazolyl carbene palladium(Ⅱ) 3-pyridinesulfonate hydrate compound 3, 1 mmol of 3,4-dichlorophenol, 1.5 mmol of 4-trifluoromethylphenylboronic acid, 1 mmol of potassium phosphate and water (5 ml) into a flask, and react at 80 °C for 12 hours; after the reaction is completed, cool, extract the reaction solution with dichloromethane three times, combine the extracted organic phases and dry with anhydrous MgSO₄ for 30 minutes, then filter; concentrate the filtrate, purify by column chromatography and dry to obtain the product 3-(4-trifluoromethyl)phenyl-4-chlorophenol with a yield of 92%.

[0105] ¹H NMR data: 1 H NMR (400 MHz, CDCl₃) δ 7.68 (d, J = 0.7 Hz, 1H), 7.62 (t, J = 8.2 Hz, 2H), 7.54 (t, J = 7.8 Hz, 1H), 7.33 (dd, J = 8.2, 0.8 Hz, 1H), 6.84–6.78 (m, 2H), 5.42 (s, 1H).

[0106] Example 12

[0107] The preparation of 3-(3-methyl)phenyl-4-chlorophenol, the synthetic route is as follows:

[0108]

[0109] Add 0.01 mmol of bidentate pyrimidinyltriazolyl carbene palladium(Ⅱ) 3-pyridinesulfonate hydrate compound 5, 1 mmol of 3,4-dichlorophenol, 1.1 mmol of 3-methylphenylboronic acid, 2.2 mmol of sodium carbonate and water (5 ml) into a flask, and react at 90 °C for 16 hours; after the reaction is completed, cool, extract the reaction solution with dichloromethane three times, combine the extracted organic phases and dry with anhydrous MgSO₄ for 30 minutes, then filter; concentrate the filtrate, purify by column chromatography and dry to obtain the product 3-(3-methyl)phenyl-4-chlorophenol with a yield of 90%.

[0110] ¹H NMR data: 1 H NMR (400 MHz, CDCl₃) δ 7.34–7.28 (m, 2H), 7.24–7.17 (m, 3H), 6.81 (d, J = 3.0 Hz, 1H), 6.76 (dd, J = 8.6, 3.0 Hz, 1H), 5.18 (s, 1H), 2.40 (s, 3H).

[0111] Example 13

[0112] The preparation of 3-(3-hydroxy)phenyl-4-chlorophenol, the synthetic route is as follows:

[0113]

[0114] Add 0.012 mmol of bidentate pyrimidinyltriazolyl carbene palladium(Ⅱ) 3 - pyridinesulfonate hydrate compound 5, 1 mmol of 3,4 - dichlorophenol, 1.3 mmol of 3 - hydroxybenzeneboronic acid, 2.5 mmol of sodium phosphate and water (5 ml) into a flask, and react at 100 °C for 20 hours; after the reaction is completed, cool it down. The reaction solution is extracted with dichloromethane three times, and the combined extracted organic phases are dried with anhydrous MgSO₄ for 30 minutes, then filtered; the filtrate is concentrated, purified by column chromatography and dried to obtain the product 3 - (3 - hydroxy)phenyl - 4 - chlorophenol with a yield of 85%.

[0115] ¹H NMR data: 1 H NMR(400 MHz, CDCl₃)δ 7.23–7.16(m, 2H), 6.83–6.68(m, 5H).

[0116] Example 14

[0117] The preparation of 3 - (3 - methoxycarbonyl)phenyl - 4 - chlorophenol, and the synthetic route is as follows:

[0118]

[0119] Add 0.009 mmol of bidentate pyrimidinyltriazolyl carbene palladium(Ⅱ) 3 - pyridinesulfonate hydrate compound 7, 1 mmol of 3,4 - dichlorophenol, 1.4 mmol of 3 - methoxycarbonylbenzeneboronic acid, 2.8 mmol of cesium carbonate and water (5 ml) into a flask, and react at 100 °C for 24 hours; after the reaction is completed, cool it down. The reaction solution is extracted with dichloromethane three times, and the combined extracted organic phases are dried with anhydrous MgSO₄ for 30 minutes, then filtered; the filtrate is concentrated, purified by column chromatography and dried to obtain the product 3 - (3 - methoxycarbonyl)phenyl - 4 - chlorophenol with a yield of 72%.

[0120] ¹H NMR data: 1 H NMR(400 MHz, CDCl₃)δ 8.08(t, J = 1.6 Hz, 1H), 8.02(m, 1H), 7.62(m, 1H), 7.46(t, J = 7.7 Hz, 1H), 7.29(d, J = 8.6 Hz, 1H), 6.86–6.81(m, 2H), 6.79(s, 1H), 3.93(s, 3H).

[0121] Example 15

[0122] The preparation of 3 - (3 - phenyl)phenyl - 4 - chlorophenol, and the synthetic route is as follows:

[0123]

[0124] Add 0.015 mmol of bidentate pyrimidinyltriazolium carbene palladium(Ⅱ) 3-pyridinesulfonate hydrate compound 7, 1 mmol of 3,4-dichlorophenol, 1.2 mmol of 3-phenylphenylboronic acid, 1.8 mmol of potassium carbonate and water (5 ml) into a flask, and react at 100 °C for 20 hours; after the reaction is completed, cool, extract the reaction solution with dichloromethane three times, combine the extracted organic phases and dry with anhydrous MgSO4 for 30 minutes, and filter; concentrate the filtrate, purify by column chromatography, and dry to obtain the product 3-(3-phenyl)phenyl-4-chlorophenol with a yield of 78%.

[0125] 1H NMR data: 1 H NMR(400MHz,CDCl3)δ7.68–7.59(m,4H),7.52–7.39(m,4H),7.38–7.32(m,2H),6.88(d,J=3.0Hz,1H),6.78(dd,J=8.6,3.0Hz,1H),5.09(s,1H).

[0126] Example 16

[0127] The preparation of 3-(2-methyl)phenyl-4-chlorophenol is as follows:

[0128]

[0129] Add 0.018 mmol of bidentate pyrimidinyltriazolium carbene palladium(Ⅱ) 3-pyridinesulfonate hydrate compound 10, 1 mmol of 3,4-dichlorophenol, 1.5 mmol of 2-methylphenylboronic acid, 3 mmol of potassium phosphate and water (5 ml) into a flask, and react at 100 °C for 24 hours; after the reaction is completed, cool, extract the reaction solution with dichloromethane three times, combine the extracted organic phases and dry with anhydrous MgSO4 for 30 minutes, and filter; concentrate the filtrate, purify by column chromatography, and dry to obtain the product 3-(2-methyl)phenyl-4-chlorophenol with a yield of 73%.

[0130] 1H NMR data: 1 H NMR(400MHz,CDCl3)δ7.32–7.18(m,3H),7.10(m,2H),6.97(d,J=2.6Hz,1H),6.78(m,1H),5.49(d,J=15.7Hz,1H),2.12(s,3H).

[0131] Example 17

[0132] The preparation of 3-(6-methyl-3-pyridyl)-4-chlorophenol is as follows:

[0133]

[0134] Add 0.01 mmol of bidentate pyrimidinyltriazolyl carbene palladium(Ⅱ) 3 - pyridinesulfonate compound 10, 1 mmol of 3,4 - dichlorophenol, 1.5 mmol of 6 - methyl - 3 - pyridineboronic acid, 2 mmol of potassium carbonate and water (5 ml) into a flask, and react at 90 °C for 20 hours; after the reaction is completed, cool, extract the reaction solution with dichloromethane three times, combine the extracted organic phases and dry with anhydrous MgSO4 for 30 minutes, then filter; concentrate the filtrate, purify by column chromatography and dry to obtain the product 3 - (6 - methyl - 3 - pyridyl) - 4 - chlorophenol with a yield of 68%.

[0135] 1H NMR data: 1 H NMR(400MHz,CDCl3)δ8.66(d,J=1.7Hz,1H),7.99(m,1H),7.35(d,J=8.7Hz,1H),7.29(d,J=8.1Hz,1H),7.00(d,J=3.0Hz,1H),6.92(dd,J=8.7,2.9Hz,1H),2.65(s,3H).

[0136] Example 18

[0137] The preparation of 3 - phenyl - 4 - chlorobenzyl alcohol has the following synthetic route:

[0138]

[0139] Add 0.007 mmol of bidentate pyrimidinyltriazolyl carbene palladium(Ⅱ) 3 - pyridinesulfonate compound 12, 1 mmol of 3,4 - dichlorobenzyl alcohol, 1.5 mmol of phenylboronic acid, 2 mmol of sodium carbonate and water (5 ml) into a flask, and react at 100 °C for 24 hours; after the reaction is completed, cool, extract the reaction solution with dichloromethane three times, combine the extracted organic phases and dry with anhydrous MgSO4 for 30 minutes, then filter; concentrate the filtrate, purify by column chromatography and dry to obtain the product 3 - phenyl - 4 - chlorobenzyl alcohol with a yield of 72%.

[0140] 1H NMR data: 1 H NMR(400MHz,CDCl3)δ7.45–7.40(m,5H),7.40–7.36(m,1H),7.31(d,J=2.2Hz,1H),7.25(dd,J=8.2,2.2Hz,1H),4.66(s,2H),2.10(s,1H).

[0141] Example 19

[0142] The preparation of 3 - (4 - ethyl)phenyl - 4 - chlorobenzyl alcohol has the following synthetic route:

[0143]

[0144] Add 0.009 mmol of bidentate pyrimidinyltriazolyl carbene palladium(Ⅱ) 3 - pyridinesulfonate compound 12, 1 mmol of 3,4 - dichlorobenzyl alcohol, 1.4 mmol of 4 - ethylphenylboronic acid, 3 mmol of potassium phosphate and water (5 ml) into a flask, and react at 100 °C for 22 hours; after the reaction is completed, cool, extract the reaction solution with dichloromethane three times, combine the extracted organic phases and dry with anhydrous MgSO₄ for 30 minutes, and filter; concentrate the filtrate, purify by column chromatography and dry to obtain the product 3 - (4 - ethyl)phenyl - 4 - chlorobenzyl alcohol with a yield of 77%.

[0145] ¹H NMR data: 1 H NMR(400 MHz, CDCl₃) δ 7.43 (d, J = 8.2 Hz, 1H), 7.36 (d, J = 8.1 Hz, 3H), 7.26 (d, J = 8.0 Hz, 3H), 4.66 (s, 2H), 2.70 (q, J = 7.6 Hz, 2H), 2.06 (s, 1H), 1.28 (t, J = 7.6 Hz, 3H).

[0146] Example 20

[0147] Preparation of 3 - (4 - cyano)phenyl - 4 - chlorobenzyl alcohol, and the synthetic route is as follows:

[0148]

[0149] Add 0.011 mmol of bidentate pyrimidinyltriazolyl carbene palladium(Ⅱ) 3 - pyridinesulfonate compound 16, 1 mmol of 3,4 - dichlorobenzyl alcohol, 1.3 mmol of 4 - cyanophenylboronic acid, 3 mmol of cesium carbonate and water (5 ml) into a flask, and react at 100 °C for 19 hours; after the reaction is completed, cool, extract the reaction solution with dichloromethane three times, combine the extracted organic phases and dry with anhydrous MgSO₄ for 30 minutes, and filter; concentrate the filtrate, purify by column chromatography and dry to obtain the product 3 - (4 - cyano)phenyl - 4 - chlorobenzyl alcohol with a yield of 81%.

[0150] ¹H NMR data: 1 H NMR(400 MHz, CDCl₃) δ 7.72 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.3 Hz, 2H), 7.48 (d, J = 8.1 Hz, 1H), 7.34 (d, J = 7.7 Hz, 2H), 4.73 (s, 2H), 1.99 (s, 1H).

[0151] Example 21

[0152] Preparation of 3 - (4 - methoxycarbonyl)phenyl - 4 - chlorobenzyl alcohol, and the synthetic route is as follows:

[0153]

[0154] Add 0.014 mmol of bidentate pyrimidinyltriazolium carbene palladium(Ⅱ) 3-pyridinesulfonate compound 16, 1 mmol of 3,4-dichlorobenzyl alcohol, 1.3 mmol of 4-(methoxycarbonyl)phenylboronic acid, 2.4 mmol of potassium carbonate and water (5 ml) into a flask, and react at 90 °C for 20 hours; after the reaction is completed, cool it, extract the reaction solution with dichloromethane three times, combine the extracted organic phases and dry them with anhydrous MgSO4 for 30 minutes, and then filter; concentrate the filtrate, purify it by column chromatography and dry it to obtain the product 3-(4-(methoxycarbonyl)phenyl)-4-chlorobenzyl alcohol with a yield of 85%.

[0155] 1H NMR data: 1 H NMR(400MHz,CDCl3)δ8.10(d,J=8.0Hz,2H),7.57–7.39(m,3H),7.37–7.24(m,2H),4.73(s,2H),3.95(s,3H),2.43(s,1H).

[0156] Example 22

[0157] The preparation of 3-(4-mercapto)phenyl-4-chlorobenzyl alcohol has the following synthetic route:

[0158]

[0159] Add 0.013 mmol of bidentate pyrimidinyltriazolium carbene palladium(Ⅱ) 3-pyridinesulfonate compound 18, 1 mmol of 3,4-dichlorobenzyl alcohol, 1.1 mmol of 4-mercaptobenzoic acid, 1.7 mmol of potassium phosphate and water (5 ml) into a flask, and react at 80 °C for 17 hours; after the reaction is completed, cool it, extract the reaction solution with dichloromethane three times, combine the extracted organic phases and dry them with anhydrous MgSO4 for 30 minutes, and then filter; concentrate the filtrate, purify it by column chromatography and dry it to obtain the product 3-(4-mercapto)phenyl-4-chlorobenzyl alcohol with a yield of 88%.

[0160] 1H NMR data: 1 H NMR(400MHz,CDCl3)δ7.43(d,J=8.1Hz,1H),7.36(d,J=8.6Hz,2H),7.29(d,J=8.5Hz,3H),7.25(dd,J=8.1,2.2Hz,1H),4.67(s,2H),2.51(s,3H),2.02(d,J=4.7Hz,1H).

[0161] Example 23

[0162] Preparation of 3-(4-fluorophenyl)-4-chlorobenzyl alcohol. The synthetic route is as follows:

[0163]

[0164] Add 0.014 mmol of bidentate pyrimidyltriazolyl carbene palladium(Ⅱ) 3-pyridinesulfonate hydrate (Compound 18), 1 mmol of 3,4-dichlorobenzyl alcohol, 1.3 mmol of 4-fluorophenylboronic acid, 2.4 mmol of sodium phosphate, and water (5 ml) into a flask. React at 100 °C for 19 hours. After the reaction is completed, cool it down. Extract the reaction solution with dichloromethane three times. Combine the extracted organic phases and dry them with anhydrous MgSO4 for 30 minutes, then filter. Concentrate the filtrate, purify it by column chromatography, and dry it to obtain the product 3-(4-fluorophenyl)-4-chlorobenzyl alcohol with a yield of 84%.

[0165] 1H NMR data: 1 H NMR(400MHz,CDCl3)δ7.65(d,J=8.1Hz,2H),7.51(d,J=7.7Hz,2H),7.43(d,J=8.6Hz,1H),7.30(d,J=8.0Hz,2H),4.70(s,2H),2.08(s,1H).

[0166] Example 24

[0167] Preparation of 3-(3-phenyl)phenyl-4-chlorobenzyl alcohol. The synthetic route is as follows:

[0168]

[0169] Add 0.01 mmol of bidentate pyrimidyltriazolyl carbene palladium(Ⅱ) 3-pyridinesulfonate hydrate (Compound 16), 1 mmol of 3,4-dichlorobenzyl alcohol, 1.3 mmol of 3-phenylphenylboronic acid, 2.6 mmol of potassium carbonate, and water (5 ml) into a flask. React at 100 °C for 21 hours. After the reaction is completed, cool it down. Extract the reaction solution with dichloromethane three times. Combine the extracted organic phases and dry them with anhydrous MgSO4 for 30 minutes, then filter. Concentrate the filtrate, purify it by column chromatography, and dry it to obtain the product 3-(3-phenyl)phenyl-4-chlorobenzyl alcohol with a yield of 87%.

[0170] 1H NMR data: 1 H NMR(400MHz,CDCl3)δ7.68–7.59(m,4H),7.52–7.40(m,5H),7.40–7.33(m,2H),7.28(dd,J=8.2,2.3Hz,1H),4.69(s,2H),2.02(d,J=14.9Hz,1H).

[0171] Example 25

[0172] Preparation of 3-(2-methyl)phenyl-4-chlorobenzyl alcohol. The synthetic route is as follows:

[0173]

[0174] Add 0.016 mmol of bidentate pyrimidinyltriazolyl carbene palladium hydrate 3-pyridinesulfonate compound 12, 1 mmol of 3,4-dichlorobenzyl alcohol, 1.4 mmol of 2-methylphenylboronic acid, 2.4 mmol of potassium carbonate and water (5 ml) into a flask, and react at 100 °C for 23 hours; after the reaction is completed, cool, extract the reaction solution with dichloromethane three times, combine the extracted organic phases and dry them with anhydrous MgSO4 for 30 minutes, and filter; concentrate the filtrate, purify it by column chromatography and dry it to obtain the product 3-(2-methyl)phenyl-4-chlorobenzyl alcohol with a yield of 79%.

[0175] 1H NMR data: 1 H NMR(400MHz,CDCl3)δ7.43(d,J=8.2Hz,1H),7.33–7.29(m,2H),7.27–7.22(m,3H),7.19(d,J=7.9Hz,1H),4.68(s,2H),2.40(s,3H),1.94(s,1H).

[0176] Example 26

[0177] Preparation of 3-(6-fluoro-3-pyridyl)-4-chlorobenzyl alcohol. The synthetic route is as follows:

[0178]

[0179] Add 0.019 mmol of bidentate pyrimidinyltriazolyl carbene palladium hydrate 3-pyridinesulfonate compound 18, 1 mmol of 3,4-dichlorobenzyl alcohol, 1.2 mmol of 6-fluoro-3-pyridylboronic acid, 3 mmol of potassium phosphate and water (5 ml) into a flask, and react at 100 °C for 24 hours; after the reaction is completed, cool, extract the reaction solution with dichloromethane three times, combine the extracted organic phases and dry them with anhydrous MgSO4 for 30 minutes, and filter; concentrate the filtrate, purify it by column chromatography and dry it to obtain the product 3-(6-fluoro-3-pyridyl)-4-chlorobenzyl alcohol with a yield of 83%.

[0180] 1H NMR data: 11H NMR (400 MHz, CDCl3) δ 8.22–8.15 (m, 1H), 7.90 (ddd, J = 8.5, 7.6, 2.5 Hz, 1H), 7.47 (d, J = 8.8 Hz, 1H), 7.34 (d, J = 7.2 Hz, 2H), 7.01 (dd, J = 8.5, 2.8 Hz, 1H), 4.74 (s, 2H), 2.92 (s, 1H).

Claims

1. A bidentate pyrimidine-based triazolium carbene palladium hydrated 3-pyridine sulfonate compound, characterized in that, The structural formula is as follows: ； Among them, R1 is hydrogen, methyl, ethyl, methoxy, trifluoromethyl, fluoro, chloro, bromo or phenyl; R2 is methyl, ethyl, n-propyl, isopropyl, n-butyl and benzyl; the monovalent anion X is BF4 - or PF6 - .

2. A method for preparing the bidentate pyrimidinyl triazolyl carbene palladium hydrated 3-pyridine sulfonate compound according to claim 1, characterized in that, Add the bidentate pyrimidinyl triazolium salt, silver oxide, palladium salt and sodium 3-pyridinesulfonate into an organic solvent, and stir at 50-90 °C for 6-12 hours to obtain the bidentate pyrimidinyl triazolium carbene palladium hydrate 3-pyridinesulfonate compound. The synthetic route is as follows: ； Among them, the palladium salt is palladium chloride, palladium acetate or palladium tetrafluoroborate.

3. The preparation method of the bidentate pyrimidinyl triazolium carbene palladium hydrated 3-pyridine sulfonate compound according to claim 2, characterized in that, The molar ratio of the bidentate pyrimidinyl triazolium salt, silver oxide, palladium salt and sodium 3-pyridinesulfonate is 1:0.5-1:1-1.2:1-1.

1.

4. The preparation method of the bidentate pyrimidinyl triazolium carbene palladium hydrated 3-pyridine sulfonate compound according to claim 2, characterized in that, The organic solvent is toluene, 1,4-dioxane, tetrahydrofuran, acetone or dichloromethane.

5. Application of the bidentate pyrimidinyl triazolium carbene palladium hydrate 3-pyridinesulfonate compound according to claim 1 in the meta-coupling reaction of phenol or benzyl alcohol.

6. The application according to claim 5, wherein The application method is as follows: Add 3,4-dichlorophenol or 3,4-dichlorobenzyl alcohol, arylboronic acid, base and the bidentate pyrimidinyl triazolium carbene palladium hydrate 3-pyridinesulfonate compound into water, and react at 80-100 °C for 12-24 hours to obtain the product 3-aryl-4-chlorophenol or 3-aryl-4-chlorobenzyl alcohol. The synthetic route is as follows: ； Among them, n is 0 or 1, R is hydrogen, methyl, ethyl, methoxy, hydroxyl, benzyloxy, trifluoromethyl, mercapto, phenyl, fluoro, cyano, acetyl or methyl formate; Y is carbon or nitrogen.

7. The application according to claim 6, characterized in that, The molar ratio of the 3,4-dichlorophenol or 3,4-dichlorobenzyl alcohol, arylboronic acid, base and the bidentate pyrimidinyl triazolium carbene palladium hydrate 3-pyridinesulfonate compound is 1:1-1.5:1-3:0.005-0.02.

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