Synthesis method of styrene compound

Abstract

The invention provides a synthesis method of styrene compounds, and belongs to the technical field of organic synthesis reaction. The method disclosed by the invention comprises the step of reacting a phenolic compound with an alkyne compound to synthesize the styrene compound in a protective atmosphere and an alkaline solvent environment under the action of a rhodium catalyst and an instantaneous positioning group. In addition, after the reaction is finished, the obtained styrene compound is subjected to column chromatography separation and purification. Compared with a traditional synthesis method, the method is simple to operate, raw materials are easy to obtain, functional groups are good in compatibility, and a substrate is wide in application range.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic synthesis reaction, and particularly relates to a synthesis method of a styrene compound. BACKGROUND

[0002] The styrene compound is a kind of potential chiral olefin compound and important chemical intermediate, has wide application in the fields of medicine, material science and chemical industry, and can be used for synthesizing drug molecules, functional materials and key intermediates of natural products. The compound is widely present in natural products. The addition reaction of C-H bond activation to alkyne is a high-efficiency and atom-economical carbon-carbon double bond construction method, which is widely applied in drug synthesis, natural product synthesis and material chemistry. Among them, the positioning group (DG) and the transient positioning group (TDG) are two important methods of C-H bond activation. Through transition metal catalysis and chiral ligand design, the high-selective C-H bond activation and alkyne addition reaction can quickly construct the olefin structure.

[0003] The traditional synthesis method of the styrene compound depends on multiple synthesis steps, has relatively narrow functional group compatibility, and has low atom economy and step economy. For example, the Wittig reaction technology usually only utilizes the carbonyl oxygen atom of aldehyde, and has poor atom economy; the Friedel-Crafts acylation reaction technology is often long in steps and needs high temperature or polymerization inhibitor to prevent product polymerization, and has harsh conditions. In addition, the reaction environment of the traditional method often needs strong base, strong acid or high temperature condition, which is easy to damage sensitive groups, and results in low functional group compatibility.

[0004] Therefore, the technology of designing and preparing the styrene compound by means of the C-H bond activation and alkyne addition reaction to quickly construct the olefin structure still needs to be researched, and it is urgent to develop a more efficient and simple synthesis strategy of the styrene compound. SUMMARY

[0005] The application aims to provide a synthesis method of a styrene compound. The transient positioning group (TDG) is combined with the substrate through a covalent bond, has high selectivity and does not need pre-modification, and is environment-friendly. The application is based on the synergistic catalysis of a rhodium catalyst and a transient positioning group, uses phenolic compounds and alkyne compounds as reactants, and prepares the styrene compound by means of the C-H bond activation and alkyne addition reaction to quickly construct the olefin structure. The method has the advantages of cheap and easily available raw materials, simple reaction operation, high yield of the target product obtained in one step, good functional group compatibility, simple post-treatment and good application potential.

[0006] This invention provides a method for synthesizing styrene compounds, comprising: reacting phenolic compound I with alkyne compound II to generate styrene compound III under a protective atmosphere and alkaline solvent environment, in the presence of a rhodium catalyst and a transient directing group;

[0007]

[0008] Among them, R 1 With R 2 C4-C are independent of each other. 60 The aromatic group, methyl, isopropyl, fluorine atom, trifluoromethyl, trifluoromethoxy, or R 1 With R 2 To form saturated or unsaturated rings; R 3 With R 4 C4-C are independent of each other. 60 Aromatic groups, ester groups, C4-C 20 Mixed aromatic compounds.

[0009] Optionally, the phenolic compound includes one of o-cresol, 1-naphthol, 2-trifluoromethylphenol, 2,3-dimethylphenol, 4-fluoro-2-methylphenol, 5,6,7,8-tetrahydro-1-naphthol, 5-fluoro-2-methylphenol, and 2-methyl-4-isopropylphenol.

[0010] Optionally, the alkyne compound includes one of diphenylalkyne, 1,2-bis(p-tolyl)acetylene, and 1,2-bis(3,5-dimethylphenyl)acetylene.

[0011] Optionally, the equivalence ratio of the phenolic compound to the alkyne compound is 1:(1.1-1.3).

[0012] Preferably, the transient directing group is tris(dimethylamino)phosphine, and the transient directing group is 28 mol%-32 mol% of a phenolic compound.

[0013] Preferably, the rhodium catalyst is [Rh(cod)Cl]2, and the rhodium catalyst is 2.4 mol%-2.6 mol% of a phenolic compound.

[0014] Optionally, the protective atmosphere includes nitrogen or argon, and the solvent includes one of toluene, benzene, cyclohexane, and xylene.

[0015] Optionally, the alkali in the alkaline solvent environment includes one of potassium phosphate, potassium carbonate, rubidium carbonate, and cesium carbonate; and / or, the equivalence ratio of the alkali in the alkaline solvent environment to the phenolic compound is (1.8-2.2):1.

[0016] Optionally, the temperature of the reaction is 90-110°C, and the duration of the reaction is 22-26 hours. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 A chemical reaction formula for synthesizing the styrene compound according to the present application;

[0018] Figure 2 A hydrogen spectrum of the product obtained in Example 1 of the present application;

[0019] Figure 3 A carbon spectrum of the product obtained in Example 1 of the present application;

[0020] Figure 4 A hydrogen spectrum of the product obtained in Example 2 of the present application;

[0021] Figure 5 A carbon spectrum of the product obtained in Example 2 of the present application;

[0022] Figure 6 A hydrogen spectrum of the product obtained in Example 3 of the present application;

[0023] Figure 7 A carbon spectrum of the product obtained in Example 3 of the present application;

[0024] Figure 8 A hydrogen spectrum of the product obtained in Example 4 of the present application;

[0025] Figure 9 A carbon spectrum of the product obtained in Example 4 of the present application;

[0026] Figure 10 A hydrogen spectrum of the product obtained in Example 5 of the present application;

[0027] Figure 11 A carbon spectrum of the product obtained in Example 5 of the present application;

[0028] Figure 12 A hydrogen spectrum of the product obtained in Example 6 of the present application;

[0029] Figure 13 A carbon spectrum of the product obtained in Example 6 of the present application;

[0030] Figure 14 A hydrogen spectrum of the product obtained in Example 7 of the present application;

[0031] Figure 15 A carbon spectrum of the product obtained in Example 7 of the present application;

[0032] Figure 16 A hydrogen spectrum of the product obtained in Example 8 of the present application;

[0033] Figure 17The carbon spectrum of the product obtained in Example 8 of the present application;

[0034] Figure 18 The hydrogen spectrum of the product obtained in Example 9 of the present application;

[0035] Figure 19 The carbon spectrum of the product obtained in Example 9 of the present application;

[0036] Figure 20 The hydrogen spectrum of the product obtained in Example 10 of the present application;

[0037] Figure 21 The carbon spectrum of the product obtained in Example 10 of the present application. DETAILED DESCRIPTION

[0038] In order to make the objects, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be described clearly and completely below. Obviously, the described embodiments are only some but not all of the embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative work fall within the protection scope of the present application. Unless otherwise defined, the technical terms or scientific terms used herein should be understood as the common meanings thereof by those of ordinary skill in the art to which the present application belongs.

[0039] The embodiments of the present application provide a synthesis method of styrene compounds, which comprises reacting a phenolic compound I and an alkyne compound II in a protective atmosphere, an alkaline solvent environment, under the action of a rhodium catalyst and a transient positioning group to generate a styrene compound III.

[0040] Specifically, when the phenolic compound I and the alkyne compound II are reacted, the reaction equation is as follows:

[0041]

[0042] wherein, R 1 and R 2 are independently C4-C 60 aromatic groups, methyl, isopropyl, fluorine atoms, trifluoromethyl, trifluoromethoxy, or R 1 and R 2 are saturated or unsaturated rings; R 3 and R 4 are independently C4-C 60 aromatic groups, ester groups, C4-C 20 heteroaromatic groups.

[0043] In some embodiments, the phenolic compound used in the reaction includes one of o-cresol, 1-naphthol, 2-trifluoromethylphenol, 2,3-dimethylphenol, 4-fluoro-2-methylphenol, 5,6,7,8-tetrahydro-1-naphthol, 5-fluoro-2-methylphenol, 2-methyl-4-isopropylphenol.

[0044] In some embodiments, the alkyne compound used in the reaction includes one of diphenylacetylene, 1,2-di(p-tolyl)acetylene, 1,2-di(p-fluorophenyl)acetylene.

[0045] In some embodiments, the equivalent ratio of the phenolic compound to the alkyne compound used in the reaction is 1:(1.1-1.3).

[0046] In some embodiments, the transient directing group used in the reaction is tris(dimethylamino)phosphine, P(NMe2)3, and the amount of P(NMe2)3 used in the reaction is 28-32 mol% of the phenolic compound used in the reaction.

[0047] In some embodiments, the rhodium catalyst used in the reaction is [Rh(cod)Cl]2, and the amount of [Rh(cod)Cl]2 used in the reaction is 2.4-2.6 mol% of the phenolic compound used in the reaction.

[0048] In some embodiments, the protective atmosphere used in the reaction includes nitrogen, argon. In practice, the reaction in the protective atmosphere is conducive to protecting the reaction system and preventing oxidation.

[0049] In some embodiments, the solvent environment used in the reaction includes one of toluene, benzene, cyclohexane, and xylene.

[0050] In some embodiments, the base used in the basic solvent environment in the reaction includes one of potassium phosphate, potassium carbonate, rubidium carbonate, and cesium carbonate, and the equivalent ratio of the base in the basic solvent environment to the phenolic compound used in the reaction is (1.8-2.2):1. In practice, in the embodiments, potassium phosphate is preferably used to provide the basic environment, which not only provides a mild and effective basic environment during the reaction, but also facilitates the progress of the reaction.

[0051] In some embodiments, the phenolic compound and the alkyne compound are reacted at 90-110°C, and the reaction duration is 22-26 h.

[0052] In practice, after the reaction is completed, the styrene compound product is further separated and purified by silica gel column chromatography, and a mixed solvent of petroleum ether and ethyl acetate with a volume ratio of (18-22):1 is used for elution and separation. Specifically, after the reaction of the phenolic compound and the alkyne compound is completed, thin layer chromatography (TLC) is used to determine the completion of the reaction, and after the system is cooled to room temperature, silica gel column chromatography is used for separation and purification.

[0053] Embodiment 1

[0054] This example 1 provides a method for preparing (E)-2-(1,2-diphenylvinyl)-6- methylphenol by reacting o-cresol with diphenylacetylene, which comprises: in a glove box filled with nitrogen atmosphere, 1.3 mg of [Rh(cod)Cl]2(0.0025 mmol, 2.5 mol%), 5.4 uL of P(NMe2)3(0.03 mmol, 0.3 equiv.), and 42.4 mg of K3PO4(0.2 mmol, 2.0 equiv.) were added to a dry 10 mL Schlenk reaction tube with a magnetic stirrer, then 10.8 mg of o-cresol (0.1 mmol, 1.0 equiv.) and 21.3 mg of diphenylacetylene (0.12 mmol, 1.2 equiv.) were added, and finally 1 mL of anhydrous toluene was added to tighten the reaction tube and take it out of the glove box. After the reaction was carried out at 100°C for 24 h, TLC detection confirmed that the reaction was completed, and the crude product was obtained. After the system was cooled to room temperature, the crude product was separated by silica gel column chromatography, the eluent was a mixture of petroleum ether and ethyl acetate with a volume ratio of 20:1, and the product was washed with ethyl acetate, the filtrate was combined and evaporated to obtain 23.5 mg of (E)-2-(1,2-diphenylvinyl)-6-methylphenol, with a yield of 82%. The structural formula of the product is as follows:

[0055]

[0056] The nuclear magnetic hydrogen spectrum (400 MHz, CDCl3) of the product prepared in Example 1 is shown in Figure 2 The nuclear magnetic carbon spectrum (100 MHz, CDCl3) is shown in Figure 3 The structural characterization data are as follows:

[0057] 1 H NMR (400 MHz, CDCl3) δ 7.26 (dt, J = 20.0, 7.0 Hz, 5H), 7.14-7.04 (m, 5H), 7.04-6.99 (m, 2H), 6.84 (d, J = 7.4 Hz, 1H), 6.78 (t, J = 7.4 Hz, 1H), 5.04 (s, 1H), 2.16 (s, 3H); 13 CNMR (100 MHz, CDCl3) δ 150.8, 141.8, 136.6, 136.2, 130.9, 130.4, 129.0, 128.5, 128.4, 128.2, 127.8, 127.1, 125.4, 124.9, 120.7, 16.2; HRMS (ESI) calculated for C 21 H 18 NaO[(M+Na+ )]: 309.1250, found: 309.1241.

[0058] Example 2

[0059] This example 2 provides a method for preparing (E)-2-(1,2-diphenylvinyl)naphthalen-1-ol by reacting 1-naphthol with diphenylacetylene, comprising: in a glove box filled with nitrogen atmosphere, adding 1.3 mg [Rh(cod)Cl]2(0.0025 mmol, 2.5 mol%), 5.4 uL P(NMe2)3(0.03 mmol, 0.3 equiv.) and 42.4 mg K3PO4(0.2 mmol, 2.0 equiv.) into a dry 10 mL Schlenk tube with a magnetic stirrer, adding 14.4 mg 1-naphthol (0.1 mmol, 1.0 equiv.), 21.3 mg diphenylacetylene (0.12 mmol, 1.2 equiv.), and finally adding 1 mL anhydrous toluene to tighten the reaction tube and transfer out of the glove box. After the reaction is carried out at 100 °C for 24 h, the completion of the reaction is confirmed by TLC detection. After the system is cooled to room temperature, the crude product is separated by silica gel column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate with a volume ratio of 20:1, and the product is washed with ethyl acetate, the filtrate is combined and evaporated to obtain 20.3 mg (E)-2-(1,2-diphenylvinyl)naphthalen-1-ol, with a yield of 63%. The structural formula of the product is as follows:

[0060]

[0061] The nuclear magnetic hydrogen spectrum (400 MHz, CDC13) of the product prepared in example 2 is shown in Figure 4 , the nuclear magnetic carbon spectrum (100 MHz, CDC13) is shown in Figure 5 , and the specific data of the structure characterization are as follows:

[0062] 1 H NMR (400 MHz, CDC13) δ 8.22 (d, J = 8.1 Hz, 1H), 7.84 (d, J = 7.9 Hz, 1H), 7.54 - 7.44 (m, 4H), 7.41 - 7.37 (m, 2H), 7.35 - 7.31 (m, 3H), 7.29 (s, 1H), 7.17 (dd, J = 14.4, 7.1 Hz, 7H), 5.67 (s, 1H); 13C NMR (100 MHz, CDC13) δ 156.4, 154.8, 146.0, 140.1, 134.8, 129.9 127.9, 127.7, 127.4, 127.3, 127.0, 126.0, 125.7, 125.0, 116.4, 116.3, 113.1, 113.0, 28.7, 15.4; HRMS (ESI) calculated for C 24 H 18 KO[(M+K + )]: 361.0989, found: 361.0981.

[0063] Example 3

[0064] This example 3 provides a method for preparing (E)-2-(1,2-diphenylvinyl)-6- (trifluoromethyl)phenol by reacting 2-trifluoromethylphenol with diphenylacetylene, which comprises: in a glove box filled with nitrogen atmosphere, adding 1.3 mg [Rh(cod)Cl]2(0.0025 mmol, 2.5 mol%), 5.4 uL P(NMe2)3(0.03 mmol, 0.3 equiv.) and 42.4 mg K3PO4(0.2 mmol, 2.0 equiv.) into a dry 10 mL Schlenk reaction tube with a magnetic stirrer, adding 16.2 mg 2-trifluoromethylphenol (0.1 mmol, 1.0 equiv.), 21.3 mg diphenylacetylene (0.12 mmol, 1.2 equiv.), and finally adding 1 mL anhydrous toluene to tighten the reaction tube and transfer out of the glove box. After the reaction is carried out at 100°C for 24 h, the completion of the reaction is confirmed by TLC detection, and the crude product is obtained. After the system is cooled to room temperature, the crude product is separated by silica gel column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate with a volume ratio of 20:1, and the product is washed with ethyl acetate, the filtrate is combined and evaporated to obtain 19.0 mg (E)-2-(1,2-diphenylvinyl)-6-(trifluoromethyl)phenol, with a yield of 56%. The structural formula of the product is as follows:

[0065]

[0066] The nuclear magnetic hydrogen spectrum (400 MHz, CDC13) of the product prepared in example 3 is shown in Figure 6 , the nuclear magnetic carbon spectrum (100 MHz, CDC13) is shown in Figure 7 , and the specific data of the structure characterization are as follows:

[0067] 1H NMR (400 MHz, CDC13) δ 7.57 (d, J = 7.7 Hz, 1H), 7.34 (s, 4H), 7.25 (d, J = 4.5 Hz, 2H), 7.20 - 7.12 (m, 3H), 7.09 - 6.95 (m, 3H), 5.58 (s, 1H); 13 C NMR (100 MHz, CDC13) δ 150.9 (t, J = 235 Hz), 148.6, 139.0, 137.9, 137.6, 135.4, 133.5, 130.7, 129.6, 129.3, 129.1, 128.8, 128.3, 126.8, 124.8, 120.8, 21.2, 16.2; HRMS (ESI) calculated for C 21 H 16 F3O[(M+H + )]: 341.1148, found: 341.1148.

[0068] Example 4

[0069] This example 4 provides a method for preparing (E)-6-(1,2-diphenylvinyl)-2,3- dimethylphenol by reacting 2,3-dimethylphenol with diphenylacetylene, comprising: in a glove box filled with nitrogen atmosphere, 1.3 mg [Rh(cod)Cl]2(0.0025 mmol, 2.5 mol%), 5.4 uL P(NMe2)3(0.03 mmol, 0.3 equiv.) and 42.4 mg K3PO4(0.2 mmol, 2.0 equiv.) were added into a dry 10 mL Schlenk tube with a magnetic stirrer, then 12.2 mg 2,3-dimethylphenol (0.1 mmol, 1.0 equiv.) and 21.3 mg diphenylacetylene (0.12 mmol, 1.2 equiv.) were added, and finally 1 mL anhydrous toluene was added to tighten the reaction tube and transfer out of the glove box. After the reaction was carried out at 100 °C for 24 h, TLC detection confirmed that the reaction was completed, and the crude product was obtained. After the system was cooled to room temperature, the crude product was separated by silica gel column chromatography, the eluent was a mixture of petroleum ether and ethyl acetate with a volume ratio of 20:1, and the product was washed with ethyl acetate, the filtrate was combined and evaporated to obtain 22.8 mg (E)-6-(1,2-diphenylvinyl)-2,3-dimethylphenol, with a yield of 76%. The structure of the product is as follows:

[0070]

[0071] The nuclear magnetic resonance hydrogen spectrum (400 MHz, CDC13) of the product prepared in example 4 is characterized as Figure 8The shown nuclear magnetic carbon spectrum (100 MHz, CDC13) represents as Figure 9 The shown structure represents the specific data as follows:

[0072] 1 H NMR (400 MHz, CDC13) δ 7.34 - 7.22 (m, 5H), 7.14 - 7.07 (m, 4H), 7.05 (dd, J = 7.2, 2.5 Hz, 2H), 6.89 (s, 1H), 6.65 (s, 1H), 4.92 (s, 1H), 2.14 (d, J = 5.9 Hz, 6H); 13 C NMR (100 MHz, CDC13) δ 150.9, 141.8, 136.6, 136.2, 130.9, 130.5, 129.0, 128.6, 128.4, 128.2, 127.9, 127.1, 125.4, 124.9, 120.7, 29.8, 16.3; HRMS (ESI) calculated for C 22 H 21 O [(M+H + )]: 301.1587, found: 301.1595.

[0073] Example 5

[0074] This example 5 provides a method for obtaining (E)-2-(1,2-diphenylvinyl)-4- fluoro-6-methylphenol by reacting 4-fluoro-2-methylphenol with diphenylacetylene, which comprises: in a glove box filled with nitrogen atmosphere, adding 1.3 mg [Rh(cod)Cl]2(0.0025 mmol, 2.5 mol%), 5.4 uL P(NMe2)3(0.03 mmol, 0.3 equiv.) and 42.4 mg K3PO4(0.2 mmol, 2.0 equiv.) into a dry 10 mL Schlenk reaction tube with a magnetic stirrer, adding 12.6 mg 4-fluoro-2-methylphenol (0.1 mmol, 1.0 equiv.), 21.3 mg diphenylacetylene (0.12 mmol, 1.2 equiv.), and finally adding 1 mL anhydrous toluene to tighten the reaction tube and transfer out of the glove box. After the reaction is continuously carried out at 100°C for 24 h, it is confirmed by TLC detection that the reaction is completed, and the crude product is obtained. After the system is cooled to room temperature, the crude product is separated by silica gel column chromatography, the eluent is a mixed solvent of petroleum ether and ethyl acetate with a volume ratio of 20:1, and the filtrate is washed with ethyl acetate, and the solvent is evaporated to obtain 15.5 mg (E)-2-(1,2-diphenylvinyl)-4-fluoro-6-methylphenol, with a yield of 51%. The product structural formula is as follows:

[0075]

[0076] The product prepared in Example 5 was characterized by nuclear magnetic hydrogen spectrum (400 MHz, CDC13) as shown in Figure 10 The product prepared in Example 5 was characterized by nuclear magnetic hydrogen spectrum (400 MHz, CDC13) as shown in Figure 11 The product prepared in Example 5 was characterized by nuclear magnetic hydrogen spectrum (400 MHz, CDC13) as shown in

[0077] 1 H NMR (400 MHz, CDC13) δ 7.33 - 7.17 (m, 6H), 7.12 (d, J = 3.8 Hz, 4H), 7.04 (dd, J = 6.7, 2.9 Hz, 2H), 6.81 (dd, J = 8.9, 3.0 Hz, 1H), 6.58 (dd, J = 8.6, 3.0 Hz, 1H), 4.91 (s, 1H), 2.15 (s, 3H); 13 C NMR (100 MHz, CDC13) δ 156.5 (d, J = 238.6 Hz), 146.0, 140.1, 134.8, 131.1, 129.9, 128.0, 127.9, 127.7, 127.4, 127.3, 127.0, 126.0, 116.4 (d, J = 21 Hz), 113.1 (d, J = 22.5 Hz), 28.3, 15.4; HRMS (ESI) calculated for C 21 H 17 FKO [(M + K + )]: 343.0895, found: 343.0901.

[0078] Example 6

[0079] This example 6 provides a method for preparing (E)-2-(1,2-diphenylvinyl)-5,6,7,8- tetrahydronaphthalen-1-ol from 5,6,7,8-tetrahydro-1-naphthalenol and diphenylacetylene, comprising: in a glove box filled with nitrogen atmosphere, 1.3 mg [Rh(cod)Cl]2(0.0025 mmol, 2.5 mol%), 5.4 uL P(NMe2)3(0.03 mmol, 0.3 equiv.) and 42.4 mg K3PO4(0.2 mmol, 2.0 equiv.) were added into a dry 10 mL Schlenk tube with a magnetic stir bar, 14.8 mg 5,6,7,8-tetrahydro-1-naphthalenol (0.1 mmol, 1.0 equiv.) and 21.3 mg diphenylacetylene (0.12 mmol, 1.2 equiv.) were added, and finally 1 mL anhydrous toluene was added to the reaction tube and taken out of the glove box. After the reaction was carried out at 100 °C for 24 h, TLC detection confirmed that the reaction was completed, and the crude product was obtained. After the system was cooled to room temperature, the crude product was separated by silica gel column chromatography, the eluent was a mixture of petroleum ether and ethyl acetate with a volume ratio of 20:1, and the product was washed with ethyl acetate, the filtrate was combined and evaporated to obtain 26.4 mg (E)-2-(1,2-diphenylvinyl)-5,6,7,8-tetrahydronaphthalen-1-ol, with a yield of 81%. The structure of the product is as follows:

[0080]

[0081] The nuclear magnetic hydrogen spectrum (400 MHz, CDC13) of the product prepared in example 6 is shown in Figure 12 The nuclear magnetic carbon spectrum (100 MHz, CDC13) is shown in Figure 13 The structure characterization data are as follows:

[0082] 1 H NMR (400 MHz, CDC13) δ 7.33-7.29 (m, 2H), 7.28-7.20 (m, 3H), 7.14-7.04 (m, 6H), 6.73 (d, J = 7.7 Hz, 1H), 6.61 (d, J = 7.7 Hz, 1H), 5.02 (s, 1H), 2.72 (d, J = 5.2 Hz, 2H), 2.54 (d, J = 6.3 Hz, 2H), 1.73 (q, J = 3.4 Hz, 4H); 13C NMR (100 MHz, CDC13) δ 149.3, 141.2, 137.8, 136.0, 135.4, 129.2, 128.0, 127.5, 127.3, 127.0, 126.7, 126.2, 126.2, 123.3, 120.5, 76.0, 28.7, 22.1, 21.8, 21.7; HRMS (ESI) calculated for C 24 H 23 O[(M+H + )]:327..1743,found:327..1723。

[0083] Example 7

[0084] This Example 7 provides a method for preparing (E)-2-(1,2-diphenylvinyl)-3- fluoro-6-methylphenol from 5-fluoro-2-methylphenol and diphenylacetylene, comprising: in a glove box filled with nitrogen atmosphere, 1.3 mg [Rh(cod)Cl]2(0.0025 mmol, 2.5 mol%), 5.4 uL P(NMe2)3(0.03 mmol, 0.3 equiv.) and 42.4 mg K3PO4(0.2 mmol, 2.0 equiv.) were added into a dry 10 mL Schlenk tube with a magnetic stir bar, then 12.6 mg 5-fluoro-2-methylphenol (0.1 mmol, 1.0 equiv.) and 21.3 mg diphenylacetylene (0.12 mmol, 1.2 equiv.) were added, finally 1 mL anhydrous toluene was added and the reaction tube was tightly capped and taken out of the glove box. After the reaction was carried out at 100 °C for 24 h, TLC detection confirmed that the reaction was completed, and the crude product was obtained. After the system was cooled to room temperature, the crude product was separated by silica gel column chromatography, the eluent was a mixture of petroleum ether and ethyl acetate with a volume ratio of 20:1, and the product was washed with ethyl acetate, the filtrate was combined and evaporated to obtain 19.8 mg (E)-2-(1,2-diphenylvinyl)-3-fluoro-6-methylphenol, with a yield of 65%. The structure of the product is as follows:

[0085]

[0086] The nuclear magnetic hydrogen spectrum (400 MHz, CDC13) of the product prepared in Example 7 is shown in Figure 14 , the nuclear magnetic carbon spectrum (100 MHz, CDC13) is shown in Figure 15 , and the structure characterization data are as follows:

[0087] 1H NMR (400 MHz, CDC13) δ 7.33 - 7.30 (m, 2H), 7.29 - 7.22 (m, 4H), 7.12 (dd, J = 5.0, 1.8 Hz, 3H), 7.08 - 7.01 (m, 3H), 6.56 (t, J = 8.5 Hz, 1H), 5.18 (s, 1H), 2.10 (s, 3H); 13 C NMR (100 MHz, CDC13) δ 158.6 (d, J = 242 Hz), 150.4, 139.5, 134.9, 129.9, 129.8, 129.6, 127.7, 127.6, 127.5, 127.3, 127.1, 125.3, 112.9, 119.17, 112.9 (d, J = 19.6 Hz), 106.2 (d, J = 21 Hz), 28.7, 14.67; HRMS (ESI) calculated for C 21 H 17 FKO [(M + K + )]: 343.0895, found: 343.0897.

[0088] Example 8

[0089] This example 8 provides a method for obtaining (E)-2-(1,2-diphenylvinyl)-4- isopropyl-6-methylphenol by reacting 2-methyl-4-isopropylphenol with diphenylacetylene, comprising: in a glove box filled with nitrogen atmosphere, adding 1.3 mg [Rh(cod)Cl]2(0.0025 mmol, 2.5 mol%), 5.4 uL P(NMe2)3(0.03 mmol, 0.3 equiv.) and 42.4 mg K3PO4(0.2 mmol, 2.0 equiv.) into a dry 10 mL Schlenk reaction tube with a magnetic stirrer, adding 15.0 mg of 2-methyl-4-isopropylphenol (0.1 mmol, 1.0 equiv.), 21.3 mg of diphenylacetylene (0.12 mmol, 1.2 equiv.), and finally adding 1 mL of anhydrous toluene to tighten the reaction tube and transfer it out of the glove box. After the reaction was carried out at 100°C for 24h, TLC detection confirmed that the reaction was completed, and the crude product was obtained. After the system cooled to room temperature, the crude product was separated by silica gel column chromatography, the eluent was a mixture of petroleum ether and ethyl acetate with a volume ratio of 20:1, and the product was washed with ethyl acetate, the filtrate was combined and evaporated to obtain 22.8 mg of (E)-2-(1,2-diphenylvinyl)-4-isopropyl-6-methylphenol, with a yield of 76%. The product structure is as follows:

[0090]

[0091] The proton NMR (400 MHz, CDC13) of the product prepared in Example 8 is shown in Figure 1, the carbon NMR (100 MHz, CDC13) is shown in Figure 2, and the structure characterization data are as follows: Figure 16 Figure 17

[0092] 1 H NMR (400 MHz, CDC13) δ 7.34 - 7.22 (m, 5H), 7.14 - 7.07 (m, 4H), 7.05 (dd, J = 7.2, 2.5 Hz, 2H), 6.89 (s, 1H), 6.65 (s, 1H), 4.92 (s, 1H), 2.14 (d, J = 5.9 Hz, 6H); 13 C NMR (100 MHz, CDC13) δ 150.94, 141.76, 136.63, 136.24, 130.90, 130.54, 129.04, 128.63, 128.39, 128.18, 127.85, 127.07, 125.42, 124.93, 120.69, 77.39, 77.07, 76.75, 29.76, 16.26; HRMS (ESI) calculated for C 22 H 21 O [(M+H + )]: 301.1587, found: 301.1595.

[0093] Example 9

[0094] ​​This example 9 provides a method for preparing (E)-2-(1,2-di-p-tolylethenyl)-6- methylphenol by reacting o-cresol with 1,2-di(p-tolyl)acetylene, comprising: in a glove box filled with nitrogen atmosphere, 1.3 mg of [Rh(cod)Cl]2(0.0025 mmol, 2.5 mol%), 5.4 uL of P(NMe2)3(0.03 mmol, 0.3 equiv.), and 42.4 mg of K3PO4(0.2 mmol, 2.0 equiv.) were added to a dry 10 mL Schlenk reaction tube with a magnetic stirrer, 10.8 mg of o-cresol (0.1 mmol, 1.0 equiv.) and 24.7 mg of 1,2-di(p-tolyl)acetylene (0.12 mmol, 1.2 equiv.) were added, and finally 1 mL of anhydrous toluene was added to the reaction tube and taken out of the glove box. After the reaction was carried out at 100°C for 24 h, TLC detection confirmed that the reaction was completed, and the crude product was obtained. After the system cooled to room temperature, the crude product was separated by silica gel column chromatography, the eluent was a mixture of petroleum ether and ethyl acetate with a volume ratio of 20:1, and the product was washed with ethyl acetate, the filtrate was combined and evaporated to obtain 27.0 mg of (E)-2-(1,2-di-p-tolylethenyl)-6-methylphenol, with a yield of 86%. The structure of the product is as follows:

[0095]

[0096] The nuclear magnetic hydrogen spectrum (400 MHz, CDC13) of the product prepared in Example 9 is shown in Figure 18 The nuclear magnetic carbon spectrum (100 MHz, CDC13) is shown in Figure 19 The structure characterization data are as follows:

[0097] 1 H NMR (400 MHz, CDC13) δ 7.25 (d, J = 7.9 Hz, 3H), 7.17-7.09 (m, 4H), 6.97 (s, 4H), 6.91 (d, J = 7.1 Hz, 1H), 6.87-6.81 (m, 1H), 5.18 (s, 1H), 2.34 (s, 3H), 2.26 (s, 3H), 2.23 (s, 3H); 13 C NMR (100 MHz, CDC13) δ 150.0, 138.0, 136.9, 136.6, 134.4, 132.5, 129.7, 128.5, 128.3, 128.1, 127.8, 127.3, 125.8, 119.5, 28.7, 20.2, 20.1, 15.2; HRMS (ESI) calculated for C 23 H 22KO[(M+K + )]: 353.1302, found: 353.1297.

[0098] Example 10

[0099] This Example 10 provides a method for preparing (E)-2-[l,2-bis(3,5- dimethylphenyl)vinyl]-6-methylphenol by reacting o-cresol with 1,2-bis(3,5- dimethylphenyl)acetylene, comprising: in a glove box filled with nitrogen atmosphere, 1.3 mg [Rh(cod)Cl]2(0.0025 mmol, 2.5 mol%), 5.4 uL P(NMe2)3(0.03 mmol, 0.3 equiv.) and 42.4 mg K3PO4(0.2 mmol, 2.0 equiv.) were added into a dry 10 mL Schlenk tube with a magnetic stir bar, followed by 10.8 mg o-cresol (0.1 mmol, 1.0 equiv.) and 28.1 mg 1,2-bis(3,5-dimethylphenyl)acetylene (0.12 mmol, 1.2 equiv.), and finally 1 mL anhydrous toluene was added to the reaction tube and taken out of the glove box. After the reaction was carried out at 100 °C for 24 h, TLC detection confirmed that the reaction was completed, and the crude product was obtained. After the system was cooled to room temperature, the crude product was separated by silica gel column chromatography, the eluent was a mixture of petroleum ether and ethyl acetate with a volume ratio of 20: 1, and the product was washed with ethyl acetate, the filtrate was combined and evaporated to obtain 28.0 mg (E)-2-[l,2-bis(3,5-dimethylphenyl)vinyl]-6-methylphenol, with a yield of 82%. The structural formula of the product is as follows:

[0100]

[0101] The nuclear magnetic hydrogen spectrum (400 MHz, CDC13) of the product prepared in Example 10 is shown in Table 1, and the nuclear magnetic carbon spectrum (100 MHz, CDC13) is shown in Table 2, and the structural characterization data are as follows: Figure 20 Figure 21

[0102] 1 H NMR (400 MHz, CDC13) δ 7.14 (d, J = 6.9 Hz, 1H), 7.08 (s, 1H), 7.00-6.87 (m, 4H), 6.84 (t, J = 7.4 Hz, 1H), 6.79 (s, 1H), 6.66 (s, 2H), 5.17 (s, 1H), 2.28 (s, 6H), 2.23 (s, 3H), 2.13 (s, 6H); 13 ​​C NMR (100 MHz, CDC13) δ 150.9, 141.9, 138.0, 137.5, 136.3, 136.18, 130.5, 130.4, 129.8, 129.4, 128.3, 126.9, 124.9, 120.5, 21.4, 21.2, 16.2; HRMS (ESI) calculated for C 25 H 27 O [(M+H + )]: 343.2056, found: 343.2049.

[0103] While the embodiments of the application have been illustrated and described in detail, it will be readily apparent to those skilled in the art that various modifications and changes can be made to the embodiments without departing from the scope and spirit of the application as described in the claims. Moreover, the application described herein can have other embodiments and be practiced or carried out in various ways.

Claims

1. A method for synthesizing a styrenic compound, characterized by, The application relates to a method for preparing a phenylethylene compound III. The phenolic compound comprises one of o-cresol, 1-naphthol, 2-trifluoromethylphenol, 2,3-dimethylphenol, 4-fluoro-2-methylphenol, 5,6,7,8-tetrahydro-1-naphthol, 5-fluoro-2-methylphenol and 2-methyl-4-isopropylphenol. wherein R 1 2 are independently of each other a C4-C 60 aromatic radical, methyl, isopropyl, fluorine atom, trifluoromethyl, trifluoromethoxy, or R 1 2 is a saturated or unsaturated ring; R 3 4 are independently of each other a C4-C 60 aromatic radical, ester radical, C4-C 20 heteroaromatic radical.​​​ 2. The method of synthesis of claim 1, wherein, The alkyne compound comprises one of diphenylacetylene, 1,2-di(p-tolyl)acetylene and 1,2-bis(3,5-dimethylphenyl)acetylene.

3. The method of synthesis of claim 1, wherein, The equivalent ratio of the phenolic compound to the alkyne compound is 1:(1.1-1.3).

4. The method of synthesis of claim 1, wherein, The transient positioning group is tris(dimethylamine)phosphine; and / or, the transient positioning group is 28mol%-32mol% of the phenolic compound.

5. The method of synthesis of claim 1, wherein, The rhodium catalyst is [Rh(cod)Cl]2; and / or, the rhodium catalyst is 2.4mol%-2.6mol% of the phenolic compound.

6. The method of synthesis of claim 1, wherein, The protective atmosphere comprises nitrogen and argon; and / or, the solvent comprises one of toluene, benzene, cyclohexane and xylene.

7. The method of synthesis of claim 1, wherein, The base in the alkaline solvent environment comprises one of potassium phosphate, potassium carbonate, rubidium carbonate and cesium carbonate; and / or, the equivalent ratio of the base in the alkaline solvent environment to the phenolic compound is (1.8-2.2):

1.

8. The method of synthesis of claim 1, wherein, The reaction temperature is 90-110 DEG C; and / or, the reaction duration is 22-26 hours.

9. The method of synthesis of claim 1, wherein, ​

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