Aryl acetylene derivative as well as preparation method and application thereof

Abstract

The invention relates to the technical field of synthesis of aryl acetylene derivatives, in particular to an aryl acetylene derivative as well as a preparation method and application thereof. Comprising the following steps: by taking pentamethylcyclopentadienyl carbonyl cobalt diiodide as a metal catalyst, jointly dissolving N-(substituted phenyl) pivalamide, an alkyne bromide derivative, the metal catalyst, a first silver salt additive and a second silver salt additive in 1, 2-dichloroethane, and performing hydrocarbon activation reaction to obtain an aryl acetylene derivative; wherein the first silver salt additive is silver trifluoromethanesulfonate, silver tetrafluoroborate or silver hexafluoroantimonate; and the second silver salt additive is silver carbonate or silver acetate. According to the preparation method of the aryl acetylene derivative, the aryl acetylene derivative can be efficiently and rapidly synthesized in one step, and the technical problems that traditional reaction conditions are harsh and operation is complex are solved. The method has the advantages of low cost, high yield, simplicity and convenience in operation and no pollution, and has a potential industrial application prospect.

Description

Technical Field

[0001] The present invention relates to the technical field of synthesis of aryl acetylene derivatives, and in particular to an aryl acetylene derivative and a preparation method and application thereof. Background Art

[0002] Arylene, as an important structural skeleton in organic molecules, is not only widely present in natural products but also serves as a key building block in organic synthesis, chemical biology, and materials science. Therefore, developing efficient methods for the synthesis of arylene derivatives has long attracted much attention.

[0003] The traditional method for synthesizing aryl acetylene derivatives mainly relies on the palladium-catalyzed Sonogashira coupling reaction of aryl halides and terminal alkynes. Although this method can prepare aryl acetylene derivatives, it has significant defects: (1) It relies on precious metal palladium catalysts, and the high cost seriously restricts industrial application; (2) The halide raw materials are highly toxic and have great environmental hazards, which violates the principles of green chemistry; (3) The yield of the target product is low when electron-deficient alkynes react with aryl halides, and the main by-product is alkyne dimer.

[0004] In addition, aryl acetylene derivatives can be prepared via the decarboxylative coupling reaction of propargyl acids with aryl halides. However, this method has multiple limitations: the need for prefunctionalized substrates, reliance on oxidants, harsh reaction conditions, limited substrate compatibility, and poor functional group tolerance. Summary of the Invention

[0005] To address the shortcomings of the existing technology, the present invention provides an aryl acetylene derivative, its preparation method, and its application. Using N-(substituted phenyl)-pivalamide and an alkynyl bromide derivative as raw materials, and pentamethylcyclopentadienylcarbonylcobalt diiodide as a metal catalyst, the N-(substituted phenyl)-pivalamide, alkynyl bromide derivative, metal catalyst, a first silver salt additive, and a second silver salt additive are dissolved in 1,2-dichloroethane. The aryl acetylene derivative is obtained through a hydrocarbon activation reaction. This preparation method eliminates the need for a pre-functionalization step and directly activates the inert C-H bond. It also avoids the use of precious palladium and toxic halides, significantly reducing costs and environmental impact. The reaction conditions are mild, requiring no specialized equipment, and the process is simple and yields excellent results. The resulting series of novel aryl acetylene compounds demonstrate promising application potential and provide an innovative solution for industrial production.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is: The first object of the present invention is to provide a method for preparing the above-mentioned aryl acetylene derivative, comprising the following steps: Using pentamethylcyclopentadienylcarbonylcobalt diiodide as a metal catalyst, N-(substituted phenyl)-pivalamide, an alkynyl bromide derivative, the metal catalyst, a first silver salt additive, and a second silver salt additive were dissolved in 1,2-dichloroethane. A hydrocarbon activation reaction was performed to obtain an aryl acetylene derivative. The metal catalyst exhibited the highest catalytic activity in 1,2-dichloroethane. The reaction was difficult to proceed in toluene, acetonitrile, or dimethyl sulfoxide (DMSO) as solvents, resulting in a yield of 0. When trifluoroethanol was used as the solvent, the yield of the aryl acetylene derivative was only 35%.

[0007] The reaction equation is: .

[0008] Among them, R 1 R is selected from hydrogen, C1-C4 alkyl, halogen, C1-C6 alkoxy, trifluoromethyl, nitro or methoxycarbonyl; 2 The first silver salt additive is selected from silver trifluoromethanesulfonate, silver tetrafluoroborate or silver hexafluoroantimonate; and the second silver salt additive is selected from silver carbonate or silver acetate.

[0009] Preferably, the hydrocarbon activation reaction is carried out at 70° C. to 90° C. in an air atmosphere for 10 to 12 hours.

[0010] Preferably, the molar ratio of the alkynyl bromide derivative to N-(substituted phenyl) pivalamide is 1.4-1.6:1.

[0011] Preferably, the molar ratio of the first silver salt additive, the second silver salt additive, and N-(substituted phenyl) pivalamide is 0.2-0.3:0.5-0.7:1.

[0012] Preferably, N-(substituted phenyl)pvaleramide is selected from N-phenylpvaleramide, N-(3-methylphenyl)pvaleramide, N-(4-methylphenyl)pvaleramide, N-(4-tert-butylphenyl)pvaleramide, N-(4-methoxyphenyl)pvaleramide, N-(4-fluorophenyl)pvaleramide, N-(4-chlorophenyl)pvaleramide, N-(4-bromophenyl)pvaleramide, N-(4-iodophenyl)pvaleramide, N-(4-trifluoromethylphenyl)pvaleramide, N-(4-nitrophenyl)pvaleramide or N-(4-methoxycarbonylphenyl)pvaleramide.

[0013] Preferably, the alkynyl bromide derivative is selected from phenyl bromoethynyl, 1-(bromoethynyl)-2-methylbenzene, 1-(bromoethynyl)-3-methylbenzene, 1-(bromoethynyl)-3-chlorobenzene, 1-(bromoethynyl)-4-methylbenzene, 4-(bromoethynyl)-1,1'-biphenyl, 1-(bromoethynyl)-4-methoxybenzene, 1-(bromoethynyl)-4-fluorobenzene, 1-(bromoethynyl)-4-chlorobenzene, (2-bromoethynyl)triisopropylsilane or 1-bromo-1 octyne.

[0014] Preferably, the column chromatography conditions are a 200-300 mesh silica gel column, and the eluent is a mixture of petroleum ether and ethyl acetate.

[0015] The second object of the present invention is to provide an aryl acetylene derivative prepared by the above preparation method, wherein the structural formula of the aryl acetylene derivative is as follows: ; Among them, R 1 R is selected from hydrogen, C1-C4 alkyl, halogen, C1-C6 alkoxy, trifluoromethyl, nitro or methoxycarbonyl; 2 The substituent of the substituted phenyl group is selected from a C1-C6 alkyl group, a triisopropylsilylethynyl group, a phenyl group or a substituted phenyl group, wherein the substituent of the substituted phenyl group is a C1-C4 alkyl group, a halogen atom, a phenyl group or a C1-C4 alkoxy group.

[0016] Preferably, the aryl acetylene derivative is selected from 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 or .

[0017] The third object of the present invention is to provide the use of the above-mentioned compound in the preparation of indole compounds.

[0018] Preferably, the indole compound is N-(pivaloyl)-2-phenylindole.

[0019] Compared with the prior art, the present invention has the following beneficial effects: 1. The present invention provides a method for preparing an aryl acetylene derivative, comprising the following steps: a reaction formula is as follows: using pentamethylcyclopentadienylcarbonylcobalt diiodide as a metal catalyst, dissolving N-(substituted phenyl) pivalamide, an acetylene bromide derivative, a metal catalyst, a first silver salt additive, and a second silver salt additive in 1,2-dichloroethane, and subjecting the mixture to a carbon-hydrogen activation reaction to obtain the aryl acetylene derivative; ; Among them, R 1 R is selected from hydrogen, C1-C4 alkyl, halogen, C1-C6 alkoxy, trifluoromethyl, nitro or methoxycarbonyl; 2 The first silver salt additive is selected from a C1-C6 alkyl group, a triisopropylsilylethynyl group, a phenyl group, or a substituted phenyl group, wherein the substituent of the substituted phenyl group is a C1-C4 alkyl group, a halogen atom, a phenyl group, or a C1-C4 alkoxy group; the first silver salt additive is silver trifluoromethanesulfonate, silver tetrafluoroborate, or silver hexafluoroantimonate; and the second silver salt additive is silver carbonate or silver acetate. The present method for preparing aryl acetylene derivatives eliminates the need for a pre-functionalization step and can directly activate inert C-H bonds. This method avoids the use of precious metal palladium and toxic halides, significantly reducing costs and environmental impact. The reaction conditions are mild, no special equipment is required, the operation is simple, and excellent yields are achieved, effectively overcoming the shortcomings of existing technologies.

[0020] 2. The aryl acetylene derivatives of the present invention are used in the preparation of indole compounds, which can achieve a one-step, efficient and rapid synthesis of indole derivatives and show important application potential in the field of organic synthesis. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of N-(2-(phenylethynyl)phenyl)-pivalamide prepared in Example 1 of the present invention.

[0022] Figure 2 This is the carbon NMR spectrum of N-(2-(phenylethynyl)phenyl)-pivalamide prepared in Example 1 of the present invention.

[0023] Figure 3 This is the hydrogen nuclear magnetic resonance spectrum of N-(4-(tert-butyl)-2-(phenylethynyl)phenyl)-pivalamide prepared in Example 4 of the present invention.

[0024] Figure 4 This is the carbon NMR spectrum of N-(4-(tert-butyl)-2-(phenylethynyl)phenyl)-pivalamide prepared in Example 4 of the present invention. DETAILED DESCRIPTION

[0025] The following will clearly and completely describe the technical solution of the present invention in conjunction with the data in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0026] It should be noted that the professional terms used in the present invention are only for the purpose of describing specific embodiments and are not intended to limit the scope of protection of the present invention. Unless otherwise specified, the various raw materials, reagents, instruments and equipment used in the following embodiments of the present invention can be purchased from the market or prepared by existing methods.

[0027] In the prior art, the method for synthesizing aryl acetylene derivatives mainly relies on the palladium-catalyzed Sonogashira coupling reaction of aryl halides and terminal alkynes. Although this method can prepare aryl acetylene derivatives, it has significant defects: (1) It relies on precious metal palladium catalysts, and the high cost seriously restricts industrial application; (2) The halide raw materials are highly toxic and have great environmental hazards, which violates the principles of green chemistry; (3) The yield of the target product is low when electron-deficient alkynes react with aryl halides, and the main by-product is alkyne dimer.

[0028] In addition, aryl acetylene derivatives can be prepared via the decarboxylative coupling reaction of propargyl acids with aryl halides. However, this method has multiple limitations: the need for prefunctionalized substrates, reliance on oxidants, harsh reaction conditions, limited substrate compatibility, and poor functional group tolerance.

[0029] In view of the problems existing in the above-mentioned prior art, the present invention provides a method for preparing an aryl acetylene derivative, comprising the following steps: Pentamethylcyclopentadienylcarbonylcobalt diiodide is used as a metal catalyst, N-(substituted phenyl) pivalamide, acetylene bromide derivative, metal catalyst, first silver salt additive and second silver salt additive are dissolved in 1,2-dichloroethane, and then a carbon-hydrogen activation reaction is performed to obtain an aryl acetylene derivative; the reaction equation is: ; Among them, R 1 R is selected from hydrogen, C1-C4 alkyl, halogen, C1-C6 alkoxy, trifluoromethyl, nitro or methoxycarbonyl; 2 The first silver salt additive is selected from C1-C6 alkyl, triisopropylsilylethynyl, phenyl or substituted phenyl, wherein the substituent of the substituted phenyl is C1-C4 alkyl, halogen atom, phenyl or C1-C4 alkoxy; the first silver salt additive is silver trifluoromethanesulfonate, silver tetrafluoroborate or silver hexafluoroantimonate; and the second silver salt additive is silver carbonate or silver acetate.

[0030] To address the problems of precious metal dependence and high costs in existing technologies, the present invention uses a cheap cobalt catalyst (pentamethylcyclopentadienylcarbonylcobalt diiodide) to replace palladium, combined with a double silver salt synergistic catalytic system, to significantly reduce catalyst costs and break through the cost bottleneck of industrialization.

[0031] In response to the raw material toxicity and environmental risk issues in the existing technology, the present invention avoids the use of halogenated aromatic hydrocarbons by directly activating the inert C-H bond of N-aryl amide, and uses silver carbonate to efficiently remove bromine from acetylenic bromide, eliminating toxic halides at the source. The reaction process meets the requirements of green chemistry.

[0032] To address the problems of low reaction efficiency and harsh conditions in the existing technology, the present invention achieves a breakthrough through a double silver salt division of labor activation mechanism and air atmosphere operation: silver trifluoromethanesulfonate removes iodine from the cobalt catalyst, improving catalytic activity; silver carbonate simultaneously debrominates to promote the formation of alkynes; and C-H alkynylation is completed in a single step under air conditions without the need for pre-functionalization or inert gas protection. This has wide substrate applicability and solves the problems of traditional methods such as harsh conditions and low yields of electron-deficient substrates.

[0033] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments: Example 1 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-phenyl-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcarbonylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of phenylacetyl bromide and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 45.5 mg of N-(2-(phenylethynyl)phenyl)-pivalamide as a light yellow solid. After drying under vacuum, the yield was calculated to be 82% and the purity was 99.9%.

[0034] 1 H NMR (400mHz, CDCl3): δ 8.49 (d, J = 8.4 Hz, 1H), 8.46 (s, 1H), 7.54-7.50 (m, 3H), 7.40-7.34 (m, 4H), 7.07 (t, J = 7.6 Hz, 1H), 1.37 (s, 9H); 13 C{ 1H} NMR (100mHz, CDCl3): δ 176.6, 139.1, 131.5, 131.3, 129.8, 128.9,128.6, 123.2, 122.3, 119.0, 111.9, 96.4, 84.4, 40.1, 27.7.

[0035] Specifically, the hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum of N-(2-(phenylethynyl)phenyl)tivalamide are as follows: Figure 1 and Figure 2 shown.

[0036] Among them, the chemical structural formula of N-(2-(phenylethynyl)phenyl)tivalamide is: .

[0037] Example 2 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-(3-methylphenyl)-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcarbonylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of phenylacetyl bromide and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 48.3 mg of N-(5-methyl-2-(phenylethynyl)phenyl)-pivalamide as a white solid. After drying under vacuum, the yield was calculated to be 83% and the purity was 99.9%.

[0038] 1 H NMR (400mHz, CDCl3): δ 8.43 (s, 1H), 8.37 (s, 1H), 7.53-7.50 (m,2H), 7.40-7.37 (m, 4H), 6.88 (d, J = 7.8 Hz, 1H), 2.38 (s, 3H), 1.37 (s, 9H); 13 C{ 1H} NMR (100mHz, CDCl3): δ 176.6, 140.3, 138.9, 131.2, 128.6, 128.5,124.0, 122.4, 119.6, 109.0, 95.8, 84.6, 40.1, 27.6, 21.9; HRMS (ESI,m / z)calcd for C 20 H 21 NONa [M + Na] + 314.1515, found 314.1505.

[0039] Among them, the chemical structural formula of N-(5-methyl-2-(phenylethynyl)phenyl)pivalamide is: .

[0040] Example 3 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-(4-methylphenyl)-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of phenylacetyl bromide and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 48.9 mg of N-(4-methyl-2-(phenylethynyl)phenyl)-pivalamide as a light yellow oil. After drying under vacuum, the yield was calculated to be 84% and the purity was 99.9%.

[0041] 1 H NMR (400mHz, CDCl3): δ 8.37-8.35 (m, 2H), 7.54-7.51 (m, 2H), 7.40-7.38 (m, 3H), 7.32 (s, 1H), 7.17 (d, J = 8.4 Hz, 1H), 2.31 (s, 3H), 1.36 (s,9H); 13 C{ 1H} NMR (100mHz, CDCl3): δ 176.4, 136.7, 132.7, 131.7, 131.3, 130.5,128.7, 128.6, 122.4, 119.0, 111.8, 96.0, 84.6, 40.0, 27.6, 20.6; HRMS (ESI,m / z) calcd for C 20 H 22 NO [M + H] + 292.1696, found 292.1707.

[0042] Among them, the chemical structural formula of N-(4-methyl-2-(phenylethynyl)phenyl)pivalamide is: .

[0043] Example 4 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-(4-tert-butylphenyl)-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of phenylacetyl bromide and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 h. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 54.0 mg of N-(4-(tert-butyl)-2-(phenylethynyl)phenyl)-pivalamide as a yellow solid. After drying under vacuum, the yield was calculated to be 81% and the purity was 99.9%.

[0044] 1 H NMR (400mHz, CDCl3): δ 8.40-8.38 (m, 2H), 7.56-7.52 (m, 3H), 7.41-7.38 (m, 4H), 1.36 (s, 9H), 1.32 (s, 9H); 13 C{ 1 H} NMR (100mHz, CDCl3): δ 176.4,146.1, 136.7, 131.3, 128.8, 128.6, 128.3, 127.0, 122.4, 118.8, 111.5, 95.8,84.9, 40.0, 34.3, 31.2, 27.6; HRMS (ESI,m / z) calcd for C23 H 28 NO [M + H] + 334.2165, found 334.2163.

[0045] Specifically, the hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum of N-(4-(tert-butyl)-2-(phenylethynyl)phenyl)tivalamide are as follows: Figure 3 and Figure 4 shown.

[0046] Among them, the chemical structural formula of N-(4-(tert-butyl)-2-(phenylethynyl)phenyl)-pivalamide is: .

[0047] Example 5 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-(4-methoxyphenyl)-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcarbonylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of phenylacetyl bromide and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 53.4 mg of N-(4-methoxy-2-(phenylethynyl)phenyl)-pivalamide as a light yellow solid. After drying under vacuum, the yield was calculated to be 87% and the purity was 99.9%.

[0048] 1 H NMR (400mHz, CDCl3): δ 8.36 (d, J = 9.1 Hz, 1H), 8.26 (s, 1H), 7.53 (d, J = 3.3 Hz, 2H), 7.39-7.38 (m, 3H), 7.03 (d, J = 2.5 Hz, 1H), 6.93-6.91(m, 1H), 3.80 (s, 3H), 1.35 (s, 9H); 13 C{ 1H} NMR (100mHz, CDCl3): δ 176.2,155.1, 132.9, 131.3, 128.9, 128.6, 122.2, 120.7, 115.9, 115.8, 113.1, 96.1,84.4, 55.5, 39.9, 27.6; HRMS (ESI,m / z) calcd for C 20 H 22 NO2[M + H]+ 308.1645, found 308.1636.

[0049] Among them, the chemical structural formula of N-(4-methoxy-2-(phenylethynyl)phenyl)pivalamide is: .

[0050] Example 6 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-(4-fluorophenyl)-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcarbonylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of phenylacetyl bromide and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 41.9 mg of N-(4-fluoro-2-(phenylethynyl)phenyl)-pivalamide as a light yellow solid. After drying under vacuum, the yield was calculated to be 71% and the purity was 99.9%.

[0051] 1 H NMR (400mHz, CDCl3): δ 8.46-8.43 (m, 1H), 8.34 (s, 1H), 7.54-7.52(m, 2H), 7.41-7.40 (m, 3H), 7.19 (dd, J = 8.5, 2.8 Hz, 1H), 7.08-7.03 (m,1H), 1.36 (s, 9H); 13 C{ 1H} NMR (100mHz, CDCl3): δ 176.4, 157.9 (d, J = 241.8Hz), 135.5 (d, J = 2.6 Hz), 131.4, 129.2, 128.7, 121.8, 120.7 (d, J = 8.1Hz), 117.7 (d, J = 24.1 Hz), 116.6 (d, J = 21.8 Hz), 113.5 (d, J = 9.5 Hz), 97.1, 83.4 (d, J = 3.1 Hz), 40.0, 27.6; 19 F NMR (376mHz, CDCl3): δ –118.9; HRMS(ESI,m / z) calcd for C 19 H 19 FNO [M + H] + 296.1445, found 296.1436.

[0052] Among them, the chemical structural formula of N-(4-fluoro-2-(phenylethynyl)phenyl)pivalamide is: .

[0053] Example 7 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-(4-chlorophenyl)-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcarbonylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of phenylacetyl bromide and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 45.4 mg of N-(4-chloro-2-(phenylethynyl)phenyl)-pivalamide as a yellow solid. After drying under vacuum, the yield was calculated to be 73% and the purity was 99.9%.

[0054] 1H NMR (400mHz, CDCl3): δ 8.45 (d, J = 9.0 Hz, 1H), 8.39 (s, 1H), 7.53-7.51 (m, 2H), 7.47 (d, J = 2.4 Hz, 1H), 7.41-7.39 (m, 3H), 7.30 (dd, J =8.9, 2.3 Hz, 1H), 1.36 (s, 9H); 13 C{ 1 H} NMR (100mHz, CDCl3): δ 176.6, 137.7,131.4, 130.9, 129.7, 129.2, 128.7, 127.9, 121.8, 120.2, 113.5, 97.4, 83.1,40.1, 27.6; HRMS (ESI,m / z) calcd for C 19 H 19 ClNO [M + H] + 312.1150, found312.1150.

[0055] Among them, the chemical structural formula of N-(4-chloro-2-(phenylethynyl)phenyl)tivalamide is: .

[0056] Example 8 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-(4-bromophenyl)-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of phenylacetyl bromide and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 52.5 mg of N-(4-bromo-2-(phenylethynyl)phenyl)-pivalamide as a light yellow solid. After drying under vacuum, the yield was calculated to be 74% and the purity was 99.9%.

[0057] 1H NMR (400mHz, CDCl3): δ 8.41-8.38 (m, 2H), 7.62 (d, J = 2.3 Hz, 1H), 7.53-7.51 (m, 2H), 7.46-7.40 (m, 4H), 1.36 (s, 9H); 13 C{ 1 H} NMR (100mHz, CDCl3): δ 176.6, 138.1, 133.7, 132.6, 131.4, 129.2, 128.7, 121.7, 120.4,115.3, 113.9, 97.5, 83.0, 40.1, 27.6; HRMS (ESI,m / z) calcd for C 19 H 19 BrNO [M +H] + 356.0645, found 356.0649.

[0058] Among them, the chemical structural formula of N-(4-bromo-2-(phenylethynyl)phenyl)tivalamide is: .

[0059] Example 9 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-(4-iodophenyl)-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of phenylacetyl bromide and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 58.8 mg of N-(4-iodo-2-(phenylethynyl)phenyl)-pivalamide as a light yellow solid. After drying under vacuum, the yield was calculated to be 73% and the purity was 99.9%.

[0060] 1H NMR (400mHz, CDCl3): δ 8.39 (s, 1H), 8.27 (d, J = 8.8 Hz, 1H), 7.81 (d, J = 1.9 Hz, 1H), 7.62 (dd, J = 8.8, 1.9 Hz, 1H), 7.53-7.50 (m, 2H), 7.41-7.39 (m, 3H), 1.35 (s, 9H); 13 C{ 1 H} NMR (100mHz, CDCl3): δ 176.6, 139.5, 138.8,138.4, 131.3, 129.2, 128.6, 121.7, 120.7, 114.1, 97.6, 85.5, 82.7, 40.2,27.5; HRMS (ESI,m / z) calcd for C 19 H 19 INO [M + H] + 404.0506, found 404.0503.

[0061] Among them, the chemical structural formula of N-(4-iodo-2-(phenylethynyl)phenyl)tivalamide is: .

[0062] Example 10 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-(4-trifluoromethylphenyl)-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcarbonylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of phenylacetyl bromide and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 h. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 41.4 mg of N-(2-(phenylethynyl)-4-(trifluoromethyl)phenyl)-pivalamide as a light yellow solid. After drying under vacuum, the yield was calculated to be 60% and the purity was 99.9%.

[0063] 1H NMR (400mHz, CDCl3): δ 8.64 (d, J = 8.8 Hz, 1H), 8.57 (s, 1H), 7.77(s, 1H), 7.60-7.53 (m, 3H), 7.43-7.41 (m, 3H), 1.38 (s, 9H); 13 C{ 1 H} NMR (100mHz, CDCl3): δ 176.9, 141.7, 131.5, 129.4, 128.7, 128.6 (q, J = 3.8 Hz), 126.6 (q, J = 3.7 Hz), 125.2 (q, J = 32.8 Hz), 123.7 (q, J = 270.1 Hz),121.6, 118.8, 112.2, 97.7, 83.0, 40.3, 27.6; 19 F NMR (376mHz, CDCl3): δ –62.3;HRMS (ESI,m / z) calcd for C 20 H 19 F3NO [M + H] + 346.1413, found 346.1402.

[0064] Among them, the chemical structural formula of N-(2-(phenylethynyl)-4-(trifluoromethyl)phenyl)-pivalamide is: .

[0065] Example 11 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-(4-nitrophenyl)-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcarbonylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of phenylacetyl bromide and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 40:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 36.1 mg of N-(4-nitro-2-(phenylethynyl)phenyl)-pivalamide as a light yellow solid. After drying under vacuum, the yield was calculated to be 56% and the purity was 99.9%.

[0066] 1H NMR (400mHz, CDCl3): δ 8.70-8.68 (m, 2H), 8.37 (s, 1H), 8.20 (d, J= 8.9 Hz, 1H), 7.55 (d, J = 7.2 Hz, 2H), 7.44-7.42 (m, 3H), 1.38 (s, 9H); 13 C{ 1 H} NMR (100mHz, CDCl3): δ 177.0, 144.1, 142.5, 131.5, 129.7, 128.8, 127.0,125.2, 121.1, 118.5, 112.5, 98.5, 82.1, 40.5, 27.5; HRMS (ESI,m / z) calcd forC 19 H 19 N2O3[M + H] + 323.1390, found 323.1386.

[0067] Among them, the chemical structural formula of N-(4-nitro-2-(phenylethynyl)phenyl)pivalamide is: .

[0068] Example 12 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-(4-methoxycarbonylphenyl)-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcarbonylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of phenylacetyl bromide and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 30:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 48.3 mg of methyl 3-(phenylethynyl)-4-pivalamidobenzoate as a white solid. After drying under vacuum, the yield was calculated to be 72% and the purity was 99.9%.

[0069] 1H NMR (400mHz, CDCl3): δ 8.61 (s, 1H), 8.58 (d, J = 8.8 Hz, 1H), 8.19 (d, J = 1.8 Hz, 1H), 8.01 (dd, J = 8.7, 1.8 Hz, 1H), 7.54-7.53 (m, 2H), 7.40-7.38 (m, 3H), 3.90 (s, 3H), 1.37 (s, 9H); 13 C{ 1 H} NMR (100mHz, CDCl3): δ 176.8,166.0, 142.6, 133.1, 131.4, 131.2, 129.2, 128.6, 124.7, 121.8, 118.2, 111.8,97.1, 83.4, 52.1, 40.3, 27.5; HRMS (ESI,m / z) calcd for C 21 H 22 NO3[M + H] + 336.1594, found 336.1599.

[0070] Among them, the chemical structural formula of methyl 3-(phenylethynyl)-4-p-valeramidobenzoate is: .

[0071] Example 13 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-phenyl-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcarbonylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of 1-(bromoethynyl)-2-methylbenzene and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 40.8 mg of N-(2-(o-tolylethynyl)phenyl)-pivalamide as a light yellow oil. After drying under vacuum, the yield was calculated to be 70% and the purity was 99.9%.

[0072] 1H NMR (400mHz, CDCl3): δ 8.50 (d, J = 8.3 Hz, 1H), 8.44 (s, 1H), 7.53-7.48 (m, 2H), 7.36 (t, J = 7.6 Hz, 1H), 7.32-7.20 (m, 2H), 7.23-7.20 (m,1H), 7.07 (t, J = 7.5 Hz, 1H), 2.54 (s, 3H), 1.36 (s, 9H); 13 C{ 1 H} NMR (100mHz, CDCl3): δ 140.0, 138.9, 131.7, 131.6, 129.7, 129.7, 128.9, 125.8, 123.2, 122.0, 119.1, 112.2, 95.3, 88.1, 40.1, 27.6, 20.8; HRMS (ESI,m / z) calcd forC 20 H 21 NONa [M + Na] + 314.1515, found 314.1505.

[0073] Among them, the chemical structural formula of N-(2-(o-tolylethynyl)phenyl)pivalamide is: .

[0074] Example 14 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-phenyl-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcarbonylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of 1-(bromoethynyl)-3-methylbenzene and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 41.9 mg of N-(2-(m-tolylethynyl)phenyl)-pivalamide as a light yellow oil. After drying under vacuum, the yield was calculated to be 72% and the purity was 99.9%.

[0075] 1H NMR (400mHz, CDCl3): δ 8.48-8.46 (m, 2H), 7.48 (d, J = 7.6 Hz, 1H), 7.34-7.31 (m, 3H), 7.28-7.24 (m, 1H), 7.19-7.18 (m, 1H), 7.04 (t, J = 7.4 Hz,1H), 2.36 (s, 3H), 1.35 (s, 9H); 13 C{ 1 H} NMR (100mHz, CDCl3): δ 176.6, 139.1,138.3, 131.9, 131.5, 129.8, 129.7, 128.5, 128.4, 123.1, 122.1, 119.0, 112.0,96.6, 84.0, 40.1, 27.6, 21.2; HRMS (ESI,m / z) calcd for C 20 H 21 NONa [M + Na] + 314.1515, found 314.1505.

[0076] Among them, the chemical structural formula of N-(2-(m-tolylethynyl)phenyl)pivalamide is: .

[0077] Example 15 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-phenyl-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcarbonylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of 1-(bromoethynyl)-3-chlorobenzene and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 48.5 mg of N-(2-((3-chlorophenyl)ethynyl)phenyl)-pivalamide as a light yellow solid. After drying under vacuum, the yield was calculated to be 78% and the purity was 99.9%.

[0078] 1H NMR (400mHz, CDCl3): δ 8.48 (d, J = 8.3 Hz, 1H), 8.37 (s, 1H), 7.50-7.48 (m, 2H), 7.41-7.29 (m, 4H), 7.07 (t, J = 7.5 Hz, 1H), 1.37 (s, 9H); 13 C{ 1 H} NMR (100mHz, CDCl3): δ 176.5, 139.2, 134.4, 131.6, 131.1, 130.1,129.8, 129.4, 129.1, 123.9, 123.2, 119.2, 111.4, 94.8, 85.6, 40.1, 27.6; HRMS(ESI,m / z) calcd for C 19 H 19 ClNO [M + H] + 312.1150, found 312.1150.

[0079] Among them, the chemical structural formula of N-(2-((3-chlorophenyl)ethynyl)phenyl)pivalamide is: .

[0080] Example 16 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-phenyl-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcarbonylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of 1-(bromoethynyl)-4-methylbenzene and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 38.4 mg of N-(2-(p-tolylethynyl)phenyl)-pivalamide as a light yellow solid. After drying under vacuum, the yield was calculated to be 66% and the purity was 99.9%.

[0081] 1H NMR (400mHz, CDCl3): δ 8.49-8.47 (m, 2H), 7.49 (d, J = 7.0 Hz, 1H), 7.43 (d, J = 7.9 Hz, 2H), 7.34 (t, J = 7.6 Hz, 1H), 7.20 (d, J = 7.8 Hz, 2H),7.06 (t, J = 7.3 Hz, 1H), 2.39 (s, 3H), 1.36 (s, 9H); 13 C{ 1 H} NMR (100mHz, CDCl3): δ 176.6, 139.1, 139.0, 131.4, 131.2, 129.6, 129.3, 123.1, 119.2, 119.0, 112.1, 96.6, 83.7, 40.1, 27.6, 21.5; HRMS (ESI,m / z) calcd forC 20 H 21 NONa [M + Na] + 314.1515, found 314.1505.

[0082] Among them, the chemical structural formula of N-(2-(p-tolylethynyl)phenyl)pivalamide is: .

[0083] Example 17 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-phenyl-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcarbonylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of 4-(bromoethynyl)-1,1'-biphenyl and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 h. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 55.1 mg of N-(2-((1,1'-biphenyl)-4-ethynyl)phenyl)-pivalamide as a yellow solid. After drying under vacuum, the yield was calculated to be 78% and the purity was 99.9%.

[0084] 1H NMR (400mHz, CDCl3): δ 8.54-8.50 (m, 2H), 7.66-7.60 (m, 6H), 7.54(d, J = 7.5 Hz, 1H), 7.48 (t, J = 7.4 Hz, 2H), 7.41-7.36 (m, 2H), 7.09 (t, J= 7.4 Hz, 1H), 1.41 (s, 9H); 13 C{ 1 H} NMR (100mHz, CDCl3): δ 176.6, 141.6,140.0, 139.1, 131.7, 131.5, 129.8, 128.9, 127.8, 127.2, 126.9, 123.2, 121.1,119.1, 112.0, 96.3, 85.1, 40.1, 27.6; HRMS (ESI,m / z) calcd for C 25 H 23 NONa [M +Na] + 376.1672, found 376.1674.

[0085] Among them, the chemical structure of N-(2-((1,1'-biphenyl)-4-ethynyl)phenyl)pivalamide is: .

[0086] Example 18 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-phenyl-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcarbonylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of 1-(bromoethynyl)-4-methoxybenzene and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 39.3 mg of N-(2-((4-methoxyphenyl)ethynyl)phenyl)-pivalamide as a white solid. After drying under vacuum, the yield was calculated to be 64% and the purity was 99.9%.

[0087] 1H NMR (400mHz, CDCl3): δ 8.48-8.46 (m, 2H), 7.48-7.45 (m, 3H), 7.33(t, J = 7.4 Hz, 1H), 7.05 (t, J = 7.5 Hz, 1H), 6.91 (d, J = 8.6 Hz, 2H), 3.84(s, 3H), 1.36 (s, 9H); 13 C{ 1 H} NMR (100mHz, CDCl3): δ 176.6, 160.1, 139.0,132.9, 131.3, 129.4, 123.1, 119.0, 114.3, 114.2, 112.3, 96.5, 83.1, 55.3,40.1, 27.6; HRMS (ESI,m / z) calcd for C 20 H 22 NO2[M + H] + 308.1645, found 308.1636.

[0088] Among them, the chemical structural formula of N-(2-((4-methoxyphenyl)ethynyl)phenyl)pivalamide is: .

[0089] Example 19 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-phenyl-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcarbonylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of 1-(bromoethynyl)-4-fluorobenzene and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 44.3 mg of N-(2-((4-fluorophenyl)ethynyl)phenyl)-pivalamide as a white solid. After drying under vacuum, the yield was calculated to be 75% and the purity was 99.9%.

[0090] 1H NMR (400mHz, CDCl3): δ 8.47 (d, J = 8.3 Hz, 1H), 8.40 (s, 1H), 7.52-7.47 (m, 3H), 7.35 (t, J = 7.8 Hz, 1H), 7.11-7.04 (m, 3H), 1.36 (s, 9H); 13 C{ 1 H} NMR (100mHz, CDCl3): δ 176.5, 162.8 (d, J = 249.3 Hz), 139.1, 133.3(d, J = 8.4 Hz), 131.5, 129.8, 123.2, 119.1, 118.4 (d, J = 3.5 Hz), 116.0 (d,J = 22.1 Hz), 111.8, 95.2, 84.2, 40.1, 27.6; 19 F NMR (376mHz, CDCl3): δ –109.6;HRMS (ESI,m / z) calcd for C 19 H 19 FNO [M + H] + 296.1445, found 296.1436.

[0091] Among them, the chemical structural formula of N-(2-((4-fluorophenyl)ethynyl)phenyl)pivalamide is: .

[0092] Example 20 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-phenyl-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcarbonylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of 1-(bromoethynyl)-4-chlorobenzene and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume) mixture of petroleum ether and ethyl acetate as eluent to obtain 51.6 mg of N-(2-((4-chlorophenyl)ethynyl)phenyl)-pivalamide as a light yellow solid. After drying under vacuum, the yield was calculated to be 83% and the purity was 99.9%.

[0093] 1H NMR (400mHz, CDCl3): δ 8.47 (d, J = 8.3 Hz, 1H), 8.38 (s, 1H), 7.49-7.44 (m, 3H), 7.37-7.35 (m, 3H), 7.06 (t, J = 7.5 Hz, 1H), 1.36 (s, 9H); 13 C{ 1 H} NMR (100mHz, CDCl3): δ 176.5, 139.1, 135.0, 132.5, 131.5, 130.0,129.0, 123.2, 120.7, 119.2, 111.6, 95.2, 85.4, 40.1, 27.6; HRMS (ESI,m / z)calcd for C 19 H 18 ClNONa [M + Na] + 334.0969, found 334.0958.

[0094] Among them, the chemical structural formula of N-(2-((4-chlorophenyl)ethynyl)phenyl)pivalamide is: .

[0095] Example 21 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-phenyl-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcarbonylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of (2-bromoethynyl)triisopropylsilane and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using an 80:1 (volume) mixture of petroleum ether and ethyl acetate as eluent to obtain 30.7 mg of N-(2-((triisopropylsilyl)ethynyl)phenyl)-pivalamide as a colorless oil. After drying under vacuum, the yield was calculated to be 43% and the purity was 99.9%.

[0096] 1H NMR (400mHz, CDCl3): δ 8.47 (d, J = 8.3 Hz, 1H), 8.37 (s, 1H), 7.45 (dd, J = 7.7, 1.3 Hz, 1H), 7.35-7.30 (m, 1H), 7.01 (td, J = 7.6, 1.0 Hz, 1H),1.33 (s, 9H), 1.15-1.14 (m, 21H); 13 C{ 1 H} NMR (100mHz, CDCl3): δ 176.8, 139.4,132.5, 129.8, 123.0, 118.9, 112.1, 102.4, 98.4, 40.1, 27.6, 18.7, 11.3; HRMS(ESI,m / z) calcd for C 22 H 35 NOSiNa [M + Na] + 380.2380, found 380.2391.

[0097] Among them, the chemical structural formula of N-(2-((triisopropylsilyl)ethynyl)phenyl)pivalamide is: .

[0098] Example 22 A method for preparing an aryl acetylene derivative comprises the following steps: 0.2 mmol of N-phenyl-pivalamide, 0.02 mmol of pentamethylcyclopentadienylcarbonylcobalt diiodide, 0.05 mmol of silver trifluoromethanesulfonate, and 1.2 mmol of silver carbonate were added to a sealed tube equipped with a magnetic stirrer. Under air, 0.3 mmol of 1-bromo-1-octyne and 1.0 mL of 1,2-dichloroethane were added to the tube. The tube was tightened and the reaction was carried out at 80°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 50:1 (volume ratio) mixture of petroleum ether and ethyl acetate as eluent to obtain 34.2 mg of N-(2-(1-octynyl)phenyl)-pivalamide as a yellow oil. After drying under vacuum, the yield was calculated to be 60% and the purity was 99.9%.

[0099] 1H NMR (400mHz, CDCl3): δ 8.44-8.40 (m, 2H), 7.36 (d, J = 7.6 Hz, 1H), 7.29 (d, J = 7.8 Hz, 1H), 6.99 (t, J = 7.6 Hz, 1H), 2.50 (t, J = 7.1 Hz, 2H),1.66-1.60 (m, 4H), 1.48-1.41 (m, 4H), 1.34 (s, 9H), 0.90 (t, J = 6.7 Hz, 3H); 13 C{ 1 H} NMR (100mHz, CDCl3): δ 176.6, 139.1, 131.4, 128.9, 123.0, 118.7,112.7, 100.0, 97.9, 40.1, 31.3, 28.8, 28.7, 27.6, 22.5, 19.5, 14.0; HRMS(ESI,m / z) calcd for C 19 H 28 NO [M + H] + 286.2165, found 286.2173.

[0100] Among them, the chemical structural formula of N-(2-(1-octynyl)phenyl)tivalamide is: .

[0101] Examples 1 to 22 of the present invention all prepared aryl acetylene derivatives. The aryl acetylene derivatives of Examples 1 to 22 can all be used as raw materials to prepare indole compounds. The following uses N-(2-(phenylethynyl)phenyl)-pivalamide of Example 1 as an example to apply it to the preparation of indole compounds, as follows: 0.3 mmol of N-(2-(phenylethynyl)phenyl)pivalamide and 0.012 mmol of platinum tetrachloride were dissolved in 5.0 mL of dichloromethane. The mixture was heated under reflux for 24 h, cooled to room temperature, and the solvent was removed by rotary evaporation. The residue was separated by column chromatography using a 60:1 by volume mixture of petroleum ether and ethyl acetate as eluent to obtain 63.1 mg of N-(pivaloyl)-2-phenylindole as a colorless oily liquid. After drying under vacuum conditions, the calculated yield was 76% and the purity was 99.9%.

[0102] 1H NMR (400 MHz, CDCl3): δ 7.55 (d, J = 7.6 Hz, 1H), 7.46 (d, J = 7.2Hz, 2H), 7.37-7.28 (m, 4H), 7.20-7.10 (m, 2H), 6.61 (s, 1H), 0.89 (s, 9H); 13 C{ 1 H} NMR (100 MHz, CDCl3): δ 187.3, 139.4, 137.2, 133.9, 129.0, 128.3, 128.2,127.7, 123.4, 121.5, 120.6, 111.2, 104.6, 45.1, 27.9.

[0103] Among them, the chemical structural formula of N-(pivaloyl)-2-phenylindole is: .

[0104] In summary, according to Examples 1 to 22, the preparation method of the present invention can obtain aryl acetylene derivatives with different substituents by changing N-(substituted phenyl) pivalamide and alkynyl bromide derivatives, and the preparation steps are simple and easy to operate. The yield of the obtained aryl acetylene derivatives is medium to good and the purity is 99.9%. This further demonstrates that the preparation method of the present invention can efficiently and quickly synthesize aryl acetylene derivatives in one step, solving the technical problems of traditional harsh reaction conditions and complex operations.

[0105] In addition, the use of the aryl acetylene derivatives of the present invention in the preparation of indole compounds can achieve a one-step, efficient, and rapid synthesis of indole derivatives, showing important application potential in the field of organic synthesis.

[0106] It should be noted that when numerical ranges are mentioned in the present invention, it should be understood that both endpoints of each numerical range and any value between the two endpoints can be selected. Since the steps and methods used are the same as those in the embodiments, in order to avoid redundancy, the present invention describes preferred embodiments. Although preferred embodiments of the present invention have been described, those skilled in the art will be able to make additional changes and modifications to these embodiments once they understand the basic inventive concepts. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the present invention.

Claims

1. A method for preparing an aryl acetylene derivative, characterized in that: The steps include: Using pentamethylcyclopentadienylcarbonylcobalt diiodide as a metal catalyst, N-(substituted phenyl) pivalamide, an alkynyl bromide derivative, a metal catalyst, a first silver salt additive and a second silver salt additive are dissolved in 1,2-dichloroethane, and an aryl acetylene derivative is obtained through a carbon-hydrogen activation reaction. The reaction equation is: ; Among them, R 1 is selected from hydrogen, a C1-C4 alkyl group, a halogen atom, a C1-C6 alkoxy group, a trifluoromethyl group, a nitro group or a methoxycarbonyl group; R 2 is selected from a C1-C6 alkyl group, a triisopropylsilylethynyl group, a phenyl group or a substituted phenyl group, wherein the substituent of the substituted phenyl group is a C1-C4 alkyl group, a halogen atom, a phenyl group or a C1-C4 alkoxy group; The first silver salt additive is selected from silver trifluoromethanesulfonate, silver tetrafluoroborate or silver hexafluoroantimonate; The second silver salt additive is selected from silver carbonate or silver acetate.

2. The method for preparing an aryl acetylene derivative according to claim 1, wherein The conditions for the hydrocarbon activation reaction are: in an air atmosphere, at 70°C to 90°C for 10h to 12h.

3. The method for preparing an aryl acetylene derivative according to claim 1, wherein The molar ratio of the alkynyl bromide derivative to N-(substituted phenyl) pivalamide is 1.4-1.6:

1.

4. The method for preparing an aryl acetylene derivative according to claim 1, wherein The molar ratio of the first silver salt additive, the second silver salt additive and N-(substituted phenyl) pivalamide is 0.2-0.3:0.5-0.7:

1.

5. The method for preparing an aryl acetylene derivative according to claim 1, wherein N-(substituted phenyl)pvaleramide is selected from N-phenylpvaleramide, N-(3-methylphenyl)pvaleramide, N-(4-methylphenyl)pvaleramide, N-(4-tert-butylphenyl)pvaleramide, N-(4-methoxyphenyl)pvaleramide, N-(4-fluorophenyl)pvaleramide, N-(4-chlorophenyl)pvaleramide, N-(4-bromophenyl)pvaleramide, N-(4-iodophenyl)pvaleramide, N-(4-trifluoromethylphenyl)pvaleramide, N-(4-nitrophenyl)pvaleramide or N-(4-methoxycarbonylphenyl)pvaleramide.

6. The method for preparing an aryl acetylene derivative according to claim 1, wherein: The alkynyl bromide derivative is selected from phenyl bromoethynyl, 1-(bromoethynyl)-2-methylbenzene, 1-(bromoethynyl)-3-methylbenzene, 1-(bromoethynyl)-3-chlorobenzene, 1-(bromoethynyl)-4-methylbenzene, 4-(bromoethynyl)-1,1'-biphenyl, 1-(bromoethynyl)-4-methoxybenzene, 1-(bromoethynyl)-4-fluorobenzene, 1-(bromoethynyl)-4-chlorobenzene, (2-bromoethynyl)triisopropylsilane or 1-bromo-1octyne.

7. An aryl acetylene derivative, characterized in that Prepared by the preparation method according to any one of claims 1 to 6, the structural formula of the aryl acetylene derivative is as follows: ; Among them, R 1 is selected from hydrogen, a C1-C4 alkyl group, a halogen atom, a C1-C6 alkoxy group, a trifluoromethyl group, a nitro group or a methoxycarbonyl group; R 2 The substituent of the substituted phenyl group is selected from a C1-C6 alkyl group, a triisopropylsilylethynyl group, a phenyl group or a substituted phenyl group, wherein the substituent of the substituted phenyl group is a C1-C4 alkyl group, a halogen atom, a phenyl group or a C1-C4 alkoxy group.

8. The aryl acetylene derivative according to claim 7, characterized in that Aryl acetylene derivatives are selected from 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 or .

9. Use of the aryl acetylene derivative according to claim 7 in the preparation of indole compounds.

10. The use according to claim 9, characterized in that The indole compound is N-(pivaloyl)-2-phenylindole.

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