Preparation method of mono-or mono-diaryl aromatic hydrocarbon derivative

Abstract

The invention discloses a preparation method of a mono-or mono-diaryl aromatic hydrocarbon derivative, and belongs to the technical field of organic synthesis. According to the method disclosed by the invention, the trimeric cyclodextrin is successfully synthesized by virtue of an efficient and green CuAAC reaction; according to the method, beta CD3-Cu (I) is generated after trimeric cyclodextrin and trace Cu (I) are coordinated, under the mild reaction condition, the trace beta CD3-Cu (I) can take an alkyne compound and dihalogenated aromatic hydrocarbon as substrates to catalyze the reaction to obtain a high-yield monosubstituted product with the proportion as high as 100%, and the method is suitable for industrial production. The reaction of the alkyne compound and the dihalogenated aromatic hydrocarbon can be selectively catalyzed only by ingeniously avoiding using a bimetallic catalyst and adding additional ligands, and an effective method is provided for modification of intermediates of small organic molecule compounds and selective catalysis of the reaction of the alkyne compound and the dihalogenated aromatic hydrocarbon. The mono / diaryl coupling product obtained by the invention enriches conjugated intermediates with potential biological activity and optical activity, and provides a teraromatic hydrocarbon derivative with various and novel structures for application in the fields of natural-like products, liquid crystal materials, organic light-emitting devices and the like.

Description

Technical Field

[0001] The invention relates to a preparation method of mono- or mono- and di-aromatic aromatic hydrocarbon derivatives, belonging to the technical field of organic synthesis. Background Art

[0002] Palladium or copper-catalyzed coupling reactions play a key role in the synthesis of mono- and diaryl coupling products. By precisely controlling the site selectivity and chemical selectivity of dihalogenated aromatics, valuable synthetic structural templates can be constructed, thereby increasing the complexity of the molecule. However, achieving selective cross-coupling reactions of dihalogenated aromatic compounds containing the same halogen to construct CC bonds has always been a very challenging task. The current method requires not only the input of equal amounts of two different metals, but also the addition of an appropriate amount of ligand, and is usually carried out at high temperatures. Summary of the Invention

[0003] In order to overcome the problems in the background technology, the object of the present invention is to provide a method for preparing mono- or mono-bis-aryl aromatic hydrocarbon derivatives.

[0004] In order to achieve the above object, the present invention is implemented through the following technical solutions:

[0005] A method for preparing a mono- or mono-diaryl aromatic derivative comprises the following steps:

[0006] (1) dissolving β-cyclodextrin in a sodium hydroxide solution, adding p-toluenesulfonyl chloride and stirring, then filtering the filtrate, adjusting the pH of the filtrate to neutral with dilute hydrochloric acid, and then filtering to obtain mono-6-TOS-based cyclodextrin;

[0007] (2) dissolving mono-6-TOS-based cyclodextrin in N,N-dimethylformamide, then adding sodium azide, reacting under a protective atmosphere, and then adding acetone to precipitate mono-6-azidocyclodextrin;

[0008] (3) Mono-6-azidocyclodextrin was dissolved in N,N-dimethylformamide, copper sulfate, sodium ascorbate and tripropargylamine were added in sequence, reacted under a protective atmosphere, and then acetone was added to precipitate trimerized cyclodextrin;

[0009] (4) adding trimeric cyclodextrin to acetonitrile, then adding CuI to react under a protective atmosphere, centrifuging and separating the solid, washing the solid with acetonitrile, and vacuum drying to obtain trimeric cyclodextrin catalyst βCD3-Cu(I);

[0010] (5) adding an alkyne compound, a dihalogenated aromatic hydrocarbon, βCD3-Cu(I), and a carbonate into a solvent to react and obtain a reaction product system;

[0011] (6) The reaction product system is concentrated under reduced pressure to obtain a crude product, and the crude product is separated and purified by silica gel column chromatography to obtain a mono- or mono- and di-aryl-substituted aromatic derivative.

[0012] The mono-6-TOS-based cyclodextrin is mono-6-O-(p-toluenesulfonyl)-β-cyclodextrin; the mono-6-azido cyclodextrin is mono-6-O-(azido)-β-cyclodextrin.

[0013] More preferably, the molar ratio of β-cyclodextrin to sodium hydroxide is 1:(1-10), the solid-liquid ratio of β-cyclodextrin to sodium hydroxide solution is (0.01-1.0) g:1 mL; and the molar ratio of β-cyclodextrin to p-toluenesulfonyl chloride is 1:1-10.

[0014] More preferably, the solid-liquid ratio of the mono-6-TOS-based cyclodextrin to N,N-dimethylformamide is (0.01-0.5) g:1 mL; and the molar ratio of the mono-6-TOS-based cyclodextrin to sodium azide is 1:1-10.

[0015] More preferably, in step (2), the reaction temperature is 50-100° C., the reaction time is 18-48 h, and the protective gas is nitrogen or an inert gas.

[0016] More preferably, the solid-liquid ratio of mono-6-azidocyclodextrin to N,N-dimethylformamide is (0.01-0.09) g:1 mL, the molar ratio of mono-6-azidocyclodextrin to copper sulfate is 1:(0.005-0.20), the molar ratio of mono-6-azidocyclodextrin to sodium ascorbate is 1:(0.006-0.80), and the molar ratio of mono-6-azidocyclodextrin to tripropargylamine is 1:(0.01-0.9).

[0017] More preferably, in step (3), the reaction temperature is 50-100° C., the reaction time is 18-48 h, and the protective gas is nitrogen or an inert gas.

[0018] More preferably, the solid-liquid ratio of the trimerized cyclodextrin to acetonitrile is (0.005-0.2) g:1 mL, and the mass ratio of the trimerized cyclodextrin to CuI is 1:0.1-2.

[0019] More preferably, in step (4), the reaction temperature is room temperature, the reaction time is 12-16 hours, and the protective gas is nitrogen or an inert gas.

[0020] More preferably, the alkyne compound is phenylacetylene, 4-methoxyphenylacetylene, 4-ethoxyphenylacetylene, 4-ethoxycarbonylphenylacetylene, 2-trifluoromethylphenylacetylene, 3-trifluoromethylphenylacetylene, 4-trifluoromethylphenylacetylene, 2-methylphenylacetylene, 3-methylphenylacetylene, 4-methylphenylacetylene, 2-fluorophenylacetylene, 2-chlorophenylacetylene, 2-bromophenylacetylene, 4-fluorophenylacetylene, 4-chlorophenylacetylene or 4-bromophenylacetylene.

[0021] When the alkyne compound is 4-methoxyphenylacetylene, 4-ethoxyphenylacetylene, 4-ethoxycarbonylphenylacetylene, 2-trifluoromethylphenylacetylene, 3-trifluoromethylphenylacetylene or 4-trifluoromethylphenylacetylene, a monoaryl-substituted aromatic derivative is produced in a ratio of 100%.

[0022] When the alkyne compound is phenylacetylene, 2-methylphenylacetylene, 3-methylphenylacetylene, 4-methylphenylacetylene, 2-fluorophenylacetylene, 2-chlorophenylacetylene, 2-bromophenylacetylene, 4-fluorophenylacetylene, 4-chlorophenylacetylene or 4-bromophenylacetylene, monoaryl-substituted aromatic derivatives and diaryl-substituted aromatic derivatives are generated, wherein the proportion of monoaryl-substituted aromatic derivatives is much higher than that of diaryl-substituted aromatic derivatives, being more than 80%, and the monoaryl-substituted aromatic derivatives and diaryl-substituted aromatic derivatives are easy to separate.

[0023] More preferably, the structural formula of the dihalogenated aromatic hydrocarbon is one of the following structural formulas:

[0024]

[0025] wherein Y is F, Cl, Br or I.

[0026] More preferably, the carbonate is Cs2CO3, Na2CO3 or K2CO3.

[0027] More preferably, the solvent is N,N-dimethylformamide, dimethyl sulfoxide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone or 1,4-dioxane.

[0028] More preferably, in step (5), the molar ratio of the alkyne compound, dihalogenated aromatic hydrocarbon and carbonate is 1:(0.5-1.5):(0.5-3.5), the reaction temperature is 90-130° C., and the reaction time is 6-24 h.

[0029] The mass ratio of the amount of the alkyne compound to the trimerized cyclodextrin catalyst is 0.5-2 mmol:10-30 mg.

[0030] More preferably, the mono- or mono-bis-aryl-substituted aromatic hydrocarbon derivative is a mono-aryl-substituted aromatic hydrocarbon derivative or a mixture of a mono-aryl-substituted aromatic hydrocarbon derivative and a bis-aryl-substituted aromatic hydrocarbon derivative;

[0031] The structural formula of the monoaryl-substituted aromatic derivative is

[0032] The structural formula of the bisaryl substituted aromatic derivative is

[0033] wherein Y is F, Cl, Br or I; and R is phenyl, 4-methoxyphenyl, 4-ethoxycarbonylphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-naphthyl, 1-H-5-indolyl, 2-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, 4-fluorophenyl, 4-chlorophenyl or 4-bromophenyl.

[0034] The principle of using βCD3-Cu(I) as a catalyst to prepare mono- / di-aryl-substituted aromatic derivatives is as follows: the present invention successfully synthesizes trimerized cyclodextrin by means of the efficient and green CuAAC reaction; after trimerized cyclodextrin is coordinated with CuI, under mild reaction conditions, a trace amount of βCD3-Cu(I) can catalyze the reaction using alkyne compounds and dihalogenated aromatic hydrocarbons as substrates to obtain monosubstituted products with high yields and a ratio of up to 100% monosubstituted products. This cleverly avoids the use of bimetallic catalysts and the addition of additional ligands in order to selectively catalyze the reaction of alkyne compounds and dihalogenated aromatic hydrocarbons, providing an effective method for the modification of intermediates of organic small molecule compounds and the selective catalysis of the reaction of alkyne compounds and dihalogenated aromatic hydrocarbons. In the reaction, the cyclodextrin cavity and Cu coordination of βCD3-Cu(I) play a crucial role in the selective catalysis of alkyne compounds and dihalogenated aromatics. The narrow end of the cyclodextrin cavity is connected to the Cu-coordinated triazole ring and is encapsulated inside the cyclodextrin, while the wide end remains open. When the Cu coordination exists, the cavity only allows one molecule of the reaction substrate to enter the interior for reaction. Once the monosubstituted product or the mono- and disubstituted products are generated and detach from the cavity, the cyclodextrin cavity continues to play its key role, providing continuous support for subsequent reactions.

[0035] Beneficial effects of the present invention:

[0036] (1) The present invention utilizes the cyclodextrin cavity and Cu coordination of the βCD3-Cu(I) catalyst to synergize. The narrow end of the cyclodextrin cavity is connected to the triazole ring coordinated by Cu and is encapsulated inside the cyclodextrin, while the wide end remains open. When the Cu coordination exists, the cavity only allows one molecule of the reaction substrate for preparing the mono- / poly-aryl-substituted aromatic derivative to enter the interior for reaction. Once the monosubstituted product is generated, it will dissociate from the cyclodextrin cavity. The cyclodextrin cavity then continues to play a key role as a molecular transport channel, providing continuous support for subsequent reactions. In addition, the βCD3-Cu(I) catalyst of the present invention can regulate the proportion of monosubstituted products to obtain monosubstituted products with higher utilization value. The present invention opens up a new approach for the specific and selective coupling reaction of symmetrical or asymmetrical dihalogenated aromatic compounds.

[0037] (2) The present invention has a wide range of substrate adaptability, mild conditions, simple operation, and is suitable for large-scale production. Monoaryl-substituted aromatic derivatives can be used as important intermediates for constructing complex terphenyl molecular structures. The terphenyl derivatives obtained by further coupling enrich the conjugated intermediates with potential biological and optical activities, providing structurally diverse and novel terphenyl derivatives for applications in the fields of natural-like products, liquid crystal materials, and organic light-emitting diodes. DETAILED DESCRIPTION

[0038] The present invention will be further described in detail below with reference to specific embodiments, but the protection scope of the present invention is not limited thereto.

[0039] Example 1

[0040] The preparation method of βCD3-Cu(I) in the embodiment of the present invention comprises the following steps:

[0041] 1) 44 mmol of β-cyclodextrin (50 g) was dissolved in 1000 mL of sodium hydroxide (16 g, 200 mmol) solution and stirred with 184 mmol of p-toluenesulfonyl chloride (35 g) for 30 minutes. The filtrate was then filtered and the pH was adjusted to neutral with dilute hydrochloric acid. The product, mono-6-TOS-ylcyclodextrin, was then filtered to obtain a white solid.

[0042] 2) Dissolve 3.2 mmol of mono-6-TOS-cyclodextrin in 30 mL of N,N-dimethylformamide (DMF), then add 12.8 mmol of sodium azide. Under a protective atmosphere, heat to 50°C and react for 48 hours. Then, add acetone dropwise to precipitate mono-6-azidocyclodextrin as a white solid.

[0043] 3) Dissolving mono-6-azidocyclodextrin in N,N-dimethylformamide (DMF), adding copper sulfate, sodium ascorbate, and tripropargylamine in sequence, heating to 80° C. under a nitrogen atmosphere and reacting for 28 hours, then adding acetone dropwise to precipitate solid trimerized cyclodextrin; the solid-liquid ratio of mono-6-azidocyclodextrin to N,N-dimethylformamide g:mL is 0.05:1, the molar ratio of mono-6-azidocyclodextrin to copper sulfate is 1:0.105, the molar ratio of mono-6-azidocyclodextrin to sodium ascorbate is 1:0.45, and the molar ratio of mono-6-azidocyclodextrin to tripropargylamine is 1:0.4.

[0044] 4) adding trimeric cyclodextrin to an acetonitrile solvent, and then adding CuI to obtain a reaction system, followed by stirring under a protective atmosphere for 14 hours, centrifuging the solid, washing the solid with acetonitrile, and vacuum drying to obtain βCD3-Cu(I); the solid-liquid ratio of the trimeric cyclodextrin to the acetonitrile solvent g:mL is 0.1:1, and the mass ratio of the trimeric cyclodextrin to CuI is 1:0.8.

[0045] The βCD3-Cu(I) prepared in Example 1 was used to synthesize 1-iodo-2-(phenylethynyl)benzene (3a) and 1,2-di(phenylethynyl)benzene (4a):

[0046] To a 25 mL Schlenk tube containing DMSO (0.5 mL) was added 1 mmol of o-diiodobenzene (1a), 1.4 mmol of phenylacetylene (2a), 20 mg of βCD3-Cu(I) (the amount of copper in βCD3-Cu(I) was 0.68 mmol% Cu), and 1.0 mmol of Na2CO3. The mixture was stirred and reacted at 120°C for 20 h. The reaction product was concentrated under reduced pressure to obtain a crude product. The crude product was separated and extracted on a silica gel (200-300 mesh) column using petroleum ether as the eluent. The eluate was collected and rotary evaporated to obtain 1-iodo-2-(phenylethynyl)benzene (3a) and 1,2-di(phenylethynyl)benzene (4a). The products were white solids with yields of 46% and 4%, respectively. The reaction equations are as follows:

[0047]

[0048] The NMR data of the compound are as follows:

[0049] 3a: 1 H NMR (600MHz, CDCl3) δ7.84 (d, J=8.0Hz, 1H), 7.59 (dd, J=6.8, 2.9Hz, 2H), 7.51 (d ,J=7.8Hz,1H),7.39–7.31(m,3H),7.29(t,J=7.6Hz,1H),6.97(t,J=6.9Hz,1H). 13C NMR (151MHz, CDCl3) δ138.78,132.47,131.70,129.76,129.47,128.75,128.48,127.92,122.94,101.33,93.13,91.74.

[0050] 4a: 1 H NMR (600MHz, CDCl3) δ7.62–7.53(m,6H),7.35(m,6H),7.32(dd,J=5.8,3.3Hz,2H). 13 C NMR (151MHz, CDCl3) δ131.93,131.80,128.58,128.52,128.16,125.93,123.40,93.71,88.43.

[0051] Example 2

[0052] The βCD3-Cu(I) prepared in Example 1 was used to synthesize 1-iodo-2-((4-methoxyphenyl)ethynyl))benzene (3b):

[0053] To DMSO (0.5 mL) in a 25 mL Schlenk tube were added 1 mmol of o-diiodobenzene (1a), 1.4 mmol of 4-methoxyphenylacetylene (2b), 20 mg of βCD3-Cu(I) (the amount of copper in βCD3-Cu(I) is 0.68 mmol% Cu), and 1.0 mmol of K2CO3. The mixture was stirred and reacted at 120°C for 20 h. The reaction product was concentrated under reduced pressure to obtain a crude product. The crude product was separated and extracted on a silica gel (200-300 mesh) column using petroleum ether as the eluent. The eluate was collected and rotary evaporated to obtain 1-iodo-2-((4-methoxyphenyl)ethynyl))benzene (3b). The product was a white solid with a yield of 44%. The reaction equation is as follows:

[0054]

[0055] The NMR data of the compound are as follows:

[0056] 3b: 1 H NMR (600MHz, CDCl3) δ7.86 (dd, J=8.0, 1.2Hz, 1H), 7.54 (d, J=8.8Hz, 2H), 7.50 (dd, J=7.7, 1.7Hz, 1H), 7.31 (td, J=7.5, 1.2Hz, 1H), 6.98 (td, J=7.7, 1.7Hz, 1H), 6.89 (d, J=8.8Hz, 2H), 3.82 (s, 3H). 13C NMR (151MHz, CDCl3) δ160.02,138.78,133.23,132.26,130.14,129.15,127.92,115.08,114.15,101.20,93.32,90.61,55.45.

[0057] Example 3

[0058] The βCD3-Cu(I) prepared in Example 1 was used to synthesize 1-iodo-2-((4-ethoxyphenyl)ethynyl))benzene (3c):

[0059] To DMSO (0.5 mL) in a 25 mL Schlenk tube were added 1 mmol of o-diiodobenzene (1a), 1.4 mmol of 4-ethoxyphenylacetylene (2c), 20 mg of βCD3-Cu(I) (the amount of copper in βCD3-Cu(I) is 0.68 mmol% Cu), and 1.0 mmol of Na2CO3. The mixture was stirred and reacted at 110°C for 24 h. The reaction product was concentrated under reduced pressure to obtain a crude product. The crude product was separated and extracted on a silica gel (200-300 mesh) column using petroleum ether as the eluent. The eluate was collected and rotary evaporated to obtain 1-iodo-2-((4-ethoxyphenyl)ethynyl))benzene (3d). The product was a white solid with a yield of 39%. The reaction equation is as follows:

[0060]

[0061] The NMR data of the compound are as follows:

[0062] 3d: 1 H NMR (600MHz, CDCl3) δ7.85 (dd, J=8.0, 1.2Hz, 1H), 7.57–7.46 (m, 3H), 7.30 (td, J=7.5, 1.2Hz, 1H) ,6.98(td,J=7.7,1.7Hz,1H),6.87(d,J=8.8Hz,2H),4.04(q,J=7.0Hz,2H),1.42(t,J=7.0Hz,3H). 13 C NMR (151MHz, CDCl3) δ159.44,138.77,133.23,132.25,130.18,129.12,127.92,114.86,114.63,101.19,93.42,90.55,63.64,14.88.

[0063] Example 4

[0064] The βCD3-Cu(I) prepared in Example 1 was used to synthesize 1-iodo-3-(phenylethynyl)benzene (3e) and 1,3-di(phenylethynyl)benzene (4e):

[0065] To DMSO (0.5 mL) in a 25 mL Schlenk tube were added 1 mmol of m-diiodobenzene (1b), 1.4 mmol of phenylacetylene (2a), 20 mg of βCD3-Cu(I) (the amount of copper in βCD3-Cu(I) is 0.68 mmol% Cu), and 1.0 mmol of Na2CO3. The mixture was stirred and reacted at 100°C for 24 h. The reaction product was concentrated under reduced pressure to obtain a crude product. The crude product was separated and extracted on a silica gel (200-300 mesh) column using petroleum ether as the eluent. The eluate was collected and rotary evaporated to obtain 1-iodo-3-(phenylethynyl)benzene (3e) and 1,3-di(phenylethynyl)benzene (4e). The products were white solids with yields of 40% and 8%, respectively. The reaction equations are as follows:

[0066]

[0067] The NMR data of the compound are as follows:

[0068] 3e:1H NMR (600MHz, CDCl3) δ7.88(s,1H),7.63(d,J=8.0Hz,1H),7.51(d,J=4.7Hz,2H),7.46(d,J=7.8Hz,1H),7.38–7.28(m,3H),7.03(t,J=7.9Hz,1H).13C NMR (151MHz, CDCl3) δ140.19,137.28,131.73,130.76,129.93,128.69,128.50,125.39,122.81,93.88,90.82,87.76.

[0069] 4e: 1 HNMR (600MHz, CDCl3) δ7.72 (s, 1H), 7.58–7.51 (m, 4H), 7.49 (dd, J = 7.7, 1.7Hz, 2H), 7.39–7.29 (m, 8H). 13 C NMR (151MHz, CDCl3) δ134.73,131.79,131.42,128.61,128.59,128.53,123.73,123.11,90.09,88.66.

[0070] Example 5

[0071] The βCD3-Cu(I) prepared in Example 1 was used to synthesize 1-iodo-3-((4-ethoxyphenyl)ethynyl))benzene (3f):

[0072] To DMSO (0.5 mL) in a 25 mL Schlenk tube were added 1 mmol of m-diiodobenzene (1b), 1.4 mmol of 4-methoxyphenylacetylene (2b), 20 mg of βCD3-Cu(I) (the amount of copper in βCD3-Cu(I) is 0.68 mmol% Cu), and 1.0 mmol of Na2CO3. The mixture was stirred and reacted at 120°C for 20 h. The reaction product was concentrated under reduced pressure to obtain a crude product. The crude product was separated and extracted on a silica gel (200-300 mesh) column using petroleum ether as the eluent. The eluate was collected and rotary evaporated to obtain 1-iodo-3-((4-ethoxyphenyl)ethynyl))benzene (3f). The product was a white solid with a yield of 43%. The reaction equation is as follows:

[0073]

[0074] The NMR data of the compound are as follows:

[0075] 3f: 1 H NMR (600MHz, CDCl3) δ7.86(t,J=1.7Hz,1H),7.62(d,J=8.1Hz,1H),7.45(d,J=8.8Hz,3H),7.04(t,J=7.9Hz,1H),6.93–6.81(m,2H),3.80(s,3H). 13 C NMR (151MHz, CDCl3) δ159.92,140.04,136.96,133.23,130.61,129.92,125.77,114.88,114.14,93.85,90.92,86.53,55.40.

[0076] Example 6

[0077] The βCD3-Cu(I) prepared in Example 1 was used to synthesize 1-iodo-3-((4-ethoxyphenyl)ethynyl))benzene (3 g):

[0078] To a 25 mL Schlenk tube containing DMSO (0.5 mL) was added 1 mmol of m-diiodobenzene (1b), 1.4 mmol of 4-ethoxyphenylacetylene (2c), 20 mg of βCD3-Cu(I) (the amount of copper in βCD3-Cu(I) is 0.68 mmol% Cu), and 1.0 mmol of Na2CO3. The mixture was stirred and reacted at 120°C for 20 h. The reaction product was concentrated under reduced pressure to obtain a crude product. The crude product was separated and extracted on a silica gel (200-300 mesh) column using petroleum ether as the eluent. The eluate was collected and rotary evaporated to obtain 1-iodo-3-((4-ethoxyphenyl)ethynyl))benzene (3 g). The product was a white solid with a yield of 51%. The reaction equation is as follows:

[0079]

[0080] The NMR data of the compound are as follows:

[0081] 3g: 1 H NMR(600MHz, CDCl3) δ7.86(t,J=1.7Hz,1H),7.62(d,J=8.0Hz,1H),7.44(dd,J=9.0,7.1Hz, 3H),7.04(t,J=7.8Hz,1H),6.92–6.79(m,2H),4.02(q,J=7.0Hz,2H),1.41(t,J=7.0Hz,3H). 13 C NMR (151MHz, CDCl3) δ159.33,140.03,136.92,133.23,130.60,129.91,125.81,114.66,114.61,93.84,91.01,86.45,63.60,14.87.

[0082] Example 7

[0083] The βCD3-Cu(I) prepared in Example 1 was used to synthesize 1-iodo-2-((4-methoxyphenyl)ethynyl))benzene (3b):

[0084] To DMSO (0.5 mL) in a 25 mL Schlenk tube, 1 mmol of o-diiodobenzene (1a), 0.5 mmol of 4-methoxyphenylacetylene (2b), 10 mg of βCD3-Cu(I), and 3.5 mmol of Cs2CO3 were added in sequence. The mixture was stirred and reacted at 90°C for 24 h. The reaction product was concentrated under reduced pressure to obtain a crude product. The crude product was separated and extracted on a silica gel (200-300 mesh) column using petroleum ether as the eluent. The eluate was collected and rotary evaporated to obtain 1-iodo-2-((4-methoxyphenyl)ethynyl))benzene (3b). The product was a white solid with a yield of 42%. The reaction equation is as follows:

[0085]

[0086] The NMR data of the compound are as follows:

[0087] 3b: 1 H NMR (600MHz, CDCl3) δ7.86 (dd, J=8.0, 1.2Hz, 1H), 7.54 (d, J=8.8Hz, 2H), 7.50 (dd, J=7.7, 1.7Hz, 1H), 7.31 (td, J=7.5, 1.2Hz, 1H), 6.98 (td, J=7.7, 1.7Hz, 1H), 6.89 (d, J=8.8Hz, 2H), 3.82 (s, 3H). 13 C NMR (151MHz, CDCl3) δ160.02,138.78,133.23,132.26,130.14,129.15,127.92,115.08,114.15,101.20,93.32,90.61,55.45.

[0088] Example 8

[0089] The preparation method of βCD3-Cu(I) in the embodiment of the present invention comprises the following steps:

[0090] 1) 44 mmol of β-cyclodextrin (50 g) was dissolved in 50 mL of sodium hydroxide (44 mmol) solution and stirred with 0.44 mol of p-toluenesulfonyl chloride (35 g) for 30 minutes. The filtrate was then filtered and the pH was adjusted to neutral with dilute hydrochloric acid. The product, mono-6-TOS-ylcyclodextrin, was then filtered to obtain a white solid.

[0091] 2) Dissolve 3.2 mmol of mono-6-TOS-cyclodextrin in 30 mL of N,N-dimethylformamide (DMF), then add 3.2 mmol of sodium azide. Under a protective atmosphere, heat to 100°C and react for 18 hours. Then, add acetone dropwise to precipitate mono-6-azidocyclodextrin as a white solid.

[0092] 3) Dissolving mono-6-azidocyclodextrin in N,N-dimethylformamide (DMF), adding copper sulfate, sodium ascorbate, and tripropargylamine in sequence, heating to 50° C. under a nitrogen atmosphere and reacting for 48 hours, then adding acetone dropwise to precipitate solid trimerized cyclodextrin; the solid-liquid ratio of mono-6-azidocyclodextrin to N,N-dimethylformamide g:mL is 0.01:1, the molar ratio of mono-6-azidocyclodextrin to copper sulfate is 1:0.005, the molar ratio of mono-6-azidocyclodextrin to sodium ascorbate is 1:0.8, and the molar ratio of mono-6-azidocyclodextrin to tripropargylamine is 1:0.9.

[0093] 4) adding trimeric cyclodextrin to an acetonitrile solvent, and then adding CuI to obtain a reaction system, followed by stirring for 16 hours under a protective atmosphere, separating the solid by centrifugation, washing the solid with acetonitrile, and vacuum drying to obtain βCD3-Cu(I); the solid-liquid ratio of the trimeric cyclodextrin to the acetonitrile solvent g:mL is 0.005:1, and the mass ratio of the trimeric cyclodextrin to CuI is 1:2.

[0094] The βCD3-Cu(I) prepared in Example 8 was used to synthesize 1-iodo-2-((4-methoxyphenyl)ethynyl))benzene (3b):

[0095] To DMSO (0.5 mL) in a 25 mL Schlenk tube, 1 mmol of o-diiodobenzene (1a), 0.5 mmol of 4-methoxyphenylacetylene (2b), 15 mg of βCD3-Cu(I), and 3.5 mmol of Cs2CO3 were added in sequence. The mixture was stirred and reacted at 110°C for 24 h. The reaction product was concentrated under reduced pressure to obtain a crude product. The crude product was separated and extracted on a silica gel (200-300 mesh) column using petroleum ether as the eluent. The eluate was collected and rotary evaporated to obtain 1-iodo-2-((4-methoxyphenyl)ethynyl))benzene (3b). The product was a white solid with a yield of 48%. The reaction equation is as follows:

[0096]

[0097] The NMR data of the compound are as follows

[0098] 3b: 1 H NMR (600MHz, CDCl3) δ7.86 (dd, J=8.0, 1.2Hz, 1H), 7.54 (d, J=8.8Hz, 2H), 7.50 (dd, J=7.7, 1.7Hz, 1H), 7.31 (td, J=7.5, 1.2Hz, 1H), 6.98 (td, J=7.7, 1.7Hz, 1H), 6.89 (d, J=8.8Hz, 2H), 3.82 (s, 3H).13 C NMR (151MHz, CDCl3) δ160.02,138.78,133.23,132.26,130.14,129.15,127.92,115.08,114.15,101.20,93.32,90.61,55.45.

[0099] Example 9

[0100] The preparation method of βCD3-Cu(I) in the embodiment of the present invention comprises the following steps:

[0101] 1) 44 mmol of β-cyclodextrin (50 g) was dissolved in 500 mL of sodium hydroxide (0.44 mol) solution and stirred with 44 mmol of p-toluenesulfonyl chloride (35 g) for 30 minutes. The filtrate was then filtered and the pH was adjusted to neutral with dilute hydrochloric acid. The product, mono-6-TOS-ylcyclodextrin, was then filtered to obtain a white solid.

[0102] 2) Dissolve 3.2 mmol of mono-6-TOS-cyclodextrin in 30 ml of N,N-dimethylformamide (DMF), then add 32 mmol of sodium azide. Under a protective atmosphere, heat to 100°C and react for 18 hours. Then, add acetone dropwise to precipitate mono-6-azidocyclodextrin as a white solid.

[0103] 3) Dissolving mono-6-azidocyclodextrin in N,N-dimethylformamide (DMF), adding copper sulfate, sodium ascorbate, and tripropargylamine in sequence, heating to 100° C. under a nitrogen atmosphere and reacting for 36 hours, then adding acetone dropwise to precipitate solid trimerized cyclodextrin; the solid-liquid ratio of mono-6-azidocyclodextrin to N,N-dimethylformamide g:mL is 0.09:1, the molar ratio of mono-6-azidocyclodextrin to copper sulfate is 1:0.2, the molar ratio of mono-6-azidocyclodextrin to sodium ascorbate is 1:0.006, and the molar ratio of mono-6-azidocyclodextrin to tripropargylamine is 1:0.01.

[0104] 4) adding trimeric cyclodextrin to an acetonitrile solvent, and then adding CuI to obtain a reaction system, followed by stirring under a protective atmosphere for 14 hours, centrifuging the solid, washing the solid with acetonitrile, and vacuum drying to obtain βCD3-Cu(I); the solid-liquid ratio of the trimeric cyclodextrin to the acetonitrile solvent g:mL is 0.2:1, and the mass ratio of the trimeric cyclodextrin to CuI is 1:0.1.

[0105] The βCD3-Cu(I) prepared in Example 8 was used to synthesize 1-iodo-2-((4-methoxyphenyl)ethynyl))benzene (3b):

[0106] To DMSO (0.5 mL) in a 25 mL Schlenk tube, 1 mmol of o-diiodobenzene (1a), 1.5 mmol of 4-methoxyphenylacetylene (2b), 20 mg of βCD3-Cu(I), and 0.5 mmol of Cs2CO3 were added in sequence, and the mixture was stirred at 130°C for 16 h. The reaction product was concentrated under reduced pressure to obtain a crude product. The crude product was separated and extracted on a silica gel (200-300 mesh) column using petroleum ether as the eluent. The eluate was collected and rotary evaporated to obtain 1-iodo-2-((4-methoxyphenyl)ethynyl))benzene (3b). The product was a white solid with a yield of 50%. The reaction equation is as follows:

[0107]

[0108] The NMR data of the compound are as follows:

[0109] 3b: 1 H NMR (600MHz, CDCl3) δ7.86 (dd, J=8.0, 1.2Hz, 1H), 7.54 (d, J=8.8Hz, 2H), 7.50 (dd, J=7.7, 1.7Hz, 1H), 7.31 (td, J=7.5, 1.2Hz, 1H), 6.98 (td, J=7.7, 1.7Hz, 1H), 6.89 (d, J=8.8Hz, 2H), 3.82 (s, 3H). 13 C NMR (151MHz, CDCl3) δ160.02,138.78,133.23,132.26,130.14,129.15,127.92,115.08,114.15,101.20,93.32,90.61,55.45.

[0110] Comparative Example 1

[0111] The preparation method of trimerized cyclodextrin in the comparative example of the present invention comprises the following specific steps:

[0112] 1) 44 mmol of β-cyclodextrin (50 g) was dissolved in 1000 mL of sodium hydroxide (16 g, 200 mmol) solution and stirred with 184 mmol of p-toluenesulfonyl chloride (35 g) for 30 minutes. The filtrate was then filtered and the pH was adjusted to neutral with dilute hydrochloric acid. The product, mono-6-TOS-ylcyclodextrin, was then filtered to obtain a white solid.

[0113] 2) Dissolve 3.2 mmol of mono-6-TOS-cyclodextrin in 30 mL of N,N-dimethylformamide (DMF), then add 12.8 mmol of sodium azide. Under a protective atmosphere, heat to 50°C and react for 48 hours. Then, add acetone dropwise to precipitate mono-6-azidocyclodextrin as a white solid.

[0114] 3) Dissolving mono-6-azidocyclodextrin in N,N-dimethylformamide (DMF), adding copper sulfate, sodium ascorbate, and tripropargylamine in sequence, heating to 80° C. under a nitrogen atmosphere and reacting for 28 hours, then adding acetone dropwise to precipitate solid trimerized cyclodextrin; the solid-liquid ratio of mono-6-azidocyclodextrin to N,N-dimethylformamide g:mL is 0.05:1, the molar ratio of mono-6-azidocyclodextrin to copper sulfate is 1:0.105, the molar ratio of mono-6-azidocyclodextrin to sodium ascorbate is 1:0.45, and the molar ratio of mono-6-azidocyclodextrin to tripropargylamine is 1:0.4.

[0115] Synthesis of 1-iodo-2-((4-methoxyphenyl)ethynyl))benzene (3b) and 1,2-bis((4-methoxyphenyl)ethynyl)benzene (4b):

[0116] To DMSO (0.5 mL) in a 25 mL Schlenk tube were added 1 mmol of o-diiodobenzene (1a), 1.4 mmol of 4-methoxyphenylacetylene (2b), 20 mg of tri-cyclodextrin, 20 mg of CuI, and 1.0 mmol of K2CO3. The mixture was stirred and reacted at 120°C for 20 h. The reaction product was concentrated under reduced pressure to obtain a crude product. The crude product was separated and extracted on a silica gel (200-300 mesh) column using petroleum ether as the eluent. The eluate was collected and rotary evaporated to obtain 1-iodo-2-((4-methoxyphenyl)ethynyl))benzene (3b) and 1,2-bis((4-methoxyphenyl)ethynyl)benzene (4b). The products were white solids with yields of 12% and 30%, respectively. The reaction equations are as follows:

[0117]

[0118] The NMR data of the compound are as follows:

[0119] 3b: 1 H NMR (600MHz, CDCl3) δ7.86 (dd, J=8.0, 1.2Hz, 1H), 7.54 (d, J=8.8Hz, 2H), 7.50 (dd, J=7.7, 1.7Hz, 1H), 7.31 (td, J=7.5, 1.2Hz, 1H), 6.98 (td, J=7.7, 1.7Hz, 1H), 6.89 (d, J=8.8Hz, 2H), 3.82 (s, 3H). 13C NMR (151MHz, CDCl3) δ160.02,138.78,133.23,132.26,130.14,129.15,127.92,115.08,114.15,101.20,93.32,90.61,55.45.

[0120] 4b: 1 H NMR (600MHz, CDCl3) δ7.68–7.67(m,1H),7.48–7.43(m,6H),7.31(t,J=7.7Hz,1H),6.90–6.87(m,4H),3.83(s,6H); 13 C NMR (151MHz, CDCl3) δ159.7,134.2,133.0,130.7,128.3,123.8,115.1,114.0,89.9,87.3,55.2

[0121] Comparative Example 2

[0122] The preparation method of the cyclodextrin catalyst in the comparative example comprises the following specific steps:

[0123] 1) adding β-cyclodextrin to an acetonitrile solvent, and then adding CuI to obtain a reaction system, followed by stirring under a protective atmosphere for 14 hours, centrifuging to separate a solid, washing the solid with acetonitrile, and vacuum drying to obtain a cyclodextrin catalyst; the solid-liquid ratio of the β-cyclodextrin to the acetonitrile solvent is 0.1:1 g:mL, and the mass ratio of the β-cyclodextrin to CuI is 1:0.8.

[0124] The cyclodextrin catalyst prepared in Comparative Example 2 was used to synthesize 1-iodo-2-((4-methoxyphenyl)ethynyl))benzene (3b) and 1,2-bis((4-methoxyphenyl)ethynyl)benzene (4b):

[0125] To DMSO (0.5 mL) in a 25 mL Schlenk tube were added 1 mmol of o-diiodobenzene (1a), 1.4 mmol of 4-methoxyphenylacetylene (2b), 20 mg of cyclodextrin catalyst (the amount of copper in the cyclodextrin catalyst was 0.68 mmol% Cu), and 1.0 mmol of K2CO3. The mixture was stirred and reacted at 120°C for 20 h. The reaction product was concentrated under reduced pressure to obtain a crude product. The crude product was separated and extracted on a silica gel (200-300 mesh) column using petroleum ether as the eluent. The eluate was collected and rotary evaporated to obtain 1-iodo-2-((4-methoxyphenyl)ethynyl))benzene (3b) and 1,2-bis((4-methoxyphenyl)ethynyl)benzene (4b). The products were white solids with yields of 17% and 36%, respectively. The reaction equations are as follows:

[0126]

[0127] The NMR data of the compound are as follows:

[0128] 3b: 1 H NMR (600MHz, CDCl3) δ7.86 (dd, J=8.0, 1.2Hz, 1H), 7.54 (d, J=8.8Hz, 2H), 7.50 (dd, J=7.7, 1.7Hz, 1H), 7.31 (td, J=7.5, 1.2Hz, 1H), 6.98 (td, J=7.7, 1.7Hz, 1H), 6.89 (d, J=8.8Hz, 2H), 3.82 (s, 3H). 13 C NMR (151MHz, CDCl3) δ160.02,138.78,133.23,132.26,130.14,129.15,127.92,115.08,114.15,101.20,93.32,90.61,55.45.

[0129] 4b: 1 H NMR (600MHz, CDCl3) δ7.68–7.67(m,1H),7.48–7.43(m,6H),7.31(t,J=7.7Hz,1H),6.90–6.87(m,4H),3.83(s,6H); 13 C NMR (151MHz, CDCl3) δ159.7,134.2,133.0,130.7,128.3,123.8,115.1,114.0,89.9,87.3,55.2.

[0130] Compared with the cyclodextrin catalyst prepared in Comparative Example 2, the catalysts prepared in Examples 1-9 of the present invention have better effects on the selective catalysis of the reaction of alkyne compounds and dihalogenated aromatics, and also increase the proportion of monosubstituted products. This is mainly because the triazole group and cyclodextrin cavity present in βCD3-Cu(I) prepared in the examples play a key role in the yield of the substitution product and the proportion of the selective generation of the monosubstituted product.

[0131] Finally, it should be noted that the above preferred embodiments are only used to illustrate the technical solutions of the present invention and are not limiting. Although the present invention has been described in detail through the above preferred embodiments, those skilled in the art should understand that various changes can be made in form and details without departing from the scope defined by the claims of the present invention.

Claims

1. A method for preparing a mono- or mono-diaryl aromatic hydrocarbon derivative, characterized in that: The steps include: (1) dissolving β-cyclodextrin in a sodium hydroxide solution, adding p-toluenesulfonyl chloride and stirring, then filtering the filtrate, adjusting the pH of the filtrate to neutral with dilute hydrochloric acid, and then filtering to obtain mono-6-TOS-based cyclodextrin; (2) dissolving mono-6-TOS-based cyclodextrin in N,N-dimethylformamide, then adding sodium azide, reacting under a protective atmosphere, and then adding acetone to precipitate mono-6-azidocyclodextrin; (3) Mono-6-azidocyclodextrin was dissolved in N,N-dimethylformamide, copper sulfate, sodium ascorbate and tripropargylamine were added in sequence, reacted under a protective atmosphere, and then acetone was added to precipitate trimerized cyclodextrin; (4) adding trimeric cyclodextrin to acetonitrile, then adding CuI to react under a protective atmosphere, centrifuging to separate the solid, washing the solid with acetonitrile, and vacuum drying to obtain a trimeric cyclodextrin catalyst; (5) adding an alkyne compound, a dihalogenated aromatic hydrocarbon, a trimerized cyclodextrin catalyst, and a carbonate into a solvent to react and obtain a reaction product system; (6) The reaction product system is concentrated under reduced pressure to obtain a crude product, and the crude product is separated and purified by silica gel column chromatography to obtain a mono- or mono- and di-aryl-substituted aromatic derivative.

2. The method for preparing mono- or mono-diaryl aromatic derivatives according to claim 1, characterized in that: The molar ratio of the beta-cyclodextrin to sodium hydroxide is 1:(1-10), the solid-liquid ratio of the beta-cyclodextrin to the sodium hydroxide solution is (0.01-1.0) g:1 mL; and the molar ratio of the beta-cyclodextrin to p-toluenesulfonyl chloride is 1:(1-10).

3. The method for preparing mono- or mono-diaryl aromatic derivatives according to claim 1, characterized in that: In the step (2), the solid-liquid ratio of mono-6-TOS-based cyclodextrin and N,N-dimethylformamide is (0.01-0.5) g:1 mL; the molar ratio of mono-6-TOS-based cyclodextrin and sodium azide is 1:(1-10); the reaction temperature is 50-100° C., the reaction time is 18-48 h, and the protective gas is nitrogen or an inert gas.

4. The method for preparing mono- or mono-diaryl aromatic derivatives according to claim 1, characterized in that: In the step (3), the solid-liquid ratio of mono-6-azidocyclodextrin to N,N-dimethylformamide is (0.01-0.09) g:1 mL, the molar ratio of mono-6-azidocyclodextrin to copper sulfate is 1:(0.005-0.20), the molar ratio of mono-6-azidocyclodextrin to sodium ascorbate is 1:(0.006-0.80), and the molar ratio of mono-6-azidocyclodextrin to tripropargylamine is 1:(0.01-0.9); the reaction temperature is 50-100° C., the reaction time is 18-48 h, and the protective gas is nitrogen or an inert gas.

5. The method for preparing mono- or mono-diaryl aromatic derivatives according to claim 1, characterized in that: In the step (4), the solid-liquid ratio of trimerized cyclodextrin to acetonitrile is (0.005-0.2) g:1 mL, and the mass ratio of trimerized cyclodextrin to CuI is 1:(0.1-2); the reaction temperature is room temperature, the reaction time is 12-16 h, and the protective gas is nitrogen or an inert gas.

6. The method for preparing mono- or mono- and di-aromatic aromatic derivatives according to claim 1, characterized in that: The alkyne compound is phenylacetylene, 4-methoxyphenylacetylene, 4-ethoxyphenylacetylene, 4-ethoxycarbonylphenylacetylene, 2-trifluoromethylphenylacetylene, 3-trifluoromethylphenylacetylene, 4-trifluoromethylphenylacetylene, 2-methylphenylacetylene, 3-methylphenylacetylene, 4-methylphenylacetylene, 2-fluorophenylacetylene, 2-chlorophenylacetylene, 2-bromophenylacetylene, 4-fluorophenylacetylene, 4-chlorophenylacetylene or 4-bromophenylacetylene; The structural formula of the dihalogenated aromatic hydrocarbon is one of the following structural formulas: wherein Y is F, Cl, Br or I; The carbonate is Cs2CO3, Na2CO3 or K2CO3; The solvent is N,N-dimethylformamide, dimethyl sulfoxide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone or 1,4-dioxane.

7. The method for preparing mono- or mono- and di-aromatic aromatic derivatives according to claim 1, characterized in that: In the step (5), the molar ratio of the alkyne compound, the dihalogenated aromatic hydrocarbon and the carbonate is 1:(0.5-1.5):(0.5-3.5), the reaction temperature is 90-130° C., and the reaction time is 6-24 hours.

8. The method for preparing mono- or mono- and di-aromatic aromatic derivatives according to claim 1, characterized in that: The mass ratio of the amount of the alkyne compound to the trimerized cyclodextrin catalyst is 0.5-2 mmol:10-30 mg.

9. The method for preparing mono- or mono- and di-aromatic aromatic derivatives according to claim 1, characterized in that: The mono- or mono-bis-aryl-substituted aromatic hydrocarbon derivative is a mono-aryl-substituted aromatic hydrocarbon derivative or a mixture of a mono-aryl-substituted aromatic hydrocarbon derivative and a bis-aryl-substituted aromatic hydrocarbon derivative; The structural formula of the monoaryl-substituted aromatic derivative is The structural formula of the bisaryl substituted aromatic derivative is wherein Y is F, Cl, Br or I; and R is phenyl, 4-methoxyphenyl, 4-ethoxycarbonylphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-naphthyl, 1-H-5-indolyl, 2-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, 4-fluorophenyl, 4-chlorophenyl or 4-bromophenyl.

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