A copper-catalyzed synthesis method of polychlorinated substituted alkyne compounds

Abstract

The invention uses polychlorinated alkane reagents, aromatic olefins, and aromatic alkynes as raw materials, copper salts as catalysts, α, α, α-terpyridine as ligands, adds potassium carbonate, reacts in a mixed solvent of acetonitrile and methanol at room temperature for 24 hours, and obtains polychlorinated substituted alkyne compounds after the reaction is completed. The synthesis method of the invention has simple and easy-to-obtain catalysts and reaction raw materials, mild reaction conditions, good functional group compatibility, convenient operation, and good industrial application prospects.

Description

Technical Field

[0001] The invention belongs to the field of organic alkyne chemical synthesis, and in particular relates to a method for synthesizing a copper-catalyzed polychlorinated substituted alkyne compound. Background Art

[0002] Functional molecules containing polychlorinated alkyl groups play many roles in organic synthesis and biochemistry. As a functional group, polychlorinated substituted alkyl groups are widely used in medicine, pesticides and advanced materials. Therefore, chemists have been attracted to conduct research on the synthesis of organic compounds containing polychlorinated functional groups.

[0003] So far, the synthesis of polychlorinated compounds mainly relies on the intramolecular cyclization reaction of polychlorinated alkane reagents and functionalized olefins (Chem. Commun. 2021, 57, 3684; Org. Lett. 2018, 20, 212; Org. Chem. Front. 2014, 1, 1289; Org. Lett. 2014, 16, 4698), or the 1,2-addition reaction between polychlorinated alkane reagents and olefin molecules (Angew. Chem. Int. Ed. 2017, 56, 8780; Chem. Commun. 2018, 54, 11013; Org. Chem. Front. 2019, 6, 512; ACS Catal. 2020, 10, 13682; Chem. Commun. 2021, 57, 3684). These two reaction strategies often require the participation of equivalent oxidants and heating conditions (100°C). So far, there has been no report on the synthesis of polychlorinated alkynes. We have developed a mild, redox-neutral copper-catalyzed multicomponent reaction route to synthesize polychlorinated alkynes via a free radical reaction pathway. Summary of the invention

[0004] The present invention aims to provide a method for synthesizing a copper-catalyzed polychlorinated substituted alkyne compound. The method has the advantages of cheap and readily available catalysts and raw materials, high reaction efficiency, good adaptability of functional groups, mild reaction conditions, simple operation, and good industrial application prospects.

[0005] A method for copper-catalyzed polychlorinated substituted alkyne compounds, the method comprising the following steps:

[0006] The method uses copper salt as catalyst, α, α, α-terpyridine as ligand, polychlorinated alkane reagent, aromatic alkyne and aromatic olefin as raw materials, potassium carbonate as base, and reacts in a mixed solvent of methanol and acetonitrile with a solvent ratio of 1:1 to prepare polychlorinated substituted alkyne compounds.

[0007] The structural formula of the polychlorinated substituted alkyne compound is: The polyhalogenated methyl reagent is: C m X n ; The structural formula of the olefin is: The alkyne structural formula is:

[0008] Among them, Ar 1 ,Ar 2 is a substituted or unsubstituted aromatic ring; substitution includes mono- to tri-substitution, and the substituents are selected from: C1-8 alkyl, C1-8 alkoxy, halogen (F, Cl, Br, I), and halogen-substituted C1-8 alkyl.

[0009] In one embodiment of the present invention, the reaction temperature is room temperature (20-30° C.) and the reaction time is 24 hours.

[0010] In one embodiment of the present invention, the aromatic ring is a benzene ring or a substituted benzene ring.

[0011] In one embodiment of the present invention, the ligand comprises any one or more of the following structures:

[0012] R 1 Selected from H, C1-4 alkyl.

[0013] In one embodiment of the present invention, R 1 Specifically, it may be H(α,α,α-terpyridine).

[0014] The method according to claim 1 is characterized in that the molar ratio of the aromatic olefin compound, the aromatic alkyne compound, and the polyhalogenated alkane reagent is 1:1.5:1.5.

[0015] The method according to claim 1, characterized in that the amount of the ligand relative to the aromatic olefin compound is 20 mol%.

[0016] The method according to claim 1, characterized in that the amount of copper salt relative to the aromatic olefin compound is 10 mol%.

[0017] The method for synthesizing a copper-catalyzed polychlorinated substituted alkyne compound according to claim 1, wherein the copper salt is selected from any one or more of the following: Cu(OAc) 2 , Cu and Cu(OTf) 2 Specifically, Cu(OTf) is preferred. 2 .

[0018] The method for synthesizing a copper-catalyzed polychlorinated substituted alkyne compound according to claim 1, wherein the alkaline solvent is selected from any one or more of the following: K 3 PO4 、Na 2 CO 3 , K 2 CO 3 and Et 3 N. Specifically, K 2 CO 3 .

[0019] The method according to claim 1, characterized in that the molar ratio of the alkaline reagent to the aromatic olefin compound is 1:1.

[0020] In one embodiment of the present invention, the organic solvent is methanol, or a mixed solvent of methanol and acetonitrile. When a mixed solvent of methanol and acetonitrile is selected, the mixed volume ratio is 1:1.

[0021] In one embodiment of the present invention, the amount of the organic solvent used is 1 mL / 0.2 mmol of the aromatic olefin compound reagent, that is, 0.5 mL / mmol of the aromatic olefin compound.

[0022] In one embodiment of the present invention, the reaction is carried out under an inert atmosphere.

[0023] In one embodiment of the present invention, the synthetic route of the reaction is as follows:

[0024]

[0025] In one embodiment of the present invention, Ar 1 ,Ar 2 The substitution in the definition specifically includes: mono-substitution, tri-substitution; the positions of multiple substitutions can be selected as ortho, meta, or para; the substituents can be selected as: -Me, -OMe, -Ph, -F, -Cl, -Br, -CF 3 、-COOMe.

[0026] In one embodiment of the present invention, the polychlorinated substituted alkyne compound specifically comprises the following structure:

[0027]

[0028] In one embodiment of the present invention, the method comprises the following specific steps:

[0029] In a reaction tube with a stirrer, N 2Under the atmosphere, catalyst, ligand, aromatic olefin compound, aromatic alkyne compound, polychlorinated alkane reagent, base, methanol, acetonitrile were added in sequence and stirred at room temperature for 24 hours. After the reaction was completed, the reaction mixture was filtered through diatomaceous earth, washed with ethyl acetate, the organic phases were combined, and the solvent was removed by rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the target compound.

[0030] Beneficial Effects

[0031] The invention uses polychlorinated alkane reagents, aromatic olefins, and aromatic alkynes as raw materials, copper salts as catalysts, α, α, α-terpyridine as ligands, adds potassium carbonate, reacts in a mixed solvent of acetonitrile and methanol at room temperature for 24 hours, and obtains polychlorinated substituted alkyne compounds after the reaction. The synthesis method of the invention has simple and easy-to-obtain catalysts and reaction raw materials, mild reaction conditions, good functional group compatibility, convenient operation, and good industrial application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 Schematic diagram of the synthetic method of the present invention. DETAILED DESCRIPTION

[0033] In order to make the contents of the present invention easier to understand, the technical solution of the present invention is further described below in conjunction with specific implementation methods, but the present invention is not limited to the scope of the embodiments.

[0034] Example 1

[0035] In a reaction tube with a stirrer, N 2 Under the atmosphere, catalyst Cu(OTf) was added successively 2 (0.02mmol, 10mol%), ligand α, α, α-terpyridine (0.04mmol, 20mol%), p-styrene (0.2mmol, 1equiv), phenylacetylene (0.3mmol, 1.5equiv), polychlorinated alkane reagent (0.3mmol, 1.5equiv), potassium carbonate (0.2mmol, 1equiv), methanol solvent (0.5mL), acetonitrile solvent (0.5mL), stirred at room temperature for 24h. After the reaction is completed, the reaction mixture is filtered through diatomaceous earth, rinsed with ethyl acetate, the organic phases are combined, and the solvent is removed by a rotary evaporator to obtain a crude product, which is separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 68%).

[0036]

[0037] 1H NMR (600MHz, Chloroform-d) δ7.50 (d, J=7.3Hz, 2H), 7.45-7.42 (m, 2H), 7.39 (t, J=7.7Hz, 2H), 7.32- 7.28 (m, 4H), 4.42 (dd, J=8.5, 3.6Hz, 1H), 3.40 (dd, J=14.8, 8.5Hz, 1H), 3.15 (dd, J=14.8, 3.6Hz, 1H). 13 C NMR (151MHz, CDCl3) δ140.4, 131.5, 128.9, 128.2, 128.1, 127.6, 127.5, 123.2, 97.9, 89.6, 84.7, 62.0, 36.5.

[0038] Example 2

[0039] In a reaction tube with a stirrer, N 2 Under the atmosphere, catalyst Cu(OTf) was added successively 2 (0.02mmol, 10mol%), ligand α, α, α-terpyridine (0.04mmol, 20mol%), p-methoxystyrene (0.2mmol, 1equiv), phenylacetylene (0.3mmol, 1.5equiv), polychlorinated alkane reagent (0.3mmol, 1.5equiv), potassium carbonate (0.2mmol, 1equiv), methanol solvent (0.5mL), acetonitrile solvent (0.5mL), stirred at room temperature for 24h. After the reaction is completed, the reaction mixture is filtered through diatomaceous earth, washed with ethyl acetate, the organic phases are combined, and the solvent is removed by a rotary evaporator to obtain a crude product, which is separated by silica gel column chromatography, using petroleum ether and ethyl acetate as eluents, and finally the compound of formula 2 (isolation yield 75%) is obtained.

[0040]

[0041] 1 H NMR (600 MHz, CDCl 3 )δ7.5-7.3 (m, 7H), 6.9-6.9 (m, 2H), 4.4 (dd, J=8.5, 3.8Hz, 1H), 3.8 (d, J=1.4Hz, 3H), 3.40-3.36 (m, 1H), 3.16-3.11 (m, 1H). 13 C NMR (151 MHz, CDCl 3 )δ158.9, 132.5, 131.5, 128.7, 128.2, 128.1, 123.3, 114.3, 97.9, 89.9, 84.5, 62.1, 55.3, 35.7.

[0042] Example 3

[0043] In a reaction tube with a stirrer, N 2 Under the atmosphere, catalyst Cu(OTf) was added successively 2 (0.02mmol, 10mol%), ligand α, α, α-terpyridine (0.04mmol, 20mol%), p-phenylstyrene (0.2mmol, 1equiv), phenylacetylene (0.3mmol, 1.5equiv), polychlorinated alkane reagent (0.3mmol, 1.5equiv), potassium carbonate (0.2mmol, 1equiv), methanol solvent (0.5mL), acetonitrile solvent (0.5mL), stirred at room temperature for 24h. After the reaction is completed, the reaction mixture is filtered through diatomaceous earth, washed with ethyl acetate, the organic phases are combined, and the solvent is removed by a rotary evaporator to obtain a crude product, which is separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain a compound of formula 3 (isolation yield 90%).

[0044]

[0045] 1 H NMR (600 MHz, CDCl 3 )δ7.64-7.56 (m, 6H), 7.49-7.15 (m, 4H), 7.39-7.29 (m, 4H), 4.48 (dd, J=8.5, 3.7Hz, 1H), 3.45 (dd, J=14.8, 8.4Hz, 1H), 3.20 (dd, J=14.8, 3.7Hz, 1H). 13 C NMR δ140.6, 140.5, 139.4, 131.5, 128.8, 128.3, 128.12, 128.07, 127.7, 127.4, 127.1, 123.2, 97.9, 89.5, 84.8, 62.0, 36.1.

[0046] Example 4

[0047] In a reaction tube with a stirrer, N 2 Under the atmosphere, catalyst Cu(OTf) was added successively 2(0.02mmol, 10mol%), ligand α, α, α-terpyridine (0.04mmol, 20mol%), p-fluorostyrene (0.2mmol, 1equiv), phenylacetylene (0.3mmol, 1.5equiv), polychlorinated alkane reagent (0.3mmol, 1.5equiv), potassium carbonate (0.2mmol, 1equiv), methanol solvent (0.5mL), acetonitrile solvent (0.5mL), stirred at room temperature for 24h. After the reaction is completed, the reaction mixture is filtered through diatomaceous earth, washed with ethyl acetate, the organic phases are combined, and the solvent is removed by a rotary evaporator to obtain a crude product, which is separated by silica gel column chromatography, using petroleum ether and ethyl acetate as eluents, and finally obtaining a compound of formula 4 (isolation yield 49%).

[0048]

[0049] 1 H NMR (600 MHz, CDCl 3 )δ7.52-7.38(m, 4H), 7.31(dd, J=5.0, 1.9Hz, 3H), 7.12-7.04(m, 2H), 4.41(dd, J=8.2, 4.0Hz, 1H), 3.39 (dd, J=14.8, 8.3Hz, 1H), 3.12 (dd, J=14.9, 4.0Hz, 1H). 13 CNMR (151 MHz, CDCl 3 ) δ162.9, 161.3, 136.1 (d, J = 3.3Hz), 131.5, 129.3 (d, J = 8.2Hz), 128.3 (d, J = 6.7Hz), 123.0, 115.8 (d, J = 21.6Hz), 97.7, 89.3, 84.8, 62.0, 35.8. 19 F NMR (565 MHz, CDCl 3 )δ-114.96.

[0050] Example 5

[0051] In a reaction tube with a stirrer, N 2 Under the atmosphere, catalyst Cu(OTf) was added successively 2(0.02mmol, 10mol%), ligand α, α, α-terpyridine (0.04mmol, 20mol%), styrene (0.2mmol, 1equiv), p-ethylphenylacetylene (0.3mmol, 1.5equiv), polychlorinated alkane reagent (0.3mmol, 1.5equiv), potassium carbonate (0.2mmol, 1equiv), methanol solvent (0.5mL), acetonitrile solvent (0.5mL), stirred at room temperature for 24h. After the reaction is completed, the reaction mixture is filtered through diatomaceous earth, rinsed with ethyl acetate, the organic phases are combined, and the solvent is removed by a rotary evaporator to obtain a crude product, which is separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain a compound of formula 5 (isolation yield 54%).

[0052]

[0053] 1 H NMR (600 MHz, CDCl 3 )δ7.52-7.47(m, 2H), 7.42-7.33(m, 4H), 7.32-7.27(m, 1H), 7.17-7.11(m, 2H), 4.41(dd, J=8.5, 3.6Hz, 1H) , 3.39 (dd, J=14.8, 8.5Hz, 1H), 3.14 (dd, J=14.8, 3.7Hz, 1H), 2.64 (q, J=7.6Hz, 2H), 1.22 (t, J=7.6Hz, 3H). 13 C NMR (151 MHz, CDCl 3 )δ144.5, 140.6, 131.5, 128.9, 127.8, 127.7, 127.4, 120.4, 97.9, 88.8, 84.8, 62.1, 36.5, 28.8, 15.4.

[0054] Example 6

[0055] In a reaction tube with a stirrer, N 2 Under the atmosphere, catalyst Cu(OTf) was added successively 2(0.02mmol, 10mo1%), ligand α, α, α-terpyridine (0.04mmol, 20mol%), styrene (0.2mmol, 1equiv), p-phenylphenylacetylene (0.3mmol, 1.5equiv), polychlorinated alkane reagent (0.3mmol, 1.5equiv), potassium carbonate (0.2mmol, 1equiv), methanol solvent (0.5mL), acetonitrile solvent (0.5mL), stirred at room temperature for 24h. After the reaction is completed, the reaction mixture is filtered through diatomaceous earth, washed with ethyl acetate, the organic phases are combined, and the solvent is removed by a rotary evaporator to obtain a crude product, which is separated by silica gel column chromatography, using petroleum ether and ethyl acetate as eluents, and finally obtaining a compound of formula 6 (isolation yield 55%).

[0056]

[0057] 1 H NMR (600 MHz, CDCl 3 )δ7.60-7.57(m, 2H), 7.56-7.49(m, 6H), 7.45(t,J=7.7Hz, 2H), 7.40(t,J=7.7Hz, 2H), 7.38-7.34(m, 1H), 7 .33-7.30 (m, 1H), 4.45 (dd, J=8.6, 3.6Hz, 1H), 3.42 (dd, J=14.9, 8.6Hz, 1H), 3.17 (dd, J=14.9, 3.6Hz, 1H). 13 C NMR (151 MHz, CDCl 3 )δ140.9, 140.44, 140.38, 131.9, 129.0, 128.8, 127.7, 127.6, 127.5, 127.0, 126.9, 122.2, 97.9, 90.3, 84.6, 62.0, 36.5.

[0058] Example 7

[0059] In a reaction tube with a stirrer, N 2 Under the atmosphere, catalyst Cu(OTf) was added successively 2(0.02mmol, 10mol%), ligand α, α, α-terpyridine (0.04mmol, 20mol%), styrene (0.2mmol, 1equiv), p-methoxyphenylacetylene (0.3mmol, 1.5equiv), polychlorinated alkane reagent (0.3mmol, 1.5equiv), potassium carbonate (0.2mmol, 1equiv), methanol solvent (0.5mL), acetonitrile solvent (0.5mL), stirred at room temperature for 24h. After the reaction is completed, the reaction mixture is filtered through diatomaceous earth, washed with ethyl acetate, the organic phases are combined, and the solvent is removed by a rotary evaporator to obtain a crude product, which is separated by silica gel column chromatography, using petroleum ether and ethyl acetate as eluents, and finally obtaining the compound of formula 7 (isolation yield 70%).

[0060]

[0061] 1 H NMR (600 MHz, CDCl 3 )δ7.52-7.49(m, 2H), 7.42-7.35(m, 4H), 7.33-7.28(m, 1H), 6.87-6.80(m, 2H), 4.41(dd, J =8.5, 3.7Hz, 1H), 3.81 (s, 3H), 3.39 (dd, J = 14.8, 8.5Hz, 1H), 3.15 (dd, J = 14.8, 3.7Hz, 1H). 13 C NMR (151 MHz, CDCl 3 )δ159.5, 140.7, 132.9, 128.9, 127.7, 127.4, 115.4, 113.9, 98.0, 88.1, 84.5, 62.1, 55.3, 36.5.

[0062] Example 8

[0063] In a reaction tube with a stirrer, N 2 Under the atmosphere, catalyst Cu(OTf) was added successively 2(0.02mmol, 10mol%), ligand α, α, α-terpyridine (0.04mmol, 20mol%), styrene (0.2mmol, 1equiv), p-chlorophenylacetylene (0.3mmol, 1.5equiv), polychlorinated alkane reagent (0.3mmol, 1.5equiv), potassium carbonate (0.2mmol, 1equiv), methanol solvent (0.5mL), acetonitrile solvent (0.5mL), stirred at room temperature for 24h. After the reaction is completed, the reaction mixture is filtered through diatomaceous earth, washed with ethyl acetate, the organic phases are combined, and the solvent is removed by a rotary evaporator to obtain a crude product, which is separated by silica gel column chromatography, using petroleum ether and ethyl acetate as eluents, and finally obtaining the compound of formula 8 (isolation yield 53%).

[0064]

[0065] 1 H NMR (600 MHz, CDCl 3 ) δ7.53-7.45 (m, 2H), 7.44-7.33 (m, 4H), 7.33-7.26 (m, 3H), 4.40 (dd, J=8.6, 3.7Hz, 1H), 3.39 (dd, J=14.8, 8.6Hz, 1H), 3.14 (dd, J=14.8, 3.6Hz, 1H). 13 C NMR (151 MHz, CDCl 3 )δ140.2, 134.1, 132.7, 129.0, 128.6, 127.6, 127.6, 121.7, 97.8, 90.6, 83.6, 61.9, 36.4.

[0066] Example 9

[0067] In a reaction tube with a stirrer, N 2 Under the atmosphere, catalyst Cu(OTf) was added successively 2(0.02mmol, 10mol%), ligand α, α, α-terpyridine (0.04mmol, 20mol%), styrene (0.2mmol, 1equiv), phenylacetylene (0.3mmol, 1.5equiv), polychlorinated alkane reagent (0.3mmol, 1.5equiv), potassium carbonate (0.2mmol, 1equiv), methanol solvent (0.5mL), acetonitrile solvent (0.5mL), stirred at room temperature for 24h. After the reaction is completed, the reaction mixture is filtered through diatomaceous earth, rinsed with ethyl acetate, the organic phases are combined, and the solvent is removed by a rotary evaporator to obtain a crude product, which is separated by silica gel column chromatography, using petroleum ether and ethyl acetate as eluents, and finally obtaining a compound of formula 9 (isolation yield 51%).

[0068]

[0069] 1 H NMR (600 MHz, CDCl 3 )δ7.47-7.44(m, 4H), 7.38(dd, J=8.5, 6.9Hz, 2H), 7.34-7.28(m, 4H), 5.88(dd, J=8 .5, 5.0Hz, 1H), 4.16 (dd, J=9.4, 6.1Hz, 1H), 2.74-2.69 (m, 1H), 2.66-2.61 (m, 1H). 13 C NMR (151 MHz, CDCl 3 )δ139.5, 131.7, 128.9, 128.3, 128.3, 127.53, 127.45, 122.9, 88.4, 84.5, 71.4, 51.6, 36.2.

[0070] Example 10

[0071] In a reaction tube with a stirrer, N 2 Under the atmosphere, catalyst Cu(OTf) was added successively 2(0.02mmol, 10mol%), ligand α, α, α-terpyridine (0.04mmol, 20mol%), p-methoxystyrene (0.2mmol, 1equiv), phenylacetylene (0.3mmol, 1.5equiv), polychlorinated alkane reagent (0.3mmol, 1.5equiv), potassium carbonate (0.2mmol, 1equiv), methanol solvent. (0.5mL), acetonitrile solvent (0.5mL), stirred at room temperature for 24h. After the reaction is completed, the reaction mixture is filtered through diatomaceous earth, washed with ethyl acetate, the organic phases are combined, and the solvent is removed by a rotary evaporator to obtain a crude product, which is separated by silica gel column chromatography, using petroleum ether and ethyl acetate as eluents, and finally obtaining a compound of formula 10 (isolation yield 68%).

[0072]

[0073] 1 H NMR (600 MHz, CDCl 3 )δ7.48-7.43(m, 4H), 7.34-7.28(m, 3H), 7.03-6.81(m, 2H), 4.48(dd, J=8.4, 3.8 Hz, 1H), 3.82 (s, 3H), 3.24 (dd, J=14.6, 8.4Hz, 1H), 3.01 (dd, J=14.6, 3.8Hz, 1H). 13 CNMR (151MHz, CDCl 3 ) δ158.9, 133.1, 131.5, 128.7, 128.2, 128.0, 123.4, 114.3, 105.2, 98.2, 90.5, 84.5, 55.3, 49.9, 35.3.

[0074] Embodiment 11

[0075] In a reaction tube with a stirrer, N 2 Under the atmosphere, catalyst Cu(OTf) was added successively 2(0.02mmol, 10mol%), ligand α, α, α-terpyridine (0.04mmol, 20mol%), styrene (0.2mmol, 1equiv), phenylacetylene (0.3mmol, 1.5equiv), polychlorinated alkane reagent (0.3mmol, 1.5equiv), potassium carbonate (0.2mmol, 1equiv), methanol solvent (0.5mL), acetonitrile solvent (0.5mL), stirred at room temperature for 24h. After the reaction is completed, the reaction mixture is filtered through diatomaceous earth, rinsed with ethyl acetate, the organic phases are combined, and the solvent is removed by a rotary evaporator to obtain a crude product, which is separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain a compound of formula 11 (isolation yield 67%).

[0076]

[0077] 1 H NMR (600 MHz, CDCl 3 )δ7.50-7.46 (m, 2H), 7.44 (dd, J=6.6, 3.0Hz, 2H), 7.36 (t, J=7.7Hz, 2H), 7.32-7.26 (m, 4H), 6.75 (br s, 1H), 6.04 (br s, 1H), 4.28 (dd, J=9.7, 4.4Hz, 1H), 3.24 (dd, J=14.5, 9.7Hz, 1H), 2.89 (dd, J=14.5, 4.4Hz, 1H). 13 C NMR (151 MHz, CDCl 3 )δ167.6, 140.4, 131.5, 128.8, 128.2, 128.1, 127.7, 127.4, 123.3, 89.1, 84.9, 84.4, 51.6, 35.6.

[0078] Example 12

[0079] In a reaction tube with a stirrer, N 2 Under the atmosphere, catalyst Cu(OTf) was added successively 2(0.02mmol, 10mol%), ligand α, α, α-terpyridine (0.04mmol, 20mol%), styrene (0.2mmol, 1equiv), phenylacetylene (0.3mmol, 1.5equiv), polychlorinated alkane reagent (0.3mmol, 1.5equiv), potassium carbonate (0.2mmol, 1equiv), acetonitrile solvent (1.0mL), stirred at room temperature for 24h. After the reaction is completed, the reaction mixture is filtered through diatomaceous earth, rinsed with ethyl acetate, the organic phases are combined, and the solvent is removed by a rotary evaporator to obtain a crude product, which is separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain a compound of formula 12 (isolation yield 66%).

[0080]

[0081] 1 H NMR (600 MHz, CDCl 3 )δ7.54-7.49 (m, 2H), 7.45 (dt, J=5.9, 3.4Hz, 2H), 7.37 (t, J=7.7Hz, 2H), 7.29 (dq, J=5.8, 3.1Hz, 4H), 4.5 3 (dd, J=8.5, 3.7Hz, 1H), 4.44-4.25 (m, 4H), 3.06-3.01 (m, 1H), 2.82-2.77 (m, 1H), 1.40 (q, J=6.8Hz, 6H). 13 C NMR (151 MHz, CDCl 3 )δ141.3, 131.4, 128.8, 128.2, 127.9, 127.7, 127.2, 123.5, 90.7, 84.2, 81.5 (d, J=179. 2Hz), 65.7 (dd, J=7.4, 4.9Hz), 50.0 (d, J=3.0Hz), 34.2 (d, J=8.4Hz), 16.4 (d, J=5.7Hz).

[0082] Example 13 Synthesis of target product with different ligands

[0083] In a reaction tube with a stirrer, N 2 Under the atmosphere, catalyst Cu(OTf) was added successively 2(0.02mmol, 10mol%), ligand (0.04mmol, 20mol%), styrene (0.2mmol, 1equiv), phenylacetylene (0.3mmol, 1.5equiv), polychlorinated alkane reagent (0.3mmol, 1.5equiv), potassium carbonate (0.2mmol, 1equiv), methanol solvent (0.5mL), acetonitrile solvent (0.5mL), stirred at room temperature for 24h. The reaction results are shown in Table 1

[0084] Table 1 Synthesis results of different ligands

[0085]

[0086] Example 14 Synthesis of target product from different copper salts

[0087] In a reaction tube with a stirrer, N 2 Under the atmosphere, catalyst copper salt (0.02mmol, 10mol%), ligand (0.04mmol, 20mol%), styrene (0.2mmol, 1equiv), phenylacetylene (0.3mmol, 1.5equiv), polychlorinated alkane reagent (0.3mmol, 1.5equiv), potassium carbonate (0.2mmol, 1equiv), methanol solvent (0.5mL), acetonitrile solvent (0.5mL) were added in sequence, and stirred at room temperature for 24h. The reaction results are shown in Table 2

[0088] Table 2 Synthesis results of different copper salts

[0089] Copper salt The NMR yield of the compound of formula 1 <![CDATA[Cu(OTf) 2 ]]> 70％ <![CDATA[Cu(OAc) 2 ]]> 53％ CuI 59％

[0090] Example 15 Synthesis of target product using different alkaline reagents

[0091] In a reaction tube with a stirrer, N 2 Under the atmosphere, catalyst copper salt (0.02mmol, 10mol%), ligand (0.04mmol, 20mol%), styrene (0.2mmol, 1equiv), phenylacetylene (0.3mmol, 1.5equiv), polychlorinated alkane reagent (0.3mmol, 1.5equiv), base (0.2mmol, 1equiv), methanol solvent (0.5mL), acetonitrile solvent (0.5mL) were added in sequence, and stirred at room temperature for 24h. The reaction results are shown in Table 3

[0092] Table 3 Synthesis results of different alkaline reagents

[0093] Alkaline reagent The NMR yield of the compound of formula 1 <![CDATA[K 3 AFTER 4 ]]> 33％ <![CDATA[Na 2 CO 3 ]]> Tarce <![CDATA[K 2 CO 3 ]]> 70(68)％ <![CDATA[Et 3 N]]> 0％

[0094] Although the present invention has been described by the specific embodiments above, it should not be construed as being limited thereto; rather, the present invention encompasses the general aspects disclosed above. Various modifications and various embodiments are possible without departing from the spirit and scope of the present invention.

Claims

1. A method for synthesizing a copper-catalyzed polychlorinated substituted alkyne compound, characterized in that: The method comprises the following steps: Using copper salt Cu(OTf)2 as catalyst, α,α,α-terpyridine as ligand, polychlorinated alkane reagents, aromatic alkynes and aromatic olefins as raw materials, potassium carbonate as base, in a mixed solvent of methanol and acetonitrile with a ratio of 1:1, polychlorinated substituted alkyne compounds were prepared by reaction. The structural formula of the polychlorinated substituted alkyne compound is: The C m X n-1 Selected from CCl3, CCl2CCl3 and CCl2CONH2; the structural formula of the aromatic olefin is: The aromatic alkyne structural formula is: wherein Ar1 and Ar2 are substituted or unsubstituted phenyl groups; the substitution includes mono- to tri-substitution, and the substituents are selected from: C1-8 alkyl, C1-8 alkoxy, halogen, and halogen-substituted C1-8 alkyl; The polychlorinated alkanes are selected from any one or more of the following: CCl4, CCl3CCl3 and CCl3CONH2 The ligand is any one or more of the following structures: R1 is selected from H, C1-4 alkyl.

2. The method according to claim 1, characterized in that The molar ratio of the aromatic olefin compound, the aromatic alkyne compound and the polychlorinated alkane reagent is 1:1.5:1.

5.

3. The method according to claim 1, characterized in that: The amount of the ligand used relative to the aromatic olefin compound is 20 mol%.

4. The method according to claim 1, characterized in that: The amount of the copper salt used relative to the aromatic olefin compound is 10 mol%.

5. The method according to claim 1, characterized in that The molar ratio of the alkaline reagent to the aromatic olefin compound is 1:1.

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