Method for synthesizing allene nitrile compound based on visible light / metal copper dual-catalysis strategy and application

Abstract

The invention belongs to the technical field of organic synthesis methodology, and particularly relates to a method for synthesizing allene nitrile compounds based on a visible light / metal copper dual-catalysis strategy and application of the allene nitrile compounds. According to the method, substituted sulfonium salt and substituted enyne are used as raw materials, trimethylsilyl cyanide is used as a cyano source, alkali is used as an additive, and an organic solvent is added; and reacting in inert gas at a certain temperature, and preparing the allene nitrile compound under the dual catalytic action of the photocatalyst and the metal copper / ligand catalyst. The method does not need harsh reaction conditions, the reaction can be completed in one step, the reaction conditions are mild, and the method is green and environment-friendly. The allene nitrile compound and the derivative thereof prepared by the method are expected to serve as lead compounds to be applied to the research and development fields of anti-cancer, antiviral and antibacterial drugs and the like.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis methodology, and specifically relates to a method for synthesizing allene nitrile compounds based on a visible light / metal copper dual catalysis strategy and its application. Background Art

[0002] Nitriles are organic compounds containing one or more cyano groups and are widely used in pharmaceuticals, agrochemicals, organic materials, and natural products. Furthermore, the cyano group is a very important synthon in organic synthesis, effectively converting it into functional groups such as carboxylic acids, amides, aldehydes, ketones, esters, and amines. Furthermore, the introduction of a cyano (CN) group into a bioactive molecule may affect the biological activity of the parent molecule. Therefore, the synthesis and application of nitrile compounds have attracted considerable attention from scientists.

[0003] On the other hand, allenes are a class of compounds containing 1,2-cumulative double bonds with unique reactivity. They are also common fragments in natural products and active pharmaceutical molecules. For example, Enprostil, a drug for treating duodenal ulcers, is more than 600 times more active than its structural analogs. At the same time, people have also modified allene structures into molecules such as pyrimidine and purine, and some of these compounds have been found to have (potential) biological activity (such as Figure 1 ). The cyanoacrylate skeleton is often used as a useful synthetic precursor for various organic motifs, and can efficiently construct various complex structures. However, so far, the synthesis methods of cyanoacrylate compounds are still very limited. The traditional method mainly relies on the CuCN-mediated cyanation reaction of propargyl alcohol and KCN in the presence of stoichiometric HBr (Chem. Commun., 1965, 14, 321.), but this method is prone to waste of resources and environmental pollution. In 2022, the Aso Akira team realized the visible light-mediated copper-catalyzed cyanation reaction of propargyl oxalate (Nat Commun., 2022, 13, 3302.), but this process mainly involves alkyl-substituted cyanoacrylate compounds; in 2023, the Liu Guosheng team used the copper-catalyzed radical relay strategy to realize sp 2 The selective cyanation reaction of allene C-H bonds (J. Am. Chem. Soc., 2023, 145, 25995) has been successfully investigated, but the site selectivity of some substrates needs to be improved. Therefore, it is particularly important to develop a green, efficient, and atom-economical method for the synthesis of allene nitriles. Summary of the Invention

[0004] In order to overcome the shortcomings and deficiencies of the prior art, the present invention aims to provide a method and application for synthesizing allene nitrile compounds based on a visible light / metallic copper dual catalytic strategy. This method does not require harsh synthesis conditions, can synthesize various allene compounds and their derivatives in one step, and has high universality for multiple functional groups.

[0005] To achieve the above object, the present invention adopts the following technical solutions:

[0006] A method for synthesizing allene nitrile compounds based on a visible light / metallic copper dual catalytic strategy: using substituted sulfonium salts and substituted enynes as raw materials, trimethylsilyl cyanide as a cyanide source, a base as an additive, an organic solvent, and reacting under an inert gas and a certain temperature, the allene nitrile compounds are prepared through the dual catalytic action of a photocatalyst and a metallic copper / ligand catalyst.

[0007] A method for synthesizing allene nitrile compounds based on a visible light / metallic copper dual catalysis strategy comprises the following steps:

[0008] (1) At room temperature, a substituted sulfonium salt of Formula I, a substituted enyne of Formula II, trimethylsilyl cyanide, a base, a photocatalyst, a metal catalyst, and a ligand are sequentially added to a reaction tube filled with an inert gas and equipped with a magnetic stirrer. An organic reaction solvent is added using a syringe under inert gas conditions to form a mixed solution. The reaction solution is irradiated with near-violet light at room temperature to promote the reaction.

[0009] (2) After the reaction is completed, an appropriate amount of deionized water is added to the reaction solution, and the mixture is shaken to ensure uniform mixing. 3 mL of ethyl acetate is used as an extractant for separation and extraction. The crude product is extracted from the reaction solution, the extracts are combined, and the solvent is removed by a rotary evaporator. The residue is purified by silica gel column chromatography (silica gel specification is 200 mesh to 300 mesh, and the eluent is petroleum ether / ethyl acetate to obtain the allene compound represented by formula III;

[0010]

[0011] Where:

[0012] R1 is selected from one or more of aryl, alkyl, halogen, ester, cyano, methoxy, aldehyde, and hydrogen substituents;

[0013] R2 is selected from one or more of halogen, methyl, hydrogen, methoxy, ester, and cyano substituents;

[0014] R3 is selected from one of aryl, n-butyl, n-pentyl, and n-hexyl substituents, preferably n-butyl or n-pentyl;

[0015] Ar is selected from a benzene ring or a thiophene ring;

[0016] X is selected from one of PF6 and BF4, preferably BF4.

[0017] Furthermore, the base is one of sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium dihydrogen phosphate, and dipotassium hydrogen phosphate, preferably potassium dihydrogen phosphate;

[0018] The photocatalyst is one of 10-phenylphenothiazine (PTH), 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) or eosin Y, preferably 10-phenylphenothiazine (PTH);

[0019] The metal catalyst is one of Cu(CH3CN)4PF6, CuCl or Cu(NO3)2, preferably Cu(CH3CN)4PF6;

[0020] The ligand is one of 2,2'-bipyridine or 4,4'-bipyridine, preferably 2,2'-bipyridine;

[0021] The inert gas is nitrogen or argon, preferably nitrogen;

[0022] The wavelength range of the near-violet light is 380nm-400nm, preferably 390nm;

[0023] The near-purple light source is a purple LED lamp.

[0024] Furthermore, the amount of the substituted sulfonium salt represented by formula II is 1-2 times, preferably 1.5 times, the amount of the substituted ene-yne represented by formula II;

[0025] The amount of trimethylsilyl cyanide is 1-3 times, preferably 2 times, the amount of the substituted ene-yne represented by formula II;

[0026] The amount of the base is 1-3 times, preferably 2 times, the amount of the substituted ene-yne represented by formula II;

[0027] The amount of the photocatalytic substance is 0.05-0.15 times, preferably 0.1 times, of the substituted ene-yne represented by formula II;

[0028] The amount of the metal copper complex is 0.1-0.2 times, preferably 0.15 times, the amount of the substituted ene yne represented by formula II;

[0029] The amount of the ligand is 0.1-0.3 times, preferably 0.2 times, the amount of the substituted ene-yne represented by formula II;

[0030] The organic solvent is one of dimethyl sulfoxide, N,N-dimethylformamide, tetrahydrofuran, dichloromethane, and n-hexane, preferably dimethyl sulfoxide;

[0031] Furthermore, the synthesis reaction is carried out under atmospheric pressure, and the reaction time is 12h-36h, preferably 24h;

[0032] Further, the reaction formula is:

[0033]

[0034] At room temperature, 0.2 mmol of substituted enyne, 0.3 mmol of sulfonium salt, 0.4 mmol of trimethylsilyl cyanide, 0.02 mmol of photocatalyst, 0.03 mmol of metal catalyst, 0.04 mmol of ligand, and 0.4 mmol of base in the above reaction formula were added to a 25 mL schlenk tube filled with nitrogen and equipped with a magnetic stirrer; 2.0 mL of dimethyl sulfoxide was added using a syringe in a nitrogen environment, and the reaction tube was placed 3 cm away from a 15-watt purple LED lamp, irradiated with purple light and stirred for 24 hours;

[0035] After the reaction is completed, 2 mL of deionized water is added to the reaction solution and stirred evenly. 3 mL of ethyl acetate is used as the extractant each time to extract the crude product from the reaction solution by liquid phase separation extraction operation. The extracts are combined and the solvent is removed by a rotary evaporator; the residue is purified by a silica gel column to obtain the target product.

[0036] Furthermore, the reaction mechanism of the synthesis is:

[0037] Under 390nm violet light irradiation, 10-phenylphenothiazine F is photoexcited to generate an excited species D. This excited species then undergoes a single-electron transfer reaction with the thianthrenesulfonium salt 1a, breaking the carbon-sulfur bond in the thianthrenesulfonium salt and generating an aryl radical A. Simultaneously, the excited species D loses an electron to generate a cation radical E. This cation radical E undergoes another single-electron transfer reaction with the monovalent copper complex G, reducing it to 10-phenylphenothiazine F. The monovalent copper complex G is oxidized to a divalent valence, generating the divalent copper complex H. Aryl radical A reacts with 1,3-enyne 1b via radical addition to generate a radical intermediate B. This radical intermediate B then undergoes resonance to generate a radical intermediate C. Radical intermediate C is then captured by the divalent copper complex H, forming a carbon-metal bond to generate the trivalent copper intermediate I. Finally, reductive elimination yields the target product 1c, and the trivalent copper complex I returns to the monovalent copper complex G to participate in the next catalytic cycle.

[0038] The present invention also includes the application of a method for synthesizing allene nitrile compounds based on a visible light / metallic copper dual catalytic strategy. The synthesis method can be used to synthesize inhibitors for treating bacterial infections, can be used to synthesize antibiotics for treating antiviral infections, can be used to prepare insect repellents, herbicides and fungicides in agricultural chemicals, and can be used as a screening for anti-cancer or antiviral biopharmaceutical lead compounds.

[0039] Allene nitriles and their derivatives have potential anticancer and antiviral activities, and can also be used as antibacterial and antifungal agents. However, the synthesis methods for these compounds are currently very limited. Therefore, the development of new synthesis methods for these compounds has important application value in the field of medicinal chemistry.

[0040] The effective effects of the method for synthesizing allene nitrile compounds based on the visible light / metallic copper dual catalysis strategy and its application are:

[0041] The present invention does not require harsh reaction conditions and can complete the reaction in a single step. It is suitable for synthesizing various allene nitrile compounds and has high universality for a variety of functional groups on the aromatic ring. There are no special restrictions on the number and type of substituents in the allene nitrile compounds. In addition, the number and type of substituents in the sulfonium salt are not particularly limited. The synthesis method of the present invention has a simple preparation process and apparatus, uses near-violet light as energy, employs an organic solvent as a solvent, has mild reaction conditions, and is environmentally friendly. Since the synthesis method is a one-pot process, no complex pretreatment is required, and it is non-toxic and environmentally friendly, conforming to the environmental protection concepts of green chemistry and atom economy. Description of the drawings:

[0042] Figure 1 These are examples of bioactive molecules having an allene skeleton according to the present invention;

[0043] Figure 2 1 is a reaction mechanism diagram of the synthesis method according to an embodiment of the present invention; DETAILED DESCRIPTION

[0044] The technical solution of the present invention is further described in detail below in conjunction with the embodiments, but the protection scope of the present invention is not limited thereto.

[0045] Example 1:

[0046]

[0047] At room temperature, the enyne (0.2 mmol), sulfonium salt (0.3 mmol), trimethylsilyl cyanide (0.4 mmol), PTH (0.02 mmol), Cu(CH3CN)4PF6 (0.03 mmol), BPY (0.04 mmol), and KH2PO4 (0.4 mmol) in the above reaction equation were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. 2.0 mL of dimethyl sulfoxide was added via syringe under nitrogen. The reaction tube was placed 3 cm from a 15-W purple LED lamp and irradiated with purple light while stirring for 24 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 3 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (7:1 v / v) as the eluent. 52 mg of the target product was obtained with a yield of 63%. The NMR spectrum data of the obtained product are as follows:

[0048] 1 H NMR (500MHz, CDCl3) δ7.42(d,J=5.0Hz,1H),7.38–7.34(m,4H),7.32–7.28(m,1H),7.15(dd,J=8.5,2.0Hz,1H),6.85(d,J=8.5H z,1H),3.87(s,3H),3.76(d,J=4.0Hz,2H),2.15(t,J=7.0Hz,2H),1.48–1.35(m,2H),1.36–1.01(m,4H),0.86(t,J=7.0Hz,3H).

[0049] 13 C NMR (125MHz, CDCl3) δ213.1,154.8,133.6,133.1,130.9,128.9,128.8,128.6,12 6.7,115.2,112.0,111.9,111.5,86.3,56.2,35.5,31.6,30.8,27.3,22.2,13.9.

[0050] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 23 H 24 BrNNaO + :432.0933;Found:432.0941.

[0051] Example 2:

[0052]

[0053] At room temperature, the enyne (0.2 mmol), sulfonium salt (0.3 mmol), trimethylsilyl cyanide (0.4 mmol), PTH (0.02 mmol), Cu(CH3CN)4PF6 (0.03 mmol), BPY (0.04 mmol), and KH2PO4 (0.4 mmol) in the above reaction equation were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. 2.0 mL of dimethyl sulfoxide was added via syringe under nitrogen. The reaction tube was placed 3 cm from a 15-W purple LED lamp and irradiated with purple light while stirring for 24 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 3 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (7:1 v / v) as the eluent. 50 mg of the target product was obtained with a yield of 70%. The NMR spectrum data of the obtained product are:

[0054] 1 H NMR (500MHz, CDCl3) δ7.41–7.33(m,4H),7.32–7.27(m,1H),7.26–7.22(m,1H),7.11(dd,J=8.5,2.0Hz,1H),6.88(d,J=8.5Hz ,1H),3.88(s,3H),3.77(d,J=4.0Hz,2H),2.15(t,J=7.5Hz,2H),1.49–1.34(m,2H),1.30–1.19(m,4H),0.85(t,J=7.0Hz,3H).

[0055] 13 C NMR (125MHz, CDCl3) δ213.0,153.9,133.0,130.5,130.4,128.8,128.5,128.1,12 6.6,122.3,115.2,112.1,111.9,86.2,56.1,35.6,31.6,30.8,27.3,22.2,13.8.

[0056] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+H] + Calcd for C 24 H 25 N2O + :357.1961;Found:357.1971.

[0057] Example 3:

[0058]

[0059] At room temperature, the enyne (0.2 mmol), sulfonium salt (0.3 mmol), trimethylsilyl cyanide (0.4 mmol), PTH (0.02 mmol), Cu(CH3CN)4PF6 (0.03 mmol), BPY (0.04 mmol), and KH2PO4 (0.4 mmol) in the above reaction equation were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. 2.0 mL of dimethyl sulfoxide was added via syringe under nitrogen. The reaction tube was placed 3 cm from a 15-W purple LED lamp and irradiated with purple light while stirring for 24 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 3 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (7:1 v / v) as the eluent. 57 mg of the target product was obtained with a yield of 68%. The NMR spectrum data of the obtained product are:

[0060] 1 H NMR (500MHz, CDCl3) δ7.70(d,J=2.5Hz,1H),7.38–7.34(m,1H),7.32(dd,J=5.0,3.0Hz,1H),7.24(dd,J=3.0,1.0Hz,1H),7.03(dd,J=5.0,1.0Hz,1H),6. 95(d,J=8.5Hz,1H),3.90(s,3H),3.88(s,3H),3.77(d,J=6.0Hz,2H),2.12(t ,J=7.5Hz,2H),1.46–1.32(m,2H),1.28–1.20(m,4H),0.85(t,J=7.5Hz,3H).

[0061] 13 C NMR (125MHz, CDCl3) δ213.4,166.4,158.2,134.3,133.9,132.1,128.9,126.5,126.4,1 22.3,119.8,115.1,112.3,107.9,86.0,56.1,52.1,36.3,31.7,30.8,27.3,22.2,13.9.

[0062] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 23 H 25 NNaO3S + :418.1447; Found:418.1455.

[0063] Example 4:

[0064]

[0065] At room temperature, the enyne (0.2 mmol), sulfonium salt (0.3 mmol), trimethylsilyl cyanide (0.4 mmol), PTH (0.02 mmol), Cu(CH3CN)4PF6 (0.03 mmol), BPY (0.04 mmol), and KH2PO4 (0.4 mmol) in the above reaction equation were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. 2.0 mL of dimethyl sulfoxide was added via syringe under nitrogen. The reaction tube was placed 3 cm from a 15-W purple LED lamp and irradiated with purple light while stirring for 24 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 3 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (7:1 v / v) as the eluent. 62 mg of the target product was obtained with a yield of 60%. The NMR spectrum data of the obtained product are:

[0066] 1 H NMR (500MHz, CDCl3) δ7.78–7.51(m,3H),7.33(dd,J=8.5,2.5Hz,1H),7.13–7.05(m,2H),6.94(d,J=8.5Hz,1H),3.89(s,3H ),3.88(s,3H),3.76(d,J=3.5Hz,2H),2.13(t,J=7.5Hz,2H),1.47–1.31(m,2H),1.29–1.14(m,4H),0.84(t,J=7.0Hz,3H).

[0067] 13C NMR (125MHz, CDCl3) δ212.8,166.3,158.2,137.9,133.7,132.6,132.0,128.5,128.3,1 19.8,114.8,112.3,111.3,94.2,86.7,56.0,52.0,35.5,31.4,30.7,27.2,22.1,13.8.

[0068] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 25 H 26 INNaO3 + :538.0850;Found:538.0846.

[0069] Example 5:

[0070]

[0071] At room temperature, the enyne (0.2 mmol), sulfonium salt (0.3 mmol), trimethylsilyl cyanide (0.4 mmol), PTH (0.02 mmol), Cu(CH3CN)4PF6 (0.03 mmol), BPY (0.04 mmol), and KH2PO4 (0.4 mmol) in the above reaction equation were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. 2.0 mL of dimethyl sulfoxide was added via syringe under nitrogen. The reaction tube was placed 3 cm from a 15-W purple LED lamp and irradiated with purple light while stirring for 24 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 3 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (7:1 v / v) as the eluent. 47 mg of the target product was obtained with a yield of 63%. The NMR spectrum data of the obtained product are:

[0072] 1H NMR(500MHz, CDCl3)δ7.70(d,J=2.5Hz,1H),7.38–7.34(m,5H),7.33–7.20(m,1H),6.94(d,J=7.5Hz,1H),3.89(s,3H), 3.88(s,3H),3.80(d,J=4.0Hz,2H),2.13(t,J=7.0Hz,2H),1.43–1.32(m,2H),1.28–1.21(m,2H),0.85(t,J=7.0Hz,3H).

[0073] 13 C NMR (125MHz, CDCl3) δ213.0,166.3,158.1,133.9,133.1,132.1,129.0,128.8,128.5 ,126.6,119.8,115.1,112.2,112.1,86.3,56.0,52.0,35.6,31.2,29.6,21.7,13.6.

[0074] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 24 H 25 NNaO3 + :398.1727;Found:398.1725.

[0075] Example 6:

[0076]

[0077] At room temperature, the enyne (0.2 mmol), sulfonium salt (0.3 mmol), trimethylsilyl cyanide (0.4 mmol), PTH (0.02 mmol), Cu(CH3CN)4PF6 (0.03 mmol), BPY (0.04 mmol), and KH2PO4 (0.4 mmol) in the above reaction equation were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. 2.0 mL of dimethyl sulfoxide was added via syringe under nitrogen. The reaction tube was placed 3 cm from a 15-W purple LED lamp and irradiated with purple light while stirring for 24 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 3 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (7:1 v / v) as the eluent. 51 mg of the target product was obtained with a yield of 60%. The NMR spectrum data of the obtained product are:

[0078] 1 H NMR (500MHz, CDCl3) δ7.69(d,J=2.5Hz,1H),7.34–7.26(m,5H),6.94(d,J=8.5Hz,1H),3.89(s,3H),3.88(s,3 H),3.77(d,J=3.0Hz,2H),2.13(t,J=7.5Hz,2H),1.45–1.33(m,2H),1.27–1.19(m,4H),0.84(t,J=7.0Hz,3H).

[0079] 13 C NMR (125MHz, CDCl3) δ213.0,166.4,158.3,134.5,133.8,132.1,131.6,129.1,128.7,1 28.0,119.9,114.9,112.4,111.3,86.7,56.1,52.1,35.7,31.5,30.8,27.3,22.2,13.9.

[0080] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 25 H 26 ClNNaO3 + :446.1493; Found:446.1501.

[0081] Example 7:

[0082]

[0083] At room temperature, the enyne (0.2 mmol), sulfonium salt (0.3 mmol), trimethylsilyl cyanide (0.4 mmol), PTH (0.02 mmol), Cu(CH3CN)4PF6 (0.03 mmol), BPY (0.04 mmol), and KH2PO4 (0.4 mmol) in the above reaction equation were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. 2.0 mL of dimethyl sulfoxide was added via syringe under nitrogen. The reaction tube was placed 3 cm from a 15-W purple LED lamp and irradiated with purple light while stirring for 24 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 3 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (7:1 v / v) as the eluent. 50 mg of the target product was obtained with a yield of 63%. The NMR spectrum data of the obtained product are:

[0084] 1 H NMR (500MHz, CDCl3) δ7.74(d,J=2.5Hz,1H),7.44–7.29(m,11H),6.89(d,J=8.5Hz,1H),3.97(d,J=2.0Hz,2H),3.85(s,3H),3.81(s,3H).

[0085] 13 C NMR (125MHz, CDCl3) δ214.5,166.2,158.2,133.7,132.2,132.1,129.2,129.1,129. 0,128.9,128.5,126.9,125.6,119.8,115.9,113.6,112.3,89.9,56.0,51.9,35.9.

[0086] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 26 H 21 NNaO3 + :418.1414; Found:418.1408.

[0087] Example 8:

[0088]

[0089] At room temperature, the enyne (0.2 mmol), sulfonium salt (0.3 mmol), trimethylsilyl cyanide (0.4 mmol), PTH (0.02 mmol), Cu(CH3CN)4PF6 (0.03 mmol), BPY (0.04 mmol), and KH2PO4 (0.4 mmol) in the above reaction equation were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. 2.0 mL of dimethyl sulfoxide was added via syringe under nitrogen. The reaction tube was placed 3 cm from a 15-W purple LED lamp and irradiated with purple light while stirring for 24 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 3 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (7:1 v / v) as the eluent. 47 mg of the target product was obtained with a yield of 65%. The NMR spectrum data of the obtained product are:

[0090] 1 H NMR (500MHz, CDCl3) δ7.49–7.32(m,12H),6.89(d,J=8.5Hz,1H),3.96(s,2H),3.87(s,3H).

[0091] 13 C NMR (125MHz, CDCl3) δ214.3,160.3,134.8,133.7,131.9,129.7,129.4,129.3,129. 3,129.2,129.0,126.9,125.6,116.1,115.6,113.5,111.7,101.9,90.2,56.1,35.7.

[0092] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 25 H 18 N2NaO + :385.1311; Found:385.1307.

[0093] Example 9:

[0094]

[0095] At room temperature, the enyne (0.2 mmol), sulfonium salt (0.3 mmol), trimethylsilyl cyanide (0.4 mmol), PTH (0.02 mmol), Cu(CH3CN)4PF6 (0.03 mmol), BPY (0.04 mmol), and KH2PO4 (0.4 mmol) in the above reaction equation were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. 2.0 mL of dimethyl sulfoxide was added via syringe under nitrogen. The reaction tube was placed 3 cm from a 15-W purple LED lamp and irradiated with purple light while stirring for 24 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 3 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (7:1 v / v) as the eluent. 49 mg of the target product was obtained with a yield of 56%. The NMR spectrum data of the obtained product are:

[0096] 1 H NMR (500MHz, CDCl3) δ7.84–7.78(m,4H),7.76(d,J=2.5Hz,1H),7.51–7.47(m,2H),7.45(dd,J=8.5,2.0Hz,1H),7.40(dd,J=8.5,2.5Hz,1H),6.95(d ,J=8.5Hz,1H),3.93(d,J=2.0Hz,2H),3.89(s,3H),3.88(s,3H),2.16(t,J =7.5Hz,2H),1.50–1.34(m,2H),1.29–1.20(m,4H),0.84(t,J=7.0Hz,3H).

[0097] 13 C NMR (125MHz, CDCl3) δ213.7,166.3,158.2,133.9,133.3,133.1,132.2,130.3,129.0,128.5,128.2,127.6,1 26.7,126.6,125.3,124.8,119.8,115.1,112.3,112.3,86.6,56.0,52.0,35.6,31.5,30.8,27.3,22.2,13.8.

[0098] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+H] + Calcd for C 29 H 30 NO3 +:440.2220;Found:440.2220.

[0099] Example 10:

[0100]

[0101] At room temperature, the enyne (0.2 mmol), sulfonium salt (0.3 mmol), trimethylsilyl cyanide (0.4 mmol), PTH (0.02 mmol), Cu(CH3CN)4PF6 (0.03 mmol), BPY (0.04 mmol), and KH2PO4 (0.4 mmol) in the above reaction equation were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. 2.0 mL of dimethyl sulfoxide was added via syringe under nitrogen. The reaction tube was placed 3 cm from a 15-W purple LED lamp and irradiated with purple light while stirring for 24 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 3 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (20:1 v / v) as the eluent. 43 mg of the target product was obtained with a yield of 50%. The NMR spectrum data of the obtained product are:

[0102] 1 H NMR (500MHz, CDCl3) δ7.87–7.79(m,4H),7.61–7.54(m,4H),7.51–7.46(m,3H),7.45–7.41(m,2H),7.39–7.31( m,3H),4.02(d,J=5.5Hz,2H),2.17(t,J=7.0Hz,2H),1.47–1.33(m,2H),1.28–1.21(m,4H),0.87–0.78(m,3H).

[0103] 13 C NMR (125MHz, CDCl3) δ213.9,140.7,139.8,136.6,133.4,133.1,132.6,130.5,129.4,128.8,128.5,128.3 ,127.7,127.3,127.0,126.7,126.6,125.5,125.0,115.3,112.2,86.4,36.5,31.7,30.9,27.3,22.3,13.9.

[0104] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+H]+ Calcd for C 32 H 30 N + :428.2373; Found:428.2375.

[0105] Example 11:

[0106]

[0107] At room temperature, the enyne (0.2 mmol), sulfonium salt (0.3 mmol), trimethylsilyl cyanide (0.4 mmol), PTH (0.02 mmol), Cu(CH3CN)4PF6 (0.03 mmol), BPY (0.04 mmol), and KH2PO4 (0.4 mmol) in the above reaction equation were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. 2.0 mL of dimethyl sulfoxide was added via syringe under nitrogen. The reaction tube was placed 3 cm from a 15-W purple LED lamp and irradiated with purple light while stirring for 24 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 3 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (7:1 v / v) as the eluent. 45 mg of the target product was obtained with a yield of 41%. The NMR spectrum data of the obtained product are as follows:

[0108] 1 H NMR(500MHz, CDCl3)δ8.14(dd,J=5.0,1.5Hz,1H),7.58–7.46(m,1H),7.41–7.20(m,5 H),7.16(d,J=8.5Hz,2H),7.02–6.82(m,7H),6.74(d,J=8.5Hz,1H),5.67–5.51(m,1H ),4.24–4.14(m,1H),4.11–4.00(m,1H),3.80(d,J=5.0Hz,2H),2.13(t,J=7.5Hz,2H) ,1.47(d,J=6.5Hz,3H),1.45–1.32(m,2H),1.31–1.16(m,4H),0.85(t,J=7.0Hz,3H).

[0109] 13C NMR (125MHz, CDCl3) δ213.2,163.1,157.4,155.2,150.3,146.8,138.7,133.3,131.4,130.0,128.8,128.5,126. 7,120.6,117.7,116.7,115.8,115.3,112.2,111.7,86.0,71.1,69.3,36.0,31.6,30.8,27.3,22.2,17.0,13.9.

[0110] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+H] + Calcd for C 36 H 37 N2O3 + :545.2799;Found:545.2798.

[0111] Example 12:

[0112]

[0113] At room temperature, the enyne (0.2 mmol), sulfonium salt (0.3 mmol), trimethylsilyl cyanide (0.4 mmol), PTH (0.02 mmol), Cu(CH3CN)4PF6 (0.03 mmol), BPY (0.04 mmol), and KH2PO4 (0.4 mmol) in the above reaction equation were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. 2.0 mL of dimethyl sulfoxide was added via syringe under nitrogen. The reaction tube was placed 3 cm from a 15-W purple LED lamp and irradiated with purple light while stirring for 24 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 3 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (7:1 v / v) as the eluent. 35 mg of the target product was obtained with a yield of 36%. The NMR spectrum data of the obtained product are as follows:

[0114] 1H NMR (500MHz, CDCl3) δ7.43–7.35(m,4H),7.34–7.28(m,1H),6.89(s,1H),6.61(s,1H),3.95–3.86(m,2H),3.78–3.62 (m,5H),2.27(s,3H),2.15(s,3H),2.04–1.92(m,2H),1.75–1.70(m,4H),1.28–1.14(m,12H),0.84(t,J=7.0Hz,1H).

[0115] 13 C NMR (125MHz, CDCl3) δ212.9,178.3,155.9,134.7,133.8,131.9,128.8,128.4,127.0,126.6,124.0,115 .2113.0,112.5,86.2,68.0,51.7,42.1,37.1,33.6,31.4,30.8,27.3,25.2,25.2,22.319.2,15.6,13.8.

[0116] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 32 H 41 NNaO3 + :510.2979;Found:510.2972.

[0117] Example 13:

[0118]

[0119] At room temperature, the enyne (0.2 mmol), sulfonium salt (0.3 mmol), trimethylsilyl cyanide (0.4 mmol), PTH (0.02 mmol), Cu(CH3CN)4PF6 (0.03 mmol), BPY (0.04 mmol), and KH2PO4 (0.4 mmol) in the above reaction equation were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. 2.0 mL of dimethyl sulfoxide was added via syringe under nitrogen. The reaction tube was placed 3 cm from a 15-W purple LED lamp and irradiated with purple light while stirring for 24 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 3 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (7:1 v / v) as the eluent. 48 mg of the target product was obtained with a yield of 40%. The NMR spectrum data of the obtained product are as follows:

[0120] 1 H NMR (500MHz, CDCl3) δ7.52(d,J=8.5Hz,2H),7.29–7.18(m,7H),6.87(s,1H),6.72(s,1H),3.83(s,3H),3.68(d,J =2.5Hz,2H),3.64(s,3H),3.61(s,2H),2.30(s,3H),1.99–1.86(m,2H),1.22–1.08(m,6H),0.73(t,J=7.0Hz,3H).

[0121] 13 C NMR (125MHz, CDCl3) δ212.9,171.3,168.2,154.1,139.2,135.4,133.6,133.3,131.1,130.2,129.3,129.1,128.7,128 .2,126.7,122.2,115.5,115.4,112.4,111.0,98.9,85.2,55.7,52.1,31.8,31.6,30.8,30.2,27.3,22.2,13.8,13.2.

[0122] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 36 H 35 ClN2NaO4 + :617.2178;Found:617.2177.

[0123] Example 14:

[0124]

[0125] At room temperature, the enyne (0.2 mmol), sulfonium salt (0.3 mmol), trimethylsilyl cyanide (0.4 mmol), PTH (0.02 mmol), Cu(CH3CN)4PF6 (0.03 mmol), BPY (0.04 mmol), and KH2PO4 (0.4 mmol) in the above reaction equation were added to a 25 mL Schlenk tube filled with nitrogen and equipped with a magnetic stirrer. 2.0 mL of dimethyl sulfoxide was added via syringe under nitrogen. The reaction tube was placed 3 cm from a 15-W purple LED lamp and irradiated with purple light while stirring for 24 hours. After the reaction, 2 mL of deionized water was added to the reaction solution and stirred thoroughly. The crude product was extracted from the reaction solution by liquid phase separation extraction using 3 mL of ethyl acetate as the extractant. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified on a silica gel column (200-300 mesh) using petroleum ether / ethyl acetate (7:1 v / v) as the eluent. The tube was filled with nitrogen and equipped with a magnetic stirrer. 2.0 mL of dichloromethane was added in a nitrogen environment using a syringe, and the reaction tube was placed 3 cm away from a 20-watt 455 wavelength blue LED lamp, irradiated with blue light and stirred for 24 hours. After the reaction was completed, 2 mL of deionized water was added to the reaction solution and stirred evenly. 3 mL of ethyl acetate was used as the extractant each time, and the crude product was extracted from the reaction solution by liquid phase separation extraction operation. The extracts were combined and the solvent was removed by rotary evaporation. The residue was purified by silica gel column (silica gel specifications were 200 mesh to 300 mesh) and the eluent was petroleum ether / ethyl acetate (7:1 v / v). 43 mg of the target product was obtained with a yield of 38%. The nuclear magnetic spectrum data of the obtained product are as follows:

[0126] 1 H NMR(500MHz, CDCl3)δ8.37(dd,J=5.0,2.0Hz,1H),8.31(d,J=8.5Hz,1H),8.11–8.03(m,2H),7.38–7.34(m,2H),7.31–7.24(m,7H),7.19(s,1H) ),7.09(d,J=2.0Hz,1H),3.81(d,J=2.0Hz,2H),2.09(t,J=7.5Hz,2H),1.57(s,1H),1.42–1.28(m,2H),1.23–1.08(m,4H),0.79–0.70(m,3H).

[0127] 13C NMR (125MHz, CDCl3) δ212.1,161.4,150.3,139.2,134.9,133.6,133.5,132.2,132.1,131.4,130.0,129.8,129.6 ,128.4,128.3,128.2,127.9,127.6,125.7,121.9,121.0,114.3,110.9,85.1,35.2,30.6,29.8,26.4,21.2,12.9.

[0128] High-resolution mass spectrometry data: HRMS (ESI) m / z: [M+H] + Calcd for C 34 H 30 Cl2N3O + :566.1760;Found:566.1761.

[0129] In the preparation method of the present invention, the order of addition of various materials and the specific reaction steps can be adjusted by those skilled in the art, making it suitable not only for small-scale preparation in the laboratory but also for large-scale industrial production in chemical plants. In industrial batch production, the specific reaction parameters can be determined by those skilled in the art through experiments.

[0130] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0131] Unless otherwise specified, the reagents and materials used in the following examples can be obtained from commercial sources or synthesized from commercially available raw materials.

[0132] The above embodiments are intended only to illustrate the technical concepts and features of the present invention. Their purpose is to enable those skilled in the art to understand the contents of the present invention and implement them accordingly. They are not intended to limit the scope of protection of the present invention. Any equivalent changes or modifications made based on the essence of the present invention are intended to be covered by the scope of protection of the present invention.

Claims

1. A method and application of synthesizing allene nitrile compounds based on visible light / metallic copper dual catalysis strategy, characterized in that: Using substituted sulfonium salts and substituted enynes as raw materials, trimethylsilyl cyanide as a cyanide source, a base as an additive, and an organic solvent, the reaction is carried out under inert gas and a certain temperature. Through the dual catalytic action of a photocatalyst and a metal copper / ligand catalyst, allene nitrile compounds are prepared.

2. The method and application of synthesizing allene nitrile compounds based on the visible light / metallic copper dual catalysis strategy according to claim 1, characterized in that it comprises the following steps: (1) At room temperature, a substituted sulfonium salt of Formula I, a substituted enyne of Formula II, trimethylsilyl cyanide, a base, a photocatalyst, a metal catalyst, and a ligand are sequentially added to a reaction tube filled with an inert gas and equipped with a magnetic stirrer. An organic reaction solvent is added using a syringe under inert gas conditions to form a mixed solution. The reaction solution is irradiated with near-violet light at room temperature to promote the reaction. (2) After the reaction is completed, an appropriate amount of deionized water is added to the reaction solution, and the mixture is shaken to ensure uniform mixing. 3 mL of ethyl acetate is used as an extractant for separation and extraction. The crude product is extracted from the reaction solution, the extracts are combined, and the solvent is removed by a rotary evaporator. The residue is purified by silica gel column chromatography (silica gel specification is 200 mesh to 300 mesh, and the eluent is petroleum ether / ethyl acetate to obtain the allene compound represented by formula III; Where: R1 is selected from one or more of aryl, alkyl, halogen, ester, cyano, methoxy, aldehyde, and hydrogen substituents; R2 is selected from one or more of halogen, methyl, hydrogen, methoxy, ester, and cyano substituents; R3 is selected from one of aryl, n-butyl, n-pentyl, and n-hexyl substituents; Ar is selected from a benzene ring or a thiophene ring; X is selected from one of PF6 and BF4.

3. The method and application of synthesizing allene nitrile compounds based on a visible light / metallic copper dual catalysis strategy according to claim 1 or 2, characterized in that: The base is one of sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium dihydrogen phosphate, and dipotassium hydrogen phosphate; The photocatalyst is one of 10-phenylphenothiazine (PTH), 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) or eosin Y; The metal catalyst is one of Cu(CH3CN)4PF6, CuCl or Cu(NO3)2; The ligand is one of 2,2'-bipyridine or 4,4'-bipyridine; The inert gas is nitrogen or argon; The wavelength range of the near-violet light is 380nm-400nm; The near-purple light source is a purple LED lamp.

4. The method and application of synthesizing allene nitrile compounds based on a visible light / metallic copper dual catalysis strategy according to claim 1 or 2, characterized in that: The amount of the substituted sulfonium salt represented by formula II is 1-2 times that of the substituted ene-yne represented by formula II; The amount of trimethylsilyl cyanide is 1-3 times the amount of the substituted ene-yne shown in formula II; The amount of the base is 1-3 times that of the substituted ene-yne shown in formula II; The amount of the photocatalytic substance is 0.05-0.15 times the substituted ene-yne shown in formula II; The amount of the metal copper complex is 0.1-0.2 times that of the substituted ene yne shown in formula II; The amount of the ligand is 0.1-0.3 times the amount of the substituted ene-yne represented by formula II; The organic solvent is one of dimethyl sulfoxide, N,N-dimethylformamide, tetrahydrofuran, dichloromethane and n-hexane.

5. The method and application of synthesizing allene nitrile compounds based on a visible light / metallic copper dual catalysis strategy according to claim 1 or 2, characterized in that: The synthesis reaction is carried out under atmospheric pressure, and the reaction time is 12h-36h.

6. An application of the visible light / metal copper dual catalytic strategy for synthesizing allene nitriles according to any one of claims 1 to 5 in anticancer, antibacterial and antiviral applications.

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