4-sulfonyl-1-naphthyl nitrile derivative and synthesis method thereof

Abstract

The invention provides a 4-sulfonyl-1-naphthyl nitrile derivative and a synthesis method thereof. The derivative has a structure as shown in a general formula I, the synthesis method comprises the following step: under the reaction conditions of a catalyst, alkali, a solvent and a light source, carrying out reaction on initial raw materials, namely a 2-(2-ethynylphenyl) acrylonitrile derivative and a sulfonyl chloride derivative to prepare the 4-sulfonyl-1-naphthylacetonitrile derivative. The synthesized 4-sulfonyl-1-naphthyl nitrile derivative contains naphthalene ring, sulfonyl and cyano functional groups, which are core pharmacophores in bioactive molecules, and the synthesis of the 4-sulfonyl-1-naphthyl nitrile derivative provides theoretical support for the design and synthesis of drug molecules. The synthesis method provided by the invention is simple, metal catalysis is not needed, conditions are mild, a substrate has good universality, and a more effective method is provided for drug design and synthesis.

Description

Technical Field

[0001] This invention relates to the field of organic chemical synthesis, and more particularly to a 4-sulfonyl-1-naphthyl nitrile derivative and its synthesis method. Background Technology

[0002] Organic sulfones possess unique structures and rich electronic properties, making them widely used in organic synthesis, biochemistry, medicinal chemistry, and materials chemistry. Their synthesis methods have consistently been a research hotspot in organic chemistry. For example, the hypoglycemic drug glibenclamide, the nonsteroidal anti-inflammatory drug celecoxib, and the antibacterial drug sulfadiazine are all important drugs containing sulfone structures. Furthermore, sulfonyl naphthol derivatives exhibit excellent charge transport properties in dye-sensitized solar cells. On the other hand, naphthalene compounds are widely found in bioactive natural products, pharmaceutical molecules, agrochemicals, and functional materials. Given their importance, the introduction of sulfonyl groups into the naphthalene skeleton has attracted widespread attention, as sulfonyl-substituted naphthalene compounds often serve as precursors or core structures for various naphthalene derivatives or bioactive molecules. However, methods for directly constructing such skeletons remain relatively limited.

[0003] For example, in 2016, Deng et al. reported the synthesis of α-sulfonylnaphthalene via a cross-coupling reaction of 2-naphthol with sodium sulfonate (Green Chemistry, 2016, 18, 1538-1546).

[0004] In the same year, Jiang et al. developed a radical cyclization reaction of 1,5-enyne with sulfonylhydrazine for the preparation of α-sulfonylnaphthalene (Organic Chemistry Frontiers, 2016, 3, 1452-1456).

[0005] Subsequently, Yan and Zhu reported the synthesis of β-arylsulfonylnaphthalene via the radical cyclization reaction of high propargyl alcohol and sulfonyl hydrazine (Organic Letters, 2019, 21, 8537-8542).

[0006] Li et al. synthesized α-sulfonyl naphthalene by Ru(II)-catalyzed cyclization reaction of nitrone with α-diazosulfonyl ketone (Chemical Communications, 2019, 55, 7339-7342).

[0007] Recently, Zhang and Xie achieved the synthesis of β-arylsulfonylnaphthalene via a tandem reaction of acylalkyne and sodium sulfonate mediated by aluminum chloride (The Journal of Organic Chemistry, 2021, 86, 6247-6258).

[0008] Although the above methods provide a new route for the synthesis of sulfonyl naphthalene, the reaction process usually requires high temperature, excess oxidant or transition metal catalyst, and the reaction conditions are relatively harsh. Summary of the Invention

[0009] In view of this, the present invention provides a 4-sulfonyl-1-naphthyl nitrile derivative and a method for synthesizing the same.

[0010] Building upon our team's accumulated research in the radical tandem cyclization of unsaturated hydrocarbons, we propose a polarity reversal strategy. By introducing a cyano group into 1,5-enyne to alter its electronic properties, we achieve the introduction of a sulfonyl group under mild conditions. This study successfully demonstrated that, at room temperature, only a catalytic amount of iodide anion can form an EDA complex with sulfonyl chloride, thereby inducing the sulfonyl group to participate in the radical tandem cyclization reaction of 1,5-enyne, efficiently constructing cyano-containing polysubstituted naphthalene derivatives. This method requires no external photocatalyst, is mild, and involves simple steps, providing a novel and practical route for the synthesis of sulfonyl naphthalene derivatives.

[0011] The first aspect of the present invention provides a 4-sulfonyl-1-naphthonitrile derivative, which has the following general structural formula:

[0012]

[0013] Wherein, R is one or more of hydrogen, halogen, trifluoromethyl, alkoxy, and alkyl;

[0014] R 1 It is one or more of phenyl, substituted phenyl, naphthyl, heteroaryl, and alkyl; the heteroaryl is one or more of pyridyl, pyrroleyl, thiopheneyl, or furanyl; the substituent in the substituted phenyl is one or more of alkyl, alkoxy, trifluoromethyl, cyano, nitro, F, Cl, Br, and I; the alkyl is one or more of C1-C5 alkyl and cycloalkyl;

[0015] R 2 It is one or more of phenyl, substituted phenyl, naphthyl, heteroaryl, and alkyl;

[0016] R 3 It is one or more of phenyl, substituted phenyl, naphthyl, heteroaryl, and alkyl;

[0017] The second aspect of this application provides a method for synthesizing the aforementioned 4-sulfonyl-1-naphthyl nitrile derivative, comprising reacting a starting material 2-(2-ethynylphenyl)acrylonitrile derivative and a sulfonyl chloride derivative under reaction conditions of a catalyst, a base, a solvent, and a light source to prepare the 4-sulfonyl-1-naphthyl nitrile derivative; the reaction formula is as follows:

[0018]

[0019] Optionally, the synthetic reaction formula for the 2-(2-ethynylphenyl)acrylonitrile derivative is as follows:

[0020]

[0021] Optionally, the synthesis steps of the 2-(2-ethynylphenyl)acrylonitrile derivative are as follows:

[0022] S1: Add tetratetraphenylphosphine palladium, cuprous iodide, and triethylamine to a toluene solution containing o-bromophenylacetonitrile derivative under nitrogen atmosphere, heat and stir for 5 minutes, add terminal alkyne compound and react for 12 hours, filter to obtain yellow reaction solution, concentrate under reduced pressure, and purify by column chromatography to obtain light yellow solid o-alkynylphenylacetonitrile derivative.

[0023] S2: Add alkali and aldehyde derivative to a methanol solution containing o-ethynylphenylacetonitrile derivative, reflux and heat for 12 hours; concentrate under reduced pressure and purify by rapid column chromatography to obtain a light yellow solid 2-(2-ethynylphenyl)acrylonitrile derivative.

[0024] Optionally, the molar ratio of the 2-(2-ethynylphenyl)acrylonitrile derivative to the sulfonyl chloride derivative is 1:1 to 4.

[0025] Optionally, the catalyst is an iodide, preferably one or more of elemental iodine, potassium iodide, sodium iodide, and tetrabutylammonium iodide.

[0026] Optionally, the molar amount of the catalyst is 1% to 100% of the molar amount of the 2-(2-ethynylphenyl)acrylonitrile derivative, preferably 10% to 50%.

[0027] Optionally, the light source is visible light, preferably one or more of the following wavelengths: 425nm, 460nm, and 520nm in 30W, 450nm in 50W, and 400-405nm, 450-455nm, and 500-505nm in 10W.

[0028] Optionally, the base is one or more selected from NaOH, NaHCO3, KHCO3, 1,8-diazabicycloundec-7-ene, triethylamine, pyridine, K2CO3, Cs2CO3, Na2HPO4, and Na2CO3.

[0029] More preferably, the molar amount of the alkali is 0.5 to 2 times the molar amount of the 2-(2-ethynylphenyl)acrylonitrile derivative.

[0030] Optionally, the solvent is one or two of N,N-dimethylacetamide, dimethyl sulfoxide, dichloromethane, acetonitrile, 1,4-dioxane, 1,2-dichloroethane, tetrahydrofuran, ethanol, methanol, and N,N-dimethylformamide.

[0031] Optionally, the solvent used is 0.5-10 mL per millimole of 2-(2-ethynylphenyl)acrylonitrile derivative.

[0032] This application also provides a third technical solution, namely, a 4-sulfonyl-1-naphthyl nitrile derivative obtained by any of the aforementioned synthetic methods.

[0033] The present invention provides a 4-sulfonyl-1-naphthyl nitrile derivative and its synthesis method, which forms an EDA complex with a catalytic amount of iodide and a sulfonyl chloride derivative, generates a sulfonyl radical intermediate under visible light irradiation, and then undergoes a radical addition and cyclization reaction with a 2-(2-ethynylphenyl)acrylonitrile derivative, thus successfully synthesizing the 4-sulfonyl-1-naphthyl nitrile derivative.

[0034] The present invention provides a 4-sulfonyl-1-naphthyl nitrile derivative and its synthesis method, which have the following advantages:

[0035] 1. The reaction does not require an external metal catalyst or excess oxidant, and only the catalytic amount of iodide is used. It does not require high temperature and can be carried out at room temperature, which is environmentally friendly.

[0036] 2. This invention features simple reaction steps, good substrate universality, and high economic efficiency, providing an effective strategy for the molecular design and synthesis of drugs and materials.

[0037] 3. The synthesized 4-sulfonyl-1-naphthyl nitrile derivative contains a naphthalene ring, a sulfonyl group, and a cyano functional group, which are the core pharmacological groups in the bioactive molecule.

[0038] It should be understood that the above general description and the following detailed description are exemplary and explanatory only, and do not limit the disclosure of the present invention. Attached Figure Description

[0039] The accompanying drawings, which are incorporated in and form part of this specification, illustrate embodiments consistent with the invention and, together with the description, serve to explain the principles of the invention.

[0040] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, for those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0041] Figure 1 The hydrogen spectrum of compound 1a in the disclosed embodiments of the present invention;

[0042] Figure 2 This is the carbon spectrum of compound 1a in the disclosed embodiments of the present invention;

[0043] Figure 3 The hydrogen spectrum of compound 3aa in Example 1 of this invention is shown below.

[0044] Figure 4 The carbon spectrum of compound 3aa in Example 1 of this invention is shown below.

[0045] Figure 5 The hydrogen spectrum of compound 3ab in Example 2 of this invention is shown below.

[0046] Figure 6 The carbon spectrum of compound 3ab in Example 2 of this invention is shown below.

[0047] Figure 7 The hydrogen spectrum of compound 3ac in Example 3 of this invention is shown below.

[0048] Figure 8 The carbon spectrum of compound 3ac in Example 3 of this invention is shown below.

[0049] Figure 9 The fluorine spectrum of compound 3ac in Example 4 of this invention is shown below.

[0050] Figure 10 The hydrogen spectrum of compound 3ad in Example 4 of this invention is shown below.

[0051] Figure 11 This is the carbon spectrum of compound 3ad in Example 4 of this invention;

[0052] Figure 12 The hydrogen spectrum of compound 3ae in Example 5 of this invention is shown below.

[0053] Figure 13 The carbon spectrum of compound 3ae in Example 5 of this invention is shown below.

[0054] Figure 14 The hydrogen spectrum of compound 3bf in Example 6 of this invention is shown below.

[0055] Figure 15 The carbon spectrum of compound 3bf in Example 6 of this invention is shown.

[0056] Figure 16 The hydrogen spectrum of compound 3cf in Example 7 of this invention is shown below.

[0057] Figure 17The carbon spectrum of compound 3cf in Example 7 of this invention is shown below.

[0058] Figure 18 The hydrogen spectrum of compound 3df in Example 8 of this invention is shown below.

[0059] Figure 19 The carbon spectrum of compound 3df in Example 8 of this invention is shown below.

[0060] Figure 20 The fluorine spectrum of compound 3df in Example 8 of this invention is shown below.

[0061] Figure 21 The hydrogen spectrum of compound 3ef in Example 9 of this invention is shown below.

[0062] Figure 22 The carbon spectrum of compound 3ef in Example 9 of this invention is shown below.

[0063] Figure 23 The hydrogen spectrum of compound 3ff in Example 10 of this invention is shown below.

[0064] Figure 24 The carbon spectrum of compound 3ff in Example 10 of this invention is shown below.

[0065] Figure 25 The hydrogen spectrum of compound 3gf in Example 11 of this invention;

[0066] Figure 26 The carbon spectrum of compound 3gf in Example 11 of this invention is shown below.

[0067] Figure 27 The hydrogen spectrum of compound 3hf in Example 12 of this invention is shown below.

[0068] Figure 28 The carbon spectrum of compound 3hf in Example 12 of this invention is shown below.

[0069] Figure 29 The fluorine spectrum of compound 3hf in Example 12 of this invention is shown below.

[0070] Figure 30 The hydrogen spectrum of compound 3if in Example 13 of this invention is shown below.

[0071] Figure 31 The carbon spectrum of compound 3if in Example 13 of this invention is shown below.

[0072] Figure 32 The hydrogen spectrum of compound 3jf in Example 14 of this invention is shown below.

[0073] Figure 33The carbon spectrum of compound 3jf in Example 14 of this invention is shown below.

[0074] Figure 34 The hydrogen spectrum of compound 3kf in Example 15 of this invention is shown below.

[0075] Figure 35 This is the carbon spectrum of compound 3kf in Example 15 of this invention. Detailed Implementation

[0076] Exemplary embodiments will now be described in detail, examples of which are illustrated in the accompanying drawings. When the following description relates to the drawings, unless otherwise indicated, the same numerals in different drawings denote the same or similar elements. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present invention. Rather, they are merely examples of apparatuses and methods consistent with some aspects of the invention as detailed in the appended claims.

[0077] This embodiment provides a 4-sulfonyl-1-naphthonitrile derivative and its synthetic method, and the specific steps of the synthesis example are as follows:

[0078] 2-(2-ethynylphenyl)acrylonitrile derivative, sulfonyl chloride derivative, catalyst-iodide, base and solvent were added sequentially to the reactor, and the reaction was carried out under light source irradiation and stirred at room temperature.

[0079] After the reaction was completed, the solvent was adjusted using a rotary evaporator, and the crude product was obtained by column chromatography.

[0080] The above reaction process can be carried out in an inert gas (nitrogen or argon) environment to improve the reaction yield; the eluent used in column chromatography is a conventional eluent, such as a mixture of petroleum ether and ethyl acetate.

[0081] The specific synthesis equations are as follows:

[0082]

[0083] Extensive experimental verification has shown that a molar ratio of 2-(2-ethynylphenyl)acrylonitrile derivative to sulfonyl chloride derivative in the reactants of 1:1 to 4 yields the best results and higher reaction yields. The optimal molar ratio is 1:2. For the catalyst-iodide, elemental iodine, potassium iodide, sodium iodide, and tetrabutylammonium iodide are all suitable catalysts, with tetrabutylammonium iodide being the optimal catalyst. The optimal amount of tetrabutylammonium iodide is 20% of the molar amount of the 2-(2-ethynylphenyl)acrylonitrile derivative. Suitable bases include NaOH, NaHCO3, KHCO3, 1,8-diazabicycloundec-7-ene (DBU), triethylamine (Et3N), pyridine, K2CO3, Cs2CO3, Na2HPO4, and Na2CO3. All methods can generate the target product, with Na2CO3 being the optimal base. The molar amount of this base is one times the molar amount of the 2-(2-ethynylphenyl)acrylonitrile derivative. The light source can be one or more of the following: 30W (425nm, 450nm, 460nm, and 520nm), 50W (450nm), and 10W (400-405nm, 450-455nm, and 500-505nm), with 30W (450nm) being the optimal light source. The solvent can be one or more of the following: N,N-dimethylacetamide, dimethyl sulfoxide, dichloromethane, acetonitrile, 1,4-dioxane, 1,2-dichloroethane, tetrahydrofuran, ethanol, methanol, and N,N-dimethylformamide, with acetone being the optimal solvent. The amount of this solvent used is 0.5-10 mL per millimole of the 2-(2-ethynylphenyl)acrylonitrile derivative.

[0084] The 4-sulfonyl-1-naphthyl nitrile derivative synthesized by the above method has the following general structural formula:

[0085]

[0086] in,

[0087] R is one or more of hydrogen, halogen, trifluoromethyl, alkoxy, and alkyl;

[0088] R 1 It is one or more of phenyl, substituted phenyl, naphthyl, heteroaryl, and alkyl; the heteroaryl is one or more of pyridyl, pyrroleyl, thiopheneyl, or furanyl; the substituent in the substituted phenyl is one or more of alkyl, alkoxy, trifluoromethyl, cyano, nitro, F, Cl, Br, and I; the alkyl is one or more of C1-C5 alkyl and cycloalkyl;

[0089] R 2It is one or more of phenyl, substituted phenyl, naphthyl, heteroaryl, and alkyl;

[0090] R 3 It is one or more of phenyl, substituted phenyl, naphthyl, heteroaryl, and alkyl.

[0091] As shown in the following general formula, the 4-sulfonyl-1-naphthyl nitrile derivatives described in this application refer to compounds as shown in general formula I, which include R, R 1 R 2 and R 3 Substituted 4-sulfonyl-1-naphthyl nitrile compounds. The 2-(2-ethynylphenyl)acrylonitrile derivatives described in this application refer to compounds as shown in general formula II, which include R, R... 2 and R 3 Substituted 2-(2-ethynylphenyl)acrylonitrile; the sulfonyl chloride derivatives described in this application refer to compounds as shown in general formula III, which include R 1 Substituted sulfonyl chloride compounds. All other derivatives described in this application are named in the same way, i.e., compounds with substituted or unsubstituted substituents. The compounds of general formulas II and III described in this application are commercially available. The compounds of general formula II can also be synthesized using the methods provided in this application, and the synthetic starting materials are all commercially available.

[0092]

[0093] R 1 SO2Cl (General Formula III)

[0094] The present invention will be further explained and described below with specific embodiments.

[0095] Example 1

[0096]

[0097] The reactor was placed in nitrogen atmosphere, and 0.2 mmol (61.1 mg) of enyne 1a, 0.4 mmol (70.6 mg) of benzenesulfonyl chloride 2a, 20 mol% (14.8 mg) of TBAI, 0.2 mmol (21.2 mg) of Na2CO3, and 2 mL of acetone were added sequentially. The mixture was stirred at room temperature for 12 h under visible light (30 W blue LED) irradiation. After the reaction was completed, the solvent was adjusted using a rotary evaporator, and the crude product was subjected to column chromatography with a mixture of petroleum ether and ethyl acetate as the eluent to obtain 58.8 mg of 2,3-diphenyl-4-benzenesulfonyl-1-naphthyl nitrile derivative 3aa, with a separation yield of 66%.

[0098] See Figures 3-4 The characterization data of compound 3aa are as follows:

[0099] 1 H NMR (400MHz, CDCl3) δ9.42-9.37(m,1H),8.44-8.39(m,1H),7.82-7.75(m,2H),7.46-7.43(m,2H),7.41-7.3 7(m,1H),7.24(t,J=7.6Hz,2H),7.18-7.12(m,3H),7.06-7.03(m,1H),6.97-6.92(m,4H),6.76-6.73(m,2H). 13 C NMR (100MHz, CDCl3) δ147.1,142.9,142.1,139.5,136.7,136.0,132.7,132.3,131.0,129 .7,129.4,129.3,128.8,128.2,127.8,127.4,127.0,126.8,126.6,126.2,116.2,116.0.

[0100] Example 2

[0101]

[0102] The reactor was placed in nitrogen atmosphere, and 0.2 mmol (61.1 mg) of enyne 1a, 0.4 mmol (82.7 mg) of 4-methoxybenzenesulfonyl chloride 2b, 20 mol% (14.8 mg) of TBAI, 0.2 mmol (21.2 mg) of Na2CO3, and 2 mL of acetone were added sequentially. The mixture was stirred at room temperature under visible light irradiation for 12 h. After the reaction was completed, the solvent was adjusted using a rotary evaporator, and the crude product was subjected to column chromatography with a mixture of petroleum ether and ethyl acetate as the eluent to obtain 57.1 mg of 2,3-diphenyl-4-(4-methoxybenzenesulfonyl)-1-naphthyl nitrile derivative 3ab, with a separation yield of 60%.

[0103] See Figures 5-6 The characterization data of compound 3ab are as follows:

[0104] 1 H NMR (400MHz, CDCl3) δ9.44-9.40(m,1H),8.42-8.38(m,1H),7.80-7.76(m,2H),7.41-7.37(m,2H),7.18 -7.12(m,3H),7.07-7.03(m,1H),6.99-6.94(m,4H),6.78-6.72(m,2H),6.71-6.68(m,2H),3.75(s,3H). 13C NMR (100MHz, CDCl3) δ162.9,147.2,141.6,140.3,136.7,136.3,134.2,132.3,130.8,129.7 ,129.3,129.1,129.1,129.1,128.0,127.7,127.4,126.9,126.1,116.0,115.9,114.0,55.6.

[0105] Example 3

[0106]

[0107] The reactor was placed in nitrogen atmosphere, and 0.2 mmol (61.1 mg) of enyne 1a, 0.4 mmol (97.8 mg) of 4-trifluoromethylbenzenesulfonyl chloride 2c, 20 mol% (14.8 mg) of TBAI, 0.2 mmol (21.2 mg) of Na2CO3, and 2 mL of acetone were added sequentially. The mixture was stirred at room temperature under visible light irradiation for 12 h. After the reaction was completed, the solvent was adjusted using a rotary evaporator, and the crude product was subjected to column chromatography with a mixture of petroleum ether and ethyl acetate as the eluent to obtain 58.9 mg of 2,3-diphenyl-(4-trifluoromethylbenzenesulfonyl)-1-naphthyl nitrile derivative 3ac, with a separation yield of 62%.

[0108] See Figures 7-9 The characterization data of compound 3ac are as follows:

[0109] 1 H NMR (400MHz, CDCl3) δ9.46-9.41(m,1H),8.48-8.44(m,1H),7.87-7.82(m,2H),7.49-7.43(m,4H),7.19-7. 12(m,3H),7.05(t,J=7.6Hz,1H),6.94-6.89(m,4H),6.66-6.64(m,2H),6.76(d,J=3.8Hz,2H),2.31(s,3H). 13 C NMR (100MHz, CDCl3) δ146.9,146.1,141.5,139.5,139.2,136.3,135.6,132.5(q,J=32.8Hz),132.4,131.4,129.7, 129.6,129.5,129.2,128.3,127.9,127.7,126.5,126.4,125.7(q,J=3.6Hz),123.0(q,J=271.3Hz),116.5,115.8. 19 F NMR (376MHz, CDCl3) δ -63.31.

[0110] Example 4

[0111]

[0112] The reactor was placed in nitrogen atmosphere, and 0.2 mmol (61.1 mg) of enyne 1a, 0.4 mmol (70.6 mg) of 2-thienylsulfonyl chloride 2d, 20 mol% (14.8 mg) of TBAI, 0.2 mmol (21.2 mg) of Na2CO3, and 2 mL of acetone were added sequentially. The mixture was stirred at room temperature under visible light irradiation for 12 h. After the reaction was completed, the solvent was adjusted using a rotary evaporator, and the crude product was subjected to column chromatography with a mixture of petroleum ether and ethyl acetate as the eluent to obtain 40.1 mg of 2,3-diphenyl-4-(thienyl-2-sulfonyl)-1-naphthyl nitrile derivative 3ad, with a separation yield of 50%.

[0113] See Figures 10-11 The characterization data of compound 3ad are as follows:

[0114] 1 H NMR (400MHz, CDCl3) δ9.42-9.37(m,1H),8.47-8.42(m,1H),7.86-7.80(m,2H),7.52(dd,J=1.2,4.8Hz,1H ),7.34(dd,J=1.2,3.6Hz,1H),7.23-7.15(m,3H),7.14-7.04(m,3H),7.0-6.97(m,2H),6.91-6.87(m,3H). 13 C NMR (100MHz, CDCl3) δ147.3,143.8,142.1,140.0,136.7,136.5,133.9,133.5,132.4,130.3, 129.7,129.4,129.4,128.8,128.2,127.8,127.5,127.2,127.0,126.8,126.4,116.4,115.9.

[0115] Example 5

[0116]

[0117] The reactor was placed in nitrogen atmosphere, and 0.2 mmol (61.1 mg) of enyne 1a, 0.4 mmol (90.7 mg) of 2-naphthalenesulfonyl chloride 2e, 20 mol% (14.8 mg) of TBAI, 0.2 mmol (21.2 mg) of Na2CO3, and 2 mL of acetone were added sequentially. The mixture was stirred at room temperature under visible light irradiation for 12 h. After the reaction was completed, the solvent was adjusted by rotary evaporator, and the crude product was subjected to column chromatography with a mixture of petroleum ether and ethyl acetate as the eluent to obtain 53.5 mg of 2,3-diphenyl-4-(naphthalene-2-sulfonyl)-1-naphthonitrile derivative 3ae, with a separation yield of 54%.

[0118] See Figures 12-13 The characterization data of compound 3ae are as follows:

[0119] 1 H NMR (400MHz, CDCl3) δ9.56-9.51(m,1H),8.46-8.42(m,1H),7.92-7.91(m,1H),7.84-7.77(m,3H),7.72-7.69(m,2H) ,7.60-7.50(m,2H),7.45-7.42(m,1H),7.18-7.10(m,3H),6.97-6.86(m,3H),6.78-6.74(m,2H),6.70-6.68(m,2H). 13 C NMR (100MHz, CDCl3) δ147.0,141.9,139.7,139.2,136.6,135.8,134.6,132.3,131.8,131.0,129.6,129.3, 129.2,129.0,129.0,128.6,128.1,127.7,127.7,127.6,127.4,126.8,126.6,126.2,121.6,116.2,115.9.

[0120] Example 6

[0121]

[0122] The reactor was placed in nitrogen atmosphere, and 0.2 mmol (63.9 mg) of enyne 1b, 0.4 mmol (76.3 mg) of p-toluenesulfonyl chloride 2f, 20 mol% (14.8 mg) of TBAI, 0.2 mmol (21.2 mg) of Na2CO3, and 2 mL of acetone were added sequentially. The mixture was stirred at room temperature under visible light irradiation for 12 h. After the reaction was completed, the solvent was adjusted using a rotary evaporator, and the crude product was subjected to column chromatography with a mixture of petroleum ether and ethyl acetate as the eluent to obtain 68.2 mg of 3-phenyl-2-(4-methylphenyl)-4-p-toluenesulfonyl-1-naphthyl nitrile derivative 3bf, with a separation yield of 72%.

[0123] See Figures 14-15 The characterization data of compound 3bf are as follows:

[0124] 1 H NMR (400MHz, CDCl3) δ9.38-9.34(m,1H),8.43-8.39(m,1H),7.83-7.70(m,2H),7.36-7.34(m,2H),7. 08-7.03(m,3H),6.99-6.95(m,4H),6.84-6.82(m,2H),6.78-6.75(m,2H),2.31(s,3H),2.24(s,3H). 13 C NMR (100MHz, CDCl3) δ147.3,143.6,142.1,139.9,139.7,137.9,136.3,133.7,132.3,130.9 ,129.6,129.4,129.2,129.1,129.0,128.5,127.4,126.8,126.7,126.2,116.2,21.5,21.3.

[0125] Example 7

[0126]

[0127] The reactor was placed in nitrogen atmosphere, and 0.2 mmol (72.3 mg) of enyne 1c, 0.4 mmol (76.3 mg) of p-toluenesulfonyl chloride 2f, 20 mol% (14.8 mg) of TBAI, 0.2 mmol (21.2 mg) of Na2CO3, and 2 mL of acetone were added sequentially. The mixture was stirred at room temperature under visible light irradiation for 12 h. After the reaction was completed, the solvent was adjusted using a rotary evaporator, and the crude product was subjected to column chromatography with a mixture of petroleum ether and ethyl acetate as the eluent to obtain 62.9 mg of 3-phenyl-2-(4-tert-butylphenyl)-4-p-toluenesulfonyl-1-naphthyl nitrile derivative 3cf, with a separation yield of 61%.

[0128] See Figures 16-17 The characterization data of compound 3cf are as follows:

[0129] 1 H NMR (400MHz, CDCl3) δ9.39-9.35(m,1H),8.45-8.40(m,1H),7.80-7.74(m,2H),7.36-7.32(m,2H),7.14-7.12( m,2H),7.06-7.01(m,3H),6.94-6.91(m,2H),6.86-6.83(m,2H),6.72-6.70(m,2H),2.30(s,3H),1.22(s,3H). 13 C NMR (100MHz, CDCl3) δ151.0,147.3,143.6,142.2,139.9,139.8,136.3,133.5,132.3,131.0,129.4,1 29.3,129.2,129.1,129.0,127.2,126.9,126.8,126.7,126.2,124.6,116.2,115.8,34.5,31.2,21.5.

[0130] Example 8

[0131]

[0132] The reactor was placed in nitrogen atmosphere, and 0.2 mmol (74.7 mg) of enyne 1d, 0.4 mmol (76.3 mg) of p-toluenesulfonyl chloride 2f, 20 mol% (14.8 mg) of TBAI, 0.2 mmol (21.2 mg) of Na2CO3, and 2 mL of acetone were added sequentially. The mixture was stirred at room temperature under visible light irradiation for 12 h. After the reaction was completed, the solvent was adjusted using a rotary evaporator, and the crude product was subjected to column chromatography with a mixture of petroleum ether and ethyl acetate as the eluent to obtain 84.4 mg of 4-p-toluenesulfonyl-1-naphthyl nitrile derivative 3df, with a separation yield of 80%.

[0133] See Figures 18-20 The characterization data of compound 3df are as follows:

[0134] 1 H NMR (400MHz, CDCl3) δ9.36-9.32(m,1H),8.35-8.31(m,1H),7.76-7.71(m,2H),7.35-7.33(m, 2H),7.28-7.25(m,2H),7.03-6.96(m,5H),6.91-6.87(m,2H),6.67-6.65(m,2H),2.23(s,3H). 13C NMR (100MHz, CDCl3) δ144.4,142.8,140.4,139.4,139.2,138.6,134.7,131.19,129.70,129.1(q,J=32.5Hz),129.18,128.54,128.53 ,128.42,128.37,126.68,126.01,125.86,125.77,125.22,123.7(q,J=3.4Hz),122.7(q,J=270.7Hz),118.65,114.86,114.65,20.49. 19 F NMR (376MHz, CDCl3) δ -62.8.

[0135] Example 9

[0136]

[0137] The reactor was placed in nitrogen atmosphere, and 0.2 mmol (61.3 mg) of enyne 1e, 0.4 mmol (76.3 mg) of p-toluenesulfonyl chloride 2f, 20 mol% (14.8 mg) of TBAI, 0.2 mmol (21.2 mg) of Na2CO3, and 2 mL of acetone were added sequentially. The mixture was stirred at room temperature under visible light irradiation for 12 h. After the reaction was completed, the solvent was adjusted using a rotary evaporator, and the crude product was subjected to column chromatography with a mixture of petroleum ether and ethyl acetate as the eluent to obtain 47.9 mg of 3-phenyl-2-(2-pyridyl)-4-p-toluenesulfonyl-1-naphthyl nitrile derivative 3ec, with a separation yield of 52%.

[0138] See Figures 21-22 The characterization data of compound 3ef are as follows:

[0139] 1 H NMR (400MHz, CDCl3) δ9.31-9.26(m,1H),8.48-8.46(m,1H),8.37-8.32(m,1H),7.73-7.68(m,2H),7.33(td,J=7.6,1 .6Hz),7.27-7.24(m,2H),7.05-6.98(m,2H),6.96-6.89(m,4H),6.80-6.79(m,2H),6.74-6.72(m,1H),2.22(s,3H). 13C NMR (100MHz, CDCl3) δ145.8,143.8,141.7,140.0,139.7,136.0,135.2,134.3,132.2,131.4,131.1 ,130.7,130.4,129.4,129.4,129.3,128.1,127.6,127.0,126.8,126.7,126.2,116.1,115.8,21.6.

[0140] Example 10

[0141]

[0142] The reactor was placed in nitrogen atmosphere, and 0.2 mmol (54.3 mg) of enyne 1f, 0.4 mmol (76.3 mg) of p-toluenesulfonyl chloride 2f, 20 mol% (14.8 mg) of TBAI, 0.2 mmol (21.2 mg) of Na2CO3, and 2 mL of acetone were added sequentially. The mixture was stirred at room temperature under visible light irradiation for 12 h. After the reaction was completed, the solvent was adjusted using a rotary evaporator, and the crude product was subjected to column chromatography with a mixture of petroleum ether and ethyl acetate as the eluent to obtain 55.3 mg of 3-phenyl-2-propyl-4-p-toluenesulfonyl-1-naphthyl nitrile derivative 3ff, with a separation yield of 65%.

[0143] See Figures 23-24 The characterization data of compound 3ff are as follows:

[0144] 1 H NMR (400MHz, CDCl3) δ9.25-9.22(m,1H),8.35-8.33(m,1H),7.75-7.65(m,2H),7.44-7.30(m,5H),7.13 -7.11(m,2H),7.09-7.06(m,2H),2.64-2.60(m,2H),2.35(s,3H),1.45-1.39(m,2H),0.77-0.73(m,3H). 13 C NMR (100MHz, CDCl3) δ147.4,143.8,142.6,140.0,139.2,136.3,132.8,129.71,129.5, 128.9,128.5,128.2,127.9,127.4,126.6,125.7,116.2,115.6,35.5,24.4,21.5,14.3.

[0145] Example 11

[0146]

[0147] The reactor was placed in nitrogen atmosphere, and 0.2 mmol (63.9 mg) of enyne 1 g, 0.4 mmol (76.3 mg) of p-toluenesulfonyl chloride 2 f, 20 mol% (14.8 mg) of TBAI, 0.2 mmol (21.2 mg) of Na2CO3 and 2 mL of acetone were added sequentially. The mixture was stirred at room temperature under visible light irradiation for 12 h. After the reaction was completed, the solvent was adjusted by rotary evaporator, and the crude product was subjected to column chromatography with a mixture of petroleum ether and ethyl acetate as the eluent to obtain 80.5 mg of 3-(4-p-tolyl)-2-phenyl-4-p-toluenesulfonyl-1-naphthyl nitrile derivative 3 g f, with a separation yield of 85%.

[0148] See Figures 25-26 The characterization data of compound 3gf are as follows:

[0149] 1 H NMR (400MHz, CDCl3) δ9.36-9.33(m,1H),8.42-8.37(m,1H),7.80-7.73(m,2H),7.35-7.33(m,2H),7.22-7.14( m,3H),7.04-7.02(m,2H),6.98-6.95(m,2H),6.77-6.74(m,2H),6.64-6.62(m,2H),2.31(s,3H),2.22(s,3H). 13 C NMR (100MHz, CDCl3) δ147.2,143.5,141.9,140.0,139.9,137.2,136.8,133.16,132.2,130.7,1 29.7,129.2,129.1,129.0,128.0,127.7,127.5,126.8,126.7,126.1,116.0,115.9,21.5,21.2.

[0150] Example 12

[0151]

[0152] The reactor was placed in nitrogen atmosphere, and 0.2 mmol (64.7 mg) of enyne for 1 h, 0.4 mmol (76.3 mg) of p-toluenesulfonyl chloride for 2 f, 20 mol% (14.8 mg) of TBAI, 0.2 mmol (21.2 mg) of Na2CO3, and 2 mL of acetone were added sequentially. The mixture was stirred at room temperature under visible light irradiation for 12 h. After the reaction was completed, the solvent was adjusted using a rotary evaporator, and the crude product was subjected to column chromatography with a mixture of petroleum ether and ethyl acetate as the eluent to obtain 78.3 mg of 3-(4-fluorophenyl)-2-phenyl-4-p-toluenesulfonyl-1-naphthyl nitrile derivative 3 hf, with a separation yield of 82%.

[0153] See Figures 27-29 The characterization data of compound 3hf are as follows:

[0154] 1 H NMR (400MHz, CDCl3) δ9.41-9.38(m,1H),8.44-8.39(m,1H),7.83-7.77(m,2H),7.36-7.33(m,2H),7. 22-7.17(m,3H),7.09-7.07(m,2H),6.96-6.94(m,2H),6.74-6.702),6.68-6.64(m,2H),2.33(s,3H). 13 C NMR (100MHz, CDCl3) δ163.2, 160.7, 147.0, 143.9, 140.8, 140.1, 139.8, 136.55, 132.6 (d, J = 8.4Hz), 132.3, 132.1 (d, J = 8.4Hz), 129. 6,129.4,129.4,129.3,129.2,127.9,127.3(d,J=257.6Hz),126.8,126.6,126.2,116.0(d,J=27.0Hz),113.9(d,J=21.6Hz),21.56. 19 F NMR (376MHz, CDCl3) δ-113.58.

[0155] Example 13

[0156]

[0157] The reactor was placed in nitrogen atmosphere, and 0.2 mmol (67.1 mg) of enyne 1i, 0.4 mmol (76.3 mg) of p-toluenesulfonyl chloride 2f, 20 mol% (14.8 mg) of TBAI, 0.2 mmol (21.2 mg) of Na2CO3, and 2 mL of acetone were added sequentially. The mixture was stirred at room temperature under visible light irradiation for 12 h. After the reaction was completed, the solvent was adjusted using a rotary evaporator, and the crude product was subjected to column chromatography with a mixture of petroleum ether and ethyl acetate as the eluent to obtain 83.2 mg of 3-(4-methoxyphenyl)-2-phenyl-4-p-toluenesulfonyl-1-naphthyl nitrile derivative 3if, with a separation yield of 85%.

[0158] See Figures 30-31 The characterization data of compound 3if are as follows:

[0159] 1H NMR (400MHz, CDCl3) δ9.42-9.38(m,1H),8.42-8.38(m,1H),7.80-7.75(m,2H),7.31-7.28(m,2H),7.20-7.14( m,3H),7.03-7.01(m,2H),6.98-6.94(m,2H),6.63-6.59(m,2H),6.47-6.43(m,2H),3.71(s,3H),2.30(s,3H). 13 C NMR (100MHz, CDCl3) δ158.9,147.4,143.4,141.5,140.4,140.0,136.7,132.3,132.1,129.7,12 9.3,129.2,129.0,128.2,128.1,127.8,126.8,126.6,126.1,116.1,115.8,112.4,55.1,21.5.

[0160] Example 14

[0161]

[0162] The reactor was placed in nitrogen atmosphere, and 0.2 mmol (62.3 mg) of enyne 1j, 0.4 mmol (76.3 mg) of p-toluenesulfonyl chloride 2f, 20 mol% (14.8 mg) of TBAI, 0.2 mmol (21.2 mg) of Na2CO3, and 2 mL of acetone were added sequentially. The mixture was stirred at room temperature under visible light irradiation for 12 h. After the reaction was completed, the solvent was adjusted using a rotary evaporator, and the crude product was subjected to column chromatography with a mixture of petroleum ether and ethyl acetate as the eluent to obtain 48.4 mg of 2-phenyl-3-(thiophen-2-yl)-4-methanesulfonyl-1-naphthyl nitrile derivative 3jf, with a separation yield of 52%.

[0163] See Figures 32-33 The characterization data of compound 3jf are as follows:

[0164] 1 H NMR (400MHz, CDCl3) δ9.40-9.37(m,1H),8.42-8.40(m,1H),7.83-7.76(m, 2H),7.40-7.38(m,2H),7.30-7.07(m,8H),6.74-6.60(m,2H),2.32(s,3H). 13C NMR (100MHz, CDCl3) δ147.6,143.6,142.1,139.7,136.5,136.2,134.5,132.5,132.4 ,129.7,129.4,129.1,128.4,127.8,126.9,126.7,126.1,125.6,115.9,115.8,21.5.

[0165] Example 15

[0166]

[0167] The reactor was placed in nitrogen atmosphere, and 0.2 mmol (53.8 mg) of enyne 1k, 0.4 mmol (76.3 mg) of p-toluenesulfonyl chloride 2f, 20 mol% (14.8 mg) of TBAI, 0.2 mmol (21.2 mg) of Na2CO3, and 2 mL of acetone were added sequentially. The mixture was stirred at room temperature under visible light irradiation for 12 h. After the reaction was completed, the solvent was adjusted using a rotary evaporator, and the crude product was subjected to column chromatography with a mixture of petroleum ether and ethyl acetate as the eluent to obtain 17.8 mg of 3-cyclopropyl-2-phenyl-4-toluenesulfonyl-1-naphthyl nitrile derivative 3kf, with a separation yield of 21%.

[0168] See Figures 34-35 The characterization data of compound 3kf are as follows:

[0169] 1 H NMR(400MHz, CDCl3)δ8.78(d,J=2.2Hz,1H),8.31(d,J=2.1Hz,1H),7.73-7.71(m,2H),7.68-7.64(m,1H),7.60-7.56(m,1H),7 .54-7.49(m,3H),7.46-7.43(m,2H),7.28-7.25(m,2H),2.41(s,3H),2.02-1.97(m,1H),0.65-0.60(m,2H),0.35-0.32(m,2H). 13 C NMR (100MHz, CDCl3) δ147.6,143.6,142.1,139.7,136.5,136.2,134.5,132.5,132.4 ,129.7,129.4,129.1,128.4,127.8,126.9,126.7,126.1,125.6,115.9,115.8,21.5.

[0170] The following series of experiments, based on the following reaction equation with only minor changes to some components and reaction conditions, are detailed in Table 1. The amounts of each reactant were: 1a (0.2 mmol), TsCl (0.4 mmol, 2.0 equiv.), base (0.2 mmol, 2.0 equiv.), catalyst (TBAI) (0.02 mmol, 20 mol%), and solvent (2 mL). The reaction was carried out at room temperature under a nitrogen atmosphere and irradiated with 30 W 450 nm blue light for 24 h. Example 32 was conducted under 30 W 450 nm irradiation, and Example 35 was conducted in darkness.

[0171]

[0172] Table 1:

[0173]

[0174]

[0175] The experimental results above show that the synthetic method for the 4-sulfonyl-1-naphthyl nitrile derivative described in this application is simple, efficient, and yields good results under mild reaction conditions. This application provides a better preparation method for such derivatives.

[0176] Other embodiments of the invention will readily occur to those skilled in the art upon consideration of the specification and practice of the invention disclosed herein. This application is intended to cover any variations, uses, or adaptations of the invention that follow the general principles of the invention and include common knowledge or customary techniques in the art not disclosed herein. The specification and examples are to be considered exemplary only, and the true scope and spirit of the invention are indicated by the following claims.

[0177] It should be understood that the present invention is not limited to the precise structure described above and shown in the accompanying drawings, and various modifications and changes can be made without departing from its scope. The scope of the invention is limited only by the appended claims.

Claims

1. A 4-sulfonyl-1-naphthyl nitrile derivative, characterized in that, The derivative has the following general structural formula: in, R is one or more of hydrogen, halogen, trifluoromethyl, alkoxy, and alkyl; R 1 It is one or more of phenyl, substituted phenyl, naphthyl, heteroaryl, and alkyl; the heteroaryl is one or more of pyridyl, pyrroleyl, thiopheneyl, or furanyl; the substituent in the substituted phenyl is one or more of alkyl, alkoxy, trifluoromethyl, cyano, nitro, F, Cl, Br, and I; the alkyl is one or more of C1-C5 alkyl and cycloalkyl; R 2 It is one or more of phenyl, substituted phenyl, naphthyl, heteroaryl, and alkyl; R 3 It is one or more of phenyl, substituted phenyl, naphthyl, heteroaryl, and alkyl.

2. The method for synthesizing the 4-sulfonyl-1-naphthyl nitrile derivative according to claim 1, characterized in that, The method includes reacting a starting material, a 2-(2-ethynylphenyl)acrylonitrile derivative, with a sulfonyl chloride derivative to prepare a 4-sulfonyl-1-naphthyl nitrile derivative under reaction conditions of catalyst, base, solvent, and light source; the reaction formula is as follows:

3. The synthesis method according to claim 2, characterized in that, The synthetic reaction formula for the 2-(2-ethynylphenyl)acrylonitrile derivative is as follows:

4. The synthesis method according to claim 3, characterized in that, The synthesis reaction of the 2-(2-ethynylphenyl)acrylonitrile derivative includes the following specific steps: S1: Add tetratetraphenylphosphine palladium, cuprous iodide, and triethylamine to a toluene solution containing o-bromophenylacetonitrile derivative under nitrogen atmosphere, heat and stir for 5 minutes, add terminal alkyne compound and react for 12 hours, filter to obtain yellow reaction solution, concentrate under reduced pressure, and purify by column chromatography to obtain light yellow solid o-alkynylphenylacetonitrile derivative. S2: Add alkali and aldehyde derivative to a methanol solution containing o-ethynylphenylacetonitrile derivative, reflux and heat for 12 hours; concentrate under reduced pressure and purify by rapid column chromatography to obtain a light yellow solid 2-(2-ethynylphenyl)acrylonitrile derivative.

5. The synthesis method according to any one of claims 2 or 3, characterized in that, The molar ratio of the 2-(2-ethynylphenyl)acrylonitrile derivative to the sulfonyl chloride derivative is 1:1 to 4.

6. The synthesis method according to any one of claims 2 or 3, characterized in that, The catalyst is an iodide, preferably one or more of elemental iodine, potassium iodide, sodium iodide, and tetrabutylammonium iodide; the molar amount of the catalyst is 1% to 100% of the molar amount of the 2-(2-ethynylphenyl)acrylonitrile derivative, preferably 10% to 50%.

7. The synthesis method according to any one of claims 2 or 3, characterized in that, The base is one or more of NaOH, NaHCO3, KHCO3, 1,8-diazabicycloundec-7-ene, triethylamine, pyridine, K2CO3, Cs2CO3, Na2HPO4, and Na2CO3; the molar amount of the base is 0.5 to 2 times the molar amount of the 2-(2-ethynylphenyl)acrylonitrile derivative.

8. The synthesis method according to any one of claims 2 or 3, characterized in that, The light source is visible light; preferably, it is one or more of the following wavelengths: 425nm, 460nm, and 520nm in 30W, 450nm in 50W, and 400-405nm, 450-455nm, and 500-505nm in 10W.

9. The synthesis method according to any one of claims 2 or 3, characterized in that, The solvent is one or more of N,N-dimethylacetamide, dimethyl sulfoxide, dichloromethane, acetonitrile, 1,4-dioxane, 1,2-dichloroethane, tetrahydrofuran, ethanol, methanol, and N,N-dimethylformamide; the amount of solvent used is 0.5-10 mL per millimole of 2-(2-ethynylphenyl)acrylonitrile derivative.

10. The 4-sulfonyl-1-naphthyl nitrile derivative obtained by any of the synthetic methods according to claims 2 to 9.

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