A method for preparing sulfonamide derivatives by visible-light catalysis without metal participation

Abstract

The present invention relates to a method for the visible-light-catalyzed preparation of sulfonamide derivatives without metal participation, belonging to the technical field of visible-light-catalyzed synthesis. The method of the present invention comprises the following steps: Under a protective atmosphere, an alkene and a sulfonyl azide react under the action of an organic photocatalyst, a Hantzsch ester and a thiophenol in a solvent under visible-light irradiation to obtain a sulfonamide derivative. Wherein, R<supgt;1< / supgt> is selected from an aryl group, a linear alkyl group or a cycloalkyl group; R<supgt;2< / supgt> is selected from hydrogen, an alkyl group with Cl-C4, an alkoxy group, an aryl group or a halogen. The raw materials used in the method of the present invention are cheap and easily available, and the substrate applicability is relatively wide; the organic photocatalyst used does not contain metal and can be used for the post-modification reaction of introducing a sulfonamide group into a drug bioactive molecule; in addition, the method has a short reaction time, mild conditions, a high yield of the target product, little pollution, and a simple reaction operation and post-treatment process, and is suitable for industrial production.

Description

Technical Field

[0001] The present invention belongs to the technical field of visible-light catalytic synthesis, and particularly relates to a method for preparing sulfonamide derivatives by visible-light catalysis without metal participation. Background Art

[0002] Sulfonamide compounds are a very important class of organic compounds, widely present in bioactive molecules, and have extensive applications in the fields of medicine, pesticides, etc. Therefore, it is of great significance to construct such compounds in a simple, efficient, and green manner under mild conditions. Traditional methods for synthesizing sulfonamide compounds include: 1) prepared by the condensation of sulfonic acid and amine under the conditions of an acid / base catalyst and heating. This method has harsh reaction conditions and is not environmentally friendly, not meeting the requirements of green chemistry; 2) prepared by the nucleophilic addition reaction of sulfonyl halide and amine. Although the reagents used in this method have high reaction activity, they are expensive, relatively dangerous, and prone to corrode equipment and pollute the environment. In the past two decades, amination / amidation reactions involving nitrene precursor compounds, such as organic azides, dioxazolones, etc., have received extensive attention. Transition-metal-catalyzed nitrene transfer reactions have become a general strategy for realizing amination / amidation reactions. For example, the hydroamidation reaction of alkenes and dioxazolones catalyzed by transition metals has achieved some Markovnikov and anti-Markovnikov hydroamidation reactions. Rovis et al. achieved the direct sulfonamidation of carbon-hydrogen bonds catalyzed by transition-metal rhodium (N. Wagner-Carlberg, T. Rovis, J. Am. Chem. Soc. 2022, 144, 22426-22432). However, the transition-metal catalysts used in the reaction are usually precious-metal catalysts, greatly increasing the cost and the difficulty of product separation. In addition, visible-light catalysis has the advantages of mild reaction conditions, simple operation, environmental friendliness, etc., and has developed vigorously in recent years, being one of the frontiers of organic chemistry. The transformation of visible-light catalytic nitrene precursors has also received extensive attention in recent years. For example, under the action of a photocatalyst, organic azides can be excited to form excited azides through a photo-mediated triplet energy transfer mechanism, and then nitrogen gas is eliminated to generate free nitrene intermediates, realizing reactions such as C-H amination and aziridination. In addition, organic azides can also be reduced by a single electron through a photocatalyst to form azide radical anions, and then N2 dissociation and protonation occur to generate nitrogen radicals, and subsequent transformations occur. Sulfonyl azide is an important organic synthesis intermediate, having the advantages of being cheap, easily available, less toxic, and convenient to use. It is of great significance to develop a method for preparing sulfonamide derivatives by metal-free visible-light catalysis using such compounds.

[0003] In summary, the currently disclosed synthetic methods of sulfonamide derivatives still have many deficiencies, such as harsh reaction conditions, reliance on precious metal catalysts, narrow substrate scope, etc. Therefore, it is very important to develop a synthetic method of sulfonamide derivatives with mild reaction conditions, no use of metal catalysts, wide substrate scope, simple reaction operation, and easily available raw materials. Summary of the Invention

[0004] To solve the above technical problems, the present invention provides a method for preparing sulfonamide derivatives by visible light catalysis without metal participation. The sulfonamide derivatives are prepared by anti-Markovnikov hydroamidation of sulfonyl azides and alkenes under visible light catalysis. The raw materials used in this method are cheap and easily available, and the substrate applicability is relatively wide; the organic photocatalyst used does not contain metal and can be used for the post-modification reaction of introducing sulfonamide groups into drug bioactive molecules; in addition, this method has a short reaction time, mild conditions, high yield of the target product, low pollution, simple reaction operation and post-treatment process, and is suitable for industrial production.

[0005] The object of the present invention is to provide a method for preparing sulfonamide derivatives by visible light catalysis without metal participation, including the following steps: under a protective atmosphere, alkenes and sulfonyl azides react under the action of an organic photocatalyst, Hantzsch ester and thiophenol in a solvent under visible light irradiation to obtain the sulfonamide derivatives;

[0006] The structural formula of the alkene is The structural formula of the sulfonyl azide is The structural formula of the sulfonamide derivative is

[0007] Wherein, R 1 is selected from aryl or C1-C20 alkyl;

[0008] R 2 is selected from hydrogen, Cl-C4 alkyl, alkoxy, aryl or halogen.

[0009] In one embodiment of the present invention, the organic photocatalyst is selected from 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN) 2,4,6-tris(diphenylamino)-3,5-difluorobenzonitrile (3DPA2FBN) 1,2,3,5-tetrakis(diphenylamino)-4,6-dicyanobenzene (4DPAIPN) or 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN)

[0010] In one embodiment of the present invention, the Hantzsch ester is selected from diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate or dimethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate

[0011] In one embodiment of the present invention, the thiophenol is selected from p-toluenethiol p-methoxythiophenol p-fluorothiophenol p-chlorothiophenol or p-bromothiophenol

[0012] In one embodiment of the present invention, the molar ratio of the alkene, sulfonyl azide, organic photocatalyst, Hantzsch ester and thiophenol is 1:(1 - 5):(0.01 - 0.05):(1 - 5):(1 - 5).

[0013] In one embodiment of the present invention, the light source wavelength of the visible light is 450 nm - 465 nm.

[0014] In one embodiment of the present invention, the solvent is selected from acetonitrile, dichloromethane, 1,2-dichloroethane, tetrahydrofuran or toluene.

[0015] In one embodiment of the present invention, the protective atmosphere is selected from a nitrogen atmosphere or an argon atmosphere.

[0016] In one embodiment of the present invention, after the reaction is completed, it further includes the step of separating and purifying the sulfonamide derivative from the reaction solution.

[0017] In one embodiment of the present invention, to determine whether the reaction is completed, methods such as TLC (thin layer chromatography), LC (liquid chromatography), GC (gas chromatography when the molecular weight is less than 300) can be used for tracking.

[0018] In one embodiment of the present invention, the separation and purification is achieved by column chromatography or liquid chromatography.

[0019] The specific reaction general formula of the present invention is shown as follows:

[0020]

[0021] The technical solution of the present invention has the following advantages compared with the prior art:

[0022] (1) In the preparation method of the present invention, the photoinduced sulfonyl azide compound efficiently generates nitrogen radicals through the hydrogen atom transfer (HAT) mechanism, which is the key for the reaction to be completed within a few minutes. The efficient conversion of organic azides to nitrogen radical intermediates through the hydrogen atom transfer strategy has not been reported in the literature. The detailed mechanism of this reaction is as Figure 1Shown as follows: First, the excited-state photosensitizer 3DPAFIPN* undergoes reductive quenching with Hantzsch ester (HE) via single electron transfer (SET), generating 3DPAFIPN ·- and HE ·+ two intermediates. Subsequently, HE ·+ and sulfonyl azide generate the key sulfonamide radical I via HAT. The formed radical I can attack the alkene via radical addition (RA) to form alkyl radical II. Finally, the generated alkyl radical II undergoes a HAT reaction with the S-H moiety of p-toluenethiol to produce the target product. The generated sulfur radical (III) undergoes a SET process with the reduced photosensitizer (3DPAFIPN ·- ) to regenerate the photocatalyst and generate the corresponding sulfur anion (IV). Next, after protonation of the sulfur anion (IV), the catalytic cycle of p-toluenethiol is completed.

[0023] (2) Compared with the existing transition metal-catalyzed preparation of sulfonamide derivatives, the preparation method of the present invention uses an organic photocatalyst without metal and can be used for the post-modification reaction of introducing sulfonamide groups into drug bioactive molecules.

[0024] (3) The preparation method of the present invention uses an alkene as the starting material, which is readily available, has low toxicity, low cost, and a wide variety; the amination reagent used is an azide, which is inexpensive, readily available, has low toxicity, and is easy to use; the reaction conditions are mild, the reaction time is short, the yield of the target product is high, the reaction operation and post-treatment process are simple, and it is suitable for industrial production. This method is not only applicable to the synthesis of activated alkene sulfonamide derivatives but also applicable to non-activated alkenes. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to make the content of the present invention easier to be clearly understood, the following further details the present invention according to specific embodiments of the present invention in conjunction with the drawings, where:

[0026] Figure 1 is the reaction mechanism of the metal-free visible light-catalyzed preparation of sulfonamide derivatives of the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0027] The following further illustrates the present invention with specific embodiments, so that those skilled in the art can better understand the present invention and be able to implement it, but the examples given are not intended to limit the present invention.

[0028] Example 1: Synthesis of 4-methyl-N-phenethylbenzenesulfonamide

[0029] Using styrene and p-toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0030]

[0031] (1) 2,4,6-Tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) were added into a reaction flask, evacuated and purged with nitrogen three times to create a nitrogen atmosphere in the reaction flask. Under nitrogen protection, 1,2-dichloroethane (1 mL), p-toluenesulfonyl azide (0.6 mmol), and styrene (0.2 mmol) were added, and the mixture was stirred and reacted at room temperature for 3 min under irradiation with a 450 nm - 465 nm blue LED lamp.

[0032] (2) The reaction was monitored by TLC until it was completely finished.

[0033] (3) The crude product obtained after the reaction was separated by column chromatography (ethyl acetate: petroleum ether = 1:20) to obtain the target product (yield 58%).

[0034] The analysis data of the product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.3 Hz, 2H), 7.34 - 7.26 (m, 4H), 7.26 - 7.22 (m, 1H), 7.11 (d, J = 6.8 Hz, 2H), 4.73 (s, 1H), 3.23 (t, J = 7.1 Hz, 2H), 2.78 (t, J = 7.1 Hz, 2H), 2.45 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 143.44, 137.79, 136.91, 129.75, 128.76, 128.73, 127.12, 126.77, 44.28, 35.83, 21.55.

[0035] Example 2: Synthesis of N-(4-methoxyphenethyl)-4-methylbenzenesulfonamide

[0036] Using p-methoxystyrene and p-toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0037]

[0038] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to make the reaction flask in a nitrogen atmosphere. Under nitrogen protection, add 1,2-dichloroethane (1 mL), p-toluenesulfonyl azide (0.6 mmol), p-methoxystyrene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp;

[0039] (2) Monitor the reaction by TLC until it is completely finished;

[0040] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate:petroleum ether = 1:10) to obtain the target product (yield 85%).

[0041] The analysis data of the product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 8.4 Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 8.6 Hz, 2H), 6.69 (d, J = 8.6 Hz, 2H), 4.70 (t, J = 6.2 Hz, 1H), 3.67 (s, 3H), 3.06 (q, J = 6.9 Hz, 2H), 2.60 (t, J = 7.1 Hz, 2H), 2.32 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 158.42, 143.39, 136.92, 129.76, 129.73, 129.72, 127.11, 114.12, 55.28, 44.49, 34.89, 21.53.

[0042] Example 3: Synthesis of 4-methyl-N-(4-methylphenethyl)benzenesulfonamide

[0043] Using p-methylstyrene and p-toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0044]

[0045] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into the reaction flask. Evacuate and replace the gas three times to create a nitrogen atmosphere in the reaction flask. Under nitrogen protection, add 1,2-dichloroethane (1 mL), p-toluenesulfonyl azide (0.6 mmol), and p-methylstyrene (0.2 mmol). Stir and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp;

[0046] (2) Monitor the reaction by TLC until it is completely finished;

[0047] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate: petroleum ether = 1:10) to obtain the target product (yield 71%).

[0048] The analysis data of the product are as follows: 1 H NMR(400MHz,CDCl3)δ7.74 - 7.65(m,2H),7.31(d,J = 8.0Hz,2H),7.10(d,J = 7.9Hz,2H),7.01 - 6.94(m,2H),4.43(s,1H),3.21(q,J = 6.1Hz,2H),2.74(t,J = 6.9Hz,2H),2.45(s,3H),2.34(s,3H). 13 C NMR(101MHz,CDCl3)δ143.40,136.94,136.42,134.50,129.70,129.44,128.62,127.12,44.28,35.31,21.54,21.02.

[0049] Example 4: Synthesis of N-(4-tert-butylphenethyl)-4-methylbenzenesulfonamide

[0050] Using p-tert-butylstyrene and p-toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0051]

[0052] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to create a nitrogen atmosphere in the reaction flask. Under nitrogen protection, add 1,2-dichloroethane (1 mL), p-toluenesulfonyl azide (0.6 mmol), 4-tert-butylstyrene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation with a 450 - 465 nm blue LED lamp;

[0053] (2) Monitor the reaction by TLC until it is completely finished;

[0054] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate:petroleum ether = 1:10) to obtain the target product (yield 71%).

[0055] The analytical data of the product are as follows: 1 H NMR(400MHz,CDCl3)δ7.74 - 7.65(m,2H),7.34 - 7.25(m,4H),7.07 - 6.91(m,2H),4.40(t,J = 6.2Hz,1H),3.20(q,J = 6.8Hz,2H),2.72(t,J = 6.9Hz,2H),2.43(s,3H),1.30(s,9H). 13 C NMR(101MHz,CDCl3)δ149.76,143.42,136.96,134.49,129.72,128.42,127.14,125.69,44.16,35.18,34.45,31.35,21.55.

[0056] Example 5: Synthesis of N-(4-phenylphenethyl)-4-methylbenzenesulfonamide

[0057] Using 4-phenylstyrene and p-toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0058]

[0059] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to create a nitrogen atmosphere in the reaction flask. Under nitrogen protection, add 1,2-dichloroethane (1 mL), p-toluenesulfonyl azide (0.6 mmol), 4-phenylstyrene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation with a 450 nm - 465 nm blue LED lamp;

[0060] (2) Monitor the reaction by TLC until it is completely finished;

[0061] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate:petroleum ether = 1:10) to obtain the target product (yield 56%).

[0062] The analytical data of the product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.78 - 7.70 (m, 2H), 7.62 - 7.55 (m, 2H), 7.55 - 7.48 (m, 2H), 7.51 - 7.42 (m, 2H), 7.42 - 7.33 (m, 1H), 7.31 (d, J = 8.1 Hz, 2H), 7.22 - 7.15 (m, 2H), 4.67 (t, J = 6.3 Hz, 1H), 3.28 (q, J = 6.7 Hz, 2H), 2.83 (t, J = 7.0 Hz, 2H), 2.43 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 143.48, 140.71, 139.76, 136.90, 136.79, 129.76, 129.21, 128.83, 127.44, 127.32, 127.13, 127.01, 44.23, 35.47, 21.54.

[0063] Example 6: Synthesis of N-(4-fluorophenethyl)-4-methylbenzenesulfonamide

[0064] Using 4-fluorostyrene and p-toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0065]

[0066] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (HE, 0.6 mmol) into a reaction flask, evacuate and replace the gas three times to make the reaction flask in a nitrogen atmosphere; under nitrogen protection, add 1,2-dichloroethane (1 mL), p-toluenesulfonyl azide (0.6 mmol), 4-fluorostyrene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp;

[0067] (2) Monitor the reaction by TLC until it is completely finished;

[0068] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate:petroleum ether = 1:20) to obtain the target product (yield 54%).

[0069] The analysis data of the product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.74 - 7.66 (m, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.10 - 7.03 (m, 2H), 7.00 - 6.89 (m, 2H), 4.57 (t, J = 5.9 Hz, 1H), 3.20 (q, J = 6.6 Hz, 2H), 2.76 (t, J = 7.0 Hz, 2H), 2.45 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 162.99, 160.55, 143.53, 136.84, 133.41, 133.38, 130.26, 130.18, 129.75, 127.08, 115.64, 115.43, 44.28, 35.07, 21.54. 19 F NMR (400 MHz, CDCl3) δ -116.09.

[0070] Example 7: Synthesis of 4-methyl-N-(2-methylphenethyl)benzenesulfonamide

[0071] Using 2-methylstyrene and p-toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0072]

[0073] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to create a nitrogen atmosphere in the reaction flask. Under nitrogen protection, add 1,2-dichloroethane (1 mL), p-toluenesulfonyl azide (0.6 mmol), 2-methylstyrene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation with a 450 nm - 465 nm blue LED lamp;

[0074] (2) Monitor the reaction by TLC until it is completely finished;

[0075] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate:petroleum ether = 1:10) to obtain the target product (yield 63%).

[0076] The analytical data of the product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.76 - 7.68 (m, 2H), 7.34 - 7.29 (m, 2H), 7.18 - 7.10 (m, 3H), 7.06 - 7.00 (m, 1H), 4.50 (s, 1H), 3.19 (q, J = 7.0 Hz, 2H), 2.81 (t, J = 7.3 Hz, 2H), 2.45 (s, 3H), 2.25 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 143.45, 136.95, 136.33, 135.80, 130.62, 129.73, 129.29, 127.11, 126.94, 126.25, 43.01, 33.32, 21.53, 19.27.

[0077] Example 8: Synthesis of N-(2-methoxyphenethyl)-4-methylbenzenesulfonamide

[0078] Using 2-methoxystyrene and p-toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0079]

[0080] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to create a nitrogen atmosphere in the reaction flask. Under nitrogen protection, add 1,2-dichloroethane (1 mL), p-toluenesulfonyl azide (0.6 mmol), and 2-methoxystyrene (0.2 mmol). Stir and react at room temperature for 3 min under irradiation with a 450 nm - 465 nm blue LED lamp.

[0081] (2) Monitor the reaction by TLC until it is completely finished.

[0082] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate:petroleum ether = 1:10) to obtain the target product (yield 72%).

[0083] The analysis data of the product is as follows: 1 H NMR(400MHz,CDCl3)δ7.71 - 7.64(m,2H),7.30 - 7.25(m,2H),7.22(td,J=7.8,1.8Hz,1H),7.02(dd,J=7.4,1.8Hz,1H),6.87(td,J=7.4,1.1Hz,1H),6.83(dd,J=8.2,1.1Hz,1H),4.63(s,1H),3.78(s,3H),3.22(q,J=6.4Hz,2H),2.78(t,J=6.8Hz,2H),2.43(s,3H). 13 C NMR(101MHz,CDCl3)δ157.41,143.15,137.01,130.72,129.59,128.18,127.08,126.16,120.73,110.43,77.39,77.07,76.75,55.23,43.08,30.61,21.52.

[0084] Example 9: Synthesis of 4-methyl-N-(3-methylphenethyl)benzenesulfonamide

[0085] Using 3-methylstyrene and p-toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0086]

[0087] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to create a nitrogen atmosphere in the reaction flask. Under nitrogen protection, add 1,2-dichloroethane (1 mL), p-toluenesulfonyl azide (0.6 mmol), 3-methylstyrene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp;

[0088] (2) Monitor the reaction by TLC until it is completely finished;

[0089] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate:petroleum ether = 1:20) to obtain the target product (yield 71%).

[0090] The analysis data of the product is as follows: 1 H NMR(400MHz,CDCl3)δ7.74 - 7.67(m,2H),7.31(d,J = 8.1Hz,2H),7.18(t,J = 7.8Hz,1H),7.05(d,J = 7.6Hz,1H),6.92 - 6.86(m,2H),4.43(s,1H),3.23(q,J = 6.5Hz,2H),2.74(t,J = 6.9Hz,2H),2.45(s,3H),2.32(s,3H). 13 C NMR(101MHz,CDCl3)δ143.42,138.43,137.53,136.91,129.72,129.53,128.68,127.58,127.12,125.72,44.19,35.63,21.55,21.36.

[0091] Example 10: Synthesis of N-(3-methoxyphenethyl)-4-methylbenzenesulfonamide

[0092] Using 3-methoxystyrene and p-toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0093]

[0094] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to create a nitrogen atmosphere in the reaction flask. Under nitrogen protection, add 1,2-dichloroethane (1 mL), p-toluenesulfonyl azide (0.6 mmol), 3-methoxystyrene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp;

[0095] (2) Monitor the reaction by TLC until it is completely finished;

[0096] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate:petroleum ether = 1:10) to obtain the target product (yield 58%).

[0097] The analysis data of the product is as follows: 1 H NMR(400MHz,CDCl3)δ7.73 - 7.68(m,2H),7.33 - 7.29(m,2H),7.23 - 7.18(m,1H),6.82 - 6.74(m,1H),6.71 - 6.67(m,1H),6.63(t,J = 2.1Hz,1H),4.46(t,J = 6.3Hz,1H),3.79(s,3H),3.23(q,J = 6.7Hz,2H),2.75(t,J = 6.9Hz,2H),2.45(s,3H). 13 C NMR(101MHz,CDCl3)δ159.88,143.44,139.23,136.89,129.79,129.73,127.11,121.01,114.45,112.16,55.17,44.10,35.79,21.53.

[0098] Example 11: Synthesis of N-(3-chlorophenethyl)-4-methylbenzenesulfonamide

[0099] Using 3-chlorostyrene and p-toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0100]

[0101] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to create a nitrogen atmosphere in the reaction flask. Under nitrogen protection, add 1,2-dichloroethane (1 mL), p-toluenesulfonyl azide (0.6 mmol), 3-chlorostyrene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp;

[0102] (2) Monitor the reaction by TLC until it is completely finished;

[0103] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate:petroleum ether = 1:10) to obtain the target product (yield 50%).

[0104] The analysis data of the product is as follows: 1 H NMR(400MHz,CDCl3)δ7.75 - 7.68(m,2H),7.32(d,J = 8.0Hz,2H),7.23 - 7.16(m,2H),7.06 - 7.03(m,1H),7.04 - 6.97(m,1H),4.55(t,J = 6.3Hz,1H),3.23(q,J = 6.8Hz,2H),2.76(t,J = 7.0Hz,2H),2.45(s,3H). 13 C NMR(101MHz,CDCl3)δ143.59,139.79,136.81,134.50,129.98,129.80,128.83,127.07,127.02,126.99,43.95,35.54,21.56.

[0105] Example 12: Synthesis of 4-methyl-N-(1-phenylpropan-2-yl)benzenesulfonamide

[0106] Using 1-propenylbenzene and p-toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0107]

[0108] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to create a nitrogen atmosphere in the reaction flask. Under nitrogen protection, add 1,2-dichloroethane (1 mL), p-toluenesulfonyl azide (0.6 mmol), 1-propenylbenzene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation with a 450 nm - 465 nm blue LED lamp;

[0109] (2) Monitor the reaction by TLC until it is completely finished;

[0110] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate:petroleum ether = 1:10) to obtain the target product (yield 59%).

[0111] The analysis data of the product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.62 (d, J = 8.3 Hz, 2H), 7.24 - 7.16 (m, 5H), 7.04 - 6.96 (m, 2H), 4.50 (d, J = 7.3 Hz, 1H), 3.58 - 3.47 (m, 1H), 2.72 - 2.62 (m, 2H), 2.41 (s, 3H), 1.09 (d, J = 6.6 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 143.14, 137.64, 137.13, 129.62, 129.39, 128.53, 127.00, 126.64, 50.91, 43.45, 21.53, 21.30.

[0112] Example 13: Synthesis of N-(2,3-dihydro-1H-inden-2-yl)-4-methylbenzenesulfonamide

[0113] Using indene and p-toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0114]

[0115] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to create a nitrogen atmosphere in the reaction flask. Under nitrogen protection, add 1,2-dichloroethane (1 mL), p-toluenesulfonyl azide (0.6 mmol), indene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp;

[0116] (2) Monitor the reaction by TLC until it is completely finished;

[0117] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate:petroleum ether = 1:20) to obtain the target product (yield 84%).

[0118] The analysis data of the product is as follows: 1 H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.3 Hz, 2H), 7.36 - 7.30 (m, 2H), 7.14 (s, 4H), 4.78 (d, J = 8.3 Hz, 1H), 4.18 - 4.03 (m, 1H), 3.11 (dd, J = 15.9, 7.2 Hz, 2H), 2.74 (dd, J = 15.9, 5.9 Hz, 2H), 2.45 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 143.54, 140.03, 137.75, 129.82, 127.15, 126.95, 124.65, 54.72, 40.35, 21.59.

[0119] Example 14: Synthesis of N-(2-tert-butoxyethyl)-4-methylbenzenesulfonamide

[0120] Using tert-butyl vinyl ether and p-toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0121]

[0122] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to create a nitrogen atmosphere in the reaction flask. Under nitrogen protection, add 1,2-dichloroethane (1 mL), p-toluenesulfonyl azide (0.6 mmol), and tert-butyl vinyl ether (0.2 mmol). Stir and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp;

[0123] (2) Monitor the reaction by TLC until it is completely finished;

[0124] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate: petroleum ether = 1:20) to obtain the target product (yield 63%).

[0125] The analysis data of the product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 7.9 Hz, 2H), 4.89 (s, 1H), 3.38 (t, J = 5.1 Hz, 2H), 3.08 (q, J = 5.4 Hz, 2H), 2.44 (s, 3H), 1.13 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 143.34, 137.04, 129.68, 127.13, 73.34, 59.84, 43.57, 27.41, 21.50.

[0126] Example 15: Synthesis of N-(cyclohexylmethyl)-4-methylbenzenesulfonamide

[0127] Using methylenecyclopropane and p-toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0128]

[0129] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to create a nitrogen atmosphere in the reaction flask. Under nitrogen protection, add 1,2-dichloroethane (1 mL), p-toluenesulfonyl azide (0.6 mmol), and methylenecyclopropane (0.2 mmol). Stir and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp;

[0130] (2) Monitor the reaction by TLC until it is completely finished;

[0131] (3) The crude product obtained after the reaction was separated by column chromatography (ethyl acetate: petroleum ether = 1:20) to give the target product (yield 81%).

[0132] The analytical data of the product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 4.41 (t, J = 6.6 Hz, 1H), 2.76 (t, J = 6.6 Hz, 2H), 2.43 (s, 3H), 1.74 - 1.60 (m, 5H), 1.46 - 1.32 (m, 1H), 1.24 - 1.05 (m, 3H), 0.93 - 0.78 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 143.28, 137.09, 129.67, 127.09, 49.40, 37.77, 30.56, 26.27, 25.65, 21.54.

[0133] Example 16: Synthesis of N-cyclopentyl-4-methylbenzenesulfonamide

[0134] Using cyclopentene and p-toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0135]

[0136] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-thiocresol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) to the reaction flask, evacuate and replace the gas three times to make the reaction flask under a nitrogen atmosphere; under nitrogen protection, add 1,2-dichloroethane (1 mL), p-toluenesulfonyl azide (0.6 mmol), cyclopentene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation with a 450 nm - 465 nm blue LED lamp;

[0137] (2) Monitor the reaction by TLC until it is completely finished;

[0138] (3) The crude product obtained after the reaction was separated by column chromatography (ethyl acetate: petroleum ether = 1:20) to give the target product (yield 56%).

[0139] The analytical data of the product are as follows: 11H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 7.9 Hz, 2H), 4.67 (d, J = 7.2 Hz, 1H), 3.58 (q, J = 6.8 Hz, 1H), 2.43 (s, 3H), 1.83 - 1.70 (m, 2H), 1.67 - 1.55 (m, 2H), 1.53 - 1.41 (m, 2H), 1.40 - 1.25 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 143.24, 137.88, 129.66, 127.14, 55.15, 33.46, 23.15, 21.54.

[0140] Example 17: Synthesis of N - cyclohexyl - 4 - methylbenzenesulfonamide

[0141] Using cyclohexene and p - toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0142]

[0143] (1) Add 2,4,6 - tris(diphenylamino) - 5 - fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p - tolyl mercaptan (0.08 mmol), diethyl 2,6 - dimethyl - 1,4 - dihydropyridine - 3,5 - dicarboxylate (HE, 0.6 mmol) into the reaction flask, evacuate and replace the gas three times to make the reaction flask in a nitrogen atmosphere; under nitrogen protection, add 1,2 - dichloroethane (1 mL), p - toluenesulfonyl azide (0.6 mmol), cyclohexene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp;

[0144] (2) Monitor the reaction by TLC until it is completely finished;

[0145] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate: petroleum ether = 1:20) to obtain the target product (yield 58%).

[0146] The analysis data of the product is as follows: 1 1H NMR (400 MHz, CDCl3) δ 7.79 - 7.73 (m, 2H), 7.29 (d, J = 7.9 Hz, 2H), 4.52 (d, J = 7.6 Hz, 1H), 3.19 - 3.04 (m, 1H), 2.43 (s, 3H), 1.80 - 1.71 (m, 2H), 1.68 - 1.57 (m, 2H), 1.54 - 1.46 (m, 1H), 1.31 - 1.04 (m, 5H). 1313C NMR (101 MHz, CDCl3) δ 143.13, 138.49, 129.64, 126.95, 52.58, 33.96, 25.16, 24.64, 21.54.

[0147] Example 18: Synthesis of N-cyclooctyl-4-methylbenzenesulfonamide

[0148] Using cyclooctene and p-toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0149]

[0150] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) to the reaction flask, evacuate and replace the gas three times to make the reaction flask under a nitrogen atmosphere; under nitrogen protection, add 1,2-dichloroethane (1 mL), p-toluenesulfonyl azide (0.6 mmol), cyclooctene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation with a 450 nm - 465 nm blue LED lamp;

[0151] (2) Monitor the reaction by TLC until it is completely finished;

[0152] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate: petroleum ether = 1:20) to obtain the target product (yield 57%).

[0153] The analysis data of the product is as follows: 1 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.3 Hz, 2H), 7.29 (d, J = 8.2 Hz, 2H), 4.63 (d, J = 7.7 Hz, 1H), 3.401 - 3.319 (m, 1H), 2.43 (s, 3H), 1.75 - 1.62 (m, 2H), 1.60 - 1.29 (m, 12H). 13 13C NMR (101 MHz, CDCl3) δ 143.09, 138.27, 129.62, 127.01, 53.86, 32.62, 27.20, 25.25, 23.15, 21.54.

[0154] Example 19: Synthesis of N-(2,3-dimethylbutan-2-yl)-4-methylbenzenesulfonamide

[0155] Using 2,3-dimethyl-2-butene and p-toluenesulfonyl azide as raw materials, the reaction steps are as follows:

[0156]

[0157] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to create a nitrogen atmosphere in the reaction flask. Under nitrogen protection, add 1,2-dichloroethane (1 mL), p-toluenesulfonyl azide (0.6 mmol), and 2,3-dimethyl-2-butene (0.2 mmol). Stir and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp.

[0158] (2) Monitor the reaction by TLC until it is completely finished.

[0159] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate: petroleum ether = 1:40) to obtain the target product (yield 51%).

[0160] The analytical data of the product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.3 Hz, 2H), 7.29 - 7.25 (m, 2H), 4.53 (s, 1H), 2.42 (s, 3H), 1.83 - 1.72 (m, 1H), 1.12 (s, 6H), 0.86 (d, J = 6.8 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 142.73, 140.70, 129.44, 127.01, 59.94, 38.17, 24.35, 21.50, 17.23.

[0161] Example 20: Synthesis of N-(4-methoxyphenethyl)-2,4,6-trimethylbenzenesulfonamide

[0162] Using p-methoxystyrene and 2,4,6-trimethylbenzenesulfonyl azide as raw materials, the reaction steps are as follows:

[0163]

[0164] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to make the reaction flask in a nitrogen atmosphere. Under nitrogen protection, add 1,2-dichloroethane (1 mL), 2,4,6-trimethylbenzenesulfonyl azide (0.6 mmol), p-methoxystyrene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp;

[0165] (2) Monitor the reaction by TLC until it is completely finished;

[0166] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate: petroleum ether = 1:20) to obtain the target product (yield 58%).

[0167] The analysis data of the product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.04 - 6.98 (m, 2H), 6.95 (s, 2H), 6.87 - 6.78 (m, 2H), 4.43 (s, 1H), 3.81 (s, 3H), 3.14 (t, J = 6.7 Hz, 2H), 2.72 (t, J = 6.7 Hz, 2H), 2.55 (s, 6H), 2.32 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 158.54, 142.15, 139.08, 133.50, 131.95, 129.67, 129.62, 114.22, 55.31, 43.79, 34.66, 22.84, 20.94.

[0168] Example 21: Synthesis of 4-methoxy-N-(4-methoxyphenethyl)benzenesulfonamide

[0169] Using p-methoxystyrene and 4-methoxybenzenesulfonyl azide as raw materials, the reaction steps are as follows:

[0170]

[0171] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into the reaction flask. Evacuate and replace the gas three times to make the reaction flask under a nitrogen atmosphere. Under nitrogen protection, add 1,2-dichloroethane (1 mL), 4-methoxybenzenesulfonyl azide (0.6 mmol), p-methoxystyrene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp;

[0172] (2) Monitor the reaction by TLC until it is completely finished;

[0173] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate:petroleum ether = 1:20) to obtain the target product (yield 68%).

[0174] The analysis data of the product are as follows: 1 H NMR(400MHz,CDCl3)δ7.83 - 7.60(m,2H),7.06 - 6.92(m,4H),6.89 - 6.73(m,2H),4.42(s,1H),3.89(s,3H),3.80(s,3H),3.18(q,J = 6.4Hz,2H),2.72(t,J = 6.9Hz,2H). 13 C NMR(101MHz,CDCl3)δ162.86,158.48,131.47,129.72,129.60,129.21,114.24,114.18,55.62,55.29,44.35,34.82.

[0175] Example 22: Synthesis of 4-tert-butyl-N-(4-methoxyphenethyl)benzenesulfonamide

[0176] Using p-methoxystyrene and 4-tert-butylbenzenesulfonyl azide as raw materials, the reaction steps are as follows:

[0177]

[0178] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into the reaction flask. Evacuate and replace the gas three times to make the reaction flask under a nitrogen atmosphere. Under nitrogen protection, add 1,2-dichloroethane (1 mL), 4-tert-butylbenzenesulfonyl azide (0.6 mmol), p-methoxystyrene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp;

[0179] (2) Monitor the reaction by TLC until it is completely finished;

[0180] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate:petroleum ether = 1:20) to obtain the target product (yield 77%).

[0181] The analysis data of the product are as follows: 1 H NMR(400MHz,CDCl3)δ7.80 - 7.71(m,2H),7.55 - 7.49(m,2H),7.06 - 6.98(m,2H),6.88 - 6.78(m,2H),4.52(t,J = 6.1Hz,1H),3.80(s,3H),3.21(q,J = 6.8Hz,2H),2.74(t,J = 7.0Hz,2H),1.37(s,9H). 13 C NMR(101MHz,CDCl3)δ158.48,156.41,136.84,129.74,129.65,126.93,126.08,114.17,55.29,44.41,35.15,34.92,31.11.

[0182] Example 23: Synthesis of 4-fluoro-N-(4-methoxyphenethyl)benzenesulfonamide

[0183] Using p-methoxystyrene and 4-fluorobenzenesulfonyl azide as raw materials, the reaction steps are as follows:

[0184]

[0185] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into the reaction flask. Evacuate and replace the gas three times to create a nitrogen atmosphere in the reaction flask. Under nitrogen protection, add 1,2-dichloroethane (1 mL), 4-fluorobenzenesulfonyl azide (0.6 mmol), and p-methoxystyrene (0.2 mmol). Stir and react at room temperature for 3 min under irradiation with a 450 nm - 465 nm blue LED lamp;

[0186] (2) Monitor the reaction by TLC until it is completely finished;

[0187] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate:petroleum ether = 1:20) to obtain the target product (yield 74%).

[0188] The analysis data of the product is as follows: 1 H NMR (400 MHz, CDCl3) δ 7.89 - 7.67 (m, 2H), 7.22 - 7.09 (m, 2H), 7.04 - 6.92 (m, 2H), 6.84 - 6.63 (m, 2H), 4.60 (t, J = 6.2 Hz, 1H), 3.78 (s, 3H), 3.18 (q, J = 6.8 Hz, 2H), 2.71 (t, J = 6.9 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 166.29, 163.76, 158.53, 136.00, 135.96, 129.81, 129.71, 129.42, 116.42, 116.19, 114.20, 55.28, 44.42, 34.85. 19 F NMR (400 MHz, CDCl3) δ -105.41.

[0189] Example 24: Synthesis of 4-chloro-N-(4-methoxyphenethyl)benzenesulfonamide

[0190] Using p-methoxystyrene and 4-chlorobenzenesulfonyl azide as raw materials, the reaction steps are as follows:

[0191]

[0192] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to make the reaction flask in a nitrogen atmosphere. Under nitrogen protection, add 1,2-dichloroethane (1 mL), 4-chlorobenzenesulfonyl azide (0.6 mmol), p-methoxystyrene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp;

[0193] (2) Monitor the reaction by TLC until it is completely finished;

[0194] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate:petroleum ether = 1:20) to obtain the target product (yield 74%).

[0195] The analysis data of the product are as follows: 1 H NMR(400MHz,CDCl3)δ7.83 - 7.66(m,2H),7.52 - 7.42(m,2H),7.05 - 6.97(m,2H),6.86 - 6.69(m,2H),4.74(t,J = 6.3Hz,1H),3.80(s,3H),3.20(q,J = 6.8Hz,2H),2.73(t,J = 6.9Hz,2H). 13 C NMR(101MHz,CDCl3)δ158.52,139.06,138.42,129.71,129.41,129.38,128.51,114.19,55.29,44.45,34.85.

[0196] Example 25: Synthesis of 4-bromo-N-(4-methoxyphenethyl)benzenesulfonamide

[0197] Using p-methoxystyrene and 4-bromobenzenesulfonyl azide as raw materials, the reaction steps are as follows:

[0198]

[0199] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to make the reaction flask in a nitrogen atmosphere. Under nitrogen protection, add 1,2-dichloroethane (1 mL), 4-bromobenzenesulfonyl azide (0.6 mmol), and p-methoxystyrene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp;

[0200] (2) Monitor the reaction by TLC until it is completely finished;

[0201] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate: petroleum ether = 1:20) to obtain the target product (yield 66%).

[0202] The analysis data of the product are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.73 - 7.57 (m, 4H), 7.07 - 6.94 (m, 2H), 6.88 - 6.73 (m, 2H), 4.68 (t, J = 6.1 Hz, 1H), 3.80 (s, 3H), 3.20 (q, J = 6.8 Hz, 2H), 2.73 (t, J = 6.9 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 158.53, 138.95, 132.36, 129.71, 129.37, 128.61, 127.54, 114.20, 55.31, 44.44, 34.85.

[0203] Example 26: Synthesis of 2-chloro-N-(4-methoxyphenethyl)benzenesulfonamide

[0204] Using p-methoxystyrene and 2-chlorobenzenesulfonyl azide as raw materials, the reaction steps are as follows:

[0205]

[0206] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to make the reaction flask in a nitrogen atmosphere. Under nitrogen protection, add 1,2-dichloroethane (1 mL), 2-chlorobenzenesulfonyl azide (0.6 mmol), and p-methoxystyrene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp;

[0207] (2) Monitor the reaction by TLC until it is completely finished;

[0208] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate:petroleum ether = 1:20) to obtain the target product (yield 69%).

[0209] The analysis data of the product are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.17 - 7.99 (m, 1H), 7.57 - 7.48 (m, 2H), 7.48 - 7.39 (m, 1H), 7.10 - 6.98 (m, 2H), 6.89 - 6.74 (m, 2H), 4.99 (t, J = 5.9 Hz, 1H), 3.80 (s, 3H), 3.18 (q, J = 6.8 Hz, 2H), 2.75 (t, J = 6.9 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 158.55, 137.02, 133.69, 131.56, 131.38, 131.32, 129.68, 129.36, 127.22, 114.21, 55.31, 44.57, 34.80.

[0210] Example 27: Synthesis of 3-chloro-N-(4-methoxyphenethyl)benzenesulfonamide

[0211] Using p-methoxystyrene and 3-fluorobenzenesulfonyl azide as raw materials, the reaction steps are as follows:

[0212]

[0213] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to create a nitrogen atmosphere in the reaction flask. Under nitrogen protection, add 1,2-dichloroethane (1 mL), 3-chlorobenzenesulfonyl azide (0.6 mmol), and p-methoxystyrene (0.2 mmol). Stir and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp.

[0214] (2) Monitor the reaction by TLC until it is completely finished.

[0215] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate:petroleum ether = 1:20) to obtain the target product (yield 72%).

[0216] The analysis data of the product are as follows: 1 H NMR(400MHz,CDCl3)δ7.77(t,J=1.9Hz,1H),7.67(ddd,J=7.8,1.8,1.1Hz,1H),7.53(ddd,J=8.1,2.1,1.1Hz,1H),7.43(t,J=7.9Hz,1H),7.03 - 6.94(m,2H),6.85 - 6.76(m,2H),4.52(t,J=6.1Hz,1H),3.78(s,3H),3.22(q,J=6.7Hz,2H),2.72(t,J=6.8Hz,2H). 13 C NMR(101MHz,CDCl3)δ158.57,141.72,135.31,132.75,130.41,129.71,129.25,127.14,125.12,114.25,55.29,44.45,34.86.

[0217] Example 28: Synthesis of N-(4-methoxyphenethyl)naphthalene-2-sulfonamide

[0218] Using p-methoxystyrene and 2-naphthalenesulfonyl azide as raw materials, the reaction steps are as follows:

[0219]

[0220] (1) Add 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN, 0.006 mmol), p-toluenethiol (0.08 mmol), diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (HE, 0.6 mmol) into a reaction flask. Evacuate and replace the gas three times to make the reaction flask under a nitrogen atmosphere. Under nitrogen protection, add 1,2-dichloroethane (1 mL), 2-naphthalenesulfonyl azide (0.6 mmol), p-methoxystyrene (0.2 mmol), stir, and react at room temperature for 3 min under irradiation of a 450 nm - 465 nm blue LED lamp;

[0221] (2) Monitor the reaction by TLC until it is completely finished;

[0222] (3) The crude product obtained after the reaction is separated by column chromatography (ethyl acetate: petroleum ether = 1:20) to obtain the target product (yield 63%).

[0223] The analysis data of the product is as follows: 1 H NMR (400 MHz, CDCl3) δ 8.41 (d, J = 1.9 Hz, 1H), 8.02 - 7.87 (m, 3H), 7.78 (dd, J = 8.7, 1.9 Hz, 1H), 7.72 - 7.58 (m, 2H), 7.03 - 6.94 (m, 2H), 6.82 - 6.74 (m, 2H), 4.59 (t, J = 5.6 Hz, 1H), 3.77 (s, 3H), 3.25 (q, J = 6.5 Hz, 2H), 2.73 (t, J = 6.9 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 158.46, 136.66, 134.80, 132.16, 129.72, 129.51, 129.48, 129.25, 128.81, 128.43, 127.92, 127.57, 122.31, 114.15, 55.26, 44.45, 34.87.

[0224] Obviously, the above embodiments are merely examples given for clear illustration and are not limitations on the implementation manners. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to enumerate all implementation manners here. And the obvious changes or modifications derived therefrom are still within the protection scope of this invention.

Claims

1. A method for preparing sulfonamide derivatives by visible light catalysis without metal participation, characterized in that: The following steps are involved: In a protective atmosphere, olefin and sulfonyl azide react in a solvent under the action of an organic photocatalyst, Hans ester and thiophenol under visible light irradiation to obtain the sulfonamide derivative; the organic photocatalyst is 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile; the Hans ester is 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylic acid diethyl ester; the thiophenol is p-toluene thiophenol; the wavelength of the visible light source is 450nm-465nm; The structural formula of the olefin is The structure of the olefin is selected from The structural formula of the sulfonyl azide is The structural formula of the sulfonamide derivative is Among them, R 2 Selected from hydrogen, C1-C4 alkyl, alkoxy, aryl or halogen.

2. The method for preparing sulfonamide derivatives by visible light catalysis without metal participation according to claim 1, characterized in that: The molar ratio of the olefin, sulfonyl azide, organic photocatalyst, hans ester and thiophenol is 1:(1-5):(0.01-0.05):(1-5):(1-5).

3. The method for preparing sulfonamide derivatives by visible light catalysis without metal participation according to claim 1, characterized in that: The solvent is selected from acetonitrile, dichloromethane, 1,2-dichloroethane, tetrahydrofuran or toluene.

4. The method for preparing sulfonamide derivatives by visible light catalysis without metal participation according to claim 1, characterized in that: The protective atmosphere is selected from a nitrogen atmosphere or an argon atmosphere.

5. The method for preparing sulfonamide derivatives by visible light catalysis without metal participation according to claim 1, characterized in that: After the reaction is completed, the method further comprises the step of separating and purifying the sulfonamide derivative from the reaction solution.

6. The method for preparing sulfonamide derivatives by visible light catalysis without metal participation according to claim 5, characterized in that: The separation and purification is achieved by column chromatography or liquid chromatography.

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