A method for selectively synthesizing 4-amino-N-(hetero)arylsulfonamide compounds

Abstract

This invention discloses a method for the selective synthesis of 4-amino-N-(hetero)arylsulfonamide compounds. Using bipyridine as a ligand and nickel as a catalyst, and inexpensive and readily available low-activity (hetero)aryl chlorides and 4-aminobenzenesulfonamides as substrates, 1,8-diazabicycloundec-7-ene and other organic bases are used, along with sodium iodide and other additives. The synthesis of various 4-amino-N-(hetero)arylsulfonamide compounds is achieved through a photo-driven nickel-catalyzed selective C-N coupling reaction of (hetero)aryl chlorides and 4-aminobenzenesulfonamides under an argon atmosphere. This invention features a simple reaction system, convenient operation, mild reaction conditions, and simple post-processing. It exhibits good selectivity for target compounds and high yields, avoiding the problems of complex catalytic systems and poor functional group compatibility caused by the use of traditional expensive metal catalysts and inorganic bases. Therefore, it has significant application value and market prospects.

Description

Technical Field

[0001] This invention belongs to the field of synthetic technology of 4-amino-N-(hetero)arylsulfonamide compounds, specifically relating to a method for synthesizing 4-amino-N-(hetero)arylsulfonamide compounds by photochemical nickel catalysis. Background Technology

[0002] N-aryl (heterocyclic aryl) sulfonamides possess significant biological activities such as antibacterial and anti-inflammatory properties, and are an important core skeleton in drug molecules, with significant application value in medicinal chemistry and agrochemicals (Top. Curr. Chem. 2018, 376, 5; Top. Curr. Chem. 2017, 375, 82; J. Med. Chem. 2012, 55, 7849; WO2006 / 024823A1, March 09, 2006). Representative molecules include the anti-infective drug sulfathiazole, dabrafenib for cancer treatment, dofetilide for arrhythmia, and celecoxib for osteoarthritis relief. Meanwhile, sulfonamides also play an important role in chemical reactions, such as as chiral catalysts (Tetrahedron Lett. 1992, 33, 6661), organic catalysts (Chem. Commun. 2009, 7, 833), and isosteres of carboxylic acids (ChemMedChem. 2013, 8, 385). In the traditional synthesis of N-arylsulfonamides, the direct condensation reaction of sulfonyl chlorides with amines is mainly used. However, the practicality of sulfonyl chlorides is limited by their sensitivity to humidity, difficulty in obtaining them, instability, and potential toxicity issues (Org. Proc. Res. Dev. 2009, 13, 285–291; Org. Proc. Res. Dev. 2010, 14, 960; Green. Chem. 2006, 8, 835; J. Am. Chem. Soc. 2013, 135, 10638). Therefore, developing synthetic methods that avoid the use of sulfonyl chlorides remains of great importance in the pharmaceutical industry. Transition metal catalysis for CN coupling reactions of aryl halides with sulfonamides is an attractive strategy.Through the development of ligands, Cu(Tetrahedron Letters. 2003, 44, 3385; Tetrahedron Lett. 2005, 46, 7295; Org. Lett. 2010, 12, 1532; Angew. Chem. Int. Ed. 2022, 61, e202210483; Org. Lett. 2014, 16, 338; ACS Catal. 2018, 8, 9560; Org. Lett. 2010, 12, 1532; ACS Catal. 2018, 8, 9560) catalyzed Ullmann coupling, Pd (Tetrahedron. 1996, 52, 7525; Org. Lett. 2003, 5, 4373; Org. Lett. 2011, 13, 2564; Org .Chem.2011,76,4552; J.Am.Chem.Soc.2013,135,10638; Org.Lett.2020,22,4593; Angew.Chem.Int.Ed.,2021,60,7353; ACS catal.2019,9,11691.), Ni(Angew.Chem.Int.Ed.2020,59,8952-8956; ACS The Buchwald–Hartwig coupling catalyzed by (Catal. 2022, 12, 2, 1475–1480. JACS Au 2021, 1, 1057–1065.) has seen rapid development. However, most of these newly developed catalytic systems can only achieve aryl bromides (iodides), with limited research on inexpensive and abundant low-activity aryl chlorides. In the limited reports, copper catalysts require high loading and high temperatures, and the phosphine-rich ligands developed with Pd and Ni are only applicable to electron-deficient and electron-neutral ligands, while electron-rich aryl chlorides still lack universality. With the development of photocatalysis (Chem.Rev.2022,122,1485; Organometallic Photosensitizers.2022,1,284-338), electrocatalysis (J.Am.Chem.Soc.2019,141,5664-5668; Angew.Chem.Int.Ed.2021,60,5056 2; JACSAu.2021,1,1057) and transition metal co-catalysis, the CN coupling reaction with sulfonamide as N-nucleophile has been further promoted.Macmillan (Angew. Chem. Int. Ed. 2018, 57, 3488) and Roizen (J. Org. Chem. 2020, 85, 6380-6391) and other groups (Org. Lett. 2023, 25, 636; Chem. Int. Ed. 2019, 58, 12440; Chem. Commun. 2016, 52, 10918; Chem. Eur. J. 2023, 29, e202202385) have developed CN coupling reactions of sulfonamides of aryl halides in a nickel-photocatalyst-co-catalyzed system, but these works have hardly involved the abundant and challenging low-activity aryl chlorides. The Rueping group (JACS Au. 2021, 1, 1057–1065) only developed two simple aryl chloride examples in their electrochemically promoted nickel-catalyzed CN coupling of aryl halides and sulfonamides. This indicates that the availability of widely used and diverse low-activity (hetero)aryl chlorides remains a significant challenge in current Ni-catalyzed systems. Most importantly, current methods almost exclusively fail to achieve selective CN coupling sulfonamide reactions with multiple NH2 functional groups. Therefore, developing efficient and versatile aryl chloride-sulfonamide selective CN coupling using readily available ligands remains crucial. Summary of the Invention

[0003] The purpose of this invention is to provide a method for synthesizing 4-amino-N-(hetero)arylsulfonamide compounds by selective CN-coupling of (hetero)aryl chlorides with 4-aminobenzenesulfonamides using an inexpensive nickel-catalyst and a bipyridine-catalyst system, with the addition of additives such as sodium iodide. This method not only solves the problem that inexpensive and abundant low-activity aryl chlorides cannot participate in the reaction, but also achieves selectivity in the presence of multiple NH2 functional groups.

[0004] To achieve the above objectives, the technical solution adopted by the present invention is as follows: the (hetero)aryl chloride shown in Formula I, 4-aminobenzenesulfonamide shown in Formula II, bipyridine, nickel catalyst, iodine-containing additive, and organic base are added to an organic solvent and reacted under light in an argon atmosphere. After the reaction is complete, the product is separated and purified to obtain the 4-amino-N-(hetero)arylsulfonamide compound shown in Formula III.

[0005]

[0006] In the formula, Ar represents any one of aryl, substituted aryl, heterocyclic aryl, and substituted heterocyclic aryl. Specifically, it can represent any one of phenyl, thienyl, thiazolyl, pyridinyl, pyrazolyl, piperidinyl, quinoxalinyl, or a phenyl containing at least one of the following substituents: C1-C6 alkyl, trimethylsilyl, halogen, C1-C4 alkoxy, trifluoromethoxy, trifluoromethyl, cyano, ester, acyl, carbonyl, or borate ester.

[0007] In the above synthesis method, the amount of 4-aminobenzenesulfonamide is preferably 1.1 to 2 times the molar amount of (hetero)aryl chloride.

[0008] In the above synthesis method, the preferred amount of bipyridine is 5% to 10% of the molar amount of (hetero)aryl chloride.

[0009] In the above synthesis method, the preferred nickel catalyst is any one of nickel bromide, nickel acetate, nickel chloride, etc., and its amount is 5% to 10% of the molar amount of (hetero)aryl chloride.

[0010] In the above synthesis method, the preferred iodine-containing additive is any one of sodium iodide, potassium iodide, cesium iodide, etc., and its amount is 1.1 to 2 times the molar amount of (hetero)aryl chloride.

[0011] In the above synthesis method, the preferred organic base is any one of 1,8-diazabicycloundec-7-ene (DBU), tetramethylguanidine (TMG), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD), and its amount is 2 to 3 times the molar amount of (hetero)aryl chloride.

[0012] In the above synthesis method, the preferred organic solvent is any one or two of dimethyl sulfoxide, toluene, isopropanol, N,N-dimethylformamide, and N,N-dimethylacetamide.

[0013] In the above synthesis method, it is preferred to react at 80-90°C for 24-36 hours under an argon atmosphere and irradiated with violet light with a wavelength of 360-430 nm.

[0014] The beneficial effects of this invention are as follows:

[0015] This invention features a simple reaction system, utilizing inexpensive nickel catalysis and a bipyridine system. The addition of iodine-containing additives, under light conditions, facilitates the reaction of (hetero)aryl chlorides with 4-aminobenzenesulfonamides to synthesize 4-amino-N-(hetero)arylsulfonamides. This invention offers high economic efficiency, is environmentally friendly, and simplifies post-reaction processing. It not only solves the problem of inexpensive and readily available low-activity aryl chlorides being unable to participate in the reaction but also addresses the selectivity and compatibility issues when multiple NH2 functional groups are present. Furthermore, the resulting 4-amino-N-(hetero)arylsulfonamides exhibit good yields and excellent functional group compatibility. This method is a simple and efficient way to synthesize 4-amino-N-(hetero)arylsulfonamides, aligning with current trends in environmentally friendly, economical, and green chemistry, and possesses significant application potential. Detailed Implementation

[0016] The present invention will be further described in detail below with reference to the embodiments, but the scope of protection of the present invention is not limited to these embodiments.

[0017] Example 1

[0018] In an argon atmosphere, 22.4 mg (0.2 mmol) of chlorobenzene, 68.8 mg (0.4 mmol) of 4-aminobenzenesulfonamide, 1.9 mg (0.01 mmol) of bipyridine, 1.3 mg (0.01 mmol) of nickel chloride, 30 mg (0.4 mmol) of sodium iodide, 90 mg (0.6 mmol) of MTBD, 2 mL of a mixed solvent of N,N-dimethylformamide and isopropanol in a volume ratio of 2:1, and a magnetic flux were added to a reaction tube. The reaction was carried out at 85 °C for 36 hours under violet light with a wavelength of 390–395 nm. After the reaction was completed, the mixture was cooled to room temperature, diluted with saturated sodium chloride aqueous solution and ethyl acetate to obtain an organic phase. The crude product was obtained by vacuum distillation. The product was separated by column chromatography using a mixture of petroleum ether and ethyl acetate in a volume ratio of 1:1 to 1:2 as the eluent, yielding a pale yellow solid product with the following structural formula, in 86% yield.

[0019]

[0020] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR(400MHz,d6-DMSO)δ9.89(br,1H),7.43(d,J=8.6Hz,2H),7.24(t,J=7.7Hz,2H) ,7.11(d,J=8.4Hz,2H),7.01(t,J=7.3Hz,1H),6.57(d,J=8.6Hz,2H),6.00(br,2H); 13C NMR(100MHz,d6-DMSO)δ153.3,139.0,129.4,129.2,124.9,123.8,119.9,113.0; HRMS(ESI)m / z C 12 H 12 N₂NaO₂S[M+Na] + Theoretical value: 271.0512, measured value: 271.0513.

[0021] Example 2

[0022] In this embodiment, 4-methyl-chlorobenzene was replaced with an equimolar amount in Example 1, and the other steps were the same as in Example 1, resulting in a pale yellow solid product with the following structural formula, with a yield of 89%.

[0023]

[0024] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR(400MHz,d6-DMSO)δ9.72(br,1H),7.40(d,J=8.5Hz,2H),7.04(d,J=8.3Hz ,2H),6.99(d,J=8.3Hz,2H),6.57(d,J=8.6Hz,2H),5.98(br,2H),2.22(s,3H); 13 C NMR(100MHz,d6-DMSO)δ153.2,136.3,133.0,129.8,129.1,125.0,120.5,113.0,20.7; HRMS(ESI)m / z C 13 H 14 N₂NaO₂S[M+Na] + Theoretical value: 285.0668, measured value: 285.0667.

[0025] Example 3

[0026] In this embodiment, 4-tert-butylchlorobenzene was used to replace the chlorobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a white solid product with the following structural formula, with a yield of 87%.

[0027]

[0028] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1H NMR(400MHz,d6-DMSO)δ9.76(br,1H),7.41(d,J=8.6Hz,2H),7.22(d,J=8.6Hz ,2H),7.00(d,J=8.6Hz,2H),6.55(d,J=8.7Hz,2H),5.95(s,2H),1.20(s,9H); 13 C NMR(100MHz,d6-DMSO)δ153.2,146.0,136.3,129.1,126.1,125.3,119.7,113.1,34.4,31.6; HRMS(ESI)m / z C 16 H 20 N₂NaO₂S[M+Na] + Theoretical value: 327.1138, measured value: 327.1136.

[0029] Example 4

[0030] In this embodiment, 4-chlorobenzene-(trimethylsilyl)benzene was replaced with an equimolar amount in Example 1, and the other steps were the same as in Example 1, resulting in a white solid product with the following structural formula, with a yield of 81%.

[0031]

[0032] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR(400MHz,d6-DMSO)δ10.01(br,1H),7.48(d,J=8.6Hz,2H),7.38(d,J=8.0H z,2H),7.11(d,J=8.0Hz,2H),6.59(d,J=8.6Hz,2H),6.02(s,2H),0.22(s,9H); 13 C NMR(100MHz,d6-DMSO)δ158.1,144.4,139.2,138.6,133.9,129.8,123.3,117.8,4.2.HRMS(ESI)m / z C 15 H 20 N₂NaO₂SSi[M+Na] + Theoretical value: 343.0907, measured value: 343.0907.

[0033] Example 5

[0034] In this embodiment, 4-methoxychlorobenzene was used to replace the chlorobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a white solid product with the following structural formula, with a yield of 83%.

[0035]

[0036] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR(400MHz,d6-DMSO)δ9.45(br,1H),7.30(d,J=8.7Hz,2H),6.95(d,J=8.9Hz ,2H),6.78(d,J=8.9Hz,2H),6.51(d,J=8.7Hz,2H),5.92(br,2H),3.66(s,3H); 13 C NMR(100MHz,d6-DMSO)δ156.5,153.1,131.5,129.1,125.0,123.3,114.6,113.0,55.6; HRMS(ESI)m / z C 13 H 14 N₂NaO₃S[M+Na] + Theoretical value: 301.0617, measured value: 301.0618.

[0037] Example 6

[0038] In this embodiment, 4-chlorotrifluoromethoxybenzene was replaced with an equimolar amount of chlorobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a yellow solid product with the following structural formula, with a yield of 83%.

[0039]

[0040] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, d6-DMSO) δ10.11(br,1H),7.42(d,J=8.7Hz,2H),7.23(d,J=8.8Hz,2H),7.19–7.12(m,2H),6.56(d,J=8.7Hz,2H),6.02(br,2H); 13 C NMR (100MHz, d6-DMSO) δ153.5, 144.4, 138.2, 129.2, 124.5, 122.4, 121.0, 121.5 (q, J = 254.0Hz), 113.1; 19 F NMR(376MHz,d6-DMSO)δ-57.14(s,OCF3); HRMS(ESI)m / zC 13 H 11 F3N2NaO3S[M+Na] + Theoretical value: 355.0335, measured value: 355.0339.

[0041] Example 7

[0042] In this embodiment, 4-acetonitrile chlorobenzene was replaced with equimolar 4-acetonitrile chlorobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a yellow solid product with the following structural formula, with a yield of 78%.

[0043]

[0044] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR(400MHz,d6-DMSO)δ9.93(br,1H),7.39(d,J=8.5Hz,2H),7.18(d,J=8.4Hz ,2H),7.08(d,J=8.3Hz,2H),6.53(d,J=8.6Hz,2H),5.97(br,2H),3.90(s,2H); 13 C NMR(100MHz,d6-DMSO)δ153.3,138.4,129.2,129.2,126.4,124.7,120.2,119.7,113.0,22.6; HRMS(ESI)m / z C 14 H 13 N3NaO2S[M+Na] + Theoretical value: 310.0621, measured value: 310.0624.

[0045] Example 8

[0046] In this embodiment, 4-cyanochlorobenzene was used to replace the chlorobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a yellow solid product with the following structural formula, with a yield of 89%.

[0047]

[0048] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, d6-DMSO) δ10.65(br,1H),7.68(d,J=8.7Hz,2H),7.50(d,J=8.7Hz,2H),7.24(d,J=8.7Hz,2H),6.61(d,J=8.7Hz,2H),6.09(br,2H); 13 C NMR(100MHz,d6-DMSO)δ153.8,143.4,133.9,129.3,124.0,119.3,118.4,113.1,105.0; HRMS(ESI)m / z C 13 H 11 N3NaO2S[M+Na] + Theoretical value: 296.0464, measured value: 296.0465.

[0049] In this embodiment, equimolar DBU was used instead of MTBD, and the yield of the product was 81%.

[0050] Example 9

[0051] In this embodiment, methyl 4-chlorobenzoate was used to replace chlorobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a white solid product with the following structural formula, with a yield of 78%.

[0052]

[0053] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR(400MHz,d6-DMSO)δ10.47(br,1H),7.81(d,J=8.6Hz,2H),7.46(d,J=8.7Hz ,2H),7.18(d,J=8.6Hz,2H),6.55(d,J=8.7Hz,2H),6.04(br,2H),3.78(s,3H); 13 C NMR(100MHz,d6-DMSO)δ166.2,153.6,143.6,131.0,129.3,124.3,124.1,118.0,113.1,52.3; HRMS(ESI)m / z C 14 H 14 N₂NaO₄S[M+Na] + Theoretical value: 329.0566, measured value: 329.0569.

[0054] Example 10

[0055] In this embodiment, 1,4-dichlorobenzene was used to replace the chlorobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a white solid product with the following structural formula, with a yield of 81%.

[0056]

[0057] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, d6-DMSO) δ10.01(br,1H),7.38(d,J=8.7Hz,2H),7.27(d,J=8.8Hz,2H),7.07(d,J=8.8Hz,2H),6.54(d,J=8.7Hz,2H),6.00(br,2H); 13C NMR(100MHz,d6-DMSO)δ153.4),138.0,129.4,129.2,127.8,124.4,121.4,113.1; HRMS(ESI)m / z C 12 H 11 ClN2NaO2S[M+Na] + Theoretical value: 305.0122, measured value: 305.0122.

[0058] Example 11

[0059] In this embodiment, 2-methylchlorobenzene was used to replace the chlorobenzene in Example 1 in equal molar amounts, and the other steps were the same as in Example 1, resulting in a white solid product with the following structural formula, with a yield of 75%.

[0060]

[0061] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, d6-DMSO) δ9.03(br,1H),7.27(d,J=8.6Hz,2H),7.15–6.97(m,4H),6.54(d,J=8.6Hz,2H),5.95(br,2H),2.02(s,3H); 13 C NMR(100MHz,d6-DMSO)δ153.1,136.0,134.1,131.0,129.0,126.6,126.5,126.3,126.0,113.0,18.1; HRMS(ESI)m / z C 13 H 14 N₂NaO₂S[M+Na] + Theoretical value: 285.0668, measured value: 285.0669.

[0062] Example 12

[0063] In this embodiment, 2-methoxychlorobenzene was used to replace the chlorobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a white solid product with the following structural formula, with a yield of 71%.

[0064]

[0065] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1H NMR(400MHz,d6-DMSO)δ8.79(br,1H),7.35(d,J=8.6Hz,2H),7.23-7.18(m,1H),7.04(t,J=7.2Hz,1 H),6.90(d,J=7.8Hz,1H),6.83(t,J=7.6Hz,1H),6.51(d,J=8.7Hz,2H),5.92(br,2H),3.60(s,3H); 13 C NMR(100MHz,d6-DMSO)δ153.1,151.7,129.2,126.9,125.9,125.6,123.4,120.8,112.7,112.1,56.0; HRMS(ESI)m / zC 13 H 14 N₂NaO₃S[M+Na] + Theoretical value: 301.0617, measured value: 301.0613.

[0066] Example 13

[0067] In this embodiment, 2-chlorotrifluoromethoxybenzene was replaced with an equimolar amount of chlorobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a white solid product with the following structural formula, with a yield of 68%.

[0068]

[0069] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.66(d,J=8.1Hz,1H),7.56(d,J=8.7Hz,2H),7.21(t,J=7.8Hz,1H),7 .13(d,J=8.3Hz,1H),7.11–7.01(m,1H),6.81(br,1H),6.58(d,J=8.7Hz,2H),4.12(br,2H); 13 C NMR (100MHz, CDCl3) δ151.1, 139.2, 129.5, 127.4, 126.7, 124.9, 121.7, 120.4 (q, J = 258.6Hz), 120.1, 116.2, 113.9; 19 F NMR (376MHz, CDCl3) δ-57.52 (s, OCF3); HRMS (ESI) m / zC 13 H 11 F3N2NaO3S[M+Na] + Theoretical value: 355.0335, measured value: 355.0333.

[0070] Example 14

[0071] In this embodiment, 2-isopropylchlorobenzene was used to replace the chlorobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a white solid product with the following structural formula, with a yield of 61%.

[0072]

[0073] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR(400MHz,d6-DMSO)δ9.10(br,1H),7.29–7.21(m,3H),7.15(t,J=7.5Hz,1H),7.07–7.00(m,1H),6.89( d,J=7.7Hz,1H),6.55(d,J=8.7Hz,2H),5.92(br,2H),3.25(dt,J=13.6,6.8Hz,1H),0.97(d,J=6.8Hz,6H); 13 C NMR(100MHz,d6-DMSO)δ153.1,145.9,134.1,129.1,127.7,127.2,126.6,126.1,126.0,112.9,27.0,24.0; HRMS(ESI)m / z C 15 H 18 N₂NaO₂S[M+Na] + Theoretical value: 313.0981, measured value: 313.0981.

[0074] Example 15

[0075] In this embodiment, 2-acetylchlorobenzene was used to replace the chlorobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a white solid product with the following structural formula, with a yield of 73%.

[0076]

[0077] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR(400MHz,d6-DMSO)δ11.23(br,1H),8.02(d,J=7.9Hz,1H),7.59(t,J=7.8Hz,1H),7.5 3–7.39(m,3H),7.18(t,J=7.6Hz,1H),6.58(d,J=8.8Hz,2H),6.15(br,2H),2.64(s,3H); 13C NMR(100MHz,d6-DMSO)δ203.8,153.9,139.8,135.2,133.1,129.5,123.4,123.1,118.7,113.2,29.0; HRMS(ESI)m / z C 14 H 14 N₂NaO₃S[M+Na] + Theoretical value: 313.0617, measured value: 313.0619.

[0078] Example 16

[0079] In this embodiment, 2,4-dimethoxychlorobenzene was used to replace the chlorobenzene in Example 1 in equal molar amounts, and the other steps were the same as in Example 1, resulting in a pale yellow solid product with the following structural formula, in a yield of 71%.

[0080]

[0081] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.43(d,J=8.9Hz,3H),6.58(br,1H),6.53(d,J=8.7Hz,2H),6.42 (dd,J=8.7,2.6Hz,1H),6.28(d,J=2.6Hz,1H),4.08(br,2H),3.75(s,3H),3.53(s,3H); 13 C NMR (100MHz, CDCl3) δ158.2, 151.8, 150.5, 129.4, 127.4, 124.3, 119.2, 113.6, 104.3, 98.8, 55.5, 55.5; HRMS (ESI) m / zC 14 H 16 N₂NaO₄S[M+Na] + Theoretical value: 331.0723; Measured value: 331.0728.

[0082] Example 17

[0083] In this embodiment, methyl 4-chloro-3-methoxybenzoate was used to replace chlorobenzene in Example 1, and the other steps were the same as in Example 1, to obtain a yellow solid product with the following structural formula, with a yield of 65%.

[0084]

[0085] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1H NMR (400MHz, d6-DMSO) δ9.30(s,1H),7.48(dd,J=14.0,5.2Hz,3H),7.38(d,J=8.6Hz,2H),6.54(d,J=8.7Hz,2H),6.01(s,2H),3.80(s,3H),3.75(s,3H); 13 C NMR(100MHz,d6-DMSO)δ166.2,153.53(s),149.8,132.2,129.3,125.4,124.9,122.7,119.6,112.9,111.9,21.2,14.6; HRMS(ESI)m / zC 15 H 16 N₂NaO₅S[M+Na] + Theoretical value: 359.0672, measured value: 359.0675.

[0086] Example 18

[0087] In this embodiment, 3,5-ditrifluoromethylchlorobenzene was used to replace the chlorobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a white solid product with the following structural formula, with a yield of 88%.

[0088]

[0089] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 HNMR (400MHz, d6-DMSO) δ10.82(br,1H),7.68(s,1H),7.62(s,2H),7.45(d,J=8.7Hz,2H),6.58(d,J=8.7Hz,2H),6.14(br,2H); 13 C NMR (100MHz, d6-DMSO) δ154.0, 141.1, 131.56 (q, J = 33.0Hz), 129.4, 123.4 (q, J = 272.8Hz)., 123.1, 118.4, 116.3 113.2; 19 F NMR(376MHz,d6-DMSO)δ-57.42(s,CF3); HRMS(ESI)m / zC 14 H 10 F6N2NaO2S[M+Na] + Theoretical value: 407.0259, measured value: 407.0265.

[0090] In this embodiment, equimolar TMG was used instead of MTBD, and the yield of the product was 85%.

[0091] Example 19

[0092] In this embodiment, 2-(5-chloro-2-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborane was used to replace the chlorobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a white solid product with the following structural formula in a yield of 84%.

[0093]

[0094] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.56 (d, J = 8.8Hz, 2H), 7.24 (br, 1H), 7.13–7.02 (m, 1H), 6. 96–6.76(m,2H),6.53(d,J=8.0Hz,2H),4.12(br,2H),2.42(s,3H),1.30(s,12H); 13 C NMR (100MHz, CDCl3) δ150.9,146.5,139.3,137.1,129.4,125.7,120.9,118.1,115.9,114.0,83.5,24.9,22.22; HRMS (ESI) m / zC 19 H 25 BN2NaO4S[M+Na] + Theoretical value: 411.1520, measured value: 411.1523.

[0095] Example 20

[0096] In this embodiment, 2-chlorothiazolium was used to replace chlorobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a white solid product with the following structural formula, with a yield of 71%.

[0097]

[0098] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, d6-DMSO) δ12.41(br,1H),7.43(d,J=8.7Hz,2H),7.18(d,J=4.6Hz,1H),6.74(d,J=4.6Hz,1H),6.62–6.51(m,2H),5.83(br,2H); 13 C NMR(100MHz,d6-DMSO)δ168.4,152.7,128.3,128.2,124.7,112.9,107.9; HRMS(ESI)m / z C9H9N3NaO2S2[M+Na] +Theoretical value: 278.0028, measured value: 278.0029.

[0099] Example 21

[0100] In this embodiment, chlorobenzene in Example 1 was replaced with equimolar chlorofibrate, and the other steps were the same as in Example 1, resulting in a yellow solid product with the following structural formula, with a yield of 81%.

[0101]

[0102] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.45(d,J=8.2Hz,2H),6.92(d,J=8.7Hz,2H),6.72(d,J=8.6Hz,2H),6.55(d,J =8.2Hz,2H),6.48(br,1H),4.21(q,J=7.1Hz,2H),4.11(br,2H),1.54(s,6H),1.23(t,J=7.1Hz,3H); 13 CNMR(100MHz, CDCl3)δ174.1,153.3,150.7,131.01,129.4,127.1,124.2,120.1,113.9,79.5,61.5,25.3,14.1.HRMS(ESI)m / z C 18 H 22 N₂NaO₅S[M+Na] + Theoretical value: 401.1142, measured value: 401.1145.

[0103] Example 22

[0104] In this embodiment, equimolar fenofibrate was used to replace chlorobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a yellow solid product with the following structural formula, with a yield of 71%.

[0105]

[0106] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.96(br,1H),7.67(d,J=8.7Hz,2H),7.62(t,J=8.7Hz,4H),7.17(d,J=8.5Hz,2H),6.84 (d,J=8.7Hz,2H),6.56(d,J=8.6Hz,2H),5.14–5.02(m,1H),4.29(br,2H),1.65(s,6H),1.20(d,J=6.2Hz,6H);13 CNMR (100MHz, CDCl3) δ194.7,173.3,159.5,151.3,141.2,133.3,131.9,131.5,1 30.6,129.5,126.4,118.5,117.3,114.0,79.4,69.4,25.4,21.5; HRMS(ESI)m / zC 26 H 28 N₂NaO₆S[M+Na] + Theoretical value: 519.1560, measured value: 519.1568.

[0107] Example 23

[0108] In this embodiment, equimolar cymoxanil was used to replace chlorobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a white solid product with the following structural formula, with a yield of 83%.

[0109]

[0110] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 HNMR(400MHz,d6-DMSO)δ9.96(br,1H),8.08(s,1H),7.93(s,1H),7.36(d,J=8.7Hz,2H),7.26(d,J=8.7Hz,2H),7.08(d,J=8.7Hz,2H),6. 56(d,J=8.7Hz,2H),5.98(d,J=9.1Hz,2H),5.74(br,2H),4.83–4.65(m,2H),2.10–1.92(m,2H),1.26–1.20(m,2H),0.79(t,J=7.1Hz,3H); 13 C NMR(100MHz,d6-DMSO)δ158.2,156.7,150.1,143.7,135.5,133.9,132.0,12 9.5,125.7,125.0,117.8,60.1,53.78,41.3,31.9,27.0,18.9; HRMS(ESI)m / z C 21 H 24 N6NaO2S[M+Na] + Theoretical value: 447.1574, measured value: 447.1579.

[0111] Example 24

[0112] In this embodiment, chlorobenzene in Example 1 was replaced with an equimolar amount of chloroestradiol ketone, and the other steps were the same as in Example 1, resulting in a white solid product amine with the following structural formula, in a yield of 78%.

[0113]

[0114] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.57(d,J=8.6Hz,2H),7.10(s,1H),7.08(br,1H),6.83(d,J=9.7Hz,2H),6.57(d,J=8.6Hz,2H),4.18(br,2H),2.8 5–2.74(m,2H),2.56–2.40(m,1H),2.33–2.29(m,1H),2.24–2.09(m,2H),2.07–1.89(m,3H),1.62–1.33(m,6H),0.88(s,3H); 13 C NMR (100MHz, CDCl3) δ221.2,150.8,137.6,136.5,134.6,129.4,127.3,126.1,121.6,118 .6,114.0,50.4,48.0,44.0,38.0,35.9,31.5,29.3,26.3,25.7,21.6,13.9; HRMS(ESI)m / z C 24 H 28 N₂NaO₃S[M+Na] + Theoretical value: 447.1713, measured value: 447.1716.

Claims

1. A method for the selective synthesis of 4-amino-N-(hetero)arylsulfonamides, characterized in that: The heteroaryl chloride shown in Formula I, along with 4-aminobenzenesulfonamide shown in Formula II, bipyridine, nickel catalyst, iodine-containing additive, and organic base, were added to an organic solvent and reacted under light in an argon atmosphere. After the reaction was complete, the product was separated and purified to obtain the 4-amino-N-(heteroarylsulfonamide) compound shown in Formula III. In the formula, Ar represents any one of phenyl, thienyl, thiazolyl, pyridinyl, pyrazolyl, quinoxalinyl, or phenyl containing at least one substituent from C1-C6 alkyl, trimethylsilyl, halogen, C1-C4 alkoxy, trifluoromethoxy, trifluoromethyl, cyano, ester, acyl, or borosilicate. The nickel catalyst is any one of nickel bromide, nickel chloride, and nickel acetate; the organic base is any one of 1,8-diazabicycloundec-7-ene, tetramethylguanidine, and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene; and the iodine-containing additive is any one of sodium iodide, potassium iodide, and cesium iodide. The organic solvent is any one or two of dimethyl sulfoxide, toluene, isopropanol, N,N-dimethylformamide, and N,N-dimethylacetamide; The photoreaction is carried out under violet light with a wavelength of 360–430 nm at 80–90°C for 24–36 hours.

2. The method of selectively synthesizing 4-amino-N-(hetero)arylsulfonamides according to claim 1, characterized by: The amount of 4-aminobenzenesulfonamide used is 1.1 to 2 times the molar amount of (hetero)aryl chloride.

3. The method for selectively synthesizing 4-amino-N-(hetero)arylsulfonamide compounds according to claim 1, characterized in that: The amount of bipyridine used is 5% to 10% of the molar amount of (hetero)aryl chloride.

4. The method for selectively synthesizing 4-amino-N-(hetero)arylsulfonamide compounds according to claim 1, characterized in that: The amount of nickel catalyst used is 5% to 10% of the molar amount of (hetero)aryl chloride.

5. The method for selectively synthesizing 4-amino-N-(hetero)arylsulfonamide compounds according to claim 1, characterized in that: The amount of the iodine-containing additive is 1.1 to 2 times the molar amount of (hetero)aryl chloride.

6. The method for selectively synthesizing 4-amino-N-(hetero)arylsulfonamide compounds according to claim 1, characterized in that: The amount of the organic base used is 2 to 3 times the molar amount of the (hetero)aryl chloride.

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