CN116730879A - Method for selectively synthesizing 4-amino-N- (hetero) aryl sulfonamide compound - Google Patents

Method for selectively synthesizing 4-amino-N- (hetero) aryl sulfonamide compound Download PDF

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CN116730879A
CN116730879A CN202310769415.4A CN202310769415A CN116730879A CN 116730879 A CN116730879 A CN 116730879A CN 202310769415 A CN202310769415 A CN 202310769415A CN 116730879 A CN116730879 A CN 116730879A
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hetero
amino
aryl
arylsulfonamides
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薛东
宋戈洋
宋佳萌
李琪
李刚
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Shaanxi Normal University
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Abstract

The invention discloses a method for selectively synthesizing 4-amino-N- (hetero) aryl sulfonamide compounds, which takes bipyridine as a ligand, metallic nickel as a catalyst, low-activity (hetero) aryl chloride and 4-amino benzene sulfonamide which are low in cost and rich in sources are taken as substrates, 1, 8-diazabicyclo undec-7-ene and the like are taken as organic bases, sodium iodide and the like are taken as additives, and the synthesis of various 4-amino-N- (hetero) aryl sulfonamide compounds is realized through the selective C-N coupling reaction of photo-driven nickel catalytic (hetero) aryl chloride and 4-amino benzene sulfonamide in an argon atmosphere. The method has the advantages of simple reaction system, simple and convenient operation, mild reaction conditions, simple post-treatment, good selectivity of the target compound and high yield, solves the problems of complex reaction, poor functional group compatibility and the like of the catalytic system caused by the use of the traditional expensive metal catalyst and inorganic base, and has good application value and market prospect.

Description

Method for selectively synthesizing 4-amino-N- (hetero) aryl sulfonamide compound
Technical Field
The invention belongs to the technical field of synthesis of 4-amino-N- (hetero) aryl sulfonamide compounds, and particularly relates to a method for synthesizing 4-amino-N- (hetero) aryl sulfonamide compounds through photochemical nickel catalysis.
Background
The N-aryl (heterocyclic aryl) sulfonamide compound has remarkable biological activities such as antibiosis, anti-inflammation and the like, is an important core skeleton in medicinal molecules, has important application value (Top.Curr.Chem.2018,376, 5;Top.Curr.Chem.2017,375,82;J.Med.Chem.2012,55,7849;WO2006/024823A1,March 09,2006.) in medicinal chemistry and agricultural chemicals, such as representative molecules including anti-infective sulfathiazole, dabrafenib for treating cancers, dofetilide for resisting arrhythmia, celecoxib for relieving osteoarthritis and the like. Meanwhile, sulfonamide compounds also play an important role in chemical reactions, such as chiral catalysts (Tetrahedron letters 1992,33,6661), organic catalysts (chem. Commun.2009,7,833), and isosteres of carboxylic acids (chemmed chem.2013,8,385), etc. In the conventional N-arylsulfonamide synthesis, direct condensation reaction of sulfonyl chloride with amine compounds is mainly used, however, sulfonyl chloride is sensitive to humidity, is not readily available, is unstable, and is easily caused to have potential toxicity problems and the like, which limit the practical applicability (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 a method for synthesizing a solution that avoids the use of sulfonyl chloride is still of great importance in the pharmaceutical industry. Transition metal catalysis is an attractive strategy to achieve C-N coupling of aryl halides with sulfonamides. By ligand development, cu (Tetrahedron letters 2003,44,3385;Tetrahedron Lett.2005,46,7295;Org.Lett.2010,12,1532;Angew.Chem.Int.Ed.2022,61,e)202210483; org.lett.2014,16,338; ACS catalyst.2018, 8,9560; org.lett.2010,12,1532; ACS catalyst.2018, 8,9560), 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; angel.chem.int.ed., 2021,60,7353; ACS cata.2019, 9,11691.), ni (angel.chem.int.ed.2020, 59,8952-8956; ACS catalyst.2022, 12,2,1475-1480.JACS Au 2021,1,1057-1065.) catalyzed Buchwald-Hartwig coupling was developed rapidly. However, most of these newly developed catalytic systems are only capable of achieving aryl bromides (iodides), and less research is conducted on inexpensive and abundant low-activity aryl chlorides. Copper catalysts require high loadings and high temperatures in the only reports, and the phosphine-rich ligands developed by Pd, ni are also suitable for electron-deficient and electron-neutral aryl chlorides which are not yet versatile. The reaction of C-N coupling of sulfonamides to N-nucleophiles is further promoted with the development of photocatalysis (chem. Rev.2022,122,1485; organometallics photositzers. 2022,1, 284-338), electrocatalysis (J. Am. Chem. Soc.2019,141,5664-5668;Angew.Chem.Int.Ed.2021,60,5056 2;JACS Au.2021,1,1057) and co-catalysis of transition metals. Macmillan (angel. 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) developed C-N coupling reactions of sulfonamides of aryl halides of photo-nickel synergistic catalytic systems, but these works hardly involved low-activity aryl chlorides of rich sources and very challenging. However, the electrochemical promotion of the C-N coupling of nickel-catalyzed aryl halides with sulfonamides developed by the ruping group (JACS Au.2021,1, 1057-1065) also only has two simple examples of aryl chlorides, which means that the use of widely used, highly heterogeneous, low-activity (hetero) aryl chlorides remains a major issue in current Ni catalytic systems. Most importantly, in these current methods, the inclusion of multiple NH's is hardly achievable 2 Selective C-N coupled sulfonamide reactions in the presence of functional groups. Therefore, the development and use of the ligand are simple and easy to obtain, and the universality is highThe selective C-N coupling of the potent aryl chlorides to the sulfonamides remains important.
Disclosure of Invention
The invention aims to provide a method for synthesizing 4-amino-N- (hetero) aryl sulfonamide compounds by using a low-cost nickel catalysis and bipyridine catalysis system and adding additives such as sodium iodide and the like to realize selective C-N coupling of (hetero) aryl chloride and 4-amino benzene sulfonamide. The method not only solves the problem that low-activity aryl chloride with low cost and abundant sources can not participate in the reaction, but also realizes that the aryl chloride contains a plurality of NH 2 The selectivity problem when functional groups are present.
Aiming at the purposes, the invention adopts the technical scheme that: adding the (hetero) aryl chloride shown in the formula I, 4-aminobenzene sulfonamide shown in the formula II, bipyridine, a nickel catalyst, an iodine-containing additive and an organic base into an organic solvent, carrying out an illumination reaction in an argon atmosphere, and separating and purifying a product after the reaction is finished to obtain a 4-amino-N- (hetero) aryl sulfonamide compound shown in the formula III;
wherein Ar represents any one of aryl, substituted aryl, heterocyclic aryl and substituted heterocyclic aryl, and specifically may represent any one of phenyl, thienyl, thiazolyl, pyridyl, pyrazolyl, piperidinyl, quinoxalinyl and the like, or C-containing 1 ～C 6 Alkyl, trimethylsilyl, halogen, C 1 ～C 4 Phenyl having at least 1 substituent among an alkoxy group, a trifluoromethoxy group, a trifluoromethyl group, a cyano group, an ester group, an acyl group, a carbonyl group, a boron ester group, and the like.
In the above synthesis method, the amount of 4-aminobenzenesulfonamide is preferably 1.1 to 2 times the molar amount of the (hetero) aryl chloride.
In the above synthesis method, the amount of bipyridine is preferably 5 to 10% of the molar amount of (hetero) aryl chloride.
In the above synthesis method, the nickel catalyst is preferably any one of nickel bromide, nickel acetate, nickel chloride and the like, and the amount thereof is 5 to 10% of the molar amount of the (hetero) aryl chloride.
In the above synthesis method, the iodine-containing additive is preferably any one of sodium iodide, potassium iodide, cesium iodide, and the like, and the amount thereof is 1.1 to 2 times the molar amount of the (hetero) aryl chloride.
In the above synthesis method, the organic base is preferably any one of 1, 8-diazabicyclo undec-7-ene (DBU), tetramethylguanidine (TMG), 7-methyl-1, 5, 7-triazabicyclo [4.4.0] dec-5-ene (MTBD), and the like, and the amount thereof is 2 to 3 times the molar amount of the (hetero) aryl chloride.
In the above synthetic method, the organic solvent is preferably one or two of dimethyl sulfoxide, toluene, isopropanol, N-dimethylformamide and N, N-dimethylacetamide.
In the above synthesis method, it is preferable to react at 80 to 90℃for 24 to 36 hours under irradiation of violet light having a wavelength of 360 to 430nm in an argon atmosphere.
The beneficial effects of the invention are as follows:
the invention has simple reaction system, uses a low-cost nickel catalysis and bipyridine system, and simultaneously, the addition of the iodine-containing additive is beneficial to the realization of the reaction of the (hetero) aryl chloride and the 4-amino benzene sulfonamide to synthesize the 4-amino-N- (hetero) aryl sulfonamide compound under the illumination condition. The invention has higher economic benefit, no harm to environment and simple post-treatment, solves the problem that the low-activity aryl chloride with low cost and abundant sources can not participate in the reaction, and realizes the preparation of the catalyst containing a plurality of NH 2 The functional groups present are subject to selective compatibility issues. In addition, the obtained 4-amino-N- (hetero) aryl sulfonamide compound has the advantages of good yield, excellent functional group compatibility and the like, is a simple and efficient method for synthesizing the 4-amino-N- (hetero) aryl sulfonamide compound, accords with the chemical concept of environment protection, economy and green pursuing at present, and has very important application prospect.
Detailed Description
The present invention will be described in further detail with reference to examples, but the scope of the present invention is not limited to these examples.
Example 1
22.4mg (0.2 mmol) of chlorobenzene, 68.8mg (0.4 mmol) of 4-aminobenzenesulfonamide, 1.9mg (0.01 mmol) of bipyridine, 1.3mg (0.01 mmol) of nickel chloride, 30mg (0.4 mmol) of sodium iodide, 90mg (0.6 mmol) of MTBD, 2mLN, a mixed solvent of N-dimethylformamide and isopropanol in a volume ratio of 2:1 and a magnet were added into a reaction tube under a purple light with a wavelength of 390-395 nm, and reacted at 85℃for 36 hours. Cooling to room temperature after the reaction is finished, adding saturated sodium chloride aqueous solution and ethyl acetate for dilution extraction to obtain an organic phase, carrying out reduced pressure distillation to obtain a crude product, and separating the product by column chromatography by taking a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 1:1 to 1:2 as a leaching agent to obtain a pale yellow solid product with a structural formula as shown in the specification, wherein the yield is 86%.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,d 6 -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)； 13 C NMR(100MHz,d 6 -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 N 2 NaO 2 S[M+Na] + theoretical 271.0512, measured 271.0513.
Example 2
In this example, the chlorobenzene in example 1 was replaced with equimolar amounts of 4-methyl-chlorobenzene, respectively, and the other steps were the same as in example 1, to give a pale yellow solid product of the following structural formula, with a yield of 89%.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,d 6 -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,d 6 -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 N 2 NaO 2 S[M+Na] + theoretical 285.0668, measured 285.0667.
Example 3
In this example, the chlorobenzene of example 1 was replaced with equimolar 4-tert-butylchlorobenzene, and the other steps were the same as in example 1, to give a white solid product of the formula below in 87% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,d 6 -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,d 6 -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 N 2 NaO 2 S[M+Na] + theoretical 327.1138, measured 327.1136.
Example 4
In this example, the chlorobenzene in example 1 was replaced with equimolar 4-chlorobenzene- (trimethylsilyl) benzene, and the other steps were the same as in example 1, to give a white solid product of the formula below in 81% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,d 6 -DMSO)δ10.01(br,1H),7.48(d,J＝8.6Hz,2H),7.38(d,J＝8.0Hz,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,d 6 -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 N 2 NaO 2 SSi[M+Na] + theory of theoryTheory 343.0907, found 343.0907.
Example 5
In this example, the chlorobenzene of example 1 was replaced with equimolar 4-methoxychlorobenzene, and the other steps were the same as in example 1, to give a white solid product of the formula below in 83% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,d 6 -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,d 6 -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 N 2 NaO 3 S[M+Na] + theoretical 301.0617, measured 301.0618.
Example 6
In this example, the chlorobenzene in example 1 was replaced with equimolar 4-chlorotrifluoromethoxybenzene, and the other steps were the same as in example 1, to give a yellow solid product of the formula below in 83% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,d 6 -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,d 6 -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,d 6 -DMSO)δ-57.14(s,OCF 3 )；HRMS(ESI)m/z C 13 H 11 F 3 N 2 NaO 3 S[M+Na] + theoretical 355.0335, measured 355.0339.
Example 7
In this example, the chlorobenzene of example 1 was replaced with equimolar 4-acetonitrile chlorobenzene, and the other steps were the same as in example 1, to give a yellow solid product of the formula below in 78% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,d 6 -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,d 6 -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 N 3 NaO 2 S[M+Na] + theoretical 310.0621, measured 310.0624.
Example 8
In this example, the chlorobenzene of example 1 was replaced with equimolar 4-cyanochlorobenzene, and the other steps were the same as in example 1, to give a yellow solid product of the formula below in 89% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,d 6 -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,d 6 -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 N 3 NaO 2 S[M+Na] + theoretical 296.0464, measured 296.0465.
In this example, the MTBD was replaced with equimolar DBU, and the yield of product was 81%.
Example 9
In this example, the chlorobenzene in example 1 was replaced with equimolar methyl 4-chlorobenzoate, and the other steps were the same as in example 1, to give a white solid product of the formula below in 78% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,d 6 -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,d 6 -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 N 2 NaO 4 S[M+Na] + theoretical 329.0566, measured 329.0569.
Example 10
In this example, the chlorobenzene of example 1 was replaced with equimolar 1, 4-dichlorobenzene, and the other steps were the same as in example 1, to obtain a white solid product of the formula below in 81% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,d 6 -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)； 13 C NMR(100MHz,d 6 -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 ClN 2 NaO 2 S[M+Na] + theoretical 305.0122, measured 305.0122.
Example 11
In this example, the chlorobenzene of example 1 was replaced with equimolar 2-methyl chlorobenzene, and the other steps were the same as in example 1, to give a white solid product of the formula below in 75% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,d 6 -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,d 6 -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 N 2 NaO 2 S[M+Na] + theoretical 285.0668, measured 285.0669.
Example 12
In this example, the chlorobenzene of example 1 was replaced with equimolar 2-methoxychlorobenzene, and the other steps were the same as in example 1, to give a white solid product of the formula below in 71% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,d 6 -DMSO)δ8.79(br,1H),7.35(d,J＝8.6Hz,2H),7.23-7.18(m,1H),7.04(t,J＝7.2Hz,1H),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,d 6 -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/z C 13 H 14 N 2 NaO 3 S[M+Na] + theoretical 301.0617, measured 301.0613.
Example 13
In this example, the chlorobenzene in example 1 was replaced with equimolar 2-chlorotrifluoromethoxybenzene, and the other steps were the same as in example 1, to give a white solid product of the formula below in 68% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,CDCl 3 )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,CDCl 3 )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,CDCl 3 )δ-57.52(s,OCF 3 )；HRMS(ESI)m/zC 13 H 11 F 3 N 2 NaO 3 S[M+Na] + theoretical 355.0335, measured 355.0333.
Example 14
In this example, the chlorobenzene of example 1 was replaced with equimolar 2-isopropyl chlorobenzene, and the other steps were the same as in example 1, to give a white solid product of the formula below in 61% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,d 6 -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,d 6 -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 N 2 NaO 2 S[M+Na] + theoretical 313.0981, measured 313.0981.
Example 15
In this example, the chlorobenzene of example 1 was replaced with equimolar 2-acetylchlorobenzene, and the other steps were the same as in example 1, to give a white solid product of the formula below in 73% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,d 6 -DMSO)δ11.23(br,1H),8.02(d,J＝7.9Hz,1H),7.59(t,J＝7.8Hz,1H),7.53–7.39(m,3H),7.18(t,J＝7.6Hz,1H),6.58(d,J＝8.8Hz,2H),6.15(br,2H),2.64(s,3H)； 13 C NMR(100MHz,d 6 -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 N 2 NaO 3 S[M+Na] + theoretical 313.0617, measured 313.0619.
Example 16
In this example, the chlorobenzene of example 1 was replaced with equimolar 2, 4-dimethoxychlorobenzene, and the other steps were the same as in example 1, to give a pale yellow solid product of the following structural formula in 71% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,CDCl 3 )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,CDCl 3 )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 N 2 NaO 4 S[M+Na] + theoretical value 331.0723 measured value 331.0728.
Example 17
In this example, the chlorobenzene in example 1 was replaced with equimolar methyl 4-chloro-3-methoxybenzoate, and the other steps were the same as in example 1, to give a yellow solid product of the formula below in 65% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,d 6 -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,d 6 -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 N 2 NaO 5 S[M+Na] + theoretical 359.0672, measured 359.0675.
Example 18
In this example, the chlorobenzene of example 1 was replaced with equimolar 3, 5-bistrifluoromethyl chlorobenzene, and the other steps were the same as in example 1, to give a white solid product of the formula below in 88% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 HNMR(400MHz,d 6 -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,d 6 -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,d 6 -DMSO)δ-57.42(s,CF 3 )；HRMS(ESI)m/z C 14 H 10 F 6 N 2 NaO 2 S[M+Na] + theoretical 407.0259, measured 407.0265.
In this example, the MTBD was replaced with equimolar TMG, and the yield of product was 85%.
Example 19
In this example, the chlorobenzene of example 1 was replaced with equimolar amounts of 2- (5-chloro-2-methylphenyl) -4, 5-tetramethyl-1, 3, 2-dioxaborolan, and the other steps were the same as in example 1, to give a white solid product of the formula below in 84% yield.
The nuclear magnetic spectrum data of the obtained product are 1 H NMR(400MHz,CDCl 3 )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,CDCl 3 )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 BN 2 NaO 4 S[M+Na] + Theoretical 411.1520, measured 411.1523.
Example 20
In this example, the chlorobenzene in example 1 was replaced with equimolar 2-chlorothiazole, and the other steps were the same as in example 1, to give a white solid product of the formula below in 71% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,d 6 -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,d 6 -DMSO)δ168.4,152.7,128.3,128.2,124.7,112.9,107.9；HRMS(ESI)m/z C 9 H 9 N 3 NaO 2 S 2 [M+Na] + theoretical 278.0028, measured 278.0029.
Example 21
In this example, the chlorobenzene of example 1 was replaced with equimolar clofibrate, and the other steps were the same as in example 1, to give a yellow solid product of the formula below in a yield of 81%.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,CDCl 3 )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,CDCl 3 )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 N 2 NaO 5 S[M+Na] + theoretical 401.1142, measured 401.1145.
Example 22
In this example, the chlorobenzene of example 1 was replaced with equimolar fenofibrate, and the other steps were the same as in example 1, to give a yellow solid product of the formula below in 71% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,CDCl 3 )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 C NMR(100MHz,CDCl 3 )δ194.7,173.3,159.5,151.3,141.2,133.3,131.9,131.5,130.6,129.5,126.4,118.5,117.3,114.0,79.4,69.4,25.4,21.5；HRMS(ESI)m/zC 26 H 28 N 2 NaO 6 S[M+Na] + theoretical 519.1560, measured 519.1568.
Example 23
In this example, the chlorobenzene in example 1 was replaced with equimolar myclobutanil, and the other steps were the same as in example 1, to give a white solid product of the following structural formula in 83% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 HNMR(400MHz,d 6 -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,d 6 -DMSO)δ158.2,156.7,150.1,143.7,135.5,133.9,132.0,129.5,125.7,125.0,117.8,60.1,53.78,41.3,31.9,27.0,18.9；HRMS(ESI)m/z C 21 H 24 N 6 NaO 2 S[M+Na] + theoretical 447.1574, measured 447.1579.
Example 24
In this example, the chlorobenzene in example 1 was replaced with equimolar chloroestrone, and the other steps were the same as in example 1, to give the amine as a white solid product of the formula below in 78% yield.
The nuclear magnetic spectrum data of the obtained product are: 1 H NMR(400MHz,CDCl 3 )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,CDCl 3 )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 N 2 NaO 3 S[M+Na] + theoretical 447.1713, measured 447.1716.

Claims (9)

1. A method for selectively synthesizing 4-amino-N- (hetero) arylsulfonamides, which is characterized in that: adding the (hetero) aryl chloride shown in the formula I, 4-aminobenzene sulfonamide shown in the formula II, bipyridine, a nickel catalyst, an iodine-containing additive and an organic base into an organic solvent, carrying out an illumination reaction in an argon atmosphere, and separating and purifying a product after the reaction is finished to obtain a 4-amino-N- (hetero) aryl sulfonamide compound shown in the formula III;
wherein Ar represents any one of aryl, substituted aryl, heterocyclic aryl and substituted heterocyclic aryl;
the nickel catalyst is any one of nickel bromide, nickel chloride and nickel acetate, the organic alkali is any one of 1, 8-diazabicyclo undec-7-ene, tetramethyl guanidine 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.
2. The method for selectively synthesizing 4-amino-N- (hetero) arylsulfonamides according to claim 1, characterized in that: ar represents any one of phenyl, thienyl, thiazolyl, pyridyl, pyrazolyl, piperidyl and quinoxalinyl, or contains C 1 ～C 6 Alkyl, trimethylsilyl, halogen, C 1 ～C 4 Phenyl of at least 1 substituent among alkoxy, trifluoromethoxy, trifluoromethyl, cyano, ester, acyl, carbonyl and boron ester.
3. The method for selectively synthesizing 4-amino-N- (hetero) arylsulfonamides according to claim 1 or 2, characterized in that: the dosage of the 4-aminobenzene sulfonamide is 1.1-2 times of the molar quantity of the (hetero) aryl chloride.
4. The method for selectively synthesizing 4-amino-N- (hetero) arylsulfonamides according to claim 1 or 2, characterized in that: the amount of bipyridine is 5% -10% of the molar amount of (hetero) aryl chloride.
5. The method for selectively synthesizing 4-amino-N- (hetero) arylsulfonamides according to claim 1 or 2, characterized in that: the nickel catalyst is used in an amount of 5 to 10% of the molar amount of the (hetero) aryl chloride.
6. The method for selectively synthesizing 4-amino-N- (hetero) arylsulfonamides according to claim 1 or 2, characterized in that: the iodine-containing additive is used in an amount of 1.1 to 2 times the molar amount of the (hetero) aryl chloride.
7. The method for selectively synthesizing 4-amino-N- (hetero) arylsulfonamides according to claim 1 or 2, characterized in that: the organic base is used in an amount of 2 to 3 times the molar amount of the (hetero) aryl chloride.
8. The method for selectively synthesizing 4-amino-N- (hetero) arylsulfonamides according to claim 1 or 2, characterized in that: the organic solvent is any one or two of dimethyl sulfoxide, toluene, isopropanol, N-dimethylformamide and N, N-dimethylacetamide.
9. The method for selectively synthesizing 4-amino-N- (hetero) arylsulfonamides according to claim 1 or 2, characterized in that: the illumination reaction is carried out for 24-36 hours at 80-90 ℃ under the irradiation of purple light with the wavelength of 360-430 nm.
CN202310769415.4A 2023-06-28 2023-06-28 Method for selectively synthesizing 4-amino-N- (hetero) aryl sulfonamide compound Pending CN116730879A (en)

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