A method for photochemical iron catalytic synthesis of arylamine compounds

Abstract

This invention discloses a photochemical iron-catalyzed synthesis method for aromatic amines. Using inexpensive and abundant aryl bromides and amines as reactants, an inexpensive iron salt as a catalyst, bipyridine as a ligand, and an organic base, the synthesis of aromatic amines is achieved through a photoexcited iron-catalyzed C-N coupling reaction of aryl bromides and amines 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 yield, avoiding the problems of complex catalytic systems and poor functional group compatibility caused by the use of traditional expensive metal catalysts and inorganic bases. It has significant application value and market prospects.

Description

Technical Field

[0001] This invention belongs to the field of aromatic amine synthesis technology, specifically relating to a method for synthesizing aromatic amine compounds by photochemical iron catalysis. Background Technology

[0002] Transition metal-catalyzed CN coupling reactions are widely used in the synthesis of pharmaceuticals and fine chemicals, and are listed as one of the 20 most commonly used reactions in modern drug synthesis (Org. Process Res.Dev. 2014, 18, 1752; Org. Process Res.Dev. 2019, 23, 1529). Based on ligand regulation strategies, palladium and nickel-catalyzed Buchwald-Hartwig amination reactions (Chem. Soc. Rev. 2011, 40, 5068) and copper-catalyzed Ullmann-Ma coupling reactions (Chin. J. Chem. 2020, 38, 879) have been rapidly developed, providing important methods for the efficient synthesis of aromatic amines. Despite significant progress in palladium, nickel, and copper-catalyzed coupling reactions, there is still a need to develop new, inexpensive, and environmentally friendly catalytic methods.

[0003] Iron is the most abundant transition metal on Earth, and various iron salts and iron complexes are readily available and inexpensive. Furthermore, iron exhibits excellent biocompatibility, being an essential trace element for the human body. Iron-containing metalloproteins participate in numerous vital life processes, making the development of iron as a metal catalyst a promising endeavor (Chem. Soc. Rev. 2008, 37, 1108). In fact, iron has achieved remarkable research progress as a catalyst over the past few decades, successfully being applied to various chemical transformations. Since the pioneering development of iron-catalyzed coupling reactions by Tamura and Kochi in 1971, iron salts have become alternative and promising catalysts for many organic transformations (J. Chem. Soc., Chem. Commun. 1972, 144). Therefore, developing iron-catalyzed CN coupling reactions represents a green and sustainable new approach. In 2007, Bolm's group (Angew. Chem. Int. Ed. 2007, 46, 8862) achieved the first iron-catalyzed CN coupling reaction of aryl halides with N-nucleophiles using bidentate nitrogen ligands (DMEDA). Subsequently, Tao (Adv. Synth. Catal. 2009, 351, 720), Kwang (Tetrahedron Lett. 2009, 50, 5868), Liu (Org. Lett. 2008, 10, 4513), Paul (Inorg. Chem. 2019, 58, 1935), and others developed CN coupling reactions of aryl iodides with ligands such as proline and phenanthroline with N-nucleophiles (pyrazole, indole, etc.). To improve the efficiency of iron-catalyzed aryl CN-bond construction, groups such as Taillefer (Angew. Chem. Int. Ed. 2007, 46, 934), Wakharkar (Catal. Commun. 2007, 8, 65), and Liu (Green Chem. 2010, 12, 276) developed Fe / Cu-bimetallic catalyzed CN coupling reactions. Iron-catalyzed CN coupling reactions were developed through the strategy of developing bidentate nitrogen ligands. However, iron-catalyzed CN coupling reactions typically require high temperatures (>100℃) and inorganic bases, leading to poor functional group compatibility and limited substrate applicability. Most importantly, Bolm and Buchwald discovered that trace amounts of residual copper are the main catalytically active substance in iron-catalyzed CN coupling (Chem. Soc. Rev. 2012, 41, 979). Since then, progress in iron-catalyzed CN coupling reactions has almost stalled.

[0004] In recent years, photocatalytic organic synthesis reactions have been considered environmentally friendly, clean, and sustainable chemical transformation processes (Asian J.Org.Chem 2020,9,1519). Combining photocatalysis with iron catalysis provides a new research strategy for the construction of carbon-carbon or carbon-heteroatom bonds in organic synthesis. Recently, iron catalysis has made some important progress in reactions that construct C-heteroatom bonds. In 2012, Bao's group (Chem.Commun.2023,59,752) reported the visible light-induced iron-catalyzed decarboxylation CN coupling reaction of α-amino acids with dioxazolone to obtain amide derivatives. In 2022, Zeng's group (ACSCatal.2021,11,13955) reported that, under photosensitizer-free conditions, inexpensive iron complexes were used as catalysts to yield amide derivatives from aldehydes or benzyl alcohols with nitroaromatics without strong oxidizing or reducing agents. In 2022, Bao's research group (Org. Lett. 2022, 24, 4766) effectively achieved photo-induced iron-catalyzed CN coupling reactions of arylboronic acids and dioxazolone aryl compounds under photosensitizer-free conditions. However, in photo- and iron-catalyzed CN coupling reactions, there are relatively few studies on coupling reactions using readily available and inexpensive aryl halides as electrophiles to N-nucleophiles. This is mainly because iron catalysts typically require low valence states for oxidative addition, and high-valence iron catalysts are difficult to use for oxidative addition. Therefore, regulating the oxidative addition of low-valence iron active species to aryl halides using Fe catalysts may be key to promoting aryl CN coupling reactions. Thus, developing efficient CN coupling reactions of aryl bromides and amines using simple and readily available ligands remains very important. Summary of the Invention

[0005] The purpose of this invention is to provide a method for synthesizing aromatic amine compounds by using an inexpensive iron salt and bipyridine catalytic system to achieve CN coupling of aryl bromides and amine compounds.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: the aryl bromide shown in Formula I, the amine compound shown in Formula II, bipyridine, iron catalyst, and organic base are added to an organic solvent, heated and irradiated in an argon atmosphere, and after the reaction is complete, the product is separated and purified to obtain the aromatic amine compound shown in Formula III.

[0007]

[0008] In the formula, Ar represents any one of aryl, substituted aryl, heterocyclic aryl, and substituted heterocyclic aryl, specifically such as: phenyl, thienyl, thiazolyl, pyridinyl, pyrazolyl, piperidinyl, pyrazinyl, quinolinyl, phenylpropenylthienyl, benzofuranyl, dibenzothienyl, quinoxalinyl, or phenyl containing at least one substituent from C1-C6 alkyl, C6-cycloalkyl, tert-butyldimethylsiloxy, sulfonyl, acridineyl, piperidinyl, trimethylsilyl, halogen, C1-C4 alkoxy, trifluoromethoxy, trifluoromethyl, cyano, ester, aldehyde, acyl, carbonyl, and borosilicate; HNNu represents any one of aromatic amine, substituted aromatic amine, heterocyclic aromatic amine, pyrazole, amide, sulfonamide, and aliphatic amine.

[0009] In the above synthesis method, the amount of amine compound used is preferably 1.1 to 2 times the molar amount of aryl bromide.

[0010] In the above synthesis method, the amount of bipyridine used is preferably 5% to 20% of the molar amount of aryl bromide.

[0011] In the above synthesis method, the preferred iron catalyst is any one of ferrous bromide, ferrous carbonate, ferrous acetate, ferrous chloride, etc., and its amount is 5% to 15% of the molar amount of aryl bromide.

[0012] 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), 1,2-dimethyl-1,4,5,6-tetrahydropyrimidine (DMTHPM), etc., and its amount is 2 to 3 times the molar amount of aryl bromide.

[0013] 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.

[0014] In the above synthesis method, it is preferred to react at 80-90°C for 24-48 hours under an argon atmosphere and irradiated with ultraviolet light with a wavelength of 360-430 nm.

[0015] The beneficial effects of this invention are as follows:

[0016] This invention utilizes an inexpensive iron salt and bipyridine catalytic system to achieve the CN coupling reaction of aryl bromides and amine compounds to synthesize aromatic amines under light irradiation. The reaction system is simple, economically efficient, environmentally friendly, and easy to process. The resulting aromatic amines exhibit good yields and excellent functional group compatibility. This method is a simple and efficient way to synthesize aromatic amines, aligning with current trends towards environmentally friendly, economical, and green chemistry, and possesses significant application potential. Detailed Implementation

[0017] 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.

[0018] Example 1

[0019] In an argon atmosphere, 31.4 mg (0.2 mmol) of bromobenzene, 29.4 mg (0.4 mmol) of n-butylamine, 1.9 mg (0.01 mmol) of bipyridine, 3.5 mg (0.01 mmol) of ferrous carbonate, 67.4 mg (0.6 mmol) of DMTHPM, 2 mL of N,N-dimethylformamide, and a magnetic flux were added to a reaction tube. The reaction was carried out at 85 °C for 36 hours under ultraviolet light irradiation at 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 organic phase was then distilled under reduced pressure to obtain a crude product. The crude product was separated by column chromatography using a mixture of petroleum ether and ethyl acetate in a volume ratio of 100:1 to 10:1 as the eluent, yielding a pale yellow oily product with the following structural formula, in 95% yield.

[0020]

[0021] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.17(t,J=7.6Hz,2H),6.69(dd,J=7.6,7.0Hz,1H),6.61(d,J=8.4Hz ,2H),3.12(t,J=7.1Hz,2H),1.65-1.60(m,2H),1.49-1.39(m,2H),0.96(t,J=7.3Hz,3H); 13 C NMR(100MHz, CDCl3)δ148.7,129.4,117.2,112.9,43.8,31.9,20.5,14.0; HRMS(ESI)m / z C 10 H 16 N[M+H] + Theoretical value: 150.1277, measured value: 150.1279.

[0022] Example 2

[0023] In this embodiment, 4-bromobenzene-(trimethylsilyl)benzene was replaced with an equimolar amount of bromobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a pale yellow oily substance with the following structural formula, in a yield of 70%.

[0024]

[0025] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.38(d,J=7.7Hz,2H),6.66(d,J=7.9Hz,2H),3.69(br,1H),3. 17(m,2H),1.69-1.61(m,2H),1.53-1.42(m,2H),1.01(t,J=7.3Hz,3H),0.28(s,9H); 13 C NMR(100MHz, CDCl3)δ134.6,129.3,112.8,112.3,43.5,31.8,20.4,14.0,-0.7; HRMS(ESI)m / z C 13 H 24 NSi[M+H] + Theoretical value: 222.1673, measured value: 222.1671.

[0026] Example 3

[0027] In this embodiment, bromobenzene in Example 1 was replaced with equimolar 4-bromophenylboronic acid pinacol ester, 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 78%.

[0028]

[0029] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR(400MHz, CDCl3)δ7.56(d,J=6.6Hz,2H),6.50(d,J=3.2Hz,2H),3.15-2.98(m, 2H),1.54-1.50(m,2H),1.38-1.30(s,2H),1.26-1.23(m,12H),0.89-0.84(m,3H); 13 C NMR (100MHz, CDCl3) δ151.2,136.5,131.1,111.8,83.3,43.3,31.7,29.8,25.0,20.4,14.0; HRMS (ESI) m / z C 16 H 27 BNO2[M+H] + Theoretical value: 276.2129, measured value: 276.2125.

[0030] Example 4

[0031] In this embodiment, 4-bromodifluoromethoxybenzene was replaced with an equimolar amount of bromobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a pale yellow oily substance with the following structural formula, in a yield of 89%.

[0032]

[0033] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ6.89(d,J=8.7Hz,2H),6.47(d,J=8.6Hz,2H),6.20(t,J=75.0Hz,1H),3.5 2(br,1H),3.01(t,J=7.1Hz,2H),1.63-1.44(m,4H),1.39-1.32(m,3H),0.89(t,J=7.3Hz,3H); 13 C NMR (100MHz, CDCl3) δ146.5, 142.2, 121.4, 117.93 (t, J = 258.6Hz), 113.1, 44.0, 31.6, 20.3, 13.9; 19 F NMR(376MHz, CDCl3)δ-79.83(s,F),-80.03(s,F); HRMS(ESI)m / z C 11 H 16 F2NO[M+H] + Theoretical value: 216.1194, measured value: 216.1197.

[0034] Example 5

[0035] In this embodiment, bromobenzene in Example 1 was replaced with an equimolar amount of N-methyl-4-bromobenzamide, 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 76%.

[0036]

[0037] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.61(d,J=8.7Hz,2H),6.54(d,J=8.7Hz,2H),6.11(br,1H),4.02(br,1H),3.13 (t,J=7.1Hz,2H),2.96(d,J=4.8Hz,3H),1.68-1.60(m,2H),1.47-1.40(m,2H),0.96(t,J=7.3Hz,3H); 13C NMR(100MHz, CDCl3)δ168.2,151.0,128.5,122.5,111.6,43.2,31.5,26.7,20.2,13.9; HRMS(ESI)m / z C 12 H 19 N₂O[M+H] + Theoretical value: 207.1492, measured value: 207.1496.

[0038] Example 6

[0039] In this embodiment, equimolar 4-bromofluorobenzene was used to replace the bromobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a pale yellow oily substance with the following structural formula, with a yield of 79%.

[0040]

[0041] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ6.88(t,J=8.7Hz,2H),6.56-6.49(m,2H),3.07(t,J=7.1Hz,2H),1.60(m,2H),1.49-1.37(m,3H),0.96(t,J=7.3Hz,3H); 13 C NMR (100MHz, CDCl3) δ155.6 (d, J = 234.4Hz), 144.9, 115.6 (d, J = 22.2Hz), 113.4 (d, J = 7.4Hz), 44.3, 31.6, 20.3, 13.9; 19 F NMR (376MHz, CDCl3) δ-128.59 (s, F); HRMS (ESI) m / z C 10 H 15 NF[M+H] + Theoretical value: 168.1183, measured value: 168.1186.

[0042] Example 7

[0043] In this embodiment, 3-chloro-5-methoxybromobenzene was used to replace the bromobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a pale yellow oily substance with the following structural formula, with a yield of 76%.

[0044]

[0045] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1H NMR (400MHz, CDCl3) δ6.28-6.31(m,2H),6.01(d,J=1.7Hz,1H),3.75(d,J=1.1Hz ,3H),3.07(t,J=7.0Hz,2H),1.65-1.57(m,2H),1.48-1.39(m,3H),0.96(m,3H); 13 C NMR(100MHz, CDCl3)δ161.4,150.5,135.6,105.9,103.0,97.1,55.5,43.6,31.6,20.4,14.0; HRMS(ESI)m / z C 11 H 17 NOCl[M+H] + Theoretical value: 214.0993, measured value: 214.0996.

[0046] Example 8

[0047] In this embodiment, 2-fluoro-4-chlorobromobenzene was used to replace the bromobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a pale yellow oily substance with the following structural formula, with a yield of 78%.

[0048]

[0049] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ6.93-6.82 (m, 2H), 6.50 (t, J = 9.1Hz, 1H), 3.74 (br, 1H), 3. 03(t,J=7.1Hz,2H),1.59-1.47(m,2H),1.38-1.27(m,2H),0.88(t,J=7.3Hz,3H); 13 C NMR (100MHz, CDCl3) δ151.0 (d, J = 241.7Hz), 135.8 (d, J = 11.6Hz), 124.5 (d, J = 3.5Hz), 120.2 ( d,J=9.6Hz),115.1(d,J=22.1Hz),112.3(d,J=4.3Hz),43.3,31.4,20.2,13.8; HRMS(ESI)m / z C 10 H 14 NFCl[M+H] + Theoretical value: 202.0793, measured value: 202.0797.

[0050] Example 9

[0051] In this embodiment, 4-bromo-2-trifluoromethylpyridine was used to replace bromobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a pale yellow oily substance with the following structural formula, in a yield of 84%.

[0052]

[0053] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 HNMR(600MHz, CDCl3)δ8.33(d,J=5.1Hz,1H),6.91(s,1H),6.66(d,J=2.1Hz,1H),5.15( br,1H),3.29(d,J=5.0Hz,2H),1.80-1.67(m,2H),1.58-1.49(m,2H),1.13-1.03(m,3H); 13 C NMR (100MHz, CDCl3) δ154.3, 149.9, 148.5 (q, J = 33.6Hz), 121.8 (q, J = 274.2Hz), 108.8, 104.1, 42.4, 30.8, 20.0, 13.6; 19 F NMR (376MHz, CDCl3) δ-68.53 (s, CF3); HRMS (ESI) m / z C 10 H 14 F3N2[M+H] + Theoretical value: 219.1104, measured value: 219.1107.

[0054] Example 10

[0055] In this embodiment, 2-bromopyrazine was used to replace bromobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a pale yellow oily substance with the following structural formula, in a yield of 81%.

[0056]

[0057] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR(400MHz, CDCl3)δ7.96(s,1H),7.86(s,1H),7.77(s,1H),4.66(br,1H),3. 39-3.27(m,2H),1.66-1.54(m,2H),1.48-1.37(m,2H),0.94(t,J=7.3Hz,3H); 13 C NMR (100MHz, CDCl3) δ154.9,142.1,132.7,131.9,41.4,31.7,20.2,13.9; HRMS (ESI) m / z C8H 14N3[M+H] + Theoretical value: 152.1182, measured value: 152.1186.

[0058] Example 11

[0059] In this embodiment, equimolar 4-bromoquinoline was used to replace bromobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a pale yellow oily substance with the following structural formula, with a yield of 79%.

[0060]

[0061] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ8.86(d,J=3.1Hz,1H),8.15(d,J=8.5Hz,1H),7.56(t,J=8.0Hz,1H),7.47(d,J=8.4Hz,1H),7.31(dd,J =8.5,4.2Hz,1H),6.63(d,J=7.6Hz,1H),3.27(t,J=7.1Hz,2H),1.82-1.69(m,2H),1.59-1.50(m,2H),1.01(t,J=7.3Hz,3H); 13 C NMR (100MHz, CDCl3) δ149.8,149.2,143.8,130.4,128.6,119.2,118.3,118.1,104.5,43.9,31.4,20.4,13.9; HRMS (ESI) m / zC 13 H 17 N2[M+H] + Theoretical value: 201.1386, measured value: 201.1389.

[0062] Example 12

[0063] In this embodiment, 5-bromobenzothiophene was used to replace bromobenzene in Example 1, and the other steps were the same as in Example 1, resulting in a pale yellow oily substance with the following structural formula, with a yield of 80%.

[0064]

[0065] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1H NMR (400MHz, CDCl3) δ7.61(d,J=8.6Hz,1H),7.35(d,J=5.4Hz,1H),7.20-7.10(m,1H),6.98(d,J=2.3Hz,1H),6.72(d d,J=8.6,2.3Hz,1H),3.62(br,1H),3.24-3.10(m,2H),1.69-1.58(m,2H),1.51-1.43(m,2H),0.97(t,J=7.3Hz,3H); 13 C NMR(100MHz, CDCl3)δ146.1,141.1,129.1,126.7,123.3,122.7,114.0,104.7,44.2,31.7,20.4,13.9; HRMS(ESI)m / z C 12 H 16 NS[M+H] + Theoretical value: 206.0998, measured value: 206.0995.

[0066] Example 13

[0067] In this embodiment, 4-trifluoromethylbromobenzene was replaced with an equimolar amount of bromobenzene in Example 1, and n-butylamine was replaced with an equimolar amount of ethylamine in Example 1. The other steps were the same as in Example 1, and a pale yellow oily substance with the following structural formula was obtained with a yield of 91%.

[0068]

[0069] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.41(d,J=8.3Hz,2H),6.59(d,J=8.3Hz,2H),3.91(br,1H),3.19(q,J=6.9Hz,2H),1.35-1.24(m,3H); 13 C NMR (100MHz, CDCl3) δ150.9, 129.3, 126.7 (q, J = 3.8Hz); 125.2 (q, J = 270.2Hz), 118.6 (q, J = 32.5Hz); 111.8, 38.2, 14.7; HRMS (ESI) m / z C9H 11 NF3[M+H] + Theoretical value: 190.0838, measured value: 190.0834.

[0070] Example 14

[0071] In this embodiment, 4-trifluoromethylbromobenzene was used to replace bromobenzene in Example 1, and 3-but-1-ene-1-amine was used to replace n-butylamine in Example 1. The other steps were the same as in Example 1, and a pale yellow oily substance with the following structural formula was obtained with a yield of 89%.

[0072]

[0073] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.41(d,J=8.5Hz,2H),6.60(d,J=8.5Hz,2H),5.88-5.76(m,1 H),5.24-5.10(m,2H),4.01(br,1H),3.22(t,J=6.1Hz,2H),2.41(q,J=6.7Hz,2H); 13 C NMR (100MHz, CDCl3) δ150.8, 135.4, 126.6 (q, J = 3.8Hz), 125.4 (q, J = 270.1Hz), 118.6 (q, J = 32.5Hz), 117.6, 112.0, 42.4, 33.5; HRMS (ESI) m / zC 11 H 13 NF3[M+H] + Theoretical value: 216.0995, measured value: 216.0998.

[0074] Example 15

[0075] In this embodiment, 4-trifluoromethylbromobenzene was replaced with an equimolar amount of bromobenzene in Example 1, and 3-methoxypropylamine was replaced with an equimolar amount of n-butylamine in Example 1. The other steps were the same as in Example 1, and a pale yellow oily substance with the following structural formula was obtained with a yield of 85%.

[0076]

[0077] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.21(d,J=7.6Hz,2H),6.58(d,J=7.7Hz,2H),3.51(t,J=5 .8Hz,2H),3.35(s,3H),3.22(t,J=6.5Hz,2H),1.96-1.93(m,2H),1.28(s,9H); 13 C NMR(100MHz, CDCl3)δ146.2,140.1,126.1,112.6,71.4,58.9,42.1,33.9,31.7,29.6; HRMS(ESI)m / z C14 H 24 NO[M+H] + Theoretical value: 222.1852, measured value: 222.1855.

[0078] Example 16

[0079] In this embodiment, 4-trifluoromethylbromobenzene was used to replace bromobenzene in Example 1, and 2-mercaptoethylamine was used to replace n-butylamine in Example 1. The other steps were the same as in Example 1, and a pale yellow oily substance with the following structural formula was obtained with a yield of 70%.

[0080]

[0081] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.33(d,J=8.3Hz,2H),6.56(d,J=8.3Hz,2H),4.33(br,1H),3.28(t,J=6.3Hz,2H),2.70(t,J=6.2Hz,2H),2.04(s,3H); 13 C NMR (100MHz, CDCl3) δ150.2, 126.7 (q, J = 3.8Hz), 124.9 (q, J = 270.3Hz), 119.2 (q, J = 32.6Hz), 112.1, 41.3, 33.4, 14.9; HRMS (ESI) m / zC 10 H 13 F3NS[M+H] + Theoretical value: 236.0715, measured value: 236.0719.

[0082] Example 17

[0083] In this embodiment, 4-trifluoromethylbromobenzene was used to replace bromobenzene in Example 1, and 1-aminobutanol was used to replace n-butylamine in Example 1. The other steps were the same as in Example 1, and a pale yellow oily substance with the following structural formula was obtained with a yield of 89%.

[0084]

[0085] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.39 (d, J = 8.4Hz, 2H), 6.59 (d, J = 8.4Hz, 2H), 3.70 (t, J = 5.7Hz, 2H), 3.18 (t, J = 6.4Hz, 2H), 1.76-1.64 (m, 4H); 13CNMR (100MHz, CDCl3) δ150.9, 126.7 (q, J = 3.8Hz), 125.3 (d, J = 270.3Hz), 118.7 (q, J = 32.5Hz), 111.9, 62.6, 43.4, 30.2, 25.9; HRMS (ESI) m / z C 11 H 15 F3NO[M+H] + Theoretical value: 234.1100, measured value: 234.1105.

[0086] Example 18

[0087] In this embodiment, 4-trifluoromethylbromobenzene was used to replace bromobenzene in Example 1, and 2-fluoroethylamine was used to replace n-butylamine in Example 1. The other steps were the same as in Example 1, and a pale yellow oily substance with the following structural formula was obtained with a yield of 87%.

[0088]

[0089] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.41 (d, J = 7.8 Hz, 2H), 6.63 (d, J = 7.9 Hz, 2H), 4.73-4.44 (m, 2H), 4.29 (s, 1H), 3.59-3.41 (m, 2H); 13 C NMR (100MHz, CDCl3) δ150.1, 126.70 (q, J = 3.7Hz), 124.9 (d, J = 270.3Hz), 119.6 ( q, J=32.9Hz), 112.2, 82.1 (d, J=168.0Hz), 43.7 (d, J=20.4Hz); HRMS (ESI) m / zC9H 10 NF4[M+H] + Theoretical value: 208.0744, measured value: 208.0749.

[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, 4-trifluoromethylbromobenzene was replaced with an equimolar amount of bromobenzene in Example 1, and 3-trifluoromethylpropylamine was replaced with an equimolar amount of n-butylamine in Example 1. The other steps were the same as in Example 1, and a pale yellow oily substance with the following structural formula was obtained with a yield of 73%.

[0093]

[0094] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.43(d,J=8.5Hz,2H),6.61(d,J=8.5Hz,2H),3.98(br,1H),3.26(t,J=7.0Hz,2H),2.30-2.12(m,2H),1.98-1.85(m,2H); 13 C NMR (100MHz, CDCl3) δ150.4, 126.9 (d, J = 276.2Hz), 126.6 (q, J = 3.7Hz), 125.12 (q, J = 270.3H z), 119.3 (q, J = 32.6Hz), 112.0, 42.3, 31.4 (q, J = 29.1Hz), 22.1 (q, J = 2.4Hz); HRMS (ESI) m / z C 11 H 12 NF6[M+H] + Theoretical value: 272.0868, measured value: 272.0864.

[0095] Example 20

[0096] In this embodiment, 4-trifluoromethylbromobenzene was replaced with an equimolar amount of bromobenzene in Example 1, and n-butylamine was replaced with an equimolar amount of cyclopropylamine in Example 1. The other steps were the same as in Example 1, and a pale yellow oily substance with the following structural formula was obtained with a yield of 89%.

[0097]

[0098] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.42(d,J=8.3Hz,2H),6.79(d,J=8.3Hz,2H),4.44(br,1H),2.46(s,1H),0.79(d,J=6.2Hz,2H),0.54(s,2H); 13 C NMR (100MHz, CDCl3) δ151.3, 126.6 (q, J = 3.7Hz), 126.1 (d, J = 276.2Hz), 119.3 (q, J = 32.7Hz), 112.5, 25.0, 7.7; 19 F NMR (376MHz, CDCl3) δ-60.96 (s, CF3); HRMS (ESI) m / zC 10 H 11 NF3[M+H] + Theoretical value: 202.0838, measured value: 202.0835.

[0099] Example 21

[0100] In this embodiment, 4-trifluoromethylbromobenzene was used to replace bromobenzene in Example 1, and 3,3-difluorocyclobutylamine was used to replace n-butylamine in Example 1. The other steps were the same as in Example 1, and a pale yellow oily substance with the following structural formula was obtained with a yield of 83%.

[0101]

[0102] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, DMSO) δ7.21 (d, J = 8.6 Hz, 2H), 6.46 (d, J = 8.6 Hz, 2H), 3.64 (br, 1H), 3.39 -3.28 (m, 1H), 3.00 - 2.76 (m, 2H), 2.41 - 2.19 (m, 2H); 13 C NMR(100MHz,DMSO)δ150.8 126.74(q,J=3.7Hz),125.2(q,J=270.1Hz),116.78(q,J=31.9Hz),112.3,42.5 9(dd,J=22.7,21.1Hz), 37.09(dd,J=16.8,7.3Hz), 37.09(dd,J=16.8,7.3Hz); 19 F NMR(376MHz, DMSO)δ-59.20(s),-81.05(tq,J=13.8,6.8Hz),-81.56(dp,J=20.7 ,6.8Hz),-93.64--93.93(m),-94.27(ttd,J=16.4,13.4,3.4Hz); HRMS(ESI)m / zC 11 H 11 NF5[M+H] + Theoretical value: 252.0806, measured value: 252.0803.

[0103] Example 22

[0104] In this embodiment, 4-trifluoromethylbromobenzene was used to replace bromobenzene in Example 1, and 3-fluoroazacyclobutane was used to replace n-butylamine in Example 1. The other steps were the same as in Example 1, and a pale yellow oily substance with the following structural formula was obtained with a yield of 79%.

[0105]

[0106] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1H NMR (400MHz, CDCl3) δ7.29 (d, J = 8.6 Hz, 2H), 6.47 (d, J = 8.6 Hz, 2H), 5.52-5.30 (m, 1H), 4.25-4.12 (m, 2H), 3.94 (m, 2H), 1.31 (s, 9H); 13 C NMR (100MHz, CDCl3) δ149.0, 141.0, 125.9, 111.7, 82.85 (d, J = 204.3Hz), 59.75 (d, J = 23.2Hz), 33.9, 31.5; HRMS (ESI) m / z C 13 H 19 NF[M+H] + Theoretical value: 208.1496, measured value: 208.1493.

[0107] Example 23

[0108] In this embodiment, 4-trifluoromethylbromobenzene was replaced with an equimolar amount of bromobenzene in Example 1, and 3-hydroxyazacyclobutane was replaced with an equimolar amount of n-butylamine in Example 1. The other steps were the same as in Example 1, and a pale yellow oily substance with the following structural formula was obtained with a yield of 79%.

[0109]

[0110] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.44(dd,J=8.0,4.6Hz,2H),6.44(dd,J=8.0,4.6Hz,2H),4.89-4.72(m,1H),4.28-4.13(m,2H),3.81-3.71(m,2H); 13 C NMR (100MHz, CDCl3) δ153.3, 126.4 (q, J = 3.4Hz), 124.4 (q, J = 270.2Hz), 119.27 (q, J = 32.2Hz), 111.1, 62.8, 61.5; HRMS (ESI) m / z C 10 H 11 NOF3[M+H] + Theoretical value: 218.0787, measured value: 218.0790.

[0111] Example 24

[0112] In this embodiment, 4-trifluoromethylbromobenzene was used to replace bromobenzene in Example 1, and isopropyl carbamate was used to replace n-butylamine in Example 1. Other steps were the same as in Example 1, and a pale yellow oily substance with the following structural formula was obtained with a yield of 79%.

[0113]

[0114] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.48(d,J=8.7Hz,2H),7.42(d,J=8.7Hz,2H),6.66(s,1H),4.96(dt,J=12.5,6.3Hz,1H),1.24(d,J=6. 3Hz, 6H); δ152.8,141.2,126.3(q,J=3.8Hz),125.2(q,J=64.3Hz).124.0(q,J=239.8Hz),1178.0,69.3,22.0; HRMS(ESI)m / z C 11 H 13 NF3O2[M+H] + Theoretical value: 248.0893, measured value: 248.0896.

[0115] Example 25

[0116] In this embodiment, 4-trifluoromethylbromobenzene was used to replace bromobenzene in Example 1, and 3,5-dimethylpyrazole was used to replace n-butylamine in Example 1. The other steps were the same as in Example 1, and a pale yellow oily substance with the following structural formula was obtained with a yield of 77%.

[0117]

[0118] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.45(dd,J=10.7,4.8Hz,2H),7.34(dd,J=11.1,4.6Hz,2H),5.98(d,J=6.5Hz,1H),2.30(d,J=5.7Hz,6H),1.35(d,J=7.1Hz,9H); 13 C NMR(100MHz, CDCl3)δ150.5,148.8,139.5,137.5,126.0,124.5,106.7,34.7,31.5,13.7,12.5; HRMS(ESI)m / z C 15 H 21 N2[M+H] + Theoretical value: 229.1699, measured value: 229.1695.

[0119] Example 26

[0120] In this embodiment, 4-trifluoromethylbromobenzene was used to replace bromobenzene in Example 1, and 4-methylaniline was used to replace n-butylamine in Example 1. The other steps were the same as in Example 1, and a pale yellow oily substance with the following structural formula was obtained with a yield of 80%.

[0121]

[0122] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.19(d,J=7.7Hz,2H),6.98(d,J=7.8Hz,2H),6.89(dd,J=7.5,2.4Hz,4H),5.45(br,1H),2.21(s,3H),1.23(s,9H); 13 CNMR(100MHz, CDCl3)δ143.6,141.3,141.0,130.4,129.9,126.2,118.3,117.3,34.2,31.6,20.8; HRMS(ESI)m / z C 17 H 22 N[M+H] + Theoretical value: 240.1747, measured value: 240.1750.

[0123] Example 27

[0124] In this embodiment, 4-trifluoromethylbromobenzene was replaced with an equimolar amount of bromobenzene in Example 1, and 4-oxotrifluoromethylaniline was replaced with an equimolar amount of n-butylamine in Example 1. The other steps were the same as in Example 1, and a pale yellow oily substance with the following structural formula was obtained with a yield of 79%.

[0125]

[0126] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.38-7.22(m,3H),7.18-7.05(m,2H),7.04-6.96(m,3H),1.32(d,J=2.8Hz,9H); 13 C NMR (100MHz, CDCl3) δ145.1, 142.9, 139.9, 126.4, 124.8 (t, J = 258.6Hz), 122.4, 119.3, 118.9, 117.5, 34.4, 31.6; 19 FNMR(376MHz,CDCl3)δ-58.33(s,OCF3).HRMS(ESI)m / zC 17 H 19NF3O[M+H] + Theoretical value: 310.1413, measured value: 310.1417.

[0127] Example 28

[0128] In this embodiment, equimolar 4-trifluoromethylbromobenzene was used to replace bromobenzene in Example 1, and 2-naphthylamine was used to replace n-butylamine in Example 1. The other steps were the same as in Example 1, and a pale yellow oily substance with the following structural formula was obtained with a yield of 81%.

[0129]

[0130] The nuclear magnetic resonance (NMR) spectral data of the obtained product are as follows: 1 H NMR (400MHz, CDCl3) δ7.70 (dd, J = 16.4, 8.3Hz, 2H), 7.54 (d, J = 7.9Hz, 2H), 7.33-7.23 (m, 6H), 7.03 (d, J = 8.7Hz, 1H), 1.41 (s, 9H); 13 C NMR (100MHz, CDCl3) δ150.4,141.3,134.1,130.6,128.7,128.1,128.0,126.4,126.2,124.6,122.2,120.1,118.2,34.8,31.6; HRMS (ESI) m / z C 20 H 22 N[M+H] + Theoretical value: 276.1747, measured value: 276.1743.

Claims

1. A method for photochemical iron-catalyzed synthesis of aromatic amine compounds, characterized in that: The aryl bromide shown in Formula I, the amine compound shown in Formula II, bipyridine, iron catalyst, and organic base were added to an organic solvent, heated in an argon atmosphere, and reacted under ultraviolet light with a wavelength of 360–430 nm. After the reaction was completed, the product was separated and purified to obtain the aryl amine compound shown in Formula III. In the formula, Ar represents any one of phenyl, thienyl, thiazolyl, pyridyl, pyrazolyl, pyrazinyl, quinolinyl, benzothienyl, benzofuranyl, dibenzothienyl, and quinoxalinyl, or a phenyl group containing at least one substituent from C1-C6 alkyl, trimethylsilyl, halogen, C1-C4 alkoxy, trifluoromethoxy, trifluoromethyl, and cyano; HNNu represents any one of n-butylamine, ethylamine, but-3-en-1-amine, 3-methoxypropylamine, 2-mercaptoethylamine, 1-aminobutanol, 2-fluoroethylamine, 3-trifluoromethylpropylamine, cyclopropylamine, 3,3-difluorocyclobutylamine, 3-fluoroazacyclobutane, 3-hydroxyazacyclobutane, isopropyl carbamate, 3,5-dimethylpyrazole, 4-methylaniline, 4-oxotrifluoromethylaniline, and 2-naphthylamine; The iron catalyst is any one of ferrous bromide, ferrous carbonate, ferrous acetate, and ferrous chloride. The organic base is any one of 1,8-diazabicycloundec-7-ene, tetramethylguanidine, 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene, and 1,2-dimethyl-1,4,5,6-tetrahydropyrimidine.

2. The method for photochemical iron-catalyzed synthesis of aromatic amine compounds according to claim 1, characterized in that: The amount of the amine compound used is 1.1 to 2 times the molar amount of the aryl bromide.

3. The method for photochemical iron-catalyzed synthesis of aromatic amine compounds according to claim 1, characterized in that: The amount of bipyridine used is 5% to 15% of the molar amount of aryl bromide.

4. The method for photochemical iron-catalyzed synthesis of aromatic amine compounds according to claim 1, characterized in that: The amount of the iron catalyst used is 5% to 15% of the molar amount of the aryl bromide.

5. The method for photochemical iron-catalyzed synthesis of aromatic amine 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 aryl bromide.

6. The method for photochemical iron-catalyzed synthesis of aromatic amine compounds according to claim 1, characterized in that: The organic solvent is any one or two of dimethyl sulfoxide, toluene, isopropanol, N,N-dimethylformamide, and N,N-dimethylacetamide.

7. The method for photochemical iron-catalyzed synthesis of aromatic amine compounds according to claim 1, characterized in that: The mixture was heated at 80–90 °C in an argon atmosphere and reacted under ultraviolet light with a wavelength of 360–430 nm for 24–36 hours.

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