Synthesis method of visible light induced copper catalyzed diarylamine compound

Abstract

The invention belongs to the technical field of chemical synthesis, and particularly relates to a visible light induced copper catalyzed diarylamine compound synthesis method. The synthesis method comprises the following steps: S1, mixing nitro-aromatic hydrocarbon with arylboronic acid, and then adding copper salt, a reducing agent and an organic solvent to obtain a mixture; s2, under the protection of inert gas, irradiating the mixture with blue light to obtain a product; s3, after the reaction is finished, separating and purifying a product to obtain a diarylamine compound; the reaction formula is as follows: # imgabs0 #, Ar is one of benzene, naphthalene, phenanthrene, pyrazine, pyridazine, benzofuran, benzothiazole, 1, 2-benzopyrone, indole, quinoline and isoquinoline, and Ar is one of benzene, naphthalene, phenanthrene, pyrazine, pyridazine, benzofuran, benzothiazole, 1, 2-benzopyrone, indole, quinoline and isoquinoline. R1 to R10 are selected from one or more of H, F, Cl, Br, I, NH2,-CN,-CHO,-Bpin, a C1-C10 alkyl group, a C2-C10 alkenyl group, a C3-C10 alkynyl group, a C1-C10 alkoxy group, a phenylacetylene group, a cyclopropane group, a halogenated alkyl group, a cyclohexenyl group, a benzaldehyde group, a tetraphenylethylene group, an ethyl acetate group and an isobutyramido group.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a method for synthesizing a diarylamine compound induced by visible light and catalyzed by copper. Background Art

[0002] Diarylamine compounds are important building blocks in organic synthesis and are widely used in medicine, military, materials, agriculture and other fields. At present, the synthesis methods of diarylamine compounds have been well developed in the past few decades, including the Chan-Lam reaction of Buchwald-Hartwig. The nitrogen-based raw materials of these methods are mainly primary aromatic amine compounds, and the reaction conditions are relatively harsh, including high temperature or the use of toxic palladium metal reagents. In view of the efficient and green diarylamine synthesis strategy, the CN coupling reaction of nitroaromatics and aromatic boronic acids using nitroaromatics as the starting material for CN bond construction and isopropanol as the reducing agent through visible light-induced copper catalysis has important application value. Summary of the invention

[0003] In view of the deficiencies in the prior art, the present invention provides a method for synthesizing a visible light-induced copper-catalyzed diarylamine compound.

[0004] The purpose of the present invention can be achieved by the following technical solutions:

[0005] A method for synthesizing a visible light-induced copper-catalyzed diarylamine compound, the method comprising the following steps:

[0006] S1, mixing nitroaromatic hydrocarbon and arylboric acid, and then adding copper salt, reducing agent and organic solvent to obtain a mixture;

[0007] S2, under the protection of inert gas, irradiate the mixture with blue light to obtain the product;

[0008] S3. After the reaction is completed, the product is separated and purified to obtain a diarylamine compound;

[0009] The reaction formula is:

[0010]

[0011] Ar is one of benzene, naphthalene, phenanthrene, pyrazine, pyridazine, benzofuran, benzothiazole, 1,2-benzopyrone, indole, quinoline, and isoquinoline;

[0012] The R 1 ~R 10One or more selected from H, F, Cl, Br, I, NH2, -CN, -CHO, -Bpin, C1-C10 alkyl, C2-C10 alkenyl, C3-C10 alkynyl, C1-C10 alkoxy, phenylethynyl, cyclopropanyl, haloalkyl, cyclohexenyl, benzaldehyde, tetraphenylethylene, ethyl acetate, isobutyramide.

[0013] Furthermore, in step S1, the molar ratio of nitroaromatic hydrocarbon, aromatic boronic acid, copper salt and isopropanol is 10:(11-20):(1-3):(20-100); the molar concentration of nitroaromatic hydrocarbon in the organic solvent is (0.1-0.5)M.

[0014] Furthermore, the aryl group is phenyl, thiophene, furan, pyrrole, pyrazole or pyridine substituted by one or more of H, F, Cl, Br, I, -CHO, C1-C10 alkoxy, C3-C10 alkoxycarbonyl, C2-C10 alkenyl, and phenyl.

[0015] Furthermore, the copper salt is selected from one of copper acetate, copper acetylacetonate, copper trifluoromethanesulfonate, hydrated copper tetrafluoroborate, tetraacetonitrile copper tetrafluoroborate, and tetraacetonitrile copper hexafluorophosphate.

[0016] Furthermore, the reducing agent is one of cyclohexanol, cyclopentanol, isopropanol and 2-butanol.

[0017] Furthermore, the organic solvent is selected from one or more of dichloromethane, dichloroethane, acetonitrile, methanol, ethanol, tetrahydrofuran, tert-butanol, ethylene glycol dimethyl ether, ethyl acetate, and 1,4-dioxane.

[0018] Furthermore, the reaction temperature in step S2 is 25°C-80°C.

[0019] Furthermore, the conditions for blue light irradiation in step S2 are: the wavelength of blue light is 395nm-400nm; and the irradiation time is 3-16 hours.

[0020] A diarylamine compound is prepared by the above-mentioned method for synthesizing a diarylamine compound induced by visible light and catalyzed by copper.

[0021] Furthermore, the structural formula of the diarylamine compound is:

[0022]

[0023] Ar is one of benzene, naphthalene, phenanthrene, pyrazine, pyridazine, benzofuran, benzothiazole, 1,2-benzopyrone, indole, quinoline, and isoquinoline;

[0024] The R 1 ~R 10One or more selected from H, F, Cl, Br, I, NH2, -CN, -CHO, -Bpin, C1-C10 alkyl, C2-C10 alkenyl, C3-C10 alkynyl, C1-C10 alkoxy, phenylethynyl, cyclopropanyl, haloalkyl, cyclohexenyl, benzaldehyde, tetraphenylethylene, ethyl acetate, isobutyramide.

[0025] Beneficial effects of the present invention: The present invention overcomes the defects of the traditional synthesis method and provides a synthesis method for preparing diarylamine compounds under simple, efficient, low-cost and environmentally friendly conditions. The method can achieve a reduction coupling reaction of nitroaromatic hydrocarbons and arylboronic acid under the action of a copper reagent under relatively neutral conditions without adding a ligand and simple illumination. The reaction can be completed under mild conditions and is compatible with almost all functional groups. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0027] Figure 1 Schematic diagram of the synthesis of the diarylamine compound of the present invention;

[0028] Figure 2 This is the NMR characterization image of the compound prepared in Example 2 of the present invention;

[0029] Figure 3 This is the NMR characterization image of the compound prepared in Example 1 of the present invention;

[0030] Figure 4 This is the NMR characterization image of the compound prepared in Example 3 of the present invention;

[0031] Figure 5 This is the NMR characterization diagram of the compound prepared in Example 6 of the present invention. DETAILED DESCRIPTION

[0032] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0033] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0034] Two types of alkyl aromatic amine selective synthesis implementation cases:

[0035]

[0036] This example takes the reaction of 4-bromonitrobenzene and p-tolueneboric acid as an example to examine the effects of copper salt and solvent on the reaction selectivity and the effect of light wavelength on the reaction yield.

[0037] Take a reaction tube, add 0.2mmol 4-bromonitrobenzene as an example, 1.5 equivalents of p-tolueneboric acid, 10mol% of copper catalyst, 10 equivalents of isopropanol, and 0.8mL (0.25M) of organic solvent, and react for 16h at room temperature in a nitrogen atmosphere under light. After the reaction is completed, spin dry, use petroleum ether / dichloromethane = 10 / 1-5 / 1 as eluent, and separate by silica gel column chromatography to calculate the yield.

[0038] By changing the copper salt, the type of reducing agent and the wavelength range of light, the CN coupling reaction conditions of nitroaromatics and p-methylphenylboronic acid were screened out, and the optimal conditions of the reaction were obtained, as shown in Table 1:

[0039] Table 1

[0040]

[0041]

[0042] The above results show that in the synthesis of diarylamines, tetraacetonitrile copper hexafluorophosphate [(CH 3 CN) 4 Cu + PF6 - ], isopropanol, tetrahydrofuran, 395nm~400nm are the optimal reaction conditions

[0043]

[0044] 1 H NMR (400 MHz, CDCl 3): δ7.32(d,J=8.8Hz,2H),7.11(d,J=8.0Hz,2H),6.99(d,J=8.0Hz,2H),6.87(d,J=8.8Hz,2H),5.58(br s,1H),2.32(s,3H).

[0045] 13 C NMR (100 MHz, CDCl 3 ): δ143.38,139.73,132.22,131.80,130.10,119.55,118.24,111.94,20.85.

[0046] HRMS(ESI + ):m / z calcd for C 13 H 12 BrN[M+H] + :262.02259,Found:262.02225.

[0047] Example 1: Investigation of the adaptability of the method of the present invention to the synthesis of different diarylamines

[0048] General method for the synthesis of diarylamines: take a reaction tube, add 0.2mmol nitroarene substrate, 1.5 equivalents of aromatic boronic acid, 10mol% of tetraacetonitrile copper hexafluorophosphate catalyst, 10 equivalents of isopropanol, and 0.8mL (0.25M) of tetrahydrofuran solvent, and react for 16h at 55°C in a nitrogen atmosphere under light. After the reaction is completed, spin dry, separate by silica gel column chromatography using an eluent of petroleum ether / dichloromethane in a ratio of 10 / 1-5 / 1, and calculate the yield.

[0049] Embodiment 1:

[0050]

[0051] The synthesis method refers to the general method for the synthesis of diarylamines: 1,2,3-trichloronitrobenzene (45 mg, 0.2 mmol), phenylboric acid (37 mg, 0.3 mmol), tetraacetonitrile copper hexafluorophosphate (7.4 mg, 10% mol), isopropanol (75 μL, 2 mmol), PE / DCM as eluent, and a yellow solid with an isolated yield of 70% was obtained.

[0052] 1 H NMR (400 MHz, CDCl 3 ): δ7.38–7.31(m,2H),7.12–7.05(m,3H),7.01(s,2H),5.71(br s,1H).

[0053] 13 C NMR (100 MHz, CDCl 3 ): δ143.46,140.77,134.63,129.84,123.53,121.56,120.33,116.21.

[0054] HRMS(ESI + ):m / z calcd for C 12 H 8 Cl 3 N[M+H] + :271.9795,Found:271.9790.

[0055] Embodiment 2:

[0056]

[0057] The synthesis method refers to the general method for the synthesis of diarylamines: tert-butyl 5-nitro-1H-indole-1-carboxylate (53 mg, 0.2 mmol), phenylboric acid (37 mg, 0.3 mmol), tetraacetonitrile copper hexafluorophosphate (7.4 mg, 10% mol), isopropanol (75 μL, 2 mmol), PE / DCM as eluent, and a colorless droplet with an isolated yield of 72% was obtained.

[0058] 1 H NMR (400 MHz, CDCl 3 ): δ8.04(d,J=8.9Hz,1H),7.57(d,J=3.7Hz,1H),7.31(d,J=2.4Hz,1H),7.26–7.22(m,2H),7.08( dd,J=8.9,2.4Hz,1H),7.04–6.98(m,2H),6.90–6.85(m,1H),6.48(dd,J=3.7,0.8Hz,1H),5.68(br s,1H),1.68(s,9H).

[0059] 13 C NMR (100 MHz, CDCl 3 ): δ149.86,144.95,138.17,131.63,131.21,129.46,126.68,120.12,118.13,116.49,115.96,111.41,107.18,83.69,28.36.

[0060] HRMS(ESI + ):m / z calcd for C 19 H 20 O2 N 2 [M+H] + :309.1598,Found:309.1593.

[0061] Embodiment 3:

[0062]

[0063] The synthesis method refers to the general method for the synthesis of diarylamines: 5-nitrobenzofuran-2-carboxylic acid ethyl ester (47 mg, 0.2 mmol), phenylboric acid (37 mg, 0.3 mmol), tetraacetonitrile copper hexafluorophosphate (7.4 mg, 10% mol), isopropanol (75 μL, 2 mmol), PE / DCM as eluent, and a light yellow solid with an isolated yield of 74% was obtained.

[0064] 1 H NMR (400 MHz, CDCl 3 ): δ7.49(d,J=8.9,1H),7.43(d,J=1.0Hz,1H),7.37(dd,J=2.3,0.6Hz,1H),7.29–7.24(m, 2H),7.19(dd,J=8.9,2.3Hz,1H),7.04–7.01(m,2H),6.92(tt,J=7.4,1.0Hz,1H),5.71(br s, 1H), 4.44 (d, J = 7.1Hz, 2H), 1.43 (t, J = 7.1Hz, 3H).

[0065] 13 C NMR (100 MHz, CDCl 3 ): δ159.70,151.87,146.44,144.22,139.51,129.55,127.94,121.53,120.83,117.07,113.70,113.09,111.42,61.63,14.48.

[0066] HRMS(ESI + ):m / z calcd for C 17 H 15 O 3 N[M+H] + :282.1125,Found:282.1122..

[0067] Embodiment 4:

[0068]

[0069] The synthesis method refers to the general method for the synthesis of diarylamines: 5-bromo-2-nitropyridine (41 mg, 0.2 mmol), phenylboronic acid (37 mg, 0.3 mmol), tetraacetonitrile copper hexafluorophosphate (7.4 mg, 10% mol), isopropanol (75 μL, 2 mmol), PE / DCM as eluent, and a white solid with an isolated yield of 78% was obtained.

[0070] 1 H NMR (400 MHz, CDCl 3 ): δ8.15(d,J=2.5Hz,1H),7.47(dd,J=8.8,2.5Hz,1H),7.30–7.21(m,4H)7.08–6.94(m,2H),6.71(d,J=8.8Hz,1H).

[0071] 13 C NMR (100 MHz, CDCl 3 ): δ154.97,149.04,140.18,129.52,123.51,120.80,109.63,109.14.

[0072] HRMS(ESI + ):m / z calcd for C 11 H 9 Bn 2 [M+H] + :249.0022,Found:.249.0018.

[0073] Embodiment 5:

[0074]

[0075] The synthesis method refers to the general method for the synthesis of diarylamines: p-bromonitrobenzene (41 mg, 0.2 mmol), 2-naphthaleneboronic acid (52 mg, 0.3 mmol), tetraacetonitrile copper hexafluorophosphate (7.4 mg, 10% mol), isopropanol (75 μL, 2 mmol), PE / DCM as eluent, and a colorless solid with an isolated yield of 90% was obtained.

[0076] 1 H NMR (400 MHz, CDCl 3 ): δ7.76(d,J=8.5Hz,2H),7.67(d,J=8.2Hz,1H),7.47–7.37(m,4H),7.34(t ,J=7.5Hz,1H),7.20(dd,J=8.8,2.3Hz,1H),7.03(d,J=8.8Hz,2H),5.83(br s,1H).

[0077] 13 C NMR (100 MHz, CDCl 3 ): δ142.35,140.29,134.63,132.41,129.58,129.47,127.81,126.70,126.69,123.99,120.25,119.63,113.22,112.57

[0078] HRMS(ESI + ):m / z calcd for C 16 H 12 BrN[M+H] + 298.0226,Found:298.0220.

[0079] Embodiment 6:

[0080]

[0081] The synthesis method refers to the general method for the synthesis of diarylamines: p-bromonitrobenzene (41 mg, 0.2 mmol), dibenzofuran-1-boric acid (64 mg, 0.3 mmol), tetraacetonitrile copper hexafluorophosphate (7.4 mg, 10% mol), isopropanol (75 μL, 2 mmol), PE / DCM as eluent, and a brown solid with an isolated yield of 74% was obtained.

[0082] 1 H NMR (400 MHz, CDCl 3 ): δ7.56(dt,J=7.8,1.0Hz,1H),7.48(dt,J=8.3,0.8Hz,1H),7.34(ddd,J=8.3,7.3,1.3Hz,1H),7.30–7.25( m,2H),7.19(dd,J=3.2,0.8Hz,1H),7.18–7.17(m,2H),7.01(d,J=7.8Hz,1H),6.81(d,J=8.8Hz,2H),5.95(br s,1H).

[0083] 13 C NMR (100 MHz, CDCl 3 ): δ157.52,155.91,142.58,137.97,132.46,128.02,126.70,123.38,122.90,122.23,119.29,116.53,113.45,113.28,111.53,106.33.

[0084] HRMS(ESI + ):m / z calcd for C 18 H 12 BrNO[M+H] + 338.0175,Found:338.0169.

[0085] Embodiment 7:

[0086]

[0087] The synthesis method refers to the general method for the synthesis of diarylamines: p-bromonitrobenzene (41 mg, 0.2 mmol), (3-bromo-5-tert-butylphenyl)boric acid (76 mg, 0.3 mmol), tetraacetonitrile copper hexafluorophosphate (7.4 mg, 10% mol), isopropanol (75 μL, 2 mmol), PE / DCM as eluent, and a yellow liquid with an isolated yield of 88% was obtained.

[0088] 1 H NMR (400 MHz, CDCl 3 ): δ7.37(d,J=8.7Hz,2H),7.09(dd,J=1.9,1.8Hz,1H),7.03(t,J=1.9,1.8Hz,1H),6.98–6.88(m,3H),5.67(br s,1H),1.28(s,9H).

[0089] 13 C NMR (100 MHz, CDCl 3 ): δ154.78,143.83,141.75,132.49,123.12,121.92,119.88,117.62,114.19,113.65,35.08,31.26.

[0090] HRMS(ESI + ):m / z calcd for C 16 H 17 Br 2 N[M+H] + 381.9801,Found:381.9794.

[0091] In the description of this specification, the description with reference to the terms "one embodiment", "example", "specific example", etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0092] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments, and the above embodiments and descriptions are only for explaining the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention may have various changes and improvements, and these changes and improvements all fall within the scope of the present invention to be protected.

Claims

1. A method for synthesizing a visible light-induced copper-catalyzed diarylamine compound, characterized in that: The synthesis method comprises the following steps: S1, mixing nitroaromatic hydrocarbon and arylboric acid, and then adding copper salt, reducing agent and organic solvent to obtain a mixture; S2, under the protection of inert gas, irradiate the mixture with blue light to obtain the product; S3. After the reaction is completed, the product is separated and purified to obtain a diarylamine compound; The reaction formula is: Ar is one of benzene, naphthalene, phenanthrene, pyrazine, pyridazine, benzofuran, benzothiazole, 1,2-benzopyrone, indole, quinoline, and isoquinoline; The R 1 ~R 10 One or more selected from H, F, Cl, Br, I, NH2, -CN, -CHO, -Bpin, C1-C10 alkyl, C2-C10 alkenyl, C3-C10 alkynyl, C1-C10 alkoxy, phenylethynyl, cyclopropanyl, haloalkyl, cyclohexenyl, benzaldehyde, tetraphenylethylene, ethyl acetate, isobutyramide.

2. The method for synthesizing a visible light-induced copper-catalyzed diarylamine compound according to claim 1, characterized in that: In step S1, the molar ratio of nitroaromatic hydrocarbon, aromatic boronic acid, copper salt and isopropanol is 10:(11-20):(1-3):(20-100); the molar concentration of nitroaromatic hydrocarbon in the organic solvent is (0.1-0.5)M.

3. The method for synthesizing a visible light-induced copper-catalyzed diarylamine compound according to claim 1, characterized in that: The aryl group is phenyl, thiophene, furan, pyrrole, pyrazole or pyridine substituted by one or more of H, F, Cl, Br, I, -CHO, C1-C10 alkoxy, C3-C10 alkoxycarbonyl, C2-C10 alkenyl, and phenyl.

4. The method for synthesizing a visible light-induced copper-catalyzed diarylamine compound according to claim 1, characterized in that: The copper salt is selected from one of copper acetate, copper acetylacetonate, copper trifluoromethanesulfonate, hydrated copper tetrafluoroborate, tetraacetonitrile copper tetrafluoroborate, and tetraacetonitrile copper hexafluorophosphate.

5. The method for synthesizing a visible light-induced copper-catalyzed diarylamine compound according to claim 1, characterized in that: The reducing agent is one of cyclohexanol, cyclopentanol, isopropanol and 2-butanol.

6. The method for synthesizing a visible light-induced copper-catalyzed diarylamine compound according to claim 1, characterized in that: The organic solvent is selected from one or more of dichloromethane, dichloroethane, acetonitrile, methanol, ethanol, tetrahydrofuran, tert-butanol, ethylene glycol dimethyl ether, ethyl acetate, and 1,4-dioxane.

7. The method for synthesizing a visible light-induced copper-catalyzed diarylamine compound according to claim 1, characterized in that: The reaction temperature in step S2 is 25°C-80°C.

8. The method for synthesizing a visible light-induced copper-catalyzed diarylamine compound according to claim 1, characterized in that: The conditions for blue light irradiation in step S2 are: the wavelength of blue light is 395nm-400nm; and the irradiation time is 3-16 hours.

9. A diarylamine compound, characterized in that The diarylamine compound is prepared by the synthesis method of a visible light induced copper-catalyzed diarylamine compound according to any one of claims 1 to 8.

10. A diarylamine compound according to claim 9, characterized in that: The structural formula of the diarylamine compound is: Ar is one of benzene, naphthalene, phenanthrene, pyrazine, pyridazine, benzofuran, benzothiazole, 1,2-benzopyrone, indole, quinoline, and isoquinoline; The R 1 ~R 10 One or more selected from H, F, Cl, Br, I, NH2, -CN, -CHO, -Bpin, C1-C10 alkyl, C2-C10 alkenyl, C3-C10 alkynyl, C1-C10 alkoxy, phenylethynyl, cyclopropanyl, haloalkyl, cyclohexenyl, benzaldehyde, tetraphenylethylene, ethyl acetate, isobutyramide.

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