Light-induced iridium metal catalytic synthesis method of N-aryl amide

Abstract

The invention relates to a synthesis method of an N-aryl amide compound. The invention relates to a photo-induced metal catalytic synthesis method of N-aryl amide, which is characterized in that aryl amide and aryl halide are taken as raw materials, and N-aryl amide is synthesized through single electron transfer under the illumination condition: the aryl amide, the aryl halide, an iridium metal complex catalyst and alkali are taken and added into a reaction container; adding a solvent into a reaction container, fully dissolving, and then carrying out a synthetic reaction under the conditions of illumination and nitrogen protection; and after the reaction is finished, taking out a final product, and carrying out column chromatography separation to obtain the N-aryl amide. According to the N-aryl amide photoinduced metal catalytic synthesis method, the difficulty of coupling of chlorobenzene, fluorobenzene and aryl amide is reduced, the problem that chlorobenzene and fluorobenzene are difficult to react due to high bond energy is solved, the reaction of electron transfer from weak electron donor amide to fluorobenzene and chlorobenzene is realized, and the reaction yield is improved.

Description

Technical Field

[0001] The invention relates to a method for synthesizing an N-aryl amide compound, in particular to a method for synthesizing N-aryl amide by light-induced iridium metal catalysis. Background Art

[0002] N-arylamide compounds are a wide range of important compounds and important intermediates in organic synthesis reactions. Their application areas involve medicine, industry, and synthesis research. N-arylamide compounds are mainly obtained by coupling aryl halides with nucleophilic reagents arylamide, but in the amide functional group, due to the electron-withdrawing conjugation effect of the carbonyl group on the nitrogen atom, the electron cloud density on the nitrogen is reduced, which weakens the nucleophilic ability of the amide, and the coupling conditions between amide and halobenzene are relatively harsh. Even the synthesis strategy of Ullmann-type nitrogen arylation, which is usually catalyzed by copper, requires high temperature heating, strong base and other harsh reaction conditions. Moreover, the electron cloud density on the copper catalyst is relatively low compared to catalysts such as palladium and nickel, and it is difficult to oxidize to form trivalent copper intermediates. For fluorobenzene and chlorobenzene with higher carbon-halogen bond energy, their aryl halides are more difficult to be directly attacked by nucleophiles. In existing reports, palladium catalysts can catalyze the coupling of chlorobenzene and amide under heating conditions, but no reports have been seen under photocatalytic conditions.

[0003] As an organic complex, transition metal complexes have been widely used in the field of biochemistry, such as the synthesis of chiral drug molecules and natural products. Among them, transition metal iridium complexes have the characteristics of long luminescence lifetime, high quantum yield and adjustable luminescence wavelength, and have gradually developed in photosynthetic chemistry. [2,2'-bipyridine]-[bis(2-phenylpyridine)]iridium hexafluorophosphate is a kind of iridium metal complex, which is often used as a catalyst in organic chemical reactions. Due to its unique photoelectric properties, this compound can also be used as an excitant in photochemical reactions. The molecular structure contains multiple aromatic rings and has unique optical properties. Due to the high catalytic activity of Ir(ppy)2(dtbpy)PF6, it has been used in various organic reaction processes in recent years, such as molecular amination, intramolecular cyclization and molecular arylation. The applicant designed to introduce Ir(ppy)2(dtbpy)PF6 as a photocatalyst into the coupling reaction of fluorobenzene, chlorobenzene and aromatic amides, and found that this strategy has high practicality. Compared with the copper-catalyzed Ullmann-type nitrogen arylation synthesis strategy, this method can greatly improve the energy efficiency of the reaction and thus increase the yield of the reaction.

[0004] After consulting the literature, there are few applications of Ir(ppy)2(dtbpy)PF6 in the synthesis of N-aryl amides, and there are no reports on the photoinduced iridium metal catalytic synthesis of N-aryl amides. Therefore, exploring a synthetic strategy for the efficient catalytic coupling of fluorobenzene, chlorobenzene and nucleophilic reagents, and exploring a method for synthesizing N-aryl amide compounds by the nucleophilic reaction of fluorobenzene and chlorobenzene under photocatalysis is of great significance for the application of such compounds in industrial production. Summary of the invention

[0005] The present invention aims to solve the problems of the prior art and proposes a method for synthesizing N-arylamide by light-induced iridium metal catalysis. The method reduces the difficulty of nucleophilic substitution of chlorobenzene and fluorobenzene, solves the problem that chlorobenzene and fluorobenzene are difficult to undergo nucleophilic substitution reaction, and enables the method to generate N-arylamide compounds with high added value with high selectivity.

[0006] The technical solution adopted by the present invention is:

[0007] A method for synthesizing N-aryl amide by light-induced metal catalysis, using aryl amide and aryl halide as raw materials, synthesizing N-aryl amide by single electron transfer under light conditions, the process comprising:

[0008] Step S1, taking aryl amide, aryl halide, catalyst and base, and adding them into a reaction container; the catalyst is an iridium metal complex, and the base is used to promote the reaction to proceed in the forward direction;

[0009] Step S2, adding a solvent into a reaction container, fully dissolving, and then performing a synthesis reaction under light and nitrogen protection conditions; the reaction equation is:

[0010]

[0011] Wherein: R is hydrogen, an electron-donating group or an electron-withdrawing group; Ar is an aromatic group; X is a F or Cl atom;

[0012] Step S3, after the reaction is completed, the final product is taken out and separated by column chromatography to obtain N-benzamide.

[0013] In the step S1, the molar ratio of the aryl amide to the aryl halide is 1:1-3.

[0014] The amount of the iridium metal complex catalyst added is 7-13 mol %, preferably 10 mol %, of the aryl halide.

[0015] The light-induced iridium metal catalytic synthesis method of N-aryl amides uses red light, blue light, green light, incandescent light, xenon lamp or 254nm ultraviolet light for illumination, the reaction temperature is controlled at 55-65°C, and the reaction time is 60-72h.

[0016] The iridium metal complex is Ir(ppy)2(acac), Ir(ppz)2(acac), Ir(ppz)(ppy)(acac), Ir(ppy)2(dtbpy)PF6 or Ir(dF-CF3-ppy)2(dtbpy)PF6.

[0017] The structural formula of Ir(ppy)2(acac) is

[0018]

[0019] The structural formula of Ir(ppz)2(acac) is

[0020]

[0021] The structural formula of Ir(ppz)(ppy)(acac) is

[0022]

[0023] The structural formula of Ir(ppy)2(dtbpy)PF6 is

[0024]

[0025] The structural formula of Ir(dF-CF3-ppy)2(dtbpy)PF6 is

[0026]

[0027] The base is Cs2CO3, t-BuOLi, t-BuOK, NaOH, K3PO4 or K2CO3.

[0028] The solvent is dimethyl sulfoxide (DMSO), acetonitrile, tetrahydrofuran or N,N-dimethylformamide.

[0029] The light-induced iridium metal catalytic synthesis method of N-aryl amides uses Ir(ppy)2(dtbpy)PF6 as the iridium metal complex, t-BuOLi as the base, and dimethyl sulfoxide as the solvent; LED blue light is used for illumination, the reaction temperature is controlled at 60°C, and the reaction time is 72h. The reaction equation is:

[0030]

[0031] The invention discloses a method for synthesizing N-aryl amides by light-induced iridium metal catalysis, wherein the electron-donating group R is methyl, methoxy, ethyl, ethoxy, isopropyl, tert-butyl, hydroxyl, methylthio, alkoxy or amino, and the electron-withdrawing group is nitro, cyano, trifluoromethyl, chlorine, fluorine, acyl, ester or sulfonyl.

[0032] Beneficial effects of the invention:

[0033] 1. The present invention reduces the energy barrier of fluorobenzene and chlorobenzene with aryl amide in the coupling reaction through the photoinduced iridium metal catalysis of N-aryl amide synthesis, successfully realizes the coupling of aryl halide with aryl amide, and overcomes the problem of low reactivity of fluorobenzene and chlorobenzene in the prior art.

[0034] 2. Compared with traditional high-temperature heating or strong alkaline conditions, the present invention adopts photocatalytic reaction to carry out the reaction under milder conditions, which not only reduces energy consumption, but also increases the yield of N-aryl amide compounds, achieving a more environmentally friendly and efficient synthesis method.

[0035] 3. The present invention utilizes iridium metal complex as a catalyst and combines the advantages of photocatalysis, which not only enhances the selectivity of the reaction, but also effectively avoids the occurrence of side reactions, so that N-aryl amide compounds can be efficiently generated, embodies obvious production cost advantages, and has significant potential for industrial application. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of N-(4-methoxyphenyl)benzanilide in Example 1 of the present invention.

[0037] Figure 2 The carbon NMR spectrum of N-(4-methoxyphenyl)benzanilide in Example 1 of the present invention.

[0038] Figure 3 It is the hydrogen nuclear magnetic resonance spectrum of benzanilide in Example 2 of the present invention.

[0039] Figure 4 It is the carbon NMR spectrum of benzanilide in Example 2 of the present invention.

[0040] Figure 5 The following is the hydrogen nuclear magnetic resonance spectrum of p-methylacetanilide in Example 3 of the present invention.

[0041] Figure 6 The carbon-1NMR spectrum of p-methylacetanilide in Example 3 of the present invention is shown.

[0042] Figure 7 This is the hydrogen nuclear magnetic resonance spectrum of N-(4-methoxyphenyl)acetanilide in Example 14 of the present invention.

[0043] Figure 8 This is the carbon nuclear magnetic resonance spectrum of N-(4-methoxyphenyl)acetanilide in Example 14 of the present invention. DETAILED DESCRIPTION

[0044] In order to make the technical concept and advantages of the invention more clearly understood, the technical solution of the invention is further described in detail below in conjunction with the accompanying drawings. It should be understood that the following embodiments are only used to explain and illustrate the preferred implementation of the invention and should not constitute a limitation on the scope of protection of the patent claim of the invention.

[0045] The raw materials, solvents, etc. described in the experiment were commercially available chemical raw materials and chemical reagents.

[0046] Example 1 Preparation of N-(4-methoxyphenyl)benzanilide

[0047] Take a quartz reaction tube, add a magnetic stirrer, then add 0.3mmol of benzamide, 10mol% of Ir(ppy)2(dtbpy)PF6, 0.6mmol of 4-methoxyfluorobenzene and 0.6mmol of t-BuOLi (lithium tert-butoxide), and then add 6mL of dimethyl sulfoxide as solvent. Freeze the reaction solution with liquid nitrogen, use an oil pump to drain the gas in the reaction tube and balloon, and fill with nitrogen. After thawing, carry out magnetic stirring at room temperature under visible light irradiation for 72h, and the reaction is monitored by TLC. Finally, the final product N-(4-methoxyphenyl)benzanilide is separated by column chromatography with a yield of 62%.

[0048] Figure 1 : is the H NMR spectrum of N-(4-methoxyphenyl)benzanilide in this example. The H NMR spectrum of N-(4-methoxyphenyl)benzanilide is characterized as follows: 1 H NMR (400MHz, DMSO-d6) δ10.1(s,1H),7.9(dd,J=6.1,3.9Hz,2H),7.8-7.4(m,5H),6.9(dd,J=9.0,2.3Hz,2H),3.8(d,J=2.2Hz,3H).

[0049] Figure 2 : is the carbon NMR spectrum of N-(4-methoxyphenyl)benzanilide in this example. The carbon NMR spectrum of N-(4-methoxyphenyl)benzanilide is characterized as follows: 13 C NMR (101MHz, Chloroform-d) δ165.7,156.6,135.0,131.7,131.0,128.8,127.0,122.1,114.3,58.5,55.5,18.5.

[0050] The reaction equation is as follows:

[0051]

[0052] The illumination conditions can be red light, blue light, green light, incandescent light, xenon lamp or 254nm ultraviolet light. In this embodiment, LED blue light is preferably used. The effects of different catalysts, illumination conditions, solvents, base selection and raw material ratio on the synthesis reaction are shown in Example 16 Reaction Condition Optimization Experiment.

[0053] Example 2 Preparation of Benzanilide

[0054] Take a quartz reaction tube, add a magnetic stirrer, then add 0.3mmol of benzamide, 10mol% of Ir(ppy)2(dtbpy)PF6, 0.6mmol of fluorobenzene and 0.6mmol of t-BuOLi, and then add 6mL of dimethyl sulfoxide as solvent. Freeze the reaction solution with liquid nitrogen, use an oil pump to drain the gas in the reaction tube and balloon, and fill with nitrogen. After thawing, react at room temperature for 72h under visible light irradiation with magnetic stirring, and the reaction is monitored by TLC. Finally, the final product, benzanilide, is separated by column chromatography with a yield of 87%.

[0055] Figure 3 The H NMR spectrum of benzanilide in this example is shown. The H NMR spectrum of benzanilide is characterized as follows: 1 H NMR (400MHz, DMSO-d6) δ10.2 (s, 1H), 8.0-7.9 (m, 2H), 7.8-7.7 (m, 2H), 7.6-7.5 (m, 3H), 7.4 (t, J = 7.9Hz, 2H), 7.1 (t, J = 7.5Hz, 1H).

[0056] Figure 4 Benzanilide is characterized by the following carbon-NMR spectra: 13 C NMR (101MHz, DMSO-d6) δ166.0,139.7,135.5,132.0,129.1,128.8,128.1,124.1,120.8.

[0057] The reaction equation is as follows:

[0058]

[0059] Example 3 Preparation of p-methylacetanilide

[0060] Take a quartz reaction tube, add a magnetic stirrer, then add 0.3mmol of acetamide, 10mol% of Ir(ppy)2(dtbpy)PF6, 0.6mmol of 4-methylfluorobenzene and 0.6mmol of t-BuOLi, and then add 6mL of dimethyl sulfoxide as solvent. Liquid nitrogen freezes the reaction solution, and the gas in the reaction tube and balloon is drained with an oil pump and filled with nitrogen. After thawing, magnetic stirring is carried out at room temperature under visible light irradiation for 72h, and the reaction is monitored by TLC. Finally, the final product p-methylacetanilide is separated by column chromatography with a yield of 65%.

[0061] Figure 5 The nuclear magnetic resonance hydrogen spectrum of p-methylacetanilide in this embodiment is shown. The nuclear magnetic resonance hydrogen spectrum of p-methoxyacetanilide is characterized as follows: 1 H NMR (400MHz, DMSO-d6) δ9.8 (s, 1H), 7.5-7.4 (m, 2H), 7.1 (d, J = 8.1Hz, 2H), 2.2 (s, 3H), 2.0 (s, 3H).

[0062] Figure 6 Shown is the carbon NMR spectrum of p-methylacetanilide in this embodiment. The carbon NMR spectrum of p-methoxyacetanilide is characterized as follows: 13 C NMR (101MHz, DMSO-d6) δ168.5,137.3,132.3,129.5,119.5,24.4,20.9.

[0063] The reaction equation is as follows:

[0064]

[0065] Example 4 Preparation of N-(4-methylphenyl)benzanilide

[0066] Take a quartz reaction tube, add a magnetic stirrer, then add 0.3mmol of acetamide, 10mol% of Ir(ppy)2(dtbpy)PF6, 0.6mmol of 4-methylfluorobenzene and 0.6mmol of t-BuOLi, and then add 6mL of dimethyl sulfoxide as solvent. Freeze the reaction solution with liquid nitrogen, use an oil pump to drain the gas in the reaction tube and balloon, and fill with nitrogen. After thawing, carry out magnetic stirring at room temperature under visible light irradiation for 72h, and the reaction is monitored by TLC. Finally, the final product N-(4-methylphenyl)benzanilide is separated by column chromatography with a yield of 63%.

[0067] The nuclear magnetic resonance hydrogen spectrum of N-(4-methylphenyl)benzanilide is characterized as follows: 1H NMR (400MHz, d6-DMSO) δ10.64(s,1H),8.09-7.90(m,4H),7.89-7.72(m,2H),7.68-7.60(m,1H),7.59-7.49(m,2H).

[0068] The carbon NMR spectrum of N-(4-methylphenyl)benzanilide is characterized as follows: 13 C NMR (100MHz, d6-DMSO) δ166.2,143.5,134.4,133.1,132.0,128.5,127.8,120.2,119.1,105.3.

[0069] The reaction equation is as follows:

[0070]

[0071] Example 5 Preparation of N-(4-trifluoromethylphenyl)benzanilide

[0072] Take a quartz reaction tube, add a magnetic stirrer, then add 0.3mmol of benzamide, 10mol% of Ir(ppy)2(dtbpy)PF6, 0.6mmol of 4-trifluoromethylfluorobenzene and 0.6mmol of t-BuOLi, and then add 6mL of dimethyl sulfoxide as solvent. Freeze the reaction solution with liquid nitrogen, use an oil pump to drain the gas in the reaction tube and balloon, and fill with nitrogen. After thawing, react at room temperature for 72h under visible light irradiation with magnetic stirring, and the reaction is monitored by TLC. Finally, the final product N-(4-trifluoromethylphenyl)benzanilide is separated by column chromatography with a yield of 57%.

[0073] The nuclear magnetic resonance hydrogen spectrum of N-(4-trifluoromethylphenyl)benzanilide is characterized as follows: 1 H NMR (400MHz, d6-DMSO) δ10.59(s,1H),8.12-7.88(m,4H),7.82-7.69(m,2H),7.67-7.45(m,3H).

[0074] The carbon NMR spectrum of N-(4-trifluoromethylphenyl)benzanilide is characterized as follows: 13 C NMR (100MHz, d6-DMSO) δ 166.5, 143.3, 135.0, 132.3, 128.8, 128.3, 126.3 (q, J = 4.8Hz), 124.2 (q, J = 31.8Hz), 124.9 (q, J = 271Hz), 120.6.

[0075] The reaction equation is as follows:

[0076]

[0077] Example 6 Preparation of N-phenyl-4-methylbenzamide

[0078] Take a quartz reaction tube, add a magnetic stirrer, then add 0.3mmol of 4-methylbenzamide, 10mol% of Ir(ppy)2(dtbpy)PF6, 0.6mmol of fluorobenzene and 0.6mmol of t-BuOLi, and then add 6mL of dimethyl sulfoxide as solvent. Freeze the reaction solution with liquid nitrogen, use an oil pump to drain the gas in the reaction tube and balloon, and fill with nitrogen. After thawing, react at room temperature for 72h under visible light irradiation with magnetic stirring, and the reaction is monitored by TLC. Finally, the final product N-phenyl-4-methylbenzamide is separated by column chromatography with a yield of 66%.

[0079] The nuclear magnetic resonance hydrogen spectrum of N-phenyl-4-methylbenzamide is characterized as follows: 1 H NMR (400MHz, d6-DMSO) δ 10.14 (s, 1H), 7.87 (d, J = 8.0Hz, 2H), 7.77 (d, J = 7.4Hz, 2H), 7.40-7.31 (m, 4H), 7.09 (t, J = 7.4Hz, 1H), 2.39 (s, 3H).

[0080] The carbon NMR spectrum of N-phenyl-4-methylbenzamide is characterized as follows: 13 C NMR (100MHz, d6-DMSO) δ165.8,142.0,139.7,132.6,129.4,129.0,128.1,124.0,120.8,21.5.

[0081] The reaction equation is as follows:

[0082]

[0083] Example 7 Preparation of N-phenyl-3-methylbenzamide

[0084] Take a quartz reaction tube, add a magnetic stirrer, then add 0.3mmol of 3-methylbenzamide, 10mol% of Ir(ppy)2(dtbpy)PF6, 0.6mmol of fluorobenzene and 0.6mmol of t-BuOLi, and then add 6mL of dimethyl sulfoxide as solvent. Freeze the reaction solution with liquid nitrogen, use an oil pump to drain the gas in the reaction tube and balloon, and fill with nitrogen. After thawing, carry out magnetic stirring and room temperature reaction for 72h under visible light irradiation, and the reaction is monitored by TLC. Finally, the final product N-phenyl-3-methylbenzamide is separated by column chromatography with a yield of 71%.

[0085] The nuclear magnetic resonance hydrogen spectrum of N-phenyl-3-methylbenzamide is characterized as follows: 1 H NMR (400MHz, DMSO-d6) δ10.19(s,1H),7.82-7.65(m,4H),7.48-7.27(m,4H),7.16-7.02(m,1H),2.40(s,3H).

[0086] The carbon NMR spectrum of N-phenyl-3-methylbenzamide is characterized as follows: 13 C NMR (100MHz, DMSO-d6) δ165.6,139.2,137.7,135.0,132.1,128.6,128.3,128.1,124.8,123.6,120.3,21.0.

[0087] The reaction equation is as follows:

[0088]

[0089] Example 8 Preparation of N-phenyl-4-tert-butylbenzamide

[0090] Take a quartz reaction tube, add a magnetic stirrer, then add 0.3mmol of 4-tert-butylbenzamide, 10mol% of Ir(ppy)2(dtbpy)PF6, 0.6mmol of fluorobenzene and 0.6mmol of t-BuOLi, and then add 6mL of dimethyl sulfoxide as solvent. Freeze the reaction solution with liquid nitrogen, use an oil pump to drain the gas in the reaction tube and balloon, and fill with nitrogen. After thawing, carry out magnetic stirring and room temperature reaction for 72h under visible light irradiation, and the reaction is monitored by TLC. Finally, the final product N-phenyl-4-tert-butylbenzamide is separated by column chromatography with a yield of 73%.

[0091] The nuclear magnetic resonance hydrogen spectrum of N-phenyl-4-tert-butylbenzamide is characterized as follows: 1 H NMR (400MHz, d6-DMSO) δ10.16 (s, 1H), 7.93-7.85 (m, 2H), 7.78 (dd, J = 8.4, 1.3 Hz,2H),7.58-7.50(m,2H),7.39-7.29(m,2H),7.14-7.04(m,1H),1.32(s,9H).

[0092] The carbon NMR spectrum of N-phenyl-4-tert-butylbenzamide is characterized as follows: 13C NMR (100MHz, d6-DMSO) δ166.0,154.8,139.7,132.8,129.0,128.0,125.6,124.0,120.7,35.1,31.4.

[0093] The reaction equation is as follows:

[0094]

[0095] Example 9 Preparation of N-phenyl-4-methoxybenzamide

[0096] Take a quartz reaction tube, add a magnetic stirrer, then add 0.3mmol of 4-methoxybenzamide, 10mol% of Ir(ppy)2(dtbpy)PF6, 0.6mmol of chlorobenzene and 0.6mmol of t-BuOLi, and then add 6mL of dimethyl sulfoxide as solvent. Freeze the reaction solution with liquid nitrogen, use an oil pump to drain the gas in the reaction tube and balloon, and fill with nitrogen. After thawing, react at room temperature for 72h under visible light irradiation with magnetic stirring, and the reaction is monitored by TLC. Finally, the final product N-phenyl-4-methoxybenzamide is separated by column chromatography with a yield of 65%.

[0097] The nuclear magnetic resonance hydrogen spectrum of N-phenyl-4-methoxybenzamide is characterized as follows: 1 H NMR (400MHz, d6-DMSO) δ10.07 (s, 1H), 8.14-7.88 (m, 2H), 7.82-7.63 (m, 2H), 7.34 (t, J = 7.9Hz, 2H), 7.13-6.96 (m, 3H), 3.84 (s, 3H).

[0098] The carbon NMR spectrum of N-phenyl-4-methoxybenzamide is characterized as follows: 13 C NMR (100MHz, d6-DMSO) δ165.3,162.3,139.8,130.0,129.0,127.5,123.9,120.8,114.0,55.9.

[0099] The reaction equation is as follows:

[0100]

[0101] Example 10 Preparation of N-phenyl-4-cyanobenzamide

[0102] Take a quartz reaction tube, add a magnetic stirrer, then add 0.3mmol of 4-cyanobenzamide, 10mol% of Ir(ppy)2(dtbpy)PF6, 0.6mmol of chlorobenzene and 0.6mmol of t-BuOLi, and then add 6mL of dimethyl sulfoxide as solvent. Freeze the reaction liquid with liquid nitrogen, use an oil pump to drain the gas in the reaction tube and balloon, and fill with nitrogen. After thawing, react at room temperature for 72h under visible light irradiation with magnetic stirring, and the reaction is monitored by TLC. Finally, the final product N-phenyl-4-methoxybenzamide is separated by column chromatography with a yield of 62%.

[0103] The nuclear magnetic resonance hydrogen spectrum of N-phenyl-4-methoxybenzamide is characterized as follows: 1 H NMR (400MHz, d6-DMSO) δ 10.47 (s, 1H), 8.10 (d, J = 8.0Hz, 2H), 8.03 (d, J = 8.0Hz, 2H), 7.77 (d, J = 8.0Hz, 2H), 7.37 (t, J = 7.7Hz, 2H), 7.13 (t, J = 7.4Hz, 1H).

[0104] The carbon NMR spectrum of N-phenyl-4-methoxybenzamide is characterized as follows: 13 C NMR (100MHz, d6-DMSO) δ164.1,139.0,138.7,132.4,128.7,128.5,124.1,120.4,118.3,113.8.

[0105] The reaction equation is as follows:

[0106]

[0107] Example 11 Preparation of N-(2-chlorophenyl)benzanilide

[0108] Take a quartz reaction tube, add a magnetic stirrer, then add 0.3mmol of benzamide, 10mol% of Ir(ppy)2(dtbpy)PF6, 0.6mmol of 1,3-dichlorobenzene and 0.6mmol of t-BuOLi, and then add 6mL of dimethyl sulfoxide as solvent. Freeze the reaction solution with liquid nitrogen, use an oil pump to drain the gas in the reaction tube and balloon, and fill with nitrogen. After thawing, carry out magnetic stirring at room temperature under visible light irradiation for 72h, and the reaction is monitored by TLC. Finally, the final product N-(2-chlorophenyl)benzanilide is separated by column chromatography with a yield of 67%.

[0109] The nuclear magnetic resonance hydrogen spectrum of N-(2-chlorophenyl)benzanilide is characterized as follows: 1H NMR (400MHz, DMSO-d6) δ10.05(s,1H),8.19-7.85(m,2H),7.66-7.48(m,5H),7.44-7.35(m,1H),7.35-7.26(m,1H).

[0110] The carbon NMR spectrum of N-(2-chlorophenyl)benzanilide is characterized as follows: 13 C NMR (101MHz, DMSO-d6) δ165.8,135.6,134.4,132.3,130.0,129.9,129.0,128.9,128.2,128.0,127.9.

[0111] The reaction equation is as follows:

[0112]

[0113] Example 12 Preparation of N-(4-chlorophenyl)benzanilide

[0114] Take a quartz reaction tube, add a magnetic stirrer, then add 0.3mmol of benzamide, 10mol% of Ir(ppy)2(dtbpy)PF6, 0.6mmol of 1,4-difluorobenzene and 0.6mmol of t-BuOLi, and then add 6mL of dimethyl sulfoxide as solvent. Freeze the reaction solution with liquid nitrogen, use an oil pump to drain the gas in the reaction tube and balloon, and fill with nitrogen. After thawing, carry out magnetic stirring at room temperature under visible light irradiation for 72h, and the reaction is monitored by TLC. Finally, the final product N-(4-chlorophenyl)benzanilide is separated by column chromatography with a yield of 74%.

[0115] The nuclear magnetic resonance hydrogen spectrum of N-(4-chlorophenyl)benzanilide is characterized as follows: 1 H NMR (400MHz, d6-DMSO) δ10.30(s,1H),8.03-7.89(m,2H),7.86-7.74(m,2H),7.63-7.48(m,3H),7.26-7.11(m,2H).

[0116] The carbon NMR spectrum of N-(4-chlorophenyl)benzanilide is characterized as follows: 13 C NMR (100MHz, d6-DMSO) δ 165.7, 164.1 (d, J = 245.1Hz), 139.5, 131.8, 130.9 (d, J = 7.8Hz), 129.1, 124.2, 120.9, 115.8 (d, J = 21.0Hz).

[0117] The reaction equation is as follows:

[0118]

[0119] Example 13 Preparation of N-(4-cyanophenyl)benzanilide

[0120] Take a quartz reaction tube, add a magnetic stirrer, then add 0.3mmol of benzamide, 10mol% of Ir(ppy)2(dtbpy)PF6, 0.6mmol of 4-cyanochlorobenzene and 0.6mmol of t-BuOLi, and then add 6mL of dimethyl sulfoxide as solvent. Freeze the reaction solution with liquid nitrogen, use an oil pump to drain the gas in the reaction tube and the balloon, and fill it with nitrogen. After thawing, carry out magnetic stirring and room temperature reaction for 72h under visible light irradiation, and the reaction is monitored by TLC. Finally, the final product N-(4-cyanophenyl)benzanilide is separated by column chromatography with a yield of 65%.

[0121] The nuclear magnetic resonance hydrogen spectrum of N-(4-cyanophenyl)benzanilide is characterized as follows: 1 H NMR (400MHz, d6-DMSO) δ10.64(s,1H),8.09-7.90(m,4H),7.89-7.72(m,2H),7.68-7.60(m,1H),7.59-7.49(m,2H).

[0122] The carbon NMR spectrum of N-(4-cyanophenyl)benzanilide is characterized as follows: 13 C NMR (100MHz, d6-DMSO) δ166.2,143.5,134.4,133.1,132.0,128.5,127.8,120.2,119.1,105.3.

[0123] The reaction equation is as follows:

[0124]

[0125] Example 14 Preparation of N-(4-methoxyphenyl)acetanilide

[0126] Take a quartz reaction tube, add a magnetic stirrer thereto, then add 0.3mmol of acetamide, 10mol% of Ir(ppy)2(dtbpy)PF6, 0.6mmol of 4-methoxychlorobenzene and 0.6mmol of t-BuOLi, and then add 6mL of dimethyl sulfoxide as solvent. Liquid nitrogen freezes the reaction solution, and the gas in the reaction tube and balloon is drained with an oil pump and filled with nitrogen. After thawing, magnetic stirring is carried out under visible light irradiation to react at room temperature for 72h, and the reaction is monitored by TLC. Finally, the final product N-(4-methoxyphenyl)acetanilide is obtained by column chromatography separation, and the yield is 69%.

[0127] Figure 7 Shown is the hydrogen nuclear magnetic resonance spectrum of N-(4-methoxyphenyl)acetanilide in this embodiment. The hydrogen nuclear magnetic resonance spectrum of N-(4-methoxyphenyl)acetanilide is characterized as follows: 1 H NMR (400MHz, DMSO-d6) δ9.8(s,1H),7.5-7.4(m,2H),6.9-6.8(m,2H),3.7(s,3H),2.0(s,3H).

[0128] Figure 8 Shown is the carbon NMR spectrum of N-(4-methoxyphenyl)acetanilide in this embodiment. The carbon NMR spectrum of N-(4-methoxyphenyl)acetanilide is characterized as follows: 13 C NMR (101MHz, DMSO-d6) δ168.2, 155.4, 133.0, 121.0, 114.2, 55.6, 24.3.

[0129] The reaction equation is as follows:

[0130]

[0131] Example 15 Preparation of N-(2-methoxyphenyl)acetanilide

[0132] Take a quartz reaction tube, add a magnetic stirrer thereto, then add 0.3mmol of acetamide, 10mol% of Ir(ppy)2(dtbpy)PF6, 0.6mmol of 2-methoxychlorobenzene and 0.6mmol of t-BuOLi, and then add 6mL of dimethyl sulfoxide as solvent. Liquid nitrogen freezes the reaction solution, and the gas in the reaction tube and balloon is drained with an oil pump and filled with nitrogen. After thawing, magnetic stirring is carried out under visible light irradiation to react at room temperature for 72h, and the reaction is monitored by TLC. Finally, the final product N-(2-methoxyphenyl)acetanilide is obtained by column chromatography separation, and the yield is 75%.

[0133] The nuclear magnetic resonance hydrogen spectrum of N-(2-methoxyphenyl)acetanilide is characterized as follows: 1 H NMR (400MHz, d6-DMSO) δ9.92 (s, 1H), 7.29 (t, J = 2.3 Hz, 1H), 7.24-7.07 (m, 2H), 6.61 (ddd, J = 8.1, 2.6, 1.0 Hz, 1H), 3.72 (s, 3H), 2.03 (s, 3H).

[0134] The carbon NMR spectrum of N-(2-methoxyphenyl)acetanilide is characterized as follows: 13C NMR (100MHz, d6-DMSO) δ168.8,159.9,141.0,129.9,111.7,108.8,105.3,55.4,24.5.

[0135] The reaction equation is as follows:

[0136]

[0137] Example 16 Optimization of reaction conditions

[0138] 1. Catalyst Optimization

[0139] Take a quartz reaction tube, add a magnetic stirrer, then add 0.3mmol of benzamide, 10mol% of iridium metal complex, 0.6mmol of fluorobenzene and 0.6mmol of t-BuOLi, and then add 6mL of dimethyl sulfoxide as solvent. Freeze the reaction solution with liquid nitrogen, use an oil pump to drain the gas in the reaction tube and balloon, and fill with nitrogen. After thawing, carry out magnetic stirring at room temperature under blue light for 72h, and the reaction is monitored by TLC. Finally, the final product, benzanilide, is separated by column chromatography with a yield of 87%.

[0140] Table 1 Yields of benzamide under different catalysts

[0141]

[0142]

[0143] The above results show that products can be obtained when different iridium metal complexes are used as catalysts. For the substrates benzamide and fluorobenzene, Ir(ppy)2(dtbpy)PF6 has a better catalytic effect.

[0144] 2. Optimization of light source

[0145] Take a quartz reaction tube, add a magnetic stirrer, then add 0.3mmol of benzamide, 10mol% of Ir(ppy)2(dtbpy)PF6, 0.6mmol of fluorobenzene and 0.6mmol of t-BuOLi, and then add 6mL of dimethyl sulfoxide as solvent. Freeze the reaction solution with liquid nitrogen, use an oil pump to drain the gas in the reaction tube and balloon, and fill with nitrogen. After thawing, react at room temperature for 72h under visible light irradiation with magnetic stirring, and the reaction is monitored by TLC. Finally, the final product, benzanilide, is separated by column chromatography with a yield of 87%.

[0146] Table 2 Yield of benzamide under different light sources

[0147]

[0148] The above results show that products can be obtained under different light sources, and for the substrates benzamide and fluorobenzene, blue light is the optimal light source.

[0149] 3. Solvent Optimization

[0150] Take a quartz reaction tube, add a magnetic stirrer, then add 0.3mmol of benzamide, 10mol% of Ir(ppy)2(dtbpy)PF6, 0.6mmol of fluorobenzene and 0.6mmol of t-BuOLi, and then add 6mL of solvent. Freeze the reaction solution with liquid nitrogen, use an oil pump to drain the gas in the reaction tube and the balloon, and fill it with nitrogen. After thawing, carry out magnetic stirring at room temperature under blue light for 72h, and the reaction is monitored by TLC. Finally, the final product, benzanilide, is separated by column chromatography with a yield of 87%.

[0151] Table 3 Yield of benzamide under different solvent conditions

[0152]

[0153]

[0154] The above results show that the products can be obtained in different solvents, and DMSO is the best solvent for the substrates benzamide and fluorobenzene.

[0155] 4. Optimization of additive base

[0156] Take a quartz reaction tube, add a magnetic stirrer, then add 0.3mmol of benzamide, 10mol% of Ir(ppy)2(dtbpy)PF6, 0.6mmol of fluorobenzene and 0.6mmol of base, and then add 6mL of dimethyl sulfoxide as solvent. Freeze the reaction liquid with liquid nitrogen, use an oil pump to drain the gas in the reaction tube and balloon, and fill it with nitrogen. After thawing, carry out magnetic stirring at room temperature under blue light for 72h, and the reaction is monitored by TLC. Finally, the final product, benzanilide, is separated by column chromatography with a yield of 87%.

[0157] Table 4 Yield of benzanilide under different additive base conditions

[0158]

[0159] The above results show that the products can be obtained by adding different bases. For the substrates benzamide and fluorobenzene, t-BuOLi is the optimal base.

[0160] 5. Optimization of the ratio

[0161] Take a quartz reaction tube, add a magnetic stirrer, then add different ratios of benzamide and fluorobenzene, 10 mol% Ir(ppy)2(dtbpy)PF6, 0.6 mmol of base, and then add 6 mL of dimethyl sulfoxide as solvent. Freeze the reaction liquid with liquid nitrogen, use an oil pump to drain the gas in the reaction tube and balloon, and fill it with nitrogen. After thawing, carry out magnetic stirring at room temperature under blue light for 72 hours, and the reaction is monitored by TLC. Finally, the final product, benzanilide, is separated by column chromatography with a yield of 87%.

[0162] Table 5 The yield of benzanilide under different ratio conditions

[0163]

[0164]

[0165] The above results show that for the substrates benzamide and fluorobenzene, 1:2 is the optimal ratio.

[0166] The method for synthesizing N-arylamide by light-induced iridium metal catalysis of the present invention comprises a molar ratio of arylamide to aryl halide of 1:1-3. The amount of solvent added is 6 mL of solvent per 0.3 mmol of arylamide. The amount of transition metal complex as catalyst added is 7-13 mol%, preferably 10 mol%, of halogenated aromatic hydrocarbon.

[0167] Relative to the prior art, the present invention reduces the difficulty of nucleophilic substitution of chlorobenzene and fluorobenzene, solves the problem that chlorobenzene and fluorobenzene are difficult to undergo nucleophilic substitution reaction, and realizes the reaction of electron transfer of weak electron donor amide to aryl halide (fluorobenzene and chlorobenzene) under relatively mild conditions. And then the energy efficiency of the reaction can be greatly improved, and the yield of the reaction can be improved. The above-described embodiments are only preferred embodiments of the present invention, and are not intended to limit the scope of implementation of the present invention. Under the guidance of the prior art, those skilled in the art can make other modifications to the implementation of the present invention without creative work, so all according to the technical conception described in the present invention, the equivalent changes or modifications made within the spirit and principles of the present invention, and the conventional techniques in the art increase or replacement (such as the adjustment of the reaction time and the addition amount of the solvent, etc., which are not the research focus of the present invention) should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing N-aryl amides by light-induced metal catalysis, using aryl amides and aryl halides as raw materials, and synthesizing N-aryl amides by single electron transfer under light conditions, characterized in that: The process includes: Step S1, taking aryl amide, aryl halide, catalyst and base, and adding them into a reaction container; the catalyst is an iridium metal complex, and the base is used to promote the reaction in the forward direction; Step S2, adding a solvent into a reaction container, fully dissolving, and then performing a synthesis reaction under light and nitrogen protection conditions; the reaction equation is: Wherein: R is hydrogen, an electron-donating group or an electron-withdrawing group; Ar is an aromatic group; X is a F or Cl atom; Step S3, after the reaction is completed, the final product is taken out and separated by column chromatography to obtain N-benzamide.

2. The method for photoinduced iridium metal catalytic synthesis of N-aryl amides according to claim 1, characterized in that: In step S1, the molar ratio of the aryl amide to the aryl halide is 1:1-3.

3. The method for light-induced iridium metal catalytic synthesis of N-aryl amides according to claim 1 or 2, characterized in that: In step S1, an iridium metal complex is used as a catalyst, and the amount of the iridium metal complex added is 7-13 mol%, preferably 10 mol%, of the aryl halide.

4. The method for photoinduced iridium metal catalytic synthesis of N-aryl amides according to claim 3, characterized in that: In step S2, the illumination conditions are red light, blue light, green light, incandescent light, xenon lamp or 254nm ultraviolet light, the reaction temperature is controlled at 55-65°C, and the reaction time is 60-72h.

5. The method for light-induced iridium metal catalytic synthesis of N-aryl amides according to claim 1, 2 or 4, characterized in that: The iridium metal complex is Ir(ppy)2(acac), Ir(ppz)2(acac), Ir(ppz)(ppy)(acac), Ir(ppy)2(dtbpy)PF6 or Ir(dF-CF3-ppy)2(dtbpy)PF6.

6. The method for light-induced iridium metal catalytic synthesis of N-aryl amides according to claim 1, 2 or 4, characterized in that: The base is Cs2CO3, t-BuOLi, t-BuOK, NaOH, K3PO4 or K2CO3.

7. The method for light-induced iridium metal catalytic synthesis of N-aryl amides according to claim 1, 2 or 4, characterized in that: The solvent is dimethyl sulfoxide, acetonitrile, tetrahydrofuran or N,N-dimethylformamide.

8. The method for light-induced iridium metal catalytic synthesis of N-aryl amides according to claim 1, 2 or 4, characterized in that: Iridium metal complex using Ir(ppy)2(dtbpy)PF 6， The base used was t-BuOLi, the solvent used was dimethyl sulfoxide, the light used was LED blue light, the reaction temperature was controlled at 60°C, the reaction time was 72h, and the reaction equation was:

9. The method for light-induced iridium metal catalytic synthesis of N-aryl amides according to claim 1, 2 or 4, characterized in that: The electron-donating group R is methyl, methoxy, ethyl, ethoxy, isopropyl, tert-butyl, hydroxyl, methylthio, alkoxy or amino, and the electron-withdrawing group is nitro, cyano, trifluoromethyl, chlorine, fluorine, acyl, ester or sulfonyl.

10. The method for photoinduced iridium metal catalytic synthesis of N-aryl amides according to claim 5, characterized in that: The structural formula of the iridium metal complex catalyst Ir(ppy)2(acac) is The structural formula of the iridium metal complex catalyst Ir(ppz)2(acac) is The structural formula of the iridium metal complex catalyst Ir(ppz)(ppy)(acac) is The structural formula of the iridium metal complex catalyst Ir(ppy)2(dtbpy)PF6 is The structural formula of the iridium metal complex catalyst Ir(dF-CF3-ppy)2(dtbpy)PF6 is

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