Preparation method of N-arylamine

Abstract

The invention provides a preparation method of N-arylamine, which comprises the following steps: reacting halogen-containing aromatic hydrocarbon with a structural general formula I with an ammonia source under the action of a copper catalyst to obtain N-arylamine with a structural general formula II, wherein X is halogen, and R1, R2, R3, R4 and R5 are respectively and independently selected from one of H, methyl, carboxyl, hydroxyl, nitryl, methoxyl and halogen. According to the invention, the process, reaction conditions and method are improved, and the high-activity copper catalyst is used, so that the Ullmann reaction of the low-activity halogen-containing aromatic hydrocarbon can be carried out under mild conditions, and harsh reaction conditions of high temperature and high pressure are avoided; an ammonia gas adsorption material with special adsorption performance on ammonia gas is introduced, so that the usage amount of an ammonia source is reduced; meanwhile, the new route avoids the generation of a large amount of waste acid, is more environment-friendly, and enables the overall process conditions to be milder.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of organic synthesis, and particularly relates to a preparation method of N-aryl amines. BACKGROUND

[0002] Primary aryl amines are one of the most important raw materials in organic chemistry, and have been widely used in the manufacture of pharmaceuticals, agrochemicals, dyes and electronic materials. So far, more than 6 million tons of primary aryl amines are produced annually, and the most common method for preparing them is the nitration of aromatic hydrocarbons followed by hydrogenation. Since this process uses a large excess of mixed HNO3 and H2, it poses a serious environmental problem. In addition, this method is also limited by the low regioselectivity of the nitration step and poor functional group tolerance, as well as the problem of chemical selectivity in the hydrogenation step. On the other hand, the chlorination of aromatic hydrocarbons is another inexpensive industrial process, which is more advantageous than nitration in some aspects. Therefore, the amination reaction of chloroarenes with ammonia gas can be used as an alternative method for the manufacture of primary aryl amines. Through literature research and experiments, it is found that halogen-containing aromatic hydrocarbons can directly undergo S N Ar nucleophilic substitution reaction with ammonia source, but it needs high temperature (more than 180℃) and high pressure (4MPa) environment, and the ammonia source is greatly excessive, which greatly limits the reaction range and is not convenient for large-scale production.

[0003] Some methods for preparing N-aryl amines are also disclosed in the prior art, such as the copper-catalyzed Ullmann coupling reaction of aryl halides with amines under harsh conditions such as high temperature in Tetrahedron 1984, 40, 1433-1456, and the yield is not satisfactory. With the development of ligand-promoted Ullmann-type reactions, this situation has changed. However, in the case of aryl chlorides as substrates, their effects are all poor. In 2015, the research group of Ma Dazhao (Org. Lett. 2015, 17, 23, 5934-5937) established a general and practical catalytic system for the amination of aryl chlorides with aqueous ammonia or gaseous ammonia using CuI as catalyst and bis(aryloxide)oxalamide as ligand. The reaction was carried out at 105-120℃ to provide various primary (hetero) aryl amines with various functional groups in high yield, but it also requires the addition of additional ligands and inorganic bases. Therefore, how to provide a preparation method of N-aryl amines with mild reaction conditions and low cost has become a problem to be solved. For this purpose, we developed a new scheme to synthesize N-aryl amines. SUMMARY

[0004] In view of the deficiencies of the prior art, the purpose of the present application is to provide a preparation method of N-aryl amines with mild reaction conditions and low cost.

[0005] To achieve the purpose of the present application, the following technical solutions are adopted:

[0006] The first object of the present application is to provide a preparation method of N-arylamine, which comprises the following steps:

[0007] reacting a halogen-containing aromatic hydrocarbon with a structure general formula of formula I with an ammonia source under the action of a copper catalyst to obtain an N-arylamine with a structure general formula of formula II;

[0008]

[0009] wherein X is halogen, R1, R2, R3, R4, R5 are each independently selected from one of H, methyl, carboxyl, hydroxyl, nitro, methoxy and halogen.

[0010] Preferably, X is Cl or Br.

[0011] Specifically, the copper catalyst is at least one selected from CuI, CuBr, Cu2O, Cu I BiOI, CuO x / SiO2 and Cu I BiOBr; wherein x = 0.5-1.

[0012] wherein CuO x / SiO2 catalyst is prepared by the method of the reference document ACS Appl. Mater. Interfaces 2021, 13, 38213-38220, Cu I BiOI and Cu I BiOBr catalyst is prepared by the method of the reference document Mol. Catal., 493 (2020), Article 111072, and the rest of the catalysts are commercially available catalysts.

[0013] Specifically, the ammonia source is at least one selected from aqueous ammonia, ammonia gas and ammonium halide;

[0014] Preferably, when the ammonia source is ammonium halide, the reaction also needs to be carried out under alkaline conditions.

[0015] Specifically, the reaction also needs an ammonia gas adsorbent.

[0016] Preferably, the ammonia gas adsorbent is MgCl2 / SiO2.

[0017] The ammonia gas adsorbent of the present application is prepared by the following method:

[0018] Anhydrous magnesium chloride and ethanol are added to a reaction vessel, and under an inert gas atmosphere, the temperature is raised to dissolve to obtain a magnesium chloride solution; a certain proportion of silicon dioxide is heated and then added to the above magnesium chloride solution to react, and after post-treatment, an ammonia gas adsorbent MgCl2 / SiO2 is obtained.

[0019] Preferably, 180 g of anhydrous magnesium chloride and 1.8 L of ethanol are added into a reaction container, and a magnesium chloride solution is obtained by refluxing for 1 h under a nitrogen atmosphere. 270 g of silica (60A pore size, 100-150 mesh) is heated to 450℃ for a period of time and then cooled; it is then immediately added to the magnesium chloride solution, and the suspension is refluxed for 1 h. After removing the solvent, the mixture is dried in a vacuum oven at 150℃ overnight to obtain an ammonia adsorbent MgCl2 / SiO2.

[0020] Preferably, the molar ratio of the halogen-containing aromatic hydrocarbon to the ammonia adsorbent is 1:(0.05-0.3); more preferably, the molar ratio of the halogen-containing aromatic hydrocarbon to the ammonia adsorbent can be 1:0.05, 1:0.1, 1:0.15, 1:0.2, 1:0.25, 1:0.3, etc., but is not limited to the listed values, and other values not listed in the value range are also applicable.

[0021] Specifically, the reaction temperature is 25-60℃, and the reaction time is 8-18 h; preferably, the reaction temperature can be 25℃, 30℃, 35℃, 40℃, 45℃, 50℃, 55℃, 60℃, etc., and the reaction time can be 8 h, 9 h, 10 h, 11 h, 12 h, 13 h, 14 h, 15 h, 16 h, 17 h, 18 h, etc.; but is not limited to the listed values, and other values not listed in the value range are also applicable.

[0022] Specifically, the molar ratio of the halogen-containing aromatic hydrocarbon, the copper catalyst, and the ammonia source is 1:(0.05-0.2):(1-3); preferably, the molar ratio of the halogen-containing aromatic hydrocarbon, the copper catalyst, and the ammonia source can be 1:0.05:1, 1:0.05:2, 1:0.05:3, 1:0.1:1, 1:0.1:2, 1:0.1:3, 1:0.15:1, 1:15:2, 1:0.15:3, 1:0.2:1, 1:0.2:2, 1:0.2:3, etc., but is not limited to the listed values, and other values not listed in the value range are also applicable.

[0023] Specifically, the halogen-containing aromatic hydrocarbon is selected from one of

[0024]

[0025] Specifically, a solvent needs to be added in the reaction, and the solvent includes at least one of DMSO, DMF, and DMAC.

[0026] Compared with the prior art, the present application has the following beneficial effects:

[0027] ​The application provides a preparation method of N-arylamine, which improves process, reaction conditions and method, uses a high-activity copper catalyst, enables the Ullmann reaction of low-activity halogen-containing aromatic hydrocarbon to occur under mild conditions, avoids harsh reaction conditions of high temperature and high pressure, introduces ammonia adsorption material with special ammonia adsorption performance, reduces the use amount of ammonia source, simultaneously avoids the generation of a large amount of waste acid in the new route, is more friendly to the environment, and makes the overall process condition more mild. DETAILED DESCRIPTION

[0028] In order to further clarify the technical means adopted by the application and its effects, the technical solutions of the application will be further described below in combination with preferred embodiments of the application, but the application is not limited in the scope of the embodiments.

[0029] Example 1

[0030] The embodiment provides a preparation method of N-arylamine, and the N-arylamine is 5-amino-2-nitrobenzoic acid, and the specific steps are as follows:

[0031] 100 mL of DMSO, 10 g (50 mmol) of 5-chloro-2-nitrobenzoic acid, 775 mg (5 mmol) of MgCl2 / SiO2, 1 g (2.5 mmol) of Cu I BiOI, 6.8 mL of ammonia water, and the temperature is increased to 60 DEG C, and the reaction is performed for 12 h. After the reaction is completed, the temperature is decreased to room temperature, the reaction solution is filtered, 6M / L hydrochloric acid aqueous solution is added to the mother liquor, at this time, yellow solid is generated, the solid is filtered, the filter cake is washed twice with ice ethanol, and the filter cake is dried at 50 DEG C for 8 h to obtain 8.3 g of 5-amino-2-nitrobenzoic acid, and the yield is 92%.

[0032] The characterization data are as follows:

[0033] 1 H NMR (400 MHz, DMSO-d6) δ 13.33 (s, 1H), 7.89 (d, J=8.9 Hz, 1H), 6.89-6.77 (m, 2H), 6.72-6.54 (m, 2H).

[0034] Example 2

[0035] The embodiment provides a preparation method of N-arylamine, and the N-arylamine is 5-amino-2-nitrobenzoic acid, and the specific steps are as follows, which are basically the same as those of Example 1, except that 388 mg (2.5 mmol) of MgCl2 / SiO2 is added, 7 g of 5-amino-2-nitrobenzoic acid is obtained, and the yield is 77%.

[0036] Example 3

[0037] The present example provides a method for preparing N-arylamines, the N-arylamines being 5-amino-2-nitrobenzoic acid, the specific steps being as follows, which are basically the same as those of Example 1, except that 2.3 g (15 mmol) of MgCl2 / SiO2 is added, and 8.5 g of 5-amino-2-nitrobenzoic acid is obtained, with a yield of 94%.

[0038] Example 4

[0039] The present example provides a method for preparing N-arylamines, the N-arylamines being 5-amino-2-nitrobenzoic acid, the specific steps being as follows, which are basically the same as those of Example 1, except that 4.0 g (10 mmol) of Cu I BiOBr is added, and 8.4 g of 5-amino-2-nitrobenzoic acid is obtained, with a yield of 93%.

[0040] Example 5

[0041] The present example provides a method for preparing N-arylamines, the N-arylamines being 5-amino-2-nitrobenzoic acid, the specific steps being as follows, which are basically the same as those of Example 1, except that 3.1 g (7.5 mmol) of Cu I BiOBr is added, and 8.3 g of 5-amino-2-nitrobenzoic acid is obtained, with a yield of 92%.

[0042] Example 6

[0043] The present example provides a method for preparing N-arylamines, the N-arylamines being 5-amino-2-nitrobenzoic acid, the specific steps being as follows, which are basically the same as those of Example 1, except that 920 mg (2.5 mmol) of Cu I BiOBr is added, and 7 g of 5-amino-2-nitrobenzoic acid is obtained, with a yield of 77%.

[0044] Example 7

[0045] The present example provides a method for preparing N-arylamines, the N-arylamines being 5-amino-2-nitrobenzoic acid, the specific steps being as follows, which are basically the same as those of Example 1, except that 0.35 g (2.5 mmol) of CuO x / SiO2 is added, and 8 g of 5-amino-2-nitrobenzoic acid is obtained, with a yield of 88%.

[0046] Example 8

[0047] The embodiment provides a preparation method of N-arylamine, and the N-arylamine is aniline. The specific steps are as follows: 100 mL of DMSO, 7.85 g (50 mmol) of bromobenzene, 775 mg (5 mmol) of MgCl2 / SiO2 and 1 g (2.5 mmol) of Cu I BiOI, and the reaction is carried out for 12 h at 60 DEG C after three times of replacement of ammonia gas. After the reaction is completed, the reaction solution is filtered, and column chromatography is performed to obtain 4.4 g of aniline, and the yield is 95%.

[0048] The characterization data are as follows:

[0049] 1 H NMR (400MHz, DMSO-d6) δ 7.08-6.93 (m, 2H), 6.66-6.54 (m, 2H), 6.50 (m, 1H), 4.99 (s, 2H).

[0050] Example 9

[0051] The embodiment provides a preparation method of N-arylamine, and the N-arylamine is 2,6-dimethylaniline. The specific steps are as follows: 100 mL of DMSO, 7 g (50 mmol) of 2,6-dimethylchlorobenzene, 775 mg (5 mmol) of MgCl2 / SiO2 and 1 g (2.5 mmol) of Cu I BiOI, and the reaction is carried out for 12 h at 60 DEG C after three times of replacement of ammonia gas. After the reaction is completed, the reaction solution is filtered, and column chromatography is performed to obtain 4.4 g of aniline, and the yield is 95%.

[0052] The characterization data are as follows:

[0053] 1 H NMR (400MHz, DMSO-d6) δ 7.08-6.93 (m, 2H), 6.66-6.54 (m, 2H), 6.50 (m, 1H), 4.99 (s, 2H).

[0054] Example 10

[0055] The embodiment provides a preparation method of N-arylamine, and the N-arylamine is 2,6-dimethylaniline. The specific steps are as follows: 100 mL of DMSO, 7 g (50 mmol) of 2,6-dimethylchlorobenzene, 775 mg (5 mmol) of MgCl2 / SiO2 and 1 g (2.5 mmol) of Cu IBiOBr, 6.8 mL of ammonia water was added, and the temperature was raised to 60 °C, and the reaction was carried out for 16 h. After the reaction was completed, the temperature was lowered to room temperature, the reaction solution was filtered, and column chromatography was used for separation to obtain 6.5 g of 4-aminobenzoic acid with a yield of 95%.

[0056] The characterization data are as follows:

[0057] 1 H NMR (400 MHz, DMSO-d6) δ 7.91 (d, J = 9.0 Hz, 1H), 6.55-6.42 (m, 4H), 2.47 (s, 3H).

[0058] Example 11

[0059] This example provides a preparation method of N-arylamine, and the N-arylamine is 4-aminobenzoic acid. The specific steps are as follows: 100 mL of DMSO, 10 g (50 mmol) of 4-bromobenzoic acid, 775 mg (5 mmol) of MgCl2 / SiO2, and 0.92 g (2.5 mmol) of Cu I BiOBr, 6.8 mL of ammonia water was added, and the temperature was raised to 60 °C, and the reaction was carried out for 16 h. After the reaction was completed, the temperature was lowered to room temperature, the reaction solution was filtered, and column chromatography was used for separation to obtain 6.5 g of 4-aminobenzoic acid with a yield of 95%.

[0060] The characterization data are as follows:

[0061] 1 H NMR (400 MHz, DMSO-d6) δ 7.91 (d, J = 9.0 Hz, 1H), 6.55-6.42 (m, 4H), 2.47 (s, 3H).

[0062] Example 12

[0063] This example provides a preparation method of N-arylamine, and the N-arylamine is 4-aminobenzoic acid. The specific steps are as follows: 100 mL of DMSO, 10 g (50 mmol) of 4-bromobenzoic acid, 775 mg (5 mmol) of MgCl2 / SiO2, and 0.92 g (2.5 mmol) of Cu I BiOBr, 6.8 mL of ammonia water was added, and the temperature was raised to 60 °C, and the reaction was carried out for 16 h. After the reaction was completed, the temperature was lowered to room temperature, the reaction solution was filtered, and column chromatography was used for separation to obtain 6.5 g of 4-aminobenzoic acid with a yield of 95%.

[0064] The characterization data are as follows:

[0065] 1H NMR (400 MHz, DMSO-d6) δ 7.06 - 6.70 (m, 1H), 6.31 - 6.13 (m, 2H), 6.10 (ddd, J = 8.1, 2.3, 1.0 Hz, 1H), 5.04 (s, 2H), 3.65 (s, 3H).

[0066] Comparative Example 1

[0067] This example provides a method for preparing N-arylamine, which is 5-chloro-2-nitrobenzoic acid, and the specific steps are as follows: 100 mL of DMSO is added to a reaction bottle, 10 g (50 mmol) of 5-chloro-2-nitrobenzoic acid, 775 mg (5 mmol) of MgCl2 / SiO2, 6.8 mL of ammonia water, and the temperature is raised to 60°C, and the reaction is carried out for 12 h. After the reaction is completed, the temperature is lowered to room temperature, the reaction solution is filtered, 6M / L hydrochloric acid aqueous solution is added to the mother liquor, at this time yellow solid is generated, it is filtered, the filter cake is washed with ice ethanol for 2 times, and it is dried at 50°C for 8 h, and 2 g of 5-amin-2-nitrobenzoic acid is obtained, and the yield is 22%. I BiOI, 6.8 mL of ammonia water is added, the temperature is raised to 60°C, and the reaction is carried out for 12 h. After the reaction is completed, the temperature is lowered to room temperature, the reaction solution is filtered, 6M / L hydrochloric acid aqueous solution is added to the mother liquor, at this time yellow solid is generated, it is filtered, the filter cake is washed with ice ethanol for 2 times, and it is dried at 50°C for 8 h, and 2 g of 5-amin-2-nitrobenzoic acid is obtained, and the yield is 22%.

[0068] Comparative Example 2

[0069] This example provides a method for preparing N-arylamine, which is 5-chloro-2-nitrobenzoic acid, and the specific steps are as follows: 100 mL of DMSO is added to a reaction bottle, 10 g (50 mmol) of 5-chloro-2-nitrobenzoic acid, 775 mg (5 mmol) of MgCl2 / SiO2, 6.8 mL of ammonia water, and the temperature is raised to 60°C, and the reaction is carried out for 12 h. After the reaction is completed, the temperature is lowered to room temperature, the reaction solution is filtered, 6M / L hydrochloric acid aqueous solution is added to the mother liquor, at this time yellow solid is generated, it is filtered, the filter cake is washed with ice ethanol for 2 times, and it is dried at 50°C for 8 h, and 2 g of 5-amin-2-nitrobenzoic acid is obtained, and the yield is 22%.

[0070] Comparative Example 3

[0071] This example provides a method for preparing N-arylamine, which is 5-chloro-2-nitrobenzoic acid, and the specific steps are as follows: 100 mL of DMSO is added to a reaction bottle, 10 g (50 mmol) of 5-chloro-2-nitrobenzoic acid, 775 mg (5 mmol) of MgCl2 / SiO2, 6.8 mL of ammonia water, and the temperature is raised to 60°C, and the reaction is carried out for 12 h. After the reaction is completed, the temperature is lowered to room temperature, the reaction solution is filtered, 6M / L hydrochloric acid aqueous solution is added to the mother liquor, at this time yellow solid is generated, it is filtered, the filter cake is washed with ice ethanol for 2 times, and it is dried at 50°C for 8 h, and 2 g of 5-amin-2-nitrobenzoic acid is obtained, and the yield is 22%.

[0072] Comparative Example 4

[0073] This example provides a method for preparing N-arylamine, which is 5-chloro-2-nitrobenzoic acid, and the specific steps are as follows: 100 mL of DMSO is added to a reaction bottle, 10 g (50 mmol) of 5-chloro-2-nitrobenzoic acid, 775 mg (5 mmol) of MgCl2 / SiO2, 6.8 mL of ammonia water, and the temperature is raised to 60°C, and the reaction is carried out for 12 h. After the reaction is completed, the temperature is lowered to room temperature, the reaction solution is filtered, 6M / L hydrochloric acid aqueous solution is added to the mother liquor, at this time yellow solid is generated, it is filtered, the filter cake is washed with ice ethanol for 2 times, and it is dried at 50°C for 8 h, and 2 g of 5-amin-2-nitrobenzoic acid is obtained, and the yield is 22%.I BiOI, 6.8 mL of ammonia water was added, and the temperature was raised to 60°C, and the reaction was carried out for 12 h. After the reaction was completed, the temperature was lowered to room temperature, the reaction solution was filtered, 6M / L hydrochloric acid aqueous solution was added to the mother liquor, at this time yellow solid was generated, and the solid was filtered, the filter cake was washed twice with ice ethanol, and the filter cake was dried at 50°C for 8 h to obtain 2.7 g of 5-amino-2-nitrobenzoic acid with a yield of 30%.

[0074] Comparative Example 5

[0075] The present embodiment provides a preparation method of N-arylamine, and the N-arylamine is 5-chloro-2-nitrobenzoic acid. The specific steps are as follows: 100 mL of DMSO, 10 g (50 mmol) of 5-chloro-2-nitrobenzoic acid, 775 mg (5 mmol) of MgCl2 / SiO2, 20.7 g (50 mmol) of Cu I BiOI, 6.8 mL of ammonia water was added, and the temperature was raised to 60°C, and the reaction was carried out for 12 h. After the reaction was completed, the temperature was lowered to room temperature, the reaction solution was filtered, 6M / L hydrochloric acid aqueous solution was added to the mother liquor, at this time yellow solid was generated, and the solid was filtered, the filter cake was washed twice with ice ethanol, and the filter cake was dried at 50°C for 8 h to obtain 2.7 g of 5-amino-2-nitrobenzoic acid with a yield of 30%.

[0076] Although the yield of the catalyst in the present comparative example is improved, the raw material cost and the post-processing cost are also increased.

[0077] From the above results, it can be found that the preparation method provided by the present application is improved in process, reaction condition and method compared with the prior art, a high-activity copper catalyst is used, so that the Ullmann reaction of low-activity halogen-containing aromatic hydrocarbon can occur under mild conditions, and the harsh reaction conditions of high temperature and high pressure are avoided; an ammonia gas adsorption material with special ammonia gas adsorption performance is introduced, so that the amount of ammonia source is reduced; at the same time, the new route avoids the generation of a large amount of waste acid, is more friendly to the environment, and makes the overall process condition more mild.

[0078] The applicant declares that the preparation method of N-arylamine of the present application is illustrated by the above embodiments, but the present application is not limited to the above embodiments, that is, it does not mean that the present application must rely on the above embodiments to be implemented. It should be understood by those skilled in the art that any improvement of the present application, equivalent replacement of each raw material of the product of the present application, addition of auxiliary ingredients, selection of specific modes, etc. fall within the protection scope and disclosure scope of the present application.

[0079] The preferred embodiments of the present application are described in detail above, but the present application is not limited to the specific details of the above-described embodiments, and various simple modifications can be made to the technical solutions of the present application within the technical concept of the present application, and these simple modifications all belong to the protection scope of the present application.

[0080] In addition, it should be noted that each specific technical feature described in the above specific embodiments can be combined in any appropriate manner without contradiction, and in order to avoid unnecessary repetition, various possible combinations are not described again by the present application.

Claims

1. A method for preparing N-arylamines, characterized in that, The preparation method includes the following steps: A halogenated aromatic hydrocarbon of general formula I is reacted with an ammonia source in the presence of a copper catalyst to obtain an N-arylamine of general formula II. Wherein: X is a halogen, and R1, R2, R3, R4, and R5 are each independently selected from one of H, methyl, carboxyl, hydroxyl, nitro, methoxy, and halogen.

2. The preparation method according to claim 1, characterized in that, The copper catalyst is selected from CuI, CuBr, Cu2O, Cu I BiOI, CuO x / SiO2 and Cu I At least one of BiOBr; where x = 0.5-1.

3. The preparation method according to claim 1, characterized in that, The ammonia source is at least one selected from ammonia water and ammonia gas.

4. The preparation method according to claim 1, characterized in that, The reaction also requires an ammonia adsorbent.

5. The preparation method according to claim 4, characterized in that, The ammonia adsorbent is MgCl2 / SiO2.

6. The preparation method according to claim 4 or 5, characterized in that, The molar ratio of the halogenated aromatic hydrocarbon and the ammonia adsorbent is 1:(0.05-0.3).

7. The preparation method according to claim 1, characterized in that, The reaction temperature is 25-60℃, and the reaction time is 8-18h.

8. The preparation method according to claim 1, characterized in that, The molar ratio of the halogenated aromatic hydrocarbon, copper catalyst, and ammonia source is 1:(0.05-0.2):(1-3).

9. The preparation method according to claim 1, characterized in that, The halogenated aromatic hydrocarbon is selected from... One of them.

10. The preparation method according to claim 1, characterized in that: The reaction also requires the addition of a solvent, which includes at least one of DMSO, DMF and DMAC.

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