Process for the preparation of aromatic amino compounds

Abstract

This invention belongs to the field of fine chemical technology, specifically relating to a method for preparing aromatic amino compounds. The steps are as follows: adding an aromatic nitro compound, a reducing agent, a reducing aid, an alkali, and a solvent into a reactor, reacting at 80–110°C for 2–4 hours to obtain a reaction product; the reaction product is then post-treated to obtain an aromatic amino compound; wherein the reducing agent is pinacol diborate, and the reducing aid is β-cyclodextrin. The preparation method of this invention can not only reduce aromatic nitro compounds containing sensitive groups such as amino, hydroxyl, and ester groups to aromatic amino compounds, but also effectively protect the sensitive groups, obtaining aromatic amino compounds containing sensitive groups; it solves the technical problems of existing methods for reducing aromatic nitro compounds containing sensitive groups to aromatic amino compounds, where the sensitive groups are destroyed, there are many reaction byproducts, and the yield and purity of the reaction product are low.

Description

Technical Field

[0001] This invention belongs to the field of fine chemical technology, specifically relating to a method for preparing an aromatic amino compound. Background Technology

[0002] Aromatic amino compounds are important intermediates in the synthesis of amides, imines, azo compounds, isocyanates, and diazonium salts, and are widely used in pharmaceutical synthesis, dyes, pesticides, herbicides, and polyurethane production. Currently, there is extensive research on reducing aromatic nitro compounds to aromatic amino compounds. Existing aromatic amino compounds are prepared by reducing aromatic nitro compounds. Reduction methods can be divided into two categories: (1) metal-involved reduction, such as Fe, Zn, Pd, Ni, Ru, etc.; (2) metal-free reduction, including boron Lewis acids, chlorosilanes, etc. Reduction method (1) has problems such as metal residues in the product or complex post-processing; reduction method (2) has the drawback of being incompatible with sensitive groups (such as amino, hydroxyl, ester groups, etc.). For example, (a) aromatic nitro compounds containing ester groups undergo hydrolysis or transesterification side reactions; (b) the nitro reduction products are complex and diverse, mainly consisting of azobenzene intermediates, requiring further reduction to obtain amino products, making the method complex and cumbersome. Summary of the Invention

[0003] In view of the problems and shortcomings of the existing technology, the purpose of this invention is to provide a method for preparing aromatic amino compounds.

[0004] To achieve the objectives of this invention, the technical solution adopted is as follows:

[0005] This invention provides a method for preparing an aromatic amino compound, comprising the following steps: adding an aromatic nitro compound, a reducing agent, a reducing aid, an alkali, and a solvent into a reactor, reacting at 80–110°C for 2–4 h to obtain a reaction product; the reaction product is then post-treated to obtain an aromatic amino compound; wherein the reducing agent is pinacol diboronic acid ester, and the reducing aid is β-cyclodextrin.

[0006] According to the above preparation method, preferably, the molar ratio of pinacol diboronic acid ester to aromatic nitro compound is (1-4):1; and the molar ratio of β-cyclodextrin to aromatic nitro compound is (0.5-2):1.

[0007] According to the above preparation method, preferably, the alkali is at least one selected from potassium tert-butoxide, sodium methoxide, sodium hydroxide, and potassium hydroxide.

[0008] According to the above preparation method, preferably, the molar ratio of the alkali to the aromatic nitro compound is (1-3):1.

[0009] According to the above preparation method, preferably, the solvent is at least one of isopropanol, methanol, and ethanol.

[0010] According to the above preparation method, preferably, the molar ratio of the solvent to the aromatic nitro compound is (50-150):1.

[0011] According to the above preparation method, preferably, the aromatic nitro compound contains a sensitive group, which is at least one of -NH2, -OH, and -COOR.

[0012] According to the above preparation method, preferably, R in -COOR is any one of methyl, ethyl, isopropyl, and n-butyl.

[0013] According to the above preparation method, preferably, the aromatic nitro compound is methyl 4-nitrobenzoate, 4-nitrophenol, 4-nitrophenylamine, ethyl 4-nitrobenzoate, isopropyl 4-nitrobenzoate, n-butyl 4-nitrobenzoate, 4-nitrotoluene, 4-nitrochlorobenzene, 3-nitrochlorobenzene, 3-nitrobromobenzene, 4-nitroiodobenzene, or 4-nitrophenylcyanide.

[0014] According to the above preparation method, preferably, the post-treatment operation is as follows: ethyl acetate is added to the reaction product, mixed evenly, and then filtered to obtain a first filtrate; the solvent and ethyl acetate in the first filtrate are removed to obtain a residue; methanol is added to the residue, stirred and dissolved, and then recrystallized at -20 to -15°C, and then filtered to obtain a second filtrate; the second filtrate is concentrated under reduced pressure and then separated by column chromatography to obtain an aromatic amino compound.

[0015] According to the above preparation method, preferably, when methanol is added to the residue, the amount of methanol used is: the molar ratio of methanol to nitro aromatic compound is (100-300):1.

[0016] According to the above preparation method, preferably, the recrystallization temperature is -20℃.

[0017] According to the above preparation method, preferably, the eluent used in the column chromatography is a mixture of petroleum ether and ethyl acetate; the volume ratio of petroleum ether to ethyl acetate in the eluent is (10-50):1.

[0018] According to the above preparation method, preferably, the molar ratio of ethyl acetate to aromatic nitro compound is (300-500):1.

[0019] Compared with the prior art, the positive and beneficial effects achieved by the present invention are as follows:

[0020] (1) In the process of reducing aromatic nitro compounds to aromatic amino compounds, this invention utilizes β-cyclodextrin as a reducing agent. The cavity of cyclodextrin provides reaction space to achieve a confinement effect, thereby protecting sensitive groups (such as amino, hydroxyl, and ester groups). Moreover, the sensitive groups are prevented from being damaged (oxidized or hydrolyzed) by other components in the environment within the cyclodextrin cavity. Therefore, the preparation method of this invention can not only reduce aromatic nitro compounds containing sensitive groups such as amino, hydroxyl, and ester groups to aromatic amino compounds, but also effectively protect the sensitive groups, obtaining aromatic amino compounds containing sensitive groups. Moreover, the yield of aromatic amino compounds reaches up to 91%, and the purity reaches 99%. This solves the technical problems of existing methods for reducing aromatic nitro compounds containing sensitive groups to aromatic amino compounds, where the sensitive groups are destroyed, there are many reaction by-products, and the reaction product yield and purity are low.

[0021] (2) The preparation method of the present invention uses pinacol diboronic acid ester as a reducing agent and β-cyclodextrin as a reducing aid. No metals are involved in the reaction process and no metal residues will appear. Moreover, the reaction time is short, the process is simple, and it is easy to realize industrial production. Attached Figure Description

[0022] Figure 1 The 1H NMR spectrum of methyl 4-aminobenzoate prepared in Example 2-1;

[0023] Figure 2 The carbon NMR spectrum of methyl 4-aminobenzoate prepared in Example 2-1;

[0024] Figure 3 The 1H NMR spectrum of 4-aminophenol prepared in Example 6;

[0025] Figure 4 The carbon NMR spectrum of 4-aminophenol prepared in Example 6;

[0026] Figure 5 The 1H NMR spectrum of 4-aminophenylamine prepared in Example 7;

[0027] Figure 6 The carbon NMR spectrum of 4-aminophenylamine prepared in Example 7;

[0028] Figure 7 The 1H NMR spectrum of ethyl 4-aminobenzoate prepared in Example 8;

[0029] Figure 8 The carbon NMR spectrum of ethyl 4-aminobenzoate prepared in Example 8;

[0030] Figure 9 The 1H NMR spectrum of isopropyl 4-aminobenzoate prepared in Example 9;

[0031] Figure 10 The carbon NMR spectrum of isopropyl 4-aminobenzoate prepared in Example 9;

[0032] Figure 11 The 1H NMR spectrum of 4-aminobenzoic acid n-butyl ester prepared in Example 10;

[0033] Figure 12 The carbon NMR spectrum of 4-aminobenzoic acid n-butyl ester prepared in Example 10;

[0034] Figure 13 The 1H NMR spectrum of 4-methylphenylamine prepared in Example 11;

[0035] Figure 14 The carbon NMR spectrum of 4-methylphenylamine prepared in Example 11;

[0036] Figure 15 The 1H NMR spectrum of 4-chlorophenylamine prepared in Example 12;

[0037] Figure 16 The carbon NMR spectrum of 4-chlorophenylamine prepared in Example 12;

[0038] Figure 17 The 1H NMR spectrum of 3-chlorophenylamine prepared in Example 13;

[0039] Figure 18 The carbon NMR spectrum of 3-chlorophenylamine prepared in Example 13;

[0040] Figure 19 The 1H NMR spectrum of 3-bromophenylamine prepared in Example 14;

[0041] Figure 20 The carbon NMR spectrum of 3-bromophenylamine prepared in Example 14;

[0042] Figure 21 The 1H NMR spectrum of 4-iodophenylamine prepared in Example 15;

[0043] Figure 22 The carbon NMR spectrum of 4-iodophenylamine prepared in Example 15;

[0044] Figure 23 The 1H NMR spectrum of 4-aminophenylcyanide prepared in Example 16;

[0045] Figure 24 The carbon NMR spectrum of 4-aminophenylcyanide prepared in Example 16. Detailed Implementation

[0046] The following detailed description is exemplary and intended to provide further illustration of the invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0047] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the exemplary embodiments of the present invention. When the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, components, and / or combinations thereof.

[0048] Unless otherwise specified, the experimental methods in the following examples all employ conventional techniques in this technical field or follow the conditions recommended by the manufacturer; reagents or instruments whose manufacturers are not specified are all commercially available products.

[0049] To enable those skilled in the art to better understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments.

[0050] Example 1: Screening experiment on the dosage of β-cyclodextrin

[0051] To investigate the effect of β-cyclodextrin dosage on the yield and conversion rate of methyl 4-aminobenzoate, Examples 1-1 to 1-3 were conducted in this invention. The specific details of Examples 1-1 to 1-3 are as follows:

[0052] Example 1-1:

[0053] The preparation method of methyl 4-aminobenzoate is as follows:

[0054] (1) An aromatic nitro compound, a reducing agent, a reducing aid, a base, and a solvent are added to a reactor and reacted at 100°C for 4 hours under normal pressure to obtain a reaction product; wherein, the aromatic nitro compound is methyl 4-nitrobenzoate, the reducing agent is pinacol diborate, and the molar ratio of pinacol diborate to the aromatic nitro compound is 3:1; the reducing aid is β-cyclodextrin, and the molar ratio of β-cyclodextrin to the aromatic nitro compound is 1:1; the base is potassium tert-butoxide, and the molar ratio of potassium tert-butoxide to the aromatic nitro compound is 1:1; the solvent is ethanol, and the molar ratio of ethanol to the aromatic nitro compound is 100:1.

[0055] The chemical reaction formula for preparing methyl 4-aminobenzoate from methyl 4-nitrobenzoate is as follows:

[0056]

[0057] (2) Ethyl acetate is added to the reaction product, with a molar ratio of ethyl acetate to aromatic nitro compound of 400:1. After mixing thoroughly, the mixture is filtered to obtain a first filtrate. The solvent and ethyl acetate in the first filtrate are removed to obtain a residue. Methanol is added to the residue, and after stirring to dissolve, it is recrystallized at -20°C with a molar ratio of methanol to methyl 4-nitrobenzoate of 300:1. The mixture is then filtered to obtain a second filtrate. The second filtrate is concentrated under reduced pressure and then separated by column chromatography to obtain the aromatic amino compound (methyl 4-aminobenzoate). The column used for column chromatography is an atmospheric pressure sintered sand column, and the eluent is a mixture of petroleum ether and ethyl acetate at a volume ratio of 50:1.

[0058] Examples 1-2:

[0059] The contents of Examples 1-2 are basically the same as those of Examples 1-1, except that the molar ratio of β-cyclodextrin to aromatic nitro compound is 0.5:1.

[0060] Examples 1-3:

[0061] The contents of Examples 1-3 are basically the same as those of Examples 1-1, except that the molar ratio of β-cyclodextrin to aromatic nitro compound is 0:1, that is, no β-cyclodextrin is added.

[0062] The reaction conversion rate and the yield of methyl 4-aminobenzoate prepared in Examples 1-1 to 1-3 were statistically analyzed (yield = actual product yield / theoretical product yield), and the results are shown in Table 1.

[0063] Table 1. Statistical results of the effect of β-cyclodextrin dosage on reaction conversion and methyl 4-aminobenzoate yield.

[0064]

[0065] As shown in Table 1, the highest conversion rate was achieved when the molar ratio of β-cyclodextrin to aromatic nitro compounds was 1:1, and the yield of methyl 4-aminobenzoate was also the highest (59%). Therefore, the preferred molar ratio of β-cyclodextrin to aromatic nitro compounds is 1:1.

[0066] Example 2: Solvent Screening Experiment

[0067] To investigate the effect of solvent type on the yield and conversion rate of methyl 4-aminobenzoate, Examples 2-1 to 2-3 were conducted in this invention. The specific details of Examples 2-1 to 2-3 are as follows:

[0068] Example 2-1:

[0069] The content of Example 2-1 is basically the same as that of Example 1-1, except that in step (1), the solvent is isopropanol, and the molar ratio of isopropanol to aromatic nitro compound is 100:1.

[0070] The 1H NMR spectrum and 1C NMR spectrum of methyl 4-aminobenzoate prepared in Example 2-1 are shown below. Figure 1 , Figure 2 As shown. By Figure 1 , Figure 2 It can be seen that the characteristic peaks of methyl groups on the formate ester are obvious, and the other hydrogens are consistent with the characteristics of the product, indicating that the synthesis of methyl 4-aminobenzoate was successful.

[0071] Example 2-2:

[0072] The content of Example 2-2 is basically the same as that of Example 1-1, except that in step (1), the solvent is 1,4-dioxane and the molar ratio of 1,4-dioxane to aromatic nitro compound is 100:1.

[0073] Examples 2-3:

[0074] The contents of Examples 2-3 are basically the same as those of Examples 1-1, except that in step (1), the solvent is water and the molar ratio of water to aromatic nitro compound is 100:1.

[0075] The reaction conversion rate and the yield of methyl 4-aminobenzoate prepared in Examples 2-1 to 2-3 were statistically analyzed (yield = actual product yield / theoretical product yield), and the results are shown in Table 2.

[0076] Table 2. Statistical results of solvent type, reaction conversion rate, and methyl 4-aminobenzoate yield.

[0077]

[0078] As shown in Table 2, the reaction conversion rate was the highest when isopropanol was used as the reaction solvent, and the yield of methyl 4-aminobenzoate also reached the highest level (64%). Therefore, isopropanol is the preferred reaction solvent.

[0079] Example 3: Screening experiment on the dosage of pinacol diboronate

[0080] To investigate the effect of the amount of pinacol diboronic acid ester on the yield and conversion rate of methyl 4-aminobenzoate, Examples 3-1 and 3-2 were conducted in this invention. The specific details of Examples 3-1 and 3-2 are as follows:

[0081] Example 3-1:

[0082] The content of Example 3-1 is basically the same as that of Example 2-1, except that in step (1), the molar ratio of the pinacol diboronic acid ester to the aromatic nitro compound is 1:1.

[0083] Example 3-2:

[0084] The content of Example 3-2 is basically the same as that of Example 2-1, except that in step (1), the molar ratio of the pinacol diboronic acid ester to the aromatic nitro compound is 2:1.

[0085] The reaction conversion rate and the yield of methyl 4-aminobenzoate prepared in Examples 3-1 to 3-2 were statistically analyzed (yield = actual product yield / theoretical product yield), and the results are shown in Table 3.

[0086] Table 3. Statistical results of solvent type, reaction conversion rate, and methyl 4-aminobenzoate yield.

[0087]

[0088] As shown in Table 3, the reaction conversion rate and the yield of methyl 4-aminobenzoate gradually increase with the increase of the molar ratio of pinacol diboronate to aromatic nitro compound. When the molar ratio of pinacol diboronate to aromatic nitro compound is 3:1, the yield of methyl 4-aminobenzoate is the highest, reaching 64%.

[0089] Example 4: Screening Experiment for Alkali Types

[0090] To investigate the effect of alkali type on the yield and conversion rate of methyl 4-aminobenzoate, Examples 4-1 to 4-5 were conducted in this invention. The specific details of Examples 4-1 to 4-5 are as follows:

[0091] Example 4-1:

[0092] The content of Example 4-1 is basically the same as that of Example 2-1, except that in step (1), the base is sodium methoxide and the molar ratio of sodium methoxide to aromatic nitro compound is 1:1.

[0093] Example 4-2:

[0094] The content of Example 4-2 is basically the same as that of Example 2-1, except that in step (1), the alkali is potassium hydroxide and the molar ratio of potassium hydroxide to aromatic nitro compound is 1:1.

[0095] Example 4-3:

[0096] The contents of Examples 4-3 are basically the same as those of Examples 2-1, except that in step (1), the alkali is sodium hydroxide and the molar ratio of sodium hydroxide to aromatic nitro compound is 1:1.

[0097] Example 4-4:

[0098] The contents of Examples 4-4 are basically the same as those of Examples 2-1, except that in step (1), the alkali is potassium carbonate and the molar ratio of potassium carbonate to aromatic nitro compound is 1:1.

[0099] Examples 4-5:

[0100] The contents of Examples 4-5 are basically the same as those of Examples 2-1, except that in step (1), the alkali is sodium carbonate and the molar ratio of sodium carbonate to aromatic nitro compound is 1:1.

[0101] The reaction conversion rates and the yields of methyl 4-aminobenzoate prepared in Examples 4-1 to 4-5 (yield = actual product yield / theoretical product yield) were statistically analyzed, and the results are shown in Table 4.

[0102] Table 4. Statistical results of solvent type, reaction conversion rate, and methyl 4-aminobenzoate yield.

[0103]

[0104] As shown in Table 4, the type of alkali has a significant impact on the conversion rate and the yield of methyl 4-aminobenzoate. When potassium tert-butoxide is used as the alkali, the conversion rate reaches the highest level (69%), and the yield of methyl 4-aminobenzoate also reaches the highest level (64%).

[0105] Example 5: Temperature Screening Experiment

[0106] To investigate the effect of temperature on the yield and conversion rate of methyl 4-aminobenzoate, Examples 5-1 to 5-3 were conducted in this invention. The specific details of Examples 5-1 to 5-3 are as follows:

[0107] Example 5-1:

[0108] The content of Example 5-1 is basically the same as that of Example 2-1, except that the reaction temperature in step (1) is 40°C.

[0109] Example 5-2:

[0110] The content of Example 5-2 is basically the same as that of Example 2-1, except that the reaction temperature in step (1) is 60°C.

[0111] Example 5-3:

[0112] The content of Example 5-3 is basically the same as that of Example 2-1, except that the reaction temperature in step (1) is 80°C.

[0113] The reaction conversion rate and the yield of methyl 4-aminobenzoate prepared in Examples 5-1 to 5-3 were statistically analyzed (yield = actual product yield / theoretical product yield), and the results are shown in Table 5.

[0114] Table 5. Statistical results of solvent type, reaction conversion rate, and methyl 4-aminobenzoate yield.

[0115]

[0116] As shown in Table 5, increasing the reaction temperature is beneficial to the reaction. The highest conversion rate and the highest yield of methyl 4-aminobenzoate (64%) were achieved at a temperature of 100℃. Therefore, the preferred reaction temperature is 100℃.

[0117] Example 6:

[0118] The preparation method of 4-aminophenol is as follows:

[0119] (1) 4-Nitrophenol (1 mmol), reducing agent, reducing aid, base and solvent are added to a reactor and reacted at 100 °C for 4 h under normal pressure to obtain the reaction product; wherein, the reducing agent is pinacol diborate, and the molar ratio of pinacol diborate to 4-nitrophenol is 3:1; the reducing aid is β-cyclodextrin, and the molar ratio of β-cyclodextrin to 4-nitrophenol is 1:1; the base is potassium tert-butoxide, and the molar ratio of potassium tert-butoxide to 4-nitrophenol is 1.2:1; the solvent is isopropanol, and the molar ratio of isopropanol to 4-nitrophenol is 100:1.

[0120] The chemical reaction formula for preparing 4-aminophenol from 4-nitrophenol is as follows:

[0121]

[0122] (2) Ethyl acetate was added to the reaction product, with a molar ratio of ethyl acetate to 4-nitrophenol of 400:1. After mixing thoroughly, the mixture was filtered to obtain a first filtrate. The solvent and ethyl acetate in the first filtrate were removed to obtain a residue. Methanol (molar ratio of methanol to 4-nitrophenol of 300:1) was added to the residue, and after stirring to dissolve, it was recrystallized at -20°C. The residue was then filtered to obtain a second filtrate. The second filtrate was concentrated under reduced pressure and then separated by column chromatography to obtain 4-aminophenol. The column used for column chromatography was an atmospheric pressure sintered sand column, and the eluent was a mixture of petroleum ether and ethyl acetate at a volume ratio of 10:1.

[0123] The 1H NMR spectrum and 1C NMR spectrum of the 4-aminophenol prepared in this embodiment are shown below. Figure 3 , Figure 4 As shown.

[0124] Depend on Figure 3 , Figure 4 It can be seen that the characteristic peaks of the amino group on 4-aminophenol are obvious, and the other hydrogens are consistent with the characteristics of the product, indicating that the synthesis of 4-aminophenol was successful.

[0125] Example 7:

[0126] The preparation method of 4-aminophenylamine is as follows:

[0127] (1) 4-Nitrophenylamine (1 mmol), reducing agent, reducing aid, base and solvent are added to a reactor and reacted at 100 °C for 3 h under normal pressure to obtain the reaction product; wherein, the reducing agent is pinacol diboronate, and the molar ratio of pinacol diboronate to 4-nitrophenylamine is 3:1; the reducing aid is β-cyclodextrin, and the molar ratio of β-cyclodextrin to 4-nitrophenylamine is 1:1; the base is potassium tert-butoxide, and the molar ratio of potassium tert-butoxide to 4-nitrophenylamine is 1.2:1; the solvent is isopropanol, and the molar ratio of isopropanol to 4-nitrophenylamine is 100:1.

[0128] The chemical reaction formula for preparing 4-aminophenylamine from 4-nitrophenylamine is as follows:

[0129]

[0130] (2) Ethyl acetate was added to the reaction product, with a molar ratio of ethyl acetate to 4-nitrophenylamine of 400:1. After mixing thoroughly, the mixture was filtered to obtain a first filtrate. The solvent and ethyl acetate in the first filtrate were removed to obtain a residue. Methanol was added to the residue, and the mixture was recrystallized at -20°C with a molar ratio of methanol to 4-nitrophenylamine of 300:1. The residue was then filtered to obtain a second filtrate. The second filtrate was concentrated under reduced pressure and then separated by column chromatography to obtain 4-aminophenylamine. The column used for column chromatography was an atmospheric pressure sintered sand column, and the eluent was a mixture of petroleum ether and ethyl acetate at a volume ratio of 10:1.

[0131] The 1H NMR spectrum and 1C NMR spectrum of the 4-aminophenylamine prepared in this embodiment are shown below. Figure 5 , Figure 6 As shown.

[0132] Depend on Figure 5 , Figure 6 It can be seen that the characteristic peaks of the amino group on 4-aminophenylamine are obvious, and the other hydrogens are consistent with the characteristics of the product, indicating that the synthesis of 4-aminophenylamine was successful.

[0133] Example 8:

[0134] The preparation method of ethyl 4-aminobenzoate is as follows:

[0135] (1) 1 mmol of 4-nitrobenzoate, a reducing agent, a reducing aid, a base, and a solvent were added to a reactor and reacted at 100 °C for 4 h under normal pressure to obtain the reaction product. The reducing agent was pinacol diboronate, and the molar ratio of pinacol diboronate to 4-nitrobenzoate was 3:1. The reducing aid was β-cyclodextrin, and the molar ratio of β-cyclodextrin to 4-nitrobenzoate was 1:1. The base was potassium tert-butoxide, and the molar ratio of potassium tert-butoxide to 4-nitrobenzoate was 1.2:1. The solvent was isopropanol, and the molar ratio of isopropanol to 4-nitrobenzoate was 100:1.

[0136] The chemical reaction formula for preparing ethyl 4-aminobenzoate from ethyl 4-nitrobenzoate is as follows:

[0137]

[0138] (2) Ethyl acetate was added to the reaction product, with a molar ratio of ethyl acetate to ethyl 4-nitrobenzoate of 400:1. After mixing thoroughly, the mixture was filtered to obtain a first filtrate. The solvent and ethyl acetate in the first filtrate were removed to obtain a residue. Methanol was added to the residue, and after stirring to dissolve, it was recrystallized at -20°C with a molar ratio of methanol to ethyl 4-nitrobenzoate of 300:1. The mixture was then filtered to obtain a second filtrate. The second filtrate was concentrated under reduced pressure and then separated by column chromatography to obtain ethyl 4-aminobenzoate. The column used for column chromatography was an atmospheric pressure sintered sand column, and the eluent was a mixture of petroleum ether and ethyl acetate at a volume ratio of 50:1.

[0139] The 1H and 1C NMR spectra of the 4-aminobenzoate ethyl ester prepared in this embodiment are shown below. Figure 7 , Figure 8 As shown.

[0140] Depend on Figure 7 , Figure 8 It can be seen that the characteristic peaks of amino groups on ethyl 4-aminobenzoate are obvious, and the other hydrogens are consistent with the product characteristics, confirming that ethyl 4-aminobenzoate was successfully synthesized.

[0141] Example 9:

[0142] The preparation method of isopropyl 4-aminobenzoate is as follows:

[0143] (1) 4-Nitrobenzoate isopropyl ester (1 mmol), reducing agent, reducing aid, base and solvent are added to a reactor and reacted at 100°C for 4 h under normal pressure to obtain the reaction product; wherein, the reducing agent is pinacol diboronate, and the molar ratio of pinacol diboronate to 4-nitrobenzoate is 3:1; the reducing aid is β-cyclodextrin, and the molar ratio of β-cyclodextrin to 4-nitrobenzoate is 1:1; the base is potassium tert-butoxide, and the molar ratio of potassium tert-butoxide to 4-nitrobenzoate is 1.2:1; the solvent is isopropanol, and the molar ratio of isopropanol to 4-nitrobenzoate is 100:1.

[0144] The chemical reaction formula for preparing isopropyl 4-aminobenzoate from isopropyl 4-nitrobenzoate is as follows:

[0145]

[0146] (2) Ethyl acetate was added to the reaction product, with a molar ratio of ethyl acetate to isopropyl 4-nitrobenzoate of 400:1. After mixing thoroughly, the mixture was filtered to obtain a first filtrate. The solvent and ethyl acetate in the first filtrate were removed to obtain a residue. Methanol was added to the residue, and after stirring to dissolve, it was recrystallized at -20°C with a molar ratio of methanol to isopropyl 4-nitrobenzoate of 300:1. The mixture was then filtered to obtain a second filtrate. The second filtrate was concentrated under reduced pressure and then separated by column chromatography to obtain isopropyl 4-aminobenzoate. The column used for column chromatography was an atmospheric pressure sintered sand column, and the eluent was a mixture of petroleum ether and ethyl acetate at a volume ratio of 50:1.

[0147] The 1H and 1C NMR spectra of isopropyl 4-aminobenzoate prepared in this embodiment are shown below. Figure 9 , Figure 10 As shown.

[0148] Depend on Figure 9 , Figure 10 It can be seen that the characteristic peaks of amino groups on isopropyl 4-aminobenzoate are obvious, and the other hydrogens are consistent with the product characteristics, indicating that isopropyl 4-aminobenzoate was successfully synthesized.

[0149] Example 10:

[0150] The preparation method of 4-aminobenzoic acid n-butyl ester is as follows:

[0151] (1) 4-Nitrobenzoate n-butyl ester (1 mmol), reducing agent, reducing aid, base and solvent are added to a reactor and reacted at 100°C for 4 h under normal pressure to obtain the reaction product; wherein, the reducing agent is pinacol diboronate, and the molar ratio of pinacol diboronate to 4-nitrobenzoate n-butyl ester is 3:1; the reducing aid is β-cyclodextrin, and the molar ratio of β-cyclodextrin to 4-nitrobenzoate n-butyl ester is 1:1; the base is potassium tert-butoxide, and the molar ratio of potassium tert-butoxide to 4-nitrobenzoate n-butyl ester is 1.2:1; the solvent is isopropanol, and the molar ratio of isopropanol to 4-nitrobenzoate n-butyl ester is 100:1.

[0152] The chemical reaction formula for preparing 4-aminobenzoic acid n-butyl ester from 4-nitrobenzoic acid n-butyl ester is as follows:

[0153]

[0154] (2) Ethyl acetate was added to the reaction product, with a molar ratio of ethyl acetate to 4-nitrobenzoate n-butyl ester of 400:1. After mixing thoroughly, the mixture was filtered to obtain a first filtrate. The solvent and ethyl acetate in the first filtrate were removed to obtain a residue. Methanol was added to the residue, and after stirring to dissolve, it was recrystallized at -20°C with a molar ratio of methanol to 4-nitrobenzoate n-butyl ester of 300:1. The mixture was then filtered to obtain a second filtrate. The second filtrate was concentrated under reduced pressure and then separated by column chromatography to obtain 4-aminobenzoate n-butyl ester. The column used for column chromatography was an atmospheric pressure sintered sand column, and the eluent was a mixture of petroleum ether and ethyl acetate at a volume ratio of 50:1.

[0155] The 1H and 1C NMR spectra of the 4-aminobenzoic acid n-butyl ester prepared in this embodiment are shown below. Figure 11 , Figure 12 As shown.

[0156] Depend on Figure 11 , Figure 12 It can be seen that the characteristic peaks of amino groups on n-butyl 4-aminobenzoate are obvious, and the other hydrogens are consistent with the product characteristics, confirming that the synthesis of n-butyl 4-aminobenzoate was successful.

[0157] Example 11:

[0158] The preparation method of 4-methylphenylamine is as follows:

[0159] (1) 4-Nitrotoluene (1 mmol), reducing agent, reducing aid, base and solvent are added to a reactor and reacted at 100 °C for 3 h under normal pressure to obtain the reaction product; wherein, the reducing agent is pinacol diborate, and the molar ratio of pinacol diborate to 4-nitrotoluene is 3:1; the reducing aid is β-cyclodextrin, and the molar ratio of β-cyclodextrin to 4-nitrotoluene is 1:1; the base is potassium tert-butoxide, and the molar ratio of potassium tert-butoxide to 4-nitrotoluene is 1.2:1; the solvent is isopropanol, and the molar ratio of isopropanol to 4-nitrotoluene is 100:1.

[0160] The chemical reaction formula for preparing 4-methylphenylamine from 4-nitrotoluene is as follows:

[0161]

[0162] (2) Ethyl acetate was added to the reaction product, with a molar ratio of ethyl acetate to 4-nitrotoluene of 400:1. After mixing thoroughly, the mixture was filtered to obtain a first filtrate. The solvent and ethyl acetate in the first filtrate were removed to obtain a residue. Methanol was added to the residue, and the mixture was recrystallized at -20°C with a molar ratio of methanol to 4-nitrotoluene of 300:1. The residue was then filtered to obtain a second filtrate. The second filtrate was concentrated under reduced pressure and then separated by column chromatography to obtain 4-methylphenylamine. The column used for column chromatography was an atmospheric pressure sintered sand column, and the eluent was a mixture of petroleum ether and ethyl acetate at a volume ratio of 50:1.

[0163] The 1H NMR spectrum and 1C NMR spectrum of the 4-methylphenylamine prepared in this embodiment are shown below. Figure 13 , Figure 14 As shown.

[0164] Depend on Figure 13 , Figure 14 It can be seen that the characteristic peaks of the amino group on 4-methylphenylamine are obvious, and the other hydrogens are consistent with the characteristics of the product, indicating that the synthesis of 4-methylphenylamine was successful.

[0165] Example 12:

[0166] The preparation method of 4-chlorophenylamine is as follows:

[0167] (1) 4-Nitrochlorobenzene (1 mmol), reducing agent, reducing aid, base and solvent are added to a reactor and reacted at 100 °C for 3 h under normal pressure to obtain the reaction product; wherein, the reducing agent is pinacol diborate, and the molar ratio of pinacol diborate to 4-nitrochlorobenzene is 3:1; the reducing aid is β-cyclodextrin, and the molar ratio of β-cyclodextrin to 4-nitrochlorobenzene is 1:1; the base is potassium tert-butoxide, and the molar ratio of potassium tert-butoxide to 4-nitrochlorobenzene is 1.2:1; the solvent is isopropanol, and the molar ratio of isopropanol to 4-nitrochlorobenzene is 100:1.

[0168] The chemical reaction formula for preparing 4-chlorophenylamine from 4-nitrochlorobenzene is as follows:

[0169]

[0170] (2) Ethyl acetate was added to the reaction product, with a molar ratio of ethyl acetate to 4-nitrochlorobenzene of 400:1. After mixing thoroughly, the mixture was filtered to obtain a first filtrate. The solvent and ethyl acetate in the first filtrate were removed to obtain a residue. Methanol was added to the residue, and after stirring to dissolve, it was recrystallized at -20°C with a molar ratio of methanol to 4-nitrochlorobenzene of 300:1. The residue was then filtered to obtain a second filtrate. The second filtrate was concentrated under reduced pressure and then separated by column chromatography to obtain 4-chlorophenylamine. The column used for column chromatography was an atmospheric pressure sintered sand column, and the eluent was a mixture of petroleum ether and ethyl acetate at a volume ratio of 50:1.

[0171] The 1H NMR spectrum and 1C NMR spectrum of the 4-chlorophenylamine prepared in this embodiment are shown below. Figure 15 , Figure 16 As shown.

[0172] Depend on Figure 15 , Figure 16 It can be seen that the characteristic peaks of the amino group on 4-chlorophenylamine are obvious, and the other hydrogens are consistent with the characteristics of the product, confirming that the synthesis of 4-chlorophenylamine was successful.

[0173] Example 13:

[0174] The preparation method of 3-chlorophenylamine is as follows:

[0175] (1) 3-Nitrochlorobenzene (1 mmol), reducing agent, reducing aid, base and solvent are added to a reactor and reacted at 100 °C for 4 h under normal pressure to obtain the reaction product; wherein, the reducing agent is pinacol diborate, and the molar ratio of pinacol diborate to 3-nitrochlorobenzene is 3:1; the reducing aid is β-cyclodextrin, and the molar ratio of β-cyclodextrin to 3-nitrochlorobenzene is 1:1; the base is potassium tert-butoxide, and the molar ratio of potassium tert-butoxide to 3-nitrochlorobenzene is 1.2:1; the solvent is isopropanol, and the molar ratio of isopropanol to 3-nitrochlorobenzene is 100:1.

[0176] The chemical reaction formula for preparing 3-chlorophenylamine from 3-nitrochlorobenzene is as follows:

[0177]

[0178] (2) Ethyl acetate was added to the reaction product, with a molar ratio of ethyl acetate to 3-nitrochlorobenzene of 400:1. After mixing thoroughly, the mixture was filtered to obtain a first filtrate. The solvent and ethyl acetate in the first filtrate were removed to obtain a residue. Methanol was added to the residue, and after stirring to dissolve, it was recrystallized at -20°C with a molar ratio of methanol to 3-nitrochlorobenzene of 300:1. The residue was then filtered to obtain a second filtrate. The second filtrate was concentrated under reduced pressure and then separated by column chromatography to obtain 3-chlorophenylamine. The column used for column chromatography was an atmospheric pressure sintered sand column, and the eluent was a mixture of petroleum ether and ethyl acetate at a volume ratio of 50:1.

[0179] The 1H NMR spectrum and 1C NMR spectrum of the 3-chlorophenylamine prepared in this embodiment are shown below. Figure 17 , Figure 18 As shown.

[0180] Depend on Figure 17 , Figure 18 It can be seen that the characteristic peaks of the amino group on 3-chlorophenylamine are obvious, and the other hydrogens are consistent with the characteristics of the product, confirming that the synthesis of 3-chlorophenylamine was successful.

[0181] Example 14:

[0182] The preparation method of 3-bromophenylamine is as follows:

[0183] (1) 3-Nitrobromobenzene (1 mmol), reducing agent, reducing aid, base and solvent are added to a reactor and reacted at 100 °C for 4 h under normal pressure to obtain the reaction product; wherein, the reducing agent is pinacol diborate, and the molar ratio of pinacol diborate to 3-nitrobromobenzene is 3:1; the reducing aid is β-cyclodextrin, and the molar ratio of β-cyclodextrin to 3-nitrobromobenzene is 1:1; the base is potassium tert-butoxide, and the molar ratio of potassium tert-butoxide to 3-nitrobromobenzene is 1.2:1; the solvent is isopropanol, and the molar ratio of isopropanol to 3-nitrobromobenzene is 100:1.

[0184] The chemical reaction formula for preparing 3-bromophenylamine from 3-nitrobromobenzene is as follows:

[0185]

[0186] (2) Ethyl acetate was added to the reaction product, with a molar ratio of ethyl acetate to 3-nitrobromobenzene of 400:1. After mixing thoroughly, the mixture was filtered to obtain a first filtrate. The solvent and ethyl acetate in the first filtrate were removed to obtain a residue. Methanol was added to the residue, and after stirring to dissolve, it was recrystallized at -20°C with a molar ratio of methanol to 300:1. The residue was then filtered to obtain a second filtrate. The second filtrate was concentrated under reduced pressure and then separated by column chromatography to obtain 3-bromophenylamine. The column used for column chromatography was an atmospheric pressure sintered sand column, and the eluent was a mixture of petroleum ether and ethyl acetate at a volume ratio of 50:1.

[0187] The 1H NMR spectrum and 1C NMR spectrum of the 3-bromophenylamine prepared in this embodiment are shown below. Figure 19 , Figure 20 As shown.

[0188] Depend on Figure 19 , Figure 20 It can be seen that the characteristic peaks of the amino group on 3-bromophenylamine are obvious, and the other hydrogens are consistent with the characteristics of the product, indicating that the synthesis of 3-bromophenylamine was successful.

[0189] Example 15:

[0190] The preparation method of 4-iodophenylamine is as follows:

[0191] (1) 4-Nitroiodobenzene (1 mmol), reducing agent, reducing aid, base and solvent are added to a reactor and reacted at 100 °C for 3 h under normal pressure to obtain the reaction product; wherein, the reducing agent is pinacol diborate, and the molar ratio of pinacol diborate to 4-nitroiodobenzene is 3:1; the reducing aid is β-cyclodextrin, and the molar ratio of β-cyclodextrin to 4-nitroiodobenzene is 1:1; the base is potassium tert-butoxide, and the molar ratio of potassium tert-butoxide to 4-nitroiodobenzene is 1.2:1; the solvent is isopropanol, and the molar ratio of isopropanol to 4-nitroiodobenzene is 100:1.

[0192] The chemical reaction formula for preparing 4-iodophenylamine from 4-nitroiodobenzene is as follows:

[0193]

[0194] (2) Ethyl acetate was added to the reaction product, with a molar ratio of ethyl acetate to 4-nitroiodobenzene of 400:1. After mixing thoroughly, the mixture was filtered to obtain a first filtrate. The solvent and ethyl acetate in the first filtrate were removed to obtain a residue. Methanol was added to the residue, and after stirring to dissolve, it was recrystallized at -20°C with a molar ratio of methanol to 4-nitroiodobenzene of 300:1. The residue was then filtered to obtain a second filtrate. The second filtrate was concentrated under reduced pressure and then separated by column chromatography to obtain 4-iodophenylamine. The column used for column chromatography was an atmospheric pressure sintered sand column, and the eluent was a mixture of petroleum ether and ethyl acetate at a volume ratio of 50:1.

[0195] The 1H NMR spectrum and 1C NMR spectrum of 4-iodophenylamine prepared in this embodiment are shown below. Figure 21 , Figure 22 As shown.

[0196] Depend on Figure 21 , Figure 22 It can be seen that the characteristic peaks of the amino group on 4-iodophenylamine are obvious, and the other hydrogens are consistent with the characteristics of the product, confirming that the synthesis of 4-iodophenylamine was successful.

[0197] Example 16:

[0198] The preparation method of 4-aminophenylcyanide is as follows:

[0199] (1) 4-Nitrophenylcyanide (1 mmol), reducing agent, reducing aid, base and solvent are added to a reactor and reacted at 100 °C for 3 h under normal pressure to obtain the reaction product; wherein, the reducing agent is pinacol diboronate, and the molar ratio of pinacol diboronate to 4-nitrophenylcyanide is 3:1; the reducing aid is β-cyclodextrin, and the molar ratio of β-cyclodextrin to 4-nitrophenylcyanide is 1:1; the base is potassium tert-butoxide, and the molar ratio of potassium tert-butoxide to 4-nitrophenylcyanide is 1.2:1; the solvent is isopropanol, and the molar ratio of isopropanol to 4-nitrophenylcyanide is 100:1.

[0200] The chemical reaction formula for the preparation of 4-aminophenylcyanide from 4-nitrophenylcyanide is as follows:

[0201]

[0202] (2) Ethyl acetate was added to the reaction product, with a molar ratio of ethyl acetate to 4-nitrophenylcyanide of 400:1. After mixing thoroughly, the mixture was filtered to obtain a first filtrate. The solvent and ethyl acetate in the first filtrate were removed to obtain a residue. Methanol was added to the residue, and after stirring to dissolve, it was recrystallized at -20°C with a molar ratio of methanol to 4-nitrophenylcyanide of 300:1. The residue was then filtered to obtain a second filtrate. The second filtrate was concentrated under reduced pressure and then separated by column chromatography to obtain 4-aminophenylcyanide. The column used for column chromatography was an atmospheric pressure sintered sand column, and the eluent was a mixture of petroleum ether and ethyl acetate at a volume ratio of 10:1.

[0203] The 1H NMR spectrum and 1C NMR spectrum of the 4-aminophenylcyanine prepared in this embodiment are shown below. Figure 23 , Figure 24 As shown.

[0204] Depend on Figure 23 , Figure 24 It can be seen that the characteristic peaks of the amino group on 4-aminophenylcyanide are obvious, and the other hydrogens are consistent with the characteristics of the product, confirming that the synthesis of 4-aminophenylcyanide was successful.

[0205] The yields of aromatic amino compounds prepared by different reactions in Examples 6-16 were statistically analyzed, and the results are shown in Table 6.

[0206] Table 6. Yields of aromatic amino compounds prepared by different reactions in Examples 6-16

[0207] Example Product Name Yield Example 6 4-Aminophenol 84％ Example 7 4-Aminophenylamine 86％ Example 8 ethyl 4-aminobenzoate 61％ Example 9 Isopropyl 4-aminobenzoate 54％ Example 10 4-Aminobenzoate n-Butyl ester 91％ Example 11 4-Methylphenylamine 75％ Example 12 4-Chlorophenylamine 85％ Example 13 3-Chlorophenylamine 78％ Example 14 3-Bromophenylamine 68％ Example 15 4-Iodophenylamine 86％ Example 16 4-Aminophenylcyanide 72％

[0208] As shown in Table 6, aromatic amino compounds can be prepared by using different aromatic nitro compounds as raw materials according to the preparation method of the present invention. The yield of aromatic amino compounds is relatively high, reaching 54% to 91%. Moreover, no metals are involved in the reaction process, and no metal residues will appear.

[0209] The above description is only a preferred embodiment of the present invention, but is not limited to the above examples. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing an aromatic amino compound, characterized in that, Includes the following steps: An aromatic nitro compound, a reducing agent, a reducing aid, an alkali, and a solvent are added to a reactor and reacted at 80–110°C for 2–4 hours to obtain a reaction product. The reaction product is then post-treated to obtain an aromatic amino compound. The reducing agent is pinacol diboronate, and the reducing aid is β-cyclodextrin. The molar ratio of pinacol diboronate to the aromatic nitro compound is (3–4):1; the molar ratio of β-cyclodextrin to the aromatic nitro compound is (1–2):1; and the aromatic nitro compound contains a sensitive group. The sensitive group is at least one of -NH2, -OH, and -COOR, where R in -COOR is any one of methyl, ethyl, isopropyl, and n-butyl; the base is at least one of potassium tert-butoxide, sodium methoxide, sodium hydroxide, and potassium hydroxide; the solvent is at least one of isopropanol, methanol, and ethanol; and the aromatic nitro compound is methyl 4-nitrobenzoate, 4-nitrophenol, 4-nitrophenylamine, ethyl 4-nitrobenzoate, isopropyl 4-nitrobenzoate, or n-butyl 4-nitrobenzoate.

2. The preparation method according to claim 1, characterized in that, The molar ratio of the alkali to the aromatic nitro compound is (1-3):

1.

3. The preparation method according to claim 2, characterized in that, The molar ratio of the solvent to the aromatic nitro compound is (50-150):

1.

4. The preparation method according to any one of claims 1-3, characterized in that, The specific post-processing steps are as follows: Ethyl acetate is added to the reaction product, mixed evenly, and then filtered to obtain the first filtrate; the solvent and ethyl acetate in the first filtrate are removed to obtain the residue; methanol is added to the residue, stirred and dissolved, and then recrystallized at -20 to -15°C, and then filtered to obtain the second filtrate; the second filtrate is concentrated under reduced pressure and then separated by column chromatography to obtain the aromatic amino compound.

5. The preparation method according to claim 4, characterized in that, The eluent used in the column chromatography is a mixture of petroleum ether and ethyl acetate; the volume ratio of petroleum ether to ethyl acetate in the eluent is (10-50):1.

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