Method, catalyst and application for synthesizing aniline compounds

Abstract

The present invention provides a method for synthesizing aniline compounds, and also provides a catalyst and its application. The method for synthesizing aniline compounds according to the present invention comprises the following steps: using a molybdenum-based oxide and activated carbon as catalysts, and hydrazine hydrate as a reducing agent to reduce an aromatic nitro compound to an aniline compound. The method for synthesizing aniline compounds provided by the present invention has the characteristics of being green and efficient, and being easy to be applied industrially, etc.

Description

Technical Field

[0001] The present invention relates to a method for synthesizing aniline compounds, in particular to a method for preparing aniline compounds by reducing aromatic nitro compounds, and also relates to a catalyst and its application in the synthesis of aniline compounds. Background Art

[0002] Aniline compounds are a class of important chemical raw materials and are widely used in antioxidants, dye intermediates, imaging materials, pharmaceuticals, and pesticide chemicals. They are mainly prepared by reducing aromatic nitro compounds to the corresponding aniline compounds. Currently, the methods for reducing aromatic nitro compounds to prepare aniline compounds in industry mainly include metal reduction method, sulfide reduction method, catalytic hydrogenation reduction method, hydrazine hydrate reduction method, and electrochemical reduction method. Among them, the hydrazine hydrate reduction method has the characteristics of environmental friendliness and simplicity, but the disadvantages are that it requires noble metal catalysts, has a long reaction time, and also requires a large amount of non-environmentally friendly solvents.

[0003] Both Chinese Patent Application CN105669338 and the literature published in Green Chem. (2016, 18, 2435 - 2442) describe a method for reducing a series of aromatic nitro compounds to aromatic amino compounds using molybdenum-based oxides as metal catalysts and hydrazine hydrate as a reducing agent. Although the catalytic system provided by this method can catalyze the reduction of simple nitro compounds such as nitrobenzene to aniline compounds, it also has obvious disadvantages: one is that the molybdenum-based oxide catalyst used needs to be specially prepared into MoO2 nanoparticles, which need to be reduced at a high temperature of 350 - 600 °C in a hydrogen atmosphere, or hydrated for a long time in an autoclave at 160 - 250 °C, or strongly reduced at 500 °C in N2 / H2 and then treated with highly corrosive hydrogen fluoride; the preparation conditions of the used MoO2 nanoparticles are very harsh and extremely dangerous, and it is not easy to obtain. The second is that the catalyst dosage is large. In the reduction of nitrobenzene, the molar feeding amount is as high as 31%, and the mass feeding ratio is 32%, which is far from the requirement of the catalytic amount. The third is that the recycling effect of the catalyst is not good, and the best number of recycling times does not exceed 3 times. The existence of these disadvantages greatly limits the practical application of this method in industrialization. The main reasons for the existence of these disadvantages are as follows: on the one hand, the self-made molybdenum-based oxide catalyst needs to go through strict preparation means, the preparation process is not easy to control, the components of the prepared catalyst are uncertain, and stable catalytic performance cannot be guaranteed; on the other hand, the molar feeding amount of the catalyst is as high as more than 30%, which is no longer suitable as a catalyst, and there are problems in the selection of the catalyst and the catalytic system. Therefore, it is necessary to develop a new method for green and efficient synthesis of aniline compounds that is more suitable for industrial application. Summary of the Invention

[0004] In order to improve the deficiencies existing in the prior art, the present invention provides a new method for synthesizing aniline compounds that is green and efficient and easy to be applied industrially. At the same time, the present invention also provides a catalyst and the application of this catalyst in the synthesis of aniline compounds.

[0005] In order to achieve its purpose, the present invention adopts the following technical solutions:

[0006] In the first aspect of the present invention, a method for synthesizing aniline compounds is provided. The method includes the following steps: using a molybdenum-based oxide and activated carbon as catalysts and hydrazine hydrate as a reducing agent to reduce an aromatic nitro compound to an aniline compound.

[0007] When synthesizing aniline compounds by the method of the present invention, using a molybdenum-based oxide and activated carbon as catalysts can reduce the amount of molybdenum-based oxide in the catalyst. The catalyst is easy to recycle. After simple filtration, the catalyst can be directly recycled multiple times, and the number of recycling times can reach more than 10 times. This can not only reduce the process cost but also reduce the production frequency of solid waste. The so-called simple filtration can be, for example, suction filtration, nitrogen pressure filtration and other filtration methods. The filtration method is not limited thereto as long as the filtration purpose can be achieved. Based on this, in a preferred embodiment of the present invention, the method of the present invention further includes the following steps: after the reaction is completed, filtering the reaction mixture obtained, and using the obtained filter residue as the recycled catalyst for recycling, which can be directly recycled without treatment. For the obtained filtrate, in some specific embodiments, the organic phase is separated by extraction and other methods, and further operations such as washing and concentration are performed on the organic phase.

[0008] When the method of the present invention synthesizes aniline compounds, the weight ratio of the molybdenum-based oxide to the activated carbon is preferably 1:1-10, more preferably 1:2-5. Under this preferred ratio, it is beneficial to uniformly load the molybdenum-based oxide on the activated carbon to increase the contact area between the catalyst and the aromatic nitro compound, thereby enhancing the catalytic effect of the molybdenum-based oxide and ultimately increasing the reaction rate.

[0009] In the method for synthesizing aniline compounds provided by the present invention, introducing activated carbon into the reaction system can greatly reduce the amount of molybdenum-based oxide in the catalyst. In a preferred embodiment, the molar ratio of the molybdenum-based oxide to the aromatic nitro compound can be 0.001-0.1:1, more preferably 0.01-0.03:1.

[0010] In a preferred embodiment of the present invention, the molybdenum-based oxide includes the chemical formula MoO xOne or more of the compounds of (x = 2-3), wherein when x = 2 or 3, it represents MoO2 or MoO3 with a uniform valence state; when x is a non-integer between 2-3, it represents a molybdenum-based oxide with a non-integer ratio of average valence state between +4 and +6 or represents partially reduced MoO3; more preferably, the molybdenum-based oxide is MoO2, and better reaction rate and product yield can be obtained.

[0011] For the method for synthesizing aniline compounds provided by the present invention, the molybdenum-based oxide and activated carbon used as catalysts can be premixed before being put into the reaction system, or the two can be separately put into the reaction system without prior mixing. The molybdenum-based oxide and activated carbon used in the present invention can be commercially available products on the market. The molybdenum-based oxide does not need to be nanoscale, and conventional commercial-grade reagents can be used. As an example, for instance, molybdenum dioxide purchased from Sinopharm Chemical Reagent Co., Ltd. etc., and activated carbon with models 772, 778, 779, 812, 862, 864 respectively purchased from the Activated Carbon Branch of Hangzhou Wood Co., Ltd. etc.

[0012] When synthesizing aniline compounds by the method of the present invention, the molar ratio of hydrazine hydrate to aromatic nitro compounds is preferably 1.5-10:1, more preferably 2-4:1, and the amount of hydrazine hydrate in the molar ratio here is calculated based on pure hydrazine hydrate.

[0013] When synthesizing aniline compounds by the method of the present invention, the temperature of the reduction reaction is preferably controlled between 25°C and the temperature that can keep the reaction system in reflux. The method of the present invention can be carried out under relatively mild conditions, and the temperature of the reduction reaction is more preferably controlled at 25-35°C. When the present invention synthesizes aniline compounds, it does not require nitrogen protection and can be carried out in an environment connected to air. The reaction process is easy to control, the operation is very simple and convenient, and the applicable range is wider.

[0014] The method for synthesizing aniline compounds of the present invention is not limited to reducing an aromatic nitro compound with a specific structure to the corresponding aniline compound. As a more preferred embodiment of the present invention, the method of the present invention reduces the aromatic nitro compound shown in structural formula (I) to the aniline compound shown in structural formula (II):

[0015]

[0016] Wherein, R1-R5 are the same or different from each other, and R1-R5 are each independently selected from a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a phenyl group or its substituted derivative, a benzyl group or its substituted derivative, SR6, OR7, COOR8, CONR9R 10 or CN; R6, R7, R8, R9 and R 10Each independently selected from a hydrogen atom, a C1-C6 alkyl group, a phenyl group or a substituted derivative thereof, a benzyl group or a substituted derivative thereof, R9 and R 10 are the same or different.

[0017] In the "phenyl group or a substituted derivative thereof" described in the text, the derivative is a mono-substituted or multi-substituted phenyl derivative, and the substituents may be the same or different. Preferably, it is a phenyl derivative having a C1-C6 alkyl group, a halogen, SR6, OR7, COOR8, CONR9R 10 or a CN substituent or the like on the phenyl group. When it is a multi-substituted phenyl derivative, each substituent may be independently selected from these preferred groups. The meaning of "multi" in the "multi-substituted" is two or more.

[0018] In the "benzyl group or a substituted derivative thereof" described in the text, the derivative is a mono-substituted or multi-substituted benzyl derivative, and the substituents may be the same or different. Preferably, it is a benzyl benzene having a C1-C6 alkyl group, a halogen, SR6, OR7, COOR8, CONR9R 10 or a CN substituent or the like on the benzyl group. When it is a multi-substituted benzyl derivative, each substituent may be independently selected from these preferred groups. The meaning of "multi" in the "multi-substituted" is two or more.

[0019] R6, R7, R8, R9 and R appearing in the text 10 are preferably each independently selected from a hydrogen atom, a C1-C6 alkyl group, a phenyl group or a substituted derivative thereof, a benzyl group or a substituted derivative thereof, R9 and R 10 are the same or different.

[0020] As an example, the aromatic nitro compound described in the present invention may be, for example, nitrobenzene, 4-nitrotoluene, 4-nitroanisole, o-chloronitrobenzene, o-fluoronitrobenzene, m-chloronitrobenzene, m-fluoronitrobenzene, p-chloroaniline, m-fluoronitrobenzene, 2-(2,4-dimethylphenylthio)nitrobenzene, 3-(2,4-dimethylphenylthio)nitrobenzene, 4-(2,4-dimethylphenylthio)nitrobenzene, p-nitrobenzonitrile, 6-fluoro-2-nitrobenzoic acid, 4,5-bis(2-methoxyethoxy)-2-nitrobenzonitrile or 4-methoxy-5-(3-morpholinopropyl)-2-nitrobenzonitrile, etc.

[0021] The reduction reaction of the present invention is carried out in the presence of a solvent, and the solvent is a proton solvent, preferably one or more of water, methanol, ethanol or isopropanol, and more preferably ethanol.

[0022] In the method for synthesizing aniline compounds of the present invention, the hydrazine hydrate used can be a commercially available raw material, which can be an aqueous solution of hydrazine hydrate with a mass concentration of 40-80%, for example, an aqueous solution of hydrazine hydrate with a mass concentration of 50% or 80%.

[0023] The second aspect of the present invention provides a catalyst, which comprises a molybdenum-based oxide and activated carbon. Preferably, the weight ratio of the molybdenum-based oxide to the activated carbon is 1:1-10, and more preferably 1:2-5.

[0024] In the catalyst of the present invention, the molybdenum-based oxide preferably comprises one or more of the compounds with the chemical formula MoO x (x = 2-3), where when x = 2 or 3, it represents MoO2 or MoO3 with a uniform valence state; when x is a non-integer between 2-3, it represents a molybdenum-based oxide with a non-integer ratio of the average valence state between +4 and +6 or represents partially reduced MoO3; more preferably, the molybdenum-based oxide is MoO2.

[0025] In the catalyst of the present invention, the molybdenum-based oxide and the activated carbon can be in a mixed form or stored separately. The molybdenum-based oxide and the activated carbon can be stored in a mixture for use and added to the reaction system in the form of a mixture, or they can be stored independently for use and added to the reaction system separately.

[0026] The third aspect of the present invention also provides the application of the above-mentioned catalyst. This catalyst can be applied to catalyze the reduction of aromatic nitro compounds to aniline compounds. Preferably, this catalyst is applied to a reaction system using hydrazine hydrate as a reducing agent to catalyze the reduction of aromatic nitro compounds to aniline compounds. The molybdenum-based oxide and the activated carbon in the catalyst are pre-mixed and then added to the reaction system, or the two are added to the reaction system separately.

[0027] Furthermore, in the preferred embodiment, after the reduction reaction is completed, the mixture obtained from the reaction is filtered, and the filter residue is recovered as a catalyst for recycling. The recovered catalyst can be recycled more than 10 times while still maintaining high catalytic activity, and only simple filtration is required for recovery.

[0028] The technical solution provided by the present invention has the following beneficial effects:

[0029] (1) Adding a small amount of activated carbon to the reduction system of the present invention can greatly reduce the usage amount of molybdenum-based oxides in the catalyst. Moreover, the used catalyst is convenient for recycling. Through simple filtration, the catalyst can be directly recycled and reused multiple times, which not only reduces the process cost but also decreases the generation frequency of solid waste and the possibility of a large amount of metal ions remaining in the product. In the prior art, for example, after the reaction with a conventional ferric chloride catalyst, direct filtration is carried out, but iron ions still cannot be completely removed. This is because ferric chloride will ionize to generate iron ions in an aqueous solution, resulting in the presence of iron ions in the reaction solution and increasing the possibility of iron ion residue. In addition, for some heavy metal catalysts such as platinum and palladium, higher requirements are imposed on the detection of their residues. For the molybdenum-based oxides of the present invention (such as molybdenum dioxide), it is in an oxidized state and will not ionize even in an aqueous solution. Therefore, metal molybdenum can be removed by direct filtration, reducing the possibility of molybdenum existing in the solution.

[0030] (2) In the reaction system of the present invention, both molybdenum dioxide and activated carbon in the used catalyst are commodity items, which are inexpensive and easily available. The most crucial point is that since commercial-grade catalysts can be used, and the composition of commercial-grade catalysts is fixed, the quality is guaranteed, and the catalytic performance is stable. The purchased catalyst can be directly used without requiring strict pre-preparation treatment. Molybdenum dioxide does not need to be nanoscale.

[0031] (3) The method for synthesizing aniline compounds provided by the present invention also has the characteristics of a wider application range, milder reaction conditions, and simpler and more convenient operation. It does not require N2 protection and can carry out the reaction in an environment connected to the air. The reaction process is easy to control, the reaction is complete, and the obtained product has relatively high purity and yield. Detailed implementation mode

[0032] To better understand the technical solution of the present invention, the content of the present invention will be further elaborated below in combination with examples. However, the content of the present invention is not limited to the following examples only.

[0033] Unless otherwise specified, the "%" involved in the examples and comparative examples is the mass percentage.

[0034] Some of the experimental raw materials and detection instruments used in the examples or comparative examples are described below:

[0035] Raw materials, reagents and solvents: All the raw materials used are commercially available products; the reagents such as 50% and 80% mass concentration hydrazine hydrate aqueous solutions, and molybdenum dioxide are all purchased from Sinopharm Chemical Reagent Co., Ltd.; the activated carbon is purchased from the activated carbon branch of Hangzhou Wood Co., Ltd.; the solvents used are domestic analytical pure reagents, all purchased from Sinopharm Chemical Reagent Co., Ltd., and have not been treated in any way before use.

[0036] Liquid chromatography: Agilent 1206.

[0037] Nuclear magnetic resonance spectrometer: Bruker DRX-400FT (Germany), 1 1H NMR was measured in CDCl3, DMSO-d6 and D2O. Chemical shifts were referenced to tetramethylsilane (TMS) in ppm.

[0038] Example 1: Synthesis of aniline

[0039] 1.58 g (10 mmol) of nitrobenzene, 25.6 mg (0.2 mmol) of molybdenum dioxide, 76.8 mg of activated carbon, 30 ml of absolute ethanol were added to a 50 ml three-necked flask. 1.2 g (20 mmol) of hydrazine hydrate (80%) was added dropwise at room temperature. After the addition was complete, the reaction was carried out at room temperature for 2 h. TLC monitoring showed that the reaction was complete, and then the mixture was filtered. The filtrate was concentrated, then 20 mL of ethyl acetate and 10 ml of water were added for extraction. The organic phase was washed with water and then concentrated to obtain 1.22 g of the target product as a light brown liquid, with a yield of 100% and an HPLC purity of 99.8%. 1 1H NMR (400 MHz, CDCl3) δ 7.10 - 7.14 (m, 2H), 6.78 - 6.73 (m, 3H).

[0040] Example 2: Synthesis of 4-methylaniline

[0041] 1.37 g (10 mmol) of 4-nitrotoluene, 25.6 mg (0.2 mmol) of molybdenum dioxide, 76.8 mg of activated carbon, 30 ml of absolute ethanol were added to a 50 ml three-necked flask. 1.2 g (20 mmol) of hydrazine hydrate (80%) was added dropwise at room temperature. After the addition was complete, the reaction was carried out at room temperature for 2 h. TLC monitoring showed that the reaction was complete, and then the mixture was filtered. The filtrate was concentrated, then 20 mL of ethyl acetate and 10 ml of water were added for extraction. The organic phase was washed with water and then concentrated to obtain 1.05 g of the target product as a colorless solid, with a yield of 98% and an HPLC purity of 99.8%. 1 1H NMR (400 MHz, CDCl3) δ 7.13 - 7.17 (m, 2H), 6.74 - 6.69 (m, 2H), 2.3 (s, 3H).

[0042] Example 3: Synthesis of 4-methoxyaniline

[0043] Add 1.53 g (10 mmol) of 4-nitroanisole, 25.6 mg (0.2 mmol) of molybdenum dioxide, 76.8 mg of activated carbon, and 30 ml of absolute ethanol to a 50 ml three-necked flask. At room temperature, add dropwise 1.2 g (20 mmol) of hydrazine hydrate (80%). After the addition is complete, react at room temperature for 1.5 h. TLC monitoring shows that the reaction is complete. Filter, concentrate the filtrate, add 20 mL of ethyl acetate and 10 ml of water, and extract. Wash the organic phase with water and concentrate to obtain 1.2 g of a colorless solid of the target product, with a yield of 97.6% and an HPLC purity of 99.6%. 1 HNMR (400 MHz, CDCl3) δ 7.11 - 7.14 (m, 2H), 6.75 - 6.71 (m, 2H), 3.65 (s, 3H).

[0044] Example 4: Synthesis of o-chloroaniline

[0045] Add 1.58 g (10 mmol) of o-chloronitrobenzene, 25.6 mg (0.2 mmol) of molybdenum dioxide, 76.8 mg of activated carbon, and 30 ml of absolute ethanol to a 50 ml three-necked flask. At room temperature, add dropwise 1.2 g (20 mmol) of hydrazine hydrate (80%). After the addition is complete, react at room temperature for 3 h. TLC monitoring shows that the reaction is complete. Filter, concentrate the filtrate, add 20 mL of ethyl acetate and 10 ml of water, and extract. Wash the organic phase with water and concentrate to obtain 1.22 g of a light brown liquid of the target product, with a yield of 95.3% and an HPLC purity of 99.7%. 1 HNMR (400 MHz, CDCl3) δ 7.31 - 7.34 (m, 1H), δ 7.13 - 7.16 (m, 1H), 6.83 - 6.86 (m, 1H), 6.71 - 6.73 (m, 1H), 5.28 (s, 2H).

[0046] Example 5: Synthesis of o-fluoroaniline

[0047] Add 1.41 g (10 mmol) of o-fluoronitrobenzene, 25.6 mg (0.2 mmol) of molybdenum dioxide, 76.8 mg of activated carbon, and 30 ml of absolute ethanol to a 50 ml three-necked flask. At room temperature, add dropwise 1.92 g (20 mmol) of hydrazine hydrate (50%). After the addition is complete, react at room temperature for 4.5 h. TLC monitoring shows that the reaction is complete. Filter, concentrate the filtrate, add 20 mL of ethyl acetate and 10 ml of water, and extract. Wash the organic phase with water and concentrate to obtain 1.05 g of a light yellow liquid of the target product, with a yield of 94.6% and an HPLC purity of 99%. 1 HNMR (400 MHz, CDCl3) δ 7.30 - 7.33 (m, 1H), δ 7.13 - 7.16 (m, 1H), 6.82 - 6.85 (m, 1H), 6.75 - 6.78 (m, 1H), 5.29 (s, 2H).

[0048] Example 6: Synthesis of m-Chloroaniline

[0049] Add 1.58 g (10 mmol) of m-chloronitrobenzene, 25.6 mg (0.2 mmol) of molybdenum dioxide, 76.8 mg of activated carbon, and 30 ml of absolute ethanol to a 50 ml three-necked flask. Dropwise add 1.25 g (20 mmol) of hydrazine hydrate (80%) at room temperature. After the addition is complete, react at room temperature for 5 h. TLC monitoring shows that the reaction is complete. Filter, concentrate the filtrate, add 20 mL of ethyl acetate and 10 ml of water, and extract. After washing the organic phase with water and concentrating, 1.21 g of a light brown liquid, the target product, is obtained, with a yield of 94.5% and an HPLC purity of 98.7%.

[0050] 1 HNMR (400 MHz, CDCl3) δ 7.15 - 7.18 (m, 1H), δ 7.09 - 7.13 (m, 1H), 6.83 - 6.86 (m, 1H), 6.64 - 6.67 (m, 1H), 5.34 (s, 2H).

[0051] Example 7: Synthesis of m-Fluoroaniline

[0052] Add 1.41 g (10 mmol) of m-fluoronitrobenzene, 25.6 mg (0.2 mmol) of molybdenum dioxide, 76.8 mg of activated carbon, and 30 ml of absolute ethanol to a 50 ml three-necked flask. Dropwise add 1.92 g (20 mmol) of hydrazine hydrate (50%) at room temperature. After the addition is complete, react at room temperature for 4.5 h. TLC monitoring shows that the reaction is complete. Filter, concentrate the filtrate, add 20 mL of ethyl acetate and 10 ml of water, and extract. After washing the organic phase with water and concentrating, 1.05 g of a light yellow liquid, the target product, is obtained, with a yield of 94.6% and an HPLC purity of 98.9%. 1 HNMR (400 MHz, CDCl3) δ 7.10 - 7.13 (m, 1H), δ 7.93 - 7.96 (m, 1H), 6.65 - 6.68 (m, 1H), 6.54 - 6.57 (m, 1H), 5.30 (s, 2H).

[0053] Example 8: Synthesis of p-Chloroaniline

[0054] Add 1.58 g (10 mmol) of p-chloronitrobenzene, 25.6 mg (0.2 mmol) of molybdenum dioxide, 76.8 mg of activated carbon, and 30 ml of absolute ethanol to a 50 ml three-necked flask. Dropwise add 1.2 g (20 mmol) of hydrazine hydrate (80%) at room temperature. After the addition is complete, react at room temperature for 5 h. TLC monitoring shows that the reaction is complete. Filter and collect the residue. Concentrate the filtrate, add 20 mL of ethyl acetate and 10 ml of water, and extract. After washing the organic phase with water and concentrating, 1.24 g of a light yellow crystalline substance, the target product, is obtained, with a yield of 96.9% and an HPLC purity of 99.5%. 1HNMR (400 MHz, CDCl3) δ 7.14 - 7.17 (m, 2H), 6.61 - 6.58 (m, 2H), 5.49 (s, 2H).

[0055] Example 9: Synthesis of p-Fluoroaniline

[0056] Add 1.41 g (10 mmol) of p-fluoronitrobenzene, 25.6 mg (0.2 mmol) of molybdenum dioxide, 76.8 mg of activated carbon, and 30 ml of absolute ethanol to a 50 ml three-necked flask. At room temperature, add 1.25 g (20 mmol) of hydrazine hydrate (80%) dropwise. After the addition, react at room temperature for 4.5 h. TLC monitoring shows that the reaction is complete. Filter, concentrate the filtrate, add 20 mL of ethyl acetate and 10 ml of water, and extract. The organic phase is washed with water and then concentrated to obtain 1.08 g of the target product as a light yellow liquid, with a yield of 97.3% and an HPLC purity of 99.4%. 1 HNMR (400 MHz, CDCl3) δ 7.04 - 7.01 (m, 2H), 6.71 - 6.68 (m, 2H), 5.45 (s, 2H).

[0057] Example 10: Synthesis of 2-(2,4-Dimethylphenylthio)aniline

[0058] Add 2.00 g (7.70 mmol) of 2-(2,4-dimethylphenylthio)nitrobenzene, 0.01 g (0.077 mmol) of molybdenum dioxide, 0.05 g of activated carbon, and 30 ml of absolute ethanol to a 50 ml three-necked flask. At room temperature, add 0.92 g (15.0 mmol) of hydrazine hydrate (80%) dropwise. After the addition, react at room temperature for 6 h. TLC monitoring shows that the reaction is complete. Filter and collect the residue. Concentrate the filtrate, add 20 mL of ethyl acetate and 10 ml of water, and extract. The organic phase is washed with water and then concentrated to obtain 1.64 g of the target product as a white solid, with a yield of 93% and an HPLC purity of 99.5%.

[0059] 1 HNMR (400 MHz, DMSO-d6) δ 7.15 - 7.20 (m, 2H), 7.02 (s, 1H), 6.81 - 6.85 (m, 2H), 6.58 - 6.65 (m, 2H), 5.28 (s, 2H), 2.31 (s, 3H), 2.20 (s, 3H).

[0060] Example 11: Synthesis of 3-(2,4-Dimethylphenylthio)aniline

[0061] Add 2.00 g (7.70 mmol) of 3-(2,4-dimethylphenylthio)nitrobenzene, 0.01 g (0.077 mmol) of molybdenum dioxide, 0.05 g of activated carbon, and 20 ml of absolute ethanol to a 50 ml three-necked flask. At room temperature, add 1.47 g (15.0 mmol) of hydrazine hydrate (50%) dropwise. After the addition is complete, react at room temperature for 5.5 h. TLC monitoring shows that the reaction is complete. Filter, concentrate the filtrate, add 20 mL of ethyl acetate and 10 ml of water, and extract. The organic phase is washed with water and concentrated to obtain 1.6 g of the target product as a white solid, with a yield of 90.4% and an HPLC purity of 99.1%. 1 HNMR (400 MHz, DMSO-d6) δ 7.35 - 7.38 (m, 1H), δ 7.17 - 7.24 (m, 2H), δ 7.09 - 7.15 (m, 1H), 7.04 (s, 1H), 6.92 - 6.98 (m, 2H), 6.58 - 6.65 (m, 1H), 5.20 (s, 2H), 2.30 (s, 3H), 2.21 (s, 3H).

[0062] Example 12: Synthesis of 4-(2,4-dimethylphenylthio)aniline

[0063] Add 2.00 g (7.70 mmol) of 4-(2,4-dimethylphenylthio)nitrobenzene, 0.01 g (0.077 mmol) of molybdenum dioxide, 0.05 g of activated carbon, and 20 ml of absolute ethanol to a 50 ml three-necked flask. At room temperature, add 1.47 g (15.0 mmol) of hydrazine hydrate (50%) dropwise. After the addition is complete, react at room temperature for 6.5 h. TLC monitoring shows that the reaction is complete. Filter, concentrate the filtrate, add 20 mL of ethyl acetate and 10 ml of water, and extract. The organic phase is washed with water and concentrated to obtain 1.67 g of the target product as a white solid, with a yield of 94.4% and an HPLC purity of 99.3%. 1 HNMR (400 MHz, DMSO-d6) δ 7.18 - 7.23 (m, 1H), 7.02 (s, 1H), 6.80 - 6.87 (m, 3H), 6.60 - 6.66 (m, 2H), 5.28 (s, 2H), 2.31 (s, 3H), 2.20 (s, 3H).

[0064] Example 13: Synthesis of p-aminobenzonitrile

[0065] Add 1.48 g (10 mmol) of p-nitrobenzonitrile, 25.6 mg (0.2 mmol) of molybdenum dioxide, 76.8 mg of activated carbon, 20 ml of absolute ethanol to a 50 ml three-necked flask, and dropwise add 1.25 g (20 mmol) of hydrazine hydrate (80%) at room temperature. After the addition is complete, react at room temperature for 5 h. TLC monitoring shows that the reaction is complete. Filter, concentrate the filtrate, add 20 mL of ethyl acetate and 10 ml of water, and extract. The organic phase is washed with water and concentrated to obtain 1.1 g of solid target product, with a yield of 93% and an HPLC purity of 99%. 1 HNMR (400 MHz, CDCl3) δ 7.23 - 7.27 (m, 2H), 6.81 - 6.87 (m, 2H), 5.63 (s, 2H).

[0066] Example 14: Synthesis of 2-amino-6-fluorobenzoic acid

[0067] Add 1.85 g (10 mmol) of 6-fluoro-2-nitrobenzoic acid, 25.6 mg (0.2 mmol) of molybdenum dioxide, 76.8 mg of activated carbon, 30 ml of absolute ethanol to a 50 ml three-necked flask, and dropwise add 1.25 g (20 mmol) of hydrazine hydrate (80%) at room temperature. After the addition is complete, react at room temperature for 7 h. TLC monitoring shows that the reaction is complete. Filter, concentrate the filtrate, add 20 mL of ethyl acetate and 10 ml of water, and extract. The organic phase is washed with water and concentrated to obtain 1.5 g of pale yellow solid target product, with a yield of 96.8% and an HPLC purity of 99.6%. 1 HNMR (400 MHz, D2O) δ 7.45 - 7.40 (m, 1H), 6.86 - 6.95 (m, 2H).

[0068] Example 15: Synthesis of 2-amino-4,5-bis(2-methoxyethoxy)benzonitrile

[0069] Add 2.96 g (10 mmol) of 4,5-bis(2-methoxyethoxy)-2-nitrobenzonitrile, 38.4 mg (0.3 mmol) of molybdenum dioxide, 0.12 g of activated carbon, 30 ml of absolute ethanol to a 50 ml three-necked flask, and dropwise add 1.88 g (30 mmol) of hydrazine hydrate (80%) at room temperature. After the addition is complete, react at room temperature for 7 h. TLC monitoring shows that the reaction is complete. Filter, concentrate the filtrate, add 20 mL of ethyl acetate and 10 ml of water, and extract. The organic phase is washed with water and concentrated to nearly dryness, and triturated with petroleum ether to obtain 2.4 g of pale yellow solid target product, with a yield of 90.2% and an HPLC purity of 99%. 1 HNMR (400 MHz, CDCl3) δ 7.41 (s, 1H), 7.04 (s, 1H), 3.61 - 3.66 (m, 4H), 2.47 - 2.55 (m, 4H), 3.24 (s, 3H), 3.21 (s, 3H).

[0070] Example 16: Synthesis of 2-Amino-4-methoxy-5-(3-morpholinopropyl)benzonitrile

[0071] Add 3.2 g (10 mmol) of 4-methoxy-5-(3-morpholinopropyl)-2-nitrobenzonitrile, 38.4 mg (0.3 mmol) of molybdenum dioxide, 0.12 g of activated carbon, and 30 ml of absolute ethanol to a 50 ml three-necked flask. At room temperature, add 1.88 g (30 mmol) of hydrazine hydrate (80%) dropwise. After the addition is complete, react at room temperature for 7 h. TLC monitoring shows that the reaction is complete. Filter, concentrate the filtrate, add 20 mL of ethyl acetate and 10 ml of water, and extract. Wash the organic phase with water and concentrate to nearly dryness. Pulverize with petroleum ether to obtain 2.65 g of the target product as a pale yellow solid, with a yield of 91% and an HPLC purity of 99.3%. 1 HNMR(400MHz,CDCl3)δ7.45(s,1H),7.02(s,1H),4.81-4.85(m,2H),3.58-3.65(m,4H),3.28(s,3H),2.41-2.48(m,2H),2.31-3.38(m,2H),1.87-1.91(m,2H).

[0072] Example 17:

[0073] The filter residue obtained by filtration after the reaction in Example 8 is the recovered catalyst. The experimental conditions when directly recycling and using it for the 10th time without treatment are as follows:

[0074] Add 1.58 g (10 mmol) of p-chloroaniline, molybdenum dioxide and activated carbon (recovered from the 9th recycling experiment), and 30 ml of absolute ethanol to a 50 ml three-necked flask. At room temperature, add 1.2 g (20 mmol) of hydrazine hydrate (80%) dropwise. After the addition is complete, react at room temperature for 5 h. TLC monitoring shows that the reaction is complete. Filter, concentrate the filtrate, add 20 mL of ethyl acetate and 10 ml of water, and extract. Wash the organic phase with water and concentrate to obtain 1.24 g of the target product as a pale yellow crystalline substance, with a yield of 96.9% and an HPLC purity of 99%.

[0075] Example 18:

[0076] The filter residue obtained by filtration after the reaction in Example 10 is the recovered catalyst. The experimental conditions when directly recycling and using it for the 10th time without treatment are as follows:

[0077] Add 2.00 g (7.70 mmol) of 2-(2,4-dimethylphenylthio)nitrobenzene, molybdenum dioxide and activated carbon (recovered from the 9th recycling experiment), 30 ml of absolute ethanol to a 50 ml three-necked flask, and dropwise add 0.92 g (15.0 mmol) of hydrazine hydrate (80%) at room temperature. After the addition, react at room temperature for 6 h. TLC monitoring shows that the reaction is complete. Filter, concentrate the filtrate, add 20 mL of ethyl acetate and 10 ml of water, and extract. The organic phase is washed with water and concentrated to obtain 1.64 g of the target product as a white solid, with a yield of 93% and an HPLC purity of 99.4%.

[0078] Comparative Example 1:

[0079] Compared with Example 1, the reaction of synthesizing aniline without adding activated carbon is as follows:

[0080] Add 1.58 g (10 mmol) of nitrobenzene, 25.6 mg (0.2 mmol) of molybdenum dioxide, 30 ml of absolute ethanol to a 50 ml three-necked flask, and dropwise add 1.2 g (20 mmol) of hydrazine hydrate (80%) at room temperature. After the addition, react at room temperature for 2 h. TLC monitoring shows that almost no product is formed. HPLC shows that the content of the raw material nitrobenzene is 99%, and aniline is only 0.8%.

[0081] Comparative Example 2:

[0082] Compared with Example 10, the reaction of synthesizing 2-(2,4-dimethylphenylthio)aniline without adding activated carbon is as follows:

[0083] Add 2.00 g (7.70 mmol) of 2-(2,4-dimethylphenylthio)nitrobenzene, 0.01 g (0.077 mmol) of molybdenum dioxide, 30 ml of absolute ethanol to a 50 ml three-necked flask, and dropwise add 0.92 g (15.0 mmol) of hydrazine hydrate (80%) at room temperature. After the addition, react at room temperature for 6 h. TLC monitoring shows that almost no product is formed. HPLC shows that the raw material content is 99.3%, and the product is only 0.3%.

[0084] Comparative Example 3:

[0085] Compared with Example 10, the reaction of synthesizing 2-(2,4-dimethylphenylthio)aniline without adding molybdenum dioxide is as follows:

[0086] Add 2.00 g (7.70 mmol) of 2-(2,4-dimethylphenylthio)nitrobenzene, 0.05 g of activated carbon, 30 ml of absolute ethanol to a 50 ml three-necked flask, and dropwise add 0.92 g (15.0 mmol) of hydrazine hydrate (80%) at room temperature. After the addition, react at room temperature for 6 h. TLC monitoring shows that almost no product is formed. HPLC shows that the raw material content is 99.3%, and the product is only 0.3%.

[0087] Example 19:

[0088] Compared with Example 10, the reaction of synthesizing 2-(2,4-dimethylphenylthio)aniline was carried out with molybdenum trioxide replacing molybdenum dioxide as the catalyst as follows:

[0089] 2.00 g (7.70 mmol) of 2-(2,4-dimethylphenylthio)nitrobenzene, 11.1 mg (0.077 mmol) of molybdenum trioxide, 0.05 g of activated carbon, and 30 ml of absolute ethanol were added to a 50 ml three-necked flask. 0.92 g (15.0 mmol) of hydrazine hydrate (80%) was added dropwise at room temperature. After the addition was completed, the reaction was carried out at room temperature for 6 h. TLC monitoring showed that the reaction was partial and there was still raw material remaining. The reaction was continued at room temperature for 6 h. TLC detection still showed that there was raw material remaining. The mixture was filtered and the filter cake was collected. After the filtrate was concentrated, 20 mL of ethyl acetate and 10 ml of water were added for extraction. The organic phase was washed with water, concentrated to dryness, and then slurried with 10 mL of n-heptane for 1 h. Filtration gave 1.42 g of the target product as a white solid, with a yield of 80.5% and an HPLC purity of 98.5%.

[0090] 1 HNMR (400 MHz, DMSO-d6) δ 7.15 - 7.20 (m, 2H), 7.02 (s, 1H), 6.81 - 6.85 (m, 2H), 6.58 - 6.65 (m, 2H), 5.28 (s, 2H), 2.31 (s, 3H), 2.20 (s, 3H).

[0091] Those skilled in the art can understand that under the teaching of this specification, some modifications or adjustments can be made to the present invention. These modifications or adjustments should also be within the scope defined by the claims of the present invention.

Claims

1. A method for synthesizing aniline compounds, characterized in that, It includes the following steps: using molybdenum-based oxide and activated carbon as catalysts and hydrazine hydrate as a reducing agent to reduce aromatic nitro compounds to aniline compounds, where both the molybdenum-based oxide and the activated carbon are commercial-grade reagents; the molybdenum-based oxide and the activated carbon are stored separately and are respectively added into the reaction system during use, or the molybdenum-based oxide and the activated carbon are stored mixed and are added into the reaction system in the form of a mixture during use; the molar ratio of the molybdenum-based oxide to the aromatic nitro compound is 0.01 - 0.03:1; the weight ratio of the molybdenum-based oxide to the activated carbon is 1:2 - 5; the molybdenum-based oxide is MoO₂.

2. The method according to claim 1, characterized in that, the molar ratio of the hydrazine hydrate to the aromatic nitro compound is 1.5 - 10:

1.

3. The method according to claim 1, characterized in that, the molar ratio of the hydrazine hydrate to the aromatic nitro compound is 2 - 4:

1.

4. The method according to claim 1, characterized in that, the temperature of the reduction reaction is controlled between 25°C and the temperature that can keep the reaction system in reflux.

5. The method according to claim 1, characterized in that, the temperature of the reduction reaction is controlled at 25 - 35°C.

6. The method according to claim 1, characterized in that, reducing the aromatic nitro compound shown in structural formula (I) to the aniline compound shown in structural formula (II): Among them, R1 - R5 are the same as or different from each other, and R1 - R5 are each independently selected from a hydrogen atom, a halogen atom, a C1 - C6 alkyl group, a phenyl group or a substituted derivative thereof, a benzyl group or a substituted derivative thereof, SR6, OR7, COOR B , CONR9R 10 or CN; wherein, R6, R7, R8, R9 and R 10 are each independently selected from a hydrogen atom, a C1 - C6 alkyl group, a phenyl group or a substituted derivative thereof, a benzyl group or a substituted derivative thereof, and R9 and R 10 are the same as or different from each other.

7. The method according to claim 1, characterized in that, the reduction reaction is carried out in the presence of a solvent, and the solvent is one or more of water, methanol, ethanol or isopropanol.

8. The method according to claim 1, characterized in that, the reduction reaction is carried out in the presence of a solvent, and the solvent is ethanol.

9. The method according to claim 1, characterized in that, the hydrazine hydrate is selected from hydrazine hydrate aqueous solutions with a mass concentration of 40 - 80%.

10. The method according to claim 1, characterized in that, It further includes the following steps: after the reaction is completed, the reaction mixture is filtered, and the obtained filter residue is used as the recycled catalyst for recycling.

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