A method for preparing 2',4-dichloro-2-aminodiphenyl ether

Abstract

This invention relates to a method for preparing 2',4-dichloro-2-aminodiphenyl ether, belonging to the field of chemical synthesis technology. The preparation method is as follows: S1, m-dinitrobenzene undergoes selective hydrogenation to obtain m-nitroaniline; S2, in a solvent, m-nitroaniline reacts with N-chlorosuccinimide to obtain 2-chloro-5-nitroaniline; S3, 2-chloro-5-nitroaniline, o-nitrophenol, a base, and a solvent undergo a co-heated reaction to obtain 2',4-dinitro-2-aminodiphenyl ether; S4, 2',4-dinitro-2-aminodiphenyl ether is dissolved in a solvent, and FeCl3 solution, sodium chloride, and Oxone are added. The reaction is catalyzed under ultraviolet light to obtain 2',4-dichloro-2-aminodiphenyl ether. The preparation method of this invention uses readily available raw materials, has good reaction efficiency, produces less waste, is cleaner and more environmentally friendly, and has a high conversion rate, making it suitable for industrial application.

Description

Technical Field

[0001] This invention relates to a method for preparing 2',4-dichloro-2-aminodiphenyl ether, belonging to the field of chemical synthesis technology. Background Technology

[0002] 2',4-Dichloro-2-aminodiphenyl ether is an important component in the chemical industry and has gained increasing attention in recent years. It is a light yellow to brown crystalline powder with a distinctive odor. It is slightly soluble in water but soluble in organic solvents such as ethanol, ether, and acetone.

[0003] 2',4-Dichloro-2-aminodiphenyl ether is an important intermediate in organic synthesis, widely used in various fields. In the pharmaceutical field, it is a key raw material for synthesizing bifonazole analogs, an antifungal drug, which works by inhibiting the synthesis of ergosterol in fungal cell membranes and is clinically used to treat various dermatophyte infections. It is also an intermediate in the preparation of anti-inflammatory drugs such as COX-2 inhibitors, reducing the gastrointestinal side effects of traditional nonsteroidal anti-inflammatory drugs. In the pesticide field, it is a core component of highly effective diphenyl ether herbicides, significantly controlling broadleaf weeds such as purslane by inhibiting the destruction of chlorophyll synthesis by porphyrinogen oxidase in weeds. It can also be used to synthesize phenyl ether insecticides that interfere with the insect nervous system, especially effective against organophosphate-resistant pests. In the dye and pigment field, it is used to synthesize azo dyes and organic pigments, providing high-fastness dyeing solutions for synthetic fibers such as polyester, or for weather-resistant coloring of inks and coatings. Furthermore, in the field of functional materials, it can regulate the phase transition temperature of liquid crystal materials for fast-response liquid crystal displays; it can also be used as an intermediate in the synthesis of reactive flame retardants, improving the fire resistance of polymer materials. With technological advancements, its applications are continuously expanding into high-end fields such as innovative pharmaceuticals and new material additives, demonstrating sustained market growth potential.

[0004] 2',4-Dichloro-2-aminodiphenyl ether is mainly used as an important pharmaceutical and dye intermediate. Purchasing 2',4-dichloro-2-aminodiphenyl ether directly would be relatively expensive. Patent application CN101830766A discloses a method for synthesizing an amino aromatic ether compound. The method involves adding 2,5-dichloronitrobenzene to diethylene glycol dimethyl ether and polyethylene glycol, then alternately adding potassium hydroxide and o-chlorophenol while heating and stirring for 240 minutes. The mixture is then cooled to 60°C, water is slowly added, and the mixture is heated to reflux. Benzyltriethylammonium chloride, hydrazine hydrate, and a reduction catalyst are added, and the mixture is refluxed for 220 minutes. The reduction reaction is carried out to the endpoint, and the product is obtained after post-treatment. This preparation method requires the use of highly toxic hydrazine hydrate, and the solvent consumption is large, making recovery difficult and waste liquid treatment challenging, thus making it unsuitable for industrial production. Furthermore, incomplete reduction can generate colored byproducts such as azobenzene (-N=N-) or azobenzene oxide (-N(O)=N-), which are common impurities in nitro reduction and can severely affect product purity and color. Hydrazine hydrate may partially decompose under strongly alkaline and high-temperature conditions, reacting with itself or intermediates and introducing unknown impurities such as ammonia-containing heterocycles. Post-processing purification relies on water washing, which effectively removes inorganic salts and some water-soluble impurities, but its ability to remove most organic impurities (such as unreacted phenols, byproducts, PTC, and PEG) is very limited. Moreover, this preparation method requires a self-made catalyst, the activity of which is highly dependent on the preparation conditions. Any batch variation can lead to insufficient catalytic active sites, resulting in a slow and incomplete reduction reaction, residual nitro intermediates, and reduced yield. Additionally, trace amounts of sulfides and other poisons carried in the raw materials or solvent can deactivate the catalyst. In practical applications, the purity of the target product prepared using this method does not exceed 90%, and the product yield does not exceed 45%.

[0005] Therefore, developing a simple preparation method for 2',4-dichloro-2-aminodiphenyl ether with high product yield and suitable for industrial application is of great value. Summary of the Invention

[0006] This invention addresses the shortcomings of existing technologies by providing a method for preparing 2',4-dichloro-2-aminodiphenyl ether. The preparation method described in this invention uses readily available raw materials, exhibits good reaction efficiency, produces less waste, is cleaner and more environmentally friendly, and has a high conversion rate, making it suitable for industrial applications. This provides a new synthetic route for 2',4-dichloro-2-aminodiphenyl ether.

[0007] The technical solution of the present invention to solve the above-mentioned technical problems is as follows: a method for preparing 2',4-dichloro-2-aminodiphenyl ether, wherein the preparation method is as follows:

[0008] S1. m-Dinitrobenzene is selectively hydrogenated to prepare m-nitroaniline;

[0009] S2. In a solvent, m-nitroaniline reacts with N-chlorosuccinimide (NCS) to prepare 2-chloro-5-nitroaniline;

[0010] 2',4-Dinitro-2-aminodiphenyl ether was prepared by a heated reaction of S3, 2-chloro-5-nitroaniline, o-nitrophenol, base and solvent.

[0011] S4,2',4-dinitro-2-aminodiphenyl ether was dissolved in a solvent, and FeCl3, sodium chloride and Oxone were added. The reaction was carried out under ultraviolet light to catalyze the reaction and obtain 2',4-dichloro-2-aminodiphenyl ether.

[0012] Based on the above technical solution, the present invention can be further improved as follows:

[0013] Furthermore, in step S1, a palladium catalyst is used, and the selective hydrogenation reaction is carried out at a temperature of 50-120°C, a pressure of 1-3 MPa, and a reaction time of 6-8 h.

[0014] Furthermore, the catalyst used in step S1 is selected from at least one of Pd, Pd / C, PdO2, and Pd[P(C6H5)3]4;

[0015] The molar ratio of m-dinitrobenzene to hydrogen used in selective hydrogenation is 1:(3.0-3.2).

[0016] Furthermore, in step S2, the molar ratio of m-nitroaniline to N-chlorosuccinimide is 1:(1.1-1.3).

[0017] In step S2, the reaction temperature is -15~15℃ and the reaction time is 3-5 h.

[0018] Furthermore, after the reaction in step S2 is completed, 2-chloro-5-nitroaniline is obtained through post-treatment;

[0019] The post-processing operation is as follows: After the reaction is completed, the reaction is quenched, and after solvent extraction, the solvent is evaporated to obtain crude 2-chloro-5-nitroaniline. The crude 2-chloro-5-nitroaniline is added to an aqueous ethanol solution with a mass concentration of 75%-80%, heated to reflux, cooled to 50-55°C, and the insoluble matter is filtered off. The filtrate is slowly cooled to 20-25°C, and the precipitated crystals are separated. The precipitated crystals are recrystallized again using an aqueous ethanol solution with a mass concentration of 55%-60%. The crystals with a final crystallization temperature of -5~0°C are separated to obtain 2-chloro-5-nitroaniline for the reaction in step S3.

[0020] Furthermore, in step S3, the reaction temperature is 120-170 ℃ and the reaction time is 2-7 h.

[0021] Furthermore, the alkali used in step S3 is at least one of potassium hydroxide, potassium carbonate, sodium carbonate, and sodium bicarbonate.

[0022] In step S3, the molar ratio of 2-chloro-5-nitroaniline and o-nitrophenol to base is (1-1.05):1:(1.2-1.5).

[0023] Furthermore, in step S4, the equivalent ratio of 2',4-dinitro-2-aminodiphenyl ether, Oxone, NaCl, and FeCl3 is 1:(0.4-0.5):(2.5-3.0):(1.5-2.0).

[0024] Furthermore, in step S4, the reaction temperature is 40-60℃ and the reaction time is 36-48h.

[0025] Furthermore, the solvent used in step S1 is at least one of methanol and ethanol;

[0026] The solvent used in step S2 is at least one of toluene, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, and 1,4-dioxane;

[0027] The solvent used in step S3 is at least one of N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, 1,3-dimethylimidazolinone, and 1,4-dioxane;

[0028] The solvent used in step S4 is acetonitrile.

[0029] The beneficial effects of this invention are:

[0030] In the preparation method described in this invention, m-dinitrobenzene is first selectively hydrogenated to generate m-nitroaniline. Then, m-nitroaniline is reacted with NCS to generate 2-chloro-5-nitroaniline. 2-chloro-5-nitroaniline then undergoes an etherification reaction with o-nitrophenol in a strongly polar aprotic solvent under alkaline catalysis to generate 2',4-dinitro-2-aminodiphenyl ether. Finally, a metal charge transfer process occurs under the action of FeCl3 to generate 2',4-dichloro-2-aminodiphenyl ether. The method described in this invention for synthesizing 2',4-dichloro-2-aminodiphenyl ether has advantages such as readily available raw materials, fewer side reactions, high yield and purity of the target product, and low cost. Furthermore, the reaction is cleaner and more environmentally friendly, producing less waste, making it suitable for industrial applications and providing a new synthetic route for 2',4-dichloro-2-aminodiphenyl ether. Attached Figure Description

[0031] Figure 1 The image shows a gas chromatogram of the 2',4-dichloro-2-aminodiphenyl ether product prepared in Example 1. Detailed Implementation

[0032] To make the above-mentioned objects, features, and advantages of the present invention more apparent and understandable, specific embodiments of the present invention are described in detail below. Many specific details are set forth in the following description to provide a thorough understanding of the present invention. However, the present invention can be practiced in many other ways different from those described herein, and those skilled in the art can make similar modifications without departing from the spirit of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0033] Unless otherwise defined, 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. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

[0034] A method for preparing 2',4-dichloro-2-aminodiphenyl ether, wherein the preparation method comprises:

[0035] S1, m-dinitrobenzene ( m-Nitroaniline was prepared by selective hydrogenation.

[0036] S2, In a solvent, m-nitroaniline reacts with N-chlorosuccinimide ( 2-Chloro-5-nitroaniline was prepared by reaction. );

[0037] S3, 2-chloro-5-nitroaniline ( o-Nitrophenol 2',4-Dinitro-2-aminodiphenyl ether was prepared by reacting a base with a solvent under heating conditions.

[0038] S4,2',4-dinitro-2-aminodiphenyl ether was dissolved in a solvent, and FeCl3, sodium chloride, and Oxone were added. The mixture was then catalyzed under ultraviolet light to prepare 2',4-dichloro-2-aminodiphenyl ether. ).

[0039] Based on the above technical solution, the present invention can be further improved as follows:

[0040] Specifically, in step S1, a palladium catalyst is used, and the selective hydrogenation reaction is carried out at a temperature of 50-120°C, a pressure of 1-3 MPa, and a reaction time of 6-8 h.

[0041] Specifically, the catalyst used in step S1 is selected from at least one of Pd, Pd / C, PdO2, and Pd[P(C6H5)3]4;

[0042] The molar ratio of m-dinitrobenzene to hydrogen used in selective hydrogenation is 1:(3.0-3.2).

[0043] Specifically, in step S2, the molar ratio of m-nitroaniline to N-chlorosuccinimide is 1:(1.1-1.3).

[0044] In step S2, the reaction temperature is -15~15℃, and the reaction time is 3-5 h. NCS must be at a lower temperature; otherwise, runaway temperature may occur, affecting the reaction effect.

[0045] Preferably, in step S2, the reaction temperature is -15~0℃.

[0046] Specifically, after the reaction in step S2 is completed, 2-chloro-5-nitroaniline is obtained through post-processing.

[0047] The post-processing operation is as follows: After the reaction is completed, the reaction is quenched, and after solvent extraction, the solvent is evaporated to obtain crude 2-chloro-5-nitroaniline. The crude 2-chloro-5-nitroaniline is added to an aqueous ethanol solution with a mass concentration of 75%-80%, heated to reflux, cooled to 50-55°C, and the insoluble matter is filtered off. The filtrate is slowly cooled to 20-25°C, and the precipitated crystals are separated. The precipitated crystals are recrystallized again using an aqueous ethanol solution with a mass concentration of 55%-60%. The crystals with a final crystallization temperature of -5~0°C are separated to obtain 2-chloro-5-nitroaniline for the reaction in step S3.

[0048] More specifically, the crude 2-chloro-5-nitroaniline and the 75%-80% aqueous ethanol solution are in a mass ratio of 1:4; the precipitated crystals and the 55%-60% aqueous ethanol solution are in a mass ratio of 1:3.

[0049] Specifically, in step S3, the reaction temperature is 120-170 ℃ and the reaction time is 2-7 h.

[0050] Specifically, the alkali used in step S3 is at least one of potassium hydroxide, potassium carbonate, sodium carbonate, and sodium bicarbonate.

[0051] In step S3, the molar ratio of 2-chloro-5-nitroaniline and o-nitrophenol to base is (1-1.05):1:(1.2-1.5).

[0052] Specifically, in step S4, the equivalent ratio of 2',4-dinitro-2-aminodiphenyl ether, Oxone, NaCl, and FeCl3 is 1:(0.4-0.5):(2.5-3.0):(1.5-2.0).

[0053] Preferably, in step S4, the equivalent ratio of 2',4-dinitro-2-aminodiphenyl ether, Oxone, NaCl, and FeCl3 is 1:0.5:3:2.

[0054] Specifically, in step S4, the reaction temperature is 40-60℃ and the reaction time is 36-48h.

[0055] Specifically, the solvent used in step S1 is an alcohol, which is selected from at least one of methanol and ethanol.

[0056] More specifically, in step S1, the mass fraction of the m-dinitrobenzene alcohol solution is 5%-30%.

[0057] Preferably, in step S1, using methanol to dissolve the raw material during hydrogenation allows for better hydrogenation reaction with palladium on carbon. When the mass fraction of m-dinitrobenzene is 10%-20%, the reaction temperature is relatively low and the system pressure is low.

[0058] Specifically, the solvent used in step S2 is at least one of toluene, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, and 1,4-dioxane.

[0059] More specifically, in step S2, the volume of solvent used is 3-5 times the mass of m-nitroaniline.

[0060] Preferably, the choice of base in step S2 has a significant impact on the reaction. Potassium carbonate has a good reaction effect. In the system with N,N-dimethylacetamide as solvent, the etherification effect is good, the yield is high, and there are few side reactions.

[0061] Specifically, the solvent used in step S3 is at least one of N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, 1,3-dimethylimidazolinone, and 1,4-dioxane;

[0062] The solvent used in step S4 is acetonitrile (analytical grade).

[0063] More specifically, in step S4, FeCl3 is added to the system as a FeCl3 solution. In this embodiment of the invention, the FeCl3 solution is an acetonitrile solution of FeCl3 with a molar concentration of 35 mmol / L.

[0064] In step S4, the key point of the nitrification-chlorination substitution of 2',4-dinitro-2-aminodiphenyl ether is the LMCT (metal charge transfer) process, which generates Cl radicals. The Cl radicals undergo a substitution reaction to give 2',4-dichloro-2-aminodiphenyl ether, accompanied by NO2 gas.

[0065] Example 1

[0066] A method for preparing 2',4-dichloro-2-aminodiphenyl ether, wherein the preparation method comprises:

[0067] (1) Selective hydrogenation of m-dinitrobenzene: In a 100 mL high-temperature and high-pressure reactor, 1.68 g of m-dinitrobenzene, 15.12 g of methanol, and 0.094 g of palladium on carbon were added and stirred until homogeneous. The mixture was purged with hydrogen 2-3 times. The temperature was set at 60 °C and the hydrogen pressure at 1.2 MPa. The reaction was completed after 6 h, with a molar ratio of m-dinitrobenzene to hydrogen of 1:3.0. The mixture was cooled to room temperature, 5 g of methanol was added, stirred until homogeneous, filtered, and the catalyst was recovered and reused. The methanol was recovered by rotary evaporation to obtain solid m-nitroaniline with a yield of 95%.

[0068] (2) Preparation of 2-chloro-5-nitroaniline: In a 100 mL three-necked round-bottom flask, 1.38 g of m-nitroaniline was dissolved in 4 mL of toluene, cooled to 0 °C, and NCS was added while stirring. The reaction was carried out for 3 h, wherein the molar ratio of m-nitroaniline to NCS was 1:1.2. After the reaction was completed, the mixture was quenched and neutralized with saturated sodium bicarbonate solution, then extracted with toluene, the organic phase was washed with water, and the organic phase was concentrated and evaporated to dryness. The crude product in the flask was a pale yellow solid with a yield of 91%.

[0069] Purification of 2-chloro-5-nitroaniline: The crude product was added to a round-bottom flask, followed by the addition of 80% aqueous ethanol solution. The mixture was heated to reflux, cooled to 50°C, and filtered to remove insoluble matter. The filtrate was slowly cooled to 25°C, and crystals precipitated. These crystals were collected by vacuum filtration. The crystals obtained at 25°C were recrystallized from the solution with 60% aqueous ethanol solution, cooled to 0°C, and filtered to obtain 2-chloro-5-nitroaniline with a yield of 82% and a purity of 98.1%.

[0070] (3) Preparation of 2',4-dinitro-2-aminodiphenyl ether: 1.39 g of o-nitrophenol, 1.66 g of potassium carbonate, 10 g of N,N-dimethylformamide and 1.72 g of 2-chloro-5-nitroaniline were added to a 250 mL flask, heated to 140 °C and reacted for 3 h. After the reaction was completed, the mixture was allowed to cool naturally to room temperature. 100 mL of water was added, and the mixture was stirred for 30 min. The mixture was then filtered and dried to obtain 2',4-dinitro-2-aminodiphenyl ether with a yield of 95%.

[0071] (4) Preparation of 2',4-dichloro-2-aminodiphenyl ether: 0.275 g of 2',4-dinitro-2-aminodiphenyl ether was dissolved in 3 mL of acetonitrile, and FeCl3 acetonitrile solution, sodium chloride, and Oxone were added. The equivalent ratio of 2',4-dinitro-2-aminodiphenyl ether, Oxone, NaCl, and FeCl3 was 1:0.5:3:2. The reaction was carried out in a photoreactor at 40 °C under ultraviolet light for 48 h to obtain a 2',4-dichloro-2-aminodiphenyl ether reaction solution. The obtained 2',4-dichloro-2-aminodiphenyl ether reaction solution was extracted, and the organic phase was concentrated to obtain a solid. The solid was recrystallized from methanol (during recrystallization, the mass ratio of solid to methanol was 1:3, the dissolution temperature was 50 °C, and the final crystallization temperature was 5 °C). The recrystallization yield was 75%, and the purity was 96.25%. The gas chromatogram is shown below. Figure 1 As shown in Table 1, the gas chromatography data are as follows.

[0072] Table 1 Gas Chromatography Data

[0073]

[0074] Example 2

[0075] A method for preparing 2',4-dichloro-2-aminodiphenyl ether, wherein the preparation method comprises:

[0076] (1) Selective hydrogenation of m-dinitrobenzene: In a high-temperature and high-pressure reactor, 1.68 g of m-dinitrobenzene, 15.12 g of methanol, and 0.094 g of palladium on carbon were added and stirred until homogeneous. The mixture was purged with hydrogen 2-3 times. The temperature was set at 70 °C and the hydrogen pressure at 1.0 MPa. The reaction was completed after 8 h, with a molar ratio of m-dinitrobenzene to hydrogen of 1:3.2. The mixture was cooled to room temperature, and 5 g of methanol was added. The mixture was stirred until homogeneous, filtered, and the catalyst was recovered and reused. The methanol was recovered by rotary evaporation to obtain a solid with a yield of 97%.

[0077] (2) Preparation of 2-chloro-5-nitroaniline: In a 100 mL three-necked round-bottom flask, 1.38 g of m-nitroaniline was dissolved in 4 mL of toluene, cooled to -10 °C, and NCS was added while stirring. The reaction was carried out for 3 h, wherein the molar ratio of m-nitroaniline to NCS was 1:1.3. After the reaction was completed, the mixture was quenched and neutralized with saturated sodium bicarbonate solution, then extracted with toluene, the organic phase was washed with water, and the organic phase was concentrated and evaporated to dryness. The crude product in the flask was a pale yellow solid with a yield of 90%.

[0078] Purification of 2-chloro-5-nitroaniline: The crude product was added to a round-bottom flask, followed by the addition of 75% aqueous ethanol solution. The mixture was heated to reflux, cooled to 55°C, and filtered to remove insoluble matter. The filtrate was slowly cooled to 20°C, and crystals precipitated. These crystals were collected by vacuum filtration. The crystals obtained at 20°C were recrystallized from the 20°C solution with 55% aqueous ethanol solution, cooled to -5°C, and filtered to obtain 2-chloro-5-nitroaniline. After recrystallization and purification, the yield was 81%, and the purity was 98.2%.

[0079] (3) Preparation of 2',4-dinitro-2-aminodiphenyl ether: 1.39 g of o-nitrophenol, 0.84 g of potassium hydroxide, 10 g of N,N-dimethylacetamide and 1.72 g of 2-chloro-5-nitroaniline were added to a 250 mL flask, heated to 140 °C and reacted for 3 h. After the reaction was completed, the mixture was allowed to cool naturally to room temperature. 100 mL of water was added, and the mixture was stirred for 30 min. The mixture was then filtered and dried to obtain 2',4-dinitro-2-aminodiphenyl ether with a yield of 96%.

[0080] (4) Preparation of 2',4-dichloro-2-aminodiphenyl ether: 0.275 g of 2',4-dinitro-2-aminodiphenyl ether was dissolved in 3 mL of acetonitrile, and FeCl3 acetonitrile solution, sodium chloride, and Oxone were added. The equivalent ratio of 2',4-dinitro-2-aminodiphenyl ether, Oxone, NaCl, and FeCl3 was 1:0.5:3:2. The reaction was carried out in a photoreactor at 50 °C under ultraviolet light for 40 h to obtain a 2',4-dichloro-2-aminodiphenyl ether reaction solution. The obtained 2',4-dichloro-2-aminodiphenyl ether reaction solution was extracted, and the organic phase was concentrated to obtain a solid. The solid was recrystallized with methanol (during recrystallization, the mass ratio of solid to methanol was 1:3, the dissolution temperature was 50 °C, and the final crystallization temperature was 5 °C). The recrystallization yield was 80%, and the purity was 95.5%.

[0081] Example 3

[0082] A method for preparing 2',4-dichloro-2-aminodiphenyl ether, wherein the preparation method comprises:

[0083] (1) Selective hydrogenation of m-dinitrobenzene: In a high-temperature and high-pressure reactor, 1.68 g of m-dinitrobenzene, 50 g of methanol, and 0.094 g of palladium on carbon were added and stirred until homogeneous. The mixture was replaced with hydrogen 2-3 times. The temperature was set at 80℃ and the hydrogen pressure at 1.8 MPa. The reaction was completed after 6 hours, with a molar ratio of m-dinitrobenzene to hydrogen of 1:3.1. The mixture was cooled to room temperature, and 30 g of methanol was added. The mixture was stirred until homogeneous, filtered, and the catalyst was recovered and reused. The methanol was recovered by rotary evaporation to obtain a solid with a yield of 97%.

[0084] (2) Preparation of 2-chloro-5-nitroaniline: 1.38 g of m-nitroaniline was dissolved in 4 mL of N,N-dimethylformamide (DMF) in a 100 mL three-necked round-bottom flask. The temperature was lowered to -10 °C, and NCS was added while stirring. The reaction was carried out for 3 h. The molar ratio of m-nitroaniline to NCS was 1:1.2. After the reaction was completed, the mixture was quenched and neutralized with saturated sodium bicarbonate solution, then extracted with toluene, the organic phase was washed with water, and the organic phase was concentrated and evaporated to dryness. The crude product in the flask was a pale yellow solid with a yield of 86%.

[0085] Purification of 2-chloro-5-nitroaniline: The crude product was added to a round-bottom flask, followed by the addition of 80% aqueous ethanol solution. The mixture was heated to reflux, cooled to 50°C, and filtered to remove insoluble matter. The filtrate was slowly cooled to 25°C, and crystals precipitated. These crystals were collected by vacuum filtration. The crystals obtained at 25°C were recrystallized from the solution with 60% aqueous ethanol solution, cooled to 0°C, and filtered to obtain 2-chloro-5-nitroaniline. After recrystallization purification, the yield was 83% and the purity was 97%.

[0086] (3) Preparation of 2',4-dinitro-2-aminodiphenyl ether: 1.39 g of o-nitrophenol, 1.38 g of sodium carbonate, 10 g of N,N-dimethylacetamide and 1.72 g of 2-chloro-5-nitroaniline were added to a 250 mL flask, heated to 140 °C and reacted for 3 h. After the reaction was completed, the mixture was allowed to cool naturally to room temperature. 100 mL of water was added, and the mixture was stirred for 30 min. The mixture was then filtered and dried to obtain 2',4-dinitro-2-aminodiphenyl ether with a yield of 96%.

[0087] (4) Preparation of 2',4-dichloro-2-aminodiphenyl ether: 0.275 g of 2',4-dinitro-2-aminodiphenyl ether was dissolved in 3 mL of acetonitrile, and FeCl3 acetonitrile solution, sodium chloride, and Oxone were added. The equivalent ratio of 2',4-dinitro-2-aminodiphenyl ether, Oxone, NaCl, and FeCl3 was 1:0.5:3:2. The reaction was carried out in a photoreactor at 60 °C under ultraviolet light for 36 h to obtain a 2',4-dichloro-2-aminodiphenyl ether reaction solution. The obtained 2',4-dichloro-2-aminodiphenyl ether reaction solution was extracted, and the organic phase was concentrated to obtain a solid. The solid was recrystallized with methanol (during recrystallization, the mass ratio of solid to methanol was 1:3, the dissolution temperature was 50 °C, and the final crystallization temperature was 5 °C). The recrystallization yield was 78%, and the purity was 93%.

[0088] Example 4

[0089] A method for preparing 2',4-dichloro-2-aminodiphenyl ether, wherein the preparation method comprises:

[0090] (1) Selective hydrogenation of m-dinitrobenzene: In a high-temperature and high-pressure reactor, 1.68 g of m-dinitrobenzene, 50 g of ethanol, and 0.094 g of Pd / C were added and stirred until homogeneous. The mixture was purged with hydrogen 2-3 times. The temperature was set at 80℃ and the hydrogen pressure at 3.0 MPa. The reaction was completed after 6 hours, with a molar ratio of m-dinitrobenzene to hydrogen of 1:3.0. The mixture was cooled to room temperature, and 30 g of methanol was added. The mixture was stirred until homogeneous, filtered, and the catalyst was recovered and reused. The methanol was recovered by rotary evaporation to obtain a solid with a yield of 97%.

[0091] (2) Preparation of 2-chloro-5-nitroaniline: 1.38 g of m-nitroaniline was dissolved in 4 mL of N,N-dimethylacetamide (DMAc) in a 100 mL three-necked round-bottom flask. The temperature was lowered to -10 °C, and NCS was added while stirring. The reaction was carried out for 3 h. The molar ratio of m-nitroaniline to NCS was 1:1.2. After the reaction was completed, the mixture was quenched and neutralized with saturated sodium bicarbonate solution, then extracted with toluene, the organic phase was washed with water, and the organic phase was concentrated and evaporated to dryness. The crude product in the flask was a pale yellow solid with a yield of 88%.

[0092] Purification of 2-chloro-5-nitroaniline: The crude product was added to a round-bottom flask, followed by 80% aqueous ethanol solution. The mixture was heated to reflux, cooled to 50°C, and filtered to remove insoluble matter. The filtrate was slowly cooled to 25°C, and crystals precipitated. These crystals were collected by vacuum filtration. The crystals obtained at 25°C were recrystallized from the solution with 60% aqueous ethanol solution, cooled to 0°C, and filtered to obtain 2-chloro-5-nitroaniline. After recrystallization purification, the yield was 80%, and the purity was 96%.

[0093] (3) Preparation of 2',4-dinitro-2-aminodiphenyl ether: 1.39 g of o-nitrophenol, 1.17 g of sodium bicarbonate, 10 g of N,N-dimethylacetamide and 1.72 g of 2-chloro-5-nitroaniline were added to a 250 mL flask, heated to 140 °C and reacted for 3 h. After the reaction was completed, the mixture was allowed to cool naturally to room temperature. 100 mL of water was added, and the mixture was stirred for 30 min. The mixture was then filtered and dried to obtain 2',4-dinitro-2-aminodiphenyl ether with a yield of 92%.

[0094] (4) Preparation of 2',4-dichloro-2-aminodiphenyl ether: 0.275 g of 2',4-dinitro-2-aminodiphenyl ether was dissolved in 3 mL of acetonitrile, and FeCl3 acetonitrile solution, sodium chloride, and Oxone were added. The reaction was carried out in a photoreactor at 50 °C under ultraviolet light for 36 h to obtain a 2',4-dichloro-2-aminodiphenyl ether reaction solution. The obtained 2',4-dichloro-2-aminodiphenyl ether reaction solution was extracted, and the organic phase was concentrated to obtain a solid. The solid was recrystallized with methanol (during recrystallization, the mass ratio of solid to methanol was 1:3, the dissolution temperature was 50 °C, and the final crystallization temperature was 5 °C). The recrystallization yield was 80%, and the purity was 95.5%.

[0095] Example 5

[0096] A method for preparing 2',4-dichloro-2-aminodiphenyl ether, wherein the preparation method comprises:

[0097] (1) Selective hydrogenation of m-dinitrobenzene: In a high-temperature and high-pressure reactor, 1.68 g of m-dinitrobenzene, 50 g of methanol, and 0.094 g of Pd / BaSO4 were added and stirred until homogeneous. The mixture was purged with hydrogen 2-3 times. The temperature was set at 80 °C and the hydrogen pressure at 1.8 MPa. The reaction was completed after 6 h, with a molar ratio of m-dinitrobenzene to hydrogen of 1:3.0. The mixture was cooled to room temperature, and 30 g of methanol was added. The mixture was stirred until homogeneous, filtered, and the catalyst was recovered and reused. The methanol was recovered by rotary evaporation to obtain a solid with a yield of 96%.

[0098] (2) Preparation of 2-chloro-5-nitroaniline: In a 100 mL three-necked round-bottom flask, 1.38 g of m-nitroaniline was dissolved in 4 mL of N-methylpyrrolidone, cooled to -10 °C, and NCS was added while stirring. The reaction was carried out for 3 h. The molar ratio of m-nitroaniline to NCS was 1:1.1. After the reaction was completed, the mixture was quenched and neutralized with saturated sodium bicarbonate solution, then extracted with toluene, washed with water, concentrated and evaporated to dryness. The crude product in the flask was a pale yellow solid with a yield of 90%.

[0099] Purification of 2-chloro-5-nitroaniline: The crude product was added to a round-bottom flask, followed by the addition of 80% aqueous ethanol solution. The mixture was heated to reflux, cooled to 50°C, and filtered to remove insoluble matter. The filtrate was slowly cooled to 25°C, and crystals precipitated. These crystals were collected by vacuum filtration. The crystals obtained at 25°C were recrystallized from the solution with 60% aqueous ethanol solution, cooled to 0°C, and filtered to obtain 2-chloro-5-nitroaniline. After recrystallization purification, the yield was 86%, and the purity was 94%.

[0100] (3) Preparation of 2',4-dinitro-2-aminodiphenyl ether: 1.39 g of o-nitrophenol, 1.38 g of sodium carbonate, 10 g of 1,4-dioxane and 1.72 g of 2-chloro-5-nitroaniline were added to a 250 mL flask, heated to 140 °C and reacted for 3 h. After the reaction was completed, the mixture was allowed to cool naturally to room temperature. 100 mL of water was added, and the mixture was stirred for 30 min. The mixture was then filtered and dried to obtain 2',4-dinitro-2-aminodiphenyl ether with a yield of 95%.

[0101] (4) Preparation of 2',4-dichloro-2-aminodiphenyl ether: 0.275 g of 2',4-dinitro-2-aminodiphenyl ether was dissolved in 3 mL of acetonitrile, and FeCl3 acetonitrile solution, sodium chloride, and Oxone were added. The equivalent ratio of 2',4-dinitro-2-aminodiphenyl ether, Oxone, NaCl, and FeCl3 was 1:0.5:3:2. The reaction was carried out in a photoreactor at 50 °C under ultraviolet light for 36 h to obtain a 2',4-dichloro-2-aminodiphenyl ether reaction solution. The obtained 2',4-dichloro-2-aminodiphenyl ether reaction solution was extracted, and the organic phase was concentrated to obtain a solid. The solid was recrystallized with methanol (during recrystallization, the mass ratio of solid to methanol was 1:3, the dissolution temperature was 50 °C, and the final crystallization temperature was 5 °C). The recrystallization yield was 80%, and the purity was 95.5%.

[0102] Example 6

[0103] A method for preparing 2',4-dichloro-2-aminodiphenyl ether, wherein the preparation method comprises:

[0104] (1) Selective hydrogenation of m-dinitrobenzene: In a high-temperature and high-pressure reactor, 1.68 g of m-dinitrobenzene, 50 g of methanol, and 0.094 g of Ru-Pd / C were added and stirred until homogeneous. The mixture was purged with hydrogen 2-3 times. The temperature was set at 80℃ and the hydrogen pressure at 1.8 MPa. The reaction was completed after 6 hours, with a molar ratio of m-dinitrobenzene to hydrogen of 1:3.0. The mixture was cooled to room temperature, and 30 g of methanol was added. The mixture was stirred until homogeneous, filtered, and the catalyst was recovered and reused. The methanol was recovered by rotary evaporation to obtain a solid with a yield of 93%.

[0105] (2) Preparation of 2-chloro-5-nitroaniline: 1.38 g of m-nitroaniline was dissolved in 4 mL of 1,4-dioxane in a 100 mL three-necked round-bottom flask. The temperature was lowered to -10 °C, and NCS was added while stirring. The reaction was carried out for 3 h. The molar ratio of m-nitroaniline to NCS was 1:1.3. After the reaction was completed, the mixture was quenched and neutralized with saturated sodium bicarbonate solution, then extracted with toluene, washed with water, and the organic phase was concentrated and evaporated to dryness. The crude product in the flask was a pale yellow solid with a yield of 83%.

[0106] Purification of 2-chloro-5-nitroaniline: The crude product was added to a round-bottom flask, followed by the addition of 80% aqueous ethanol solution. The mixture was heated to reflux, cooled to 50°C, and filtered to remove insoluble matter. The filtrate was slowly cooled to 25°C, and crystals precipitated. These crystals were collected by vacuum filtration. The crystals obtained at 25°C were recrystallized from the solution with 60% aqueous ethanol solution, cooled to 0°C, and filtered to obtain 2-chloro-5-nitroaniline. After recrystallization purification, the yield was 84%, and the purity was 94%.

[0107] (3) Preparation of 2',4-dinitro-2-aminodiphenyl ether: 1.39 g of o-nitrophenol, 1.38 g of sodium carbonate, 10 g of 1,4-dioxane and 1.72 g of 2-chloro-5-nitroaniline were added to a 250 mL flask, heated to 140 °C and reacted for 3 h. After the reaction was completed, the mixture was allowed to cool naturally to room temperature. 100 mL of water was added, and the mixture was stirred for 30 min. The mixture was then filtered and dried to obtain 2',4-dinitro-2-aminodiphenyl ether with a yield of 95%.

[0108] (4) Preparation of 2',4-dichloro-2-aminodiphenyl ether: 0.275 g of 2',4-dinitro-2-aminodiphenyl ether was dissolved in 3 mL of acetonitrile, and FeCl3 acetonitrile solution, sodium chloride, and Oxone were added. The equivalent ratio of 2',4-dinitro-2-aminodiphenyl ether, Oxone, NaCl, and FeCl3 was 1:0.5:3:2. The reaction was carried out in a photoreactor at 50 °C under ultraviolet light for 36 h to obtain a 2',4-dichloro-2-aminodiphenyl ether reaction solution. The obtained 2',4-dichloro-2-aminodiphenyl ether reaction solution was extracted, and the organic phase was concentrated to obtain a solid. The solid was recrystallized with methanol (during recrystallization, the mass ratio of solid to methanol was 1:3, the dissolution temperature was 50 °C, and the final crystallization temperature was 5 °C). The recrystallization yield was 80%, and the purity was 95.5%.

[0109] Example 7

[0110] A method for preparing 2',4-dichloro-2-aminodiphenyl ether, wherein the preparation method comprises:

[0111] (1) Selective hydrogenation of m-dinitrobenzene: In a 100 mL high-temperature and high-pressure reactor, 1.68 g of m-dinitrobenzene, 18 g of ethanol, and 0.094 g of palladium on carbon were added and stirred until homogeneous. The mixture was purged with hydrogen 2-3 times. The temperature was set at 60 °C and the hydrogen pressure at 2.0 MPa. The reaction was completed after 6 h, with a molar ratio of m-dinitrobenzene to hydrogen of 1:3.0. The mixture was cooled to room temperature, and 5 g of ethanol was added. The mixture was stirred until homogeneous, filtered, and the catalyst was recovered and reused. The ethanol was recovered by rotary evaporation to obtain solid m-nitroaniline with a yield of 94%.

[0112] (2) Preparation of 2-chloro-5-nitroaniline: In a 100 mL three-necked round-bottom flask, 1.38 g of m-nitroaniline was dissolved in 4 mL of toluene, cooled to -15 °C, and NCS was added while stirring. The reaction was carried out for 5 h, wherein the molar ratio of m-nitroaniline to NCS was 1:1.2. After the reaction was completed, the mixture was quenched and neutralized with saturated sodium bicarbonate solution, then extracted with toluene, the organic phase was washed with water, concentrated and evaporated to dryness, and the crude product in the flask was a pale yellow solid with a yield of 93%.

[0113] Purification of 2-chloro-5-nitroaniline: The crude product was added to a round-bottom flask, followed by the addition of 80% aqueous ethanol solution. The mixture was heated to reflux, cooled to 50°C, and filtered to remove insoluble matter. The filtrate was slowly cooled to 25°C, and crystals precipitated. These crystals were collected by vacuum filtration. The crystals obtained at 25°C were recrystallized from the solution with 60% aqueous ethanol solution, cooled to 0°C, and filtered to obtain 2-chloro-5-nitroaniline with a yield of 84% and a purity of 98.9%.

[0114] (3) Preparation of 2',4-dinitro-2-aminodiphenyl ether: 1.39 g of o-nitrophenol, 1.66 g of potassium carbonate, 10 g of N,N-dimethylacetamide and 1.80 g of 2-chloro-5-nitroaniline were added to a 250 mL flask, heated to 120 °C and reacted for 7 h. After the reaction was completed, the mixture was allowed to cool naturally to room temperature. 100 mL of water was added, and the mixture was stirred for 30 min. The mixture was then filtered and dried to obtain 2',4-dinitro-2-aminodiphenyl ether with a yield of 96%.

[0115] (4) Preparation of 2',4-dichloro-2-aminodiphenyl ether: 0.275 g of 2',4-dinitro-2-aminodiphenyl ether was dissolved in 3 mL of acetonitrile, and FeCl3 acetonitrile solution, sodium chloride, and Oxone were added. The equivalent ratio of 2',4-dinitro-2-aminodiphenyl ether, Oxone, NaCl, and FeCl3 was 1:0.5:3:2. The reaction was carried out in a photoreactor at 45 °C under ultraviolet light for 40 h to obtain a 2',4-dichloro-2-aminodiphenyl ether reaction solution. The obtained 2',4-dichloro-2-aminodiphenyl ether reaction solution was extracted, and the organic phase was concentrated to obtain a solid. The solid was recrystallized from methanol (during recrystallization, the mass ratio of solid to methanol was 1:3, the dissolution temperature was 50 °C, and the final crystallization temperature was 5 °C). The recrystallization yield was 80%, and the purity was 95.4%.

[0116] Example 8

[0117] A method for preparing 2',4-dichloro-2-aminodiphenyl ether, wherein the preparation method comprises:

[0118] (1) Selective hydrogenation of m-dinitrobenzene: In a 100 mL high-temperature and high-pressure reactor, 1.68 g of m-dinitrobenzene, 15.12 g of methanol, and 0.094 g of palladium on carbon were added and stirred until homogeneous. The mixture was purged with hydrogen 2-3 times. The temperature was set at 60 °C and the hydrogen pressure at 1.2 MPa. The reaction was completed after 6 h, with a molar ratio of m-dinitrobenzene to hydrogen of 1:3.0. The mixture was cooled to room temperature, 5 g of methanol was added, stirred until homogeneous, filtered, and the catalyst was recovered and reused. The methanol was recovered by rotary evaporation to obtain solid m-nitroaniline with a yield of 95%.

[0119] (2) Preparation of 2-chloro-5-nitroaniline: In a 100 mL three-necked round-bottom flask, 1.38 g of m-nitroaniline was dissolved in 4 mL of toluene, cooled to 15 °C, and NCS was added while stirring. The reaction was carried out for 3 h, wherein the molar ratio of m-nitroaniline to NCS was 1:1.2. After the reaction was completed, the mixture was quenched and neutralized with saturated sodium bicarbonate solution, then extracted with toluene, the organic phase was washed with water, concentrated and evaporated to dryness, and the crude product in the flask was a pale yellow solid with a yield of 78%. By comparing the experimental results of Example 8 and Examples 1-7, it can be seen that the reaction temperature in step (2) is more conducive to improving the yield when it is -15~0 °C.

[0120] Purification of 2-chloro-5-nitroaniline: The crude product was added to a round-bottom flask, followed by the addition of 80% aqueous ethanol solution. The mixture was heated to reflux, cooled to 50°C, and filtered to remove insoluble matter. The filtrate was slowly cooled to 25°C, and crystals precipitated. These crystals were collected by vacuum filtration. The crystals obtained at 25°C were then recrystallized from the solution with 60% aqueous ethanol solution, cooled to 0°C, and filtered to obtain 2-chloro-5-nitroaniline with a yield of 68% and a purity of 97%.

[0121] (3) Preparation of 2',4-dinitro-2-aminodiphenyl ether: 1.39 g of o-nitrophenol, 1.66 g of potassium carbonate, 10 g of N-methylpyrrolidone and 1.75 g of 2-chloro-5-nitroaniline were added to a 250 mL flask, heated to 170 °C and reacted for 2 h. After the reaction was completed, the mixture was allowed to cool naturally to room temperature. 100 mL of water was added, and the mixture was stirred for 30 min. The mixture was then filtered and dried to obtain 2',4-dinitro-2-aminodiphenyl ether with a yield of 95%.

[0122] (4) Preparation of 2',4-dichloro-2-aminodiphenyl ether: 0.275 g of 2',4-dinitro-2-aminodiphenyl ether was dissolved in 3 mL of acetonitrile, and FeCl3 acetonitrile solution, sodium chloride, and Oxone were added. The equivalent ratio of 2',4-dinitro-2-aminodiphenyl ether, Oxone, NaCl, and FeCl3 was 1:0.5:3:2. The reaction was carried out in a photoreactor at 55 °C under ultraviolet light for 40 h to obtain a 2',4-dichloro-2-aminodiphenyl ether reaction solution. The obtained 2',4-dichloro-2-aminodiphenyl ether reaction solution was extracted, and the organic phase was concentrated to obtain a solid. The solid was recrystallized from methanol (during recrystallization, the mass ratio of solid to methanol was 1:3, the dissolution temperature was 50 °C, and the final crystallization temperature was 5 °C). The recrystallization yield was 75%, and the purity was 95.3%.

[0123] Comparative Example 1

[0124] A method for preparing 2',4-dichloro-2-aminodiphenyl ether. In the preparation method of Comparative Example 1, m-dinitrobenzene is directly used as a raw material to prepare 2,4-dinitrochlorobenzene. The specific preparation process is as follows:

[0125] (1) Preparation of 2,4-dinitrochlorobenzene: In a 100 mL three-necked round-bottom flask, 1.68 g of m-dinitrobenzene was dissolved in 4 mL of toluene, cooled to -10 °C, and NCS was added while stirring. The reaction was carried out for 3 h, wherein the molar ratio of m-dinitrobenzene to NCS was 1:1.2. After the reaction was completed, the mixture was quenched and neutralized with saturated sodium bicarbonate solution, then extracted with toluene, washed with water, concentrated and evaporated to dryness, and the contents of the flask were yellow solid with a yield of 47%. After recrystallization purification, the yield was 40% and the purity was 94%. The recrystallization purification method was as follows: the obtained yellow solid was dissolved in 1 mass of toluene (2 g toluene) and 3 mass of n-heptane (6 g n-heptane) equal to the theoretical yield (theoretical yield 2.02 g), heated to 60 °C, cooled naturally to room temperature, and then cooled to 0 °C to precipitate. The product was filtered, washed with low-temperature cooled n-heptane, and dried at low temperature.

[0126] (2) Preparation of 2-chloro-5-nitroaniline: 2.02 g of 2,4-dinitrochlorobenzene was dissolved in 50 g of methanol, and 0.094 g of Pd / C was added and stirred until homogeneous. The mixture was purged with hydrogen 2-3 times, and the temperature was set at 60 ℃ and the hydrogen pressure at 1.5 MPa. The reaction was stopped after 6 h. The mixture was cooled to room temperature, and 30 g of methanol was added. The mixture was stirred until homogeneous, filtered, and the catalyst was recovered and reused. The methanol was recovered by rotary evaporation to obtain a solid with a yield of 75%.

[0127] (3) Preparation of 2',4-dinitro-2-aminodiphenyl ether: 1.39 g of o-nitrophenol, 1.66 g of potassium carbonate, 10 g of N,N-dimethylformamide and 1.72 g of 2-chloro-5-nitroaniline were added to a 250 mL flask, heated to 140 °C and reacted for 3 h. After the reaction was completed, the mixture was allowed to cool naturally to room temperature. 100 mL of water was added, and the mixture was stirred for 30 min. The mixture was then filtered and dried to obtain 2',4-dinitro-2-aminodiphenyl ether with a yield of 95%.

[0128] (4) Preparation of 2',4-dichloro-2-aminodiphenyl ether: 0.275 g of 2',4-dinitro-2-aminodiphenyl ether was dissolved in 3 mL of acetonitrile, and FeCl3 acetonitrile solution, sodium chloride, and Oxone were added. The equivalent ratio of 2',4-dinitro-2-aminodiphenyl ether, Oxone, NaCl, and FeCl3 was 1:0.5:3:2. The reaction was carried out in a photoreactor at 40 °C under ultraviolet light to obtain 2',4-dichloro-2-aminodiphenyl ether. The obtained 2',4-dichloro-2-aminodiphenyl ether reaction solution was extracted, and the organic phase was concentrated to obtain a solid. The solid was crystallized from methanol, and the recrystallization yield was 75% with a purity of 95%.

[0129] Comparative Example 1 above revealed that directly using m-dinitrobenzene as a raw material to prepare 2,4-dinitrochlorobenzene, followed by selective hydrogenation to obtain 2-chloro-5-nitroaniline, resulted in low yields. The yield of 2,4-dinitrochlorobenzene was only 47%, requiring multiple batches of reaction to obtain the next raw material, and the purity also needed further improvement. The yield of 2-chloro-5-nitroaniline after selective hydrogenation reduction was also low, possibly due to the influence of chloride ions. This indicates that selectively hydrogenating m-dinitrobenzene before the reaction can effectively improve the reaction conversion rate and increase the yield.

[0130] Comparative Example 2

[0131] A method for preparing 2',4-dichloro-2-aminodiphenyl ether is described, using the same method as in Example 1, except that step (3) of Comparative Example 2 uses o-chlorophenol as a raw material. The specific preparation method is as follows:

[0132] (1) Selective hydrogenation of m-dinitrobenzene: In a 100 mL high-temperature and high-pressure reactor, 1.68 g of m-dinitrobenzene, 15.12 g of methanol, and 0.094 g of palladium on carbon were added and stirred until homogeneous. The mixture was purged with hydrogen 2-3 times. The temperature was set at 60 °C and the hydrogen pressure at 1.2 MPa. The reaction was completed after 6 h, with a molar ratio of m-dinitrobenzene to hydrogen of 1:3.0. The mixture was cooled to room temperature, 5 g of methanol was added, stirred until homogeneous, filtered, and the catalyst was recovered and reused. The methanol was recovered by rotary evaporation to obtain solid m-nitroaniline with a yield of 95%.

[0133] (2) Preparation of 2-chloro-5-nitroaniline: In a 100 mL three-necked round-bottom flask, 1.38 g of m-nitroaniline was dissolved in 4 mL of toluene, cooled to 0 °C, and NCS was added while stirring. The reaction was carried out for 3 h, with a molar ratio of m-nitroaniline to NCS of 1:1.2. After the reaction was completed, the mixture was quenched and neutralized with saturated sodium bicarbonate solution, then extracted with toluene, washed with water, concentrated and evaporated to dryness. The crude product in the flask was a pale yellow solid with a yield of 91%. Purification of 2-chloro-5-nitroaniline: The crude product was added to a round-bottom flask, 80% aqueous ethanol solution was added, heated to reflux, cooled to 50 °C, and insoluble matter was removed by filtration. The filtrate was slowly cooled to 25 °C, and crystals precipitated. The crystals were collected by vacuum filtration. The crystals crystallized at 25 °C were recrystallized with 60% aqueous ethanol solution, cooled to 0 °C, and 2-chloro-5-nitroaniline was obtained by vacuum filtration with a yield of 82% and a purity of 98.1%.

[0134] (3) Preparation of 2',4-dinitro-2-aminodiphenyl ether: 1.28 g of o-chlorophenol, 1.66 g of potassium carbonate, 10 g of N,N-dimethylformamide and 1.72 g of 2-chloro-5-nitroaniline were added to a 250 mL flask, heated to 140 °C and reacted for 3 h. After the reaction was completed, the mixture was allowed to cool naturally to room temperature. 100 mL of water was added, and the mixture was stirred for 30 min. The mixture was then filtered and dried to obtain 2'-chloro-4-nitro-2-aminodiphenyl ether with a yield of 75%.

[0135] (4) Preparation of 2',4-dichloro-2-aminodiphenyl ether: 0.264 g of 2'-chloro-4-nitro-2-aminodiphenyl ether was dissolved in 3 mL of acetonitrile, and FeCl3 acetonitrile solution, sodium chloride, and Oxone were added. The equivalent ratio of 2',4-dinitro-2-aminodiphenyl ether, Oxone, NaCl, and FeCl3 was 1:0.5:3:2. The reaction was carried out in a photoreactor at 40 °C under ultraviolet light to obtain 2',4-dichloro-2-aminodiphenyl ether. The obtained 2',4-dichloro-2-aminodiphenyl ether reaction solution was extracted, and the organic phase was concentrated to obtain a solid. The solid was crystallized from methanol, and the recrystallization yield was 75% with a purity of 95%.

[0136] By comparing the experimental results of Example 1 and Comparative Example 2, it can be seen that in step (3), the yield of o-nitrophenol is significantly higher than that of o-chlorophenol, and the required reaction time is shorter. The main reason is that the inductive effect of chloride ions in o-chlorophenol is less than that of conjugation, making it more difficult for hydrogen on the phenolic hydroxyl group to ionize, resulting in a worse reaction effect.

[0137] Comparative Example 3

[0138] 2',4-Dichloro-2-aminodiphenyl ether was prepared using the same method as in Example 1, except that the recrystallization purification of 2-chloro-5-nitroaniline was not performed in step (2) of Comparative Example 3.

[0139] In step (4) of Comparative Example 3, the yield of the 2',4-dichloro-2-aminodiphenyl ether product was 60%, and the purity was 87%.

[0140] A comparison of the experimental results from Example 1 and Comparative Example 3 shows that if the recrystallization purification of 2-chloro-5-nitroaniline is not performed in step (2), the purity and yield of the final 2',4-dichloro-2-aminodiphenyl ether product will be affected. This is because unpurified 2-chloro-5-nitroaniline contains the isomer 4-chloro-5-nitroaniline, which will also react with o-nitrophenol to generate impurities, thus affecting the purity of the final product.

[0141] Comparative Example 4

[0142] 2',4-Dichloro-2-aminodiphenyl ether was prepared using the same method as in Example 1, except that in step (4) of Comparative Example 4, the reaction temperature was 30°C (lower than the temperature conditions specified in this invention).

[0143] In Comparative Example 4, the yield of the 2',4-dichloro-2-aminodiphenyl ether product was 58%, and the purity was 88%.

[0144] A comparison of the experimental results of Example 1 and Comparative Example 4 shows that if the reaction temperature is reduced in step (4), the reaction activity will decrease, ultimately leading to a decrease in the yield of the target product.

[0145] Comparative Example 5

[0146] 2',4-Dichloro-2-aminodiphenyl ether was prepared using the same method as in Example 1, except that sodium chloride was not added in step (4) of Comparative Example 5.

[0147] In Comparative Example 5, the yield of the 2',4-dichloro-2-aminodiphenyl ether product was 46%, and the purity was 85%.

[0148] A comparison of the experimental results of Example 1 and Comparative Example 5 shows that if sodium chloride is not added in step (4), the catalytic activity will decrease significantly, ultimately leading to a decrease in the yield and purity of the target product.

[0149] Comparative Example 6

[0150] 2',4-Dichloro-2-aminodiphenyl ether was prepared using the same method as in Example 1, except that Oxone was not added in step (4) of Comparative Example 6.

[0151] In Comparative Example 6, the yield of the 2',4-dichloro-2-aminodiphenyl ether product was 23%, and the purity was 71%.

[0152] A comparison of the experimental results from Example 1 and Comparative Example 6 shows that if Oxone is not added in step (4), the catalytic activity decreases significantly, ultimately leading to a decrease in the yield and purity of the target product. Therefore, in step (4), a reasonable combination of Oxone, NaCl, and FeCl3 is more conducive to the catalytic reaction, resulting in a high-yield and high-purity target product.

[0153] The beneficial effects of this invention are as follows: using m-dinitrobenzene as a raw material, m-nitroaniline is first selectively hydrogenated to obtain m-nitroaniline. Then, m-nitroaniline is chlorinated with NCS to generate 2-chloro-5-nitroaniline. 2-chloro-5-nitroaniline reacts with o-nitrophenol under the action of a basic condensing agent to generate 2',4-dinitro-2-aminodiphenyl ether. Finally, metal nuclear transfer occurs under ultraviolet light catalysis to obtain 2',4-dichloro-2-aminodiphenyl ether. This invention utilizes readily available and inexpensive m-dinitrobenzene as a raw material to synthesize 2',4-dichloro-2-aminodiphenyl ether. The method is simple, has a high yield, few side reactions, and the product has high economic value, providing technical support for industrial production.

[0154] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0155] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this invention patent should be determined by the appended claims.

Claims

1. A method for preparing 2',4-dichloro-2-aminodiphenyl ether, characterized in that, The preparation method is as follows: S1. m-Dinitrobenzene is selectively hydrogenated to prepare m-nitroaniline; S2. In a solvent, m-nitroaniline reacts with N-chlorosuccinimide to prepare 2-chloro-5-nitroaniline; the reaction temperature is -15~15℃. 2',4-Dinitro-2-aminodiphenyl ether was prepared by a combined heating reaction of S3, 2-chloro-5-nitroaniline, o-nitrophenol, base, and solvent at a temperature of 120-170 °C. S4, 2',4-dinitro-2-aminodiphenyl ether is dissolved in a solvent, and FeCl3, sodium chloride, and Oxone are added. The reaction is catalyzed under ultraviolet light at a temperature of 40-60℃ to prepare 2',4-dichloro-2-aminodiphenyl ether. The equivalent ratio of 2',4-dinitro-2-aminodiphenyl ether, Oxone, NaCl, and FeCl3 is 1:(0.4-0.5):(2.5-3.0):(1.5-2.0). After the reaction in step S2 is completed, 2-chloro-5-nitroaniline is obtained through post-treatment; the solvent used in step S4 is acetonitrile. The post-processing operation is as follows: After the reaction is completed, the reaction is quenched, and after solvent extraction, the solvent is evaporated to obtain crude 2-chloro-5-nitroaniline. The crude 2-chloro-5-nitroaniline is added to an aqueous ethanol solution with a mass concentration of 75%-80%, heated to reflux, cooled to 50-55°C, and the insoluble matter is filtered off. The filtrate is slowly cooled to 20-25°C, and the precipitated crystals are separated. The precipitated crystals are recrystallized again using an aqueous ethanol solution with a mass concentration of 55%-60%. The crystals with a final crystallization temperature of -5~0°C are separated to obtain 2-chloro-5-nitroaniline for the reaction in step S3.

2. The method for preparing 2',4-dichloro-2-aminodiphenyl ether according to claim 1, characterized in that, In step S1, a palladium catalyst is used, and the selective hydrogenation reaction is carried out at a temperature of 50-120°C, a pressure of 1-3 MPa, and a reaction time of 6-8 h.

3. The method for preparing 2',4-dichloro-2-aminodiphenyl ether according to claim 1, characterized in that, The catalyst used in step S1 is selected from at least one of Pd, Pd / C, PdO2, and Pd[P(C6H5)3]4; The molar ratio of m-dinitrobenzene to hydrogen used in selective hydrogenation is 1:(3.0-3.2).

4. The method for preparing 2',4-dichloro-2-aminodiphenyl ether according to claim 1, characterized in that, In step S2, the molar ratio of m-nitroaniline to N-chlorosuccinimide is 1:(1.1-1.3). In step S2, the reaction time is 3-5 h.

5. The method for preparing 2',4-dichloro-2-aminodiphenyl ether according to claim 1, characterized in that, In step S3, the reaction time is 2-7 h.

6. The method for preparing 2',4-dichloro-2-aminodiphenyl ether according to claim 1, characterized in that; The alkali used in step S3 is at least one of potassium hydroxide, potassium carbonate, sodium carbonate, and sodium bicarbonate. In step S3, the molar ratio of 2-chloro-5-nitroaniline and o-nitrophenol to base is (1-1.05):1:(1.2-1.5).

7. The method for preparing 2',4-dichloro-2-aminodiphenyl ether according to claim 1, characterized in that, In step S4, the reaction time is 36-48 hours.

8. The method for preparing 2',4-dichloro-2-aminodiphenyl ether according to claim 1, characterized in that, The solvent used in step S1 is at least one of methanol and ethanol; The solvent used in step S2 is at least one of toluene, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, and 1,4-dioxane; The solvent used in step S3 is at least one of N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, 1,3-dimethylimidazolinone, and 1,4-dioxane.

Images