Preparation method of 3, 4 '-diaminodiphenyl ether

Abstract

The invention relates to the technical field of organic chemical synthesis, in particular to a preparation method of 3, 4 '-diaminodiphenyl ether.The preparation method comprises the steps that S1, under inert gas and in a first solvent, m-dinitrobenzene and p-acetamidophenol are subjected to a heating reaction under the condition of a weak base catalyst, and 3-nitro-4-acetamido diphenyl ether is prepared; s2, in a second solvent, the 3-nitro-4-acetamido diphenyl ether is subjected to a hydrogenation reduction reaction, and 3-amino-4-acetamido diphenyl ether is prepared; and S3, dissolving the 3-amino-4-acetaminodiphenyl ether in an alcohol solvent system, adding an aqueous solution of alkali, controlling the reaction temperature, carrying out a hydrolysis reaction, and after the reaction is finished, carrying out post-treatment to obtain the 3, 4 '-diaminodiphenyl ether. The preparation method provided by the invention has the advantages of easily available raw materials, low price, good selectivity and high product yield, and is more suitable for industrial production by comprehensively considering economical efficiency and safety.

Description

Technical Field

[0001] This invention relates to a method for preparing 3,4'-diaminodiphenyl ether, belonging to the field of organic chemical synthesis technology. Background Technology

[0002] 3,4'-Diaminodiphenyl ether (3,4'-ODA) is an important organic synthesis intermediate widely used in polymer materials, pharmaceuticals, dyes, and other fields. 3,4'-Diaminodiphenyl ether can react with various dianhydride monomers to generate polyimide materials with special properties, which can be applied in flexible printed circuit boards, liquid crystal display devices, high-temperature resistant coatings and adhesives, gas separation membranes, and advanced composite materials.

[0003] Currently, the preparation methods for this product mainly suffer from problems such as harsh reaction conditions, numerous side reactions, low yields, and significant environmental pollution. Traditional preparation methods typically employ complex multi-step reaction processes, which not only increase production costs but also reduce production efficiency. For example, some methods require the use of expensive and highly toxic reagents, and the reaction process must be carried out under high temperature and pressure, placing high demands on equipment. Furthermore, the large amounts of wastewater and waste gas generated are difficult to treat, which is inconsistent with the development concept of green chemistry.

[0004] Patent application CN119528747A discloses a method for preparing 3,4'-diaminodiphenyl ether. Using m-dinitrobenzene as a raw material, selective hydrogenation is first performed to generate m-nitroaniline. Then, m-nitroaniline is reacted with sodium hydroxide to generate m-aminophenol salt. The m-aminophenol salt then undergoes an etherification reaction with p-nitroiodobenzene in a strongly polar aprotic solvent under alkaline catalysis to generate 3-amino-4'-nitrodiphenyl ether. Further hydrogenation is then performed to finally produce 3,4'-diaminodiphenyl ether. This preparation method requires multiple hydrogenation reactions, hydrogen gas is relatively dangerous, and the purity of the target product is low. Patent application CN118791390A discloses a method for preparing 3,4'-diaminodiphenyl ether. Using m-dinitrobenzene as a raw material, it is first selectively hydrogenated to generate m-nitroaniline. Then, using m-nitroaniline as a raw material, it reacts with sodium hydroxide to generate m-aminophenol salt. The m-aminophenol salt reacts with p-nitroiodobenzene in a strongly polar aprotic solvent under alkaline catalysis to generate 3-amino-4'-nitrodiphenyl ether. Finally, it is hydrogenated to generate 3,4'-diaminodiphenyl ether. However, the yield of this method is relatively low. Patent application CN1485315A discloses a method for preparing 3,4'-diaminodiphenyl ether, using nitrodiphenyl ether as a raw material and hydrazine hydrate as a reducing agent, and carrying out a reduction reaction in the presence of a catalyst, thereby obtaining the 3,4'-diaminodiphenyl ether under relatively low pressure. However, this method requires the use of hydrazine hydrate, iron powder, etc. for the reduction reaction. The hydrazine hydrate used is a flammable and explosive material, and the reduction of iron powder will generate a large amount of solid waste, and the post-reaction treatment is difficult. These methods are difficult to apply in industrial production.

[0005] Therefore, developing a method for preparing 3,4'-diaminodiphenyl ether with mild reaction conditions, high yield, environmental friendliness, and suitability for industrial application is of great practical significance. Summary of the Invention

[0006] This invention addresses the shortcomings of existing technologies by providing a method for preparing 3,4'-diaminodiphenyl ether, which solves the problems of harsh reaction conditions, low yield, and significant environmental pollution in existing technologies, and achieves efficient and green synthesis of 3,4'-diaminodiphenyl ether, suitable for industrial applications.

[0007] The technical solution of the present invention to solve the above-mentioned technical problems is as follows: a method for preparing 3,4'-diaminodiphenyl ether, wherein the preparation method is as follows: S1. Under inert gas and in a first solvent, m-dinitrobenzene and p-acetaminophenol are reacted under a weak base catalyst to prepare 3-nitro-4-acetaminodiphenyl ether. S2. In a second solvent, 3-nitro-4-acetamidodiphenyl ether is subjected to a hydrogenation reduction reaction to obtain 3-amino-4-acetamidodiphenyl ether. S3,3-amino-4-acetamidodiphenyl ether was dissolved in an alcohol solvent system and an aqueous solution of alkali was added. The reaction temperature was controlled to carry out the hydrolysis reaction. After the reaction was completed, 3,4'-diaminodiphenyl ether was obtained through post-treatment.

[0008] Furthermore, in step S1, the molar ratio of m-dinitrobenzene to p-acetaminophen is 1:(1-1.5), and the molar ratio of m-dinitrobenzene to the weak base catalyst is 1:(1-2.5).

[0009] Furthermore, in step S1, the weak base catalyst is at least one of potassium carbonate and sodium carbonate; The first solvent is any one of N,N-dimethylformamide, N,N-dimethylacetamide, and dimethyl sulfoxide.

[0010] Furthermore, in step S1, the heating reaction temperature is 120-160℃, and the reaction time is 4-6h; The water content in the first solvent of step S1 does not exceed 200 ppm, and the weak base catalyst is dried.

[0011] Furthermore, in step S2, the second solvent is any one of N,N-dimethylformamide, N,N-dimethylacetamide, methanol, ethanol, and dimethyl sulfoxide.

[0012] Furthermore, in step S2, the catalyst used in the hydrogenation reduction reaction is a Pd / C catalyst, and the amount of Pd / C catalyst added is 0.1%-0.5% of the mass of 3-nitro-4-acetamidodiphenyl ether.

[0013] Furthermore, in step S2, the hydrogenation reduction reaction temperature is 40-80℃, the reaction pressure is 0.5-2 MPa, and the reaction time is 2-5 h.

[0014] Furthermore, in step S3, the alkali is any one of potassium hydroxide, sodium hydroxide, potassium ethoxide, and sodium ethoxide; The concentration of the aqueous solution of the alkali is 2-5 mol / L; The alcohol solvent is methanol or ethanol; the mass ratio of the aqueous solution of the base to the alcohol solvent is 1:(3-5).

[0015] Furthermore, in step S3, the hydrolysis reaction temperature is 40-60℃, and the hydrolysis reaction time is 1-3h.

[0016] Further, the post-reaction processing is as follows: after the reaction is completed, the reaction system is cooled to room temperature, insoluble matter is filtered out, ethyl acetate is added for extraction, the extract is dried with anhydrous sodium sulfate, and ethyl acetate is removed by vacuum distillation to obtain crude product. The crude product is recrystallized with a mixed solvent of ethanol and water to obtain 3,4'-diaminodiphenyl ether product.

[0017] The beneficial effects of this invention are: In the preparation method of 3,4'-diaminodiphenyl ether described in this invention, m-dinitrobenzene and p-acetaminophen are used as starting materials. The reaction system has a relatively light color. With appropriate reaction conditions, a high-yield and high-purity 3,4'-diaminodiphenyl ether product can be obtained. The yield of 3,4'-diaminodiphenyl ether is significantly improved (above 85%) in the preparation method described in this invention, and the yield can even reach above 97%. The purity of the 3,4'-diaminodiphenyl ether product is not less than 99.95%.

[0018] In the preparation method of 3,4'-diaminodiphenyl ether described in this invention, the etherification condensation uses dried potassium carbonate / sodium carbonate as a promoter, which is beneficial to the smooth progress of the reaction. At the same time, potassium chloride is generated as a byproduct, which can be sold as a potassium salt after separation and purification, thereby improving economic benefits.

[0019] In the preparation method of 3,4'-diaminodiphenyl ether described in this invention, the reaction can be carried out directly in a single solvent, which reduces the difficulties in recovery and environmental problems caused by mixed solvents. Moreover, the preparation method described in this invention has a relatively low reaction temperature and mild and controllable reaction conditions, avoiding harsh conditions such as high temperature and high pressure, reducing the requirements for equipment, and reducing energy consumption.

[0020] The preparation method of 3,4'-diaminodiphenyl ether described in this invention uses a relatively common solvent with low toxicity, generates less wastewater and waste gas during the reaction, and can use relatively conventional purification methods to recover and reuse the solvent in the waste liquid, further reducing environmental pollution and meeting the requirements of green chemistry.

[0021] The preparation method of 3,4'-diaminodiphenyl ether described in this invention is simple and convenient to operate. This invention adopts a one-step continuous reaction process of etherification, reduction and hydrolysis, which is relatively simple to operate, reduces the separation and purification steps of intermediate products, improves production efficiency and reduces production costs. Attached Figure Description

[0022] Figure 1 The gas chromatogram of 3,4'-diaminodiphenyl ether prepared in Example 1 is shown. Figure 2 The NMR spectrum of 3,4'-diaminodiphenyl ether prepared in Example 1 is shown. Detailed Implementation

[0023] The specific embodiments of the present invention will be described in detail below. The present invention can be implemented 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.

[0024] 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 is for describing particular embodiments only and is not intended to limit the invention.

[0025] A method for preparing 3,4'-diaminodiphenyl ether, wherein the preparation method comprises: S1. Under inert gas and in a first solvent, m-dinitrobenzene and p-acetaminophenol are heated to prepare intermediate 1 (3-nitro-4-acetaminodiphenyl ether). S2. In a second solvent, 3-nitro-4-acetamidodiphenyl ether is subjected to a hydrogenation reduction reaction to obtain 3-amino-4-acetamidodiphenyl ether. S3,3-amino-4-acetamidodiphenyl ether was dissolved in an alcohol solvent system and an aqueous solution of alkali was added. The reaction temperature was controlled to carry out the hydrolysis reaction. After the reaction was completed, 3,4'-diaminodiphenyl ether was obtained through post-treatment.

[0026] Specifically, in step S1, the molar ratio of m-dinitrobenzene to p-acetaminophen is 1:(1-1.5), and the molar ratio of m-dinitrobenzene to the weak base catalyst is 1:(1-2.5).

[0027] Specifically, in step S1, the weak base catalyst is at least one of potassium carbonate and sodium carbonate; The first solvent is any one of N,N-dimethylformamide, N,N-dimethylacetamide, and dimethyl sulfoxide.

[0028] Specifically, in step S1, the heating reaction temperature is 120-160℃, and the reaction time is 4-6 hours; In step S1, the water content in the first solvent does not exceed 200 ppm, and the weak base catalyst is dried (dried at 120°C for at least 2 hours). That is, during the reaction, the raw materials, catalyst, and solvent used should be kept as anhydrous as possible, which is beneficial to improving the purity and yield of the target product.

[0029] Preferably, in step S1, the heating reaction temperature is 135-145℃.

[0030] More specifically, the feeding sequence in step S1 is as follows: add the first solvent, acetaminophen, and a weak base catalyst to the reactor. After the system is heated to 80-90°C, add m-dinitrobenzene. The first solvent is added to disperse the raw materials in the system; the amount of the first solvent added is only enough to achieve uniform dispersion of the raw materials.

[0031] Specifically, in step S2, the second solvent is any one of N,N-dimethylformamide, N,N-dimethylacetamide, methanol, ethanol, and dimethyl sulfoxide.

[0032] Specifically, in step S2, the catalyst used in the hydrogenation reduction reaction is a Pd / C catalyst, and the amount of Pd / C catalyst added is 0.1%-0.5% of the mass of 3-nitro-4-acetamidodiphenyl ether.

[0033] Specifically, in step S2, the hydrogenation reduction reaction temperature is 40-80℃, the reaction pressure is 0.5-2 MPa, and the reaction time is 2-5 h.

[0034] More specifically, the hydrogenation reduction reaction is carried out in a fixed-bed reactor, making the reaction more controllable and safer.

[0035] More specifically, in step S2, the weight ratio of 3-nitro-4-acetamidodiphenyl ether to the second solvent is 1:(2-5).

[0036] Specifically, in step S3, the alkali is any one of potassium hydroxide, sodium hydroxide, potassium ethoxide, and sodium ethoxide; The concentration of the aqueous solution of the alkali is 2-5 mol / L; The alcohol solvent is methanol or ethanol; the mass ratio of the aqueous solution of the base to the alcohol solvent is 1:(3-5); Specifically, in step S3, the hydrolysis reaction temperature is 40-60℃ and the hydrolysis reaction time is 1-3h.

[0037] More specifically, after the reaction in step S1 is completed, the first solvent is recovered by vacuum distillation, and then 3-nitro-4-acetamidodiphenyl ether is obtained by washing with water, filtering and drying. After the reaction in step S2 is completed, a solvent system containing 3-amino-4-acetamidodiphenyl ether is obtained. If the second solvent used in step S2 is methanol or ethanol, then after the reaction in step S2 is completed, no solvent removal treatment is required. The aqueous solution of alkali is directly added to the system to carry out the reaction in step S3, as long as the mass ratio of the aqueous solution of alkali to the alcohol solvent in the system meets the requirements of this invention.

[0038] Specifically, the post-reaction processing is as follows: After the reaction is completed, the reaction system is cooled to room temperature, insoluble matter is filtered out, ethyl acetate is added for extraction, the extract is dried with anhydrous sodium sulfate, and ethyl acetate is removed by vacuum distillation to obtain crude product. The crude product is recrystallized with a mixed solvent of ethanol and water to obtain 3,4'-diaminodiphenyl ether product.

[0039] More specifically, during recrystallization, the mass ratio of ethanol to water in the mixed solvent is 1:1, and the mass ratio of crude product to mixed solvent is 1:4. During recrystallization, the crude product is dissolved in the mixed solvent at 40°C, then cooled to -5°C and kept at that temperature for 1 hour. Finally, the solid and liquid are separated at a constant temperature and dried to obtain the 3,4'-diaminodiphenyl ether product.

[0040] Example 1 A method for preparing 3,4'-diaminodiphenyl ether, wherein the preparation method comprises: S1. Etherification reaction: Under inert gas protection, N,N-dimethylacetamide (DMAC) was added to a reactor, along with m-dinitrobenzene, p-acetaminophen, and potassium carbonate. The molar ratio of m-dinitrobenzene, p-acetaminophen, and potassium carbonate was 1:1.1:2 (the potassium carbonate used in the reaction was dried, and the first solvent was dehydrated, with a water content not exceeding 200 ppm). Under stirring, the reaction system was heated to 140°C and reacted for 4 hours. DMAC with a purity of 99.85% was recovered by vacuum distillation. After washing with water and filtration, 3-nitro-4-acetaminophen diphenyl ether with a purity of over 99% and a yield of 97% was obtained. S2. Reduction reaction: The etherification reaction product, Pd / C catalyst (0.5% of the mass of 3-nitro-4-acetamidodiphenyl ether), and methanol as the second solvent (the weight ratio of 3-nitro-4-acetamidodiphenyl ether to the second solvent is 1:3) are added to the hydrogenation reduction reactor. Hydrogen gas is introduced, and the reaction pressure is controlled at 1.5 MPa, the reaction temperature is 60℃, and the reaction time is 3 h. After the reaction is completed, a system containing 3-amino-4-acetamidodiphenyl ether is obtained. S3. Hydrolysis reaction: Add sodium hydroxide aqueous solution (concentration of 4 mol / L) to the above system containing 3-amino-4-acetamidodiphenyl ether. The mass ratio of sodium hydroxide aqueous solution to methanol solvent in the system is 1:4. React at 60℃ for 2 hours.

[0041] Product separation and purification: After the reaction was completed, the reaction system was cooled to room temperature and filtered. The filter residue was washed with deionized water. The filtrate and washing liquid were combined and extracted with ethyl acetate. The extract was dried with anhydrous sodium sulfate and then the ethyl acetate was removed by vacuum distillation to obtain the crude product. The crude product was recrystallized with an ethanol-water mixture (volume ratio 1:1) to obtain 3,4'-diaminodiphenyl ether with a yield of 98.5% and a purity of 99.95%.

[0042] Gas phase characterization spectra, such as Figure 1 As shown in Table 1, the gas phase test data are as follows.

[0043] Table 1 Gas phase detection data

[0044] MRI scans as follows Figure 2 As shown, the NMR data are as follows: Deuterated DMSO was used as the solvent. 1. Sample pretreatment: Ensure the sample is dry and pure. Weigh the sample (5~10 mg, concentration 5~10 mg / mL); 2. Solvent selection: Take a clean NMR tube and add approximately 0.5 mL of DMSO-d6 at 400 MHz (deuteration ≥99.8%, providing a deuterium signal for field locking); 3. Sample dissolution: Add the sample to the NMR tube, tighten the cap, and gently agitate or sonicate (gently heat if necessary) until the sample is completely dissolved into a clear solution (incomplete dissolution will result in peak broadening and weak signal).

[0045] Example 2 A method for preparing 3,4'-diaminodiphenyl ether, wherein the preparation method comprises: S1. Etherification reaction: Under inert gas protection, N,N-dimethylacetamide (DMAC) was added to a reactor, along with m-dinitrobenzene, p-acetaminophen, and potassium carbonate. The molar ratio of m-dinitrobenzene, p-acetaminophen, and potassium carbonate was 1:1.3:2 (the potassium carbonate used in the reaction was dried, and the first solvent was dehydrated, with a water content not exceeding 200 ppm). Under stirring, the reaction system was heated to 120°C and reacted for 6 hours. DMAC with a purity of over 99% was recovered by vacuum distillation. After washing with water, pH adjustment, and filtration, 3-nitro-4-acetaminophen diphenyl ether with a purity of over 99% and a yield of 95.0% was obtained. S2. Reduction reaction: The etherification reaction product, Pd / C catalyst (0.3% of the mass of 3-nitro-4-acetamidodiphenyl ether), and second solvent ethanol (the weight ratio of 3-nitro-4-acetamidodiphenyl ether to the second solvent is 1:2) are added to the hydrogenation reduction reactor. Hydrogen gas is introduced, and the reaction pressure is controlled at 2 MPa, the reaction temperature at 40℃, and the reaction time at 2 h. After the reaction is completed, a system containing 3-amino-4-acetamidodiphenyl ether is obtained. S3. Hydrolysis reaction: Add sodium hydroxide aqueous solution (concentration of 2 mol / L) to the above system containing 3-amino-4-acetamidodiphenyl ether. The mass ratio of sodium hydroxide aqueous solution to methanol solvent in the system is 1:3. React at 40℃ for 2 hours.

[0046] Product separation and purification: After the reaction was completed, the reaction system was cooled to room temperature and filtered. The filter residue was washed with deionized water. The filtrate and washing liquid were combined and extracted with ethyl acetate. The extract was dried with anhydrous sodium sulfate and then the ethyl acetate was removed by vacuum distillation to obtain the crude product. The crude product was recrystallized with an ethanol-water mixture (volume ratio 1:1) to obtain 3,4'-diaminodiphenyl ether with a yield of 98.7% and a purity of 99.95%.

[0047] Example 3 A method for preparing 3,4'-diaminodiphenyl ether, wherein the preparation method comprises: S1. Etherification reaction: Under inert gas protection, N,N-dimethylacetamide (DMAC) was added to a reactor, along with m-dinitrobenzene, p-acetaminophen, and sodium carbonate, wherein the molar ratio of m-dinitrobenzene, p-acetaminophen, and sodium carbonate was 1:1:2.5 (the sodium carbonate used in the reaction was dried, and the first solvent was dehydrated, with a water content not exceeding 200 ppm). Under stirring, the reaction system was heated to 140°C and reacted for 4 hours. DMAC with a purity of over 99% was recovered by vacuum distillation. After washing with water, pH adjustment, and filtration, 3-nitro-4-acetaminophen diphenyl ether with a purity of over 99% and a yield of 96.0% was obtained. S2. Reduction reaction: The etherification reaction product, Pd / C catalyst (0.1% of the mass of 3-nitro-4-acetamidodiphenyl ether), and the second solvent N,N-dimethylformamide (the weight ratio of 3-nitro-4-acetamidodiphenyl ether to the second solvent is 1:5) are added to the hydrogenation reduction reactor. Hydrogen gas is introduced, and the reaction pressure is controlled at 2 MPa, the reaction temperature is 40℃, and the reaction time is 4 h. After the reaction is completed, the solvent is removed to obtain 3-amino-4-acetamidodiphenyl ether. S3, Hydrolysis reaction: 3-amino-4-acetamidodiphenyl ether was added to ethanol, and potassium hydroxide aqueous solution (concentration of 2 mol / L) was added. The mass ratio of potassium hydroxide aqueous solution to ethanol solvent in the system was 1:5. The reaction was carried out at 60℃ for 2 hours.

[0048] Product separation and purification: After the reaction was completed, the reaction system was cooled to room temperature and filtered. The filter residue was washed with deionized water. The filtrate and washing liquid were combined and extracted with ethyl acetate. The extract was dried with anhydrous sodium sulfate and then the ethyl acetate was removed by vacuum distillation to obtain the crude product. The crude product was recrystallized with an ethanol-water mixture (volume ratio 1:1) to obtain 3,4'-diaminodiphenyl ether with a yield of 97.2% and a purity of 99.95%.

[0049] Example 4 A method for preparing 3,4'-diaminodiphenyl ether, wherein the preparation method comprises: S1. Etherification reaction: Under inert gas protection, N,N-dimethylacetamide (DMAC) was added to the reactor, along with m-dinitrobenzene, p-acetaminophen, and potassium carbonate. The molar ratio of m-dinitrobenzene, p-acetaminophen, and potassium carbonate was 1:1.5:2 (the potassium carbonate used in the reaction was dried, and the first solvent was dehydrated, with a water content not exceeding 200 ppm). Under stirring, the reaction system was heated to 140°C and reacted for 6 hours. DMAC with a purity of over 99% was recovered by vacuum distillation. After washing with water, pH adjustment, and filtration, 3-nitro-4-acetaminophen diphenyl ether with a purity of over 99% and a yield of 95.7% was obtained. S2. Reduction reaction: The etherification reaction product, Pd / C catalyst (0.4% of the mass of 3-nitro-4-acetaminodiphenyl ether), and the second solvent N,N-dimethylacetamide (the weight ratio of 3-nitro-4-acetaminodiphenyl ether to the second solvent is 1:2) are added to the hydrogenation reduction reactor. Hydrogen gas is introduced, and the reaction pressure is controlled at 1.5 MPa, the reaction temperature is 80℃, and the reaction time is 2 h. After the reaction is completed, the solvent is removed to obtain 3-amino-4-acetaminodiphenyl ether. S3, Hydrolysis reaction: 3-amino-4-acetamidodiphenyl ether was added to methanol, and potassium hydroxide aqueous solution (concentration of 3 mol / L) was added. The mass ratio of potassium hydroxide aqueous solution to methanol solvent in the system was 1:3. The reaction was carried out at 60℃ for 2 hours.

[0050] Product separation and purification: After the reaction was completed, the reaction system was cooled to room temperature and filtered. The filter residue was washed with deionized water. The filtrate and washing liquid were combined and extracted with ethyl acetate. The extract was dried with anhydrous sodium sulfate and then the ethyl acetate was removed by vacuum distillation to obtain the crude product. The crude product was recrystallized with an ethanol-water mixture (volume ratio 1:1) to obtain 3,4'-diaminodiphenyl ether with a yield of 97.0% and a purity of 99.97%.

[0051] Example 5 A method for preparing 3,4'-diaminodiphenyl ether, wherein the preparation method comprises: S1. Etherification reaction: Under inert gas protection, N,N-dimethylacetamide (DMAC) was added to the reactor, along with m-dinitrobenzene, p-acetaminophen, and potassium carbonate. The molar ratio of m-dinitrobenzene, p-acetaminophen, and potassium carbonate was 1:1.5:2.5 (the potassium carbonate used in the reaction was dried, and the first solvent was dehydrated, with a water content not exceeding 200 ppm). Under stirring, the reaction system was heated to 160°C and reacted for 4 hours. DMAC with a purity of over 99% was recovered by vacuum distillation. After washing with water, pH adjustment, and filtration, 3-nitro-4-acetaminophen diphenyl ether with a purity of over 99% and a yield of 93.4% was obtained. S2. Reduction reaction: The etherification reaction product, Pd / C catalyst (0.2% of the mass of 3-nitro-4-acetamidodiphenyl ether), and methanol as the second solvent (the weight ratio of 3-nitro-4-acetamidodiphenyl ether to the second solvent is 1:5) are added to the hydrogenation reduction reactor. Hydrogen gas is introduced, and the reaction pressure is controlled at 1.5 MPa, the reaction temperature is 80℃, and the reaction time is 2 h. After the reaction is completed, a system containing 3-amino-4-acetamidodiphenyl ether is obtained. S3, Hydrolysis reaction: Add potassium hydroxide aqueous solution (concentration of 3 mol / L) to the above system containing 3-amino-4-acetamidodiphenyl ether. The mass ratio of potassium hydroxide aqueous solution to methanol solvent in the system is 1:3. React at 60℃ for 2 hours.

[0052] Product separation and purification: After the reaction was completed, the reaction system was cooled to room temperature and filtered. The filter residue was washed with deionized water. The filtrate and washing liquid were combined and extracted with ethyl acetate. The extract was dried with anhydrous sodium sulfate and then the ethyl acetate was removed by vacuum distillation to obtain the crude product. The crude product was recrystallized with an ethanol-water mixture (volume ratio 1:1) to obtain 3,4'-diaminodiphenyl ether with a yield of 97.0% and a purity of 99.95%.

[0053] Example 6 A method for preparing 3,4'-diaminodiphenyl ether, wherein the preparation method comprises: S1. Etherification reaction: Under inert gas protection, dimethyl sulfoxide, m-dinitrobenzene, p-acetaminophen, and potassium carbonate are added to the reactor, wherein the molar ratio of m-dinitrobenzene, p-acetaminophen, and potassium carbonate is 1:1.5:1 (the potassium carbonate used in the reaction is dried, and the first solvent is dehydrated, with a water content not exceeding 200 ppm). Under stirring, the reaction system is heated to 135°C and reacted for 4 hours. DMAC with a purity of over 99% is recovered by vacuum distillation. After washing with water, adjusting the pH, and filtering, 3-nitro-4-acetaminophen diphenyl ether with a purity of over 99% and a yield of 97.0% is obtained. S2. Reduction reaction: The etherification reaction product, Pd / C catalyst (0.2% of the mass of 3-nitro-4-acetamidodiphenyl ether), and second solvent ethanol (the weight ratio of 3-nitro-4-acetamidodiphenyl ether to the second solvent is 1:3) are added to the hydrogenation reduction reactor. Hydrogen gas is introduced, and the reaction pressure is controlled at 0.5 MPa, the reaction temperature is 80℃, and the reaction time is 4 h. After the reaction is completed, a system containing 3-amino-4-acetamidodiphenyl ether is obtained. S3. Hydrolysis reaction: Add sodium ethoxide aqueous solution (concentration of 4 mol / L) to the above system containing 3-amino-4-acetamidodiphenyl ether. The mass ratio of sodium ethoxide aqueous solution to methanol solvent in the system is 1:4. React at 50°C for 1 hour.

[0054] Product separation and purification: After the reaction was completed, the reaction system was cooled to room temperature and filtered. The filter residue was washed with deionized water. The filtrate and washing liquid were combined and extracted with ethyl acetate. The extract was dried with anhydrous sodium sulfate and then the ethyl acetate was removed by vacuum distillation to obtain the crude product. The crude product was recrystallized with an ethanol-water mixture (volume ratio 1:1) to obtain 3,4'-diaminodiphenyl ether with a yield of 97.2% and a purity of 99.95%.

[0055] Example 7 A method for preparing 3,4'-diaminodiphenyl ether, wherein the preparation method comprises: S1. Etherification reaction: Under inert gas protection, N,N-dimethylformamide, m-dinitrobenzene, p-acetaminophen, and potassium carbonate are added to the reactor, wherein the molar ratio of m-dinitrobenzene, p-acetaminophen, and potassium carbonate is 1:1.5:2 (the potassium carbonate used in the reaction is dried, and the first solvent is dehydrated, with a water content not exceeding 200 ppm). Under stirring, the reaction system is heated to 145°C and reacted for 3 hours. DMAC with a purity of over 99% is recovered by vacuum distillation. After washing with water, adjusting the pH, and filtering, 3-nitro-4-acetaminophen diphenyl ether with a purity of over 99% and a yield of 96.9% is obtained. S2. Reduction reaction: The etherification reaction product, Pd / C catalyst (0.2% of the mass of 3-nitro-4-acetamidodiphenyl ether), and second solvent ethanol (the weight ratio of 3-nitro-4-acetamidodiphenyl ether to the second solvent is 1:3) are added to the hydrogenation reduction reactor. Hydrogen gas is introduced, and the reaction pressure is controlled at 1.0 MPa, the reaction temperature is 50℃, and the reaction time is 4 h. After the reaction is completed, a system containing 3-amino-4-acetamidodiphenyl ether is obtained. S3. Hydrolysis reaction: Add potassium ethoxide aqueous solution (concentration of 3 mol / L) to the above system containing 3-amino-4-acetamidodiphenyl ether. The mass ratio of potassium ethoxide aqueous solution to methanol solvent in the system is 1:5. React at 45℃ for 2 hours.

[0056] Product separation and purification: After the reaction was completed, the reaction system was cooled to room temperature and filtered. The filter residue was washed with deionized water. The filtrate and washing liquid were combined and extracted with ethyl acetate. The extract was dried with anhydrous sodium sulfate and then the ethyl acetate was removed by vacuum distillation to obtain the crude product. The crude product was recrystallized with an ethanol-water mixture (volume ratio 1:1) to obtain 3,4'-diaminodiphenyl ether with a yield of 97.3% and a purity of 99.95%.

[0057] Comparative Example 1 3,4'-diaminodiphenyl ether was prepared using the same method as in Example 1, except that the catalyst used in step S1 of Comparative Example 1 was sodium hydroxide in the same molar amount.

[0058] The 3-nitro-4-acetaminodiphenyl ether obtained in step S1 of Comparative Example 1 has a purity of 92% and a yield of 86.0%.

[0059] A comparison of the experimental results from Example 1 and Comparative Example 1 shows that if a strong base is used as the base catalyst in step S1, the product yield and purity decrease. This is because the key to the reaction is the nucleophilic substitution of the phenolic hydroxyl group (-OH): the base gently abstracts the proton from the phenolic hydroxyl group (-OH → -O). - This process generates a phenoxy anion with moderate nucleophilicity. This anion preferentially attacks the potentiophilic site of m-dinitrobenzene, forming the target ether bond (O-linked). However, the strong alkalinity of NaOH disrupts this selectivity, initiating N-nucleophilic substitution of acetaminophen (-NHCOCH3). From a stability perspective, strong bases can accelerate the hydrolysis of acetaminophen and the oxidation of phenolic hydroxyl groups, generating a large number of difficult-to-separate impurities.

[0060] Comparative Example 2 3,4'-Diaminodiphenyl ether was prepared using the same method as in Example 1, except that the molar ratio of intermediate dinitrobenzene to acetaminophen in step S1 of Comparative Example 2 was 1:2.5 (increasing the amount of acetaminophen).

[0061] The 3-nitro-4-acetaminodiphenyl ether obtained in step S1 of Comparative Example 2 has a purity of 91% and a yield of 88.1%.

[0062] A comparison of the experimental results from Example 1 and Comparative Example 2 shows that if too much acetaminophen is used in step S1, the yield and purity of the target product will also decrease. This is because, under a suitable molar ratio, acetaminophen can only preferentially attack one potentiophilic site of m-dinitrobenzene to generate the target monosubstituted product, and the disubstituted reaction is inhibited. When too much acetaminophen is used, the concentration of the nucleophile (phenolic hydroxyl group) in the system is too high, and the already generated target monosubstituted product will be further attacked by the excess acetaminophen, resulting in a disubstituted reaction to generate disubstituted byproducts such as 3,5-bis(4-acetaminophenoxy)nitrobenzene, which leads to a decrease in purity and yield.

[0063] Comparative Example 3 3,4'-diaminodiphenyl ether was prepared using the same method as in Example 1, except that the reaction temperature in step S1 of Comparative Example 3 was 100°C (lower than the temperature conditions specified in this invention).

[0064] The 3-nitro-4-acetaminodiphenyl ether obtained in step S1 of Comparative Example 3 has a purity of 93% and a yield of 85.2%.

[0065] A comparison of the experimental results from Example 1 and Comparative Example 3 shows that lowering the reaction temperature in step S1 leads to a decrease in the yield and purity of the target product. This is because the proportion of reactant molecules in the system that can reach the "activated state" is significantly reduced, resulting in a significant slowdown in the reaction rate. Incomplete conversion leaves a large amount of unreacted raw materials in the system. These unreacted raw materials cannot be converted into the target intermediate 3-nitro-4-acetamidodiphenyl ether, directly leading to a decrease in the yield of the target product. Generally, in organic reactions, the rate advantage of the target reaction is more pronounced, and side reactions are suppressed. When the temperature drops to 100°C, the decrease in the target reaction rate is much greater than that of the side reactions. These side reaction products are difficult to completely separate from the target intermediate (3-nitro-4-acetamidodiphenyl ether) through conventional post-processing (such as filtration and crystallization), ultimately resulting in a decrease in the purity of the target intermediate to 93%.

[0066] Comparative Example 4 3,4'-diaminodiphenyl ether was prepared using the same method as in Example 1, except that the reaction temperature in step S1 of Comparative Example 4 was reflux temperature (166°C, which is higher than the temperature conditions specified in this invention).

[0067] The 3-nitro-4-acetaminodiphenyl ether obtained in step S1 of Comparative Example 4 has a purity of 95% and a yield of 89%.

[0068] A comparison of the experimental results from Example 1 and Comparative Example 4 shows that if the reaction temperature in step S1 increases, the yield and purity of the target product will decrease. This is because the acetaminophen, phenolic hydroxyl group, and nitro group in the reaction system are prone to stability degradation at high temperatures. The phenolic hydroxyl group (-OH) of acetaminophen has reducing properties and is easily oxidized by oxidants in the system (such as m-dinitrobenzene, which can act as a weak oxidant, or oxygen in the air) at high temperatures, generating quinone derivatives (such as acetaminophenquinone) or phenolic dimers (such as 4,4'-diacetaminophen diphenyl ether). These oxidation products are dark-colored impurities that are difficult to separate. Above the solvent boiling point, the solvent boiling leads to intense convection in the system, which may result in local enrichment of raw materials, leading to a decrease in purity and yield.

[0069] Comparative Example 5 3,4'-diaminodiphenyl ether was prepared using the same method as in Example 1, except that in step S1 of Comparative Example 5, the catalyst and solvent were not dried or dehydrated, and the water content in the system was higher than 500 ppm.

[0070] The 3-nitro-4-acetaminodiphenyl ether obtained in step S1 of Comparative Example 5 has a purity of 93% and a yield of 90%.

[0071] A comparison of the experimental results from Example 1 and Comparative Example 5 shows that a high water content in the system during step S1 leads to a decrease in the yield and purity of the target product. This is because water is a protic solvent and will undergo a protonation reaction with sodium phenolate, which has strong nucleophilicity. The resulting free phenol (Ar-OH) has a much lower nucleophilicity than sodium phenolate (O). - The electron cloud density of the sodium phenolate is much higher than that of the -OH group, which cannot effectively attack the activation site of the m-dinitrobenzene. At the same time, the decrease in sodium phenolate concentration will lead to a significant slowdown in the reaction rate. Some m-dinitrobenzene and p-acetaminophen cannot react completely, which ultimately results in a decrease in the yield of the target product.

[0072] Comparative Example 6 3,4'-diaminodiphenyl ether was prepared using the same method as in Example 1, except that the concentration of the aqueous solution of alkali in step S3 of Comparative Example 6 was 1 mol / L (lower than the temperature conditions specified in this invention). The 3,4'-diaminodiphenyl ether obtained in step S3 of Comparative Example 6 had a yield of 92.4% and a purity of 94.15%.

[0073] A comparison of the experimental results from Example 1 and Comparative Example 6 shows that a decrease in the concentration of the alkali aqueous solution in step S3 leads to a decrease in the yield and purity of the target product. This is because when the alkali concentration decreases from the specified value to 1 mol / L, the OH- content in the system decreases. - The concentration decreased significantly, leading to a slower rate of amide bond cleavage and a decrease in the concentration of OH groups in the system. - "Insufficient supply" prevents the acetylamino group from being completely hydrolyzed, and the remaining intermediate cannot be converted into the target product (3,4'-diaminodiphenyl ether), directly causing a decrease in the yield of the target product.

[0074] Comparative Example 7 3,4'-diaminodiphenyl ether was prepared using the same method as in Example 1, except that the concentration of the aqueous solution of alkali in step S3 of Comparative Example 7 was 10 mol / L (higher than the temperature conditions specified in this invention). The 3,4'-diaminodiphenyl ether obtained in step S3 of Comparative Example 7 had a yield of 90.8% and a purity of 92.36%.

[0075] A comparison of the experimental results from Example 1 and Comparative Example 7 shows that if the concentration of the alkali aqueous solution in step S3 is too high, it will lead to a decrease in the yield and purity of the target product, because high concentrations of OH... -Excessive reaction of the amino group exacerbates the formation of coupling / substitution impurities (a major factor in decreased purity). Both 3,4'-diaminodiphenyl ether and 3-amino-4-acetamidodiphenyl ether contain free amino groups (-NH2). These amino groups are activated in high-concentration strong bases (increased lone pair electron activity), initiating amino coupling reactions and substitution reactions between the amino group and impurities. Therefore, using the aqueous solution concentration of the base specified in this invention is more conducive to obtaining the target product with high yield and high purity.

[0076] Comparative Example 8 3,4'-diaminodiphenyl ether was prepared using the same method as in Example 1, except that in step S3 of Comparative Example 8, the mass ratio of the aqueous solution of the base and the second solvent was 1:2 (equivalent to keeping the amount of the second solvent constant while increasing the mass ratio of the aqueous solution of the base). The 3,4'-diaminodiphenyl ether obtained in step S3 of Comparative Example 8 had a yield of 92.5% and a purity of 93.30%.

[0077] A comparison of the experimental results from Example 1 and Comparative Example 8 shows that increasing the proportion of the aqueous alkali solution in step S3 leads to a decrease in the yield and purity of the target product. This is because the molecular core of 3,4'-diaminodiphenyl ether is an aromatic ether bond (-Ar-O-Ar-), and increasing the amount of alkali solution means that OH... - The total amount increases, and the excess OH- - The ether bonds preferentially attack aromatic rings with lower electron cloud density (such as aromatic rings containing amino groups, where the electron-donating effect of the amino group increases the electron cloud at the ortho and para positions, making the meta position or another aromatic ring a weak site), leading to the ether bond breaking and generating sodium 3-aminophenol and 4-aminophenol.

[0078] Comparative Example 9 3,4'-diaminodiphenyl ether was prepared using the same method as in Example 1, except that in step S3 of Comparative Example 9, the mass ratio of the aqueous solution of the base to the second solvent was 1:8 (equivalent to keeping the amount of the second solvent unchanged while reducing the mass ratio of the aqueous solution of the base). The 3,4'-diaminodiphenyl ether obtained in step S3 of Comparative Example 9 had a yield of 90.8% and a purity of 93.90%.

[0079] A comparison of the experimental results from Example 1 and Comparative Example 9 shows that reducing the proportion of the aqueous alkali solution in step S3 leads to a decrease in the yield and purity of the target product. This is because the alkaline hydrolysis of the amide bond is a nucleophilic substitution reaction (SN2), requiring sufficient OH-. - As a nucleophile, it attacks the carbonyl carbon of the acetyl group, driving the reaction to completion. The reduced amount of alkali water leads to the OH group... -The insufficient total amount of amide bond hydrolysis and the resulting incomplete hydrolysis exacerbated the uneven reaction due to system polarity imbalance. The combined effect of these multiple factors led to a lower yield (90.8%) and purity (93.90%) of 3,4'-diaminodiphenyl ether compared to Example 1. This also demonstrates that the specified "mass ratio of alkaline water to the second solvent" in Example 1 was designed to balance OH-... - The key conditions for supply quantity and system homogeneity are to ensure that the deprotection reaction is efficient and selective.

[0080] 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 exhaustively listed. 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.

[0081] For those skilled in the art, various modifications and improvements can be made without departing from the concept of the present invention, and these modifications and improvements are all within the scope of protection of the present invention. The scope of protection of the present invention is defined by the appended claims.

Claims

1. A method for preparing 3,4'-diaminodiphenyl ether, characterized in that, The preparation method is as follows: S1. Under inert gas and in a first solvent, m-dinitrobenzene and p-acetaminophenol are reacted under a weak base catalyst to prepare 3-nitro-4-acetaminodiphenyl ether. S2. In a second solvent, 3-nitro-4-acetamidodiphenyl ether is subjected to a hydrogenation reduction reaction to obtain 3-amino-4-acetamidodiphenyl ether. S3,3-amino-4-acetamidodiphenyl ether was dissolved in an alcohol solvent system and an aqueous solution of alkali was added. The reaction temperature was controlled to carry out the hydrolysis reaction. After the reaction was completed, 3,4'-diaminodiphenyl ether was obtained through post-treatment.

2. The method for preparing 3,4'-diaminodiphenyl ether according to claim 1, characterized in that, In step S1, the molar ratio of m-dinitrobenzene to p-acetaminophen is 1:(1-1.5), and the molar ratio of m-dinitrobenzene to the weak base catalyst is 1:(1-2.5).

3. The method for preparing 3,4'-diaminodiphenyl ether according to claim 1, characterized in that, In step S1, the weak base catalyst is at least one of potassium carbonate and sodium carbonate; The first solvent is any one of N,N-dimethylformamide, N,N-dimethylacetamide, and dimethyl sulfoxide.

4. The method for preparing 3,4'-diaminodiphenyl ether according to claim 1, characterized in that, In step S1, the heating reaction temperature is 120-160℃, and the reaction time is 4-6 hours. The water content in the first solvent of step S1 does not exceed 200 ppm, and the weak base catalyst is dried.

5. The method for preparing 3,4'-diaminodiphenyl ether according to claim 1, characterized in that, In step S2, the second solvent is any one of N,N-dimethylformamide, N,N-dimethylacetamide, methanol, ethanol, and dimethyl sulfoxide.

6. The method for preparing a 3,4'-diaminodiphenyl ether according to claim 1, characterized in that, In step S2, the catalyst used in the hydrogenation reduction reaction is a Pd / C catalyst, and the amount of Pd / C catalyst added is 0.1%-0.5% of the mass of 3-nitro-4-acetamidodiphenyl ether.

7. The method for preparing a 3,4'-diaminodiphenyl ether according to claim 1, characterized in that, In step S2, the hydrogenation reduction reaction temperature is 40-80℃, the reaction pressure is 0.5-2 MPa, and the reaction time is 2-5 h.

8. The method for preparing 3,4'-diaminodiphenyl ether according to claim 1, characterized in that, In step S3, the alkali is any one of potassium hydroxide, sodium hydroxide, potassium ethoxide, and sodium ethoxide; The concentration of the aqueous solution of the alkali is 2-5 mol / L; The alcohol solvent is methanol or ethanol; The mass ratio of the aqueous solution of the alkali to the alcohol solvent is 1:(3-5).

9. The method for preparing a 3,4'-diaminodiphenyl ether according to claim 1, characterized in that, In step S3, the hydrolysis reaction temperature is 40-60℃ and the hydrolysis reaction time is 1-3h.

10. The method for preparing a 3,4'-diaminodiphenyl ether according to claim 1, characterized in that, The post-reaction processing was as follows: After the reaction was completed, the reaction system was cooled to room temperature, the insoluble matter was filtered off, ethyl acetate was added for extraction, the extract was dried with anhydrous sodium sulfate, and the ethyl acetate was removed by vacuum distillation to obtain the crude product. The crude product was recrystallized with a mixed solvent of ethanol and water to obtain the 3,4'-diaminodiphenyl ether product.

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