Process for the preparation of n-(2,4-diaminophenyl)-4-aminobenzamide

Abstract

This invention relates to the field of organic synthesis technology, specifically disclosing a method for preparing N-(2,4-diaminophenyl)-4-aminobenzamide. The method involves using N-(2,4-dinitrophenyl)-4-nitrobenzamide as a raw material, adding a catalyst, buffer salt, and water, mixing the mixture, and then purging with nitrogen gas to maintain pressure. The nitrogen gas is then replaced with hydrogen gas, and a hydrogenation reaction is carried out under a hydrogen atmosphere. After the reaction is complete, an acid is added to quench the reaction, the catalyst is removed by filtration, and then an alkali is added to adjust the pH to above 8. The mixture is then filtered to obtain crude N-(2,4-diaminophenyl)-4-aminobenzamide. The crude product is purified by recrystallization and finally dried to obtain N-(2,4-diaminophenyl)-4-aminobenzamide. The method provided by this invention has high selectivity, few side reactions, protects the amide bond from hydrolysis, and produces a product with high purity.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, and specifically discloses a method for preparing N-(2,4-diaminophenyl)-4-aminobenzamide. Background Technology

[0002] Aromatic amines are important intermediates in the fields of fine chemicals, pharmaceuticals, dyes, and polymer materials. Among them, polyaminobenzamides, due to their abundance of active amino sites, have significant application value in epoxy resin curing agents, organic fluorescent materials, and intermediates for anticancer drugs. Currently, the industrial preparation of polyamino compounds mainly uses polynitro aromatic compounds as raw materials, obtained through catalytic hydrogenation reduction. Compared with traditional routes such as iron powder reduction and alkali sulfide reduction, this process has advantages such as less waste, higher atom economy, and higher product purity, and has become the mainstream production method in the industry.

[0003] CN1104629A discloses a continuous process for preparing aromatic amines, which uses aromatic nitro compounds as raw materials and continuously introduces hydrogen gas in the presence of a catalyst to carry out a reduction reaction, thereby achieving continuous production of aromatic amines. This process improves production efficiency to some extent. However, when using this method to produce N-(2,4-diaminophenyl)-4-aminobenzamide, the polynitrobenzamide molecule contains both nitro and amide bonds. Under high temperature, high pressure, and a strong reducing atmosphere, side reactions such as amide bond hydrolysis, excessive reduction of the benzene ring, deamination, and decarbonylation easily occur, leading to low yield of the target product and a large variety of impurities that are difficult to separate. Summary of the Invention

[0004] To address the aforementioned problems, this invention provides a method for preparing N-(2,4-diaminophenyl)-4-aminobenzamide, which exhibits high selectivity, few side reactions, protection of the amide bond from hydrolysis, and high product purity.

[0005] The technical solution of the present invention is a method for preparing N-(2,4-diaminophenyl)-4-aminobenzamide, comprising the following steps: S1. Using N-(2,4-dinitrophenyl)-4-nitrobenzamide as a raw material, a catalyst, buffer salt and water are added and mixed, and the mixture is heated in a hydrogen atmosphere to carry out a hydrogenation reaction. S2. After the reaction is complete, acid is added to quench the reaction, the catalyst is removed by filtration, and then alkali is added to adjust the pH to above 8. After filtration, crude N-(2,4-diaminophenyl)-4-aminobenzamide is obtained. The crude product is purified by recrystallization and finally dried to obtain N-(2,4-diaminophenyl)-4-aminobenzamide.

[0006] Furthermore, the catalyst is prepared by coating modification using Raney nickel as a raw material; the amount of catalyst added is 1~10% of the mass of N-(2,4-dinitrophenyl)-4-nitrobenzamide. Furthermore, the coating modification is performed using the sol-gel method, and the coating materials used include, but are not limited to, TEOS or ZrOCl2.

[0007] Furthermore, the pH of the S1 reaction system is adjusted to 6.5-8.5 using a buffer salt. Sodium dihydrogen phosphate / disodium hydrogen phosphate is preferred.

[0008] Furthermore, nitrogen gas is first introduced into S1 for pressure testing and leak testing, and then replaced with hydrogen gas for heating reaction; the pressure is controlled at 2~5MPa during the reaction.

[0009] Furthermore, the reaction temperature in S1 is 100℃-150℃; the reaction pressure is 2MPa-5MPa; and the reaction time is 24-48h.

[0010] Furthermore, the acid in S2 is hydrochloric acid, and the temperature is controlled between -10 and 30°C during the addition of hydrochloric acid; the pH of the system is adjusted to 1 to 3.

[0011] Furthermore, the alkali in S2 is ammonia water. During the addition of ammonia water, the temperature is controlled at -10~25℃. After adding ammonia water, the pH of the reaction system is adjusted to 8~9.

[0012] Furthermore, during crystallization purification, ethanol-water, methanol, isopropanol, and DMF-water are used as solvents.

[0013] Furthermore, during recrystallization and refining, activated carbon is added to the dissolved material for mixing. The heating temperature is 30-60℃, the stirring time is 0.5-1.5h, and the mixture is filtered while hot.

[0014] The present invention has the following beneficial effects: This invention uses N (2,4 dinitrophenyl) 4 Using nitrobenzamide as a raw material, and with the aid of a Raney nickel catalyst modified by SiO2 or activated carbon, the pH of the reaction system was stabilized to 6.5 using a phosphate buffer salt. 8.5, using water as a medium for catalytic hydrogenation significantly improves reduction selectivity from the reaction source. Coating and modifying the Raney nickel catalyst reduces its basicity and activity, prevents runaway temperatures, and protects the amide bonds from hydrolysis; in 2 The system achieves efficient reduction of trinitrogen under 5MPa hydrogen pressure, while avoiding side reactions such as excessive hydrogenation, deamination, and coking of the benzene ring. Combined with buffer salts to stabilize the pH of the system, the reaction process is more stable and controllable, effectively ensuring the yield and purity of the target product.

[0015] After the reaction is complete, a post-treatment method of low-temperature acid quenching followed by alkalization and crystallization is employed. 10 Adjust the pH to 1 with hydrochloric acid at 30°C. 3. Dissolves reaction intermediates and organic impurities; filters to remove catalyst, then adjusts pH to 8 with ammonia at low temperature. 9. This process precipitates the target product in high purity, significantly simplifying the separation and purification process and reducing impurity residue. The crude product is recrystallized and decolorized with activated carbon stirring, effectively removing trace organic impurities and colored components, ultimately yielding N... (2,4 (diaminophenyl) 4 Aminobenzamide products are characterized by high purity, regular crystal form, and excellent color.

[0016] The preparation method of this invention uses water as the reaction medium, is mild, safe to operate, and produces low levels of waste. It can achieve highly selective synthesis without the need for high-temperature and high-pressure continuous equipment, and solves the defects of traditional high-temperature hydrogenation processes, such as numerous side reactions, easy catalyst deactivation, difficulty in product purification, and poor applicability. It has significant technical advantages and application value in industrial production. Attached Figure Description

[0017] Figure 1 This is the liquid phase detection spectrum of the product in Example 1 of the present invention. Detailed Implementation

[0018] Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Unless otherwise specified, all raw materials and reagents used are commercially available. The preparation methods for coated Raney nickel used in the following examples and comparative examples are as follows: Raney nickel was first treated with 1 mol / L hydrochloric acid to remove the oxide layer on its surface, and then ultrasonically dispersed in water to form a suspension. Tetraethoxysilane (TEOS) was then added dropwise to the Raney nickel suspension. The mixture was stirred continuously at 60-80℃ for 4 hours, and the colloid condensed on the surface of the Raney nickel to form a coating layer. After filtration, washing, vacuum drying, and calcination, the gel was converted into an oxide layer, and a SiO2-coated Raney nickel catalyst was obtained. The mass ratio of SiO2 to Raney nickel was 1:100.

[0019] To make the objectives, technical solutions, and advantages of the present invention clearer, the embodiments of the present invention will be described in detail below. It should be noted that, unless otherwise specified, the embodiments and features described in this application can be combined with each other.

[0020] Example 1 Add 105g of N-(2,4-dinitrophenyl)-4-nitrobenzamide (NDBA), 472.5g of water, 52.5g of ethanol, 10.5g of Raney nickel coating, and 2.5g of buffer salt (sodium dihydrogen phosphate / disodium hydrogen phosphate) to a high-pressure reactor. After covering the reactor, stir well. After pressure testing and leak testing, replace the air with nitrogen, and then replace the nitrogen with hydrogen. After the replacement is completed, introduce hydrogen to 3MPa, and then heat the reaction system to 125℃ and react for 36 hours. Continuously introduce hydrogen throughout the process to ensure that the hydrogen pressure is stable at 3MPa. After the reaction is complete, the temperature is reduced and the pressure is released, and the reaction system is transferred to a 2L beaker. The reaction system is placed in a coolant and cooled to -10℃. Then, hydrochloric acid is added dropwise until the pH of the solution is 2. Then, the solution is filtered and the filtrate is transferred to a flask. The filtrate is cooled to -10℃, and ammonia is slowly added dropwise until the pH of the solution is 8-9. The crude solid is obtained by filtration. The crude product was transferred to a beaker, and a water-ethanol solution (mass ratio 9:1) was added. Hydrochloric acid was slowly added dropwise while stirring until the solid was completely dissolved. Then, 5g of activated carbon was added, and the mixture was heated to 50℃ and stirred for 30min. The activated carbon and impurities were filtered off while hot. The mixture was cooled to room temperature, and ammonia was added dropwise until the pH of the solution reached 8-9. The product was then filtered to obtain the final product. After washing with water and vacuum drying, 75.32g of dry product was obtained, with a yield of 98.41% and a purity of 99.86%. The liquid chromatography spectrum is shown below. Figure 1 .

[0021] Example 2 Add 105g of N-(2,4-dinitrophenyl)-4-nitrobenzamide (NDBA), 472.5g of water, 52.5g of ethanol, 10.5g of Raney nickel coating, and 2.5g of buffer salt (sodium dihydrogen phosphate / disodium hydrogen phosphate) to a high-pressure reactor. After covering the reactor, stir well. After pressure testing and leak testing, replace the air with nitrogen, and then replace the nitrogen with hydrogen. After replacement, introduce hydrogen to 3MPa, and then heat the reaction system to 170℃ and react for 30h. Continuously introduce hydrogen throughout the process to ensure that the hydrogen pressure is stable at 3MPa. After the reaction is complete, the temperature is reduced and the pressure is released, and the reaction system is transferred to a 2L beaker. The reaction system is placed in a coolant and cooled to -10℃. Then, hydrochloric acid is added dropwise until the pH of the solution is 2. Then, the solution is filtered and the filtrate is transferred to a flask. The filtrate is cooled to -10℃, and ammonia is slowly added dropwise until the pH of the solution is 8-9. The crude solid is obtained by filtration. The crude product was transferred to a beaker, and a water-ethanol solution (mass ratio 9:1) was added. Hydrochloric acid was slowly added dropwise under stirring until the solid was completely dissolved. Then, 5g of activated carbon was added, and the mixture was heated to 50℃ and stirred for 30min. The activated carbon and impurities were removed while the mixture was hot. The mixture was cooled to room temperature, and ammonia water was added dropwise until the pH of the solution was 8-9. The product was then filtered to obtain the final product. After washing with water and vacuum drying, 35.47g of dry product was obtained, with a yield of 46.34% and a purity of 75.34%.

[0022] Example 3 Add 105g of N-(2,4-dinitrophenyl)-4-nitrobenzamide (NDBA), 472.5g of water, 52.5g of ethanol, 10.5g of Raney nickel coating, and 2.5g of buffer salt (sodium dihydrogen phosphate / disodium hydrogen phosphate) to a high-pressure reactor. After covering the reactor, stir well. After pressure testing and leak testing, replace the air with nitrogen, and then replace the nitrogen with hydrogen. After replacement, introduce hydrogen to 5MPa, and then heat the reaction system to 125℃ and react for 36 hours. Continuously introduce hydrogen throughout the process to ensure that the hydrogen pressure is stable at 5MPa. After the reaction is complete, the temperature is reduced and the pressure is released, and the reaction system is transferred to a 2L beaker. The reaction system is placed in a coolant and cooled to -10℃. Then, hydrochloric acid is added dropwise until the pH of the solution is 2. Then, the solution is filtered and the filtrate is transferred to a flask. The filtrate is cooled to -10℃, and ammonia is slowly added dropwise until the pH of the solution is 8-9. The crude solid is obtained by filtration. The crude product was transferred to a beaker, and a water-ethanol solution (mass ratio 9:1) was added. Hydrochloric acid was slowly added dropwise under stirring until the solid was completely dissolved. Then, 5g of activated carbon was added, and the mixture was heated to 50℃ and stirred for 30min. The activated carbon and impurities were removed while the mixture was hot. The mixture was cooled to room temperature, and ammonia water was added dropwise until the pH of the solution was 8-9. The product was then filtered to obtain the final product. After washing with water and vacuum drying, 74.96g of the dry product was obtained, with a yield of 97.94% and a purity of 99.78%.

[0023] Example 4 Add 105g of N-(2,4-dinitrophenyl)-4-nitrobenzamide (NDBA), 472.5g of water, 52.5g of ethanol, 10.5g of Raney nickel coating, and 2.5g of buffer salt (sodium dihydrogen phosphate / disodium hydrogen phosphate) to a high-pressure reactor. After covering the reactor, stir well. After pressure testing and leak testing, replace the air with nitrogen, and then replace the nitrogen with hydrogen. After the replacement is completed, introduce hydrogen to 3MPa, and then heat the reaction system to 125℃ and react for 36 hours. Continuously introduce hydrogen throughout the process to ensure that the hydrogen pressure is stable at 3MPa. After the reaction is complete, the temperature is reduced and the pressure is released, and the reaction system is transferred to a 2L beaker. The reaction system is placed in a coolant and cooled to 20°C. Then, hydrochloric acid is added dropwise until the pH of the solution is 2. The solution is then filtered, and the filtrate is transferred to a flask. The filtrate is cooled to -10°C, and ammonia is slowly added dropwise until the pH of the solution is 8-9. The crude solid is obtained by filtration. The crude product was transferred to a beaker, and a water-ethanol solution (mass ratio 9:1) was added. Hydrochloric acid was slowly added dropwise under stirring until the solid was completely dissolved. Then, 5g of activated carbon was added, and the mixture was heated to 50℃ and stirred for 30min. The activated carbon and impurities were filtered out while hot. The mixture was cooled to room temperature, and ammonia water was added dropwise until the pH of the solution was 8-9. The product was then filtered to obtain the final product. After washing with water and vacuum drying, 75.05g of dry product was obtained, with a yield of 94.53% and a purity of 98.31%.

[0024] Example 5 Add 105g of N-(2,4-dinitrophenyl)-4-nitrobenzamide (NDBA), 472.5g of water, 52.5g of ethanol, 10.5g of Raney nickel coating, and 2.5g of buffer salt (sodium dihydrogen phosphate / disodium hydrogen phosphate) to a high-pressure reactor. After covering the reactor, stir well. After pressure testing and leak testing, replace the air with nitrogen, and then replace the nitrogen with hydrogen. After the replacement is completed, introduce hydrogen to 3MPa, and then heat the reaction system to 125℃ and react for 36 hours. Continuously introduce hydrogen throughout the process to ensure that the hydrogen pressure is stable at 3MPa. After the reaction is complete, the temperature is reduced and the pressure is released, and the reaction system is transferred to a 2L beaker. The reaction system is placed in a coolant and cooled to -10℃. Then, hydrochloric acid is added dropwise until the pH of the solution is 2. Then, the solution is filtered and the filtrate is transferred to a flask. The filtrate is cooled to -10℃, and ammonia is slowly added dropwise until the pH of the solution is 8-9. The crude solid is obtained by filtration. The crude product was transferred to a beaker, and DMF-water solution (mass ratio 1:9) was added. Hydrochloric acid was slowly added dropwise under stirring until the solid was completely dissolved. Then, 5g of activated carbon was added, and the mixture was heated to 50℃ and stirred for 30min. The activated carbon and impurities were filtered out while hot. The mixture was cooled to room temperature and ammonia water was added dropwise until the pH of the solution was 8-9. The product was filtered to obtain the final product. After washing with water and vacuum drying, 74.93g of dry product was obtained, with a yield of 97.90% and a purity of 99.67%.

[0025] Example 6 Add 105g of N-(2,4-dinitrophenyl)-4-nitrobenzamide (NDBA), 472.5g of water, 52.5g of ethanol, 5.3g of Raney nickel coating, and 2.5g of buffer salt (sodium dihydrogen phosphate / disodium hydrogen phosphate) to a high-pressure reactor. After covering the reactor, stir well. After pressure testing and leak testing, replace the air with nitrogen, and then replace the nitrogen with hydrogen. After replacement, introduce hydrogen to 3MPa, and then heat the reaction system to 125℃ and react for 42h. Continuously introduce hydrogen throughout the process to ensure that the hydrogen pressure is stable at 3MPa. After the reaction is complete, the temperature is reduced and the pressure is released, and the reaction system is transferred to a 2L beaker. The reaction system is placed in a coolant and cooled to -10℃. Then, hydrochloric acid is added dropwise until the pH of the solution is 2. Then, the solution is filtered and the filtrate is transferred to a flask. The filtrate is cooled to -10℃, and ammonia is slowly added dropwise until the pH of the solution is 8-9. The crude solid is obtained by filtration. The crude product was transferred to a beaker, and DMF-water solution (mass ratio 1:9) was added. Hydrochloric acid was slowly added dropwise under stirring until the solid was completely dissolved. Then, 5g of activated carbon was added, and the mixture was heated to 50℃ and stirred for 30min. The activated carbon and impurities were filtered out while hot. The mixture was cooled to room temperature and ammonia water was added dropwise until the pH of the solution was 8-9. The product was filtered to obtain the final product. After washing with water and vacuum drying, 75.02g of dry product was obtained, with a yield of 98.02% and a purity of 99.8%.

[0026] Comparative Example 1 The catalyst used was 10.5g of uncoated Raney nickel, and the rest was the same as in Example 1.

[0027] After final refining, 60.61g of dried product was obtained, with a yield of 79.19% and a purity of 83.67%.

[0028] Comparative Example 2 Same as Example 1, but without adding buffer salt.

[0029] After final refining, 57.32g of dried product was obtained, with a yield of 74.89% and a purity of 75.35%.

[0030] The above embodiments describe preferred embodiments of the present invention, but the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other way. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention. Therefore, the protection scope of this patent should be determined by the appended claims.

Claims

1. A method for preparing N-(2,4-diaminophenyl)-4-aminobenzamide, characterized in that, Includes the following steps: S1. Using N-(2,4-dinitrophenyl)-4-nitrobenzamide as a raw material, a catalyst, buffer salt and water are added and mixed, and the mixture is heated in a hydrogen atmosphere to carry out a hydrogenation reaction. S2. After the reaction is complete, acid is added to quench the reaction, the catalyst is removed by filtration, and then alkali is added to adjust the pH to above 8. After filtration, crude N-(2,4-diaminophenyl)-4-aminobenzamide is obtained. The crude product is purified by recrystallization and finally dried to obtain N-(2,4-diaminophenyl)-4-aminobenzamide.

2. The preparation method according to claim 1, characterized in that: The catalyst is prepared by coating and modifying Raney nickel as raw material; the amount of catalyst added is 1 to 10% of the mass of N-(2,4-dinitrophenyl)-4-nitrobenzamide.

3. The preparation method according to claim 2, characterized in that: The coating modification was performed using the sol-gel method, and the coating materials used included, but were not limited to, TEOS or ZrOCl2.

4. The preparation method according to claim 1, characterized in that: The pH of the S1 reaction system was adjusted to 6.5-8.5 using buffer salts.

5. The preparation method according to claim 1, characterized in that: Nitrogen gas is first introduced into S1 for pressure testing and leak detection, and then replaced with hydrogen gas for heating reaction; the pressure is controlled at 2~5MPa during the reaction.

6. The preparation method according to claim 1, characterized in that: The reaction temperature in S1 is 100℃-150℃; the reaction pressure is 2MPa-5MPa; and the reaction time is 24-48h.

7. The preparation method according to any one of claims 1 to 6, characterized in that: The acid in S2 is hydrochloric acid. During the addition of hydrochloric acid, the temperature is controlled between -10 and 30°C; the pH of the system is adjusted to 1 to 3.

8. The preparation method according to claim 7, characterized in that: The alkali in S2 is ammonia water. During the addition of ammonia water, the temperature is controlled between -10 and 25°C. After adding ammonia water, the pH of the reaction system is adjusted to 8 to 9.

9. The preparation method according to claim 1, characterized in that: During recrystallization purification, ethanol-water, methanol, isopropanol, and DMF-water are used as solvents.

10. The preparation method according to claim 1, characterized in that: During recrystallization refining, activated carbon is added to the dissolved material for mixing. The heating temperature is 30-60℃, the stirring time is 0.5-1.5h, and the mixture is filtered while hot.

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