A process for the preparation of 2-(4-aminophenyl)-5-aminobenzimidazole

Abstract

The application provides a preparation method of 2-(4-aminophenyl)-5-aminobenzimidazole, which comprises the following steps: (1) reacting 4-cyanonitrobenzene and 1,2-diamino-4-nitrobenzene in an organic solvent under the action of a catalyst to generate an intermediate product; (2) removing insoluble substances in the material after the reaction in the step (1) through filtration, then adding a reducing agent and an acid, and reacting the intermediate product with the reducing agent under acidic conditions to generate 2-(4-aminophenyl)-5-aminobenzimidazole; and (3) obtaining high-purity 2-(4-aminophenyl)-5-aminobenzimidazole product through post-treatment of the material after the reaction in the step (2). The preparation method has the advantages of mild reaction conditions, simple operation, relatively cheap and easily-obtained raw materials and catalyst, high selectivity of the reaction, high purity and yield of the prepared product, and the like.

Description

Technical Field

[0001] This invention relates to the field of organic chemical synthesis technology, and in particular to a method for preparing 2-(4-aminophenyl)-5-aminobenzimidazole. Background Technology

[0002] Aromatic polyimides, as high-performance polymer materials, possess excellent high-temperature mechanical properties, dielectric properties, radiation resistance, and solvent resistance, and have gained widespread recognition worldwide. Their superior properties have led to their successful applications in numerous fields, including aerospace, 5G, microelectronics, liquid crystal displays, and separation membranes. 2-(4-aminophenyl)-5-aminobenzimidazole is an important diamine monomer raw material for polyimides. Introducing it into the polyimide backbone structure yields tough and elastic polyimide films with superior high-temperature resistance and machinability compared to traditional polyimides. Furthermore, in the electronics industry, it exhibits excellent comprehensive performance in applications such as flexible printed circuit boards, liquid crystal display alignment films, and fuel cell proton exchange membranes.

[0003] Currently, the main methods for synthesizing 2-(4-aminophenyl)-5-aminobenzimidazole are:

[0004] (1) 2-(4-aminophenyl)-5-aminobenzimidazole was synthesized by substitution, cyclization and catalytic reduction of p-nitrobenzoyl chloride and 1-amino-2,4-dinitrobenzene. The synthetic route is as follows:

[0005]

[0006] The raw materials for this route are relatively cheap and readily available, but it is difficult to reduce all three nitro groups to amino groups in the final step, which affects the reaction conditions and yield. In addition, this route has very high requirements for the catalyst.

[0007] (2) Using 1,2-diamino-4-nitrobenzene and p-nitrobenzyl chloride, condensation, high-temperature cyclization dehydration and catalytic reduction were used to obtain 2-(4-aminophenyl)-5-aminobenzimidazole. The synthetic route is as follows:

[0008]

[0009] This reaction route first uses 1-methyl-2-pyrrolidone as a solvent to obtain 2-(4-nitrophenyl)-5-nitrobenzene via a one-pot condensation, cyclization, and dehydration process at 185–190 °C. Then, catalytic hydrogenation reduction yields 2-(4-aminophenyl)-5-aminobenzimidazole. This route requires high temperatures and consumes a large amount of energy; it also requires a large quantity of phosphoric acid, which can easily cause pollution.

[0010] (3) 2-(4-aminophenyl)-5-aminobenzimidazole was synthesized by reacting 1,2-diamino-4-nitrobenzene and p-aminobenzaldehyde polymers. The synthetic route is as follows:

[0011]

[0012] The p-aminobenzaldehyde polymer used in this route is expensive and difficult to obtain, thus limiting the source of raw materials for this reaction route.

[0013] (4) The direct dehydration reaction of 1,2,4-triaminobenzene and p-aminobenzoic acid reduces the reduction steps compared to other methods. The synthetic route is as follows:

[0014]

[0015] Because all three amino groups of 1,2,4-triaminobenzene can react in this reaction route, the reaction selectivity is poor and the product yield is low. Summary of the Invention

[0016] To address the aforementioned problems, this invention proposes a method for preparing 2-(4-aminophenyl)-5-aminobenzimidazole. Using p-nitrobenzenenitrile and 1,2-diamino-4-nitrobenzene as raw materials, 2-(4-aminophenyl)-5-aminobenzimidazole is obtained through substitution, cyclization, and reduction reactions. This preparation method features mild reaction conditions, simple operation, relatively inexpensive and readily available raw materials and catalysts, high reaction selectivity, and high product purity and yield.

[0017] Specifically, the synthetic route for preparing 2-(4-aminophenyl)-5-aminobenzimidazole according to the present invention is as follows:

[0018]

[0019] Includes the following steps:

[0020] (1) In an organic solvent, p-nitrobenzene (I) and 1,2-diamino-4-nitrobenzene (II) react under the action of a catalyst to generate intermediate product (III);

[0021] (2) Filter to remove insoluble matter from the material after reaction in step (1), and then add reducing agent and acid. The intermediate product (III) reacts with the reducing agent under acidic conditions to generate 2-(4-aminophenyl)-5-aminobenzimidazole (IV).

[0022] (3) The material after the reaction in step (2) is post-processed to obtain a high-purity 2-(4-aminophenyl)-5-aminobenzimidazole (IV) product.

[0023] The raw materials used in this invention, p-nitrobenzenenitrile and 1,2-diamino-4-nitrobenzene, are relatively simple and readily available, the process is simple, and the reaction selectivity is high. Furthermore, this invention eliminates the need for phosphoric acid, thus avoiding the environmental pollution problems caused by it. The embodiments of this invention demonstrate that the yield of 2-(4-aminophenyl)-5-aminobenzimidazole prepared using the method of this invention can reach up to 95.64%, and the purity of the prepared product can reach up to 99.73%.

[0024] Based on the above technical solution, the research and development team of this invention explored and optimized the dosage of the added raw materials, catalyst, reducing agent, acid, and solvent. Specifically, the molar ratio of p-nitrobenzene, 1,2-diamino-4-nitrobenzene, catalyst, organic solvent in step (1), and reducing agent and acid in step (2) can be selected as 1∶(1-1.5):(0.1-0.5):(8-20):(1-5):(1-6), and can be further selected as 1∶1.2∶0.3∶12∶2∶3. Further embodiments of this invention show the preparation process and results of 2-(4-aminophenyl)-5-aminobenzimidazole with different ratios of added raw materials, catalyst, reducing agent, acid, and solvent.

[0025] Based on the above technical solution, the catalyst can be selected from one or two of zirconium sulfate, zirconium nitrate, anhydrous magnesium sulfate, 4A molecular sieve, anhydrous sodium sulfate, activated alumina, phosphorus pentoxide, and anhydrous calcium chloride; further, it can be selected from zirconium sulfate, zirconium nitrate, magnesium sulfate, anhydrous sodium sulfate, and anhydrous calcium chloride; even further, it can be selected from zirconium sulfate. Further embodiments of the present invention show the preparation process and results using different catalysts.

[0026] Based on the above technical solution, the organic solvent can be selected from one or more of methanol, ethanol, isopropanol, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, methyl tert-butyl ether, diethylene glycol methyl ether, N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, 1,2-dichloroethane, chloroform, carbon tetrachloride, toluene, xylene, chlorobenzene, ethyl acetate, acetone, acetonitrile, and C3-C12 saturated alkyl nitrile; further selected from diethylene glycol monomethyl ether, isopropanol, N,N-dimethylacetamide, xylene, or N-methylpyrrolidone; even further selected from N-methylpyrrolidone or diethylene glycol monomethyl ether; and still further selected from diethylene glycol monomethyl ether.

[0027] Based on the above technical solution, the reducing agent used in this invention can be hydrogen gas, or one or more of zinc powder, iron powder, and indium powder, preferably indium powder. The research team of this invention discovered that using hydrogen gas or metal powders (such as zinc powder, iron powder, and indium powder) as reducing agents can effectively reduce organic intermediates (III), and can achieve rapid reaction and efficient reduction under relatively mild conditions; furthermore, using hydrogen gas or metal powders (such as zinc powder, iron powder, and indium powder) as reducing agents also has high selectivity.

[0028] Based on the above technical solution, adding acid in step (2) can promote the activity of the reducing agent, which helps the reduction reaction of intermediate product (III) to proceed efficiently. This invention has explored and optimized the types of acids added. Specifically, the acid added in step (2) can be hydrochloric acid, acetic acid, sulfuric acid, or propionic acid, and more specifically, acetic acid. Further embodiments of this invention illustrate the preparation process and results of adding different types of acids.

[0029] Based on the above technical solution, the reaction temperatures of steps (1) and (2) of this invention have been optimized. Specifically, the reaction temperature of step (1) is 60℃-190℃, preferably 130℃; the reaction temperature of step (2) is 20℃-80℃, preferably 60℃. Compared with the stringent temperature requirements in existing reaction routes, the reaction conditions of the preparation process of this invention are milder, more operable, and can reduce energy consumption loss.

[0030] It should be noted that in the specific process, step (1) includes adding the catalyst, p-nitrobenzenenitrile, 1,2-diamino-4-nitrobenzene and organic solvent in sequence to a dry reaction vessel, and then stirring until the raw materials react completely to generate intermediate product (III); the insoluble matter filtered in step (2) includes undissolved inorganic substances, such as catalysts.

[0031] Based on the above technical solution, the post-processing operation in step (3) is specifically as follows: the material after the reaction in step (2) is filtered, concentrated, crystallized, and dried to obtain a high-purity 2-(4-aminophenyl)-5-aminobenzimidazole (IV) product; further, the concentration operation is specifically as follows: the filtrate is subjected to vacuum distillation to recover 50%-80% of the solvent for recycling back to step (1), thereby realizing the recycling of the solvent and saving process costs.

[0032] Compared with the prior art, the present invention uses p-nitrobenzonitrile and 1,2-diamino-4-nitrobenzene as raw materials to prepare 2-(4-aminophenyl)-5-aminobenzimidazole. The reaction conditions are mild, the operation is simple, and the raw materials and catalysts used are relatively cheap and readily available, which helps to reduce energy consumption and process costs. In addition, the reaction has high selectivity, and the purity and yield of the obtained product are high. Detailed Implementation

[0033] To facilitate understanding of the present invention, a more comprehensive description is provided below, along with preferred embodiments. However, it should be understood that these embodiments are merely for more detailed explanation and should not be construed as limiting the invention in any way, i.e., not limiting the scope of protection of the invention. Unless otherwise defined, the technical terms used in the following embodiments have the same meaning as commonly understood by those skilled in the art to which this invention pertains. Unless otherwise specified, the experimental reagents used in the following embodiments are conventional biochemical reagents; and the experimental methods, unless otherwise specified, are conventional methods.

[0034] This invention proposes a method for preparing 2-(4-aminophenyl)-5-aminobenzimidazole, the synthetic route of which is as follows:

[0035]

[0036] Examples 1-6 will demonstrate the process flow for preparing 2-(4-aminophenyl)-5-aminobenzimidazole under specific operating conditions. It should be noted that these process flows are only demonstrations of preferred processes and do not limit the scope of protection of this invention.

[0037] Example 1

[0038] A method for preparing 2-(4-aminophenyl)-5-aminobenzimidazole, the specific process flow includes:

[0039] In a dry three-necked flask, 8.5 g of zirconium sulfate, 14.8 g of p-nitrobenzenenitrile, 18.4 g of 1,2-diamino-4-nitrobenzene, and 150 g of diethylene glycol monomethyl ether were added sequentially. The mixture was then heated to 130 °C and stirred until the reaction was complete. After the reaction was complete, the mixture was cooled to 40 °C and filtered to remove insoluble matter. Subsequently, 18 g of acetic acid and 23 g of indium were added to the filtrate, and the mixture was heated to 60 °C until the reaction was complete. The mixture was then filtered, and the filtrate was distilled under reduced pressure to recover 50-80% of the solvent. The system was further cooled to allow crystals to precipitate, filtered, washed with water, and dried under vacuum to obtain 21 g of 2-(4-aminophenyl)-5-aminobenzimidazole product. (See attached image for product image.) Figure 1 The prepared product is a white powder; the yield in this example is 93.75%, and the purity is 99.73%.

[0040] Example 2

[0041] A method for preparing 2-(4-aminophenyl)-5-aminobenzimidazole, the specific process flow includes:

[0042] In a dry three-necked flask, 3g of zirconium sulfate, 14.8g of p-nitrobenzenenitrile, 15.3g of 1,2-diamino-4-nitrobenzene, and 96g of diethylene glycol monomethyl ether were added sequentially. The mixture was then heated to 130°C and stirred until the reaction was complete. After the reaction was complete, the mixture was cooled to 40°C and filtered to remove insoluble matter. Subsequently, 6g of acetic acid and 12g of indium were added to the filtrate, and the mixture was heated to 60°C until the reaction was complete. The mixture was then filtered, and the filtrate was distilled under reduced pressure to recover 50-80% of the solvent. The system was further cooled to allow crystallization, filtered, washed with water, and dried under vacuum to obtain 15g of 2-(4-aminophenyl)-5-aminobenzimidazole product, which was a white powder. The yield of this example was 67%, and the purity was 90.62%.

[0043] Example 3

[0044] A method for preparing 2-(4-aminophenyl)-5-aminobenzimidazole, the specific process flow includes:

[0045] In a dry three-necked flask, 14 g of zirconium sulfate, 14.8 g of p-nitrobenzenenitrile, 23 g of 1,2-diamino-4-nitrobenzene, and 240 g of diethylene glycol monomethyl ether were added sequentially. The mixture was then heated to 130 °C and stirred until the reaction was complete. After the reaction was complete, the mixture was cooled to 40 °C and filtered to remove insoluble matter. Subsequently, 36 g of acetic acid and 57 g of indium were added to the filtrate, and the mixture was heated to 60 °C until the reaction was complete. The mixture was then filtered, and the filtrate was distilled under reduced pressure to recover 50-80% of the solvent. The system was further cooled to allow crystallization, filtered, washed with water, and dried under vacuum to obtain 21.2 g of 2-(4-aminophenyl)-5-aminobenzimidazole product, which was a white powder. The yield of this example was 94.64%, and the purity was 98.65%.

[0046] Example 4

[0047] Based on the preparation method of 2-(4-aminophenyl)-5-aminobenzimidazole shown in Example 1, this example sets up Examples 4.1-4.4 with different types of catalysts added while keeping other parameters unchanged. The specific parameter settings and experimental results are shown in Table 1.

[0048] Table 1

[0049]

[0050] As can be seen from Table 1, the catalyst used in this invention is preferably zirconium sulfate.

[0051] Example 5

[0052] Based on the preparation method of 2-(4-aminophenyl)-5-aminobenzimidazole shown in Example 1, this example sets up Examples 5.1-5.4 with different types of added organic solvents while keeping other parameters unchanged. The specific parameter settings and experimental results are shown in Table 2.

[0053] Table 2

[0054]

[0055] As can be verified from Table 2, the preferred organic solvent used in this invention is diethylene glycol monomethyl ether.

[0056] Example 6

[0057] Based on the preparation method of 2-(4-aminophenyl)-5-aminobenzimidazole shown in Example 1, this example sets up Examples 6.1-6.3 with different types of added acids while keeping other parameters unchanged. The specific parameter settings and experimental results are shown in Table 3.

[0058] Table 3

[0059]

[0060] As can be seen from Table 3, the acid added in step (2) of the present invention is preferably acetic acid.

[0061] Furthermore, it should be noted that the specific embodiments described in this specification may have similar structures but different names. All equivalent or simple variations made to the construction, features, and principles described in this patent concept are included within the protection scope of this patent. Those skilled in the art can make various modifications or additions to the described specific embodiments or use similar methods to replace them, as long as they do not deviate from the structure of this invention or exceed the scope defined by these claims, all of which should fall within the protection scope of this invention.

Claims

1. A method for preparing 2-(4-aminophenyl)-5-aminobenzimidazole, characterized in that, The synthetic route is as follows: ； Includes the following steps: (1) In an organic solvent, p-nitrobenzene (I) and 1,2-diamino-4-nitrobenzene (II) react under the action of a catalyst to generate intermediate product (III). (2) Filter to remove insoluble matter from the material after reaction in step (1), and then add reducing agent and acid. The intermediate product (III) reacts with the reducing agent under acidic conditions to generate 2-(4-aminophenyl)-5-aminobenzimidazole (IV). (3) The material after the reaction in step (2) is post-processed to obtain a high-purity 2-(4-aminophenyl)-5-aminobenzimidazole (IV) product; The catalyst is zirconium sulfate; The reducing agent is one of hydrogen, zinc powder, iron powder, and indium powder; The acid added in step (2) is hydrochloric acid, acetic acid, sulfuric acid or propionic acid; The reaction temperature in step (2) is 20℃-80℃.

2. The method for preparing 2-(4-aminophenyl)-5-aminobenzimidazole according to claim 1, characterized in that, The molar ratio of p-nitrobenzenenitrile, 1,2-diamino-4-nitrobenzene, catalyst, organic solvent in step (1) and reducing agent and acid in step (2) is: 1:(1-1.5):(0.1-0.5):(8-20):(1-5):(1-6).

3. The method for preparing 2-(4-aminophenyl)-5-aminobenzimidazole according to claim 2, characterized in that, The molar ratio of p-nitrobenzenenitrile, 1,2-diamino-4-nitrobenzene, catalyst, organic solvent in step (1) and reducing agent and acid in step (2) is 1:1.2:0.3:12:2:

3.

4. The method for preparing 2-(4-aminophenyl)-5-aminobenzimidazole according to claim 1, characterized in that, The organic solvent is one or more selected from methanol, ethanol, isopropanol, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, methyl tert-butyl ether, diethylene glycol methyl ether, N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, 1,2-dichloroethane, chloroform, carbon tetrachloride, toluene, xylene, chlorobenzene, ethyl acetate, acetone, acetonitrile, and C3-C12 saturated alkyl nitrile.

5. The method for preparing 2-(4-aminophenyl)-5-aminobenzimidazole according to claim 1, characterized in that, The reaction temperature in step (1) is 60℃-190℃.

6. The method for preparing 2-(4-aminophenyl)-5-aminobenzimidazole according to claim 1, characterized in that, The post-processing operation in step (3) specifically involves filtering, concentrating, crystallizing, and drying the material after the reaction in step (2) to obtain a high-purity 2-(4-aminophenyl)-5-aminobenzimidazole (IV) product.

7. The method for preparing 2-(4-aminophenyl)-5-aminobenzimidazole according to claim 6, characterized in that, The concentration operation specifically involves: performing vacuum distillation on the filtrate to recover 50%-80% of the solvent for recycling back to step (1).

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