Preparation method of nitrobenzimidazole and aminobenzimidazole compounds

Abstract

The invention relates to the technical field of compound preparation, in particular to a preparation method of nitrobenzimidazole and aminobenzimidazole compounds, which comprises the following steps of: adding an inorganic base catalyst into an organic solvent by taking 4-nitro-o-phenylenediamine and a nitrobenzoyl chloride compound as raw materials; the preparation method comprises the following steps: reacting at a temperature lower than room temperature to obtain a condensation reaction solution, continuously raising the temperature of the condensation reaction solution to carry out cyclization reaction, and after the reaction is finished, carrying out post-treatment to obtain the 2-nitrobenzimidazole compound. Taking the 2-nitrobenzimidazole compound as a raw material, adding a reduction catalyst, carrying out hydrogenation reduction reaction in a solvent, and after the reaction is finished, carrying out post-treatment to obtain the 2-aminobenzimidazole compound. According to the preparation method, the inorganic base catalyst is used for replacing a conventional acid catalyst to realize one-pot synthesis, and the preparation method is high in selectivity, high in product quality and yield, mild in reaction condition, simple and convenient to operate, environment-friendly and suitable for batch production.

Description

Technical Field

[0001] The invention relates to a preparation method of nitrobenzimidazole and aminobenzimidazole compounds, belonging to the technical field of compound preparation. Background Art

[0002] 2-aminobenzimidazole compounds belong to benzimidazole compounds. Due to their unique asymmetric conjugated imidazole ring, active hydrogen and a pair of non-shared electron pairs, introducing them into the polymer main chain will greatly improve the heat resistance of the polymer and change the interaction between molecules. The synthesized polyimide materials are widely used in motors, aircraft, automobile parts and high-temperature resistant materials due to their good high-temperature resistance, mechanical processing performance and electrical properties. The polymer film of 2-aminobenzimidazole polyimide can be used to prepare the preferred material of flexible printed circuit boards and liquid crystal display (LCD) orientation films. It has a wide range of applications and an increasing market demand. Therefore, it is of great significance to find an efficient, low-cost and green synthesis method of 2-aminobenzimidazole compounds.

[0003] At present, the preparation methods for synthesizing 2-aminobenzimidazole compounds mainly include:

[0004] The preparation method reported in Chinese patent application CN117164521A is as follows: p-nitrobenzonitrile and 1,2-diamino-4-nitrobenzene are used as raw materials, an intermediate product is generated under the action of zirconium sulfate catalyst, and then 2-(4-aminophenyl)-5-aminobenzimidazole is obtained under the catalytic reduction of glacial acetic acid and indium. The synthetic route is as follows:

[0005]

[0006] Although the synthesis route is simple, the raw material p-nitrobenzonitrile is highly toxic and explosive, which makes transportation and operation difficult. The zirconium sulfate and indium waste are polluting to the environment and are not environmentally friendly, thus limiting industrial mass production.

[0007] The preparation method reported in Chinese patent CN114031557B is as follows: p-nitrobenzoyl chloride and p-aminobenzoic acid are used as raw materials, and 2-(4-aminophenyl)-5-aminobenzimidazole is obtained through condensation, acylation dehydration, oxidation, cyclization and catalytic reduction reaction. The synthesis route is as follows:

[0008]

[0009] The raw materials required for this synthetic route are easy to obtain and cheap, but the synthetic steps are relatively long, requiring five steps of reaction. In addition, the raw materials used are highly corrosive dichlorothionyl and highly oxidizing sodium hypochlorite, which have high requirements on equipment, storage and safety. Post-processing also produces a large amount of wastewater, which is not friendly to the environment and is not suitable for industrial production.

[0010] The preparation method reported in French patent application FR2502151A is: using p-nitrobenzoyl chloride and 1-amino-2,4-dinitrobenzene as raw materials, 2-(4-aminophenyl)-5-aminobenzimidazole is obtained by substitution, cyclization and catalytic reduction reaction. The synthesis route is as follows:

[0011]

[0012] The raw material 1-amino-2,4-dinitrobenzene and intermediates in this synthetic route are all dangerous and explosive (same as benzene ring) polynitro compounds, with high risks in the production and storage processes. In addition, when the polynitro compounds are reduced, a large number of by-products are generated, which are difficult to remove, and the product purity and yield are low. Therefore, it is not suitable for industrial production. Summary of the invention

[0013] The present invention aims at the deficiencies in the prior art and provides a method for preparing nitrobenzimidazole and aminobenzimidazole compounds. The preparation method uses an inorganic base catalyst to replace the conventional acid catalyst to achieve one-pot synthesis, has high selectivity, high product quality and yield, mild reaction conditions, simple operation, no need to separate intermediate products, easy to obtain raw materials and catalysts, low cost and safety, is environmentally friendly, and is suitable for mass production.

[0014] The technical solution of the present invention to solve the above technical problem is as follows: a preparation method of nitrobenzimidazole compounds, the preparation method is:

[0015] In an organic solvent, 4-nitro-o-phenylenediamine and nitrobenzoyl chloride compounds are used as raw materials, an inorganic base catalyst is added, and a condensation reaction liquid is obtained under a condition below room temperature. The condensation reaction liquid is further heated to perform a cyclization reaction. After the reaction is completed, a 2-nitrobenzimidazole compound is obtained through post-treatment.

[0016] The nitrobenzoyl chloride compound is:

[0017] The 2-nitrobenzimidazole compound is:

[0018] Specifically, the inorganic base catalyst is at least one of potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, calcium hydroxide, sodium hydroxide and potassium hydroxide.

[0019] Specifically, the organic solvent is selected from at least one of N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, N-ethyl-2-pyrrolidone and dimethyl sulfoxide.

[0020] Specifically, the molar ratio of the 4-nitro-o-phenylenediamine to the nitrobenzoyl chloride compound is 1:(1-5).

[0021] Specifically, the molar ratio of the 4-nitro-o-phenylenediamine to the inorganic base is 1:(1.05-2).

[0022] Specifically, the temperature for preparing the condensation reaction liquid is -20 to 10°C; the temperature for the cyclization reaction is 80 to 200°C.

[0023] Specifically, the post-treatment operation is: after the reaction is completed, the solid matter is removed by solid-liquid separation operation, and then the solvent is removed to obtain the 2-nitrobenzimidazole compound.

[0024] The present invention also discloses a preparation method of an aminobenzimidazole compound, which comprises the following steps: preparing a 2-nitrobenzimidazole compound according to the preparation method of the present invention, taking the 2-nitrobenzimidazole compound as a raw material, adding a reduction catalyst, carrying out a hydrogenation reduction reaction in a solvent, and after the reaction is completed, performing post-treatment to obtain the 2-aminobenzimidazole compound.

[0025] Specifically, the temperature condition of the hydrogenation reduction reaction is 60-70° C., and the pressure condition is 5-10 atm.

[0026] Specifically, the reduction catalyst is selected from Raney Ni, Pd / C or Pt / C;

[0027] The solvent is selected from at least one of tetrahydrofuran, ethyl acetate, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, dimethyl sulfoxide, methanol and anhydrous ethanol.

[0028] The beneficial effects of the present invention are:

[0029] The present invention uses an inorganic base catalyst to achieve one-pot synthesis, has high reaction selectivity, mild reaction conditions, no need to separate intermediate products, no need for subsequent refining and purification of products, and has high product quality and yield, safe and simple operation, low raw material cost, and conforms to the green and environmentally friendly production concept. The preparation method overcomes the problems of high cost, high energy consumption and low safety factor in the prior art, and is conducive to industrial production.

[0030] In the preparation process of the 2-nitrobenzimidazole compounds of the present invention, 4-nitro-o-phenylenediamine and nitrobenzoyl chloride compounds are used as raw materials, an inorganic base catalyst is added, and a condensation reaction is carried out under a relatively low temperature condition, so that the selectivity in the reaction process can be controlled, so that only one amino group in the structure of 4-nitro-o-phenylenediamine participates in the condensation reaction, thereby avoiding the occurrence of side reactions. In addition, hydrochloric acid is generated during the reaction process, and the inorganic base catalyst can play the role of acid binding, thereby improving the reaction conversion efficiency and reducing the difficulty of environmental treatment. In addition, the remaining inorganic base catalyst in the reaction system can play a catalytic role in the subsequent cyclization reaction process, thereby accelerating the reaction speed and reducing the occurrence of side reactions, and high-yield and high-purity 2-nitrobenzimidazole compounds (yield not less than 92.5%, purity not less than 99.8%) can be obtained without complicated post-processing operations. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 is the H NMR spectrum of 2-(3-nitrophenyl)-5-nitrobenzimidazole described in Example 1;

[0032] Figure 2 for Figure 1 A partial enlarged view of

[0033] Figure 3 is the NMR carbon spectrum of 2-(3-aminophenyl)-5-aminobenzimidazole described in Example 1;

[0034] Figure 4 is the H NMR spectrum of 2-(3-aminophenyl)-5-aminobenzimidazole described in Example 1;

[0035] Figure 5 for Figure 4 A partial enlarged view of

[0036] Figure 6 is the H NMR spectrum of 2-(4-nitrophenyl)-5-nitrobenzimidazole described in Example 3;

[0037] Figure 7 for Figure 6 A partial enlarged view of

[0038] Figure 8 is the NMR carbon spectrum of 2-(4-aminophenyl)-5-aminobenzimidazole described in Example 3;

[0039] Fig. 9 is the H NMR spectrum of 2-(4-aminophenyl)-5-aminobenzimidazole described in Example 3;

[0040] Fig.10 for Fig. 9 A partial enlarged view of . DETAILED DESCRIPTION

[0041] The specific implementation of the present invention is described in detail below. The present invention can be implemented in many other ways than those described herein, and those skilled in the art can make similar improvements without violating the connotation of the present invention, so the present invention is not limited by the specific embodiments disclosed.

[0042] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which the present invention belongs. The terms used are only for describing specific embodiments and are not intended to limit the present invention.

[0043] A preparation method of nitrobenzimidazole compounds, the preparation method comprising:

[0044] In an organic solvent, 4-nitro-o-phenylenediamine and nitrobenzoyl chloride compounds are used as raw materials, an inorganic base catalyst is added, and a condensation reaction liquid is obtained under a condition below room temperature. The condensation reaction liquid is further heated to perform a cyclization reaction. After the reaction is completed, a 2-nitrobenzimidazole compound is obtained through post-treatment.

[0045] The nitrobenzoyl chloride compound is:

[0046] The 2-nitrobenzimidazole compound is:

[0047] Specifically, the inorganic base catalyst is at least one of potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, calcium hydroxide, sodium hydroxide and potassium hydroxide.

[0048] Specifically, the organic solvent is selected from at least one of N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, N-ethyl-2-pyrrolidone, and dimethyl sulfoxide. The mass ratio of the organic solvent to 4-nitro-o-phenylenediamine is (2-10):1.

[0049] Specifically, the molar ratio of the 4-nitro-o-phenylenediamine to the nitrobenzoyl chloride compound is 1:(1-5).

[0050] Specifically, the molar ratio of the 4-nitro-o-phenylenediamine to the inorganic base is 1:(1.05-2).

[0051] Specifically, the temperature for preparing the condensation reaction liquid is -20 to 10°C; the temperature for the cyclization reaction is 80 to 200°C.

[0052] Specifically, the post-treatment operation is: after the reaction is completed, the solid matter is removed by solid-liquid separation operation, and then the solvent is removed to obtain the 2-nitrobenzimidazole compound.

[0053] A method for preparing an aminobenzimidazole compound, the method comprising: using a 2-nitrobenzimidazole compound as a raw material, adding a reduction catalyst, performing a hydrogenation reduction reaction in a solvent, and after the reaction is completed, performing post-treatment to obtain the 2-aminobenzimidazole compound. The reaction principle involved in the preparation process of the 2-aminobenzimidazole compound is:

[0054]

[0055] Specifically, the temperature condition of the hydrogenation reduction reaction is 60-70° C., and the pressure condition is 5-10 atm.

[0056] Specifically, the reduction catalyst is selected from Raney Ni, Pd / C or Pt / C; the mass ratio of the reduction catalyst to the 2-nitrobenzimidazole compound is (0.01%-3%):1.

[0057] The solvent is selected from at least one of tetrahydrofuran, ethyl acetate, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, dimethyl sulfoxide, methanol, and anhydrous ethanol. The mass ratio of the solvent to the 2-nitrobenzimidazole compound is (2-20):1.

[0058] Example 1

[0059] N 2 Under protection, 122.4g 4-nitro-o-phenylenediamine, 134.4g sodium carbonate and 612g N,N-dimethylacetamide were added to a 2L three-necked flask and placed in a -10℃ low-temperature bath. 170.8g m-nitrobenzoyl chloride was dissolved in 367g N,N-dimethylacetamide and slowly added to the reaction system. The reaction temperature in the system was controlled to be -10~-5℃. After the addition was completed, a condensation reaction liquid was obtained. The temperature was continued to rise to 125-130℃ for 2h, filtered, desolventized, cooled to 0-5℃, filtered and dried to obtain 227.2g 2-(3-nitrophenyl)-5-nitrobenzimidazole, DSC: 278.15-280.34℃. The NMR spectrum is as follows Figure 1-Figure 2 As shown, the NMR measurement conditions are: resonance frequency: 400 MHz, solvent: DMSO-D6.

[0060] 227.2g 2-(3-nitrophenyl)-5-aminobenzimidazole, 0.7g Pt / C and 2272g tetrahydrofuran were added to a sealed reactor, hydrogen was introduced, and the reaction was carried out at 60-70°C, 5-10atm for 3h. After the reaction, the catalyst was filtered, the solvent was removed and dried to obtain 177.4g 2-(3-aminophenyl)-5-aminobenzimidazole, DSC: 290.55-294.92°C, HPLC: 99.91%, and the total yield was 99.0%. The NMR spectrum is shown as follows Figure 3-Figure 5As shown, the NMR measurement conditions are: resonance frequency: 101 MHz, solvent: DMSO-D6.

[0061] Example 2

[0062] N 2 Under protection, 122.4g 4-nitro-o-phenylenediamine, 122.4g sodium carbonate and 612g N,N-dimethylacetamide were added to a 2L three-necked flask and placed in a -10°C low-temperature bath. 297g m-nitrobenzoyl chloride was dissolved in 367g N,N-dimethylacetamide and slowly added dropwise to the reaction system. The reaction temperature in the system was controlled to be -10 to -5°C. After the addition was completed, a condensation reaction liquid was obtained. The temperature was continued to rise to 125-130°C for reaction for 2h, filtered, desolventized, cooled to 0-5°C, filtered and dried to obtain 220g 2-(3-nitrophenyl)-5-nitrobenzimidazole.

[0063] 220 g of 2-(3-nitrophenyl)-5-aminobenzimidazole, 0.7 g of Pt / C and 2200 g of tetrahydrofuran were added into a sealed kettle, hydrogen was introduced, and the reaction was carried out at 60-70° C., 5-10 atm for 3 h. After the reaction was completed, the catalyst was filtered, the solvent was removed and dried to obtain 171.7 g of 2-(3-aminophenyl)-5-aminobenzimidazole, HPLC: 99.80%, total yield 95.8%.

[0064] Example 3

[0065] N 2 Under protection, 122.4g of 4-nitro-o-phenylenediamine, 122.4g of sodium carbonate and 612g of N,N-dimethylacetamide were added to a 2L three-necked flask and placed in a -10℃ low-temperature bath. 170.8g of p-nitrobenzoyl chloride was dissolved in 367g of N,N-dimethylacetamide and slowly added to the reaction system. The reaction temperature in the system was controlled to be -10~-5℃. After the addition was completed, a condensation reaction liquid was obtained. The temperature was continued to rise to 125-130℃ for 2h, filtered, desolventized, cooled to 0-5℃, filtered and dried to obtain 210.2g of 2-(4-nitrophenyl)-5-nitrobenzimidazole, DSC: 353.85-357.78℃. The NMR spectrum is shown as follows Figure 6-Figure 7 As shown, the NMR measurement conditions are: resonance frequency: 400 MHz, solvent: DMSO-D6.

[0066] 210.2g 2-(4-nitrophenyl)-5-aminobenzoxazole, 0.6g Pt / C and 2102g tetrahydrofuran were added to a sealed reactor, hydrogen was introduced, and the reaction was carried out at 60-70°C, 5-10atm for 3h. After the reaction, the catalyst was filtered, the solvent was removed and dried to obtain 165.7g 2-(4-aminophenyl)-5-aminobenzoxazole, DSC: 236.75-240.55°C, HPLC: 99.85%, and the total yield was 92.5%. The NMR spectrum is shown as follows Figure 8-Figure 10 As shown, the NMR measurement conditions are: resonance frequency: 101 MHz, solvent: DMSO-D6.

[0067] Example 4

[0068] N 2 Under protection, 122.4g 4-nitro-o-phenylenediamine, 70.6g sodium carbonate and 612g N,N-dimethylacetamide were added to a 2L three-necked flask and placed in a -10°C low-temperature bath. 270.8g p-nitrobenzoyl chloride was dissolved in 367g N,N-dimethylacetamide and slowly added dropwise to the reaction system. The reaction temperature in the system was controlled to be -10 to -5°C. After the addition was completed, a condensation reaction liquid was obtained. The temperature was continued to rise to 125-130°C for reaction for 2h, filtered, desolventized, cooled to 0-5°C, filtered and dried to obtain 225.2g 2-(4-nitrophenyl)-5-nitrobenzimidazole.

[0069] 225.2 g of 2-(4-nitrophenyl)-5-aminobenzoxazole, 0.7 g of Pt / C and 2252 g of tetrahydrofuran were added into a sealed kettle, hydrogen was introduced, and the reaction was carried out at 60-70°C, 5-10 atm for 3 h. After the reaction was completed, the catalyst was filtered, the solvent was removed and dried to obtain 176.5 g of 2-(4-aminophenyl)-5-aminobenzoxazole, HPLC: 99.9%, total yield 98.5%.

[0070] Example 5

[0071] N 2 Under protection, 122.4g 4-nitro-o-phenylenediamine, 120g potassium bicarbonate and 620g dimethyl sulfoxide were added to a 2L three-necked flask and placed in a -20°C low-temperature bath. 148.32g m-nitrobenzoyl chloride was dissolved in 370g dimethyl sulfoxide and slowly added dropwise to the reaction system. The reaction temperature in the system was controlled to be -20 to -10°C. After the addition was completed, a condensation reaction liquid was obtained. The temperature was continued to rise to 80-90°C for reaction for 2.5h, filtered, desolventized, cooled to 0-5°C, filtered and dried to obtain 227.1g 2-(3-nitrophenyl)-5-nitrobenzimidazole.

[0072] 227.1 g of 2-(3-nitrophenyl)-5-aminobenzimidazole, 1.0 g of Raney Ni and 2272 g of ethyl acetate were added to a closed kettle, hydrogen was introduced, and the reaction was carried out at 60-70° C., 5-10 atm for 3 h. After the reaction was completed, the catalyst was filtered, the solvent was removed and dried to obtain 177.2 g of 2-(3-aminophenyl)-5-aminobenzimidazole, HPLC: 99.9%, total yield 98.9%.

[0073] Example 6

[0074] N 2 Under protection, 122.4g 4-nitro-o-phenylenediamine, 38.5g sodium hydroxide and 620g N-methyl-2-pyrrolidone were added to a 2L three-necked flask and placed in a 5°C low-temperature bath. 444.95g m-nitrobenzoyl chloride was dissolved in 500g N-methyl-2-pyrrolidone and slowly added dropwise to the reaction system. The reaction temperature in the system was controlled to be 5-10°C. After the addition was completed, a condensation reaction liquid was obtained. The temperature was continued to rise to 190-200°C for reaction for 1h, filtered, desolventized, cooled to 0-5°C, filtered and dried to obtain 227.0g 2-(3-nitrophenyl)-5-nitrobenzimidazole.

[0075] 227.0 g of 2-(3-nitrophenyl)-5-aminobenzimidazole, 2.0 g of Pd / C and 2272 g of N-methyl-2-pyrrolidone were added to a closed kettle, hydrogen was introduced, and the reaction was carried out at 60-70° C., 5-10 atm for 3 h. After the reaction was completed, the catalyst was filtered, the solvent was removed and dried to obtain 176.8 g of 2-(3-aminophenyl)-5-aminobenzimidazole, HPLC: 99.9%, total yield 98.7%.

[0076] Comparative Example 1

[0077] 2-(3-aminophenyl)-5-aminobenzimidazole is prepared by the conventional method, and the specific preparation process is as follows:

[0078] Under nitrogen protection, 980g of N,N-dimethylacetamide was added to the reaction bottle, and then 122.4g of 4-nitro-o-phenylenediamine and 170.8g of m-nitrobenzoyl chloride were added to the reaction bottle under stirring conditions, and then the temperature in the reaction system was raised to 125-130°C at a heating rate of 5°C / min, and then kept warm for reaction for 2h. After the reaction was completed, the temperature was lowered to below 100°C, and the reaction solution was slowly added to methanol, slowly stirred until solids precipitated, and then allowed to stand and cool to room temperature, and then slurried with methanol, filtered, and dried to obtain 136g of 2-(3-nitrophenyl)-5-nitrobenzimidazole.

[0079] 136 g of 2-(3-nitrophenyl)-5-aminobenzimidazole, 0.7 g of Pt / C and 2272 g of tetrahydrofuran were added to a closed kettle, hydrogen was introduced, and the reaction was carried out at 60-70°C, 5-10 atm for 3 h. After the reaction was completed, the catalyst was filtered, the solvent was removed and dried to obtain 102.4 g of 2-(3-aminophenyl)-5-aminobenzimidazole, HPLC: 83.2%, total yield 57.1%.

[0080] From the comparison of the experimental data of Comparative Example 1 and Example 1, it can be seen that if a conventional preparation method is adopted and no inorganic base is added as a catalyst during the preparation process, the yield and purity of the product will be significantly reduced. Inorganic base as a catalyst can selectively control only one amino group in the structure of 4-nitro-o-phenylenediamine to participate in the condensation reaction, avoiding the occurrence of side reactions in which two amino groups participate in the condensation. Not adding inorganic base as a catalyst will result in a significant decrease in the yield and purity of the product.

[0081] Comparative Example 2

[0082] 2-(3-aminophenyl)-5-aminobenzimidazole was prepared by the same method as in Example 1, except that when preparing 2-(3-nitrophenyl)-5-nitrobenzimidazole, the reaction temperature in the condensation reaction liquid preparation system was increased. In this comparative example 2, the reaction temperature of the system when preparing the condensation reaction liquid was 30-35° C. The specific preparation process is as follows:

[0083] N 2 Under protection, 122.4g 4-nitro-o-phenylenediamine, 134.4g sodium carbonate and 612g N,N-dimethylacetamide were added to a 2L three-necked flask and placed in a 30°C constant temperature bath. 170.8g m-nitrobenzoyl chloride was dissolved in 367g N,N-dimethylacetamide and slowly added dropwise to the reaction system. The reaction temperature in the system was controlled to be 30-35°C. After the addition was completed, a condensation reaction liquid was obtained. The temperature was continued to rise to 125-130°C for reaction for 2h, filtered, desolventized, cooled to 0-5°C, filtered and dried to obtain 164g 2-(3-nitrophenyl)-5-nitrobenzimidazole.

[0084] 164 g of 2-(3-nitrophenyl)-5-aminobenzimidazole, 0.7 g of Pt / C and 2272 g of tetrahydrofuran were added into a closed kettle, hydrogen was introduced, and the reaction was carried out at 60-70°C, 5-10 atm for 3 h. After the reaction was completed, the catalyst was filtered, the solvent was removed and dried to obtain 126. g of 2-(3-aminophenyl)-5-aminobenzimidazole, HPLC: 90.2%, total yield 70.3%.

[0085] From the comparison of the experimental results of Example 1 and Comparative Example 2, it can be seen that if the temperature in the system is increased when preparing the condensation reaction liquid, the purity and yield of the target product will decrease, because the increased temperature will lead to poor selectivity of the inorganic base catalyst, resulting in the condensation reaction of the two amino groups of the raw material 4-nitro-o-phenylenediamine with m-nitrobenzoyl chloride to generate by-products, thereby reducing the purity and yield of the target product.

[0086] Comparative Example 3

[0087] 2-(3-aminophenyl)-5-aminobenzimidazole was prepared by the same method as in Example 1, except that the amount of inorganic base catalyst was reduced when preparing 2-(3-nitrophenyl)-5-nitrobenzimidazole. In this comparative example 3, the molar ratio of 4-nitro-o-phenylenediamine to the inorganic base was 1:0.8. The specific preparation process is as follows:

[0088] N 2 Under protection, 122.4g 4-nitro-o-phenylenediamine, 42.4g sodium carbonate and 612g N,N-dimethylacetamide were added to a 2L three-necked flask and placed in a -10°C low-temperature bath. 170.8g m-nitrobenzoyl chloride was dissolved in 367g N,N-dimethylacetamide and slowly added dropwise to the reaction system. The reaction temperature in the system was controlled to be -10 to -5°C. After the addition was completed, a condensation reaction liquid was obtained. The temperature was continued to rise to 125-130°C for reaction for 2h, filtered, desolventized, cooled to 0-5°C, filtered and dried to obtain 177.2g 2-(3-nitrophenyl)-5-nitrobenzimidazole.

[0089] 177.2 g of 2-(3-nitrophenyl)-5-aminobenzimidazole, 0.7 g of Pt / C and 2272 g of tetrahydrofuran were added into a sealed kettle, hydrogen was introduced, and the reaction was carried out at 60-70° C., 5-10 atm for 3 h. After the reaction was completed, the catalyst was filtered, the solvent was removed and dried to obtain 135.6 g of 2-(3-aminophenyl)-5-aminobenzimidazole, HPLC: 93.2%, total yield 75.7%.

[0090] From the comparison of the experimental results of Example 1 and Comparative Example 2, it can be seen that if the amount of inorganic base catalyst added is reduced during the preparation process, the yield and purity of the target product will also decrease, because the inorganic base catalyst plays a catalytic role in the subsequent cyclization reaction, accelerates the reaction rate, and reduces the occurrence of side reactions. A slight increase in the amount of inorganic base catalyst added will result in a decrease in yield.

[0091] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described 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.

[0092] For those skilled in the art, several modifications and improvements may be made without departing from the concept of the present invention, all of which belong to the protection scope of the present invention. The protection scope of the present invention shall be based on the attached claims.

Claims

1. A method for preparing a nitrobenzimidazole compound, characterized in that: The preparation method is: In an organic solvent, 4-nitro-o-phenylenediamine and nitrobenzoyl chloride compounds are used as raw materials, an inorganic base catalyst is added, and a condensation reaction liquid is obtained under a condition below room temperature. The condensation reaction liquid is further heated to perform a cyclization reaction. After the reaction is completed, a 2-nitrobenzimidazole compound is obtained through post-treatment. The nitrobenzoyl chloride compound is: The 2-nitrobenzimidazole compound is:

2. The method for preparing a nitrobenzimidazole compound according to claim 1, characterized in that: The inorganic base catalyst is at least one of potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, calcium hydroxide, sodium hydroxide and potassium hydroxide.

3. The method for preparing a nitrobenzimidazole compound according to claim 1, characterized in that: The organic solvent is selected from at least one of N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, N-ethyl-2-pyrrolidone and dimethyl sulfoxide.

4. The method for preparing a nitrobenzimidazole compound according to claim 1, characterized in that: The molar ratio of the 4-nitro-o-phenylenediamine to the nitrobenzoyl chloride compound is 1:(1-5).

5. The method for preparing a nitrobenzimidazole compound according to claim 1, characterized in that: The molar ratio of the 4-nitro-o-phenylenediamine to the inorganic base is 1:(1.05-2).

6. The method for preparing a nitrobenzimidazole compound according to claim 1, characterized in that: The temperature for preparing the condensation reaction liquid is -20 to 10°C; the temperature for the cyclization reaction is 80 to 200°C.

7. The method for preparing a nitrobenzimidazole compound according to claim 1, characterized in that: The post-treatment operation is: after the reaction is completed, the solid matter is removed by solid-liquid separation operation, and then the solvent is removed to obtain the 2-nitrobenzimidazole compound.

8. A method for preparing an aminobenzimidazole compound, characterized in that: The preparation method comprises: preparing a 2-nitrobenzimidazole compound according to any one of claims 1 to 7, using the 2-nitrobenzimidazole compound as a raw material, adding a reduction catalyst, and performing a hydrogenation reduction reaction in a solvent. After the reaction is completed, post-treatment is performed to obtain a 2-aminobenzimidazole compound.

9. The method for preparing an aminobenzimidazole compound according to claim 8, characterized in that: The temperature condition of the hydrogenation reduction reaction is 60-70° C., and the pressure condition is 5-10 atm.

10. The method for preparing an aminobenzimidazole compound according to claim 8, characterized in that: The reduction catalyst is selected from Raney Ni, Pd / C or Pt / C; The solvent is selected from at least one of tetrahydrofuran, ethyl acetate, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, dimethyl sulfoxide, methanol and anhydrous ethanol.

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