Method for preparing 5-nitrobenzimidazolone through continuous nitration

Abstract

The invention belongs to the technical field of chemical product preparation, and particularly relates to a method for preparing 5-nitrobenzimidazolone through continuous nitration. According to the method, a sulfonic acid group modified Ni-resin material is used as a catalyst, and a tubular reactor-multi-reaction module microchannel reactor combined system is combined, so that continuous preparation of 5-nitrobenzimidazolone can be efficiently realized, a high-purity product can be obtained by adopting the method, meanwhile, the reaction process is safe and stable, and the method is suitable for industrial production. The method has significant value in industrial production.

Description

Technical Field

[0001] The invention belongs to the field of chemical product preparation technology, and specifically relates to a method for preparing 5-nitrobenzimidazolone by continuous nitration. Background Art

[0002] 5-Nitrobenzimidazolone is a green crystalline powder and an important raw material for synthesizing 5-acetoacetylaminobenzimidazolone. At present, the industry mainly uses benzimidazolone as a raw material to prepare 5-nitrobenzimidazolone through nitration reaction.

[0003] The nitration reaction process mainly includes three categories: intermittent, semi-intermittent and continuous. Intermittent reactions have the disadvantages of large heat release and sticky materials, local over-reactions, and difficulty in control, resulting in low purity of the produced 5-nitrobenzimidazolone and low safety factor. In order to improve the mass transfer and heat transfer capacity of the process, reduce heat accumulation in the reactor and improve the safety of the nitration process, the intermittent and semi-intermittent processes are continuously transformed to reduce the stock of hazardous chemicals in the system. In the prior art, there are relatively few processes for preparing 5-nitrobenzimidazolone by continuous nitration, which are usually carried out by connecting two to three reactors in series for continuous nitration. Although the safety factor of the process flow of the intermittent method has been significantly improved, the product purity is still low. Therefore, exploring a continuous nitration process of 5-nitrobenzimidazolone with high product purity and few by-products will have significant industrial value. Summary of the invention

[0004] In view of the problems in the prior art, the present invention provides a method for preparing 5-nitrobenzimidazolone by continuous nitration. The method uses a Ni-resin material modified with a sulfonic acid group as a catalyst and combines a tubular reactor-multi-reaction module microchannel reactor combined system to efficiently achieve continuous preparation of 5-nitrobenzimidazolone. The method can obtain a high-purity product, and the reaction process is safe and stable, which has significant value in industrial production.

[0005] The present invention provides a method for preparing 5-nitrobenzimidazolone by continuous nitration, comprising the following steps: S1: p-Hydroxybenzenesulfonic acid, nickel nitrate hexahydrate, and epoxy resin are dispersed in N,N-dimethylformamide to form a mixed solution, which is then placed in a three-necked flask after being fully stirred, and the temperature is raised to reflux. 3-isocyanatepropyltrimethoxysilane is slowly added dropwise under reflux, and then the reflux is continued for 3-4 hours to react, and finally an acetic acid solution is added dropwise, and the mixture is fully stirred and allowed to stand to obtain a Ni-resin material modified with a sulfonic acid group; S2: The Ni-resin material modified with sulfonic acid groups is loaded into a tubular reactor as a catalyst; S3: Preheating the benzimidazolone and nitric acid solution respectively and then passing them into the tubular reactor at the same time, and then passing them into the microchannel reactor, and then passing through different reaction modules of the microchannel reactor in sequence and then flowing out to separate and obtain the product 5-nitrobenzimidazolone.

[0006] Furthermore, the addition ratio of p-hydroxybenzenesulfonic acid, nickel nitrate hexahydrate, epoxy resin, and N,N-dimethylformamide is 0.01 mol: 0.005 mol: 1.2-1.5 g: 50-60 mL.

[0007] Further, the mixed solution is stirred at 60-80° C. for 2-3 h, placed in a three-necked flask, and heated to reflux at a heating rate of 5-10° C. / min.

[0008] Furthermore, the molar ratio of p-hydroxybenzenesulfonic acid, 3-isocyanatepropyltrimethoxysilane and acetic acid is 1:0.8~1:1.5~2.

[0009] Furthermore, the mass concentration of the acetic acid solution is 5-10wt%.

[0010] Further, acetic acid solution was added dropwise, stirred thoroughly and allowed to stand for 10 to 15 hours.

[0011] Furthermore, the filling amount of the catalyst in the tubular reactor is 20-30 g.

[0012] Furthermore, the feeding rate of benzimidazolone is 15-20 mL / min, the feeding rate of nitric acid solution is 40-60 mL / min; and the mass concentration of the nitric acid solution is 40 wt%.

[0013] Furthermore, the preheating temperature is 35-40°C.

[0014] Furthermore, in the tubular reactor, the pressure is 0.1~1MPa, the reaction temperature is 45~50°C, and the reaction time is 30~50min.

[0015] Furthermore, in the microchannel reactor, the pressure is 0.5~1MPa, the reaction temperature is 75~85°C, and the reaction time is 1~2min.

[0016] Furthermore, the microchannel reactor has 8 to 16 reaction modules.

[0017] The beneficial effects achieved by one or more technical solutions of the present invention are as follows: 1. The present invention dopes Ni into a resin material, and under reflux conditions, through the coupling effect of 3-isocyanate propyltrimethoxysilane, the sulfonic acid group on the p-hydroxybenzenesulfonic acid can be coupled to the Ni-resin material. The finally prepared sulfonic acid group-modified Ni-resin material has excellent catalytic performance in the nitration process of benzimidazolone, can significantly reduce the generation of by-products, and improve the purity of the product.

[0018] 2. The present invention adopts a tubular reactor-microchannel reactor combined system of multiple reaction modules, which can fully combine the respective advantages of the tubular reactor and the microchannel reactor, thereby efficiently realizing the continuous preparation of 5-nitrobenzimidazolone. At the same time, the reaction process is safe and stable, and has significant value in industrial production. DETAILED DESCRIPTION

[0019] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below in combination with specific embodiments and comparative examples.

[0020] Example 1 This embodiment provides a method for preparing 5-nitrobenzimidazolone by continuous nitration, comprising the following steps: S1: p-Hydroxybenzenesulfonic acid, nickel nitrate hexahydrate, and epoxy resin are dispersed in N,N-dimethylformamide to form a mixed solution (the addition ratio of p-hydroxybenzenesulfonic acid, nickel nitrate hexahydrate, epoxy resin, and N,N-dimethylformamide is 0.01 mol: 0.005 mol: 1.2 g: 50 mL), stirred at 70°C for 2 hours, placed in a three-necked flask, heated to reflux at a rate of 5°C / min, 3-isocyanatepropyltrimethoxysilane is slowly added dropwise while maintaining reflux, and then refluxed for 3 hours to react, and finally acetic acid solution is added dropwise (the molar ratio of p-hydroxybenzenesulfonic acid, 3-isocyanatepropyltrimethoxysilane, and acetic acid is 1:0.8:1.5, and the mass concentration of the acetic acid solution is 5wt%), stirred thoroughly, and then allowed to stand for 10 hours to obtain a catalyst; S2: 20 g of catalyst was loaded into a tubular reactor; S3: Preheat benzimidazolone and a nitric acid solution with a mass concentration of 40wt% to 40°C respectively and then simultaneously introduce them into a tubular reactor for reaction. The feed rate of benzimidazolone is 15mL / min, and the feed rate of nitric acid solution is 40mL / min. In the tubular reactor, the pressure is 0.5MPa, the reaction temperature is 50°C, and the reaction time is 30min. After the reaction materials come out of the tubular reactor, they continue to be introduced into a microchannel reactor for reaction. The microchannel reactor has 8 reaction modules, which are connected in series. The pressure in the microchannel reactor is 0.5MPa, the reaction temperature is 80°C, and the reaction time is 1min. The reaction materials flow out after passing through different reaction modules of the microchannel reactor in turn, and the product 5-nitrobenzimidazolone is separated.

[0021] Example 2 This embodiment provides a method for preparing 5-nitrobenzimidazolone by continuous nitration, comprising the following steps: S1: p-Hydroxybenzenesulfonic acid, nickel nitrate hexahydrate, and epoxy resin are dispersed in N,N-dimethylformamide to form a mixed solution (the addition ratio of p-hydroxybenzenesulfonic acid, nickel nitrate hexahydrate, epoxy resin, and N,N-dimethylformamide is 0.01 mol: 0.005 mol: 1.5 g: 60 mL), stirred at 80°C for 2 h, placed in a three-necked flask, heated to reflux at a rate of 5°C / min, 3-isocyanatepropyltrimethoxysilane is slowly added dropwise while maintaining reflux, and then reflux is continued for 3 h to react, and finally acetic acid solution is added dropwise (the molar ratio of p-hydroxybenzenesulfonic acid, 3-isocyanatepropyltrimethoxysilane, and acetic acid is 1:1:2, and the mass concentration of the acetic acid solution is 8 wt%), stirred thoroughly, and then allowed to stand for 15 h to obtain a catalyst; S2: 20 g of catalyst was loaded into a tubular reactor; S3: Preheat benzimidazolone and a nitric acid solution with a mass concentration of 40wt% to 40°C respectively and then simultaneously introduce them into a tubular reactor for reaction. The feed rate of benzimidazolone is 20mL / min, and the feed rate of nitric acid solution is 50mL / min. In the tubular reactor, the pressure is 1MPa, the reaction temperature is 45°C, and the reaction time is 30min. After the reaction materials come out of the tubular reactor, they continue to be introduced into a microchannel reactor for reaction. The microchannel reactor has 10 reaction modules, which are connected in series. The pressure in the microchannel reactor is 1MPa, the reaction temperature is 80°C, and the reaction time is 1min. The reaction materials flow out after passing through different reaction modules of the microchannel reactor in turn, and the product 5-nitrobenzimidazolone is separated.

[0022] Example 3 This embodiment provides a method for preparing 5-nitrobenzimidazolone by continuous nitration, comprising the following steps: S1: p-Hydroxybenzenesulfonic acid, nickel nitrate hexahydrate, and epoxy resin are dispersed in N,N-dimethylformamide to form a mixed solution (the addition ratio of p-hydroxybenzenesulfonic acid, nickel nitrate hexahydrate, epoxy resin, and N,N-dimethylformamide is 0.01 mol: 0.005 mol: 1.2 g: 50 mL), stirred at 70°C for 3 hours, placed in a three-necked flask, heated to reflux at a rate of 10°C / min, 3-isocyanatepropyltrimethoxysilane is slowly added dropwise while maintaining reflux, and then refluxed for 4 hours to react, and finally acetic acid solution is added dropwise (the molar ratio of p-hydroxybenzenesulfonic acid, 3-isocyanatepropyltrimethoxysilane, and acetic acid is 1:0.8:2, and the mass concentration of the acetic acid solution is 5wt%), stirred thoroughly, and allowed to stand for 15 hours to obtain a catalyst; S2: 30 g of catalyst was loaded into a tubular reactor; S3: Preheat benzimidazolone and a nitric acid solution with a mass concentration of 40wt% to 35°C respectively and then simultaneously introduce them into a tubular reactor for reaction. The feed rate of benzimidazolone is 20mL / min, and the feed rate of nitric acid solution is 50mL / min. In the tubular reactor, the pressure is 0.1MPa, the reaction temperature is 45°C, and the reaction time is 40min. After the reaction materials come out of the tubular reactor, they continue to be introduced into a microchannel reactor for reaction. The microchannel reactor has 16 reaction modules, which are connected in series. The pressure in the microchannel reactor is 0.5MPa, the reaction temperature is 85°C, and the reaction time is 1min. The reaction materials flow out after passing through different reaction modules of the microchannel reactor in turn, and the product 5-nitrobenzimidazolone is separated.

[0023] Example 4 This embodiment provides a method for preparing 5-nitrobenzimidazolone by continuous nitration, comprising the following steps: S1: p-Hydroxybenzenesulfonic acid, nickel nitrate hexahydrate, and epoxy resin are dispersed in N,N-dimethylformamide to form a mixed solution (the addition ratio of p-hydroxybenzenesulfonic acid, nickel nitrate hexahydrate, epoxy resin, and N,N-dimethylformamide is 0.01 mol: 0.005 mol: 1.2 g: 60 mL), stirred at 70°C for 3 h, placed in a three-necked flask, heated to reflux at a rate of 5°C / min, 3-isocyanatepropyltrimethoxysilane is slowly added dropwise while maintaining reflux, and then reflux is continued for 4 h to react, and finally acetic acid solution is added dropwise (the molar ratio of p-hydroxybenzenesulfonic acid, 3-isocyanatepropyltrimethoxysilane, and acetic acid is 1:1:2, and the mass concentration of the acetic acid solution is 10 wt%), stirred thoroughly, and then allowed to stand for 15 h to obtain a catalyst; S2: 20 g of catalyst was loaded into a tubular reactor; S3: Preheat benzimidazolone and a nitric acid solution with a mass concentration of 40wt% to 40°C respectively and then simultaneously introduce them into a tubular reactor for reaction. The feed rate of benzimidazolone is 15mL / min, and the feed rate of nitric acid solution is 50mL / min. In the tubular reactor, the pressure is 0.5MPa, the reaction temperature is 50°C, and the reaction time is 50min. After the reaction materials come out of the tubular reactor, they continue to be introduced into a microchannel reactor for reaction. The microchannel reactor has 10 reaction modules, which are connected in series. The pressure in the microchannel reactor is 0.5MPa, the reaction temperature is 75°C, and the reaction time is 2min. The reaction materials flow out after passing through different reaction modules of the microchannel reactor in turn, and the product 5-nitrobenzimidazolone is separated.

[0024] Comparative Example 1 This comparative example provides a method for preparing 5-nitrobenzimidazolone by continuous nitration, comprising the following steps: Benzimidazolone and a nitric acid solution with a mass concentration of 40wt% are preheated to 40°C respectively and then simultaneously introduced into a tubular reactor for reaction, wherein the feeding rate of benzimidazolone is 15mL / min, the feeding rate of the nitric acid solution is 40mL / min, the pressure in the tubular reactor is 0.5MPa, the reaction temperature is 50°C, and the reaction time is 30min; after the reaction materials come out of the tubular reactor, they continue to be introduced into a microchannel reactor for reaction, the microchannel reactor has 8 reaction modules, which are connected in series, the pressure in the microchannel reactor is 0.5MPa, the reaction temperature is 80°C, and the reaction time is 1min, the reaction materials flow out after passing through different reaction modules of the microchannel reactor in turn, and the product 5-nitrobenzimidazolone is separated.

[0025] Table 1 shows the contents of benzimidazolone, 5-nitrobenzimidazolone and polynitrate impurities obtained by liquid chromatography analysis of the products of Examples 1 to 4 and Comparative Example 1.

[0026] Table 1

[0027] It can be concluded from Table 1 that in the products obtained in Examples 1 to 4 of the present invention, the content of 5-nitrobenzimidazolone can reach more than 99%, and the content of the remaining unreacted benzimidazolone is low, and the content of polynitrate impurities is less than 0.5%, while in the product obtained in Comparative Example 1, the content of 5-nitrobenzimidazolone can only reach 96.076%, and the content of the remaining unreacted benzimidazolone is high, and the content of polynitrate impurities exceeds 1%, which fully demonstrates that the method for preparing 5-nitrobenzimidazolone by continuous nitration provided by the present invention can promote the conversion of reactants, significantly reduce the generation of by-products, and effectively improve the purity of the product.

Claims

1. A method for preparing 5-nitrobenzimidazolone by continuous nitration, characterized in that: The steps include: S1: p-Hydroxybenzenesulfonic acid, nickel nitrate hexahydrate, and epoxy resin are dispersed in N,N-dimethylformamide to form a mixed solution, which is then placed in a three-necked flask after being fully stirred, and the temperature is raised to reflux. 3-isocyanatepropyltrimethoxysilane is slowly added dropwise under reflux, and then the reflux is continued for 3-4 hours to react, and finally an acetic acid solution is added dropwise, and the mixture is fully stirred and allowed to stand to obtain a Ni-resin material modified with a sulfonic acid group; S2: The Ni-resin material modified with sulfonic acid groups is loaded into a tubular reactor as a catalyst; S3: Preheating the benzimidazolone and nitric acid solution respectively and then passing them into the tubular reactor at the same time, and then passing them into the microchannel reactor after exiting the tubular reactor, and then passing through different reaction modules of the microchannel reactor in sequence and then flowing out to separate and obtain the product 5-nitrobenzimidazolone; The addition ratio of p-hydroxybenzenesulfonic acid, nickel nitrate hexahydrate, epoxy resin, and N,N-dimethylformamide is 0.01 mol: 0.005 mol: 1.2~1.5 g: 50~60 mL; The molar ratio of p-hydroxybenzenesulfonic acid, 3-isocyanatepropyltrimethoxysilane and acetic acid is 1:0.8~1:1.5~2.

2. The method for preparing 5-nitrobenzimidazolone by continuous nitration as claimed in claim 1, characterized in that: The mixed solution was stirred at 60-80°C for 2-3 h, placed in a three-necked flask, and heated to reflux at a heating rate of 5-10°C / min.

3. The method for preparing 5-nitrobenzimidazolone by continuous nitration as claimed in claim 1, characterized in that: The mass concentration of the acetic acid solution is 5~10wt%.

4. The method for preparing 5-nitrobenzimidazolone by continuous nitration as claimed in claim 1, characterized in that: Add acetic acid solution dropwise, stir thoroughly and let stand for 10 to 15 hours.

5. The method for preparing 5-nitrobenzimidazolone by continuous nitration as claimed in claim 1, characterized in that: The catalyst loading amount in the tubular reactor is 20-30 g.

6. The method for preparing 5-nitrobenzimidazolone by continuous nitration as claimed in claim 1, characterized in that: The feeding rate of benzimidazolone is 15-20 mL / min, and the feeding rate of nitric acid solution is 40-60 mL / min; the mass concentration of the nitric acid solution is 40 wt%.

7. The method for preparing 5-nitrobenzimidazolone by continuous nitration as claimed in claim 1, characterized in that: The preheating temperature is 35~40℃.

8. The method for preparing 5-nitrobenzimidazolone by continuous nitration as claimed in claim 1, characterized in that: In the tubular reactor, the pressure is 0.1~1MPa, the reaction temperature is 45~50℃, and the reaction time is 30~50min.

9. The method for preparing 5-nitrobenzimidazolone by continuous nitration as claimed in claim 1, characterized in that: In the microchannel reactor, the pressure is 0.5~1MPa, the reaction temperature is 75~85℃, and the reaction time is 1~2min.

10. The method for preparing 5-nitrobenzimidazolone by continuous nitration according to claim 1, characterized in that: The microchannel reactor has 8 to 16 reaction modules.

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