Synthesis process of 5, 6-dimethyl benzimidazole
By simplifying the synthesis process of 5,6-dimethylbenzimidazole and using Ru-Zn/ZSM-5 catalyst and hydrochloric acid-assisted condensation, the problems of highly toxic raw materials, harsh operation, multiple steps, and low yield in the existing technology have been solved, and a highly efficient synthesis method has been achieved.
Patent Information
- Application Number
- CN202311747916.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-12-19
- Publication Date
- 2026-01-23
AI Technical Summary
Existing synthetic routes for 5,6-dimethylbenzimidazole suffer from problems such as highly toxic raw materials, demanding operation, numerous steps, and low yield, making it difficult to achieve industrial-scale production.
Using 3,4-methylaniline as the initial raw material, the reaction proceeded through acetylation, nitration, reduction with a reducing agent, and formic acid condensation. A Ru-Zn/ZSM-5 catalyst was used to simplify the reaction steps and improve the yield. Finally, hydrochloric acid was used to assist in the condensation.
This method achieves fewer reaction steps, simpler operation, higher yield, and stable product quality. The synergistic effect of the catalyst improves selectivity and yield.
Smart Images
Figure CN121378145A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The application belongs to the field of preparation of pharmaceutical compounds, and mainly relates to a 5,6-dimethylbenzimidazole, and in particular to a synthesis process of 5,6-dimethylbenzimidazole. BACKGROUND
[0002] 5,6-dimethylbenzimidazole is a white crystalline powder, is an important pre-raw material for synthesizing vitamin B 12 by biological fermentation, and is also called a vitamin B 12 precursor. Previously, almost all of the vitamin B -1 precursors were imported. At present, there are mainly two synthesis routes at home and abroad: (1) taking p-nitrotoluene as raw material, synthesizing 3,4-dimethylaniline through chloromethylation, and then obtaining 5,6-dimethylbenzimidazole through nitration, hydrolysis and reduction cyclization; and (2) taking o-xylene as raw material, obtaining 3,-dimethyl-N-acetylaniline (4) through acetylation, oximation and rearrangement, and then obtaining 5,6-dimethylbenzimidazole through nitration, hydrolysis, reduction and cyclization. In route (1), dichloromethyl ether or formaldehyde and chlorine gas are used as chloromethylation reagents, the raw material is toxic and has a low boiling point, and is not easy to be industrialized. In route (2), processes such as extraction and gas catalytic hydrolysis are involved, the steps are many, the yield is low, and super-low-temperature operation is adopted, the conditions are harsh, and the total yield is only 23%. Therefore, the application reports a synthesis method with few reaction steps, simple operation and high yield. SUMMARY
[0003] In view of the deficiencies of the prior art, the application provides a synthesis process of 5,6-dimethylbenzimidazole, which adopts 3,4-methylaniline as an initial raw material, and obtains 5,6-dimethylbenzimidazole through acetylation, nitration, reduction by a reducing agent and polycondensation with formic acid. The method has few steps and high yield, and specifically comprises the following steps:
[0004] S1, preparation of a catalyst Ru-Zn / ZSM-5: 8-12 g of sodium metaaluminate, 25-28 g of tetrapropylammonium bromide, 3.5-4 g of sodium hydroxide and 500-600 mL of distilled water are sequentially added into a 1000 mL three-necked flask, the temperature of a water bath is maintained at 26℃, and the three-necked flask is rotated at 800 r / min -1The mixture was stirred for 30-40 minutes, then 1.5-2 mL of tetraethyl orthosilicate was added dropwise. The reaction temperature was then raised to 35°C, and the mixture was stirred for 5 hours to obtain a milky white solution. This solution was then transferred to a high-pressure hydrothermal reactor, and the crystallization temperature was set to 177-186°C. After crystallization for 24 hours, the hydrothermal reactor was removed and rapidly cooled in an ice-water mixture. The crystallized solution was then centrifuged and washed until the supernatant was nearly neutral. The precipitate was collected by centrifugation, and the bottom white precipitate was dried at 110°C to obtain a solid powder. This powder was then placed in a muffle furnace and heated at a rate of 3°C / min. The temperature was raised to 600℃ and calcined at 600℃ for 6-7 hours to obtain ZSM-5 molecular sieve. Then, ZSM-5 was impregnated in a mixed solution of RuCl3 with a concentration of 5wt%-10wt% and Zn(NO3)2 with a concentration of 3wt%-5wt% and stirred at 50-60℃ for 2-3 hours. The precipitate was then collected by centrifugation and dried at 110℃ to obtain powder. The solid powder was heated to 600℃ in a tube furnace under N2 atmosphere at a heating rate of 5℃ / min and calcined at 600℃ for 4-5 hours to obtain Ru-Zn / ZSM-5 for later use.
[0005] S2. In a 500mL flask, add 18.2g of 3,4-dimethylaniline (0.15mol), 10-15mL of acetic acid, 25-35mL of acetic anhydride, and 0.1-0.2mL of a mixed acid solution of concentrated sulfuric acid and concentrated nitric acid in a volume ratio of 3:1. Stir and heat to 130-140℃, then maintain the temperature under reflux for 2 hours. Distill off the foremilk fraction. When the distillation temperature reaches 105-110℃, stop heating and wait for the temperature to drop to 50℃. Then replace the water bath with ice water. When the reagent in the flask cools down... The temperature was raised to 8°C. 30-40 ml of fuming nitric acid was slowly added dropwise while stirring, and the reaction temperature was maintained at 8-10°C. After the addition was complete, the temperature was maintained at 8-10°C and the reaction was carried out for 10-20 minutes. Then the reagent in the flask was poured into 150 ml of ice-water mixture and stirred rapidly at 700-800 r / min. The mixture was then immediately filtered. The filter cake was washed with ice water 3-5 times and dried under vacuum to obtain 4,5-dimethyl-2-nitroacetanilide.
[0006]
[0007] S3. Add 48.3g (0.29mol) of 4,5-dimethyl-2-nitroacetanilide prepared in step S1, 120-140mL of anhydrous ethanol, 5-10g of solid sodium hydroxide, and 50mL of deionized water to a 500mL flask. Heat to 80-90℃ and reflux for 1h, maintaining a pH value ≥10. Add the Ru-Zn / ZSM-5 powder prepared in step S1 as a catalyst in portions until completely added. Maintain the reactants in a gentle boiling state and continue the reaction at 80-90℃. When the reaction solution turns grayish-white, add 3-5g of activated carbon and 80-90mL of anhydrous ethanol to the flask. Stir and heat to 55-65℃ and maintain heating for 10-20min. Filter the solution and collect the filtrate in a 500mL flask. Remove the ethanol under vacuum until the reagent in the flask becomes a paste. Stir and filter, collect the filter cake, and dry to obtain 4,5-dimethyl-1,2-phenylenediamine.
[0008]
[0009] S4. Add 20.7 g (0.15 mol) of 4,5-dimethyl-1,2-phenylenediamine, 55-67 mL of water, 58-66 mL of 35 wt% hydrochloric acid, and 13 mL (0.26 mol) of formic acid to a 500 mL flask. Stir and heat to 105-116 °C and reflux for 9-10 h. Pour in 550-630 mL of hot water at 70-80 °C and add 1.5-3.0 g of activated carbon. After stirring, filter under vacuum. Add saturated sodium carbonate solution to the filter to neutralize until pH > 10. Cool to 10 °C, filter and collect the solid, and dry to obtain 5,6-dimethylbenzimidazole.
[0010]
[0011] Preferably, in step S1 of the present invention, 10g of sodium aluminate, 26g of tetrapropylammonium bromide, 3.7g of sodium hydroxide, and 560mL of distilled water are added sequentially to a 1000mL three-necked flask.
[0012] Preferably, the crystallization temperature in step S1 of the present invention is set to 180°C.
[0013] Preferably, in step S1 of the present invention, ZSM-5 is impregnated in a mixed solution of RuCl3 with a concentration of 10 wt% and Zn(NO3)2 with a concentration of 3 wt%.
[0014] Preferably, in step S2 of the present invention, 18.2 g of 3,4-dimethylaniline (0.15 mol), 10 mL of acetic acid, and 25 mL of acetic anhydride are added.
[0015] Preferably, in step S2 of the present invention, 30 ml of fuming nitric acid is slowly added dropwise while stirring, and the reaction temperature is maintained at 10°C.
[0016] Preferably, in step S3 of the present invention, 120 mL of anhydrous ethanol, 5 g of solid sodium hydroxide, and 50 mL of deionized water are heated to 90 °C.
[0017] Preferably, in step S3 of the present invention, 5g of activated carbon and 90mL of anhydrous ethanol are added to the flask, and the mixture is stirred and heated to 60°C and kept heated for 20min.
[0018] Preferably, in step S4 of the present invention, the mixture is stirred and heated to 116°C, refluxed for 9 hours, and then 630 mL of hot water at a temperature of 70-80°C is poured in.
[0019] Compared with the prior art, the present invention has the following beneficial effects:
[0020] 1. This invention uses 3,4-dimethylaniline as raw material and completes acetylation and nitration in a one-pot process, which reduces reaction steps, simplifies operation, improves yield, and ensures stable product quality.
[0021] 2. The Ru-Zn / ZSM-5 catalyst prepared by this invention has a large specific surface area and high porosity, and the synergistic effect between Ru and Zn metals can effectively improve the catalytic effect, selectivity and yield.
[0022] 3. In the preparation of 5,6-dimethylbenzimidazole, the final cyclization process of this invention uses hydrochloric acid for assisted condensation, which improves the yield of 5,6-dimethylbenzimidazole. Attached Figure Description
[0023] Figure 1 This is a scan image of Ru-Zn / ZSM-5 prepared in Example 1 of the present invention.
[0024] Figure 2 This is a scan image of Zn / ZSM-5 prepared in Comparative Example 1 of this invention.
[0025] Figure 3 This is a scan image of Ru / ZSM-5 prepared in Comparative Example 2 of this invention.
[0026] Figure 4 The yield diagrams for the preparation of 5,6-dimethylbenzimidazole in Example 1 and Comparative Examples 1-2 of this invention are shown.
[0027] Figure 5 The yield diagrams are for the preparation of 5,6-dimethylbenzimidazole in Examples 2-3 and Comparative Examples 4-5 of this invention. Detailed Implementation
[0028] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention. It should be noted that, unless otherwise specified, the following embodiments and features described therein can be combined with each other.
[0029] Example 1
[0030] S1. In a 1000mL three-necked flask, add 8g of sodium aluminate, 25g of tetrapropylammonium bromide, 3.5g of sodium hydroxide, and 500mL of distilled water sequentially. Maintain the water bath temperature at 26℃ and operate at 800r / min. -1 The mixture was stirred for 30 min, then 1.5 mL of tetraethyl orthosilicate was added dropwise. The reaction temperature was then raised to 35 °C, and the mixture was stirred for 5 h to obtain a milky white solution. This solution was then transferred to a high-pressure hydrothermal reactor, and the crystallization temperature was set to 177 °C. After crystallization for 24 h, the hydrothermal reactor was removed and rapidly cooled in an ice-water mixture. The crystallized solution was then centrifuged and washed until the supernatant was nearly neutral. The precipitate was collected by centrifugation, and the bottom white precipitate was dried at 110 °C to obtain a solid powder. This powder was then placed in a muffle furnace and heated at 3 °C / min. The temperature was increased to 600℃ and calcined at 600℃ for 6 hours to obtain ZSM-5 molecular sieve. Then, ZSM-5 was impregnated in a mixed solution of 5wt% RuCl3 and 3wt% Zn(NO3)2 and stirred at 50-60℃ for 2 hours. The precipitate was collected by centrifugation and dried at 110℃ to obtain powder. The solid powder was heated to 600℃ at a heating rate of 5℃ / min in a tube furnace under N2 atmosphere and calcined at 600℃ for 4 hours to obtain Ru-Zn / ZSM-5 for later use.
[0031] S2. In a 500mL flask, add 18.2g of 3,4-dimethylaniline (0.15mol), 10mL of acetic acid, 25mL of acetic anhydride, and 0.1mL of a mixed acid solution of concentrated sulfuric acid and concentrated nitric acid in a volume ratio of 3:1. Stir and heat to 130℃, then maintain the temperature under reflux for 2 hours. Distill off the foremilk fraction. When the distillation temperature reaches 105℃, stop heating and wait for the temperature to drop to 50℃. Replace the water bath with ice water. When the reagent in the flask cools to 8℃, slowly add 30mL of fuming nitric acid while stirring, and maintain the reaction temperature at 8℃. After the addition is complete, maintain the temperature at 8℃ and react for 10 minutes. Then pour the reagent in the flask into 150mL of ice water mixture and stir rapidly at 700r / min. Then filter immediately. Wash the filter cake three times with ice water and dry under vacuum to obtain 4,5-dimethyl-2-nitroacetaniline.
[0032] S3. Add 48.3g (0.29mol) of 4,5-dimethyl-2-nitroacetanilide prepared in step S1, 120mL of anhydrous ethanol, 5g of solid sodium hydroxide, and 50mL of deionized water to a 500mL flask. Heat to 80℃ and reflux for 1h, maintaining the pH value ≥10. Add the Ru-Zn / ZSM-5 powder prepared in step S1 as a catalyst in portions until completely added. Keep the reactants in a gentle boiling state and maintain the reaction temperature at 80℃. When the reaction solution turns grayish-white, add 3g of activated carbon and 80mL of anhydrous ethanol to the flask. Stir and heat to 55℃ and maintain heating for 10min. Filter the solution and collect the filtrate in a 500mL flask. Remove the ethanol under vacuum until the reagent in the flask becomes a paste. Stir and filter. Collect the filter cake and dry to obtain 4,5-dimethyl-1,2-phenylenediamine.
[0033] S4. Add 20.7 g (0.15 mol) of 4,5-dimethyl-1,2-phenylenediamine, 55 mL of water, 58 mL of 35 wt% hydrochloric acid, and 13 mL (0.26 mol) of formic acid to a 500 mL flask. Stir and heat to 105 °C and reflux for 9 h. Pour in 550 mL of hot water at 70-80 °C and add 1.5 g of activated carbon. After stirring, filter under vacuum. Add saturated sodium carbonate solution to the filter to neutralize until pH > 10. Cool to 10 °C, filter and collect the solid, and dry to obtain 5,6-dimethylbenzimidazole.
[0034] Comparative Example 1: Except for step S1, which does not include RuCl3, all other steps are the same as in Example 1.
[0035] Comparative Example 2: Except for step S1, which does not include Zn(NO3)2, all other steps are the same as in Example 1.
[0036] Table 1. Pore structures of Ru-Zn / ZSM-5, Ru / ZSM-5 and Zn / ZSM-5 samples
[0037] Sample Specific surface area (m 2 / g) Pore volume (cm 2 / g) Average pore diameter (nm) Ru-Zn / ZSM-5 482.54 0.287 27.58 Zn / ZSM-5 331.79 0.171 24.63 Ru / ZSM-5 357.81 0.182 22.15
[0038] In this invention, the yield is calculated as follows: (actual yield of 5,6-dimethylbenzimidazole / theoretical yield of 5,6-dimethylbenzimidazole) × 100%
[0039] Actual yield: The actual mass of 5,6-dimethylbenzimidazole obtained;
[0040] Theoretical yield: The mass calculated based on the raw material feed rate and the stoichiometric ratio in the chemical equation.
[0041] Figure 1 This is a scan image of Ru-Zn / ZSM-5 prepared in Example 1 of the present invention. From... Figure 1As can be seen, the surface of this material is very rough, exposing more active sites. Furthermore, according to the results in Table 1, the sample Ru-Zn / ZSM-5 has the largest specific surface area, which is beneficial for the reaction. Figure 2 The yield diagrams for the preparation of 5,6-dimethylbenzimidazole in Example 1 and Comparative Examples 1-2 of this invention are shown. Figure 2 It can be seen that the yields of 5,6-dimethylbenzimidazole in Comparative Examples 1 and 2 were only half or less than those in the Examples, indicating that the synergistic effect between Ru and Zn in the catalyst and the effective matching of orbitals are more conducive to the reaction.
[0042] Example 2
[0043] S1. In a 1000mL three-necked flask, add 12g sodium aluminate, 28g tetrapropylammonium bromide, 4g sodium hydroxide, and 600mL distilled water sequentially. Maintain the water bath temperature at 26℃ and operate at 800r / min. -1 The mixture was stirred for 40 min, then 2 mL of tetraethyl orthosilicate was added dropwise. The reaction temperature was then raised to 35 °C, and the mixture was stirred for 5 h to obtain a milky white solution. This solution was then transferred to a high-pressure hydrothermal reactor, and the crystallization temperature was set to 186 °C. After crystallization for 24 h, the hydrothermal reactor was removed and rapidly cooled in an ice-water mixture. The crystallized solution was then centrifuged and washed until the supernatant was nearly neutral. The precipitate was collected by centrifugation, and the bottom white precipitate was dried at 110 °C to obtain a solid powder. This powder was then placed in a muffle furnace and heated at 3 °C / min. The temperature was increased to 600℃ and calcined at 600℃ for 7 hours to obtain ZSM-5 molecular sieve. Then, ZSM-5 was impregnated in a mixed solution of 10wt% RuCl3 and 5wt% Zn(NO3)2 and stirred at 60℃ for 3 hours. The precipitate was collected by centrifugation and dried at 110℃ to obtain powder. The solid powder was heated to 600℃ at a heating rate of 5℃ / min in a tube furnace under N2 atmosphere and calcined at 600℃ for 5 hours to obtain Ru-Zn / ZSM-5 for later use.
[0044] S2. In a 500 mL flask, add 18.2 g of 3,4-dimethylaniline (0.15 mol), 15 mL of acetic acid, 35 mL of acetic anhydride, and 0.2 mL of a mixed acid solution of concentrated sulfuric acid and concentrated nitric acid in a volume ratio of 3:1. Stir and heat to 140 °C, then maintain the temperature under reflux for 2 hours. Distill off the fore-distillate. When the distillation temperature reaches 110 °C, stop heating and wait for the temperature to drop to 50 °C. Replace the water bath with ice water. When the reagent in the flask cools to 8 °C, slowly add 40 mL of fuming nitric acid while stirring, and maintain the reaction temperature at 10 °C. After the addition is complete, maintain the temperature at 10 °C and react for 20 min. Then pour the reagent in the flask into 150 mL of ice water mixture and stir rapidly at 800 r / min. Then filter immediately. Wash the filter cake 5 times with ice water and dry under vacuum to obtain 4,5-dimethyl-2-nitroacetaniline.
[0045] S3. Add 48.3g (0.29mol) of 4,5-dimethyl-2-nitroacetanilide prepared in step S1, 140mL of anhydrous ethanol, 10g of solid sodium hydroxide, and 50mL of deionized water to a 500mL flask. Heat to 90℃ and reflux for 1h, maintaining the pH value ≥10. Add the Ru-Zn / ZSM-5 powder prepared in step S1 as a catalyst in portions until completely added. Maintain the reactants in a gentle boiling state and continue the reaction at 90℃. When the reaction solution turns grayish-white, add 5g of activated carbon and 90mL of anhydrous ethanol to the flask. Stir and heat to 65℃ and maintain heating for 20min. Filter the solution and collect the filtrate in a 500mL flask. Remove the ethanol under vacuum until the reagent in the flask becomes a paste. Stir and filter. Collect the filter cake and dry to obtain 4,5-dimethyl-1,2-phenylenediamine.
[0046] S4. Add 20.7 g (0.15 mol) of 4,5-dimethyl-1,2-phenylenediamine, 67 mL of water, 66 mL of 35 wt% hydrochloric acid, and 13 mL (0.26 mol) of formic acid to a 500 mL flask. Stir and heat to 116 °C and reflux for 10 h. Pour in 630 mL of hot water at 70-80 °C and add 3.0 g of activated carbon. After stirring, filter under vacuum. Add saturated sodium carbonate solution to the filter to neutralize until pH > 10. Cool to 10 °C, filter and collect the solid, and dry to obtain 5,6-dimethylbenzimidazole.
[0047] Comparative Example 4: Except for replacing the mixed acid in step S2 with concentrated sulfuric acid, all other steps are the same as in Example 2.
[0048] Example 3
[0049] S1. In a 1000mL three-necked flask, add 10g sodium aluminate, 27g tetrapropylammonium bromide, 3.7g sodium hydroxide, and 550mL distilled water sequentially. Maintain the water bath temperature at 26℃ and operate at 800r / min. -1 The mixture was stirred for 35 min, then 1.7 mL of tetraethyl orthosilicate was added dropwise. The reaction temperature was then raised to 35 °C, and the mixture was stirred for 5 h to obtain a milky white solution. This solution was then transferred to a high-pressure hydrothermal reactor, and the crystallization temperature was set to 180 °C. After crystallization for 24 h, the hydrothermal reactor was removed and rapidly cooled in an ice-water mixture. The crystallized solution was then centrifuged and washed until the supernatant was nearly neutral. The precipitate was collected by centrifugation, and the bottom white precipitate was dried at 110 °C to obtain a solid powder. This powder was then placed in a muffle furnace and heated at 3 °C / min. The temperature of n was increased to 600℃, and calcined at 600℃ for 7h to obtain ZSM-5 molecular sieve. Then, ZSM-5 was impregnated in a mixed solution of 8wt% RuCl3 and 4wt% Zn(NO3)2, stirred at 55℃ for 3h, and then the precipitate was collected by centrifugation and dried at 110℃ to obtain powder. The solid powder was heated to 600℃ in a tube furnace under N2 atmosphere at a heating rate of 5℃ / min and calcined at 600℃ for 5h to obtain Ru-Zn / ZSM-5 for later use.
[0050] S2. In a 500 mL flask, add 18.2 g of 3,4-dimethylaniline (0.15 mol), 15 mL of acetic acid, 25 mL of acetic anhydride, and 0.2 mL of a mixed acid solution of concentrated sulfuric acid and concentrated nitric acid in a volume ratio of 3:1. Stir and heat to 130 °C, then maintain the temperature under reflux for 2 hours. Distill off the foremilk fraction. When the distillation temperature reaches 110 °C, stop heating and wait for the temperature to drop to 50 °C. Replace the water bath with ice water. When the reagent in the flask cools to 8 °C, slowly add 35 mL of fuming nitric acid while stirring, and maintain the reaction temperature at 10 °C. After the addition is complete, maintain the temperature at 10 °C and react for 15 min. Then pour the reagent in the flask into 150 mL of the ice water mixture and stir rapidly at 800 r / min. Then filter immediately. Wash the filter cake three times with ice water and dry under vacuum to obtain 4,5-dimethyl-2-nitroacetaniline.
[0051] S3. Add 48.3g (0.29mol) of 4,5-dimethyl-2-nitroacetanilide prepared in step S1, 130mL of anhydrous ethanol, 8g of solid sodium hydroxide, and 50mL of deionized water to a 500mL flask. Heat to 90℃ and reflux for 1h, maintaining the pH value ≥10. Add the Ru-Zn / ZSM-5 powder prepared in step S1 as a catalyst in portions until completely added. Keep the reactants in a gentle boiling state and maintain the reaction temperature at 90℃. When the reaction solution turns grayish-white, add 4g of activated carbon and 90mL of anhydrous ethanol to the flask. Stir and heat to 60℃ and maintain heating for 15min. Filter the solution and collect the filtrate in a 500mL flask. Remove the ethanol under vacuum until the reagent in the flask becomes a paste. Stir and filter. Collect the filter cake and dry to obtain 4,5-dimethyl-1,2-phenylenediamine.
[0052] S4. Add 20.7 g (0.15 mol) of 4,5-dimethyl-1,2-phenylenediamine, 60 mL of water, 60 mL of 35 wt% hydrochloric acid, and 13 mL (0.26 mol) of formic acid to a 500 mL flask. Stir and heat to 110 °C and reflux for 10 h. Pour in 600 mL of hot water at 70-80 °C and add 3.0 g of activated carbon. After stirring, filter under vacuum. Add saturated sodium carbonate solution to the filter to neutralize until pH > 10. Cool to 10 °C, filter and collect the solid, and dry to obtain 5,6-dimethylbenzimidazole.
[0053] Comparative Example 5: Except for step S3, in which Ru-Zn / ZSM-5 powder is added all at once, all other steps are the same as in Example 3.
[0054] Figure 3 The yield diagrams for the preparation of 5,6-dimethylbenzimidazole in Examples 2-3 and Comparative Examples 4-5 of this invention are shown. Figure Three It is evident that replacing the mixed acid in step S2 with concentrated sulfuric acid alone leads to a decrease in the yield of 5,6-dimethylbenzimidazole. This may be because the absence of concentrated nitric acid results in a decrease in the yield of 4,5-dimethyl-2-nitroacetanilide, which in turn leads to a decrease in the yield of 5,6-dimethylbenzimidazole. Similarly, adding the catalyst Ru-Zn / ZSM-5 all at once also leads to a decrease in the yield of 5,6-dimethylbenzimidazole. This may be because the added catalyst did not react completely and was either encapsulated by the product or poisoned, resulting in loss of activity.
[0055] Example 4
[0056] S1. In a 1000mL three-necked flask, add 12g sodium aluminate, 26g tetrapropylammonium bromide, 4g sodium hydroxide, and 560mL distilled water sequentially. Maintain the water bath temperature at 26℃ and operate at 800r / min. -1The mixture was stirred for 40 min, then 2 mL of tetraethyl orthosilicate was added dropwise. The reaction temperature was then raised to 35 °C, and the mixture was stirred for 5 h to obtain a milky white solution. This solution was then transferred to a high-pressure hydrothermal reactor, and the crystallization temperature was set to 185 °C. After crystallization for 24 h, the hydrothermal reactor was removed and rapidly cooled in an ice-water mixture. The crystallized solution was then centrifuged and washed until the supernatant was nearly neutral. The precipitate was collected by centrifugation, and the bottom white precipitate was dried at 110 °C to obtain a solid powder. This powder was then placed in a muffle furnace and heated at a rate of 3 °C / min. The temperature was raised to 600℃ at a rate of 5 wt% and calcined at 600℃ for 6.5 h to obtain ZSM-5 molecular sieve. Then, ZSM-5 was impregnated in a mixed solution of 5 wt% RuCl3 and 3 wt% Zn(NO3)2 and stirred at 55℃ for 2.5 h. The precipitate was collected by centrifugation and dried at 110℃ to obtain powder. The solid powder was heated to 600℃ at a rate of 5℃ / min in a tube furnace under N2 atmosphere and calcined at 600℃ for 5 h to obtain Ru-Zn / ZSM-5 for later use.
[0057] S2. In a 500mL flask, add 18.2g of 3,4-dimethylaniline (0.15mol), 10mL of acetic acid, 25mL of acetic anhydride, and 0.15mL of a mixed acid solution of concentrated sulfuric acid and concentrated nitric acid in a volume ratio of 3:1. Stir and heat to 138℃, then maintain the temperature under reflux for 2 hours. Distill off the foremilk fraction. When the distillation temperature reaches 105℃, stop heating and wait for the temperature to drop to 50℃. Replace the water bath with ice water. When the reagent in the flask cools to 8℃, slowly add 30mL of fuming nitric acid while stirring, and maintain the reaction temperature at 8℃. After the addition is complete, maintain the temperature at 8℃ and react for 10 minutes. Then pour the reagent in the flask into 150mL of ice water mixture and stir rapidly at 700r / min. Then filter immediately. Wash the filter cake 5 times with ice water and dry under vacuum to obtain 4,5-dimethyl-2-nitroacetaniline.
[0058] S3. Add 48.3g (0.29mol) of 4,5-dimethyl-2-nitroacetanilide prepared in step S1, 140mL of anhydrous ethanol, 6g of solid sodium hydroxide, and 50mL of deionized water to a 500mL flask. Heat to 85℃ and reflux for 1h, maintaining a pH value ≥10. Add the Ru-Zn / ZSM-5 powder prepared in step S1 as a catalyst in portions until completely added. Maintain the reactants in a gentle boiling state and continue the reaction at 80-90℃. When the reaction solution turns grayish-white, add 4g of activated carbon and 88mL of anhydrous ethanol to the flask. Stir and heat to 65℃ and maintain heating for 20min. Filter the solution and collect the filtrate in a 500mL flask. Remove the ethanol under vacuum until the reagent in the flask becomes a paste. Stir and filter, collect the filter cake, and dry to obtain 4,5-dimethyl-1,2-phenylenediamine.
[0059] S4. Add 20.7 g (0.15 mol) of 4,5-dimethyl-1,2-phenylenediamine, 55 mL of water, 62 mL of 35 wt% hydrochloric acid, and 13 mL (0.26 mol) of formic acid to a 500 mL flask. Stir and heat to 115 °C and reflux for 9 h. Pour in 550 mL of hot water at 70-80 °C and add 1.8 g of activated carbon. After stirring, filter under vacuum. Add saturated sodium carbonate solution to the filter to neutralize until pH > 10. Cool to 10 °C, filter and collect the solid, and dry to obtain 5,6-dimethylbenzimidazole.
[0060] Comparative Example 6: Except for not adding 35wt% hydrochloric acid in step S4, all other steps are the same as in Example 4.
[0061] Table 2. Yields of 5,6-dimethylbenzimidazole in Example 4 and Comparative Example 6.
[0062] Group Yield (%) Example 4 98.7±2.32 Comparative Example 6 43.3±2.78
[0063] As shown in Table 2, the yield decreased significantly without the addition of hydrochloric acid. This is because the reactants changed color shortly after the reaction started when only formic acid was added. After neutralization and cooling, they formed a black gel that was difficult to separate from the product. Adding hydrochloric acid made the process easier, the product was easier to separate, and the product yield was improved, resulting in higher product quality.
[0064] The above-described embodiments are merely illustrative of specific implementations of the present invention, and while the descriptions are detailed, they should not be construed as limiting the scope of protection of the present invention. It should be noted that for those skilled in the art, any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention should be considered equivalent substitutions and are included within the scope of protection of the present invention.
Claims
1. A process for synthesizing 5,6-dimethylbenzimidazole, characterized in that: The specific preparation method is as follows: S1. In a 1000mL three-necked flask, add 8-12g of sodium aluminate, 25-28g of tetrapropylammonium bromide, 3.5-4g of sodium hydroxide, and 500-600mL of distilled water sequentially. Maintain the water bath temperature at 26℃ and operate at 800r / min. -1 The mixture was stirred for 30-40 minutes, then 1.5-2 mL of tetraethyl orthosilicate was added dropwise. The reaction temperature was then raised to 35°C, and the mixture was stirred for 5 hours to obtain a milky white solution. This solution was then transferred to a high-pressure hydrothermal reactor, and the crystallization temperature was set to 177-186°C. After crystallization for 24 hours, the hydrothermal reactor was removed and rapidly cooled in an ice-water mixture. The crystallized solution was then centrifuged and washed until the supernatant was nearly neutral. The precipitate was collected by centrifugation, and the bottom white precipitate was dried at 110°C to obtain a solid powder. This powder was then placed in a muffle furnace and heated at a rate of 3°C / min. The temperature was raised to 600℃ and calcined at 600℃ for 6-7 hours to obtain ZSM-5 molecular sieve. Then, ZSM-5 was impregnated in a mixed solution of RuCl3 with a concentration of 5wt%-10wt% and Zn(NO3)2 with a concentration of 3wt%-5wt% and stirred at 50-60℃ for 2-3 hours. The precipitate was then collected by centrifugation and dried at 110℃ to obtain powder. The solid powder was heated to 600℃ in a tube furnace under N2 atmosphere at a heating rate of 5℃ / min and calcined at 600℃ for 4-5 hours to obtain Ru-Zn / ZSM-5 for later use. S2. Add 18.2g to a 500mL flask. 3,4-Dimethylaniline, 10-15 mL acetic acid, 25-35 mL acetic anhydride, and 0.1-0.2 mL of a mixed acid solution of concentrated sulfuric acid and concentrated nitric acid in a volume ratio of 3:1 were stirred and heated to 130-140°C. The temperature was then maintained under reflux for 2 hours. The foremilk was distilled off, and heating was stopped when the distillation temperature reached 105-110°C. The temperature was then lowered to 50°C, and the water bath was replaced with ice water. When the reagent in the flask cooled to 8°C, 30-40 mL of fuming nitric acid was slowly added dropwise while stirring, and the reaction temperature was maintained at 8-10°C. After the addition was complete, the temperature was maintained at 8-10°C and the reaction was carried out for 10-20 minutes. Then, the reagent in the flask was poured into 150 mL of the ice-water mixture and stirred rapidly at a stirring speed of 700-800 r / min. The mixture was then immediately filtered, and the filter cake was washed with ice water 3-5 times and dried under vacuum to obtain 4,5-dimethyl-2-nitroacetaniline. S3. Add 48.3g of 4,5-dimethyl-2-nitroacetanilide prepared in step S1, 120-140mL of anhydrous ethanol, 5-10g of solid sodium hydroxide, and 50mL of deionized water to a 500mL flask. Heat to 80-90℃ and reflux for 1h, maintaining a pH value ≥10. Add the Ru-Zn / ZSM-5 powder prepared in step S1 as a catalyst in portions until completely added. Maintain the reactants in a gentle boiling state and continue the reaction at 80-90℃. When the reaction solution turns grayish-white, add 3-5g of activated carbon and 80-90mL of anhydrous ethanol to the flask. Stir and heat to 55-65℃ and maintain heating for 10-20min. Filter the solution and collect the filtrate in a 500mL flask. Remove the ethanol under vacuum until the reagent in the flask becomes a paste. Stir and filter, collect the filter cake, and dry to obtain 4,5-dimethyl-1,2-phenylenediamine. S4. Add 20.7 g of 4,5-dimethyl-1,2-phenylenediamine, 55-67 mL of water, 58-66 mL of 35 wt% hydrochloric acid, and 13 mL of formic acid to a 500 mL flask. Stir and heat to 105-116 °C and reflux for 9-10 h. Pour in 550-630 mL of hot water at 70-80 °C and add 1.5-3.0 g of activated carbon. After stirring, filter under vacuum. Add saturated sodium carbonate solution to the filter to neutralize until pH > 10. Cool to 10 °C, filter and collect the solid, and dry to obtain 5,6-dimethylbenzimidazole.
2. The synthesis process of 5,6-dimethylbenzimidazole according to claim 1, characterized in that: In step S1, 10g of sodium aluminate, 26g of tetrapropylammonium bromide, 3.7g of sodium hydroxide, and 560mL of distilled water are added sequentially to a 1000mL three-necked flask.
3. The synthesis process of 5,6-dimethylbenzimidazole according to claim 2, characterized in that: In step S1, the crystallization temperature is set to 180°C.
4. The synthesis process of 5,6-dimethylbenzimidazole according to claim 3, characterized in that: In step S1, ZSM-5 is immersed in a mixed solution of 10 wt% RuCl3 and 3 wt% Zn(NO3)2.
5. The synthesis process of 5,6-dimethylbenzimidazole according to claim 4, characterized in that: In step S2, 18.2 g of 3,4-dimethylaniline, 10 mL of acetic acid, and 25 mL of acetic anhydride are added.
6. The synthesis process of 5,6-dimethylbenzimidazole according to claim 5, characterized in that: In step S2, 30 ml of fuming nitric acid is slowly added dropwise while stirring, and the reaction temperature is maintained at 10°C.
7. The synthesis process of 5,6-dimethylbenzimidazole according to claim 6, characterized in that: In step S3, 120 mL of anhydrous ethanol, 5 g of solid sodium hydroxide, and 50 mL of deionized water are heated to 90 °C.
8. The synthesis process of 5,6-dimethylbenzimidazole according to claim 7, characterized in that: In step S3, 5g of activated carbon and 90mL of anhydrous ethanol are added to the flask, and the mixture is stirred and heated to 60°C and maintained at that temperature for 20 minutes.
9. The synthesis process of 5,6-dimethylbenzimidazole according to claim 8, characterized in that: In step S4, the mixture is stirred and heated to 116°C, refluxed for 9 hours, and then 630 mL of hot water at a temperature of 70-80°C is poured in.