Method for catalytic synthesis of 2-substituted benzimidazoles by using nano copper-zinc alloy
The synthesis of 2-substituted benzimidazole under mild conditions using a nano-copper-zinc alloy catalyst solves the problems of high energy consumption and severe pollution in existing technologies, achieving a synthesis effect of high yield and low pollution.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- WUHAN TEXTILE UNIV
- Filing Date
- 2023-08-23
- Publication Date
- 2026-05-15
AI Technical Summary
Existing technologies for synthesizing 2-substituted benzimidazoles suffer from problems such as high energy consumption, severe pollution, low yield, and difficulty in separating and reusing catalysts.
Using nano-copper-zinc alloy as a catalyst, under nitrogen protection, 2-substituted benzimidazole was prepared from o-phenylenediamine and naphthyl derivatives through alkaline washing, activated carbon adsorption, and recrystallization. The reaction conditions were mild, and the catalyst was easy to separate and could be reused.
This method achieves high-yield, high-quality synthesis of 2-substituted benzimidazoles under mild reaction conditions. The catalyst is easy to separate and can be reused, reducing environmental pollution and energy consumption.
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Figure CN117263868B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of chemical synthesis technology, and in particular to a method for the catalytic synthesis of 2-substituted benzimidazole using a nano-copper-zinc alloy. Background Technology
[0002] Benzimidazole is a nitrogen-containing heterocyclic compound containing both a benzene ring and an imidazole ring. With a pKa value of 12.75, it exhibits strong acidity. It is not only an important molecular skeleton in organic compounds but also found in some natural products. As a structural framework for pharmaceutical agents, benzimazole has become an important component of many clinical drugs. Furthermore, the imine bond (C=N) in the benzimazole structure is considered an excellent electron conductor due to its electron-deficient properties; therefore, many derivatives based on the benzimazole structure have been designed, synthesized, and applied in the field of organic light emission.
[0003] Given the wide applications of benzimidazole derivatives in functional materials, pharmaceuticals, and luminescent materials, designing and constructing their derivative structures and exploring their applications has been a popular pursuit among researchers in recent years. Therefore, they have been striving to develop an efficient and economical method to synthesize new benzimidazole derivatives, hoping for continuous breakthroughs and innovations in their future applications across various fields. Furthermore, the exploration of their synthesis and applications plays a crucial role in the development of heterocyclic chemistry and organic synthesis theory. To date, numerous reports have been published on C-2 monosubstituted benzimidazole derivatives (2-substituted benzimidazoles). A common method for synthesizing 2-substituted benzimidazoles involves the condensation reaction of o-phenylenediamine or its derivatives (2-nitroaniline, 2-haloaniline, etc.) with carboxylic acids, aldehydes, alcohols, nitriles, and their derivatives. These reactions typically require catalytic oxidation under strong acids or strong oxidants, and sometimes also require high temperatures or light radiation. Yields are generally low, and some reactions generate many byproducts, posing significant challenges to equipment, purification processes, and environmental protection in industrial applications.
[0004] In view of this, it is necessary to design an improved method for preparing 2-substituted benzimidazoles to solve the above problems. Summary of the Invention
[0005] In view of the shortcomings of the prior art, the purpose of this invention is to provide an environmentally friendly, low-energy-consumption, low-pollution, high-yield, catalyst-easy-to-separate and reusable method for preparing 2-substituted benzimidazole.
[0006] To achieve the above objectives, the present invention provides a method for the catalytic synthesis of 2-substituted benzimidazole using a nano-copper-zinc alloy, comprising the following steps:
[0007] Under nitrogen protection, o-phenylenediamine and naphthyl derivatives were used as raw materials. The raw materials were mixed with solvent and nano-copper-zinc alloy was added as a catalyst. After fully reacting at a predetermined reaction temperature, 2-substituted benzimidazole was obtained after alkaline washing, activated carbon adsorption and recrystallization.
[0008] The general structural formula of the naphthyl derivative is as follows:
[0009]
[0010] Wherein, R1 is Cl or Br; R2 is -H or -COR1; and R3 is -H or -CH3.
[0011] As a further improvement of the present invention, the molar ratio of the o-phenylenediamine and the naphthyl derivative is 1:1 to 1.2.
[0012] As a further improvement of the present invention, the mass ratio of the o-phenylenediamine to the catalyst is 1:0.5 to 1.
[0013] As a further improvement of the present invention, the predetermined reaction temperature is 80-160°C, preferably 140°C.
[0014] As a further improvement of the present invention, the reaction time at the predetermined reaction temperature is 3.5 to 4.5 hours, preferably 4 hours.
[0015] As a further improvement of the present invention, the size of the nano-copper-zinc alloy is less than 200 nanometers.
[0016] As a further improvement of the present invention, the naphthyl derivative is one of 1-naphthoyl chloride, 1-naphthoacetyl chloride, 2-naphthoyl chloride, 2-naphthoacetyl chloride, and 2,6-naphthodicarboxyl chloride.
[0017] As a further improvement of the present invention, the solvent is ethylene glycol.
[0018] As a further improvement of the present invention, after the reaction is fully completed at a predetermined reaction temperature, the solvent is recovered by vacuum distillation.
[0019] As a further improvement of the present invention, the organic solvent used in the recrystallization process is methanol or ethanol.
[0020] The beneficial effects of this invention are:
[0021] 1. The method for synthesizing 2-substituted benzimidazole by catalysis of nano-copper-zinc alloy provided by the present invention uses o-phenylenediamine and naphthyl derivatives as raw materials and nano-copper-zinc alloy as catalyst to form 2-substituted benzimidazole under nitrogen protection. The reaction process is simple, easy to implement, highly controllable, and the reaction conditions are mild with a short reaction time, effectively preventing the oxidation of o-phenylenediamine. The yield and quality of the product are both high.
[0022] 2. The method for synthesizing 2-substituted benzimidazole by catalysis of nano-copper-zinc alloy provided by the present invention uses nano-level copper-zinc alloy as a catalyst, which not only has good selectivity for benzimidazole compounds, but also facilitates separation from the product and can be reused.
[0023] 3. The method for synthesizing 2-substituted benzimidazole by catalysis of nano-copper-zinc alloy provided by the present invention not only meets the reaction requirements by selecting high-boiling-point ethylene glycol as solvent, but also has low toxicity. Most of it can be recovered by vacuum distillation, effectively avoiding the environmental pollution problems caused by organic solvents. Attached Figure Description
[0024] Figure 1 The molecular structure of 2-(naphthylethyl)benzimidazole prepared in Example 1 was obtained by X-ray diffraction analysis. Detailed Implementation
[0025] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be described in detail below with reference to the accompanying drawings and specific embodiments.
[0026] It should also be noted that, in order to avoid obscuring the present invention with unnecessary details, only the structures and / or processing steps closely related to the present invention are shown in the accompanying drawings, while other details that are not closely related to the present invention are omitted.
[0027] Additionally, it should be noted that the terms “comprising,” “including,” or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.
[0028] This invention provides a method for the catalytic synthesis of 2-substituted benzimidazole using a nano-copper-zinc alloy, comprising the following steps:
[0029] Under nitrogen protection, o-phenylenediamine and naphthyl derivatives were used as raw materials. The raw materials were mixed with solvent and nano-copper-zinc alloy was added as a catalyst. After fully reacting at a predetermined reaction temperature, 2-substituted benzimidazole was obtained after alkaline washing, activated carbon adsorption and recrystallization.
[0030] The general structural formula of the naphthyl derivative is as follows:
[0031]
[0032] The reaction equation is as follows:
[0033]
[0034] Wherein, R1 is Cl or Br; R2 is -H or -COR1; and R3 is -H or -CH3.
[0035] The above methods can obtain high-quality products with mild reaction conditions and short reaction time, and the product yield is high. The overall reaction process is simple, easy to implement, and highly controllable. It has the advantages of being environmentally friendly, low-energy consumption, low-pollution, high-yield, and having easy-to-separate and reusable catalysts.
[0036] Preferably, the molar ratio of the o-phenylenediamine to the naphthyl derivative is 1:1 to 1.2; and the mass ratio of the o-phenylenediamine to the catalyst is 1:0.5 to 1.
[0037] The predetermined reaction temperature is 80–160°C, preferably 140°C; the reaction time at the predetermined reaction temperature is 3.5–4.5 h, preferably 4 h.
[0038] The nano-copper-zinc alloy has a size of less than 200 nanometers, and the mass fraction of copper in the nano-copper-zinc alloy is 60% and the mass fraction of zinc is 40%.
[0039] Preferably, the naphthyl derivative is one of 1-naphthoyl chloride, 1-naphthoacetyl chloride, 2-naphthoyl chloride, 2-naphthoacetyl chloride, and 2,6-naphthodicarboxyl chloride; and the solvent is ethylene glycol.
[0040] More specifically, during the reaction, the reaction process was tracked by TLC, and the developing solvent was chloroform and methanol prepared in a volume ratio of 9:1.
[0041] After the reaction is completed at the predetermined reaction temperature, the solvent is recovered by vacuum distillation. After the solvent is recovered, the alkaline washing, activated carbon adsorption and recrystallization treatment specifically includes the following steps: adding ethanol and alkaline solution, adjusting the pH to 8-9, and filtering to obtain crude product; after fully dissolving the crude product with hot recrystallization organic solvent, adding activated carbon, stirring at a constant temperature to dissolve and decolorize, filtering the activated carbon while hot, allowing it to cool naturally, and after the product recrystallizes, filtering, washing with hot pure water, filtering again, and drying to obtain 2-substituted benzimidazole.
[0042] Preferably, the recrystallization organic solvent is methanol or ethanol.
[0043] The method for catalytic synthesis of 2-substituted benzimidazole using nano-copper-zinc alloys provided by the present invention will be specifically described below with reference to specific embodiments.
[0044] Example 1
[0045] This embodiment provides a method for the catalytic synthesis of 2-substituted benzimidazole using a nano-copper-zinc alloy, specifically including the following steps:
[0046] 10.81 g of o-phenylenediamine and 20.47 g of 1-naphthylacetyl chloride were added to a 250 mL three-necked round-bottom flask, along with 100 mL of ethylene glycol. The mixture was stirred for 5 minutes, and then 5 g of nano-copper-zinc alloy catalyst (particle size less than 200 nm, with copper and zinc mass fractions of 60% and 40%, respectively) was added. A water separator was attached, and the mixture was heated to reflux at 140 °C for 4 hours. The reaction process was monitored by TLC, with chloroform and methanol prepared in a volume ratio of 9:1 as the developing solvent. After the reaction was completed, the solvent was recovered by vacuum distillation. When approximately 85 mL of ethylene glycol was recovered, vacuum distillation was stopped, and 150 mL of ethanol and 5% sodium hydroxide solution were added to adjust the pH to 8-9. The crude product was obtained by filtration. The crude product was thoroughly dissolved in hot ethanol, and 0.5 g of 200-mesh activated carbon was added. The mixture was stirred at a constant temperature for 30 minutes to dissolve and decolorize. The activated carbon was filtered while hot, and the product was allowed to cool naturally. After recrystallization, the product was filtered, washed twice with hot pure water, filtered again, and dried to obtain 23.76 g of 2-(naphthylethyl)benzimidazole, with a yield of 92%. The product had a good appearance. The molecular structure obtained by X-ray diffraction analysis is shown below. Figure 1 As shown.
[0047] Examples 2-7
[0048] Examples 2-7 provide a method for synthesizing 2-substituted benzimidazole by catalysis of nano-copper-zinc alloy. Compared with Example 1, the only difference is the type and amount of naphthyl derivative. The types and amounts of naphthyl derivatives corresponding to each example are shown in Table 1. The remaining steps and parameters are the same as those in Example 1, and will not be repeated here.
[0049] Table 1. Types and amounts of naphthyl derivatives used in Examples 1-7
[0050]
[0051]
[0052] The types and yields of 2-substituted benzimidazoles prepared according to the above method are shown in Table 2.
[0053] Table 2. Types and yields of 2-substituted benzimidazoles obtained in Examples 1-7.
[0054] Example 2-Substituted Benzimidazoles Product mass (g) Product yield (%) Example 1 2-(naphthylethyl)benzimidazole 23.76 92 Example 2 2-(naphthylethyl)benzimidazole 25.31 98 Example 3 2-(naphthylethyl)benzimidazole 24.28 94 Example 4 2-(naphthyl)benzimidazole 22.96 94 Example 5 2-(naphthyl)benzimidazole 22.23 91 Example 6 2-(naphthylethyl)benzimidazole 24.54 95 Example 7 2-(2,6-naphthyl)benzimidazole 34.23 94
[0055] As can be seen from Table 2, the method provided by the present invention can be applied to different naphthyl derivatives to obtain different 2-substituted benzimidazole products; and the yield of the 2-substituted benzimidazole products prepared based on the method provided by the present invention is 91% to 98%, all of which have high yields.
[0056] Comparative Examples 1-3
[0057] Comparative Examples 1-3 each provide a method for synthesizing 2-substituted benzimidazoles, differing from Example 2 only in the type of catalyst. Specifically, Comparative Example 1 used nano-copper as the catalyst, Comparative Example 2 used nano-zinc as the catalyst, and Comparative Example 3 used polyphosphoric acid as the catalyst.
[0058] Table 3. Types and yields of 2-substituted benzimidazoles obtained in Comparative Examples 1–3.
[0059] Comparative Example 2-Substituted Benzimidazoles Product mass (g) Product yield (%) Comparative Example 1 2-(naphthylethyl)benzimidazole 23.51 91 Comparative Example 2 2-(naphthylethyl)benzimidazole 21.69 84 Comparative Example 3 2-(naphthylethyl)benzimidazole 21.18 82
[0060] Experimental results show that using nano-sized copper or zinc alone as a catalyst resulted in significantly lower product yields than in Example 2, indicating that using nano-copper-zinc alloy as a catalyst is more advantageous. Comparative Example 3, using a traditional catalyst, not only had lower catalytic efficiency but was also environmentally unfriendly.
[0061] In summary, this invention provides a method for the synthesis of 2-substituted benzimidazole via a nano-copper-zinc alloy catalyst. The method involves mixing o-phenylenediamine and a naphthyl derivative as raw materials under nitrogen protection with a solvent, adding a nano-copper-zinc alloy as a catalyst, and reacting thoroughly at a predetermined reaction temperature. Following alkaline washing, activated carbon adsorption, and recrystallization, 2-substituted benzimidazole is obtained. Through this method, this invention can obtain high-quality products with mild reaction conditions and a short reaction time, achieving a high product yield. The overall reaction process is simple, easy to implement, and highly controllable, offering advantages such as environmental friendliness, low energy consumption, low pollution, high yield, easy catalyst separation, and reusability after treatment.
[0062] The above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.
Claims
1. A method for the catalytic synthesis of 2-substituted benzimidazole using a nano-copper-zinc alloy, characterized in that, Includes the following steps: Under nitrogen protection, o-phenylenediamine and naphthyl derivatives were used as raw materials. The raw materials were mixed with solvent and nano-copper-zinc alloy was added as a catalyst. After fully reacting at a predetermined reaction temperature, 2-substituted benzimidazole was obtained after alkaline washing, activated carbon adsorption and recrystallization. The general structural formula of the naphthyl derivative is as follows: The equation for the reaction is as follows: Wherein, R1 is Cl or Br; R2 is -H or -COR1; and R3 is -H or -CH3.
2. The method for catalytic synthesis of 2-substituted benzimidazole using nano-copper-zinc alloy according to claim 1, characterized in that: The molar ratio of the o-phenylenediamine to the naphthyl derivative is 1:1 to 1.
2.
3. The method for catalytic synthesis of 2-substituted benzimidazole using nano-copper-zinc alloy according to claim 1, characterized in that: The mass ratio of o-phenylenediamine to the catalyst is 1:0.5~1.
4. The method for catalytic synthesis of 2-substituted benzimidazole using nano-copper-zinc alloy according to claim 1, characterized in that: The predetermined reaction temperature is 80~160℃.
5. The method for catalytic synthesis of 2-substituted benzimidazole using nano-copper-zinc alloy according to claim 4, characterized in that: The predetermined reaction temperature is 140°C.
6. The method for catalytic synthesis of 2-substituted benzimidazole using nano-copper-zinc alloy according to claim 4, characterized in that: The reaction time at the predetermined reaction temperature is 3.5 to 4.5 hours.
7. The method for catalytic synthesis of 2-substituted benzimidazole using nano-copper-zinc alloy according to claim 6, characterized in that: The reaction time at the predetermined reaction temperature is 4 hours.
8. The method for catalytic synthesis of 2-substituted benzimidazole using nano-copper-zinc alloy according to claim 1, characterized in that: The size of the nano-copper-zinc alloy is less than 200 nanometers.
9. The method for catalytic synthesis of 2-substituted benzimidazole using nano-copper-zinc alloy according to claim 1, characterized in that: The naphthyl derivative is 1-naphthylacetyl chloride.
10. The method for catalytic synthesis of 2-substituted benzimidazole using nano-copper-zinc alloy according to claim 1, characterized in that: The solvent is ethylene glycol.
11. The method for catalytic synthesis of 2-substituted benzimidazole using nano-copper-zinc alloy according to claim 1, characterized in that: After the reaction is completed at the predetermined reaction temperature, the solvent is recovered by vacuum distillation.
12. The method for catalytic synthesis of 2-substituted benzimidazole using nano-copper-zinc alloy according to claim 1, characterized in that: The organic solvent used in the recrystallization process is methanol or ethanol.