Method for preparing benzimidazole antibacterial agent by using ionic liquid functionalized polymeric material as catalyst
By using ionic liquid functionalized polymer catalysts, the problems of low preparation efficiency and environmental pollution of benzimidazole antibacterial agents in existing technologies have been solved, realizing the synthesis of efficient and environmentally friendly benzimidazole antibacterial agents, which are suitable for the production of diverse antibacterial agents.
Patent Information
- Application Number
- CN202510802842.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-06-16
- Publication Date
- 2025-11-18
AI Technical Summary
Existing catalysts have low catalytic efficiency and low yield in the preparation of benzimidazole antibacterial agents, making it difficult to meet the needs of large-scale production, and they also pose environmental pollution problems.
Ionic liquid functionalized polymers are synthesized through specific steps using ionic liquid functionalized polymers as catalysts. These polymers are then used to catalyze the reaction of o-phenylenediamine with aromatic aldehydes of different substituents to prepare benzimidazole antibacterial agents. The materials are reusable.
It improves catalytic efficiency and yield to 87-91%, is environmentally friendly and widely applicable, reduces production costs, and is in line with the development direction of green chemistry.
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Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of polymeric materials, in particular to a method for preparing a benzimidazole antibacterial agent by using an ionic liquid functionalized polymeric material as a catalyst. BACKGROUND
[0002] Ionic liquids (ILs) are a class of environmentally friendly organic molten salts composed of specific ions. Common cations include [NRxH4-x] + , [RPy] + , [PRxH4-x] + , and anions include BF4 - , PF6 - , and X - (X = F, Cl, Br, I) and the like. Due to their unique properties, ILs are widely used in many organic synthesis reaction systems, such as Friedel-Crafts reaction, Diels-Alder cycloaddition reaction, catalytic hydrogenation, and polymerization reaction, etc. In these reactions, ILs play an important role as mediators or catalysts, promoting the continuous development of chemical synthesis.
[0003] Porous organic polymeric materials (POPs) are materials with a porous structure mainly composed of light elements (such as C, H, N, O, B, etc.). They have a series of excellent properties, such as high specific surface area, good adsorption, adjustable pore structure, etc. When ionic liquids are combined with porous organic polymeric materials to form ionic liquid functionalized POPs materials, this new type of material not only inherits the advantages of ionic liquids, but also combines the characteristics of porous organic polymeric materials, thus showing broad application prospects in the field of catalysis and opening up new ways and methods for chemical catalytic synthesis.
[0004] Benzimidazole compounds are a class of bicyclic nitrogen-containing organic compounds with fused benzene and imidazole nuclei. Their unique chemical structure endows them with significant biological antibacterial activity. Based on this property, benzimidazole compounds have become a hot spot in many medical fields and can be used as important precursors for anti-inflammatory drugs, antiviral drugs, and antitumor drugs, which are of great significance for human health. Currently, the main method for synthesizing benzimidazole compounds is condensation reaction using o-phenylenediamine (o-PDA) as a reactant. In the reaction process, some inorganic acids such as H2SO4, HNO3 or Lewis acids such as AlCl3 and BF3 are often used as catalysts for preparing benzimidazole compounds. However, these conventional catalysts have many problems in practical application. On the one hand, the catalytic efficiency is low, which makes the reaction rate slow and it is difficult to obtain a large amount of target product in a short time. On the other hand, the actual yield is low, which cannot meet the demand of large-scale production, limiting the widespread application and industrial development of benzimidazole antibacterial agents.
[0005] The following synthetic route is the synthetic route of the existing benzimidazole antibacterial agent:
[0006]
[0007] In view of the above-mentioned shortcomings of the conventional catalyst in the prior art for the preparation of benzimidazole antibacterial agents, the present application aims to provide a new type of catalytic system, which uses an ionic liquid functionalized POP material as a catalyst for the reaction of o-phenylenediamine (o-PDA) with aromatic aldehydes containing different substituents (R=Br, Cl, CN) to prepare the corresponding benzimidazole antibacterial agents. SUMMARY
[0008] The purpose of the present application is to overcome the shortcomings of the prior art and provide a method for preparing benzimidazole antibacterial agents using an ionic liquid functionalized polymeric material as a catalyst.
[0009] To achieve the above-mentioned purpose, the technical solution adopted by the present application is as follows:
[0010] The present application provides a method for preparing benzimidazole antibacterial agents using an ionic liquid functionalized polymeric material as a catalyst, which comprises the following steps:
[0011] Step one: under N2 environment, 1,4-p-dichlorobenzene and N-methyl imidazole are added to a round-bottom flask containing 1,2-dichloroethane, and the first reaction is carried out by stirring and heating to 80-90℃ reflux, obtaining a first reaction mixture, then anhydrous ferric chloride is added, and the second reaction is carried out by continuing to stir and heat to 80-90℃ reflux, obtaining a second reaction product;
[0012] Step two: the second reaction product is subjected to cooling treatment, suction filtration treatment, washing treatment, extraction treatment and vacuum drying treatment in sequence, obtaining an ionic liquid functionalized polymeric material;
[0013] Step three: o-phenylenediamine, aromatic aldehyde and ionic liquid functionalized polymeric material are added to a round-bottom flask containing ethanol, and the third reaction is carried out by stirring and heating to 80-90℃ reflux, obtaining a benzimidazole antibacterial agent;
[0014] Step four: repeat step three, and the benzimidazole antibacterial agent is subjected to solvent evaporation and filtration separation of ionic liquid functionalized polymeric material in sequence, and the filtered and separated ionic liquid functionalized polymeric material is washed with ethyl acetate, which can be reused in step three.
[0015] Further, in step one, the molar ratio of 1,4-p-dichlorobenzene, N-methyl imidazole and anhydrous ferric chloride is 1:(6-12):(6-12).
[0016] Further, the washing treatment is washing with ethanol, the extraction treatment is extraction with a Soxhlet extractor for 48-60 hours, and the vacuum drying treatment is drying in a vacuum oven at 60-70 DEG C for 24-30 hours.
[0017] Further, the aromatic aldehyde is a benzaldehyde substituted with bromine or chlorine or cyano.
[0018] Further, in step three,
[0019] The molar ratio of the ionic liquid functionalized polymer material to the o-phenylenediamine is 1:2.5-3;
[0020] The molar ratio of the ionic liquid functionalized polymer material to the benzaldehyde substituted with bromine, chlorine or cyano is 1:(2-3):(2-3):(2-3).
[0021] Further, the first reaction time is 10-12 hours, the second reaction time is 12-14 hours, and the third reaction time is 4-6 hours.
[0022] The ionic liquid functionalized polymer material is used as a catalyst, and a high-efficiency and environmentally friendly synthesis method of a benzimidazole antibacterial agent is provided. BRIEF DESCRIPTION OF DRAWINGS
[0023] Figure 1 It is an infrared IR contrast spectrum of the ionic liquid functionalized polymer material in different proportions in the application.
[0024] Figure 2 It is a nuclear magnetic resonance NMR spectrum of the ionic liquid functionalized polymer material in Example 1 and the polymer material in the comparative example.
[0025] Figure 3 It is a hydrogen spectrum (HNMR) of the benzimidazole antibacterial agent in Example 1 of the application. 1
[0026] Figure 4 It is a hydrogen spectrum (HNMR) of the benzimidazole antibacterial agent in Example 3 of the application. 1
[0027] Figure 5 HNMR) chart of the benzimidazole antibacterial agent of Example 4 in the present application; 1 HNMR) chart of the benzimidazole antibacterial agent of Example 4 in the present application;
[0028] Figure 6 Yield column chart of N-methyl imidazole and 1,4-p-dichlorobenzene in different proportions in the experiment of catalytic synthesis of benzimidazole antibacterial agent (R=Br) of Example 1 and Example 2 in the present application. DETAILED DESCRIPTION
[0029] The detailed description of the specific embodiments of the present application will be described below.
[0030] Unless otherwise defined, technical and scientific terms used in the claims and specification shall have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.
[0031] The use of "including" or "comprising" or similar words in the present application specification and claims means that the object appearing before "including" or "comprising" covers the object listed after "including" or "comprising" or its equivalent, and does not exclude other objects.
[0032] The numerical values mentioned in the present application include all the values increasing one unit by one unit from low to high, and it is assumed that there are at least two units between any lower value and higher value. For example, if it is said that a component quantity or a physical quantity is from 1 to 100, 10 to 90 is more optimal, and 20 to 80 is optimal, it is intended to express that the values of 5 to 95, 14 to 76, 23 to 67, 32 to 58, 41 to 49, etc. are clearly listed in this specification; for values less than 1, 0.0001, 0.001, 0.01 or 0.1 are considered as a more appropriate unit. The foregoing examples are for illustration only, and in fact, all combinations of values between the lowest value and the highest value listed are considered to be clearly listed in the specification in a similar manner.
[0033] Example 1
[0034] This Example 1 provides a method for preparing a benzimidazole antibacterial agent using an ionic liquid functionalized polymeric material as a catalyst, comprising the following steps:
[0035]
[0036] Step one, under N2 environment, 5.5 mmol or 0.963 g of 1,4-p-dichlorobenzene (p-DCX) and 0.458 mmol or 37.6 mg of N-methylimidazole (N-MI) were added into a round bottom flask containing 40 ml of 1,2-dichloroethane (DCE), the molar ratio of N-methylimidazole (N-MI) to 1,4-p-dichlorobenzene (p-DCX) was 1:12, and the mixture was stirred and heated to 80°C reflux, and kept at this temperature for 10 h until N-methylimidazole (N-MI) was completely reacted (by thin layer chromatography (TLC) analysis), to obtain a first reaction mixture;
[0037] 5.5 mmol or 0.894 g of anhydrous ferric chloride was added to the above first reaction mixture, and the second reaction was continued by stirring and heating to 80°C reflux, and the reaction time was 12 h, to obtain a second reaction mixture;
[0038] The second reaction mixture was sequentially subjected to cooling treatment, suction filtration treatment, washing with methanol for 3 times, Soxhlet extractor extraction for 48 h, and drying in a vacuum oven at 60°C for 24 h, to obtain a brown solid, which was an ionic liquid functionalized polymer material (labeled as POPs-B20).
[0039] Step two, 2.5 mmol of o-phenylenediamine and 2.0 mmol of benzaldehyde containing a bromine substituent were used as reactants, 1 mmol of the above prepared ionic liquid functionalized polymer material (POPs-B20) was weighed as a catalyst, and was added into a round bottom flask containing 10 mL of ethanol, and was stirred and heated to 80°C reflux, and kept at this temperature for 4 h, to obtain a benzimidazole antibacterial agent (4-bromophenyl)-1H-benzimidazole.
[0040] Step three, the above reaction mixture was subjected to solvent evaporation operation, and then the ionic liquid functionalized polymer material POPs-B20 was separated by filtration and washed with 15 mL of ethyl acetate for 3 times.
[0041] The washed ionic liquid functionalized polymer material (labeled as POPs-B20) was returned to the reaction system in step two, and was reused for the next round of catalytic reaction.
[0042] Example 2
[0043] The present example 2 provides a method for preparing a benzimidazole antibacterial agent using an ionic liquid functionalized polymer material as a catalyst, which comprises the following steps:
[0044] Step one, under N2 environment, 5.5 mmol or 0.963 g of 1,4-p-dichlorobenzene (p-DCX) and 0.917 mmol or 75.2 mg of N-methylimidazole (N-MI) were added into a round bottom flask containing 40 ml of 1,2-dichloroethane (DCE), the molar ratio of N-methylimidazole (N-MI) to 1,4-p-dichlorobenzene (p-DCX) was 1:6, and the mixture was stirred and heated to 80°C reflux, and the temperature was kept for 10 h until N-methylimidazole (N-MI) was completely reacted (by thin layer chromatography (TLC) analysis), to obtain a first reactant mixture;
[0045] 5.5 mmol or 0.894 g of anhydrous ferric chloride was added to the above first reactant mixture, and the second reaction was continued by stirring and heating to 80°C reflux, and the reaction time was 12 h, to obtain a second reactant;
[0046] The second reactant was sequentially subjected to cooling treatment, suction filtration treatment, washing with methanol for 3 times, Soxhlet extractor extraction for 48 h, and drying in a vacuum oven at 60°C for 24 h, to obtain a brown solid, which was an ionic liquid functionalized polymeric material (labeled as POPs-B10).
[0047] Step two, 2.5 mmol of o-phenylenediamine and 2.0 mmol of benzaldehyde containing bromine or chlorine or cyano-substituted benzaldehyde were used as reactants, 1 mmol of the above prepared ionic liquid functionalized polymeric material (POPs-B10) was weighed as a catalyst, and was added into a round bottom flask containing 10 mL of ethanol, and was stirred and heated to 80°C reflux, and the temperature was kept for 4 h, to obtain a benzimidazole antibacterial agent (4-bromophenyl) or (4-chlorophenyl) or (4-cyanophenyl)-1H-benzimidazole.
[0048] Step three, the above reaction mixture was subjected to solvent evaporation operation, and then the ionic liquid functionalized polymeric material (labeled as POPs-B10) was separated by filtration and washed with 15 mL of ethyl acetate for 3 times.
[0049] The washed ionic liquid functionalized polymeric material was returned to the reaction system in step two, and was reused for the next round of catalytic reaction.
[0050] Example 3
[0051] The example 3 provides a method for preparing a benzimidazole antibacterial agent using an ionic liquid functionalized polymeric material as a catalyst, which comprises the following steps:
[0052] Step one, under N2 environment, 5.5 mmol or 0.963 g of 1,4-p-dichlorobenzene (p-DCX) and 0.458 mmol or 37.6 mg of N-methylimidazole (N-MI) were added into a round bottom flask containing 40 ml of 1,2-dichloroethane (DCE), the molar ratio of N-methylimidazole (N-MI) to 1,4-p-dichlorobenzene (p-DCX) was 1:12, and the mixture was stirred and heated to 80°C reflux, and the temperature was kept for 10 h until N-methylimidazole (N-MI) was completely reacted (by thin layer chromatography (TLC) analysis), to obtain a first reactant mixture;
[0053] 5.5 mmol or 0.894 g of anhydrous ferric chloride was added to the above first reactant mixture, and the second reaction was continued by stirring and heating to 80°C reflux, and the reaction time was 12 h, to obtain a second reactant;
[0054] The second reactant was sequentially subjected to cooling treatment, suction filtration treatment, washing with methanol for 3 times, Soxhlet extractor extraction for 48 h, and drying in a vacuum oven at 60°C for 24 h, to obtain a brown solid, which was an ionic liquid functionalized polymer material.
[0055] Step two, 2.5 mmol of o-phenylenediamine and 2.0 mmol of benzaldehyde containing a chloro substituent were used as reactants, 1 mmol of the above prepared ionic liquid functionalized polymer material was weighed as a catalyst, and was added into a round bottom flask containing 10 mL of ethanol, and was stirred and heated to 80°C reflux, and the temperature was kept for 4 h, to obtain a benzimidazole antibacterial agent (4-chlorophenyl)-1H-benzimidazole.
[0056] Step three, the above reaction mixture was subjected to solvent evaporation operation, and then the ionic liquid functionalized polymer material was separated by filtration and washed with 15 mL of ethyl acetate for 3 times.
[0057] The washed ionic liquid functionalized polymer material was returned to the reaction system in step two, and was reused for the next round of catalytic reaction.
[0058] Example 4
[0059] The present example 4 provides a method for preparing a benzimidazole antibacterial agent using an ionic liquid functionalized polymer material as a catalyst, which comprises the following steps:
[0060] Step one, under N2 environment, 5.5 mmol or 0.963 g of 1,4-p-dichlorobenzene (p-DCX) and 0.458 mmol or 37.6 mg of N-methylimidazole (N-MI) were added into a round bottom flask containing 40 ml of 1,2-dichloroethane (DCE), the molar ratio of N-methylimidazole (N-MI) to 1,4-p-dichlorobenzene (p-DCX) was 1:12, and the mixture was stirred and heated to 80 °C to reflux, and the temperature was kept for 10 h until N-methylimidazole (N-MI) was completely reacted (by thin layer chromatography (TLC) analysis), to obtain a first reactant mixture;
[0061] 5.5 mmol or 0.894 g of anhydrous ferric chloride was added to the above-mentioned first reactant mixture, and the second reaction was continued by stirring and heating to 80 °C to reflux for 12 h to obtain a second reactant;
[0062] The second reactant was sequentially subjected to cooling treatment, suction filtration treatment, washing with methanol for 3 times, Soxhlet extractor extraction for 48 h, and drying in a vacuum oven at 60 °C for 24 h to obtain a brown solid, which was an ionic liquid functionalized polymer material.
[0063] Step two, 2.5 mmol of o-phenylenediamine and 2.0 mmol of benzaldehyde containing a cyano substituent were used as reactants, 1 mmol of the above-prepared ionic liquid functionalized polymer material was weighed as a catalyst, and was added into a round bottom flask containing 10 mL of ethanol, and was stirred and heated to 80 °C to reflux, and the temperature was kept for 4 h to obtain a benzimidazole antibacterial agent (4-cyanophenyl)-1H-benzimidazole.
[0064] Step three, the above-mentioned reaction mixture was subjected to solvent evaporation operation, and then the ionic liquid functionalized polymer material was separated by filtration and washed with 15 mL of ethyl acetate for 3 times.
[0065] The washed ionic liquid functionalized polymer material was returned to the reaction system in step two for reuse in the next round of catalytic reaction.
[0066] Blank comparative example
[0067] 2.5 mmol of o-phenylenediamine and 2.0 mmol of benzaldehyde containing a bromine or chlorine or cyano substituent were used as reactants, and were added into a round bottom flask containing 10 mL of ethanol, and were stirred and heated to 80 °C to reflux, and the temperature was kept for 4 h to obtain a benzimidazole antibacterial agent.
[0068] Comparative example
[0069] This comparative example provides a preparation method of a polymer material, and the specific steps are as follows:
[0070] Step one, under N2 atmosphere, 5.5 mmol or 0.963 g of 1,4-p-dichlorobenzene (p-DCX) was added to a round bottom flask containing 40 ml of 1,2-dichloroethane (DCE), and heated to 80℃ reflux with stirring to obtain a mixed solution.
[0071] Step two, 5.5 mmol or 0.894 g of anhydrous ferric chloride was added to the above mixed solution, and the stirring reflux was continued at 80℃ for 12 h to obtain a polymeric material semi-finished product.
[0072] Step three, the polymeric material semi-finished product was sequentially cooled and dried: stop heating, cool and suction filtration, the product was washed with methanol (MeOH) for 3 times, extracted by a Soxhlet extractor for 48 h, and dried in a vacuum oven at 60℃ for 24 h to obtain a polymeric material (labeled as POPs-B0).
[0073] The above prepared POPs-B0 was used as a catalyst to perform the synthesis experiment of benzimidazole antibacterial agent according to steps two and three in examples 1, 3 and 4.
[0074] The following table 1 is the reaction yield of the synthesis of benzimidazole antibacterial agent using the ionic liquid functionalized polymeric material POPs as a catalyst:
[0075] Table 1
[0076]
[0077] According to table 1, it can be found that the catalytic performance of the existing benzimidazole antibacterial agent is significantly lower than that of the ionic liquid functionalized polymeric material (such as POPs-B10 or POPs-B20) in the examples of the present application;
[0078] This indicates that N-methyl imidazole (N-MI) is not added during the preparation of the polymeric material, resulting in insufficient catalytic active sites of the material, which cannot efficiently catalyze the reaction of o-phenylenediamine and aromatic aldehyde, thereby verifying the key role of N-methyl imidazole (N-MI) in preparing high-performance catalysts.
[0079] In summary, the present application uses ionic liquid functionalized polymeric material as a catalyst to provide an efficient and environmentally friendly synthesis method of benzimidazole antibacterial agent; compared with the prior art, the catalyst exhibits higher catalytic efficiency and yield, which can reach 87-91%, and has excellent recyclability and reusability; in addition, the catalyst has wide applicability to different substituted aromatic aldehydes, which is conducive to the synthesis of diversified antibacterial agents; the environmentally friendly characteristics further reduce the pollution in the production process; overall, the present application improves the production efficiency and reduces the cost, and also meets the development direction of green chemistry, which has significant economic and social benefits.
[0080] The above merely preferred embodiments of the present application and are not intended to limit the embodiments and protection scope of the present application. Those skilled in the art should be able to understand that any equivalent substitutions and obvious changes made according to the present application description and drawings should be included in the protection scope of the present application.
Claims
1. A method for preparing benzimidazole antibacterial agents using ionic liquid functionalized polymeric materials as catalysts, characterized in that, Includes the following steps: Step 1: Under N2 environment, 1,4-dichlorobenzyl and N-methylimidazole are added to a round-bottom flask containing 1,2-dichloroethane. The mixture is stirred and heated to 80-90°C under reflux for the first reaction to obtain the first reactant mixture. Anhydrous ferric chloride is added to the mixture, and the mixture is stirred and heated to 80-90°C under reflux for the second reaction to obtain the second reactant. Step 2: The second reactant is subjected to cooling, filtration, washing, extraction and vacuum drying in sequence to obtain the ionic liquid functionalized polymer material. Step 3: Add o-phenylenediamine, aromatic aldehyde, and the ionic liquid functionalized polymer material to a round-bottom beaker containing ethanol, stir and heat to 80℃-90℃ and reflux for a third reaction to obtain benzimidazole antibacterial agent; Step 4: Repeat Step 3, sequentially evaporating the solvent and filtering the benzimidazole antibacterial agent to separate the ionic liquid functionalized polymer material. Wash the filtered ionic liquid functionalized polymer material with ethyl acetate, and then return to Step 3 for reuse.
2. The method for preparing benzimidazole antibacterial agents using ionic liquid functionalized polymeric materials as catalysts according to claim 1, characterized in that, In step one, The molar ratio of the 1,4-dichlorobenzyl, the N-methylimidazolium, and the anhydrous ferric chloride is 1:(6-12):(6-12).
3. The method for preparing benzimidazole antibacterial agents using ionic liquid functionalized polymeric materials as catalysts according to claim 1, characterized in that, The washing process uses ethanol, the extraction process uses a Soxhlet extractor for 48-60 hours, and the vacuum drying process uses a vacuum oven at 60-70°C for 24-30 hours.
4. The method for preparing benzimidazole antibacterial agents using ionic liquid functionalized polymeric materials as catalysts according to claim 1, characterized in that, The aromatic aldehyde is benzaldehyde containing bromine, chlorine, or cyanide substituted groups.
5. The method for preparing benzimidazole antibacterial agents using ionic liquid functionalized polymeric materials as catalysts according to claim 4, characterized in that, In step three The molar ratio of the ionic liquid functionalized polymeric material to the o-phenylenediamine is 1:2.5-3; The molar ratio of the ionic liquid functionalized polymeric material to bromine-substituted benzaldehyde, chlorine-substituted benzaldehyde, and cyano-substituted benzaldehyde is 1:(2-3):(2-3):(2-3).
6. The method for preparing benzimidazole antibacterial agents using ionic liquid functionalized polymeric materials as catalysts according to claim 1, characterized in that, The first reaction time is 10h-12h, the second reaction time is 12h-14h, and the third reaction time is 4h-6h.