A method for non-metallic catalytic synthesis of benzimidazole or its derivatives from CO2

Abstract

The application discloses a method for nonmetal catalytic synthesis of benzimidazole or its derivative by taking CO2 as raw material, which takes CO2 and o-phenylenediamine compounds as raw material, takes hydrosilane as a reducing agent, and generates benzimidazole or its derivative under the catalysis of a catalyst N,N-diethylacetoacetamide. Compared with a traditional transition metal catalyst, the N,N-diethylacetoacetamide used in the synthesis method has the advantages of stable chemical property, low price, convenient use and the like, can overcome the toxicity generated in the transition metal catalysis, and is a novel alternative environment-friendly catalyst; in addition, the reaction takes CO2 as raw material, can convert the gas causing the greenhouse effect into the benzimidazole with high economic value, realizes waste utilization, and protects the environment.

Description

Technical Field

[0001] This invention relates to a method for synthesizing a compound, specifically a method for synthesizing benzimidazole or its derivatives using CO2 as a raw material via nonmetallic catalysis. Background Technology

[0002] Benzimidazole is an important organic compound with wide applications in various industries. It is a crucial structural unit in the synthesis of many pharmaceuticals, pesticides, dyes, cosmetics, and high-temperature polymer products. As a core compound in heterocyclic compounds, benzimidazole has a long history of use in medicinal chemistry. Beyond these applications, it is used in chiral chemistry for the synthesis of chiral benzimidazoles and as an organic catalyst in many chemical reactions. Recently, it has become a popular "nano" material for use in optical devices, chemical sensors, medicine, chemical technology, and environmental science, offering several advantages over other sensor devices. Benzimidazole and its derivatives are also used as supramolecular components in thermally stable polymer materials, as adsorbents for small molecules, and as nanocontainers for electronic conduction in liquid crystal technology. Due to its excellent nonlinear optical properties, the application prospects of benzimidazole and its derivatives in photonics technology are receiving extensive research. Polybenzimidazole fibers and their wide range of applications (protective coatings, flame retardants, matrix films, etc.) are also well-known. A few benzimidazole derivative fungicides, such as carbendazim and benzoyl, have applications in agriculture because they have low toxicity, require low dosages, and have no carcinogenic, mutagenic, or teratogenic effects. Similarly, the literature reports the use of common benzimidazoles as insecticides, pesticides, and herbicides. Benzimidazole derivatives have been explored as potential corrosion inhibitors for metals such as copper, iron, and zinc under acidic conditions. Due to the molecular physical and chemical properties of benzimidazole, researchers have also investigated their use as basic color elements in organic dyes. Furthermore, benzimidazole is an important core molecule in organic light-emitting diodes (OLEDs), exhibiting good thermal properties, phosphorescence, and morphological stability.

[0003] Benzimidazole is typically a carbonyl compound prepared from o-phenylenediamine. Constructing benzimidazole using carbon dioxide as a carbon source is an environmentally friendly method, and several methods have been reported. Cantat et al. reported the reaction of o-phenylenediamine and CO2 catalyzing the formation of imidazole from N-heterocyclic carbenes in the presence of hydrosilanes. Using metal catalysts such as RuCl2(dppe)2 and Au / TiO2, o-phenylenediamine / 2-nitroaniline cyclization to benzimidazole was achieved under a CO2 / H2 atmosphere. However, these methods utilize expensive and toxic transition metal catalysts and have poor atom economy. Furthermore, CO2 is a source of greenhouse gases; converting it into economically valuable products would contribute to environmental protection. Therefore, developing a simple and readily available non-metallic catalyst for the direct synthesis of benzimidazole from CO2 is an ideal goal, but it also presents certain technical challenges. Summary of the Invention

[0004] Purpose of the invention: The present invention aims to provide a simple, mild, pollution-free and efficient method for the non-metallic catalytic synthesis of benzimidazole or its derivatives using CO2 as a raw material.

[0005] Technical solution: The method for synthesizing benzimidazole or its derivatives using CO2 as a raw material via non-metallic catalysis according to the present invention includes the following steps: under the catalysis of N,N-diethylacetylacetamide, benzimidazole or its derivatives are synthesized using hydrosilane as a reducing agent.

[0006] The reaction route is shown below:

[0007]

[0008] Further, R1 group is hydrogen, aryl, alkyl or halogen-substituted alkyl, halogen, aryl, carbonyl, cyano, carboxylic acid or nitro; R2 group is hydrogen, alkyl or aryl; more preferably, R1 is hydrogen, halogen, alkyl or halogen-substituted alkyl; R2 is hydrogen or alkyl.

[0009] Preferably, the reaction temperature is 90℃-120℃ and the reaction time is 10-12 hours.

[0010] Preferably, the reaction is carried out in a closed environment.

[0011] Preferably, the amount of N,N-diethylacetylacetamide added is 1.0-2.0% of the molar mass of o-phenylenediamine, the amount of reducing agent hydrosilane added is 200-400% of the molar mass of o-phenylenediamine, and the amount of CO2 used is in the range of 1 MPa to 5 MPa.

[0012] Preferably, the reaction solvent is selected from one of tetrahydrofuran (THF), N,N-dimethylformamide (DMF), toluene, and dichloromethane.

[0013] Preferably, the reaction further includes the following steps: after the reaction is completed, the solution is cooled with water, the organic layers are combined by extraction, the solvent is removed under reduced pressure, and the remaining solution is subjected to rapid column chromatography to obtain benzimidazole or its derivatives.

[0014] Preferably, the product yield obtained by this reaction is >79%.

[0015] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages:

[0016] (1) A metal-free catalytic reaction using N,N-diethylacetylacetamide as a catalyst is provided. Compared with traditional transition metal catalysts, N,N-diethylacetylacetamide has the advantages of stable chemical properties, low price and convenient use. The catalyst used in this invention can overcome the toxicity produced in transition metal catalysis and is a new type of environmentally friendly alternative catalyst.

[0017] (2) The reaction uses CO2 as raw material to convert this greenhouse gas into benzimidazole with high economic value, realizing waste utilization and protecting the environment.

[0018] (3) This method improves the tolerance of functional groups such as carbonyl, cyano, carboxylic acid, halogen, and nitro, has a wide range of substrate selection, and produces benzimidazole in a variety of forms. Attached Figure Description

[0019] Figure 1 This is the 1H NMR spectrum of 1H-benzimidazole prepared in Example 1 of this invention;

[0020] Figure 2 This is the carbon NMR spectrum of 1H-benzimidazole prepared in Example 1 of this invention;

[0021] Figure 3 This is the 1H NMR spectrum of 5-methylbenzimidazole prepared in Example 2 of this invention;

[0022] Figure 4 This is the carbon NMR spectrum of 5-methylbenzimidazole prepared in Example 2 of this invention;

[0023] Figure 5 This is the 1H NMR spectrum of 5,6-dimethylbenzimidazole prepared in Example 3 of this invention;

[0024] Figure 6 This is the carbon NMR spectrum of 5,6-dimethylbenzimidazole prepared in Example 3 of this invention;

[0025] Figure 7 This is the 1H NMR spectrum of 5-chlorobenzimidazole prepared in Example 4 of this invention;

[0026] Figure 8 This is the carbon NMR spectrum of 5-chlorobenzimidazole prepared in Example 4 of this invention;

[0027] Figure 9 This is the 1H NMR spectrum of 5-fluorobenzimidazole prepared in Example 5 of this invention;

[0028] Figure 10 This is the carbon NMR spectrum of 5-fluorobenzimidazole prepared in Example 5 of this invention;

[0029] Figure 11 This is the 1H NMR spectrum of 5-trifluoromethylbenzimidazole prepared in Example 6 of this invention;

[0030] Figure 12 This is the carbon NMR spectrum of 5-trifluoromethylbenzimidazole prepared in Example 6 of this invention. Detailed Implementation

[0031] The technical solution of the present invention will be further described below with reference to the accompanying drawings.

[0032] Example 1

[0033] This embodiment provides a method for preparing benzimidazole using a non-metallic catalyst, wherein the raw material is o-phenylenediamine, the hydrosilane is PhSiH3, the catalyst is N,N-diethylacetylacetamide, and the product is 1H-benzimidazole. The reaction route is shown below:

[0034]

[0035] The preparation method of 1H-benzimidazole (1a) includes the following steps:

[0036] (1) Place o-phenylenediamine (1 mmol), PhSiH3 (2 mmol), N,N-diethylacetylacetamide (0.1 mol) and tetrahydrofuran (THF) (2 mL) into a 20 mL stainless steel reactor equipped with a magnetic stirrer, and then pressurize the sealed mixture with 1 MPa CO2.

[0037] (2) Heat and stir at 90℃ for 10 hours.

[0038] (3) After the reaction was complete, add water (15 mL) and cool to room temperature. Extract the aqueous layer with 3 × 10 mL of dichloromethane (DCM). Combine the organic layers and dry with anhydrous MgSO4, then remove the solvent under reduced pressure.

[0039] (4) The product (1a) was purified by column chromatography on silica gel using petroleum ether and ethyl acetate (1:2) as eluents.

[0040] The product obtained from the reaction was a white solid, totaling 103.9 mg, with a yield of 88.1%. Nuclear magnetic resonance (NMR) analysis confirmed it to be 1H-benzimidazole. The proton NMR spectrum of 1H-benzimidazole is shown below. Figure 1 As shown, the carbon NMR spectrum is as follows Figure 2 As shown;

[0041] The NMR data are shown below:

[0042] 1 H NMR (400MHz, DMSO, 293k): δ12.42 (s, 1H), 8.20 (s, 1H), 7.58 (dd, J = 5.9, J = 3.2Hz, 2H), 7.19-7.17 (m, 2H); 13 C NMR (100MHz, DMSO, 293k): δ141.92(CH), 138.07(C), 121.70(CH), 115.31(CH).

[0043] Example 2

[0044] This embodiment provides a method for preparing a non-metal-catalyzed benzimidazole derivative, wherein the starting material is 3,4-diaminotoluene, the hydrosilane is PhSiH3, the catalyst is N,N-diethylacetylacetamide, and the product is 5-methylbenzimidazole. The reaction route is shown below:

[0045]

[0046] The preparation method of 5-methylbenzimidazole (2a) includes the following steps:

[0047] (1) 3,4-Diaminotoluene (1 mmol), PhSiH3 (2 mmol), N,N-diethylacetylacetamide (0.1 mol) and tetrahydrofuran (THF) (2 mL) were placed into a 20 mL stainless steel reactor equipped with a magnetic stirrer, and then the sealed mixture was charged with 1 MPa CO2.

[0048] (2) Heat and stir at 90℃ for 10 hours.

[0049] (3) After the reaction is complete, add water (15 mL) and cool to room temperature. Extract the aqueous layer with 3 × 10 mL of DCM. Combine the organic layers and dry with anhydrous MgSO4, then remove the solvent under reduced pressure.

[0050] (4) The product (2a) was purified by column chromatography on silica gel using petroleum ether and ethyl acetate (1:2) as eluents.

[0051] The product obtained from the reaction was a yellow solid, totaling 104.8 mg, with a yield of 79.4%. Nuclear magnetic resonance (NMR) analysis confirmed that the product was 5-methylbenzimidazole. The proton NMR spectrum of 5-methylbenzimidazole is shown below. Figure 3 As shown, the carbon NMR spectrum is as follows Figure 4 As shown;

[0052] The NMR data are shown below:

[0053] 1 H NMR (400MHz, DMSO) δ12.32(s,1H),8.10(s,1H),7.46(d,J=8.2Hz,1H),7.35(s,1H),7.00(d,J=8.2Hz,1H),2.40(s,3H). 13 C NMR (100MHz, CDCl3) δ139.42(CH), 136.42(C), 135.36(C), 131.80(C), 123.43(CH), 114.52(CH), 113.84(CH), 20.66(CH3).

[0054] Example 3

[0055] This embodiment provides a method for preparing a non-metal-catalyzed benzimidazole derivative, wherein the starting material is 4,5-dimethyl-1,2-phenylenediamine, the hydrosilane is PhSiH3, the catalyst is N,N-diethylacetylacetamide, and the product is 5,6-dimethylbenzimidazole. The reaction route is shown below:

[0056]

[0057] The preparation method of 5,6-dimethylbenzimidazole (3a) includes the following steps:

[0058] (1) 4,5-dimethyl-1,2-phenylenediamine (1 mmol), PhSiH3 (2 mmol), N,N-diethylacetylacetamide (0.1 mol) and tetrahydrofuran (THF) (2 mL) were placed into a 20 mL stainless steel reactor equipped with a magnetic stirrer, and then the sealed mixture was charged with 1 MPa CO2.

[0059] (2) Heat and stir at 90℃ for 10 hours.

[0060] (3) After the reaction is complete, add water (15 mL) and cool to room temperature. Extract the aqueous layer with 3 × 10 mL of DCM. Combine the organic layers and dry with anhydrous MgSO4, then remove the solvent under reduced pressure.

[0061] (4) The product (3a) was purified by column chromatography on silica gel using petroleum ether and ethyl acetate (1:2) as eluents.

[0062] The product obtained from the reaction was a yellow solid, totaling 133.7 mg, with a yield of 91.6%. Nuclear magnetic resonance (NMR) analysis confirmed the product to be 5,6-dimethylbenzimidazole. The proton NMR spectrum of 5,6-dimethylbenzimidazole is shown below. Figure 5 As shown, the carbon NMR spectrum is as follows Figure 6 As shown;

[0063] The NMR data are shown below:

[0064] 1 H NMR (400MHz, DMSO) δ12.24(s,1H),8.05(s,1H),7.35(s,2H),2.28(s,6H). 13 CNMR(100MHz,DMSO)δ140.50(C),136.21(CH),129.62(CH),114.81(CH),19.43(CH3).

[0065] Example 4

[0066] This embodiment provides a method for preparing a non-metal-catalyzed benzimidazole derivative, wherein the starting material is 4-chloro-1,2-phenylenediamine, the hydrosilane is PhSiH3, the catalyst is N,N-diethylacetylacetamide, and the product is 5-chlorobenzimidazole. The reaction route is shown below:

[0067]

[0068] The preparation method of 5-chlorobenzimidazole (4a) includes the following steps:

[0069] (1) 4-chloro-1,2-phenylenediamine (1 mmol), PhSiH3 (2 mmol), N,N-diethylacetylacetamide (0.1 mol) and tetrahydrofuran (THF) (2 mL) were placed into a 20 mL stainless steel reactor equipped with a magnetic stirrer, and then the sealed mixture was charged with 1 MPa CO2.

[0070] (2) Heat and stir at 90℃ for 10 hours.

[0071] (3) After the reaction is complete, add water (15 mL) and cool to room temperature. Extract the aqueous layer with 3 × 10 mL of DCM. Combine the organic layers and dry with anhydrous MgSO4, then remove the solvent under reduced pressure.

[0072] (4) The product (4a) was purified by column chromatography on silica gel using petroleum ether and ethyl acetate (1:2) as eluents.

[0073] The product obtained from the reaction was a yellow solid, totaling 130.3 mg, with a yield of 85.7%. Nuclear magnetic resonance (NMR) analysis confirmed that the product was 5-chlorobenzimidazole. The proton NMR spectrum of 5-chlorobenzimidazole is shown below. Figure 7 As shown, the carbon NMR spectrum is as follows Figure 8 As shown;

[0074] The NMR data are shown below:

[0075] 1 H NMR (400MHz, DMSO) δ12.60 (s, 1H), 8.26 (s, 1H), 7.68 (s, 1H), 7.60 (d, J = 8.5Hz, 1H), 7.21 (dd, J = 8.5, J = 1.8Hz, 1H). 13 C NMR (100MHz, DMSO) δ143.45(CH), 139.28(C), 136.60(C), 126.18(C), 122.05(CH), 116.38(CH), 115.22(CH).

[0076] Example 5

[0077] This embodiment provides a method for preparing a non-metal-catalyzed benzimidazole derivative, wherein the starting material is 4-fluoro-1,2-phenylenediamine, the hydrosilane is PhSiH3, the catalyst is N,N-diethylacetylacetamide, and the product is 5-fluorobenzimidazole. The reaction route is shown below:

[0078]

[0079] The preparation method of 5-fluorobenzimidazole (5a) includes the following steps:

[0080] (1) 4-fluoro-1,2-phenylenediamine (1 mmol), PhSiH3 (2 mmol), N,N-diethylacetylacetamide (0.1 mol) and tetrahydrofuran (THF) (2 mL) were placed into a 20 mL stainless steel reactor equipped with a magnetic stirrer, and then the sealed mixture was charged with 1 MPa CO2.

[0081] (2) Heat and stir at 90℃ for 10 hours.

[0082] (3) After the reaction is complete, add water (15 mL) and cool to room temperature. Extract the aqueous layer with 3 × 10 mL of DCM. Combine the organic layers and dry with anhydrous MgSO4, then remove the solvent under reduced pressure.

[0083] (4) The product (5a) was purified by column chromatography on silica gel using petroleum ether and ethyl acetate (1:2) as eluent.

[0084] The product obtained from the reaction was a yellow solid, totaling 122.1 mg, with a yield of 89.8%. Nuclear magnetic resonance (NMR) analysis confirmed that the product was 5-fluorobenzimidazole. The proton NMR spectrum of 5-fluorobenzimidazole is shown below. Figure 9 As shown, the carbon NMR spectrum is as follows Figure 10 As shown;

[0085] The NMR data are shown below:

[0086] 1 H NMR (400MHz, DMSO) δ12.80(s,1H),8.36(s,1H),7.63(dd,J=8.5,4.9Hz,1H),7.47(d,J=7.8Hz,1H),7.05(td,J=9.7,1.9Hz,1H). 13 C NMR (100MHz, DMSO) δ159.45(C), 157.12(C), 143.00(CH), 134.59(CH), 115.70(CH), 109.62(CH), 100.92(CH).

[0087] Example 6

[0088] This embodiment provides a method for preparing a non-metal-catalyzed benzimidazole derivative, wherein the starting material is 4-trifluoromethyl-1,2-phenylenediamine, the hydrosilane is PhSiH3, the catalyst is N,N-diethylacetylacetamide, and the product is 5-trifluoromethylbenzimidazole. The reaction route is shown below:

[0089]

[0090] The preparation method of 5-trifluoromethylbenzimidazole (6a) includes the following steps:

[0091] (1) 4-trifluoromethyl-1,2-phenylenediamine (1 mmol), PhSiH3 (2 mmol), N,N-diethylacetylacetamide (0.1 mol) and tetrahydrofuran (THF) (2 mL) were placed into a 20 mL stainless steel reactor equipped with a magnetic stirrer, and then the sealed mixture was charged with 1 MPa CO2.

[0092] (2) Heat and stir at 90℃ for 10 hours.

[0093] (3) After the reaction is complete, add water (15 mL) and cool to room temperature. Extract the aqueous layer with 3 × 10 mL of DCM. Combine the organic layers and dry with anhydrous MgSO4, then remove the solvent under reduced pressure.

[0094] (4) The product (6a) was purified by column chromatography on silica gel using petroleum ether and ethyl acetate (1:2) as eluents.

[0095] The product obtained from the reaction was a yellow solid, totaling 164.1 mg, with a yield of 88.2%. Nuclear magnetic resonance (NMR) analysis confirmed that the product was 5-trifluoromethylbenzimidazole. The proton NMR spectrum of 5-trifluoromethylbenzimidazole is shown below. Figure 11 As shown, the carbon NMR spectrum is as follows Figure 12 As shown;

[0096] The NMR data are shown below:

[0097] 1 H NMR (400MHz, DMSO) δ12.88(s,1H),8.45(s,1H),7.98(s,1H),7.78(d,J=8.4Hz,1H),7.48(dd,J=8.5,1.1Hz,1H). 13 C NMR (100MHz, DMSO) δ144.26(C), 128.67(CF3), 125.98(CF3), 123.26(CF3), 122.27(CH), 121.96(CH), 120.58(CF3), 118.03(CH).

Claims

1. A method for synthesizing benzimidazole or its derivatives using CO2 as a raw material via nonmetallic catalysis, characterized in that, The method includes the following steps: raw materials in N,N Benzimidazole or its derivatives are synthesized by using diethylacetylacetamide as a catalyst and hydrosilane as a reducing agent. The reaction route is shown below: ， Wherein, R1 is hydrogen, aryl, alkyl, halogen-substituted alkyl, halogen, cyano, carboxylic acid, or nitro; R2 is hydrogen; the reaction solvent is tetrahydrofuran; the reaction temperature is 90℃-120℃; the reaction time is 10-12 hours; the reaction is carried out in a closed environment; N,N The amount of diethylacetylacetamide added is 10.0-20.0% of the molar mass of o-phenylenediamine, and the hydrosilane is phenyl hydrosilane.

2. The method for synthesizing benzimidazole or its derivatives using CO2 as a raw material via non-metallic catalysis according to claim 1, characterized in that, R1 is a hydrogen, halogen, alkyl, or halogen-substituted alkyl group.

3. The method for synthesizing benzimidazole or its derivatives using CO2 as a raw material via non-metallic catalysis according to claim 1, characterized in that, The amount of reducing agent hydrosilane added is 200-400% of the molar mass of o-phenylenediamine.

4. The method for synthesizing benzimidazole or its derivatives using CO2 as a raw material via non-metallic catalysis according to claim 1, characterized in that, The CO2 dosage range is 1 MPa to 5 MPa.

5. The method for synthesizing benzimidazole or its derivatives using CO2 as a raw material via non-metallic catalysis according to claim 1, characterized in that, The reaction further includes the following steps: after the reaction is completed, the solution is cooled with water, the organic layers are combined by extraction, the solvent is removed under reduced pressure, and the remaining solution is subjected to rapid column chromatography to obtain benzimidazole or its derivatives.

6. The method for synthesizing benzimidazole or its derivatives using CO2 as a raw material via non-metallic catalysis according to claim 1, characterized in that, Product yield > 79%.

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