Method for synthesizing benzimidazole compound through photocatalytic C-H bond activation
By activating the reaction of arylmethane and aryl o-diamine under visible light using a crystalline carbon nitride catalyst, the problems of harsh synthesis conditions and insufficient catalyst stability of benzimidazole compounds have been solved, enabling efficient and low-cost industrial production.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- GUANGDONG UNIV OF TECH
- Filing Date
- 2026-01-13
- Publication Date
- 2026-04-21
AI Technical Summary
In the existing technology, the synthesis methods of benzimidazole compounds are subject to harsh conditions, high energy consumption, poor selectivity, and high raw material costs, making them unsuitable for large-scale industrial production. Furthermore, the insufficient stability of homogeneous photocatalysts limits their application.
Using crystalline carbon nitride as a catalyst, arylmethane and aryl o-diamine react in acetic acid solution under visible light irradiation, and benzimidazole compounds are directly synthesized through Csp3-H bond activation. Oxygen is used as an oxidant, and acetic acid is used to protect the aryl o-diamine and activate the carbonyl group to accelerate the condensation reaction.
This method enables the simple and efficient synthesis of benzimidazole compounds at room temperature. The catalyst is inexpensive, stable, and reusable, and the product yield is good, making it suitable for large-scale production and meeting the requirements of green chemistry development.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of organic synthesis technology, and specifically to a method for synthesizing benzimidazole compounds by photocatalytic CH bond activation. Background Technology
[0002] Benzimidazole compounds are important organic functional molecules and are key active skeletons for many drugs and pesticides. Chem. Biol. Drug Des. , 2015, 86, 19). Due to its important role, many synthetic methods have been developed over the past few decades. The classic synthetic methods are of the following two types: (1) coupling of o-aryl diamines with carboxylic acids and their derivatives, which usually requires strong acid and high temperature conditions; (2) condensation of o-aryl diamines with aldehydes, but requires an equivalent amount of strong oxidizing agent (such as persulfate, DDQ or lead acetate). The above methods have relatively harsh conditions, high energy consumption, poor selectivity, and high raw material costs, which are not conducive to large-scale industrial production.
[0003] Solar energy, as a renewable and clean energy source, is an important direction for national energy strategy development. Introducing visible light into organic synthesis to achieve chemical bond transformation is more in line with the concept of green and sustainable development. In the process of light energy conversion, photosensitizers, as carriers of light energy conversion, are crucial. In the past decade or so, the field of CH bond activation under visible light irradiation has seen vigorous development using homogeneous photocatalysts such as ruthenium-iridium complexes and organic dyes. However, the synthesis of ruthenium-iridium complexes is complex and expensive, organic dyes are prone to decomposition under prolonged light exposure, and homogeneous photosensitizers are difficult to recycle and reuse due to their inherent properties. These factors limit their large-scale synthetic application. Polymeric carbon nitride semiconductor materials, due to their lack of transition metals, stable photothermal properties, simple preparation, low cost, ease of modification, and tunable band gap, are ideal heterogeneous photocatalyst materials. Meanwhile, arylmethane is a relatively inexpensive bulk industrial raw material. Therefore, using inexpensive and readily available polymeric carbon nitride materials as photocatalysts to activate arylmethane CH bonds to construct high-value-added chemicals under visible light irradiation is a very promising synthetic approach.
[0004] However, currently, Csp is being utilized using arylmethane via photocatalysis. 3 Research on the direct synthesis of benzimidazole via -H bond activation and the reaction with o-aryl diamines is relatively limited. In 2017, Srivastava et al. synthesized a novel heterogeneous photocatalyst by combining carbon quantum dots (CD) with Bi₂MoO₆ nanosheets, which could achieve Csp synthesis of toluene under visible light irradiation. 3 The activation of the -H bond and the reaction with o-phenylenediamine directly produce 2-phenylbenzimidazole, but this reaction also requires heating, and only one example shows a yield of only 20%. ACS Appl. Nano Mater. 2018, 1, 1, 426). The above-mentioned nano-photocatalysts are difficult to prepare and have poor reaction effects, making them unsuitable for industrial production. In 2023, Lida's research group used riboflavin derivatives as photosensitizers to achieve a large number of benzimidazole compounds by coupling arylmethane and aryl o-diamine in a two-step process. The reaction first converts arylmethane to arylformaldehyde under the catalysis of riboflavin, and then condenses, cyclizes, and dehydrogenates with aryl o-diamine to obtain the target product. The authors also attempted a direct one-step synthesis of benzimidazole, but the target product was rarely obtained, presumably due to the degradation of aryl o-diamine under standard conditions. Org. Biomol. Chem. In the same year, Singh and Srivastava et al. used Eosin Y as a photocatalyst and oxygen as an oxidant to directly and in one step achieve the oxidative cyclization of arylmethane and o-phenylenediamine to synthesize benzimidazole compounds. The reaction operation was simple and the substrate applicability was good. However, both of the above reactions were carried out under the catalysis of homogeneous organic photosensitizers, and the catalyst stability was insufficient, which limited their large-scale application. Summary of the Invention
[0005] In order to overcome the shortcomings of the prior art, the present invention aims to provide a method for the photocatalytic activation of CH bonds to synthesize benzimidazole compounds. This method has the advantages of simple process, convenient control, mild reaction conditions, inexpensive, stable and easy-to-prepare and reusable catalyst, good product yield, and suitability for large-scale production.
[0006] To achieve the objectives of the invention described above, the technical solution adopted by the present invention is as follows:
[0007] This invention provides a method for synthesizing benzimidazole compounds by photocatalytic CH bond activation, comprising the following steps: adding arylmethane and aryl o-diamine as reactants to acetic acid, using crystalline carbon nitride as a catalyst and oxygen as an oxidant, and stirring the reaction at room temperature under visible light irradiation to synthesize the benzimidazole compounds.
[0008] This invention discloses a photocatalytic method for the synthesis of benzimidazole compounds via CH bond activation. This method utilizes highly reactive crystalline carbon nitride as a catalyst to catalyze the synthesis of arylmethane via Csp under visible light irradiation at room temperature. 3 The -H bond activation method couples directly with aryl o-diamines to form benzimidazole compounds. This synthetic method has the advantages of simple process, easy operation, convenient control, mild reaction conditions, inexpensive and stable catalyst that is easy to prepare and reuse, good product yield, and suitability for large-scale production.
[0009] In addition, acetic acid is used as the solution system in the reaction of arylmethane and aryl o-diamine. The acetic acid used in this invention is pure acetic acid. Acetic acid plays the following important roles in the smooth progress of the whole reaction: (1) Since aryl o-diamine has a low oxidation potential, it is easily oxidized first under oxidation conditions and cannot smoothly obtain the target product. Acetic acid can protonate o-phenylenediamine to reduce its electron cloud density, thereby protecting aryl o-diamine; (2) After arylmethane is successfully oxidized into the reaction intermediate aryl formaldehyde, acetic acid can form hydrogen bonds with the carbonyl group of aryl formaldehyde, thereby activating the carbonyl group and accelerating the condensation reaction of aryl formaldehyde and aryl o-diamine.
[0010] Furthermore, after the reaction is stirred at room temperature, a saturated NaHCO3 solution is added to quench the reaction, and the organic phase is obtained by extraction with ethyl acetate. Then, anhydrous sodium sulfate is added to the organic phase for drying, and the solvent ethyl acetate is evaporated using a rotary evaporator. The crude product obtained is then subjected to column chromatography to obtain the target product, benzimidazole compounds.
[0011] Furthermore, the chemical structural formula of the arylmethane is shown in Formula I:
[0012] Formula I;
[0013] In Equation I, R 1 It is one of alkyl, alkoxy, aryl, halogen, cyano or their derivative groups.
[0014] Furthermore, the chemical structural formula of the aryl o-diamine is shown in Formula II:
[0015] Formula II;
[0016] In formula II, R 2 It is one of alkyl, alkoxy, aryl, halogen, cyano or their derivative groups.
[0017] Furthermore, the mass-volume ratio of the arylmethane, aryl o-diamine, crystalline carbon nitride, and acetic acid is (35~65) mg: (20~80) mg: (12~18) mg: 1.
[0018] Furthermore, the stirring reaction at room temperature is carried out for 30 to 40 hours.
[0019] Furthermore, the method for preparing the crystalline carbon nitride includes the following steps:
[0020] S1. Melamine powder is placed in a crucible and calcined under a nitrogen atmosphere to obtain carbon nitride precursor;
[0021] S2. The carbon nitride precursor is ground and mixed with inorganic salt and then calcined under a nitrogen atmosphere to obtain a crystalline carbon nitride precursor.
[0022] S3. Wash with water to remove excess inorganic salts from the crystalline carbon nitride precursor, and then dry to obtain the crystalline carbon nitride.
[0023] Furthermore, in step S1, the calcination temperature is 540℃~560℃, and the calcination time is 3.5h~4.5h.
[0024] Furthermore, in step S2, the mass ratio of the carbon nitride precursor to the inorganic salt is 1:(8~12); and / or
[0025] The inorganic salt is a mixture of potassium chloride and lithium chloride; and / or, the mass ratio of potassium chloride to lithium chloride is (10~12):(8~10); and / or
[0026] The calcination temperature is 540℃~560℃, and the calcination time is 3.5h~4.5h.
[0027] Furthermore, in step S3, the drying process involves placing the item in an oven at 55℃~65℃ for 20h~30h.
[0028] Compared with the prior art, the beneficial effects of the present invention are as follows:
[0029] (1) A photocatalytic method for the synthesis of benzimidazole compounds by CH bond activation according to the present invention utilizes highly reactive crystalline carbon nitride as a catalyst to achieve Csp of arylmethane through single-electron transfer in conjunction with oxygen under visible light irradiation. 3 Activation of the -H bond, thereby catalyzing arylmethanes at room temperature via Csp... 3 The -H bond activation method couples directly with aryl o-diamines to form benzimidazole compounds. This synthetic method is simple, easy to control, and operates under mild conditions at room temperature. The catalyst is inexpensive, stable, easy to prepare, and reusable. The yield of the target product is good, and the reaction is driven by visible light, which meets the requirements of green chemistry development.
[0030] (2) In the present invention, a method for photocatalytic CH bond activation to synthesize benzimidazole compounds is provided. In the reaction of arylmethane and aryl o-diamine, acetic acid is used as the solution system. On the one hand, acetic acid can protonate o-phenylenediamine to reduce its electron cloud density, thereby protecting aryl o-diamine. On the other hand, after arylmethane is successfully oxidized to the reaction intermediate arylformaldehyde, acetic acid can form hydrogen bonds with the carbonyl group of arylformaldehyde to activate the carbonyl group, thereby accelerating the condensation reaction of arylformaldehyde and aryl o-diamine, resulting in a good product yield.
[0031] (3) The method of photocatalytic CH bond activation for the synthesis of benzimidazole compounds of the present invention is universally applicable to a variety of arylmethanes and o-aryldiamines. The reaction synthesis method is simple, the raw materials are easy to obtain, the cost is low, the operation is simple, and it is suitable for large-scale industrial production. Detailed Implementation
[0032] To make the technical problem to be solved, the technical solution, and the beneficial effects of the present invention clearer, the present invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the present invention and are not intended to limit the present invention.
[0033] The terminology used in the embodiments of this invention is for the purpose of describing particular embodiments only and is not intended to limit the invention. In this invention, the singular forms “a,” “described,” and “the” as used in the embodiments and appended claims are also intended to include the plural forms unless the context clearly indicates otherwise.
[0034] In this embodiment of the invention, a method for photocatalytic CH bond activation to synthesize benzimidazole compounds includes the following steps: adding arylmethane and aryl o-diamine as reactants to acetic acid, using crystalline carbon nitride as a catalyst and oxygen as an oxidant, and stirring the reaction at room temperature under visible light irradiation to synthesize the benzimidazole compounds.
[0035] In some embodiments, after the room temperature stirring reaction, a saturated NaHCO3 solution is added to quench the reaction, and the organic phase is obtained by extraction with ethyl acetate. Then, anhydrous sodium sulfate is added to the organic phase for drying, and the solvent ethyl acetate is evaporated using a rotary evaporator. The crude product obtained is then subjected to column chromatography to obtain the target product, benzimidazole compounds.
[0036] In some embodiments, the chemical structural formula of the arylmethane is shown in Formula I:
[0037] Formula I;
[0038] In Equation I, R 1 It is one of alkyl, alkoxy, aryl, halogen, cyano or their derivative groups.
[0039] In some embodiments, the chemical structural formula of the aryl o-diamine is shown in Formula II:
[0040] Formula II;
[0041] In formula II, R 2 It is one of alkyl, alkoxy, aryl, halogen, cyano or their derivative groups.
[0042] In some embodiments, the mass-volume ratio of arylmethane, aryl o-diamine, crystalline carbon nitride, and acetic acid is (35~65) mg:(20~80) mg:(12~18) mg:1.
[0043] In some embodiments, the room temperature stirring reaction time is 30h to 40h.
[0044] In some embodiments, the method for preparing the crystalline carbon nitride includes the following steps:
[0045] S1. Melamine powder is placed in a crucible and calcined under a nitrogen atmosphere to obtain carbon nitride precursor;
[0046] S2. The carbon nitride precursor is ground and mixed with inorganic salt and then calcined under a nitrogen atmosphere to obtain a crystalline carbon nitride precursor.
[0047] S3. Wash with water to remove excess inorganic salts from the crystalline carbon nitride precursor, and then dry to obtain the crystalline carbon nitride.
[0048] In some embodiments, in step S1, the calcination temperature is 540℃~560℃, and the calcination time is 3.5h~4.5h.
[0049] In some embodiments, in step S2, the mass ratio of the carbon nitride precursor to the inorganic salt is 1:(8~12); and / or
[0050] The inorganic salt is a mixture of potassium chloride and lithium chloride; and / or, the mass ratio of potassium chloride to lithium chloride is (10~12):(8~10); and / or
[0051] The calcination temperature is 540℃~560℃, and the calcination time is 3.5h~4.5h.
[0052] In some embodiments, in step S3, the drying process involves placing the item in an oven at 55°C to 65°C for 20 to 30 hours.
[0053] The following description is based on specific embodiments. Example 1
[0054] A method for photocatalytic CH bond activation to synthesize benzimidazole compounds, comprising the following steps:
[0055] The preparation of crystalline carbon nitride includes the following steps:
[0056] S1. Place 5g of melamine powder in a crucible and calcine it at 550℃ for 4h under a nitrogen atmosphere to obtain carbon nitride precursor.
[0057] S2. The carbon nitride precursor and inorganic salt are ground and mixed in a mortar, and then calcined at 550°C for 4 hours under a nitrogen atmosphere to obtain a crystalline carbon nitride precursor. In this embodiment, the mass ratio of carbon nitride precursor to inorganic salt is 1:10, and the inorganic salt is a mixture of potassium chloride and lithium chloride with a mass ratio of 11:9.
[0058] S3. Wash with water to remove excess inorganic salts from the crystalline carbon nitride precursor, and then dry in an oven at 60°C for 24 hours to obtain crystalline carbon nitride.
[0059] In this embodiment, the synthesis method of benzimidazole compounds is shown in the reaction equation as shown in Formula III:
[0060] Formula III;
[0061] In this embodiment, the synthesis method of benzimidazole compounds includes the following steps: 15 mg of crystalline carbon nitride (K-PHI), 36.8 mg of compound 1a, 21.6 mg of compound 2a, and 1 mL of acetic acid (HOAc) are added to a reaction flask. The mixture is irradiated with 420 nm light under an oxygen atmosphere and magnetically stirred at room temperature for 36 h. Then, 4 mL of saturated NaHCO3 solution is added to quench the reaction, and the mixture is extracted three times with ethyl acetate (5 mL each time) to obtain an organic phase. Anhydrous sodium sulfate is added to the organic phase for drying, and the solvent ethyl acetate is evaporated using a rotary evaporator. The crude product is then subjected to column chromatography to obtain the target product 3aa, with a yield of 70%. The product 3aa is characterized by 1H NMR spectroscopy as follows:
[0062] 1 H NMR (400 MHz, DMSO- d 6) δ 12.81 (s, 1H), 8.31-8.15 (m, 2H), 7.63 (s,1H), 7.71-7.57 (m, 3H), 7.50 (d, 1H), 7.49-7.20 (m, 2H). 13 CNMR (101 MHz, DMSO- d 6) δ 152.77, 143.83, 135.56, 131.09, 130.45, 128.78, 127.33, 122.69,121.92, 118.83, 112.12.
[0063] HRMS (ESI): calcd. for C 13 H 11 N2 + [M+H] +: 195.0917; found: 195.0920.
[0064] As can be seen from the 1H NMR spectrum, this embodiment successfully synthesized the benzimidazole compound 3aa. Example 2
[0065] A method for photocatalytic CH bond activation to synthesize benzimidazole compounds, comprising the following steps:
[0066] The preparation of crystalline carbon nitride includes the following steps:
[0067] S1. Place 5g of melamine powder in a crucible and calcine it at 550℃ for 4h under a nitrogen atmosphere to obtain carbon nitride precursor.
[0068] S2. The carbon nitride precursor and inorganic salt are ground and mixed in a mortar, and then calcined at 550°C for 4 hours under a nitrogen atmosphere to obtain a crystalline carbon nitride precursor. In this embodiment, the mass ratio of carbon nitride precursor to inorganic salt is 1:9, and the inorganic salt is a mixture of potassium chloride and lithium chloride with a mass ratio of 11:9.
[0069] S3. Wash with water to remove excess inorganic salts from the crystalline carbon nitride precursor, and then dry in an oven at 60°C for 25 hours to obtain crystalline carbon nitride.
[0070] In this embodiment, the synthesis method of benzimidazole compounds is shown in the reaction equation as shown in Formula IV:
[0071] Formula IV;
[0072] In this embodiment, the synthesis method of benzimidazole compounds includes the following steps: 15 mg of crystalline carbon nitride (K-PHI), 48.8 mg of compound 1b, 78.8 mg of compound 2a, and 1 mL of acetic acid (HOAc) are added to a reaction flask. The reaction is carried out under an oxygen atmosphere with 420 nm light and magnetic stirring at room temperature for 36 h. Then, 4 mL of saturated NaHCO3 solution is added to quench the reaction, and the mixture is extracted three times with ethyl acetate (5 mL each time) to obtain an organic phase. Anhydrous sodium sulfate is then added to the organic phase for drying, and the solvent ethyl acetate is evaporated using a rotary evaporator. The crude product is then subjected to column chromatography to obtain the target product 3ba, with a yield of 75%. The product is characterized by 1H NMR spectroscopy as follows:
[0073] 1 H NMR (400 MHz, DMSO- d 6) δ ppm: 12.71 (s, 1H), 8.12 (d, J =8.4 Hz, 2H), 7.61 (s, 1H), 7.52 (s, 1H), 7.17-7.11 (m, 4H), 3.84 (s, 3H); 13 C NMR (101MHz, DMSO- d 6) δ ppm: 160.1, 152.2, 144.4, 134.2, 129.4, 123.6, 122.3, 119.5,116.9, 116.8, 112.7, 56.4.
[0074] HRMS (ESI): calcd. for C 14 H 13 N2O + [M+H] + : 225. 0947; found: 225.0950.
[0075] As can be seen from the 1H NMR spectrum, the benzimidazole compound 3ba was successfully synthesized in this embodiment. Example 3
[0076] A method for photocatalytic CH bond activation to synthesize benzimidazole compounds, comprising the following steps:
[0077] The preparation of crystalline carbon nitride includes the following steps:
[0078] S1. Place 5g of melamine powder in a crucible and calcine it at 540℃ for 4.5h under a nitrogen atmosphere to obtain carbon nitride precursor;
[0079] S2. The carbon nitride precursor and inorganic salt are ground and mixed in a mortar, and then calcined at 540°C for 4.5 hours under a nitrogen atmosphere to obtain a crystalline carbon nitride precursor. In this embodiment, the mass ratio of carbon nitride precursor to inorganic salt is 1:8, and the inorganic salt is a mixture of potassium chloride and lithium chloride with a mass ratio of 10:8.
[0080] S3. Wash with water to remove excess inorganic salts from the crystalline carbon nitride precursor, and then dry in an oven at 55°C for 30 hours to obtain crystalline carbon nitride.
[0081] In this embodiment, the synthesis method of benzimidazole compounds is shown in equation V:
[0082] Formula V;
[0083] In this embodiment, the synthesis method of benzimidazole compounds includes the following steps: 15 mg of crystalline carbon nitride (K-PHI), 42.4 mg of compound 1c, 21.6 mg of compound 2a, and 1 mL of acetic acid (HOAc) are added to a reaction flask. The reaction is carried out under an oxygen atmosphere with 420 nm light and magnetic stirring at room temperature for 36 h. Then, 4 mL of saturated NaHCO3 solution is added to quench the reaction, and the mixture is extracted three times with ethyl acetate (5 mL each time) to obtain an organic phase. Anhydrous sodium sulfate is then added to the organic phase for drying, and the solvent ethyl acetate is evaporated using a rotary evaporator. The crude product is then subjected to column chromatography to obtain the target product 3ca, with a yield of 72%. The product is characterized by 1H NMR spectroscopy as follows:
[0084] 1 H NMR (400 MHz, DMSO- d 6) δ 12.81 (s, 1H), 8.05 (d, J = 8.1 Hz, 2H), 7.62 (d, J = 6.7 Hz, 1H), 7.52 (d, J = 6.3 Hz, 1H), 7.36 (d, J = 8.0 Hz, 2H), 7.16 (d, J = 3.3 Hz, 2H), 2.38 (s, 3H); 13 C NMR (101 MHz, DMSO- d 6) δ 151.7,144.2, 140.1, 130.2, 128.1, 127.2, 123.0, 122.1, 119.2, 111.8, 21.5.
[0085] HRMS (ESI): calcd. for C 14 H 13 N2 + [M+H] + : 209.1073; found: 209.1078.
[0086] As can be seen from the 1H NMR spectrum, the benzimidazole compound 3ca was successfully synthesized in this embodiment. Example 4
[0087] A method for photocatalytic CH bond activation to synthesize benzimidazole compounds, comprising the following steps:
[0088] The preparation of crystalline carbon nitride includes the following steps:
[0089] S1. Place 5g of melamine powder in a crucible and calcine it at 560℃ for 3.5h under a nitrogen atmosphere to obtain carbon nitride precursor;
[0090] S2. The carbon nitride precursor and inorganic salt are ground and mixed in a mortar, and then calcined at 560°C for 3.5 hours under a nitrogen atmosphere to obtain a crystalline carbon nitride precursor. In this embodiment, the mass ratio of carbon nitride precursor to inorganic salt is 1:12, and the inorganic salt is a mixture of potassium chloride and lithium chloride with a mass ratio of 12:10.
[0091] S3. Wash with water to remove excess inorganic salts from the crystalline carbon nitride precursor, and then dry in an oven at 65°C for 20 hours to obtain crystalline carbon nitride.
[0092] In this embodiment, the synthesis method of benzimidazole compounds is shown in the reaction equation as shown in Formula VI:
[0093] Formula VI;
[0094] In this embodiment, the synthesis method of benzimidazole compounds includes the following steps: 15 mg of crystalline carbon nitride (K-PHI), 42.4 mg of compound 1d, 21.6 mg of compound 2a, and 1 mL of acetic acid (HOAc) are added to a reaction flask. The mixture is irradiated with 420 nm light under an oxygen atmosphere and magnetically stirred at room temperature for 36 h. Then, 4 mL of saturated NaHCO3 solution is added to quench the reaction, and the mixture is extracted three times with ethyl acetate (5 mL each time) to obtain an organic phase. Anhydrous sodium sulfate is then added to the organic phase for drying, and the solvent ethyl acetate is evaporated using a rotary evaporator. The crude product is then subjected to column chromatography to obtain the target product 3da, with a yield of 74%. The product is characterized by 1H NMR spectroscopy as follows:
[0095] 1 H NMR (400 MHz, DMSO- d 6) δ ppm: 12.82 (s, 1H), δ 8.10 (d, J = 7.6 Hz, 2H), 7.65 (s, 2H), 7.34 (d, J = 7.6 Hz, 2H), 7.22 (d, J = 8.0 Hz (2H), 2.33 s (3H); 13 C NMR (101 MHz, DMSO- d 6) δ ppm: 152.1, 142.3, 140.3, 136.4, 130.8, 127.7, 127.1, 123.4, 22.3.
[0096] HRMS (ESI): calcd. for C 14 H 13 N2 + [M+H] + : 209.1073; found: 209.1080.
[0097] As can be seen from the 1H NMR spectrum, the benzimidazole compound 3da was successfully synthesized in this embodiment. Example 5
[0098] A method for photocatalytic CH bond activation to synthesize benzimidazole compounds, comprising the following steps:
[0099] The preparation of crystalline carbon nitride includes the following steps:
[0100] S1. Place 5g of melamine powder in a crucible and calcine it at 545℃ for 4.2h under a nitrogen atmosphere to obtain carbon nitride precursor;
[0101] S2. The carbon nitride precursor and inorganic salt are ground and mixed in a mortar, and then calcined at 545°C for 4.2 hours under a nitrogen atmosphere to obtain a crystalline carbon nitride precursor. In this embodiment, the mass ratio of carbon nitride precursor to inorganic salt is 1:9, and the inorganic salt is a mixture of potassium chloride and lithium chloride with a mass ratio of 10.5:8.5.
[0102] S3. Wash with water to remove excess inorganic salts from the crystalline carbon nitride precursor, and then dry in an oven at 57°C for 28 hours to obtain crystalline carbon nitride.
[0103] In this embodiment, the synthesis method of benzimidazole compounds is shown in the reaction equation as shown in Formula VII:
[0104] Formula VII;
[0105] In this embodiment, the synthesis method of benzimidazole compounds includes the following steps: 15 mg of crystalline carbon nitride (K-PHI), 42.4 mg of compound 1e, 21.6 mg of compound 2a, and 1 mL of acetic acid (HOAc) are added to a reaction flask. The reaction is carried out under an oxygen atmosphere with 420 nm light and magnetic stirring at room temperature for 36 h. Then, 4 mL of saturated NaHCO3 solution is added to quench the reaction, and the mixture is extracted three times with ethyl acetate (5 mL each time) to obtain an organic phase. Anhydrous sodium sulfate is then added to the organic phase for drying, and the solvent ethyl acetate is evaporated using a rotary evaporator. The crude product is then subjected to column chromatography to obtain the target product 3ea, with a yield of 71%. The product is characterized by 1H NMR spectroscopy as follows:
[0106] 1 H NMR (400 MHz, DMSO- d 6) δ ppm: 12.86 (s, 1H), 8.15 (d, J = 8.2 Hz, 2H), 7.67- 7.59 (m, 4H), 7.21 (s, 2H); 13 C NMR (101 MHz, DMSO- d 6) δ ppm: 151.2, 145.4, 135.4, 128.7, 128.1, 127.5, 122.1, 121.4, 118.3, 116.2, 116.4.
[0107] HRMS (ESI): calcd. for C 14 H 13 N2 + [M+H] + : 209.1073; found: 209.1077.
[0108] As can be seen from the 1H NMR spectrum, the benzimidazole compound 3ea was successfully synthesized in this embodiment. Example 6
[0109] A method for photocatalytic CH bond activation to synthesize benzimidazole compounds, comprising the following steps:
[0110] The preparation of crystalline carbon nitride includes the following steps:
[0111] S1. Place 5g of melamine powder in a crucible and calcine it at 555℃ for 3.8h under a nitrogen atmosphere to obtain carbon nitride precursor;
[0112] S2. The carbon nitride precursor and inorganic salt are ground and mixed in a mortar, and then calcined at 555°C for 3.8 hours under a nitrogen atmosphere to obtain a crystalline carbon nitride precursor. In this embodiment, the mass ratio of carbon nitride precursor to inorganic salt is 1:11, and the inorganic salt is a mixture of potassium chloride and lithium chloride with a mass ratio of 11.5:9.5.
[0113] S3. Wash with water to remove excess inorganic salts from the crystalline carbon nitride precursor, and then dry in an oven at 63°C for 22 hours to obtain crystalline carbon nitride.
[0114] In this embodiment, the synthesis method of benzimidazole compounds is shown in the reaction equation as shown in Formula VIII:
[0115] Formula VIII;
[0116] In this embodiment, the synthesis method of benzimidazole compounds includes the following steps: 15 mg of crystalline carbon nitride (K-PHI), 64 mg of compound 1f, 21.6 mg of compound 2a, and 1 mL of acetic acid (HOAc) are added to a reaction flask. The mixture is irradiated with 420 nm light under an oxygen atmosphere and magnetically stirred at room temperature for 36 h. Then, 4 mL of saturated NaHCO3 solution is added to quench the reaction, and the mixture is extracted three times with ethyl acetate (5 mL each time) to obtain an organic phase. Anhydrous sodium sulfate is then added to the organic phase for drying, and the solvent ethyl acetate is evaporated using a rotary evaporator. The crude product is then subjected to column chromatography to obtain the target product 3fa, with a yield of 70%. The product is characterized by 1H NMR spectroscopy as follows:
[0117] 1 H NMR (400 MHz, DMSO- d 6) δ 13.14 (s, 1H), 8.37 (d, J = 8.1 Hz, 2H), 7.91 (d, J = 8.3 Hz, 2H), 7.62 (s, 2H), 7.26-7.24 (m, 2H); 13 C NMR (101 MHz, DMSO- d 6) δ 149.3, 133.7, 129.4, 129.6(d, J C-F = 31.89 Hz), 129.2, 127.0,126.3, 125.84 (d, J C-F = 3.55 Hz), 124.02(d, J C-F = 272.1 Hz), 122.1.
[0118] HRMS (ESI): calcd. for C 14 H 10 F3N2 + [M+H] + : 263.0791; found: 263.0796.
[0119] As can be seen from the 1H NMR spectrum, the benzimidazole compound 3fa was successfully synthesized in this embodiment. Example 7
[0120] A method for photocatalytic CH bond activation to synthesize benzimidazole compounds, comprising the following steps:
[0121] The preparation of crystalline carbon nitride includes the following steps:
[0122] S1. Place 5g of melamine powder in a crucible and calcine it at 550℃ for 4h under a nitrogen atmosphere to obtain carbon nitride precursor.
[0123] S2. The carbon nitride precursor and inorganic salt are ground and mixed in a mortar, and then calcined at 550°C for 4 hours under a nitrogen atmosphere to obtain a crystalline carbon nitride precursor. In this embodiment, the mass ratio of carbon nitride precursor to inorganic salt is 1:9, and the inorganic salt is a mixture of potassium chloride and lithium chloride with a mass ratio of 11:9.
[0124] S3. Wash with water to remove excess inorganic salts from the crystalline carbon nitride precursor, and then dry in an oven at 60°C for 24 hours to obtain crystalline carbon nitride.
[0125] In this embodiment, the synthesis method of benzimidazole compounds is shown in the reaction equation as shown in Formula IX:
[0126] Formula IX;
[0127] In this embodiment, the synthesis method of benzimidazole compounds includes the following steps: 15 mg of crystalline carbon nitride (K-PHI), 44 mg of compound 1 g, 21.6 mg of compound 2a, and 1 mL of acetic acid (HOAc) are added to a reaction flask. The mixture is irradiated with 420 nm light under an oxygen atmosphere and magnetically stirred at room temperature for 36 h. The reaction is then quenched with 4 mL of saturated NaHCO3 solution, and extracted three times with ethyl acetate (5 mL each time) to obtain the organic phase. Anhydrous sodium sulfate is added to the organic phase for drying, and the solvent ethyl acetate is evaporated using a rotary evaporator. The crude product is then subjected to column chromatography to obtain the target product 3ga, with a yield of 75%. The product is characterized by 1H NMR spectroscopy as follows:
[0128] 1 H NMR (400 MHz, DMSO- d 6) δ ppm: 12.84 (br s,1H), 8.12 (m, 2H), 7.74(d, J = 7.6 Hz, 2H), 7.63 (s, 1H), 7.54 (s, 1H), 7.21 (s, 2H); 13 C NMR (101MHz, DMSO- d 6) δ ppm: 151.4, 144.1, 135.4, 129.3, 129.2, 128.2, 123.1, 123.4,122.3, 118.5, 112.2.
[0129] HRMS (ESI): calcd. for C 13 H 10 FN2 + [M+H] + : 213.0823; found: 213.0826.
[0130] As can be seen from the 1H NMR spectrum, the benzimidazole compound 3ga was successfully synthesized in this embodiment. Example 8
[0131] A method for photocatalytic CH bond activation to synthesize benzimidazole compounds, comprising the following steps:
[0132] The preparation of crystalline carbon nitride includes the following steps:
[0133] S1. Place 5g of melamine powder in a crucible and calcine it at 548℃ for 4.1h under a nitrogen atmosphere to obtain carbon nitride precursor;
[0134] S2. The carbon nitride precursor and inorganic salt are ground and mixed in a mortar, and then calcined at 548°C for 4.1 h under a nitrogen atmosphere to obtain a crystalline carbon nitride precursor. In this embodiment, the mass ratio of carbon nitride precursor to inorganic salt is 1:9, and the inorganic salt is a mixture of potassium chloride and lithium chloride with a mass ratio of 10:9.
[0135] S3. Wash with water to remove excess inorganic salts from the crystalline carbon nitride precursor, and then dry in an oven at 56°C for 27 hours to obtain crystalline carbon nitride.
[0136] In this embodiment, the synthesis method of benzimidazole compounds is shown in the reaction equation as shown in Formula X:
[0137] Formula X;
[0138] In this embodiment, the synthesis method of benzimidazole compounds includes the following steps: 15 mg of crystalline carbon nitride (K-PHI), 50.6 mg of compound 1h, 21.6 mg of compound 2a, and 1 mL of acetic acid (HOAc) are added to a reaction flask. The mixture is irradiated with 420 nm light under an oxygen atmosphere and magnetically stirred at room temperature for 36 h. Then, 4 mL of saturated NaHCO3 solution is added to quench the reaction, and the mixture is extracted three times with ethyl acetate (5 mL each time) to obtain an organic phase. Anhydrous sodium sulfate is then added to the organic phase for drying, and the solvent ethyl acetate is evaporated using a rotary evaporator. The crude product is then subjected to column chromatography to obtain the target product 3ha, with a yield of 76%. The product is characterized by 1H NMR spectroscopy as follows:
[0139] 1H NMR (400 MHz, DMSO- d 6) δ ppm: 12.94 (br s, 1H), 7.80 (d, J = 3.6Hz, 1H), 7.74 (d, J = 5.4 Hz, 1H), 7.65 (s, 1H), 7.54 (s, 1H), 7.25- 7.23 (m,3H); 13 C NMR (101 MHz, DMSO- d 6) δ ppm: 148.5, 144.3, 134.7, 134.5, 128.5, 128.2, 127.4, 122.8, 122.20, 117.4, 112.2.
[0140] HRMS (ESI): calcd. for C 13 H 10 ClN2 + [M+H] + :229.0527, found 229.0532.
[0141] As can be seen from the 1H NMR spectrum, the benzimidazole compound 3ha was successfully synthesized in this embodiment. Example 9
[0142] A method for photocatalytic CH bond activation to synthesize benzimidazole compounds, comprising the following steps:
[0143] The preparation of crystalline carbon nitride includes the following steps:
[0144] S1. Place 5g of melamine powder in a crucible and calcine it at 552℃ for 3.9h under a nitrogen atmosphere to obtain carbon nitride precursor;
[0145] S2. The carbon nitride precursor and inorganic salt are ground and mixed in a mortar, and then calcined at 552°C for 3.9 h under a nitrogen atmosphere to obtain a crystalline carbon nitride precursor. In this embodiment, the mass ratio of carbon nitride precursor to inorganic salt is 1:11, and the inorganic salt is a mixture of potassium chloride and lithium chloride with a mass ratio of 11:8.
[0146] S3. Wash with water to remove excess inorganic salts from the crystalline carbon nitride precursor, and then dry in an oven at 59°C for 26 hours to obtain crystalline carbon nitride.
[0147] In this embodiment, the synthesis method of benzimidazole compounds is shown in the reaction equation as shown in Formula XI:
[0148] Formula XI;
[0149] In this embodiment, the synthesis method of benzimidazole compounds includes the following steps: 15 mg of crystalline carbon nitride (K-PHI), 50.6 mg of compound 1i, 21.6 mg of compound 2a, and 1 mL of acetic acid (HOAc) are added to a reaction flask. The reaction is carried out under an oxygen atmosphere with 420 nm light and magnetic stirring at room temperature for 36 h. Then, 4 mL of saturated NaHCO3 solution is added to quench the reaction, and the mixture is extracted three times with ethyl acetate (5 mL each time) to obtain an organic phase. Anhydrous sodium sulfate is then added to the organic phase for drying, and the solvent ethyl acetate is evaporated using a rotary evaporator. The crude product is then subjected to column chromatography to obtain the target product 3ia, with a yield of 78%. The product is characterized by 1H NMR spectroscopy as follows:
[0150] 1 H NMR (400MHz, DMSO- d 6) δ 13.02 (s, 1H), 8.21 (s, 1H), 8.13-8.15 (m,1H), 7.66 (d, J=7.6 Hz, 1H), 7.62-7.55 (m, 3H), 7.26-7.19 (m, 2H); 13 C NMR (101 MHz, DMSO-) d 6) δ 150.3, 134.1, 132.6, 131.3, 130.0, 126.5, 125.4, 123.0.
[0151] HRMS (ESI): calcd. for C 13 H 10 ClN2 + [M+H] + : 229.0527, found 229.0530.
[0152] As can be seen from the 1H NMR spectrum, the benzimidazole compound 3ia was successfully synthesized in this embodiment. Example 10
[0153] A method for photocatalytic CH bond activation to synthesize benzimidazole compounds, comprising the following steps:
[0154] The preparation of crystalline carbon nitride includes the following steps:
[0155] S1. Place 5g of melamine powder in a crucible and calcine it at 558℃ for 3.7h under a nitrogen atmosphere to obtain carbon nitride precursor;
[0156] S2. The carbon nitride precursor and inorganic salt are ground and mixed in a mortar, and then calcined at 558°C for 3.7 h under a nitrogen atmosphere to obtain a crystalline carbon nitride precursor. In this embodiment, the mass ratio of carbon nitride precursor to inorganic salt is 1:10, and the inorganic salt is a mixture of potassium chloride and lithium chloride with a mass ratio of 12:9.
[0157] S3. Wash with water to remove excess inorganic salts from the crystalline carbon nitride precursor, and then dry in an oven at 62°C for 23 hours to obtain crystalline carbon nitride.
[0158] In this embodiment, the synthesis method of benzimidazole compounds is shown in the reaction equation as shown in Formula XII:
[0159] Formula XII;
[0160] In this embodiment, the synthesis method of benzimidazole compounds includes the following steps: 15 mg of crystalline carbon nitride (K-PHI), 36.8 mg of compound 1a, 28.5 mg of compound 2b, and 1 mL of acetic acid (HOAc) are added to a reaction flask. The reaction is carried out under an oxygen atmosphere with 420 nm light and magnetic stirring at room temperature for 36 h. Then, 4 mL of saturated NaHCO3 solution is added to quench the reaction, and the mixture is extracted three times with ethyl acetate (5 mL each time) to obtain an organic phase. Anhydrous sodium sulfate is then added to the organic phase for drying, and the solvent ethyl acetate is evaporated using a rotary evaporator. The crude product is then subjected to column chromatography to obtain the target product 3ab, with a yield of 72%. The product is characterized by 1H NMR spectroscopy as follows:
[0161] 1 H NMR (400 MHz, DMSO- d 6) δ 13.07 (s, 1H), 8.18-8.17 (m, 2H), 7.64-7.51 (m, 5H), 7.23-7.22 (m, 1H); 13 C NMR (101 MHz, DMSO- d 6) δ 153.2, 130.8, 130.2, 129.6, 127.2, 122.9.
[0162] HRMS (ESI): calcd. for C 13 H 10 ClN2 + [M+H] + : 229.0527, found 229.0533.
[0163] As can be seen from the 1H NMR spectrum, the benzimidazole compound 3ab was successfully synthesized in this embodiment. Example 11
[0164] A method for photocatalytic CH bond activation to synthesize benzimidazole compounds, comprising the following steps:
[0165] The preparation of crystalline carbon nitride includes the following steps:
[0166] S1. Place 5g of melamine powder in a crucible and calcine it at 550℃ for 4h under a nitrogen atmosphere to obtain carbon nitride precursor.
[0167] S2. The carbon nitride precursor and inorganic salt are ground and mixed in a mortar, and then calcined at 550°C for 4 hours under a nitrogen atmosphere to obtain a crystalline carbon nitride precursor. In this embodiment, the mass ratio of carbon nitride precursor to inorganic salt is 1:8, and the inorganic salt is a mixture of potassium chloride and lithium chloride with a mass ratio of 11:8.
[0168] S3. Wash with water to remove excess inorganic salts from the crystalline carbon nitride precursor, and then dry in an oven at 60°C for 25 hours to obtain crystalline carbon nitride.
[0169] In this embodiment, the synthesis method of benzimidazole compounds is shown in equation i:
[0170] Formula i;
[0171] In this embodiment, the synthesis method of benzimidazole compounds includes the following steps: 15 mg of crystalline carbon nitride (K-PHI), 36.8 mg of compound 1a, 35.4 mg of compound 2c, and 1 mL of acetic acid (HOAc) are added to a reaction flask. The reaction is carried out under an oxygen atmosphere with 420 nm light and magnetic stirring at room temperature for 36 h. Then, 4 mL of saturated NaHCO3 solution is added to quench the reaction, and the mixture is extracted three times with ethyl acetate (5 mL each time) to obtain an organic phase. Anhydrous sodium sulfate is then added to the organic phase for drying, and the solvent ethyl acetate is evaporated using a rotary evaporator. The crude product is then subjected to column chromatography to obtain the target product 3ac, with a yield of 71%. The product is characterized by 1H NMR spectroscopy as follows:
[0172] 1 H NMR (400MHz, DMSO- d 6) δ13.26 (s, 1H), 8.25-8.22 (m, 2H), 7.91 (s,2H), 7.64-7.58 (m, 3H); 13 C NMR (101 MHz, DMSO-d 6) δ 154.3, 131.1, 129.9,129.4, 127.1, 125.1.
[0173] HRMS (ESI): calcd. for C 13 H9Cl2N2 + [M+H] + : 263.0137; found: 263.0142.
[0174] As can be seen from the 1H NMR spectrum, the benzimidazole compound 3ac was successfully synthesized in this embodiment. Example 12
[0175] A method for photocatalytic CH bond activation to synthesize benzimidazole compounds, comprising the following steps:
[0176] The preparation of crystalline carbon nitride includes the following steps:
[0177] S1. Place 5g of melamine powder in a crucible and calcine it at 5530℃ for 3.8h under a nitrogen atmosphere to obtain carbon nitride precursor;
[0178] S2. The carbon nitride precursor and inorganic salt are ground and mixed in a mortar, and then calcined at 550°C for 4 hours under a nitrogen atmosphere to obtain a crystalline carbon nitride precursor. In this embodiment, the mass ratio of carbon nitride precursor to inorganic salt is 1:12, and the inorganic salt is a mixture of potassium chloride and lithium chloride with a mass ratio of 11:10.
[0179] S3. Wash with water to remove excess inorganic salts from the crystalline carbon nitride precursor, and then dry in an oven at 61°C for 23 hours to obtain crystalline carbon nitride.
[0180] In this embodiment, the synthesis method of benzimidazole compounds is shown in equation ii:
[0181] Formula II;
[0182] In this embodiment, the synthesis method of benzimidazole compounds includes the following steps: 15 mg of crystalline carbon nitride (K-PHI), 42.4 mg of compound 1c, 35.4 mg of compound 2c, and 1 mL of acetic acid (HOAc) are added to a reaction flask. The reaction is carried out under an oxygen atmosphere with 420 nm light and magnetic stirring at room temperature for 36 h. Then, 4 mL of saturated NaHCO3 solution is added to quench the reaction, and the mixture is extracted three times with ethyl acetate (5 mL each time) to obtain the organic phase. Anhydrous sodium sulfate is then added to the organic phase for drying, and the solvent ethyl acetate is evaporated using a rotary evaporator. The crude product is subjected to column chromatography to obtain 3 cc of the target product, with a yield of 74%. The product is characterized by 1H NMR spectroscopy as follows:
[0183] 1 H NMR (400MHz, DMSO- d 6) δ 13.13 (s, 1H), 8.04 (d, J = 8.2 Hz, 2H), 7.81 (s, 2H), 7.37 (d, J=8.0 Hz, 2H), 2.39 (s, 3H); 13 C NMR (101 MHz, DMSO- d 6)δ 154.4, 140.8, 130.2, 127.3, 127.2, 124.8, 124.8, 21.4.
[0184] HRMS (ESI): calcd. for C 14 H 11 Cl2N2 + [M+H] + : 277.0294; found: 277.0299.
[0185] As can be seen from the 1H NMR spectrum, the benzimidazole compound 3cc was successfully synthesized in this embodiment.
[0186] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this application should be included within the protection scope of this application.
Claims
1. A method for synthesizing benzimidazole compounds by photocatalytic CH bond activation, characterized in that, The process includes the following steps: adding arylmethane and aryl o-diamine as reactants into acetic acid, using crystalline carbon nitride as a catalyst and oxygen as an oxidant, and stirring the reaction at room temperature under visible light irradiation to synthesize the benzimidazole compounds.
2. The method for synthesizing benzimidazole compounds by photocatalytic CH bond activation as described in claim 1, characterized in that, After stirring the reaction at room temperature, a saturated NaHCO3 solution was added to quench the reaction, and the organic phase was obtained by extraction with ethyl acetate. Then, anhydrous sodium sulfate was added to the organic phase for drying, and the solvent ethyl acetate was evaporated using a rotary evaporator. The crude product was then subjected to column chromatography to obtain the target product, benzimidazole compounds.
3. The method for synthesizing benzimidazole compounds by photocatalytic CH bond activation as described in claim 1, characterized in that, The chemical structural formula of the arylmethane is shown in Formula I: Formula I; In Equation I, R 1 It is one of alkyl, alkoxy, aryl, halogen, cyano or their derivative groups.
4. The method for synthesizing benzimidazole compounds by photocatalytic CH bond activation as described in claim 1, characterized in that, The chemical structural formula of the aryl o-diamine is shown in Formula II: Formula II; In formula II, R 2 It is one of alkyl, alkoxy, aryl, halogen, cyano or their derivative groups.
5. The method for synthesizing benzimidazole compounds by photocatalytic CH bond activation as described in claim 1, characterized in that, The mass-volume ratio of the arylmethane, aryl o-diamine, crystalline carbon nitride, and acetic acid is (35~65) mg: (20~80) mg: (12~18) mg:
1.
6. The method for synthesizing benzimidazole compounds by photocatalytic CH bond activation as described in claim 1, characterized in that, The stirring reaction at room temperature is carried out for 30 to 40 hours.
7. The method for synthesizing benzimidazole compounds by photocatalytic CH bond activation as described in claim 1, characterized in that, The method for preparing the crystalline carbon nitride includes the following steps: S1. Melamine powder is placed in a crucible and calcined under a nitrogen atmosphere to obtain carbon nitride precursor; S2. The carbon nitride precursor is ground and mixed with inorganic salt and then calcined under a nitrogen atmosphere to obtain a crystalline carbon nitride precursor. S3. Wash with water to remove excess inorganic salts from the crystalline carbon nitride precursor, and then dry to obtain the crystalline carbon nitride.
8. The method for synthesizing benzimidazole compounds by photocatalytic CH bond activation as described in claim 7, characterized in that, In step S1, the calcination temperature is 540℃~560℃, and the calcination time is 3.5h~4.5h.
9. The method for photocatalytic CH bond activation synthesis of benzimidazole compounds as described in claim 7, characterized in that, In step S2, the mass ratio of the carbon nitride precursor to the inorganic salt is 1:(8~12); and / or The inorganic salt is a mixture of potassium chloride and lithium chloride; and / or, the mass ratio of potassium chloride to lithium chloride is (10~12):(8~10); and / or The calcination temperature is 540℃~560℃, and the calcination time is 3.5h~4.5h.
10. The method for photocatalytic CH bond activation synthesis of benzimidazole compounds as described in claim 7, characterized in that, In step S3, the drying process involves placing the item in an oven at 55℃~65℃ for 20h~30h.