Method for catalyzing meta-alkylation of 2-arylimidazole by ruthenium

Abstract

The invention discloses a method for catalyzing meta-alkylation of 2-aroyl imidazole by ruthenium, which comprises the following steps: by taking 2-aroyl imidazole and alkyl bromide as raw materials, catalyzing meta-alkylation reaction of the 2-aroyl imidazole by using a ruthenium catalyst to prepare alkylated 2-aroyl imidazole. According to the method, an efficient ruthenium catalysis system is developed, selective activation and alkylation of a meta-position C-H bond of a benzene ring are realized by utilizing accurate guidance of a ruthenium catalyst, and direct alkylation of a meta-position C-H bond of a 2-aroyl imidazole aromatic ring is successfully realized. The method has the prominent advantages of simplicity and convenience in operation, mild conditions, high regioselectivity, good functional group compatibility, good atom economy and the like, is successfully expanded to modification of various drug derivative compounds and glycoside molecules, provides a novel and efficient synthesis approach for construction of imidazole functional molecules, and is suitable for industrial production. Wide application prospects are shown in the fields of medicinal chemistry and material science.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, and particularly relates to a ruthenium-catalyzed method for meta-alkylation of 2-aromatic imidazole. Background Technology

[0002] Imidazole compounds are an important class of nitrogen-containing heterocyclic structures, widely found in drug molecules, natural products, and functional materials. Their molecules are rich in multiple coordination sites, enabling them to form stable coordination bonds with metal ions, thus playing a crucial role in drug design and providing strong support for the development of drug molecules with multiple mechanisms of action. For example, representative drugs such as ondansetron (a 5-HT3 receptor antagonist used to prevent and treat nausea and vomiting caused by chemotherapy, radiotherapy, or surgery), mizoribine (an immunosuppressant), flumazenil (a benzodiazepine receptor antagonist), and fenteconazole (an antifungal drug) all have an imidazole ring as their core pharmacophore, fully demonstrating the wide application of this type of structure in drug design and its significant value in the pharmaceutical market. Therefore, developing novel synthetic methods for imidazoles and their derivatives is of great significance to fields such as medicinal chemistry, biochemistry, and materials chemistry.

[0003] Significant progress has been made in transition metal-catalyzed C-H functionalization reactions in recent decades. Against this backdrop, the development of novel strategies for direct C-H functionalization has attracted widespread attention. However, due to the chemical inertness of the C-H bond itself and the high kinetic energy barrier required for its breakage, research on alkylation reactions in the field of transition metal catalysis remains relatively limited. Traditional alkylation methods, such as Friedel-Crafts alkylation, while achieving some success, are constrained by harsh reaction conditions, poor regioselectivity, and a narrow substrate applicability range, significantly limiting their practical application. Therefore, developing cost-effective, efficient, and mild direct C-H alkylation methods has become an important direction in current organic synthesis research.

[0004] In recent years, researchers have developed various strategies to achieve efficient alkylation modification of heteroaromatic hydrocarbons, including the use of directing groups, electronic effects, and weak hydrogen-bonded ligands, which have effectively promoted the construction of alkylation products. Transition metal catalysis provides a powerful tool for the alkylation modification of C-H bonds in heteroaromatic hydrocarbons. In 2017, the Ackermann research group at the University of Göttingen, Germany, reported the ruthenium-catalyzed meta-C-H alkylation reaction of ketimine compounds, and further converted the obtained meta-alkylated products into ketones, acids, amines, and phenolic derivatives. This strategy shows broad application prospects in materials science, medicinal chemistry, and pharmaceutical engineering.

[0005] 2-Acylimidazoles, as key backbones of drug and functional material molecules, have attracted much attention for their direct functionalization. In recent years, significant progress has been made in the functionalization of 2-acylimidazoles; however, reports on their functionalization under ruthenium catalysis are still relatively limited, especially regarding the meta-alkylation modification of 2-aromatic imidazoles, which has yet to be reported. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide a simple and mild method for the meta-alkylation of 2-aramidyl imidazole catalyzed by ruthenium. This method has good compatibility with a variety of functional groups, excellent regioselectivity and atom economy, and can realize the efficient synthesis of alkylated 2-aramidyl imidazole.

[0007] To solve the above-mentioned technical problems, the present invention adopts the following technical solution:

[0008] A ruthenium-catalyzed meta-alkylation method for 2-aromatic imidazole involves using 2-aromatic imidazole and bromoalkane as raw materials, and employing a ruthenium catalyst to catalyze the meta-alkylation reaction of 2-aromatic imidazole to obtain alkylated 2-aromatic imidazole.

[0009] The above method involves adding compound 1, compound 2, ruthenium catalyst, base, and solvent to a reactor, stirring the mixture under argon atmosphere at a certain temperature for a certain time, and then cooling it to room temperature for concentration. The crude mixture is then purified by silica gel column chromatography to obtain alkylated 2-aramidylimidazole. Compound 1 is 2-aramidylimidazole, and compound 2 is a bromoalkane.

[0010] The reaction conforms to the following reaction formula:

[0011] .

[0012] The ruthenium catalyst is one or more of the following: dichloro(pentamethylcyclopentadienyl)ruthenium polymer, triphenylphosphine ruthenium chloride, tri(acetylacetonate)ruthenium, dichlorodicarbonylbis(triphenylphosphine)ruthenium, ruthenium trichloride hydrate, and dichlorobis(4-methylisopropylphenyl)ruthenium; the base is sodium carbonate, potassium dihydrogen phosphate, potassium benzoate, lithium acetate, potassium pivalate, potassium phosphate, sodium bicarbonate, sodium trifluoroacetate, potassium acetate, disodium hydrogen phosphate, and carbonate. The solvent is one or more of the following: lithium, sodium p-toluenesulfonate, cesium carbonate, cesium acetate, potassium trifluoroacetate, sodium phosphate, sodium benzenesulfonate, sodium dihydrogen phosphate, sodium acetate, and lithium trifluoroacetate; the solvent is one or more of the following: hexafluoroisopropanol, tetrahydrofuran, toluene, ethanol, dimethyl sulfoxide, 1,2-dichloroethane, trifluorotoluene, tert-butanol, chlorobenzene, 1,4-dioxane, acetonitrile, isopropanol, fluorobenzene, methanol, and dichloromethane.

[0013] The ruthenium catalyst is dichlorobis(4-methylisopropylphenyl)ruthenium; the base is potassium acetate; and the solvent is fluorobenzene.

[0014] The molar ratio of compound 1 to compound 2 is 1:1 to 6.

[0015] The reaction temperature is 0–150 °C, and the reaction time is 0–48 h.

[0016] The molar ratio of compound 1 to compound 2 was 1:1.5, the reaction temperature was 120 °C, and the reaction time was 12 h.

[0017] The reactor is a Schlenk tube.

[0018] To address the challenge of controlling regioselectivity in the direct alkylation of 2-aryl imidazolium, particularly the lack of reported techniques for meta-alkylation, the inventors have developed a ruthenium-catalyzed method for the meta-alkylation of 2-aryl imidazolium. Using 2-aryl imidazolium and bromoalkane as raw materials, a ruthenium catalyst is employed to catalyze the meta-alkylation of 2-aryl imidazolium, yielding alkylated 2-aryl imidazolium. This method develops a highly efficient ruthenium catalytic system, utilizing the precise direction of the ruthenium catalyst to achieve selective activation and alkylation of the meta-C–H bond in the benzene ring, successfully realizing the direct alkylation of the meta-CH bond in the aromatic ring of 2-aryl imidazolium. This invention employs a ruthenium catalyst to precisely control the regioselectivity of the reaction, overcoming the limitations of traditional alkylation methods such as harsh conditions and poor regioselectivity, achieving the efficient synthesis of meta-alkylated products. This technology boasts outstanding advantages such as ease of operation, mild conditions, high regioselectivity, good functional group compatibility, and good atom economy. It has been successfully extended to the modification of various drug-derived compounds and glycoside molecules, providing a novel and efficient synthetic route for the construction of imidazole functional molecules, and showing broad application prospects in the fields of medicinal chemistry and materials science. Attached Figure Description

[0019] Figure 1 The image shows the hydrogen spectrum of the product obtained in Example 1.

[0020] Figure 2 The image shows the carbon spectrum of the product obtained in Example 1.

[0021] Figure 3 The image shows the hydrogen spectrum of the product obtained in Example 2.

[0022] Figure 4 The image shows the carbon spectrum of the product obtained in Example 2.

[0023] Figure 5 The image shows the hydrogen spectrum of the product obtained in Example 3.

[0024] Figure 6 The image shows the carbon spectrum of the product obtained in Example 3.

[0025] Figure 7 The image shows the hydrogen spectrum of the product obtained in Example 4.

[0026] Figure 8 The image shows the carbon spectrum of the product obtained in Example 4.

[0027] Figure 9 The image shows the hydrogen spectrum of the product obtained in Example 5.

[0028] Figure 10 The image shows the carbon spectrum of the product obtained in Example 5.

[0029] Figure 11 The image shows the hydrogen spectrum of the product obtained in Example 6.

[0030] Figure 12 The image shows the carbon spectrum of the product obtained in Example 6.

[0031] Figure 13 The image shows the hydrogen spectrum of the product obtained in Example 7.

[0032] Figure 14 The image shows the carbon spectrum of the product obtained in Example 7.

[0033] Figure 15 The image shows the hydrogen spectrum of the product obtained in Example 8.

[0034] Figure 16 The carbon spectrum of the product obtained in Example 8 is shown below. Detailed Implementation

[0035] Example 1

[0036] (1-Methyl-1H-imidazol-2-yl)benzophenone (0.2 mmol, 1 equiv.), KOAc (0.4 mmol, 2 equiv.), [Ru(p-cymene)Cl2]2 (0.01 mmol, 5 mol%), methyl 2-bromoisobutyrate (0.3 mmol, 1.5 equiv.), and fluorobenzene (1.5 mL) were sequentially added to a dry 15 mL Schlenk tube. The reaction mixture was stirred at 120 °C for 12 hours under argon atmosphere. The reaction was cooled and concentrated, and the crude product was purified by column chromatography (PE:EA = 15:1) to obtain the desired meta-alkylated 2-aramidyl imidazolium.

[0037] The proton and carbon spectra of the obtained products are as follows: Figure 1 and Figure 2 As shown, the structural characterization data are as follows:

[0038] 1H NMR (600 MHz, CDCl3) δ 8.20 – 8.17 (m, 2H), 7.53 (d, J = 9.5 Hz,1H), 7.42 (t, J = 8.0 Hz, 1H), 7.20 (s, 1H), 7.09 (s, 1H), 4.06 (s, 3H), 3.64(s, 3H), 1.61(s, 6H).

[0039] 13 C NMR (151 MHz, CDCl3) δ 184.3, 177.0, 144.8, 143.2, 137.5, 130.4,129.8, 129.4, 128.1, 127.8, 126.9, 52.3, 46.7, 36.5, 26.6.

[0040] HRMS (ESI) m / z: [M+H] + Calcd for C 16 H 19 N2O3 287.1390; Found 287.1386.

[0041] Based on the above data, the structure of the product is inferred as follows:

[0042]

[0043] Example 2

[0044] (1-Methyl-1H-imidazol-2-yl)benzophenone (0.2 mmol, 1 equiv.), KOAc (0.4 mmol, 2 equiv.), [Ru(p-cymene)Cl2]2 (0.01 mmol, 5 mol%), ethyl 2-bromoisobutyrate (0.3 mmol, 1.5 equiv.), and fluorobenzene (1.5 mL) were sequentially added to a dry 15 mL Schlenk tube. The reaction mixture was stirred at 120 °C for 12 hours under argon atmosphere. The reaction was cooled and concentrated, and the crude product was purified by column chromatography (PE:EA = 15:1) to give the desired meta-alkylated 2-aramidyl imidazolium.

[0045] The proton and carbon spectra of the obtained products are as follows: Figure 3 and Figure 4 As shown, the structural characterization data are as follows:

[0046] 1H NMR (600 MHz, CDCl3) δ 8.20 (d, J = 1.9 Hz, 2H), 7.54 (d, J = 7.8Hz, 1H), 7.43 (t, J = 8.0 Hz, 1H), 7.21 (s, 1H), 7.10 (s, 1H), 4.12 (q, J =7.1 Hz, 2H), 4.07 (s, 3H), 1.61 (s, 6H), 1.18 (t, J = 7.1 Hz, 3H).

[0047] 13 C NMR (151 MHz, CDCl3) δ 184.4, 176.6, 145.0, 143.3, 137.4, 130.5,129.8, 129.4, 128.1, 127.8, 126.9, 61.1, 46.7, 36.5, 26.6, 14.2.

[0048] HRMS (ESI) m / z: [M+H] + Calcd for C 17 H 21 N2O3 301.1546; Found 301.1542.

[0049] Based on the above data, the structure of the product is inferred as follows:

[0050]

[0051] Example 3

[0052] (1-Methyl-1H-imidazol-2-yl)benzophenone (0.2 mmol, 1 equiv.), KOAc (0.4 mmol, 2 equiv.), [Ru(p-cymene)Cl2]2 (0.01 mmol, 5 mol%), isopropyl 2-bromoisobutyrate (0.3 mmol, 1.5 equiv.), and fluorobenzene (1.5 mL) were sequentially added to a dry 15 mL Schlenk tube. The reaction mixture was stirred at 120 °C for 12 hours under argon atmosphere. The reaction was cooled and concentrated, and the crude product was purified by column chromatography (PE:EA = 15:1) to obtain the desired meta-alkylated 2-aramidyl imidazolium.

[0053] The proton and carbon spectra of the obtained products are as follows: Figure 5 and Figure 6 As shown, the structural characterization data are as follows:

[0054] 1 H NMR (600 MHz, CDCl3) δ 8.20 (d, J = 6.3 Hz, 2H), 7.52 (d, J = 9.1Hz, 1H), 7.41 (t, J = 8.6 Hz, 1H), 7.19 (s, 1H), 7.09 (s, 1H), 5.02 – 4.95(m, 1H), 4.05 (s, 3H), 1.58 (s, 6H), 1.14 (dt, J = 6.3, 1.3 Hz, 6H).

[0055] 13 C NMR (151 MHz, CDCl3) δ 184.3, 176.0, 145.1, 143.3, 137.4, 130.5,129.7, 129.4, 128.0, 127.7, 126.9, 68.2, 46.7, 36.5, 26.6, 21.6.

[0056] HRMS (ESI) m / z: [M+H] + Calcd for C 18 H 23 N2O3 315.1703; Found 315.1700.

[0057] Based on the above data, the structure of the product is inferred as follows:

[0058]

[0059] Example 4

[0060] (1-Methyl-1H-imidazol-2-yl)benzophenone (0.2 mmol, 1 equiv.), KOAc (0.4 mmol, 2 equiv.), [Ru(p-cymene)Cl2]2 (0.01 mmol, 5 mol%), phenyl 2-bromoisobutyrate (0.3 mmol, 1.5 equiv.), and fluorobenzene (1.5 mL) were sequentially added to a dry 15 mL Schlenk tube. The reaction mixture was stirred at 120 °C for 12 hours under argon atmosphere. The reaction was cooled and concentrated, and the crude product was purified by column chromatography (PE:EA = 15:1) to obtain the desired meta-alkylated 2-aramidyl imidazolium.

[0061] The proton and carbon spectra of the obtained products are as follows: Figure 7 and Figure 8 As shown, the structural characterization data are as follows:

[0062] 1 H NMR (600 MHz, CDCl3) δ 8.37 (s, 1H), 8.26 (d, J = 7.7 Hz, 1H), 7.67(d, J = 7.8 Hz, 1H), 7.50 (t, J = 7.8 Hz, 1H), 7.33 (t, J = 7.9 Hz, 2H), 7.22(s, 1H), 7.18 (t, J = 7.4 Hz, 1H), 7.10 (s, 1H), 7.02 (d, J = 7.9 Hz, 2H), 4.06 (s, 3H), 1.77 (s, 6H).

[0063] 13 C NMR (151 MHz, CDCl3) δ 184.1, 175.1, 151.0, 144.3, 143.2, 137.7,130.2, 129.9, 129.43, 129.36, 128.4, 128.0, 127.0, 125.8, 121.5, 47.0, 36.5,26.5.

[0064] HRMS (ESI) m / z: [M+H] + Calcd for C 21 H 21 N2O3 349.1546; Found 349.1544.

[0065] Based on the above data, the structure of the product is inferred as follows:

[0066]

[0067] Example 5

[0068] (1-Methyl-1H-imidazol-2-yl)benzophenone (0.2 mmol, 1 equiv.), KOAc (0.4 mmol, 2 equiv.), [Ru(p-cymene)Cl2]2 (0.01 mmol, 5 mol%), benzyl 2-bromoisobutyrate (0.3 mmol, 1.5 equiv.), and fluorobenzene (1.5 mL) were sequentially added to a dry 15 mL Schlenk tube. The reaction mixture was stirred at 120 °C for 12 hours under argon atmosphere. The reaction was cooled and concentrated, and the crude product was purified by column chromatography (PE:EA = 15:1) to give the desired meta-alkylated 2-aramidyl imidazolium.

[0069] The proton and carbon spectra of the obtained products are as follows: Figure 9 and Figure 10 As shown, the structural characterization data are as follows:

[0070] 1 H NMR (600 MHz, CDCl3) δ 8.26 (s, 1H), 8.23 ​​(d, J = 7.7 Hz, 1H), 7.53 (d, J = 8.6 Hz, 1H), 7.42 (t, J = 7.8 Hz, 1H), 7.31 – 7.25 (m, 3H), 7.24 (s,1H), 7.22 (d, J = 5.4 Hz, 2H), 7.10 (s, 1H), 5.12 (s, 2H), 4.06 (s, 3H), 1.66(s, 6H).

[0071] 13 C NMR (151 MHz, CDCl3) δ 184.1, 176.2, 144.6, 143.2, 137.4, 136.1,130.5, 129.8, 129.4, 128.5, 128.1, 128.0, 127.9, 127.8, 126.9, 66.6, 46.7,36.5, 26.5.

[0072] HRMS (ESI) m / z: [M+H] + Calcd for C 22 H 23 N2O3 363.1703; Found 363.1699.

[0073] Based on the above data, the structure of the product is inferred as follows:

[0074]

[0075] In Example 6, (1-methyl-1H-imidazol-2-yl)benzophenone (0.2 mmol, 1 equiv.), KOAc (0.4 mmol, 2 equiv.), [Ru(p-cymene)Cl2]2 (0.01 mmol, 5 mol%), methyl 2-bromopropionate (0.3 mmol, 1.5 equiv.), and fluorobenzene (1.5 mL) were sequentially added to a dry 15 mL Schlenk tube. The reaction mixture was stirred at 120 °C for 12 hours under argon atmosphere. The reaction was cooled and concentrated, and the crude product was purified by column chromatography (PE:EA = 15:1) to obtain the desired meta-alkylated 2-aramidyl imidazolium.

[0076] The proton and carbon spectra of the obtained products are as follows: Figure 11 and Figure 12 As shown, the structural characterization data are as follows:

[0077] 1 H NMR (600 MHz, CDCl3) δ 8.18 (d, J = 7.8 Hz, 1H), 8.12 (s, 1H), 7.50 (d, J = 7.7 Hz, 1H), 7.42 (t, J = 7.7 Hz, 1H), 7.19 (s, 1H), 7.09 (s, 1H), 4.04 (s, 3H), 3.80 (q, J = 7.2 Hz, 1H), 3.63 (s, 3H), 1.52 (d, J = 7.2 Hz, 3H).

[0078] 13 C NMR (151 MHz, CDCl3) δ 184.1, 174.7, 143.2, 140.5, 137.7, 131.8,130.0, 129.9, 129.4, 128.4, 126.9, 52.1, 45.4, 36.4, 18.5.

[0079] HRMS (ESI) m / z: [M+H] + Calcd for C 15 H 17 N2O3 273.1233; Found 273.1231.

[0080] Based on the above data, the structure of the product is inferred as follows:

[0081]

[0082] In Example 7, (1-methyl-1H-imidazol-2-yl)benzophenone (0.2 mmol, 1 equiv.), KOAc (0.4 mmol, 2 equiv.), [Ru(p-cymene)Cl2]2 (0.01 mmol, 5 mol%), methyl difluorobromoacetate (0.3 mmol, 1.5 equiv.), and fluorobenzene (1.5 mL) were sequentially added to a dry 15 mL Schlenk tube. The reaction mixture was stirred at 120 °C for 12 hours under argon atmosphere. The reaction was cooled and concentrated, and the crude product was purified by column chromatography (PE:EA = 15:1) to obtain the desired meta-alkylated 2-aramidyl imidazolium.

[0083] The proton and carbon spectra of the obtained products are as follows: Figure 13 and Figure 14 As shown, the structural characterization data are as follows:

[0084] 1 H NMR (600 MHz, CDCl3) δ 8.50 (s, 1H), 8.45 (d, J = 7.8 Hz, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.58 (t, J = 7.8 Hz, 1H), 7.24 (s, 1H), 7.14 (s, 1H), 4.30 (q, J = 7.1 Hz, 2H), 4.09 (s, 3H), 1.31 (t, J = 7.1 Hz, 3H).

[0085] 13 C NMR (151 MHz, CDCl3) δ 183.0, 164.0, 142.9, 137.9, 133.6, 133.1,131.0, 129.7, 129.6, 129.5, 129.5, 128.6, 128.03, 127.99, 127.95, 127.4,113.2, 63.4, 36.6, 14.0.

[0086] 19 F NMR (565 MHz, CDCl3) δ -103.77 (s).

[0087] HRMS (ESI) m / z: [M+H] + Calcd for C 15 H 15 F2N2O3 309.1045; Found 309.1040.

[0088] Based on the above data, the structure of the product is inferred as follows:

[0089]

[0090] In Example 8, (1-methyl-1H-imidazol-2-yl)benzophenone (0.2 mmol, 1 equiv.), KOAc (0.4 mmol, 2 equiv.), [Ru(p-cymene)Cl2]2 (0.01 mmol, 5 mol%), brominated glycoside (0.3 mmol, 1.5 equiv.), and fluorobenzene (1.5 mL) were sequentially added to a dry 15 mL Schlenk tube. The reaction mixture was stirred at 120 °C for 12 hours under argon atmosphere. The reaction was cooled and concentrated, and the crude product was purified by column chromatography (PE:EA = 15:1) to obtain the desired meta-alkylated 2-aramidyl imidazolium.

[0091] The proton and carbon spectra of the obtained products are as follows: Figure 15 and Figure 16 As shown, the structural characterization data are as follows:

[0092] 1 H NMR (600 MHz, CDCl3) δ 8.22 (d, J = 7.7 Hz, 1H), 8.18 (s, 1H), 7.48 (d, J = 8.2 Hz, 1H), 7.41 (t, J = 7.7 Hz, 1H), 7.20 (s, 1H), 7.10 (s, 1H),5.84 (s, 1H), 5.39 (d, J = 3.3 Hz, 1H), 5.19 (t, J = 9.5 Hz, 1H), 5.09 (dd, J= 9.7, 3.4 Hz, 1H), 4.22 (dd, J = 12.2, 5.4 Hz, 1H), 4.10 (d, J = 7.2 Hz,1H), 4.06 (s, 3H), 3.77 – 3.73 (m, 1H), 2.04 (s, 3H), 2.02 (s, 3H), 1.97 (s,3H), 1.95 (s, 3H), 1.62 (s, 3H), 1.60 (s, 3H).

[0093] 13C NMR (151 MHz, CDCl3) δ 184.0, 174.1, 170.7, 170.0, 169.9, 169.7,143.6, 143.2, 137.5, 130.6, 130.1, 129.4, 128.3, 127.8, 126.9, 90.9, 73.2,70.4, 67.8, 65.9, 62.3, 46.8, 36.5, 26.3, 26.2, 20.83, 20.78, 20.63, 20.58.

[0094] HRMS (ESI) m / z: [M+H] + Calcd for C 29 H 35 N2O 12 603.2184; Found 603.2180.

[0095] Based on the above data, the structure of the product is inferred as follows:

[0096]

Claims

1. A method for ruthenium-catalyzed meta-alkylation of 2-aramidyl imidazole, characterized in that: Alkyl 2-aryl imidazole was prepared by meta-alkylation of 2-aryl imidazole using ruthenium catalyst catalyzing the reaction of 2-aryl imidazole as raw materials.

2. The method according to claim 1, characterized in that: Compound 1, Compound 2, ruthenium catalyst, base and solvent were added to the reactor and stirred under argon atmosphere. After the reaction was completed, the mixture was cooled to room temperature and concentrated. The crude mixture was then purified by silica gel column chromatography to obtain alkylated 2-aramidazole. Compound 1 was 2-aramidazole and Compound 2 was a bromoalkane.

3. The method according to claim 2, characterized in that... The reaction conforms to the following reaction formula: 。 4. The method according to claim 2, characterized in that: The ruthenium catalyst is one or more of the following: dichloro(pentamethylcyclopentadienyl)ruthenium polymer, triphenylphosphine ruthenium chloride, tri(acetylacetonate)ruthenium, dichlorodicarbonylbis(triphenylphosphine)ruthenium, ruthenium trichloride hydrate, and dichlorobis(4-methylisopropylphenyl)ruthenium; the base is sodium carbonate, potassium dihydrogen phosphate, potassium benzoate, lithium acetate, potassium pivalate, potassium phosphate, sodium bicarbonate, sodium trifluoroacetate, potassium acetate, disodium hydrogen phosphate, and carbon. The solvent is one or more of the following: lithium trifluoroacetate, sodium p-toluenesulfonate, cesium carbonate, cesium acetate, potassium trifluoroacetate, sodium phosphate, sodium benzenesulfonate, sodium dihydrogen phosphate, sodium acetate, and lithium trifluoroacetate; the solvent is one or more of the following: hexafluoroisopropanol, tetrahydrofuran, toluene, ethanol, dimethyl sulfoxide, 1,2-dichloroethane, trifluorotoluene, tert-butanol, chlorobenzene, 1,4-dioxane, acetonitrile, isopropanol, fluorobenzene, methanol, and dichloromethane.

5. The method according to claim 4, characterized in that: The ruthenium catalyst is dichlorobis(4-methylisopropylphenyl)ruthenium; the base is potassium acetate; and the solvent is fluorobenzene.

6. The method according to claim 2, characterized in that: The molar ratio of compound 1 to compound 2 is 1:1 to 6.

7. The method according to claim 6, characterized in that: The reaction temperature is 0–150 °C, and the reaction time is 0–48 h.

8. The method according to claim 7, characterized in that: The molar ratio of compound 1 to compound 2 is 1:1.5, the reaction temperature is 120 °C, and the reaction time is 12 h.

9. The method according to claim 2, characterized in that: The reactor is a Schlenk tube.

Images