阅读说明：本技术 一种铜催化制备n-苯基-4-苯磺酰基咪唑类化合物的方法 (Method for preparing N-phenyl-4-benzenesulfonyl imidazole compound by copper catalysis ) 是由 徐润生 韩伊潇 叶悦宇 吴鸿杰 于 2020-05-29 设计创作，主要内容包括：本发明公开了一种铜催化制备式(Ⅳ)所示的N-苯基-4-苯磺酰基咪唑类化合物的方法,其特征在于制备方法为：式(Ⅰ)所示的乙烯基苯基硫醚类化合物、式(Ⅱ)所示的尿素和式(Ⅲ)所示的卤代苯类化合物,以乙醇为介质,以氯化铜为催化剂,在过氧化氢的促进下充分反应,制得目标产物,所述产物通过后处理制得N-苯基-4-苯磺酰基咪唑类化合物。本发明方法产率良好；催化剂高效,符合绿色环保要求；催化体系适应性广,适用于大规模工业化中间体生产。<Image he="97" wi="700" file="DDA0002516927630000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(The invention discloses a method for preparing an N-phenyl-4-benzenesulfonyl imidazole compound shown in a formula (IV) by copper catalysis, which is characterized by comprising the following steps: the method comprises the following steps of (1) sufficiently reacting vinyl phenyl sulfide compounds shown in a formula (I), urea shown in a formula (II) and halogenated benzene compounds shown in a formula (III) under the promotion of hydrogen peroxide by using ethanol as a medium and copper chloride as a catalyst to obtain a target product, and carrying out post-treatment on the product to obtain the N-phenyl-4-benzenesulfonyl imidazole compounds. The method has good yield; the catalyst is efficient and meets the requirements of green environmental protection; the catalytic system has wide adaptability and is suitable for large-scale industrial intermediate production.)

1. A method for preparing an N-phenyl-4-benzenesulfonyl imidazole compound shown in a formula (IV) by copper catalysis is characterized by comprising the following steps: the method comprises the following steps of (1) sufficiently reacting a vinyl phenyl sulfide compound shown in a formula (I), urea shown in a formula (II) and a halogenated benzene compound shown in a formula (III) under the promotion of hydrogen peroxide by taking an organic solvent as a medium and transition metal salt as a catalyst to prepare a target product, and carrying out post-treatment on the product to prepare an N-phenyl-4-benzenesulfonyl imidazole compound; the transition metal salt catalyst is copper chloride, and the organic solvent is ethanol;

in the reaction formula, R is selected from one of the following: methyl, methoxy; r¹Selected from one of the following: hydrogen, methyl, phenyl; x is selected from one of the following: bromine and chlorine.

2. The method for preparing N-phenyl-4-benzenesulfonyl imidazole compounds under catalysis of copper according to claim 1, wherein the ratio of the vinyl phenyl sulfide compounds, urea and halogenated benzene compounds is 5 mmol: 6 mmol: 5 mmol.

3. The method for preparing N-phenyl-4-benzenesulfonyl imidazole compounds under catalysis of copper according to claim 1, wherein the ratio of vinyl phenyl sulfide compounds, urea and solvent ethanol is 5 mmol: 6 mmol: 15 mL.

4. The method for preparing N-phenyl-4-benzenesulfonyl imidazole compounds under catalysis of copper according to claim 1, wherein the ratio of vinyl phenyl sulfide compounds, urea and copper chloride is 5 mmol: 5 mmol: 0.5 mmol.

5. The method for preparing N-phenyl-4-benzenesulfonyl imidazole compounds under catalysis of copper according to claim 1, wherein the equivalent ratio of the vinyl phenyl sulfide compounds, urea and halogenated benzene compounds is 1 (1-1.2): 1.

6. the method for preparing the N-phenyl-4-benzenesulfonyl imidazole compounds under the catalysis of copper according to claim 1, wherein the reaction temperature is 100 ℃ and the reaction time is 10 hours.

7. The method for preparing the N-phenyl-4-benzenesulfonyl imidazole compounds under the catalysis of copper according to claim 1, wherein the post-treatment comprises the following steps:

1) and (3) extraction: after the reactant is cooled to room temperature at normal temperature, 20mL of saturated sodium chloride aqueous solution is added into the reactant, then ethyl acetate is used for extraction for 3 times, 20mL of the saturated sodium chloride aqueous solution is used for each time, and the extraction liquid is combined;

2) concentration: drying the extract with anhydrous sodium sulfate, and rotary drying with rotary evaporator to obtain concentrate;

3) adsorbing the obtained concentrate by using column chromatography silica gel, adding the concentrate into a 200-mesh 300-mesh chromatography silica gel column, and adding normal hexane: and (3) carrying out fast column chromatography on ethyl acetate according to a certain proportion, combining eluent, carrying out spin-drying on a rotary evaporator, and pumping by an oil pump to obtain the product N-phenyl-4-benzenesulfonyl imidazole compound.

8. The copper-catalyzed method for preparing N-phenyl-4-benzenesulfonyl imidazoles according to claim 7, wherein the drying time in step 2) is 5 hours.

9. The method for preparing N-phenyl-4-benzenesulfonyl imidazole compounds under catalysis of copper according to claim 7, which is characterized in that the volume ratio of N-hexane to ethyl acetate in the step 3) is 1:1-2: 1.

Technical Field

The invention belongs to the technical field of pharmaceutical and chemical intermediate preparation, and particularly relates to a method for preparing an N-phenyl-4-benzenesulfonyl imidazole compound by copper catalysis.

Background

The N-phenyl-4-benzenesulfonyl imidazole compounds are very important chemical intermediates. The N-phenyl-4-benzenesulfonyl imidazole compound has good mechanical property, can be used as an epoxy resin curing agent, can improve the tensile resistance, the insulating property and the chemical agent resistance of a high polymer product, and accounts for less than half of the consumption of imidazoles in Japan, and the consumption of the N-phenyl-4-benzenesulfonyl imidazole compound is 0.5-10% of that of epoxy resin. The N-phenyl-4-benzenesulfonyl imidazoles can also be used as copper rust inhibitors for printed circuit boards and integrated circuits. The N-phenyl-4-benzenesulfonylimidazole compounds can also be used as medicinal raw materials for preparing antifungal agents, hypoglycemia therapeutic agents, trichomonad therapeutic agents, anti-rash agents and the like. In addition, the N-phenyl-4-benzenesulfonyl imidazole compound can be used as a raw material for synthesizing pesticides, is used for synthesizing synergists and preparing insecticides and bactericides, and is an intermediate of the antifungal medicaments of diclofenazole, econazole, ketoconazole and clotrimazole.

The reported preparation method of the N-phenyl-4-benzenesulfonyl imidazole compound is mainly obtained through metal catalysis and multi-step C-N coupling and condensation, and has the defects of more reaction steps, low reaction efficiency, complex post-treatment and the like. The method adopts cheap copper chloride as a catalyst, and realizes the high-efficiency preparation of the N-phenyl-4-benzenesulfonyl imidazole compound by a multi-component one-pot method. Has the advantages of low cost, simple operation, low requirement on equipment, excellent yield and the like. Has important application prospect in the industrial field of the synthesis of drug intermediates related to N-phenyl-4-benzenesulfonylimidazole compounds.

Disclosure of Invention

Aiming at the problems in the prior art, the invention aims to provide a method for preparing an N-phenyl-4-benzenesulfonyl imidazole compound by copper catalysis.

The invention is realized by the following technical scheme:

a method for preparing an N-phenyl-4-benzenesulfonyl imidazole compound shown in a formula (IV) by copper catalysis is characterized by comprising the following steps: the method comprises the following steps of (1) sufficiently reacting a vinyl phenyl sulfide compound shown in a formula (I), urea shown in a formula (II) and a halogenated benzene compound shown in a formula (III) under the promotion of hydrogen peroxide by taking an organic solvent as a medium and transition metal salt as a catalyst to prepare a target product, and carrying out post-treatment on the product to prepare an N-phenyl-4-benzenesulfonyl imidazole compound; the transition metal salt catalyst is copper chloride, and the organic solvent is ethanol;

in the reaction formula, R is selected from one of the following: hydrogen, methyl, methoxy; r¹Selected from one of the following: hydrogen, methyl, methoxy; x is selected from one of the following: bromine and chlorine.

The method for preparing the N-phenyl-4-benzenesulfonyl imidazole compound by copper catalysis is characterized in that the ratio of the vinyl phenyl sulfide compound to the urea to the halogenated benzene compound is 5 mmol: 6 mmol: 5 mmol.

The method for preparing the N-phenyl-4-benzenesulfonyl imidazole compound by copper catalysis is characterized in that the ratio of the vinyl phenyl sulfide compound to urea to a solvent ethanol is 5 mmol: 6 mmol: 15 mL.

The method for preparing the N-phenyl-4-benzenesulfonyl imidazole compound by copper catalysis is characterized in that the ratio of the vinyl phenyl sulfide compound to urea to copper chloride is 5 mmol: 5 mmol: 0.5 mmol.

The method for preparing the N-phenyl-4-benzenesulfonyl imidazole compound by copper catalysis is characterized in that the equivalent ratio of the vinyl phenyl sulfide compound to the urea to the halogenated benzene compound is 1 (1-1.2): 1.

the method for preparing the N-phenyl-4-benzenesulfonyl imidazole compound by copper catalysis is characterized in that the reaction temperature is 100 ℃, and the reaction time is 10 hours.

The method for preparing the N-phenyl-4-benzenesulfonyl imidazole compound by copper catalysis is characterized by comprising the following steps of:

1) and (3) extraction: after the reactant is cooled to room temperature at normal temperature, 20mL of saturated sodium chloride aqueous solution is added into the reactant, then ethyl acetate is used for extraction for 3 times, 20mL of the saturated sodium chloride aqueous solution is used for each time, and the extraction liquid is combined;

2) concentration: drying the extract with anhydrous sodium sulfate, and rotary drying with rotary evaporator to obtain concentrate;

3) adsorbing the obtained concentrate by using column chromatography silica gel, adding the concentrate into a 200-mesh 300-mesh chromatography silica gel column, and adding normal hexane: and (3) carrying out fast column chromatography on ethyl acetate according to a certain proportion, combining eluent, carrying out spin-drying on a rotary evaporator, and pumping by an oil pump to obtain the product N-phenyl-4-benzenesulfonyl imidazole compound.

The method for preparing the N-phenyl-4-benzenesulfonyl imidazole compound by copper catalysis is characterized in that the drying time in the step 2) is 5 hours.

The method for preparing the N-phenyl-4-benzenesulfonyl imidazole compounds by copper catalysis is characterized in that the volume ratio of N-hexane to ethyl acetate in the step 3) is 1:1-2: 1.

Drawings

FIG. 1 is a drawing of product 4a of the present invention¹H NMR spectrum;

FIG. 2 shows the product 4a of the present invention¹³C NMR spectrum;

FIG. 3 shows the product 4b of the present invention¹H NMR spectrum;

FIG. 4 shows the product 4b of the present invention¹³C-NMR spectrum;

FIG. 5 shows the preparation of 4c according to the invention¹H NMR spectrum;

FIG. 6 shows the preparation of 4c according to the invention¹³C-NMR spectrum;

FIG. 7 shows the product 4d of the present invention¹H NMR spectrum;

FIG. 8 is a drawing showing the production of 4d in the present invention¹³C NMR spectrum;

FIG. 9 shows the preparation of 4e according to the invention¹H NMR spectrum;

FIG. 10 shows the preparation of 4e according to the invention¹³C-NMR spectrum;

FIG. 11 shows the preparation of 4f of the present invention¹H NMR spectrum;

FIG. 12 shows the preparation of 4f of the present invention¹³C NMR spectrum;

Detailed Description

The present invention will be described in more detail with reference to specific examples.

The synthesis method comprises the steps of sequentially adding 5mmol of vinyl phenyl sulfide compound 1, 6mmol of urea 2 and 5mmol of halogenated benzene compound 3 into a 25mL round-bottom flask, then sequentially adding 15mL of absolute ethyl alcohol, 0.5mmol of copper chloride and 10mmol of hydrogen peroxide, and reacting at 100 ℃ for 10 hours under stirring. After cooling, 20mL of saturated sodium sulfite aqueous solution is added into the system, extraction is carried out for 3 times by ethyl acetate, 20mL of saturated sodium sulfite aqueous solution is carried out each time, organic phases are combined, after drying by anhydrous sodium sulfate, solvent is evaporated, and the pure product of the N-phenyl-4-benzenesulfonyl imidazole compound 4 is obtained by 200-mesh and 300-mesh silica gel column chromatography, wherein the yield is 81-93%. Specific examples and characterization data all product structures were determined by comparison of nuclear magnetic resonance and mass spectrometry results as follows.