Synthesis method of 4-bromo-2-(4-chlorphenyl)-1-ethoxymethyl-5-(trifluoromethyl) pyrrole-3-nitrile

Abstract

The invention discloses a synthesis method of 4-bromo-2-(4-chlorphenyl)-1-ethoxymethyl-5-(trifluoromethyl) pyrrole-3-nitrile, and belongs to the technical field of organic synthesis.The synthesis method comprises the steps of preparation of mixed raw materials, preparation of an adsorbent, condensation reaction and aftertreatment. The preparation of the mixed raw material comprises the following steps: mixing an acid-binding agent and sodium perfluorooctanoate, and stirring at room temperature to obtain the mixed raw material; the preparation of the adsorbent comprises the following steps: mixing magnetic ferroferric oxide particles, perfluorooctanoic acid and water, stirring at room temperature, adjusting the pH value to 10, centrifuging, taking a precipitate, and drying to obtain the adsorbent; the yield and the purity of the synthetic product are slightly influenced by the environment temperature, and a large amount of washing water is not required to be used for washing after the synthesis is finished.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and in particular to a method for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile. Background Art

[0002] 4-Bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile, also known as bromofenapyr and chlorfenapyr, is a novel aromatic substituted pyrrole compound. With increasing environmental awareness, 4-Bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile has been widely used in agricultural production due to its low toxicity and high efficacy.

[0003] Among the currently available methods for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile, one of the most commonly used methods involves using 4-bromo-2-(4-chlorophenyl)-5-trifluoromethyl-1H-pyrrole-3-carbonitrile (bromopyrrolecarbonitrile) as an intermediate and subjecting it to a condensation reaction with chloromethyl ether to obtain 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile. In the condensation reaction, toluene is used as the solvent, and triethylamine is added as an acid-binding agent. After the condensation reaction, the solvent is removed and crystallization is performed using methanol. The product is then centrifuged and dried.

[0004] The above method has the following problems: First, in order to control the reaction exothermic rate, the commonly used addition order is to first put toluene and bromopyrrole carbonitrile into the reactor, stir and mix, control the temperature of the reactor to 25-30 ° C, and add triethylamine and chloromethyl ether dropwise. By controlling the dripping speed of triethylamine and chloromethyl ether, the reaction speed is controlled, thereby controlling the reaction exothermic rate. However, during the dripping, since the temperature of the dripped triethylamine and chloromethyl ether is greatly affected by the ambient temperature, if the ambient temperature is high, the dripped triethylamine and chloromethyl ether will be heated to 0.05 ℃. The temperature of amine and chloromethyl ether is relatively high, and their dropwise addition will cause a local rapid reaction and heat release, resulting in a local temperature increase and an increase in side reactions, which will affect the purity and yield of the product. Secondly, triethylamine, as an acid binding agent, will react with the by-product hydrochloric acid to generate hydrochloride, thereby promoting the reaction. However, the addition of triethylamine will affect the color of the product, resulting in a yellow product. After the synthesis is completed, a large amount of washing water needs to be used to wash the product. The amount of washing water used is large, and the washing time is long, which further leads to an increase in the amount of wastewater and an extension of the synthesis time. Summary of the Invention

[0005] In view of the shortcomings of the existing technology, the present invention provides a method for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile. The yield and purity of the synthesized product are less affected by the ambient temperature, and no large amount of washing water is required for washing after the synthesis.

[0006] In order to solve the above technical problems, the technical solutions adopted by the present invention are as follows: A method for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile, comprising: preparing a mixed raw material, preparing an adsorbent, performing a condensation reaction, and performing post-processing; The mixed raw material is prepared by adding the acid binding agent and sodium perfluorooctanoate into a reaction kettle, and stirring at a stirring speed of 100-300 rpm for 20-40 minutes at room temperature to obtain a mixed raw material; In the preparation of the mixed raw materials, the mass ratio of the acid binding agent to sodium perfluorooctanoate is 100:6-7; The acid binding agent is one of triethylamine or N,N-diisopropylethylamine; The adsorbent is prepared by adding magnetic ferrosoferric oxide particles, perfluorooctanoic acid, and water into a reaction kettle, stirring at room temperature at a stirring speed of 100-300 rpm for 10-30 minutes, adding sodium hydroxide aqueous solution to adjust the pH to 10, transferring the mixture into a centrifuge, and centrifuging at a stirring speed of 8000-9000 rpm for 15-20 minutes, collecting the precipitate, and drying it to obtain the adsorbent; In the preparation of the adsorbent, the mass ratio of magnetic ferroferric oxide particles, perfluorooctanoic acid, and water is 100-120:80-85:1000-1300; The particle size of the magnetic ferroferric oxide particles is 200 nm; The concentration of the sodium hydroxide aqueous solution is 10wt%; The condensation reaction comprises the following steps: replacing the air in the reactor with nitrogen, sequentially adding toluene, bromopyrrole carbonitrile, and an acid binding agent into the reactor, controlling the temperature of the reactor to 25-30° C., controlling the stirring speed to 100-300 rpm, simultaneously adding chloromethyl ether and a mixed raw material dropwise into the reactor, then controlling the temperature of the reactor to 50-60° C., stirring for 50-60 min, adding a first washing water into the reactor, stirring for 30-40 min, standing for 60-70 min, collecting the water layer as a first water layer, adding a second washing water and an adsorbent into the toluene layer, stirring for 30-40 min, removing the adsorbent by a magnet, standing for 60-70 min, collecting the water layer as a second water layer, taking the toluene layer as a condensation reaction product, combining the first water layer and the second water layer, and respectively recovering triethylamine and magnetic ferrosoferric oxide particles; In the condensation reaction, the mass ratio of toluene, bromopyrrole carbonitrile, acid binding agent, chloromethyl ether, mixed raw material, first washing water, second washing water, and adsorbent is 6-6.5:1-1.1:0.21-0.24:0.3-0.34:0.27-0.35:10-11:5-5.5:0.17-0.2; The dropwise addition time of the chloromethyl ether and the mixed raw material is 40-50 min; The acid binding agent is one of triethylamine or N,N-diisopropylethylamine; The post-treatment is as follows: adding the condensation reaction product to a vacuum desolventizer, collecting the removed toluene, transferring the product in the vacuum desolventizer to a reactor, adding methanol, controlling the temperature of the reactor to 60-62° C., stirring and reflux for 50-60 minutes, cooling to 0-5° C., standing for 60-70 minutes, transferring to a centrifuge, centrifuging at a centrifugal speed of 6000-7000 rpm for 10-15 minutes, taking the precipitate, and drying it to obtain 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile; In the post-treatment, the temperature of the vacuum desolventizer during vacuum desolventization is 93-98° C., and the vacuum degree is 0.05-0.1 MPa; The mass ratio of bromopyrrolecarbonitrile in the condensation reaction to methanol in the post-treatment is 1-1.1:10-11.

[0007] Compared with the prior art, the present invention has the following beneficial effects: (1) The synthesis method of 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile of the present invention, in order to prevent the temperature of the dripped triethylamine and chloromethyl ether from being affected by the ambient temperature, sodium perfluorooctanoate is added to the triethylamine during the dripping process. In toluene, sodium perfluorooctanoate can undergo intermolecular bonding with triethylamine hydrochloride to form micelles. Therefore, during the dripping process of triethylamine, if the ambient temperature is high, the dripped chloromethyl ether reacts rapidly with bromopyrrole carbonitrile to generate hydrochloric acid as a by-product. At the same time, the dripped triethylamine combines with hydrochloric acid to generate triethylamine hydrochloride. Sodium perfluorooctanoate can form micelles with triethylamine hydrochloride to wrap the triethylamine, thereby avoiding the local reaction temperature from being too high. If the reaction temperature continues to increase, the interaction between sodium perfluorooctanoate and triethylamine hydrochloride will be destroyed. Heat can be absorbed during the destruction process, thereby reducing the local reaction temperature, thereby reducing side reactions and avoiding the influence of the local temperature increase on the purity and yield of the product. (2) The synthesis method of 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile of the present invention, in the second washing process after the condensation reaction is completed, an adsorbent is also added, the raw materials of the adsorbent are magnetic ferroferric oxide particles, perfluorooctanoic acid, and sodium hydroxide. In the preparation, the magnetic ferroferric oxide particles are first mixed with perfluorooctanoic acid, and the perfluorooctanoic acid can be adsorbed on the surface of the magnetic ferroferric oxide particles, and then react with the added sodium hydroxide to generate sodium perfluorooctanoate, thereby obtaining magnetic ferroferric oxide particles with sodium perfluorooctanoate adsorbed on the surface, i.e., the adsorbent. The sodium perfluorooctanoate on the surface of the adsorbent can be adsorbed with the residual triethylamine hydrochloride and the triethylamine hydrochloride on the surface of the generated 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile to compete for adsorption. The magnetic ferroferric oxide particles can also play a certain role in adsorbing triethylamine hydrochloride, thereby reducing the amount of washing water used; (3) The method for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile of the present invention, wherein when the ambient temperature is 23°C, the purity of the synthesized 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile is 99.4-99.5%, and the molar yield is 98.0-98.4%; (4) The method for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile of the present invention has a product yield and purity that are less affected by ambient temperature. When the ambient temperature is 40°C, the purity of the synthesized 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile is 99.5-99.6%, and the molar yield is 98.3%; (5) The method for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile of the present invention does not require the use of a large amount of washing water for washing after the synthesis is completed. When the amount of the raw material bromopyrrole carbonitrile used is 1-1.1 kg, 10-11 kg of water is used for the first washing and 5-5.5 kg of water is used for the second washing, thereby obtaining 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile in the form of a white powder. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 This is a gas chromatogram of 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile obtained in Example 1; Figure 2 This is the gas chromatogram of 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile obtained in Example 2. DETAILED DESCRIPTION

[0009] In order to have a clearer understanding of the technical features, purposes and effects of the present invention, the specific embodiments of the present invention are now described.

[0010] Examples 1-5 were all carried out at a temperature of 23° C., and the purity of the raw material bromopyrrolecarbonitrile used was 99%.

[0011] Example 1 A method for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile, specifically: 1. Prepare a mixed raw material: add an acid binding agent and sodium perfluorooctanoate in a mass ratio of 100:6 into a reactor, and stir at room temperature at a stirring speed of 100 rpm for 20 minutes to obtain a mixed raw material; The acid binding agent is triethylamine; 2. Preparation of adsorbent: Magnetic ferroferric oxide particles, perfluorooctanoic acid, and water were added to a reactor in a mass ratio of 100:80:1000. The mixture was stirred at 100 rpm for 10 minutes at room temperature. Aqueous sodium hydroxide solution was added to adjust the pH to 10. The mixture was transferred to a centrifuge and centrifuged at 8000 rpm for 15 minutes. The precipitate was collected and dried to obtain an adsorbent. The particle size of the magnetic ferroferric oxide particles is 200 nm; The concentration of the sodium hydroxide aqueous solution is 10wt%; 3. Condensation reaction: using nitrogen to replace the air in the reactor, 6kg of toluene, 1kg of bromopyrrole carbonitrile, and 0.21kg of acid binding agent were added to the reactor in sequence, the temperature of the reactor was controlled to 25-30°C, the stirring speed was controlled to 100rpm, 0.3kg of chloromethyl ether and 0.27kg of mixed raw materials were simultaneously added dropwise to the reactor, and the addition time was controlled to be 40min. Then, the temperature of the reactor was controlled to 50°C and stirred for 50min. 10kg of water was added to the reactor, stirred for 30min, and allowed to stand for 60min. The water layer was collected as the first water layer, 5kg of water and 0.17kg of adsorbent were added to the toluene layer, stirred for 30min, the adsorbent was removed by a magnet, and allowed to stand for 60min. The water layer was collected as the second water layer, and the toluene layer was taken as the condensation reaction product. After combining the first and second water layers, triethylamine and magnetic ferrosoferric oxide particles were recovered respectively; The acid binding agent is triethylamine; 4. Post-treatment: All the condensation reaction products obtained in step 3 were added to a vacuum desolventizer, the temperature of the vacuum desolventizer was controlled to 93 ° C, the vacuum degree was controlled to 0.05 MPa, and after collecting the removed toluene, the product in the vacuum desolventizer was transferred to a reactor, 10 kg of methanol was added, and the reactor was controlled to 60 ° C., stirred and refluxed for 50 minutes, cooled to 0 ° C, and allowed to stand for 60 minutes. Transferred to a centrifuge, centrifuged at a centrifugal speed of 6000 rpm for 10 minutes, the precipitate was taken, and dried to obtain 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile.

[0012] The 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile obtained in this example was subjected to gas chromatography analysis, and the obtained gas chromatogram is shown in FIG. Figure 1 .

[0013] Example 2 A method for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile, specifically: 1. Prepare a mixed raw material: add an acid binding agent and sodium perfluorooctanoate in a mass ratio of 100:7 to a reactor, and stir at room temperature at a stirring speed of 300 rpm for 40 minutes to obtain a second raw material; The acid binding agent is N,N-diisopropylethylamine; 2. Preparation of adsorbent: Magnetic ferrosoferric oxide particles, perfluorooctanoic acid, and water were added to a reactor in a mass ratio of 120:85:1300, stirred at 300 rpm for 30 minutes at room temperature, and then adjusted to pH 10 by adding sodium hydroxide aqueous solution. The mixture was transferred to a centrifuge and centrifuged at 9000 rpm for 20 minutes. The precipitate was collected and dried to obtain an adsorbent. The particle size of the magnetic ferroferric oxide particles is 200 nm; The concentration of the sodium hydroxide aqueous solution is 10wt%; 3. Condensation reaction: using nitrogen to replace the air in the reactor, 6.5kg of toluene, 1.1kg of bromopyrrole carbonitrile, and 0.24kg of acid binding agent were added to the reactor in sequence, the temperature of the reactor was controlled to 30°C, the stirring speed was controlled to 300rpm, 0.34kg of chloromethyl ether and 0.35kg of mixed raw materials were added dropwise to the reactor at the same time, and the addition time was controlled to 50min. Then, the temperature of the reactor was controlled to 60°C and stirred for 50-60min. 11kg of water was added to the reactor, stirred for 40min, and allowed to stand for 70min. The water layer was collected as the first water layer, 5.5kg of water and 0.2kg of adsorbent were added to the toluene layer, stirred for 40min, the adsorbent was removed by a magnet, and allowed to stand for 70min. The water layer was collected as the second water layer, and the toluene layer was taken as the condensation reaction product. After combining the first and second water layers, triethylamine and magnetic ferrosoferric oxide particles were recovered respectively; The acid binding agent is N,N-diisopropylethylamine; 4. Post-treatment: All the condensation reaction products obtained in step 3 were added to a vacuum desolventizer, the temperature of the vacuum desolventizer was controlled to 98 ° C, the vacuum degree was controlled to 0.1 MPa, and after collecting the removed toluene, the product in the vacuum desolventizer was transferred to a reactor, 11 kg of methanol was added, and the reactor was controlled to 62 ° C., stirred and refluxed for 60 min, cooled to 5 ° C, and allowed to stand for 70 min. The mixture was transferred to a centrifuge and centrifuged at a centrifugal speed of 7000 rpm for 15 min. The precipitate was taken and dried to obtain 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile.

[0014] The 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile obtained in this example was subjected to gas chromatography analysis, and the obtained gas chromatogram is shown in FIG. Figure 2 .

[0015] Example 3 A method for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile, specifically: 1. Preparation of adsorbent: Magnetic ferrosoferric oxide particles, perfluorooctanoic acid, and water were added to a reactor in a mass ratio of 100:80:1000. The mixture was stirred at room temperature at 100 rpm for 10 minutes. A sodium hydroxide solution was added to adjust the pH to 10. The mixture was transferred to a centrifuge and centrifuged at 8000 rpm for 15 minutes. The precipitate was collected and dried to obtain an adsorbent. The particle size of the magnetic ferroferric oxide particles is 200 nm; The concentration of the sodium hydroxide aqueous solution is 10wt%; 2. Condensation reaction: using nitrogen to replace the air in the reactor, 6kg of toluene, 1kg of bromopyrrole carbonitrile, and 0.21kg of triethylamine were added to the reactor in sequence, the temperature of the reactor was controlled to 25°C, the stirring speed was controlled to 100rpm, and 0.3kg of chloromethyl ether and 0.25kg of triethylamine were added dropwise to the reactor at the same time, and the addition time was controlled to be 40min. Then, the temperature of the reactor was controlled to 50°C and stirred for 50min. 10kg of water was added to the reactor, stirred for 30min, and allowed to stand for 60min. The water layer was collected as the first water layer, 5kg of water and 0.17kg of adsorbent were added to the toluene layer, stirred for 30min, the adsorbent was removed by a magnet, and allowed to stand for 60min. The water layer was collected as the second water layer, and the toluene layer was taken as the condensation reaction product. After combining the first and second water layers, triethylamine and magnetic ferrosoferric oxide particles were recovered respectively; 3. Post-treatment: All the condensation reaction products obtained in step 2 were added to a vacuum desolventizer, the temperature of the vacuum desolventizer was controlled to 93 ° C, the vacuum degree was controlled to 0.05 MPa, and after collecting the removed toluene, the product in the vacuum desolventizer was transferred to a reactor, 10 kg of methanol was added, and the reactor was controlled to 60 ° C., stirred and refluxed for 50 minutes, cooled to 0 ° C, and allowed to stand for 60 minutes. The mixture was transferred to a centrifuge and centrifuged at a centrifugal speed of 6000 rpm for 10 minutes. The precipitate was taken and dried to obtain 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile.

[0016] Example 4 A method for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile, specifically: 1. Prepare a mixed raw material: add an acid binding agent and sodium perfluorooctanoate in a mass ratio of 100:6 into a reactor, and stir at room temperature at a stirring speed of 100 rpm for 20 minutes to obtain a second raw material; The acid binding agent is triethylamine; 2. Condensation reaction: using nitrogen to replace the air in the reactor, 6kg of toluene, 1kg of bromopyrrole carbonitrile, and 0.21kg of acid binding agent were added to the reactor in sequence, the temperature of the reactor was controlled to 25°C, the stirring speed was controlled to 100rpm, and 0.3kg of chloromethyl ether and 0.27kg of mixed raw materials were added dropwise to the reactor at the same time, and the addition time was controlled to 40min. Then, the temperature of the reactor was controlled to 50°C and stirred for 50min. 10kg of water was added to the reactor, stirred for 30min, and allowed to stand for 60min. The water layer was collected as the first water layer, 5kg of water was added to the toluene layer, stirred for 30min, and allowed to stand for 60min. The water layer was collected as the second water layer, and the toluene layer was taken as the condensation reaction product. After combining the first and second water layers, triethylamine and magnetic ferrosoferric oxide particles were recovered respectively; The acid binding agent is triethylamine; 3. Post-treatment: All the condensation reaction products obtained in step 2 were added to a vacuum desolventizer, the temperature of the vacuum desolventizer was controlled to 93 ° C, the vacuum degree was controlled to 0.05 MPa, and after collecting the removed toluene, the product in the vacuum desolventizer was transferred to a reactor, 10 kg of methanol was added, and the reactor was controlled to 60 ° C., stirred and refluxed for 50 minutes, cooled to 0 ° C, and allowed to stand for 60 minutes. The mixture was transferred to a centrifuge and centrifuged at a centrifugal speed of 6000 rpm for 10 minutes. The precipitate was taken and dried to obtain 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile.

[0017] Example 5 A method for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile, specifically: 1. Prepare a mixed raw material: add an acid binding agent and sodium perfluorooctanoate in a mass ratio of 100:6 into a reactor, and stir at room temperature at a stirring speed of 100 rpm for 20 minutes to obtain a second raw material; The acid binding agent is triethylamine; 2. Condensation reaction: using nitrogen to replace the air in the reactor, 6kg of toluene, 1kg of bromopyrrole carbonitrile, and 0.21kg of acid binding agent were added to the reactor in sequence, the temperature of the reactor was controlled to 25°C, the stirring speed was controlled to 100rpm, and 0.3kg of chloromethyl ether and 0.27kg of mixed raw materials were added dropwise to the reactor at the same time, and the addition time was controlled to 40min. Then, the temperature of the reactor was controlled to 50°C and stirred for 50min. 10kg of water was added to the reactor, stirred for 30min, and allowed to stand for 60min. The water layer was collected as the first water layer, 10kg of water was added to the toluene layer, stirred for 30min, and allowed to stand for 60min. The water layer was collected as the second water layer, and the toluene layer was taken as the condensation reaction product. After combining the first and second water layers, triethylamine and magnetic ferrosoferric oxide particles were recovered respectively; The acid binding agent is triethylamine; 3. Post-treatment: All the condensation reaction products obtained in step 2 were added to a vacuum desolventizer, the temperature of the vacuum desolventizer was controlled to 93 ° C, the vacuum degree was controlled to 0.05 MPa, and after collecting the removed toluene, the product in the vacuum desolventizer was transferred to a reactor, 10 kg of methanol was added, and the reactor was controlled to 60 ° C., stirred and refluxed for 50 minutes, cooled to 0 ° C, and allowed to stand for 60 minutes. The mixture was transferred to a centrifuge and centrifuged at a centrifugal speed of 6000 rpm for 10 minutes. The precipitate was taken and dried to obtain 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile.

[0018] Test Example 1 The mass, purity, molar yield (calculated as bromopyrrolecarbonitrile), and state of 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile obtained in Examples 1-5 were statistically analyzed. The statistical results are as follows:

[0019] Test Example 2 Comparative Examples 1-5 were prepared based on Examples 1-5. In Comparative Examples 1-5, the ambient temperature of Examples 1-5 was changed to 40° C. The mass, purity, molar yield (calculated as bromopyrrolecarbonitrile), and state of 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile obtained in Comparative Examples 1-5 were statistically analyzed. The statistical results are as follows:

[0020] It can be seen from the results of Test Example 1 that the molar yield of Example 3 is worse than that of Example 1, and the state of Example 4 is worse than that of Example 1. It can be seen from the results of Test Example 2 that after changing the ambient temperature, the quality, purity and molar yield of Comparative Examples 1-2 and Comparative Examples 4-5 change little, but the molar yield of Comparative Example 3 decreases significantly, indicating that the synthesis method of Example 3 is greatly affected by the ambient temperature.

[0021] Unless otherwise specified, all percentages used in the present invention are by mass.

[0022] Finally, it should be noted that the above descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art will be able to modify the technical solutions described in the aforementioned embodiments or substitute equivalents for some of the technical features. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. A method for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile, characterized in that: include: Preparation of mixed raw materials, preparation of adsorbent, condensation reaction, post-processing; The mixed raw material is prepared by mixing the acid binding agent and sodium perfluorooctanoate, and stirring at room temperature to obtain a mixed raw material; The adsorbent is prepared by mixing magnetic ferrosoferric oxide particles, perfluorooctanoic acid, and water, stirring at room temperature, adjusting the pH to 10, centrifuging, collecting the precipitate, and drying to obtain the adsorbent; The condensation reaction comprises the following steps: mixing toluene, bromopyrrolecarbonitrile and an acid binding agent in a nitrogen atmosphere to obtain a mixture; simultaneously adding chloromethyl ether and the mixed raw materials to the mixture at 25-30° C.; heating the mixture to 50-60° C.; stirring the mixture for 50-60 minutes; adding the first washing water to the reactor; stirring the mixture for 30-40 minutes; standing the mixture for 60-70 minutes; adding the second washing water and an adsorbent to the toluene layer; stirring the mixture for 30-40 minutes; removing the adsorbent by a magnet; standing the mixture for 60-70 minutes; and collecting the toluene layer as a condensation reaction product.

2. The method for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile according to claim 1, wherein: In the preparation of the mixed raw materials, the mass ratio of the acid binding agent to sodium perfluorooctanoate is 100:6-7; The acid binding agent is one of triethylamine and N,N-diisopropylethylamine.

3. The method for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile according to claim 1, wherein: In the preparation of the adsorbent, the mass ratio of magnetic ferroferric oxide particles, perfluorooctanoic acid, and water is 100-120:80-85:1000-1300; The particle size of the magnetic ferrosoferric oxide particles is 200 nm.

4. The method for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile according to claim 1, wherein: In the condensation reaction, the mass ratio of toluene, bromopyrrole carbonitrile, acid binding agent, chloromethyl ether, mixed raw material, first washing water, second washing water, and adsorbent is 6-6.5:1-1.1:0.21-0.24:0.3-0.34:0.27-0.35:10-11:5-5.5:0.17-0.2; The dropwise addition time of the chloromethyl ether and the mixed raw material is 40-50 min; The acid binding agent is one of triethylamine and N,N-diisopropylethylamine.

5. The method for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile according to claim 1, wherein: The post-treatment is to vacuum desolventize the condensation reaction product, collect the removed toluene, recrystallize it with methanol, and dry it to obtain 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile.

6. The method for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile according to claim 5, wherein: In the post-treatment, the temperature during vacuum desolventization is 93-98° C., and the vacuum degree is 0.05-0.1 MPa.

7. The method for synthesizing 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-(trifluoromethyl)pyrrole-3-carbonitrile according to claim 5, wherein: In the post-treatment, the methanol is recrystallized, the vacuum desolvent is mixed with methanol, stirred and refluxed at 60-62°C for 50-60 minutes, cooled to 0-5°C, allowed to stand for 60-70 minutes, centrifuged, and the precipitate is collected; The mass ratio of bromopyrrolecarbonitrile in the condensation reaction to methanol in the methanol recrystallization is 1-1.1:10-11.

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