阅读说明：本技术 2-氯-4-三氟甲基苯基-4′-硝基-3′-乙氧基苯基醚的合成方法 (Synthesis method of 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxy phenyl ether ) 是由 叶炎婵 汪召 杨金珠 于 2021-08-31 设计创作，主要内容包括：本发明公开了一种2-氯-4-三氟甲基苯基-4′-硝基-3′-乙氧基苯基醚的合成方法,其技术方案是以3-氯-4-硝基苯酚和3,4-二氯三氟甲苯为起始原料,在催化剂和碱的作用下,采用声共振对反应液体充分混合,加热反应一定时间后得到中间产物2-氯-4-三氟甲基苯基-4′-硝基-3′-氯苯；中间体2-氯-4-三氟甲基苯基-4′-硝基-3′-氯苯与乙醇盐反应得到目标产物2-氯-4-三氟甲基苯基-4′-硝基-3′-乙氧基苯基醚；本发明所采用的合成方法反应步骤少,操作简单、混合效率高、条件温和、三废少、收率高,是一种可工业化2-氯-4-三氟甲基苯基-4′-硝基-3′-乙氧基苯基醚的合成方法；本发明属于农药合成领域。(The invention discloses a synthesis method of 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxy phenyl ether, which adopts the technical scheme that 3-chloro-4-nitrophenol and 3, 4-dichlorobenzotrifluoride are taken as initial raw materials, under the action of a catalyst and alkali, acoustic resonance is adopted to fully mix reaction liquid, and an intermediate product, namely 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -chlorobenzene, is obtained after heating reaction for a certain time; reacting the intermediate 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -chlorobenzene with ethoxide to obtain a target product 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxy phenyl ether; the synthesis method adopted by the invention has the advantages of few reaction steps, simple operation, high mixing efficiency, mild conditions, less three wastes and high yield, and is a synthesis method of the industrialized 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxy phenyl ether; the invention belongs to the field of pesticide synthesis.)

1. A synthetic method of 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxy phenyl ether is characterized by sequentially comprising the following steps:

1) adding 3-chloro-4-nitrophenol, 3, 4-dichlorotrifluorotoluene, a solvent 1 and a catalyst 1 into a reaction bottle, fully mixing and stirring reaction liquid by adopting acoustic resonance, adjusting the pH value of the reaction liquid to be 8-10 by adopting an alkali 1, heating to 60-140 ℃, reacting for 3-8h, stopping the reaction, filtering to obtain a filtrate containing an intermediate product 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -chlorobenzene, and directly using the filtrate in the next step without separation and purification;

the mol ratio of the 3-chloro-4-nitrophenol to the 3, 4-dichlorotrifluorotoluene in the step 1) is as follows: 1-1.2: 1-1.5;

2) adding a solvent 2 and a catalyst 2 into the filtrate obtained in the step 1), adding alkali 2 and ethoxide in batches, fully stirring the reaction solution by adopting acoustic resonance, controlling the pH of the reaction solution to be 8-10, heating to 40-100 ℃ for reacting for 1-5h, dropwise adding acid after the reaction is finished, adjusting the pH of the reaction solution to be 7, filtering, leaching a filter cake, collecting the filtrate, and filtering at 40-130 DEG C^℃And concentrating the filtrate at 500-2000 Pa to separate out a solid, thereby obtaining an off-white solid, namely the target product 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxy phenyl ether.

2. The method for synthesizing 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether according to claim 1, wherein the solvent 1) and the solvent 2) are each one or a mixture of two or more of N, N-dimethylformamide, N-dimethylacetamide, xylene, toluene, and dimethylsulfoxide.

3. The method for synthesizing 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether according to claim 1, wherein the solvent 1 in step 1) is used in an amount of: adding 300ml to 800ml of solvent into each mole of 3-chloro-4-nitrophenol; the using amount of the solvent 2 in the step 2) is as follows: 100ml to 300ml of solvent is added per mole of 3-chloro-4-nitrophenol.

4. The method for synthesizing 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether according to claim 1, wherein the catalysts 1) and 2) of the steps 1) and 2) are all one or a mixture of two or more of tetramethylammonium bromide, tetramethylammonium chloride, tetrabutylammonium chloride, triethylbenzylammonium chloride, potassium iodide, 18-crown-6, copper oxide, and copper chloride.

5. The method for synthesizing 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether according to claim 1, wherein the amount of the catalyst 1 added in the step 1) is 1 to 5 wt% of 3-chloro-4-nitrophenol; the addition amount of the catalyst 2 in the step 2) is 0.4 to 2 weight percent of the 3-chloro-4-nitrophenol.

6. The method for synthesizing 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether according to claim 1, wherein the base 1 in the step 1) is one or a mixture of two or more of potassium carbonate, sodium carbonate, triethylamine, sodium hydride, sodium hydroxide, potassium hydroxide, and potassium bicarbonate.

7. The method for synthesizing 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether according to claim 1, wherein the base 2 in step 2) is one or a mixture of two or more of potassium carbonate, sodium hydride, sodium hydroxide, and potassium hydroxide.

8. The method for synthesizing 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether according to claim 1, wherein the acid in step 2) is one of or any combination of diluted hydrochloric acid, diluted sulfuric acid, acetic acid and diluted nitric acid.

9. The method for synthesizing 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether according to claim 1, wherein the ethoxide in step 2) is sodium ethoxide or potassium ethoxide.

10. The method for synthesizing 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether as claimed in claim 1, wherein the acoustic resonance vibration frequency in step 1) and step 2) is 500-2000 times/min.

Technical Field

The invention belongs to the field of pesticide synthesis, and particularly relates to a synthesis method of 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether.

Background

2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxy phenyl ether is an important agricultural broad-spectrum herbicide and is commonly named as oxyfluorfen. It is a broad-spectrum preemergence and postemergence herbicide with high weed-killing rate, no residue, low toxicity, small dosage per mu, dual purposes of paddy field and dry field and high selectivity.

The domestic reports that the synthesis routes of more industrialized oxyfluorfen mainly comprise the following two routes: route one: the diether method (patent CN 1363548A; Ganoderma lucidum, etc., oxyfluorfen intermediate condensate synthesis research, chemical engineering management, 1 month in 2015) uses resorcinol and 3, 4-dichlorotrifluorotoluene as raw materials, and carries out condensation to obtain a diether compound 1, 3-bis [ 2-chloro-4- (trifluoromethyl) phenoxy ] benzene, then carries out nitration to obtain a diether nitration product, and finally carries out alcoholysis three-step reaction to obtain oxyfluorfen; and a second route: the monoether hydroxyl protecting method (CN1068106A) is to take 3, 4-dichlorobenzotrifluoride and resorcinol as raw materials, condense the raw materials under the action of alkali to generate monoether, generate ethoxy monoether through the ethylation of diethyl sulfate, and then nitrify the ethoxy monoether to obtain the oxyfluorfen. The analysis shows that: the method has the advantages of long route, high addition ratio of the catalyst to the alkali in the synthesis process, high solid content of the system, and the problems of extremely dark reaction product color, more byproducts, low yield, high unit consumption of 3, 4-dichlorobenzotrifluoride and the like caused by the fact that the traditional stirring cannot effectively mix. Although the route is adopted in the current industrial production, the atom economy of the route is poorer, and the problems of high production cost and great pollution exist. And a company also adopts a second route to carry out industrial production, but the synthesis route needs to protect hydroxyl and then carry out deprotection to generate the target product oxyfluorfen, and diethyl sulfate with higher toxicity is used in the synthesis process. The route has the problems of high raw material and production cost and great pollution.

The acoustic resonance mixing technology is a novel mixing process for realizing uniform dispersion of materials by using a vibration exciter to output a vibration frequency close to or the same as the resonance frequency of a mixed material system. (Jiangholong, Wangxing, Chensong, etc.. Sound resonance mixed technology and its application in fire explosive [ J ] chemical new material, 2017(2): 236. supplement 238; face constancy, Qin Yihong, Zhao Chunfang, etc.. agglomeration of ultrafine powder and its control [ C ] 2004. Chinese materials workshop discussion collection, Beijing, 2004:400 supplement 406). The acoustic resonance mixing has no contact between a mechanical rotating part and the material, and has the characteristics of high mixing speed, good mixing uniformity, high safety, material saving, simplicity in cleaning and the like. The acoustic resonance technology can effectively solve the problems that the oxyfluorfen can not be effectively mixed by traditional stirring due to high system solid content in the synthesis process, the number of byproducts is large, the color of the product is dark, the yield is low and the like.

Disclosure of Invention

In order to overcome the defects of the prior art, the invention aims to provide the synthesis method of the 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether, which has the advantages of less reaction steps, mild conditions, simple operation, less three wastes and high yield.

In order to solve the technical problems, the invention provides a method for synthesizing oxyfluorfen by continuous acoustic resonance, which comprises the following technical route:

in the formula: r ═ Na or K;

the synthesis method sequentially comprises the following steps:

1) adding 3-chloro-4-nitrophenol, 3, 4-dichlorotrifluorotoluene, a solvent 1 and a catalyst 1 into a reaction bottle, fully mixing and stirring reaction liquid by adopting acoustic resonance, adjusting the pH value of the reaction liquid to be 8-10 by adopting an alkali 1, heating to 60-140 ℃, reacting for 3-8h, stopping the reaction, filtering to obtain a filtrate containing an intermediate product 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -chlorobenzene, and directly using the filtrate in the next step without separation and purification;

the mol ratio of the 3-chloro-4-nitrophenol to the 3, 4-dichlorotrifluorotoluene in the step 1) is as follows: 1-1.2: 1-1.5;

2) adding a solvent 2 and a catalyst 2 into the filtrate obtained in the step 1), adding alkali 2 and an ethoxide in batches, fully stirring the reaction solution by adopting acoustic resonance, controlling the pH of the reaction solution to be 8-10, heating to 40-100 ℃ to react for 1-5h, dropwise adding an acid after the reaction is finished, adjusting the pH of the reaction solution to be 7, filtering, leaching a filter cake, collecting the filtrate, concentrating the filtrate at 40-130 ℃/500-2000 Pa, and separating out a solid to obtain an off-white solid, namely the target product 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether.

Further, in the above method for synthesizing 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether, the solvent 1) and the solvent 2) are all one or a mixture of two or more of N, N-dimethylformamide, N-dimethylacetamide, xylene, toluene and dimethyl sulfoxide.

Further, in the above method for synthesizing 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether, the amount of the solvent 1 used in step 1) is: adding 300ml to 800ml of solvent into each mole of 3-chloro-4-nitrophenol; the using amount of the solvent 2 in the step 2) is as follows: 100ml to 300ml of solvent is added per mole of 3-chloro-4-nitrophenol.

Further, in the above method for synthesizing 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether, the catalysts 1) and 2) described in step 1) and step 2) are all one or a mixture of two or more of tetramethylammonium bromide, tetramethylammonium chloride, tetrabutylammonium chloride, triethylbenzylammonium chloride, potassium iodide, 18-crown-6, copper oxide and copper chloride.

Further, in the above method for synthesizing 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether, the amount of the catalyst 1 added in the step 1) is 1 wt% -5 wt% of 3-chloro-4-nitrophenol; the addition amount of the catalyst 2 in the step 2) is 0.4 to 2 weight percent of the 3-chloro-4-nitrophenol.

Further, in the above method for synthesizing 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether, the base 1 in step 1) is one or a mixture of two or more of potassium carbonate, sodium carbonate, triethylamine, sodium hydride, sodium hydroxide, potassium hydroxide and potassium bicarbonate.

Further, in the above method for synthesizing 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether, the base 2 in step 2) is one or a mixture of two or more of potassium carbonate, sodium hydride, sodium hydroxide and potassium hydroxide.

Further, in the above method for synthesizing 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether, the acid in step 2) is one or any combination of dilute hydrochloric acid, dilute sulfuric acid, acetic acid and dilute nitric acid.

Further, in the above method for synthesizing 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether, the ethoxide in step 2) is sodium ethoxide or potassium ethoxide.

Further, in the above method for synthesizing 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether, the acoustic resonance vibration frequency in step 1) and step 2) is 500-;

compared with the prior art, the invention has the beneficial effects that:

(1) in the synthesis process, the reaction liquid is mixed and stirred by adopting acoustic resonance, so that the mixing efficiency is effectively improved, the reaction rate is improved, the generation of byproducts is reduced, and the quality of the product is improved;

(2) the synthesis route is short, the diether preparation or hydroxyl protection process in the traditional synthesis process is avoided, the reaction yield is improved, and the operation steps and the discharge of three wastes are reduced.

Drawings

FIG. 1 is a chromatogram of 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether prepared in example 1;

FIG. 2 is a chromatogram of 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether prepared in example 2.

Detailed Description

The following examples are intended to further illustrate the synthesis of 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether in the present invention, but the present invention is by no means limited to the following examples.

Example 1

The invention provides a synthesis method of 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxy phenyl ether, which comprises the following steps:

step (1): adding 17.3g (0.1mol) of 3-chloro-4-nitrophenol, 14.5g (0.1mol) of 3, 4-dichlorobenzotrifluoride, 30ml of solvent toluene and 0.17g (1%) of tetramethylammonium chloride into a reaction bottle, fully mixing and stirring the reaction liquid by adopting acoustic resonance, adjusting the pH value of the reaction liquid to be 8 by using sodium hydroxide, heating to 60 ℃ for reaction for 5 hours, stopping the reaction, filtering to obtain a filtrate containing an intermediate product 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -chlorobenzene, and directly using the filtrate for synthesis in the next step without separation and purification;

step (2): adding 10ml of N, N-dimethylformamide and 18-crown-60.0184 g into the filtrate obtained in the step 1, adding 6.8g of potassium hydroxide and sodium ethoxide, fully stirring the reaction solution by adopting acoustic resonance, controlling the pH of the reaction solution to be 8, heating to 70 ℃ for reaction for 3 hours, after the reaction is finished, dropwise adding dilute sulfuric acid, adjusting the pH of the reaction solution to be 7, filtering, leaching a filter cake, collecting the filtrate, concentrating the filtrate at 100 ℃/500Pa, separating out a solid, and detecting an off-white solid (shown in figure 1), namely 26.1g of the target product 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether, wherein the total yield is 72.25%.

Example 2

The invention provides another synthesis method of 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxy phenyl ether, which comprises the following steps:

step (1): adding 17.3g (0.1mol) of 3-chloro-4-nitrophenol, 17.4g (0.12mol) of 3, 4-dichlorotrifluorotoluene, 50ml of N, N-dimethylformamide as a solvent and 0.346g (2%) of copper oxide into a reaction bottle, fully mixing and stirring the reaction solution by adopting acoustic resonance, adjusting the pH value of the reaction solution to 10 by using potassium hydroxide, heating to 110 ℃ for reacting for 8 hours, stopping the reaction, and filtering to obtain a filtrate containing an intermediate product, namely 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -chlorobenzene, wherein the filtrate is directly used for synthesis in the next step without separation and purification;

step (2): adding 10ml of toluene and 0.346g of potassium iodide into the filtrate obtained in the step 1, adding 10.2g of potassium carbonate and sodium ethoxide in batches, fully stirring the reaction solution by adopting acoustic resonance, controlling the pH of the reaction solution to be 10, heating to 100 ℃ for reaction for 5 hours, dropwise adding dilute hydrochloric acid after the reaction is finished, adjusting the pH of the reaction solution to be 7, filtering, leaching filter cakes, collecting filtrate, and filtering at 130 DEG C^℃Concentrating the filtrate at 1000Pa, separating out solid to obtain off-white solid, and detecting (figure 2) to obtain target product 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxy phenyl ether29.9g, total yield 82.8%.

Example 3

The invention provides a synthesis method of 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxy phenyl ether, which comprises the following steps:

step (1): adding 17.3g (0.1mol) of 3-chloro-4-nitrophenol, 21.75g (0.15mol) of 3, 4-dichlorotrifluorotoluene, 80ml of solvent xylene and 0.865g (5%) of copper chloride into a reaction bottle, fully mixing and stirring the reaction liquid by adopting acoustic resonance, adjusting the pH value of the reaction liquid to be 9 by using potassium carbonate at the frequency of 500 times/minute, heating to 140 ℃ for reaction for 3 hours, stopping the reaction, filtering to obtain a filtrate containing an intermediate product of 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -chlorobenzene, and directly using the filtrate for the next step synthesis without separation and purification;

step (2): adding 30ml of toluene and 0.173g of triethylbenzylammonium chloride into the filtrate obtained in the step 1, adding 10.08g of sodium carbonate and 10.08g of potassium ethoxide in batches, fully stirring the reaction solution by adopting acoustic resonance, controlling the pH of the reaction solution to be 9, heating to 40 ℃ for reaction for 1h, dropwise adding dilute nitric acid after the reaction is finished, adjusting the pH of the reaction solution to be 7, filtering, leaching a filter cake, collecting filtrate, concentrating the filtrate at 100 ℃/2000Pa, and separating out solids to obtain 27.3g of an off-white solid menses detection body, namely the target product 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether, wherein the total yield is 75.6%.

Example 4

The invention provides a synthesis method of 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxy phenyl ether, which comprises the following steps:

step (1): adding 17.3g (0.1mol) of 3-chloro-4-nitrophenol, 17.4g (0.11mol) of 3, 4-dichlorotrifluorotoluene, 60ml of N, N-dimethylformamide as a solvent and 0.346g (2%) of copper oxide into a reaction bottle, fully mixing and stirring the reaction liquid by adopting acoustic resonance, adjusting the pH value of the reaction liquid to be 9 by adopting potassium hydroxide, heating to 110 ℃ for reaction for 7 hours, stopping the reaction, and filtering to obtain a filtrate containing an intermediate product of 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -chlorobenzene, wherein the filtrate is directly used for synthesis in the next step without separation and purification;

step (2): adding 20ml of N, N-dimethylformamide and 18-crown-60.0184 g into the filtrate obtained in the step 1, adding 7.48g of potassium carbonate and sodium ethoxide in batches, fully stirring the reaction solution by adopting acoustic resonance, controlling the pH of the reaction solution to be 8-10, heating to 70 ℃ for reaction for 3 hours, dropwise adding dilute hydrochloric acid after the reaction is finished, adjusting the pH of the reaction solution to be 7, filtering, leaching a filter cake, collecting the filtrate, concentrating the filtrate at 100 ℃/900Pa, separating out a solid, and detecting to obtain an off-white solid, namely 31.9g of the target product 2-chloro-4-trifluoromethylphenyl-4 '-nitro-3' -ethoxyphenyl ether, wherein the total yield is 88.35%.