Production method of quizalofop-p-ethyl

Abstract

The invention relates to a production method of quizalofop-p-ethyl, which comprises the following steps: reacting 2-(4-hydroxyphenoxy) propionic acid with absolute ethyl alcohol to obtain ethyl 2-(4-hydroxyphenoxy) propionate, and replacing the original process of reacting p-toluenesulfonyl chloride with L-ethyl lactate to obtain an intermediate, namely ethyl p-toluenesulfonyl lactate, with a process of reacting 2-(4-hydroxyphenoxy) propionic acid with absolute ethyl alcohol to obtain ethyl 2-(4-hydroxyphenoxy) propionate; meanwhile, in the post-treatment method, centrifugal separation replaces plate-and-frame pressure filtration, closed-circuit flash drying replaces original rake drying, racemization of quizalofop-p-ethyl is effectively avoided, the optical purity and yield of quizalofop-p-ethyl are improved, and the environmental protection benefits of the process are improved. Experiments show that the optical purity of the quizalofop-p-ethyl produced by the method provided by the invention is 99% or above, the yield is 98% or above, and the method is suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticide synthesis, and particularly relates to a production method of Quizalofop-P-ethyl. Background Art

[0002] Quizalofop-p-ethyl, commonly known in English as quizalofop-p-ethyl, is an aromatic oxyphenoxycarboxylic acid herbicide developed by Nissan Chemical Industries, Ltd. Its chemical name is (R)-ethyl 2-[4-(6-chloroquinoxaline-2-yloxy)phenoxy]propionate, its molecular formula is C19H17ClN2O4, CAS number: 100646-51-3, and its structural formula is as follows:

[0003]

[0004] There are many methods for preparing Quizalofop-Ph-ethyl. The currently common production method is: p-toluenesulfonyl chloride reacts with L-ethyl lactate to obtain an intermediate p-toluenesulfonyl ethyl lactate, and the intermediate p-toluenesulfonyl ethyl lactate reacts with the compound 6-chloro-2-(4-hydroxyphenoxy)quinoxaline to obtain Quizalofop-Ph-ethyl. This method produces a lot of wastewater during the production process, and the finished product contains some impurities of p-toluenesulfonyl ethyl lactate, resulting in low optical purity of the finished product. During the extraction process of the finished product, the finished product can only be filtered out of the solvent using a plate and frame filter press. In large-scale industrial production, the production of a batch of ethyl p-toluenesulfonyl lactate (5000L reactor) usually generates 3000L of wastewater (containing impurities and solvents) to be treated; in the reaction process of the intermediate ethyl p-toluenesulfonyl lactate and the compound 6-chloro-2-(4-hydroxyphenoxy)quinoxaline, a batch of (500 kg of 96% quizalofop-p-ethyl from a 5000L reactor) materials generates 4000 kg of sewage wastewater (containing impurities and solvents) to be treated; when separating quizalofop-p-ethyl from the solvent, a plate and frame filter is used, and then the finished product needs to be manually transported to a rake dryer for drying and packaging, and the optical content is unstable, and the product qualification rate is reduced.

[0005] Based on the quality requirements and environmental benefits of Quizalofop-Ph-ethyl, it is necessary to develop a production method of Quizalofop-Ph-ethyl that has high optical purity and is environmentally friendly and can achieve industrial production. Summary of the invention

[0006] The invention provides a production method of quizalofop-p-ethyl, wherein the process of 2-(4-hydroxyphenoxy)ethyl propionate is used to replace the original process of reacting p-toluenesulfonyl chloride with L-ethyl lactate to obtain an intermediate p-toluenesulfonyl ethyl lactate, thereby reducing the sewage discharge of the original process, and the centrifugal separation combined with flash drying in the post-treatment method of quizalofop-p-ethyl is environmentally friendly and effectively improves the optical purity of the product.

[0007] The technical solution adopted to achieve the above invention object is:

[0008] A method for producing Quizalofop-P-ethyl comprises the following steps:

[0009] 1) Under the condition of hydrochloric acid and ethanol, 2-(4-hydroxyphenoxy)propionic acid and ethanol are reacted to prepare ethyl 2-(4-hydroxyphenoxy)propionate;

[0010] 2) Under the condition of an acid-binding agent, condensing the ethyl 2-(4-hydroxyphenoxy)propionate obtained in step 1) with 2,6-dichloroquinoxaline in a first solvent to obtain a crude product of quizalofop-p-ethyl;

[0011] 3) removing the first solvent from the crude quizalofop-ethyl obtained in step 2), adding a second solvent to dissolve it, performing secondary desolventization, adding ethanol to cool and crystallize it, and centrifuging to obtain a refined quizalofop-ethyl;

[0012] 4) flash-drying the quizalofop-ethyl product obtained in step 3) to obtain a quizalofop-ethyl finished product.

[0013] Wherein, the acid binding agent in step 2) is sodium carbonate or potassium carbonate.

[0014] Wherein, the molar ratio of the 2,6-dichloroquinoxaline to the acid binding agent in step 2) is 1:1.75-1.85.

[0015] Wherein, in step 2) the first solvent is a polar organic solvent, preferably acetonitrile

[0016] Wherein, the molar ratio of ethyl 2-(4-hydroxyphenoxy)propionate to 2,6-dichloroquinoxaline in step 2) is 1-1:1.1.

[0017] Wherein, in step 3), the second solvent is toluene.

[0018] Wherein, the temperature of the cooling crystallization in step 3) is 0-2°C.

[0019] The technical solution of the present invention has at least the following beneficial technical effects:

[0020] 1. The process of reacting 2-(4-hydroxyphenoxy)propionic acid with anhydrous ethanol in the presence of hydrochloric acid and ethanol to obtain ethyl 2-(4-hydroxyphenoxy)propionate replaces the original process of reacting p-toluenesulfonyl chloride with ethyl L-lactate to obtain the intermediate ethyl p-toluenesulfonyl lactate, thereby reducing the wastewater discharge of the original process. The invention now produces only 500 kg of wastewater per batch in the synthesis process, which is 3,500 kg / batch less than that of the original process. At the same time, the optical purity of the product is effectively improved.

[0021] 2. The present invention replaces plate and frame filter pressing with centrifugal separation, and combines closed-circuit flash drying to replace the original rake drying, thereby effectively avoiding the racemization of Quizalofop-Ph-ethyl and improving the optical purity and yield of Quizalofop-Ph-ethyl. Experiments show that the optical purity of Quizalofop-Ph-ethyl produced by the method provided by the present invention is above 99%, and the yield is above 98%. It is suitable for industrial production. DETAILED DESCRIPTION

[0022] The present invention will be further described below in conjunction with specific examples. It should be understood that the following examples are only used to illustrate the present invention and are not used to limit the scope of the present invention.

[0023] In the following examples, ethyl 2-(4-hydroxyphenoxy)propionate was prepared by reacting 2-(4-hydroxyphenoxy)propionic acid with ethanol under hydrochloric acid and ethanol conditions.

[0024] In the following examples and comparative examples, the total ester content and optical content of Quizalofop-Ph-ethyl were detected according to the industry standard "HG3671-2018 Quizalofop-Ph-ethyl Technical Drug".

[0025] Example 1

[0026] 415 kg of ethyl 2-(4-hydroxyphenoxy)propionate was added to 2500 kg of acetonitrile in an ester dissolving kettle and dissolved. Then the mixture was put into a synthesis reactor. After 400 kg of 2,6-dichloroquinoxaline and 550 kg of potassium carbonate were added, the temperature was raised to reflux, and the reaction was maintained under reflux for 5 hours. After the analysis results were qualified, the temperature was lowered to 40°C and the material was discharged to a plate and frame filter press to filter out the potassium carbonate, and then the acetonitrile was distilled out of the desolventizing kettle. In the early stage, acetonitrile was distilled under normal pressure, and in the later stage, the temperature was controlled not to exceed 110°C under a negative pressure of -0.09MPa or more and the desolventizing was completed for 5 minutes; the temperature was lowered to 85°C, 2500 kg of toluene was added, the temperature was maintained at about 45°C, and the mixture was stirred and dissolved, and then the mixture was transferred to a decolorizing kettle. After adding activated carbon, the temperature of the decolorizing kettle was maintained at about 60°C, and the mixture was kept warm and decolorized for one hour. After filtering through a precision filter, the mixture was put into a water washing kettle. 500 kg of water was added to the water washing kettle, stirred and washed, and the lower aqueous phase was separated into a sewage tank after standing for one hour. The oil layer was put into a toluene concentration kettle for negative pressure concentration. Toluene was removed by pressure; after all the toluene was removed, 3200 kg of ethanol was added to dissolve it and then the material was transferred to the dropping kettle. 500 kg of ethanol was prepared in the crystallization kettle, and the temperature was lowered to below -5°C, and the material in the dropping kettle was slowly added dropwise to the crystallization kettle. The temperature of the crystallization kettle was controlled to be below 15°C for crystallization. After crystallization, the material was cooled to about 0-2°C and then discharged to a centrifuge to separate Quizalofop-Ph-ethyl and closed-circuit flash drying was performed to obtain 743 kg of Quizalofop-Ph-ethyl crystals with a content of more than 98%. After testing, the chemical content of Quizalofop-Ph-ethyl was 98.0%, the yield was 98.0%, and the optical purity was 99.8%.

[0027] Comparative Example 1

[0028] Add 460kg and 53kg of caustic soda flakes into the kettle for phenol salt preparation and stir for 30 minutes. After nitrogen replacement, add 136kg of hydroquinone, slightly open the nitrogen protection, stir for 1 hour, and then use a pump to pump into the phenol salt high-level tank; after adding 700kg of water into the etherification kettle, add 215kg of dichloroethane, 2kg of toluene, and 25kg of ethanol in turn; open the kettle and stir, slowly raise the temperature to about 90℃, and start dripping the phenol salt pre-injected into the tank, the dripping temperature is between 90-92℃, and the dripping is completed in 2.5-3 hours, and the temperature is kept at 92-95℃ for 8 hours. After the insulation is completed, add water 600kg is diluted and cooled, and the material is passed into the acidification kettle. After the material is passed, 5% hydrochloric acid is added dropwise to adjust the pH to 10. After fully stirring for 30 minutes, the material is discharged into the centrifuge; the centrifuge is fully cleaned with about 7000L of 80°C water, and the solid product is separated and enters the flash dryer. After drying, 260kg of dry product phenoxyquinoxaline [6-chloro-2-(4-hydroxyphenoxy)quinoxaline, referred to as etherified product] with a content of 96% is obtained and packed in bags and transported to the next stage for feeding.

[0029] Put 2100 kg of toluene and measured magnesium sulfate into the reactor, then cool it to 0°C and add measured flake caustic soda. Continue to cool it to -5°C and add 450 kg of acid chloride. After stirring for half an hour, start adding ethyl lactate dropwise, keeping the temperature below -5°C until 320 kg is added. After the sampling is qualified, add 1000 kg of water and raise the temperature to 18°C. Then transfer the material to the washing kettle for acidification to adjust the pH value. After acidification, let it stand for separation of sodium salt. Then add 2000 kg of water in 2 batches for washing. After the water is separated, measure the pH value to neutral, then transfer the material to the distillation kettle for negative pressure distillation to separate the toluene. After the toluene is evaporated, cool it to 80°C and discharge the material to obtain 720 kg of 97% sulfonate (ethyl p-toluenesulfonyl lactate), which is barreled and put into the drying room for insulation and standby.

[0030] After 1700 kg of petroleum ether, 425 kg of etherified product and 325 kg of potassium carbonate were added into the synthesis reactor, 430 kg of ethyl p-toluenesulfonyl lactate was slowly added dropwise. After the addition was completed, the mixture was kept warm and refluxed for several hours, and the sample was tested and qualified to end the reaction. After adding 1000 kg of water, it was stirred and allowed to stand for half an hour to start sealing the potassium carbonate wastewater. After the water separation was completed, activated carbon was added for decolorization. After pressure filtration, the filtrate entered the washing kettle and 1000 kg of water was added to wash. After the water washing and stratification, the water was separated. The oil layer entered the desolventizing kettle under negative pressure to recover the petroleum ether. The temperature was raised to 83°C, the steam valve was closed, and the temperature was naturally raised and dried for 30 minutes. The final temperature did not exceed 95°C. The negative pressure was -0.08-0.09 MPa and the petroleum ether recovery was completed. After slowly adding 2600 kg of ethanol and 10 kg of activated carbon, it was hot filtered through a plate and frame filter press to a crystallization kettle. After the crystallization was completed, the plate and frame filter was pressed. The filter cake was sent to a rake dryer for drying and then packaged to obtain 500 kg of quizalofop-ethyl finished product. The filtrate was recycled for secondary treatment. After testing, the chemical content of Quizalofop-Ph-ethyl was 96.0%, the yield was 94.3%, and the optical purity was 95%.

[0031] Comparative Example 2

[0032] The same process as in Example 1 was performed except that the centrifugal separation step was replaced by plate and frame filtration to obtain 710 kg of product.

[0033] The chemical content of Quizalofop-Ph-ethyl is 93.3%, the yield is 93.6%, and the optical purity is 95%.

[0034] Comparative Example 3

[0035] The same process as in Example 1 was followed except that the rake drying step was replaced by flash drying to obtain 720 kg of product.

[0036] The chemical content of Quizalofop-Ph-ethyl is 96.5%, the yield is 94.5%, and the optical purity is 96%.

[0037] Comparison table of embodiments and comparative examples

[0038]

[0039] As can be seen from the table, the Quizalofop-ethyl obtained by the production method provided by the present invention has high single-batch yield, high content, easy separation, high degree of automation, low occupational hazards, and has a wider range of applications.

[0040] The above embodiments are only used to help understand the method and core idea of ​​the present invention. It should be noted that, for those skilled in the art, several improvements and modifications can be made to the present invention without departing from the principles of the present invention, and these improvements and modifications also fall within the scope of protection of the claims of the present invention.

Claims

1. A method for producing Quizalofop-P-ethyl, comprising the following steps: 1) Under the condition of hydrochloric acid and ethanol, 2-(4-hydroxyphenoxy)propionic acid and ethanol are reacted to prepare ethyl 2-(4-hydroxyphenoxy)propionate; 2) Under the condition of an acid-binding agent, condensing the ethyl 2-(4-hydroxyphenoxy)propionate obtained in step 1) with 2,6-dichloroquinoxaline in a first solvent to obtain a crude product of quizalofop-p-ethyl; 3) removing the first solvent from the crude quizalofop-ethyl obtained in step 2), adding a second solvent to dissolve it, performing secondary desolventization, adding ethanol to cool and crystallize it, and centrifuging to obtain a refined quizalofop-ethyl; 4) flash-drying the quizalofop-ethyl product obtained in step 3) to obtain a quizalofop-ethyl finished product.

2. The production method according to claim 1, characterized in that Step 2) the acid binding agent is sodium carbonate or potassium carbonate.

3. The production method according to claim 1, characterized in that In step 2), the molar ratio of 2,6-dichloroquinoxaline to the acid-binding agent is 1:1.75-1.

85.

4. The production method according to claim 1, characterized in that Step 2) The first solvent is a polar organic solvent.

5. The production method according to claim 4, characterized in that The polar organic solvent is acetonitrile.

6. The production method according to claim 1, characterized in that In step 2), the molar ratio of ethyl 2-(4-hydroxyphenoxy)propionate to 2,6-dichloroquinoxaline is 1-1:1.

1.

7. The production method according to claim 1, characterized in that Step 3) The second solvent is toluene.

8. The production method according to claim 1, characterized in that Step 3) The temperature of the cooling crystallization is 0-2°C.

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