CN114380771B - The preparation method of flufenacet - Google Patents

Abstract

The invention relates to the technical field of organic synthesis, in particular to a method for preparing flufenacet. The preparation method of the flufenacet comprises the following steps: (a) 2-methylsulfonyl-5-trifluoromethyl-1, 3, 4-thiadiazole or 2-chloro-5-trifluoromethyl-1, 3, 4-thiadiazole reacts with a compound A in a solvent containing alkali to obtain a compound B; (b) And (3) carrying out transesterification reaction on the compound B and 4-fluoro-N-isopropylaniline in a solvent under the action of a catalyst to obtain the flufenacet. The preparation method of the flufenacet has the advantages of easily available raw materials, safe and reliable raw materials, and no chlorine-containing waste in the preparation process. In addition, the flufenacet is prepared from the glycolate as the initial raw material, and the flufenacet product can be obtained in two steps, so that the reaction route is greatly shortened, the post-treatment operation is simplified, and the like.

Description

The preparation method of flufenacet

technical field

The invention relates to the technical field of organic synthesis, in particular to a preparation method of flufenacet.

Background technique

Flufenacet (Flufenacet) chemical name is 4'-fluoro-N-isopropyl-2-(5-trifluoromethyl-1,3,4-thiadiazol-2-yloxy) acetylanilide, 4'-fluoro-N-isopropyl-2-(5-trifluoromethyl-1,3,4-thiadiazol-2-yloxy)acetanilide, is an aryloxyamide herbicide, mainly by inhibiting Cell division and growth play a role. It has the advantages of high herbicidal activity, wide herbicidal spectrum, wide range of applicable crops, and high safety. It can effectively control annual grass weeds and broad-leaved weeds before and after early weeding. It was first introduced by Bayer CropScience in 1998. During the preparation process, 2-thiamphenicol-5-trifluoromethyl-1,3,4-thiadiazole was used as the starting material to react with 2-hydroxy-N-(4-fluoroaniline)-N-(1-methylethyl)acetamide to obtain the product flufenacet. The synthetic route is as follows:

The disadvantage of the above synthesis route is that a large amount of chlorine-containing waste products are formed during the synthesis of the intermediate 2-hydroxyl-N-(4-fluoroaniline)-N-(1-methylethyl)acetamide. Secondly, chloroacetyl chloride is a dangerous product, and its transportation and storage are restricted; during use, it releases heat quickly, and if it is added too quickly, it will easily heat up and flush the material. In addition, the above-mentioned synthetic route has many steps, and each additional step will lead to a decrease in yield and increase the number of purifications, resulting in a poor final yield. How to reduce or even not produce chlorine-containing waste products, reduce safety risks without using hazardous materials, and reduce reaction steps to increase yield are problems to be solved urgently in the preparation process of flufenacet.

In view of this, the present invention is proposed.

Contents of the invention

The purpose of the present invention is to provide a preparation method of flufenacet to solve the technical problems of low raw material safety, cumbersome steps and low yield in the prior art.

In order to realize the above-mentioned purpose of the present invention, special adopt following technical scheme:

The preparation method of flufenacet, comprises the steps:

(a) 2-thiamphenicol-5-trifluoromethyl-1,3,4-thiadiazole or 2-chloro-5-trifluoromethyl-1,3,4-thiadiazole reacts with compound A in a solvent containing alkali to obtain compound B;

(b) Compound B and 4-fluoro-N-isopropylaniline are subjected to a transesterification reaction in a solvent under the action of a catalyst to obtain flufenacet;

Wherein, the structural formulas of compound A and compound B are respectively as follows:

R is selected from any one or more of alkyl groups with 1 to 4 carbon atoms.

In the preparation method of flufenacet of the present invention, the raw materials are easy to obtain, and the raw materials are safe and reliable, and at the same time, chlorine-containing wastes are basically not generated in the preparation process. Moreover, the flufenacet of the present invention uses glycolate as the starting material, and only two steps are needed to obtain the flufenacet product, which greatly shortens the reaction route and simplifies post-treatment operations.

In a specific embodiment of the present invention, the R is selected from any one or more of methyl (Me), ethyl (Et), n-butyl (n-Bu) and tert-butyl (t-Bu).

In a specific embodiment of the present invention, in step (a), the molar ratio of the compound A to the 2-thiasulfonyl-5-trifluoromethyl-1,3,4-thiadiazole or the 2-chloro-5-trifluoromethyl-1,3,4-thiadiazole is 1:(0.5-2).

In a specific embodiment of the present invention, in step (a), the alkali includes any one or more of sodium hydroxide, sodium carbonate, potassium carbonate and sodium methoxide.

In a specific embodiment of the present invention, in step (a), the temperature of the reaction is -5-40°C.

In a specific embodiment of the present invention, in step (a), the solvent includes water and an organic solvent. Further, the organic solvent includes toluene.

In a specific embodiment of the present invention, in step (b), the molar ratio of the compound B to the 4-fluoro-N-isopropylaniline is 1:(0.5-2).

In a specific embodiment of the present invention, in step (b), the catalyst includes any one or more of sodium hydroxide, sodium carbonate, potassium carbonate, sodium methylate, triethylamine, potassium tert-butoxide, ammonia, pyridine, nickel trifluoromethanesulfonate and acetic acid.

In a specific embodiment of the present invention, in step (b), the temperature of the reaction is 20-100°C.

In a specific embodiment of the present invention, in step (b), the solvent includes water and an organic solvent. Further, the organic solvent includes toluene.

Compared with prior art, the beneficial effect of the present invention is:

The present invention uses glycolate as a starting raw material, only needs two steps to obtain the flufenacet product, has a short reaction route, high product yield, and good product quality; and glycolate is used as a raw material, has high safety and non-corrosion, basically does not generate chlorine-containing waste in the preparation process, and has a wide range of sources.

Detailed ways

The technical solution of the present invention will be clearly and completely described below in conjunction with specific embodiments, but those skilled in the art will understand that the embodiments described below are some embodiments of the present invention, rather than all embodiments, and are only used to illustrate the present invention, and should not be considered as limiting the scope of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts belong to the protection scope of the present invention. Those who do not indicate the specific conditions in the examples are carried out according to the conventional conditions or the conditions suggested by the manufacturer. The reagents or instruments used were not indicated by the manufacturer, and they were all conventional products that could be purchased from the market.

The preparation method of flufenacet, comprises the steps:

(a) 2-thiamphenicol-5-trifluoromethyl-1,3,4-thiadiazole or 2-chloro-5-trifluoromethyl-1,3,4-thiadiazole reacts with compound A in a solvent containing alkali to obtain compound B;

(b) Compound B and 4-fluoro-N-isopropylaniline are subjected to a transesterification reaction in a solvent under the action of a catalyst to obtain flufenacet;

Wherein, the structural formulas of compound A and compound B are respectively as follows:

R is selected from any one or more of alkyl groups with 1 to 4 carbon atoms.

In the preparation method of flufenacet of the present invention, the raw materials are easy to obtain, and the raw materials are safe and reliable, and at the same time, chlorine-containing wastes are basically not generated in the preparation process. Moreover, the flufenacet of the present invention uses glycolate as the starting material, and only two steps are needed to obtain the flufenacet product, which greatly shortens the reaction route and simplifies post-treatment operations.

In the prior art, chloroacetyl chloride is used as the starting material, and four-step reactions are required to obtain the flufenacet product. Moreover, chloroacetyl chloride is a hazardous chemical with acidic and corrosive properties. The transportation process of chloroacetyl chloride requires a dangerous goods vehicle, and special storage tanks are required for storage. The storage and transportation safety is low and the cost is high. When chloroacetyl chloride is heated or decomposed with water, it will release toxic and corrosive fumes, causing potential safety hazards. The glycolic acid ester used in the present invention is not a hazardous chemical, stable in water and non-corrosive.

Chloroacetyl chloride is used to produce sodium chloride, which can only be treated as solid hazardous waste, and the treatment cost is expensive. However, the use of glycolic acid ester in the present invention does not produce sodium chloride, and the methanol or ethanol produced can be recycled.

Chloroacetyl chloride is used as the starting raw material, and the impurity dichloroacetyl chloride content in the raw material is usually about 0.5%, which will affect the quality of the obtained flufenacet product. There is no corresponding impurity in the glycolic acid ester, and the obtained flufenacet product is of good quality.

In addition, in the process of using chloroacetyl chloride as the starting material to prepare flufenacet, it is necessary to carry out substitution reaction with sodium acetate, and then hydrolyze with sodium hydroxide. The reaction operation is complicated, which increases the amount of materials and solvents, and both require heating operation, which increases energy consumption.

In a specific embodiment of the present invention, the R is selected from any one or more of methyl (Me), ethyl (Et), propyl (n-Pr), isopropyl (i-Pr), n-butyl (n-Bu), isobutyl (i-Bu) and tert-butyl (t-Bu). Further, the R is selected from any one or more of methyl (Me), ethyl (Et), n-butyl (n-Bu) and tert-butyl (t-Bu).

When R is methyl, the compound A is methyl glycolate; when R is ethyl, the compound A is ethyl glycolate; when R is n-butyl, the compound A is butyl glycolate; when R is tert-butyl, the compound A is tert-butyl glycolate. Wherein, R is selected from any one or more of various groups, and one or more than two compounds A can be used as raw materials to prepare flufenacet.

In a specific embodiment of the present invention, in step (a), the molar ratio of the compound A to the 2-thiasulfonyl-5-trifluoromethyl-1,3,4-thiadiazole or the 2-chloro-5-trifluoromethyl-1,3,4-thiadiazole is 1:(0.5-2).

As in different embodiments, in step (a), the molar ratio of the compound A to the 2-thiamphenyl-5-trifluoromethyl-1,3,4-thiadiazole or the 2-chloro-5-trifluoromethyl-1,3,4-thiadiazole can be 1:0.5, 1:0.8, 1:1, 1:1.2, 1:1.5, 1:1.8, 1:2.

In a specific embodiment of the present invention, in step (a), the alkali includes any one or more of sodium hydroxide, sodium carbonate, potassium carbonate and sodium methoxide.

In a specific embodiment of the present invention, in step (a), the molar ratio of the base to the compound A is (1-1.5):1.

As in different embodiments, in step (a), the molar ratio of the base to the compound A can be 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1 and so on. In actual operation, the amount of the alkali can be adjusted according to the actual situation.

In a specific embodiment of the present invention, in step (a), the temperature of the reaction is -5-40°C.

As in different embodiments, in step (a), the temperature of the reaction may be -5°C, 0°C, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C and so on.

In actual operation, the reaction time of step (a) can be adjusted according to the reaction degree monitored by actual TLC, and can be 1-4 hours, such as 2 hours and so on.

In a specific embodiment of the present invention, in step (a), the solvent includes water and an organic solvent. Further, the organic solvent includes toluene.

As in different embodiments, in step (a), the ratio of the amount of the organic solvent to the compound A can be 400-600 mL/1 mol, which means that the amount of the organic solvent used is 400-600 mL per 1 mol of compound A.

In a specific embodiment of the present invention, step (a) includes: mixing 2-thiamphenicol-5-trifluoromethyl-1,3,4-thiadiazole or 2-chloro-5-trifluoromethyl-1,3,4-thiadiazole with compound A in an organic solvent, adding an aqueous alkali solution, and reacting to obtain a reaction solution containing compound B, which is collected after post-processing.

As in different embodiments, in step (a), the alkali can be dissolved in water in advance to obtain an aqueous alkali solution, and then added to the remaining materials (2-thiamphenicol-5-trifluoromethyl-1,3,4-thiadiazole or the 2-chloro-5-trifluoromethyl-1,3,4-thiadiazole, compound A and organic solvent). The volume ratio of the organic solvent to the alkali aqueous solution may be (2-3):1; the mass fraction of the alkali aqueous solution may be 10wt%-40wt%.

In a specific embodiment of the present invention, the post-treatment includes: collecting the organic phase in the reaction solution, and then distilling off the solvent under reduced pressure to obtain the compound B. Further, the temperature of the vacuum distillation is 70-75°C.

In actual operation, step (a) may not be post-treated first, and the reaction solution containing compound B obtained by the reaction is directly subjected to the next step reaction to prepare flufenacet.

In a specific embodiment of the present invention, in step (b), the molar ratio of the compound B to the 4-fluoro-N-isopropylaniline is 1:(0.5-2).

As in different embodiments, in step (b), the molar ratio of the compound B to the 4-fluoro-N-isopropylaniline can be 1:0.5, 1:0.8, 1:1, 1:1.2, 1:1.5, 1:1.8, 1:2.

In a specific embodiment of the present invention, in step (b), the catalyst includes any one or more of sodium hydroxide, sodium carbonate, potassium carbonate, sodium methylate, triethylamine, potassium tert-butoxide, ammonia, pyridine, nickel trifluoromethanesulfonate, sodium phosphate and acetic acid.

In a specific embodiment of the present invention, in step (b), the molar ratio of the catalyst to the compound B is (0.05-1.5):1.

As in different embodiments, the molar ratio of the catalyst to the compound B can be 0.05:1, 0.1:1, 0.5:1, 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1 and so on. In actual operation, the dosage of the catalyst can be adjusted according to the actual situation, for example, it can also be 0.0005:1, etc., as long as the catalytic reaction can proceed.

In a specific embodiment of the present invention, in step (b), the temperature of the reaction is 20-100°C.

As in different embodiments, in step (b), the temperature of the reaction may be 20°C, 30°C, 40°C, 50°C, 60°C, 70°C, 80°C, 90°C, 100°C and so on.

In actual operation, the reaction time of step (b) can be adjusted according to the reaction degree monitored by actual TLC, and can be 1-4 hours, such as 2 hours and so on.

In a specific embodiment of the present invention, in step (b), the solvent includes water and an organic solvent. Further, the organic solvent includes toluene.

As in different embodiments, in step (b), the ratio of the amount of the organic solvent to the compound B can be 400-600 mL/1 mol, which means that the amount of the organic solvent used is 400-600 mL per 1 mol of compound B.

In a specific embodiment of the present invention, step (b) includes: mixing compound B and 4-fluoro-N-isopropylaniline in an organic solvent, adding a catalyst, reacting to obtain a reaction solution containing flufenacet, and collecting the flufenacet after post-processing.

In practice, the catalyst can be added in the form of an aqueous solution.

As in different embodiments, in step (b), the catalyst can be dissolved in water in advance to obtain an aqueous solution of the catalyst, and then added to the remaining materials (compound B, 4-fluoro-N-isopropylaniline and organic solvent). The volume ratio of the organic solvent to the catalyst aqueous solution may be (2-3):1; the mass fraction of the catalyst aqueous solution may be 1wt%-30wt%.

In a specific embodiment of the present invention, the preparation method of flufenacet comprises the following steps:

(a) reacting 2-thiamphenicol-5-trifluoromethyl-1,3,4-thiadiazole or 2-chloro-5-trifluoromethyl-1,3,4-thiadiazole with compound A in a solvent containing alkali to obtain a reaction solution containing compound B;

(b) The reaction solution containing compound B is mixed with 4-fluoro-N-isopropylaniline to carry out transesterification reaction to obtain flufenacet.

In the preparation method of flufenacet of the present invention, after the reaction in step (a) is completed, post-treatment may not be performed first, and 4-fluoro-N-isopropylaniline is directly added to the reaction solution obtained in step (a) for mixed reaction to obtain a reaction solution containing flufenacet, and the pure flufenacet is obtained by separation, which simplifies the post-treatment operation.

In actual operation, the aqueous solution of the catalyst and 4-fluoro-N-isopropylaniline can be added to the reaction solution obtained in step (a), or the amount of alkali and solvent in step (a) can be directly increased (the capacity of the added alkali and solvent is adjusted according to the amount required in step (b)), and the reaction solution can be obtained, and then 4-fluoro-N-isopropylaniline can be added to the reaction solution in step (b) for reaction.

In actual operation, step (a) and step (b) can be carried out in tank reactor or microchannel reactor. If carried out in a microchannel reactor, the inner diameter of the microchannel reactor can be 1-50mm, the residence time can be 20-200s, and the flow rate of the reaction solution in the microchannel reactor can be 1-5m/min.

The synthetic route of the present invention can refer to as follows:

Example 1

This embodiment provides the preparation method of flufenacet, the synthetic route is as follows:

Specifically, the following steps are included:

(1) Weigh 90g (1mol) of methyl glycolate, 232g (1mol, 1.0eq) of 2-thiamphenyl-5-trifluoromethyl-1,3,4-thiadiazole, and 500mL of toluene, and add them to a 1000mL three-neck flask at one time, stir and mix to obtain a mixed solution; add 200mL of 20wt% sodium hydroxide aqueous solution to the mixed solution, and stir the reaction at 20°C for 2h to obtain a reaction solution; separate and remove the water phase in the reaction solution, collect organic phase, and then the organic phase was distilled off toluene under reduced pressure at 70～75°C to obtain 2-glycolic acid methyl ester-5-trifluoromethyl-1,3,4-thiadiazole (compound B₁) 235g, the yield is 97.0%, and the HPLC detection content is 99.3%.

(2) Weigh the whole batch of product 2-glycolic acid methyl ester-5-trifluoromethyl-1,3,4-thiadiazole (235g), 4-fluoro-N-isopropylaniline 149g (1.0eq) and toluene (500mL) into a 2000mL three-necked flask at one time, stir and mix to obtain a mixed solution; add 20wt% sodium hydroxide aqueous solution to the mixed solution. React for 2 hours to obtain a reaction solution; separate and remove the water phase in the reaction solution, collect the organic phase, then distill the organic phase at 70-75° C. to remove toluene under reduced pressure to collect the solid, and dry the solid to obtain 335 g of flufenacet, with a yield of 95.1%. The content detected by HPLC was 99.6%.

Example 2

This embodiment refers to the preparation method of flufenacet in Example 1, the only difference is that the base in step (1) is different. This embodiment adopts the aqueous solution of 35.3wt% sodium carbonate of 300mL to replace the aqueous solution of 200mL of 20wt% sodium hydroxide in the step (1) of embodiment 1. The mass of methyl 2-glycolate-5-trifluoromethyl-1,3,4-thiadiazole (compound B ₁ ) obtained in step (1) was 230 g, the yield was 95.0%, and the content detected by HPLC was 99.1%.

Example 3

This embodiment refers to the preparation method of flufenacet in Example 1, the only difference is that the catalysts in step (2) are different. In this embodiment, 1000 mL of an aqueous solution of 38 wt % sodium phosphate (calculated as sodium phosphate dodecahydrate) is used to replace the 200 mL aqueous solution of 20 wt % sodium hydroxide in step (2) of Example 1. The mass of flufenacet obtained in step (2) was 340 g, the yield was 96.5%, and the content detected by HPLC was 99.1%.

Example 4

This embodiment refers to the preparation method of flufenacet in Example 1, the only difference is that the catalysts in step (2) are different. In this embodiment, 20 mL of 20 wt % aqueous acetic acid was used to replace the 200 mL of 20 wt % sodium hydroxide aqueous solution in step (2) of Example 1. The mass of flufenacet obtained in step (2) was 330 g, the yield was 93.6%, and the content detected by HPLC was 99.3%.

Example 5

This embodiment refers to the preparation method of flufenacet in Example 1, the only difference is that the catalysts in step (2) are different. In this embodiment, 10 mL of 2 wt % nickel trifluoromethanesulfonate aqueous solution was used to replace the 200 mL of 20 wt % sodium hydroxide aqueous solution in step (2) of Example 1. The mass of flufenacet obtained in step (2) was 331 g, the yield was 93.9%, and the content detected by HPLC was 99.0%.

Example 6

This embodiment provides the preparation method of flufenacet, comprising the following steps:

(1) Weigh 90g (1mol) of methyl glycolate, 232g (1mol, 1.0eq) of 2-thiamphenyl-5-trifluoromethyl-1,3,4-thiadiazole, and 500mL of toluene, and add them to a 1000mL three-neck flask at one time, stir and mix to obtain a mixed solution; add 400mL of 20wt% sodium hydroxide aqueous solution to the mixed solution, and stir the reaction at 20°C for 2h to obtain a reaction solution.

(2) Add 153 g (1 mol, 1.0 eq) of 4-fluoro-N-isopropylaniline to the reaction liquid obtained in step (1), raise the temperature to 50° C., stir and react for 2 hours to obtain a reaction liquid; separate and remove the water phase in the reaction liquid, collect the organic phase, then distill the organic phase at 70 to 75° C. to remove toluene to collect a solid, and dry the solid to obtain 359 g of flufenacet, with a total yield of 98.8%. The content detected by HPLC was 99.1%.

Example 7

This embodiment provides the preparation method of flufenacet, comprising the following steps:

500mL of toluene, 232g (1mol, 1.0eq) of 2-thiamphenicol-5-trifluoromethyl-1,3,4-thiadiazole were mixed evenly, and 90g (1mol) of methyl glycolate and 200mL of 20wt% sodium hydroxide aqueous solution were put into the mixer. The feed liquid at the discharge port and 153g (1mol, 1.0eq) of 4-fluoro-N-isopropylaniline enter the mixer, and after mixing evenly, enter the microchannel reactor with an inner diameter of 15mm. The residence time is set to 20s, the temperature is 50-55°C, and the flow rate of the reaction solution in the reactor is 5.0m/min. Collect the feed liquid at the discharge port, separate and remove the water phase, collect the organic phase, then distill the organic phase at 70-75° C. to remove the toluene to collect the solid, and dry the solid to obtain 362 g of flufenacet, with a total yield of 99.6%. HPLC content 99.5%.

Example 8

This embodiment provides the preparation method of flufenacet, the synthetic route is as follows:

Concrete reference example 1, the difference is only: the methyl glycolate of step (1) is replaced by equimolar ethyl glycolate.

238 g of ethyl 2-glycolate-5-trifluoromethyl-1,3,4-thiadiazole (compound B ₂ ) obtained in step (1), the yield was 92.9%, and the content detected by HPLC was 99.3%;

Step (2) Weigh the entire batch of product 2-glycolic acid ethyl ester-5-trifluoromethyl-1,3,4-thiadiazole (238g) in the step (1) to obtain 316g of flufenacet, the yield is 93.6%, and the content detected by HPLC is 98.1%.

Example 9

This embodiment provides the preparation method of flufenacet, the synthetic route is as follows:

Concrete reference example 1, the difference is only: the methyl glycolate of step (1) is replaced by equimolar butyl glycolate.

274 g of 2-butyl glycolate-5-trifluoromethyl-1,3,4-thiadiazole (compound B ₃ ) obtained in step (1), the yield was 96.4%, and the content detected by HPLC was 97.1%;

Step (2) Weigh 274 g of the whole batch of product 2-butyl glycolate-5-trifluoromethyl-1,3,4-thiadiazole in step (1) to obtain 310 g of flufenacet, the yield is 88.5%, and the content detected by HPLC is 97.3%.

Example 10

This embodiment provides the preparation method of flufenacet, the synthetic route is as follows:

Concrete reference example 1, the only difference is: the methyl glycolate of step (1) is replaced by equimolar tert-butyl glycolate.

266 g of 2-tert-butyl glycolate-5-trifluoromethyl-1,3,4-thiadiazole (compound B ₄ ) obtained in step (1), the yield was 93.6%, and the content detected by HPLC was 97.1%;

Step (2) Weigh 266 g of the whole batch of product 2-tert-butyl glycolate-5-trifluoromethyl-1,3,4-thiadiazole in step (1) to obtain 313 g of flufenacet, the yield is 92.1%, and the content detected by HPLC is 96.3%.

Example 11

This embodiment provides the preparation method of flufenacet, the synthetic route is as follows:

Specifically, the following steps are included:

(1) Weigh 90g (1mol) of methyl glycolate, 188g (1mol, 1.0eq) of 2-chloro-5-trifluoromethyl-1,3,4-thiadiazole, and 500mL of toluene, and add them to a 1000mL three-neck flask at one time, stir and mix to obtain a mixed solution; add 200mL of an aqueous solution of 20wt% sodium hydroxide to the mixed solution, and stir the reaction at 20°C for 2h to obtain a reaction solution; separate and remove the water phase in the reaction solution, and collect the organic phase , and then the organic phase was distilled off toluene under reduced pressure at 70～75° C. to obtain methyl 2-glycolate-5-trifluoromethyl-1,3,4-thiadiazole (compound B₁) 230g, the yield is 95.0%, and the HPLC detection content is 99.1%.

(2)称取步骤(1)中全批产物2-乙醇酸甲酯-5-三氟甲基-1,3,4-噻二唑230g(化合物B ₁ )、4-氟-N-异丙基苯胺146g(1.0eq)及甲苯(500mL)一次性加入2000mL三口瓶中，搅拌混合得到混合溶液；向所述混合溶液中加入20wt％氢氧化钠水溶液200mL，升温，在50℃的条件下，搅拌反应2h得到反应液；分离除去所述反应液中的水相，收集有机相，然后将所述有机相于70～75℃减压蒸馏除去甲苯收集固体，将固体烘干得到氟噻草胺330g，收率95.6％。 The content detected by HPLC was 99.2%.

Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, but not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: it can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements for some or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.

Claims (8)

1. The preparation method of the flufenacet is characterized by comprising the following steps:

(a) 2-methylsulfonyl-5-trifluoromethyl-1, 3, 4-thiadiazole or 2-chloro-5-trifluoromethyl-1, 3, 4-thiadiazole reacts with a compound A in a solvent containing alkali to obtain a compound B;

(b) Under the action of a catalyst, the compound B and 4-fluoro-N-isopropylaniline perform transesterification in a solvent to obtain flufenacet;

wherein, the structural formulas of the compound A and the compound B are respectively as follows:

and->The method comprises the steps of carrying out a first treatment on the surface of the R is selected from any one or more of alkyl groups with carbon number of 1-4;

in the step (a), the alkali is any one or more of sodium hydroxide, sodium carbonate, potassium carbonate and sodium methoxide;

in step (a), the solvent comprises water and an organic solvent comprising toluene;

in the step (a), the molar ratio of the compound A to the 2-methylsulfonyl-5-trifluoromethyl-1, 3, 4-thiadiazole or the 2-chloro-5-trifluoromethyl-1, 3, 4-thiadiazole is 1: (0.5-2);

in the step (a), the molar ratio of the alkali to the compound A is (1-1.5) to 1;

in the step (a), the reaction temperature is-5-40 ℃.

2. The method for preparing flufenacet according to claim 1, wherein R is selected from any one or more of methyl, ethyl, n-butyl and t-butyl.

3. The method for producing flufenacet according to claim 1, wherein in the step (B), the molar ratio of the compound B to the 4-fluoro-N-isopropylaniline is 1: (0.5-2).

4. The method for preparing flufenacet according to claim 1, wherein in the step (b), the catalyst comprises any one or more of sodium hydroxide, sodium carbonate, potassium carbonate, sodium methoxide, triethylamine, potassium tert-butoxide, ammonia gas, pyridine, nickel triflate and acetic acid.

5. The method according to claim 4, wherein in the step (B), the molar ratio of the catalyst to the compound B is (0.05 to 1.5):1.

6. The method for preparing flufenacet according to claim 1, wherein in the step (b), the reaction temperature is 20-100 ℃.

7. The method for preparing flufenacet according to claim 1, wherein in the step (b), the solvent comprises water and an organic solvent.

8. The method for preparing flufenacet according to claim 7, wherein in the step (b), the organic solvent comprises toluene.