阅读说明：本技术 氟虫腈的合成方法 (Method for synthesizing fipronil ) 是由 K·H·格哈达 D·谢诺伊 L·谢特 Y·萨曼加德卡尔 A·S·卡瓦德 于 2020-02-24 设计创作，主要内容包括：本公开涉及广谱杀虫剂(I)氟虫腈的合成方法。本公开的方法提供了产率范围为75％至90％并且纯度范围为95％至97％的氟虫腈。通过本公开的方法,在氟虫腈中观察到的砜杂质,即5-氨基-1-(2,6-二氯-4-三氟甲基苯基)-3-氰基-4-三氟甲基磺酰基吡唑的量的范围为0％至0.5％。(The present disclosure relates to a process for the synthesis of the broad spectrum insecticide, fipronil (I). The process of the present disclosure provides fipronil in a yield ranging from 75% to 90% and in a purity ranging from 95% to 97%. The amount of sulfone impurity, 5-amino-1- (2, 6-dichloro-4-trifluoromethylphenyl) -3-cyano-4-trifluoromethylsulfonyl pyrazole, observed in fipronil by the process of the present disclosure ranges from 0% to 0.5%.)

1. A method for synthesizing fipronil, comprising the steps of:

a) reacting trifluoromethyl sulfinyl chloride with 5-amino-3-cyano-1- (2, 6-dichloro-4-trifluoromethylphenyl) -pyrazole and amine hydrochloride in a halogenated fluid medium to obtain a reaction mixture;

b) cooling the reaction mixture to a temperature in the range of 20 ℃ to 35 ℃ to obtain a cooled reaction mixture;

c) adding a mixture of said halogenated fluid medium and water to said cooled reaction mixture to obtain a blend;

d) neutralizing the blend with a neutralizing agent to provide a two-phase mixture comprising an organic phase and an aqueous phase;

e) separating the organic phase comprising fipronil, followed by cooling the separated organic phase to a temperature in the range of 2 ℃ to 30 ℃ to obtain a precipitate of fipronil; and

f) filtering the precipitate to obtain a solid, washing the solid and drying the washed solid to obtain fipronil with a purity of 95-97%.

2. The process according to claim 1, wherein fipronil is obtained in a yield of 75% to 90%.

3. The method of claim 1, wherein said step a) is performed at a temperature in the range of 40 ℃ to 80 ℃.

4. The method of claim 1, wherein step a) is performed for a time of 2 hours to 8 hours.

5. The method of claim 1 wherein the halogenated fluid medium is selected from the group consisting of dichloromethane, dichloroethane, dibromoethane, chlorobromomethane, chloroform, carbon tetrachloride, chlorobenzene, dichlorobenzene, and bromobenzene.

6. The process according to claim 1, wherein the molar ratio of trifluoromethylsulfinyl chloride to 5-amino-3-cyano-1- (2, 6-dichloro-4-trifluoromethylphenyl) -pyrazole is 1:1 to 2: 1.

7. the process according to claim 1, wherein the purity of the trifluoromethylsulfinyl chloride is from 95% to 99.9%.

8. The process of claim 1 wherein the molar ratio of amine hydrochloride to 5-amino-3-cyano-1- (2, 6-dichloro-4-trifluoromethylphenyl) -pyrazole is 1:1 to 3: 1.

9. the method according to claim 1, wherein the amount of 5-amino-1- (2, 6-dichloro-4-trifluoromethylphenyl) -3-cyano-4-trifluoromethylsulfonyl pyrazole in fipronil is between 0% and 0.5%.

10. The method of claim 1, wherein the neutralizing agent is selected from the group consisting of water, aqueous ammonia, aqueous NaOH, aqueous KOH, Na₂CO₃Solution, NaHCO₃Solution and CaCl₂At least one of the group consisting of aqueous solutions.

11. The process of claim 1 wherein amine hydrochloride, water and halogenated fluid medium are recovered from the aqueous phase.

12. The process of claim 1, wherein the amine hydrochloride is selected from the group consisting of diethylamine hydrochloride, N' -tetraethylethane-1, 2-diamine dihydrochloride, and amine sulfate.

13. The method of claim 1, wherein boric acid and CaCl₂Added as a hydrofluoric acid binder prior to neutralization.

14. The process of claim 1, wherein in step (d) the neutralized blend is heated at a temperature in the range of from 65 ℃ to 70 ℃ to obtain the biphasic mixture containing the organic phase and the aqueous phase.

15. The process of claim 1, wherein in step (f), the washing is carried out with a halogenated fluid medium.

16. The method of claim 1, wherein in step (f), the drying comprises vacuum drying and further drying at a temperature range of 90 ℃ to 115 ℃.

17. The method according to claim 1, wherein the method comprises the sub-steps of:

i. immersing the blend obtained in step (c) in a neutralizing agent to obtain a neutralized blend;

heating the neutralized blend to obtain a two-phase mixture comprising a bottom organic layer and a top aqueous layer; and

separating the bottom organic layer and using the bottom organic layer in said step (d).

18. The method of claim 17, wherein the neutralizing agent is CaCl₂An aqueous solution.

19. The method of claim 17, wherein in step (ii), the heating is carried out at a temperature in the range of 65 ℃ to 70 ℃.

Technical Field

The present disclosure relates to a method for synthesizing fipronil.

Background

The background information below relates to the present disclosure, but is not necessarily prior art.

Fipronil is a broad-spectrum insecticide, belonging to the 1-phenylpyrazole insecticides. Fipronil is characterized by high efficiency, low toxicity, especially low residue.

IUPAC name: (R, S) -5-amino-1- [2, 6-dichloro-4- (trifluoromethyl) phenyl ] -4- (trifluoromethylsulfinyl) -pyrazole-3-carbonitrile

CAS number: 120068-37-3

A commercial process for fipronil synthesis involves oxidation in a final step in which the sulfinyl precursor of fipronil is oxidized using a suitable oxidizing agent. However, during the oxidation, a certain amount of fipronil (the product thus obtained) undergoes further oxidation, forming the corresponding sulfone compound impurity 5-amino-1- [2, 6-dichloro-4- (trifluoromethyl) phenyl ] -4- [ (trifluoromethyl) sulfonyl ] -1H-pyrazole-3-carbonitrile. Thus, the commercial routes described above provide fipronil with a lower purity. In addition, the sulfone impurities are difficult to separate from fipronil.

Another commercial method of fipronil synthesis involves the use of trifluoromethylsulfinyl chloride (trifluoromethanesulfonyl chloride) [ CAS number: 20621-29-8] Trifluoromethanesulfinylation of the corresponding aryl-pyrazole intermediate. Unfortunately, the processes known to date for the preparation of trifluoromethanesulphinyl chloride are complex and provide trifluoromethanesulphinyl chloride in low purity and low yields. Further, the trifluoromethanesulphinyl chloride may contain the corresponding sulfone impurity, such as trifluoromethanesulfonyl chloride, which may lead to the formation of the sulfone impurity (5-amino-1- [2, 6-dichloro-4- (trifluoromethyl) phenyl ] -4- [ (trifluoromethyl) sulfonyl ] -1H-pyrazole-3-carbonitrile) during the synthesis of fipronil.

Therefore, it is required to develop a simple preparation method that can obtain fipronil with high yield and high purity.

Purpose(s) to

As follows, at least one embodiment herein meets some of the objects of the present disclosure.

It is an object of the present disclosure to ameliorate one or more of the problems of the prior art, or at least to provide a useful alternative.

It is an object of the present disclosure to provide a method for the synthesis of fipronil with high yield and purity.

It is another object of the present disclosure to provide a simple and efficient synthesis method of fipronil.

Other objects and advantages of the present disclosure will become more apparent in the following description, which is not intended to limit the scope of the present disclosure.

Disclosure of Invention

The present disclosure provides a method for synthesizing fipronil. The process comprises reacting 5-amino-3-cyano-1- (2, 6-dichloro-4-trifluoromethylphenyl) -pyrazole with trifluoromethylsulfinyl chloride and amine hydrochloride in a halogenated organic fluid medium to obtain a reaction mixture. The reaction mixture is cooled to a temperature in the range of 20 ℃ to 35 ℃ to obtain a cooled reaction mixture. A mixture of halogenated organic fluid medium and water is added to the cooled reaction mixture to obtain a blend. The blend thus obtained is neutralized with a neutralizing agent to obtain a two-phase mixture comprising an organic phase and an aqueous phase. Separating the organic phase containing fipronil and cooling to a temperature of 2-30 ℃ to obtain a precipitate of fipronil. The precipitate thus obtained is filtered, washed and dried in vacuo to obtain fipronil with a purity in the range of 95% to 97%. Reacting 5-amino-3-cyano-1- (2, 6-dichloro-4-trifluoromethylphenyl) -pyrazole with trifluoromethylsulfinyl chloride and amine hydrochloride at a temperature of 40 ℃ to 80 ℃ in a time range of 2 hours to 8 hours. According to embodiments of the present disclosure, fipronil is obtained in a yield of 75% to 90%. According to the present disclosure, the amine hydrochloride is selected from the group consisting of diethylamine hydrochloride, N' -tetraethylethane-1, 2-diamine dihydrochloride, and amine sulfate salts thereof.

Detailed Description

The embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art. Numerous details are set forth regarding specific components and methods in order to provide a thorough understanding of embodiments of the present disclosure. It will be apparent to one skilled in the art that the details provided in the embodiments should not be construed as limiting the scope of the disclosure. In some embodiments, well-known processes, well-known device structures, and well-known technologies are not described in detail.

The terminology used in the present disclosure is for the purpose of explaining particular embodiments only, and such terminology should not be taken as limiting the scope of the present disclosure. As used in this disclosure, the forms "a", "an" and "the" may also be used to include the plural forms unless the context clearly indicates otherwise. The terms "comprises," "comprising," and "having," are open-ended transition phrases such that the presence of stated features, integers, steps, operations, elements, modules, elements, and/or components are expressly stated but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. The particular order of the steps disclosed in the methods and processes of the present disclosure should not be construed as necessarily requiring their performance as described or illustrated. It should also be understood that additional or alternative steps may be employed.

As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed elements.

The terms first, second, third and the like should not be construed to limit the scope of the present disclosure, as the foregoing terms may be used only to distinguish one element, component, region, layer or section from another component, region, layer or section. Terms such as first, second, third, etc., when used herein do not imply a particular order or sequence unless explicitly stated in the present disclosure.

Fipronil is a broad spectrum insecticide. The conventional synthetic method of fipronil is complex and provides fipronil with low purity. In addition, fipronil obtained by the conventional method may contain 5-amino-1- [2, 6-dichloro-4- (trifluoromethyl) phenyl ] -4- [ (trifluoromethyl) sulfonyl ] -1H-pyrazole-3-carbonitrile, which is a corresponding sulfone compound impurity, and is difficult to separate from fipronil.

The present disclosure contemplates a simple preparation method of fipronil with high yield and high purity. Further, it is desirable that the fipronil synthesized contain less than 0.5%, more preferably negligible sulfone impurity, i.e. 5-amino-1- [2, 6-dichloro-4- (trifluoromethyl) phenyl ] -4- [ (trifluoromethyl) sulfonyl ] -1H pyrazole-3-carbo-nitrile.

In one aspect, the invention provides a method for synthesizing fipronil.

The process of the present disclosure is hereinafter represented as scheme 1.

Scheme 1: synthesis of fipronil

The method of the present disclosure is described in detail.

According to the process of the present disclosure, 5-amino-3-cyano-1- (2, 6-dichloro-4-trifluoromethylphenyl) -pyrazole is reacted with trifluoromethylsulfinyl chloride and amine hydrochloride in a halogenated organic fluid medium to provide a reaction mixture.

According to an embodiment of the present disclosure, the halogenated organic fluid medium is at least one selected from the group consisting of dichloromethane, dichloroethane, dibromoethane, chlorobromomethane, chloroform, carbon tetrachloride, chlorobenzene, dichlorobenzene, and bromobenzene.

In one embodiment, the amine hydrochloride is selected from the group consisting of diethylamine hydrochloride, N' -tetraethylethane-1, 2-diamine dihydrochloride, and amine sulfates thereof.

5-amino-3-cyano-1- (2, 6-dichloro-4-trifluoromethylphenyl) -pyrazole was reacted with trifluoromethylsulfinyl chloride and amine hydrochloride at a temperature ranging from 40 ℃ to 80 ℃. In one embodiment, the reaction is carried out at a temperature in the range of 48 to 55 ℃.

The reaction time of 5-amino-3-cyano-1- (2, 6-dichloro-4-trifluoromethylphenyl) -pyrazole with trifluoromethylsulfinyl chloride and amine hydrochloride ranges from 2 hours to 8 hours. In one embodiment, the reaction time is 5 hours.

According to an embodiment of the present disclosure, the molar ratio of trifluoromethylsulfinyl chloride to 5-amino-3-cyano-1- (2, 6-dichloro-4-trifluoromethylphenyl) -pyrazole is in the range of 1:1 to 2: 1. In an exemplary embodiment, the molar ratio of trifluoromethylsulfinyl chloride to 5-amino-3-cyano-1- (2, 6-dichloro-4-trifluoromethylphenyl) -pyrazole is in the range of 1.1: 1 to 1.2: 1.

the trifluoromethyl sulfinyl chloride used in the methods of the present disclosure can have a purity ranging from 95% to 99.9%. Further, the trifluoromethanesulphinyl chloride contains 0 to 0.5% of the sulfone impurity trifluoromethanesulfonyl chloride.

The molar ratio of amine hydrochloride to 5-amino-3-cyano-1- (2, 6-dichloro-4-trifluoromethylphenyl) -pyrazole was in the range of 1:1 to 3: 1. In an exemplary embodiment of the present disclosure, the molar ratio of diethylamine hydrochloride to 5-amino-3-cyano-1- (2, 6-dichloro-4-trifluoromethylphenyl) -pyrazole is in the range of 1.5: 1.0 to 2.5: 1.

the reaction mixture is cooled at a temperature in the range of 20 ℃ to 35 ℃ to obtain a cooled reaction mixture. A mixture of halogenated organic fluid medium and water is added to the cooled reaction mixture to obtain a blend. The blend thus obtained is neutralized with a neutralizing agent to obtain a two-phase mixture comprising an organic phase and an aqueous phase. Separating the organic phase containing fipronil and cooling to a temperature ranging from 2 ℃ to 30 ℃ to obtain a precipitate of fipronil. The precipitate thus obtained is filtered, washed and dried in vacuo to obtain fipronil with a purity ranging from 95% to 97%.

The neutralizing agent is selected from the group consisting of aqueous solution, NaOH aqueous solution, KOH aqueous solution, Na₂CO₃Solution, NaHCO₃Solution and CaCl₂At least one of the group consisting of aqueous solutions.

According to embodiments of the present disclosure, fipronil is obtained in a yield of 75% to 90%.

According to an embodiment of the present disclosure, the amount of the sulfone impurity 5-amino-1- (2, 6-dichloro-4-trifluoromethylphenyl) -3-cyano-4-trifluoromethylsulfonyl pyrazole in fipronil obtained by the process of the present disclosure ranges from 0% to 0.5%.

According to embodiments of the present disclosure, the amine hydrochloride and halogenated organic fluid medium are recovered from the aqueous phase. The recovered amine hydrochloride can be reused in the fipronil preparation process.

According to one embodiment of the present disclosure, fipronil is recrystallized using a halogenated organic fluid medium.

The halogenated organic fluid medium used for the recrystallization of fipronil can be further recovered and reused.

The process of the present application further comprises adding boric acid and CaCl prior to neutralization₂As a hydrofluoric acid binder. Boric acid and CaCl₂The addition of (a) prevents the corrosion of the glass reactor by hydrofluoric acid.

The process of the present disclosure is simple and efficient and provides fipronil in high yield and purity. The process of the present disclosure is carried out using a small amount of halogenated fluid medium. The halogenated fluid medium used in the process step is continued in a distillation step. Recovering the used halogenated organic fluid medium and reusing the recovered halogenated organic fluid medium. Thus, the methods of the present disclosure are environmentally friendly.

The foregoing description of the embodiments has been provided for the purposes of illustration and is not intended to limit the scope of the present disclosure. The individual components of a particular embodiment are generally not limited to that particular embodiment, but are interchangeable. Such variations are not to be regarded as a departure from the disclosure, and all such modifications are intended to be included within the scope of the disclosure.

The present disclosure is further described in terms of the following experiments, which are presented for illustrative purposes only and should not be construed to limit the scope of the present disclosure. The following experiments can be scaled up to industrial/commercial scale and the results obtained can be generalized to industrial scale.

Details of the experiment

Fipronil is prepared according to the disclosed method:

example I:

500ml is driedThe dichloroethane was placed in a 1-liter vertical reactor equipped with a stirrer, a thermometer sleeve and a condenser with a scrubber. 321 g of 5-amino-1- [2, 6-dichloro-4- (trifluoromethyl) phenyl]-1H-pyrazole-3-carbonitrile, 1.0 g boric acid, 2.0 g CaCl₂And 197.1 g diethylamine hydrochloride (dry powder) were added to dichloroethane and heated to 50 ℃ with stirring to give a mixture. 175.3 g of trifluoromethanesulphinyl chloride was added to the mixture under stirring and the reaction was carried out at 50 ℃ for 5 hours to obtain a reaction mixture. The reaction mixture thus obtained was cooled to 25 ℃ to obtain a cooled reaction mixture. To the cooled reaction mixture was added 3000ml of dichloroethane and 400ml of water (H)₂O) to obtain a blend. The blend was neutralized to pH 7 with aqueous ammonia solution (8-10N) to give a neutralized blend. After neutralization, the neutralized blend was heated to 65 ℃ to give a two-phase mixture comprising a bottom organic layer and a top aqueous layer. The bottom organic layer was separated and cooled to 5 ℃ to give a precipitate. The precipitate thus obtained was filtered and washed twice with dichloroethane to minimize impurities in the fipronil material. The fipronil material was dried under vacuum and then at 100 c to yield 335 g fipronil with a purity of 96% (yield 76.66%).

Example II:

600ml of dry dichloroethane are placed in a 1-liter vertical reactor equipped with stirrer, thermometer sleeve and condenser with scrubber. 321 g of 5-amino-1- [2, 6-dichloro-4- (trifluoromethyl) phenyl]-1H-pyrazole-3-carbonitrile, 1.0 g boric acid, 2.0 g CaCl₂And 219 g of diethylamine hydrochloride (dry powder) were added to dichloroethane, and heated to 45 ℃ with stirring to obtain a mixture. 175.3 g of trifluoromethanesulphinyl chloride was added to the mixture, and stirred at 45 ℃ for 5 hours to obtain a reaction mixture. The reaction mixture thus obtained was cooled to 25 ℃ to obtain a cooled reaction mixture. To the cooled reaction mixture 2900ml of dichloroethane and 400ml of water (H) were added₂O) to obtain a blend. The blend was neutralized to pH 7 with aqueous ammonia solution (8-10N) to give a neutralized blend. After neutralization, the neutralized blend was heated to 70 ℃ to yield a mixture comprising a bottom organic layer and a top aqueous layerA two-phase mixture of (a). The bottom organic layer was separated and cooled to 5 ℃ to give a precipitate. The precipitate thus obtained was filtered and washed twice with dichloroethane. The filtered fipronil material was dried under vacuum and then at 100 c to give 338 g fipronil with a purity of 96.4% (yield 77.34%).

Example III:

500ml of dry dichloroethane are placed in a 1-liter vertical reactor equipped with stirrer, thermometer sleeve and condenser with scrubber. 321 g of 5-amino-1- [2, 6-dichloro-4- (trifluoromethyl) phenyl]-1H-pyrazole-3-carbonitrile, 1.0 g boric acid, 2.0 g CaCl₂And 164.25 g diethylamine hydrochloride (dry powder) were added to dichloroethane and heated to 60 ℃ with stirring to give a mixture. 175.3 g of trifluoromethanesulphinyl chloride was added to the mixture under stirring, and stirring was carried out at 60 ℃ for 5 hours to obtain a reaction mixture. The reaction mixture thus obtained was cooled to 20 ℃ to obtain a cooled reaction mixture. To the cooled reaction mixture was added 3000ml of dichloroethane and 400ml of water (H)₂O) to obtain a blend. The blend was neutralized to pH 7 with aqueous ammonia solution (8-10N) to give a neutralized blend. The neutralized blend was heated to 65 ℃ to give a two-phase mixture comprising a bottom organic layer and a top aqueous layer. The bottom organic layer was separated and cooled to 3 ℃ to give a precipitate. The precipitate thus obtained was filtered and washed twice with dichloroethane. The filtered fipronil material was dried under vacuum and then at 110 c to yield 330 g fipronil with a purity of 95.8% (yield 75.51%).

Example IV:

500ml of dry dichloroethane are placed in a 1-liter vertical reactor equipped with stirrer, thermometer sleeve and condenser with scrubber. 321 g of 5-amino-1- [2, 6-dichloro-4- (trifluoromethyl) phenyl]-1H-pyrazole-3-carbonitrile, 1.0 g boric acid, 2.0 g CaCl₂And 219 g of diethylamine hydrochloride (dry powder) were added to dichloroethane, and heated to 50 ℃ with stirring to obtain a mixture. 175.3 g of trifluoromethanesulphinyl chloride was added to the mixture under stirring and heated at 50 ℃ for 5 hours to give a reaction mixture. Will thisThe reaction mixture thus obtained was cooled to 25 ℃ to obtain a cooled reaction mixture. To the cooled reaction mixture was added 3000ml of dichloroethane and 400ml of water (H)₂O) to obtain a blend. The blend was neutralized to pH 7 with aqueous ammonia solution (8-10N) to give a neutralized blend. The neutralized blend was heated to 70 ℃ to give a two-phase mixture comprising a bottom organic layer and a top aqueous layer. The bottom organic layer was separated and concentrated, and the dichloroethane content was adjusted to 800 ml by recovering 2700ml of dichloroethane at 85 ℃ and then cooling to 20 ℃ to obtain a precipitate. The precipitate thus obtained was filtered and washed twice with dichloroethane. The solid material was dried in vacuo and then at 110 ℃ to give 360 g of fipronil with a purity of 96.5% (yield 82.38%).

example-V:

600ml of dry dichloroethane are placed in a 1-liter vertical reactor equipped with stirrer, thermometer sleeve and condenser with scrubber. 321 g of 5-amino-1- [2, 6-dichloro-4- (trifluoromethyl) phenyl]-1H-pyrazole-3-carbonitrile, 1.0 g boric acid, 2.0 g CaCl₂And 273.75 g diethylamine hydrochloride (dry powder) were added to dichloroethane and heated to 50 ℃ to give a mixture. To the mixture was added 183 g of trifluoromethanesulphinyl chloride with stirring, and the mixture was heated and stirred at 50 ℃ for 5 hours to obtain a reaction mixture. The reaction mixture thus obtained was cooled to 25 ℃ to obtain a cooled reaction mixture. 2900ml of dichloroethane and 400ml of water (H) were added to the reaction mixture₂O) to obtain a blend. The blend was neutralized to pH 7 with aqueous ammonia solution (8-10N) to give a neutralized blend. The neutralized blend was heated to 70 ℃ to give a two-phase mixture comprising a bottom organic layer and a top aqueous layer. The bottom organic layer was separated and concentrated, and the dichloroethane content was adjusted to 800 ml by recovering 2700ml of dichloroethane at 85 ℃ and then cooling to 20 ℃ to obtain a precipitate. The precipitate thus obtained was filtered and washed twice with a chlorinated solvent to obtain a filter cake. The filter cake was dried under vacuum and then at 100 c to yield 375 g fipronil with a purity of 96.3% (yield 85.81%).

Example VI:

600ml of dry dichloroethane are placed in a 1-liter vertical reactor equipped with stirrer, thermometer sleeve and condenser with scrubber. 321 g of 5-amino-1- [2, 6-dichloro-4- (trifluoromethyl) phenyl]-1H-pyrazole-3-carbonitrile, 1.0 g boric acid, 2.0 g CaCl₂And 490 g of N, N, N ', N' -tetraethylethane-1, 2-diamine dihydrochloride (dry powder) was added to dichloroethane, and heated to 50 ℃ with stirring to obtain a mixture. To the mixture was added 183 g of trifluoromethanesulphinyl chloride, and the mixture was stirred at 50 ℃ for 5 hours to obtain a reaction mixture. The reaction mixture thus obtained was cooled to 25 ℃ to obtain a cooled reaction mixture. 2900ml of dichloroethane and 400ml of water (H) were added to the reaction mixture₂O) to obtain a blend. The blend was neutralized to pH 7 with aqueous ammonia solution (8-10N) to give a neutralized blend. The neutralized blend was heated to 70 ℃ to give a two-phase mixture comprising a bottom organic layer and a top aqueous layer. The bottom organic layer was separated and concentrated, and the dichloroethane content was adjusted to 800 ml by recovering 2700ml of dichloroethane at 85 ℃ and then cooling to 20 ℃ to obtain a precipitate. The precipitate thus obtained was filtered and washed twice with dichloroethane solvent to obtain fipronil as a solid substance. The fipronil solid was dried in vacuo and then at 90 c to yield 345 g of fipronil with a purity of 95.5% (yield 78.95%).

example-VII:

600ml of dry dichloroethane are placed in a 1-liter vertical reactor equipped with stirrer, thermometer sleeve and condenser with scrubber. 321 g of 5-amino-1- [2, 6-dichloro-4- (trifluoromethyl) phenyl]-1H-pyrazole-3-carbonitrile, 1.0 g boric acid, 2.0 g CaCl₂And 273.75 g diethylamine hydrochloride (dry powder) were added to dichloroethane and heated to 50 ℃ with stirring to give a mixture. To the mixture was added 183 g of trifluoromethanesulphinyl chloride with stirring, and the mixture was stirred at 50 ℃ for 5 hours to obtain a reaction mixture. The reaction mixture thus obtained was cooled to 25 ℃ to obtain a cooled reaction mixture. 2900ml of dichloroethane and 400ml of water (H) were added to the reaction mixture₂O) to obtain a blend. Blending the mixtureThe mixture was neutralized to pH 7 with aqueous ammonia (8-10N) to give a neutralized blend. The neutralized blend was heated to 70 ℃ to give a two-phase mixture comprising a bottom organic layer and a top aqueous layer. The bottom organic layer was separated and concentrated, 3500ml of dichloroethane was recovered at 85-90 ℃, and then 1000ml of chlorobenzene was added to the concentrated substance, followed by cooling to 20 ℃ to obtain a precipitate. The precipitate thus obtained was filtered and washed twice with chlorobenzene to obtain a fipronil solid substance. The fipronil solid was dried in vacuo and then at 115 c to yield 375 g fipronil with a purity of 97% (yield 85.81%).

Example VIII:

500ml of dry dichloroethane are placed in a 1-liter vertical reactor equipped with stirrer, thermometer sleeve and condenser with scrubber. 321 g of 5-amino-1- [2, 6-dichloro-4- (trifluoromethyl) phenyl]-1H-pyrazole-3-carbonitrile, 1.0 g boric acid, 2.0 g CaCl₂And 219 g of diethylamine hydrochloride (dry powder) were added to dichloroethane, and heated to 50 ℃ with stirring to obtain a mixture. 175.3 g of trifluoromethanesulphinyl chloride was added to the mixture under stirring and heated at 50 ℃ for 5 hours to give a reaction mixture. The reaction mixture was immersed in 3000ml of dichloroethane and 1000ml of 10.0% W/V CaCl at 30 deg.C₂In solution, a blend is obtained. The neutralized blend thus obtained was heated to 70 ℃ to obtain a two-phase mixture comprising a bottom organic layer and a top aqueous layer. The bottom organic layer was separated and neutralized to pH 7 with aqueous ammonia (0.5-1.0N) to give a neutralized blend. The neutralized blend thus obtained was heated to 70 ℃ to obtain a two-phase mixture comprising a bottom organic layer and a top aqueous layer. The bottom organic layer was separated and concentrated, and the dichloroethane content was adjusted to 800 ml by recovering 2700ml of dichloroethane at 85 ℃ and then cooling to 20 ℃ to obtain a precipitate. The precipitate thus obtained was filtered and washed twice with dichloroethane. The solid material was dried under vacuum and then at 110 c to give 380 g fipronil with a purity of 96.5% (yield 87.00%).

To achieve a fipronil yield of greater than 85% per mole of batch size catalyst (diethylamine hydrochloride)Salt) should be at least 219 g and the reaction mass is immersed in CaCl compared to the other examples₂Better yields will result in solution. Diethylamine hydrochloride is a preferred catalyst over other amine hydrochlorides.

Technical progress and economic significance

The present disclosure described above has several technical advantages, including but not limited to the implementation of the following methods:

-simple and efficient;

-providing fipronil in high yield and purity; and

-environmentally friendly.

Throughout this specification, variations of the word "comprise" or "comprising" will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

The use of the expression "at least" or "at least one" indicates the use of one or more elements or components or quantities, as the use may achieve one or more desired purposes or results in embodiments of the present disclosure.

Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present disclosure. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present disclosure as it existed anywhere before the priority date of this application.

The numerical values for the various physical parameters, dimensions or quantities mentioned are only approximations and it is contemplated that the numerical values above/below the assigned parameters, dimensions or quantities fall within the scope of the disclosure unless stated to the contrary in the specification.

While considerable emphasis has been placed herein on the components and component parts of the preferred embodiments, it will be appreciated that many embodiments can be made and that many changes can be made in the preferred embodiments without departing from the principles of the disclosure. These and other variations in the preferred embodiments of the invention and other embodiments thereof will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the present disclosure and not as a limitation.