CN111574511A - Synthesis method and application of sulfuryl pyraflufen - Google Patents

Abstract

The invention relates to the technical field of pesticides, and provides a synthesis method of sulfuryl pyraflufen, which comprises the following preparation steps: step (1): carrying out hydroxyalkylation, fluoromethylation and chlorination on the reactant (I) to prepare an intermediate 2; step (2): mixing the intermediate 1 and the intermediate 2, adding water to separate an organic phase to obtain a transition intermediate, and adding a solvent and an oxidant to react to obtain the intermediate; also provides an application of the sulfuryl pyraflufen-ethyl applied to pesticides; the sulfonepyraflufen-ethyl is prepared by the synthesis method. The invention can not only improve the overall yield of the target product, but also reduce the generation of byproducts, perfectly reduce the generation of three wastes and realize the recycling of the solvent.

Description

A kind of synthetic method and application of sulfofenazone

technical field

The invention relates to the technical field of pesticides, in particular to a method for synthesizing sulfofenapyr and its application.

Background technique

Pyroxasulfone (pyroxasulfone), molecular formula C ₁₂ H ₁₄ F ₅ N ₃ O ₄ S, chemical name is 3-[5-(difluoromethoxy)-1-methyl-3-(trifluoromethoxy) ) pyrazol-4-ylmethylsulfonyl]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole. Trifenapyr is an isoxazole herbicide that inhibits plant cell division. The herbicide was first discovered by Japan's KI Chemical Research Institute, and later industrialized by Japan Combination Chemical Company and Japan's Anhara Chemical Company. Sufenapyr is mainly used to control some grass weeds and broadleaf weeds. Sufenapyr is mainly absorbed through the coleoptiles of monocotyledonous plants or the hypocotyls of dicotyledonous plants. After absorption, it conducts upwards, inhibits cell growth by hindering protein synthesis, and also inhibits plant respiration, so that weed shoots, young Root growth stops and then dies; it also acts as an inhibitor and uncoupler of the electron transport chain, which can inhibit plant photosynthesis, interfere with plant protein biosynthesis, affect cell division, and affect membrane biosynthesis and integrity. Widely used in corn, cotton, beans, peanuts, potatoes, rapeseed, garlic, tobacco, sunflower, castor, green onions and other fields to control annual grass weeds and some broad-leaved weeds with small seeds. It has special effects on annual grass weeds such as crabgrass, foxtail, beef tendon, barnyardgrass, chinensis, kangaroo, wild oat, bluegrass, hard grass, teff, etc. Broadleaf weeds such as Commelina, Niu chickweed, and Cuscuta also have certain control effects. However, the existing synthetic methods for fenfenpyr have obvious shortcomings such as low yield and high content of by-products.

SUMMARY OF THE INVENTION

In order to solve the above-mentioned technical problems, a first aspect of the present invention provides a method for synthesizing sulfofenazone, and the preparation steps include:

Step (1): reaction body (I) is subjected to hydroxyalkylation, fluoromethylation and chlorination to obtain intermediate 2;

Step (2): mix the intermediate 1 and the intermediate 2, add water to separate the organic phase, obtain a transition intermediate, add a solvent and an oxidizing agent to react, to obtain the final product;

The structure of the reactant (I) is shown in formula 1; the structural formula of the intermediate 1 is formula 2;

As a preferred technical solution, the structure of R1 in the present invention is selected from one of -SH and formula 3; the formula 3 is as follows, wherein the R2 represents an amino group, a hydrogen atom, substituted or unsubstituted One of the C1-C12 alkyl and alkoxy groups;

As a preferred technical solution, a chlorination reagent is included in the chlorination reaction process in step (1) in the present invention; the chlorination reagent includes thionyl chloride, phosphorus trichloride, sulfonyl chloride, chlorine, carbon At least one of acid chloride and benzoyl chloride.

As a preferred technical solution, the solvent in step (2) described in the present invention comprises C1-C8 small molecular alcohol, dichloromethane, 1,2-dichloroethane, chlorobenzene, dichlorobenzene, acetic acid At least one of ethyl ester and butyl acetate.

As a preferred technical solution, the oxidant of step (2) in the present invention comprises at least one of hydrogen peroxide, m-chloroperoxybenzoic acid, and potassium monopersulfate composite salt.

As a preferred technical solution, the C1-C8 small molecular alcohol in the present invention is selected from methanol, ethanol, tert-butanol, butanediol, propylene glycol, isobutanol, isoamyl alcohol, isopropanol, ethylene glycol At least one of at least one of alcohol and glycerol.

As a preferred technical solution, the purity of the intermediate 1 in the present invention is greater than or equal to 90%; the purity of the intermediate 2 is greater than or equal to 85%.

As a preferred technical solution, the oxidant in the present invention also includes sodium tungstate; the molar ratio between the hydrogen peroxide and sodium tungstate dihydrate is 1:(0.005-0.35).

As a preferred technical solution, the raw materials for the preparation of the reactant (I) in the present invention include ethyl trifluoroacetoacetate; the raw materials for the preparation of the intermediate 1 include glyoxylic acid, thiourea, hydrosulfide, bromine at least one of them.

The second aspect of the present invention provides an application of fenfenpyr, which is applied to pesticides; the fenfenazole is prepared by the synthetic method.

Compared with the prior art, the present invention has the following excellent beneficial effects:

The present invention provides a new method for synthesizing sulfofenazone. By improving the production route, firstly, the intermediate 2 is synthesized by performing O-difluoromethylation on the reactant (I), and then the intermediate 1 is docked. , and finally generate the target product through the oxidation reaction. This production method avoids the by-products caused by the first reaction of the reactant (I) and the intermediate 1 during the fluoromethylation process, and improves the purity and yield of the final product; the inventor unexpectedly found that in the intermediate 1 , In the process of the reaction of intermediate 2, selecting small molecular alcohol as the reaction solvent can reduce the generation of by-products in the reaction process, avoid using acetic acid as the solvent in the existing method, and it is difficult to recover the solvent and generate a large amount of waste water. In addition, in the process of the whole production route, the synthesis process of the intermediates 1 and 2 does not need to be discharged, and the synthesis process of the next step reaction can be directly carried out. In this process, the present invention can not only improve the overall quality of the target product It can also reduce the generation of by-products, perfectly reduce the generation of three wastes and realize solvent recovery and reuse.

Description of drawings

Fig. 1 is the liquid phase test result of the sulfofenapyr obtained by the sulfofenazone synthesis method described in Example 1.

Detailed ways

The technical features in the technical solutions provided by the present invention will be further clearly and completely described below with reference to the specific embodiments. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

It will be understood by those skilled in the art that, unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It should also be understood that terms such as those defined in general dictionaries should be understood to have meanings consistent with their meanings in the context of the prior art and, unless defined as herein, are not to be taken in an idealized or overly formal sense. explain.

The words "preferred", "preferably", "more preferred" and the like in the present invention refer to embodiments of the invention which, under certain circumstances, may provide certain benefits. However, other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not available, nor is it intended to exclude other embodiments from the scope of the present invention.

A first aspect of the present invention provides a method for synthesizing sulfofenazone, the preparation step comprising:

Step (1): reaction body (I) is subjected to hydroxyalkylation, fluoromethylation and chlorination to obtain intermediate 2;

Step (2): mix the intermediate 1 and the intermediate 2, add water to separate the organic phase, obtain a transition intermediate, add a solvent and an oxidizing agent to react, to obtain the final product;

The structure of the reactant (I) is shown in formula 1; the structural formula of the intermediate 1 is formula 2;

In some embodiments, the general reaction formula in the method for synthesizing sulfofenapyr is as follows:

Intermediate 1

In some embodiments, the structure of the R1 is selected from one of -SH and formula 3; the formula 3 is as follows, wherein the R2 represents an amino group, a hydrogen atom, a substituted or unsubstituted C1-C12 One of alkyl and alkoxy;

In some preferred embodiments, the structural formula of the intermediate 1 is one of formula 2-1 and formula 2-2; preferably, the structural formula of the intermediate 1 is formula 2-1; wherein, the The structures of formula 2-1 and formula 2-2 are as follows:

In some embodiments, the source of the intermediate 1 is not particularly limited. Preferably, the intermediate 1 in the present invention is prepared by the synthesis method of the intermediate 1 as described below.

In some embodiments, the method for synthesizing Intermediate 1 includes at least the steps of: using glyoxylic acid as a raw material to prepare 3-bromo-5,5-dimethyldihydrogen through oxime formation, bromination and cyclization reactions Isoxazole, followed by reaction with a substitution reagent, affords intermediate 1.

In some embodiments, the substitution reagent is selected from one of thiourea, sodium hydrosulfide, and potassium hydrosulfide; preferably, the substitution reagent is thiourea.

In some preferred embodiments, the synthetic method of described intermediate 1, the step comprises at least:

1) In the first reaction vessel, add glyoxylic acid aqueous solution, hydroxylamine compound, and water, stir and mix, heat up to 60-80 ° C, and stir for 1-5 hours; lower the temperature to below 0 ° C, add the first inorganic base, organic Solvent, add liquid bromine dropwise, return the temperature to 20-35 ° C after the end, and keep the temperature for 5-10 hours, separate the organic phase, and use it as the first product;

2) adding the second inorganic base to the first product, stirring and warming up to 70-90 ° C, feeding isobutene gas, reacting for 1-5 hours, adding water, separating the organic phase, removing the solvent, and obtaining the second product;

3) The substitution reagent, alcohol solvent and hydrogen halide solution are added into the second reaction vessel and mixed, and the second product is added dropwise to the second reaction vessel.

In some more preferred embodiments, the synthetic method of described intermediate 1, the step comprises at least:

1) In the first reaction vessel, add 80 g of glyoxylic acid aqueous solution (50% aqueous solution, 0.50 mol), hydroxylamine compound (0.55 mol, 1.1 eq), 120 g of water, stir to dissolve, then heat up to 60-80 ° C and stir for 3 hour; the reaction temperature was lowered to 0 °C, the first inorganic base (1.10 mol, 2.2 eq) and an organic solvent were added, 80 g of liquid bromine (0.50 mol, 1.0 eq) was added dropwise, and the temperature was returned to 20-35 ° C after completion, and Incubate for 5-10 hours, separate the organic phase as the first product;

2) The second inorganic base (1.44mol, 3.0eq) was added to the first product, the temperature was raised to 70-90°C with stirring, and finally isobutylene gas was introduced at a rate of 10g/min to react for 2 hours. After the reaction finishes, add 600g of water, separate out the organic phase, remove the solvent, and obtain the second product;

3) Add the substitution reagent (0.33mol, 1.1eq), 50-200mL of alcohol solvent and hydrogen halide solution into the second reaction vessel and mix, then add 0.5-2.5mL of hydrogen halide solution, and add the second product dropwise to In the second reaction vessel, after the end, the solvent is removed, and the tert-butanol is recrystallized to obtain.

In some embodiments, the hydroxylamine compound is selected from at least one of hydroxylamine hydrochloride, hydroxylamine sulfate, and hydroxylamine aqueous solution; preferably, the hydroxylamine compound is hydroxylamine hydrochloride.

In some embodiments, the molar ratio between the hydroxylamine compound and glyoxylic acid solute in the glyoxylic acid aqueous solution in step 1) is (1-3): 1; preferably, the hydroxylamine compound, glyoxylic acid The molar ratio between the glyoxylic acid solutes in the aqueous solution is 2.2:1; the mass concentration of the glyoxylic acid aqueous solution is 50%.

In some embodiments, the mass ratio of water and glyoxylic acid aqueous solution in step 1) is (1-2):1; preferably, the mass ratio of water and glyoxylic acid aqueous solution is 1.5:1.

In some embodiments, the first inorganic base in step 1) is selected from at least one of sodium carbonate, potassium carbonate, sodium bicarbonate, sodium hydroxide, and potassium hydroxide; preferably, the first inorganic base for sodium carbonate.

In some embodiments, the molar ratio between the first inorganic base and the glyoxylic acid solute in the glyoxylic acid aqueous solution described in step 1) is (2-2.5): 1; preferably, the molar ratio described in step 1) The molar ratio between the first inorganic base and the glyoxylic acid solute in the glyoxylic acid aqueous solution is 2.2:1.

In some embodiments, the organic solvent in step 1) is selected from at least one of 1,2-dichloroethane, dichloromethane, chloroform, toluene, xylene, and chlorobenzene; preferably, step 1) The organic solvent described in the above is 1,2-dichloroethane.

In some embodiments, the mass ratio of the organic solvent and the glyoxylic acid aqueous solution in step 1) is (1.5-2): 1; preferably, the mass ratio of the organic solvent and glyoxylic acid aqueous solution in step 1) 1.8:1.

In some embodiments, the molar ratio between the liquid bromine and the glyoxylic acid solute in the glyoxylic acid aqueous solution in step 1) is (0.1-1.5): 1; preferably, the liquid bromine and glyoxylic acid are The molar ratio between the glyoxylic acid solutes in the aqueous solution is 1:1.

In some embodiments, the second inorganic base in step 2) is selected from at least one of sodium bicarbonate, sodium carbonate, sodium hydroxide, potassium carbonate and potassium hydroxide; preferably, the second inorganic base for sodium bicarbonate.

In some embodiments, the molar ratio between the second inorganic base described in step 2) and the content of dibromoformaldoxime in the first product is (2.5-4): 1; preferably, described in step 2) The molar ratio between the second inorganic base and the content of dibromoformaloxime in the first product is 3:1.

In some embodiments, the alcoholic solvent in step 3) includes at least one of methanol, ethanol, isopropanol, and tert-butanol; preferably, the alcoholic solvent in step 3) is tert-butanol.

In some embodiments, the substitution reagent in step 3) is selected from one of thiourea, sodium hydrosulfide, and potassium hydrosulfide; preferably, the substitution reagent is thiourea.

In some embodiments, the molar ratio between the amount of the substitution reagent described in step 3) and the 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole in the second product is ( 0.5-1.5): 1; preferably, the molar ratio between the amount of the substitution reagent and the 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole in the second product is 1.1 :1.

In some embodiments, the hydrogen halide solution in step 3) is selected from a hydrogen bromide solution, a hydrogen chloride solution, and a hydrogen fluoride solution; preferably, the hydrogen halide solution is a hydrogen bromide solution.

In some embodiments, the content and yield of dibromoformaldoxime in the first product described in step 1) are detected by HPLC.

In some embodiments, the content and yield of the second product 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole in step 2) are detected by HPLC.

In some embodiments, the purity of the intermediate 1 in step 3) is detected by HPLC.

The intermediate 1 described in the present invention is a salt, so the identification method is mass spectrometry, HRMS (ESI): calcd. ForC ₆ H ₁₂ BrN ₃ OS: [M] ⁺ m/z 253.0.

Intermediate 2

In some embodiments, the step (1) is to perform hydroxyalkylation, fluoromethylation and chlorination on the reactant (I) to obtain the intermediate 2.

In some preferred embodiments, the step (1) is as follows: mixing the reactant (I) and the first inorganic alkali solution, adding formaldehyde solution dropwise, and adding the second inorganic alkali solution, the first organic alkali solution after the end Solvent, introduce chlorodifluoromethane gas, stir, stand for stratification, separate the upper organic phase, concentrate to obtain the initial reactant; dissolve the initial reactant in the second organic solvent, add dropwise below 0 °C Chlorinating reagent, return the temperature to 20-30 °C, react for at least 30 min, add water and mix, separate the lower organic phase, and concentrate to obtain Intermediate Intermediate 2.

In some more preferred embodiments, the step (1) is as follows: take 50g (0.30mol) reactant (I), 36g aqueous sodium hydroxide solution (50%, 0.45mol, 1.5eq) and mix, dropwise Add 33g formaldehyde solution (30%, 0.33mol), add 36g aqueous sodium hydroxide solution (50%, 0.45mol, 1.5eq) and acetonitrile after the end, pass into chlorodifluoromethane gas, stir, stand for stratification, The separated upper organic phase was concentrated to obtain the initial reactant; the initial reactant was dissolved in 1,2-dichloroethane, and 35.7g of thionyl chloride (0.30mol) was added dropwise below 0°C, and the temperature was returned to 20 -30°C, react for at least 30 min, add water and mix, separate the lower organic phase, and concentrate to obtain Intermediate 2.

In the present invention, the preparation process of sulfofenazone is improved. The inventor finds that the intermediate 2 of the intermediate substance is first synthesized by O-difluoromethylation, and then the docking reaction is carried out with the intermediate 1, and finally the oxidation is carried out again. The target product can be obtained, and the purity and yield of the reaction product of sulfometazone obtained at the end can be significantly improved. The inventor believes that it may be because, in the present invention, the intermediate substance is synthesized through O-difluoromethylation first. The intermediate 2 is then docked with the intermediate 1, which can avoid the by-product of N-difluoromethylation when the intermediate 1 is reacted with the reactant (I) first and then the O-difluoromethylation is carried out. , the inventor believes that if the intermediate 1 is reacted with the reactant (I) first, the reaction intermediate prepared by this route will contain carbon-nitrogen double bonds and carbon-sulfur bonds, and the structural properties are very unstable, but The reaction intermediate in this route also needs to undergo various reaction processes with high activity such as various chlorination and oxidation, and the easily formed N-difluoromethylation by-product is not easy to remove, resulting in the final preparation of fenflufenac The content and yield of N-difluoromethyl are relatively low, and the use of intermediate 2, which first synthesizes the intermediate substance through O-difluoromethylation, and then docking with intermediate 1, can well avoid the resulting N-difluoromethyl. by-products.

In the present invention, the nuclear magnetic test results of the intermediate 2 are: ¹ H NMR (400MHz, CDCl3): 6.69 (1H, t, J=71.5Hz), 4.51 (2H,s), 3.82 (3H,s).

In some embodiments, the purity of the intermediate 1 is ≥90%; the purity of the intermediate 2 is ≥85%; preferably, the purity of the intermediate 1 is 95%; the purity of the intermediate 2 is 90%.

In some preferred embodiments, in the step (1), the first inorganic alkali solution and the second inorganic alkali solution are independently selected from at least one of sodium hydroxide aqueous solution, potassium hydroxide, potassium carbonate and potassium bicarbonate Preferably, the first inorganic alkali solution and the second inorganic alkali solution in the step (1) are respectively an aqueous sodium hydroxide solution; more preferably, the mass concentration of the aqueous sodium hydroxide solution is 40-60%; more preferably , the mass concentration of sodium hydroxide aqueous solution is 50%.

In some preferred embodiments, the first organic solvent and the second organic solvent in the step (1) are independently selected from at least one of acetonitrile, 1,2-dichloroethane, dichloromethane, and chlorobenzene more preferably, the first organic solvent in the step (1) is acetonitrile; the second organic solvent in the step (1) is 1,2-dichloroethane.

In some embodiments, a chlorination reagent is included during the chlorination reaction in the step (1); the chlorination reagent includes thionyl chloride, phosphorus trichloride, sulfonyl chloride, chlorine, phosgene, and benzoyl chloride At least one of; preferably, the chlorination reagent is thionyl chloride.

In some embodiments, the raw materials for the preparation of the reactant (I) include ethyl trifluoroacetoacetate; the raw materials for the preparation of the intermediate 1 include at least one of glyoxylic acid, thiourea, hydrosulfide, and bromine .

In some embodiments, the preparation method of the reactant (I) is as follows:

Take 92 g of ethyl trifluoroacetoacetate (0.50 mol) and 150 mL of solvent (which can be replaced by ethanol, methanol and other solvents), at 0 °C, add 64 g of methylhydrazine (40%, 0.55 mol, 1.1 eq) dropwise, and then react The temperature was raised to 80°C and stirred for 5 hours. After the reaction was completed, 200 mL of water was added to the reaction and stirred for 30 minutes, a white solid was precipitated, suction filtration, and the filter cake was washed three times with water to obtain 78 g of reaction body (I); the content of the reaction body (I) was 97 g. %, yield: 96%.

In some embodiments, the solvent in the method for preparing the reactant (I) is selected from at least one of acetic acid, ethanol, methanol, and tert-butanol; preferably, the solvent is acetic acid.

The reactant (I) is N-methyl-3-trifluoromethyl-5-hydroxypyrazole.

In some embodiments, the step (2): mix the intermediate 1 and the intermediate 2, add water to separate the organic phase, obtain a transition intermediate, add a solvent and an oxidant to react, and then obtain;

In some preferred embodiments, the step (2): stir and mix the intermediate 1, the first inorganic base and the first organic solvent, continue to drop the intermediate 2, stir for 2-6 hours, add water and stand for mixing and separation The organic phase is taken out and concentrated to obtain the transition intermediate; the transition intermediate and solvent are mixed, sodium tungstate dihydrate, 0.5-5 mL concentrated sulfuric acid and oxidizing agent are added, and after stirring for 1-10 hours, water is added, stirring, and filtration and drying.

In some more preferred embodiments, the step (2): 42g of intermediate 1 (0.20mol), 41.4g of potassium carbonate (0.30mol), and acetonitrile were stirred and mixed, and 58.7g of intermediate 2 (0.20mol) was added dropwise. , 90%), stir for 4 hours, add water and stand to mix to separate out the organic phase, and concentrate to obtain the transition intermediate; mix the transition intermediate and 300 mL of solvent, add 1.25 g of sodium tungstate dihydrate (3.80 mmol), 1 mL of concentrated sulfuric acid ( 98%), 64.6g hydrogen peroxide (0.57mol, 30%), continue stirring for 6 hours, add water, stir, filter and dry.

The nuclear magnetic test of sulfofenazone prepared by step (2) in the present invention is: ¹ H NMR (400MHz, CDCl3) δ: 6.83(t, J=71.9Hz, 1H, ), 4.60(s, 2H), 3.88 (s, 3H), 3.11 (s, 2H), 1.52 (s, 6H).

In some embodiments, the oxidant in the step (2) comprises at least one of hydrogen peroxide, m-chloroperoxybenzoic acid, and potassium monopersulfate composite salt; preferably, the oxidant in the step (2) is hydrogen peroxide .

In some embodiments, the oxidizing agent further comprises sodium tungstate dihydrate; the molar ratio between the hydrogen peroxide and sodium tungstate dihydrate is 1:(0.005-0.35); The molar ratio between sodium tungstate is 1:0.007.

In some embodiments, the solvent in the step (2) comprises C1-C8 small molecular alcohol, dichloromethane, 1,2-dichloroethane, chlorobenzene, dichlorobenzene, ethyl acetate, butyl acetate At least one of esters; preferably, the solvent in the step (2) contains C1-C8 small molecular alcohol.

In some embodiments, the C1-C8 small molecule alcohol is selected from methanol, ethanol, tert-butanol, butanediol, propylene glycol, isobutanol, isoamyl alcohol, isopropanol, ethylene glycol, glycerol At least one of; preferably, the C1-C8 small molecular alcohol is selected from methanol, ethanol, and tert-butanol; more preferably, the C1-C8 small molecular alcohol is methanol.

In the present invention, the intermediate 2 of the intermediate substance is first synthesized by O-difluoromethylation, and then the docking reaction is carried out with the intermediate 1, and the prepared transition intermediate needs further oxidation reaction. The purity of the process intermediate 1 and the conditions of the oxidation process have a great influence on the purity and yield of the prepared target product, and the inventor unexpectedly found that in the oxidation process, a C1-C8 small molecule alcohol is used as a solvent, Combined use of hydrogen peroxide and sodium tungstate catalyst, where the purity of intermediate 1 needs to be ≥90%, the final purity of the prepared target product can reach 99%, and the yield can reach 92%. The inventor believes that it may be the use of C1- When the small molecular alcohol of C8 is used as the solvent, especially when methanol is used as the solvent, the generation of by-products in the oxidation process can be reduced. Second, the solvent in the last step uses small molecular alcohol instead of conventional formic acid as the solvent, which can be beneficial to recovery. solvent, and avoids the problem of being difficult to recover the solvent when acetic acid is used as the solvent, and generates a large amount of waste water, causing the defect of pollution. In addition, in the present invention, in the process of synthesizing intermediate 1 and intermediate 2, it is not necessary to extract and purify the material, and the synthesis process of the next reaction can be directly carried out, which improves the overall yield of the target product and reduces the three wastes. Produce and realize excellent effects such as solvent recovery and application.

The second aspect of the present invention provides an application of fenfenapyr, which is applied to a pesticide; the fenfenapyr is prepared by the method for synthesizing the fenfenpyr.

The present invention will be specifically described by the following examples. The following examples can only be used to further illustrate the present invention, and should not be construed as a limitation of the protection of the present invention. Corrections and adjustments still fall within the protection scope of the present invention.

Example 1

A method for synthesizing sulfofenazone, the preparation steps comprising:

Step (1): Mix 50g (0.30mol) reactant (I) and 36g aqueous sodium hydroxide solution (50%, 0.45mol, 1.5eq), dropwise add 33g formaldehyde solution (30%, 0.33mol), after the end Add 36g sodium hydroxide aqueous solution (50%, 0.45mol, 1.5eq), 100mL acetonitrile, pass into chlorodifluoromethane gas, stir, stand for layering, the separated upper organic phase is concentrated to obtain the initial reactant; The initial reactant was dissolved in 1,2-dichloroethane, 35.7 g of thionyl chloride (0.3 mol) was added dropwise at 0 °C, the temperature was returned to 25 °C, the reaction was performed for at least 30 min, water was added to mix, and the lower organic phase was separated. , and concentrated to obtain intermediate 2.

The step (2): 42g of intermediate 1 (0.20mol), 41.4g of potassium carbonate (0.30mol), and 200mL of acetonitrile were stirred and mixed, and 58.7g of intermediate 2 (0.20mol, 90%) was added dropwise, and stirred for 4 hours , add water to stand and mix to separate the organic phase, and concentrate to obtain the transition intermediate; mix the transition intermediate and 300 mL of methanol, add 1.25 g of sodium tungstate dihydrate (3.80 mmol), 1 mL of concentrated sulfuric acid (98%), 64.6 g of hydrogen peroxide ( 0.57mol, 30%), continue stirring for 6 hours, add water, stir, filter and dry.

The purity of the intermediate 1 is 95%; the purity of the intermediate 2 is 90%.

The synthetic method of described intermediate 1, the step comprises:

1) In the first reaction vessel, add 80 g of glyoxylic acid aqueous solution (50% aqueous solution, 0.50 mol), hydroxylamine hydrochloride (0.55 mol, 1.1 eq), 120 g of water, stir to dissolve, then be warmed to 70 ° C and stirred for 3 hours; The reaction temperature was lowered to 0 °C, 117 g of sodium carbonate (1.10 mol, 2.2 eq) and 150 g of 1,2-dichloroethane were added, 80 g of liquid bromine (0.50 mol, 1 eq) was added dropwise, and the temperature was returned to 25 ° C after completion, and Incubate for 8 hours, separate the organic phase, and use it as the first product; the mass ratio of water and glyoxylic acid aqueous solution in step 1) is 1.5:1.

2) 120 g of sodium bicarbonate (1.44 mol, 3 eq) was added to the first product, the temperature was raised to 80° C. with stirring, and finally isobutylene gas was introduced at a rate of 10 g/min to react for 2 hours. After the reaction finishes, add 600g of water, separate out the organic phase, remove the solvent, and obtain the second product;

3) Add the substitution reagent (0.33mol, 1.1eq), 100mL tert-butanol and hydrogen halide solution into the second reaction vessel and mix, then add 1mL hydrogen bromide (48wt%), and add the second product dropwise to the second reaction vessel. In the reaction vessel, after the end, the solvent is removed, and the tert-butanol is recrystallized to obtain; the substitution reagent is thiourea.

The structure of the reactant (I) is shown in formula 1; the structural formula of the intermediate 1 is formula 2-1;

Example 2

A method for synthesizing sulfofenazone, the preparation steps comprising:

Step (1): get 50g (0.30mol) reactant (I), 50g potassium hydroxide aqueous solution (50%, 0.45mol, 1.5eq) and mix, dropwise add 33g formaldehyde solution (30%, 0.33mol), after finishing Add 50 g of potassium hydroxide aqueous solution (50%, 0.45 mol, 1.5 eq), 100 mL of 1,2-dichloroethane, pass chlorodifluoromethane gas, stir, stand for stratification, and separate the upper organic phase, Concentrate to obtain the initial reactant; dissolve the initial reactant in 1,2-dichloroethane, add 29.7 g of phosgene (0.30 mol) dropwise at 0 °C, return the temperature to 25 °C, react for 30 min, add water and mix, and separate out The lower organic phase was concentrated to obtain Intermediate 2.

The step (2): 42g of intermediate 1 (0.20mol), 41.4g of potassium carbonate (0.30mol), and 200mL of dichloromethane were stirred and mixed, and 58.7g of intermediate 2 (0.20mol, 90%) was added dropwise, and stirred For 4 hours, add water to stand and mix to separate the organic phase, and concentrate to obtain the transition intermediate; mix the transition intermediate and 300 mL of tert-butanol, add 1.25 g of sodium tungstate dihydrate (3.80 mmol), 1 mL of concentrated sulfuric acid (98%), 64.6 g of hydrogen peroxide (0.57 mol, 30%) was continuously stirred for 6 hours, then added with water, stirred, filtered and dried.

The purity of the intermediate 1 is 95%; the purity of the intermediate 2 is 90%.

The synthetic method of described intermediate 1, the step comprises:

1) In the first reaction vessel, add 80g glyoxylic acid aqueous solution (50% aqueous solution, 0.5mol), hydroxylamine hydrochloride (0.55mol, 1.1eq), 120g water, stir to dissolve, then be warming up to 70 ° C and stir for 3 hours; The reaction temperature was lowered to 0 °C, 117 g of sodium carbonate (1.10 mol, 2.2 eq) and 150 g of 1,2-dichloroethane were added, 80 g of liquid bromine (0.50 mol, 1 eq) was added dropwise, and the temperature was returned to 25 ° C after completion, and Incubate for 8 hours, separate the organic phase, and use it as the first product; the mass ratio of water and glyoxylic acid aqueous solution in step 1) is 1.5:1.

2) 120 g of sodium bicarbonate (1.44 mol, 3 eq) was added to the first product, the temperature was raised to 80° C. with stirring, and finally isobutylene gas was introduced at a rate of 10 g/min to react for 2 hours. After the reaction finishes, add 600g of water, separate out the organic phase, remove the solvent, and obtain the second product;

3) Add the substitution reagent (0.33mol, 1.1eq), 100mL tert-butanol and hydrogen halide solution into the second reaction vessel and mix, then add 1mL hydrogen bromide (48wt%), and add the second product dropwise to the second reaction vessel. In the reaction vessel, after the end, the solvent is removed, and the tert-butanol is recrystallized to obtain; the substitution reagent is thiourea.

The structure of the reactant (I) is shown in formula 1; the structural formula of the intermediate 1 is formula 2-1;

Example 3

A method for synthesizing sulfofenazone, the preparation steps comprising:

Step (1): Mix 50g (0.30mol) reactant (I) and 36g aqueous sodium hydroxide solution (50%, 0.45mol, 1.5eq), dropwise add 33g formaldehyde solution (30%, 0.33mol), after the end Add 36g sodium hydroxide aqueous solution (50%, 0.45mol, 1.5eq), 100mL acetonitrile, pass into chlorodifluoromethane gas, stir, stand for layering, the separated upper organic phase is concentrated to obtain the initial reactant; Dissolve the initial reactant in 1,2-dichloroethane, add 35.7 g of thionyl chloride (0.30 mol) dropwise at 0 °C, return the temperature to 25 °C, react for at least 30 min, add water and mix, and separate the lower organic phase , and concentrated to obtain intermediate 2.

The step (2): 42g of intermediate 1 (0.20mol), 41.4g of potassium carbonate (0.30mol), and 200mL of acetonitrile were stirred and mixed, and 58.7g of intermediate 2 (0.20mol, 90%) was added dropwise, and stirred for 4 hours , add water to stand and mix to separate out the organic phase, and concentrate to obtain the transition intermediate; mix the transition intermediate and 300 mL of dichloromethane, 98.36 g of m-chloroperoxybenzoic acid (0.57 mol), continue stirring for 6 hours, add water and stir, Filter and dry.

The purity of the intermediate 1 is 95%; the purity of the intermediate 2 is 90%.

The synthetic method of described intermediate 1, the step comprises:

1) In the first reaction vessel, add 80 g of glyoxylic acid aqueous solution (50% aqueous solution, 0.50 mol), hydroxylamine hydrochloride (0.55 mol, 1.1 eq), 120 g of water, stir to dissolve, then be warmed to 70 ° C and stirred for 3 hours; The reaction temperature was lowered to 0 °C, 117 g of sodium carbonate (1.10 mol, 2.2 eq) and 150 g of 1,2-dichloroethane were added, 80 g of liquid bromine (0.50 mol, 1 eq) was added dropwise, and the temperature was returned to 25 ° C after completion, and Incubate for 8 hours, separate the organic phase, and use it as the first product; the mass ratio of water and glyoxylic acid aqueous solution in step 1) is 1.5:1.

2) 120 g of sodium bicarbonate (1.44 mol, 3 eq) was added to the first product, the temperature was raised to 80° C. with stirring, and finally isobutylene gas was introduced at a rate of 10 g/min to react for 2 hours. After the reaction finishes, add 600g of water, separate out the organic phase, remove the solvent, and obtain the second product;

3) Add the substitution reagent (0.33mol, 1.1eq), 100mL tert-butanol and hydrogen halide solution into the second reaction vessel and mix, then add 1mL hydrogen bromide (48wt%), and add the second product dropwise to the second reaction vessel. In the reaction vessel, after the end, the solvent is removed and the tert-butanol is recrystallized to obtain; the substitution reagent is sodium hydrosulfide.

The structure of the reactant (I) is shown in formula 1; the structural formula of the intermediate 1 is formula 2-2;

Example 4

A method for synthesizing sulfofenazone, the preparation steps comprising:

Step (1): Mix 50g (0.30mol) reactant (I) and 36g aqueous sodium hydroxide solution (50%, 0.45mol, 1.5eq), dropwise add 33g formaldehyde solution (30%, 0.33mol), after the end Add 36g sodium hydroxide aqueous solution (50%, 0.45mol, 1.5eq), 100mL acetonitrile, pass into chlorodifluoromethane gas, stir, stand for layering, the separated upper organic phase is concentrated to obtain the initial reactant; Dissolve the initial reactant in 1,2-dichloroethane, add 35.7 g of thionyl chloride (0.30 mol) dropwise at 0 °C, return the temperature to 25 °C, react for at least 30 min, add water and mix, and separate the lower organic phase , and concentrated to obtain intermediate 2.

The step (2): 42g of intermediate 1 (0.20mol), 41.4g of potassium carbonate (0.30mol), and 200mL of acetonitrile were stirred and mixed, and 58.7g of intermediate 2 (0.20mol, 90%) was added dropwise, and stirred for 4 hours , add water to stand and mix to separate the organic phase, and concentrate to obtain the transition intermediate; mix the transition intermediate and 300 mL of methanol, add 1 mL of concentrated sulfuric acid (98%), 64.6 g of hydrogen peroxide (0.57 mol, 30%), and continue to stir for 6 hours. , add water, stir, filter and dry.

The purity of the intermediate 1 is 95%; the purity of the intermediate 2 is 90%.

The synthetic method of described intermediate 1, the step comprises:

1) In the first reaction vessel, add 80g glyoxylic acid aqueous solution (50% aqueous solution, 0.5mol), hydroxylamine hydrochloride (0.55mol, 1.1eq), 120g water, stir to dissolve, then be warming up to 70 ° C and stir for 3 hours; The reaction temperature was lowered to 0 °C, 117 g of sodium carbonate (1.1 mol, 2.2 eq) and 150 g of 1,2-dichloroethane were added, 80 g of liquid bromine (0.5 mol, 1 eq) was added dropwise, and the temperature was returned to 25 ° C after completion, and Incubate for 8 hours, separate the organic phase, and use it as the first product; the mass ratio of water and glyoxylic acid aqueous solution in step 1) is 1.5:1.

2) 120 g of sodium bicarbonate (1.44 mol, 3 eq) was added to the first product, the temperature was raised to 80° C. with stirring, and finally isobutylene gas was introduced at a rate of 10 g/min to react for 2 hours. After the reaction finishes, add 600g of water, separate out the organic phase, remove the solvent, and obtain the second product;

3) Add the substitution reagent (0.33mol, 1.1eq), 100mL tert-butanol and hydrogen halide solution into the second reaction vessel and mix, then add 1mL hydrogen bromide (48wt%), and add the second product dropwise to the second reaction vessel. In the reaction vessel, after the end, the solvent is removed, and the tert-butanol is recrystallized to obtain; the substitution reagent is thiourea.

The structure of the reactant (I) is shown in formula 1; the structural formula of the intermediate 1 is formula 2-1;

Example 5

A method for synthesizing sulfofenazone, the preparation steps comprising:

Step (1): Mix 50g (0.30mol) reactant (I) and 36g aqueous sodium hydroxide solution (50%, 0.45mol, 1.5eq), dropwise add 33g formaldehyde solution (30%, 0.33mol), after the end Add 36g sodium hydroxide aqueous solution (50%, 0.45mol, 1.5eq), 100mL acetonitrile, pass into chlorodifluoromethane gas, stir, stand for layering, the separated upper organic phase is concentrated to obtain the initial reactant; Dissolve the initial reactant in 1,2-dichloroethane, add 35.7 g of thionyl chloride (0.30 mol) dropwise at 0 °C, return the temperature to 25 °C, react for at least 30 min, add water and mix, and separate the lower organic phase , and concentrated to obtain intermediate 2.

The step (2): 42g of intermediate 1 (0.20mol), 41.4g of potassium carbonate (0.30mol), and 200mL of acetonitrile were stirred and mixed, and 58.7g of intermediate 2 (0.20mol, 90%) was added dropwise, and stirred for 4 hours , add water to stand and mix to separate the organic phase, and concentrate to obtain the transition intermediate; mix the transition intermediate and 300 mL of acetic acid, add 1.25 g of sodium tungstate dihydrate (3.80 mmol), 1 mL of concentrated sulfuric acid (98%), 64.6 g of hydrogen peroxide ( 0.57mol, 30%), continue stirring for 6 hours, add water, stir, filter and dry.

The purity of the intermediate 1 is 95%; the purity of the intermediate 2 is 90%.

The synthetic method of described intermediate 1, the step comprises:

1) In the first reaction vessel, add 80 g of glyoxylic acid aqueous solution (50% aqueous solution, 0.50 mol), hydroxylamine hydrochloride (0.55 mol, 1.1 eq), 120 g of water, stir to dissolve, then be warmed to 70 ° C and stirred for 3 hours; The reaction temperature was lowered to 0 °C, 117 g of sodium carbonate (1.10 mol, 2.2 eq) and 150 g of 1,2-dichloroethane were added, 80 g of liquid bromine (0.50 mol, 1 eq) was added dropwise, and the temperature was returned to 25 ° C after completion, and Incubate for 8 hours, separate the organic phase, and use it as the first product; the mass ratio of water and glyoxylic acid aqueous solution in step 1) is 1.5:1.

2) 120 g of sodium bicarbonate (1.44 mol, 3 eq) was added to the first product, the temperature was raised to 80° C. with stirring, and finally isobutylene gas was introduced at a rate of 10 g/min to react for 2 hours. After the reaction finishes, add 600g of water, separate out the organic phase, remove the solvent, and obtain the second product;

3) Add the substitution reagent (0.33mol, 1.1eq), 100mL tert-butanol and hydrogen halide solution into the second reaction vessel and mix, then add 1mL hydrogen bromide (48wt%), and add the second product dropwise to the second reaction vessel. In the reaction vessel, after the end, the solvent is removed, and the tert-butanol is recrystallized to obtain; the substitution reagent is thiourea.

The structure of the reactant (I) is shown in formula 1; the structural formula of the intermediate 1 is formula 2-1;

Example 6

A method for synthesizing sulfofenazone, the preparation steps comprising:

Step (1): Mix 50g (0.30mol) reactant (I) and 36g aqueous sodium hydroxide solution (50%, 0.45mol, 1.5eq), dropwise add 33g formaldehyde solution (30%, 0.33mol), after the end Add 36g sodium hydroxide aqueous solution (50%, 0.45mol, 1.5eq), 100mL acetonitrile, pass into chlorodifluoromethane gas, stir, stand for layering, the separated upper organic phase is concentrated to obtain the initial reactant; Dissolve the initial reactant in 1,2-dichloroethane, add 35.7 g of thionyl chloride (0.30 mol) dropwise at 0 °C, return the temperature to 25 °C, react for at least 30 min, add water and mix, and separate the lower organic phase , and concentrated to obtain intermediate 2.

The step (2): 42g of intermediate 1 (0.20mol), 41.4g of potassium carbonate (0.30mol), and 200mL of acetonitrile were stirred and mixed, and 58.7g of intermediate 2 (0.20mol, 90%) was added dropwise, and stirred for 4 hours , add water to stand and mix to separate out the organic phase, and concentrate to obtain the transition intermediate; mix the transition intermediate and 300 mL of methanol, 98.36 g m-chloroperoxybenzoic acid (0.57 mol), continue stirring for 6 hours, add water and stir, filter and dry That's it.

The purity of the intermediate 1 is 95%; the purity of the intermediate 2 is 90%.

The synthetic method of described intermediate 1, the step comprises:

1) In the first reaction vessel, add 80g glyoxylic acid aqueous solution (50% aqueous solution, 0.5mol), hydroxylamine hydrochloride (0.55mol, 1.1eq), 120g water, stir to dissolve, then be warming up to 70 ° C and stir for 3 hours; The reaction temperature was lowered to 0 °C, 117 g of sodium carbonate (1.1 mol, 2.2 eq) and 150 g of 1,2-dichloroethane were added, 80 g of liquid bromine (0.5 mol, 1 eq) was added dropwise, and the temperature was returned to 25 ° C after completion, and Incubate for 8 hours, separate the organic phase, and use it as the first product; the mass ratio of water and glyoxylic acid aqueous solution in step 1) is 1.5:1.

2) 120 g of sodium bicarbonate (1.44 mol, 3 eq) was added to the first product, the temperature was raised to 80° C. with stirring, and finally isobutylene gas was introduced at a rate of 10 g/min to react for 2 hours. After the reaction finishes, add 600g of water, separate out the organic phase, remove the solvent, and obtain the second product;

3) Add the substitution reagent (0.33mol, 1.1eq), 100mL tert-butanol and hydrogen halide solution into the second reaction vessel and mix, then add 1mL hydrogen bromide (48wt%), and add the second product dropwise to the second reaction vessel. In the reaction vessel, after the end, the solvent is removed, and the tert-butanol is recrystallized to obtain; the substitution reagent is thiourea.

The structure of the reactant (I) is shown in formula 1; the structural formula of the intermediate 1 is formula 2-1;

Example 7

A method for synthesizing sulfofenazone, the preparation steps comprising:

Step (1): Mix 50g (0.3mol) of reactant (I) and 36g of aqueous sodium hydroxide solution (50%, 0.45mol, 1.5eq), dropwise add 33g of formaldehyde solution (30%, 0.33mol), after the end Add 36g sodium hydroxide aqueous solution (50%, 0.45mol, 1.5eq), 100mL acetonitrile, pass into chlorodifluoromethane gas, stir, stand for layering, the separated upper organic phase is concentrated to obtain the initial reactant; The initial reactant was dissolved in 1,2-dichloroethane, 35.7 g of thionyl chloride (0.3 mol) was added dropwise at 0 °C, the temperature was returned to 25 °C, the reaction was performed for at least 30 min, water was added to mix, and the lower organic phase was separated. , and concentrated to obtain intermediate 2.

The step (2): 42g of intermediate 1 (0.20mol), 41.4g of potassium carbonate (0.30mol), and 200mL of acetonitrile were stirred and mixed, and 58.7g of intermediate 2 (0.20mol, 90%) was added dropwise, and stirred for 4 hours , add water to stand and mix to separate the organic phase, and concentrate to obtain the transition intermediate; mix the transition intermediate and 300 mL of ethanol, add 1.25 g of sodium tungstate dihydrate (3.80 mmol), 1 mL of concentrated sulfuric acid (98%), 64.6 g of hydrogen peroxide ( 0.57mol, 30%), continue stirring for 6 hours, add water, stir, filter and dry.

The purity of the intermediate 1 is 90%; the purity of the intermediate 2 is 90%.

The synthetic method of described intermediate 1, the step comprises:

1) In the first reaction vessel, add 80g glyoxylic acid aqueous solution (50% aqueous solution, 0.5mol), hydroxylamine compound (0.55mol, 1.1eq), 120g water, stir to dissolve, then be warming up to 70 ° C and stir for 3 hours; The reaction temperature was lowered to 0 °C, 117 g of sodium carbonate (1.1 mol, 2.2 eq) and 150 g of 1,2-dichloroethane were added, 80 g of liquid bromine (0.5 mol, 1 eq) was added dropwise, and the temperature was returned to 25 ° C after completion, and Incubate for 8 hours, separate the organic phase, and use it as the first product; the mass ratio of water and glyoxylic acid aqueous solution in step 1) is 1.5:1.

2) 120 g of sodium bicarbonate (1.44 mol, 3 eq) was added to the first product, the temperature was raised to 80° C. with stirring, and finally isobutylene gas was introduced at a rate of 10 g/min to react for 2 hours. After the reaction finishes, add 600g of water, separate out the organic phase, remove the solvent, and obtain the second product;

3) Add the substitution reagent (0.33mol, 1.1eq), 100mL tert-butanol and hydrogen halide solution into the second reaction vessel and mix, then add 1mL hydrogen bromide (48wt%), and add the second product dropwise to the second reaction vessel. In the reaction vessel, after the end, the solvent is removed, and the tert-butanol is recrystallized to obtain; the substitution reagent is thiourea.

The structure of the reactant (I) is shown in formula 1; the structural formula of the intermediate 1 is formula 2-1;

Example 8

A method for synthesizing sulfofenazone, the preparation steps comprising:

Step (1): Mix 50g (0.3mol) of reactant (I) and 36g of aqueous sodium hydroxide solution (50%, 0.45mol, 1.5eq), dropwise add 33g of formaldehyde solution (30%, 0.33mol), after the end Add 36g sodium hydroxide aqueous solution (50%, 0.45mol, 1.5eq), 100mL acetonitrile, pass into chlorodifluoromethane gas, stir, stand for layering, the separated upper organic phase is concentrated to obtain the initial reactant; The initial reactant was dissolved in 1,2-dichloroethane, 35.7 g of thionyl chloride (0.3 mol) was added dropwise at 0 °C, the temperature was returned to 25 °C, the reaction was performed for at least 30 min, water was added to mix, and the lower organic phase was separated. , and concentrated to obtain intermediate 2.

The step (2): 42g of intermediate 1 (0.20mol), 41.4g of potassium carbonate (0.30mol), and 200mL of acetonitrile were stirred and mixed, and 58.7g of intermediate 2 (0.20mol, 90%) was added dropwise, and stirred for 4 hours , add water to stand and mix to separate the organic phase, and concentrate to obtain the transition intermediate; mix the transition intermediate and 300 mL of dichloromethane, add 1.25 g of sodium tungstate dihydrate (3.80 mmol), 1 mL of concentrated sulfuric acid (98%), 64.6 g Hydrogen peroxide (0.57mol, 30%), after stirring for 6 hours, adding water, stirring, filtering and drying.

The purity of the intermediate 1 is 95%; the purity of the intermediate 2 is 90%.

The synthetic method of described intermediate 1, the step comprises:

1) In the first reaction vessel, add 80g glyoxylic acid aqueous solution (50% aqueous solution, 0.5mol), hydroxylamine compound (0.55mol, 1.1eq), 120g water, stir to dissolve, then be warming up to 70 ° C and stir for 3 hours; The reaction temperature was lowered to 0 °C, 117 g of sodium carbonate (1.1 mol, 2.2 eq) and 150 g of 1,2-dichloroethane were added, 80 g of liquid bromine (0.5 mol, 1 eq) was added dropwise, and the temperature was returned to 25 ° C after completion, and Incubate for 8 hours, separate the organic phase, and use it as the first product; the mass ratio of water and glyoxylic acid aqueous solution in step 1) is 1.5:1.

2) 120 g of sodium bicarbonate (1.44 mol, 3 eq) was added to the first product, the temperature was raised to 80° C. with stirring, and finally isobutylene gas was introduced at a rate of 10 g/min to react for 2 hours. After the reaction finishes, add 600g of water, separate out the organic phase, remove the solvent, and obtain the second product;

3) Add the substitution reagent (0.33mol, 1.1eq), 100mL tert-butanol and hydrogen halide solution into the second reaction vessel and mix, then add 1mL hydrogen bromide (48wt%), and add the second product dropwise to the second reaction vessel. In the reaction vessel, after the end, the solvent is removed, and the tert-butanol is recrystallized to obtain; the substitution reagent is thiourea.

The structure of the reactant (I) is shown in formula 1; the structural formula of the intermediate 1 is formula 2-1;

Example 9

A method for synthesizing sulfofenazone, the preparation steps comprising:

Step (1): Mix 50g (0.3mol) of reactant (I) and 36g of aqueous sodium hydroxide solution (50%, 0.45mol, 1.5eq), dropwise add 33g of formaldehyde solution (30%, 0.33mol), after the end Add 36g sodium hydroxide aqueous solution (50%, 0.45mol, 1.5eq), 100mL acetonitrile, pass into chlorodifluoromethane gas, stir, stand for layering, the separated upper organic phase is concentrated to obtain the initial reactant; The initial reactant was dissolved in 1,2-dichloroethane, 35.7 g of thionyl chloride (0.3 mol) was added dropwise at 0 °C, the temperature was returned to 25 °C, the reaction was performed for at least 30 min, water was added to mix, and the lower organic phase was separated. , and concentrated to obtain intermediate 2.

The step (2): 42g of intermediate 1 (0.20mol), 41.4g of potassium carbonate (0.30mol), and 200mL of acetonitrile were stirred and mixed, and 58.7g of intermediate 2 (0.20mol, 90%) was added dropwise, and stirred for 4 hours , add water to stand and mix to separate the organic phase, and concentrate to obtain the transition intermediate; mix the transition intermediate and 300 mL of methanol, add 1.25 g of sodium tungstate dihydrate (3.80 mmol), 1 mL of concentrated sulfuric acid (98%), 64.6 g of hydrogen peroxide ( 0.57mol, 30%), continue stirring for 6 hours, add water, stir, filter and dry.

The purity of the intermediate 1 is 89%; the purity of the intermediate 2 is 90%.

The synthetic method of described intermediate 1, the step comprises:

1) In the first reaction vessel, add 80g glyoxylic acid aqueous solution (50% aqueous solution, 0.5mol), hydroxylamine compound (0.55mol, 1.1eq), 120g water, stir to dissolve, then be warming up to 70 ° C and stir for 3 hours; The reaction temperature was lowered to 0 °C, 117 g of sodium carbonate (1.1 mol, 2.2 eq) and 150 g of 1,2-dichloroethane were added, 80 g of liquid bromine (0.5 mol, 1 eq) was added dropwise, and the temperature was returned to 25 ° C after completion, and Incubate for 8 hours, separate the organic phase, and use it as the first product; the mass ratio of water and glyoxylic acid aqueous solution in step 1) is 1.5:1.

2) 120 g of sodium bicarbonate (1.44 mol, 3 eq) was added to the first product, the temperature was raised to 80° C. with stirring, and finally isobutylene gas was introduced at a rate of 10 g/min to react for 2 hours. After the reaction finishes, add 600g of water, separate out the organic phase, remove the solvent, and obtain the second product;

3) The substitution reagent (0.27mol, 0.9eq), 100mL of tert-butanol and hydrogen halide solution were added to the second reaction vessel and mixed, then 1mL of hydrogen bromide (48wt%) was added, and the second product was added dropwise to the second reaction vessel. In the reaction vessel, after the end, the solvent is removed, and the tert-butanol is recrystallized to obtain; the substitution reagent is thiourea.

The structure of the reactant (I) is shown in formula 1; the structural formula of the intermediate 1 is formula 2-1;

Example 10

A method for synthesizing sulfofenazone, the preparation steps comprising:

The step (1): take 50.0g (0.16mol) of the reactant (II) and dissolve it in 200mL of N,N-dimethylformamide, and then add 66.2g of K ₂ CO ₃ (0.48mol) to the reaction system. ) and the solution was stirred for 1 hour. After that, 81 g (0.8 mol) of monochlorodifluoromethane was passed into the solution within half an hour. The reaction was stirred at 25°C for 6 hours. Control the reaction in the liquid phase. After the reaction is completed, add 300 mL of water and 100 mL of 1,1-dichloromethane to the reaction solution, wash with 200 mL of water and 200 mL of saturated sodium chloride solution, and dry the separated organic phase. The solvent was distilled off under pressure to obtain 46 g of the transition intermediate. Mix the transition intermediate and 200 mL of methanol, add 1.0 g (3.04 mmol) of sodium tungstate dihydrate, 1 mL (98%) of concentrated sulfuric acid, and 51.7 g (0.46 mol, 30%) of hydrogen peroxide, continue stirring for 6 hours, then add water and stir , filtered and dried.

The purity of the reactant (II) was 95%.

The synthetic method of described reactant (II), the step comprises:

1) In the first reaction vessel, add 80.0 g of glyoxylic acid aqueous solution (50% aqueous solution, 0.54 mol), hydroxylamine compound (0.55 mol, 1.1 eq), 120 g of water, stir to dissolve, then heat up to 70 ° C and stir for 3 hours ; Reduce the reaction temperature to 0°C, add 117g of sodium carbonate (1.1mol, 2.2eq) and 150g of 1,2-dichloroethane, dropwise add 80g of liquid bromine (0.5mol, 1eq), return to 25°C after the end, And keep the temperature for 8 hours, separate the organic phase as the first product; the mass ratio of water and glyoxylic acid aqueous solution in step 1) is 1.5:1.

2) 120 g of sodium bicarbonate (1.44 mol, 3 eq) was added to the first product, the temperature was raised to 80° C. with stirring, and finally isobutylene gas was introduced at a rate of 10 g/min to react for 2 hours. After the reaction finishes, add 600g of water, separate out the organic phase, remove the solvent, and obtain the second product;

3) The substitution reagent (0.27mol, 0.9eq), 100mL of tert-butanol and hydrogen halide solution were added to the second reaction vessel and mixed, then 1mL of hydrogen bromide (48wt%) was added, and the second product was added dropwise to the second reaction vessel. In the reaction vessel, after the end, the solvent is removed and the tert-butanol is recrystallized to obtain; the substitution reagent is thiourea salt.

4) Add 40 g of reactant (I) (0.24 mol) and 34 g of NaOH (0.84 mol) into 200 mL of water, until it is completely dissolved, and then dropwise add 52 g of formaldehyde (31%, 0.48 mol) solution. Add dropwise for half an hour. After completion, it was stirred at 25°C for 1 hour. 50 g (0.24 mol) of the thiourea salt obtained above was dissolved in 150 mL of water, and then added dropwise to the reaction for 20 minutes. The reaction was continued to stir at 25°C for 5 hours. The reaction was controlled in the liquid phase. After the reaction was completed, 20 mL of hydrochloric acid (35%, 0.2 mol) was added to adjust the pH of the reaction solution to 6. There was solid precipitation in the reaction solution, and stirring was continued for 1 hour. After water, suction filtration is carried out, the filter cake is washed with water, and the filter cake is dried to obtain the reaction body (II) as a light yellow solid.

The structural formula 2 of the reactant (II) is shown;

Performance Testing

1. Test of the content and yield of fenfenapyr: The content and yield of fenfenapyr obtained by the synthesis method of fenfenapyr described in Example 1-Example 10 were tested.

Test method: isocratic scanning, A mobile phase is acetic acid aqueous solution with pH=4, B mobile phase is methanol. The injection volume is 10 μL; the running time is 30.0 minutes; the conditions are shown in Table 3; the test results are shown in Table 1.

2. Liquid phase chromatogram test: liquid phase test was carried out on the sulfofenapyr obtained by the synthetic method of sulfofenapyr described in Example 1, the chromatographic peak results of the test were as shown in Table 2, and the liquid phase chromatogram results were as shown in Table 2. Figure 1.

Liquid chromatography test conditions: isocratic scanning, A mobile phase is acetic acid aqueous solution with pH=4, B mobile phase is methanol. The sample injection volume is 10 μL; the running time is 30.0 minutes; the conditions are as shown in Table 3. The liquid chromatogram test results: the sulfofenapyr obtained by the synthetic method of sulfofenapyr described in Example 1 has an impurity in 17.308 minutes Peak; method is isocratic scan, A mobile phase is aqueous acetic acid pH=4, B mobile phase is methanol.

Table 1

Example content(%) Yield (%) Example 1 99% 92% Example 2 96% 90% Example 3 98% 91% Example 4 99% 81% Example 5 99% 90% Example 6 99% 91% Example 7 95% 78% Example 8 94% 67% Example 9 92% 82% Example 10 99% 91%

Table 2

table 3

The above descriptions are only preferred embodiments of the present invention, and are not intended to limit the invention in other forms. Any person skilled in the art may use the technical contents disclosed above to make changes or change to equivalent embodiments with equivalent changes. However, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention without departing from the content of the technical solution of the present invention still belong to the protection scope of the technical solution of the present invention.

Claims (10)

1. a synthetic method of sulfofenapyr, is characterized in that, preparation step comprises: Step (1): reaction body (I) is subjected to hydroxyalkylation, fluoromethylation and chlorination to obtain intermediate 2; Step (2): mix the intermediate 1 and the intermediate 2, add water to separate the organic phase, obtain a transition intermediate, add a solvent and an oxidizing agent to react, to obtain the final product; The structure of the reactant (I) is shown in formula 1; the structural formula of the intermediate 1 is formula 2;

2. the synthetic method of sulfofenazone as claimed in claim 1, is characterized in that, the structure of described R1 is selected from-SH, a kind of in formula 3; Described formula 3 is as follows, wherein said R2 Represents one of amino group, hydrogen atom, substituted or unsubstituted C1-C12 alkyl group and alkoxy group;

3. the synthetic method of sulfofenazone as claimed in claim 1, is characterized in that, in described step (1), comprises chlorination reagent in chlorination reaction process; Described chlorination reagent comprises thionyl chloride, trichloride At least one of phosphorus chloride, sulfonyl chloride, chlorine gas, phosgene, and benzoyl chloride. 4. the synthetic method of sulfofenazone as claimed in claim 1, is characterized in that, the solvent in described step (2) comprises the small molecular alcohol of C1-C8, methylene dichloride, 1,2-dichloroethane At least one of alkane, chlorobenzene, dichlorobenzene, ethyl acetate, and butyl acetate. 5. the synthetic method of fenfenpyr as claimed in claim 1, is characterized in that, the oxidant of described step (2) comprises at least one in hydrogen peroxide, m-chloroperoxybenzoic acid, potassium monopersulfate composite salt kind. 6. the synthetic method of sulfofenazone as claimed in claim 4, is characterized in that, the small molecular alcohol of described C1-C8 is selected from methanol, ethanol, tert-butanol, butanediol, propylene glycol, isobutanol, At least one of at least one of isoamyl alcohol, isopropanol, ethylene glycol, and glycerol. 7 . The method for synthesizing sulfofenazone according to claim 1 , wherein the purity of the intermediate 1 is greater than or equal to 90%; the purity of the intermediate 2 is greater than or equal to 85%. 8 . 8. the synthetic method of sulfofenapyr as claimed in claim 5, is characterized in that, also comprises sodium tungstate in the described oxidizing agent; The mol ratio between described hydrogen peroxide, sodium tungstate dihydrate is 1:(0.005 -0.35). 9. The method for synthesizing sulfofenazone according to any one of claims 1-8, wherein the raw material for the preparation of the reactant (I) comprises ethyl trifluoroacetoacetate; The raw materials for preparation include at least one of glyoxylic acid, thiourea, hydrosulfide and bromine. 10 . An application of fenfenapyr, characterized in that, it is applied to a pesticide; the fenfenazim is prepared by the synthetic method described in any one of claims 1-9.

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