Synthesis method of insecticide sulfoxaflor

Abstract

The invention provides a synthesis method of insecticide sulfoxaflor, which comprises the following steps: taking methyl ethyl sulfide as a raw material, and sequentially carrying out N-cyano amination reaction and oxidation reaction to obtain N-cyano ethyl methylsulfonyl imide; the preparation method comprises the following steps: carrying out dehydrogenation coupling reaction on N-cyanoethyl methylsulfonyl imide and 2-trifluoromethyl-5-pyridine boric acid, and realizing C-H arylation of ortho-methylene with high selectivity, so as to obtain the insecticide sulfoxaflor. Compared with a traditional sulfoxaflor synthesis route in which a pyridine ring is firstly constructed and then other functional groups are introduced, the synthesis method disclosed by the invention has the advantages that the introduction of the pyridine ring is carried out in the last step of the synthesis route, so that the N-cyano amination and oxidation reaction yield is increased, the consumption of a pyridine ring raw material is reduced, and the cost is reduced. And the sulfoxaflor is effectively prepared at high yield.

Description

Technical Field

[0001] This invention belongs to the field of pesticide synthesis technology, and relates to insecticides, specifically to a method for synthesizing the insecticide flonicamid. Background Technology

[0002] Sulfoxaflor is a new sulfonamide insecticide for controlling sap-sucking pests, announced by Dow AgroSciences in 2010. It is characterized by high efficiency, broad spectrum, safety, rapid action, and long residual effect. It is mainly used to control various piercing-sucking pests such as aphids, mirid bugs, stink bugs, whiteflies, scale insects, planthoppers, certain psyllids, and thrips on cotton, rapeseed, fruit trees, soybeans, fruits, small grains, vegetables, rice, lawns, and ornamental plants. It is a preferred agent for integrated pest management.

[0003] The earliest report on the synthesis method of flonicamid is found in patent WO2007095229 (Insecticidal N-Substituted(6-haloalkyl pyridin-3-yl)alkyl Sulfoximines, DOW AGROSCIENCESLLC, 2007-08-23.), and the synthetic route is as follows: 3-chloromethyl-6-(trifluoromethyl)pyridine is used as the starting material, which undergoes a nucleophilic substitution reaction with sodium methanethiol to generate 3-[1-(methylthio)methyl]-6-(trifluoromethyl)pyridine (intermediate A). The latter reacts with cyanamide in diethyl iodophenyl ester to generate methyl[1-(2-trifluoromethylpyridin-5-yl)ethyl-N-cyano]thioimine, which is then subjected to a two-step reaction of oxidation and methylation to obtain flonicamid. However, the high price of raw materials and the low reaction yield limit the widespread application of this process. Subsequently, a series of studies were conducted to optimize the synthesis process of the key pyridine sulfide intermediate A in the above process. Depending on the type of raw materials, it can be divided into the 3-methylthio-n-butyraldehyde route and the n-butyraldehyde route.

[0004] Dow patents CN101516847B (Method for the preparation of 2-substituted-5-((1-alkylthio)alkyl)pyridine, Dow AgroSciences, 2011-11-16) and CN103814031B (Improved method for the preparation of 2-trifluoromethyl-5-(1-substituted)alkylpyridine, Dow AgroSciences, 2016-10-19) disclose a synthetic route for obtaining the intermediate 3-[1-(methylthio)methyl]-6(trifluoromethyl)pyridine by reacting 3-methylthiobutyraldehyde as a raw material with tetrahydropyrrole under the condition of potassium carbonate as an acid-binding agent, followed by a two-step reaction of condensation and cyclization with 4-ethoxy-1,1,1-trifluoro-but-3-en-2-one. Dow patent WO2008066558 describes a process in the synthesis of enamines where n-butyraldehyde replaces the regulated 2-butenal. It reacts with tetrahydropyrrole to generate 1-tetrahydropyrrole-1-butene, which then undergoes condensation cyclization with 1-ethoxy-4,4,4-trifluoro-1-butene to produce 5-ethyl-2-(trifluoromethyl)pyridine. This is followed by a two-step bromination and methylthiolation reaction to yield 3-[1-(methylthio)methyl]-6-(trifluoromethyl)pyridine. While this improved process reduces raw material costs to some extent, the reaction steps are too long, the post-reaction processing is complex, and the improvement in reaction efficiency is limited. Furthermore, the presence of the pyridine heterocycle in the subsequent N-cyanoamination and oxidation processes of the 3-[1-(methylthio)methyl]-6-(trifluoromethyl)pyridine intermediate leads to numerous side reactions, difficult post-processing, and low final product yield. Therefore, developing an efficient and high-yield synthetic process for flonicamid nitrile synthesis is urgently needed. Summary of the Invention

[0005] In view of the shortcomings of the existing technology, the purpose of this invention is to provide a method for synthesizing the insecticide flonicamid, thereby solving the technical problem that the efficiency and yield of the synthesis methods in the existing technology need to be further improved.

[0006] To solve the above-mentioned technical problems, the present invention adopts the following technical solution.

[0007] A method for synthesizing the insecticide flonicamid, wherein the method uses methyl ethyl sulfide as a raw material and proceeds through two steps of N-cyanoacetylamine reaction and oxidation reaction to obtain N-cyanoethyl methanesulfonyl imide; N-cyanoethyl methanesulfonyl imide undergoes a dehydrogenation coupling reaction with 2-trifluoromethyl-5-pyridineboronic acid to achieve CH arylation of the ortho-methylene group with high selectivity, thereby obtaining the insecticide flonicamid.

[0008] The present invention also has the following technical features.

[0009] The reaction temperatures for the N-cyanoamine reaction, oxidation reaction, and dehydrogenation coupling reaction are each independently between 0°C and 60°C.

[0010] Preferably, the reaction temperature for the N-cyanoamine reaction is 0°C to room temperature.

[0011] Specifically, the method includes the following steps.

[0012] Step 1, Synthesis of N-cyanoethylmethylthioimine: Methyl ethyl sulfide, cyanamide, base I, and solvent I were added sequentially to the reaction vessel. After stirring and dissolving, oxidant I was added to the reaction system, and the mixture was heated to the reaction temperature to carry out the N-cyanoamine reaction. Stirring was stopped after the sulfide disappeared as monitored by TLC. The reaction was quenched with a saturated solution of sodium thiosulfate or sodium sulfite. Subsequently, the mixture was extracted with solvent I, and after evaporating the organic phase to dryness, N-cyanoethyl methyl thioimine was obtained by column chromatography.

[0013] Step 2, Synthesis of N-cyanoethylmethanesulfonylimide: N-cyanoethylmethylthioimide, base II, and solvent II were added sequentially to the reaction vessel. After stirring and dissolving, oxidant II was added to the reaction system, and the mixture was heated to the reaction temperature for oxidation. Stirring was stopped after the thioimide raw material disappeared, as monitored by TLC. The reaction was quenched with a saturated solution of sodium thiosulfate or sodium sulfite, and then extracted with solvent II. After evaporating the organic phase to dryness, N-cyanoethylmethylsulfonylimide was obtained by column chromatography.

[0014] Step 3, Synthesis of the insecticide flonicamid: N-cyanoethyl methanesulfonyl imide, 2-trifluoromethyl-5-pyridineboronic acid, oxidant III, non-precious metal catalyst, base III, and solvent III were added sequentially to the reaction vessel. The mixture was heated to the reaction temperature to carry out a dehydrogenation coupling reaction. Stirring was stopped after the sulfonyl imide raw material disappeared, as monitored by TLC. The reaction was quenched with a saturated solution of sodium thiosulfate or sodium sulfite. The mixture was then extracted with solvent III, and the organic phase was evaporated to dryness before column chromatography was used to separate the insecticide flonicamid.

[0015] In step one, the oxidant I is one or more of (diacetoxyiodine)benzene, [bis(trifluoroacetoxy)iodine]benzene, N-bromosuccinimide, 1,3-dibromo-5,5-dimethylhydantoin, and sodium hypochlorite.

[0016] In step two, the oxidant II is one or more of the following: m-chloroperoxybenzoic acid, hydrogen peroxide, sodium periodate, potassium permanganate, and sodium permanganate.

[0017] In step three, the oxidant III is one or more of the following: tert-butyl hydroperoxide, di-tert-butyl peroxide, benzoyl peroxide, tert-butyl peroxybenzoate, tetramethylpiperidine oxide, (diacetoxyiodine)benzene, [bis(trifluoroacetoxy)iodine]benzene, manganese dioxide, potassium persulfate, sodium persulfate, ammonium persulfate, and oxygen.

[0018] In step three, the non-precious metal catalyst is one or more of the following: bis(1,5-cyclooctadiene) nickel, nickel chloride, nickel bromide, nickel acetylacetonate, nickel acetate, nickel trifluoromethanesulfonate, bis(triphenylphosphine)dichloride, 1,2-bis(diphenylphosphine)ethane nickel chloride, nickel(II) chloride ethylene glycol dimethyl ether complex, nickel oxalate, bis(8-hydroxyquinoline)copper(II), copper trifluoroacetate, copper acetylacetonate, copper tetra(acetonitrile)tetrafluoroborate, copper trifluoromethanesulfonate, copper tetraacetonitrile hexafluorophosphate, cuprous bromide, copper bromide, cuprous iodide, etc., as well as copper catalysts.

[0019] In steps one through three, solvent I, solvent II, and solvent III are independently selected from one or more combinations of dichloromethane, tetrahydrofuran, 1,2-dichloroethane, acetonitrile, methanol, ethanol, N,N-dimethylformamide, N,N-dimethylacetamide, and dimethyl sulfoxide.

[0020] In steps one to three, the base I, base II and base III are independently selected from one or more combinations of potassium tert-butoxide, sodium tert-butoxide, potassium methoxide, sodium methoxide, sodium hydride, potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, potassium acetate, sodium acetate, sodium phosphate, pyridine, triethylamine, N,N-diisopropylethylamine, 4-dimethylaminopyridine, 1,8-diazabicycloundec-7-ene (DBU) and 1,4-diazabicyclo[2.2.2]octane (DABCO).

[0021] In step one, the molar ratio of methyl ethyl sulfide to cyanamide is 1.0:(1.0~2.0), the molar ratio of methyl ethyl sulfide to oxidant I is 1.0:(1.0~3.0), and the molar ratio of methyl ethyl sulfide to base I is 1:(1.5~3.0).

[0022] In step two, the molar ratio of N-cyanoethyl methyl thioimide to oxidant II is 1.0:(1.5-3.0), and the molar ratio of N-cyanoethyl methyl thioimide to base II is 1.0:(1.5-3.0).

[0023] In step three, the molar ratio of N-cyanoethyl methanesulfonylimide to 2-trifluoromethyl-5-pyridineboronic acid is 1.0:(1.0~2.0), the molar ratio of N-cyanoethyl methanesulfonylimide to oxidant III is 1.0:(1.5~3.0), the molar ratio of N-cyanoethyl methanesulfonylimide to non-precious metal catalyst is 1.0:(0.05~0.2), and the molar ratio of N-cyanoethyl methanesulfonylimide to base III is 1.0:(1.5~3.0).

[0024] Compared with the prior art, the present invention has the following technical effects.

[0025] (I) Compared with the traditional flonicamid synthesis route in which the pyridine ring is constructed first and other functional groups are introduced, the present invention places the introduction of the pyridine ring in the last step of the synthesis route, which improves the yield of N-cyanoamine and oxidation reaction, while reducing the consumption of pyridine ring raw materials, and prepares flonicamid in an effective and high-yield manner.

[0026] (II) The method for synthesizing flonicamid provided by this invention uses inexpensive and readily available methyl ethyl sulfide as the starting material. Compared with the more structurally complex 3-[1-(methylthio)methyl]-6-(trifluoromethyl)pyridine, methyl ethyl sulfide effectively avoids the electronic induction effect and steric hindrance effect caused by the introduction of pyridine heterocycles in the N-cyanoamination and subsequent oxidation reactions, thereby significantly improving the reaction yield and reducing the occurrence of side reactions. The intermediate N-cyanoethylmethylthioimine has a low boiling point, and a high-purity product can be obtained with simple distillation, overcoming the yield loss problem caused by repeated recrystallization.

[0027] (III) In the synthesis method of the present invention, the total yield of the two-step reaction of N-cyanoamine and oxidation is increased by 20%–25% (when the original process uses 3-[1-(methylthio)methyl]-6(trifluoromethyl)pyridine as raw material, the total yield of the two steps is only 15%–35%).

[0028] (IV) The synthesis method of this invention employs a non-precious metal catalytic system, achieving efficient dehydrogenation coupling between the α-position C(sp³)-H bond of sulfoneimide and pyridineboronic acid. This catalytic system operates under mild conditions, can be carried out at room temperature, has a low catalyst cost, exhibits no significant scale-up effect, and possesses good potential for large-scale production.

[0029] (V) The synthesis method of the present invention can solve the problems of numerous side reactions, difficult post-processing, and low final product yield in the preparation of flonicamid from 3-[1-(methylthio)methyl]-6(trifluoromethyl)pyridine intermediate in the prior art.

[0030] The specific content of the present invention will be further explained in detail below with reference to the embodiments. Detailed Implementation

[0031] It should be noted that, unless otherwise specified, all raw materials and equipment used in this invention are those known in the prior art.

[0032] The reaction formula for the synthesis method of the insecticide flonicamid of the present invention is as follows: .

[0033] The following are specific embodiments of the present invention. It should be noted that the present invention is not limited to the following specific embodiments. All equivalent modifications made based on the technical solutions of this application fall within the protection scope of the present invention.

[0034] Example 1: This embodiment provides a method for synthesizing N-cyanoethyl methyl thioimine. The method includes the following steps: At 0°C, methyl ethyl sulfide (76.2 mg, 1.0 mmol), cyanamide (63.2 mg, 1.5 mmol), potassium tert-butoxide (168.3 mg, 1.5 mmol), and dichloromethane (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. After stirring and dissolving, (diacetoxyiodine)benzene (483.2 mg, 1.5 mmol) is slowly added to the reaction system. After half an hour, the mixture is brought back to room temperature and stirred for another 3 hours. Stirring is stopped after the sulfide disappears as monitored by TLC (thin-layer chromatography). The reaction is quenched with a saturated solution of sodium thiosulfate or sodium sulfite, followed by extraction with dichloromethane. After evaporating the organic phase to dryness, column chromatography (dichloromethane / methanol = 20 / 1) is used to separate the product, yielding 104.5 mg of a colorless oily liquid product (90% yield).

[0035] The product characterization results are as follows: 1 H NMR (500 MHz, CDCl3) δ 3.19 – 3.02 (m, 2H), 2.88 – 2.74 (m, 3H), 1.53 – 1.35 (m, 3H) ppm; 13 C NMR (125 MHz, CDCl3) δ 120.55, 43.83, 32.35, 7.90 ppm. HRMS (ESI) calculated for C4H9N2S 117.0481, found 117.0486 [M+H] + .

[0036] Nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) confirmed that the structure of the colorless oily liquid product obtained in this example is N-cyanoethylmethylthioimine.

[0037] Example 2: This embodiment provides a method for synthesizing N-cyanoethyl methyl thioimide, which includes the following steps: At 0°C, methyl ethyl sulfide (76.2 mg, 1.0 mmol), cyanamide (63.2 mg, 1.5 mmol), potassium hydroxide (168.3 mg, 1.5 mmol), and dichloromethane (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. After stirring and dissolving, N-bromosuccinimide (267.0 mg, 1.5 mmol) is slowly added to the reaction system. After half an hour, the mixture is brought back to room temperature and stirred for another 3 hours. Stirring is stopped after the sulfide disappears as monitored by TLC (thin-layer chromatography). The reaction is quenched with a saturated solution of sodium thiosulfate or sodium sulfite, followed by extraction with dichloromethane. After evaporating the organic phase to dryness, column chromatography (dichloromethane / methanol = 20 / 1) is used to separate the product, yielding 94.1 mg of a colorless oily liquid, with a yield of 87%.

[0038] The characterization results of the product in this embodiment are the same as those of the product in Example 1, confirming that the structure of the colorless oily liquid product obtained in this embodiment is N-cyanoethylmethylthioimine.

[0039] Example 3: This embodiment provides a method for synthesizing N-cyanoethyl methyl thioimine. The method includes the following steps: At 0°C, methyl ethyl sulfide (76.2 mg, 1.0 mmol), cyanamide (63.2 mg, 1.5 mmol), and acetonitrile (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. After stirring and dissolving, a 5.7 wt% sodium hypochlorite aqueous solution (1.96 g, 1.5 mmol) is slowly added to the reaction system. After half an hour, the mixture is brought back to room temperature and stirred for another 3 hours. Stirring is stopped after the sulfide disappears as monitored by TLC (thin-layer chromatography). The reaction is quenched with a saturated solution of sodium thiosulfate or sodium sulfite, followed by extraction with dichloromethane. After evaporating the organic phase to dryness, column chromatography (dichloromethane / methanol = 20 / 1) is used to separate the product, yielding 106.3 mg of a colorless oily liquid, with a yield of 91.5%.

[0040] The characterization results of the product in this embodiment are the same as those of the product in Example 1, confirming that the structure of the colorless oily liquid product obtained in this embodiment is N-cyanoethylmethylthioimine.

[0041] Example 4: This embodiment provides a method for synthesizing N-cyanoethyl methyl thioimide, which includes the following steps: At 0°C, methyl ethyl sulfide (76.2 mg, 1.0 mmol), cyanamide (84.3 mg, 2.0 mmol), sodium tert-butoxide (144.2 mg, 1.5 mmol), and acetonitrile (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. After stirring and dissolving, N-bromosuccinimide (267.9 mg, 1.5 mmol) is slowly added to the reaction system. After half an hour, the mixture is brought back to room temperature and stirred for another 4 hours. Stirring is stopped after the sulfide disappears as monitored by TLC. The reaction is quenched with a saturated solution of sodium thiosulfate, followed by extraction with dichloromethane. After evaporating the organic phase to dryness, column chromatography (dichloromethane / methanol = 20 / 1) is used to separate the product, yielding 102.1 mg of a colorless oily liquid, with a yield of 88%.

[0042] The characterization results of the product in this embodiment are the same as those of the product in Example 1, confirming that the structure of the colorless oily liquid product obtained in this embodiment is N-cyanoethylmethylthioimine.

[0043] Example 5: This embodiment provides a method for synthesizing N-cyanoethyl methyl thioimine. The method includes the following steps: At 0°C, methyl ethyl sulfide (76.2 mg, 1.0 mmol), cyanamide (63.2 mg, 1.5 mmol), sodium hydride (72.1 mg, 3.0 mmol, 60% dispersed in mineral oil), and tetrahydrofuran (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. After stirring and dissolving, 1,3-dibromo-5,5-dimethylhydantoin (283.9 mg, 1.0 mmol) is slowly added to the reaction system. After half an hour, the mixture is brought back to room temperature and stirred for another 2.5 h. Stirring is stopped after the sulfide disappears as monitored by TLC. The reaction is quenched with a saturated solution of sodium sulfite, followed by extraction with dichloromethane. After evaporating the organic phase to dryness, column chromatography (dichloromethane / methanol = 20 / 1) is used to separate the product, yielding 94.8 mg of a colorless oily liquid product, with a yield of 81%.

[0044] The characterization results of the product in this embodiment are the same as those of the product in Example 1, confirming that the structure of the colorless oily liquid product obtained in this embodiment is N-cyanoethylmethylthioimine.

[0045] Example 6: This embodiment provides a method for synthesizing N-cyanoethyl methyl thioimine. The method includes the following steps: At 0°C, methyl ethyl sulfide (76.2 mg, 1.0 mmol), cyanamide (63.2 mg, 1.5 mmol), potassium carbonate (414.6 mg, 3.0 mmol), and 1,2-dichloroethane (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stirrer. After stirring and dissolving, [bis(trifluoroacetoxy)iodo]benzene (645.1 mg, 1.5 mmol) is slowly added to the reaction system. After half an hour, the mixture is brought back to room temperature and stirred for another 5 h. Stirring is stopped after the sulfide disappears as monitored by TLC. The reaction is quenched with a saturated solution of sodium thiosulfate, followed by extraction with dichloromethane. After evaporating the organic phase to dryness, the product is separated by column chromatography (dichloromethane / methanol = 20 / 1) to obtain 98.1 mg of a colorless oily liquid product, with a yield of 84%.

[0046] The characterization results of the product in this embodiment are the same as those of the product in Example 1, confirming that the structure of the colorless oily liquid product obtained in this embodiment is N-cyanoethylmethylthioimine.

[0047] The characterization results of the product in this embodiment are the same as those of the product in Example 1, confirming that the structure of the colorless oily liquid product obtained in this embodiment is N-cyanoethylmethylthioimine.

[0048] Example 7: This embodiment provides a method for synthesizing N-cyanoethyl methyl thioimine. The method includes the following steps: At 0°C, methyl ethyl sulfide (76.2 mg, 1.0 mmol), cyanamide (84.3 mg, 2.0 mmol), sodium methoxide (162.1 mg, 3.0 mmol), and N,N-dimethylformamide (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. After stirring and dissolving, an aqueous solution of sodium hypochlorite (with an available chlorine content of 1.5 mmol) is slowly added dropwise to the reaction system. After half an hour, the mixture is brought back to room temperature and stirred for another 3.5 h. Stirring is stopped after the sulfide disappears as monitored by TLC. The reaction mixture is diluted with water and extracted with dichloromethane. The organic phase is washed with brine, evaporated to dryness, and then separated by column chromatography (dichloromethane / methanol = 20 / 1) to obtain 108.9 mg of a colorless oily liquid product, with a yield of 93%.

[0049] The characterization results of the product in this embodiment are the same as those of the product in Example 1, confirming that the structure of the colorless oily liquid product obtained in this embodiment is N-cyanoethylmethylthioimine.

[0050] Example 8: This embodiment provides a method for synthesizing N-cyanoethyl methyl thioimine. The method includes the following steps: At 0°C, methyl ethyl sulfide (76.2 mg, 1.0 mmol), cyanamide (63.2 mg, 1.5 mmol), sodium phosphate (492.1 mg, 3.0 mmol), and dimethyl sulfoxide (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stirrer. After stirring and dissolving, (diacetoxyiodine)benzene (644.3 mg, 2.0 mmol) is slowly added to the reaction system. After half an hour, the mixture is brought back to room temperature and stirred for another 4.5 h. Stirring is stopped after the sulfide disappears as monitored by TLC. The reaction is quenched with a saturated solution of sodium thiosulfate, followed by extraction with dichloromethane. After evaporating the organic phase to dryness, column chromatography (dichloromethane / methanol = 20 / 1) is used to separate the product, yielding 112.4 mg of a colorless oily liquid, with a yield of 96%.

[0051] The characterization results of the product in this embodiment are the same as those of the product in Example 1, confirming that the structure of the colorless oily liquid product obtained in this embodiment is N-cyanoethylmethylthioimine.

[0052] Example 9: This embodiment provides a method for synthesizing N-cyanoethylmethylsulfonylimide, which includes the following steps: At 0 °C, N-cyanoethylmethylthioimide (116.1 mg, 1.0 mmol), potassium carbonate (165.6 mg, 1.2 mmol), and dichloromethane (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. After stirring and dissolving, m-chloroperoxybenzoic acid (189.9 mg, 1.2 mmol) is slowly added to the reaction system. The mixture is then brought back to room temperature and stirred for 1 h. Stirring is stopped after the thioimide starting material disappears as monitored by TLC (thin-layer chromatography). The reaction is quenched with a saturated solution of sodium bisulfite or sodium sulfite, followed by extraction with dichloromethane. After evaporating the organic phase to dryness, column chromatography (dichloromethane / methanol = 50 / 1) is used to separate the product, yielding 122.8 mg of a colorless oily liquid, with a yield of 93%.

[0053] The product characterization results are as follows: 1 H NMR (500 MHz, CDCl3) δ 3.47 – 3.33 (m, 1H), 3.20 (s, 2H), 1.47 (t,J = 7.4 Hz, 2H) ppm; 13 C NMR (126 MHz, CDCl3) δ 112.57, 49.92, 39.48, 7.07 ppm. HRMS (ESI) calculated for C4H9N2OS 133.0430, found 133.0434 [M+H] + .

[0054] Nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) confirmed that the structure of the colorless oily liquid product obtained in this example is N-cyanoethylmethylsulfonylimide.

[0055] Example 10: This embodiment provides a method for synthesizing N-cyanoethylmethylsulfonylimide, which includes the following steps: At 0 °C, N-cyanoethylmethylsulfonylimide (116.1 mg, 1.0 mmol) and acetonitrile (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. After stirring and dissolving, a 40 wt% potassium permanganate aqueous solution (474.3 mg, 1.2 mmol) is slowly added to the reaction system. The mixture is then brought back to room temperature and stirred for 1 h. Stirring is stopped after the sulfonylimide starting material disappears as monitored by TLC (thin-layer chromatography). The reaction is quenched with a saturated solution of sodium bisulfite or sodium sulfite. The mixture is then extracted with dichloromethane. After evaporating the organic phase to dryness, column chromatography (dichloromethane / methanol = 50 / 1) is used to separate the product, yielding 118.8 mg of a colorless oily liquid, with a yield of 90%.

[0056] The characterization results of the product in this embodiment are the same as those of the product in Example 9, confirming that the structure of the colorless oily liquid product obtained in this embodiment is N-cyanoethyl methanesulfonylimide.

[0057] Example 11: This embodiment provides a method for synthesizing N-cyanoethylmethylsulfonylimide, which includes the following steps: At 0 °C, N-cyanoethylmethylthioimide (116.1 mg, 1.0 mmol) and acetonitrile (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. After stirring and dissolving, 30 wt% hydrogen peroxide aqueous solution (170.0 mg, 1.5 mmol) is slowly added to the reaction system. The mixture is then brought back to room temperature and stirred for 1 h. Stirring is stopped after the thioimide starting material disappears as monitored by TLC (thin-layer chromatography). The reaction is quenched with a saturated solution of sodium thiosulfate or sodium sulfite. The mixture is then extracted with dichloromethane. After evaporating the organic phase to dryness, column chromatography (dichloromethane / methanol = 50 / 1) is used to separate the product, yielding 117.5 mg of a colorless oily liquid, with a yield of 89%.

[0058] The characterization results of the product in this embodiment are the same as those of the product in Example 9, confirming that the structure of the colorless oily liquid product obtained in this embodiment is N-cyanoethyl methanesulfonylimide.

[0059] Example 12: This embodiment provides a method for synthesizing N-cyanoethylmethylsulfonylimide, which includes the following steps: At 0 °C, N-cyanoethylmethylthioimide (116.1 mg, 1.0 mmol), sodium carbonate (397.8 mg, 3.0 mmol), and tetrahydrofuran (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. After stirring and dissolving, a 40 wt% potassium permanganate aqueous solution (474.3 mg, 1.2 mmol) is slowly added to the reaction system. The mixture is then brought back to room temperature and stirred for 2 h. Stirring is stopped after the thioimide starting material disappears as monitored by TLC. The reaction is quenched with a saturated sodium sulfite solution, followed by extraction with dichloromethane. After evaporating the organic phase to dryness, column chromatography (dichloromethane / methanol = 50 / 1) is used to separate the product, yielding 118.8 mg of a colorless oily liquid, with a yield of 90%.

[0060] The characterization results of the product in this embodiment are the same as those of the product in Example 9, confirming that the structure of the colorless oily liquid product obtained in this embodiment is N-cyanoethyl methanesulfonylimide.

[0061] Example 13: This embodiment provides a method for synthesizing N-cyanoethylmethylsulfonylimide, which includes the following steps: At 0 °C, N-cyanoethylmethylthioimide (116.1 mg, 1.0 mmol), potassium hydroxide (168.3 mg, 3.0 mmol), and methanol (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. After stirring and dissolving, an aqueous solution of sodium periodate (641.8 mg, 3.0 mmol) (5 mL) is slowly added to the reaction system. The mixture is then brought back to room temperature and stirred for 3 h. Stirring is stopped after the thioimide starting material disappears as monitored by TLC. The reaction is quenched with a saturated solution of sodium bisulfite, followed by extraction with dichloromethane. After evaporating the organic phase to dryness, column chromatography (dichloromethane / methanol = 50 / 1) is used to separate the product, yielding 99.1 mg of a colorless oily liquid, with a yield of 75%.

[0062] The characterization results of the product in this embodiment are the same as those of the product in Example 9, confirming that the structure of the colorless oily liquid product obtained in this embodiment is N-cyanoethyl methanesulfonylimide.

[0063] Example 14: This embodiment provides a method for synthesizing N-cyanoethylmethylsulfonylimide, which includes the following steps: At 0 °C, N-cyanoethylmethylthioimide (116.1 mg, 1.0 mmol), potassium tert-butoxide (336.5 mg, 3.0 mmol), and acetonitrile (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. After stirring and dissolving, 30 wt% hydrogen peroxide aqueous solution (170.1 mg, 1.5 mmol) is slowly added to the reaction system. The mixture is then brought back to room temperature and stirred for 4 h. Stirring is stopped after the thioimide starting material disappears as monitored by TLC. The reaction is quenched with a saturated sodium sulfite solution, followed by extraction with dichloromethane. After evaporating the organic phase to dryness, column chromatography (dichloromethane / methanol = 50 / 1) is used to separate the product, yielding 114.0 mg of a colorless oily liquid, with a yield of 86%.

[0064] The characterization results of the product in this embodiment are the same as those of the product in Example 9, confirming that the structure of the colorless oily liquid product obtained in this embodiment is N-cyanoethyl methanesulfonylimide.

[0065] Example 15: This embodiment provides a method for synthesizing N-cyanoethylmethylsulfonylimide, which includes the following steps: At 0 °C, N-cyanoethylmethylthioimide (116.1 mg, 1.0 mmol), sodium hydride (120.0 mg, 3.0 mmol, 60% dispersed in mineral oil), and N,N-dimethylformamide (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stirrer. After stirring and dissolving, m-chloroperoxybenzoic acid (569.7 mg, 3.0 mmol) is added in portions to the reaction system. The mixture is then brought back to room temperature and stirred for 1.5 h. Stirring is stopped after the thioimide starting material disappears as monitored by TLC. The reaction is quenched with a saturated solution of sodium bisulfite, followed by extraction with dichloromethane. After evaporating the organic phase to dryness, column chromatography (dichloromethane / methanol = 50 / 1) is used to separate the product, yielding 122.8 mg of a colorless oily liquid, with a yield of 93%.

[0066] The characterization results of the product in this embodiment are the same as those of the product in Example 9, confirming that the structure of the colorless oily liquid product obtained in this embodiment is N-cyanoethyl methanesulfonylimide.

[0067] Example 16: This embodiment provides a method for synthesizing N-cyanoethylmethylsulfonylimide, which includes the following steps: At 0 °C, N-cyanoethylmethylthioimide (116.1 mg, 1.0 mmol), sodium phosphate (492.1 mg, 3.0 mmol), and 1,2-dichloroethane (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. After stirring and dissolving, an aqueous solution (5 mL) of sodium permanganate (240.0 mg, 1.5 mmol) is slowly added to the reaction system. The mixture is then brought back to room temperature and stirred for 2.5 h. Stirring is stopped after the thioimide starting material disappears as monitored by TLC. The reaction is quenched with a saturated solution of sodium sulfite, followed by extraction with dichloromethane. After evaporating the organic phase to dryness, column chromatography (dichloromethane / methanol = 50 / 1) is used to separate the product, yielding 116.1 mg of a colorless oily liquid, with a yield of 88%.

[0068] The characterization results of the product in this embodiment are the same as those of the product in Example 9, confirming that the structure of the colorless oily liquid product obtained in this embodiment is N-cyanoethyl methanesulfonylimide.

[0069] Example 17: This embodiment provides a method for synthesizing the insecticide flonicamid. The method includes the following steps: N-cyanoethyl methanesulfonyl imide (132.2 mg, 1.0 mmol), 2-trifluoromethyl-5-pyridineboronic acid (381.8 mg, 2.0 mmol), nickel acetylacetonate (25.7 mg, 0.1 mmol), potassium carbonate (276.0 mg, 2.0 mmol), and methanol (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar at room temperature. Di-tert-butyl peroxide (292.6 mg, 2.0 mmol) is slowly added dropwise. The mixture is stirred at room temperature for 24 h. Stirring is stopped after the sulfonyl imide starting material disappears as monitored by TLC (thin-layer chromatography). The mixture is then extracted with ethyl acetate, and the organic phase is evaporated to dryness. The product is then separated by column chromatography (dichloromethane / methanol = 50 / 1) to obtain a white solid powder product of 202.4 mg, with a yield of 83%.

[0070] The product characterization results are as follows: 1 H NMR (500 MHz, CDCl3) δ8.81 (d, J = 2.6 Hz, 1H), 8.10 (dd, J = 8.3,2.3 Hz, 1H), 7.81 (d, J = 8.2 Hz, 1H), 4.76 (q, J = 7.1 Hz, 1H), 3.15 (s,1H), 3.11 (s, 2H), 2.00 (d, J = 7.2 Hz, 3H) ppm; 13 C NMR (125 MHz, CDCl3) δ150.79, 149.97 (q, J = 35.3 Hz), 138.69,130.98, 121.16 (m), 121.13 (q, J = 274.5 Hz), 111.79, 63.95, 38.46, 14.13ppm. HRMS (ESI) calculated for C 10 H 11 F3N3OS 278.0569, found 278.0574 [M+H] + .

[0071] Nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) confirmed that the structure of the white solid powder product obtained in this example is flonicamid.

[0072] Example 18: This embodiment provides a method for synthesizing the insecticide flonicamid. The method includes the following steps: under room temperature, N-cyanoethyl methanesulfonylimide (132.2 mg, 1.0 mmol), 2-trifluoromethyl-5-pyridineboronic acid (381.8 mg, 2.0 mmol), copper acetate (18.2 mg, 0.1 mmol), potassium carbonate (276.0 mg, 2.0 mmol), and methanol (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. Potassium persulfate (540.3 mg, 2.0 mmol) is slowly added dropwise. The mixture is stirred at room temperature for 24 h. Stirring is stopped after the sulfonylimide starting material disappears as monitored by TLC (thin-layer chromatography). The mixture is then extracted with ethyl acetate, and the organic phase is evaporated to dryness. The product is then separated by column chromatography (dichloromethane / methanol = 50 / 1) to obtain a white solid powder product of 207.4 mg, with a yield of 85%.

[0073] The characterization results of the product in this embodiment are the same as those of the product given in Example 17, confirming that the structure of the white solid powder product obtained in this embodiment is flonicamid.

[0074] Example 19: This embodiment provides a method for synthesizing the insecticide flonicamid. The method includes the following steps: N-cyanoethyl methanesulfonyl imide (132.2 mg, 1.0 mmol), 2-trifluoromethyl-5-pyridineboronic acid (381.8 mg, 2.0 mmol), copper trifluoromethanesulfonate (36.2 mg, 0.1 mmol), 1,4-diazabicyclo[2.2.2]octane (224.4 mg, 2.0 mmol), and acetonitrile (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar at room temperature. Potassium persulfate (540.3 mg, 2.0 mmol) is slowly added dropwise. The mixture is stirred at room temperature for 24 h. Stirring is stopped after the sulfonyl imide starting material disappears as monitored by TLC (thin-layer chromatography). The mixture is then extracted with ethyl acetate, and the organic phase is evaporated to dryness. The product is then separated by column chromatography (dichloromethane / methanol = 50 / 1) to obtain a white solid powder product of 214.6 mg, with a yield of 88%.

[0075] The characterization results of the product in this embodiment are the same as those of the product given in Example 17, confirming that the structure of the white solid powder product obtained in this embodiment is flonicamid.

[0076] Example 20: This embodiment provides a method for synthesizing the insecticide flonicamid. The method includes the following steps: N-cyanoethyl methanesulfonyl imide (132.2 mg, 1.0 mmol), 2-trifluoromethyl-5-pyridineboronic acid (381.8 mg, 2.0 mmol), cuprous bromide (14.3 mg, 0.1 mmol), potassium carbonate (276.4 mg, 2.0 mmol), and acetonitrile (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar at room temperature. Benzoyl peroxide (484.5 mg, 2.0 mmol) is slowly added dropwise. The mixture is stirred at room temperature for 24 h. Stirring is stopped after the sulfonyl imide starting material disappears as monitored by TLC. The mixture is then extracted with ethyl acetate. After evaporating the organic phase to dryness, the product is separated by column chromatography (dichloromethane / methanol = 50 / 1) to obtain a white solid powder product of 207.5 mg, with a yield of 85%.

[0077] The characterization results of the product in this embodiment are the same as those of the product given in Example 17, confirming that the structure of the white solid powder product obtained in this embodiment is flonicamid.

[0078] Example 21: This embodiment provides a method for synthesizing the insecticide flonicamid. The method includes the following steps: At room temperature, N-cyanoethyl methanesulfonyl imide (132.2 mg, 1.0 mmol), 2-trifluoromethyl-5-pyridineboronic acid (381.8 mg, 2.0 mmol), nickel acetylacetonate (38.5 mg, 0.15 mmol), triethylamine (253.0 mg, 2.5 mmol), and acetonitrile (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. Tert-butyl hydroperoxide (180.2 mg, 2.0 mmol) is slowly added dropwise. The mixture is stirred at room temperature for 18 h. Stirring is stopped after the sulfonyl imide starting material disappears as monitored by TLC. The mixture is then extracted with ethyl acetate. After evaporating the organic phase to dryness, column chromatography (dichloromethane / methanol = 50 / 1) is used to separate the product into a white solid powder of 190.2 mg, with a yield of 78%.

[0079] The characterization results of the product in this embodiment are the same as those of the product given in Example 17, confirming that the structure of the white solid powder product obtained in this embodiment is flonicamid.

[0080] Example 22: This embodiment provides a method for synthesizing the insecticide flonicamid. The method includes the following steps: At room temperature, N-cyanoethyl methanesulfonylimide (132.2 mg, 1.0 mmol), 2-trifluoromethyl-5-pyridineboronic acid (381.8 mg, 2.0 mmol), nickel trifluoromethanesulfonate (31.1 mg, 0.1 mmol), 4-dimethylaminopyridine (183.3 mg, 1.5 mmol), and acetonitrile (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. Then, (diacetoxyiodine)benzene (805.3 mg, 2.5 mmol) is slowly added dropwise. The mixture is stirred at room temperature for 36 h. Stirring is stopped after the sulfonylimide starting material disappears as monitored by TLC. The mixture is then extracted with ethyl acetate, and the organic phase is evaporated to dryness. The product is then separated by column chromatography (dichloromethane / methanol = 50 / 1) to obtain a white solid powder product of 200.0 mg, with a yield of 82%.

[0081] The characterization results of the product in this embodiment are the same as those of the product given in Example 17, confirming that the structure of the white solid powder product obtained in this embodiment is flonicamid.

[0082] Example 23: This embodiment provides a method for synthesizing the insecticide flonicamid. The method includes the following steps: N-cyanoethyl methanesulfonylimide (132.2 mg, 1.0 mmol), 2-trifluoromethyl-5-pyridineboronic acid (381.8 mg, 2.0 mmol), cuprous iodide (38.1 mg, 0.2 mmol), 1,8-diazabicycloundec-7-ene (304.5 mg, 2.0 mmol), and acetonitrile (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar at room temperature. Ammonium persulfate (684.6 mg, 3.0 mmol) is slowly added dropwise. The mixture is stirred at room temperature for 24 h. Stirring is stopped after the sulfonylimide starting material disappears as monitored by TLC. The mixture is then extracted with ethyl acetate. After evaporating the organic phase to dryness, the product is separated by column chromatography (dichloromethane / methanol = 50 / 1) to obtain a white solid powder product of 219.5 mg, with a yield of 90%.

[0083] The characterization results of the product in this embodiment are the same as those of the product given in Example 17, confirming that the structure of the white solid powder product obtained in this embodiment is flonicamid.

[0084] Example 24: This embodiment provides a method for synthesizing the insecticide flonicamid. The method includes the following steps: under room temperature, N-cyanoethyl methanesulfonylimide (132.2 mg, 1.0 mmol), 2-trifluoromethyl-5-pyridineboronic acid (381.8 mg, 2.0 mmol), bis(triphenylphosphine) nickel dichloride (32.7 mg, 0.05 mmol), sodium acetate (246.1 mg, 3.0 mmol), and acetonitrile (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. Tetramethylpiperidine oxide (312.5 mg, 2.0 mmol) is slowly added dropwise. The mixture is stirred at room temperature for 48 h. Stirring is stopped after the sulfonylimide starting material disappears as monitored by TLC. The mixture is then extracted with ethyl acetate. After evaporating the organic phase to dryness, the product is separated by column chromatography (dichloromethane / methanol = 50 / 1) to obtain a white solid powder product of 182.9 mg, with a yield of 75%.

[0085] The characterization results of the product in this embodiment are the same as those of the product given in Example 17, confirming that the structure of the white solid powder product obtained in this embodiment is flonicamid.

[0086] Example 25: This embodiment provides a method for synthesizing the insecticide flonicamid. The method includes the following steps: N-cyanoethyl methanesulfonyl imide (132.2 mg, 1.0 mmol), 2-trifluoromethyl-5-pyridineboronic acid (381.8 mg, 2.0 mmol), copper trifluoroacetate (25.0 mg, 0.1 mmol), pyridine (158.2 mg, 2.0 mmol), and acetonitrile (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar at room temperature. Oxygen (2.0 mmol) is introduced, and the mixture is stirred at room temperature for 24 h. Stirring is stopped after the sulfonyl imide starting material disappears as monitored by TLC. The mixture is then extracted with ethyl acetate, and the organic phase is evaporated to dryness. The product is then separated by column chromatography (dichloromethane / methanol = 50 / 1) to obtain 200.0 mg of a white solid powder product, with a yield of 82%.

[0087] The characterization results of the product in this embodiment are the same as those of the product given in Example 17, confirming that the structure of the white solid powder product obtained in this embodiment is flonicamid.

[0088] Example 26: This embodiment provides a method for synthesizing the insecticide flonicamid. The method includes the following steps: N-cyanoethyl methanesulfonyl imide (132.2 mg, 1.0 mmol), 2-trifluoromethyl-5-pyridineboronic acid (381.8 mg, 2.0 mmol), nickel oxalate (14.7 mg, 0.1 mmol), sodium phosphate (327.9 mg, 2.0 mmol), and acetonitrile (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar at room temperature. Di-tert-butyl peroxide (292.5 mg, 2.0 mmol) is slowly added dropwise. The mixture is stirred at room temperature for 24 h. Stirring is stopped after the sulfonyl imide starting material disappears as monitored by TLC. The mixture is then extracted with ethyl acetate. After evaporating the organic phase to dryness, the product is separated by column chromatography (dichloromethane / methanol = 50 / 1) to obtain a white solid powder product of 195.1 mg, with a yield of 80%.

[0089] The characterization results of the product in this embodiment are the same as those of the product given in Example 17, confirming that the structure of the white solid powder product obtained in this embodiment is flonicamid.

[0090] Example 27: This embodiment provides a method for synthesizing the insecticide flonicamid. The method includes the following steps: At room temperature, N-cyanoethyl methanesulfonylimide (132.2 mg, 1.0 mmol), 2-trifluoromethyl-5-pyridineboronic acid (381.8 mg, 2.0 mmol), copper tetra(acetonitrile)tetrafluoroborate (31.8 mg, 0.1 mmol), N,N-diisopropylethylamine (258.5 mg, 2.0 mmol), and acetonitrile (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. [bis(trifluoroacetoxy)iodide]benzene (645.1 mg, 1.5 mmol) is slowly added dropwise. The mixture is stirred at room temperature for 30 h. Stirring is stopped after the sulfonylimide starting material disappears as monitored by TLC. The mixture is then extracted with ethyl acetate, and the organic phase is evaporated to dryness. The product is then separated by column chromatography (dichloromethane / methanol = 50 / 1) to obtain a white solid powder product of 214.6 mg, with a yield of 88%.

[0091] The characterization results of the product in this embodiment are the same as those of the product given in Example 17, confirming that the structure of the white solid powder product obtained in this embodiment is flonicamid.

[0092] Example 28: This embodiment provides a method for synthesizing the insecticide flonicamid. The method includes the following steps: under room temperature, N-cyanoethyl methanesulfonyl imide (132.2 mg, 1.0 mmol), 2-trifluoromethyl-5-pyridineboronic acid (381.8 mg, 2.0 mmol), copper bromide (22.3 mg, 0.1 mmol), potassium acetate (196.3 mg, 2.0 mmol), and acetonitrile (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar. Manganese dioxide (260.8 mg, 3.0 mmol) is slowly added dropwise. The mixture is stirred at room temperature for 24 h. After the sulfonyl imide starting material disappears as monitored by TLC, stirring is stopped. The mixture is then extracted with ethyl acetate. After evaporating the organic phase to dryness, the product is separated by column chromatography (dichloromethane / methanol = 50 / 1) to obtain a white solid powder product of 202.4 mg, with a yield of 83%.

[0093] The characterization results of the product in this embodiment are the same as those of the product given in Example 17, confirming that the structure of the white solid powder product obtained in this embodiment is flonicamid.

[0094] Example 29: This embodiment provides a method for synthesizing the insecticide flonicamid. The method includes the following steps: N-cyanoethyl methanesulfonylimide (132.2 mg, 1.0 mmol), 2-trifluoromethyl-5-pyridineboronic acid (381.8 mg, 2.0 mmol), bis(8-hydroxyquinoline)copper(II) (35.2 mg, 0.1 mmol), sodium carbonate (212.0 mg, 2.0 mmol), and acetonitrile (5.0 mL) are added sequentially to a three-necked round-bottom flask equipped with a stir bar at room temperature. Tert-butyl peroxybenzoate (388.5 mg, 2.0 mmol) is slowly added dropwise. The mixture is stirred at room temperature for 24 h. Stirring is stopped after the sulfonylimide starting material disappears as monitored by TLC. The mixture is then extracted with ethyl acetate, and the organic phase is evaporated to dryness. The product is then separated by column chromatography (dichloromethane / methanol = 50 / 1) to obtain a white solid powder product of 212.2 mg, with a yield of 87%.

[0095] The characterization results of the product in this embodiment are the same as those of the product given in Example 17, confirming that the structure of the white solid powder product obtained in this embodiment is flonicamid.

Claims

1. A method for synthesizing the insecticide flonicamid, characterized in that, This method uses methyl ethyl sulfide as a raw material, and obtains N-cyanoethyl methanesulfonyl imide through a two-step reaction of N-cyanoamine and oxidation. N-cyanoethyl methanesulfonyl imide undergoes a dehydrogenation coupling reaction with 2-trifluoromethyl-5-pyridineboronic acid to achieve CH arylation of the ortho-methylene group with high selectivity, thus obtaining the insecticide flonicamid.

2. The method for synthesizing the insecticide flonicamid as described in claim 1, characterized in that, The reaction temperatures for the N-cyanoamine reaction, oxidation reaction, and dehydrogenation coupling reaction are each independently between 0°C and 60°C.

3. The method for synthesizing the insecticide flonicamid as described in claim 2, characterized in that, The reaction temperature for the N-cyanoamine reaction is 0°C to room temperature.

4. The method for synthesizing the insecticide flonicamid as described in claim 1, characterized in that, The method includes the following steps: Step 1, Synthesis of N-cyanoethylmethylthioimine: Methyl ethyl sulfide, cyanamide, base I, and solvent I were added sequentially to the reaction vessel. After stirring and dissolving, oxidant I was added to the reaction system, and the mixture was heated to the reaction temperature to carry out the N-cyanoamine reaction. Stirring was stopped after the sulfide disappeared as monitored by TLC. The reaction was quenched with a saturated solution of sodium thiosulfate or sodium sulfite. The mixture was then extracted with solvent I, and after evaporating the organic phase to dryness, N-cyanoethyl methyl thioimine was obtained by column chromatography. Step 2, Synthesis of N-cyanoethylmethanesulfonylimide: N-cyanoethylmethylthioimide, base II, and solvent II were added sequentially to the reaction vessel. After stirring and dissolving, oxidant II was added to the reaction system, and the system was heated to the reaction temperature for oxidation. Stirring was stopped after the thioimide raw material disappeared, as monitored by TLC. The reaction was quenched with a saturated solution of sodium thiosulfate or sodium sulfite. Subsequently, the system was extracted with solvent II, and after evaporating the organic phase to dryness, N-cyanoethylmethylsulfonylimide was obtained by column chromatography. Step 3, Synthesis of the insecticide flonicamid: N-cyanoethyl methanesulfonyl imide, 2-trifluoromethyl-5-pyridineboronic acid, oxidant III, non-precious metal catalyst, base III, and solvent III were added sequentially to the reaction vessel. The mixture was heated to the reaction temperature to carry out a dehydrogenation coupling reaction. Stirring was stopped after the sulfonyl imide raw material disappeared, as monitored by TLC. The reaction was quenched with a saturated solution of sodium thiosulfate or sodium sulfite. The mixture was then extracted with solvent III, and the organic phase was evaporated to dryness before column chromatography was used to separate the insecticide flonicamid.

5. The method for synthesizing the insecticide flonicamid as described in claim 4, characterized in that, In step one, the oxidant I is one or more of (diacetoxyiodine)benzene, [bis(trifluoroacetoxy)iodine]benzene, N-bromosuccinimide, 1,3-dibromo-5,5-dimethylhydantoin, and sodium hypochlorite. In step two, the oxidant II is one or more of the following: m-chloroperoxybenzoic acid, hydrogen peroxide, sodium periodate, potassium permanganate, and sodium permanganate. In step three, the oxidant III is one or more of the following: tert-butyl hydroperoxide, di-tert-butyl peroxide, benzoyl peroxide, tert-butyl peroxybenzoate, tetramethylpiperidine oxide, (diacetoxyiodine)benzene, [bis(trifluoroacetoxy)iodine]benzene, manganese dioxide, potassium persulfate, sodium persulfate, ammonium persulfate, and oxygen.

6. The method for synthesizing the insecticide flonicamid as described in claim 4, characterized in that, In step three, the non-precious metal catalyst is one or more of the following: bis(1,5-cyclooctadiene) nickel, nickel chloride, nickel bromide, nickel acetylacetonate, nickel acetate, nickel trifluoromethanesulfonate, bis(triphenylphosphine)dichloride, 1,2-bis(diphenylphosphine)ethane nickel chloride, nickel(II) chloride ethylene glycol dimethyl ether complex, nickel oxalate, bis(8-hydroxyquinoline)copper(II), copper trifluoroacetate, copper acetylacetonate, copper tetra(acetonitrile)tetrafluoroborate, copper trifluoromethanesulfonate, copper tetraacetonitrile hexafluorophosphate, cuprous bromide, copper bromide, cuprous iodide, etc., as well as copper catalysts.

7. The method for synthesizing the insecticide flonicamid as described in claim 4, characterized in that, In steps one through three, solvent I, solvent II, and solvent III are independently selected from one or more combinations of dichloromethane, tetrahydrofuran, 1,2-dichloroethane, acetonitrile, methanol, ethanol, N,N-dimethylformamide, N,N-dimethylacetamide, and dimethyl sulfoxide.

8. The method for synthesizing the insecticide flonicamid as described in claim 4, characterized in that, In steps one to three, the base I, base II and base III are independently selected from one or more combinations of potassium tert-butoxide, sodium tert-butoxide, potassium methoxide, sodium methoxide, sodium hydride, potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, potassium acetate, sodium acetate, sodium phosphate, pyridine, triethylamine, N,N-diisopropylethylamine, 4-dimethylaminopyridine, 1,8-diazabicycloundec-7-ene and 1,4-diazabicyclo[2.2.2]octane.

9. The method for synthesizing the insecticide flonicamid as described in claim 4, characterized in that, In step one, the molar ratio of methyl ethyl sulfide to cyanamide is 1.0:(1.0~2.0), the molar ratio of methyl ethyl sulfide to oxidant I is 1.0:(1.0~3.0), and the molar ratio of methyl ethyl sulfide to base I is 1:(1.5~3.0). In step two, the molar ratio of N-cyanoethyl methyl thioimide to oxidant II is 1.0:(1.5-3.0), and the molar ratio of N-cyanoethyl methyl thioimide to base II is 1.0:(1.5-3.0). In step three, the molar ratio of N-cyanoethyl methanesulfonylimide to 2-trifluoromethyl-5-pyridineboronic acid is 1.0:(1.0~2.0), the molar ratio of N-cyanoethyl methanesulfonylimide to oxidant III is 1.0:(1.5~3.0), the molar ratio of N-cyanoethyl methanesulfonylimide to non-precious metal catalyst is 1.0:(0.05~0.2), and the molar ratio of N-cyanoethyl methanesulfonylimide to base III is 1.0:(1.5~3.0).