An imidazole heterocyclic compound and its application

Abstract

The present invention discloses an imidazole heterocyclic compound and its application. The imidazole heterocyclic compound represented by the general formula (I) provided by the present invention shows good biological activity against pests in the fields of agriculture, forestry and other fields, and can be used as an insecticide. In particular, the compound of the general formula (I) has good toxic effects on agricultural pests such as Plutella xylostella, Spodoptera frugiperda, Spodoptera exigua, and Spodoptera litura.

Description

Technical Field

[0001] The present invention belongs to the field of pesticides, and particularly relates to an imidazoleazole heterocyclic compound and its use in the field of insecticidal applications. Background Art

[0002] Insecticides are essential production materials for agricultural production. With the long-term use of insecticides, pests will develop varying degrees of resistance, significantly reducing the efficacy of insecticides. Developing new insecticides with different action mechanisms has always been a technical challenge in pesticide creation. Currently, most of the developed pesticides have a nitrogen heterocyclic structure. For example, newly developed pesticides in recent years such as cycloxaprid, cyantraniliprole, sulfoxaflor, flupyradifurone, flonicamid, tebufenpyrad, pyridaben, spirotetramat, Flupyrimin, chlorantraniliprole, etc. are all nitrogen heterocyclic derivatives, mainly derived from nitrogen heterocycles such as pyrazole or pyridine. Conducting structural innovation and developing new insecticides with entirely new skeletons is of great significance. Based on the research progress of existing insecticides, through a large number of research practices, the inventor has creatively developed imidazoleazole heterocyclic compounds with novel skeletons and excellent insecticidal activities. Summary of the Invention

[0003] The primary object of the present invention is to provide an imidazoleazole heterocyclic compound that can control various agricultural and forestry pests or pests in other fields.

[0004] Another object of the present invention is to provide a route and method for synthesizing imidazoleazole heterocyclic compounds.

[0005] Yet another object of the present invention is to provide the use of imidazoleazole heterocyclic compounds in pest control in the agricultural field or other fields.

[0006] The objects of the present invention are achieved through the following technical solutions:

[0007] An amidoazole compound or an agriculturally acceptable salt thereof for controlling agricultural and forestry pests and pests in other fields, characterized in that the structure of the amidoazole compound is shown in the general formula (I):

[0008]

[0009] In the general formula (I), R 1 is selected from substituted or unsubstituted C 6-20 aryl, substituted or unsubstituted C 2-20 heteroaryl; wherein, the substituents in the substituted or unsubstituted are selected from halogen, cyano, hydroxyl, amino, nitro, C 1-6 alkyl, halo C 1-6 alkyl, C 1-6 alkoxy, halo C 1 - 6 alkoxy, C3-6 Naphthenyl, C 1-6 alkoxycarbonyl, phenyl, halophenyl, benzyl;

[0010] W is selected from O or S;

[0011] Y 1 is selected from O, S, Se or N;

[0012] represents a double bond or a single bond;

[0013] R a , R b , R c , R d are independently selected from hydrogen, halogen, hydroxyl, cyano, carboxyl, amino, nitro, C 1-6 alkyl, halo C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, C 3-6 naphthenyl, halo C 3-6 naphthenyl, substituted or unsubstituted C 6-20 aryl, substituted or unsubstituted C 2-20 heteroaryl, C 1-6 alkoxycarbonyl; wherein the substituents in the substituted or unsubstituted are selected from halogen, cyano, hydroxyl, amino, nitro, C 1-6 alkyl, halo C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, C 3-6 naphthenyl, C 1-6 alkoxycarbonyl, phenyl, halophenyl, benzyl; or when represents a single bond, R a / R b and / or R c / R d together form =O; when represents a double bond, one of R a / R b does not exist, and one of R c / R d does not exist;

[0014] R 2 is selected from substituted or unsubstituted C 6-20 aryl-C 1-6 alkyl, substituted or unsubstituted C 6-20 aryl, substituted or unsubstituted C 2-20 heteroaryl; wherein the substituents in the substituted or unsubstituted are selected from halogen, cyano, hydroxyl, amino, nitro, C 1-6 alkyl, halo C1-6 alkyl, C 1-6 alkoxy, halo-C 1-6 alkoxy, C 1-6 alkylthio, halo-C 1-6 alkylthio, C 3-6 cycloalkyl, C 1-6 alkoxycarbonyl, phenyl, halophenyl, benzyl,

[0015] provided that the compound of formula I is not compound I-15, I-17, I-19, I-20.

[0016] Preferably, in general formula (I), R 1 is selected from substituted or unsubstituted phenyl, furyl, thienyl, pyrimidinyl, pyrazinyl, pyrazolyl, thiazolyl, oxazolyl, imidazolyl, triazolyl, indolyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, benzofuryl, benzothienyl; wherein the substituents in the substituted or unsubstituted are selected from fluorine, chlorine, bromine, iodine, cyano, hydroxyl, amino, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl; methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl substituted by fluorine, chlorine, bromine and / or iodine; methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy; methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy substituted by fluorine, chlorine, bromine and / or iodine; cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, phenyl; phenyl substituted by fluorine, chlorine, bromine and / or iodine; benzyl;

[0017] W is selected from O;

[0018] Y 1 is selected from S, Se;

[0019] represents a double bond or a single bond;

[0020] R a , R b are independently of each other selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl; methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl substituted by fluorine, chlorine, bromine and / or iodine; phenyl;

[0021] R c , R dEach independently selected from hydrogen, hydroxyl, amino, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl; methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl substituted with fluorine, chlorine, bromine and / or iodine; methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy; methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy substituted with fluorine, chlorine, bromine and / or iodine; cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, substituted or unsubstituted phenyl, substituted or unsubstituted pyrazolyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl; wherein the substituent in the substituted or unsubstituted is selected from fluorine, chlorine, bromine, iodine, cyano, hydroxyl, amino, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl; methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl substituted with fluorine, chlorine, bromine and / or iodine; methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy; methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy substituted with fluorine, chlorine, bromine and / or iodine; cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, phenyl; phenyl substituted with fluorine, chlorine, bromine and / or iodine; benzyl; or, when represents a single bond, R a / R b and / or R c / R d together form =O; when represents a double bond, one of R a / R b is absent, and one of R c / R d is absent;

[0022] R 2Selected from substituted or unsubstituted benzyl, substituted or unsubstituted phenyl, substituted or unsubstituted pyrazolyl, furyl, thienyl, pyrimidinyl, pyrazinyl, pyrazolyl, thiazolyl, oxazolyl, imidazolyl, triazolyl, indolyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, benzofuryl, benzothienyl; wherein, the substituents in the substituted or unsubstituted are selected from fluorine, chlorine, bromine, iodine, cyano, hydroxyl, amino, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl; methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl substituted by fluorine, chlorine, bromine and / or iodine; methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy; methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy substituted by fluorine, chlorine, bromine and / or iodine; methylthio, ethylthio, tert-butylthio; methylthio, ethylthio, tert-butylthio substituted by fluorine, chlorine, bromine and / or iodine; cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, phenyl; phenyl substituted by fluorine, chlorine, bromine and / or iodine; benzyl,

[0023] Further preferably, R 1 is selected from 2,6-difluorophenyl, phenyl, 2-chlorophenyl, 4-fluorophenyl, 2-furyl,

[0024] W is selected from O;

[0025] Y 1 is selected from S, Se;

[0026] represents a double bond or a single bond;

[0027] R a , R b are independently of each other selected from hydrogen, methyl, 1,1,1-trifluoroethyl, phenyl;

[0028] R c , R d are independently of each other selected from hydrogen, hydroxyl, amino, tert-butyl, cyclopropyl, methyl, trifluoromethyl, 4-chlorophenyl, methoxycarbonyl, ethoxy; or, when represents a single bond, R c / R d together form ═O;

[0029] When represents a double bond, one of R a / R b is absent, and one of R c / R d is absent;

[0030] R 2Selected from 3-fluoro-5-chlorophenylmethyl; substituted or unsubstituted phenyl, wherein the substituent is fluorine, chlorine, bromine, trifluoromethyl, trifluoromethoxy, tert-butoxycarbonyl, methoxy, nitro, trifluoromethylthio, substituted or unsubstituted pyrazolyl, wherein the substituent is methyl and / or trifluoromethyl.

[0031] The specific compounds of the general formula (I) compounds of the present invention are exemplified by the following compounds, but the present invention is not limited to these compounds:

[0032]

[0033]

[0034] The synthetic routes of the general formula (I) compounds of the present invention, such as compounds I-1 to I-64, I-71 to I-81, are shown in the following formula:

[0035]

[0036] In the formula, the substituent R 1 , R 2 , Y 1 , R a , R b , R c , R d and are as defined above; X is chlorine or bromine.

[0037] The base mentioned refers to one or more of sodium carbonate, potassium carbonate, cesium carbonate, potassium phosphate, sodium acetate, potassium acetate, triethylamine, diisopropylethylamine, pyridine.

[0038] The catalyst is one or more of polyethylene glycol-200, polyethylene glycol-400, polyethylene glycol-600.

[0039] The heating temperature is 40 to 120 °C.

[0040] The reaction solvent is one or a mixed solvent of two or more of N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, 1,4-dioxane, acetone, dichloromethane, ethanol, 1,2-dichloroethane, 2-butanone.

[0041] The synthetic steps of the specific examples are as follows:

[0042] Step 1: Add potassium selenocyanate (thiocyanate) shown in Formula 2 (2 mmol) into a 250 ml flask, selectively add a catalyst, dissolve the solid with a solvent, and add the acyl chloride shown in Formula 1 (2 mmol) during stirring. After sealing, stir and react at room temperature for 2 h. After the reaction is completed, add the amine shown in Formula 3 (2 mmol) and continue to react for 1 h. After monitoring the end of the reaction by TLC plate, filter off the solid residue, and then evaporate the solvent under reduced pressure. The residue is purified by column chromatography, and the solvent is evaporated under reduced pressure to obtain the product, which is acyl selenourea (thiourea) shown in Formula 4.

[0043] Step 2: Take the acyl selenourea (thiourea) product shown in Formula 4 obtained in the first step (0.5 mmol) in a sealed tube, dissolve it with a solvent, and then add the alpha-bromo derivative shown in Formula 5 (0.75 mmol). After sealing the reaction tube, place it in an oil bath at 70 °C and stir and react for 5 h. After monitoring the end of the reaction by TLC plate, filter off the solid residue, and then evaporate the solvent under reduced pressure. The residue is purified by column chromatography, and the solvent is evaporated under reduced pressure to obtain the final product shown in Formula 6.

[0044] The synthetic routes of the compounds of general formula (I) in the present invention, such as compounds I-65 to I-67 and I-82, are shown as follows:

[0045]

[0046] In the formula, the substituent R 1 is 2,6-difluorophenyl; R 2 is 3-chloro-4-trifluoromethylphenyl, 3-chloro-4-trifluoromethoxyphenyl, p-chlorophenyl; R a is hydrogen, methyl or 1,1,1-trifluoroethyl; R b , R c , R d is hydrogen.

[0047] The base mentioned in the first-step reaction refers to one or more of sodium carbonate, potassium carbonate, potassium phosphate, cesium carbonate, sodium acetate, potassium acetate, triethylamine, diisopropylethylamine, and pyridine.

[0048] The heating temperature is 40-120 °C.

[0049] The base mentioned in the second-step reaction refers to one or more of sodium carbonate, potassium carbonate, potassium phosphate, cesium carbonate, sodium acetate, potassium acetate, triethylamine, diisopropylethylamine, and pyridine.

[0050] The reaction solvent can be one or a mixed solvent of two or more of N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, 1,4-dioxane, acetone, dichloromethane, ethanol, 1,2-dichloroethane, and 2-butanone.

[0051] The synthesis steps of the specific embodiments are as follows:

[0052] Step 1: Heat and reflux the N-cyanamide derivative shown in Formula 7 (1.638 mmol), the episulfide derivative shown in Formula 8 (1.646 mmol), and the base (1.720 mmol) in a solvent. After 2 hours, cool the reaction, dilute with 100 mL of dichloromethane, and wash with water (2 × 75 mL) and brine (75 mL). Dry the organic phase with magnesium sulfate, filter, and concentrate under reduced pressure to obtain the imine compound shown in Formula 9.

[0053] Step 2: Place the imine compound shown in Formula 9 (0.5 mmol) obtained above in a sealed tube, add a solvent, add the acyl chloride shown in Formula 1 (0.5 mmol), seal it, and stir at room temperature for 1 h. After monitoring the reaction by TLC plate and the reaction is completed, filter off the solid residue, and then evaporate the solvent under reduced pressure. The residue is purified by column chromatography and concentrated under reduced pressure to obtain the target product shown in Formula 10.

[0054] The synthesis route of Compound I-68 in the general formula (I) compound of the present invention is as follows:

[0055]

[0056] wherein the substituent R 1 is 2,6-difluorophenyl; R 2 is phenyl.

[0057] The catalyst in the first-step reaction is one or more of polyethylene glycol-200, polyethylene glycol-400, and polyethylene glycol-600.

[0058] The catalyst in the second-step reaction is one or more of cuprous bromide, cuprous iodide, cuprous chloride, ferric trichloride, or cobalt dichloride.

[0059] The base refers to one or more of potassium carbonate, sodium hydroxide, sodium carbonate, potassium phosphate, diisopropylethylamine, pyridine, sodium tert-butoxide, potassium tert-butoxide, or cesium carbonate.

[0060] The heating temperature is 40-120 °C.

[0061] The reaction solvent can be one or a mixed solvent of two or more of N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, 1,4-dioxane, acetone, dichloromethane, ethanol, 1,2-dichloroethane, and 2-butanone.

[0062] The synthesis steps of the specific embodiments are as follows:

[0063] Step 1: Add potassium thiocyanate (2 mmol) into a 250 ml flask, dissolve it with a solvent, selectively add a catalyst, add acyl chloride (2 mmol) during stirring, seal it, and stir at room temperature for 2 h. After the reaction is completed, filter off the solid residue, evaporate the solvent under reduced pressure to obtain benzoyl isothiocyanate.

[0064] Step 2: Take the isothiocyanate prepared in the first step into a reaction tube, add allylamine (0.2 mmol) under nitrogen protection and stir for 1 hour, then add 1-(trifluoromethyl)-1,2-benziodoxol-3(1H)-one (0.3 mmol), a catalyst (10 mol%), a base (0.5 mmol) and a solvent, seal it and place it in an oil bath at 75 °C for 4 h. After monitoring the reaction by TLC plate and the reaction is completed, filter off the solid residue, and then evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate), and the target product is obtained after concentration under reduced pressure.

[0065] The synthetic routes of the compounds I-69 and I-70 of the general formula (I) of the present invention are shown as follows:

[0066]

[0067] In the formula, the substituent R 1 is 2,6-difluorophenyl; R 2 is phenyl; Y 1 is S, R a is hydrogen or phenyl; R b is hydrogen.

[0068] The catalyst described in the first-step reaction is one or more of polyethylene glycol-200, polyethylene glycol-400, and polyethylene glycol-600.

[0069] The reaction solvent described in the first step can be one of acetonitrile, 1,4-dioxane, acetone, dichloromethane, ethanol, and 1,2-dichloroethane.

[0070] The reaction solvent described in the second step can be one or more of N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, 1,4-dioxane, acetone, dichloromethane, ethanol, and 1,2-dichloroethane.

[0071] The base refers to one or more of sodium carbonate, potassium carbonate, potassium phosphate, cesium carbonate, sodium acetate, potassium acetate, triethylamine, diisopropylethylamine, and pyridine.

[0072] The synthetic steps of the specific examples are as follows:

[0073] Step 1: Add potassium selenocyanate (thiocyanate) (2 mmol) into a 250 ml flask, dissolve it with a solvent, selectively add a catalyst, add acyl chloride (2 mmol) during stirring, seal it and stir at room temperature for 2 h. After the reaction is completed, add amine (2 mmol) and continue the reaction for 1 h. After monitoring the end of the reaction by TLC plate, filter off the solid residue and remove the solvent by rotary evaporation under reduced pressure. The residue is purified by column chromatography, and the obtained product is benzoylurea.

[0074] Dissolve the benzoylurea compound (2 mmol) synthesized in the first step in a solvent, add a base (10.50 equivalents), and stir at room temperature (25 - 30 °C) for 10 minutes until the solution turns light yellow. Dropwise add a bromocyan derivative (2.05 mmol, which is dissolved in a solvent) thereto for 10 minutes, and then obtain a precipitate after 15 minutes. Concentrate the solvent under reduced pressure to separate the solid material; filter or wash with n-hexane to remove the excess base. The obtained crystalline compound is purified to obtain the target product.

[0075] The compound of general formula (I) shows efficacy against pests in the field of agricultural technology. Therefore, another technical solution of the present invention relates to the use of the compound of general formula (I) or its agrochemically acceptable salt as an insecticide, that is, the use of the compound of general formula (I) or its agrochemically acceptable salt for preparing a composition for controlling pests in agriculture or other fields.

[0076] The compounds of the present invention can be used to control and eliminate a wide range of agricultural and forestry pests, sanitary pests, and pests that endanger animal health. In this specification, "insecticide" is a general term for preventing and controlling all the pests mentioned above. Examples of pests include, but are not limited to: Lepidoptera insects: for example, Plutella xylostella, Spodoptera frugiperda, S. exigua, S. litura, Lymantria dispar, Malacoscma neustria testacea, Diaphania perspectalis, Clania variegata, Cnidocampa flauescens, Dendrolimus punctatus, Orgyia antiqua, Paranthrene tabaniformis, Chilo suppressalis, Ostrinia nubilalis, Ephestia cautella, Adoxophyes orana, laspyresia splendana, Agrotis fucosa, Galleria mellonella, Phyllocnistis citrella, Mythimna separata, etc.;Coleoptera insects: for example, Sitophilus zeamais, Tribolium castaneum, Henosepilachna vigintioctcmaculata, H. spars a, Agriotes fusciollis, Ancmala cupripes, Popillia quadriguttata, Monolepta hieroglyphica, Monochamus alternatus, Echinocnemus squameus, Basiprionotabisignata, Anoplophora chinensis, Apripona germari, Soclytus schevy, or Agriotes fuscicollis, etc.; Hemiptera insects: for example, Stephanitis nashi, Nezara viridula, Poecilocoris latus, Cletus punctiger, Dimorphopterus japonicus, Dysdercus cingulatus, etc.; Homoptera insects: for example, Nephotettix cincticeps, Unaspis yanonensis, Myzus persicae, Aphis gossydii, Bemisia tabaci, Laodelphax striatellus, Nilaparvata lugens, Sogatella furcifera, etc.; Orthoptera insects: for example, Gryllotalpa africana, Locus migratoria, etc.; Hymenoptera insects: for example, Solenopsis invicta, Tremexfuscicornis, etc.;Insects of the order Blattodea: for example, Blattella germanica, Periplaneta americana, Coptotermes formosanus, etc.; Insects of the order Diptera: for example, Musca domestica, Aedes aegypti, Delia platura, Culex fatigans, Anopheles sinensis, etc.; Plant parasitic nematodes: for example, root-knot nematodes, root rot nematodes, rice white-tip nematodes, pine wood nematodes, etc. Pests harmful to animal health include Boophilus microplus, Haemaphysalis longicornis, Hyalomma anatolicum, Hypoderma bovis, Fasciola hepatica, Moniezia blanchard, Trypanosoma enansi, Babesia bigemina, etc.

[0077] The present invention also provides an insecticidal composition, which contains an active ingredient (a compound of general formula (I)) and an agriculturally acceptable carrier, and the weight percentage content of the active ingredient in the composition is 0.01–99.99%.

[0078] Preparation method of the composition as defined above: Mix the compound of general formula (I) with the carrier. The active ingredient in this composition can contain a single compound of the present invention or a mixture of several compounds.

[0079] The above composition can be applied in the form of a formulation. When the compound of general formula (I) is used as an active ingredient and is dissolved or dispersed in the carrier or formulated into a preparation, it is more easily dispersed for use as an insecticide; for example: these chemical preparations can be made into powders, wettable powders, emulsifiable concentrates, thick emulsions and microemulsions, suspension emulsions, granules, oils and ultra-low volume sprays, smoke types, slow-release agents, and other pesticide dosage forms. In these compositions, at least one liquid or solid carrier is added, and when necessary, a suitable surfactant can be added.

[0080] The carrier in the composition of the present invention is a substance that meets the following conditions: it is convenient to be applied to the site to be treated after being formulated with the active ingredient, and can be a plant, seed or soil; or is beneficial to storage, transportation or operation. The carrier can be solid or liquid, including substances that are usually gases but have been compressed into liquids, and usually the carriers used in formulating insecticidal compositions can be used.

[0081] The above-mentioned agricultural composition can be used for killing or preventing pests in agriculture and forestry, sanitary pests, or pests harmful to animal health, pesticides, killing or preventing plant pathogens, and killing or preventing agricultural weeds.

[0082] The specific method of the above application: applying the pesticide on the pests or the medium on which the pests grow.

[0083] For certain applications, such as in agriculture, one or more other types of pesticides, nematicides, acaricides, plant growth regulators, or fertilizers can be added to the pesticide composition of the present invention, thereby producing additional advantages and effects.

[0084] It should be clear that within the scope defined by the claims of the present invention, various transformations and modifications can be made.

[0085] In addition, the present invention also provides the use of the imidazoleazole heterocyclic compound represented by the general formula (I) or its agrochemically acceptable salt in the preparation of a pesticide, and the pesticide is used to kill pests, and the pests refer to Plutella xylostella, Spodoptera frugiperda, Spodoptera exigua, Spodoptera litura, Aedes aegypti, Solenopsis invicta, and Meloidogyne incognita.

[0086] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0087] The general formula (I) shows good biological activity against pests in agriculture, forestry, and other fields; the general formula (I) compound can be used as a pesticide, and in particular, the general formula (I) compound has a good toxic effect on agricultural pests such as Plutella xylostella, Spodoptera frugiperda, Spodoptera exigua, and Spodoptera litura. Detailed Description of the Embodiment

[0088] The present invention will be further described in detail below in conjunction with the embodiments, but the embodiments of the present invention are not limited thereto. The raw materials involved in the present invention can be directly purchased from the market. For the process parameters not specifically noted, conventional techniques can be referred to.

[0089] Synthesis Example 1: Preparation of Compound I-3

[0090]

[0091] Step 1: Add potassium selenocyanate (2 mmol) into a 250 ml flask, dissolve it with 8 mL of acetone, add 2,6-difluorobenzoyl chloride (2 mmol) during stirring, seal it and stir at room temperature for 2 h. After the reaction is completed, add tert-butyl 4-aminobenzoate (2 mmol) and continue the reaction for 1 h. After monitoring the reaction by TLC plate and filtering off the solid residue, evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a yellow solid product, which is the target benzoyl selenourea.

[0092] Step 2: Take the benzoyl selenourea product obtained in the first step (0.5 mmol) in a sealed tube, dissolve it with 4 ml of DCM, then add 1-bromo-3,3-dimethyl-2-butanone (0.75 mmol), seal the reaction tube and place it in an oil bath at 70 °C and stir for 5 h. After monitoring the reaction by TLC plate and filtering off the solid residue, evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a white solid product.

[0093] By taking the same steps above and changing the corresponding raw materials, compounds I-1 to I-2, I-4, I-81 can be synthesized.

[0094] Compound I-1: Pale yellow solid: 1 H NMR (500 MHz, CDCl 3 ): δ 7.84 (d, J = 8.4 Hz, 1H), 7.54 (s, 1H), 7.39 (d, J = 8.3 Hz, 1H), 7.30 - 7.21 (m, 1H), 7.05 (s, 1H), 6.84 (t, J = 8.3 Hz, 2H), 1.21 (s, 9H).

[0095] Compound I-2: White solid: 1 H NMR (500 MHz, CDCl 3 ): δ 7.84 (d, J = 8.4 Hz, 1H), 7.73 (s, 1H), 7.44 (dd, J = 7.4, 1.6 Hz, 1H), 7.29 - 7.23 (m, 1H), 7.05 (s, 1H), 6.84 (t, J = 8.1 Hz, 2H), 1.21 (s, 9H).

[0096] Compound I-3: White solid: 1 H NMR (500 MHz, CDCl 3):δ 8.11 (d, J = 8.1 Hz, 2H), 7.39 (d, J = 8.1 Hz, 2H), 7.25–7.15 (m, 1H), 7.04 (s, 1H), 6.80 (t, J = 8.0 Hz, 2H), 1.63 (s, 9H), 1.17 (s, 9H).

[0097] Compound I-4: Pale yellow solid: 1 H NMR (500 MHz, CDCl 3 ):δ 7.69 (d, J = 8.1 Hz, 1H), 7.24 (tt, J = 8.4, 6.1 Hz, 1H), 7.05 (s, 1H), 7.04 - 6.98 (m, 2H), 6.82 (t, J = 8.1 Hz, 2H), 3.92 (s, 3H), 1.22 (s, 9H).

[0098] Compound I-81: White solid: δ 7.49 (d, J = 2.6 Hz, 1H), 7.46 (dd, J = 8.8, 1.5 Hz, 1H), 7.30 (dd, J = 8.8, 2.6 Hz, 1H), 7.28–7.20 (m, 1H), 7.03 (s, 1H), 6.83 (t, J = 8.1 Hz, 2H), 1.22 (s, 9H).

[0099] Synthesis Example 2: Preparation of Compound I-5

[0100]

[0101] First step: Add potassium selenocyanate (2 mmol) to a 250 ml flask, dissolve it with 8 mL of acetone, add 2,6-difluorobenzoyl chloride (2 mmol) during stirring, seal it and stir at room temperature for 2 h. After the reaction is completed, add 4-chloro-3-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)oxy)aniline (2 mmol) and continue the reaction for 1 h. After monitoring the reaction by TLC plate and completion, filter off the solid residue and remove the solvent by distillation under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a yellow solid product, which is the target benzoylselenourea.

[0102] Second step: Take the benzoylthiourea product obtained in the first step (0.5 mmol) in a sealed tube, dissolve it with 4 ml of DCM, then add 1-cyclopropyl-2-bromoethanone (0.75 mmol), seal the reaction tube and place it in an oil bath at 70 °C and stir for 5 h. After monitoring the reaction by TLC plate and completion, filter off the solid residue and remove the solvent by distillation under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a pale yellow solid product.

[0103] Compound I-5: Pale yellow solid: MS(ESI) m / z (M+H) + : 633.96. EA: C, 47.44; H, 2.25; N, 6.66.

[0104] Synthesis Example 3: Preparation of Compound I-10

[0105]

[0106] First step: Add potassium selenocyanate (2 mmol) to a 250 ml flask, dissolve it with 8 mL of dichloromethane (DCM), then add polyethylene glycol-400 (PEG-400, 6 - 7 drops). During stirring, add 2,6-difluorobenzoyl chloride (2 mmol). After sealing, stir the reaction at room temperature for 2 h. After the reaction is completed, add 2-methyl-5-trifluoromethyl-2H-pyrazol-3-amine (2 mmol) and continue the reaction for 1 h. After monitoring the reaction by TLC plate and completion, filter off the solid residue, and then evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a yellow solid product, which is the target benzoyl selenourea.

[0107] Second step: Take the benzoyl selenourea product obtained in the first step (0.5 mmol) in a sealed tube, dissolve it with 4 ml of DCM, then add 1-cyclopropyl-2-bromoethanone (0.75 mmol). Seal the reaction tube and place it in an oil bath at 70 °C and stir the reaction for 5 h. After monitoring the reaction by TLC plate and completion, filter off the solid residue, and then evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a pale yellow solid product.

[0108] Using the same experimental procedure above and changing the corresponding reaction raw materials, Compounds I-6 - I-9 and I-21 can be synthesized.

[0109] Compound I-6: Pale yellow solid: 1 H NMR (500 MHz, CDCl 3 ): δ 7.87 (d, J = 8.4 Hz, 1H), 7.54 (d, J = 2.0 Hz, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.28 (t, J = 8.4 Hz, 1H), 6.93 (s, 1H), 6.86 (t, J = 8.1 Hz, 2H), 2.09 (s, 3H).

[0110] Compound I-7: Pale yellow solid: MS(ESI) m / z (M+H) + : 463.03, EA: C, 46.88; H, 2.41; N, 6.09.

[0111] Compound I-8: Pale yellow solid; MS(ESI) m / z (M+H) + : 496.99, EA: C, 43.60; H, 2.04; N, 5.63.

[0112] Compound I-9: Pale yellow solid 1 H NMR (500 MHz, CDCl 3 ): δ 8.15 (d, J = 8.5 Hz, 2H), 7.37 (d, J = 8.5 Hz, 2H), 7.24 (t, J = 8.4, Hz, 1H), 6.92 (s, 1H), 6.83 (t, J = 8.0 Hz, 2H), 2.05 (s, 3H), 1.63 (s, 9H).

[0113] Compound I-10: Pale yellow solid 1 H NMR (500 MHz, CDCl 3 ): δ 7.33 (t, J = 8.4 Hz, 1H), 6.93–6.87 (m, 3H), 6.59 (s, 1H), 3.77 (s, 3H), 2.10 (m, 3H).

[0114] Compound I-21: White solid: δ 8.07 (d, J = 7.4 Hz, 1H), 7.65–7.54 (m, 3H), 7.45–7.40 (m, 1H), 7.37–7.31 (m, 4H), 6.84 (s, 1H), 2.07 (s, 3H).

[0115] Synthesis Example 4: Preparation of Compound I-11

[0116]

[0117] First step: Add potassium selenocyanate (2 mmol) to a 250 ml flask, dissolve it with 8 mL of dichloromethane (DCM), then add polyethylene glycol - 400 (PEG - 400, 6 - 7 drops). During stirring, add 2,6 - difluorobenzoyl chloride (1.5 mmol). After sealing, stir at room temperature for 2 h. After the reaction is completed, add 3 - chloro - 4 - trifluoromethylaniline (2 mmol) and continue the reaction for 1 h. After monitoring the reaction by TLC plate and filtering off the solid residue, evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a yellow solid product, which is the target benzoyl selenourea.

[0118] Step 2: Take the benzoyl selenourea product obtained in the first step (0.5 mmol) in a sealed tube, dissolve it with 4 ml of DCM, then add 1-bromo-3,3,3-trifluoroacetone (0.75 mmol) and triethylamine (0.5 mmol). After sealing the reaction tube, place it in an oil bath at 70 °C and stir for 5 h. After monitoring the reaction by TLC plate and the reaction is completed, filter off the solid residue, and then evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a pale yellow solid product.

[0119] Step 3: Take the product of the second step (0.2 mmol) in a 100 ml flask, add 6 ml of dichloromethane (DCM), add triethylamine (0.4 mmol), cool to 0 °C, then add trifluoroacetic anhydride (0.3 mmol), and then react at room temperature for 12 h. After the reaction is completed, pour 6 ml of water into it, extract with DCM, separate the organic layer, wash with brine and dry with anhydrous sodium sulfate. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain the target product.

[0120] Compound I-11: Pale yellow solid: MS(ESI) m / z (M+H) + : 534.97. EA: C, 40.50; H, 1.34; N, 5.27

[0121] Synthesis Example 5: Preparation of Compound I-13

[0122]

[0123] Step 1: Add potassium selenocyanate (2 mmol) to a 250 ml flask, dissolve it with 8 mL of dichloromethane (DCM), then add polyethylene glycol-400 (PEG-400, 6 - 7 drops). During stirring, add 2,6-difluorobenzoyl chloride (2 mmol), seal it and stir at room temperature for 2 h. After the reaction is completed, add 3,5-dichloroaniline (2 mmol) and continue the reaction for 1 h. After monitoring the reaction by TLC plate and the reaction is completed, filter off the solid residue, and then evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a yellow solid product, which is the target benzoyl selenourea.

[0124] Step 2: Take the benzoyl selenourea product obtained in the first step (0.5 mmol) in a sealed tube, dissolve it with 4 ml of DCM, then add α-bromo-4-chloroacetophenone (0.75 mmol) and triethylamine (0.5 mmol). After sealing the reaction tube, place it in an oil bath at 70 °C and stir for 5 h. After monitoring the reaction by TLC plate and the reaction is completed, filter off the solid residue, and then evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a pale yellow solid product.

[0125] Using the same experimental procedures as above, changing the corresponding reaction raw materials can synthesize compounds I-12, I-15 to I-20, and I-80.

[0126] Compound I-12: White solid, MS(ESI): m / z(M+H) + : 576.98. EA: C, 47.97; H, 1.93; N, 4.88.

[0127] Compound I-13: Pale yellow solid, 1 H NMR(500MHz, CDCl 3 ): δ7.35–7.28(m, 4H), 7.23(s, 1H), 7.17(d, J=1.8Hz, 1H), 7.09(d, J=8.5Hz, 2H), 6.91(t, J=8.2Hz, 2H).

[0128] Compound I-15: Pale yellow solid, 1 H NMR(500MHz, CDCl 3 ): δ8.14(dd, J=8.4, 1.4Hz, 2H), 7.47–7.43(m, 1H), 7.37(t, J=7.2Hz, 2H), 7.21(d, J=8.5Hz, 2H), 7.15(d, J=9.0Hz, 2H), 7.13(s, 1H), 7.08(d, J=8.5Hz, 2H), 6.91(d, J=9.0Hz, 2H), 3.85(s, 3H).

[0129] Compound I-16: White solid, 1 H NMR(500MHz, CDCl 3 ): δ8.13(d, J=7.4Hz, 1H), 7.49–7.35(m, 6H), 7.30–7.24(m, 2H), 7.23–7.18(m, 3H), 7.09(d, J=4.8Hz, 2H).

[0130] Compound I-17: White solid, 1 H NMR(500MHz, CDCl 3 ): δ8.13(dd, J=7.8, 1.7Hz, 2H), 7.45(t, J=7.2Hz, 1H), 7.35(t, J=7.5Hz, 2H), 7.22–7.15(m, 4H), 7.15(s, 1H), 7.14–7.05(m, 4H,), 2.41(s, 3H).

[0131] Compound I-18: Pale yellow solid, 1¹H NMR (500 MHz, CDCl 3 ): δ 7.90 (dd, J = 7.8, 1.7 Hz, 1H), 7.41 (dd, J = 8.1, 1.3 Hz, 1H), 7.33 (td, J = 7.6, 1.8 Hz, 1H), 7.31–7.22 (m, 8H), 7.07 (d, J = 8.5 Hz, 2H).

[0132] Compound I-19: White solid, 1 ¹H NMR (500 MHz, CDCl 3 ): δ 8.17–8.11 (m, 2H), 7.21 (d, J = 8.5 Hz, 2H), 7.16–7.11 (m, 3H), 7.11–7.01 (m, 4H), 6.90 (d, J = 8.6 Hz, 2H), 3.85 (s, 3H).

[0133] Compound I-20: White solid, 1 ¹H NMR (500 MHz, CDCl 3 ): δ 8.30 (d, J = 8.7 Hz, 2H), 8.09 (dd, J = 8.5, 1.6 Hz, 2H), 7.45–7.51 (m, 3H), 7.40 (t, J = 7.6 Hz, 2H), 7.24 (d, J = 8.5 Hz, 2H), 7.22 (s, 1H), 7.06 (d, J = 8.5 Hz, 2H).

[0134] Compound I-80: Pale yellow solid, 1 ¹H NMR (500 MHz, CDCl 3 ): δ 7.66 (d, J = 8.5 Hz, 1H), 7.56 (s, 1H), 7.38–7.31 (m, 1H), 7.29 (d, J = 8.5 Hz, 2H), 7.26 (s, 1H), 7.18 (d, J = 8.4, 1H), 7.08 (d, J = 6.6 Hz, 2H), 6.92 (t, J = 8.2 Hz, 2H).

[0135] Synthesis Example 6: Preparation of Compound I-22

[0136]

[0137] Step 1: Add potassium selenocyanate (2 mmol) into a 250 ml flask, dissolve it with 8 mL of dichloromethane (DCM), then add polyethylene glycol - 400 (PEG - 400, 6 - 7 drops). During stirring, add 2,6 - difluorobenzoyl chloride (2 mmol). After sealing, stir the reaction at room temperature for 2 h. After the reaction is completed, add 3 - chloro - 4 - trifluoromethylaniline (2 mmol) and continue the reaction for 1 h. After monitoring the reaction by TLC plate and completion, filter off the solid residue, and remove the solvent by rotary evaporation under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a yellow solid product, which is the target benzoyl selenourea.

[0138] Step 2: Take the benzoyl selenourea product obtained in Step 1 (0.5 mmol) in a sealed tube, dissolve it with 4 ml of DCM, then add 1 - bromo - 3,3,3 - trifluoroacetone (0.75 mmol) and triethylamine (0.5 mmol). Seal the reaction tube and place it in an oil bath at 70 °C and stir the reaction for 5 h. After monitoring the reaction by TLC plate and completion, filter off the solid residue, and remove the solvent by rotary evaporation under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a white solid product.

[0139] Compounds I - 26 to I - 31 and I - 78 can all be synthesized through this step.

[0140] Compound I - 22: White solid, 1 H NMR (500 MHz, CDCl 3 ): δ 7.38 (d, J = 6.7 Hz, 2H), 7.35–7.29 (m, 1H), 7.28 (d, J = 8.5 Hz, 2H), 6.86 (t, J = 8.3 Hz, 2H), 5.40 (m, 1H), 3.77 (d, J = 12.5 Hz, 1H), 3.36 (d, J = 12.1 Hz, 1H).

[0141] Compound I - 26: Pale yellow solid, 1 H NMR (500 MHz, CDCl 3 ): δ 7.76 (d, J = 3.8 Hz, 1H), 7.74 (s, 1H), 7.46 (d, J = 8.4, 2.0 Hz, 1H), 7.36 (t, J = 8.4 Hz, 1H), 6.90 (t, J = 8.3 Hz, 1H), 6.13 (s, 1H), 3.80 (d, J = 12.6 Hz, 1H), 3.43 (d, J = 12.6 Hz, 1H).

[0142] Compound I - 27: White solid, MS(ESI): m / z(M + H) +: 518.96, EA: C, 39.43; H, 1.72; N, 5.41.

[0143] Compound I-28: White solid, 1 H NMR(500MHz, DMSO-d 6 ) δ8.88(s, 1H), 7.65–7.60(m, 2H), 7.42(dd, J = 8.8, 2.4Hz, 1H), 7.41–7.34(m, 1H), 7.00(t, J = 8.2Hz, 2H), 3.83(d, J = 12.7Hz, 1H), 3.56(d, J = 12.7Hz, 1H).

[0144] Compound I-29: Pale yellow solid, 1 H NMR(500MHz, CDCl 3 ): δ7.63(d, J = 8.2Hz, 1H), 7.37–7.30(m, 1H), 7.06–6.99(m, 2H), 6.86(t, J = 8.3Hz, 2H), 5.24–4.76(s, 1H), 3.91(s, 3H), 3.78(d, J = 12.5Hz1H), 3.39(d, J = 12.5Hz, 1H).

[0145] Compound I-30: White solid, 1 H NMR(500MHz, CDCl 3 ): δ8.06(d, J = 8.3Hz, 2H), 7.39(d, J = 8.2Hz, 2H), 7.33–7.26(m, 1H), 6.84(t, J = 8.2Hz, 2H), 4.82(s, 1H), 3.77(d, J = 12.4Hz, 1H), 3.37(d, J = 12.4Hz, 1H), 1.61(s, 9H).

[0146] Compound I-31: Pale yellow solid, 1 H NMR(500MHz, CDCl 3 ): δ7.76(d, J = 8.4Hz, 1H), 7.57(s, 1H), 7.41(d, J = 8.4Hz, 1H), 7.35(t, J = 8.4Hz, 1H), 6.89(t, J = 8.3Hz, 2H), 5.86(s, 1H), 3.80(d, J = 12.5Hz, 1H), 3.41(d, J = 12.5Hz, 1H).

[0147] Compound I-78: Pale yellow solid, 1 H NMR(500MHz, CDCl 3δ 8.12 (s, 1H), 8.03 (s, 1H), 7.55 (d, J = 8.5 Hz, 1H), 7.37–7.22 (m, 3H), 6.83 (t, J = 8.2 Hz, 2H), 5.54 (s, 1H), 3.74 (d, J = 12.4 Hz, 1H), 3.37 (d, J = 12.6 Hz, 1H).

[0148] Synthesis Example 7: Preparation of Compound I-23

[0149]

[0150] First step: Potassium selenocyanate (2 mmol) was added to a 250 ml flask and dissolved in 8 mL of acetone. During stirring, 2,6-difluorobenzoyl chloride (2 mmol) was added. After sealing, the reaction was stirred at room temperature for 2 h. After the reaction was completed, 4-chloro-3-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)oxy)aniline (2 mmol) was added and the reaction continued for 1 h. After monitoring the reaction by TLC plate and completion, the solid residue was filtered off, and then the solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a yellow solid product, which was the target benzoylselenourea.

[0151] Second step: The benzoylselenourea product obtained in the first step (0.5 mmol) was taken in a sealed tube, dissolved in 4 ml of DCM, and then methyl bromopyruvate (0.75 mmol) was added. After sealing the reaction tube, it was placed in an oil bath at 50 °C and stirred for 5 h. After monitoring the reaction by TLC plate and completion, the solid residue was filtered off, and then the solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a pale yellow solid product.

[0152] Compounds I-24 to I-25 can all be synthesized by this step.

[0153] Compound I-23: Pale yellow solid, 1 H NMR (500 MHz, CDCl 3 ) δ 8.12 (s, 1H), 8.02 (s, 1H), 7.49 (d, J = 8.5 Hz, 1H), 7.35–7.24 (m, 3H), 6.79 (t, J = 8.1 Hz, 2H), 5.18 (s, 1H), 3.79 (d, J = 11.4 Hz, 1H), 3.76 (s, 3H), 3.33 (d, J = 11.4 Hz, 1H).

[0154] Compound I-24: Pale yellow solid, MS (ESI): m / z (M + H) +: 540.99. EA: C, 42.33; H, 2.44; N, 5.20; S, 5.95.

[0155] Compound I-25: Pale yellow solid, MS(ESI): m / z(M+H) + : 558.97. EA: C, 40.94; H, 2.18; N, 5.04.

[0156] Synthesis Example 8: Preparation of Compound I-35

[0157]

[0158] First step: Add potassium thiocyanate (2 mmol) to a 250 ml flask, dissolve it with 8 mL of acetone, add 2,6-difluorobenzoyl chloride (2 mmol) during stirring, seal it and stir at room temperature for 2 h. After the reaction is completed, add tert-butyl 4-aminobenzoate (2 mmol) and continue the reaction for 1 h. After monitoring the reaction by TLC plate and filtering off the solid residue, evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a yellow solid product, which is the target benzoylthiourea.

[0159] Second step: Take the benzoylthiourea product obtained in the first step (0.5 mmol) in a sealed tube, dissolve it with 4 ml of DCM, then add 1-bromo-3,3-dimethyl-2-butanone (0.75 mmol), seal the reaction tube and place it in an oil bath at 70 °C and stir for 5 h. After monitoring the reaction by TLC plate and filtering off the solid residue, evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a white solid product.

[0160] Compounds I-33, I-34, and I-36 can all be synthesized by this step.

[0161] Compound I-33: White solid, MS(ESI) m / z(M+H) + : 491.07. EA: C, 51.40; H, 3.30; N, 5.73; S, 6.53.

[0162] Compound I-34: White solid, MS(ESI) m / z(M+H) + : 519.06. EA: C, 48.58; H, 3.13; N, 5.40; S, 6.19.

[0163] Compound I-35: White solid, MS(ESI) m / z(M+H) + : 473.18. EA: C, 63.54; H, 5.55; N, 5.93; S, 6.78.

[0164] Compound I-36: White solid, MS(ESI) m / z (M+H) + : 471.14. EA: C, 56.19; H, 4.09; N, 5.96; S, 6.83.

[0165] Synthesis Example 9: Preparation of Compound I-37

[0166]

[0167] First step: Add potassium thiocyanate (2 mmol) to a 250 ml flask, dissolve it with 8 mL of acetone, add 2,6-difluorobenzoyl chloride (2 mmol) during stirring, seal it and stir at room temperature for 2 h. After the reaction is completed, add 4-chloro-3-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)oxy)aniline (2 mmol) and continue the reaction for 1 h. After monitoring the reaction by TLC plate and filtering off the solid residue, evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a yellow solid product, which is the target benzoylthiourea.

[0168] Second step: Take the benzoylthiourea product obtained in the first step (0.5 mmol) in a sealed tube, dissolve it with 4 ml of DCM, then add 1-cyclopropyl-2-bromoethanone (0.75 mmol), seal the reaction tube and place it in an oil bath at 70 °C and stir for 5 h. After monitoring the reaction by TLC plate and filtering off the solid residue, evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a light yellow solid product.

[0169] Compound I-37: Light yellow solid, MS(ESI) m / z (M+H) + : 586.03. EA: C, 51.22; H, 2.42; N, 7.19 S, 5.49.

[0170] Synthesis Example 10: Preparation of Compound I-43

[0171]

[0172] Step 1: Add potassium thiocyanate (2 mmol) into a 250 ml flask, dissolve it with 8 mL of dichloromethane (DCM), then add polyethylene glycol - 400 (PEG - 400, 6 - 7 drops). During stirring, add 2,6 - difluorobenzoyl chloride (1.5 mmol). After sealing, stir the reaction at room temperature for 2 h. After the reaction is completed, add 3 - chloro - 4 - trifluoromethylaniline (2 mmol) and continue the reaction for 1 h. After monitoring the reaction by TLC plate and the reaction is completed, filter off the solid residue, and then remove the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a yellow solid product, which is the target benzoylthiourea.

[0173] Step 2: Take the benzoylthiourea product obtained in the first step (0.5 mmol) in a sealed tube, dissolve it with 4 ml of DCM, then add 1 - bromo - 3,3,3 - trifluoroacetone (0.75 mmol) and triethylamine (0.5 mmol). Seal the reaction tube and place it in an oil bath at 70 °C and stir the reaction for 5 h. After monitoring the reaction by TLC plate and the reaction is completed, filter off the solid residue, and then remove the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a white solid product.

[0174] Step 3: Take the product of the second step (0.2 mmol) in a 100 ml flask, add 6 ml of dichloromethane (DCM), add triethylamine (0.4 mmol), cool it to 0 °C, then add trifluoroacetic anhydride (0.3 mmol), and then react at room temperature for 12 h. After the reaction is completed, pour it into 6 ml of water, extract with DCM, separate the organic layer, wash with brine and dry with anhydrous sodium sulfate. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain the target product.

[0175] Compound I - 43: White solid; MS(ESI) m / z(M + H) + : 487.03, EA: C, 44.44; H, 1.43; N, 5.77; S, 6.60.

[0176] Synthesis Example 11: Preparation of Compound I - 45

[0177]

[0178] Step 1: Add potassium thiocyanate (2 mmol) into a 250 mL flask, dissolve it with 8 mL of dichloromethane (DCM), then add polyethylene glycol - 400 (PEG - 400, 6 - 7 drops). During stirring, add 2,6 - difluorobenzoyl chloride (1.5 mmol). After sealing, stir the reaction at room temperature for 2 h. After the reaction is completed, add 3,5 - dichloroaniline (1.5 mmol) and continue the reaction for 1 h. After monitoring the reaction completion by TLC plate, filter off the solid residue, and then evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a pale yellow solid product, which is the target benzoylthiourea.

[0179] Step 2: Take the benzoylthiourea product obtained in the first step (0.5 mmol) in a sealed tube, dissolve it with 4 mL of DCM, then add α - bromo - 4 - chloroacetophenone (0.75 mmol) and triethylamine (0.5 mmol). Seal the reaction tube and place it in an oil bath at 70 °C and stir the reaction for 5 h. After monitoring the reaction completion by TLC plate, filter off the solid residue, and then evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a pale yellow solid product.

[0180] Compounds I - 44, I - 47 - I - 52 can all be synthesized through this step.

[0181] Compound I - 44: Pale yellow solid, MS(ESI) m / z(M + H) + : 529.01. EA: C, 52.20; H, 2.11; N, 5.27; S, 6.04.

[0182] Compound I - 45: Pale yellow solid, MS(ESI) m / z(M + H) + : 494.98. EA: C, 53.31; H, 2.24; N, 5.67; S, 6.49.

[0183] Compound I - 47: Pale yellow solid, MS(ESI) m / z(M + H) + : 421.11. EA: C, 65.65; H, 4.10; N, 6.66; S, 7.60.

[0184] Compound I - 48: White solid, MS(ESI) m / z(M + H) + : 391.09. EA: C, 67.59; H, 3.89; N, 7.18; S, 8.22.

[0185] Compound I - 49: White solid, MS(ESI) m / z(M + H) +: 405.05. EA: C, 68.25; H, 4.24; N, 6.90; S, 7.90.

[0186] Compound I-50: White solid, MS(ESI) m / z (M+H) + : 509.01. EA: C, 54.26; H, 2.59; N, 5.52; S, 6.30.

[0187] Compound I-51: Pale yellow solid, MS(ESI) m / z (M+H) + : 439.02. EA: C, 62.96; H, 3.69; N, 6.40; S, 7.32.

[0188] Compound I-52: Pale yellow solid, MS(ESI) m / z (M+H) + : 436.09. EA: C, 60.65; H, 3.26; N, 9.61; S, 7.38.

[0189] Synthesis Example 12: Preparation of Compound I-54

[0190]

[0191] First step: Add potassium thiocyanate (2 mmol) to a 250 ml flask, dissolve it with 8 mL of dichloromethane (DCM), then add polyethylene glycol-400 (PEG-400, 6 - 7 drops). During stirring, add 2,6-difluorobenzoyl chloride (1.5 mmol). After sealing, stir the reaction at room temperature for 2 h. After the reaction is completed, add p-trifluoromethoxyaniline (2 mmol) and continue the reaction for 1 h. After monitoring the reaction by TLC plate and filtering off the solid residue, evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a yellow solid product, which is the target benzoylthiourea.

[0192] Second step: Take the benzoylthiourea product obtained in the first step (0.5 mmol) in a sealed tube, dissolve it with 4 ml of DCM, then add 1-bromo-3,3,3-trifluoroacetone (0.75 mmol) and triethylamine (0.5 mmol). Seal the reaction tube and place it in an oil bath at 70 °C and stir the reaction for 5 h. After monitoring the reaction by TLC plate and filtering off the solid residue, evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a white solid product.

[0193] Compounds I-58 to I-64 can all be synthesized by this step.

[0194] Compound I-54: White solid, MS(ESI) m / z (M+H) +: 487.06. EA: C, 44.43; H, 2.09; N, 5.78; S, 6.61.

[0195] Compound I-58: Pale yellow solid, MS(ESI) m / z (M+H) + : 548.99. EA: C, 39.34; H, 1.63; N, 5.11; S, 5.85.

[0196] Compound I-59: Pale yellow solid, MS(ESI) m / z (M+H) + : 480.00. EA: C, 43.35; H, 1.95; N, 5.96; S, 6.81.

[0197] Compound I-60: White solid, MS(ESI) m / z (M+H) + : 521.01. EA: C, 41.53; H, 1.75; N, 5.40; S, 6.17.

[0198] Compound I-61: Pale yellow solid, MS(ESI) m / z (M+H) + : 501.08. EA: C, 45.63; H, 2.40; N, 5.61; S, 6.40.

[0199] Compound I-62: White solid, MS(ESI) m / z (M+H) + : 503.09. EA: C, 52.58; H, 3.79; N, 5.56; S, 6.36.

[0200] Compound I-63: White solid, MS(ESI) m / z (M+H) + : 505.01. EA: C, 42.85; H, 1.82; N, 5.53; S, 6.37.

[0201] Compound I-64: Pale yellow solid, MS(ESI) m / z (M+H) + : 475.02. EA: C, 40.50; H, 1.93; N, 5.91; S, 6.77.

[0202] Synthesis Example 13: Preparation of Compound I-55

[0203]

[0204] Step 1: Add potassium thiocyanate (2 mmol) into a 250 mL flask, dissolve it with 8 mL of acetone, add 2,6-difluorobenzoyl chloride (2 mmol) during stirring, seal it and stir at room temperature for 2 h. After the reaction is completed, add 4-chloro-3-((3-chloro-5-(trifluoromethyl)pyridin-2-yl)oxy)aniline (2 mmol) and continue the reaction for 1 h. After monitoring the end of the reaction by TLC plate, filter off the solid residue, and then evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a yellow solid product, which is the target benzoylthiourea.

[0205] Step 2: Take the benzoylthiourea product obtained in the first step (0.5 mmol) in a sealed tube, dissolve it with 4 mL of DCM, then add methyl bromopyruvate (0.75 mmol), seal the reaction tube and place it in an oil bath at 50 °C and stir for 5 h. After monitoring the end of the reaction by TLC plate, filter off the solid residue, and then evaporate the solvent under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a yellow solid product.

[0206] Compounds I-56 to I-57 and I-79 can be synthesized by this step.

[0207] Compound I-55: Yellow solid, MS(ESI) m / z (M+H) + : 622.00, EA: C, 46.34; H, 2.30; N, 6.78; S, 5.17.

[0208] Compound I-56: Pale yellow solid, MS(ESI) m / z (M+H) + : 493.03, EA: C, 46.36; H, 2.67; N, 5.69; S, 13.04.

[0209] Compound I-57: Pale yellow solid, MS(ESI) m / z (M+H) + : 511.03, EA: C, 44.70; H, 2.39; N, 5.49; S, 6.30.

[0210] Compound I-79: Pale yellow solid, 1 H NMR (500 MHz, CDCl 3 ): δ 7.37 (d, J = 7.6 Hz, 2H), 7.30–7.20 (m, 3H), 6.82 (t, J = 8.2 Hz, 2H), 4.77 (s, 1H), 3.90 (d, J = 12.3 Hz, 1H), 3.78 (s, 3H), 3.49 (d, J = 12.3 Hz, 1H).

[0211] Synthesis Example 14: Preparation of Compound I-73

[0212]

[0213] First step: Potassium selenocyanate (2 mmol) was added to a 250 ml flask, dissolved in 8 mL of dichloromethane (DCM), and then polyethylene glycol - 400 (PEG - 400, 6 - 7 drops) was added. During stirring, furan carbonyl chloride (2 mmol) was added, and after sealing, the reaction was stirred at room temperature for 2 h. After the reaction was completed, 3 - chloro - 4 - trifluoromethoxyaniline (2 mmol) was added and the reaction continued for 1 h. After monitoring the reaction by TLC plate and completion, the solid residue was filtered off, and then the solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a yellow solid product, which was the target furanoyl selenourea.

[0214] Second step: The furanoyl selenourea product obtained in the first step (0.5 mmol) was taken in a sealed tube, dissolved in 4 ml of DCM, and then methyl bromopyruvate (0.75 mmol) was added. After sealing the reaction tube, it was placed in an 80 °C oil bath and stirred for 5 h. After monitoring the reaction by TLC plate and completion, the solid residue was filtered off, and the solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a pale yellow solid product.

[0215] Compound I - 14 can be synthesized through this step

[0216] Compound I - 14: Pale yellow solid, MS(ESI) m / z(M + H) + : 524.98, EA: C, 43.59; H, 1.95; N, 5.33.

[0217] Compound I - 73: Pale yellow solid, MS(ESI) m / z(M + H) + : 478.94 EA: C, 42.75; H, 2.10; N, 5.87.

[0218] Synthesis Example 15: Preparation of Compound I - 74

[0219]

[0220] Step 1: Add potassium selenocyanate (2 mmol) into a 250 ml flask, dissolve it with 8 mL of dichloromethane (DCM), then add polyethylene glycol - 400 (PEG - 400, 6 - 7 drops). During stirring, add 2,6 - difluorobenzoyl chloride (2 mmol). After sealing, stir the reaction at room temperature for 2 h. After the reaction is completed, add 2 - chloro - 4 - trifluoromethylaniline (2 mmol) and continue the reaction for 1 h. After monitoring the reaction by TLC plate and the reaction is completed, filter off the solid residue, and remove the solvent by reduced pressure distillation. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a yellow solid product, which is the target benzoyl selenourea.

[0221] Step 2: Take the benzoyl selenourea product obtained in the first step (0.5 mmol) in a sealed tube, dissolve it with 4 ml of DCM, then add ethyl bromoacetate (0.75 mmol). After sealing the reaction tube, place it in an oil bath at 70 °C and stir the reaction for 5 h. After monitoring the reaction by TLC plate and the reaction is completed, filter off the solid residue, and remove the solvent by reduced pressure distillation. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a pale yellow solid product.

[0222] Compound I - 32 can be synthesized through this step.

[0223] Compound I - 32: Pale yellow solid, MS(ESI) m / z(M + H) + : 509.02. EA: C, 45.00; H, 2.57; N, 5.53; S, 6.34.

[0224] Compound I - 74: Pale yellow solid, MS(ESI) m / z(M + H) + : 510.97. EA: C, 44.75; H, 2.39; N, 5.51.

[0225] Synthesis Example 16: Preparation of Compound I - 75

[0226]

[0227] Step 1: Add potassium thiocyanate (2 mmol) into a 250 ml flask, dissolve it with 8 mL of acetone, add o - chlorobenzoyl chloride (1.5 mmol) during stirring. After sealing, stir the reaction at room temperature for 2 h. After the reaction is completed, add 3 - chloro - 5 - fluorobenzylamine (1.5 mmol) and continue the reaction for 1 h. After monitoring the reaction by TLC plate and the reaction is completed, filter off the solid residue, and remove the solvent by reduced pressure distillation. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a pale yellow solid product, which is the target benzoyl thiourea.

[0228] Step 2: Take the benzoylthiourea product (0.5 mmol) obtained in the first step in a sealed tube, add 4 ml of DCM to dissolve it, then add bromoacetone (0.75 mmol). After sealing the reaction tube, place it in an oil bath at 70 °C and stir for 5 h. After monitoring the reaction by TLC plate and completion, filter off the solid residue, and remove the solvent by rotary evaporation under reduced pressure. The residue was purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a pale yellow solid product.

[0229] Compounds I-38 to I-42 and I-53 can all be synthesized by this step.

[0230] Compound I-38: Pale yellow solid, MS(ESI) m / z (M+H) + : 433.02. EA: C, 49.97; H, 2.31; N, 6.49; S, 7.43.

[0231] Compound I-39: Pale yellow solid, MS(ESI) m / z (M+H) + : 415.09. EA: C, 52.20; H, 2.69; N, 6.78; S, 7.74.

[0232] Compound I-40: Pale yellow solid, MS(ESI) m / z (M+H) + : 449.05. EA: C, 48.19; H, 2.27; N, 6.25; S, 7.11.

[0233] Compound I-41: Pale yellow solid, MS(ESI) m / z (M+H) + : 431.14. EA: C, 61.39; H, 4.65; N, 6.53; S, 7.42.

[0234] Compound I-42: Pale yellow solid, MS(ESI) m / z (M+H) + : 403.10. EA: C, 47.73; H, 2.78; N, 13.95; S, 7.97.

[0235] Compound I-53: Pale yellow solid, MS(ESI) m / z (M+H) + : 295.11. EA: C, 69.38; H, 4.80; N, 9.52; S, 10.91.

[0236] Compound I-75: Pale yellow solid, MS(ESI) m / z (M+H) + : 395.03. EA: C, 54.73; H, 3.31; N, 7.11; S, 8.08.

[0237] Synthesis Example 17: Preparation of Compound I-76

[0238]

[0239] First step: Potassium thiocyanate (2 mmol) was added to a 250 ml flask and dissolved in 8 mL of dichloromethane (DCM). Subsequently, polyethylene glycol-400 (PEG-400, 6 - 7 drops) was added. During stirring, furan carbonyl chloride (1.5 mmol) was added. After sealing, the reaction was stirred at room temperature for 2 h. After the reaction was completed, 3-chloro-4-trifluoromethoxyaniline (1.5 mmol) was added and the reaction continued for 1 h. After monitoring the reaction by TLC plate and completion, the solid residue was filtered off, and the solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a white solid product, which was the target furanoylthiourea.

[0240] Second step: The furanoylthiourea product obtained in the first step (0.5 mmol) was taken in a sealed tube, dissolved in 4 ml of DCM, and then methyl bromopyruvate (0.75 mmol) was added. After sealing the reaction tube, it was placed in an 80 °C oil bath and stirred for 5 h. After monitoring the reaction by TLC plate and completion, the solid residue was filtered off, and the solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a pale yellow solid product.

[0241] Compound I-46 can be synthesized through this step.

[0242] Compound I-46: Yellow solid, MS(ESI) m / z(M + H) + : 477.03. EA: C, 47.88; H, 2.13; N, 5.89; S, 6.74.

[0243] Compound I-76: Pale yellow solid, MS(ESI) m / z(M + H) + : 431.02. EA: C, 47.40; H, 2.34; N, 6.50; S, 7.44.

[0244] Synthesis Example 18: Preparation of Compound I-77

[0245]

[0246] Step 1: Add potassium thiocyanate (2 mmol) into a 250 mL flask, dissolve it with 8 mL of dichloromethane (DCM), then add polyethylene glycol - 400 (PEG - 400, 6 - 7 drops). During stirring, add 2,6 - difluorobenzoyl chloride (1.5 mmol). After sealing, stir the reaction at room temperature for 2 h. After the reaction is completed, add 2 - chloro - 4 - trifluoromethylaniline (1.5 mmol) and continue the reaction for 1 h. After monitoring the reaction by TLC plate and completion, filter off the solid residue, and remove the solvent by distillation under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a pale yellow solid product, which is the target benzoylthiourea.

[0247] Step 2: Take the benzoylthiourea product obtained in the first step (0.5 mmol) in a sealed tube, dissolve it with 4 mL of DCM, then add ethyl bromoacetate (0.75 mmol). After sealing the reaction tube, place it in an oil bath at 70 °C and stir the reaction for 5 h. After monitoring the reaction by TLC plate and completion, filter off the solid residue, and remove the solvent by distillation under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a pale yellow solid product.

[0248] Compound I - 72 can be synthesized through this step.

[0249] Compound I - 72: Pale yellow solid, MS(ESI) m / z(M + H) + : 460.03. EA: C, 49.58; H, 2.87; N, 6.04; S, 13.92.

[0250] Compound I - 77: Pale yellow solid, MS(ESI) m / z(M + H) + : 463.00. EA: C, 49.32; H, 2.61; N, 6.03; S, 6.95.

[0251] Synthesis Example 19, Preparation of Compound I - 82

[0252]

[0253] Step 1: Heat - reflux N - (4 - chlorophenyl)cyanamide (1.638 mmol), episulfide (1.646 mmol) and potassium carbonate (1.720 mmol) in 2 - butanone. After 2 h, cool the reaction, dilute it with 100 mL of dichloromethane, and wash it with water (2×75 mL) and brine (75 mL). Dry the organic phase with magnesium sulfate, filter, and concentrate it under reduced pressure to obtain an imine compound.

[0254] Step 2: Add 4 mL of dichloromethane (DCM) to the above-obtained imine compound (0.5 mmol) in a sealed tube, then add 2,6-difluorobenzoyl chloride (0.5 mmol). After sealing, stir the reaction at room temperature for 1 h. After monitoring the end of the reaction by TLC plate, filter off the solid residue, and remove the solvent by rotary evaporation under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate), and concentrated under reduced pressure to obtain the target product.

[0255] Compounds I-65 to I-67 can all be synthesized according to this step.

[0256] Compound I-65: Pale yellow solid, MS(ESI) m / z (M+H) + : 432.99, EA: C, 49.91; H, 2.30; N, 6.48; S, 7.39.

[0257] Compound I-66: Pale yellow solid, MS(ESI) m / z (M+H) + : 449.05, EA: C, 48.19; H, 2.22; N, 6.25; S, 7.12.

[0258] Compound I-67: Pale yellow solid, MS(ESI) m / z (M+H) + : 349.01, EA: C, 58.60; H, 3.19; N, 8.02; S, 9.21.

[0259] Compound I-82: Pale yellow solid, MS(ESI) m / z (M+H) + : 350.99, EA: C, 54.81; H, 2.58; N, 7.97; S, 9.16.

[0260] Synthesis Example 20, Preparation of Compound I-68

[0261]

[0262] Step 1: Add potassium thiocyanate (2 mmol) to a 250 ml flask, dissolve it with 2 mL of dichloromethane (DCM), then add polyethylene glycol-400 (PEG-400, 6 - 7 drops). During stirring, add benzoyl chloride (2 mmol). After sealing, stir the reaction at room temperature for 2 h. After the reaction is completed, filter off the solid residue, and remove the solvent by rotary evaporation under reduced pressure to obtain benzoyl isothiocyanate.

[0263] Step 2: Take the isothiocyanate obtained in the first step in a reaction tube, and under nitrogen protection, add allylaniline (0.2 mmol) and react for 1 h. Then add 1-(trifluoromethyl)-1,2-benziodoxol-3(1H)-one (0.3 mmol), copper(I) chloride (10 mol%), cesium carbonate (0.5 mmol), and 8 ml of 1,2-dichloroethane (DCE). After sealing, place it in an oil bath at 75 °C and react for 4 h. After monitoring the reaction by TLC plate and the reaction is completed, filter off the solid residue, and remove the solvent by rotary evaporation under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate), and the target product is obtained after concentration under reduced pressure.

[0264] Compound I-68: Pale yellow solid, MS(ESI) m / z (M+H) + : 401.10. EA: C, 54.01; H, 3.25; N, 6.99; S, 8.02.

[0265] Synthesis Example 21, Preparation of Compound I-70

[0266]

[0267] Step 1: Add potassium thiocyanate (2 mmol) to a 250 ml flask, dissolve it with 2 mL of dichloromethane (DCM), then add polyethylene glycol-400 (PEG-400, 6 - 7 drops). During stirring, add 2,6-difluorobenzoyl chloride (2 mmol). After sealing, stir at room temperature for 2 h. After the reaction is completed, add aniline (2 mmol) and continue to react for 1 h. After monitoring the reaction by TLC plate and the reaction is completed, filter off the solid residue, and remove the solvent by rotary evaporation under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a white solid product, which is benzoylthiourea.

[0268] Step 2: Dissolve the thiourea derivative synthesized in the first step (2 mmol) in an acetone solution, add triethylamine (10.50 equivalents), and stir at room temperature (25 - 30 °C) for 10 minutes until the solution turns pale yellow. Add benzyl cyanide bromide (2.05 mmol, dissolved in 1 mL of acetonitrile) dropwise thereto for 10 minutes, and then a yellow precipitate is obtained after 15 minutes. Concentrate the solvent under reduced pressure to separate the solid material; filter and wash with n-hexane to remove the excess triethylamine. The obtained yellow crystal compound is purified to obtain the target product.

[0269] Compound I-69 can be synthesized according to this procedure.

[0270] Compound I-69: Yellow solid, MS(ESI) m / z (M+H) + : 332.11. EA: C, 57.99; H, 3.36; N, 12.69; S, 9.70.

[0271] Compound I-70: Yellow solid, MS(ESI) m / z (M+H) + : 408.11. EA: C, 64.82; H, 3.68; N, 10.29; S, 7.84.

[0272] Synthesis Example 22, Preparation of Compound I-71

[0273]

[0274] First step: Add potassium thiocyanate (2 mmol) to a 250 ml flask, dissolve it with 8 mL of dichloromethane (DCM), then add polyethylene glycol-400 (PEG-400, 6 - 7 drops). During stirring, add 2,6-difluorobenzoyl chloride (1.5 mmol). After sealing, stir the reaction at room temperature for 2 h. After the reaction is completed, add 2-chloro-4-trifluoromethylaniline (1.5 mmol) and continue the reaction for 1 h. After monitoring the reaction by TLC plate and the reaction is completed, filter off the solid residue, and remove the solvent by distillation under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a pale yellow solid product, which is the target benzoylthiourea.

[0275] Second step: Take the benzoylthiourea product obtained in the first step (0.5 mmol) in a sealed tube, then add sodium acetate (1.0 mmol) and acetone (4 mL) in sequence. Subsequently, add ethyl bromoacetate (0.75 mmol). Seal the reaction tube and place it in an oil bath at 60 °C and stir the reaction for 4 h. After monitoring the reaction by TLC plate and the reaction is completed, filter off the solid residue, and remove the solvent by distillation under reduced pressure. The residue is purified by column chromatography (eluted with a mixed solvent of petroleum ether and ethyl acetate) to obtain a white solid product I-71.

[0276] Compound I-71: White solid, MS(ESI) m / z (M+H) + : 333.01. EA: C, 57.80; H, 3.01; N, 8.45; S, 9.65.

[0277] Biological Activity Assay Example

[0278] The compounds of the present invention show good activities against various pests in the agricultural field. The results of the insecticidal activity assay are shown in the following examples.

[0279] Example 1: Evaluation of the Insecticidal Activity of Some Compounds against Plutella xylostella

[0280] The test insects are Plutella xylostella of Lepidoptera, and the sensitive strain is reared indoors. The 3rd instar larvae of Plutella xylostella are used as the test objects, and the test method is the leaf dipping method.

[0281] Operation procedure: Weigh each sample accurately, dissolve them in DMSO respectively to prepare a stock solution of 10 g / L, and dilute it with an aqueous solution containing 0.5% Tween-80. Use a punch with a diameter of 1.0 cm to make leaf discs from clean Chinese flowering cabbage leaves and immerse them in the medicinal solution. Take them out after 10 s, air-dry naturally, and transfer them into a clean container. Introduce 3rd instar larvae of Plutella xylostella with consistent growth into the container, with 10 test insects introduced for each treatment, and raise them at a constant temperature of 28 °C. Set 3 replicates, and the control group is treated with an aqueous solution containing the same amount of 0.5% Tween-80 - DMSO. Observe the test results after 96 h, and calculate the mortality rate (%) according to the formula. Mortality rate (%) = number of dead insects / number of test insects × 100%.

[0282] The synthesized compound (I) was tested according to the above experimental steps.

[0283] When the concentration of the compound was 50 mg / L, the compounds with a mortality rate of Plutella xylostella greater than 50% were: I-6~I-11, I-14, I-22~I-32, I-38~I-43, I-46, I-54~I-68, I-72~I-79.

[0284] When the concentration of the compound was 10 mg / L, the compounds with a mortality rate of Plutella xylostella greater than 80% were:

[0285] I-14, I-22~I-31, I-43, I-46, I-55~I-63, I-73, I-76, I-78.

[0286] Example 2: Evaluation of the insecticidal activity of some compounds against Spodoptera frugiperda

[0287] The test insects were Spodoptera frugiperda of Lepidoptera, and the sensitive strain was reared indoors. The late 2nd instar larvae of Spodoptera frugiperda were used as the test objects, and the test method was the leaf immersion method.

[0288] Operation procedure: Weigh each sample accurately, dissolve them in DMSO respectively to prepare a stock solution of 10 g / L, and dilute it to 50 ppm with an aqueous solution containing 0.5% Tween-80. Use a punch with a diameter of 1.0 cm to make leaf discs from clean corn leaves and immerse them in the medicinal solution. Take them out after 10 s, air-dry naturally, and transfer them into a clean container. Introduce late 2nd instar larvae of Spodoptera frugiperda with consistent growth into the container, with 10 test insects introduced for each treatment, and raise them at a constant temperature of 28 °C. Set 3 replicates, and the control group is treated with an aqueous solution containing the same amount of 0.5% Tween-80 - DMSO aqueous solution. Observe the test results after 96 h, and calculate the mortality rate (%) according to the formula. Mortality rate (%) = number of dead insects / number of test insects × 100%. The test results are shown in Table 1.

[0289] The synthesized compound (I) was tested according to the above experimental steps.

[0290] When the compound concentration is 50 mg / L, the compounds with a mortality rate of Spodoptera frugiperda greater than 50% are:

[0291] I-6 to I-11, I-14, I-22 to I-32, I-38 to I-43, I-46, I-54 to I-68, I-72 to I-79.

[0292] Example 3: Evaluation of the insecticidal activity of some compounds against Spodoptera exigua

[0293] The test insects were Spodoptera exigua of Lepidoptera, and a sensitive strain was reared indoors. The mid-first-instar larvae of Spodoptera exigua were used as the test objects, and the leaf-dipping method was used as the test method.

[0294] Operation process: Weigh each sample accurately, add DMSO to prepare a 10 g / L stock solution respectively, and dilute it to 50 ppm with an aqueous solution containing 0.5% Tween-80. Use a punch with a diameter of 1.0 cm to make leaf discs from clean Chinese cabbage leaves and immerse them in the medicated solution. After 10 s, take them out, let them dry naturally, and transfer them to a clean container. Introduce mid-first-instar larvae of Spodoptera exigua with consistent growth into the container, with 10 test insects introduced for each treatment, and rear them in a constant temperature incubator at 28 °C. Set 3 replicates, and the control group was treated with an aqueous solution containing an equal amount of 0.5% Tween-80 - DMSO. Observe the test results after 96 h, and calculate the mortality rate (%) according to the formula. Mortality rate (%) = number of dead insects / number of test insects × 100%. The test results are shown in Table 1.

[0295] The synthesized compound (I) was tested according to the above experimental steps.

[0296] When the compound concentration is 50 mg / L, the compounds with a mortality rate of Spodoptera exigua greater than 50% are: I-6 to I-11, I-14, I-22 to I-32, I-38 to I-43, I-46, I-54 to I-68, I-72 to I-79.

[0297] Example 4: Evaluation of the insecticidal activity of some compounds against Prodenia litura

[0298] The test insects were Prodenia litura of Lepidoptera, and a sensitive strain was reared indoors. The late-first-instar larvae of Prodenia litura were used as the test objects, and the leaf-dipping method was used as the test method.

[0299] Operation procedure: Weigh each sample accurately, and dissolve them in DMSO respectively to prepare a stock solution of 10 g / L. Dilute it to 50 ppm with an aqueous solution containing 0.5% Tween-80. Use a punch with a diameter of 1.0 cm to make leaf discs from clean Chinese cabbage leaves, immerse them in the medicinal solution, take them out after 10 s, air dry naturally, and transfer them into a clean container. Introduce the late first-instar larvae of Spodoptera litura with consistent growth into the container, with 10 test insects introduced for each treatment, and raise them at a constant temperature of 28°C. Set 3 replicates, and the control group is treated with an aqueous solution containing the same amount of 0.5% Tween-80-DMSO. Observe the test results after 96 h, and calculate the mortality rate (%) according to the formula. Mortality rate (%) = number of dead insects / number of test insects × 100%. The test results are shown in Table 1.

[0300] The synthesized compound (I) was tested according to the above experimental steps.

[0301] When the concentration of the compound was 50 mg / L, the compounds with a mortality rate of Spodoptera litura greater than 50% were:

[0302] I-6~I-11, I-14, I-22~I-32, I-38~I-43, I-46, I-54~I-68, I-72~I-79.

[0303] The above embodiments are the preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principle of the present invention shall be equivalent replacement methods and are all included in the protection scope of the present invention.

Claims

1. An amideazole compound for controlling pests in agriculture and forestry and other fields or its agriculturally acceptable salt, characterized in that, the structure of the amideazole compound is shown in the general formula (I): In general formula (I), R 1 is selected from substituted or unsubstituted phenyl, substituted or unsubstituted furyl; wherein the substituent in the substituted or unsubstituted is selected from halogen; W is selected from O or S; Y 1 Selected from O, S, Se; represents a single bond; R a , R b , R c , R d Each independently selected from hydrogen, halogen, hydroxy, C 1-6 alkyl, halo C 1-6 alkyl, C 1-6 alkoxycarbonyl; R 2 selected from substituted or unsubstituted phenyl; wherein the substituents in the substituted or unsubstituted phenyl are selected from halogen, C 1-6 alkyl, halo-C 1-6 alkyl, C 1-6 alkoxy, halo-C 1-6 alkoxy, C 1-6 alkylthio, halo-C 1-6 alkylthio, C 1-6 alkoxycarbonyl, 2. The amideazole compound or its agriculturally acceptable salt according to claim 1, characterized in that, In general formula (I), R 1 is selected from substituted or unsubstituted phenyl or furyl; wherein the substituents in the substituted or unsubstituted are selected from fluorine, chlorine, bromine, iodine; W is selected from O; Y 1 selected from S, Se; represents a single bond; R a ,R b each independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl; methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl substituted with fluorine, chlorine, bromine and / or iodine; R c ,R d each independently selected from hydrogen, hydroxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl; methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl substituted with fluorine, chlorine, bromine and / or iodine; methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl; R 2 selected from substituted or unsubstituted phenyl; wherein the substituents in the substituted or unsubstituted phenyl are selected from fluorine, chlorine, bromine, iodine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl; methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl substituted by fluorine, chlorine, bromine and / or iodine; methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy; methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy substituted by fluorine, chlorine, bromine and / or iodine; methylthio, ethylthio, tert-butylthio; methylthio, ethylthio, tert-butylthio substituted by fluorine, chlorine, bromine and / or iodine; methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, 3. The amideazole compound or its agriculturally acceptable salt according to claim 1, characterized in that, In general formula (I), R 1 is selected from 2,6-difluorophenyl, phenyl, 2-chlorophenyl, 4-fluorophenyl, 2-furyl; W is selected from O; Y 1 selected from S, Se; represents a single bond; R a ,R b each independently selected from hydrogen, methyl, 1,1,1-trifluoroethyl; R c ,R d each independently selected from hydrogen, hydroxy, tert-butyl, methyl, trifluoromethyl, methoxycarbonyl; R 2 selected from substituted or unsubstituted phenyl, wherein the substituent is fluorine, chlorine, bromine, trifluoromethyl, trifluoromethoxy, tert-butoxycarbonyl, methoxy, trifluoromethylthio, 4. The amideazole compound or its agriculturally acceptable salt according to claim 1, characterized in that, the compound of general formula (I) is selected from the following compounds:

5. An amideazole compound or its agriculturally acceptable salt, characterized in that, the amideazole compound is selected from the following compounds:

6. The preparation method of the amideazole compound according to claim 1, characterized in that, The synthetic route of the described method is as follows: Substituent R in the reaction formula 1 , R 2 , Y 1 , R a , R b , R c , R d are defined as described in claim 1; X is chlorine or bromine; the catalyst is one or more of polyethylene glycol-200, polyethylene glycol-400, polyethylene glycol-600; the base refers to one or more of sodium carbonate, potassium carbonate, cesium carbonate, potassium phosphate, sodium acetate, potassium acetate, triethylamine, diisopropylethylamine, pyridine; the heating temperature is 40 - 120 °C.

7. The preparation method of the amideazole compound according to claim 1, characterized in that, the synthetic route of the method is as follows: Substituent R in the reaction formula 1 is 2,6-difluorophenyl; R 2 is phenyl; the catalyst in the first step reaction is one or more of polyethylene glycol-200, polyethylene glycol-400, polyethylene glycol-600; the catalyst in the second step reaction is one or more of cuprous bromide, cuprous iodide, cuprous chloride, ferric trichloride or cobalt dichloride; the base refers to one or more of potassium carbonate, sodium hydroxide, sodium carbonate, potassium phosphate, diisopropylethylamine, pyridine, sodium tert-butoxide, potassium tert-butoxide or cesium carbonate; the heating temperature is 40 - 120 °C.

8. The use of the amideazole compound or its agriculturally acceptable salt according to general formula (I) in claim 1 for preparing a drug for controlling and eliminating pests in agriculture and forestry, wherein the pests in agriculture and forestry are Lepidoptera insects.

9. The use according to claim 8, wherein the Lepidoptera insects are Plutella xylostella, Spodoptera frugiperda, Spodoptera exigua, Spodoptera litura.

10. An insecticidal composition, which contains an active ingredient and an agriculturally acceptable carrier, characterized in that, the active ingredient is one or more of the amideazole compounds or their agriculturally acceptable salts according to general formula (I) in claim 1; or the active ingredient is one or more of the amideazole compounds or their agriculturally acceptable salts according to claim 5.

11. The composition according to claim 10, characterized in that, the weight percentage content of the active ingredient in the composition is 0.01 - 99.99%.

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