An amide compound and use thereof

Abstract

Disclosed are an amide compound and use thereof. The compound has a structure represented by general formula I: wherein definitions of the substituents are described in the specification. The specification also discloses use of the compound as an insecticide and an animal parasitic worm control agent.

Description

[0001] This application is a divisional application of Chinese invention patent application filed on July 8, 2022, with application number 202210800664.0 and invention title "An amide compound and its use". Technical Field

[0002] This invention relates to a compound, specifically to a novel amide compound and its uses. Background Technology

[0003] Patent JP2007099761A discloses the following specific compounds KC1 (CAS Registry No.: 934532-14-6) and KC2 (CAS Registry No.: 934532-15-7), which have certain insecticidal activity.

[0004]

[0005] Patent CN102119143A discloses the following insecticidal compounds: KC3 (compound number: 7-1574, CAS Registry No.: 1207727-04-5), KC4 (compound number: 7-1577, CAS Registry No.: 1207727-08-9), and KC5 (compound number: 7-1733, CAS Registry No.: 1207727-07-8). Compound KC3 is commercially available as an agricultural insecticide, with the common Chinese name broflanilide and the common English name broflanilide.

[0006]

[0007] Patent CN102119143A also discloses the following compounds with insecticidal activity: KC6 (compound number: 6-1772, CAS Registry No.: 1331922-53-2), KC7 (compound number: 7-1616, CAS Registry No.: 1207979-50-7), and KC8 (compound number: 7-1772, CAS Registry No.: 1332266-07-5).

[0008] Compound KC6 is being developed as an insecticide, and its common English name is mivorilaner.

[0009]

[0010] However, the control effect of existing insecticides is still not ideal, and there is still a need to continuously develop new, more efficient, and broader-spectrum insecticides to meet market demand.

[0011] No compounds of general formula I as described in this invention and their insecticidal activities have been reported in the prior art. Summary of the Invention

[0012] The purpose of this invention is to provide an amide compound with excellent insecticidal activity. It can be used to prepare pesticides for pest control in agriculture and other fields, as well as in veterinary medicine for controlling animal parasites.

[0013] To achieve the objective of this invention, the following technical solution is provided:

[0014] An amide compound, as shown in general formula I:

[0015]

[0016] In general formula I:

[0017] R1 is selected from hydrogen, fluorine, cyano, trifluoromethyl, or difluoromethyl;

[0018] R2 is selected from allyl or propargyl;

[0019] R3 is selected from halogens;

[0020] R4 is selected from halogens, C1-C3 haloalkyl groups, or C1-C3 haloalkoxy groups;

[0021] X is selected from CH or N.

[0022] In one possible implementation, in general formula I,

[0023] R1 is selected from hydrogen, fluorine, cyano, trifluoromethyl, or difluoromethyl;

[0024] R2 is selected from allyl or propargyl;

[0025] R3 is selected from bromine or iodine;

[0026] R4 is selected from bromine, iodine, trifluoromethyl, or difluoromethoxy;

[0027] X is selected from CH or N.

[0028] In one possible implementation, the amide compound is selected from the compounds in Table 1, which have a structure as shown in general formula I and R1, X, R2, R3 and R4 are as shown in Table 1:

[0029] Table 1

[0030]

[0031]

[0032]

[0033] In one possible implementation, the amide compound is selected from the compounds in Table 2, which have a structure as shown in general formula I and R1, X, R2, R3, and R4 are as shown in Table 2:

[0034] Table 2

[0035]

[0036]

[0037] In one possible implementation, the amide compound is selected from the compounds in Table 3, which have a structure as shown in general formula I and R1, X, R2, R3, and R4 are as shown in Table 3:

[0038] Table 3

[0039]

[0040]

[0041] The present invention also includes an intermediate compound for preparing the above-mentioned amide compounds (i.e., compounds of general formula I), said intermediate compound being shown in general formula II:

[0042]

[0043] In general formula II:

[0044] R1 is selected from hydrogen, fluorine, cyano, trifluoromethyl, or difluoromethyl;

[0045] R2 is selected from allyl or propargyl;

[0046] X is selected from CH or N.

[0047] In one possible implementation, the intermediate compound is selected from the compounds in Table 4, which have a structure as shown in general formula II and R1, X, and R2 are as shown in Table 4:

[0048] Table 4

[0049]

[0050]

[0051] The present invention also includes an intermediate compound for preparing the above-described general formula II compound, said intermediate compound being as shown in general formula III:

[0052]

[0053] In general formula III:

[0054] R1 is selected from hydrogen, fluorine, cyano, trifluoromethyl, or difluoromethyl;

[0055] X is selected from CH or N;

[0056] R2 is selected from allyl or propargyl;

[0057] R5 is selected from C1-C6 alkyl groups.

[0058] In one possible implementation, the intermediate compound is selected from the compounds in Table 5, which have a structure as shown in general formula III and R1, X, R2 and R5 are as shown in Table 5:

[0059] Table 5

[0060]

[0061]

[0062] The present invention also includes an intermediate compound for preparing the above-described general formula III compound, said intermediate compound being as shown in general formula IV:

[0063]

[0064] In general formula IV:

[0065] R2 is selected from allyl or propargyl;

[0066] R5 is selected from C1-C6 alkyl groups.

[0067] In one possible implementation, the intermediate compound is selected from the compounds in Table 6, which have the structure of general formula IV and R2 and R5 as shown in Table 6:

[0068] Table 6

[0069] IV.1 Allyl <![CDATA[CH3]]> IV.2 Allyl <![CDATA[CH2CH3]]> IV.3 Allyl <![CDATA[CH2CH2CH3]]> IV.4 Allyl <![CDATA[CH2CH2CH2CH3]]> IV.5 Allyl <![CDATA[CH2CH2CH2CH2CH3]]> IV.6 Allyl <![CDATA[CH2CH2CH2CH2CH2CH3]]> IV.7 propargyl <![CDATA[CH3]]> IV.8 propargyl <![CDATA[CH2CH3]]> IV.9 propargyl <![CDATA[CH2CH2CH3]]> IV.10 propargyl <![CDATA[CH2CH2CH2CH3]]> IV.11 propargyl <![CDATA[CH2CH2CH2CH2CH3]]> IV.12 propargyl <![CDATA[CH2CH2CH2CH2CH2CH3]]> .

[0070] The present invention also includes an intermediate compound for preparing the above-mentioned amide compounds (i.e., compounds of general formula I), said intermediate compound being as shown in general formula V:

[0071]

[0072]

[0073] In general formula V:

[0074] R2 is selected from allyl or propargyl;

[0075] R3 is selected from halogens;

[0076] R4 is selected from halogens, C1-C3 haloalkyl groups, or C1-C3 haloalkoxy groups.

[0077] In one possible implementation, in the general formula V,

[0078] R2 is selected from allyl or propargyl;

[0079] R3 is selected from bromine or iodine;

[0080] R4 is selected from bromine, iodine, trifluoromethyl, or difluoromethoxy.

[0081] In one possible implementation, the intermediate compound is selected from the compounds in Table 7, which have a structure as shown in general formula V and R2, R3, and R4 are as shown in Table 7:

[0082] Table 7

[0083] V.1 Allyl Br Br V.2 Allyl Br I V.3 Allyl Br <![CDATA[CF3]]> V.4 Allyl I <![CDATA[CF3]]> V.5 Allyl Br <![CDATA[OCHF2]]> V.6 Allyl I <![CDATA[OCHF2]]> V.7 propargyl Br Br V.8 propargyl Br I V.9 propargyl Br <![CDATA[CF3]]> V.10 propargyl I <![CDATA[CF3]]> V.11 propargyl Br <![CDATA[OCHF2]]> V.12 propargyl I <![CDATA[OCHF2]]> .

[0084] In one possible implementation, the intermediate compound is selected from the compounds in Table 8, which have a structure as shown in general formula V and R2, R3, and R4 are as shown in Table 8:

[0085] Table 8

[0086] V.3 Allyl Br <![CDATA[CF3]]> V.4 Allyl I <![CDATA[CF3]]> V.9 propargyl Br <![CDATA[CF3]]> V.10 propargyl I <![CDATA[CF3]]> .

[0087] The present invention also includes an intermediate compound for preparing the above-mentioned amide compounds (i.e., compounds of general formula I), said intermediate compound being shown in general formula VI:

[0088] In general formula VI:

[0089] R1 is selected from hydrogen, fluorine, cyano, trifluoromethyl, or difluoromethyl;

[0090] R2 is selected from allyl or propargyl;

[0091] R4 is selected from halogens, C1-C3 haloalkyl groups, or C1-C3 haloalkoxy groups;

[0092] X is selected from CH or N.

[0093] In one possible implementation, in general VI,

[0094] R1 is selected from hydrogen, fluorine, cyano, trifluoromethyl, or difluoromethyl;

[0095] R2 is selected from allyl or propargyl;

[0096] R4 is selected from bromine, iodine, trifluoromethyl, or difluoromethoxy;

[0097] X is selected from CH or N.

[0098] In one possible implementation, the intermediate compound is selected from the compounds in Table 9, which have a structure as shown in general formula VI and R1, X, R2 and R4 are as shown in Table 9:

[0099] Table 9

[0100] VI.1 H CH Allyl <![CDATA[CF3]]> VI.2 F CH Allyl <![CDATA[CF3]]> VI.3 CN CH Allyl <![CDATA[CF3]]> VI.4 F N Allyl <![CDATA[CF3]]> VI.5 CN N Allyl <![CDATA[CF3]]> VI.6 <![CDATA[CF3]]> N Allyl <![CDATA[CF3]]> VI.7 H CH propargyl <![CDATA[CF3]]> VI.8 F CH propargyl <![CDATA[CF3]]> VI.9 CN CH propargyl <![CDATA[CF3]]> VI.10 F N propargyl <![CDATA[CF3]]> VI.11 CN N propargyl <![CDATA[CF3]]> VI.12 <![CDATA[CF3]]> N propargyl <![CDATA[CF3]]> VI.13 H CH Allyl <![CDATA[OCHF2]]> VI.14 F CH Allyl <![CDATA[OCHF2]]> VI.15 CN CH Allyl <![CDATA[OCHF2]]> VI.16 F N Allyl <![CDATA[OCHF2]]> VI.17 CN N Allyl <![CDATA[OCHF2]]> VI.18 <![CDATA[CF3]]> N Allyl <![CDATA[OCHF2]]> VI.19 H CH propargyl <![CDATA[OCHF2]]> VI.20 F CH propargyl <![CDATA[OCHF2]]> VI.21 CN CH propargyl <![CDATA[OCHF2]]> VI.22 F N propargyl <![CDATA[OCHF2]]> VI.23 CN N propargyl <![CDATA[OCHF2]]> VI.24 <![CDATA[CF3]]> N propargyl <![CDATA[OCHF2]]> .

[0101] In one possible implementation, the intermediate compound is selected from the compounds in Table 10, which have a structure as shown in general formula VI and R1, X, R2 and R4 are as shown in Table 10:

[0102] Table 10

[0103] VI.1 H CH Allyl <![CDATA[CF3]]> VI.2 F CH Allyl <![CDATA[CF3]]> VI.3 CN CH Allyl <![CDATA[CF3]]> VI.4 F N Allyl <![CDATA[CF3]]> VI.5 CN N Allyl <![CDATA[CF3]]> VI.6 <![CDATA[CF3]]> N Allyl <![CDATA[CF3]]> VI.7 H CH propargyl <![CDATA[CF3]]> VI.8 F CH propargyl <![CDATA[CF3]]> VI.9 CN CH propargyl <![CDATA[CF3]]> VI.10 F N propargyl <![CDATA[CF3]]> VI.11 CN N propargyl <![CDATA[CF3]]> VI.12 <![CDATA[CF3]]> N propargyl <![CDATA[CF3]]> .

[0104] The present invention also includes an intermediate compound for preparing the above-described general formula VI compound, said intermediate compound being as shown in general formula VII:

[0105]

[0106] In general formula VII:

[0107] R2 is selected from allyl or propargyl;

[0108] R4 is selected from halogens, C1-C3 haloalkyl groups, or C1-C3 haloalkoxy groups.

[0109] In one possible implementation, in general formula VII,

[0110] R2 is selected from allyl or propargyl;

[0111] R4 is selected from bromine, iodine, trifluoromethyl, or difluoromethoxy.

[0112] In one possible implementation, the intermediate compound is selected from the compounds in Table 11, which have the structure of general formula VII and R2 and R4 are as shown in Table 11:

[0113] Table 11

[0114] VII.1 Allyl <![CDATA[CF3]]> VII.2 Allyl <![CDATA[OCHF2]]> VII.3 propargyl <![CDATA[CF3]]> VII.4 propargyl <![CDATA[OCHF2]]> .

[0115] The present invention also provides methods for preparing the above-mentioned amide compounds, as follows: five methods in total (unless otherwise specified, the definitions of each group are the same as above, and LG = Cl, Br or I):

[0116] Option 1:

[0117]

[0118] Step 1: Preparation of Compounds of Formula IV

[0119] Compound of general formula VIII can be reacted with compound of general formula R2-LG in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours to produce compound of general formula IV. The reaction is carried out in the presence of a base.

[0120] Step 2: Preparation of Compounds of General Formula III

[0121] Compound of general formula III can be prepared by reacting compounds of general formula IV and general formula IX in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours. The reaction is carried out in the presence of a base or catalyst.

[0122] Step 3: Preparation of Compounds of General Formula II

[0123] Compound of general formula III can be hydrolyzed to prepare compound of general formula II in the presence of a base at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours. Suitable bases include lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, a mixture of lithium bromide and triethylamine, or a mixture of sodium bromide and triethylamine. Suitable solvents include any one or a mixture of at least two of water, methanol, ethanol, tetrahydrofuran, or dioxane.

[0124] Step 4: Preparation of compound of general formula X

[0125] Compounds of general formula X can be prepared by reacting compounds of general formula II with thionyl chloride, oxalyl chloride, carbonyl chloride, phosphoryl chloride, phosphorus pentachloride, phosphorus trichloride, triphosgene, etc. using conventional methods.

[0126] Step 5: Preparation of compound of general formula I

[0127] Compound of general formula I can be prepared by reacting compound of general formula X and compound of general formula XI in a suitable solvent at a temperature ranging from -70°C to the boiling point of the solvent for 0.5-48 hours. The reaction is carried out in the presence of a base or catalyst.

[0128] In steps 1, 2, and 5, suitable solvents may be aromatic hydrocarbons such as benzene, toluene, and xylene; ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone; halogenated hydrocarbons such as chloroform and dichloromethane; esters such as methyl acetate and ethyl acetate; ethers such as tetrahydrofuran, dioxane, diethyl ether, and 1,2-dimethoxyethane; polar solvents such as water, acetonitrile, N,N-dimethylformamide, N-methylpyrrolidone, and dimethyl sulfoxide; or mixtures of the above solvents; the base may be the same or different, such as trimethylamine, triethylamine, pyridine, or DBU. Organic bases such as 4-dimethylaminopyridine, N,N-diisopropylmethylamine, and N,N-diisopropylethylamine; alkali metal hydrides such as sodium hydride and potassium hydride; alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkaline earth metal hydroxides such as calcium hydroxide; alkali metal carbonates such as sodium carbonate and potassium carbonate; alkali metal bicarbonates such as sodium bicarbonate; and metal alkoxides such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, and sodium tert-butoxide. The catalysts may be the same or different, such as potassium iodide, sodium iodide, potassium fluoride, sodium fluoride, potassium bromide, or sodium bromide.

[0129] Option 2:

[0130]

[0131] Step 1: Preparation of compound of general formula XII

[0132] Compound of general formula XI can be prepared by reacting 2-fluoro-3-nitrobenzoyl chloride with a suitable solvent in a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours, with the reaction carried out in the presence of a base or catalyst.

[0133] Step 2: Preparation of compound of general formula XIII

[0134] Compound of general formula XII is used to prepare compound of general formula XIII by reduction reaction.

[0135] As a reduction reaction, examples include methods using hydrogenation reactions and methods using metal compounds (such as stannous chloride) or metals (zinc powder, iron powder, etc.).

[0136] Hydrogenation can be carried out in a suitable solvent, in the presence of a catalyst, under normal or pressurized pressure, and in a hydrogen atmosphere. Catalysts used in hydrogenation include palladium-carbon catalysts, cobalt catalysts, rhodium catalysts, platinum catalysts, etc. Solvents can be alcohols such as methanol and ethanol; aromatic hydrocarbons such as benzene and toluene; chain or cyclic ethers such as acetaldehyde and tetrahydrofuran; and esters such as ethyl acetate.

[0137] Preferably, the pressure of the hydrogenation reaction is 0.1-10 MPa, for example 0.1 MPa, 0.5 MPa, 0.8 MPa, 1 MPa, 1.5 MPa, 2 MPa, 3 MPa, 4 MPa, 5 MPa, 6 MPa, 7 MPa, 8 MPa, 9 MPa or 10 MPa.

[0138] Preferably, the hydrogenation reaction is carried out at a temperature greater than or equal to -20°C and less than or equal to the boiling point of the reaction solvent, such as -20°C, -10°C, -5°C, 0°C, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 60°C, 70°C, 75°C, 80°C, etc., or at the boiling point of the solvent, i.e., under reflux conditions.

[0139] Preferably, the hydrogenation reaction time is 0.5-48 hours, for example 0.5 hours, 1 hour, 3 hours, 5 hours, 8 hours, 10 hours, 12 hours, 15 hours, 18 hours, 20 hours, 23 hours, 25 hours, 28 hours, 30 hours, 33 hours, 35 hours, 38 hours, 40 hours, 44 hours or 48 hours.

[0140] Preferably, the method using a metal compound or metal is carried out in any one or a mixture of at least two of methanol, ethanol, or ethyl acetate.

[0141] Preferably, the metal compound is stannous chloride, and the metal is any one or a combination of at least two of zinc powder or iron powder.

[0142] Preferably, the reaction temperature using the metal compound or metal method is greater than or equal to -10°C and less than or equal to the boiling point of the reaction solvent, such as -10°C, -5°C, 0°C, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 60°C, 70°C, 75°C, 80°C, etc., or the reaction is carried out at the boiling point of the solvent, i.e., under reflux conditions.

[0143] Preferably, the reaction time of the method using a metal compound or metal is 0.5-48 hours, for example 0.5 hours, 1 hour, 3 hours, 5 hours, 8 hours, 10 hours, 12 hours, 15 hours, 18 hours, 20 hours, 23 hours, 25 hours, 28 hours, 30 hours, 33 hours, 35 hours, 38 hours, 40 hours, 44 hours or 48 hours.

[0144] Step 3: Preparation of compound of general formula V

[0145] Compound of general formula V can be prepared by reacting compound of general formula XIII with compound of general formula R2-LG in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours. The reaction is carried out in the presence of a base or catalyst.

[0146] Step 4: Preparation of compound of general formula I

[0147] Compound of general formula I can be prepared by reacting compound of general formula V and compound of general formula IX in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours. The reaction is carried out in the presence of a base or catalyst.

[0148] In steps 1, 3, and 4, suitable solvents may be the same or different, including aromatic hydrocarbons such as benzene, toluene, and xylene; ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone; halogenated hydrocarbons such as chloroform and dichloromethane; esters such as methyl acetate and ethyl acetate; ethers such as tetrahydrofuran, dioxane, diethyl ether, and 1,2-dimethoxyethane; polar solvents such as water, acetonitrile, N,N-dimethylformamide, N-methylpyrrolidone, and dimethyl sulfoxide; or mixtures of the above solvents. The base may be the same or different, including trimethylamine, triethylamine, pyridine, and D... Organic bases such as BU, 4-dimethylaminopyridine, N,N-diisopropylmethylamine, and N,N-diisopropylethylamine; alkali metal hydrides such as sodium hydride and potassium hydride; alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkaline earth metal hydroxides such as calcium hydroxide; alkali metal carbonates such as sodium carbonate and potassium carbonate; alkali metal bicarbonates such as sodium bicarbonate; and metal alkoxides such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, and sodium tert-butoxide. The catalysts may be the same or different, such as potassium iodide, sodium iodide, potassium fluoride, sodium fluoride, potassium bromide, or sodium bromide.

[0149] Option 3:

[0150]

[0151] Step 1: Preparation of compounds of general formula VI

[0152] Compound of general formula X and compound of general formula XIV can be reacted in a suitable solvent at temperatures ranging from -10°C to the solvent's boiling point for 0.5–48 hours to yield compound of general formula VI. The reaction can be facilitated by adding an appropriate amount of base or catalyst. Suitable solvents include aromatic hydrocarbons such as benzene, toluene, and xylene; ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone; halogenated hydrocarbons such as chloroform and dichloromethane; esters such as methyl acetate and ethyl acetate; ethers such as tetrahydrofuran, dioxane, diethyl ether, and 1,2-dimethoxyethane; polar solvents such as water, acetonitrile, N,N-dimethylformamide, N-methylpyrrolidone, and dimethyl sulfoxide; or mixtures of the above solvents. The base can be the same or different, such as trimethylamine, triethylamine, pyridine, DBU, or 4-dimethylamino. Organic bases such as pyridine, N,N-diisopropylmethylamine, and N,N-diisopropylethylamine; alkali metal hydrides such as sodium hydride and potassium hydride; alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkaline earth metal hydroxides such as calcium hydroxide; alkali metal carbonates such as sodium carbonate and potassium carbonate; alkali metal bicarbonates such as sodium bicarbonate; and metal alkoxides such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, and sodium tert-butoxide. The catalysts may be the same or different, including potassium iodide, sodium iodide, potassium fluoride, sodium fluoride, potassium bromide, or sodium bromide.

[0153] Step 2: Preparation of compound of general formula I

[0154] Compounds of general formula VI can be reacted with suitable halogenating agents in suitable solvents to prepare compounds of general formula I.

[0155] The reaction usually requires the participation of a suitable base, which can be selected from trimethylamine, triethylamine, pyridine, DBU, 4-dimethylaminopyridine, N,N-diisopropylmethylamine, N,N-diisopropylethylamine, sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, or sodium tert-butoxide; preferably sodium hydride, potassium hydride, sodium hydroxide, or potassium hydroxide.

[0156] Suitable halogenated reagents are selected from chlorine, liquid bromine, iodine, NBS, NCS, NIS, mixtures of hydrogen peroxide and hydrobromic acid, mixtures of hydrogen peroxide and hydroiodic acid, mixtures of sodium hypochlorite and hydrobromic acid, mixtures of sodium hypochlorite and hydroiodic acid, mixtures of sodium chlorate and hydrobromic acid, or mixtures of sodium chlorate and hydroiodic acid.

[0157] Suitable solvents are selected from benzene, toluene, xylene, acetone, methyl ethyl ketone, methyl isobutyl ketone, chloroform, dichloromethane, methyl acetate, ethyl acetate, tetrahydrofuran, dioxane, diethyl ether, 1,2-dimethoxyethane, water, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, or mixtures of the above solvents.

[0158] The reaction temperature is from -10°C to the boiling point of the selected solvent; preferably, the reaction temperature is 0°C-100°C, more preferably 25°C-80°C.

[0159] The reaction time is 0.5-48 hours, preferably 1-10 hours.

[0160] Option 4:

[0161]

[0162] Step 1: Preparation of compounds of general formula XV

[0163] Compound of general formula XIV can be prepared by reacting 2-fluoro-3-nitrobenzoyl chloride with a suitable solvent in a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours. The reaction is carried out in the presence of a base or catalyst.

[0164] Step 2: Preparation of compounds of general formula XVI

[0165] Compounds of general formula XV can be prepared into compounds of general formula XVI through reduction reactions.

[0166] As a reduction reaction, examples include methods using hydrogenation reactions and methods using metal compounds (such as stannous chloride) or metals (zinc powder, iron powder, etc.).

[0167] Hydrogenation can be carried out in a suitable solvent, in the presence of a catalyst, under normal or pressurized pressure, and in a hydrogen atmosphere. Catalysts used in hydrogenation include palladium-carbon catalysts, cobalt catalysts, rhodium catalysts, platinum catalysts, etc. Solvents can be alcohols such as methanol and ethanol; aromatic hydrocarbons such as benzene and toluene; chain or cyclic ethers such as acetaldehyde and tetrahydrofuran; and esters such as ethyl acetate.

[0168] Preferably, the pressure of the hydrogenation reaction is 0.1-10 MPa, for example 0.1 MPa, 0.5 MPa, 0.8 MPa, 1 MPa, 1.5 MPa, 2 MPa, 3 MPa, 4 MPa, 5 MPa, 6 MPa, 7 MPa, 8 MPa, 9 MPa or 10 MPa.

[0169] Preferably, the hydrogenation reaction is carried out at a temperature greater than or equal to -20°C and less than or equal to the boiling point of the reaction solvent, such as -20°C, -10°C, -5°C, 0°C, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 60°C, 70°C, 75°C, 80°C, etc., or at the boiling point of the solvent, i.e., under reflux conditions.

[0170] Preferably, the hydrogenation reaction time is 0.5-48 hours, for example 0.5 hours, 1 hour, 3 hours, 5 hours, 8 hours, 10 hours, 12 hours, 15 hours, 18 hours, 20 hours, 23 hours, 25 hours, 28 hours, 30 hours, 33 hours, 35 hours, 38 hours, 40 hours, 44 hours or 48 hours.

[0171] Preferably, the method using a metal compound or metal is carried out in any one or a mixture of at least two of methanol, ethanol, or ethyl acetate.

[0172] Preferably, the metal compound is stannous chloride, and the metal is any one or a combination of at least two of zinc powder or iron powder.

[0173] Preferably, the reaction temperature using the metal compound or metal method is greater than or equal to -10°C and less than or equal to the boiling point of the reaction solvent, such as -10°C, -5°C, 0°C, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 60°C, 70°C, 75°C, 80°C, etc., or the reaction is carried out at the boiling point of the solvent, i.e., under reflux conditions.

[0174] Preferably, the reaction time of the method using a metal compound or metal is 0.5-48 hours, for example 0.5 hours, 1 hour, 3 hours, 5 hours, 8 hours, 10 hours, 12 hours, 15 hours, 18 hours, 20 hours, 23 hours, 25 hours, 28 hours, 30 hours, 33 hours, 35 hours, 38 hours, 40 hours, 44 hours or 48 hours.

[0175] Step 3: Preparation of compounds of general formula VII

[0176] Compound of general formula VII can be prepared by reacting compound of general formula XVI with compound of general formula R2-LG in a suitable solvent at a temperature from -10°C to the boiling point of the solvent for 0.5-48 hours. The reaction is carried out in the presence of a base or catalyst.

[0177] Step 4: Preparation of compound of general formula VI

[0178] Compound of general formula VII can be prepared by reacting compounds of general formula IX in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours, with the reaction carried out in the presence of a base or catalyst.

[0179] Step 5: Preparation of compound of general formula I

[0180] Same as step 2 of scheme 3.

[0181] In steps 1, 3, and 4, suitable solvents may be the same or different, including aromatic hydrocarbons such as benzene, toluene, and xylene; ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone; halogenated hydrocarbons such as chloroform and dichloromethane; esters such as methyl acetate and ethyl acetate; ethers such as tetrahydrofuran, dioxane, diethyl ether, and 1,2-dimethoxyethane; polar solvents such as water, acetonitrile, N,N-dimethylformamide, N-methylpyrrolidone, and dimethyl sulfoxide; or mixtures of the above solvents. The base may be the same or different, including trimethylamine, triethylamine, pyridine, and D... Organic bases such as BU, 4-dimethylaminopyridine, N,N-diisopropylmethylamine, and N,N-diisopropylethylamine; alkali metal hydrides such as sodium hydride and potassium hydride; alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkaline earth metal hydroxides such as calcium hydroxide; alkali metal carbonates such as sodium carbonate and potassium carbonate; alkali metal bicarbonates such as sodium bicarbonate; and metal alkoxides such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, and sodium tert-butoxide. The catalysts may be the same or different, such as potassium iodide, sodium iodide, potassium fluoride, sodium fluoride, potassium bromide, or sodium bromide.

[0182] Option 5:

[0183]

[0184] Step 1: Preparation of compounds of general formula XVII

[0185] Compound of general formula XVII can be prepared by reacting compounds of general formula VIII and general formula IX in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours. The reaction is carried out in the presence of a base or catalyst.

[0186] Step 2: Preparation of Compounds of General Formula III

[0187] Compound of general formula XVII can be reacted with compound of general formula R2-LG in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours to produce compound of general formula III. The reaction is carried out in the presence of a base or catalyst.

[0188] Step 3: Preparation of Compounds of General Formula II

[0189] Same as step 3 of Option 1.

[0190] Step 4: Preparation of compound of general formula X

[0191] Same as step 4 of Option 1.

[0192] Step 5: Preparation of compound of general formula I

[0193] Same as step 5 of Option 1.

[0194] In steps 1 and 2, suitable solvents may be the same or different, including aromatic hydrocarbons such as benzene, toluene, and xylene; ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone; halogenated hydrocarbons such as chloroform and dichloromethane; esters such as methyl acetate and ethyl acetate; ethers such as tetrahydrofuran, dioxane, diethyl ether, and 1,2-dimethoxyethane; polar solvents such as water, acetonitrile, N,N-dimethylformamide, N-methylpyrrolidone, and dimethyl sulfoxide; or mixtures of the above solvents. The base may be the same or different, including trimethylamine, triethylamine, pyridine, and DBU. Organic bases such as 4-dimethylaminopyridine, N,N-diisopropylmethylamine, and N,N-diisopropylethylamine; alkali metal hydrides such as sodium hydride and potassium hydride; alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkaline earth metal hydroxides such as calcium hydroxide; alkali metal carbonates such as sodium carbonate and potassium carbonate; alkali metal bicarbonates such as sodium bicarbonate; and metal alkoxides such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, and sodium tert-butoxide. The catalysts may be the same or different, including potassium iodide, sodium iodide, potassium fluoride, sodium fluoride, potassium bromide, or sodium bromide.

[0195] Compounds of general formula XI and general formula XIV can be prepared by known methods, for example, referring to WO20110201687, WO2011093415, WO2005021488, WO2005073165, WO2006137395, JP2007099761, WO2008000438, WO2008074427, WO2008107091, WO2010013567, WO2010018714, WO2010090282, WO2010127926, WO2010127928, JP Compounds of general formula VIII, general formula IX and general formula R2-LG are prepared by the methods reported in WO2011063549, WO2012020483, WO2012020484, WO2012077221, WO2012164698, WO2013050261, WO2014069665, WO2014067838, WO2014161848, WO2014161850, WO2015097091 or WO2015097094; they are generally commercially available and can also be prepared by conventional methods.

[0196] The embodiments of the present invention also provide the use of the above-mentioned amide compounds in the preparation of insecticides.

[0197] In one possible implementation, the insecticide is used to control one or more of the following insects:

[0198] Beetles (Coleopteran insects), such as the bean weevil (Callosobruchus Chinensis), the corn weevil (Sitophilus zeamais), the red flour beetle (Tribolium Castaneum), the potato ladybug (Epilachnavigintioctomaculata), the slender-throated click beetle (Agriotes ogurae fuscicollis), the multicolored scarab beetle (Anomala rufocuprea), the potato leaf beetle (Leptinotarsa ​​decemlineata), the leaf beetle genus (Diabroticaspp.), the pine longhorn beetle (Monochamus alternatus endai), the rice root weevil (Lissorhoptrusoryzophilus), and the brown powder beetle (Lyctus bruneus);

[0199] Lepidopteran pests, such as the gypsy moth (Lymantria dispar), the brown tent caterpillar (Malacosoma neustria), the Japanese subspecies of the cabbage white butterfly (Pieris rapae crucivora), the beet armyworm (Spodoptera litura), the cabbage cutworm (Mamestra brassicae), the rice stem borer (Chilo suppressalis), the European corn borer (Ostrinia nubilalis), the dry fruit leaf roller (Cadra cautella), the chyanokokakumonhamaki (Adoxophyes honmai), the apple leafroller (Cydiapomonella), the yellow cutworm (Agrotis segetum), the large wax moth (Galleria mellonella), the diamondback moth (Plutellaxylostella), the tobacco bud cutworm (Heliothisvirescens), and the citrus leafminer (Phyllocnistis citrella);

[0200] Hemipterous pests, such as the black-tailed leafhopper (Nephotettix cincticeps), brown planthopper (Nilaparvata lugens), Comstock mealybug (Pseudococcus comstocki), arrowhead scale (Unaspisyanonensis), peach aphid (Myzus persicas), apple aphid (Aphis pomi), cotton aphid (Aphis gossypii), turnip aphid (Lipaphis erysimi), pear lace bug (Stephanitis nashi), green ailanthus (Nezara spp.), greenhouse whitefly (Trialeurodes vaporariorum), and Pshylla spp.;

[0201] Thysanoptera pests, such as palm thrips and western flower thrips (Franklinella occidentalis);

[0202] Orthoptera pests, such as the African mole cricket (Gryllotalpa Africana) and the African migratory locust (Locusta migratoria);

[0203] Blattarian pests, such as the German cockroach (Blattella germanica), the American cockroach (Periplaneta americana), the yellow-breasted subterranean termite (Reticulitermes speratus), and the domestic termite (Coptotermes formosanus);

[0204] Dipterous pests, such as houseflies (Musca domestica), Aedes aegypti, Delia platura, Culex pipiens pallens, Anopheles sinensis, Culex tritaeniorhynchus, and Liriomyza trifolii.

[0205] Agricultural pests include the carmine spider mite (Tetranychus cinnabarinus), the cotton spider mite (Tetrahychus urticae), the citrus pteris (Panonychus citri), the citrus gall mite (Aculops pelekassi), and the tarsiforme mite (Tarsonemus spp.).

[0206] In one possible implementation, the insecticide is used to control one or more of the following: diamondback moth, armyworm, beet armyworm, cotton bollworm, rice stem borer, peach aphid, thrips, and flea beetle.

[0207] This invention also provides an insecticide formulation containing the aforementioned amide compounds as active ingredients, and one or more excipients.

[0208] In one possible implementation, the insecticide formulation is selected from the following dosage forms: solutions, emulsions, wettable powders, granular wettable powders, suspensions, powders, foams, pastes, tablets, granules, aerosols, natural reagents impregnated with active compounds, synthetic reagents impregnated with active compounds, microcapsules, seed coating agents, formulations equipped with combustion devices (such as chimneys and fogging cans, canisters and coils, etc.), and ULVs (cold fog agents, hot fog agents), etc. These insecticide formulations or animal parasite control agents can be prepared by known methods, for example, by mixing the active ingredient with fillers (such as liquid diluents or carriers, liquefied gas diluents or carriers, solid diluents or carriers), and optionally with surfactants (i.e., emulsifiers and / or dispersants and / or foaming agents).

[0209] In one possible implementation, the excipients include one or more of the following: fillers (e.g., liquid diluents or carriers, liquefied gas diluents or carriers, solid diluents or carriers), surfactants (e.g., emulsifiers and / or dispersants and / or foaming agents), binders, and colorants.

[0210] Liquid diluents or carriers may include, for example, aromatic hydrocarbons (xylene, toluene, alkylnaphthalene, etc.), chlorinated aromatic hydrocarbons or chlorinated aliphatic hydrocarbons (e.g., chlorobenzene, vinyl chloride, dichloromethane, etc.), aliphatic hydrocarbons (e.g., cyclohexane or paraffin (e.g., mineral oil fractions)), alcohols (e.g., butanol, ethylene glycol, and their ethers or esters, etc.), ketones (e.g., acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, etc.), highly polar solvents (e.g., dimethylformamide, dimethyl sulfoxide), water, etc. When water is used as a filler, for example, an organic solvent may be used as a co-solvent;

[0211] Liquefied gas diluents or carriers may include those that exist in gaseous form at atmospheric pressure and temperature, such as propane, nitrogen, carbon dioxide, and aerosol propellants such as halogenated hydrocarbons;

[0212] Solid diluents may include pulverized natural minerals (such as kaolin, clay, talc, chalk, quartz, palygorskite, montmorillonite, or diatomaceous earth) and pulverized synthetic minerals (such as finely dispersed silica, alumina, and silicates).

[0213] Emulsifiers and / or foaming agents may include nonionic and anionic emulsifiers [e.g., polyoxyethylene fatty acid esters, polyoxyethylene fatty acid alcohol ethers (such as alkyl aryl polyethylene glycol ethers), alkyl sulfonates, alkyl sulfates and aryl sulfonates] and albumin hydrolysates, etc.

[0214] Dispersants may include lignin sulfite waste liquid and methylcellulose;

[0215] Adhesives may include carboxymethyl cellulose, natural or synthetic polymers (such as gum arabic, polyvinyl alcohol, and polyvinyl acetate);

[0216] Colorants may include inorganic pigments (such as iron oxide, titanium oxide, and Prussian blue), organic dyes such as alizarin dyes, azo dyes, or metal phthalocyanine dyes; and trace elements such as iron salts, manganese salts, boron salts, copper salts, cobalt salts, molybdenum salts, or zinc salts.

[0217] Furthermore, the amide compounds of the present invention can exist as a mixture with a synergist, which itself need not be active. More precisely, it is a compound that enhances the activity of the active compound.

[0218] In one possible implementation, the amount of the aforementioned amide compound contained in the insecticide formulation is from 0.1 to 99% by weight, optionally from 0.5 to 90% by weight.

[0219] This invention also provides an insecticide composition comprising the above-mentioned amide compounds and other active compounds (e.g., insecticides, baits, disinfectants, acaricides, nematicides, fungicides, growth regulators, herbicides, etc.). This mixture may be provided as an active pharmaceutical ingredient, as a commercially available useful formulation, or as an application form prepared from such formulations.

[0220] This invention also provides a method for controlling agricultural or forestry pests, comprising the following steps: applying an effective dose of material to the pest to be controlled or its growth medium, wherein the material is selected from one or more of the following groups: the above-mentioned amide compounds, the above-mentioned insecticide formulations, and the above-mentioned insecticide compositions.

[0221] The embodiments of the present invention also provide the use of the above-mentioned amide compounds in the preparation of animal parasite control agents. In the veterinary field, that is, in veterinary science, the amide compounds of the present invention can be effectively used to combat a variety of harmful animal parasites, especially internal and external parasites.

[0222] In one possible implementation, animal parasites include one or more of the following:

[0223] The order Anoplurida includes genera such as Haematopinus spp., Linognathus spp., Pediculus spp., Phtirus spp., and Solenopotes spp.; in particular, representative examples include the spiny-jawed louse Linognathus setosus and the cow tube louse Solenopotes capillatus.

[0224] The order Mallophagus (including the cattle gnater (Linognathus vituli), sheep gnater (Linognathus ovillus), Linognathus oviformis, foot gnater (Linognathus pedalis), goat gnater (Linognathus stenopsis), donkey blood louse (Haematopinus asini macrocephalus), cattle blood louse (Haematopinus eurysternus), pig blood louse (Haematopinus suis), head lice (Pediculus humanuscapitis), body lice (Pediculus humanus corporis), grape phylloxera (Phylloera vastatrix), pubic lice (Phthirus pubis) gida) and the suborders Amblycerina and Ischnocerin, such as the genera *Trimenopon* spp., *Menopon* spp., and *Trinoton*. The genera *Bovicola* (spp.), *Bovicola* (spp.), *Werneckiella* (spp.), *Lepikentron* (spp.), *Damalina* (spp.), *Trichodectes* (spp.), and *Felicola* (spp.) are included. Representative examples include, in particular, *Bovicola bovis*, *Bovicola ovis*, *Bovicola limbata*, *Damalina bovis*, *Trichodectes canis*, *Felicola subrostratus*, *Bovicola caprae*, *Lepikentron ovis*, and *Werneckiella equi*.

[0225] Diptera and its suborders Nematocerina and Brachycerina, including genera such as Aedes spp., Anopheles spp., Culex spp., Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyia spp., Culicoides spp., Chrysops spp., Odagmia spp., Wilhelmia spp., Hybomitra spp., and Atylotus. spp.), Tabanus spp., Haematopota spp., Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Lucilia spp., Chrysomyia spp., Wohlfahrtia spp., Sarcophaga spp., Oestrus spp., Hypoderma The genera *Gasterophilus* spp., *Hippobosca* spp., *Lipoptena* spp., *Melophagus* spp., *Rhinoestrus* spp., and *Tipula* spp. are included. Notably, representative examples include *Aedes aegypti*, *Aedes albopictus*, *Aedes taeniorhynchus*, *Anopheles gambiae*, *Anopheles maculipennis*, *Calliphora erythrocephala*, *Chrysozona pluvialis*, and *Culex pipiens pallens*.The following mosquitoes are listed: *Culex quinquefasciatus*, *Culexpipiens*, *Culex tarsalis*, *Fannia canicularis*, *Sarcophagacarnaria*, *Stomoxys calcitrans*, *Tipulapaludosa*, *Luciliacuprina*, *Lucilia sericata*, *Simulium reptans*, *Phlebotomus papatasi*, *Phlebotomus longipalpis*, *Odagmiaornata*, *Wilhelmia equina*, *Boophthora erythrocephala*, *Tabanus bromius*, *Tabanus spodopterus*, and *Tabanus spodopterus*. atratus), pig fly (Tabanus sudeticus), horsefly (Hybomitra ciurea), blind horsefly (Chrysops caecutiens), yellow-margined horsefly (Chrysops relictus), high-horned horsefly (Haematopota pluvialis), Haematopotaitalica, autumn housefly (Musca autumnalis), housefly (Musca domestica), western hornfly (Haematobia irritans irritans), western hornfly (Haematobia irritans exigua), stabbing blood fly (Haematobia stimulans), Hydrotaea irritans, white-spotted toothed fly (Hydrotaea albipuncta), Chrysomyachloropyga, maggot-infested golden fly (Chrysomyabezziana), sheep mad fly (Oestrus ovis), cow wart fly (Hypoderma bovis), striped wart fly (Hypoderma lineatum), Przhevalskiana silenus, human skin fly (Dermatobia hominis), sheep tick fly (Melophagus ovinus), Lipoptena capreoli, deer and sheep tick fly (Lipoptena cervi), Hippobosca variegata, horse tick fly (Hippoboscaequina), gastropod fly (Gasterophilus intestinalis), red-tailed gastropod fly (Gasterophilus haemorroidalis), naked-segmented gastropod fly (Gasterophilus interrnis), nasal gastropod fly (Gasterophilus nasalis), black-horned gastropod fly (Gasterophilus nigricornis), black-bellied gastropod fly (Gasterophilus pecorum), bee fly (Braulacoeca);

[0226] Siphonapterida, including genera such as *Pulex* spp., *Ctenocephalides* spp., *Tunga* spp., *Xenopsylla* spp., and *Ceratophyllus* spp.; particularly representative examples include *Ctenocephalides canis*, *Ctenocephalides felis*, *Pulex irritans*, *Tunga penetrans*, and *Xenopsylla cheopis*.

[0227] Heteropterida, for example, genera such as Cimex spp., Triatomas spp., Rhodnius spp., and Panstrongylus spp.;

[0228] Blattodea, including species such as the Oriental cockroach (Blatta orientalis), the American cockroach, the German cockroach, and the genus Supella (e.g., Suppella longipalpa);

[0229] Acari (or Acarina), Metastigmata, and Mesostigmata, including genera such as *Argas* spp., *Ornithodorus* spp., *Otobius* spp., *Ixodes* spp., *Amblyomma* spp., *Rhipicephalus (Boophilus)* spp., *Dermacentor* spp., *Haemophysalis* spp., *Hyalomma* spp., *Dermanyssus* spp., *Rhipicephalus* spp. (the original genus of heteroparasitic mites), and *Ornithonyssus*. The genera *Pneumonyssus*, *Pneumonyssus*, *Raillietia*, *Sternostoma*, *Varroa*, and *Acarapis* are mentioned. Notably, representative examples include *Argas persicus*, *Argas reflexus*, *Ornithodorus moubata*, and *Otobius*. The following ticks are listed: megnini, Rhipicephalus (Boophilus) microplus, Rhipicephalus (Boophilus) decoloratus, Rhipicephalus (Boophilus) annulatus, Rhipicephalus (Boophilus) calceratus, Hyalomma anatolicum, Hyalomma aegypticum, Hyalomma marginatum, Hyalomma transiens, Rhipicephalusevertsi, Ixodes ricinus, Ixodes hexagonus, Ixodes canisuga, Ixodes pilosus, and Ixodes canisuga.The following ticks are listed: *Ixodes rubicundus*, *Ixodes scapularis*, *Ixodesholocyclus*, *Haemaphysalis concinna*, *Haemaphysalis punctata*, *Haemaphysalis cinnabarina*, *Haemaphysalis otophila*, *Haemaphysalis leachi*, *Haemaphysalis longicorni*, *Dermacentor marginatus*, *Dermacentor reticulatus*, *Dermacentor pictus*, *Dermacentor albipictus*, *Dermacentor andersoni*, *Dermacentor variabilis*, *Hyalomma mauritanicum*, *Rhipicephalus sanguineus*, and *Rhipicephalus sac-like*. The following ticks are listed: *Rhipicephalus appendiculatus*, *Rhipicephalus capensis*, *Rhipicephalus turanicus*, *Rhipicephalus zambeziensis*, *Amblyomma americanum*, *Amblyomma variegatum*, *Amblyomma maculatum*, *Amblyomma hebraeum*, *Amblyomma cajennense*, *Dermanyssus gallinae*, *Ornithonyssus bursa*, *Ornithonyssus sylviarum*, and *Varroajacobsconi*.

[0230] The order Actinedida (prostigmata) and Acaridida (Astigmata) includes species such as *Acarapis* spp., *Cheyletiella* spp., *Ornithocheyletia* spp., *Myobia* spp., *Psorergates* spp., *Demodex* spp., *Trombicula* spp., *Listrophorus* spp., *Acarus* spp., *Tyrophagus* spp., *Caloglyphus* spp., *Hypodectes* spp., *Pterolichus* spp., and *Psoroptes*. *Demodex* spp., *Chorioptes* spp., *Otodectes* spp., *Sarcoptes* spp., *Notoedres* spp., *Knemidocoptes* spp., *Cytodites* spp., and *Laminosioptes* spp.; particularly, *Cheyletiella yasguri*, *Cheyletiella blakei*, *Demodex canis*, *Demodex bovis*, *Demodex ovis*, *Demodex caprae*, *Demodex equi*, *Demodex cabalii*, *Demodex suis*, *Neotrombicula autumnalis*, *Neotrombicula desaleli*, and *Neoschonegastia*. xerothermobia, autumn harvest chigger (Trombiculaakamushi), dog ear mite (Otodectes cynotis), cat scabies mite (Notoedres cati), dog scabies mite (Sarcoptiscanis), cattle scabies mite (Sarcoptes bovis), sheep scabies mite (Sarcoptes ovis), goat scabies mite (Sarcoptesrupicaprae (=S)).The following are mites: caprae, Sarcoptes equi, Sarcoptes suis, Psoroptes ovis, Psoroptes cuniculi, Psoroptes equi, Chorioptes bovis, Psoergates ovis, Pneumonyssoidic mange, Pneumonyssoides caninum, and Acarapis woodi.

[0231] Nematodes, such as southern root-knot nematode (Meloidogyne incognita), pine wood nematode (Bursaphelenchus xylophilus), rice dry tip nematode (Aphelenchoides besseyi), soybean heteroderma nematode (Heteroderaglycines), and short-bodied nematodes (Pratylenchus spp.).

[0232] Arthropods, worms, and malaria parasites that infest animals. Controlling arthropods, worms, and / or malaria parasites can reduce mortality in domestic animals and improve animal productivity (meat, milk, wool, fur, eggs, and honey) and health.

[0233] In one possible implementation, the animal parasite control agent is used to control one or more of cat fleas and American ticks.

[0234] In one possible implementation, the animals include one or more of the following: agricultural animals, such as cattle, sheep, goats, horses, pigs, donkeys, camels, buffalo, rabbits, chickens, turkeys, ducks, geese, farmed fish, bees, etc.; pets known as companion animals, such as dogs, cats, caged birds, ornamental fish; and animals used for experiments, such as hamsters, guinea pigs, rats, and mice.

[0235] This invention also provides an animal parasite control agent, which contains the above-mentioned amide compounds as active ingredients and one or more excipients.

[0236] In one possible implementation, the animal parasite control agent is selected from the following dosage forms: tablets, capsules, oral liquids, edible medicines, granules, ointments and pills, suppositories, injections (intramuscular, subcutaneous, intravenous, intraperitoneal, etc.), smears, aerosols, and pressureless sprays (e.g., pump sprays and nebulizer sprays).

[0237] In one possible implementation, the amount of the above-mentioned active ingredient contained in the animal parasite control agent is 1 to 80% by weight.

[0238] This invention also provides an animal parasite control composition comprising the aforementioned amide compounds and other animal parasite control active compounds (e.g., acaricides, insecticides, parasiteicides, antimalarial agents, etc.). This mixture may be provided as an active pharmaceutical ingredient, as a commercially available effective formulation, or as an application form prepared from such formulations.

[0239] This invention also provides a method for controlling animal parasites, comprising the following steps: applying an effective dose of material to the animal parasite to be controlled or its growth medium, wherein the material is selected from one or more of the following groups: the above-mentioned amide compounds; the above-mentioned animal parasite control agents; and the above-mentioned animal parasite control compositions. For example, administration can be made via enteral methods such as tablets, capsules, decoctions, edible medicines, granules, ointments, pills, and suppositories; non-enteric administration based on skin application, such as injection (intramuscular, subcutaneous, intravenous, intraperitoneal, etc.), implantation, nasal administration, including bathing or soaking, spraying, pouring, dripping, washing, and powdering; and application via the use of model articles containing the active compound, such as collars, ear tags, labels, leg braces, nets, and markers. The active compound of this invention has low toxicity and can be safely used in warm-blooded animals.

[0240] Beneficial effects

[0241] The amide compounds of this invention exhibit unexpectedly excellent insecticidal effects, demonstrating suitable control efficacy against toxic pests, and are non-phytotoxic to cultivated crops. Furthermore, the compounds of this invention can be used to control a variety of pests, such as harmful piercing-sucking insects, chewing insects, other plant parasitic pests, stored grain pests, and sanitary pests, and can also be used for disinfection and eradication. Detailed Implementation

[0242] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0243] Furthermore, to better illustrate the present invention, numerous specific details are provided in the following detailed embodiments. Those skilled in the art should understand that the present invention can be practiced without certain specific details. In some embodiments, materials, elements, methods, and means well known to those skilled in the art are not described in detail in order to highlight the spirit of the invention.

[0244] Unless otherwise expressly stated, throughout the specification and claims, the term "comprising" or its variations such as "including" or "comprises" shall be understood to include the stated elements or components without excluding other elements or other components.

[0245] Unless otherwise noted, all raw materials used are commercially available.

[0246] In this invention, the terms used have the following meanings:

[0247] Halogens: refer to fluorine, chlorine, bromine or iodine.

[0248] Halogenated alkyl groups: straight-chain or branched alkyl groups in which hydrogen atoms can be partially or completely replaced by halogens, such as difluoromethyl (CHF2), trifluoromethyl (CF3), etc.

[0249] Halogenated alkoxy groups: The hydrogen atoms on the alkoxy group can be partially or completely replaced by halogens, such as difluoromethoxy (OCHF2) and trifluoromethoxy (OCF3).

[0250] Allyl: -CH2-CH=CH2.

[0251] Prolyl: -CH2-C≡CH.

[0252] Insecticides: Substances that kill pests.

[0253] Animal parasite control agents: These are active compounds that can effectively reduce the incidence of various parasites in animals infected with parasites. Control means that the active compounds can effectively kill parasites or inhibit their growth or reproduction.

[0254] Synthesis Examples

[0255] Following the synthetic routes described above, compounds of general formulas I to VII of this invention can be prepared by using different starting materials, as further described in detail below:

[0256] Example 1: Preparation of intermediate compound II.7

[0257]

[0258] (1) Preparation of 2-fluoro-3-(N-(prop-2-yn-1-yl)benzoylamino)benzoate (III.7)

[0259] 0.50 g (2.96 mmol) of methyl 2-fluoro-3-aminobenzoate, 0.70 g (5.94 mmol) of bromopropyne, and 1.15 g (8.90 mmol) of N,N-diisopropylethylamine were added to 10 mL of toluene, and the mixture was refluxed. The reaction was monitored by TLC. After the reactants had reacted completely, 0.58 g (4.14 mmol) of benzoyl chloride was added. After the reaction was completed by TLC, water and ethyl acetate were added for extraction. The organic phase was dissolved under reduced pressure, and the residue was purified by column chromatography to give 0.72 g of white solid, namely methyl 2-fluoro-3-(N-(prop-2-yn-1-yl)benzoylamino)benzoate (III.7). The NMR and mass spectrometry data of intermediate III.7 are as follows:

[0260] 1 H NMR (600MHz, Chloroform-d) δ7.82(t,1H),7.42-7.13(m,6H),7.07(t,1H),5.05(s,1H),4.28(s,1H),3.91(s,3H),2.23(t,1H). LC-MS(m / z,ESI):312.10(M+H) + .

[0261] (2) Preparation of 2-fluoro-3-(N-(prop-2-yn-1-yl)benzoamide)benzoic acid (II.7)

[0262] 0.58 g (1.86 mmol) of methyl 2-fluoro-3-(N-(propan-2-yn-1-yl)benzoamide)benzoate, 1.62 g (18.65 mmol) of lithium bromide, 0.94 g (9.29 mmol) of triethylamine, and 0.17 g (9.44 mmol) of water were added to 10 mL of acetonitrile, and the mixture was heated to 50 °C. After the reaction was completed by TLC monitoring, the pH was adjusted to approximately 2-3 with dilute hydrochloric acid, and the mixture was extracted with water and ethyl acetate. The organic phase was dissolved under reduced pressure to obtain 0.52 g of a white solid, which is intermediate II.7. The NMR and mass spectrometry data of intermediate II.7 are as follows:

[0263] 1 HNMR (600MHz, DMSO-d6) δ7.79-7.64(m,2H),7.42-7.17(m,6H),4.61(s,2H),3.22(s,1H). LC-MS(m / z,ESI):296.11(MH) - .

[0264] Example 2: Preparation of intermediate compound V.3

[0265]

[0266] 1.00 g (1.84 mmol) of 3-amino-N-(2-bromo-4-(perfluoroprop-2-yl)-6-(trifluoromethyl)phenyl)-2-fluorobenzamide (prepared according to the method reported in WO2011093415 or WO2010018714) and 0.30 g (2.00 mmol) of sodium iodide were added to 10 mL of DMF. 0.22 g (1.83 mmol) of bromopropene was added dropwise with stirring, and the reaction was allowed to proceed at room temperature. After the reaction was complete as detected by TLC, water and ethyl acetate were added for extraction. The organic phase was dissolved under reduced pressure, and the residue was purified by column chromatography to give 0.34 g of a white solid, which is intermediate compound V.3. The NMR and mass spectrometry data of intermediate compound V.3 are as follows:

[0267] 1 H NMR(600MHz,Chloroform-d)δ8.26(d,1H),8.14(d,1H),7.91(d,1H),7.42-7.36(m,1H),7.14(t, 1H),6.95-6.87(m,1H),6.03-5.91(m,1H),5.34(dd,1H),5.24(dd,1H),4.26(s,1H),3.87(d,2H). LC-MS(m / z,ESI):585.08(M+H) + .

[0268] Example 3: Preparation of intermediate compound V.4

[0269]

[0270] 2.00 g (3.38 mmol) of 3-amino-2-fluoro-N-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)benzamide (prepared according to the method reported in WO2011093415 or WO2010018714) and 0.30 g (3.81 mmol) of sodium iodide were added to 20 mL of DMF. 0.41 g (3.42 mmol) of bromopropene was added dropwise with stirring, and the reaction was allowed to proceed at room temperature. After the reaction was complete as detected by TLC, water and ethyl acetate were added for extraction. The organic phase was dissolved under reduced pressure, and the residue was purified by column chromatography to give 0.60 g of a white solid, which is intermediate compound V.4. The NMR and mass spectrometry data of intermediate compound V.4 are as follows:

[0271] 1H NMR(600MHz,Chloroform-d)δ8.35(d,1H),8.30(d,1H),7.93(d,1H),7.40(td,1H),7.15(t, 1H),6.92(td,1H),6.02-5.92(m,1H),5.34(dd,1H),5.24(dd,1H),4.26(s,1H),3.88(d,2H). LC-MS(m / z,ESI):633.07(M+H) + .

[0272] Example 4: Preparation of intermediate compound V.9

[0273]

[0274] 1.00 g (1.84 mmol) of 3-amino-N-(2-bromo-4-(perfluoroprop-2-yl)-6-(trifluoromethyl)phenyl)-2-fluorobenzamide and 0.31 g (2.07 mmol) of sodium iodide were added to 10 mL of DMF. 0.22 g (1.87 mmol) of bromopropyne was added dropwise with stirring, and the mixture was heated to 40°C. After the reaction was complete as detected by TLC, water and ethyl acetate were added for extraction. The organic phase was dissolved under reduced pressure, and the residue was purified by column chromatography to give 0.26 g of a white solid, which is intermediate compound V.9. The NMR and mass spectrometry data of intermediate compound V.9 are as follows:

[0275] 1 H NMR(600MHz,Chloroform-d)δ8.24(d,1H),8.14(d,1H),7.91(d,1H),7.51-7.45( m,1H),7.21(t,1H),7.05(td,1H),4.41-4.34(m,1H),4.05(dd,2H),2.28(t,1H). LC-MS(m / z,ESI):583.06(M+H) + .

[0276] Example 5: Preparation of intermediate compound V.10

[0277]

[0278] 1.00 g (1.69 mmol) of 3-amino-2-fluoro-N-(2-iodo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)phenyl)benzamide and 0.30 g (2.00 mmol) of sodium iodide were added to 10 mL of DMF. 0.20 g (1.70 mmol) of bromopropyne was added dropwise with stirring, and the mixture was heated to 40 °C. After the reaction was complete as detected by TLC, water and ethyl acetate were added for extraction. The organic phase was dissolved under reduced pressure, and the residue was purified by column chromatography to give 0.31 g of a white solid, which is intermediate compound V.10. The NMR and mass spectrometry data of intermediate compound V.10 are as follows:

[0279] 1 H NMR(600MHz,Chloroform-d)δ8.35(d,1H),8.28(d,1H),7.96-7.92(m,1H),7.49( td,1H),7.22(t,1H),7.05(td,1H),4.38(s,1H),4.08-4.03(m,2H),2.28(t,1H). LC-MS(m / z,ESI):631.05(M+H) + .

[0280] Example 6: Preparation of Compound 7

[0281]

[0282] 0.15 g (0.26 mmol) of intermediate V.3, 0.04 g (0.27 mmol) of sodium iodide, and 0.04 g (0.25 mmol) of p-fluorobenzoyl chloride were added to 10 mL of toluene, and the mixture was heated to reflux. After the reaction was complete as detected by TLC, the solvent was removed under reduced pressure, and the residue was purified by column chromatography to give 0.13 g of a white solid, namely compound 7. The NMR and mass spectrometry data of compound 7 are as follows:

[0283] 1 H NMR(600MHz,Chloroform-d)δ8.12(d,1H),8.07-7.95(m,2H),7.89(d,1H),7.51-7.44(m,1H),7 .36(s,2H),7.32-7.25(m,1H),6.90(s,2H),6.06-5.92(m,1H),5.26-5.15(m,2H),4.50(d,2H). LC-MS(m / z,ESI):707.04(M+H) + .

[0284] Example 7: Preparation of Compound 8

[0285]

[0286] 0.15 g (0.24 mmol) of intermediate V.4, 0.04 g (0.27 mmol) of sodium iodide, and 0.04 g (0.25 mmol) of p-fluorobenzoyl chloride were added to 10 mL of toluene, and the mixture was heated to reflux. After the reaction was complete as detected by TLC, the solvent was removed under reduced pressure, and the residue was purified by column chromatography to give 0.11 g of a white solid, namely compound 8. The NMR and mass spectrometry data of compound 8 are as follows:

[0287] 1 H NMR(600MHz,Chloroform-d)δ8.33(d,1H),8.11-7.98(m,2H),7.94-7.89(m,1H),7.48(dt,1H) ),7.36(s,2H),7.29(t,1H),6.90(s,2H),6.07-5.90(m,1H),5.26-5.15(m,2H),4.52(d,2H). LC-MS(m / z,ESI):755.07(M+H) + .

[0288] Example 8: Preparation of Compound 19

[0289]

[0290] 0.15 g (0.26 mmol) of intermediate V.3, 0.06 g (0.40 mmol) of sodium iodide, and 0.06 g (0.38 mmol) of 6-fluoronicotinic acid chloride were added to 10 mL of toluene, and the mixture was heated to reflux. After the reaction was complete as detected by TLC, the solvent was removed under reduced pressure, and the residue was purified by column chromatography to give 0.14 g of a yellow oil, namely compound 19. The NMR and mass spectrometry data of compound 19 are as follows:

[0291] 1 H NMR(600MHz,Chloroform-d)δ8.18(s,1H),8.13(d,1H),8.08-8.02(m,1H),8.01-7.79(m,3H),7 .54-7.48(m,1H),7.34(t,1H),6.83(s,1H),6.05-5.91(m,1H),5.27-5.18(m,2H),4.53(d,2H). LC-MS(m / z,ESI):708.05(M+H) + .

[0292] Example 9: Preparation of Compound 20

[0293]

[0294] 0.15 g (0.24 mmol) of intermediate V.4, 0.05 g (0.33 mmol) of sodium iodide, and 0.05 g (0.31 mmol) of 6-fluoronicotinic acid chloride were added to 10 mL of toluene, and the mixture was heated to reflux. After the reaction was complete as detected by TLC, the solvent was removed under reduced pressure, and the residue was purified by column chromatography to give 0.09 g of a white solid, namely compound 20. The NMR and mass spectrometry data of compound 20 are as follows:

[0295] 1 H NMR(600MHz,Chloroform-d)δ8.35-8.31(m,1H),8.19(s,1H),8.09-8.03(m,1H),8.02-7.79(m, 3H),7.52(dt,1H),7.35(t,1H),6.83(s,1H),6.05-5.93(m,1H),5.28-5.19(m,2H),4.53(d,2H). LC-MS(m / z,ESI):756.05(M+H) + .

[0296] Example 10: Preparation of Compound 31

[0297] Method 1:

[0298]

[0299] 0.15 g (0.26 mmol) of intermediate V.9, 0.04 g (0.27 mmol) of sodium iodide, and 0.04 g (0.29 mmol) of benzoyl chloride were added to 10 mL of toluene, and the mixture was heated to reflux. After the reaction was complete as detected by TLC, the solvent was removed under reduced pressure, and the residue was purified by column chromatography to give 0.09 g of a yellow oil, namely compound 31. The NMR and mass spectrometry data of compound 31 are as follows:

[0300] 1 H NMR(600MHz,Chloroform-d)δ8.13(d,1H),8.09-7.95(m,2H),7.92-7.88(m,1H) ,7.63-7.53(br,1H),7.43-7.14(m,6H),4.93(s,1H),4.51(s,1H),2.30(t,1H). LC-MS(m / z,ESI):687.07(M+H) + .

[0301] Method 2:

[0302]

[0303] Add 0.22 g (0.68 mmol) of intermediate II.7 and 0.44 g (3.70 mmol) of thionyl chloride to 10 mL of toluene, heat under reflux for 4 hours, and desolvent under reduced pressure to obtain intermediate 2-fluoro-3-(N-(prop-2-yn-1-yl)benzoamide)benzoyl chloride for later use.

[0304] The intermediate 2-fluoro-3-(N-(prop-2-yn-1-yl)benzoamide)benzoyl chloride, prepared above, 0.08 g (0.78 mmol) sodium bromide, and 0.30 g (0.74 mmol) 2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline (prepared according to the methods reported in WO2011093415 or WO2010018714) were added to 10 mL of acetonitrile and heated to reflux. After the reaction was completed as detected by TLC, the solvent was removed under reduced pressure, and the residue was purified by column chromatography to give 0.23 g of a white solid, namely compound 31. The NMR and mass spectrometry data of compound 31 are as follows:

[0305] 1 H NMR(600MHz,Chloroform-d)δ8.13(d,1H),8.09-7.95(m,2H),7.92-7.88(m,1H) ,7.63-7.53(br,1H),7.43-7.14(m,6H),4.93(s,1H),4.51(s,1H),2.30(t,1H). LC-MS(m / z,ESI):687.07(M+H) + .

[0306] Method 3:

[0307]

[0308] (1) Preparation of intermediate compound VI.7

[0309] 0.29 g (0.68 mmol) of intermediate 2-fluoro-3-(N-(prop-2-yn-1-yl)benzoamido)benzoyl chloride, 0.09 g (0.87 mmol) of sodium bromide, and 0.30 g (0.91 mmol) of 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline (prepared according to the methods reported in WO2011093415 or WO2010018714) were added to 10 mL of acetonitrile, and the mixture was heated to reflux. After the reaction was completed as detected by TLC, water and ethyl acetate were added for extraction, the organic phase was dissolved under reduced pressure, and the residue was purified by column chromatography to give 0.39 g of white solid, namely intermediate compound VI.7.

[0310] (2) Preparation of compound 31

[0311] 0.30 g (0.49 mmol) of intermediate VI.7, 0.02 g (0.50 mmol) of sodium hydride (60% by mass), and 0.10 g (0.56 mmol) of N-bromosuccinimide were added to 10 mL of N,N-dimethylformamide, and the mixture was heated to 40 °C. After the reaction was complete as detected by TLC, water and ethyl acetate were added for extraction, the organic phase was dissolved under reduced pressure, and the residue was purified by column chromatography to give 0.06 g of a white solid, namely compound 31. The NMR and mass spectrometry data of compound 31 are as follows:

[0312] 1 H NMR(600MHz,Chloroform-d)δ8.13(d,1H),8.09-7.95(m,2H),7.92-7.88(m,1H) ,7.63-7.53(br,1H),7.43-7.14(m,6H),4.93(s,1H),4.51(s,1H),2.30(t,1H). LC-MS(m / z,ESI):687.07(M+H) + .

[0313] Method 4:

[0314]

[0315] 0.50 g (0.82 mmol) of intermediate VI.7, 0.12 g (1.17 mmol) of sodium bromide, 0.02 g (0.50 mmol) of sodium hydroxide, and 0.21 g of water were added to 10 mL of dichloromethane, and the mixture was heated to 40 °C. 0.64 g (1.21 mmol) of an aqueous solution of sodium hypochlorite (14% by mass) was added dropwise to the reaction solution, and the reaction was continued at 40 °C. After the reaction was complete as detected by TLC, water and ethyl acetate were added for extraction. The organic phase was dissolved under reduced pressure, and the residue was purified by column chromatography to give 0.23 g of a white solid, compound 31. The NMR and mass spectrometry data of compound 31 are as follows:

[0316] 1 H NMR(600MHz,Chloroform-d)δ8.13(d,1H),8.09-7.95(m,2H),7.92-7.88(m,1H) ,7.63-7.53(br,1H),7.43-7.14(m,6H),4.93(s,1H),4.51(s,1H),2.30(t,1H). LC-MS(m / z,ESI):687.07(M+H) + .

[0317] Example 11: Preparation of Compound 36

[0318]

[0319] 0.15 g (0.24 mmol) of intermediate V.10, 0.04 g (0.27 mmol) of sodium iodide, and 0.04 g (0.25 mmol) of p-fluorobenzoyl chloride were added to 10 mL of toluene, and the mixture was heated to reflux. After the reaction was complete as detected by TLC, the solvent was removed under reduced pressure, and the residue was purified by column chromatography to give 0.13 g of a yellow oil, namely compound 36. The NMR and mass spectrometry data of compound 36 are as follows:

[0320] 1 H NMR(600MHz,Chloroform-d)δ8.34(d,1H),8.19-8.01(m,2H),7.98-7.89(m,1H),7.60(t,1H),7.47-7.36(br s,2H),7.33(t,1H),7.03-6.83(br s,2H),4.90(s,1H),4.53(s,1H),2.31(t,1H). LC-MS(m / z,ESI):753.04(M+H) + .

[0321] Example 12: Preparation of Compound 47

[0322]

[0323] 0.15 g (0.26 mmol) of intermediate V.9, 0.06 g (0.40 mmol) of sodium iodide, and 0.06 g (0.38 mmol) of 6-fluoronicotinic acid chloride were added to 10 mL of toluene, and the mixture was heated to reflux. After the reaction was complete as detected by TLC, the solvent was removed under reduced pressure, and the residue was purified by column chromatography to give 0.09 g of a white solid, namely compound 47. The NMR and mass spectrometry data of compound 47 are as follows:

[0324] 1 H NMR(600MHz,Chloroform-d)δ8.22(s,1H),8.13(d,1H),8.12-8.08(m,1H),8.03(d,1H),7.94-7 .81(m,2H),7.62(t,1H),7.37(t,1H),6.85(d,1H),4.90(s,1H),4.54(s,1H),2.39-2.26(m,1H). LC-MS(m / z,ESI):706.03(M+H) + .

[0325] Example 13: Preparation of Compound 48

[0326]

[0327] 0.15 g (0.24 mmol) of intermediate V.10, 0.05 g (0.33 mmol) of sodium iodide, and 0.06 g (0.38 mmol) of 6-fluoronicotinic acid chloride were added to 10 mL of toluene, and the mixture was heated to reflux. After the reaction was complete as detected by TLC, the solvent was removed under reduced pressure, and the residue was purified by column chromatography to give 0.09 g of a yellow oil, namely compound 48. The NMR and mass spectrometry data of compound 48 are as follows:

[0328] 1 H NMR(600MHz,Chloroform-d)δ8.34(d,1H),8.22(s,1H),8.14-7.99(m,2H),7.96-7.90(m,1H),7 .86(s,1H),7.69-7.59(m,1H),7.38(t,1H),6.84(d,1H),4.90(s,1H),4.55(s,1H),2.33(t,1H). LC-MS(m / z,ESI):754.05(M+H) + .

[0329] Other compounds of general formulas I to VII of the present invention can be prepared by referring to the above embodiments.

[0330] The physicochemical properties, NMR and mass spectrometry data of some compounds in this invention are as follows:

[0331] Compound 3:

[0332]

[0333] White solid. 1 HNMR(600MHz,Chloroform-d)δ8.12(d,1H),7.98(t,1H),7.89(d,1H),7.46(t,1H),7.42-7.11(m,7H),6.07-5.93(br s,1H),5.27-5.15(m,2H),4.53(d,3H). LC-MS(m / z,ESI):689.10(M+H) + .

[0334] Compound 4:

[0335]

[0336] Yellow solid. 1HNMR(600MHz,Chloroform-d)δ8.32(d,1H),7.98(t,1H),7.92(d,1H),7.51-7.44(m,1H),7.43-7.10(m,7H),6.10-5.90(br s,1H),5.28-5.14(m,2H),4.54(d,2H). LC-MS(m / z,ESI):737.07(M+H) + .

[0337] Compound 11:

[0338]

[0339] White solid. 1 HNMR(600MHz,Chloroform-d)δ8.13(d,1H),8.03(t,1H),7.99-7.86(m,2H),7.6 7-7.37(m,5H),7.30(t,1H),6.07-5.89(br,1H),5.29-5.16(m,2H),4.54(d,2H). LC-MS(m / z,ESI):714.11(M+H) + .

[0340] Compound 12:

[0341]

[0342] White solid. 1 H NMR (600MHz, Chloroform-d) δ8.34(d,1H),8.10-7.90(m,3H),7.61-7.37(m,5H),7.31(t,1H),6.06-5.91(br,1H),5.29-5.17(m,2H),4.54(d,2H). LC-MS(m / z,ESI):762.05(M+H) + .

[0343] Compound 23:

[0344]

[0345] Oily substance. 1HNMR(600MHz,Chloroform-d)δ8.62(s,1H),8.13(d,1H),8.06(t,1H),7.97-7.89(m,2H),7.82(d ,1H),7.58(d,1H),7.51(t,1H),7.35(t,1H),6.07-5.89(m,1H),5.28-5.21(m,2H),4.55(d,2H). LC-MS(m / z,ESI):715.11(M+H) + .

[0346] Compound 24:

[0347]

[0348] Yellow solid. 1 H NMR(600MHz,Chloroform-d)δ8.62(s,1H),8.36-8.31(m,1H),8.07(t,1H),8.01-7.89(m,2H),7.82 (d,1H),7.58(d,1H),7.52(d,1H),7.36(t,1H),6.06-5.90(m,1H),5.30-5.19(m,2H),4.56(d,2H). LC-MS(m / z,ESI):763.04(M+H) + .

[0349] Compound 27:

[0350]

[0351] White solid. 1 H NMR(600MHz,Chloroform-d)δ8.64(s,1H),8.15-8.10(m,1H),8.07(t,1H),7.97-7.84(m, 3H),7.64-7.50(m,2H),7.36(t,1H),6.07-5.92(br,1H),5.29-5.20(m,2H),4.57(s,2H). LC-MS(m / z,ESI):758.09(M+H) + .

[0352] Compound 28:

[0353]

[0354] White solid. 1HNMR(600MHz,Chloroform-d)δ8.65(s,1H),8.32(s,1H),8.07(t,1H),8.02-7.80(m,3H ),7.64-7.50(m,2H),7.37(t,1H),6.07-5.92(br,1H),5.29-5.21(m,2H),4.57(s,2H). LC-MS(m / z,ESI):806.08(M+H) + .

[0355] Compound 32:

[0356]

[0357] Oily substance. 1 H NMR(600MHz,Chloroform-d)δ8.35-8.31(m,1H),8.17-7.96(m,2H),7.95-7.90(m, 1H),7.63-7.55(br,1H),7.51-7.04(m,6H),4.93(s,1H),4.52(s,1H),2.30(t,1H). LC-MS(m / z,ESI):735.06(M+H) + .

[0358] Compound 35:

[0359]

[0360] White solid. 1 H NMR(600MHz,Chloroform-d)δ8.13(d,1H),8.11-7.99(m,2H),7.93-7.88(m,1H),7.63-7.54(m, 1H),7.47-7.35(m,2H),7.32(t,1H),7.02-6.82(br,2H),4.89(s,1H),4.51(s,1H),2.30(t,1H). LC-MS(m / z,ESI):705.04(M+H) + .

[0361] Compound 39:

[0362]

[0363] Oily substance. 1H NMR(600MHz,Chloroform-d)δ8.14(d,1H),8.09(t,1H),8.05-7.95(brs,1H),7.9 1(d,1H),7.72-7.38(m,5H),7.34(t,1H),4.93(s,1H),4.52(s,1H),2.33(s,1H). LC-MS(m / z,ESI):712.07(M+H) + .

[0364] Compound 40:

[0365]

[0366] White solid. 1 H NMR (600MHz, Chloroform-d) δ8.34(d,1H),8.19-7.97(m,2H),7.93(d,1H),7.72-7.39(m,5H),7.34(t,1H),4.94(s,1H),4.53(s,1H),2.33(s,1H). LC-MS(m / z,ESI):760.04(M+H) + .

[0367] Compound 51:

[0368]

[0369] White solid. 1 H NMR(600MHz,Chloroform-d)δ8.64(s,1H),8.16-8.08(m,2H),7.97(d,1H),7.91(d,1H) ),7.85(s,1H),7.68-7.56(m,2H),7.38(t,1H),4.93(d,1H),4.55(d,1H),2.35(s,1H). LC-MS(m / z,ESI):735.05(M+Na) + .

[0370] Compound 52:

[0371]

[0372] White solid. 1H NMR(600MHz,Chloroform-d)δ8.64(s,1H),8.34(d,1H),8.12(t,1H),8.07-7.96(m,1H),7.93 (d,1H),7.84(s,1H),7.70-7.54(m,2H),7.39(t,1H),4.93(d,1H),4.56(d,1H),2.35(s,1H). LC-MS(m / z,ESI):761.00(M+H) + .

[0373] Compound 55:

[0374]

[0375] White solid. 1 H NMR(600MHz,Chloroform-d)δ8.67(s,1H),8.17-8.07(m,2H),8.03-7.85(m,3H ),7.70-7.55(m,2H),7.43-7.34(m,1H),4.93(d,1H),4.58(d,1H),2.35(s,1H). LC-MS(m / z,ESI):756.09(M+H) + .

[0376] Compound 56:

[0377]

[0378] White solid. 1 H NMR(600MHz,Chloroform-d)δ8.67(s,1H),8.36-8.31(m,1H),8.12(t,1H),8.00(d,1H),7.95-7 .85(m,2H),7.68(t,1H),7.63-7.55(m,1H),7.40(t,1H),4.93(d,1H),4.59(d,1H),2.35(s,1H). LC-MS(m / z,ESI):804.07(M+H) + .

[0379] Bioactivity assay

[0380] Example 14: Insecticidal Bioactivity Determination

[0381] Insecticidal activity assays were conducted on several insects using the compounds of this invention. The assay methods are as follows:

[0382] The test compound was dissolved in a 1:1 mixture of acetone and methanol and then diluted with water containing 0.1% (wt) Tween 80 to the required concentration.

[0383] The activity of armyworm, diamondback moth, rice stem borer, beet armyworm, peach aphid, and western flower thrips was determined using the Airbrush spray method.

[0384] (1) Assay for the activity of killing armyworms

[0385] Measurement method: Corn leaves were cut into 2cm long segments, and the airbrush spray pressure was 10psi (approximately 0.7kg / cm). 2 Spray 0.5 mL of the test compound onto both sides of each leaf segment. After air-drying, inoculate each treatment with 10 third-instar larvae, with each treatment replicated three times. After treatment, incubate in an observation room at 25°C and 60–70% relative humidity. Observe the number of surviving insects and calculate the mortality rate three days after treatment.

[0386] The partial test results for armyworms are as follows:

[0387] At a dose of 0.05 mg / L, three days after administration, compounds 3, 4, 7, 8, 11, 12, 19, 20, 23, 24, 27, 28, 31, 32, 35, 36, 39, 40, 47, 48, 51, 52, 55, and 56 had a mortality rate of over 90% against armyworms.

[0388] (2) Activity assay for killing diamondback moth

[0389] Measurement method: Cabbage leaves were perforated to form leaf discs with a diameter of 2 cm using a perforator. The airbrush spray pressure was 10 psi (approximately 0.7 kg / cm²). 2 Spray 0.5 mL of the test compound onto both sides of each leaf disc. After air-drying, inoculate each treatment with 10 third-instar larvae, with each treatment replicated three times. After treatment, incubate in an observation room at 25°C and 60–70% relative humidity. Observe the number of surviving insects three days after treatment and calculate the mortality rate.

[0390] The following are some of the test results for the diamondback moth:

[0391] At a dose of 1.25 mg / L, compounds 3, 4, 7, 8, 11, 12, 19, 20, 23, 24, 27, 28, 31, 32, 35, 36, 39, 40, 47, 48, 51, 52, 55, and 56 had a mortality rate of over 90% against diamondback moth.

[0392] Following the above experimental methods, some compounds of this invention and control compounds KC1, KC2, KC9, and KC10 were further selected to conduct parallel determinations of the activity against diamondback moth. The experimental results are shown in Table 12.

[0393] Table 12 Parallel comparative tests of the insecticidal activity of some compounds of the present invention and control compounds KC1, KC2, KC9, and KC10 against diamondback moth.

[0394]

[0395]

[0396]

[0397]

[0398] Note: KC9 and KC10 in the table are reference compounds provided in this application, which can be obtained by referring to the method of Example 10 of this invention. The raw materials can be prepared according to the method of this invention, or can be purchased, or can be prepared by conventional methods.

[0399] By comparing the compounds of the present invention with control compounds KC1, KC2, KC9, and KC10, by comparing KC9 with KC1, and by comparing KC10 with KC2, it can be seen that the compounds of the present invention have unexpectedly high insecticidal activity and substantial progress compared with the prior art.

[0400] Following the above experimental methods, compounds 3, 7, 8, 19, 20, 31, 35, 36, 47, and 48 of this invention, along with control compounds KC3, KC4, KC5, KC6, KC7, and KC8, were further selected to conduct parallel determinations of the activity against diamondback moth. The experimental results are shown in Table 13.

[0401] Table 13 Parallel comparison test of the insecticidal activity of some compounds of the present invention and control compounds against diamondback moth.

[0402]

[0403]

[0404]

[0405] As shown in Table 13, by comparing compounds 3 and 31 with control compound KC3, by comparing compounds 7 and 35 with control compound KC4, by comparing compounds 8 and 36 with control compound KC5, by comparing compounds 19 and 47 with control compound KC7, and by comparing compounds 20 and 48 with control compounds KC6 and KC8, it can be seen that in the embodiments of the present invention, by introducing allyl and propargyl groups into R2 of the compound of formula I, compounds with better insecticidal effects were obtained compared with the prior art.

[0406] (3) Activity determination of killing rice stem borer

[0407] Test methods: 1) Rice seedling preparation: Rice seedlings were cultured in a constant temperature greenhouse (temperature 26-28℃, relative humidity 60-80%, light intensity 16hL:8hD) using plastic cups with a diameter of 4.5cm and a height of 4cm. When the rice seedlings reached the 4-5 leaf stage, healthy seedlings with uniform growth were selected for pesticide treatment. Each treatment was replicated three times. 2) Insect preparation: Rice stem borers (3rd instar larvae) were continuously reared indoors. 3) Rice stem spraying for insect inoculation: The entire rice seedling was uniformly sprayed using a spraying method, with 15mL of pesticide per treatment. A blank control was treated first, and then the above operation was repeated in order of increasing experimental concentration. After spraying the rice seedlings, the pesticide solution was dried in a cool place, and about 5cm of the stem base was cut off to feed the insects. Prepare 90mm diameter glass petri dishes, line the bottom with filter paper, add water to keep moist, place about 5 rice stalks in each dish, inoculate with 10 larvae, seal the petri dishes with non-woven fabric, and place them in a temperature-controlled room for incubation. Investigate the number of remaining live insects 3 days after the treatment.

[0408] The following are some of the test results for the rice stem borer:

[0409] At a dose of 0.625 mg / L, compounds 3, 4, 7, 8, 11, 12, 19, 20, 23, 24, 27, 28, 31, 32, 35, 36, 39, 40, 47, 48, 51, 52, 55, and 56 had a lethality of over 90% against rice stem borer.

[0410] (4) Activity determination of killing beet armyworm

[0411] Test method: The activity test was conducted using the leaf-dip feeding method. Leaf discs were immersed in the pesticide solution for 10 seconds, dried, and then placed in petri dishes (4 dishes per dish). Filter paper was placed in each petri dish to maintain humidity. Ten beet armyworms were inoculated into each dish, with three replicates. The dishes were placed in a light incubator at 25℃ with a light intensity of 14 hL:10 hD. The number of dead beet armyworms was assessed 1, 2, and 3 days after application, and the mortality rate was calculated.

[0412] The test results for the beet armyworm are as follows:

[0413] At a dose of 0.625 mg / L, 3 days after administration, compounds 3, 4, 7, 8, 11, 12, 19, 20, 23, 24, 27, 28, 31, 32, 35, 36, 39, 40, 47, 48, 51, 52, 55, and 56 had a mortality rate of over 90% against the beet armyworm.

[0414] (5) Activity assay for killing peach aphids

[0415] Measurement method: Take a 6cm diameter petri dish, cover the bottom with a layer of filter paper, and add an appropriate amount of tap water to keep it moist. Cut a suitable-sized cabbage leaf (about 3cm in diameter) with 15-30 aphids from the cabbage plant culturing peach aphids. Remove winged aphids and aphids on the upper surface of the leaf, and place the leaf in the petri dish with the underside facing up. The airbrush spraying pressure is 10psi (about 0.7kg / cm2), and the spray volume is 0.5mL. Each treatment is repeated 3 times. After treatment, place the dishes in an observation room at 25℃ and 60-70% relative humidity. After 48 hours, count the number of surviving insects and calculate the mortality rate.

[0416] The test results for the peach aphid are as follows:

[0417] At a dose of 50 mg / L, compounds 3, 4, 7, 8, 11, 12, 19, 20, 23, 24, 27, 28, 31, 32, 35, 36, 39, 40, 47, 48, 51, 52, 55, and 56 had a mortality rate of over 90% against peach aphids.

[0418] (6) Assay for the activity of killing western flower thrips

[0419] Assay method: Select fresh green bean leaves grown in a greenhouse, spray them evenly with a handheld airbrush, 1 mL per treatment, allow them to air dry naturally, and then place them in finger tubes. Inoculate each treatment with neat and healthy western flower thrips nymphs, 15 per treatment. The experiment was repeated in 3 replicates, with a water treatment as a blank control. After treatment, the tubes were placed indoors at 24℃, 60%-70% relative humidity, and natural light. After 72 hours, the number of surviving insects was counted, and the mortality rate was calculated.

[0420] The test results for western flower thrips are as follows:

[0421] At a dose of 100 mg / L, compounds 3, 4, 7, 8, 11, 12, 19, 20, 23, 24, 27, 28, 31, 32, 35, 36, 39, 40, 47, 48, 51, 52, 55, and 56 had a lethality of over 90% against western flower thrips.

[0422] Following the above experimental methods, compounds 3, 7, 8, 19, 20, 31, 35, 36, 47, and 48 of this invention, along with control compounds KC3, KC4, KC5, KC6, KC7, and KC8, were further selected to conduct parallel determinations of their activity against western flower thrips nymphs. The experimental results are shown in Table 14.

[0423] Table 14 Parallel comparison test of the insecticidal activity of some compounds of the present invention and control compounds against western flower thrips nymphs.

[0424]

[0425]

[0426]

[0427] As shown in Table 14, by comparing compounds 3 and 31 with control compound KC3, by comparing compounds 7 and 35 with control compound KC4, by comparing compounds 8 and 36 with control compound KC5, by comparing compounds 19 and 47 with control compound KC7, and by comparing compounds 20 and 48 with control compounds KC6 and KC8, it can be seen that in the embodiments of the present invention, by introducing allyl and propargyl groups into R2 of the compound of formula I, compounds with better insecticidal effects were obtained compared with the prior art.

[0428] Example 15: Insecticidal test on cat fleas

[0429] 4 mg of the test compound was dissolved in 40 mL of acetone to obtain an acetone solution with a concentration of 100 mg / L. 400 μL of the solution was then coated onto the bottom and sides of a petri dish with an inner diameter of 5.3 cm. After the acetone evaporated, a thin film of the compound of this invention was formed on the inner wall of the petri dish. The inner wall of the petri dish used was 40 cm. 2 The treatment dosage was 1 μg / cm³. 2 Ten adult cat fleas (mixed male and female) were placed in the mixture, which was then covered and stored in a constant temperature chamber at 25°C. The number of dead fleas was checked after 72 hours, and the mortality rate was calculated. The experiment was repeated three times. Test results: Compounds 3, 4, 7, 8, 11, 12, 19, 20, 23, 24, 27, 28, 31, 32, 35, 36, 39, 40, 47, 48, 51, 52, 55, and 56 showed a mortality rate of over 90%.

[0430] Example 16: Insecticidal test against American ticks

[0431] 4 mg of the test compound was dissolved in 40 mL of acetone to obtain an acetone solution with a concentration of 100 mg / L. 400 μL of the solution was then coated onto the bottom and sides of two 5.3 cm inner diameter culture dishes. After the acetone evaporated, a thin film of the compound of this invention was formed on the inner wall of the culture dishes. The inner wall of the culture dishes used was 40 cm. 2 The treatment dosage was 1 μg / cm³. 2Ten first-generation nymphs (mixed sexes) of *Ixodes natans* were placed in each culture dish, and two petri dishes were combined. The joints were sealed with tape to prevent escape, and the dishes were stored in a constant temperature chamber at 25°C. The number of dead nymphs was checked after 24 hours, and the mortality rate was calculated. The experiment was repeated three times. Test results: Compounds 3, 4, 7, 8, 11, 12, 19, 20, 23, 24, 27, 28, 31, 32, 35, 36, 39, 40, 47, 48, 51, 52, 55, and 56 showed mortality rates of over 90%.

Claims

1. An amide compound, characterized in that: The structure of the amide compound is shown in general formula I: ； In general formula I: R1 is selected from fluorine, cyano, or trifluoromethyl; R2 is selected from propargyl; R3 is selected from iodine; R4 is selected from trifluoromethyl or difluoromethoxy; X is selected from CH.

2. The amide compound according to claim 1, characterized in that, R1, X, R2, R3, and R4 are shown below; 。 3. The amide compound according to claim 2, characterized in that, R1, X, R2, R3, and R4 are shown below; 。 4. The amide compound according to claim 3, characterized in that... R1, X, R2, R3, and R4 are shown below; 。 5. A compound, said compound being an intermediate for the preparation of an amide compound as described in any one of claims 1-4, characterized in that, The compound has the structure shown in general formula V: ； In general formula V: R2 is selected from propargyl; R3 is selected from iodine; R4 is selected from trifluoromethyl or difluoromethoxy.

6. The compound according to claim 5, characterized in that, R2, R3 and R4 are shown below; 。 7. The compound according to claim 6, characterized in that, R2, R3 and R4 are shown below; 。 8. A compound, said compound being an intermediate for the preparation of an amide compound as described in any one of claims 1-4, characterized in that, The compound has the structure shown in general formula VI: ； In general formula VI: R1 is selected from fluorine, cyano, or trifluoromethyl; R2 is selected from propargyl; R4 is selected from trifluoromethyl or difluoromethoxy; X is selected from CH.

9. The compound according to claim 8, characterized in that, R1, X, R2 and R4 are shown below; 。 10. The compound according to claim 9, characterized in that, R1, X, R2 and R4 are shown below; Table 10 。 11. A method for preparing an amide compound as described in any one of claims 1-4, characterized in that, The preparation method includes reacting an intermediate compound, as shown in general formula VI, with a halogenated reagent in a solvent to obtain a compound of general formula I. The reaction formula of the compound is as follows: 。 12. The method for preparing the amide compound according to claim 11, characterized in that, Compound of general formula VI is prepared by reacting a base or halogenated reagent with a solvent in a solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours.

13. The method for preparing the amide compound as described in claim 11 or 12, characterized in that: The halogenated reagent is selected from chlorine, liquid bromine, iodine, NBS, NCS, NIS, a mixture of hydrogen peroxide and hydrobromic acid, a mixture of hydrogen peroxide and hydroiodic acid, a mixture of sodium hypochlorite and hydrobromic acid, or a mixture of sodium hypochlorite and hydroiodic acid. The solvent is selected from benzene, toluene, xylene, acetone, methyl ethyl ketone, methyl isobutyl ketone, chloroform, dichloromethane, methyl acetate, ethyl acetate, tetrahydrofuran, dioxane, diethyl ether, 1,2-dimethoxyethane, water, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, or a mixture of the above solvents. The reaction temperature is 0°C-100°C.

14. The method for preparing the amide compound according to claim 11 or 12, characterized in that: The reaction temperature is 25°C-80°C.

15. The method for preparing the amide compound according to claim 12, characterized in that: The base is selected from trimethylamine, triethylamine, pyridine, DBU, 4-dimethylaminopyridine, N,N-diisopropylmethylamine, N,N-diisopropylethylamine, sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, or sodium tert-butoxide.

16. The method for preparing the amide compound according to claim 12, characterized in that: The alkali is selected from sodium hydride, potassium hydride, sodium hydroxide, or potassium hydroxide.

17. Use of an amide compound according to any one of claims 1-4 in the preparation of an insecticide.

18. The use according to claim 17, characterized in that: The insecticide is used to control one or more of the following: diamondback moth, armyworm, beet armyworm, cotton bollworm, rice stem borer, peach aphid, thrips, and flea beetle.

19. An insecticide formulation, characterized in that: The insecticide formulation contains an amide compound as an active ingredient as described in any one of claims 1-4, and also contains one or more excipients.

20. The insecticide formulation according to claim 19, characterized in that: The amount of the amide compound according to any one of claims 1-4 in the insecticide formulation is from 0.1 to 99% by weight.

21. The insecticide formulation according to claim 19, characterized in that: The amount of the amide compound according to any one of claims 1-4 in the insecticide formulation is from 0.5 to 90% by weight.

22. An insecticide composition, characterized in that: The mixture includes the amide compounds as described in any one of claims 1-4 and other active compounds, wherein the other active compounds are selected from one or more of insecticides, poison baits, disinfectants, acaricides, nematicides, fungicides, growth regulators, and herbicides.

23. Use of an amide compound according to any one of claims 1-4 in the preparation of an animal parasite control agent.

24. The use according to claim 23, characterized in that: The animal parasite control agent is used to control one or more of cat fleas and American ticks.

25. An animal parasite control agent, characterized in that: The animal parasite control agent contains an amide compound as described in any one of claims 1-4 as an active ingredient, and also contains one or more excipients.

26. The animal parasite control agent according to claim 25, characterized in that: The amount of the amide compound as described in any one of claims 1-4 in the animal parasite control agent is 1 to 80 by weight.

27. A composition for the prevention and control of animal parasites, characterized in that: The mixture comprises the amide compounds as described in any one of claims 1-4 and other animal parasite control active compounds, wherein the other animal parasite control active compounds are selected from one or more of acaricides, insecticides, parasiteicides, and antimalarial agents.

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