Amide compound and application thereof

Abstract

The invention discloses an amide compound and application thereof. The structure of the compound is shown as a general formula I, wherein the definition of each substituent group in a # imgabs0 # formula is shown in the specification; also disclosed in the description are their use as insecticides and animal parasite control agents.

Description

[0001] This application is a divisional application of the Chinese invention patent application with the application date of July 8, 2022, application number 202210800664.0, and invention name “A kind of amide compound and its use”. Technical Field

[0002] The present invention relates to a compound, in particular to a novel amide compound and application thereof. Background Art

[0003] Patent JP2007099761A discloses the following specific compounds KC1 (CAS registration number: 934532-14-6) and KC2 (CAS registration number: 934532-15-7), which have certain insecticidal activity.

[0004]

[0005] Patent CN102119143A discloses the following insecticidal compounds KC3 (compound number: 7-1574, CAS registration number: 1207727-04-5), KC4 (compound number: 7-1577, CAS registration number: 1207727-08-9) and KC5 (compound number: 7-1733, CAS registration number: 1207727-07-8). Among them, compound KC3 has been commercialized as an agricultural insecticide, and its Chinese common name is brofenac and its English common name is broflanilide.

[0006]

[0007] Patent CN102119143A also discloses the following insecticidal compounds KC6 (compound number: 6-1772, CAS registration number: 1331922-53-2), KC7 (compound number: 7-1616, CAS registration number: 1207979-50-7) and KC8 (compound number: 7-1772, CAS registration number: 1332266-07-5).

[0008] Among them, 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] In the prior art, there is no report on the compound represented by the general formula I of the present invention and its insecticidal activity. Summary of the invention

[0012] The object of the present invention is to provide an amide compound with excellent insecticidal activity, which can be used to prepare drugs for controlling pests in agriculture and other fields and to prepare drugs for controlling animal parasites in the field of veterinary medicine.

[0013] In order to achieve the purpose of the invention, the present invention provides the following technical solutions:

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

[0015]

[0016] In the 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 halogen;

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

[0021] X is selected from CH or N.

[0022] In a possible implementation, in the 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 a possible implementation, the amide compound is selected from the compounds in Table 1, wherein the compounds in Table 1 have a structure as shown in Formula I, and R1, X, R2, R3 and R4 are as shown in Table 1:

[0029] Table 1

[0030]

[0031]

[0032]

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

[0034] Table 2

[0035]

[0036]

[0037] In a possible implementation, the amide compound is selected from the compounds in Table 3, wherein the compounds in Table 3 have a structure as shown in 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 compound (i.e., the compound of general formula I), and the intermediate compound is shown in general formula II:

[0042]

[0043] In the 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, wherein the compounds in Table 4 have a structure as shown in 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 compound of the general formula II, wherein the intermediate compound is as shown in the general formula III:

[0052]

[0053] In the 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.

[0058] In one possible implementation, the intermediate compound is selected from the compounds in Table 5, wherein the compounds in Table 5 have a structure as shown in 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 compound of the general formula III, wherein the intermediate compound is as shown in the general formula IV:

[0063]

[0064] In the general formula IV:

[0065] R2 is selected from allyl or propargyl;

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

[0067] In one possible implementation, the intermediate compound is selected from the compounds in Table 6, wherein the compounds in Table 6 have a structure as shown in Formula IV, and R2 and R5 are as shown in Table 6:

[0068] Table 6

[0069] Compound No. <![CDATA[R2]]> <![CDATA[R5]]> 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 compound (i.e., the compound of general formula I), wherein the intermediate compound is shown in general formula V:

[0071]

[0072]

[0073] In the general formula V:

[0074] R2 is selected from allyl or propargyl;

[0075] R3 is selected from halogen;

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

[0077] In a 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, wherein the compounds in Table 7 have a structure as shown in Formula V and R2, R3 and R4 are as shown in Table 7:

[0082] Table 7

[0083] Compound No. <![CDATA[R2]]> <![CDATA[R3]]> <![CDATA[R4]]> 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, wherein the compounds in Table 8 have a structure as shown in Formula V and R2, R3 and R4 are as shown in Table 8:

[0085] Table 8

[0086] Compound No. <![CDATA[R2]]> <![CDATA[R3]]> <![CDATA[R4]]> 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 compound (i.e., the compound of general formula I), wherein the intermediate compound is 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 halogen, C1-C3 haloalkyl or C1-C3 haloalkoxy;

[0092] X is selected from CH or N.

[0093] In a possible implementation, in the general formula 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, wherein the compounds in Table 9 have a structure as shown in Formula VI and R1, X, R2 and R4 are as shown in Table 9:

[0099] Table 9

[0100] Compound No. <![CDATA[R1]]> X <![CDATA[R2]]> <![CDATA[R4]]> 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, wherein the compounds in Table 10 have a structure as shown in Formula VI and R1, X, R2 and R4 are as shown in Table 10:

[0102] Table 10

[0103] Compound No. <![CDATA[R1]]> X <![CDATA[R2]]> <![CDATA[R4]]> 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 compound of the general formula VI, wherein the intermediate compound is as shown in the general formula VII:

[0105]

[0106] In the general formula VII:

[0107] R2 is selected from allyl or propargyl;

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

[0109] In a possible implementation, in the 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, wherein the compounds in Table 11 have a structure as shown in Formula VII, and R2 and R4 are as shown in Table 11:

[0113] Table 11

[0114] Compound No. <![CDATA[R2]]> <![CDATA[R4]]> 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 a method for preparing the above-mentioned amide compounds, which includes five schemes as follows (the groups in the formula are defined as above unless otherwise specified, and LG=Cl, Br or I):

[0116] Solution 1:

[0117]

[0118] Step 1: Preparation of compounds of formula IV

[0119] The compound of general formula VIII is reacted with the 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 obtain the compound of general formula IV. The reaction is carried out in the presence of a base.

[0120] Step 2: Preparation of compounds of formula III

[0121] The compound of formula IV and the compound of formula IX are reacted in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain the compound of formula III. The reaction is carried out in the presence of a base or a catalyst.

[0122] Step 3: Preparation of compounds of formula II

[0123] The compound of formula III can be hydrolyzed 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 to obtain the compound of formula II; the suitable base can be 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; the suitable solvent can be any one of water, methanol, ethanol, tetrahydrofuran or dioxane, or a mixed solvent of at least two of them.

[0124] Step 4: Preparation of compounds of formula X

[0125] The compound of general formula X can be prepared by reacting the compound of general formula II with thionyl chloride, oxalyl chloride, phosgene, phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride, triphosgene, etc. using conventional methods.

[0126] Step 5: Preparation of compounds of formula I

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

[0128] In step 1, step 2 and step 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, water, acetonitrile, N,N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, and other polar solvents or mixed solvents of the above solvents; the bases may be the same or different and may be trimethylamine, triethylamine, pyridine, DBU, Organic bases such as 4-dimethylaminopyridine, N,N-diisopropylmethylamine, 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, metal alkoxides such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, sodium tert-butoxide, etc.; the catalysts may be the same or different and may be potassium iodide, sodium iodide, potassium fluoride, sodium fluoride, potassium bromide or sodium bromide, etc.

[0129] Option 2:

[0130]

[0131] Step 1: Preparation of compounds of formula XII

[0132] The compound of general formula XI is reacted with 2-fluoro-3-nitrobenzoyl chloride in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain the compound of general formula XII. The reaction is carried out in the presence of a base or a catalyst.

[0133] Step 2: Preparation of compounds of formula XIII

[0134] The compound of general formula XII is subjected to reduction reaction to obtain the compound of general formula XIII.

[0135] As the reduction reaction, there can be mentioned a method utilizing a hydrogenation reaction and a method utilizing a metal compound (eg, stannous chloride) or a metal (zinc powder, iron powder, etc.).

[0136] The method utilizing the hydrogenation reaction can be carried out in a suitable solvent, in the presence of a catalyst, at normal pressure or under pressure, in a hydrogen atmosphere. The catalyst in the hydrogenation reaction may be a palladium catalyst such as palladium-carbon, a cobalt catalyst, a rhodium catalyst, a platinum catalyst, etc. The solvent may be an alcohol such as methanol and ethanol; an aromatic hydrocarbon such as benzene and toluene; a chain or cyclic ether such as acetaldehyde and tetrahydrofuran; or an ester 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 temperature of the hydrogenation reaction is greater than or equal to -20°C and less than or equal to the boiling point of the reaction solvent, for example, -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 the reaction is carried out at the boiling point of the solvent, i.e., under reflux.

[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 a metal is carried out in any one of methanol, ethanol or ethyl acetate or a mixed solvent of at least two of them.

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

[0142] Preferably, the reaction temperature of the method utilizing a metal compound or metal is greater than or equal to -10°C and less than or equal to the boiling point of the reaction solvent, for example, -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.

[0143] Preferably, the reaction time of the method utilizing 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 compounds of formula V

[0145] The compound of general formula XIII and the compound of general formula R2-LG are reacted in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain the compound of general formula V. The reaction is carried out in the presence of a base or a catalyst.

[0146] Step 4: Preparation of compounds of formula I

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

[0148] In step 1, step 3 and step 4, the suitable solvents may be the same or different and 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, water, acetonitrile, N,N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, and other polar solvents or mixed solvents of the above solvents; the bases may be the same or different and may be trimethylamine, triethylamine, pyridine, D BU, 4-dimethylaminopyridine, N,N-diisopropylmethylamine, N,N-diisopropylethylamine and other organic bases, sodium hydride, potassium hydride and other alkali metal hydrides, sodium hydroxide, potassium hydroxide and other alkali metal hydroxides, calcium hydroxide and other alkaline earth metal hydroxides, sodium carbonate, potassium carbonate and other alkali metal carbonates, sodium bicarbonate and other alkali metal bicarbonates, sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, sodium tert-butoxide and other metal alkoxides; the catalysts may be the same or different and may be potassium iodide, sodium iodide, potassium fluoride, sodium fluoride, potassium bromide or sodium bromide and the like.

[0149] Option 3:

[0150]

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

[0152] The compound of formula X and the compound of formula XIV are reacted in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain the compound of formula VI; an appropriate amount of base or catalyst may be added to the reaction to help the reaction proceed better. 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, water, acetonitrile, N,N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, and other polar solvents or mixed solvents of the above solvents; the bases may be the same or different and may be trimethylamine, triethylamine, pyridine, DBU, 4-dimethylamino Organic bases such as pyridine, N,N-diisopropylmethylamine, N,N-diisopropylethylamine, etc., 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, metal alkoxides such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, sodium tert-butoxide, etc.; the catalysts may be the same or different and may be potassium iodide, sodium iodide, potassium fluoride, sodium fluoride, potassium bromide or sodium bromide, etc.

[0153] Step 2: Preparation of compounds of formula I

[0154] The compound of general formula VI can be prepared by reacting a compound of general formula I with a suitable halogenating agent in a suitable solvent.

[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 halogenating agents are selected from chlorine gas, 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, a mixture of sodium hypochlorite and hydroiodic acid, a mixture of sodium chlorate and hydrobromic acid or a mixture 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 a mixed solvent 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 from 0°C to 100°C, more preferably from 25°C to 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] The compound of general formula XV can be prepared by reacting the compound of general formula XIV with 2-fluoro-3-nitrobenzoyl chloride 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 a catalyst.

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

[0165] The compound of general formula XV can be prepared by reduction reaction to obtain the compound of general formula XVI.

[0166] As the reduction reaction, there can be mentioned a method utilizing a hydrogenation reaction and a method utilizing a metal compound (eg, stannous chloride) or a metal (zinc powder, iron powder, etc.).

[0167] The method utilizing the hydrogenation reaction can be carried out in a suitable solvent, in the presence of a catalyst, at normal pressure or under pressure, in a hydrogen atmosphere. The catalyst in the hydrogenation reaction may be a palladium catalyst such as palladium-carbon, a cobalt catalyst, a rhodium catalyst, a platinum catalyst, etc. The solvent may be an alcohol such as methanol and ethanol; an aromatic hydrocarbon such as benzene and toluene; a chain or cyclic ether such as acetaldehyde and tetrahydrofuran; or an ester 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 temperature of the hydrogenation reaction is greater than or equal to -20°C and less than or equal to the boiling point of the reaction solvent, for example, -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 the reaction is carried out at the boiling point of the solvent, i.e., under reflux.

[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 a metal is carried out in any one of methanol, ethanol or ethyl acetate or a mixed solvent of at least two of them.

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

[0173] Preferably, the reaction temperature of the method utilizing a metal compound or metal is greater than or equal to -10°C and less than or equal to the boiling point of the reaction solvent, for example, -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.

[0174] Preferably, the reaction time of the method utilizing 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 formula VII

[0176] The compound of general formula XVI is reacted with the 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 obtain the compound of general formula VII. The reaction is carried out in the presence of a base or a catalyst.

[0177] Step 4: Preparation of compounds of formula VI

[0178] The compound of formula VII is reacted with the compound of 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 to obtain the compound of formula VI. The reaction is carried out in the presence of a base or a catalyst.

[0179] Step 5: Preparation of compounds of formula I

[0180] Same as step 2 of solution 3.

[0181] In step 1, step 3 and step 4, the suitable solvents may be the same or different and 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, water, acetonitrile, N,N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, and other polar solvents or mixed solvents of the above solvents; the bases may be the same or different and may be trimethylamine, triethylamine, pyridine, D BU, 4-dimethylaminopyridine, N,N-diisopropylmethylamine, N,N-diisopropylethylamine and other organic bases, sodium hydride, potassium hydride and other alkali metal hydrides, sodium hydroxide, potassium hydroxide and other alkali metal hydroxides, calcium hydroxide and other alkaline earth metal hydroxides, sodium carbonate, potassium carbonate and other alkali metal carbonates, sodium bicarbonate and other alkali metal bicarbonates, sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, sodium tert-butoxide and other metal alkoxides; the catalysts may be the same or different and may be potassium iodide, sodium iodide, potassium fluoride, sodium fluoride, potassium bromide or sodium bromide and the like.

[0182] Option 5:

[0183]

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

[0185] The compound of formula VIII and the compound of formula IX are reacted in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain the compound of formula XVII. The reaction is carried out in the presence of a base or a catalyst.

[0186] Step 2: Preparation of compounds of formula III

[0187] The compound of general formula XVII is reacted with the 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 obtain the compound of general formula III. The reaction is carried out in the presence of a base or a catalyst.

[0188] Step 3: Preparation of compounds of formula II

[0189] Same as step 3 of solution 1.

[0190] Step 4: Preparation of compounds of formula X

[0191] Same as step 4 of solution 1.

[0192] Step 5: Preparation of compounds of formula I

[0193] Same as step 5 of solution 1.

[0194] In step 1 and step 2, suitable solvents may be the same or different, such as 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, water, acetonitrile, N,N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, and other polar solvents or mixed solvents of the above solvents; the bases may be the same or different, such as trimethylamine, triethylamine, pyridine, DBU , 4-dimethylaminopyridine, N,N-diisopropylmethylamine, N,N-diisopropylethylamine and other organic bases, 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, metal alkoxides such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, sodium tert-butoxide, etc.; the catalysts may be the same or different and may be potassium iodide, sodium iodide, potassium fluoride, sodium fluoride, potassium bromide or sodium bromide, etc.

[0195] The compound of formula XI and the compound of formula XIV can be prepared according to known methods, for example, with reference to WO20110201687, WO2011093415, WO2005021488, WO2005073165, WO2006137395, JP2007099761, WO2008000438, WO2008074427, WO2008107091, WO2010013567, WO2010018714, WO2010090282, WO2010127926, WO2010127928, JP 2011063549, WO2012020483, WO2012020484, WO2012077221, WO2012164698, WO2013050261, WO2014069665, WO2014067838, WO2014161848, WO2014161850, WO2015097091 or WO2015097094; the compound of formula VIII, the compound of formula IX and the compound of formula R2-LG are usually commercially available or can be prepared in-house according to conventional methods.

[0196] The embodiment of the present invention also provides the use of the above 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), for example Callosobruchus chinensis, Sitophilus zeamais, Tribolium castaneum, Epilachnavigintioctomaculata, Agriotes ogurae fuscicollis, Anomala rufocuprea, Leptinotarsa ​​decemlineata, Diabrotica spp., Monochamus alternatus endai, Lissorhoptrus oryzophilus, Lyctus bruneus;

[0199] Pests of the order of the Lepidopteran, for example, Lymantria dispar, Malacosoma neustria, Pieris rapae crucivora, Spodoptera litura, Mamestra brassicae, Chilo suppressalis, Ostrinia nubilalis, Cadra cautella, Adoxophyes honmai, Cydia pomonella, Agrotis segetum, Galleria mellonella, Plutellaxylostella, Heliothis virescens, Phyllocnistis citrella;

[0200] Pests from the order of the Hemipterous, for example, Nephotettix cincticeps, Nilaparvata lugens, Pseudococcus comstocki, Unaspisyanonensis, Myzus persicas, Aphis pomi, Aphis gossypii, Lipaphis erysimi, Stephanitis nashi, Nezara spp., Trialeurodes vaporariorum, Pshylla spp.;

[0201] Pests of the order Thysanoptera, e.g. Thrips palmi, Franklinella occidentalis;

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

[0203] Pests of the order Blattarian, for example, German cockroach (Blattella germanica), American cockroach (Periplaneta americana), yellow-breasted termite (Reticulitermes speratus), house termite (Coptotermes formosanus);

[0204] Dipterous pests, for example, Musca domestica, Aedes aegypti, Delia platura, Culex pipiens pallens, Anopheles sinensis, Culex tritaeniorhynchus, Liriomyza trifolii, etc.

[0205] Agricultural pest mites, such as Tetranychus cinnabarinus, Tetrahychus urticae, Panonychus citri, Aculops pelekassi, Tarsonemus spp., etc.

[0206] In a possible implementation, the insecticide is used to control one or more of the group consisting of diamondback moth, armyworm, beet armyworm, Spodoptera litura, striped stem borer, peach aphid, thrips, and flea beetles.

[0207] The embodiment of the present invention further provides an insecticide preparation, which contains the above-mentioned amide compound as an active component and one or more auxiliary materials.

[0208] In one possible implementation, the pesticide formulation is selected from the following dosage forms: solution, emulsion, wettable powder, granular wettable powder, suspension, powder, foam, paste, tablet, granule, aerosol, natural agent impregnated with active compound, synthetic agent impregnated with active compound, microcapsule, seed coating agent, formulation equipped with combustion device (the combustion device may be a chimney and mist cylinder, tank and coil, etc.) and ULV (cold fog, hot fog), etc. These pesticide formulations or animal parasite control agents can be prepared by known methods, for example, by mixing the active component with a filler (such as a liquid diluent or carrier, a liquefied gas diluent or carrier, a solid diluent or carrier), and optionally with a surfactant (i.e., an emulsifier and / or a dispersant and / or a foaming agent), etc.

[0209] In a possible implementation, the auxiliary material includes one or more of the following: a filler (such as a liquid diluent or carrier, a liquefied gas diluent or carrier, a solid diluent or carrier), a surfactant (such as an emulsifier and / or a dispersant and / or a foaming agent), a binder, and a colorant;

[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, methylene chloride, etc.), aliphatic hydrocarbons (e.g., cyclohexane or paraffin (e.g., mineral oil fractions)), alcohols (e.g., butanol, ethylene glycol, and ethers or esters thereof, etc.), ketones (e.g., acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, etc.), strong polar solvents (e.g., dimethylformamide, dimethyl sulfoxide), water, etc. When water is used as the extender, for example, an organic solvent may be used as a cosolvent;

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

[0212] Solid diluents may include crushed natural minerals (e.g., kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, etc.) and crushed synthetic minerals (e.g., finely dispersed silicic acid, alumina and silicates, etc.);

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

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

[0215] Binders may include carboxymethyl cellulose, natural or synthetic polymers (e.g., gum arabic, polyvinyl alcohol, and polyvinyl acetate, etc.);

[0216] Colorants may include inorganic pigments (such as iron oxide, titanium oxide and Prussian blue, etc.), 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 invention may be present as a mixture with a synergist, which need not be active itself but rather is a compound which enhances the activity of the active compound.

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

[0219] The present invention also provides an insecticide composition, which includes a mixture of the above-mentioned amide compound and other active compounds (such as insecticides, baits, disinfectants, acaricides, nematicides, fungicides, growth regulators, herbicides, etc.). The mixture can be provided in the form of a bulk drug, or in the form of a commercially available preparation or in a use form prepared from the preparation.

[0220] An embodiment of the present invention also provides a method for controlling agricultural or forestry pests, which comprises the following steps: applying an effective dose of a material to the pests to be controlled or their growth medium, wherein the material is selected from one or more of the following groups: the above-mentioned amide compounds, the above-mentioned insecticide preparations, and the above-mentioned insecticide compositions.

[0221] The present invention also provides the use of the above-mentioned amide compounds in the preparation of an animal parasite control agent. 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, particularly internal and external parasites.

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

[0223] From the order of the Anoplurida, for example, Haematopinus spp., Linognathus spp., Pediculus spp., Phtirus spp. and Solenopotes spp.; in particular, representative examples are Linognathus setosus and Solenopotes capillatus;

[0224] From the order Mallophaga (Linognathus vituli, Linognathus ovillus, Linognathus oviformis, Linognathus pedalis, Linognathus stenopsis, Haematopinus asini macrocephalus, Haematopinus eurysternus, Haematopinus suis, Pediculus humanus capitis, Pediculus humanus corporis, Phylloxera vastatrix, Phthirus pubis) and from the suborders Amblycerina and Ischnocerin, for example, Trimenopon spp., Menopon spp., Trinoton spp. spp.), Bovicola spp., Werneckiella spp., Lepikentron spp., Damalina spp., Trichodectes spp., and Felicola spp.; in particular, representative examples are Bovicola bovis, Bovicola ovis, Bovicola limbata, Damalina bovis, Trichodectes canis, Felicola subrostratus, Bovicola caprae, Lepikentron ovis, Werneckiella equi;

[0225] From the order Diptera and its suborders Nematocerina and Brachycerina, for example, Aedes spp., Anopheles spp., Culex spp., Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyia spp., Culicoides spp., Chrysops spp., Odagmia spp., Wilhelmia spp., Hybomitra spp., Atylotus spp. 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 spp.), Gasterophilus spp., Hippobosca spp., Lipoptena spp., Melophagus spp., Rhinoestrus spp., Tipula spp.; in particular, representative examples are Aedes aegypti, Aedes albopictus, Aedes taeniorhynchus, Anopheles gambiae, Anopheles maculipennis, Calliphora erythrocephala, Chrysozona pluvialis, Culex five-bandedquinquefasciatus), Culexpipiens, Culex tarsalis, Fannia canicularis, Sarcophagacarnaria, Stomoxys calcitrans, Tipulapaludosa, Lucilia cuprina, Lucilia sericata, Simulium reptans, Phlebotomus papatasi, Phlebotomus longipalpis, Odagmiaornata, Wilhelmia equina, Boophthora erythrocephala, Tabanus bromius, Tabanus spodopterus, Tabanus sericata, atratus), Tabanus sudeticus, Hybomitra ciurea, Chrysops caecutiens, Chrysops relictus, Haematopota pluvialis, Haematopotaitalica, Musca autumnalis, Musca domestica, Haematobia irritansirritans, Haematobia irritans exigua, Haematobiastimulans, Hydrotaea irritans, Hydrotaea albipuncta, Chrysomyachloropyga, Chrysomyabezziana, Oestrus ovis, Hypoderma bovis, Hypoderma lineatum), Przhevalskiana silenus, Dermatobia hominis, Melophagus ovinus, Lipoptena capreoli, Lipoptena cervi, Hippobosca variegata, Hippoboscaequina), Gasterophilus intestinalis, Gasterophilus haemorroidalis, Gasterophilus interrnis, Gasterophilus nasalis, Gasterophilus nigricornis, Gasterophilus pecorum, Braulacoeca;

[0226] From the order of the Siphonapterida, for example, Pulex spp., Ctenocephalides spp., Tunga spp., Xenopsylla spp., Ceratophyllus spp.; in particular, representative examples are Ctenocephalides canis, Ctenocephalides felis, Pulex irritans, Tunga penetrans, Xenopsylla cheopis;

[0227] From the order of the Heteropterida, for example, Cimex spp., Triatomaspp., Rhodnius spp., Panstrongylus spp.;

[0228] From the order of the Blattarida, for example, Blatta orientalis, Periplaneta americana, German cockroach, Supella spp. (for example, Suppella longipalpa);

[0229] From the order of the Acari (or Acarina), the orders Metastigmata and Mesostigmata, for example, 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), Ornithonyssus spp. spp.), Pneumonyssus spp., Pneumonyssus spp., Raillietia spp., Pneumonyssus spp., Sternostoma spp., Varroa spp., Acarapis spp.; in particular, representative examples are Argas persicus, Argas reflexus, Ornithodorus moubata, Otobius megnini), Rhipicephalus (Boophilus) microplus, Rhipicephalus (Boophilus) decoloratus, Rhipicephalus (Boophilus) annulatus, Rhipicephalus (Boophilus) calceratus, Hyalomma anatolicum, Hyalomma aegypticum, Hyalomma marginatum, Hyalomma transiens, Rhipicephalus evertsi, Ixodes ricinus, Ixodes hexagonus, Ixodes canisuga, Ixodes pilosus, Ixodes rubrumrubicundus), 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, Rhipicephalus sac bursa), African fanhead tick (Rhipicephalus appendiculatus), Cape fanhead tick (Rhipicephalus capensis), Turan fanhead tick (Rhipicephalus turanicus), Rhipicephalus zambeziensis, American flower tick (Amblyomma americanum), colored flower tick (Amblyomma variegatum, Amblyomma maculatum, Hebrew flower tick (Amblyomma hebraeum), Kayan flower tick (Amblyomma cajennense), Dermanyssus gallinae, Ornithonyssus bursa, Ornithonyssus sylviarum, Varroajacobsconi;

[0230] From the orders Actinedida (Prostigmata) and Acaridida (Astigmata), for example, 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., Psoroptes spp. spp.), Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Cytodites spp. and Laminosioptes spp.; in particular, Cheyletiella yasguri, Cheyletiella blakei, Demodex canis, Demodex bovis, Demodex ovis, Demodex caprae, Demodex equi, Demodex caballi, Demodex suis, Neotrombicula autumnalis, Neotrombicula desaleli, Neoschonegastia xerothermobia, Trombicula akamushi, Otodectes cynotis, Notoedres cati, Sarcoptes canis, Sarcoptes bovis, Sarcoptes ovis, Sarcoptes rupicaprae (= S.caprae), Sarcoptes equi, Sarcoptes suis, Psoroptes ovis, Psoroptes cuniculi, Psoroptes equi, Chorioptes bovis, Psoergates ovis, Pneumonyssoidic mange, Pneumonyssoides caninum, Acarapis woodi;

[0231] Nematodes, for example, Meloidogyne incognita, Bursaphelenchus xylophilus, Aphelenchoides besseyi, Heteroderaglycines, Pratylenchus spp., and the like.

[0232] Arthropods, worms and malarial parasites that attack animals. Controlling arthropods, worms and / or malarial parasites reduces mortality in domestic animals and improves the productivity (meat, milk, wool, hides, eggs and honey) and health of the animals.

[0233] In a possible implementation, the animal parasite control agent is used to control one or more of cat fleas and American dog 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, buffaloes, rabbits, chickens, turkeys, ducks, geese, farmed fish, bees, etc.; also include pets known as companion animals, such as dogs, cats, caged birds, ornamental fish; also include animals used for experiments, such as hamsters, guinea pigs, rats and mice, etc.

[0235] The embodiment of the present invention further provides an animal parasite control agent, which contains the above-mentioned amide compound as an active component and one or more auxiliary materials.

[0236] In one possible implementation, the animal parasite control agent is selected from the following dosage forms: tablets, capsules, drinks, drinkable medicines, granules, ointments and pills, suppositories, injections (muscular, subcutaneous, intravenous, intraperitoneal, etc.), ointments, aerosols, non-pressure sprays (such as pump sprays and atomized sprays).

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

[0238] The present invention also provides an animal parasite control composition, which includes a mixture of the above-mentioned amide compounds and other animal parasite control active compounds (such as acaricides, insecticides, parasiticides, antimalarial protozoa, etc.). The mixture can be provided in the form of a bulk drug, or in the form of a commercially available preparation or a use form prepared from the preparation.

[0239] The embodiment of the present invention also provides a method for controlling animal parasites, which comprises the following steps: applying an effective dose of a material to the animal parasites to be controlled or their 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 agent; the above-mentioned animal parasite control composition. For example: enteral administration using tablets, capsules, potions, drinkable medicines, granules, ointments, pills, suppositories; non-enteral administration based on skin administration, such as injection (muscle, subcutaneous, intravenous, intraperitoneal, etc.), implantation, nasal administration, including bathing or soaking, spraying, pouring, dripping, washing and dusting, and administration by using model products containing active compounds, such as collars, ear tags, tags, leg braces, nets, markers, etc. The active compounds of the present invention have low toxicity and can be safely used in warm-blooded animals.

[0240] Beneficial Effects

[0241] The amide compounds of the present invention have unexpectedly excellent insecticidal effects, and they also show suitable control effects on toxic pests, and have no phytotoxicity to cultivated crop plants. In addition, the compounds of the present invention can be used to control a variety of pests, such as harmful piercing-sucking insects, chewing insects and other plant parasitic pests, stored grain pests, sanitary pests, etc., and can be used to disinfect and kill them. DETAILED DESCRIPTION

[0242] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be described clearly and completely below. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0243] In addition, in order to better illustrate the present invention, numerous specific details are provided in the specific embodiments below. It should be understood by those skilled in the art that the present invention can also be implemented without certain specific details. In some embodiments, raw materials, elements, methods, means, etc. well known to those skilled in the art are not described in detail, so as to highlight the main purpose of the present invention.

[0244] Unless explicitly stated otherwise, throughout the specification and claims, the term “comprise” or variations such as “include” or “comprising”, etc., will be understood to include the stated elements or components but not to exclude other elements or components.

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

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

[0247] Halogen: refers to fluorine, chlorine, bromine or iodine.

[0248] Haloalkyl: a straight-chain or branched alkyl group, in which the hydrogen atoms may be partially or completely replaced by halogens, such as difluoromethyl (CHF2), trifluoromethyl (CF3), etc.

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

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

[0251] Propargyl: -CH2-C≡CH.

[0252] Pesticide: A substance that has an insecticidal effect on pests.

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

[0254] Synthesis Example

[0255] According to the synthetic route described above, different raw material compounds can be used to prepare the compounds represented by general formulas I to VII of the present invention, which are further described as follows:

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

[0257]

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

[0259] 0.50 g (2.96 mmol) of methyl 2-fluoro-3-aminobenzoate, 0.70 g (5.94 mmol) of propargyl bromide, and 1.15 g (8.90 mmol) of N,N-diisopropylethylamine were added to 10 ml of toluene, and the temperature was raised to reflux for reaction. The reaction progress was monitored by TLC. After the reaction of the raw materials was complete, 0.58 g (4.14 mmol) of benzoyl chloride was added. After the reaction was completed by TLC monitoring, water and ethyl acetate were added for extraction. The organic phase was desolvated under reduced pressure, and the residue was purified by column chromatography to obtain 0.72 g of a white solid, namely methyl 2-fluoro-3-(N-(prop-2-yn-1-yl)benzamido)benzoate (III.7); the NMR and mass spectrometry data of the 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)benzamido)benzoic acid (II.7)

[0262] To 10 ml of acetonitrile, 0.58 g (1.86 mmol) of methyl 2-fluoro-3-(N-(prop-2-yn-1-yl)benzamido)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, and the temperature was raised to 50 degrees for reaction. After the reaction was completed by TLC monitoring, the pH value was adjusted to about 2-3 with dilute hydrochloric acid, and water and ethyl acetate were added for extraction. The organic phase was desolvated under reduced pressure to obtain 0.52 g of a white solid, namely, 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-(perfluoropropan-2-yl)-6-(trifluoromethyl)phenyl)-2-fluorobenzamide (prepared by the method reported in WO2011093415 or WO2010018714) and 0.30 g (2.00 mmol) of sodium iodide were added to 10 ml of DMF, and 0.22 g (1.83 mmol) of allyl bromide was added dropwise under stirring, and the reaction was carried out at room temperature. After the reaction was completed by TLC detection, water and ethyl acetate were added for extraction, the organic phase was desolvated under reduced pressure, and the residue was purified by column chromatography to obtain 0.34 g of a white solid, i.e., the intermediate compound V.3. The NMR and mass spectrometry data of the 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 by the method reported in WO2011093415 or WO2010018714) and 0.30 g (3.81 mmol) of sodium iodide were added to 20 ml of DMF, and 0.41 g (3.42 mmol) of allyl bromide was added dropwise under stirring, and the reaction was carried out at room temperature. After the reaction was completed by TLC detection, water and ethyl acetate were added for extraction, the organic phase was desolvated under reduced pressure, and the residue was purified by column chromatography to obtain 0.60 g of a white solid, i.e., the intermediate compound V.4. The NMR and mass spectrometry data of the 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-(perfluoropropan-2-yl)-6-(trifluoromethyl)phenyl)-2-fluorobenzamide and 0.31 g (2.07 mmol) of sodium iodide were added to 10 ml of DMF, and 0.22 g (1.87 mmol) of propyne bromide was added dropwise under stirring, and the temperature was raised to 40 degrees for reaction. After the reaction was completed by TLC detection, water and ethyl acetate were added for extraction, the organic phase was desolvated under reduced pressure, and the residue was purified by column chromatography to obtain 0.26 g of a white solid, namely, the intermediate compound V.9. The NMR and mass spectrometry data of the 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, and 0.20 g (1.70 mmol) of propyne bromide was added dropwise under stirring, and the temperature was raised to 40 degrees for reaction. After the reaction was completed by TLC detection, water and ethyl acetate were added for extraction, the organic phase was desolvated under reduced pressure, and the residue was purified by column chromatography to obtain 0.31 g of a white solid, namely, the intermediate compound V.10. The NMR and mass spectrometry data of the 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 heated to reflux. After the reaction was completed by TLC, the solvent was removed under reduced pressure and the residue was purified by column chromatography to obtain 0.13 g of a white solid, i.e., 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 heated to reflux. After the reaction was completed by TLC, the solvent was removed under reduced pressure and the residue was purified by column chromatography to obtain 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-fluoronicotinoyl chloride were added to 10 ml of toluene and heated to reflux. After the reaction was completed by TLC, the solvent was removed under reduced pressure and the residue was purified by column chromatography to obtain 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-fluoronicotinoyl chloride were added to 10 ml of toluene and heated to reflux. After the reaction was completed by TLC, the solvent was removed under reduced pressure and the residue was purified by column chromatography to obtain 0.09 g of a white solid, i.e., 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 heated to reflux. After the reaction was completed by TLC, the solvent was removed under reduced pressure and the residue was purified by column chromatography to obtain 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] To 10 ml of toluene, add 0.22 g (0.68 mmol) of intermediate II.7 and 0.44 g (3.70 mmol) of thionyl chloride, and heat under reflux for 4 hours; remove the solvent under reduced pressure to obtain the intermediate 2-fluoro-3-(N-(prop-2-yn-1-yl)benzamido)benzoyl chloride, which is sealed for later use.

[0304] The intermediate 2-fluoro-3-(N-(prop-2-yn-1-yl)benzamido)benzoyl chloride prepared above and 0.08 g (0.78 mmol) of sodium bromide and 0.30 g (0.74 mmol) of 2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline (prepared by the method reported in WO2011093415 or WO2010018714) were added to 10 ml of acetonitrile and heated to reflux; after the reaction was completed by TLC detection, the solvent was removed under reduced pressure and the residue was purified by column chromatography to obtain 0.23 g of a white solid, i.e., 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 the intermediate 2-fluoro-3-(N-(prop-2-yn-1-yl)benzamido)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 by the method reported in WO2011093415 or WO2010018714) were added to 10 ml of acetonitrile and heated to reflux. After the reaction was completed by TLC detection, water and ethyl acetate were added for extraction, the organic phase was desolvated under reduced pressure, and the residue was purified by column chromatography to obtain 0.39 g of a white solid, namely, the intermediate compound VI.7.

[0310] (2) Preparation of Compound 31

[0311] To 10 ml of N,N-dimethylformamide, 0.30 g (0.49 mmol) of intermediate VI.7, 0.02 g (0.50 mmol) of sodium hydride (60% mass fraction), and 0.10 g (0.56 mmol) of N-bromosuccinimide were added, and the temperature was raised to 40 degrees for reaction. After the reaction was completed by TLC, water and ethyl acetate were added for extraction, the organic phase was desolvated under reduced pressure, and the residue was purified by column chromatography to obtain 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 temperature was raised to 40 degrees; 0.64 g (1.21 mmol) of sodium hypochlorite aqueous solution (14% mass fraction) was added dropwise to the reaction solution, and the reaction was continued at 40 degrees. After the reaction was completed by TLC detection, water and ethyl acetate were added for extraction, the organic phase was desolvated under reduced pressure, and the residue was purified by column chromatography to obtain 0.23 g of a white solid, namely 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 heated to reflux. After the reaction was completed by TLC, the solvent was removed under reduced pressure and the residue was purified by column chromatography to obtain 0.13 g of a yellow oil, i.e., 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-fluoronicotinoyl chloride were added to 10 ml of toluene and heated to reflux. After the reaction was completed by TLC, the solvent was removed under reduced pressure and the residue was purified by column chromatography to obtain 0.09 g of a white solid, i.e., 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-fluoronicotinoyl chloride were added to 10 ml of toluene and heated to reflux. After the reaction was completed by TLC, the solvent was removed under reduced pressure and the residue was purified by column chromatography to obtain 0.09 g of a yellow oil, i.e., 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 the general formula I to VII of the present invention can be prepared by referring to the above examples.

[0330] The physicochemical properties, NMR and mass spectrometry data of some compounds of the present 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] Biological activity assay

[0380] Example 14: Insecticidal biological activity assay

[0381] The compounds of the present invention were used to carry out insecticidal activity tests on several insects. The test method is as follows:

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

[0383] The activity was determined by the Airbrush spray method, with armyworm, diamondback moth, striped stem borer, beet armyworm, green peach aphid and western flower thrips as targets.

[0384] (1) Activity determination against armyworms

[0385] Test method: Cut corn leaves into 2 cm long segments and spray with Airbrush at a pressure of 10 psi (about 0.7 kg / cm 2 ), spray each leaf segment on both sides, with a spray volume of 0.5 mL of the test compound. After drying in the shade, inoculate 10 3rd instar larvae per treatment, with 3 replicates per treatment. After treatment, place in an observation room at 25°C and relative humidity of 60-70% for incubation. 3 days after the drug application, investigate the number of surviving insects and calculate the mortality rate.

[0386] Some of the test results on armyworms are as follows:

[0387] At a dosage of 0.05 mg / L, 3 days after administration, the lethality of 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 to armyworms was over 90%.

[0388] (2) Determination of activity against Plutella xylostella

[0389] Test method: Use a punch to punch cabbage leaves into leaf discs with a diameter of 2 cm and use an Airbrush spray to treat them at a pressure of 10 psi (about 0.7 kg / cm 2 ), spray each leaf disc on both sides, with the spray volume of the test compound being 0.5 mL. After drying in the shade, 10 3rd instar larvae were inoculated for each treatment, and each treatment was repeated 3 times. After treatment, the leaves were placed in an observation room at 25°C and a relative humidity of 60-70% for cultivation. The number of surviving insects was investigated 3 days after the application, and the mortality rate was calculated.

[0390] Some of the test results on Plutella xylostella are as follows:

[0391] At a dosage of 1.25 mg / L, the mortality rates of 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 to Plutella xylostella were over 90%.

[0392] According to the above test method, some compounds of the present invention and reference compounds KC1, KC2, KC9, KC10 were further selected for parallel determination of their activities against Plutella xylostella. The test results are shown in Table 12.

[0393] Table 12 Parallel comparison test of insecticidal activity of some compounds of the present invention and reference compounds KC1, KC2, KC9 and KC10 against Plutella xylostella

[0394]

[0395]

[0396]

[0397]

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

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

[0400] According to the above test method, the compounds 3, 7, 8, 19, 20, 31, 35, 36, 47, 48 of the present invention and the control compounds KC3, KC4, KC5, KC6, KC7, KC8 were further selected for parallel determination of their activities against Plutella xylostella. The test results are shown in Table 13.

[0401] Table 13 Parallel comparison test of insecticidal activity of some compounds of the present invention and control compounds against Plutella xylostella

[0402]

[0403]

[0404]

[0405] As shown in Table 13, by comparing compounds 3 and 31 with the control compound KC3, by comparing compounds 7 and 35 with the control compound KC4, by comparing compounds 8 and 36 with the control compound KC5, by comparing compounds 19 and 47 with the control compound KC7, and by comparing compounds 20 and 48 with the 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 in the compound of formula I, a compound with better insecticidal effect is obtained compared with the prior art.

[0406] (3) Determination of activity against Chilo suppressalis

[0407] Determination method: 1) Preparation of rice seedlings: Cultivate rice in a plastic cup with a diameter of 4.5 cm and a height of 4 cm in a constant temperature room (temperature 26-28°C, relative humidity of about 60-80%, and light 16hL:8hD). When the rice grows to the 4-5 leaf stage, select strong and uniformly growing rice seedlings for drug treatment, and set up 3 replicates for each treatment. 2) Preparation of test insects: 3rd instar larvae of the Chilo suppressalis continuously raised indoors. 3) Spraying of rice stems for insect inoculation. Use the spray method to evenly spray the entire rice seedling, with 15 mL of drug used for each treatment. Treat the blank control first, and then repeat the above operation in the order of test concentration from low to high. After the rice seedlings are sprayed, place them in a cool place to dry the drug solution, and cut about 5 cm of the stem base to feed the test insects. Prepare a glass culture dish with a diameter of 90 mm, place filter paper on the bottom of the dish, add water to keep it moist, put about 5 rice stems in each dish, pick up 10 larvae, seal the dish with non-woven fabric, and place it in a constant temperature room for cultivation. 3 days after the drug is applied, check the number of remaining live insects.

[0408] Some test results on Chilo suppressalis are as follows:

[0409] At a dosage of 0.625 mg / L, the mortality rates of 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 to Chilo suppressalis were above 90%.

[0410] (4) Determination of activity against beet armyworm

[0411] Determination method: Use the leaf disc feeding method to test the activity. Dip the leaf disc into the drug solution for 10 seconds, dry it and place it in a culture dish, 4 discs per dish, and put filter paper in the culture dish to keep it moist. Inoculate 10 beet armyworms in each dish, and repeat 3 times. Place it in a light incubator at 25℃ and 14hL:10hD for cultivation. Investigate the number of dead beet armyworms 1, 2, and 3 days after drug administration, and calculate the mortality rate.

[0412] The results of the test on Spodoptera exigua were as follows:

[0413] At a dosage of 0.625 mg / L, 3 days after application, the mortality rate of 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 to beet armyworm was over 90%.

[0414] (5) Determination of activity against peach aphid

[0415] Determination method: Take a 6cm diameter culture dish, cover the bottom of the dish with a layer of filter paper, and add an appropriate amount of tap water to keep it moist. Cut a cabbage leaf of appropriate size (about 3cm in diameter) with 15 to 30 aphids from the cabbage plant where peach aphids are cultured, remove the winged aphids and the aphids on the front of the leaf, and place the leaf with the back facing up in the culture dish. The pressure of the airbrush spray treatment is 10psi (about 0.7kg / cm2), the spray volume is 0.5mL, and each treatment is repeated 3 times. After treatment, place it in an observation room at 25℃ and relative humidity of 60-70% for culture. After 48 hours, investigate the number of surviving insects and calculate the mortality rate.

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

[0417] At a dosage of 50 mg / L, the mortality rate of 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 to peach aphid was over 90%.

[0418] (6) Determination of activity against western flower thrips

[0419] Determination method: Select fresh bean leaves grown in the greenhouse, spray them evenly with a handheld Airbrush sprayer, 1 mL per treatment, dry them naturally in the shade, place them in finger-shaped tubes, and inoculate neat and healthy western flower thrips nymphs, 15 per treatment, the test is repeated 3 times, and water treatment is used as a blank control. After treatment, place them in a room at 24°C, relative humidity 60%-70%, and natural light for cultivation. After 72 hours, investigate the number of surviving insects and calculate the mortality rate.

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

[0421] At a dosage 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 mortality rate of more than 90% against western flower thrips.

[0422] According to the above test method, the compounds 3, 7, 8, 19, 20, 31, 35, 36, 47, 48 of the present invention and the control compounds KC3, KC4, KC5, KC6, KC7, KC8 were further selected for parallel determination of their activities against western flower thrips nymphs. The test results are shown in Table 14.

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

[0424]

[0425]

[0426]

[0427] As shown in Table 14, by comparing compounds 3 and 31 with the control compound KC3, by comparing compounds 7 and 35 with the control compound KC4, by comparing compounds 8 and 36 with the control compound KC5, by comparing compounds 19 and 47 with the control compound KC7, and by comparing compounds 20 and 48 with the 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 in the compound of formula I, a compound with better insecticidal effect is obtained compared with the prior art.

[0428] Example 15: Insecticidal test on cat fleas

[0429] 4 mg of the compound to be tested 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 applied to the bottom and sides of a culture dish with an inner diameter of 5.3 cm. After the acetone evaporated, a thin film of the compound of the present invention was formed on the inner wall of the culture dish. The inner wall of the culture dish used was 40 cm. 2 , the treatment dose is 1μg / cm 2 ; 10 adult cat fleas (mixed males and females) were placed therein, and the mixture was covered and stored in a constant temperature room at 25°C. The number of dead fleas after 72 hours was checked, and the mortality rate was calculated. The test was repeated 3 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 more than 90%.

[0430] Example 16: Insecticidal test on American dog tick

[0431] 4 mg of the compound to be tested 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 applied to the bottom and side surfaces of two culture dishes with an inner diameter of 5.3 cm. After the acetone evaporated, a thin film of the compound of the present invention was formed on the inner wall of the culture dish. The inner wall of the culture dish used was 40 cm. 2 , the treatment dose is 1μg / cm 2. 10 first nymphs of American dog ticks (mixed males and females) were placed therein, two culture dishes were combined, the joints were sealed with tape to prevent escape, and the dishes were stored in a constant temperature room at 25°C. The number of dead insects after 24 hours was checked, and the mortality rate was calculated. The test was repeated 3 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 more than 90%.

Claims

1. An amide compound, characterized in that: The structure of the amide compound is shown in general formula I: In the general formula I: R1 is selected from hydrogen, 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 The amide compound is selected from: The compound of Table 1, the compound of Table 1 has a structure as shown in Formula I and R1, X, R2, R3 and R4 are as shown in Table 1; Table 1 3. The amide compound according to claim 2, characterized in that The amide compound is selected from: The compound of Table 2, the compound of Table 2 has a structure as shown in Formula I and R1, X, R2, R3 and R4 are as shown in Table 2; Table 2 4. The amide compound according to claim 3, characterized in that The amide compound is selected from: The compound of Table 3, the compound of Table 3 has a structure as shown in Formula I and R1, X, R2, R3 and R4 are as shown in Table 3; Table 3 5. A compound, which is an intermediate for preparing the amide compound according to any one of claims 1 to 4, characterized in that: The compound has a structure shown in the following general formula V: In the 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 The compound is selected from: The compound of Table 7, the compound of Table 7 has a structure as shown in Formula V and R2, R3 and R4 are as shown in Table 7; Table 7 7. The compound according to claim 6, characterized in that The compound is selected from: The compound of Table 8, the compound of Table 8 has a structure as shown in Formula V and R2, R3 and R4 are as shown in Table 8; Table 8 。 8. A compound, which is an intermediate for preparing the amide compound according to any one of claims 1 to 4, characterized in that: The compound has the structure shown in the following general formula VI: In general formula VI: R1 is selected from hydrogen, 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 The compound is selected from: The compound of Table 9, the compound of Table 9 has a structure as shown in Formula VI and R1, X, R2 and R4 are as shown in Table 9; Table 9 。 10. The compound according to claim 9, characterized in that The compound is selected from: The compound of Table 10, the compound of Table 10 has a structure as shown in Formula VI and R1, X, R2 and R4 are as shown in Table 10; Table 10 。 11. A method for preparing an amide compound as claimed in any one of claims 1 to 4, characterized in that: The preparation method comprises reacting an intermediate compound as shown in the general formula VI with a suitable halogenating agent in a suitable solvent to obtain a compound of the general formula I. The compound reaction formula is as follows:

12. The method for preparing an amide compound according to claim 11, characterized in that: The compound of general formula VI is reacted with a suitable base and a halogenating agent in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain a compound of general formula I.

13. The method for preparing an amide compound according to claim 11 or 12, characterized in that: Suitable halogenating agents are selected from chlorine gas, 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; 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 mixed solvents thereof; The reaction temperature is preferably 0°C-100°C; more preferably 25°C-80°C.

14. The method for preparing an amide compound according to claim 12, wherein: Suitable bases are 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.

15. Use of the amide compound according to any one of claims 1 to 4 in the preparation of pesticides.

16. The use according to claim 15, characterized in that: The insecticide is used for preventing and controlling one or more of the group consisting of diamondback moth, armyworm, beet armyworm, Spodoptera litura, striped stem borer, peach aphid, thrips and flea beetle.

17. An insecticide preparation, characterized in that: The insecticide preparation contains the amide compound according to any one of claims 1-4 as an active ingredient, and also contains one or more adjuvants; optionally, the amount of the amide compound according to any one of claims 1-4 in the insecticide preparation is 0.1 to 99% by weight, further optionally 0.5 to 90% by weight.

18. An insecticide composition, characterized in that: A mixture comprising the amide compound according to any one of claims 1 to 4 and other active compounds, wherein the other active compounds are selected from one or more of insecticides, baits, disinfectants, miticides, nematicides, fungicides, growth regulators, and herbicides.

19. A method for controlling agricultural or forestry pests, characterized in that: An effective amount of material is applied to the pest to be controlled or its growth medium, wherein the material is selected from one or more of the following groups: The amide compound according to any one of claims 1 to 4; The insecticide preparation according to claim 17; The insecticide composition according to claim 18.

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

21. The use according to claim 20, characterized in that: The animal parasite control agent is used for controlling one or more of cat fleas and American dog ticks.

22. An animal parasite control agent, characterized in that: The animal parasite control agent contains the amide compound according to any one of claims 1 to 4 as an active ingredient, and also contains one or more auxiliary materials; optionally, the amount of the amide compound according to any one of claims 1 to 4 in the animal parasite control agent is 1 to 80% by weight.

23. An animal parasite control composition, characterized in that: A mixture comprising the amide compound according to any one of claims 1 to 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, parasiticides, and antimalarials.

24. A method for controlling animal parasites, characterized in that: The following steps are involved: An effective dose of material is applied 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 amide compound according to any one of claims 1 to 4; The animal parasite control agent according to claim 22; The animal parasite control composition according to claim 23.

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