4-(trifluoromethyl) picolinamide compound and application thereof

Abstract

The invention provides a 4-(trifluoromethyl) picolinamide compound and application thereof. The 4-(trifluoromethyl) picolinamide compound is a compound represented by a formula I, or a stereoisomer, a tautomer, an isotope derivative and a pesticide acceptable salt thereof. The 4-(trifluoromethyl) picolinamide compound disclosed by the invention has particularly excellent insecticidal activity on piercing-sucking mouthpart pests and filing-sucking mouthpart pests such as aphids and thrips, and has an excellent effect on preventing and treating hemiptera, thysanoptera and diptera, and the prevention and treatment effect is superior to that of a commercially available commercial insecticide flonicamid.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of agricultural insecticides, and particularly relates to a 4-(trifluoromethyl) pyridine amide compound and application thereof. BACKGROUND

[0002] Nicotinamide enzyme, as a key enzyme in the synthesis pathway of nicotinamide adenine dinucleotide (NAD, coenzyme I), its function is to convert nicotinamide into nicotinic acid, an intermediate of NAD. When the activity of nicotinamide enzyme is inhibited, a large amount of nicotinamide will accumulate in the cell, which will excessively activate the transient receptor potential vanilloid ion channel (TRPV) on the chordotonal organ of insects, resulting in toxic symptoms of pests and eventually death. This finding provides a new idea for the research and development of new insecticides.

[0003] At present, only two kinds of nicotinamide enzyme insecticides have been developed, namely, flonicamid and 4-(trifluoromethyl) nicotinamide. The 4-(trifluoromethyl) nicotinamide is a metabolic product of flonicamid. Both of them have high activity on piercing-sucking mouthpart pests and thrips and other rasping-sucking mouthpart pests, and have low pest resistance, high activity, low dosage, and good environmental compatibility. Moreover, nicotinamide enzyme only exists in insects and microorganisms, and does not exist in vertebrates, which makes the insecticide targeting nicotinamide enzyme have low toxicity to mammals and aquatic organisms, and has broad development prospects.

[0004] Some 4-(trifluoromethyl) pyridine amide compounds have been reported as insecticides, but these insecticides have low activity. Therefore, there is still a need in the art to develop new 4-(trifluoromethyl) pyridine amide insecticides with high insecticidal activity to solve the problem of pest control in agricultural, forestry and horticultural production. SUMMARY

[0005] The purpose of the present application is to provide a 4-(trifluoromethyl) pyridine amide compound with high insecticidal activity, which has excellent insecticidal effect on piercing-sucking mouthpart pests and rasping-sucking mouthpart pests, such as aphids.

[0006] To achieve the above purpose, in a first aspect, the present application provides a 4-(trifluoromethyl) pyridine amide compound, which is a compound represented by formula I, or a stereoisomer, a tautomer, an isotopic derivative and a pesticide-acceptable salt thereof: , wherein R1, R2 are each independently selected from H, alkyl, alkynyl, -C(=NH)-S-alkyl, -C(=NH)-S-alkylene-COOH, -alkylene-O-CO-carbocyclyl, -alkylene-O-CO-heterocyclyl, -CO-O-alkyl, -CO-O-carbocyclyl, -CO-O-heterocyclyl, -CO-alkyl, -CO-carbocyclyl, -CO-heterocyclyl, ; L is selected from -NR3-, -CR4=N-*, -alkylene-NR3-*, -alkenylene-NR3-*, - alkynylene-NR3-*, * represents the point of attachment to -CO-; R3is selected from H, alkylene; R4is selected from halogen, amino, hydroxyl, nitro, cyano, thiol, alkyl, alkyloxy, alkylthio, or alkylamino; at least one of R1, R2is not selected from H or alkyl; alternatively, R1, R2together with the nitrogen to which they are attached form a nitrogen containing heterocyclyl group; said carbocyclyl, heterocyclyl is optionally substituted with one or more substituents selected from oxo, halogen, amino, hydroxyl, nitro, cyano, thiol, alkyl, alkyloxy, alkylthio, or alkylamino; said alkyl, alkynyl, alkylene, alkenylene, alkynylene, alkyloxy, alkylthio, or alkylamino is optionally substituted with one or more substituents selected from halogen, amino, hydroxyl, nitro, cyano, thiol, alkylsilyl.

[0007] In some embodiments, the alkyl is a C1-10straight chain or branched chain alkyl, preferably a C1-8alkyl, C1-6alkyl, C3-6alkyl (such as C3-6branched chain alkyl), C1-C4alkyl, such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, n-pentyl, neopentyl, n-hexyl, and the like.

[0008] In some embodiments, the alkylene is a C1-8alkylene, preferably a C1-8alkylene, C1-6alkylene, C1-C4alkylene, such as methylene, ethylene, propylene, butylene, and the like.

[0009] In some embodiments, the alkenylene is a C2-10alkenylene, preferably a C2-8alkenylene, C2-6alkenylene, C2-C4alkenylene, such as ethenylene, propenylene, butenylene, and the like.

[0010] In some embodiments, the alkynyl is a C2-10alkynyl, preferably a C2-8alkynyl, C2-6alkynyl, C2-C4alkynyl, such as ethynyl, 1-propynyl, 2-propynyl, propargyl, 2-butyn-1-yl, and the like.

[0011] In some embodiments, the alkynylene is a C2-10alkynylene, preferably a C2-8alkynylene, C2-6alkynylene, C2-C4alkynylene, such as ethynylene, propynylene, butynylene, -CH2-C C-CH2-, and the like.

[0012] In some embodiments, the carbocyclyl represents a saturated, unsaturated or partially unsaturated monocyclic or polycyclic ring system containing 3-10 carbon atoms, such as a monocyclic ring system containing 3-6 carbon atoms, or a polycyclic ring system containing 7-10 carbon atoms (such as a bicyclic ring). The carbocyclyl can be a saturated cycloalkyl group, or an unsaturated aryl group. The cycloalkyl group is a C3-10 cycloalkyl group, preferably a C3-8 cycloalkyl group, a C3-6 cycloalkyl group, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like. The aryl group is a C6-10 aryl group, preferably a phenyl group, a naphthyl group (such as 1-naphthyl, 2-naphthyl).

[0013] In some embodiments, the heterocyclyl represents a saturated, unsaturated or partially unsaturated monocyclic or polycyclic ring system containing a 3-10 membered structure, wherein 1, 2, 3, 4 or more ring atoms are heteroatoms and the remaining atoms are carbon, the heteroatoms being independently selected from O, N or S. The heterocyclyl can be a monocyclic ring system containing a 3-6 membered structure, or a polycyclic ring system containing a 7-10 membered structure (such as a bicyclic ring). The heterocyclyl can be a saturated heterocycloalkyl group, or an unsaturated heteroaryl group. The heterocycloalkyl group is a 3-10 membered heterocycloalkyl group, a 3-8 membered heterocycloalkyl group, a 3-6 membered heterocycloalkyl group. The heterocycloalkyl group contains 1-3 heteroatoms selected from N, O, S. The heterocycloalkyl group is a 3-10 membered heterocycloalkyl group, a 3-8 membered heterocycloalkyl group, containing 1-3 heteroatoms selected from N, O, S, such as a 3-6 membered heterocycloalkyl group containing 1-2 heteroatoms selected from N, O, S. The heterocycloalkyl group is a 3-10 membered heterocycloalkyl group, a 3-8 membered heterocycloalkyl group, containing 1 nitrogen atom and additionally 0-2 heteroatoms selected from N, O, S, such as a 3-6 membered heterocycloalkyl group additionally containing 0-1 heteroatom selected from N, O, S. The heteroaryl group is a 5-10 membered heteroaryl group. The heteroaryl group contains 1-3 heteroatoms selected from N, O, S. The heteroaryl group is a 5-10 membered heteroaryl group containing 1-3 heteroatoms selected from N, O, S, such as a 5-6 membered heteroaryl group containing 1-2 heteroatoms selected from N, O, S. The heterocyclyl can be a tetrahydrothiazolyl group, a tetrahydrooxazolyl group, a pyrrolidinyl group, an imidazolidinyl group, a pyrazolidinyl group, a piperidinyl group, a piperazinyl group, a morpholinyl group, a thiomorpholinyl group, a pyridyl group, a pyrazinyl group, an indolyl group, a phthalimidyl group, and the like.

[0014] In some embodiments, the halogen is fluorine, chlorine, bromine, iodine.

[0015] (I) In some embodiments, R1is selected from H, C1-6 alkyl, C2-6 alkynyl, and R2is selected from C2-6 alkynyl; the alkyl, alkynyl groups are optionally substituted with one or more substituents selected from halogen, amino, hydroxyl, nitro, cyano, thiol, C1-6 alkylsilyl groups.

[0016] In some embodiments, R1is selected from H, C1-6alkyl; preferably, R1is selected from H, C1-4alkyl; more preferably, R1is selected from H, methyl, ethyl.

[0017] In some embodiments, R2is selected from C2-6alkynyl, C2-6haloalkynyl, C1-6alkylsilyl-substituted C2-6alkynyl. Preferably, R2is selected from C2-4alkynyl, C2-4fluoroalkynyl, C2-4chloroalkynyl, C2-4bromoalkynyl, C2-4iodoalkynyl, trimethylsilyl-substituted C2-4alkynyl, triethylsilyl-substituted C2-4alkynyl. More preferably, R2is selected from -CH2-C CH, -CH2-C C-Br, -CH2-C C-I, -CH2-C C-CH3, -CH2-C C-Si(CH3)3.

[0018] In particular, the compound of formula I is one of the following compounds: , , , , .

[0019] (II) In some embodiments, R1is selected from H, C1-6alkyl, C2-6alkynyl, -C(=NH)-S-C1-6alkyl, -C(=NH)-S-C1-6alkylene-COOH, R2is selected from -C(=NH)-S-C1-6alkyl, -C(=NH)-S-C1-6alkylene-COOH; said alkyl, alkynyl, alkylene are optionally substituted with one or more substituents selected from halogen, amino, hydroxyl, nitro, cyano, mercapto, C1-6alkylsilyl.

[0020] In some embodiments, R1is selected from H, C1-4alkyl, C2-4alkynyl, preferably, R1is selected from H, methyl, ethyl.

[0021] In some embodiments, R2is selected from -C(=NH)-S-C1-6alkyl, -C(=NH)-S-C1-6alkylene-COOH. Preferably, R2is selected from -C(=NH)-S-C1-4alkyl, -C(=NH)-S-C1-4alkylene-COOH. More preferably, R2is selected from -C(=NH)-S-methyl, -C(=NH)-S-ethyl, -C(=NH)-S-n-propyl, -C(=NH)-S-i-propyl, -C(=NH)-S-n-butyl, -C(=NH)-S-CH2-COOH, -C(=NH)-S-CH2CH2-COOH, -C(=NH)-S-CH2CH2CH2-COOH, -C(=NH)-S-CH2CH2CH2CH2-COOH.

[0022] In particular, the compound of formula I is one of the following compounds: , .

[0023] (III) In some embodiments, R1is selected from H, C1-6alkyl, C2-6alkynyl, -C1-6alkylene-O-CO-C3-10carbocyclyl, -C1-6alkylene-O-CO-3-10membered heterocyclyl, -CO-O-C1-6alkyl, -CO-O-C3-10carbocyclyl, -CO-O-3-10membered heterocyclyl, -CO-C1-6alkyl, -CO-C3-10carbocyclyl, -CO-3-10membered heterocyclyl; R2is selected from -C1-6alkylene-O-CO-C3-10carbocyclyl, -C1-6alkylene-O-CO-3-10membered heterocyclyl, -CO-O-C1-6alkyl, -CO-O-C3-10carbocyclyl, -CO-O-3-10membered heterocyclyl, -CO-C1-6alkyl, -CO-C3-10carbocyclyl, -CO-3-10membered heterocyclyl; said carbocyclyl, heterocyclyl is optionally substituted with one or more substituents selected from oxo, halo, amino, hydroxyl, nitro, cyano, thiol, alkyl, alkyl-oxyl, alkyl-thiol, or alkyl-amine; said alkyl, alkynyl, alkylene, alkyl-oxyl, alkyl-thiol, or alkyl-amine is optionally substituted with one or more substituents selected from halo, amino, hydroxyl, nitro, cyano, thiol, alkyl-silyl.

[0024] In some embodiments, R1is selected from H, C1-6alkyl, C2-6alkynyl, -C1-6alkylene-O-CO-C3-10cycloalkyl, -C1-6alkylene-O-CO-3-10 membered heterocycloalkyl, -CO-O-C1-6alkyl, -CO-O-C3-10cycloalkyl, -CO-O-3-10 membered heterocycloalkyl, -CO-C1-6alkyl, -CO-C3-10cycloalkyl, -CO-3-10 membered heterocycloalkyl; R2is selected from C1-6alkylene-O-CO-C3-10cycloalkyl, -C1-6alkylene-O-CO-3-10 membered heterocycloalkyl, -CO-O-C1-6alkyl, -CO-O-C3-10cycloalkyl, -CO-O-3-10 membered heterocycloalkyl, -CO-C1-6alkyl, -CO-C3-10cycloalkyl, -CO-3-10 membered heterocycloalkyl.

[0025] In some embodiments, the C1-6alkyl is selected from C3-6alkyl (e.g., branched alkyl), C1-4alkyl, which can be selected from methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, t-butyl, n-pentyl, neopentyl, n-hexyl.

[0026] In some embodiments, the C2-6alkynyl is selected from C2-4alkynyl, preferably ethynyl, 1-propynyl, 2-propynyl, propargyl.

[0027] In some embodiments, the C1-6alkylene is selected from C1-4alkylene, e.g., methylene, ethylene, propylene.

[0028] In some embodiments, the C3-10cycloalkyl is selected from C3-6cycloalkyl; preferably, from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl.

[0029] In some embodiments, R1is selected from H, C1-4alkyl, C2-4alkynyl, -methylene-O-CO-C3-6cycloalkyl, -CO-O-C3-6alkyl, -CO-O-C3-6cycloalkyl, -CO-C3-6alkyl, -CO-C3-6cycloalkyl; R2is selected from -methylene-O-CO-C3-6cycloalkyl, -CO-O-C3-6alkyl, -CO-O-C3-6cycloalkyl, -CO-C3-6alkyl, -CO-C3-6cycloalkyl. The C3-6alkyl is preferably C3-6branched alkyl.

[0030] Preferably, R1 is selected from H, methyl, ethyl, propargyl, -methylene-O-CO-cyclopropyl, -methylene-O-CO-cyclobutyl, -methylene-O-CO-cyclopentyl, -methylene-O-CO-cyclohexyl, -CO-O-isopropyl, -CO-O-tert-butyl, -CO-O-neopentyl, -CO-O-cyclopropyl, -CO-O-cyclobutyl, -CO-O-cyclopentyl, -CO-O-cyclohexyl, -CO-isopropyl, -CO-tert-butyl, -CO-neopentyl, -CO-cyclopropyl, -CO-cyclobutyl, -CO-cyclopentyl, -CO-cyclohexyl; R2 is selected from -methylene-O-CO-cyclopropyl, -methylene-O-CO-cyclobutyl, -methylene-O-CO-cyclopentyl, -methylene-O-CO-cyclohexyl, -CO-O-isopropyl, -CO-O-tert-butyl, -CO-O-neopentyl, -CO-O-cyclopropyl, -CO-O-cyclobutyl, -CO-O-cyclopentyl, -CO-O-cyclohexyl, -CO-isopropyl, -CO-tert-butyl, -CO-neopentyl, -CO-cyclopropyl, -CO-cyclobutyl, -CO-cyclopentyl, -CO-cyclohexyl.

[0031] In some embodiments, R1 and R2 are the same group.

[0032] Specifically, the compound of formula I is one of the following compounds: , , , , , , , , , , , .

[0033] (IV) In some embodiments, R1 is selected from H, C1-6 alkyl, C2-6 alkynyl, ... R2 is selected from L is selected from -NR3-, -CR4=N-*, -C1-6 alkylene-NR3-*, -C2-6 alkenyl-NR3-*, and -C2-6 ynylene-NR3-*. R3 is selected from H, C1-6 alkylene groups; R4 is selected from halogen, amino, hydroxy, nitro, cyano, mercapto, C1-6 alkyl, C1-6 alkyloxy, C1-6 alkylthio, or C1-6 alkylamino. said alkylene, alkenylene, alkynylene, alkyl, alkyloxy, alkylthio, or alkylamino is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, hydroxyl, nitro, cyano, thiol, C1-6alkylsilyl.

[0034] In some embodiments, R1is selected from H, C1-4alkyl, C2-4alkynyl, preferably R1is selected from H, methyl, ethyl.

[0035] In some embodiments, R2is selected from ; L is selected from -NR3-, -CR4=N-*, -C2-4alkynylene-NR3-*, R3is selected from H, C1-4alkylene; R4is selected from C1-4alkyloxy, C1-4alkylthio. Preferably, L is selected from -NR3-, -CR4=N-*, -C2-4alkynylene-NR3-*, -CH2-C C-NR3-*, -CH2-C C-NR3-*, -C C-CH2-NR3-*, -CH2-C C-CH2- NR3-*. R3is selected from H, methylene, ethylene. R4is selected from methoxy, ethoxy, methylthio, ethylthio.

[0036] In particular, the compound of formula I is one of the following compounds: , , .

[0037] (V) In some embodiments, R1, R2and the nitrogen to which they are attached form a 3-10 membered nitrogen-containing heterocyclyl; said heterocyclyl is optionally substituted with one or more substituents selected from oxo, halogen, amino, hydroxyl, nitro, cyano, thiol, alkyl, alkyloxy, alkylthio, or alkylamino; said alkyl, alkyloxy, alkylthio, or alkylamino is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, hydroxyl, nitro, cyano, thiol, C1-6alkylsilyl.

[0038] In some embodiments, R1, R2and the nitrogen to which they are attached form a 3-10 membered nitrogen-containing heterocyclyl, said heterocyclyl further containing 0-3 (e.g. 0, 1, 2, 3) heteroatoms selected from N, O, S, preferably further containing 0 or 1 heteroatoms selected from N, O, S. Said heterocyclyl is optionally substituted with oxo. Said heterocyclyl is a saturated, partially unsaturated or unsaturated ring.

[0039] In some embodiments, R1, R2, and the nitrogen to which they are attached form a tetrahydrothiazolyl, tetrahydrooxazolyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, phthalimidyl group.

[0040] In particular, the compound of Formula I is one of the following compounds: , , .

[0041] In a second aspect, the present application provides a method for preparing the 4- (trifluoromethyl) picolinamide compound, the synthetic route is shown in (1), (2) or (3) as follows: .

[0042] The appropriate reaction route can be selected according to the specific structure of the compound. For example, when R1, R2are each independently selected from -CO-O-alkyl, -CO-O-carbocyclyl, -CO-O-heterocyclyl, -CO-alkyl, -CO-carbocyclyl, -CO-heterocyclyl, the synthetic route shown in reaction formula (2) can be used. For example, when R1, R2are each independently selected from -alkylene-O-CO-carbocyclyl, -alkylene-O-CO-heterocyclyl, the synthetic route shown in reaction formula (3) or similar can be used. When R1, R2are selected from other groups, the synthetic route shown in reaction formula (1) can be used.

[0043] In some embodiments, compound 1 4- (trifluoromethyl) nicotinic acid is used as a reaction raw material, compound 1 is dissolved in an organic solvent, a chlorinating agent (such as dichlorosulfoxide) is added to react to obtain compound 2.

[0044] In some embodiments, in route (1) step two, compound 2 is dissolved in an organic solvent, an acid binding agent and a corresponding amine reactant are added to react to obtain the final product.

[0045] In some embodiments, in route (2), (3) step two, compound 2 is added dropwise into ammonia water (such as ammonia water with a mass fraction of 25%), and compound 3 can be obtained after reaction and filtration.

[0046] In some embodiments, in route (2) step three, compound 3 is dissolved in an organic solvent, sodium hydride (such as sodium hydride with a mass fraction of 60%) is added to react (which can be reacted under low temperature stirring), and then a corresponding acyl chloride compound or a dicarbonic acid ester compound is added dropwise to react to obtain the final product.

[0047] In some embodiments, in route (3) step three, compound 3 is dissolved in water, and formaldehyde (such as formaldehyde with a mass fraction of 20%) is added to react under alkaline conditions to obtain the product.

[0048] In some embodiments, route (3) step four dissolves the product of step three in an organic solvent, adds an acid binding agent, and reacts with the corresponding acyl chloride compound to obtain the final product.

[0049] In some embodiments, the acid binding agent used in routes (1), (2), (3) is an organic base or an inorganic base, such as triethylamine, N,N- diisopropylethylamine, potassium carbonate, sodium carbonate, sodium bicarbonate, sodium hydroxide, preferably one of triethylamine, potassium carbonate, sodium carbonate, and preferably triethylamine.

[0050] In some embodiments, the reaction in the steps described in routes (1), (2), (3) can be carried out in an organic solvent, which can be one of toluene, tetrahydrofuran, dichloromethane, acetonitrile; preferably toluene or tetrahydrofuran.

[0051] In some embodiments, when R1, R2 of the 4- (trifluoromethyl) pyridine amide compound described in the present application contains an alkynyl group, an aminoalkynyl derivative intermediate needs to be synthesized, which can be prepared by reacting a haloalkynyl compound (such as chloroalkynyl, bromoalkynyl) with an alkali metal salt (such as sodium salt, potassium salt) of phthalimide to obtain N an alkynyl phthalimide compound, which is then reacted with hydrazine hydrate to prepare the corresponding aminoalkynyl derivative compound; N the alkynyl phthalimide compound can be further halogenated (such as using N halogenated succinimide) and then reacted with hydrazine hydrate to prepare the corresponding halogenated aminoalkynyl derivative compound. Haloalkynyl compounds (such as chloroalkynyl, bromoalkynyl) can also be used to prepare Boc-protected aminoalkynyl derivative compounds, and then the protecting group is removed to obtain the aminoalkynyl derivative intermediate.

[0052] Several aminoalkynyl derivative intermediates can be synthesized by the following routes:

[0053] In some embodiments, the aminoalkynyl derivative intermediate is synthesized, and route (4), (5), (6) step one dissolves bromoalkynyl and potassium phthalimide in N,N- dimethylformamide to carry out coupling reaction to obtain N-substituted phthalimide structure product.

[0054] In some embodiments, route (6) step two dissolves the obtained N- propargyl phthalimide in N,N- dimethylformamide, adds N- bromosuccinimide to carry out bromination, to obtain N- (3-bromoprop-2-yn-1-yl) phthalimide.

[0055] In some embodiments, route (4), (5) step two and route (6) step three, the generated N-substituted phthalimide structure product is reacted with hydrazine hydrate in methanol to hydrolyze, to obtain the target amino acetylene derivative compound, and the reactant exists in the form of hydrochloride.

[0056] In some embodiments, route (7) for synthesizing compound 2-acetylene-1,4-butanediamine hydrochloride intermediate, step one, 1,4-dichloro-2-butyne is dissolved in dimethylformamide, and reacted under the basic condition provided by potassium carbonate, to obtain the product, and then step two is hydrolysis under the condition of hydrochloric acid dioxane to obtain 2-acetylene-1,4-butanediamine hydrochloride. N,N-

[0057] In a third aspect, the present application provides an insecticidal composition, at least one of the 4-(trifluoromethyl) pyridine amide compounds described in the first aspect of the present application as an effective component; the insecticidal composition further comprises a pesticide-acceptable carrier and / or adjuvant.

[0058] The insecticidal composition of the present application can be applied in the form of a preparation, and the 4-(trifluoromethyl) pyridine amide compound is dissolved or dispersed in the carrier or formulated into a preparation so as to be more easily dispersed when used as an insecticide. The insecticide composition can be prepared into various liquid agents, emulsifiable concentrates, suspensions, water suspensions, microemulsions, emulsions, water emulsions, powders, wettable powders, soluble powders, granules, water dispersible granules, or capsules, etc.

[0059] One or more other insecticides, fungicides, herbicides, plant growth regulators, or fertilizers, etc. can be added to the insecticidal composition of the present application.

[0060] In a fourth aspect, the present application also provides the use of the 4-(trifluoromethyl) pyridine amide compounds described in the first aspect or the insecticidal composition described in the third aspect in controlling pests, especially in controlling plant pests; preferably for use in the fields of agriculture, forestry, horticulture, and health. Preferably, an insecticidally effective amount of the 4-(trifluoromethyl) pyridine amide compound as described above or the insecticidal composition as described above is applied on plants, pests, and / or habitats.

[0061] The present application also provides the use of the 4-(trifluoromethyl) pyridine amide compounds described in the first aspect or the insecticidal composition described in the third aspect as nicotinamide enzyme inhibitors.

[0062] In a fifth aspect, the present application also provides a method for preventing and treating pests, comprising applying an insecticidally effective amount of the 4-(trifluoromethyl) pyridine amide compound described in the first aspect or the insecticidal composition described in the third aspect on plants and / or pests and / or habitats.​

[0063] The pests described in the present application can be piercing-sucking mouthpart pests or rasping-sucking mouthpart pests. The pests described in the present application include Hemiptera, Thysanoptera, Diptera, etc. Preferably, the pests include, but are not limited to, aphids (such as Sitobion avenae), whiteflies, thrips, planthoppers, leafhoppers, and the like.

[0064] The 4-(trifluoromethyl)pyridine amide compound of the first aspect of the present application is suitable for use in the control of various agricultural, forestry, and horticultural pests, sanitary pests, and nematodes that damage plants. The 4-(trifluoromethyl)pyridine amide compound of the first aspect of the present application and the insecticidal composition of the third aspect can be used together with one or more other insecticides, fungicides, herbicides, plant growth regulators, or fertilizers, etc.

[0065] The present application has the following advantageous effects: The present application provides a 4-(trifluoromethyl)pyridine amide compound, which has particularly excellent insecticidal activity against piercing-sucking mouthpart pests or rasping-sucking mouthpart pests, such as aphids, thrips, and the like, and has excellent effects on the control of Hemiptera, Thysanoptera, Diptera, and the like, and the control effect is superior to that of the commercially available insecticide flonicamid. DETAILED DESCRIPTION

[0066] The specific embodiments of the present application are described in detail below. It should be understood that the specific embodiments described herein are merely illustrative and are not intended to limit the present application.

[0067] The endpoints of the ranges and any values disclosed herein are not limited to the precise values stated. The endpoints of the ranges and the values are approximate values and are understood to be encompassed by the ranges and values they approximate. For ranges, the endpoints are included within the ranges. For values, the value includes the value stated and any value approximately equal to the value stated. For numerical values, the value includes the value stated and any value approximately equal to the value stated. Numerical values are not intended to be limited to the precision of the number. Numerical values include values approximating the stated value within reasonable significant figures used in the art.

[0068] Before describing the present application in detail, it is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present application which is defined solely by the claims. In order to more fully understand the present application, the following terms are defined as follows. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.

[0069] Definitions Unless otherwise defined, the following terms used in the present application have the following definitions.

[0070] Features illustrated or described as part of one embodiment, or group of embodiments, can be used in another embodiment or group of embodiments, to produce yet a further embodiment.

[0071] The "4-(trifluoromethyl)picolinamide compound" described in the present application includes a compound represented by Formula I, or a stereoisomer, a tautomer, an isotopically enriched compound, and a pesticidally acceptable salt thereof; and the specifically described preferred embodiments. The stereoisomer, the tautomer, the isotopically enriched compound, or the pesticidally acceptable salt thereof of the compound is obtained by a conventional technical means in the art, and exerts the same or similar effects in vivo or in vitro with substantially the same mechanism of action as the compound.

[0072] In the present application, " indicates a connection site in some substituents.

[0073] Unless otherwise specified, the "optionally substituted" means that the hydrogen on the substituent group is not substituted or one or more substitutable positions of the substituent group is independently substituted with a substituent independently selected from one or more of deuterium, halogen, amino, hydroxyl, nitro, cyano, thiol, oxo, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkyloxy, optionally substituted alkylthio, optionally substituted alkylsilyl, optionally substituted alkylamino; the substituents on the aryl, heteroaryl, cycloalkyl, heterocycloalkyl can be one or more of deuterium, halogen, amino, hydroxyl, nitro, cyano, thiol, oxo, optionally substituted alkyl, optionally substituted alkyloxy, optionally substituted alkylthio, optionally substituted alkylsilyl, optionally substituted alkylamino; the substituents on the alkyl are selected from one or more of deuterium, halogen, amino, hydroxyl, nitro, cyano, thiol, alkylsilyl; the case where the substituent is "oxo" means that two hydrogen atoms at the same substitution position are replaced by an oxygen atom, such as C atom oxo forming -CO-, N atom oxo forming -NO-, S atom oxo forming -SO-, -SO2-.

[0074] The term "carbocyclyl" means a saturated, unsaturated, or partially unsaturated monocyclic or polycyclic ring system containing 3-14 carbon atoms, which can contain 3-14, 3-12, 3-10, 7-10, 6-10, 6-9, 3-8, 3-6, 4-6, 5-6 carbon atoms, such as a monocyclic ring system containing 3-6 carbon atoms, or a polycyclic ring system (such as a bicyclic ring) containing 7-10 carbon atoms. The carbocyclyl can be a saturated cycloalkyl, or an unsaturated aryl.

[0075] ​The term "aryl" denotes a monocyclic, bicyclic or tricyclic aromatic carbocyclic ring system containing 6 to 14 carbon atoms, preferably 6 to 10 carbon atoms. Examples of aryl groups include phenyl, naphthyl, such as 1 -naphthyl, 2-naphthyl, 3-naphthyl, 4-naphthyl.

[0076] The term "cycloalkyl" denotes a saturated monocyclic, bicyclic or tricyclic ring system containing 3 to 12 carbon atoms, wherein the monocyclic, bicyclic or tricyclic ring does not contain an aromatic ring, including bridged ring groups, spiro ring groups, fused ring groups and the like. Preferably 3 to 10 carbon atoms (C3-10 cycloalkyl), further preferably 3 to 8 carbon atoms (C3-8 cycloalkyl), 3 to 6 carbon atoms (C3-6 cycloalkyl), 4 to 6 carbon atoms (C4-6 cycloalkyl), 5 to 6 carbon atoms (C5-6 cycloalkyl). Examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like.

[0077] The term "heterocyclyl" denotes a saturated, unsaturated or partially unsaturated monocyclic or polycyclic ring system containing a 3 to 14 membered structure, wherein 1, 2, 3, 4 or more ring atoms are heteroatoms and the remaining atoms are carbon, the heteroatoms being independently selected from O, N or S, the number of heteroatoms preferably being 1, 2, 3 or 4. The heterocyclyl group can be a 3 to 14 membered structure, a 3 to 12 membered structure, a 3 to 10 membered structure, a 6 to 10 membered structure, a 6 to 9 membered structure, a 7 to 10 membered structure, a 3 to 8 membered structure, a 3 to 6 membered structure, a 4 to 6 membered structure, a 5 to 6 membered structure. The heterocyclyl group can be a saturated heterocycloalkyl group, an unsaturated heteroaryl group or a partially unsaturated heterocyclyl group.

[0078] Heteroaryl represents an aromatic monocyclic ring containing a 5-14 membered structure, or preferably a 5-10 membered structure, a 5-8 membered structure, or a 6-14 membered structure, a 6-10 membered structure, a 7-10 membered structure, a 6-8 membered structure, a 5-6 membered structure, such as a 5-6 membered structure, or a 7-10 membered structure, wherein 1, 2, 3, 4, or more ring atoms are heteroatoms and the remaining atoms are carbon, the heteroatoms being independently selected from O, N, or S, the number of heteroatoms preferably being 1, 2, 3, or 4. Heteroaryl can be an aromatic monocyclic ring containing 1-2 5-6 membered structures selected from N, S, O, preferably 1-2 5-6 membered structures selected from N or S. Examples of heteroaryl include, but are not limited to, furanyl, thienyl, oxazolyl, thiazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, thiadiazolyl, triazinyl, phthalazinyl, quinolinyl, isoquinolinyl, pteridinyl, purinyl, indolyl, isoindolyl, indazolyl, benzofuranyl, benzothienyl, benzopyridyl, benzopyrimidyl, benzopyrazinyl, benzimidazolyl, benzophthalazinyl, pyrrolo[2,3-b]pyridyl, imidazo[l,2-a]pyridyl, pyrazolo[l,5-a]pyridyl, pyrazolo[l,5-a]pyrimidyl, imidazo[l,2-b]pyridazinyl, [l,2,4]triazolo[4,3-b]pyridazinyl, [l,2,4]triazolo[l,5-a]pyrimidyl, [l,2,4]triazolo[l,5-a]pyridyl, pyridin-1-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, quinolin-2-yl, quinolin-3-yl, quinolin-4-yl, quinolin-5-yl, quinolin-6-yl, quinolin-7-yl, quinolin-8-yl, phthalimidyl, and the like.

[0079] Heterocycloalkyl can comprise 3-12 ring atoms, of which 1, 2, 3, 4 or more ring atoms are selected from N, O or S, with the remaining ring atoms being C, including bridged ring groups, spirocyclic groups, fused ring groups, and the like. Preferably 3-10 ring atoms (3-10 membered heterocycloalkyl), or 3-8 ring atoms (3-8 membered heterocycloalkyl), or 3-6 ring atoms (3-6 membered heterocycloalkyl), or 4-6 ring atoms (4-6 membered heterocycloalkyl), or 5-6 ring atoms (5-6 membered heterocycloalkyl). Preferably 1-4, more preferably 1-3 (i.e. 1, 2 or 3) heteroatoms. Heterocycloalkyl can be a 5-6 membered monocyclic heterocycloalkyl group containing 1-2 N or O. Examples of heterocycloalkyl groups include pyrrolidinyl, imidazolidinyl, pyrazolidinyl, 1,2,3-triazolidinyl, 1,2,4-triazolidinyl, 1,2,3,4-tetrazolidinyl, tetrahydrofuranyl, piperidinyl, hexahydropyridazine, hexahydropyrimidinyl, hexahydro-1,3,5-triazinyl, piperazinyl, tetrahydropyranyl, aziridinyl, oxiridinyl, thiiridinyl, azetidinyl, oxetidinyl, thietidinyl, oxepanyl, morpholinyl, thiomorpholinyl, oxazinanyl, dioxanyl, dithianyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, imidazolidinyl, tetrahydrofuran-1-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydropyran-1-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, piperidin-1-yl, piperidin-4-yl, and the like, oxepan-4-yl.

[0080] The term "alkyl" refers to a monovalent saturated aliphatic hydrocarbon group, preferably comprising 1-20, 1-18, or 1-10 carbon atoms, preferably 1-8 carbon atoms (C1-8 alkyl), with the number of carbon atoms being between 1-8, specifically 1, 2, 3, 4, 5, 6, 7, or 8, more preferably comprising 1-6 carbon atoms (i.e. C1-6 alkyl, with the number of carbon atoms being between 1-6, specifically 1, 2, 3, 4, 5, or 6). Examples include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, sec-butyl, n-pentyl, neopentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, n-heptyl, n-octyl, and the like. The terms "alkyloxy," "alkylthio," "alkylamino," and dialkylamino" refer to -O-alkyl, -S-alkyl, -NH-alkyl, and -N(alkyl)2, respectively, where alkyl is as defined above. Representative examples include, but are not limited to, methoxy, ethoxy, propyloxy, isopropoxy, butoxy, 1-methylpropyloxy, 2-methylpropyloxy, t-butoxy, and the like; methylthio, ethylthio, propylthio, isopropylthio, butylthio, 1-methylpropylthio, 2-methylpropylthio, t-butylthio, and the like; methylamino, ethylamino, propylamino, dimethylamino, diethylamino, dipropylamino, methylethylamino, and the like.

[0081] The term "alkenyl" refers to a straight or branched chain, unsaturated aliphatic hydrocarbon group having at least one double bond and consisting of carbon and hydrogen atoms. Alkenyl groups preferably contain 2 to 20, 2 to 18, or 2 to 10 carbon atoms, preferably 2 to 8 carbon atoms (C2-8alkenyl), more preferably 2 to 6 carbon atoms (i.e., C2-6alkenyl), 2 to 5 carbon atoms (i.e., C2-5alkenyl), 2 to 4 carbon atoms (i.e., C2-4alkenyl), 2 to 3 carbon atoms (i.e., C2-3alkenyl). For example, "C2-6alkenyl" means that the group is alkenyl and the number of carbon atoms is between 2 and 6 (specifically 2, 3, 4, 5, or 6). Non-limiting examples of alkenyl groups include, but are not limited to, ethenyl, propen-1-yl, propen-2-yl, propen-3-yl, buten-1-yl, buten-2-yl, buten-3-yl, buten-4-yl, isobutenyl, and 1,3-butadienyl, and the like.

[0082] The term "alkynyl" refers to a straight or branched chain, unsaturated aliphatic hydrocarbon group having at least one triple bond and consisting of carbon and hydrogen atoms. Alkynyl groups preferably contain 2 to 20, 2 to 18, or 2 to 10 carbon atoms, preferably 2 to 8 carbon atoms (C2-8alkynyl), more preferably 2 to 6 carbon atoms (i.e., C2-6alkynyl), 2 to 5 carbon atoms (i.e., C2-5alkynyl), 2 to 4 carbon atoms (i.e., C2-4alkynyl), 2 to 3 carbon atoms (i.e., C2-3alkynyl). For example, "C2-6alkynyl" means that the group is alkynyl and the number of carbon atoms is between 2 and 6 (specifically 2, 3, 4, 5, or 6). Non-limiting examples of alkynyl groups include, but are not limited to, ethynyl, propyn-1-yl, propyn-2-yl, propargyl, butyn-1-yl, 2-butyn-1-yl, and the like.

[0083] The terms "alkylene," "alkenylene," and "alkynylene" refer to divalent saturated or unsaturated aliphatic hydrocarbon groups, as specifically defined above for "alkyl," "alkenyl," and "alkynyl."

[0084] The term "halogen" or "halo" means F, Cl, Br, I. The term "stereoisomers" refers to isomers that have the same molecular formula but different spatial arrangement of atoms. Stereoisomers include conformational isomers and configurational isomers. Configurational isomers include geometric isomers (or cis-trans isomers), and optical isomers (including enantiomeric isomers and diastereomeric isomers). Geometric isomers can exist in the present compounds. Optical isomers refer to compounds that are mirror images of one another and are not superimposable. The compounds of the present application can contain asymmetrically substituted carbon atoms in the R or S configuration, where the terms "R" and "S" are defined in accordance with IUPAC 1974 Recommendations for Section E, Fundamental Stereochemistry, Pure Appl. Chem. (1976) 45, 13-10. Compounds having asymmetrically substituted carbon atoms (with equal numbers of R and S configurations) are racemic at those carbon atoms. An atom having an excess of one configuration (over the other) is present in a higher number of that configuration, preferably an excess of about 85-90%, more preferably an excess of about 95-99%, and even more preferably an excess of greater than about 99%. Accordingly, the present application includes racemic mixtures, the individual and absolute optical isomers, and mixtures of the individual and absolute optical isomers.

[0085] The term "tautomer" refers to structural isomers that exist in equilibrium with each other. Tautomers have different energy and can interconvert through a low energy barrier. If tautomerization is possible (as in solution), a chemical equilibrium of tautomers can be achieved. For example, prototropic tautomers (also known as proton-shift tautomers) include interconversions that occur through the migration of a proton, such as keto-enol isomerization and imine-enamine isomerization. Valence tautomers include interconversions that occur through the rearrangement of some bonding electrons.

[0086] The term "isotopic derivatives" refers to compounds of the present application that can exist in isotopically-labeled or enriched forms, containing one or more atoms having an atomic mass or mass number different from the atomic mass or mass number of the most abundant prime isotope of that atom commonly found in nature. Isotopes can be radioactive or non-radioactive. Isotopes of atoms such as hydrogen, carbon, phosphorus, sulfur, fluorine, chlorine, bromine, and iodine include, but are not limited to: 2 H, 3 H, 13 C, 14 C, 15 N, 18 O, 32 P, 35 S, 18 F, 36 Cl, 80 Br and 125Compounds containing the other isotopes of these and / or other atoms are within the scope of the present application. Isotopically-labeled compounds of the present application can generally be prepared by conventional techniques known to those skilled in the art.

[0087] The term "agriculturally acceptable salt" is a salt of the 4-(trifluoromethyl)pyridinecarboxamide compound of the present application, which is prepared by reacting the 4-(trifluoromethyl)pyridinecarboxamide compound of the present application with a chemically acceptable acid, which can be an inorganic acid or an organic acid; or by reacting the 4-(trifluoromethyl)pyridinecarboxamide compound of the present application with a chemically acceptable base, which can be an inorganic base (such as sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, or potassium bicarbonate) or an organic base (such as trimethylamine, triethylamine, or the like).

[0088] The term "agriculturally acceptable carrier and / or adjuvant" includes, but is not limited to, a surfactant, which includes an ionic surfactant or a non-ionic surfactant. The surfactant includes an emulsifier, a dispersant, or a wetting agent. Among them, the emulsifier can be a polyoxyethylene fatty acid ester, a polyoxyethylene fatty alcohol ether, a polyoxyethylene fatty amine, or a commercially available emulsifier; the dispersant includes sodium lignosulfonate, sodium lignosulfonate, calcium lignosulfonate, or a methyl naphthalene sulfonic acid formaldehyde condensate, or the like; the wetting agent includes sodium lauryl sulfate, sodium dodecylbenzenesulfonate, or sodium alkyl naphthalene sulfonate, or the like. The agriculturally acceptable carrier includes a solid carrier and / or a liquid carrier. Preferably, the solid carrier includes a natural or synthetic clay and a silicate, such as natural silica and diatomite; magnesium silicate, such as talc; aluminum magnesium silicate, such as kaolinite, kaolin, montmorillonite, and mica; white carbon black, calcium carbonate, light calcium carbonate; calcium sulfate; limestone; sodium sulfate; amine salts such as ammonium sulfate, hexamethylene diamine. Preferably, the liquid carrier includes water and an organic solvent; when water is used as a solvent or a diluent, the organic solvent can be used as an auxiliary agent or an antifreezing additive. Preferably, the organic solvent includes an aromatic hydrocarbon (such as benzene, xylene, or toluene, or the like), a chlorinated hydrocarbon (such as chlorobenzene, chloroethylene, trichloromethane, or dichloromethane, or the like), an aliphatic hydrocarbon (such as a petroleum fraction, cyclohexane, or light mineral oil, or the like), an alcoholic solvent (such as isopropyl alcohol, butanol, ethylene glycol, glycerol, or cyclohexanol, or the like), an ether solvent, an ester solvent, a ketone solvent (such as acetone, cyclohexanone, or N-methyl pyrrolidone, or the like), or dimethylformamide, or the like. The insecticide composition can be prepared by mixing the active ingredient with the liquid carrier and / or the solid carrier, while adding a surfactant (such as an emulsifier, a dispersant, a stabilizer, a wetting agent), and further adding other adjuvants (such as a binder, an antifoaming agent, an oxidizing agent, or the like) during the formulation process.

[0089] According to the present application, the 4-(trifluoromethyl)pyridine amide compound can be used with one or more other insecticides, fungicides, herbicides, plant growth regulators or fertilizers, etc., and each component can be applied simultaneously, sequentially or separately.

[0090] The preparation method and effects of specific compounds of the present application will be described in detail below by way of examples. In the following examples, the determination of nuclear magnetic resonance data uses AVANCE NMR 600MHz nuclear magnetic resonance instrument, and the determination of mass spectrometry data uses UPLCI-Class / Xevo G2-XS QTOF mass spectrometer.

[0091] Preparation Examples Preparation of intermediate compound 3 in Example 1 The 4-(trifluoromethyl)pyridine amide compound involved in the present application generally uses compounds 2 and 3 in the synthesis process. The specific synthesis route of compounds 2-3 is as follows:

[0092] 1) Method for preparing compound 2 from compound 1: 10 mmol of compound 1 (4-trifluoromethyl nicotinic acid) was dissolved in 50 ml of toluene, 20 mmol of dichloro sulfoxide and 1 mmol of dimethyl formamide were added dropwise, heated to reflux under nitrogen, the temperature was 60-120 ℃, and after about 2-4 hours of reaction, TLC detection showed that the raw material disappeared, the solvent and dichloro sulfoxide were evaporated under vacuum, and black oily compound 2 crude product was obtained. N,N-

[0093] 2) Synthesis method from compound 2 to compound 3: 10 mmol of compound 2 was added dropwise into 30 ml of 25% mass fraction of ammonia water at 0 ℃, brown solid was precipitated, and compound 3 was obtained by filtration and drying.

[0094] Example 2 Preparation of thiazolidin-3-yl (4-(trifluoromethyl)pyridin-3-yl)methanone (BL-9) 10 mmol of compound 2, 50 ml of tetrahydrofuran was added into a 150 ml flask, 15 mmol of triethylamine and 15 mmol of tetrahydrothiazole were added at 25 ℃. After about 12 hours of reaction, TLC detection showed that the raw material disappeared, 3 mol / L hydrochloric acid was used to adjust the pH value to acidic, and thiazolidin-3-yl (4-(trifluoromethyl)pyridin-3-yl)methanone was obtained by extraction and column chromatography separation, which was an oily liquid with a yield of 62%. 1 H NMR (600 MHz, DMSO- d 6) δ 8.95 (d, J = ​5.2 Hz, 1H), 8.88 (d, J = 17.6 Hz, 1H), 7.89 (dd, J = 5.2, 2.3 Hz, 1H), 4.72 – 4.21 (m, 2H), 3.85 (t, J = 6.5 Hz,1H), 3.54 – 3.44 (m, 1H), 3.12 (t, J = 6.5 Hz, 1H), 3.00 (t, J = 6.2 Hz, 1H); HRMS (ES) + C 10 H9F3N2OS(M+H) + Calculated value: 263.0466; Measured value: 263.0470.

[0095] The structural formula is as follows:

[0096] Example 3 4-(trifluoromethyl)- N' Preparation of 4-(trifluoromethyl)nicotinyl)nicotinic hydrazide (BL-16) 10 mmol of compound 2 was added to a 150 mL three-necked flask along with 50 mL of tetrahydrofuran. At 25 °C, 15 mmol of triethylamine and 5 mmol of hydrazine hydrate were added. After approximately 12 hours of reaction, the reaction proceeded as determined by TLC until the starting material disappeared. The pH was adjusted to acidic with 3 mol / L hydrochloric acid. The mixture was extracted and separated by column chromatography to obtain 4-(trifluoromethyl)- N' -(4-(trifluoromethyl)nicotinyl)nicotinamide, yield 58%. mp 267.5-267.6℃. 1 H NMR (600 MHz, DMSO- d 6) δ 11.06 (s, 1H), 9.03-8.99 (m,1H), 8.92 (s, 1H), 7.93 (d, J = 5.2 Hz, 1H); HRMS (ES) + C 14 H8F6N4O2(M+H) + Calculated value: 379.0629; Measured value: 379.0627.

[0097] The structural formula is as follows:

[0098] Example 4 N- methyl- N-Preparation of (2-propyn-l-yl)-4-(trifluoromethyl)nicotinamide (BL-20) To a 150 ml flask was added 10 mmol of compound 2, 50 ml of tetrahydrofuran and 15 mmol of triethylamine at 25°C. Then 15 mmol of methyl propargyl amine was added. After about 12 hours of reaction, TLC was used to detect the disappearance of the starting material, 3 mol / L hydrochloric acid was used to adjust the pH to acidic, and extraction and column chromatography were used to isolate to obtain (2-propyn-l-yl)-4-(trifluoromethyl)nicotinamide, an oily liquid, with a yield of 85%. N- To a 150 ml flask was added 10 mmol of compound 2, 50 ml of tetrahydrofuran and 15 mmol of triethylamine at 25°C. Then 15 mmol of methyl propargyl amine was added. After about 12 hours of reaction, TLC was used to detect the disappearance of the starting material, 3 mol / L hydrochloric acid was used to adjust the pH to acidic, and extraction and column chromatography were used to isolate to obtain (2-propyn-l-yl)-4-(trifluoromethyl)nicotinamide, an oily liquid, with a yield of 85%. N- To a 150 ml flask was added 10 mmol of compound 2, 50 ml of tetrahydrofuran and 15 mmol of triethylamine at 25°C. Then 15 mmol of methyl propargyl amine was added. After about 12 hours of reaction, TLC was used to detect the disappearance of the starting material, 3 mol / L hydrochloric acid was used to adjust the pH to acidic, and extraction and column chromatography were used to isolate to obtain (2-propyn-l-yl)-4-(trifluoromethyl)nicotinamide, an oily liquid, with a yield of 85%. N- To a 150 ml flask was added 10 mmol of compound 2, 50 ml of tetrahydrofuran and 15 mmol of triethylamine at 25°C. Then 15 mmol of methyl propargyl amine was added. After about 12 hours of reaction, TLC was used to detect the disappearance of the starting material, 3 mol / L hydrochloric acid was used to adjust the pH to acidic, and extraction and column chromatography were used to isolate to obtain (2-propyn-l-yl)-4-(trifluoromethyl)nicotinamide, an oily liquid, with a yield of 85%. 1 H NMR (600 MHz, DMSO- d 6) δ 8.94 (d, J = 5.2 Hz, 1H), 8.76 (d, J = 10.6 Hz, 1H), 7.88 (t, J = 5.3 Hz, 1H), 3.97 (d, J = 2.5 Hz, 2H), 3.41-3.27 (m,1H), 2.94 (s, 3H);HRMS(ES + )C 11 H9F3N2O(M+H) + , calculated: 243.0745; found: 243.0745.

[0099] The structural formula is as follows:

[0100] Preparation of (4-(trifluoromethyl)nicotinoyl)carbamothioyl ethyl ester (BL-21) To a 150 ml flask was added 10 mmol of compound 2, 50 ml of tetrahydrofuran and 15 mmol of triethylamine at 25°C. Then 15 mmol of methyl propargyl amine was added. After about 12 hours of reaction, TLC was used to detect the disappearance of the starting material, 3 mol / L hydrochloric acid was used to adjust the pH to acidic, and extraction and column chromatography were used to isolate to obtain (2-propyn-l-yl)-4-(trifluoromethyl)nicotinamide, an oily liquid, with a yield of 85%. 1 H NMR (600 MHz, DMSO- d 6) δ 9.63 (s, 1H), 9.32 (s,1H), 9.07 (s, 1H), 8.89 (d, J = 5.1 Hz, 1H), 7.80 (d, J =5.1 Hz, 1H), 3.04 (q, J = 7.4 Hz, 2H), 1.27-1.24 (m, 3H);HRMS(ES + )C 10 H 10 F3N3OS (M+H) + Calcd: 278.0575; Found: 278.0570.

[0101] The structural formula is as follows:

[0102] Example 6 N, N' Preparation of Bis(4-(trifluoromethyl)nicotinoyl)carbamothioylate (BL-22) Compound 2, 10 mmol, 50 ml of tetrahydrofuran was added into a 150 ml three-necked flask, 30 mmol of triethylamine and 20 mmol of S-ethyl isothiourea hydrobromide were added at 25°C. After about 12 hours of reaction, TLC detection showed that the raw material disappeared, 3 mol / L hydrochloric acid was used to adjust the pH value to acidic, extraction and column chromatography separation gave N' Bis(4-(trifluoromethyl)nicotinoyl)carbamothioylate, yield 63%. m.p. 167.7-167.8°C. 1 H NMR (600 MHz, DMSO- d 6) δ 12.14 (s, 1H), 9.02(s, 1H), 8.98 (s, 1H), 8.94 (s, 1H), 8.83 (s, 1H), 7.94 (s, 1H), 7.88 (s,1H), 2.92 (p, J = 6.8 Hz, 2H), 1.22 (s, 3H);HRMS(ES + )C 17 H 12 F6N4O2S (M+H) + Calcd: 452.0663; Found: 452.0668.

[0103] The structural formula is as follows:

[0104] Example 7 3-( N- Preparation of 3-(4-(trifluoromethyl)nicotinoyl)carbamothioyl)propionic acid (BL-23) To a 150 ml flask was added 10 mmol of compound 2, 50 ml of tetrahydrofuran, 25 mmol of triethylamine and 15 mmol of S-carboxyethyl isothiourea chloride at 25 °C. After about 12 hours of reaction, the disappearance of the starting material was detected by TLC, the pH was adjusted to acidic with 3 mol / L hydrochloric acid, extracted and separated by column chromatography to obtain 3-((4- (trifluoromethyl) nicotinoyl) carbamoyl)thio)propanoic acid in a yield of 31%. m.p. 232.2-233.6 °C. N- (4- (trifluoromethyl) nicotinoyl) carbamoyl)thio)propanoic acid, yield 31%. m.p. 232.2-233.6 °C. 1 H NMR (600 MHz, DMSO- d 6) δ 11.83 (s, 1H), 9.16 (s, 1H), 8.96 (d, J = 5.1 Hz, 1H), 7.87 (d, J = 5.1 Hz, 1H), 3.28-3.23 (m, 2H), 2.90-2.80 (m, 2H); HRMS (ES + ) C 11 H 10 F3N3O3S (M+H) + , calculated: 322.0473; found: 322.0472.

[0105] The structural formula is as follows:

[0106] Example 8 Preparation of 4- (4- (trifluoromethyl) nicotinoyl) piperazin-2-one (BL-24) To a 150 ml flask was added 10 mmol of compound 2, 50 ml of tetrahydrofuran, 25 mmol of triethylamine and 15 mmol of S-carboxyethyl isothiourea chloride at 25 °C. After about 12 hours of reaction, the disappearance of the starting material was detected by TLC, the pH was adjusted to acidic with 3 mol / L hydrochloric acid, extracted and separated by column chromatography to obtain 3-((4- (trifluoromethyl) nicotinoyl) carbamoyl)thio)propanoic acid in a yield of 31%. m.p. 232.2-233.6 °C. 1 H NMR (600 MHz, DMSO- d 6) δ 8.94 (d, J = 5.3 Hz, 1H), 8.86 (d, J = 35.8 Hz, 1H), 8.18 (s, 1H), 7.91-7.87 (m, 1H), 4.29-3.50 (m, 4H), 3.28-3.03 (m, 2H); HRMS (ES + ) C 11 H 10F3N3O2(M+H) + Calculated value: 274.0803; Measured value: 274.0806.

[0107] The structure is as follows:

[0108] Example 9 N- Preparation of (2-butyn-1-yl)-4-(trifluoromethyl)nicotinamide (BL-25) Step A: Preparation of 1-phenylenediamide-2-butyne Dissolve 30 mmol of 1-bromo-2-butyne and 20 mmol of potassium phthalimide in 50 ml of water. N,N- Dimethylformamide was stirred at 100°C for 24 hours until the starting material disappeared by TLC. The reaction solution was extracted with ethyl acetate and washed with saturated brine. After concentration under reduced pressure and recrystallization, 1-phenylenediamide-2-butyne was obtained.

[0109] Step B: Preparation of 2-butyn-1-amine hydrochloride Dissolve 20 mmol of 1-phenylenediamine-2-butyne in 50 mL of methanol, add 30 mmol of hydrazine hydrate dropwise, reflux for 4 hours, cool to room temperature, add 3 mol / L hydrochloric acid to adjust the pH to 6, concentrate under reduced pressure to evaporate methanol, dissolve the residue in water, add 10% sodium hydroxide aqueous solution, adjust the pH to 8, extract with dichloromethane, adjust the pH with 3M dioxane hydrochloride solution until solid precipitates, filter and dry to obtain 2-butyne-1-amine hydrochloride.

[0110] Step C: N- Preparation of (2-butyn-1-yl)-4-(trifluoromethyl)nicotinamide 10 mmol of compound 2 was added to 50 mL of tetrahydrofuran in a 150 mL three-necked flask. 30 mmol of triethylamine and 15 mmol of 2-butyn-1-amine hydrochloride were added at 25 °C. After reacting for approximately 12 hours, the reaction proceeded as determined by TLC until the starting material disappeared. The pH was adjusted to acidic with 3 mol / L hydrochloric acid, and the mixture was extracted and separated by column chromatography. N- (2-Butyn-1-yl)-4-(trifluoromethyl)nicotinamide, yield 91%. mp 102.9-103.6℃. 1 H NMR (600 MHz, DMSO- d 6) δ 9.13 (t, J = 5.4 Hz, 1H), 8.91 (d, J = 6.1 Hz, 1H), 8.77 (s, 1H), 7.83 (d, J =5.2 Hz, 1H), 4.03-4.01 (m,2H), 1.80 (t, J = 2.5 Hz, 3H); HRMS (ES) + C 11 H 10 F3N3O2(M+H) + Calculated value: 343.0745; Measured value: 243.0739.

[0111] The structure is as follows:

[0112] Example 10 4-(trifluoromethyl)- N- Preparation of (3-(trimethylsilyl)prop-2-yn-1-yl)nicotinamide (BL-26) Step A: Preparation of 2-(3-(trimethylsilyl)prop-2-yn-1-yl)isoindole-1,3-dione Dissolve 30 mmol of 3-bromo-1-trimethylsilyl-1-propyne and 20 mmol of potassium phthalimide in 50 ml of water. N,N- Dimethylformamide was stirred at 100°C for 24 hours until the starting material disappeared by TLC. The reaction solution was extracted with ethyl acetate and washed with saturated brine. After concentration and recrystallization under reduced pressure, 2-(3-(trimethylsilyl)prop-2-yn-1-yl)isoindol-1,3-dione was obtained.

[0113] Step B: Preparation of 3-(trimethylsilyl)-2-propynyl-1-amine hydrochloride 20 mmol of 2-(3-(trimethylsilyl)prop-2-yn-1-yl)isoindol-1,3-dione was dissolved in 50 mL of methanol, and 30 mmol of hydrazine hydrate was added dropwise. After reflux for 4 hours, the mixture was cooled to room temperature, and the pH was adjusted to 6 by adding 3 mol / L hydrochloric acid. The methanol was concentrated under reduced pressure and evaporated to dryness. The residue was dissolved in water, and a 10% sodium hydroxide aqueous solution was added. The pH was adjusted to 8, and the mixture was extracted with dichloromethane. The pH was then adjusted to precipitate with a 3M dioxane solution. After filtration and drying, 3-(trimethylsilyl)-2-propyn-1-amine hydrochloride was obtained.

[0114] Step C: 4-(trifluoromethyl)- N- Preparation of (3-(trimethylsilyl)prop-2-yn-1-yl)nicotinamide 10 mmol of compound 2 was added to a 150 mL three-necked flask along with 50 mL of tetrahydrofuran. At 25 °C, 30 mmol of triethylamine and 15 mmol of 3-(trimethylsilyl)-2-propyn-1-amine hydrochloride were added. After reacting for approximately 12 hours, the reaction proceeded as observed by TLC until the starting material disappeared. The pH was adjusted to acidic with 3 mol / L hydrochloric acid. The mixture was extracted and separated by column chromatography to obtain 4-(trifluoromethyl)- N- (3-(trimethylsilyl)prop-2-yn-1-yl)nicotinamide, yield 79%. mp 104.9-105.5℃. 1 H NMR (600 MHz, DMSO- d 6)δ 9.26 (t, J = 5.5 Hz, 1H), 8.97 (d, J = 4.3 Hz, 1H), 8.82 (s, 1H), 7.89 (d, J = 5.2 Hz, 1H), 4.15 (d, J = 5.5 Hz, 2H), 0.20 (s, 9H); HRMS(ES + C 13 H 15 F3N2OSi(M+H) + Calculated value: 343.0745; Measured value: 243.0739.

[0115] The structure is as follows:

[0116] Example 11 N- Preparation of (3-bromoprop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide (BL-27) Step A: N- Preparation of propyne-based phthalimide Dissolve 30 mmol of 3-bromopropyne and 20 mmol of potassium phthalimide in 50 ml of water. N,N- Dimethylformamide was stirred at 100°C for 24 hours until the starting material disappeared, and the reaction solution was extracted with ethyl acetate and washed with saturated brine. The product was then concentrated under reduced pressure and recrystallized to obtain... N- Propylene-based phthalimide.

[0117] Step B: Preparation of 2-(3-bromoprop-2-yn-1-yl)isoindole-1,3-dione 20 mmol N- Propylene phthalimide was dissolved in 50 ml of acetone, and 30 mmol was added. N-Bromosuccinimide, 2 mmol silver nitrate, stirring at room temperature for 12 hours, TLC detection until the raw material disappears, extraction and recrystallization to obtain 2- (3-bromoprop-2-yn-1-yl) isoindole-1, 3-dione.

[0118] Step C: Preparation of 3-bromoprop-2-yn-1-amine hydrochloride Dissolve 20 mmol of 2- (3-bromoprop-2-yn-1-yl) isoindole-1, 3-dione in 50 ml of methanol, drop 30 mmol of hydrazine hydrate, after refluxing for 4 hours, cool to room temperature, add 3 mol / L hydrochloric acid to adjust pH to 6, concentrate and evaporate methanol under reduced pressure, dissolve the residue in water, add 10% mass fraction of sodium hydroxide aqueous solution, adjust pH to 8, extract with dichloromethane, and then adjust pH to solid precipitation with 3M concentration of hydrogen chloride dioxane solution, filter and dry to obtain 3-bromoprop-2-yn-1-amine hydrochloride.

[0119] Step D: N- Preparation of (3-bromoprop-2-yn-1-yl) -4- (trifluoromethyl) nicotinamide Put 10 mmol of compound 2, 50 ml of tetrahydrofuran into a 150 ml three-necked flask, add 30 mmol of triethylamine and 15 mmol of 3-bromoprop-2-yn-1-amine hydrochloride at 25℃. After about 12 hours of reaction, TLC detection until the raw material disappears, adjust pH to acidic with 3 mol / L hydrochloric acid, extract and separate by column chromatography to obtain N- (3-bromoprop-2-yn-1-yl) -4- (trifluoromethyl) nicotinamide, yield 88%. m.p. 102.9-103.6℃. 1 H NMR (600 MHz, DMSO- d 6) δ 9.25 (t, J = 5.5 Hz,1H), 8.93 (d, J = 5.2 Hz, 1H), 8.80 (s, 1H), 7.84 (d, J = 5.2 Hz, 1H), 4.13 (d, J = 5.5 Hz, 2H);HRMS(ES + )C 10 H6BrF3N2O(M+H) + , calculated value: 306.9694; measured value: 306.9699.

[0120] The structural formula is as follows:

[0121] Example 12 N-Preparation of (3-iodopropyl-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide (BL-28) Step A: N- Preparation of propyne-based phthalimide Dissolve 30 mmol of 3-bromopropyne and 20 mmol of potassium phthalimide in 50 ml of water. N,N- Dimethylformamide was stirred at 100°C for 24 hours until the starting material disappeared, and the reaction solution was extracted with ethyl acetate and washed with saturated brine. The product was then concentrated under reduced pressure and recrystallized to obtain... N- Propylene-based phthalimide.

[0122] Step B: Preparation of 2-(3-iodoprop-2-yn-1-yl)isoindole-1,3-dione 20 mmol N- Propylene phthalimide was dissolved in 50 ml of acetone, and 30 mmol was added. N- Iodosuccinimide, 2 mmol silver nitrate, stirred at 70°C for 12 hours, TLC was used to detect the disappearance of the starting material, and extraction and recrystallization were performed to obtain 2-(3-iodoprop-2-yn-1-yl)isoindole-1,3-dione.

[0123] Step C: Preparation of 3-iodoprop-2-ynyl-1-amine hydrochloride 20 mmol of 2-(3-iodoprop-2-yn-1-yl)isoindol-1,3-dione was dissolved in 50 mL of methanol, and 30 mmol of hydrazine hydrate was added dropwise. After reflux for 4 hours, the mixture was cooled to room temperature, and the pH was adjusted to 6 with 3 mol / L hydrochloric acid. The methanol was concentrated under reduced pressure and evaporated to dryness. The residue was dissolved in water, and 10% sodium hydroxide aqueous solution was added. The pH was adjusted to 8, and the mixture was extracted with dichloromethane. The pH was adjusted to precipitate with 3M dioxane hydrochloride solution. After filtration and drying, 3-iodoprop-2-yn-1-amine hydrochloride was obtained.

[0124] Step D: N- Preparation of (3-iodoprop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide 10 mmol of compound 2 was added to 50 mL of tetrahydrofuran in a 150 mL three-necked flask. 30 mmol of triethylamine and 15 mmol of 3-iodoprop-2-yn-1-amine hydrochloride were then added at 25 °C. After reacting for approximately 12 hours, the reaction proceeded as determined by TLC until the starting material disappeared. The pH was adjusted to acidic with 3 mol / L hydrochloric acid, and the mixture was extracted and separated by column chromatography. N- (3-Iodoprop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide, 90% yield. mp 160.9-161.4℃. 1 H NMR (600 MHz, DMSO- d6) δ 9.23 (t, J = 5.5 Hz,1H), 8.92 (d, J = 5.2 Hz, 1H), 8.79 (s, 1H), 7.83 (d, J = 5.2 Hz, 1H), 4.21 (d, J = 5.5 Hz, 2H).;HRMS(ES + )C 10 H6F3IN2O(M+H) + , calculated: 354.9555; found: 354.9555.

[0125] The structural formula is as follows:

[0126] Example 13 N, N' Preparation of (but-2-yn-1,4-diyl)bis(4-(trifluoromethyl)nicotinamide) (BL-29) Step A: Preparation of di-tert-butyl but-2-yn-1,4-diyl dicarbamate 30 mmol of 1,4-dichloro-2-butyne and 60 mmol of bis(tert-butoxycarbonyl)amine were dissolved in 80 ml of dimethylformamide, 60 mmol of potassium carbonate was added, and stirring was performed at room temperature for 24 hours. The reaction solution was extracted with ethyl acetate and washed with saturated brine, and di-tert-butyl but-2-yn-1,4-diyl dicarbamate was obtained by recrystallization after concentration under reduced pressure. N,N- 30 mmol of 1,4-dichloro-2-butyne and 60 mmol of bis(tert-butoxycarbonyl)amine were dissolved in 80 ml of dimethylformamide, 60 mmol of potassium carbonate was added, and stirring was performed at room temperature for 24 hours. The reaction solution was extracted with ethyl acetate and washed with saturated brine, and di-tert-butyl but-2-yn-1,4-diyl dicarbamate was obtained by recrystallization after concentration under reduced pressure.

[0127] Step B: Preparation of 1,4-diamino-2-butyne hydrochloride 20 mmol of di-tert-butyl but-2-yn-1,4-diyl dicarbamate was dissolved in a 3M concentration of hydrogen chloride dioxane solution, stirred for 30 minutes, concentrated, filtered, washed with dichloromethane, and dried to obtain 1,4-diamino-2-butyne hydrochloride.

[0128] Step C: Preparation of N, N' - (but-2-yn-1,4-diyl)bis(4-(trifluoromethyl)nicotinamide) 20 mmol of compound 2 and 50 ml of tetrahydrofuran were added to a 150 ml flask, 30 mmol of triethylamine and 10 mmol of 1,4-diamino-2-butyne hydrochloride were added at 25°C. After about 12 hours of reaction, TLC detection was performed, 3 mol / L hydrochloric acid was used to adjust the pH value to be acidic, and extraction and column chromatography separation were performed to obtain N, N'- (but-2-yn-1, 4-diyl) bis (4- (trifluoromethyl) nicotinamide), yield 65%. m.p. 198.1-198.9 °C. 1 H NMR (600 MHz, DMSO- d 6) δ 9.25-9.20 (m, 2H),8.92 (d, J = 5.2 Hz, 2H), 8.78 (s, 2H), 7.84 (d, J = 5.2 Hz, 2H), 4.13 (d, J = 5.3Hz, 4H);HRMS(ES + )C 19 H 13 F6N3O2(M+H) + , calculated: 430.0990; found: 430.1001.

[0129] The structural formula is as follows:

[0130] Example 14 Preparation of 2- (4- (trifluoromethyl) nicotinoyl) isoindole-1, 3-dione (BL-30) Into a 150 ml three-necked flask, 10 mmol of phthalimide, 50 ml of tetrahydrofuran were added, 15 mmol of sodium hydride was added at 0 °C under nitrogen, after 0.5 hours, 11 mmol of compound 2 was added, and after stirring at room temperature for about 6 hours, TLC detection showed that the raw material disappeared, saturated ammonium chloride aqueous solution was used for quenching, ethyl acetate extraction and column chromatography separation to obtain 2- (4- (trifluoromethyl) nicotinoyl) isoindole-1, 3-dione, yield 91%. m.p. 186.7-186.8 °C. 1 H NMR (600MHz, DMSO- d 6) δ 9.21 (s, 1H), 9.06 (d, J = 5.3 Hz, 1H), 8.04-8.00 (m, 5H);HRMS(ES + )C 15 H7F3N2O3(M+H) + , calculated: 321.0487; found: 321.0485.

[0131] The structural formula is as follows:

[0132] Example 15 Preparation of tert-butyl (4- (trifluoromethyl) nicotinoyl) carbamate (BL-31) To a 150 ml flask was added 10 mmol of compound 3, 50 ml of tetrahydrofuran, 15 mmol of sodium hydride at 0°C under nitrogen. After half an hour of reaction at 0°C, 15 mmol of di-tert-butyl dicarbonate was added. After stirring at room temperature for about 6 hours, the reaction was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The product, (4- (trifluoromethyl) nicotinoyl) carbamic acid tert-butyl ester, was isolated by column chromatography in 92% yield. m.p. 114.3-114.5°C. 1 H NMR (600 MHz, DMSO- d 6) δ 11.25 (s, 1H), 8.92 (d, J = 5.3 Hz, 1H), 8.87 (s, 1H), 7.84 (d, J = 5.2 Hz,1H), 1.33 (s, 9H);HRMS(ES + )C 12 H 13 F3N2O3(M+H) + , calc. 291.0956; found 291.0952.

[0133] The structure is as follows:

[0134] Example 16 N- Preparation of (cyclopropanecarbonyl)-4-(trifluoromethyl)nicotinamide (BL-32) To a 150 ml flask was added 10 mmol of compound 3, 50 ml of tetrahydrofuran, 15 mmol of sodium hydride at 0°C under nitrogen. After half an hour of reaction at 0°C, 15 mmol of di-tert-butyl dicarbonate was added. After stirring at room temperature for about 6 hours, the reaction was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The product, (4- (trifluoromethyl) nicotinoyl) carbamic acid tert-butyl ester, was isolated by column chromatography in 92% yield. m.p. 114.3-114.5°C. N- (cyclopropanecarbonyl)-4-(trifluoromethyl)nicotinamide, in 36% yield. m.p. 150.8-151.2°C. 1 H NMR (600 MHz, DMSO- d 6) δ11.84 (s, 1H), 8.91 (d, J = 5.2 Hz, 1H), 8.87 (s, 1H), 7.84 (d, J = 5.2 Hz, 1H),2.06-2.02 (m, 1H), 0.95-0.91 (m, 2H), 0.82-0.79 (m, 2H);HRMS(ES + )C 11H9F3N2O2 (M+H) + Calculated: 259.0694; Found: 259.0688.

[0135] The structural formula is as follows:

[0136] Example 17 N- Preparation of Bis(cyclopropanecarbonyl)-4-(trifluoromethyl)nicotinamide (BL-33) Into a 150 ml three-necked flask, 10 mmol of compound 3 and 50 ml of tetrahydrofuran were added, 30 mmol of sodium hydride was added at 0°C under nitrogen, after reacting for half an hour at 0°C, 30 mmol of cyclopropane carbonyl chloride was added, after stirring for about 6 hours at room temperature, TLC detection was performed until the raw material disappeared, saturated ammonium chloride aqueous solution was used for quenching, ethyl acetate extraction and column chromatography separation to obtain N, N- Bis(cyclopropanecarbonyl)-4-(trifluoromethyl)nicotinamide, yield 58%. m.p. 110.6-111.6°C. 1 H NMR (600 MHz, DMSO- d 6) δ 9.20 (d, J = 3.3 Hz, 1H), 9.01 (d, J = 4.5 Hz, 1H), 7.93 (s, 1H), 2.22-2.18(m, 2H), 1.15-1.10 (m, 8H);HRMS(ES + )C 15 H 13 F3N2O3 (M+H) + Calculated: 327.0956; Found: 327.0952.

[0137] The structural formula is as follows:

[0138] Example 18 N- Preparation of (Cyclohexanecarbonyl)-4-(trifluoromethyl)nicotinamide (BL-34) Into a 150 ml three-necked flask, 10 mmol of compound 3 and 50 ml of tetrahydrofuran were added, 30 mmol of sodium hydride was added at 0°C under nitrogen, after reacting for half an hour at 0°C, 30 mmol of cyclopropane carbonyl chloride was added, after stirring for about 6 hours at room temperature, TLC detection was performed until the raw material disappeared, saturated ammonium chloride aqueous solution was used for quenching, ethyl acetate extraction and column chromatography separation to obtain N, N- (Cyclohexanecarbonyl)-4-(trifluoromethyl)nicotinamide, yield 40%. m.p. 153.1-153.2°C. 1H NMR (600 MHz, DMSO- d 6) δ 11.48 (s, 1H), 8.92 (d, J = 5.2 Hz, 1H), 8.84 (s, 1H), 7.85 (d, J = 5.2 Hz, 1H),1.86-1.08 (m, 11H); HRMS(ES + C 14 H 15 F3N2O2(M+H) + Calculated value: 301.1164; Measured value: 301.1160.

[0139] The structure is as follows:

[0140] Example 19 N, N- Preparation of bis(cyclohexanecarbonyl)-4-(trifluoromethyl)nicotinamide (BL-35) 10 mmol of compound 3 and 50 mL of tetrahydrofuran were added to a 150 mL three-necked flask. 30 mmol of sodium hydride was added at 0 °C, and the reaction was carried out under nitrogen atmosphere at 0 °C for 30 minutes. Then, 30 mmol of cyclohexyl chloride was added, and the mixture was stirred at room temperature for approximately 6 hours. The reaction was monitored by TLC until the starting material disappeared. The reaction was quenched with saturated ammonium chloride aqueous solution, extracted with ethyl acetate, and separated by column chromatography to obtain N, N- 2(cyclohexanecarbonyl)-4-(trifluoromethyl)nicotinamide, oily liquid, yield 61%. 1 H NMR (600 MHz, DMSO- d 6) δ 9.15 (s, 1H), 9.02 (d, J = 5.1 Hz, 1H), 7.97 (d, J = 5.2 Hz, 1H), 2.66-2.62 (m, 2H), 2.06-1.97 (m, 4H), 1.77-1.54 (m, 8H), 1.28-1.11 (m, 8H); HRMS(ES + C 21 H 25 F3N2O3(M+H) + Calculated value: 411.1895; Measured value: 411.1893.

[0141] The structure is as follows:

[0142] Example 20 N-Preparation of (cyclopentanecarbonyl)-4-(trifluoromethyl)nicotinamide (BL-36) Into a 150 ml flask was placed 10 mmol of compound 3, 50 ml of tetrahydrofuran, and 30 mmol of sodium hydride at 0 °C under nitrogen. After 0.5 h, 30 mmol of cyclopentanecarbonyl chloride was added. After stirring at room temperature for about 6 h, TLC detection showed that the starting material was consumed. The reaction was quenched with saturated ammonium chloride aqueous solution, extracted with ethyl acetate, and separated by column chromatography to give N, N- (cyclopentanecarbonyl)-4-(trifluoromethyl)nicotinamide, yield 50%. Oil liquid. 1 H NMR (600 MHz, DMSO- d 6) δ 11.55 (s, 1H), 8.93 (d, J = 5.2 Hz, 1H), 8.86 (s, 1H), 7.85 (d, J = 5.3 Hz, 1H), 3.03-2.95 (m, 1H), 1.89-1.80 (m, 2H), 1.71-1.61 (m, 2H), 1.61-1.48 (m, 4H);HRMS(ES + )C 13 H 13 F3N2O2(M+H) + , calculated: 287.1007; found: 287.1015.

[0143] The structural formula is as follows:

[0144] Example 21 N,N- Preparation of bis(cyclopentanecarbonyl)-4-(trifluoromethyl)nicotinamide (BL-37) Into a 150 ml flask was placed 10 mmol of compound 3, 50 ml of tetrahydrofuran, and 30 mmol of sodium hydride at 0 °C under nitrogen. After 0.5 h, 30 mmol of cyclopentanecarbonyl chloride was added. After stirring at room temperature for about 6 h, TLC detection showed that the starting material was consumed. The reaction was quenched with saturated ammonium chloride aqueous solution, extracted with ethyl acetate, and separated by column chromatography to give N, N- bis(cyclopentanecarbonyl)-4-(trifluoromethyl)nicotinamide, oil liquid, yield 50%. 1 H NMR (600 MHz, DMSO- d 6) δ9.15 (s, 1H), 9.03 (d, J = 5.2 Hz, 1H), 7.97 (d, J =5.1 Hz, 1H), 3.17-3.13 (m,2H), 2.01-1.53 (m, 16H); HRMS (ES + )C 19 H 21 F3N2O3(M+H) + Calcd: 383.1582; Found: 383.1579.

[0145] The structural formula is as follows:

[0146] Example 22 N- Preparation of isobutyryl-4-(trifluoromethyl)nicotinamide (BL-38) Into a 150 ml three-necked flask, 10 mmol of compound 3, 50 ml of tetrahydrofuran were added, 15 mmol of sodium hydride was added at 0°C under nitrogen, after 0.5 hours, 15 mmol of isobutyryl chloride was added, after stirring at room temperature for about 6 hours, TLC detection showed that the raw material disappeared, saturated aqueous ammonium chloride was added for quenching, ethyl acetate extraction and column chromatography separation to obtain N- isobutyryl-4-(trifluoromethyl)nicotinamide, yield 41%. m.p. 116.8-117.1°C. 1 H NMR (600 MHz, DMSO- d 6) δ11.54 (s, 1H), 8.93 (d, J = 5.2 Hz, 1H), 8.86 (s, 1H), 7.86 (d, J = 5.1 Hz, 1H),2.79-2.74 (m, 1H), 1.06 (d, J = 7.1 Hz, 6H); HRMS (ES + )C 11 H 11 F3N2O2(M+H) + Calcd: 261.0851; Found: 261.0845.

[0147] The structural formula is as follows:

[0148] Example 23 N 、 N- Preparation of diisobutyryl-4-(trifluoromethyl)nicotinamide (BL-39) Compound 3, 50 ml of tetrahydrofuran were added into a 150 ml flask, 30 mmol of sodium hydride was added at 0°C, after 0.5 hours under nitrogen, 30 mmol of isobutyryl chloride was added, after stirring at room temperature for about 6 hours, TLC detection until the raw material disappeared, saturated aqueous ammonium chloride solution was quenched, ethyl acetate extraction and column chromatography separation to obtain N, N- Diisobutyryl-4-(trifluoromethyl)nicotinamide, yield 52%. m.p. 123.3-123.6°C. 1 H NMR (600 MHz, DMSO- d 6) δ 9.17 (s, 1H), 9.04 (d, J = 5.2 Hz, 1H), 7.98 (d, J = 5.2 Hz, 1H), 2.97-2.90(m, 2H), 1.22-1.17 (m, 12H);HRMS(ES + )C 15 H 17 F3N2O3(M+H) + , calculated: 331.1269; found: 331.1264.

[0149] The structural formula is as follows:

[0150] Example 24 N- Preparation of (3,3-dimethylbutanoyl)-4-(trifluoromethyl)nicotinamide (BL-40) Compound 3, 50 ml of tetrahydrofuran were added into a 150 ml flask, 30 mmol of sodium hydride was added at 0°C, after 0.5 hours under nitrogen, 30 mmol of isobutyryl chloride was added, after stirring at room temperature for about 6 hours, TLC detection until the raw material disappeared, saturated aqueous ammonium chloride solution was quenched, ethyl acetate extraction and column chromatography separation to obtain N, N- (3,3-dimethylbutanoyl)-4-(trifluoromethyl)nicotinamide, yield 55%. m.p. 141.0-141.1°C. 1 H NMR(600 MHz, DMSO- d 6) δ 11.47 (s, 1H), 8.92 (d, J = 9.3 Hz, 1H), 8.82 (s, 1H),7.86 (d, J = 9.3 Hz, 1H), 2.31 (s, 2H), 0.96 (s, 9H);HRMS(ES + )C13 H 15 F3N2O2(M+H) + , found: 289.1164; 289.1158.

[0151] Structure is as follows:

[0152] Example 25 N- (3,3-dimethylbutanoyl)- N- Preparation of (prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide (BL-41) Step A: N- Preparation of (prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide Into a 150 ml three-necked flask, 10 mmol of compound 2, 50 ml of tetrahydrofuran, 15 mmol of triethylamine and 15 mmol of propynylamine were added at 25 °C. After about 12 hours of reaction, the disappearance of the raw material was detected by TLC, the pH value was adjusted to acidic with 3 mol / L hydrochloric acid, and extraction and column chromatography were performed to obtain N- (prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide.

[0153] Step B: N- (3,3-dimethylbutanoyl)- N- Preparation of (prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide Into a 150 ml three-necked flask, 10 mmol of compound 2, 50 ml of tetrahydrofuran, 15 mmol of triethylamine and 15 mmol of propynylamine were added at 25 °C. After about 12 hours of reaction, the disappearance of the raw material was detected by TLC, the pH value was adjusted to acidic with 3 mol / L hydrochloric acid, and extraction and column chromatography were performed to obtain N- (prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide, 50 ml of tetrahydrofuran, 15 mmol of sodium hydride were added at 0 °C, and after reaction for half an hour under nitrogen at 0 °C, 15 mmol of 3,3-dimethylbutanoyl chloride was added. After stirring at room temperature for about 6 hours, the disappearance of the raw material was detected by TLC, saturated aqueous ammonium chloride solution was used for quenching, ethyl acetate was extracted, and column chromatography was performed to obtain N- (3,3-dimethylbutanoyl)- N- (prop-2-yn-1-yl)-4-(trifluoromethyl)nicotinamide, oily liquid, yield 43%. 1 H NMR (600 MHz, DMSO-d6) δ 8.91 (d, J = 5.2 Hz, 1H), 8.74(s, 1H), 7.87 (d, J = 5.3 Hz, 1H), 4.66 (s, 2H), 3.39 (s, 1H), 2.72 (s, 2H),0.96 (s, 9H);HRMS(ES + )C16 H 17 F3N2O2(M+H) + , calculated: 327.1320; found: 327.1314.

[0154] The structural formula is as follows:

[0155] Preparation of Example 26 (4-(trifluoromethyl)nicotinamide)methylcyclopropane carboxylate (BL-42) Step A: N- Preparation of hydroxymethyl-4-trifluoromethyl nicotinamide 20 mmol of compound 3 was stirred in 50 ml of water, 2 mol of potassium carbonate was added, 5 ml of formaldehyde was added dropwise at 60°C, and stirred for 8 hours. TLC detection showed that the raw material disappeared, and extraction, drying, and separation gave N- hydroxymethyl-4-trifluoromethyl nicotinamide oily liquid.

[0156] Step B: Preparation of (4-(trifluoromethyl)nicotinamide)methylcyclopropane carboxylate 10 mmol of N- hydroxymethyl-4-trifluoromethyl nicotinamide, 50 ml of tetrahydrofuran was added to a 150 ml three-necked flask, 15 mmol of triethylamine and 15 mmol of cyclopropane carboxylic chloride were added at room temperature. After about 6 hours of reaction, TLC detection showed that the raw material disappeared, 3 mol / L hydrochloric acid was used to adjust the pH value to acidic, and extraction and column chromatography separation gave (4-(trifluoromethyl)nicotinamide)methylcyclopropane carboxylate, oily liquid, yield 31%. 1 H NMR (600 MHz, DMSO- d 6) δ 9.81 (t, J = 6.8 Hz, 1H), 8.95 (d, J = 5.2 Hz, 1H), 8.81 (s, 1H), 7.86 (d, J = 5.2 Hz, 1H), 5.28 (d, J = 6.8Hz, 2H), 1.68-1.64 (m, 1H), 0.95-0.82 (m, 4H); HRMS (ES + )C 12 H 11 F3N2O3(M+H) + , calculated: 289.0800; found: 289.0797.

[0157] The structural formula is as follows:

[0158] Example 27 Toxicity test of compounds containing 4-(trifluoromethyl)pyridine amides against wheat aphid Toxicity was determined according to the national agricultural standard NY / T1154, 6-2006, with slight modifications. 1g of the 4-(trifluoromethyl)pyridine amide compound described in this application was dissolved in 100 mL of acetone to obtain a stock solution of the technical grade compound. Flupyradifurone was used as a positive control. The stock solution was then sequentially diluted to four concentration gradients (100, 10, 1, and 0.1 mg / mL) with 0.1% Tween-80 solution. Healthy samples infested with wheat aphids (… Sitobion avenae Wheat seedlings were treated by removing adult aphids and other impurities, keeping only third-instar nymphs of uniform size. The infested leaves were immersed in pesticide solutions of varying concentrations for 15 seconds, then removed and air-dried. They were then placed in 90 mm glass petri dishes, with 3-4 replicates per concentration, using 15 aphids per replicate. A 0.1% Tween-80 aqueous solution was used as a blank control. The dishes were placed in an artificial climate chamber, and the mortality rate was recorded and the LC50 was calculated after 48 hours. 50 The values ​​and results are shown in Table 1: Table 1: Inhibitory activity of 4-(trifluoromethyl)pyridine amide compounds and control drugs against wheat aphid.

[0159] As shown in Table 1, the 4-(trifluoromethyl)pyridine amide compounds described in this application exhibit good inhibitory activity against wheat aphids, with the vast majority of compounds showing good LC-response ratios. 50 At concentrations below 50 mg / L, it exhibited excellent activity; in particular, BL-22, BL-25 to BL-42 showed superior activity compared to the commercially available control agent, flonicamid. Among these, BL-22, BL-25, BL-26, BL-28, BL-29, BL-30, BL-34, BL-36, BL-37, BL-38, BL-40, and BL-41 showed significantly superior activity compared to the commercially available control agent, flonicamid; the LC50 of BL-22, BL-28, BL-36, and BL-41... 50 It even reached approximately 1 mg / L.

[0160] As can be seen from the above data, the 4-(trifluoromethyl)pyridine amide compounds prepared by this invention have excellent insecticidal effects and can be used to control piercing-sucking pests such as aphids and rasping-sucking pests such as thrips. Moreover, the insecticidal effect of the compounds is better than that of the commercial insecticide flonicamid.

[0161] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0162] It should also be noted that various technical features described in the above detailed description are capable of being combined in any suitable manner, and that the application is not limited to the specific combinations set out in the above detailed description.

Claims

1. A 4-(trifluoromethyl)picolinamide compound, characterized by, A compound represented by Formula I, or a stereoisomer, a tautomer, an isotopic derivative, and a pesticidally acceptable salt thereof: wherein R1, R2are each independently selected from H, alkyl, alkynyl, -C(=NH)-S-alkyl, -C(=NH)-S-alkylene-COOH, -alkylene-O-CO-carbocyclyl, -alkylene-O-CO-heterocyclyl, -CO-O-alkyl, -CO-O-carbocyclyl, -CO-O-heterocyclyl, -CO-alkyl, -CO-carbocyclyl, -CO-heterocyclyl, ; L is selected from -NR3-, -CR4=N-*, -alkylene-NR3-*, -alkenylene-NR3-*, -alkynylene-NR3-*, * representing the point of attachment to -CO-; R3 is selected from H, alkylene; R4 is selected from halogen, amino, hydroxyl, nitro, cyano, thiol, alkyl, alkyloxy, alkylthio, or alkylamino; at least one of R1, R2 is not selected from H or alkyl; alternatively, R1, R2 together with the nitrogen to which they are attached form a nitrogen-containing heterocyclyl; said carbocyclyl, heterocyclyl is optionally substituted with one or more substituents selected from oxo, halogen, amino, hydroxyl, nitro, cyano, thiol, alkyl, alkyloxy, alkylthio, or alkylamino; said alkyl, alkynyl, alkylene, alkenylene, alkynylene, alkyloxy, alkylthio, or alkylamino is optionally substituted with one or more substituents selected from halogen, amino, hydroxyl, nitro, cyano, thiol, alkylsilyl.

2. The 4-(trifluoromethyl)picolinamide compound according to claim 1, characterized by R1 is selected from H, C1-6 alkyl, C2-6 alkynyl, R2 is selected from C2-6 alkynyl; said alkyl, alkynyl is optionally substituted with one or more substituents selected from halogen, amino, hydroxyl, nitro, cyano, thiol, C1-6 alkylsilyl. Preferably, R1 is selected from H, C1-4 alkyl; more preferably, R1 is selected from H, methyl, ethyl.

3. The 4-(trifluoromethyl)picolinamide compound according to claim 2, characterized by R2 is selected from C2-6 alkynyl, C2-6 haloalkynyl, C1-6 alkylsilyl-substituted C2-6 alkynyl; Preferably, R2 is selected from C2-4 alkynyl, C2-4 fluoroalkynyl, C2-4 chloroalkynyl, C2-4 bromoalkynyl, C2-4 iodoalkynyl, trimethylsilyl-substituted C2-4 alkynyl, triethylsilyl-substituted C2-4 alkynyl; More preferably, R2is selected from -CH2-C CH, -CH2-C C-Br, -CH2-C C-I, -CH2-C C-CH3, -CH2-C C-Si(CH3)3.

4. The 4-(trifluoromethyl)picolinamide compound according to claim 1, wherein R1 is selected from H, C1-6 alkyl, C2-6 alkynyl, -C(=NH)-S-C1-6 alkyl, -C(=NH)-S-C1-6 alkylene-COOH, R2 is selected from -C(=NH)-S-C1-6 alkyl, -C(=NH)-S-C1-6 alkylene-COOH; said alkyl, alkynyl, alkylene is optionally substituted with one or more substituents selected from halogen, amino, hydroxyl, nitro, cyano, thiol, C1-6 alkylsilyl. Preferably, R1 is selected from H, C1-4 alkyl, C2-4 alkynyl; more preferably, R1 is selected from H, methyl, ethyl.

5. The 4-(trifluoromethyl)picolinamide compound according to claim 4, wherein R2 is selected from -C(=NH)-S-C1-6 alkyl, -C(=NH)-S-C1-6 alkylene-COOH; Preferably, R2 is selected from -C(=NH)-S-C1-4 alkyl, -C(=NH)-S-C1-4 alkylene-COOH; More preferably, R2 is selected from -C(=NH)-S-methyl, -C(=NH)-S-ethyl, -C(=NH)-S-n-propyl, -C(=NH)-S-i-propyl, -C(=NH)-S-n-butyl, -C(=NH)-S-CH2-COOH, -C(=NH)-S-CH2CH2-COOH, -C(=NH)-S-CH2CH2CH2-COOH -C(=NH)-S-CH2CH2CH2CH2-COOH.

6. The 4-(trifluoromethyl)picolinamide compound according to claim 1, wherein R1 is selected from the group consisting of H, C1-6 alkyl, C2-6 alkynyl, -C1-6 alkylene-O-CO-C3-10 carbocyclyl, -C1-6 alkylene-O-CO-3-10 membered heterocyclyl, -CO-O-C1-6 alkyl, -CO-O-C3-10 carbocyclyl, -CO-O-3-10 membered heterocyclyl, -CO-C1-6 alkyl, -CO-C3-10 carbocyclyl, -CO-3-10 membered heterocyclyl; R2 is selected from the group consisting of -C1-6 alkylene-O-CO-C3-10 carbocyclyl, -C1-6 alkylene-O-CO-3-10 membered heterocyclyl, -CO-O-C1-6 alkyl, -CO-O-C3-10 carbocyclyl, -CO-O-3-10 membered heterocyclyl, -CO-C1-6 alkyl, -CO-C3-10 carbocyclyl, -CO-3-10 membered heterocyclyl; the carbocyclyl, heterocyclyl is optionally substituted with one or more substituents selected from the group consisting of oxo, halogen, amino, hydroxyl, nitro, cyano, thiol, alkyl, alkyloxy, alkylthio, or alkylamino; the alkyl, alkynyl, alkylene, alkyloxy, alkylthio, or alkylamino is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, hydroxyl, nitro, cyano, thiol, alkylsilyl; and the pharmaceutically acceptable salt thereof.

7. The 4-(trifluoromethyl)picolinamide compound according to claim 6, wherein R1 is selected from the group consisting of H, C1-4 alkyl, C2-4 alkynyl, -methylene-O-CO-C3-6 cycloalkyl, -CO-O-C3-6 alkyl, -CO-O-C3-6 cycloalkyl, -CO-C3-6 alkyl, -CO-C3-6 cycloalkyl; R2 is selected from the group consisting of -methylene-O-CO-C3-6 cycloalkyl, -CO-O-C3-6 alkyl, -CO-O-C3-6 cycloalkyl, -CO-C3-6 alkyl, -CO-C3-6 cycloalkyl; and the pharmaceutically acceptable salt thereof. ​ ​ ​ ​ ​ ​ ​ R2is selected from the group consisting of -methylene-O-CO-cyclopropyl, -methylene-O-CO-cyclobutyl, -methylene-O-CO-cyclopentyl, -methylene-O-CO-cyclohexyl, -CO-O- isopropyl, -CO-O-tert-butyl, -CO-O-neopentyl, -CO-O-cyclopropyl, -CO-O-cyclobutyl, -CO-O-cyclopentyl, -CO-O-cyclohexyl, -CO-isopropyl, -CO-tert-butyl, -CO-neopentyl, -CO-cyclopropyl, -CO-cyclobutyl, -CO-cyclopentyl, -CO-cyclohexyl. R2is selected from the group consisting of -methylene-O-CO-cyclopropyl, -methylene-O-CO-cyclobutyl, -methylene-O-CO-cyclopentyl, -methylene-O-CO-cyclohexyl, -CO-O- isopropyl, -CO-O-tert-butyl, -CO-O-neopentyl, -CO-O-cyclopropyl, -CO-O-cyclobutyl, -CO-O-cyclopentyl, -CO-O-cyclohexyl, -CO-isopropyl, -CO-tert-butyl, -CO-neopentyl, -CO-cyclopropyl, -CO-cyclobutyl, -CO-cyclopentyl, -CO-cyclohexyl.

8. The 4-(trifluoromethyl)picolinamide compound according to claim 6 or 7, characterized by R1, R2are the same group.

9. The 4-(trifluoromethyl)picolinamide compound according to claim 1, wherein R1is selected from H, Ci-6alkyl, C2-6alkynyl, ; R2is selected from ; L is selected from -NR3-, -CR4=N-*, -Ci-6alkylene-NR3-*, -C2-6alkenylene-NR3-*, -C2-6alkynylene-NR3-; R3is selected from the group consisting of H, C1-6alkylene; R4is selected from the group consisting of halogen, amino, hydroxyl, nitro, cyano, thiol, C1-6alkyl, C1-6alkyloxy, C1-6alkylthio, or C1-6alkylamino; said alkylene, alkenylene, alkynylene, alkyl, alkyloxy, alkylthio, or alkylamino is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, hydroxyl, nitro, cyano, thiol, C1-6alkylsilyl; Preferably, R1is selected from the group consisting of H, C1-4alkyl, C2-4alkynyl; more preferably, R1is selected from the group consisting of H, methyl, ethyl.

10. The 4-(trifluoromethyl)picolinamide compound according to claim 9, wherein R2is selected from ; L is selected from -NR3-, -CR4=N-*, -C2-4alkynylene-NR3-*; R3is selected from H, C1-4alkylene; R4is selected from C1-4alkyloxy, C1-4alkylthio; Preferably, L is selected from -NR3-, -CR4=N-*, -C C-NR3-*, -CH2-C C-NR3-*, -C C-CH2-NR3-*, -CH2-C C-CH2-NR3-*. More preferably, R3is selected from the group consisting of H, methylene, ethylene, R4is selected from the group consisting of methoxy, ethoxy, methylthio, ethylthio.

11. The 4-(trifluoromethyl)picolinamide compound according to claim 1, wherein R1, R2together with the nitrogen to which they are attached form a 3-10 membered nitrogen containing heterocyclyl; said heterocyclyl is optionally substituted with one or more substituents selected from the group consisting of oxo, halogen, amino, hydroxyl, nitro, cyano, thiol, alkyl, alkyloxy, alkylthio, or alkylamino; said alkyl, alkyloxy, alkylthio, or alkylamino is optionally substituted with one or more substituents selected from the group consisting of halogen, amino, hydroxyl, nitro, cyano, thiol, alkylsilyl; Preferably, said heterocyclyl further contains 0-3 heteroatoms selected from the group consisting of N, O, S.

12. The 4-(trifluoromethyl)picolinamide compound according to claim 11, wherein R1, R2together with the nitrogen to which they are attached form a tetrahydrothiazolyl, tetrahydrooxazolyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, phthalimidyl.

13. The 4-(trifluoromethyl)picolinamide compound according to claim 1, wherein The compound represented by Formula I is one of the following compounds: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 。 14. An insecticidal composition comprising, at least one of the 4-(trifluoromethyl)pyridine amide compounds according to any one of claims 1-13 as an active ingredient; preferably, the pesticidal composition further comprises a pesticidally acceptable carrier and / or adjuvant.

15. Use of a 4-(trifluoromethyl)picolinamide compound according to any one of claims 1 to 13 or of a pesticidal composition according to claim 14 for controlling pests; preferably, a pesticidally effective amount of a 4-(trifluoromethyl)picolinamide compound as described above or of a pesticidal composition as described above is applied to plants, and / or to pests, and / or to habitats.

16. Use according to claim 15, characterized in that, The pests are piercing-sucking pests or rasping-sucking pests; preferably, the pests are Hemiptera, Thysanoptera, Diptera; more preferably, the pests are aphids, whiteflies, thrips, planthoppers, leafhoppers.

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