Aryl amide derivative containing five-membered heterocycle and preparation and nematode killing application thereof

Abstract

The invention relates to an aryl amide derivative containing a five-membered heterocycle as well as preparation and nematode killing application of the aryl amide derivative. Specifically, the invention discloses a compound as shown in a formula I and a pharmaceutical composition thereof, and the definition of each group or substituent group is described in the specification. The invention also provides a preparation method of the compound and application of the compound in pesticide science. The compound has excellent nematicidal activity. # imgabs0 #

Description

Technical Field

[0001] The present invention belongs to the field of pesticides, and specifically, relates to an arylamide derivative containing a five-membered heterocycle, and its preparation and application in nematocidal activity. Background Art

[0002] The phylum Nematoda is one of the largest phyla in the animal kingdom. Nematodes are pseudocoelomate animals, and more than 28,000 species have been recorded, with a large number of species yet to be named. The vast majority are small and cylindrical, also known as roundworms. They can be found everywhere in fresh water, seawater, and on land. In terms of both the number of individuals and species, they often exceed other animals, and can even be found in extreme environments such as Antarctica and deep sea trenches. Classified by lifestyle, nematodes can be divided into several categories such as non-parasitic nematodes, entomopathogenic nematodes, animal parasitic nematodes, and plant parasitic nematodes. The best-known non-parasitic nematode is Caenorhabditis elegans, which is an important model organism in the research of pesticides and pharmaceuticals and plays an irreplaceable role in the R & D of pesticides and pharmaceuticals. Plant parasitic nematodes are one of the important reasons for global crop yield reduction. Every year, about 8% - 15% of crop losses are caused by plant parasitic nematodes, with a value of approximately $173 billion. To date, more than 4,100 species of plant parasitic nematodes have been reported, among which the obligate biotrophic root-knot nematodes (Meloidogyne spp.) are the most destructive. Due to nematode infestation, one-tenth of the world's vegetable production is affected, and 50% of these losses are caused by root-knot nematodes. Their harm mainly begins with the second-stage juvenile (J2) infecting the elongation zone of the plant root. The J2 releases cell wall lytic enzymes into the host plant root epidermis through its stylet, and then migrates through the cortex to the root tip area inside to parasitize the selected vascular tissue cells. The root-knot nematode secretions regulate the complex parasitic relationship between it and the host cells, and then affect the development and gene expression of the host cells, causing the host cells to evolve into larger multinucleated cells, namely giant cells, which thus become the single nutrient supply for the nematodes. With the development of giant cells, the adjacent vascular bundles and cortical cells proliferate and hypertrophy, forming root knots.

[0003] As the first nematicide acting on mitochondrial complex II, Fluopyram was initially developed by Bayer as a new broad-spectrum fungicide and was put on the market in 2012. This agent can be used for the control of more than 70 diseases of various crops such as grapes, pome fruits, stone fruits, vegetables, and field crops. What is different is that Fluopyram has no cross-resistance with other SDHI fungicides. Research shows that Fluopyram has excellent lethal activity against both Caenorhabditis elegans and Meloidogyne incognita.

[0004] Due to environmental pressure, some nematicides have been gradually phased out in the market and even some have been banned because of their high toxicity, the continuous increase in nematode resistance caused by long-term use, and some effects such as neurotoxicity to non-target organisms. Currently, there are few types of nematicides available for selection, and the development of novel nematicides is still indispensable.

[0005] Therefore, there is an urgent need in this field to develop a new class of compounds with excellent nematicidal activity and environmental friendliness. Summary of the Invention

[0006] The object of the present invention is to provide an arylamide derivative of a five-membered heterocycle, which has the characteristics of novel structure and environmental friendliness, and has excellent lethal activity against nematodes.

[0007] In the first aspect of the present invention, there is provided a compound represented by formula I, or its optical isomer, or its agriculturally acceptable salt,

[0008]

[0009] wherein,

[0010] R 1 represents 0 - 5 substituents each independently selected from the group consisting of: halogen, -OH, -NO 2 , -CN, substituted or unsubstituted C1 - C6 alkyl, substituted or unsubstituted C2 - C6 alkenyl, substituted or unsubstituted C2 - C6 alkynyl, substituted or unsubstituted C1 - C6 alkoxy, substituted or unsubstituted C3 - C8 cycloalkyl, substituted or unsubstituted C3 - C8 heterocycloalkyl containing 1, 2 or 3 heteroatoms selected from N, O or S, substituted or unsubstituted C6 - C10 aryl, substituted or unsubstituted 5 - 7 - membered heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S;

[0011] X is selected from the group consisting of: NR 6 , O, S; R 6 is selected from the group consisting of: H, halogen, substituted or unsubstituted C1 - C6 alkyl, substituted or unsubstituted C1 - C6 alkoxy, substituted or unsubstituted C3 - C8 cycloalkyl, substituted or unsubstituted C3 - C8 heterocycloalkyl containing 1, 2 or 3 heteroatoms selected from N, O or S, substituted or unsubstituted C6 - C10 aryl, substituted or unsubstituted 5 - 7 - membered heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S;

[0012] Y represents 0 - 3 substituents each independently selected from the group consisting of: substituted or unsubstituted C1 - C6 alkyl, substituted or unsubstituted C3 - C8 cycloalkyl, substituted or unsubstituted C3 - C8 heterocycloalkyl containing 1, 2 or 3 heteroatoms selected from N, O or S, substituted or unsubstituted C6 - C10 aryl, substituted or unsubstituted 5 - 7 - membered heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S;

[0013] Said substitution means being substituted by one or more substituents selected from the group consisting of: halogen, C1 - C6 alkyl, halo - C1 - C6 alkyl, C1 - C6 alkoxy, halo - C1 - C6 alkoxy, C3 - C8 cycloalkyl, C3 - C8 heterocycloalkyl containing 1, 2 or 3 heteroatoms selected from N, O or S, substituted or unsubstituted C6 - C10 aryl.

[0014] In another preferred embodiment, R 1 represents 0 - 5 substituents each independently selected from the group consisting of: halogen, -OH, -NO 2 , -CN, substituted or unsubstituted C1 - C6 alkyl, substituted or unsubstituted C1 - C6 alkoxy, substituted or unsubstituted C3 - C8 cycloalkyl.

[0015] In another preferred embodiment, R 1 represents 0 - 5 substituents each independently selected from the group consisting of: trifluoromethyl, halogen, -NO 2 .

[0016] In another preferred embodiment, X is selected from the group consisting of: NR 6 , O, S; R 6 is selected from the group consisting of: H, halogen, substituted or unsubstituted C1 - C6 alkyl, substituted or unsubstituted C1 - C6 alkoxy, substituted or unsubstituted C3 - C8 cycloalkyl.

[0017] In another preferred embodiment, X is selected from the group consisting of: NH, N - CH 3 , O, S.

[0018] In another preferred embodiment, X is S.

[0019] In another preferred embodiment, the compound of formula I is the compound of formula II:

[0020]

[0021] wherein, the definitions of each group are as described in the first aspect of the present invention.

[0022] Y represents 0 - 3 substituents each independently selected from the group consisting of: substituted or unsubstituted C3 - C8 cycloalkyl, substituted or unsubstituted C6 - C10 aryl, substituted or unsubstituted 5 - 7 - membered heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S.

[0023] In another preferred embodiment, the 5- to 7-membered heteroaryl refers to a substituent containing 1 heteroatom selected from N, O or S.

[0024] In another preferred embodiment, the compound of formula I is a compound of formula III:

[0025]

[0026] wherein R 1 and Y are as defined above.

[0027] In another preferred embodiment, the structure of Y is selected from the group consisting of:

[0028]

[0029] R 2 represents 0 to 4 substituents each independently selected from the group consisting of: halogen, C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C3-C8 heterocycloalkyl containing 1, 2 or 3 heteroatoms selected from N, O or S, substituted or unsubstituted C6-C10 aryl.

[0030] In another preferred embodiment, R 2 represents 0 to 4 substituents each independently selected from the group consisting of: halogen, C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, substituted or unsubstituted C3-C8 cycloalkyl.

[0031] In another preferred embodiment, the structure of Y is In another preferred embodiment, the compound is selected from the group consisting of:

[0032]

[0033]

[0034] In a second aspect of the present invention, there is provided a pesticidal composition comprising:

[0035] i) a compound as described in the first aspect of the present invention, or an optical isomer thereof, or a pesticidally acceptable salt thereof; and

[0036] ii) a pesticidally acceptable carrier.

[0037] In a third aspect of the present invention, there is provided a use of a compound as described in the first aspect of the present invention, or an optical isomer thereof, or a pesticidally acceptable salt thereof,

[0038] i) for killing and / or controlling nematodes; and / or

[0039] ii) for preparing an insecticidal and / or nematicidal composition or preparation.

[0040] A fourth aspect of the present invention provides a method for killing nematodes, the method comprising applying the compound as described in the first aspect of the present invention, or its optical isomer, or its agrochemically acceptable salt, to a plant body suffering from or likely to suffer from pest damage or the soil or environment around it.

[0041] A fifth aspect of the present invention provides a method for preparing a compound of formula I, comprising the following steps:

[0042] Reacting compound aa and compound bb in an inert solvent in the presence of a base to obtain the compound of formula I.

[0043]

[0044] Wherein each group is as defined above.

[0045] It should be understood that within the scope of the present invention, the above technical features of the present invention and the technical features specifically described below (such as in the examples) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be repeated here one by one. Detailed Embodiments

[0046] Through extensive and in-depth research, the inventors have synthesized for the first time a novel class of arylamide derivatives containing a five-membered heterocycle, and the compounds have excellent nematicidal activity. On this basis, the inventors have completed the present invention.

[0047] Terms

[0048] In the present invention, unless otherwise specified, the terms used have the general meanings known to those skilled in the art.

[0049] In the present invention, the halogen is F, Cl, Br or I.

[0050] In the present invention, the term "C1-C6 alkyl" refers to a straight-chain or branched-chain alkyl having 1 to 6 carbon atoms, including but not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl and n-hexyl, etc. Similar terms such as "C1-C4 alkyl" have similar definitions.

[0051] In the present invention, the term "C1-C6 alkoxy" refers to a straight-chain or branched-chain alkoxy group having 1 to 6 carbon atoms, including but not limited to methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, etc. Similar terms such as "C1-C3 alkoxy" have similar definitions.

[0052] In the present invention, the term "C2-C8 alkenyl" refers to a straight-chain or branched-chain alkenyl group having 2 to 6 carbon atoms and containing at least one double bond, including but not limited to vinyl, propenyl, butenyl, isobutenyl, pentenyl, hexenyl, etc. Similar terms such as "C2-C6 alkenyl" have similar definitions.

[0053] In the present invention, the term "C2-C8 alkynyl" refers to a straight-chain or branched-chain alkynyl group having 2 to 6 carbon atoms and containing at least one triple bond, including but not limited to ethynyl, propynyl, butynyl, isobutynyl, pentynyl, hexynyl, etc. Similar terms such as "C2-C6 alkynyl" have similar definitions.

[0054] In the present invention, the term "C3-C8 cycloalkyl" represents a cyclic aliphatic hydrocarbon group composed of 3 to 8 ring-forming carbon atoms, and so on; it should be understood that the "cycloalkyl" described in the present invention includes not only monocyclic aliphatic hydrocarbon groups, but also fused-ring, spiro-ring, and bridged-ring systems composed of multiple cyclic aliphatic hydrocarbons; the "cycloalkyl" described in the present invention includes not only aliphatic hydrocarbon groups with completely saturated carbon atoms, but also aliphatic hydrocarbon groups with unsaturated bonds in some carbon atoms; examples of the "cycloalkyl" described in the present invention include but are not limited to: etc. When "cycloalkyl" is used as a substituent, the connection site with the molecular main body can occur at any position allowed by the chemical bonds on the "cycloalkyl". Similar terms such as "C3-C6 cycloalkyl" have similar definitions.

[0055] In the present invention, the term "aryl" represents a monocyclic system and a bicyclic system composed of a specific number of carbon atoms and obeying Hückel's rule; it should be understood that when the "aryl" described in the present invention is a bicyclic system, it includes not only the case where all rings are aromatic rings, but also the case where only one ring is an aromatic ring and the other ring is a non-aromatic aliphatic ring.

[0056] In the present invention, the term "C6-C10 aryl" refers to a cyclic system having 6 to 10 carbon atoms and at least one of the rings being an aromatic ring; examples of the "aryl" described in the present invention include but are not limited to etc.; when "aryl" is used as a substituent, the connection site with the molecular main body occurs on the aromatic ring.

[0057] In the present invention, the term "heterocycloalkyl" refers to a cyclic group that indicates a specific number of ring atoms, contains at least one ring heteroatom (N, O or S), is saturated or partially unsaturated, and is non-aromatic; it should be understood that the "heterocyclic group" described in the present invention includes not only monocyclic heterocyclic ring systems, but also polycyclic heterocyclic ring systems, such as cyclic, spirocyclic and bridged rings; when the "heterocyclic group" is a polycyclic system, at least one ring contains a ring heteroatom, and the other rings may contain ring heteroatoms or may be cycloalkyl; for example, the term "4-8 membered heterocycloalkyl" refers to a monocyclic or polycyclic system with 4 to 8 ring atoms, at least one of which is a heteroatom, saturated or partially unsaturated; the definitions of other similar terms are similar; preferably, the number of heteroatoms is 1 to 3. Including (but not limited to) the following groups: etc.; it should be understood that when a "heterocyclic group" is used as a substituent, the connection site with the main body of the molecule can occur at any position on the "heterocyclic group" that is allowed by a chemical bond.

[0058] In the present invention, the term "heteroaryl" refers to a cyclic group with a specific number of ring atoms, containing at least one ring heteroatom (N, O or S), and having aromaticity; unless otherwise specified, the "heteroaryl" described in the present invention includes not only a monocyclic heteroaromatic system, but also a polycyclic heteroaromatic system, such as a bicyclic heteroaromatic, a tricyclic heteroaromatic, and a tetracyclic heteroaromatic; when the "heteroaryl" described is a polycyclic heteroaromatic system, at least one ring is aromatic, the other rings may be aromatic or non-aromatic, and the heteroatom may be in an aromatic ring or in a non-aromatic ring; the polycyclic heteroaromatic system includes not only a paracyclic system, but also a bridged ring and a spirocyclic system. The term "5-7 membered heteroaryl" refers to a cyclic group with 5 to 7 ring atoms, at least one of which is a heteroatom and having aromaticity. The definitions of other similar terms are similar.

[0059] In the present invention, the term "halo" means substituted with halogen.

[0060] In the present invention, the term "optionally" means that when there are a series of candidate groups to choose from, some of them can be selected, or none of them can be selected.

[0061] The term "independently" used in the present invention means that when several substituents defined simultaneously are selected from the same series of candidate groups, they do not affect each other and may be the same or different.

[0062] In the present invention, the term "substituted" means that one or more hydrogen atoms on a specific group are replaced by specific substituents. The specific substituents are the substituents described correspondingly in the foregoing text, or the substituents appearing in each embodiment. Unless otherwise specified, a substituted group may have a substituent selected from a specific group at any substitutable site of the group, and the substituents may be the same or different at each position. Those skilled in the art should understand that the combinations of substituents contemplated by the present invention are those that are stable or chemically achievable combinations.

[0063] In the present invention, the term "1-6" means having 1, 2, 3, 4, 5 or 6, and other similar terms each independently have a similar meaning.

[0064] It should be understood that when a certain group exists at multiple different positions in a compound, its definitions at each position are independent of each other and may be the same or different. That is to say, the term "selected from the group consisting of:" has the same meaning as the term "each independently selected from the group consisting of:".

[0065] Caenorhabditis elegans

[0066] Caenorhabditis elegans is a model organism that usually feeds on various bacteria, generally lives in soil, and has no parasitic effect on other organisms. Caenorhabditis elegans has the characteristics of small body size, short life cycle, complete gene sequencing, stable inheritance, convenient cultivation and observation, and is evolutionarily closest to plant parasitic nematodes. Therefore, in the laboratory, Caenorhabditis elegans is often used as a tool for studying plant parasitic nematodes.

[0067] The "nematodes" described in the present invention include all species of the order Nematoda, especially parasitic species or those that cause health problems in plants or fungi (such as species of the order Aphelenchida, Meloidogyne, Tylenchida and other orders) or in humans and animals (such as species of the order Ascaradida, Oxyurida, Stronglida, Stronglyloides and Trichocephalida).

[0068] The active ingredient compound of the present invention

[0069] For the first or second aspect of the present invention, the compounds represented by the general formula (I) may contain one or more chiral centers, and enantiomers and diastereomers exist. The compounds represented by the general formula (I) of the present invention may also contain many geometric isomers such as olefins, C=N double bonds, amides, etc. Unless otherwise specified, all the above-mentioned chiral (enantiomers, diastereomers, axial chiral isomers), racemates, cis geometric isomers, trans geometric isomers, mixtures of cis and trans geometric isomers, rotational isomers and their mixtures are included in the present invention. Those of ordinary skill in the art can use common separation or synthesis methods in the laboratory to separate or prepare the compounds containing asymmetric centers in the present invention to obtain single isomers. For example, for enantiomers, two enantiomers can be obtained by using general chiral resolution methods or asymmetric synthesis methods. For diastereomers, they can be separated by methods such as stepwise recrystallization or chromatographic separation, which does not destroy the novelty of the compounds of the present invention.

[0070] The compounds of the present invention have the structure shown in Formula I:

[0071]

[0072] Wherein, the definitions of each group are as described above;

[0073] In another preferred embodiment, in the said compound, R 1 、R 2 、R 6 、X and Y, any one of them is independently the corresponding group in the specific compounds described in the present invention.

[0074] As used herein, the term "agronomically acceptable salts" may include inorganic salts, organic acid salts, salts of basic amino acids or acidic amino acids. The inorganic acid salts in the present invention include, for example: hydrochloric acid, hydroboric acid, nitric acid, sulfuric acid or phosphoric acid. The organic acids in the present invention include, for example: lactic acid, formic acid, acetic acid (i.e., acetic acid), trifluoroacetic acid, fumaric acid, oxalic acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, or p-toluenesulfonic acid. Acidic amino acids include, for example: glycine, aspartic acid, or glutamic acid.

[0075] Preparation methods of the compounds of the present invention

[0076] The preparation methods of the compounds of Formula I of the present invention will be described more specifically below, but these specific methods do not constitute any limitation to the present invention. The compounds of the present invention can also be conveniently prepared by optionally combining various synthesis methods described in this specification or known in the art, and such combinations can be easily carried out by those skilled in the art to which the present invention pertains.

[0077] Typically, the preparation process of the compounds of the present invention is as follows. The raw materials and reagents used can be purchased through commercial channels unless otherwise specified.

[0078] The present invention provides a method for preparing arylamide derivatives containing a five-membered heterocycle (compounds of formula I), and the specific steps are as follows:

[0079] Preparation method one:

[0080] In an inert solvent, in the presence of a base, react compound aa with compound A1 to obtain a compound of formula I;

[0081]

[0082] In the formula, R 1 , R 2 and R 6 are defined as described above.

[0083] The inert solvent is selected from the following group: dichloromethane, ethyl acetate, tetrahydrofuran, N,N-dimethylformamide, dioxane, dichloroethane, chloroform, toluene, xylene, dimethyl sulfoxide, etc.;

[0084] The base is selected from the following group: triethylamine, potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, etc.

[0085] Preparation method two:

[0086] In an inert solvent, in the presence of a base, react compound aa with compound B1 to obtain a compound of formula I;

[0087]

[0088] In the formula, R 1 and R 2 are defined as described above.

[0089] The inert solvent is selected from the following group: dichloromethane, ethyl acetate, tetrahydrofuran, N,N-dimethylformamide, dioxane, dichloroethane, chloroform, toluene, xylene, dimethyl sulfoxide, etc.;

[0090] The base is selected from the following group: triethylamine, potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, etc.

[0091] Preparation method three:

[0092] In an inert solvent, in the presence of a base, react compound aa with compound C1 to obtain a compound of formula I;

[0093]

[0094] In the formula, R 1 and R 2 are defined as described above.

[0095] The inert solvent is selected from the following group: methylene chloride, ethyl acetate, tetrahydrofuran, N,N-dimethylformamide, dioxane, dichloroethane, chloroform, toluene, xylene, dimethyl sulfoxide, etc.;

[0096] The base is selected from the following group: triethylamine, potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, etc.

[0097] The nematicide combination containing the active substance of the present invention

[0098] The active substance of the present invention can be prepared into an insecticide composition by a conventional method. These active compounds can be made into conventional preparations, such as solutions, emulsions, suspensions, powders, foams, pastes, granules, aerosols, natural and synthetic materials impregnated with the active substance, microcapsules in polymers, coating compounds for seeds, and preparations used with combustion devices, such as fumigation cartridges, fumigation cans and fumigation trays, as well as ULV cold mist and warm mist preparations.

[0099] These preparations can be produced by known methods. For example, the active compound is mixed with an extender, which is a liquid or liquefied gas or solid diluent or carrier, and surfactants, namely emulsifiers and / or dispersants and / or foam formers, can be optionally used. For example, when water is used as an extender, organic solvents can also be used as auxiliaries.

[0100] When a liquid solvent is used as a diluent or carrier, it is basically suitable, such as: aromatic hydrocarbons, such as xylene, toluene or alkylnaphthalene; chlorinated aromatic or chlorinated aliphatic hydrocarbons, such as chlorobenzene, vinyl chloride or methylene chloride; aliphatic hydrocarbons, such as cyclohexane or paraffin, such as mineral oil fractions; alcohols, such as ethanol or ethylene glycol and their ethers and esters; ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone; or less common polar solvents, such as dimethylformamide and dimethyl sulfoxide, as well as water.

[0101] The liquefied gas diluent or carrier refers to a liquid that will become a gas at normal temperature and pressure, such as aerosol propellants, such as halogenated hydrocarbons and butane, propane, nitrogen and carbon dioxide.

[0102] Solid carriers can be ground natural minerals such as kaolin, clay, talc, quartz, activated clay, montmorillonite, or diatomaceous earth, and ground synthetic minerals such as highly disperse silicic acid, alumina, and silicates. Solid carriers for granules are crushed and classified natural stones such as calcite, marble, pumice, sepiolite, and dolomite, as well as inorganic and organic coarse powder synthetic granules, and granules of organic materials such as sawdust, coconut shells, corn cobs, and tobacco stems, etc.

[0103] Nonionic and anionic emulsifiers can be used as emulsifiers and / or foam formers. For example, polyoxyethylene-fatty acid esters, polyoxyethylene-fatty alcohol ethers such as alkylaryl polyethylene glycol ethers, alkyl sulfonates, alkyl sulfates, aryl sulfonates, and albumin hydrolysis products. Dispersants include, for example, lignosulfite waste liquor and methyl cellulose.

[0104] Binders can be used in the formulation, such as carboxymethyl cellulose and natural and synthetic polymers in the form of powders, granules, or emulsions, such as gum arabic, polyvinyl alcohol, and polyvinyl acetate.

[0105] Colorants can be used, such as inorganic dyes like iron oxide, cobalt oxide, and Prussian blue; organic dyes such as azo dyes or metal phthalocyanine dyes; and trace nutrients such as salts of iron, manganese, boron, copper, cobalt, aluminum, and zinc, etc.

[0106] The compounds of formula I of the present invention can be present as a mixture with other active compounds in their commercial formulations or in the use forms prepared from these formulations. These other active compounds are insecticides, fungicides, fungicides, herbicides, growth control agents, etc. Insecticides include, for example, phosphate esters, carbamates, chlorinated hydrocarbons, and substances produced by microorganisms such as avermectin, etc. Fungicides include methoxyacrylates, amides, triazoles, etc.

[0107] In addition, the compounds of formula I of the present invention can also be present as a mixture with synergists in their commercial formulations or in the use forms prepared from these formulations. These synergists are compounds that enhance the action of the active compounds. Since the active compounds themselves are active, it may not be necessary to add synergists.

[0108] These formulations generally contain 0.001 - 99.99% by weight, preferably 0.01 - 99.9% by weight, more preferably 0.05 - 90% by weight of the active compounds of the present invention based on the pesticide composition. The concentration of the active compounds in the use forms prepared from the commercial formulations can vary within a wide range. The concentration of the active compounds in the use forms can range from 0.0000001 - 100% (g / v), preferably between 0.0001 and 1% (g / v).

[0109] Compared with the prior art, the main advantages of the present invention are as follows:

[0110] 1. It is first discovered that the compound of the present invention has nematicidal activity against Caenorhabditis elegans.

[0111] 2. The compound of the present invention has a novel structure and excellent nematicidal activity.

[0112] 3. The synthesis steps of the compound of the present invention are simple, environmentally friendly, with high yield and good purity.

[0113] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. The experimental methods without specific conditions noted in the following embodiments are usually carried out under conventional conditions or according to the conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are weight percentages and weight parts.

[0114] Unless otherwise defined, all professional and scientific terms used herein have the same meaning as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to the described content can be applied to the method of the present invention. The preferred implementation methods and materials described herein are for illustrative purposes only.

[0115] In the present invention, the structure of the compound is determined by nuclear magnetic resonance (NMR) or / and mass spectrometry (MS). The NMR measurement is performed using a Bruker AVANCE-400 nuclear magnetic resonance instrument. The LCMS measurement is performed using a Waters2695 liquid chromatography-mass spectrometry combined instrument (MS model: Micromass ZQ).

[0116] In the examples, the silica gel plate used for thin layer chromatography (TLC) has a specification of 0.2 mm ± 0.03 mm. The specification of the preparative thin layer chromatography (prep-TLC) used for purifying the compound is 0.4 mm to 0.5 mm; for column chromatography, silica gel with 200 - 300 mesh from Yantai Huanghai is generally used as the carrier; the automatic medium pressure rapid purification instrument (Combi Flash Rf+UV-VIS) is used, and the separation column models include: Silica Flash Column 4g, 12g, 25g. The eluent system for column chromatography and the developing system for thin layer chromatography include: A: dichloromethane and methanol system; B: petroleum ether and ethyl acetate system. The volume ratio of the solvents is adjusted according to the polarity of the compound, and a small amount of basic or acidic reagents such as ammonia water or acetic acid can also be added for adjustment.

[0117] Preparation of Compound 7a

[0118] Example 1: Preparation of Intermediate 2a

[0119]

[0120] 50 mL of pyrrole (compound 1a), 10 mmol of diphenyliodotrifluoromethanesulfonate, and 15 mmol of sodium hydroxide were added to a 250 mL round-bottom flask in sequence, and the reaction was stirred at 80°C for 10 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the reaction residue was dissolved in 50 mL of deionized water, extracted with ethyl acetate (3×30 mL), and the extracts were combined. The crude product was separated by column chromatography to obtain intermediate 2a with a yield of 75%. MS (GC-MS): C 10 H 9 N[M] + m / z 143.1.

[0121] Example 2: Preparation of intermediate 3a

[0122]

[0123] 5 mmol of intermediate 2a and 15 mL of N,N-dimethylformamide were added to a 50 mL round-bottom flask. 550 μL of phosphorus oxychloride was slowly added to the solution under an ice bath at 0 °C. After stirring for 10 min, the temperature was raised to 40 °C for reaction for 1 h. After the reaction solution cooled to room temperature, ice water was added and the pH of the reaction solution was adjusted to 8-9 with 2 M sodium hydroxide solution. The reaction solution was then heated to reflux and continued to react for 30 min. After the reaction was completed, the solution was extracted with ethyl acetate (3 × 20 mL), the extracts were combined, and the solvent was removed under reduced pressure to obtain the crude product 3a, which can be directly used in the next step.

[0124] Example 3: Preparation of intermediate 4a

[0125]

[0126] 5 mmol of intermediate 3a, 6.5 mmol of ammonium acetate, and 20 mL of nitromethane were added to a 50 mL round-bottom flask in sequence, and the reaction solution was placed in an oil bath at 100°C for 2 h. After the reaction, the solvent was removed by rotary evaporation, 10 mL of deionized water was added, and ethyl acetate (3×20 mL) was extracted. The organic phases were combined and the solvent was removed under reduced pressure to obtain a crude product. The yellow solid was separated by column chromatography to obtain intermediate 4a with a yield of 82%. MS (GC-MS): C 12 H 10 N 2 O 2 [M] + m / z 214.1.

[0127] Example 4: Preparation of Intermediate 5a

[0128]

[0129] Into a 50 mL reaction flask, 5 mmol of intermediate 4a and 25 mL of methanol were successively added. The reaction solution was placed in an ice-water bath, stirred and cooled to 0 °C, and then 22 mmol of sodium borohydride was added in portions. After addition, the ice bath was removed, and the reaction solution was stirred at room temperature for 30 min. After the reaction was completed, glacial acetic acid was added dropwise to quench the reaction, the solvent was evaporated to dryness, and the intermediate 5a as a yellow oily liquid was obtained by silica gel column chromatography with a yield of 70%. MS (GC-MS): C 12 H 12 N 2 O 2 [M] + m / z 216.1.

[0130] Example 5: Preparation of intermediate 6a

[0131]

[0132] Into a 25 mL round-bottom flask, 2 mmol of intermediate 5a, 6 mmol of iron powder, 8 mmol of ammonium chloride, 8 mL of ethanol and 2 mL of water were successively added. The reaction solution was heated to reflux and reacted for 2 h. After the reaction was completed, it was filtered through diatomaceous earth, the solvent was removed by rotary evaporation, the residue was diluted with water, and extracted with dichloromethane (10 mL × 3). The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated to dryness. The crude product intermediate 6a was directly used for the next step without purification.

[0133] Example 6: Preparation of the target product 7a

[0134]

[0135] Into a 10 mL round-bottom flask, 1 mmol of intermediate 6a, 1.5 mmol of triethylamine and 5 mL of dichloromethane were successively added. The reaction solution was placed in an ice-water bath, stirred and cooled to 0 °C, and then 1.5 mmol of 2,6-bis(trifluoromethyl)benzoyl chloride was slowly added dropwise. After addition, the ice bath was removed, and the reaction solution was stirred at room temperature for 30 min. After the reaction was completed, the solvent was removed by rotary evaporation, and the crude product was purified by flash chromatography to obtain the target compound 7a with a yield of 60%.

[0136] Preparation of compound 13

[0137] Example 1: Preparation of intermediate 9

[0138]

[0139] 10.0 mmol 5-bromofuran-2-carboxaldehyde (compound 8), 11 mmol phenylboric acid, 5% tetrakis(triphenylphosphine)palladium, 20 mL sodium carbonate aqueous solution (2M), 80 mL toluene, 80 mL ethanol were added in sequence to a 100 mL round-bottom flask. The reaction solution was replaced with nitrogen three times and reacted at 80°C for 5 h under a nitrogen atmosphere. After the reaction was completed, the solvent was removed by rotary evaporation, the reaction residue was dissolved in 20 mL deionized water, extracted with ethyl acetate (3×20 mL), the extracts were combined, and the crude product was separated by column chromatography to obtain intermediate 9 with a yield of 85%. MS (GC-MS): C 11 H 8 O 2 [M] + m / z 172.1.

[0140] Example 2: Preparation of Intermediate 10

[0141]

[0142] 10.0 mmol of intermediate 9, 13.0 mmol of ammonium acetate, and 30 mL of nitromethane were added to a 100 mL round-bottom flask in sequence, and the reaction solution was placed in a 100°C oil bath for 2 h. After the reaction, the solvent was removed by rotary evaporation, 30 mL of deionized water was added, and ethyl acetate (3×10 mL) was extracted. The organic phases were combined and the solvent was removed under reduced pressure to obtain a crude product. The yellow solid was separated by column chromatography to obtain intermediate 10 with a yield of 60%. MS (GC-MS): C 12 H 9 NO 3 [M] + m / z 215.1.

[0143] Example 3: Preparation of Intermediate 11

[0144]

[0145] In a 50 mL reaction bottle, 5 mmol of compound 10 and 25 mL of methanol were added in sequence. The reaction solution was placed in an ice-water bath, stirred and cooled to 0°C, and then 22 mmol of sodium borohydride was added in batches. After the addition, the ice bath was removed and the reaction solution was stirred at room temperature for 30 min. After the reaction was completed, glacial acetic acid was added dropwise to quench, the solvent was dried, and a yellow oily liquid was obtained by silica gel column chromatography with a yield of 78%. MS (GC-MS): C 12 H 11 NO 3 [M] + m / z 217.1.

[0146] Example 4: Preparation of Intermediate 12

[0147]

[0148] In a 25 mL round-bottom flask, 2 mmol of intermediate 11, 6 mmol of iron powder, 8 mmol of ammonium chloride, 8 mL of ethanol and 2 mL of water were successively added, and the reaction solution was heated to reflux and reacted for 2 h. After the reaction was completed, it was filtered through diatomaceous earth, the solvent was removed by rotary evaporation, the residue was diluted with water, and extracted with dichloromethane (10 mL×3). The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated to dryness. The crude product was directly subjected to the next step without purification. MS(GC-MS): C 12 H 13 NO[M] + m / z 187.1.

[0149] Example 5: Preparation of target product 13

[0150]

[0151] In a 10 mL round-bottom flask, 1 mmol of intermediate 12, 1.5 mmol of triethylamine and 5 mL of dichloromethane were successively added. The reaction solution was placed in an ice-water bath, stirred and cooled to 0 °C, and then 1.5 mmol of o-trifluoromethylbenzoyl chloride was slowly added dropwise. After the addition, the ice bath was removed, and the reaction solution was stirred at room temperature for 30 min. After the reaction was completed, the solvent was removed by rotary evaporation, and the crude product was purified by flash chromatography to obtain the target compound 13.

[0152] Preparation of compound 19a

[0153] Example 1: Preparation of intermediate 15a

[0154]

[0155] In a 100 mL round-bottom flask, 10.0 mmol of 5-bromothiophene-2-carbaldehyde (compound 14), 11 mmol of phenylboronic acid, 5% tetrakis(triphenylphosphine)palladium, 20 mL of aqueous sodium carbonate solution (2 M), 80 mL of toluene, and 80 mL of ethanol were successively added. The reaction solution was purged with nitrogen three times and reacted at 80 °C under a nitrogen atmosphere for 5 h. After the reaction was completed, the solvent was removed by rotary evaporation. The reaction residue was dissolved in 20 mL of deionized water and extracted with ethyl acetate (3×20 mL). The combined extracts were separated by column chromatography to obtain intermediate 15a with a yield of 90%. MS(GC-MS): C 11 H 8 OS[M] + m / z 188.0.

[0156] Example 2: Preparation of intermediate 16a

[0157]

[0158] In a 100 mL round-bottom flask, 10.0 mmol of intermediate 15a, 13.0 mmol of ammonium acetate, and 30 mL of nitromethane were successively added. The reaction mixture was placed in an oil bath at 100 °C and reacted for 2 h. After the reaction, the solvent was removed by rotary evaporation. 30 mL of deionized water was added, and the mixture was extracted with ethyl acetate (3 × 10 mL). The organic phases were combined, and the solvent was removed under reduced pressure to obtain the crude product. The yellow solid 16a was obtained by column chromatography with a yield of 85%. MS (GC-MS): C 12 H 9 NO 2 S[M] + m / z 231.0

[0159] Example 3: Preparation of intermediate 17a

[0160]

[0161] In a 50 mL reaction flask, 5 mmol of compound 16a and 25 mL of methanol were successively added. The reaction mixture was placed in an ice-water bath, stirred and cooled to 0 °C, and then 22 mmol of sodium borohydride was added in batches. After the addition, the ice bath was removed, and the reaction mixture was stirred at room temperature for 30 min. After the reaction, glacial acetic acid was added dropwise to quench the reaction, and the solvent was removed by rotary evaporation. The yellow oily liquid 17a was obtained by silica gel column chromatography with a yield of 73%. MS (GC-MS): C 12 H 11 NO 2 S[M] + m / z233.1

[0162] Example 4: Preparation of intermediate 18a

[0163]

[0164] In a 25 mL round-bottom flask, 2 mmol of intermediate 17a, 6 mmol of iron powder, 8 mmol of ammonium chloride, 8 mL of ethanol, and 2 mL of water were successively added. The reaction mixture was heated to reflux and reacted for 2 h. After the reaction, it was filtered through diatomaceous earth, and the solvent was removed by rotary evaporation. The residue was diluted with water and extracted with dichloromethane (10 mL × 3). The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed by rotary evaporation. The crude product intermediate 18a was directly used for the next step without purification.

[0165] Example 5: Preparation of the target product 19a

[0166]

[0167] In a 10 mL round-bottom flask, 1 mmol of intermediate 18a, 1.5 mmol of triethylamine and 5 mL of dichloromethane were successively added. The reaction solution was placed in an ice-water bath, stirred and cooled to 0 °C, and then 1.5 mmol of o-(trifluoromethyl)benzoyl chloride was slowly added dropwise. After the addition, the ice bath was removed, and the reaction solution was stirred at room temperature for 30 min. After the reaction was completed, the solvent was removed by rotary evaporation, and the crude product was purified by flash chromatography to obtain the target compound 19a with a yield of 66%.

[0168] Preparation of Compound 25a

[0169] Step 1: Preparation of Intermediate 21a

[0170]

[0171] To a 250 mL round-bottom flask, 12 mmol of 5-formyl-2-thiopheneboronic acid (Compound 20), 10 mmol of 2-bromopyridine, 6% tetrakis(triphenylphosphine)palladium, 6% triphenylphosphine were successively added. Then, 30 mL of aqueous potassium carbonate solution (3 M), 30 mL of ethanol and 90 mL of dioxane were added. The reaction solution was purged with nitrogen three times and refluxed under a nitrogen atmosphere for 24 h. After the raw materials were completely reacted, the reaction solution was cooled to room temperature, 20 mL of deionized water was added, and the mixture was extracted with ethyl acetate (20 mL × 3). After combining the extracts and removing the solvent, the crude product intermediate 21a was separated by column chromatography and used for the next step of the reaction.

[0172] Step 2: Using intermediate 21a as the reaction raw material, the specific implementation method was the same as that in Examples 2-4 of the preparation of Compound 19a above to obtain intermediates 22a - 24a.

[0173] Step 3: Using intermediate 24a as the reaction raw material, the specific implementation method was the same as that in Example 5 of the preparation of Compound 19a above to obtain the target product 25a.

[0174] Preparation of Compound 30

[0175] Step 1: Preparation of Intermediate 26

[0176]

[0177] 10 mmol of 5-bromothiophene-2-carbaldehyde (Compound 14), 15 mmol of furanboronic acid, 2% of 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, 2% of palladium acetate, and 30 mmol of potassium carbonate were successively added to a 100 mL round-bottom flask. Then, 30 mL of acetonitrile and 20 mL of deionized water were added. The reaction solution was purged with nitrogen three times and stirred overnight at room temperature. After the reaction was completed, the solvent was removed by rotary evaporation. The reaction residue was added with 20 mL of deionized water and extracted with dichloromethane (20 mL × 3). The combined extracts were concentrated to remove the solvent, and the crude product was separated by column chromatography for the next reaction step.

[0178] Step 2: Using Compound 26 as the reaction raw material, the specific implementation method was the same as that in Examples 2 to 4 of the preparation of Compound 19a above, to obtain Intermediates 27 - 29.

[0179] Step 3: Using Compound 29 as the reaction raw material, the specific implementation method was the same as that in Example 5 of the preparation of Compound 19a above, to obtain the target product 30.

[0180] Preparation of Compound 19p

[0181] Step 1: Preparation of Intermediate 32

[0182]

[0183] 10.0 mmol of 3-bromothiophene-2-carbaldehyde (Compound 31), 11 mmol of phenylboronic acid, 5% of tetrakis(triphenylphosphine)palladium, 20 mL of sodium carbonate aqueous solution (2 M), 80 mL of toluene, and 80 mL of ethanol were successively added to a 100 mL round-bottom flask. The reaction solution was purged with nitrogen three times and reacted at 80 °C for 5 h under a nitrogen atmosphere. After the reaction was completed, the solvent was removed by rotary evaporation. The reaction residue was dissolved in 20 mL of deionized water and extracted with ethyl acetate (3 × 20 mL). The combined extracts were concentrated, and the crude product was separated by column chromatography to obtain Intermediate 32.

[0184] Step 2: Using Compound 32 as the reaction raw material, the specific implementation method was the same as that in Examples 2 to 4 of the preparation of Compound 19a above, to obtain Intermediates 33 - 35.

[0185] Step 3: Using Compound 35 as the reaction raw material, the specific implementation method was the same as that in Example 5 of the preparation of Compound 19a above, to obtain the target product 19p.

[0186] Preparation of Compound 19q

[0187] Step 1: Preparation of Intermediate 37

[0188]

[0189] In a 100 mL round-bottom flask, 10.0 mmol of 4-bromothiophene-2-carbaldehyde (Compound 36), 11 mmol of phenylboronic acid, 5% tetrakis(triphenylphosphine)palladium, 20 mL of aqueous sodium carbonate solution (2 M), 80 mL of toluene, and 80 mL of ethanol were successively added. The reaction solution was purged with nitrogen three times and reacted at 80 °C for 5 h under a nitrogen atmosphere. After the reaction, the solvent was removed by rotary evaporation. The reaction residue was dissolved in 20 mL of deionized water and extracted with ethyl acetate (3 × 20 mL). The combined extracts were separated by column chromatography to obtain Intermediate 37.

[0190] Step 2: Using Compound 37 as the reaction raw material, the specific implementation method was the same as that in Examples 2 to 4 in the preparation of Compound 19a above to obtain Intermediates 38 - 40.

[0191] Step 3: Using Compound 40 as the reaction raw material, the specific implementation method was the same as that in Example 5 in the preparation of Compound 19a above to obtain the target product 19q.

[0192] According to the preparation method of Compound 7a above, 7b - 7h were prepared using different starting materials; according to the preparation method of Compound 19a above, 19b - 19o, 19r, 19s were prepared using different starting materials; according to the preparation method of Compound 25a above, 25b was prepared using different starting materials.

[0193] The nuclear magnetic resonance hydrogen spectrum ( 1 1H NMR) and carbon spectrum ( 13 13C NMR) characterization data of all target products in the present invention are as follows:

[0194]

[0195] 1 1H NMR (400 MHz, Chloroform-d) δ 8.93 (s, 1H), 7.71–7.66 (m, 1H), 7.57–7.41 (m, 6H), 7.32 (t, J = 7.8 Hz, 2H), 7.15 (t, J = 7.4 Hz, 1H), 6.42 (t, J = 3.0 Hz, 1H), 6.09 (d, J = 6.4 Hz, 1H), 6.02 (t, J = 3.0 Hz, 1H), 3.74 (q, J = 6.5 Hz, 2H), 2.98 (t, J = 6.7 Hz, 2H) ppm; 13CNMR (101 MHz, Chloroform-d) δ 168.46, 135.77, 132.86, 132.23, 131.73, 130.09, 130.04, 128.95, 128.65, 127.28 (q, J = 31.3 Hz), 126.51 (q, J = 5.1 Hz), 125.96, 123.78 (q, J = 274.7 Hz), 123.57, 108.10, 106.18, 40.05, 28.12 ppm.

[0196]

[0197] 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.96 (s, 1H), 8.61 (t, J = 5.6 Hz, 1H), 7.77

[0198] (d, J = 8.1 Hz, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.63 (t, J = 7.6 Hz, 1H), 7.48 (d, J = 8.2 Hz, 3H), 7.13 (d, J = 7.9 Hz, 2H), 6.35–6.31 (m, 1H), 5.91–5.85 (m, 1H), 3.48 (q, J = 7.0 Hz, 2H), 2.82 (t, J = 7.7 Hz, 2H), 2.27 (s, 3H) ppm; 13 C NMR (101 MHz, DMSO-d 6 ) δ 167.04, 136.69, 133.97, 132.38, 130.58, 130.48, 130.24, 129.59, 129.23, 129.15, 128.52, 126.18 (q, J = 5.1 Hz), 125.88 (q, J = 31.3 Hz), 123.81 (q, J = 274.7 Hz), 122.98, 106.83, 104.95, 39.46, 27.21, 20.65 ppm.

[0199] 1 H NMR (400 MHz, DMSO-d 6)δ11.03(s,1H),8.61(t,J=5.6Hz,1H),7.77(d,J=7.8Hz,1H),7.71(t,J=7.5Hz,1H),7.67–7.56(m,3H),7.48(d,J=7.5Hz,1H),7.16(t,J=8.8Hz,2H),6.42–6.30(m,1H),5.90(t,J=2.9Hz,1H),3.49(q,J=7.2Hz,2H),2.82(t,J=7.7Hz,2H)ppm; 13 C NMR(101MHz,DMSO-d 6 )δ167.05,160.11(d,J=242.4Hz),136.66,132.38,131.03,129.86(d,J=3.0Hz),129.60,129.26,128.51,126.18(q,J=5.1Hz),125.88(q,J=31.3Hz),124.77,124.70,123.80(q,J=274.7Hz),115.49,115.28,107.02,105.54,39.41,27.21ppm.

[0200]

[0201] 1 H NMR(400MHz,DMSO-d 6 )δ11.12(s,1H),8.61(t,J=5.6Hz,1H),7.77(d,J=7.9Hz,1H),7.71(t,J=7.5Hz,1H),7.64(d,J=7.7Hz,1H),7.60(d,J=8.1Hz,2H),7.48(d,J=7.5Hz,1H),7.36(d,J=7.3Hz,2H),6.48–6.40(m,1H),5.92(t,J=3.0Hz,1H),3.49(q,J=7.2Hz,2H),2.82(t,J=7.6Hz,2H)ppm; 13 C NMR(101MHz,DMSO-d 6 )δ172.31,141.91,137.65,137.28,136.93,134.87,134.32,134.21,133.81,133.77,131.44(q,J=5.1Hz),131.13(q,J=31.3Hz),129.79,129.06(q,J=274.7Hz),112.55,111.63,44.60,32.46ppm.

[0202]

[0203] 1 1H NMR (400 MHz, DMSO-d 6 ) δ 8.67 (t, J = 5.7 Hz, 1H), 7.79 (d, J = 7.8 Hz, 1H), 7.72 (t, J = 7.5 Hz, 1H), 7.64 (t, J = 7.7 Hz, 1H), 7.50 (d, J = 7.5 Hz, 1H), 7.41 (d, J = 6.5 Hz, 4H), 7.31–7.26 (m, 1H), 6.08 (d, J = 3.6 Hz, 1H), 5.97 (d, J = 3.5 Hz, 1H), 3.55 (s, 3H), 3.49 (q, J = 7.0 Hz, 2H), 2.85 (t, J = 7.6 Hz, 2H) ppm; 13 13C NMR (101 MHz, DMSO-d 6 ) δ 167.09, 136.57, 133.51, 133.44, 132.40, 131.73, 129.66, 128.50, 128.46, 128.09, 126.32, 126.21 (q, J = 5.1 Hz), 125.89 (q, J = 31.3 Hz), 123.79 (q, J = 274.7 Hz), 107.42, 106.13, 38.56, 31.55, 26.40 ppm.

[0204]

[0205] 1 1H NMR (400 MHz, DMSO-d 6 ) δ 11.00 (s, 1H), 8.61 (t, J = 5.6 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.71 (t, J = 7.5 Hz, 1H), 7.64 (t, J = 7.7 Hz, 1H), 7.49 (d, J = 7.5 Hz, 1H), 7.43 (s, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.20 (t, J = 7.6 Hz, 1H), 6.92 (d, J = 7.5 Hz, 1H), 6.38 (t, J = 3.0 Hz, 1H), 5.90 (t, J = 2.9 Hz, 1H), 3.49 (q, J = 7.0 Hz, 2H), 2.82 (t, J = 7.6 Hz, 2H), 2.31 (s, 3H) ppm; 13 13C NMR (101 MHz, DMSO-d 6) δ 167.04, 137.53, 136.69, 133.06, 132.38, 130.92, 130.20, 129.59, 128.52, 128.48, 126.19 (q, J = 32.3 Hz), 126.18 (q, J = 5.1 Hz), 125.69, 123.80 (q, J = 274.7 Hz), 123.56, 120.25, 106.95, 105.48, 39.44, 27.21, 21.18 ppm.

[0206]

[0207] 1 H NMR (400 MHz, DMSO-d 6 ) δ 11.31 (s, 1H), 8.63 (t, J = 5.6 Hz, 1H), 7.82–7.75 (m, 3H), 7.71 (t, J = 7.5 Hz, 1H), 7.65 (d, J = 8.6 Hz, 3H), 7.49 (d, J = 7.5 Hz, 1H), 6.61 (t, J = 3.0 Hz, 1H), 5.99 (t, J = 2.9 Hz, 1H), 3.51 (q, J = 6.9 Hz, 2H), 2.85 (t, J = 7.6 Hz, 2H) ppm; 13 C NMR (101 MHz, DMSO-d 6 ) δ 167.08, 136.81, 136.64, 132.88, 132.38, 129.61, 128.64, 128.51, 126.15 (q, J = 5.1 Hz), 125.90 (q, J = 31.3 Hz), 125.58 (q, J = 4.0 Hz), 124.75 (q, J = 31.3 Hz), 124.61 (q, J = 272.7 Hz), 123.80 (q, J = 273.7 Hz), 122.99, 108.00, 107.75, 39.31, 27.20 ppm.

[0208]

[0209] 1 H NMR (400 MHz, DMSO-d 6) δ 10.89 (s, 1H), 8.59 (t, J = 5.6 Hz, 1H), 7.77 (d, J = 8.0 Hz, 2H), 7.70 (d, J = 7.5 Hz, 1H), 7.64 (d, J = 7.4 Hz, 1H), 7.53–7.47 (m, 4H), 6.94–6.87 (m, 3H), 6.25 (t, J = 2.8 Hz, 1H), 5.86 (t, J = 2.8 Hz, 1H), 3.75 (s, 3H), 3.48 (q, J = 7.1 Hz, 2H), 2.81 (t, J = 7.6 Hz, 2H) ppm; 13 C NMR (101 MHz, DMSO-d 6 ) δ 167.04, 157.07, 132.39, 130.15, 130.11, 129.60, 128.52, 126.20, 126.18 (q, J = 5.1 Hz), 125.86 (q, J = 29.3 Hz), 124.35, 123.50 (q, J = 274.7 Hz), 114.15, 114.07, 106.69, 104.22, 55.05, 39.38, 27.23 ppm.

[0210]

[0211] 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.69 (t, J = 5.7 Hz, 1H), 7.78 (d, J = 7.3 Hz, 1H), 7.73–7.60 (m, 4H), 7.49 (d, J = 7.4 Hz, 1H), 7.40 (t, J = 7.7 Hz, 2H), 7.26 (t, J = 7.4 Hz, 1H), 6.85 (d, J = 3.2 Hz, 1H), 6.33 (d, J = 3.3 Hz, 1H), 3.57 (q, J = 6.7 Hz, 2H), 2.95 (t, J = 7.0 Hz, 2H) ppm; 13 C NMR (101 MHz, DMSO-d 6 ) δ 167.17, 153.17, 151.85, 136.51 (q, J = 2.0 Hz), 132.35, 130.58, 129.68, 128.80, 128.51, 127.03, 126.22 (q, J = 5.1 Hz), 125.97 (q, J = 31.3 Hz), 123.78 (q, J = 274.7 Hz), 123.11, 108.43, 106.56, 37.85, 27.61 ppm.

[0212]

[0213] 1 ¹H NMR (400 MHz, DMSO-d 6 ) δ 8.72 (t, J = 5.7 Hz, 1H), 7.79 (d, J = 7.8 Hz, 1H), 7.73 (t, J = 7.5 Hz, 1H), 7.65 (d, J = 7.7 Hz, 1H), 7.64–7.59 (m, 2H), 7.51 (d, J = 7.5 Hz, 1H), 7.40 (t, J = 7.7 Hz, 2H), 7.37 (d, J = 3.6 Hz, 1H), 7.28 (t, J = 7.4 Hz, 1H), 6.95 (d, J = 3.6 Hz, 1H), 3.52 (q, J = 6.9 Hz, 2H), 3.06 (t, J = 7.1 Hz, 2H) ppm; 13 ¹³C NMR (101 MHz, DMSO-d 6 ) δ 167.66, 141.91, 141.84, 136.98, 134.45, 132.93, 130.22, 129.61, 128.99, 127.81, 127.18, 126.76 (q, J = 5.1 Hz), 126.47 (q, J = 31.3 Hz), 125.54, 124.29 (q, J = 274.7 Hz), 123.97, 41.16, 29.81 ppm.

[0214]

[0215] 1 ¹H NMR (400 MHz, DMSO-d 6 ) δ 8.70 (t, J = 5.7 Hz, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.72 (t, J = 7.5 Hz, 1H), 7.68 - 7.59 (m, 3H), 7.49 (d, J = 7.5 Hz, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 3.6 Hz, 1H), 6.95 (d, J = 3.6 Hz, 1H), 3.50 (q, J = 6.7 Hz, 2H), 3.04 (t, J = 7.1 Hz, 2H) ppm; 13 ¹³C NMR (101 MHz, DMSO-d 6) δ 167.66, 142.47, 140.46, 136.95, 133.35, 132.94, 132.18, 130.24, 129.58, 128.99, 127.37, 127.16, 126.77 (q, J = 5.1 Hz), 126.45 (q, J = 31.3 Hz), 124.70, 124.28 (q, J = 274.7 Hz), 41.10, 29.80 ppm.

[0216]

[0217] 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.71 (t, J = 5.7 Hz, 1H), 7.82 (d, J = 8.2 Hz, 2H), 7.78 (d, J = 7.8 Hz, 1H), 7.76–7.69 (m, 3H), 7.64 (t, J = 7.7 Hz, 1H), 7.54 (d, J = 3.6 Hz, 1H), 7.50 (d, J = 7.5 Hz, 1H), 7.01 (d, J = 3.6 Hz, 1H), 3.53 (q, J = 6.7 Hz, 2H), 3.08 (t, J = 7.1 Hz, 2H) ppm; 13 C NMR (101 MHz, DMSO-d 6 ) δ 167.68, 143.81, 139.97, 138.28, 136.96, 132.92, 130.22, 128.99, 127.91, 127.75 (q, J = 31.3 Hz), 126.75 (q, J = 5.1 Hz), 126.54 (q, J = 4.0 Hz), 126.48 (q, J = 32.3 Hz), 126.00, 125.95, 124.78 (q, J = 272.7 Hz), 124.28 (q, J = 274.7 Hz), 41.06, 29.83 ppm.

[0218]

[0219] 1 H NMR (400 MHz, DMSO-d 6) δ 8.69 (t, J = 5.7 Hz, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.72 (t, J = 7.5 Hz, 1H), 7.64 (t, J = 7.7 Hz, 1H), 7.53–7.45 (m, 3H), 7.29 (d, J = 3.6 Hz, 1H), 7.20 (d, J = 7.9 Hz, 2H), 6.92 (d, J = 3.6 Hz, 1H), 3.51 (q, J = 6.7 Hz, 2H), 3.03 (t, J = 7.1 Hz, 2H), 2.30 (s, 3H) ppm; 13 C NMR (101 MHz, DMSO-d 6 ) δ 167.64, 142.07, 141.19, 137.17, 136.99, 132.91, 131.74, 130.21, 130.13, 128.99, 127.04, 126.75 (q, J = 5.1 Hz), 126.47 (q, J = 31.3 Hz), 125.46, 124.29 (q, J = 274.7 Hz), 123.32, 41.17, 29.80, 21.20 ppm.

[0220]

[0221] 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.71 (t, J = 5.5 Hz, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.75 - 7.69 (m, 3H), 7.64 (t, J = 7.7 Hz, 1H), 7.50 (d, J = 7.4 Hz, 1H), 7.43–7.35 (m, 3H), 6.97 (d, J = 3.6 Hz, 1H), 3.52 (q, J = 6.6 Hz, 2H), 3.06 (t, J = 7.1 Hz, 2H) ppm; 13 C NMR (101 MHz, DMSO-d 6 ) δ 167.67, 147.83, 142.74, 140.17, 136.97, 133.82, 132.92, 130.22, 128.98, 127.38, 127.27, 126.75 (q, J = 5.1 Hz), 126.47 (q, J = 31.3 Hz), 124.97, 124.28 (q, J = 274.7 Hz), 122.23, 120.62 (q, J = 257.6 Hz), 41.09, 29.78 ppm.

[0222]

[0223] 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.70 (t, J = 5.7 Hz, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.72 (t, J = 7.3 Hz, 1H), 7.64 (t, J = 7.6 Hz, 1H), 7.53 - 7.45 (m, 3H), 7.29 (d, J = 3.6 Hz, 1H), 7.20 (d, J = 7.9 Hz, 2H), 6.91 (d, J = 3.6 Hz, 1H), 3.50 (q, J = 6.7 Hz, 2H), 3.03 (t, J = 7.1 Hz, 2H), 2.30 (s, 3H) ppm; 13 C NMR (101 MHz, DMSO-d 6 ) δ 172.38, 146.80, 145.92, 141.91, 141.71, 137.67, 136.47, 134.96, 134.88, 133.73, 131.80, 131.50 (q, J = 5.1 Hz), 131.19 (q, J = 31.3 Hz), 130.20, 129.02 (q, J = 274.7 Hz), 128.08, 45.91, 34.54, 25.95 ppm.

[0224]

[0225] 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.70 (t, J = 5.7 Hz, 1H), 7.78 (d, J = 7.7 Hz, 1H), 7.72 (t, J = 7.5 Hz, 1H), 7.69–7.61 (m, 2H), 7.55 (d, J = 7.9 Hz, 1H), 7.50 (d, J = 7.5 Hz, 1H), 7.47 (d, J = 3.6 Hz, 1H), 7.42 (t, J = 7.9 Hz, 1H), 7.36–7.30 (m, 1H), 6.97 (d, J = 3.6 Hz, 1H), 3.52 (q, J = 6.8 Hz, 2H), 3.06 (t, J = 7.1 Hz, 2H) ppm; 13 C NMR (101 MHz, DMSO-d 6)δ 167.67, 142.93, 140.03, 136.96 (q, J = 1.0 Hz), 136.51, 134.39, 132.91, 131.46, 130.22, 128.99, 127.47, 127.38, 126.76 (q, J = 5.1 Hz), 126.47 (q, J = 31.3 Hz), 125.27, 124.93, 124.28 (q, J = 274.7 Hz), 124.20, 41.08, 29.80 ppm.

[0226]

[0227] 1 H NMR (400 MHz, Chloroform - d) δ 7.73 (d, J = 7.5 Hz, 1H), 7.63–7.49 (m, 5H), 7.36–7.23 (m, 3H), 6.93 (d, J = 3.6 Hz, 1H), 6.28 (t, J = 5.7 Hz, 1H), 3.79 (q, J = 6.5 Hz, 2H), 3.21 (t, J = 6.8 Hz, 2H) ppm; 13 C NMR (101 MHz, Chloroform - d) δ 168.05, 142.20, 138.79, 135.86 (q, J = 2.0 Hz), 133.16, 132.13, 132.08, 131.22, 130.61, 129.88, 128.60, 128.55, 127.80, 127.33 (q, J = 31.3 Hz), 127.04, 126.44 (q, J = 4.0 Hz), 125.76, 123.70 (q, J = 275.7 Hz), 41.39, 29.86 ppm.

[0228]

[0229] 1 H NMR (400 MHz, DMSO - d 6 ) δ 8.72 (t, J = 5.6 Hz, 1H), 7.96 (d, J = 1.9 Hz, 1H), 7.87 (d, J = 8.2 Hz, 1H), 7.79–7.69 (m, 3H), 7.64 (t, J = 7.9 Hz, 1H), 7.53–7.47 (m, 2H), 7.05 (d, J = 3.7 Hz, 1H), 3.54 (q, J = 7.0 Hz, 2H), 3.10 (t, J = 7.0 Hz, 2H) ppm; 13 C NMR (101 MHz, DMSO - d 6) δ 167.68, 145.18, 136.95, 135.95, 132.89, 132.05, 131.52, 130.23, 129.85, 129.36 (q, J = 32.3 Hz), 128.98, 127.98 (q, J = 4.0 Hz), 126.76 (q, J = 4.0 Hz), 126.56, 126.48 (q, J = 31.3 Hz), 124.95 (q, J = 3.0 Hz), 124.27 (q, J = 274.7 Hz), 123.80 (q, J = 273.7 Hz), 41.03, 29.57 ppm.

[0230]

[0231] 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.70 (t, J = 5.7 Hz, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.72 (t, J = 7.4 Hz, 1H), 7.68–7.61 (m, 3H), 7.58 (d, J = 3.6 Hz, 1H), 7.52–7.46 (m, 2H), 6.99 (d, J = 3.7 Hz, 1H), 3.51 (q, J = 7.1 Hz, 2H), 3.06 (t, J = 7.1 Hz, 2H) ppm; 13 C NMR (101 MHz, DMSO-d 6 ) δ 167.14, 143.46, 137.88, 137.30, 136.40, 134.81, 132.41, 129.73, 128.47, 127.07, 126.35, 126.24 (q, J = 5.0 Hz), 126.04, 125.91 (q, J = 31.6 Hz), 123.75 (q, J = 275.1 Hz), 123.31, 40.47, 29.28 ppm.

[0232]

[0233] 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.71 (t, J = 5.3 Hz, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.74–7.68 (m, 2H), 7.67–7.61 m, 2H), 7.52–7.45 (m, 2H), 7.34 (d, J = 3.6 Hz, 1H), 7.00 (d, J = 3.6 Hz, 1H), 3.52 (q, J = 6.7 Hz, 2H), 3.08 (t, J = 7.1 Hz, 2H) ppm;13 C NMR (101 MHz, DMSO-d 6 ) δ 167.14, 143.53, 136.43, 135.86, 132.59, 132.38, 132.04, 131.52, 131.41, 129.89, 129.72, 128.46, 128.32, 127.86, 126.24 (q, J = 5.0 Hz), 125.94 (q, J = 31.6 Hz), 125.81, 123.75 (q, J = 275.1 Hz), 40.55, 29.04 ppm.

[0234]

[0235] 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.73 (t, J = 5.7 Hz, 1H), 7.89 (d, J = 2.2 Hz, 1H), 7.80 (d, J = 7.9 Hz, 1H), 7.74 (t, J = 7.6 Hz, 1H), 7.69–7.63 (m, 2H), 7.58 (dd, J = 8.4, 2.2 Hz, 1H), 7.55–7.49 (m, 2H), 6.99 (d, J = 3.6 Hz, 1H), 3.53 (q, J = 6.7 Hz, 2H), 3.07 (t, J = 7.1 Hz, 2H) ppm; 13 C NMR (101 MHz, DMSO-d 6 ) δ 167.15, 142.90, 138.39, 136.41, 134.57, 132.41, 131.85, 131.16, 129.72, 129.40, 128.47, 127.02, 126.32, 126.24 (q, J = 5.0 Hz), 125.93 (q, J = 31.6 Hz), 125.34, 125.10, 123.76 (q, J = 275.1 Hz), 40.53, 29.29 ppm.

[0236]

[0237] 1 H NMR (400 MHz, DMSO-d 6)δ8.74 (t, J = 5.7 Hz, 1H), 7.97–7.92 (m, 1H), 7.85–7.75 (m, 2H), 7.75–7.68 (m, 2H), 7.67–7.60 (m, 2H), 7.51 (d, J = 7.5 Hz, 1H), 7.02 (d, J = 3.7 Hz, 1H), 3.54 (q, J = 6.7 Hz, 2H), 3.08 (t, J = 7.0 Hz, 2H) ppm; 13 C NMR (101 MHz, DMSO-d 6 )δ167.20, 144.42, 139.42, 137.74, 136.41 (q, J = 1.9 Hz), 132.41, 131.64, 129.73, 128.65 (q, J = 5.4 Hz), 128.50, 127.31, 126.98, 126.79, 126.26 (q, J = 5.0 Hz), 125.99 (q, J = 31.6 Hz), 124.50 (q, J = 31.2 Hz), 123.78 (q, J = 274.7 Hz), 123.65, 122.96 (q, J = 273.5 Hz), 40.50, 29.35 ppm.

[0238]

[0239] 1 H NMR (400 MHz, DMSO-d 6 )δ8.65 (t, J = 5.7 Hz, 1H), 8.00–7.95 (m, 1H), 7.88 (d, J = 8.2 Hz, 1H), 7.76 (dd, J = 8.5, 1.9 Hz, 1H), 7.66 (dd, J = 8.0, 1.2 Hz, 1H), 7.51 (d, J = 3.7 Hz, 1H), 7.47–7.41 (m, 1H), 7.41–7.33 (m, 2H), 7.08 (d, J = 3.7 Hz, 1H), 3.56 (q, J = 7.0 Hz, 2H), 3.14 (t, J = 7.0 Hz, 2H) ppm; 13 C NMR (101 MHz, DMSO-d 6 )δ167.79, 145.23, 139.62, 136.95, 135.92, 133.22, 132.04, 131.50, 131.35, 129.84,

[0240] 129.21, 129.32 (q, J = 32.3 Hz), 128.02, 127.98 (q, J = 4.0 Hz), 126.63, 124.95 (q, J = 4.0 Hz), 123.80 (q, J = 272.7 Hz), 119.46, 40.93, 29.64 ppm.

[0241]

[0242] 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.59 (t, J = 5.6 Hz, 1H), 7.98–7.93 (m, 1H), 7.91–7.83 (m, 2H), 7.75 (dd, J = 8.4, 2.2 Hz, 1H), 7.49 (d, J = 3.7 Hz, 1H), 7.43 (td, J = 7.5, 1.2 Hz, 1H), 7.31 (dd, J = 7.6, 1.7 Hz, 1H), 7.16 (td, J = 7.7, 1.7 Hz, 1H), 7.08 (d, J = 3.7 Hz, 1H), 3.53 (q, J = 7.0 Hz, 2H), 3.13 (t, J = 7.0 Hz, 2H) ppm; 13 C NMR (101 MHz, DMSO-d 6 ) δ 168.95, 144.71, 142.93, 139.10, 136.42, 135.40, 131.53, 130.98, 130.74, 129.34, 128.80 (q, J = 32.3 Hz), 127.95, 127.91, 127.46 (q, J = 1.5 Hz), 126.11, 124.43 (q, J = 4.0 Hz), 123.28 (q, J = 272.7 Hz), 93.50, 40.46, 29.15 ppm.

[0243]

[0244] 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.70 (t, J = 5.7 Hz, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.71 (t, J = 7.5 Hz, 1H), 7.63 (t, J = 7.6 Hz, 1H), 7.51–7.42 (m, 6H), 7.39–7.32 (m, 1H), 7.12 (d, J = 5.2 Hz, 1H), 3.48 (q, J = 7.0 Hz, 2H), 3.10 (t, J = 7.6 Hz, 2H) ppm; 1313C NMR (101 MHz, DMSO-d 6 ) δ 167.57, 139.40, 136.92, 136.90, 136.59, 136.49, 132.87, 130.19, 129.69, 129.10, 129.04, 128.94, 127.47, 126.72 (q, J = 5.1 Hz), 126.46 (q, J = 31.3 Hz), 124.26 (q, J = 274.7 Hz), 123.87, 41.36, 28.32 ppm.

[0245]

[0246] 1 1H NMR (400 MHz, DMSO-d 6 ) δ 8.74 (t, J = 5.7 Hz, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.76–7.64 (m, 5H), 7.52 (d, J = 7.4 Hz, 1H), 7.46–7.38 (m, 3H), 7.31 (t, J = 7.4 Hz, 1H), 3.56 (q, J = 7.1 Hz, 2H), 3.10 (t, J = 7.1 Hz, 2H) ppm; 13 13C NMR (101 MHz, DMSO-d 6 ) δ 167.66, 142.90, 141.55, 137.00 (q, J = 1.0 Hz), 135.86, 132.91, 130.22, 129.36, 128.98, 127.53, 126.76 (q, J = 5.1 Hz), 126.44 (q, J = 32.3 Hz), 126.39, 124.88, 124.29 (q, J = 274.7 Hz), 119.64, 41.13, 29.77 ppm.

[0247]

[0248] 1 1H NMR (400 MHz, DMSO-d 6 ) δ 8.66 (t, J = 5.6 Hz, 1H), 7.96 (d, J = 1.9 Hz, 1H), 7.86 (d, J = 8.6 Hz, 1H), 7.75 (dd, J = 8.3, 2.0 Hz, 1H), 7.51–7.47 (m, 2H), 7.46–7.37 (m, 3H), 7.06 (d, J = 3.7 Hz, 1H), 3.55 (q, J = 6.9 Hz, 2H), 3.12 (t, J = 7.0 Hz, 2H) ppm; 1313C NMR (101 MHz, DMSO-d 6 ) δ 166.40, 144.74, 136.96, 136.44, 135.44, 131.53, 130.99, 130.75, 129.94, 129.63, 129.34, 128.82 (q, J = 33.3 Hz), 128.80, 127.50 (q, J = 4.0 Hz), 127.05, 126.13, 124.46 (q, J = 3.7 Hz), 123.31 (q, J = 273.5 Hz), 40.44, 29.15 ppm.

[0249]

[0250] 1 1H NMR (400 MHz, DMSO-d 6 ) δ 8.93 (t, J = 5.6 Hz, 1H), 8.04 (dd, J = 8.1, 1.2 Hz, 1H), 7.95 (d, J = 2.0 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.79 (td, J = 7.5, 1.3 Hz, 1H), 7.74 (dd, J = 8.4, 2.0 Hz, 1H), 7.69 (td, J = 7.8, 1.5 Hz, 1H), 7.59 (dd, J = 7.5, 1.5 Hz, 1H), 7.49 (d, J = 3.7 Hz, 1H), 7.07 (d, J = 3.7 Hz, 1H), 3.54 (q, J = 6.6 Hz, 2H), 3.12 (t, J = 7.0 Hz, 2H) ppm; 13 13C NMR (101 MHz, DMSO-d 6 ) δ 165.58, 147.14, 144.68, 136.43, 135.51, 133.58, 132.47, 131.56, 131.01, 130.79, 129.40, 129.00, 128.85 (q, J = 33.3 Hz), 127.51 (q, J = 4.0 Hz), 126.17, 124.47 (q, J = 3.7 Hz), 124.13, 123.32 (q, J = 273.5 Hz), 40.65, 29.01 ppm.

[0251]

[0252] 1 1H NMR (400 MHz, DMSO-d 6) δ 8.72 (t, J = 5.7 Hz, 1H), 8.53–8.46 (m, 1H), 7.89–7.83 (m, 1H), 7.82–7.75 (m, 2H), 7.72 (t, J = 7.4 Hz, 1H), 7.67–7.61 (m, 2H), 7.50 (d, J = 7.5 Hz, 1H), 7.26–7.19 (m, 1H), 6.97 (d, J = 3.6 Hz, 1H), 3.52 (q, J = 6.7 Hz, 2H), 3.05 (t, J = 7.1 Hz, 2H) ppm; 13 C NMR (101 MHz, DMSO-d 6 ) δ 167.14, 151.97, 149.31, 144.11, 142.54, 137.04, 136.45, 132.41, 129.72, 128.48, 126.60, 126.25 (q, J = 5.0 Hz), 125.95 (q, J = 31.6 Hz), 125.16, 123.77 (q, J = 274.6 Hz), 121.99, 118.25, 40.56, 29.47 ppm.

[0253]

[0254] 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.93–8.82 (m, 1H), 8.73 (t, J = 5.6 Hz, 1H), 8.19 (dd, J = 8.5, 2.4 Hz, 1H), 8.09 (d, J = 8.5 Hz, 1H), 7.85 (d, J = 3.8 Hz, 1H), 7.78 (d, J = 7.9 Hz, 1H), 7.72 (t, J = 7.4 Hz, 1H), 7.64 (t, J = 7.6 Hz, 1H), 7.49 (d, J = 7.5 Hz, 1H), 7.05 (d, J = 3.8 Hz, 1H), 3.53 (q, J = 6.9 Hz, 2H), 3.08 (t, J = 7.0 Hz, 2H) ppm; 13 C NMR (101 MHz, DMSO-d 6) δ 167.15, 155.51, 146.57, 146.27 (q, J = 4.1 Hz), 140.76, 136.41, 134.49 (q, J = 4.1 Hz), 132.43, 129.75, 128.47, 127.78, 127.20, 126.27 (q, J = 5.0 Hz), 125.94 (q, J = 31.3 Hz), 123.76 (q, J = 274.7 Hz), 122.85, 122.53, 118.24, 40.44, 29.50 ppm.

[0255]

[0256] 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.71 (t, J = 5.8 Hz, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.72 (t, J = 7.5 Hz, 1H), 7.68–7.60 (m, 2H), 7.49 (d, J = 7.5 Hz, 1H), 7.20 (d, J = 3.6 Hz, 1H), 6.92 (d, J = 3.6 Hz, 1H), 6.67 (d, J = 3.4 Hz, 1H), 6.56 (dd, J = 3.4, 1.8 Hz, 1H), 3.50 (q, J = 6.7 Hz, 2H), 3.04 (t, J = 7.1 Hz, 2H) ppm; 13 C NMR (101 MHz, DMSO-d 6 ) δ 167.16, 148.76, 142.24, 140.85, 136.45, 132.42, 131.08, 129.73, 128.47, 126.27 (q, J = 5.0 Hz), 126.26, 125.97 (q, J = 31.6 Hz), 123.78 (q, J = 274.7 Hz), 122.70, 112.05, 104.92, 40.60, 29.10 ppm.

[0257] Biological experiment examples

[0258] Example 1: Nematicidal test of the compound of the present invention

[0259] Caenorhabditis elegans was selected in the present invention to test and determine the nematicidal activity of the compound of the present invention.

[0260] Specific test operation process:

[0261] Accurately weigh the positive control drug and the target compound respectively with an electronic analytical balance, dissolve them with dimethyl sulfoxide, and then dilute them with an aqueous solution containing 0.5% Tween 80 to form a mother liquor with a certain concentration. The content of the organic solvent in water should be less than 0.5%, and the concentration of the mother liquor is 2 times the highest concentration required for testing. During actual testing, take appropriate amounts of the mother liquor and the aqueous solution containing 0.5% Tween 80 and dilute them to the required concentration for standby. Add the prepared liquid medicine into a 96-well plate, 60 μL per well, and repeat each drug twice. Use a continuous pipette to add 60 μL of nematode suspension (about 100 nematodes) to the drug, cover it, and place it in an observation room at 20 ± 1 °C. Set an aqueous solution containing 4 μL of dimethyl sulfoxide per milliliter of 0.5% Tween 80 as the CK control group, and Fluopyram and Tioxazafen as the positive control groups. Check the number of dead nematodes at 24 hours, 48 hours, and 72 hours, and calculate the average mortality rate of nematodes in the two repeated experiments.

[0262] Corrected mortality rate = (mortality rate of treatment group - mortality rate of control group) / (1 - mortality rate of control group) × 100%

[0263] Table 1 Lethality rates (%) of the compounds of the present invention against two kinds of nematodes at different concentrations

[0264]

[0265]

[0266] Note: CK is the blank control.

[0267] As can be seen from Table 1, the said compounds all have good nematicidal activities. Among them, at a concentration of 40 ppm, the compounds of the present invention all exhibit excellent nematicidal activities, and the lethality rates of Caenorhabditis elegans of compounds 19a, 19b, 19c, 19e, 19g, 19i, 19j, 19k, 19l, 19m, 19o, 19r, and 25b are 100%. At a concentration of 5 ppm, the lethality rates of Caenorhabditis elegans of compounds 19b, 19c, 19e, 19i, 19l, 19m, 19o, 19r, and 25b all exceed 50%, which is better than the commercial drug Tioxazafen.

[0268] All the documents mentioned in the present invention are cited in this application as references, just as if each document is cited separately as a reference. In addition, it should be understood that after reading the above teachings of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of this application.

Claims

1. A compound of formula I, or an optical isomer thereof, or a pesticide-acceptable salt thereof, in, R1 represents 0-5 substituents each independently selected from the following group: halogen, -OH, -NO2, -CN, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C3-C8 heterocycloalkyl containing 1, 2 or 3 heteroatoms selected from N, O or S, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted 5-7 membered heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S; X is selected from the group consisting of NR6, O, S; R6 is selected from the group consisting of H, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C3-C8 heterocycloalkyl containing 1, 2 or 3 heteroatoms selected from N, O or S, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted 5-7 membered heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S; Y represents 0-3 substituents each independently selected from the following group: substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C3-C8 heterocycloalkyl containing 1, 2 or 3 heteroatoms selected from N, O or S, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted 5-7 membered heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S; The substitution refers to substitution by one or more substituents selected from the following groups: halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, C3-C8 cycloalkyl, C3-C8 heterocycloalkyl containing 1, 2 or 3 heteroatoms selected from N, O or S, substituted or unsubstituted C6-C10 aryl.

2. The compound according to claim 1, characterized in that R1 represents 0-5 substituents each independently selected from the following group: halogen, -OH, -NO2, -CN, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C3-C8 cycloalkyl.

3. The compound according to claim 1, characterized in that X is selected from the following group: NR6, O, S; R6 is selected from the following group: H, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C3-C8 cycloalkyl.

4. The compound according to claim 1, characterized in that The compound of formula I is a compound of formula II: Wherein, each group is defined as in claim 1; Y is selected from the following group: H, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted 5-7 membered heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S.

5. The compound according to claim 4, characterized in that The structure of Y is selected from the following group: R2 represents 0-4 substituents each independently selected from the following group: halogen, C1-C6 alkyl, halo C1-C6 alkyl, C1-C6 alkoxy, halo C1-C6 alkoxy, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C3-C8 heterocycloalkyl containing 1, 2 or 3 heteroatoms selected from N, O or S, substituted or unsubstituted C6-C10 aryl.

6. The compound according to claim 4, characterized in that The structure of Y is 7. The compound according to any one of claims 1 to 6, characterized in that The compound is selected from the group consisting of:

8. A pesticide composition, characterized in that: Include: i) the compound according to claim 1, or its optical isomer, or its pesticide-acceptable salt; and ii) a pesticide-acceptable carrier.

9. Use of the compound according to claim 1, or its optical isomer, or its pesticide acceptable salt, characterized in that: i) for killing and / or controlling nematodes; and / or ii) for use in the preparation of insecticidal and / or nematicidal compositions or formulations.

10. A method for killing nematodes, characterized in that: The method comprises applying the compound as claimed in claim 1, or an optical isomer thereof, or an agrochemically acceptable salt thereof to a plant body that is or may be infested with insects, or to the soil or environment around it.

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