O-nitrophenyl benzyl compound as well as preparation and application thereof

Abstract

The invention discloses an o-nitrophenyl benzyl compound as well as preparation and application thereof. Specifically, the o-nitrophenyl benzyl compound with a novel structure as shown in a formula (I) is synthesized by introducing an o-nitrobenzene structure on the basis of existing or researched pesticide molecules and derivatives or prodrug active molecules thereof. The compound provided by the invention can release active substances in a light-controlled manner, and has remarkable insecticidal and bactericidal activity or plant growth regulating effect.

Description

Technical Field

[0001] This invention relates to the field of pesticides, specifically to an o-nitrophenylbenzyl compound and its preparation and uses. Background Technology

[0002] Controlled release technology for pesticides can precisely regulate the control of target pests and diseases. This method can minimize the need for pesticides in crops and has advantages such as improving the physicochemical properties of compounds, effectively prolonging the release time of active substances, and reducing the volatilization and degradation of active substances to improve their utilization rate.

[0003] Currently developed pesticide formulations such as nanopesticide microspheres, nanocapsules, nanoemulsions, and microcapsules have improved water solubility and addressed the problem of low utilization rate to some extent. However, they cannot achieve precise and time-controlled release, which limits their application scope and also makes it difficult to elucidate the toxicological mechanism of pesticides. Therefore, there is an urgent need in this field to develop a new type of controlled release technology. Summary of the Invention

[0004] To address the aforementioned problems, this invention provides a novel o-nitrobenzene compound, which is a light-controlled green pesticide that can release pesticide active substances under sunlight and has significant insecticidal, fungicidal, and plant growth-regulating effects.

[0005] In a first aspect, the present invention provides a compound of formula (I), an optical isomer thereof, a cis-trans isomer thereof, or

[0006] Its pesticide-acceptable salts:

[0007]

[0008] In the formula,

[0009] X is a group selected from the following group that has insecticidal, fungicidal, or plant growth-regulating activities:

[0010]

[0011]

[0012] R1, R2, R3, and R4 are each independently selected from the following group: hydrogen, halogen, hydroxyl, nitro, cyano, C1-C8 carboxylic acid, C1-C8 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C8 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C1-C6 haloalkoxy, C3-C8 cycloalkyl, C5-C7 cycloalkenyl, 3-8 membered heterocyclic, C6-C 10 Aryl, 5-14 heteroaryl;

[0013] R5 is selected from the following group: hydrogen, C1-C4 alkyl, halogen, nitro, cyano, C1-C4 haloalkyl;

[0014] Among them, the C1-C8 carboxylic acid group, C1-C8 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C3-C8 cycloalkyl group, C5-C7 cycloalkenyl group, 3-8 membered heterocyclic group, C6-C 10 The aryl and 5-14 heteroaryl groups may be further optionally substituted with one or more groups selected from the group consisting of: halogen, hydroxyl, nitro, cyano;

[0015] The heterocyclic group contains 1, 2 or 3 heteroatoms selected from N, O or S.

[0016] In a preferred example, X is selected from the following group:

[0017]

[0018] In a preferred embodiment, R1, R2, R3, and R4 are each independently selected from the group consisting of halogens, C1-C2 alkyl groups, C1-C2 alkoxy groups, C1-C2 haloalkyl groups, and C1-C2 haloalkoxy groups.

[0019] In a preferred embodiment, R1 and R4 are each independently H, methoxy, or ethoxy.

[0020] In a preferred embodiment, R2 and R3 are each independently H, methoxy, ethoxy, OCH2F, OCHF2, and OCF3.

[0021] In a preferred embodiment, R5 is selected from the group consisting of: hydrogen, methyl, halogen, hydroxyl, nitro, cyano, trifluoromethyl, trichloromethyl, and tribromomethyl.

[0022] In another preferred embodiment, the halogen is fluorine or chlorine.

[0023] In a preferred embodiment, the compound of formula (I) is selected from the following table:

[0024]

[0025]

[0026]

[0027]

[0028]

[0029]

[0030]

[0031]

[0032] In another preferred embodiment, the groups in the compound of formula I may optionally be the groups that correspond independently to those in Table 1 of this application.

[0033] In another preferred example, the compound of formula I is the compound shown in Table 1.

[0034] A second aspect of the present invention provides a method for preparing a compound of formula (I) as described in the first aspect of the present invention, characterized by comprising the following steps:

[0035]

[0036] (i) In conventional solvents It reacts with sodium borohydride to give compound II;

[0037] (ii) In an inert solvent, compound II reacts with p-nitrophenyl chloroformate to give compound III;

[0038] (iii) In an inert solvent, compound III reacts with HX to give compound I;

[0039] The definitions of R1, R2, R3, R4, R5 and X are as described in claim 1.

[0040] In another preferred embodiment, in step (i), the conventional solvent is methanol or ethanol.

[0041] In another preferred embodiment, in step (i), the reaction temperature is 0 to 10°C, preferably 0 to 5°C, and more preferably 0°C.

[0042] In another preferred embodiment, in step (i), the reaction time is 0 to 10 hours, preferably 1 to 8 hours, and more preferably 2 to 5 hours.

[0043] In another preferred embodiment, in step (ii), the inert solvent is dichloromethane.

[0044] In another preferred embodiment, in step (ii), an alkali is also added; the alkali is selected from the group consisting of N,N-diisopropylethylamine, pyridine, triethylamine, potassium carbonate, sodium carbonate, or combinations thereof.

[0045] In another preferred embodiment, in step (ii), the reaction temperature is 0 to 5°C, preferably 0°C.

[0046] In another preferred embodiment, in step (ii), the reaction time is 0 to 15 hours, preferably 3 to 10 hours, and more preferably 4 to 8 hours.

[0047] In another preferred embodiment, in steps (ii) and (iii), an inert gas protection is required; the inert gas is selected from the group consisting of nitrogen, argon, or combinations thereof.

[0048] In another preferred embodiment, in step (iii), the inert solvent is N,N-dimethylformamide.

[0049] In another preferred embodiment, in step (iii), an alkali is also added; the alkali is selected from N,N-diisopropylethylamine, 4-dimethylaminopyridine, or a combination thereof.

[0050] In another preferred embodiment, in step (iii), the reaction temperature is 0 to 5°C, preferably 0°C.

[0051] In another preferred embodiment, in step (iii), the reaction time is 10 to 40 hours, preferably 15 to 30 hours, and more preferably 20 to 28 hours.

[0052] In another preferred embodiment, the reaction in steps (ii) and (iii) needs to be carried out in the dark.

[0053] A third aspect of the present invention provides an agricultural composition comprising:

[0054] (a) 0.001% to 99.99% by weight of the compound as described in the first aspect of the invention, its optical isomers, cis-trans isomers, or pesticide-acceptable salts, or combinations thereof; and

[0055] (b) Pesticide-acceptable carriers and / or excipients.

[0056] In another preferred embodiment, component (a) accounts for 0.01-99.9% by weight, preferably 0.05-90% by weight, of the agricultural composition.

[0057] In another preferred embodiment, the agricultural composition further comprises other active substances selected from the group consisting of insecticides, baits, fungicides, acaricides, nematicides, fungicides, insect growth regulators, or combinations thereof.

[0058] In another preferred embodiment, a method for preparing an agricultural composition is provided, comprising the steps of: mixing (a) the compound described in the first aspect of the invention, its optical isomers, cis-trans isomers, or pesticide-acceptable salts, or combinations thereof, with (b) a pesticide-acceptable carrier and / or excipient to form an agricultural composition.

[0059] A fourth aspect of the present invention provides the use of a compound, an optical isomer, a cis-trans isomer, or a pesticide-acceptable salt thereof, or an agricultural composition as described in the first aspect of the present invention, characterized in that it is used for the prevention and control of agricultural pests and diseases or for the regulation of plant growth, or for the preparation of insecticides, fungicides, or plant growth regulators for the prevention and control of agricultural pests and diseases or for the regulation of plant growth.

[0060] In another preferred embodiment, a method for controlling agricultural pests and diseases is provided, the method comprising applying a compound, optical isomer thereof, cis-trans isomer thereof, or pesticide-acceptable salt thereof, or an agricultural composition thereof, as described in the first aspect of the invention, to a plant, animal, surrounding soil, or environment that is suffering from or may be suffering from pests and diseases.

[0061] In another preferred embodiment, the pests and diseases are selected from the group consisting of: wheat scab, rapeseed sclerotinia, cucumber gray mold, alfalfa aphid, armyworm, and Aedes albopictus larvae.

[0062] In another preferred embodiment, a method for regulating plant growth is provided, the method comprising applying a compound, an optical isomer thereof, a cis-trans isomer thereof, or a pesticide-acceptable salt thereof, or an agricultural composition as described in the first aspect of the invention, to a plant, a part of a plant, a plant organ, plant propagation material, or a plant growing site.

[0063] In another preferred embodiment, the plant is selected from the group consisting of corn and soybean plants.

[0064] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described in detail here. Detailed Implementation

[0065] Through long-term and in-depth research and extensive screening, the inventors have developed a novel o-nitrobenzene compound that can release pesticide active substances under sunlight, exhibiting significant insecticidal, fungicidal, and plant growth-regulating effects. Specifically, the combination of the photosensitive protective group and the active molecule enables rapid release under sunlight, offering high spatiotemporal control and eliminating the need for additional chemical substances. The inventors unexpectedly discovered that combining insecticides, fungicides, or plant growth regulators with o-nitrobenzene photoprotective groups yields a novel o-nitrobenzene compound that releases pesticide molecules and their derivatives via photocontrolled release, exhibiting significant insecticidal, fungicidal, and plant growth-regulating effects, making it an effective insecticide, fungicide, or plant growth regulator.

[0066] the term

[0067] In this invention, unless otherwise specified, the terms used have the general meanings known to those skilled in the art.

[0068] In this invention, the term "C1-C8 alkyl" refers to a straight-chain or branched alkyl group having 1, 2, 3, 4, 5, 6, 7, or 8 carbon atoms, preferably a C1-C6 alkyl group. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, or similar groups. In this invention, alkyl groups also include substituted alkyl groups, and the substituents can be halogenated, hydroxyl, cyano, nitro, etc.

[0069] In this invention, the term "C2-C6 alkenyl" refers to a straight-chain or branched alkenyl group having 2, 3, 4, 5, or 6 carbon atoms, including but not limited to vinyl, allyl, 1-propenyl, isopropenyl, 1-butenyl, 2-butenyl, or similar groups. In this invention, alkenyl groups also include substituted alkenyl groups, which can be halogenated, hydroxyl, cyano, nitro, etc.

[0070] In this invention, the term "C2-C6 alkynyl" refers to a straight-chain or branched alkynyl group having 2, 3, 4, 5, or 6 carbon atoms, including but not limited to ethynyl, propynyl, or similar groups. In this invention, the alkynyl group also includes substituted alkynyl groups, which can be halogenated, hydroxyl, cyano, nitro, etc.

[0071] In this invention, the term "C3-C8 cycloalkyl" refers to a cyclic alkyl group having 3, 4, 5, 6, 7, or 8 carbon atoms, including but not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or similar groups, preferably C3-C6 cycloalkyl. In this invention, cycloalkyl also includes substituted cycloalkyl groups, where the substituent can be halogenated, hydroxyl, cyano, nitro, etc.

[0072] In this invention, the term "C5-C7 cycloalkenyl" refers to a cyclic alkenyl group having 5, 6, or 7 carbon atoms and one or more double bonds, including but not limited to cyclopentenyl, cyclohexenyl, cycloheptenyl, 1,3-cyclohexadienyl, 1,4-cyclohexadienyl, or similar groups. In this invention, cycloalkenyl also includes substituted cycloalkenyl groups, which can be halogenated, hydroxyl, cyano, nitro, etc.

[0073] In this invention, the term "C1-C6 alkoxy" refers to a straight-chain or branched alkoxy group having 1, 2, 3, 4, 5, or 6 carbon atoms, such as C1-C6 alkyl-O- or C1-C5 alkyl-O-C1-C5 alkyl. Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, or similar groups. In this invention, alkoxy groups also include substituted alkoxy groups, where the substituent can be halogenated, hydroxyl, cyano, nitro, etc.

[0074] In this invention, the term "halogen" refers to fluorine, chlorine, bromine, or iodine.

[0075] The term "halogenated" refers to a group that is substituted by one or more of the same or different halogen atoms described above.

[0076] The term "C1-C8 haloalkyl" refers to an alkyl group that is substituted with one or more halogen atoms, including but not limited to trifluoromethyl, pentafluoroethyl, heptafluoroisopropyl or similar groups.

[0077] In this invention, the term "ring" or "cyclic system" refers to a carbon ring or a heterocyclic ring.

[0078] In this invention, the term "ring system" refers to a fused ring consisting of two or more rings joined together.

[0079] The term "heterocyclic group" refers to a fully saturated or partially unsaturated cyclic group (including, but not limited to, 3-7 membered monocyclic, 6-11 membered bicyclic, or 8-16 membered tricyclic systems), wherein at least one heteroatom is present in a ring containing at least one carbon atom. Each heterocycle containing a heteroatom may have 1, 2, 3, or 4 heteroatoms selected from nitrogen, oxygen, or sulfur atoms, wherein the nitrogen or sulfur atom may be oxidized or quaternized. The heterocyclic group may be attached to any heteroatom or carbon atom residue in a ring or cyclic molecule. In this invention, the heterocyclic group is preferably a 3-8 membered heterocyclic group, more preferably a 5-7 membered heterocyclic group. Typical monocyclic heterocyclic compounds include, but are not limited to, tetrahydrofuranyl, 4,5-dihydrothiazolyl-2-yl, 2-cyanoimino-4-oxo-1,3-thiazolyl-3-yl, 2-cyanoimino-4-oxo-1,3-thiazinyl-3-yl, azacyclic butyl, pyrrolidinyl, oxacyclic butyl, pyrazolinyl, imidazolinyl, imidazolyl, oxazolinyl, isoxazolinyl, thiazolyl, isothiazolinyl, piperidinyl, piperazinyl, 2-oxopiperidinyl, 2-oxopiperidinyl, 2-oxopiperrolidinyl, hexahydroacoxenyl, 4-piperidinoneyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, thiomorpholinyl sulfoxide, thiomorpholinyl sulfone, 1,3-dioxyl, and tetrahydro-1,1-dioxothiophene. Polycyclic heterocyclic compounds include spirocyclic, fused-ring, and bridged-ring heterocyclic compounds. In this invention, the heterocyclic group includes substituted heterocyclic groups, and the substituents can be halogenated, hydroxyl, cyano, nitro, etc.

[0080] The term "hybrid aromatic ring system" refers to a ring system in which at least one ring is an aromatic ring.

[0081] As used herein, the term "heteroaryl" refers to a heteroaryl system with 1-4 (e.g., 1, 2, 3, or 4) heteroatoms and 5-14 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, or 13) ring atoms, including monocyclic (e.g., "5, 6, or 7-membered heteroaryl") and polycyclic (e.g., "8-14-membered heteroaryl bicyclic or tricyclic ring system" or "8-12-membered heteroaryl bicyclic ring system"), wherein the heteroatoms are selected from oxygen, nitrogen, and sulfur, and the heteroaryl group includes... But not limited to: pyridinyl, thiazolyl, isothiazolyl, thiophene, furanyl, pyrroloyl, pyrazolyl, pyrimidinyl, oxazolyl, isoxazolyl, 1H-tetrazoleyl, 1H-1,2,3-triazolyl, 4H-1,2,4-triazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, tetrazolyl, benzene Furan, benzo[b]thiophene, indole, quinoline, isoquinoline, 1H-indazole, 1H-benzo[d]imidazolium, benzo[d]thiazole, benzo[d]oxazole, benzo[d]isoxazole, benzo[d][1,2,3]thiadiazole, 2,3-dihydroimidazo[1,2-a]pyridine, quinazoline, quinoxaline, cyclophosphine, phthalazine, 1,8-naphthidine, 4,5,6,7-tetrahydrobenzo[b]thiophene, benzo[b]thiophene-1,1- Dioxane, 8H-indeno[2,1-b]thiophene, 7,8-dihydro-6H-cyclopentane[4,5]thieno[2,3-d]pyrimidine, 3,5,6,7-tetrahydro-4H-cyclopentane[4,5]thieno[2,3-d]pyrimidine-4-one, spiro[indoline-3,2'-[1,3]dioxolane]-2-one, spiro[indoline-3,2'-[1,3]dioxane]-2-one, or indoline-2,3-dione, etc. In this invention, heteroaryl groups include substituted heteroaryl groups, and the substituents can be halogenated, hydroxyl, cyano, nitro, etc.

[0082] Unless otherwise stated, it is assumed that any heteroatom in a suboptimal valence state has enough hydrogen atoms to compensate for its valence state.

[0083] When the substituent is a non-terminal substituent, it is a subunit of the corresponding group. For example, alkyl corresponds to alkylene, cycloalkyl corresponds to cycloalkylene, heterocyclic corresponds to heterocyclic, alkoxy corresponds to alkoxy, etc.

[0084] In this invention, the term "substitution" refers to the substitution of one or more hydrogen atoms on a specific group by a specific substituent. The specific substituent is the substituent described accordingly above, or the substituent appearing in the various embodiments. When multiple positions in a particular structure are substituted by multiple specific substituents, each position of the substituent may be the same or different. The term "substitution" as used herein includes all permissible substitutions in organic compounds. In a broad sense, permissible substituents include acyclic, cyclic, branched-unbranched, carbocyclic, and heterocyclic, aromatic and non-aromatic organic compounds. In this invention, heteroatom nitrogen may be supplemented with hydrogen substituents or any permissible organic compound described above to complete its valence state. Furthermore, this invention is not intended to limit permissible substituted organic compounds in any way.

[0085] As described herein, the compounds of this invention may be substituted with any number of substituents or functional groups to broaden their scope.

[0086] The term "inert solvent" refers to various solvents that do not react with the raw materials, including various straight-chain, branched or cyclic alcohols, ethers or ketones, haloalkanes, 1,4-dioxane, acetonitrile, tetrahydrofuran, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), etc.

[0087] The term "pesticide-acceptable salt" means that the anion of the salt is known and acceptable in forming a fungicide-pesticide-acceptable salt. Preferably, the salt is water-soluble. Suitable acid addition salts formed by compounds of formula (I) include salts formed from inorganic acids, such as hydrochlorides, phosphates, sulfates, and nitrates; and salts formed from organic acids, such as acetates, benzoates, etc. Salts that may be formed from the compounds of this invention are also within the scope of this invention. Unless otherwise stated, compounds of this invention are understood to include their salts. The term "salt" as used herein refers to a salt formed from an inorganic or organic acid and a base in an acidic or basic form.

[0088] Specific functional groups and chemical terminology definitions are detailed below. For the purposes of this invention, chemical elements are defined in the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75. th The definitions in Ed. are consistent. The definitions of specific functional groups are also described there. In addition, the basic principles of organic chemistry, as well as specific functional groups and reactivity, are explained in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausalito: 1999, the full contents of which are included in the references.

[0089] Some compounds of this invention may exist in specific geometric or stereoisomeric forms. This invention covers all compounds, including their cis and trans isomers, R and S enantiomers, diastereomers, (D) isomers, (L) isomers, racemic mixtures, and other mixtures. Additionally, the asymmetric carbon atom may represent a substituent, such as an alkyl group. All isomers and mixtures thereof are included in this invention.

[0090] According to the present invention, the ratio of isomers in a mixture of isomers can be varied. For example, a mixture containing only two isomers can have the following combinations: 50:50, 60:40, 70:30, 80:20, 90:10, 95:5, 96:4, 97:3, 98:2, 99:1, or 100:0. All ratios of isomers are within the scope of the present invention. Similar ratios readily understood by those skilled in the art, as well as ratios for mixtures of more complex isomers, are also within the scope of the present invention.

[0091] This invention also includes isotopically labeled compounds, equivalent to the original compounds disclosed herein. However, in practice, it is common for one or more atoms to be replaced by atoms with different atomic weights or mass numbers. Examples of isotopes that can be included in the compounds of this invention include hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chlorine isotopes, respectively as follows: 2 H, 3 H, 13 C 11 C 14 C 15 N、 18 O、 17 O、 31 P, 32 P, 35 S, 18 F and 36 Cl. The compounds of this invention, or enantiomers, diastereomers, isomers, or pharmaceutically acceptable salts or solvates, wherein the isotopes or other isotopic atoms of the aforementioned compounds are all within the scope of this invention. Certain isotopically labeled compounds of this invention, for example... 3 H and 14 Radioactive isotopes of carbon are also included, and are useful in tissue distribution experiments of drugs and substrates. Tritium, i.e. 3 H and carbon-14, i.e. 14 C, their preparation and detection are relatively easy. They are the preferred isotopes. In addition, heavier isotopes such as deuterium are used for substitution. 2H, due to its excellent metabolic stability, offers advantages in certain therapies, such as increasing half-life or reducing dosage in vivo, and therefore may be preferred in some cases. Isotopically labeled compounds can be prepared using general methods, by replacing the non-isotopic reagent with an readily available isotopically labeled reagent, according to the scheme described in the examples.

[0092] To design the synthesis of a specific enantiomer of the compound of this invention, it can be prepared asymmetrically or derivatized with a chiral auxiliary. The resulting diastereomeric mixture is then separated, and the chiral auxiliary is removed to obtain the pure enantiomer. Alternatively, if the molecule contains a basic functional group, such as an amino acid, or an acidic functional group, such as a carboxyl group, it can be formed with a suitable optically active acid or base to form a diastereomer salt, which is then separated by conventional methods such as separation crystallization or chromatography to obtain the pure enantiomer.

[0093] In this invention, the term "plant" refers to all tangible parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, culms, leaves, and fruits.

[0094] As used herein, the term "site" means the place in which or on which a plant grows, or the place where the seeds of a cultivated plant are sown, or the place where the seeds will be placed in the soil. It includes the soil, the seeds, and the seedlings, along with the established vegetation.

[0095] The term "plant propagation material" refers to all reproductive parts of a plant, such as seeds or vegetative parts like cuttings and tubers. It includes seeds in the strict sense, as well as roots, fruits, tubers, bulbs, rhizomes, and other parts of the plant.

[0096] In this invention, the term "regulating plant growth" includes, but is not limited to: prolonging the dormancy of storage organs, breaking dormancy and promoting germination, promoting stem and leaf growth, promoting rooting, inhibiting the growth of stem and leaf buds, promoting flower bud formation, inhibiting flower bud formation, thinning flowers and fruits, preserving flowers and fruits, prolonging the flowering period, inducing the production of female flowers, inducing the production of male flowers, preserving cut flowers, forming seedless fruits, promoting fruit ripening, delaying fruit ripening, delaying senescence, increasing amino acid content, increasing protein content, increasing sugar content, promoting fruit coloring, increasing fat content, and improving stress resistance.

[0097] The active material of this invention

[0098] "Compounds of the present invention", "active substances of the present invention" or "active compounds of the present invention" all refer to compounds with the structure shown in general formula (I) or their optical isomers, cis-trans isomers or pesticide-acceptable salts thereof, which have significant inhibitory activity against plant pathogens.

[0099] Specifically, the compounds of the present invention refer to compounds having the formula (I), their optical isomers, cis-trans isomers, or pesticide-acceptable salts thereof:

[0100]

[0101] Wherein, X is selected from any group that has insecticidal, bactericidal or plant growth regulating activities;

[0102] R1, R2, R3, and R4 refer to one or more groups selected from the group consisting of: hydrogen, halogen, hydroxyl, nitro, cyano, C1-C8 carboxylic acid, C1-C8 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C8 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C1-C6 haloalkoxy, C3-C8 cycloalkyl, C5-C7 cycloalkenyl, 3-8 membered heterocyclic group, C6-C 10 Aryl, 5-14 membered heteroaryl; R5 refers to one or more groups selected from the group consisting of: hydrogen, methyl, halogen, nitro, cyano, trichloromethyl, tribromomethyl, trifluoromethyl;

[0103] Among them, the C1-C8 carboxylic acid group, C1-C8 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C3-C8 cycloalkyl group, C5-C7 cycloalkenyl group, 3-8 membered heterocyclic group, C6-C 10 The aryl and 5-14 heteroaryl groups may be further optionally substituted with one or more groups selected from the group consisting of: halogen, hydroxyl, nitro, cyano;

[0104] The heterocyclic group contains 1, 2 or 3 heteroatoms selected from N, O or S.

[0105] As used herein, the term "optical isomer" refers to a compound in which the chiral carbon atom can be in the R configuration, the S configuration, or a combination thereof. This invention includes any one of such optical isomers and mixtures containing them in any proportion. As used herein, the term "cis-trans isomer" refers to isomers in a compound molecule that differ in the spatial arrangement of groups due to a constraint on free rotation. This constraint is generally caused by non-rotating functional groups in the structure of organic compounds, such as C=C double bonds, C=N double bonds, C=S double bonds, N=N double bonds, heterocycles, or cycloalkanes. Organic molecules containing such isomers, such as alkenes, azo compounds, and cyclic hydrocarbons, are considered cis-trans isomers. "Cis" indicates that the same ligands are in adjacent positions, generally denoted by "cis" or "cis-"; "trans" indicates that the same ligands are in diagonal positions, generally denoted by "trans" or "trans-". This invention includes any one of such cis-trans isomers and mixtures containing them in any proportion.

[0106] As used herein, the term "pesticide-acceptable salt" can include inorganic acid salts, organic acid salts, inorganic base salts, organic base salts, salts of basic amino acids, or salts of acidic amino acids. The aforementioned inorganic acids include, but are not limited to, hydrochloric acid, hydroboric acid, nitric acid, sulfuric acid, or phosphoric acid. The aforementioned organic acids 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, benzoic acid, p-toluenesulfonic acid, or fumaric acid. The aforementioned inorganic base salts include, but are not limited to, sodium salts, potassium salts, lithium salts, ammonium salts, calcium salts, magnesium salts, iron salts, zinc salts, copper salts, manganese salts, and aluminum salts. The aforementioned organic base salts include, but are not limited to, primary amines, secondary amines, and tertiary amines, substituted amines, including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins. The aforementioned acidic amino acids include, for example, glycine, aspartic acid, or glutamic acid.

[0107] In another preferred embodiment, the salt is water-soluble.

[0108] The insecticidal, bactericidal, or plant growth-regulating activities of the substances of this invention.

[0109] The substances of this invention have significant insecticidal, bactericidal, or plant growth-regulating effects, and can be used to prevent and control agricultural pests and diseases or regulate plant growth, or to prepare insecticides, bactericides, or plant growth regulators for preventing and controlling agricultural pests and diseases or regulating plant growth.

[0110] Examples of pests / insect pests include, but are not limited to: Coleoptera insects such as the corn weevil (Sitophilus zeamais), the red flour beetle (Tribolium castaneum), the potato ladybug (Henosepilachna vigintioctomaculata), the twenty-eight-spotted ladybug (Henosepilachna sparsa), the slender-throated click beetle (Agriotes fuscicollis), the red-legged green beetle (Anomala cupripes), the four-striped beetle (Popillia quadriguttata), the potato leaf beetle (Monolepta hieroglyphica), the pine longhorn beetle (Monochamus alternatus), the rice root weevil (Echinocnemus squameus), the paulownia leaf beetle (Basiprionota bisignata), the star longhorn beetle (Anoplophora chinensis), the mulberry longhorn beetle (Apripona germari), and the umbilical bark beetle (Scolytus). schevy), or wireworm (Agriotes fuscicollis); Lepidoptera insects, such as rice leaf roller (Cnaphalocrocis medinalis Guenee), gypsy moth (Lymantria dispar), tent caterpillar (Malacosoma neustria testacea), boxwood leaf roller (Diaphania perspectalis), large bagworm moth (Clania variegata), yellow tussock moth (Cnidocampaflauescens), pine caterpillar (Dendrolimus punctatus), ancient tussock moth (Orgyiagonostigma), poplar clearwing moth (Paranthrene tabaniformis), beet armyworm (Spodoptera litura), rice stem borer (Chilo suppressalis), corn borer (Ostrinia nubilalis), white spot moth (Ephestia cautella), cotton leaf roller (Adoxophyes) Orana, Chestnut leafroller (laspyresia splendana), Small cutworm (Agrotis fucosa), Large wax moth (Galleria mellonella), Diamondback moth (Plutella xylostella), Orange leafminer (Phyllocnistis citrella), or Eastern armyworm (Mythimna separata).Homoptera, such as the black-tailed leafhopper (Nephotettix cincticeps), brown planthopper (Nilaparvata lugens), Comstock mealybug (Pseudococcus comstocki), arrow scale (Unaspis yanonensis), peach aphid (Myzus persicae), cotton aphid (Aphisgossydii), turnip aphid (Lipaphis erysimi pseudobrassicae), pear lace bug (Stephanitisnashi), or whitefly (Bemisia tabaci); Orthoptera, such as the German cockroach (Blattella germanica), American cockroach (Periplaneta americana), African mole cricket (Gryllotalpa africana), or Asian migratory locust (Locus migratoria); Isoptera, such as invasive red imported fire ant (Solenopsis). Invicta (or domestic termite (Coptotermesformosanus)); Diptera insects, such as housefly (Musca domestica), Aedes aegypti, Delia platura, Culex sp., or Anopheles sinensis; Homoptera insects, such as red-backed long bug (Tropidothorax elegans Distant), green rice bug (Nezara viridula Linnaeus), and pear bug (Urochela luteovaria Distant).

[0111] Examples of diseases include, but are not limited to: downy mildew (downy mildew of cucumber, rapeseed, soybean, beet, sugarcane, tobacco, pea, loofah, winter melon, cantaloupe, Chinese cabbage, spinach, radish, grape, and onion), white rust (white rust of rapeseed and other Chinese cabbage species), damping-off (dampness of rapeseed, tobacco, tomato, pepper, eggplant, cucumber, and cotton seedlings), cottony rot (cottony rot of pepper, loofah, and winter melon), blight (blight of broad bean, cucumber, winter melon, watermelon, cantaloupe, pepper, leek, garlic, and cotton), and late blight (late blight of potato and tomato).Root rot (root rot of peppers, eggplants, beans, cucumbers, bitter gourds, cotton, broad beans), damping-off (dampness of cotton seedlings, sesame, peppers, cucumbers, cabbage), Verticillium wilt (Verticillium wilt of cotton, sunflowers, tomatoes, peppers, eggplants), black spot (black spot of zucchini, winter melon, cantaloupe), gray mold (black and gray mold of cotton bolls, gray mold of kenaf, gray mold of tomatoes, gray mold of peppers, gray mold of beans, gray mold of mustard greens, gray mold of ferns, gray mold of kiwifruit, gray mold of wild clover), brown spot (brown spot of cotton, yellow... Brown spot disease (including brown spot on flax, beet, peanut, pepper, winter melon, soybean, sunflower, pea, and broad bean); black spot disease (including false black spot on flax, rapeseed, sesame, sunflower, castor bean, tomato, pepper, eggplant, green bean, cucumber, celery, carrot, apple, and peanut); leaf spot disease (including leaf spot on tomato, pepper, and celery); early blight disease (including early blight on tomato, pepper, eggplant, potato, and celery); and ring spot disease (including soybean ring spot). Diseases include: sesame ring rot, bean ring rot; leaf blight (sesame leaf blight, sunflower leaf blight, watermelon leaf blight, melon leaf blight); stem base rot (tomato stem base rot, bean stem base rot); and others (corn round spot, kenaf waist break, rice blast, chestnut black sheath disease, sugarcane eye spot, cotton boll blight, peanut crown rot, soybean stem rot, soybean black spot, melon large spot, peanut net spot, tea red leaf spot, pepper white star disease, winter melon leaf spot, sprout black rot, cabbage heart rot, kenaf leaf mold, kenaf spot, jute stem spot, soybean purple spot, sesame leaf spot, castor bean gray spot, tea brown leaf spot, eggplant brown round star disease, vegetable... Red spot disease of soybeans, white spot disease of bitter gourd, spot disease of watermelon, wilt disease of jute, root and stem rot of sunflower, carbon rot of common bean, leaf spot of eggplant, target spot disease of cucumber, leaf mold of tomato, leaf mold of eggplant, red spot disease of broad bean, etc.; Basidiomycete diseases, such as rust (wheat stripe rust, wheat stem rust, wheat leaf rust, flower rust, sunflower rust, deer rust, leek rust, onion rust, chestnut rust, soybean rust), smut (corn silk smut, corn smut, sorghum silk smut, sorghum loose smut, sorghum sturdy smut, sorghum pillar smut, chestnut smut, sugarcane smut, common bean rust) and others (such as wheat sheath blight, rice sheath blight, etc.).Ascomycete diseases, such as powdery mildew (wheat powdery mildew, rapeseed powdery mildew, sesame powdery mildew, sunflower powdery mildew, beet powdery mildew, eggplant powdery mildew, pea powdery mildew, loofah powdery mildew, pumpkin powdery mildew, zucchini powdery mildew, winter melon powdery mildew, cantaloupe powdery mildew, grape powdery mildew, broad bean powdery mildew), sclerotinia rot (flax sclerotinia rot, rapeseed sclerotinia rot, soybean sclerotinia rot, peanut sclerotinia rot, tobacco sclerotinia rot, pepper sclerotinia rot, eggplant sclerotinia rot, common bean sclerotinia rot, pea sclerotinia rot, cucumber sclerotinia rot, bitter gourd sclerotinia rot, winter melon sclerotinia rot, watermelon sclerotinia rot, celery sclerotinia rot), black spot (apple black spot, pear black spot), clubroot (cabbage clubroot, Chinese cabbage clubroot, cauliflower clubroot, scallion clubroot, mustard clubroot, radish clubroot, turnip clubroot, rapeseed clubroot).

[0112] These compounds and compositions of the present invention can be applied as plant growth regulators to dicotyledonous or monocotyledonous crops. The useful plant crops to which the compositions according to the invention can be used include perennial and annual crops, such as berry plants like blackberries, blueberries, cranberries, raspberries, and strawberries; cereals like barley, corn, millet, oats, rice, rye, sorghum, triticale, and wheat; fiber plants like cotton, flax, hemp, jute, and sisal; field crops like sugar beets and forage beets, coffee beans, hops, mustard, rapeseed (canola), poppies, sugarcane, sunflowers, tea, and tobacco; fruit trees like apples, apricots, avocados, bananas, cherries, citrus fruits, nectarines, peaches, pears, and plums; and grasses like Bermuda grass, bluegrass, benjamina, sedge, sedge, ryegrass, ryegrass, and St. Augustine grass. And zoysia grass; herbs such as basil, borage, chives, coriander, lavender, angelica, mint, oregano, parsley, rosemary, sage, and thyme; legumes such as kidney beans, lentils, peas, and soybeans; nuts such as almonds, cashews, peanuts, hazelnuts, peanuts, pecans, pistachios, and walnuts; palm plants such as oil palm; ornamental plants such as flowers, shrubs, and trees; other trees such as cocoa trees, coconut trees, olive trees, and rubber trees; vegetables such as asparagus, eggplant, broccoli, cabbage, carrots, cucumbers, garlic, lettuce, zucchini, melons, okra, onions, peppers, potatoes, squash, rhubarb, spinach, and tomatoes; and grapevines such as grapes.

[0113] Pesticide compositions containing "the active substance of the present invention"

[0114] The active substances of the present invention can be prepared into insecticide, fungicide, or plant growth regulator compositions using conventional methods. These active compounds can be formulated into conventional preparations, such as solutions, emulsions, suspensions, powders, foams, pastes, granules, aerosols, natural and synthetic materials impregnated with the active substances, microcapsules in polymers, seed coating compounds, and preparations for use with combustion devices, such as fumigation cylinders, fumigation canisters, and fumigation trays, as well as ULV cold mist and warm mist preparations.

[0115] These formulations can be produced using known methods, such as mixing the active compound with a expander, which can be a liquid, liquefied gas, or solid diluent or carrier, and can be any type of surfactant, i.e., emulsifier and / or dispersant and / or foaming agent. For example, when water is used as the expander, organic solvents can also be used as adjuvants.

[0116] Liquid solvents are generally suitable as diluents or carriers, such as: aromatic hydrocarbons, such as xylene, toluene, or alkylnaphthalene; chlorinated aromatic or chlorinated aliphatic hydrocarbons, such as chlorobenzene, vinyl chloride, or dichloromethane; aliphatic hydrocarbons, such as cyclohexane or paraffins, 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 commonly used polar solvents, such as dimethylformamide, dimethyl sulfoxide, and water.

[0117] A liquefied gas diluent or carrier refers to a liquid that will become a gas at normal temperature and pressure, such as aerosol propellants, halogenated hydrocarbons, and butane, propane, nitrogen, and carbon dioxide.

[0118] 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 dispersed silica, alumina, and silicates. Solid carriers for granulation are crushed and graded natural zircon, such as calcite, marble, pumice, sepiolite, dolomite, inorganic and organic coarse powders synthesized into granules, and organic materials such as sawdust, coconut husks, corncobs, and tobacco stalks.

[0119] Nonionic and anionic emulsifiers can be used as emulsifiers and / or foam forming agents. Examples include polyoxyethylene-fatty acid esters, polyoxyethylene-fatty alcohol ethers, alkylaryl polyethylene glycol ethers, alkyl sulfonates, alkyl sulfates, aryl sulfonates, and albumin hydrolysates. Dispersants include lignin sulfite waste and methylcellulose.

[0120] Binders, 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, can be used in the formulation.

[0121] Coloring agents such as inorganic dyes, such as 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, can be used.

[0122] The "active compounds of the present invention" can be mixed with other active compounds and exist in their commercial formulations or in dosage forms prepared from these formulations. These other active compounds are insecticides, fungicides, herbicides, growth regulators, etc. Insecticides include, for example, phosphate esters, carbamates, chlorinated hydrocarbons, and substances produced by microorganisms, such as avermectin. Fungicides include methoxyacrylates, amides, triazoles, etc.

[0123] Furthermore, the "active compounds of the present invention" may also be mixed with synergists in their commercial formulations or in dosage forms prepared from these formulations. These synergists are compounds that enhance the activity of the active compounds. Since the active compounds themselves are active, it is not necessary to add synergists.

[0124] These formulations typically contain 0.001 to 99.99% by weight of the total pesticide composition, preferably 0.01 to 99.9% by weight, more preferably 0.05 to 90% by weight of the "active compound of the invention". The concentration of the active compound in commercial formulations or application formulations can vary over a wide range. The concentration of the active compound in application formulations can range from 0.0000001 to 100% (g / v), preferably between 0.0001 and 1% (g / v).

[0125] The compound shown in formula (I), its optical isomers, cis-trans isomers, or pesticide-acceptable salts thereof, are particularly effective against alfalfa aphids or Aedes albopictus larvae or armyworms or cucumber gray mold and rapeseed sclerotinia disease, and have a good regulatory effect on the growth of corn or soybean plants.

[0126] All stereoisomers of compounds (e.g., those with asymmetric carbon atoms due to various substitutions), including their enantiomers and diastereomeric forms, are within the scope of this invention. The independent stereoisomers of the compounds in this invention may not coexist with other isomers (e.g., possessing special activity as a pure or substantially pure optical isomer), or may be mixtures, such as racemates, or mixtures formed with all other stereoisomers or a portion thereof. The chiral center of this invention has two configurations, S or R, as defined by the International Union of Theoretical and Applied Chemistry (IUPAC) in 1974. Racemic forms can be resolved by physical methods, such as stepwise crystallization, or by derivatization into diastereomers followed by crystallization, or by chiral column chromatography. Individual optical isomers can be obtained from racemates by suitable methods, including but not limited to conventional methods, such as recrystallization after salting with an optically active acid.

[0127] The compounds of this invention, obtained sequentially through preparation, separation, and purification, have a weight content equal to or greater than 90%, for example, equal to or greater than 95%, or equal to or greater than 99% (“very pure” compounds), as listed in the text description. Such “very pure” compounds of this invention are also included as part of this invention.

[0128] All configurational isomers of the compounds of this invention are included within the scope of this invention, whether in mixtures, pure or very pure forms. The definition of compounds in this invention includes both cis (Z) and trans (E) olefin isomers, as well as cis and trans isomers of carbocyclic and heterocyclic compounds.

[0129] Throughout the specification, groups and substituents can be selected to provide stable fragments and compounds.

[0130] Preparation method

[0131] The compounds represented by the general formula of this invention can be prepared by the following method; however, the conditions of this method, such as reactants, solvents, bases, amounts of compounds used, reaction temperatures, and reaction times, are not limited to those explained below. The compounds of this invention can also be conveniently prepared by optionally combining various synthetic methods described in this specification or known in the art, such combinations being readily performed by those skilled in the art. Reagents can be commercially available if feasible.

[0132] The method for preparing the compound of the present invention includes the following steps:

[0133]

[0134] (1) In a suitable solvent, R-substituted 2-nitrobenzaldehyde analogs react with sodium borohydride at 0–10 °C to form compounds of the following formula (II);

[0135]

[0136] (2) In a suitable solvent, compound (II) reacts with p-nitrophenyl chloroformate under argon protection at 0–5 °C to form compound (III);

[0137]

[0138] (3) In a suitable solvent, in a dark environment, compound (III) reacts with X at 0-5°C under argon protection to obtain compound (I); or in step (3), compound (III) can react with HX in two steps to obtain compound (I).

[0139] Wherein, R is defined as R1, R2, R3, R4 and / or R5 as described above;

[0140] X is defined as described above.

[0141] The synthetic reaction parameters can be used, for example, the general methods and procedures described below, to prepare the compounds of the present invention from readily available starting materials. It will be appreciated that other method conditions may also be used, unless otherwise indicated, given typical or optimized method conditions (i.e., reaction temperature, time, molar ratio of reactants, solvent, catalyst, pressure, etc.). Optimal reaction conditions may vary depending on the specific reactants or solvents used, but such conditions can be determined by those skilled in the art through conventional optimization procedures.

[0142] The starting materials used in the following reactions are generally known compounds, or can be prepared by known steps or by obvious modifications thereof. For example, many starting materials are available from commercial suppliers, while others can be prepared by steps or obvious modifications described in the text of standard references, such as the method described in CN104530037A.

[0143] In the preparation method of the present invention, each reaction is typically carried out in an inert solvent at a reaction temperature of -20 to 120°C (preferably -10 to 0°C, 20 to 30°C, or 80 to 100°C). The reaction time is typically 2 to 24 hours, preferably 4 to 18 hours, and the reaction time can be appropriately extended according to the needs of the reaction. The specific reaction time depends on the degree of reaction.

[0144] The bases used in the reaction include (but are not limited to): triethylamine, diisopropylethylamine, diethylamine, piperidine, piperazine, morpholine, N-methylmorpholine, triethylenediamine (DABCO), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), pyridine, potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, or combinations thereof.

[0145] The present invention has the following main advantages:

[0146] (1) This invention provides a novel o-nitrobenzene compound with high efficiency, low toxicity, good environmental compatibility, and novel structure;

[0147] (2) The compounds of the present invention can release active substances in a light-controlled manner and have significant insecticidal, bactericidal and plant growth-regulating effects.

[0148] (3) The compounds of the present invention are particularly suitable for the control of alfalfa aphids or Aedes albopictus larvae or armyworms or cucumber gray mold, rapeseed sclerotinia disease, and for the regulation of plant growth of corn or soybean.

[0149] (4) The compounds of the present invention have a relatively long overall half-life.

[0150] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. Unless otherwise stated, percentages and parts are by weight.

[0151] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as are familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to the methods of this invention. The preferred embodiments and materials described herein are for illustrative purposes only.

[0152] The structures of the compounds of the present invention were determined by nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS).

[0153] The starting materials used in the embodiments of the present invention are all known and commercially available, or can be synthesized using or in accordance with literature reported in the art.

[0154] Unless otherwise specified, all reactions in this invention are carried out under the protection of a dry inert gas (such as nitrogen or argon) by continuous magnetic stirring, and the reaction temperature is [degrees Celsius].

[0155] Example 1: Preparation of (2,3-dichloro-4-(1-methylcyclohexane-1-carbamoyl)phenyl((6-nitrobenzo[d][1,3]dioxy-5-yl)methyl)carbonate (Ⅰ-2)

[0156] The process is as follows:

[0157]

[0158] Reagents and conditions: (a) methanol, 0℃, 3 hours; (b) dichloromethane, N,N-diisopropylethylamine, 0℃→room temperature, protected from light, argon protection, 6 hours; (c) anhydrous N,N-dimethylformamide, N,N-diisopropylethylamine, 0℃→room temperature, protected from light, argon protection, 24 hours.

[0159] Synthesis of intermediate 1, 4,5-dimethoxy-2-nitrobenzyl alcohol (step a)

[0160]

[0161] Add 0.211 g (1 mmol) of 6-nitroveratrol to a 50 mL three-necked round-bottom flask, and place under argon protection.

[0162] Dissolved in anhydrous methanol (15 mL), sodium borohydride (0.113 g, 3 mmol) was slowly added in portions under ice bath conditions. After stirring for half an hour in an ice bath, the mixture was transferred to room temperature and reacted for two hours. After the reaction was complete, water was added to quench the reaction, and the solvent methanol was removed by rotary evaporation under reduced pressure. The crude product was dissolved in dichloromethane and washed once with water. The aqueous phase was extracted with dichloromethane (40 mL × 2), the organic layers were combined, washed with saturated brine (40 mL), and dried over anhydrous magnesium sulfate. The organic solvent was then evaporated to dryness. The crude product was dissolved in dichloromethane, and after adding an appropriate amount of silica gel and evaporating to dryness, silica gel column chromatography was performed. The eluent was n-heptane:ethyl acetate = 3:1 (v:v), and the solvent was evaporated to dryness to give intermediate 1 (yellow solid, 0.189 g, 89%). 1 H NMR (400MHz, CDCl3) δ7.61 (s, 1H), 7.16 (s, 1H), 4.90 (d, J = 6.4Hz, 2H), 4.00 (d, J = 15.8Hz, 6H)

[0163] Synthesis of intermediate 2,4,5-dimethoxy-2-nitrobenzyl (4-nitrophenyl) carbonate (step b)

[0164]

[0165] Intermediate 1 (0.213 g, 1 mmol) was added to a 50 mL three-necked flask. Under argon protection, 15 mL of anhydrous dichloromethane was added to dissolve it. Under ice bath conditions, 5 mL of anhydrous dichloromethane solution of p-nitrophenyl chloroformate (0.403 g, 2 mmol) and 1 mL of anhydrous dichloromethane solution of N,N-diisopropylethylamine (0.53 mL, 3 mmol) were slowly added dropwise. After reacting for 5 minutes, the mixture was transferred to room temperature and reacted in the dark for 24 hours. The reaction solution changed from yellow to reddish-brown and then to yellow turbidity. After the reaction was completed, the solution was filtered through a funnel, diluted with dichloromethane (30 mL), washed once with water, and the aqueous phase was extracted with dichloromethane (40 mL × 2). The organic phases were combined, washed with saturated brine (40 mL), dried over anhydrous magnesium sulfate, and the organic solvent was evaporated to dryness. The crude product was dissolved in dichloromethane, and after adding an appropriate amount of silica gel and evaporating to dryness, it was subjected to silica gel column chromatography with n-heptane:ethyl acetate = 3:1 (v:v) as elution. After evaporating the solvent, intermediate 2 (yellow solid, 0.260 g, 69%) was obtained. 1 H NMR (400MHz, CDCl3) δ8.29(d,J=6.0Hz,2H),7.77(s,1H),7.41(d,J=6.0Hz,2H),7.10(s,1H),5.71(s,2H),4.00(d,J=15.8Hz,6H).

[0166] Synthesis of compound I-2, 2,3-dichloro-4-(1-methylcyclohexane-1-carboxamido)phenyl(4,5-dimethoxy-2-nitrobenzyl) carbonate (step c).

[0167]

[0168] Add cyclohexyl amide, namely N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexyl amide, to a 50 mL three-necked round-bottom flask.

[0169] Amine (0.302 g, 1 mmol) was dissolved in 10 mL of anhydrous N,N-dimethylformamide under argon protection. Then, under ice bath conditions, 8 mL of anhydrous N,N-dimethylformamide solution of intermediate 2 (0.181 g, 0.5 mmol) and 3 mL of anhydrous N,N-diisopropylethylamine (0.11 mL, 1.5 mmol) solution were slowly added dropwise. After reacting on ice for 5 minutes, the mixture was transferred to room temperature and reacted for 24 hours. The reaction solution was concentrated under vacuum, diluted with 10 mL of dichloromethane, washed once with water, and the aqueous phase was extracted with 10 mL of dichloromethane (2 times). The combined organic phases were washed with 20 mL of saturated brine, dried over anhydrous magnesium sulfate, and the organic solvent was evaporated to dryness. The crude product was dissolved in dichloromethane, and after adding an appropriate amount of silica gel and evaporating to dryness, it was subjected to silica gel column chromatography with n-heptane:ethyl acetate = 2:1 (v:v) as elution. After evaporating the solvent, compound I-2 (white solid, 0.189 g, 35%) was obtained. 1 H NMR (400MHz, CDCl3) δ9.15(s,1H),7.65(d,J=9.0Hz,1H),7.54(s,1H),7.25(dd,J=6.4,5.0Hz,2H),5.59(s,2H),3.95(s,3H),3.90(s, 3H),,1.93(ddd,J=12.2,7.2,5.7Hz,2H),1.70–1.65(m,2H),1.63–1.56(m,4H),1.60–1.47(m,2H),1.18(s,3H).HRMS(ESI)m / z[M+Na] + C 24 H 26 Cl2N2O8, calculated values: 563.0958, 565.0929, 567.0899; measured values: 563.0960, 565.0932, 567.0895.

[0170] Example 2 Preparation of 4,5-dimethoxy-2-nitrobenzyl-2-(thiazolyl-4-yl)-1H-benzo[d]imidazolium-1-carboxylate (Ⅰ-10)

[0171]

[0172] Compound I-10 was synthesized using a synthetic method similar to that in Example 1, except that:

[0173] The cyclophosphamide mentioned in step (c) is replaced with thiabendazole.

[0174] Step (c) is as follows: Thiamethoxam, i.e., 2-(4-thiazolyl)-benzimidazole (0.402 g, 2 mmol), was added to a 50 mL three-necked round-bottom flask. Under argon protection, 8 mL of anhydrous N,N-dimethylformamide was added to dissolve it. Under ice bath conditions, 4 mL of anhydrous N,N-dimethylformamide solution of intermediate 2 (0.8 mmol, 0.290 g) and 3 mL of anhydrous N,N-diisopropylethylamine solution (2.4 mmol, 0.42 mL) were slowly added dropwise to the reaction mixture. After reacting on ice for 5 minutes, the mixture was transferred to room temperature and reacted in the dark for 24 hours. The reaction solution was concentrated under vacuum, diluted with dichloromethane (10 mL), washed once with water, and the aqueous phase was extracted with dichloromethane (10 mL × 2). The organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous magnesium sulfate, and the organic solvent was evaporated to dryness. The crude product was dissolved in dichloromethane, and after adding an appropriate amount of silica gel and evaporating to dryness, it was subjected to silica gel column chromatography with n-heptane:ethyl acetate = 2:1 (v:v) as elution. After evaporating the solvent, compound I-10 (light yellow solid, 0.186 g, 22%) was obtained. 1 H NMR(400MHz, CDCl3)δ8.96(d,J=1.6Hz,1H),7.84(dd,J=6.6,1.1Hz,1H),7.69–7.64(m,2H),7.56(s,1H) ,7.49–7.39(m,2H),7.20(t,J=1.0Hz,1H),5.62(s,2H),3.90(s,3H),3.86(s,3H),.HRMS(ESI)m / z[M+Na] + C 20 H 16 N4O6S, calculated value: 463.0682, measured value: 463.0685.

[0175] Example 3 Preparation of ethyl(Z)-2-cyano-3-(((4,5-dimethoxy-2-nitrobenzyl)oxy)carbonyl)amino)-3-phenylacrylate (I-18)

[0176]

[0177] The N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide was synthesized in a similar manner to that in Example 1, but with (E)-3-amino-2-cyano-3-phenylacrylate ethyl ester instead.

[0178] The characterization results are as follows: 1H NMR (400MHz, CDCl3) δ10.90(s,1H),7.60(s,1H),7.53(t,J=6.6Hz,3H),7.52–7.46(m,2H),7.10(s,1H),5 .60(s,2H),4.24(q,J=7.1Hz,2H),3.93(s,3H),3.88(s,3H),1.24(t,J=7.1Hz,3H).HRMS(ESI)m / z[M+Na] + C 22 H 21 N3O8, calculated value: 478.1328, measured value: 478.1228.

[0179] Example 4 Preparation of 4,5-dimethoxy-2-nitrobenzyl-2-((methoxycarbonyl)amino)-1H-benzo[d]imidazolium-1-carboxylate (I-26)

[0180]

[0181] Compound I-26 was synthesized using a synthetic method similar to that in Example 1, except that:

[0182] The N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide described in step (c) is replaced with methyl 2-benzimidazole carbamate.

[0183] The characterization results are as follows: 1 H NMR(400MHz, CDCl3)δ9.80(s,1H)7.73-–7.67(m,2H),7.52(s,1H),7.39–7.35(m,2H),7.20(t,J= 0.9Hz,1H),6.20(s,2H),5.63(s,2H),3.88(s,3H),3.70(s,3H)3.68(s,3H).HRMS(ESI)m / z[M+Na] + C 19 H 18 N4O8, calculated value: 453.1017, measured value: 453.1020.

[0184] Example 5: Preparation of S-allyl 5-(((((((4,5-dimethoxy-2-nitrobenzyl)oxy)carbonyl)amino)-2-isopropyl-3-oxo-4-(o-tolyl)-2,3-dihydro-1H-pyrazole-1-thiocarbamate)(I-34)

[0185]

[0186] Compound I-34 was synthesized using a synthetic method similar to that in Example 1, except that:

[0187] The N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide described in step (c) is replaced with S-allyl5-amino-2,3-dihydro-2-isopropyl-3-oxo-4-(o-tolyl)pyrazole-1-thiocarboxylate.

[0188] The characterization results are as follows: 1 H NMR (400MHz, CDCl3) δ9.16 (s, 1H), 7.65 (s, 1H), 7.35–7.29 (m, 1H), 7.20 (ddd, J = 7.3, 3.9,1.4Hz,2H),7.15–7.10(m,1H),7.04(t,J=1.0Hz,1H),6.20(s,2H),6.16(s,1H),5 .51(s,2H),5.13–5.09(m,2H),3.90(s,3H),3.83(s,3H),3.79–3.73(m,1H),3.52(dt, J=6.2,1.0Hz,2H),2.36(d,J=0.6Hz,3H),1.23(d,J=7.4Hz,6H).HRMS(ESI)m / z[M+Na] + C 27 H 30 N4O8S, calculated value: 593.1677, measured value: 593.1675.

[0189] Example 6 Preparation of 4,5-dimethoxy-2-nitrobenzyl (5-ethyl-6-octyl-[1,2,4]triazol[1,5-a]pyrimidin-7-yl)carbamate (I-42)

[0190]

[0191] Compound I-42 was synthesized using a synthetic method similar to that in Example 1, except that:

[0192] The N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide described in step (c) is replaced with 5-ethyl-6-octyl-[1,2,3]triazolo[1,5-a]pyrimidine-7-amine.

[0193] The characterization results are as follows: 1H NMR (400MHz, CDCl3) δ9.95(s,1H),8.45(s,1H),7.64(s,1H),7.34(t,J=1.0Hz,1H),5.60(s,2H),3.95(s,3H),3.86(s,3H),2.90(q,J=7.7 Hz,2H),2.58(t,J=6.6Hz,2H),1.57–1.51(m,2H),1.34–1.23(m,10H),1.20(t,J=7.7Hz,3H),0.86(t,J=6.9Hz,3H).HRMS(ESI)m / z[M+Na] + C 25 H 34 N6O6, calculated value: 537.2432, measured value: 537.2435

[0194] Example 7 Preparation of (Z)-1-(2,4-dichlorophenyl)-4,4-dimethyl-2-(4H-1,2,4-triazol-4-yl)pent-1-en-3-yl(4,5-dimethoxy-2-nitrobenzyl) carbonate (I-50)

[0195]

[0196] Compound I-50 was synthesized using a synthetic method similar to that in Example 1, except that:

[0197] The N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide described in step (c) is replaced with 5-ethyl-6-octyl-[1,2,3]triazolo[1,5-a]pyrimidine-7-amine.

[0198] The characterization results are as follows: 1 H NMR (400MHz, CDCl3) δ8.63(s,1H),8.09(d,J=7.0Hz,1H),7.68(d,J=8.4Hz,1H),7.62–7.60(m,2H),7.46(dd,J=8.3,2.1Hz,1H ),7.28(s,1H),7.18(s,1H),5.55(s,2H),5.47(d,J=4.5Hz,1H),3.99(s,3H),3.88(s,3H),0.67(s,9H).HRMS(ESI)m / z[M+Na] + C 25 H 26 Cl2N4O7, calculated values: 587.1071, 589.1041, 591.1012, measured values: 587.1078, 589.1044, 591.1021.

[0199] Example 8 Preparation of 3-((1H-1,2,4-triazol-1-yl)methyl)-1-(4-chlorophenyl)-2,4,4-trimethylpentane-3-yl(4,5-dimethoxy-2-nitrobenzyl) carbonate (I-58)

[0200]

[0201] Compound I-58 was synthesized using a synthetic method similar to that in Example 1, except that:

[0202] The N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide described in step (c) is replaced with 3-((1-hydro-1,2,4-triazol-1-yl)methyl)-1-(4-chlorophenyl)-2,4,4-trimethylpentan-3-ol.

[0203] The characterization results are as follows: 1 H NMR (400MHz, CDCl3) δ8.25 (s, 1H), 8.02 (s, 1H), 7.49 (s, 1H), 7.30 (d, J = 8.0Hz, 2H),7.16(dd,J=5.1,4.2Hz,3H),5.67(s,2H),4.52(d,J=15.0Hz,1H),4.40(d, J=15.0Hz,1H),3.99(s,3H),3.85(s,3H),2.65(dd,J=4.3,3.3Hz,2H),2.40(dd ,J=12.9,6.4Hz,1H),1.04(s,9H),1.00(d,J=6.4Hz,3H).HRMS(ESI)m / z[M+Na] + C 27 H 33 ClN4O7, calculated values: 583.1930, 585.1900, measured values: 5583.1936, 585.190

[0204] Example 9 Preparation of 4,5-dimethoxy-2-nitrobenzyl (3-cyano-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-((trifluoromethyl)sulfoxide)-1H-pyrazol-5-yl)carbamate (I-66)

[0205]

[0206] Compound I-66 was synthesized using a synthetic method similar to that in Example 1, except that:

[0207] The N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide described in step (c) is replaced with 5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-((trifluoromethyl)sulfinyl)-1-hydropyrazole-3-cyano.

[0208] The characterization results are as follows: 1 H NMR (400MHz, CDCl3) δ9.30 (s, 1H), 7.65 (s, 2H), 7.46 (s, 1H), 7.16 (t, J = 1.0Hz, 1H), 5.56 (s, 2H), 3.99 (s, 3H), 3.88 (s, 3H). HRMS (ESI) m / z [M+Na] + C 22 H 13 F6Cl2N5O7S, calculated values: 697.1079, 699.9680, 701.9650. Measured values: 697.1075, 699.9686, 701.9655.

[0209] Example 10: Preparation of S-ethyl 1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-5-((((4,5-dimethoxy-2-nitrobenzyl)oxy)carbonyl)amino)-1H-pyrazole-4-thiocarbamate (Ⅰ-74)

[0210]

[0211] Compound I-74 was synthesized using a synthetic method similar to that in Example 1, except that:

[0212] The N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide described in step (c) is replaced with 5-amino-1-(2,6-dichloro-A,A,A-trifluoro-p-tolyl)-4-(ethylsulfinyl)pyrazole-3-carboxynitrile.

[0213] The characterization results are as follows: 1 H NMR(400MHz, CDCl3)δ8.09(s,1H),7.79(s,2H),7.59(s,1H),7.20(s,1H),5.65(s,2H),3. 10(q,J=6.3Hz,2H),3.94(s,3H),3.88(s,3H),1.20(t,J=6.3Hz,3H).HRMS(ESI)m / z[M+Na] + C 23 H 19Cl2F3N4O7S, calculated values: 645.0196, 647.0156, 649.0137; measured values: 645.0198, 647.0159, 649.0133.

[0214] Example 11 Preparation of 4,5-dimethoxy-2-nitrobenzyl-(((1-methyl-2-nitro-3-((tetrahydrofuran-3-yl)methyl)guanidin-1-yl)iminocarbamate (I-82)

[0215]

[0216] Compound I-82 was synthesized using a synthetic method similar to that in Example 1, except that:

[0217] The N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide described in step (c) is replaced with fipronil, i.e., 1-methyl-2-nitro-3-((tetrahydrofuran-3-yl)methyl)guanidine.

[0218] The characterization results are as follows: 1 H NMR (400MHz, CDCl3) δ7.62(s,1H),7.43(s,1H),5.62(s,2H),3.95(s,3H),3.85(s,3H) ),3.76(ddd,J=12.2,4.2,2.4Hz,1H),3.68–3.62(m,2H),3.52(s,2H),3.35(ddd,J=1 1.9,5.9,4.2Hz,1H),3.09(s,3H),2.57(s,1H),2.32–2.23(m,1H),2.01(dddd,J=12. 4,5.9,4.2,2.4Hz,1H),1.80(dddd,J=6.0,5.5,4.3,2.4Hz,1H).HRMS(ESI)m / z[M+Na] + C 17 H 23 N5O9, calculated value: 464.1388, measured value: 464.1392.

[0219] Example 12 Preparation of 4,5-dimethoxy-2-nitrobenzyl(E)-3-((6-chloropyridin-3-yl)methyl)-2-(nitromethylene)imidazoline-1-carboxylate (I-90)

[0220]

[0221] Compound I-90 was synthesized using a synthetic method similar to that in Example 1, except that:

[0222] The N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide described in step (c) is replaced with 1-((6-chloropyridin-3-yl)methyl)-3-nitroimidazolidine-2-imine.

[0223] The characterization results are as follows: 1 H NMR (400MHz, CDCl3) δ8.45(d,J=2.3Hz,1H),7.56(dd,J=8.0,2.3Hz,1H),7.59(s,1H),7.32(d,J=8.0Hz,1H),7.10(s,1H),6.70(s,1H),5.6 0(s,2H),4.75(s,2H),3.95(s,3H),3.85(s,3H),3.77(ddd,J=6.4,5.1,3.2Hz,2H),3.71(ddd,J=8.3,5.0,3.2Hz,2H).HRMS(ESI)m / z[M+Na] + C 20 H 20 ClN5O8, calculated values: 516.0893, 518.0863, measured values: 516.0897, 518.0869.

[0224] Example 13 Preparation of 4,5-dimethoxy-2-nitrobenzyl-((1-(2-chloro-5-thiazolylmethyl)-3-methyl-2-nitroguanidine)iminocarbamate (I-98)

[0225]

[0226] Compound I-98 was synthesized using a synthetic method similar to that in Example 1, except that:

[0227] The N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide described in step (c) is replaced with 1-(2-chloro-5-thiazolylmethyl)-3-methyl-2-nitroguanidine.

[0228] The characterization results are as follows: 1 H NMR (400MHz, CDCl3) δ7.68 (s, 1H), 7.23 (s, 1H), 7.14 (t, J = 4.9Hz, 1H), 6.92 (s, 1H), 5.60 ( s,2H),4.40(d,J=4.9Hz,2H),3.90(s,3H),3.79(s,3H),3.12(s,3H).HRMS(ESI)m / z[M+Na] + C 16 H 17ClN6O8S, calculated values: 511.0409, 513.0380, measured values: 511.0413, 513.0385.

[0229] Example 14 Preparation of 4,5-dimethoxy-2-nitrobenzyl (3-(2,5-dimethylphenyl)-8-methoxy-2-oxy-1-azaspirocyclic[4.5]dec-3-en-4-yl) carbonate (I-106)

[0230]

[0231] Compound I-106 was synthesized using a synthetic method similar to that in Example 1, except that:

[0232] The N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide described in step (c) is replaced with the hydrolysis product of (5s,8s)-3-(2,5-dimethylphenyl)-8-methoxy-2-oxy-1-azaspirocyclo[4.5]dec-3-en-4-yl ethyl carbonate.

[0233] The characterization results are as follows: 1 H NMR(400MHz, CDCl3)δ7.65(s,1H),7.24(s,1H),7.16–7.14(m,2H),7.12–7.09(m,1H),6.30(s,1H),5.60(s,2H),3.99(s,3H),3.85(s,3H),3.7 9(ddt,J=6.6,5.1,1.5Hz,1H),3.33(s,3H),2.39–2.28(m,6H),2.10–1.99(m,2H),1.92–1.79(m,4H),1.65–1.50(m,2H).HRMS(ESI)m / z[M+Na] + C 28 H 32 N2O9, calculated value: 563.2000, measured value: 563.2006.

[0234] Example 15 Preparation of 4-phenoxybenzyl-2-(((4,5-dimethoxy-2-nitrobenzyl)oxy)carbonyl)amino)-6-methylnicotinic acid ester (I-114)

[0235]

[0236] Compound I-114 was synthesized using a synthetic method similar to that in Example 1, except that:

[0237] The N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide described in step (c) is replaced with 4-phenoxybenzyl-2-amino-6-methylnicotinic acid ester.

[0238] The characterization results are as follows: 1 H NMR (400MHz, CDCl3) δ7.99 (d, J=8.1Hz, 1H), 7.80 (s, 1H), 7.42–7.33 (m, 4H), 7.19 (dd, J=8.0, 0.5Hz, 1H), 7.16–7. 10(m,2H),7.00–6.90(m,4H),5.56(s,4H),3.99(s,3H),3.88(s,3H),2.46(d,J=0.6Hz,3H).HRMS(ESI)m / z[M+Na] + C 30 H 27 N3O9, calculated value: 596.1640, measured value: 596.0645.

[0239] Example 16 Preparation of (4,5-dimethoxy-2-nitrobenzylcarbonate)(2E,4E)-5-((R)-1-hydroxy-2,6,6-trimethyl-4-oxocyclohexane-2-en-1-yl)-3-methylpenta-2,4-dienoic anhydride (I-122)

[0240]

[0241] Compound I-122 was synthesized using a synthetic method similar to that in Example 1, except that:

[0242] The N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide described in step (c) is replaced with (2E,4E)-5-((R)-1-hydroxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl)-3-methylpentane-2,4-dienoic acid.

[0243] The characterization results are as follows: 1HNMR(400MHz, CDCl3)δ7.60(s,1H),7.19(t,J=0.9Hz,1H),6.90(d,J=16.7Hz,1H),6.30(d,J=16.7Hz,1H),5.90–5.86(s,1H)5.80(s,1H),5.62(s,2H ),4.60(s,1H),3.90(s,3H),3.78(s,3H),2.50(d,J=16.3Hz,1H),2.36(d, J=16.3Hz,1H)2.10(s,3H),1.95(s,3H),1.10(s,6H).HRMS(ESI)m / z[M+Na] + C 25 H 29 NO 10 Calculated value: 526.1684, measured value: 526.1689.

[0244] Example 17 Preparation of (4,5-dimethoxy-2-nitrobenzylcarbonate)(1R,2S)-3-oxy-2-((E)-pent-2-en-1-yl)cyclopentane-1-carboxylic anhydride (I-130)

[0245]

[0246] Compound I-130 was synthesized using a synthetic method similar to that in Example 1, except that:

[0247] The N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide described in step (c) is replaced with (1R,2S)-3-oxo-2-((E)-pent-2-en-1-yl)cyclopentane-1-carboxylic acid.

[0248] The characterization results are as follows: 1 H NMR (400MHz, CDCl3) δ7.57(s,1H),7.16(s,1H),5.66(s,2H),5.40–5.35(m,2H),3.9 9(s,3H),3.78(s,3H),3.05(ddd,J=9.3,6.0,4.2Hz,1H),2.83(dtd,J=9.1,7.2,1.8H z,1H),2.60(m,1H),2.50–2.45(m,1H),2.39–2.34(m,1H),2.28–2.22(m,1H),2.13–2 .08(m,2H),2.00–1.95(m,1H),1.80–1.75(m,1H),0.84(t,3H).HRMS(ESI)m / z[M+Na] + C 21 H25 NO9, calculated value: 458.1422, measured value: 458.1429.

[0249] Example 18 Preparation of benzo[d][1,2,3]thiadiazole-7-carboxylic acid (4,5-dimethoxy-2-nitrobenzylcarbonate) anhydride (I-130)

[0250]

[0251] Compound I-138 was synthesized using a synthetic method similar to that in Example 1, except that:

[0252] The N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide described in step (c) is replaced with benzo[1,2,3]thiadiazole-7-carboxylic acid.

[0253] The characterization results are as follows: 1 H NMR(400MHz, CDCl3)δ8.30(d,1H),8.10(d,1H),7.99(m,1H),7.60(s,1H),7.20(s,1H),5.61(s,2H),3.88(s,3H),3.70(s,3H).HRMS(ESI)m / z[M+Na] + C 17 H 13 N3O8S, calculated value: 442.0316, measured value: 442.0320.

[0254] Example 19: Preparation of other compounds in Table 1

[0255] The methods in Examples 1-3 were repeated, except that different starting materials, different bases, and different pesticide molecules and their derivatives or prodrug active molecules were used to prepare other compounds shown in Table 1.

[0256] Example 20: Bioactivity Experiment

[0257] (1) Bactericidal activity test of the compounds of the present invention

[0258] 1) Activation culture of pathogenic fungi of the tested plants

[0259] Use an inoculation needle to pick up slant cultures of plant pathogenic fungi (Fusarium graminearum, Sclerotinia sclerotiorum, and Gray mold of cucumber) and inoculate them onto potato dextrose agar plates for activation. Incubate at 25°C for 2-4 days until the mycelium covers about 80-90% of the plate area before use.

[0260] 2) Compound Solution Preparation: Dissolve the test compounds separately in dimethyl sulfoxide (DMSO). Take a certain amount of the DMSO stock solution and dilute it with anhydrous methanol-water solution (1:1). Divide the solution into three groups for testing. Group 1: Irradiate these solutions of different concentrations under ultraviolet light for 2 hours. Group 2: Irradiate these solutions of different concentrations under sunlight for 2 hours. Group 3: Store in the dark. After the irradiation, dilute the three groups of samples in a clean bench. First, dilute with anhydrous methanol-water solution (1:1) to a series of concentrations, then dilute with ultrapure water containing Tween 80 (mass fraction 0.1%) and thoroughly sonicated to 1 mL. The volume of DMSO in the solution should be less than 5%. The control group uses the same solvent composition as the drug solution, without adding any other chemicals. (The methanol-water ratio is maintained at 1:1, and minor adjustments can be made according to the water solubility of the compound.)

[0261] 3) Determination of antibacterial activity by mycelial growth rate method

[0262] The pre-prepared drug-containing solution (1 mL) includes a drug-containing methanol aqueous solution (0.5 mL) and a 0.1% Tween 80 aqueous solution (0.5 mL), wherein the blank control uses a methanol aqueous solution (0.5 mL) + a 0.1% Tween 80 aqueous solution (0.5 mL).

[0263] In a sterile laminar flow hood, activated plant pathogenic fungi of similar growth (within 1 cm in diameter) were selected. Fungal discs (5 mm in diameter) were obtained by punching holes along the outer edge of the colony. Using an inoculation needle, the discs were transferred to the center of pre-prepared culture media of different concentrations, ensuring the mycelial side of the discs adhered to the PDA medium surface. The culture dishes were then sealed with disposable sealing film (to prevent contamination). The plates inoculated with different plant pathogenic fungi were placed in a constant temperature incubator at 25°C in the dark for 48-96 hours.

[0264] The colony diameter was determined using the cross-cross method, and the inhibition rate was calculated using the following formula:

[0265]

[0266] The list of compounds prepared by formula (Ⅰ) and their antibacterial activities (inhibition rate of mycelial growth of Fusarium graminearum, Sclerotinia sclerotiorum, or Gray mold of cucumber at a concentration of 5 ppm) are shown in Table 1.

[0267] (2) Insecticidal activity test of the compounds of the present invention

[0268] a. Alfalfa aphid activity test

[0269] The test subject was adult alfalfa aphids, and the test method was the leaf immersion method:

[0270] 1) Preparatory work: Prepare moist fine sand for planting broad beans one week in advance, and water it regularly to keep the sand moist and prevent it from drying out; 2) Remove adult aphids from the broad bean plants and starve them in the dark for 2 hours; 3) Select broad bean seedlings with sprouts 3-4cm long and healthy, rot-free roots from the seedlings planted a week ago. Wash the seedlings with clean water to remove the fine sand, remove the roots, and insert them into a saturated sponge; 4) Dissolve the compounds to be tested in dimethyl sulfoxide (DMSO). Take a certain amount of the DMSO stock solution and dilute it with an aqueous solution containing Triton (2-3 drops of Triton in 500mL of water) that has been sonicated for half an hour to create a series of concentrations, ensuring that the volume concentration of DMSO is less than 5%. Test in three groups: one group exposes the solutions of different concentrations to ultraviolet light for 2 hours, and the other group exposes the solutions of different concentrations to sunlight. 2 hours, three groups were stored in the dark; 5) Select healthy, shiny black adult aphids, use a brush to drive them away, and distribute them evenly around the broad bean seedlings in the sponge. Place them at 25℃ for 2 hours to ensure that each seedling has a sufficient number of aphids adhering to it; 6) Place the broad bean seedlings with the stems firmly adhering to the aphids upside down in a series of solutions of different concentrations, immerse them for about 3-5 seconds, remove them and place them for 1 second, then repeat the above operation twice. Gently blot the excess solution on the seedlings with paper to prevent the aphids from falling off. There are 3 parallel samples for each concentration; 7) Insert the treated broad bean seedlings vertically into the fully moistened sponge, with all the seedlings facing the same direction, cover them with a lantern cover (the top is covered with gauze), and place them at a constant temperature of 25℃ in the dark for 48 hours; 8) After 48 hours, observe the mortality of the aphids and calculate the mortality rate (%) according to the formula: Mortality rate (%) = (Number of live control insects - Number of live treated insects) / Number of live control insects × 100%. Then use SPSS software to calculate the LC. 50 (The criteria for death: The insect's body is dark black, and if the limbs show no stress response when lightly touched with a brush, it is considered dead.)

[0271] b. Aedes albopictus larvae

[0272] The test subject was fourth-instar Aedes albopictus mosquito larvae. The experimental testing method is as follows:

[0273] Method 1:

[0274] 1) Dissolve the test compounds in dimethyl sulfoxide (DMSO). Take a certain amount of the DMSO stock solution and dilute it with deionized water to prepare a series of concentrations, ensuring that the volume concentration of DMSO is less than 5%. Test in three groups: the first group is irradiated under UV light for 1 hour; the second group is irradiated under sunlight for 1 hour; and the third group is placed in a dark environment. 2) Select 10 active and robust fourth-instar larvae and aspirate them into 5mL centrifuge tubes using a pipette. 3) Add the prepared drug solutions of different concentrations to the centrifuge tubes, with three replicates for each concentration. Blank and positive controls are provided for all experimental groups. 4) Observe and count the mortality of Aedes albopictus larvae after 24 hours, and calculate the mortality rate (%) using the formula: Mortality rate (%) = (Number of live control larvae - Number of live treated larvae) / Number of live control larvae × 100%. Then, calculate the LC50 using SPSS software. 50 (Criterion for death: The insect is considered dead if there is no stress response in its limbs when gently touched with a disposable medical syringe.)

[0275] Method 2:

[0276] 1) Dissolve the test compounds in dimethyl sulfoxide (DMSO). Take a certain amount of the DMSO stock solution and dilute it with deionized water to a series of concentrations, ensuring that the volume concentration of DMSO is less than 5%. Test in three groups. 2) Add 10 Aedes albopictus larvae to each test solution (10 ml) and incubate in the dark for 4 hours. 3) After 4 hours of incubation, replace the solution with the same volume of water. Group 1 was placed in a constant temperature room for further incubation in the dark. Group 2 was placed under LED light for 1 hour, then placed in a constant temperature room for further incubation in the dark. After 24 hours, check the mortality of the test insects. Group 3 was placed under sunlight for 1 hour, then placed in a constant temperature room for further incubation in the dark. After 24 hours, check the mortality of the test insects. Each concentration was tested in triplicate. 4) After 24 hours, observe and count the mortality of Aedes albopictus larvae, and calculate the mortality rate (%) according to the formula: Mortality rate (%) = (Number of live control insects - Number of live treatment insects) / Number of live control insects × 100%. Then use SPSS software to calculate the LC. 50 (Criterion for death: The insect is considered dead if there is no stress response in its limbs when gently touched with a disposable medical syringe.)

[0277] The difference between Method 1 and Method 2 is that Method 1 involves applying the drug and feeding Aedes albopictus larvae after applying the drug, while Method 2 involves feeding Aedes albopictus larvae after applying the drug and then applying the drug.

[0278] c. Armyworms

[0279] The test subject was the third instar larvae of armyworms, and the test method was the leaf immersion method:

[0280] Method 1:

[0281] 1) Remove third-instar larvae from corn seedlings and starve them in the dark for 2 hours; 2) Select fresh, healthy corn seedlings, cut off the roots, tie ten seedlings together, and store them in a dark place; 3) Dissolve the target compound separately in dimethyl sulfoxide (DMSO). Take a certain amount of the DMSO stock solution and dilute it in a gradient with an aqueous solution containing Triton (2-3 drops of Triton in 500 mL of water) that has been sonicated for half an hour beforehand, ensuring that the volume concentration of DMSO is less than 5%, and store it in the dark; 4) Immerse the tied corn seedlings in the prepared solution for 10 seconds three times, place them in a petri dish lined with filter paper, and air dry them naturally in the dark. Perform three replicates for each concentration; 5) Place the dried corn seedlings... Place the active and robust 3rd instar armyworm larvae into a 100mL wide-mouthed bottle lined with filter paper. Use a paintbrush to drive the larvae into the bottle, seal the bottle with gauze, and incubate in a dark, constant-temperature environment for 24 hours. Then, remove the treated corn seedlings and test them in three groups. The first group exposed the larvae to ultraviolet light for 1 hour, then placed them in the wide-mouthed bottle with fresh, untreated corn seedlings. The second group exposed the larvae to sunlight for 1 hour, then placed them in the wide-mouthed bottle with fresh, untreated corn seedlings. The third group was not exposed to light, but placed in the wide-mouthed bottle with fresh, untreated corn seedlings. 6) After 72 hours, observe and count the mortality of armyworms in the light-exposed and non-light-exposed groups. Touching the larvae with a paintbrush; no stress response was considered death. Blank and positive controls were provided for all experimental groups.

[0282] Method 2:

[0283] 1) Remove third-instar larvae from corn seedlings and starve them for 2 hours in the dark; 2) Select fresh, healthy corn seedlings, cut off the roots, tie ten seedlings together, and store them in a dark place; 3) Dissolve the test compounds in dimethyl sulfoxide (DMSO). Take a certain amount of the DMSO stock solution and dilute it in a gradient with an aqueous solution containing Triton (2-3 drops of Triton in 500 mL of water) that has been sonicated for half an hour to ensure that the volume concentration of DMSO is less than 5%. Test in three groups. The first group irradiates these solutions of different concentrations under ultraviolet light for 1 hour. The second group... Different concentrations of solutions were exposed to sunlight for 1 hour, while the third group was stored in darkness; 4) The tied corn seedlings were soaked in the prepared solution for 10 seconds, three times in a row, and then air-dried in the dark, with three replicates for each concentration; 5) Active and robust third-instar larvae were selected, and the armyworms were driven into a 100mL wide-mouthed bottle lined with filter paper using a paintbrush. The dried corn seedlings were placed in the wide-mouthed bottle, and the bottle was sealed with gauze and placed in the dark for 48 hours; 6) After 48 hours, the mortality of armyworms in the light and non-light groups was observed and counted. The armyworms were considered dead if they did not show any stress response when touched with a paintbrush. Blank and positive controls were provided for all experimental groups. After 48 hours, the mortality of armyworms was observed and counted, and the mortality rate (%) was calculated according to the formula: Mortality rate (%) = (Number of live control larvae - Number of live treated larvae) / Number of live control larvae × 100%. The LC was then calculated using SPSS software. 50 .

[0284] The difference between Method 1 and Method 2 is that Method 1 involves applying the pesticide solution after exposure to light and then feeding the armyworms, while Method 2 involves applying the pesticide solution, feeding the armyworms, and then exposing the insects to light.

[0285] The results of the above experiments are shown in Table 1.

[0286] (3) Experiment on the plant growth regulation activity of the compounds of the present invention

[0287] a. Reduce water utilization in corn plants

[0288] The effects of the compounds on reducing plant water use were tested as follows. These compounds were applied by foliar spraying to 12-day-old maize plants grown in a controlled environment plant growth chamber. All compounds were applied using an emulsifiable concentrate (EC) formulation, which was diluted to the desired concentration with water containing 0.4% rapeseed methyl ester adjuvant. The drug-containing solutions were tested in three groups: one group exposed the solutions of different concentrations to UV light for 0.5 hours, another group exposed the solutions of different concentrations to sunlight for 0.5 hours, and the third group was stored in darkness; a blank control was not treated. Plant water use during the day was assessed by repeatedly weighing the pots in which the plants were grown at specified time points (expressed as days after application (DAA)) before and after compound application. Pre-application water use data were used to correct for any differences in water use due to non-treatment effects (e.g., differences in plant size). Analysis of covariance was performed on the unconverted water use values ​​to fit the treatment effects, using baseline water use one day before application as a covariate.

[0289] These chemicals (ODAA) are applied approximately between 08:00 a.m. and 09:30 a.m. During the daytime (with indoor lights on from 06:00 to 20:00), moisture use (WU) is measured at these times: ODAA a.m. (10:30–12:50) and ODAA p.m. (14:00–19:50).

[0290] Table 1-2: Percentage increase or decrease in daytime water use (WU) of maize plants sprayed with compounds indicated by 500 PM compared to the negative control treatment (e.g., 0 = same as the negative control; -8.5 = -8.5% decrease in water use compared to the negative control treatment).

[0291] Table 1 shows the average WU values ​​for six pots (each containing three plants) for each treatment.

[0292] b. Reduce soybean plant water utilization

[0293] The effect of the compound on reducing plant water use was tested as follows. The compound was applied by foliar spray to 12-day-old soybean plants grown in a controlled environment plant growth chamber. All compounds were applied using an emulsifiable concentrate (EC) formulation, which was then diluted to the desired concentration with water containing an additional surfactant (EXTRAVON 1g / 20L). The drug-containing solutions were tested in three groups: one group was exposed to UV light for 1 hour, another group was exposed to sunlight for 1 hour, and the third group was stored in darkness; a blank control was not treated. Daytime plant water use was assessed by repeatedly weighing the pots in which the plants were grown at specified time points (expressed as days after application (DAA)) before and after compound application. Pre-application water use data were used to correct for any differences in water use due to non-treatment effects (e.g., differences in plant size). Analysis of covariance was performed on the unconverted water use values ​​to fit the treatment effect, using baseline water use 1 day before application as a covariate.

[0294] These chemicals (ODAA) are applied approximately between 08:00 a.m. and 09:30 a.m. During the daytime (with indoor lights on from 06:00 to 20:00), moisture utilization (WU) is measured at these times: ODAA a.m. (10:30–12:50) and ODAA p.m. (14:00–19:50).

[0295] Table 1: Percentage increase or decrease in daytime water use (WU) of soybean plants sprayed with compounds indicated at 125 PM compared to the negative control treatment (e.g., 0 = same as the negative control; -8.5 = -8.5% decrease in water use compared to the negative control treatment).

[0296] Table 1 shows the average WU values ​​for six pots (each containing three plants) for each treatment.

[0297]

[0298]

[0299]

[0300]

[0301]

[0302]

[0303]

[0304]

[0305]

[0306]

[0307]

[0308]

[0309] Cyclocyclam is an amide-based systemic fungicide, mainly used to control plant diseases such as gray mold, sclerotinia rot, and black spot. Its structure is... The results showed that cyclophosphamide was highly effective in inhibiting the mycelial growth of cucumber gray mold, with an inhibition rate of 70-85% at 5 μg / mL.

[0310] Thiamethoxam is a benzimidazole fungicide, mainly used to control diseases of fruits and vegetables during storage (such as mold and rot pathogens). Its structure is... The results showed that thiabendazole (5 μg / mL) had an inhibition rate of 65-80% against wheat scab and 60-75% against rapeseed sclerotinia.

[0311] Dinotefuran is a third-generation neonicotinoid insecticide with triple action: contact, stomach poison, and systemic. It exhibits outstanding efficacy against piercing-sucking pests (aphids, planthoppers, whiteflies) and is also effective against resistant pests. Its structure is... The results showed that the median lethal concentration of fipronil against alfalfa sprouts was 15-20 μM, against armyworms it was 60-80 μM, and against Aedes albopictus larvae it was 2.0-3.0 μM.

[0312] Experimental results show that most of the compounds in Table 1 (I-1-56) above have an inhibition rate of >60% against cucumber gray mold.

[0313] (I-193-224) Most of the compounds showed an inhibition rate of >60% against Fusarium graminearum, the causal agent of wheat blight;

[0314] (I-65-88) Most compounds have a lethal median concentration (LC50) for armyworms. 50 <30μM;

[0315] (I-145-161) The median lethal concentration (LC50) of all compounds against Aedes albopictus larvae. 50 <1μM;

[0316] Most of the compounds (I-121-145) and (I-266-280) reduced water use (WU) in corn or soybean plants by more than 20%.

[0317] Therefore, it can be seen that the compounds of the present invention have insecticidal activity that is basically equivalent to or even better than that of fipronil, or have antibacterial activity that is basically equivalent to or even better than that of cyclooxygenase and thiamethoxam, or have a good regulatory effect on plant growth.

[0318] All documents mentioned in this invention are incorporated herein by reference as if each document were individually incorporated by reference. Furthermore, it should be understood that after reading the foregoing teachings of this invention, those skilled in the art can make various alterations or modifications to this invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A compound of formula (I), its optical isomer, cis-trans isomer, or a pesticide-acceptable salt thereof: In the formula, X is a group selected from the following group that has insecticidal, fungicidal, or plant growth-regulating activities: R1, R2, R3, and R4 are each independently selected from the following group: hydrogen, halogen, hydroxyl, nitro, cyano, C1-C8 carboxylic acid, C1-C8 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C8 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C1-C6 haloalkoxy, C3-C8 cycloalkyl, C5-C7 cycloalkenyl, 3-8 membered heterocyclic, C6-C 10 Aryl, 5-14 heteroaryl; R5 is selected from the following group: hydrogen, C1-C4 alkyl, halogen, nitro, cyano, C1-C4 haloalkyl; in, The C1-C8 carboxylic acid group, C1-C8 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C3-C8 cycloalkyl group, C5-C7 cycloalkenyl group, 3-8 membered heterocyclic group, C6-C 10 The aryl and 5-14 heteroaryl groups may be further optionally substituted with one or more groups selected from the group consisting of: halogen, hydroxyl, nitro, cyano; The heterocyclic group contains 1, 2 or 3 heteroatoms selected from N, O or S.

2. The compound of claim 1, its optical isomers, cis-trans isomers, or pesticide-acceptable salts thereof, characterized in that, X is selected from the following group:

3. The compound of claim 1, its optical isomers, cis-trans isomers, or pesticide-acceptable salts thereof, characterized in that, R1, R2, R3, and R4 are each independently selected from the following group: halogen, C1-C2 alkyl, C1-C2 alkoxy, C1-C2 haloalkyl, and C1-C2 haloalkoxy.

4. The compound of claim 1, its optical isomers, cis-trans isomers, or pesticide-acceptable salts thereof, characterized in that, R1 and R4 are each independently H, methoxy, or ethoxy.

5. The compound of claim 1, its optical isomers, cis-trans isomers, or pesticide-acceptable salts thereof, characterized in that, R2 and R3 are independently H, methoxy, ethoxy, OCH2F, OCHF2, and OCF3, respectively.

6. The compound of claim 1, its optical isomers, cis-trans isomers, or pesticide-acceptable salts thereof, characterized in that, R5 is selected from the following group: hydrogen, methyl, halogen, hydroxyl, nitro, cyano, trifluoromethyl, trichloromethyl, tribromomethyl.

7. The compound of claim 1, its optical isomers, cis-trans isomers, or pesticide-acceptable salts thereof, characterized in that, The compounds of formula (I) are selected from the following table:

8. A method for preparing the compound of formula (I) as described in claim 1, characterized in that, Includes the following steps: (i) In conventional solvents It reacts with sodium borohydride to give compound II; (ii) In an inert solvent, compound II reacts with p-nitrophenyl chloroformate to give compound III; (iii) In an inert solvent, compound III reacts with HX to give compound I; The definitions of R1, R2, R3, R4, R5 and X are as described in claim 1.

9. An agricultural composition, characterized in that, The agricultural composition comprises: (a) 0.001% to 99.99% by weight of the compound as described in any one of claims 1-7, its optical isomer, cis-trans isomer, or a pesticide-acceptable salt, or a combination thereof; and (b) Pesticide-acceptable carriers and / or excipients.

10. Use of a compound, an optical isomer, a cis-trans isomer, or a pesticide-acceptable salt thereof, or an agricultural composition as described in claim 9, as characterized in that, Used for the prevention and control of agricultural pests and diseases or for regulating plant growth, or for the preparation of insecticides, fungicides, and plant growth regulators for the prevention and control of agricultural pests and diseases or for regulating plant growth.

Images