CN115340495A - O-nitrobenzene compound and preparation method and application thereof - Google Patents

O-nitrobenzene compound and preparation method and application thereof Download PDF

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CN115340495A
CN115340495A CN202110529602.6A CN202110529602A CN115340495A CN 115340495 A CN115340495 A CN 115340495A CN 202110529602 A CN202110529602 A CN 202110529602A CN 115340495 A CN115340495 A CN 115340495A
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compound
group
cis
pharmaceutically acceptable
acceptable salt
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邵旭升
李忠
杜康
徐琪
邵忠莉
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East China University of Science and Technology
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    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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Abstract

The invention relates to a preparation method and application of an o-nitrobenzene-containing compound, wherein the compound has a structure shown in a general formula I, and the definition of each substituent group is described in the specification and the claims. The compound can optically control to release active substances, and has remarkable insecticidal activity, bactericidal activity and plant growth regulating effect.

Description

O-nitrobenzene compound and preparation method and application thereof
Technical Field
The invention relates to an o-nitrobenzene compound and a preparation method and application thereof.
Background
The controlled release of the pesticide has the advantages of improving bioavailability, prolonging action time, improving physicochemical property, reducing phytotoxicity, reducing environmental pollution and the like. Controlled release pesticide technologies based on nanoparticles, microcapsules and polymers have been developed. Although these technologies solve the problem of low utilization rate to a certain extent, they cannot realize precise and space-time regulation of the release process, limit the application range thereof, and bring certain difficulty to elucidate the toxicological mechanism of pesticides, so that a novel release control technology needs to be developed.
Disclosure of Invention
The invention aims to provide an o-nitrobenzene compound with a novel structure. The compound can release pesticide active substances under sunlight, and has remarkable insecticidal and bactericidal activities, plant growth regulation and other effects.
In a first aspect of the present invention, there is provided a compound represented by formula (I), an optical isomer, a cis-trans isomer, or an agriculturally pharmaceutically acceptable salt thereof:
Figure BDA0003066834160000011
wherein W, X are each independently a pesticide molecule;
R 1 、R 2 、R 3 、R 4 each independently is: hydrogen, halogen, hydroxy, nitro, cyano, C 1 -C 8 Carboxylic acid group, C 1 -C 8 Alkyl radical, C 2 -C 6 Alkenyl radical, C 2 -C 6 Alkynyl, C 1 -C 6 Alkoxy radical, C 1 -C 8 Haloalkyl, C 2 -C 6 Haloalkenyl, C 2 -C 6 Halogenated alkynyl, C 1 -C 6 Haloalkoxy, C 3 -C 8 Cycloalkyl, C 5 -C 7 Cycloalkenyl, 3-8 membered heterocyclyl, C 6 -C 10 Aryl, 5-14 membered heteroaryl;
wherein, the C 1 -C 8 Carboxylic acid group, C 1 -C 8 Alkyl radical, C 2 -C 6 Alkenyl radical, C 2 -C 6 Alkynyl, C 1 -C 6 Alkoxy radical, C 3 ～C 8 Cycloalkyl radical, C 5 ～C 7 Cycloalkenyl, 3-8 membered heterocyclyl, C 6 -C 10 Aryl, 5-14 membered heteroaryl optionally substituted with one or more groups selected from: halogen, hydroxy, nitro, cyano;
wherein said heterocyclyl, heteroaryl, contains 1,2 or 3 heteroatoms selected from N, O or S.
In another preferred embodiment, the pesticide molecule is selected from the group consisting of a plant insecticide, a plant fungicide, a plant growth regulator.
In another preferred embodiment, W or X are each independently selected from the group consisting of:
Figure BDA0003066834160000021
in another preferred embodiment, W or X are each independently selected from the following groups:
Figure BDA0003066834160000022
in another preferred embodiment, R 1 、R 2 、R 3 、R 4 Each independently selected from the group consisting of: hydrogen, halogen, C 1 -C 4 Alkyl radical, C 1 -C 4 Alkoxy radical, C 1 -C 4 Haloalkyl, C 1 -C 4 A haloalkoxy group.
In another preferred embodiment, R 1 、R 2 、R 3 、R 4 Each independently selected from the group consisting of: hydrogen, halogen, C 1 -C 2 Alkyl radical, C 1 -C 2 Alkoxy radical, C 1 -C 2 Haloalkyl, C 1 -C 2 A haloalkoxy group.
In another preferred embodiment, halogen is fluorine or chlorine.
In another preferred embodiment, the compound is any one of the compounds shown in table 1.
In a second aspect of the invention, there is provided a process for the preparation of a compound of formula (i) as defined in the first aspect, comprising the steps of:
Figure BDA0003066834160000031
(i) In the presence of an inert solvent, the reaction mixture is,
Figure BDA0003066834160000032
reacting with 2-mercaptoethanol to obtain a compound II;
(ii) Reacting the compound II with p-nitrophenyl chloroformate in an inert solvent to obtain a compound III;
(iii) And reacting the compound III with pesticide molecules in an inert solvent to obtain a compound I.
In another preferred embodiment, the pesticide molecule is selected from the group consisting of:
Figure BDA0003066834160000033
in another preferred embodiment, in step (i), the inert solvent is selected from: dichloromethane.
In another preferred embodiment, in step (i), an acid is further added, wherein the acid is selected from: acetic acid, formic acid, trifluoroacetic acid.
In another preferred embodiment, in step (i), a solution of boron trifluoride in diethyl ether is also added.
In another preferred embodiment, in step (i), the reaction temperature at the time of mixing the reaction substrates is 0 to 10 ℃, preferably 2 to 8 ℃.
In another preferred embodiment, in step (ii), the inert solvent is selected from: dichloromethane.
In another preferred embodiment, in step (ii), a base is further added, wherein the base is selected from: n, N-diisopropylethylamine, pyridine, triethylamine, potassium carbonate and sodium carbonate.
In another preferred embodiment, in step (ii), the reaction temperature is 0 to 5 ℃, preferably 0 ℃.
In another preferred embodiment, in steps (ii) and (iii), an inert gas is used for protection, and the inert gas is selected from: nitrogen, argon.
In another preferred embodiment, in step (iii), the inert solvent is N, N-dimethylformamide.
In another preferred embodiment, in step (iii), a base is further added, wherein the base is selected from: n, N-diisopropylethylamine and 4-dimethylaminopyridine.
In another preferred embodiment, in step (iii), the reaction temperature at the time of mixing the reaction substrates is 0 to 5 ℃, preferably 0 ℃.
In another preferred embodiment, in step (iii), the reaction is carried out under conditions that require protection from light.
In a third aspect of the present invention, there is provided an agricultural composition comprising:
(a) 0.001 to 99.99% by weight of the compound of the first aspect, an optical isomer, a cis-trans isomer, or
An agriculturally pharmaceutically acceptable salt, or a combination thereof; and
(b) An agriculturally pharmaceutically acceptable carrier and/or excipient.
In another preferred embodiment, component (a) constitutes from 0.01 to 99.9% by weight, preferably from 0.05 to 90% by weight, of the agricultural composition.
In another preferred embodiment, the agricultural composition further comprises an additional active substance selected from the group consisting of: an insecticide, a bait, a fungicide, an acaricide, a nematicide, a fungicide or an insect growth regulator.
In another preferred embodiment, there is provided a method of preparing an agricultural composition comprising the steps of: contacting (a) a compound of the first aspect, an optical isomer, a cis-trans isomer, or an agriculturally pharmaceutically acceptable salt thereof, or a combination thereof; mixing with (b) an agriculturally pharmaceutically acceptable carrier and/or excipient, thereby forming an agricultural composition.
In a fourth aspect of the present invention, there is provided a use of the compound according to the first aspect, an optical isomer, a cis-trans isomer, or an agriculturally pharmaceutically acceptable salt thereof, or the agricultural composition according to the third aspect, for controlling an agricultural pest or regulating plant growth, or for preparing a pesticide, a bactericide, or a plant growth regulator for controlling an agricultural pest or regulating plant growth.
In a fifth aspect of the invention there is provided a method of controlling an agricultural pest, which method comprises applying a compound of the first aspect, an optical isomer, a cis-trans isomer or an agriculturally pharmaceutically acceptable salt thereof, or an agricultural composition of the third aspect, to a plant, animal, soil surrounding it or to an environment in which a pest is or may be encountered.
In a sixth aspect of the present invention there is provided a method of regulating plant growth, the method comprising applying a compound of the first aspect, an optical isomer, a cis-trans isomer, or an agriculturally pharmaceutically acceptable salt thereof, or an agricultural composition of the third aspect, to a plant, a part of a plant, a plant organ, a plant propagation material, or a plant growing locus.
In a seventh aspect of the present invention, there is provided a compound represented by formula (III):
Figure BDA0003066834160000051
R 1 、R 2 、R 3 and R 4 The definition of (2) is as before.
The invention surrounds an insecticide, a bactericide and a plant growth regulator, combines the insecticide, the bactericide and the plant growth regulator with an o-nitrobenzene photo-protection group to obtain an o-nitrobenzene compound with a novel structure, and releases pesticide molecules and derivatives thereof through light control, so that the application of the o-nitrobenzene compound to the insecticide, the bactericide or the plant growth regulator becomes the technical problem to be solved by the invention.
It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.
Detailed Description
Term(s) for
In the present invention, unless otherwise specified, the terms used have the ordinary meaning known to those skilled in the art.
In the present invention, the term "C 1 -C 8 Alkyl "means a straight or branched chain alkyl group having 1,2,3, 4,5,6,7 or 8 carbon atoms, preferably C 1 -C 6 Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, or the like. In the present invention, an alkyl groupAlso includes substituted alkyl, and the substituent can be halogeno, hydroxyl, cyano, nitro, etc.
In the present invention, the term "C 2 -C 6 Alkenyl "means a straight or branched chain 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 the like. In the present invention, the alkenyl group also includes substituted alkenyl groups, and the substituent group can be halogen, hydroxyl, cyano, nitro, etc.
In the present invention, the term "C 2 -C 6 Alkynyl "refers to straight or branched chain alkynyl groups having 2,3, 4,5 or 6 carbon atoms, including but not limited to ethynyl, propynyl or the like. In the invention, alkynyl also includes substituted alkynyl, and the substituent can be halogen, hydroxyl, cyano, nitro and the like.
In the present invention, the term "C 3 -C 8 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 the like, preferably C 3 -C 6 A cycloalkyl group. In the present invention, the cycloalkyl group also includes substituted cycloalkyl groups, and the substituents may be halo, hydroxy, cyano, nitro, etc.
In the present invention, the term "C 5 -C 7 Cycloalkenyl "refers to a cyclic alkenyl group having 5,6, or 7 carbon atoms with one or more double bonds, including but not limited to cyclopentenyl, cyclohexenyl, cycloheptenyl, 1,3-cyclohexadienyl, 1,4-cyclohexadienyl, or the like. In the present invention, cycloalkenyl also includes substituted cycloalkenyl, and the substituent may be halo, hydroxy, cyano, nitro, etc.
In the present invention, the term "C 1 -C 6 Alkoxy "refers to a straight or branched chain alkoxy group having 1,2,3, 4,5, or 6 carbon atoms, such as: c 1 -C 6 alkyl-O-or C 1 -C 5 alkyl-O-C 1 -C 5 Examples of alkyl, alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy or the like. In the present invention, the alkoxy group also includes substituted alkoxy groups, and the substituent group can be halo, hydroxyl, cyano, nitro, etc.
In the present invention, the term "halogen" means fluorine, chlorine, bromine or iodine.
The term "halogenated" refers to a group substituted by one or more of the above halogen atoms, which may be the same or different.
The term "C 1 -C 8 Haloalkyl "refers to an alkyl group substituted with one or more halogen atoms, including but not limited to: trifluoromethyl, pentafluoroethyl, heptafluoroisopropyl, or the like.
In the present invention, the term "ring" or "ring system" refers to a carbocyclic or heterocyclic ring.
In the present invention, the term "ring system" refers to a fused ring in which two or more rings are merged together.
The term "heterocyclyl" refers to a fully saturated or partially unsaturated cyclic group (including but not limited to, e.g., a 3-7 membered monocyclic, 6-11 membered bicyclic, or 8-16 membered tricyclic ring system) in which at least one heteroatom is present in the ring having at least one carbon atom. Each heteroatom-containing heterocyclic ring may carry 1,2,3 or 4 heteroatoms selected from nitrogen atoms, oxygen atoms or sulfur atoms, wherein the nitrogen or sulfur atoms may be oxidized and the nitrogen atoms may also be quaternized. The heterocyclic group may be attached to the residue of any heteroatom or carbon atom of the ring or ring system molecule. In the present invention, the heterocyclic group is preferably a 3-to 8-membered heterocyclic group, more preferably a 5-to 7-membered heterocyclic group. Typical monocyclic heterocycles include, but are not limited to, tetrahydrofuranyl, 4,5-dihydrothiazol-2-yl, 2-cyanoimino-4-oxo-1,3-thiazolidin-3-yl, 2-cyanoimino-4-oxo-1,3-thiazinan-3-yl, azetidinyl, pyrrolidinyl, oxetanyl, pyrazolinyl, imidazolinyl, imidazolidinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, hexahydroazepinyl, 4-piperidinonyl, tetrahydropyranyl, morphinyl, thiomorpholinyl, thiomorpholino sulfoxide, thiomorpholino sulfone, 1,3-dioxanyl, and tetrahydro-1,1-dioxythiophene. Polycyclic heterocyclic groups include spiro, fused and bridged heterocyclic groups. In the present invention, the heterocyclic group includes a substituted heterocyclic group, and the substituent may be a halogen, a hydroxyl group, a cyano group, a nitro group or the like.
The term "heteroaromatic ring system" refers to a ring system in which at least one ring of the ring system is aromatic.
As used herein, the term "heteroaryl" refers to heteroaromatic systems of 1 to 4 heteroatoms, 5 to 14 ring atoms, including monocyclic (e.g., "5-, 6-, or 7-membered heteroaryl") and polycyclic (e.g., "8-14 membered heteroaromatic bicyclic or tricyclic ring systems" or "8-12 membered heteroaromatic bicyclic ring systems"), wherein the heteroatoms are selected from oxygen, nitrogen, and sulfur, including but not limited to: pyridyl, thiazolyl, isothiazolyl, thienyl, furyl, pyrrolyl, pyrazolyl, pyrimidinyl, oxazolyl, isoxazolyl, 1H-tetrazolyl, 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, benzofuran, benzo [ b ] thiophene, indole, quinoline, isoquinoline, 1H-indazole, 1H-benzo [ d ] imidazole, benzo [ d ] thiazole, benzo [ d ] oxazole, benzo [ d ] isoxazole, benzo [ d ] [ 39 zxft 7439 ] thiadiazole 2,3-dihydroimidazo [1,2-a ] pyridine, quinazoline, quinoxaline, cinnoline, phthalazine, 1,8-naphthyridine, 4,5,6,7-tetrahydrobenzo [ b ] thiophene, benzo [ b ] thiophene-1,1-dioxane, 8H-indeno [2,1-b ] thiophene, 7,8-dihydro-6H-cyclopentyl [ 3592 zxft 92 ] thieno [2,3-d ] pyrimidine, 3,5,6,7-tetrahydro-4H-cyclopentyl [4,5] thieno [ 5252-d ] pyrimidin-4-one, spiro [ indole-3,2' - [ 3,2 ] dioxolane ] -2-one, spiro [ indole-58 zxft 6258 ] oxo-2-dione, and the like. In the present invention, the heteroaryl group includes substituted heteroaryl groups, and the substituent may be a halogen, a hydroxyl group, a cyano group, a nitro group, or the like.
Unless otherwise stated, it is assumed that any heteroatom that is not in a valence state has sufficient hydrogen to replenish its valence state.
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, heterocyclyl corresponds to heterocyclylene, alkoxy corresponds to alkyleneoxy, and the like.
In the present invention, the term "substituted" means that one or more hydrogen atoms on a specified group are replaced with a specified substituent. Particular substituents are those described correspondingly in the foregoing, or as appearing in the examples. When a plurality of the specified structures are substituted at a position with a plurality of the specified substituents, each position of the substituents may be the same or different. The term "substituted" as used herein includes all permissible substitutions of organic compounds. In a broad sense, permissible substituents include acyclic, cyclic, branched, unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic organic compounds. In the present invention, the heteroatom nitrogen may have a hydrogen substituent or any permissible organic compound described hereinabove to supplement its valence state. Furthermore, the present invention is not intended to be limited in any way as to the permissible substitution of organic compounds.
As described herein, the compounds of the present invention may be substituted with any number of substituents or functional groups to extend their inclusion range.
The term "inert solvent" refers to a variety of solvents that do not react with the starting materials, including various straight, branched or cyclic alcohols, ethers or ketones, alkyl halides, 1,4-dioxane, acetonitrile, tetrahydrofuran, N-Dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and the like.
The term "agriculturally pharmaceutically acceptable salt" means that the anion of the salt is known and acceptable in forming a pharmaceutically acceptable salt of the antimicrobial agent. Preferably, the salt is water soluble. Suitably, the acid addition salts formed by the compounds of formula (I) include salts formed with inorganic acids, such as hydrochlorides, phosphates, sulphates, nitrates; and salts formed with organic acids such as acetates, benzoates, and the like. The salts which the compounds of the invention may form are also within the scope of the invention. Unless otherwise indicated, the compounds of the present invention are understood to include salts thereof. The term "salt" as used herein, means a salt formed from an inorganic or organic acid and a base in either acid or base form.
Specific functional groups and definitions of chemical terms are described in detail below. For purposes of the present invention, the chemical Elements are combined with a Periodic Table of the Elements, CAS version, handbook of Chemistry and Physics,75 th Agreement as defined in ed. The definition of a particular functional group is also described herein. In addition, the basic principles of Organic Chemistry, as well as specific functional groups and reactivities are also described in "Organic Chemistry", thomas Sorrell, university Science Books, sausaltito: 1999, which is incorporated by reference in its entirety.
Certain compounds of the present invention may exist in specific geometric or stereoisomeric forms. The present invention encompasses all compounds, including cis and trans isomers, R and S enantiomers, diastereomers, (D) isomer, (L) isomer, racemic mixtures and other mixtures thereof. Further the asymmetric carbon atom may represent a substituent such as an alkyl group. All isomers, as well as mixtures thereof, are encompassed by the present invention.
According to the present invention, the mixture of isomers may contain a variety of isomer ratios. For example, in a mixture of only two isomers, the following combinations are possible: 50, 60, 30, 80. Similar ratios, as well as ratios that are mixtures of more complex isomers, are also within the scope of the invention, as would be readily understood by one of ordinary skill in the art.
The invention also includes isotopically-labeled compounds, equivalent to those disclosed herein for the original compound. In practice, however, it will often occur that one or more atoms are replaced by an atom having a different atomic weight or mass number. Examples of isotopes that can be listed as compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine and chlorine, respectively 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 and (4) Cl. The compounds of the present invention, or enantiomers, diastereomers, isomers, or pharmaceutically acceptable salts or solvates thereof, wherein isotopes or other isotopic atoms containing those compounds are within the scope of the present invention. Certain isotopically-labeled compounds of the present invention,for example 3 H and 14 among these, the radioactive isotope of C is 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. Is the first choice among isotopes. In addition, heavier isotopes such as deuterium, i.e. 2 H, due to its good metabolic stability, may be advantageous in certain therapies, such as increased half-life in vivo or reduced dose, and therefore, may be preferred in certain circumstances. Isotopically labeled compounds can be prepared by conventional methods by substituting a readily available isotopically labeled reagent for a non-isotopically labeled reagent using the protocols disclosed in the examples.
If it is desired to design the synthesis of a particular enantiomer of a compound of the invention, it may be prepared by asymmetric synthesis or by derivatization with chiral auxiliary agents, separation of the resulting diastereomeric mixture and removal of the chiral auxiliary agent to give 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, diastereomeric salts can be formed therewith with an appropriate optically active acid or base, and the isolated enantiomers can be obtained in pure form by conventional means such as fractional crystallization or chromatography.
In the present invention, the term "plant" refers to all tangible parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, leaves and fruits.
As used herein, the term "locus" means a place in or on which plants are grown, or a place where seeds of cultivated plants are sown, or a place where seeds are to be placed in soil. It includes soil, seeds, and seedlings, along with established vegetation.
The term "plant propagation material" denotes all reproductive parts of a plant, for example seeds or vegetative parts of a plant such as cuttings and tubers. It includes seeds in the strict sense, as well as roots, fruits, tubers, bulbs, rhizomes and plant parts.
In the present invention, the term "regulating plant growth" includes, but is not limited to: prolonging the dormancy of storage organs, breaking the dormancy to promote germination, promoting the growth of stems and leaves, promoting rooting, inhibiting the growth of stem and leaf buds, promoting the formation of flower buds, inhibiting the formation of flower buds, thinning flowers and fruits, protecting flowers and fruits, prolonging the flowering period, inducing the generation of female flowers, inducing the generation of male flowers, cutting flowers and keeping fresh, forming seedless fruits, promoting the ripening of fruits, delaying senility, improving the content of amino acids, improving the content of proteins, improving the content of sugars, promoting the coloring of fruits, increasing the content of fat and improving the stress resistance.
Active substances according to the invention
The compound of the invention, the active substance of the invention or the active compound of the invention refers to a compound with a structure shown in a general formula (I) or an optical isomer, a cis-trans isomer or an agriculturally and pharmaceutically acceptable salt thereof, and the compound has obvious activity of inhibiting phytopathogen.
Specifically, the compound of the present invention is a compound having the formula (I), an optical isomer, a cis-trans isomer, or an agriculturally pharmaceutically acceptable salt thereof:
Figure BDA0003066834160000091
examples of pest control include, but are not limited to: coleopteran insects, such as elephant corn (Sitophilus zeamais), tribophytes castanea (Tribolium castaneum), harpagophytum procumbens (Henosporacaena virginiana), elaeis icornis (Henospora castanea spicata), elaeis quinata (Agriotes fuscolis), rhynchophylla (Anomala cuprina), rhynchophylla quadrata (Popilia quadrata), torulopsis arborvita (Monosepta hieron), monochamomile (Monochamus alternatus), monochamus alternatus (Monochamus alternatus), root image (Echinococcus squamosus), paulophylla japonica (Basidiomonas binata), apriona stelleri (Anophora longifolia), apriona filiformis (Aprionalis), lonicera bella bellata (Agrimonia ventralis), or Oryza bellina (Agrioticus). Lepidopteran insects, such as Cnaphalocrocis medinalis Guenee, gypsylla moth (Lymantria dispar), trichoplusia (Malacosma neosteria testacea), ostertagia chrysalis (Diaphania persica), bombycis punctiferalis (Clania variegata), bombycis mori (Cnodomapa fluescens), trichoplusia massoniana (Dendrolimus punctata), trichoplusia (Dendrolimus punctata), glyphylla venenum (Orgyia gossypigma), populus populifera (Paranthrene tabaniformis), spodoptera litura (Spodoptera litura), chilo suppressalis (Chisupressalis), zea mays (Ostrinia nubilalis), phlebia punctifera (Ephemella calis), cotton gossypiella roller (Adenopsis), spodoptera castellata indica (Spodoptera), and Castanea sativa
(lasyresia spleena), agrotis furacana (Agrotis furaca), greater wax moth (Galleria mellonella), plutella xylostella (Plutella xylostella), citrus fruit moth (phyllocnitis citrus), or oriental armyworm (Mythimna sepata); homopterans, such as Nephotettix cincticeps (Nephotettix cincticeps), nilaparvata lugens (Nilaparvata lugens), tokay scales (Pseudococcus comstocki), arrowhead scales (Unaspis yanonensis), myzus persicae (Myzus persicae), aphis gossypii (Aphis gossypii), lipophis erysimi pseudobasilica (Lipophis erysimi), nepholygus pyrus (Stephaniae nashi), or Bemisia tabaci (Bemisia tabaci); orthoptera insects, such as german cockroach (Blattella germanica), american cockroach (Periplaneta americana), african mole cricket (Gryllotalpa africana), or locusta migratoria (Locus migratoria); isoptera insects, such as imported fire ants (Solenopsis invicta), or termites (coptottermes formosanus); dipteran insects, such as housefly (Musca domestica), aedes aegypti (Aedes aegypti), seed fly (Delia platura), culex (Culex sp.), or Hua Anwen (Anopheles sinensis); homopterans, such as, for example, orius erythropolis (Tropidothorax elegans Distant), orius oryzae (Nezara viridula Linnaeus), orius pyricularis (Urochela luteovaria Distant).
Examples of controlling diseases include, but are not limited to: downy mildew (cucumber downy mildew, rape downy mildew, soybean downy mildew, beet downy mildew, sugarcane downy mildew, tobacco downy mildew, pea downy mildew, luffa downy mildew, wax gourd downy mildew, melon downy mildew, cabbage downy mildew, spinach downy mildew, radish downy mildew, grape downy mildew, onion downy mildew), white rust (rape white rust, cabbage white rust), damping-off (rape damping-off, tobacco damping-off, tomato damping-off, pepper damping-off, eggplant damping-off, cucumber damping-off, cotton seedling damping-off), cotton rot (pepper blight, luffa blight, wax gourd blight), blight (broad bean blight, cucumber blight, watermelon blight, melon blight, pepper blight, leek blight, garlic blight, cotton disease), late blight (potato blight, tomato blight), and the like; root rot (pepper root rot, eggplant root rot, kidney bean root rot, cucumber root rot, bitter gourd root rot, cotton root rot, broad bean root rot), damping-off (seedling blight of cotton, sesame damping-off, pepper damping-off, cucumber damping-off, cabbage damping-off), chlorosis (cotton verticillium wilt, sunflower verticillium wilt, tomato yellow wilt, pepper yellow wilt, eggplant yellow wilt), scab (pumpkin scab, wax gourd scab, melon scab), gray mold (cotton boll black gray mold, red ramie gray mold, tomato gray mold, pepper gray mold, bean gray mold, sequent vegetable gray mold, fatigue vegetable gray mold, kiwi fruit gray mold, grass gray mold), brown spot (cotton brown spot, beet brown spot, peanut brown spot, pepper brown spot, white gourd brown spot, soybean brown spot, sunflower brown spot, pea brown spot, brown spot, broad bean brown spot), black spot (pseudoblack spot of flax, black spot of rape, black spot of sesame, black spot of sunflower, black spot of castor-oil plant, black spot of tomato, black spot of pepper, black spot of eggplant, black spot of kidney bean, black spot of cucumber, black spot of celery, black spot of carrot, black spot of apple, black spot of peanut), spot blight (tomato spot blight, pepper spot blight, celery spot blight), early blight (tomato early blight, pepper early blight, eggplant early blight, potato early blight, celery early blight), ring spot (soybean ring spot, sesame ring spot, bean ring spot), leaf blight (sesame leaf blight, sunflower leaf blight, watermelon leaf blight, melon leaf blight), stem basal rot (tomato calyx rot, kidney bean stem basal rot), and others (corn northern leaf blight, red ramie waist breaking, rice blast, chestnut scab, sugarcane eye spot, boll Qu Ran disease, peanut crown rot, soybean stem rot, soybean black spot disease, melon northern leaf blight, peanut net blotch, tea red leaf spot, pepper leaf spot, white gourd leaf spot, bud black rot, fatigue heart rot, red ramie leaf mold, red ramie spot disease, yellow ramie stem spot, soybean purple spot, sesame leaf spot, castor gray leaf spot, tea brown leaf spot, eggplant brown cabbage star disease, kidney bean red spot, bitter gourd white spot, watermelon spot, jute rot, sunflower root rot, kidney bean carbon rot, eggplant leaf spot, cucumber target spot, tomato leaf mold, eggplant leaf mold, broad bean red spot), etc.: basidiomycetous diseases such as rust (wheat stripe rust, wheat stalk rust, wheat leaf rust, peanut rust, sunflower rust, gan Lu rust, leek rust, onion rust, chestnut rust, soybean rust), smut (corn head smut, corn smut, sorghum head smut, sorghum panicle disease, sorghum smut, sorghum column smut, chestnut grain black panicle, sugarcane black panicle, kidney bean rust) and others (such as wheat sharp eyespot, rice sheath blight, etc.); ascomycetous diseases, such as powdery mildew (wheat powdery mildew, shancai powdery mildew, sesame powdery mildew, sunflower powdery mildew, beet powdery mildew, eggplant powdery mildew, pea powdery mildew, towel gourd powdery mildew, pumpkin powdery mildew, wax gourd powdery mildew, melon powdery mildew, grape powdery mildew, broad bean powdery mildew), sclerotinia rot (flax sclerotinia sclerotiorum, rape sclerotinia sclerotiorum, soybean sclerotinia sclerotiorum, peanut sclerotinia sclerotiorum, tobacco sclerotinia sclerotiorum, hot pepper sclerotinia sclerotiorum, eggplant sclerotinia sclerotiorum, kidney bean sclerotinia sclerotiorum, pea sclerotiorum, cucumber sclerotiorum, balsam pear sclerotiorum, wax gourd sclerotinia sclerotiorum, watermelon sclerotiorum, celery sclerotiorum, scab (apple scab, pear scab), clubroot (cabbage clubroot, cauliflower clubroot, skimming, radix isatidis, radish clubrood, turnip clubroot).
The compounds and compositions of the invention may be applied as plant growth regulators on dicotyledonous or monocotyledonous crops. Crops of useful plants in which the compositions according to the invention may be used include perennial and annual crops, such as berry plants, for example blackberries, blueberries, cranberries, raspberries and strawberries; cereals, such as barley, maize, millet, oats, rice, rye, sorghum, triticale and wheat; fiber plants, such as cotton, flax, hemp, jute, and sisal; field crops such as sugar and feed beets, coffee beans, hops, mustard, canola, poppy, sugar cane, sunflowers, tea and tobacco; fruit trees such as apple, apricot, avocado, banana, cherry, citrus, nectarine, peach, pear, and plum; grasses, such as bermuda grass, blue grass, bentgrass, centipede, beefwood, ryegrass, saint osbeckia and zoysia; herbs such as basil, borage, chive, coriander, lavender, detached grass, mint, oregano, parsley, rosemary, sage, and thyme; legumes, such as beans, lentils, peas and soybeans; nuts such as almonds, cashews, peanuts, hazelnuts, peanuts, pecans, pistachios, and walnuts; palm bundles, such as oil palm bundles; ornamental plants such as flowers, shrubs and trees; other trees, such as cacao, coconut, olive and rubber trees; vegetables such as asparagus, eggplant, broccoli, cabbage, carrot, cucumber, garlic, witloof, zucchini, melon, okra, onion, pepper, potato, pumpkin, rhubarb, spinach, and tomato; and grapevines, such as grapes.
Pesticidal compositions containing the active substances according to the invention
The "active substance of the present invention" can be prepared into an insecticide, a fungicide or a plant growth regulator composition in a conventional manner. These active compounds can be formulated in the customary formulations, for example as solutions, emulsions, suspensions, powders, foams, pastes, granules, aerosols, natural and synthetic materials impregnated with active substance, microcapsules in polymers, coating compositions for seeds, and formulations for use with combustion devices, for example smoking cartridges, smoking pots and smoking trays, and ULV Cold mist (Cold mist) and hot mist (Warm mist) formulations.
These formulations can be produced by known methods, for example by mixing the active compounds with extenders, that is, liquid or liquefied gas or solid diluents or carriers, and optionally surfactants, that is, emulsifiers and/or dispersants and/or foam formers. Organic solvents may also be used as adjuvants, for example when water is used as extender.
When a liquid solvent is used as the diluent or carrier, it is basically suitable, for example: 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 lipids; ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone; or less commonly used polar solvents such as dimethylformamide, dimethylsulfoxide and water.
Liquid gas diluents or carriers refer to liquids that will become gases at normal temperature and pressure, such as aerosol propellants, such as halogenated hydrocarbons, as well as butane, propane, nitrogen and carbon dioxide.
The solid carrier may be a finely divided natural mineral such as kaolin, clay, talc, quartz, floridin, montmorillonite, or diatomaceous earth; and ground synthetic minerals such as highly dispersed silicic acid, alumina and silicates. Solid carriers for granules are crushed and classified natural zircon, such as calcite, marble, pumice, sepiolite, dolomite, synthetic granules of inorganic and organic meals, and granules of organic materials, such as sawdust, coconut shells, corn cobs and tobacco stalks, among others.
Nonionic and anionic emulsifying trains may be used as emulsifiers and/or foam formers. Such as polyoxyethylene-fatty acid esters, polyoxyethylene-fatty alcohol ethers, alkylaryl polyglycol ethers, alkylsulfonates, alkylsulfates, arylsulfonates and albumin hydrolysates. The dispersant comprises lignin sulfite waste liquor and methyl cellulose.
Binders such as carboxymethylcellulose and natural and synthetic polymers in the form of powders, granules or emulsions, for example gum arabic, polyvinyl alcohol and polyvinyl acetate, may be used in the formulations.
Colorants such as inorganic dyes, e.g., iron oxide, cobalt oxide, and prussian blue; organic dyes such as azo dyes or metal phthalocyanine dyes; trace nutrients such as salts of iron, manganese, boron, copper, cobalt, aluminum, and zinc, and the like.
The "active compounds of the present invention" may be present in their commercial preparations as a mixture with other active compounds, such as insecticides, bactericides, fungicides, herbicides, growth control agents, etc., or in the use forms prepared from these preparations. Insecticides include, for example, phosphates, carbamates, chlorinated hydrocarbons and substances produced by microorganisms, such as avermectins and the like, and fungicides include strobilurins, amides, triazoles and the like.
Furthermore, the "active compounds according to the invention" can also be present in their commercial preparations in a mixture with synergists, which are compounds which increase the action of the active compounds, or in the use forms prepared from these preparations, it being possible for no synergists to be added, since the active compounds themselves are active.
These preparations generally contain "the active compound of the present invention" in an amount of 0.001 to 99.99% by weight, preferably 0.01 to 99.9% by weight, more preferably 0.05 to 90% by weight, based on the total weight of the pesticidal composition. The concentration of the active compound in the commercial preparations or dosage forms to be used can vary within wide limits. The active compound is used in a dosage form at a concentration of 0.0000001 to 100% by weight, preferably between 0.0001 and 1% by weight.
The compound shown in the formula (I), an optical isomer, a cis-trans isomer or an agriculturally and pharmaceutically acceptable salt thereof has a good control effect on alfalfa aphid or aedes albopictus larvae or armyworm or cucumber gray mold and rape sclerotinia rot, and has a good regulation effect on plant growth of corn or soybean.
All stereoisomers of the compounds (e.g., those asymmetric carbon atoms that may exist due to various substitutions), including enantiomeric and diastereomeric forms thereof, are contemplated within the invention. The individual stereoisomers of the compounds of the invention may not be present in combination with the other isomers (e.g. as a pure or substantially pure optical isomer having a particular activity), or may be present as a mixture, e.g. as a racemate, or as a mixture with all or a portion of the other stereoisomers. The chiral center of the invention has two S or R configurations, and is defined by the International Union of theory and applied chemistry (IUPAC) proposed in 1974. Racemic forms can be resolved by physical methods such as fractional crystallization, or by separation of the crystals by derivatization into diastereomers, or by chiral column chromatography. The individual optical isomers can be obtained from the racemates by any suitable method, including, but not limited to, conventional methods such as salt formation with an optically active acid followed by crystallization.
The compounds of the present invention, which are obtained by preparing, isolating and purifying the compound in order to obtain the compound in an amount of 90% by weight or more, for example, 95% by weight or more, or 99% by weight or more ("very pure" compounds), are listed in the text description. Such "very pure" compounds of the invention are also part of the invention herein.
All configurational isomers of the compounds of the present invention are within the scope of the invention, whether in admixture, pure or very pure form. The definition of compounds in the present invention encompasses both cis (Z) and trans (E) olefin isomers, as well as cis and trans isomers of carbocyclic and heterocyclic rings.
Throughout the specification, groups and substituents may be selected to provide stable fragments and compounds.
Preparation method
The compound represented by the general formula of the present invention can be produced by the following method, however, the conditions of the method, such as reactants, solvent, base, amount of the compound used, reaction temperature, time required for the reaction, etc., are not limited to the following explanation. The compounds of the present invention may also be conveniently prepared by optionally combining various synthetic methods described in the present specification or known in the art, and such combinations may be readily carried out by those skilled in the art to which the present invention pertains. Reagents may be purchased commercially if feasible.
The preparation method of the compound comprises the following steps:
Figure BDA0003066834160000141
(1) In a proper solvent, R-substituted 2-nitrobenzaldehyde analog reacts with 2-mercaptoethanol at 0-10 ℃ to form a compound shown as a formula (II);
Figure BDA0003066834160000142
(2) Reacting a compound shown in the formula (II) with p-nitrophenyl chloroformate in a proper solvent at 0-5 ℃ under the protection of argon to form a compound shown in the formula (III);
Figure BDA0003066834160000151
(3) Reacting a compound shown in the formula (III) with a compound selected from the following group in a proper solvent under the protection of argon at 0-5 ℃ to obtain a compound shown in the formula (I); or in step (3), the compound of formula (III) may be reacted with a compound selected from the group consisting of in two steps to give a compound of formula (I),
Figure BDA0003066834160000152
synthetic reaction parameters the compounds of the present invention can be prepared from readily available starting materials using, for example, the following general methods and procedures. It will be appreciated that where typical or optimized process conditions (i.e., reaction temperatures, times, molar ratios of reactants, solvents, catalysts, pressures, etc.) are given, other process conditions may also be used, unless otherwise indicated. Optimal reaction conditions may vary with the particular reactants or solvents used, but such conditions may be determined by one skilled in the art by routine optimization procedures.
The starting materials for the following reactions are generally known compounds or can be prepared by known procedures or obvious modifications thereof. For example, many starting materials are available from commercial suppliers, others can be prepared by procedures described in the text of standard references or obvious modifications, for example, the method described in CN104530037 a.
In the production process of the present invention, each reaction is usually carried out in an inert solvent at a reaction temperature of-20 to 120 ℃ (preferably-10 to 0 ℃ or 20 to 30 ℃ or 80 to 100 ℃). The reaction time is usually 2 to 24 hours, preferably 4 to 18 hours, and the reaction time can be appropriately extended according to the reaction requirement, and the specific reaction time is determined according to the degree of reaction.
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 a combination thereof.
The invention has the following main advantages:
(1) The invention provides the o-nitrobenzene-containing compound with high efficiency, low toxicity, good environmental compatibility and novel structure;
(2) The compound can optically control to release active substances, and has remarkable insecticidal and bactericidal activities, plant growth regulation and the like.
(3) The compounds of the invention are particularly suitable for controlling alfalfa aphid or aedes albopictus larvae or armyworm or cucumber gray mold, sclerotinia rot of colza and for regulating the plant growth of maize or soybean.
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Experimental procedures without specific conditions noted in the following examples, generally according to conventional conditions, or according to conditions recommended by the manufacturer. Unless otherwise indicated, percentages and parts are by weight.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any methods and materials similar or equivalent to those described herein can be used in the methods of the present invention. The preferred embodiments and materials described herein are intended to be exemplary only.
The structure of the compounds of the invention is determined by Nuclear Magnetic Resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS).
The starting materials in the examples of the present invention are known and commercially available or may be used or synthesized according to literature reports in the art.
All reactions of the present invention are carried out under continuous magnetic stirring under the protection of a dry inert gas (e.g., nitrogen or argon) except for the specific indications, and the reaction temperatures are all in degrees centigrade.
Example 1 preparation of (((4,5-dimethoxy-2-nitrophenyl) methylene) bis (sulfanediyl)) bis (ethane-2,1-diyl) bis ((3-cyano-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1 h-pyrazol-5-yl) carbamate (I-2)
The flow is as follows:
Figure BDA0003066834160000171
reaction reagents and conditions: (a) Dichloromethane, acetic acid, boron trifluoride in ether, 5 ℃→ room temperature, for 3 hours; (b) Dichloromethane, N, N-diisopropylethylamine, 0 ℃, argon protection and 6 hours; (c) Anhydrous N, N-dimethylformamide and 4-dimethylaminopyridine at room temperature under the protection of light and argon for 24 hours;
synthesis of intermediate 1 (((4,5-dimethoxy-2-nitrophenyl) methylene) bis (thio)) bis (ethan-1-ol)
Figure BDA0003066834160000172
4,5-dimethoxy-2-nitrobenzaldehyde (1.40g, 6.63mmol) was added to a 250mL eggplant-shaped bottle, dissolved in 40mL dichloromethane, and stirred in an ice bath. To the solution were slowly added 2-mercaptoethanol (1.12mL, 15.91mmol), acetic acid (0.91mL, 15.91mmol) and BF 3 ·Et 2 O (0.98mL, 7.96mmol). Stirring the reaction solution at 5 ℃ for 1h and returning to room temperature; a second portion of 2-mercaptoethanol (1.12mL, 15.91mmol) and BF were added 3 ·Et 2 O (0.98mL, 7.96mmol) with stirringStirring for 2 hours till the reaction is finished. The reaction was diluted with dichloromethane (40 mL) and saturated NaHCO was added 3 After stirring the solution (40 mL) for 1 hour, the organic layer was separated and retained. The aqueous phase was extracted with dichloromethane (40 mL. Times.2), the organic layers were combined, washed with saturated brine (40 mL), dried over anhydrous magnesium sulfate, and the organic solvent was spin dried. The crude product obtained was dissolved in dichloromethane, and silica gel column chromatography was performed after addition of an appropriate amount of silica gel, eluting with dichloromethane: methanol =30 (V: V), and the solvent was dried by spin to give intermediate 1 (pale yellow solid, 1.76g, 70.1%). 1 H NMR(400MHz,MeOD)δ7.54(s,1H),7.49(s,1H),6.09(s,1H),3.95(s,3H),3.89(s,3H),3.68(t,J＝6.6Hz,4H),2.81(dt,J＝13.3,6.6Hz,2H),2.68(dt,J＝13.5,6.7Hz,2H).
Synthesis of intermediate 2 (((4,5-dimethoxy-2-nitrophenyl) methylene) bis (sulfodiyl)) bis (ethane-2,1-diyl) bis (4-nitrophenyl) bis (carbonate)
Figure BDA0003066834160000181
A100 mL three-necked flask was charged with intermediate 1 (349.10mg, 1.00mmol), dissolved in 30mL of anhydrous dichloromethane, and then, under argon protection, 5mL of an anhydrous dichloromethane solution of p-nitrophenyl chloroformate (401.96mg, 2.00mmol) and 5mL of an anhydrous dichloromethane solution of N, N-diisopropylethylamine (258.31mg, 2.00mmol) were added dropwise to the reaction in this order under ice-cooling. After 3 hours of reaction, a second portion of 4-nitrophenyl chloroformate (402.01mg, 2.00mmol) and N, N-diisopropylethylamine (258.32mg, 2.00mmol) was added and stirred for 3 hours. The reaction mixture was diluted with dichloromethane (30 mL), washed with water 1 time, and the aqueous phase was extracted with dichloromethane (40 mL. Times.2). The organic phases were combined, washed with saturated brine (40 mL), dried over anhydrous magnesium sulfate, and the organic solvent was spin dried. The crude product obtained was dissolved in dichloromethane and silica gel column chromatography was performed after addition of appropriate amount of silica gel, eluting with dichloromethane: methanol =30 (V: V), solvent was dried to give intermediate 2 (dark yellow solid, 468.50mg, 69.1%). 1 H NMR(400MHz,DMSO)δ8.30(d,J＝9.1Hz,4H),7.61(s,1H),7.52(d,J＝9.1Hz,4H),7.44(s,1H),6.03(s,1H),4.40(t,J＝5.7Hz,4H),3.92(s,3H),3.86(s,3H),3.09(dt,J＝12.6,6.2Hz,2H),3.02–2.91(m,2H).
Synthesis of Compound I-2 (((4,5-dimethoxy-2-nitrophenyl) methylene) bis (sulfanyldiyl)) bis (ethane-2,1-diyl) bis ((3-cyano-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1 h-pyrazol-5-yl) carbamate)
Figure BDA0003066834160000182
A25 mL three-necked flask was charged with intermediate 2 (679.10mg, 1.00mmol), and 5mL of anhydrous N, N-dimethylformamide was added to dissolve the mixture, and then under argon protection, 5mL of an anhydrous N, N-dimethylformamide solution of 5-amino-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1H-pyrazole-3-cyano (2179.50mg, 5.00mmol) and 5mL of an anhydrous N, N-dimethylformamide solution of 4-dimethylaminopyridine (610.91mg, 5.00mmol) were added dropwise to the reaction under ice, and the reaction was carried out at room temperature with exclusion of light for 24 hours. The reaction was concentrated in vacuo, diluted with dichloromethane (10 mL), washed with water 1 time, and the aqueous phase extracted with dichloromethane (10 mL. Times.2). The organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous magnesium sulfate, and the organic solvent was spin-dried. The obtained crude product was dissolved in dichloromethane, and silica gel column chromatography was performed after addition of an appropriate amount of silica gel, eluting dichloromethane: methanol =45 (V: V), and the solvent was spin-dried to obtain compound I-2 (pale yellow solid, 318.21mg, 25.1%). 1 H NMR(400MHz,DMSO)δ11.47(s,2H),8.32(d,J＝10.5Hz,4H),7.58(s,1H),7.31(s,1H),5.86(s,1H),4.22(t,J＝6.6Hz,4H),3.87(d,J＝2.5Hz,6H),3.04–2.74(m,4H).HRMS(ESI)m/z[M+Na] + C 39 H 23 Cl 4 F 12 N 9 O 10 S 4 Calculating the value: 1295.8911,1297.8881,1299.8839,1301.8810,1303.8780; found 1295.8904,1297.8954,1299.8845,1301.8822,1303.8744.
Example 2 preparation of (((4,5-dimethoxy-2-nitrophenyl) methylene) bis (sulfanediyl)) bis (ethane-2,1-diyl) bis ((1-methyl-2-nitro-3- ((tetrahydrofuran-3-yl) methyl) guanidin-1-yl) iminoformate) (I-10)
Figure BDA0003066834160000191
Compound i-10 was synthesized in a similar manner to example 1, except that:
replacing fipronil in the step (c) with dinotefuran; the 4-dimethylaminopyridine in the reaction process is replaced by N, N-diisopropylethylamine.
The step (c) is as follows: a25 mL three-necked flask was charged with intermediate 2 (679.10mg, 1.00mmol), and 5mL of anhydrous N, N-dimethylformamide was added to dissolve the intermediate, and under argon protection, 5mL of an anhydrous N, N-dimethylformamide solution of 1-methyl-2-nitro-3- ((tetrahydrofuran-3-yl) methyl) guanidine (1010.01mg, 5.00mmol) and 5mL of an anhydrous N, N-dimethylformamide solution of N, N-diisopropylethylamine (645.21mg, 5.00mmol) were added dropwise to the reaction in this order under ice-cooling, and the reaction was carried out for 16 hours at room temperature under dark conditions. The reaction was concentrated in vacuo, diluted with dichloromethane (10 mL), washed with water 1 time, and the aqueous phase extracted with dichloromethane (10 mL. Times.2). The organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous magnesium sulfate, and the organic solvent was spin-dried. The obtained crude product was dissolved in dichloromethane, added with an appropriate amount of silica gel, and subjected to silica gel column chromatography after spin-drying, dichloromethane: methanol =25 (V: V) elution, and the solvent was spin-dried to obtain compound I-10 (pale yellow solid, 248.62mg, 31.1%). 1 H NMR(400MHz,CDCl 3 )δ7.44(s,1H),7.33(s,1H),6.01(s,1H),4.30(t,J＝6.4Hz,4H),3.95(s,3H),3.89(s,3H),3.88–3.81(m,2H),3.75(dd,J＝8.9,6.9Hz,2H),3.67(dd,J＝15.8,7.9Hz,2H),3.50(dd,J＝9.0,4.7Hz,2H),3.31(t,J＝6.0Hz,4H),3.14(s,6H),2.95–2.85(m,2H),2.83–2.73(m,2H),2.53(td,J＝12.6,6.6Hz,2H),2.13–2.01(m,2H),1.56(td,J＝12.9,7.4Hz,2H).HRMS(ESI)m/z[M+Na] + C 29 H 43 N 9 O 14 S 2 Calculating the value: 828.2371, found 828.2271.
EXAMPLE 3 preparation of 2- ((((2- (((3-cyano-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1 h-pyrazol-5-yl) carbamoyl) oxy) ethyl) thia) (4,5-dimethoxy-2-nitrophenyl) methyl) thia) ethyl-3- (1-methyl-2-nitro-3- ((tetrahydrofuran-3-yl) methyl) guanidin-1-yl) iminocarboxylate (I-18)
Figure BDA0003066834160000201
The flow is as follows:
Figure BDA0003066834160000202
reaction reagents and conditions: (a) Dichloromethane, acetic acid, boron trifluoride in ether, 5 ℃→ room temperature, for 3 hours; (b) Dichloromethane, N, N-diisopropylethylamine, 0 ℃, argon protection and 6 hours; (c) 1 ) Anhydrous N, N-dimethylformamide, N, N-diisopropylethylamine, room temperature, light protection and argon protection for 8 hours; (c) 2 ) Anhydrous N, N-dimethylformamide and 4-dimethylaminopyridine at room temperature under the protection of light and argon for 18 hours;
the synthesis of the intermediate 1 and the intermediate 2 is the same as that of the example 1;
synthesis of intermediate 3- ((((2- (4-nitrophenyl-carbonate) ethyl) thia) (4,5-dimethoxy-2-nitrophenyl) methyl) thia) ethyl-3- (1-methyl-2-nitro-3- ((tetrahydro-furan-3-yl) methyl) guanidin-1-yl) iminoformate (((4,5-dimethoxy-2-nitrophenyl) methylene) bis (sulfodiyl)) bis (ethane-2,1-diyl) - ((4-nitrophenyl) -carbonate) - (1-methyl-2-nitro-3- ((tetrahydro-furan-3-yl) methyl) guanidin-1-yl) -iminoformate)
Figure BDA0003066834160000203
A25 mL three-necked flask was charged with intermediate 2 (814.90mg, 1.20mmol), dissolved in 4mL of anhydrous N, N-dimethylformamide, and then, under argon protection, 3mL of an anhydrous N, N-dimethylformamide solution of 1-methyl-2-nitro-3- ((tetrahydrofuran-3-yl) methyl) guanidine (202.10mg, 1.00mmol) and 3mL of an anhydrous N, N-dimethylformamide solution of N, N-diisopropylethylamine (154.81mg, 1.20mmol) were added dropwise to the reaction in this order under ice, and the reaction was carried out at room temperature for 8 hours while keeping out of light. The reaction was concentrated in vacuo, diluted with dichloromethane (10 mL), washed with water 1 time, and the aqueous phase extracted with dichloromethane (10 mL. Times.2). The combined organic phases were washed with brine (20 mL) and dried over anhydrous magnesium sulfate, and the organic solvent was dried to give a mixture containing intermediate 3, which was not purified for further use.
Synthesis of Compound I-18 2- ((((2- (((3-cyano-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1 hydro-pyrazol-5-yl) carbamoyl) oxa) ethyl) thia) (4,5-dimethoxy-2-nitrophenyl) methyl) thia) ethyl-3- (1-methyl-2-nitro-3- ((tetrahydrofuran-3-yl) methyl) guanidin-1-yl) iminoformate
Figure BDA0003066834160000211
A25 mL three-necked flask was charged with intermediate 3 (742.20mg, 1.00mmol), and 5mL of anhydrous N, N-dimethylformamide was added to dissolve the intermediate, and under argon protection, 5mL of an anhydrous N, N-dimethylformamide solution of 5-amino-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1H-pyrazole-3-cyano (1307.70mg, 3.00mmol) and 5mL of an anhydrous N, N-dimethylformamide solution of 4-dimethylaminopyridine (366.51mg, 3.00mmol) were added dropwise to the reaction under ice-cooling, and the reaction was carried out at room temperature for 18 hours while keeping out the sun. The reaction was concentrated in vacuo, diluted with dichloromethane (10 mL), washed with water 1 time, and the aqueous phase extracted with dichloromethane (10 mL. Times.2). The organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous magnesium sulfate, and the organic solvent was spin-dried. The obtained crude product was dissolved in dichloromethane, added with an appropriate amount of silica gel, and subjected to silica gel column chromatography after spin-drying, dichloromethane: methanol =40 (V: V) elution, and the solvent was spin-dried to obtain compound I-18 (pale yellow solid, 228.61mg, 22.1%). 1 H NMR(400MHz,CDCl 3 )δ7.44(s,1H),7.39(s，2H)，7.33(s,1H),6.01(s,1H),4.30(t,J＝6.4Hz,4H),3.95(s,3H),3.89(s,3H),3.88–3.81(m,1H),3.75(dd,J＝8.9,6.9Hz,2H),3.67(dd,J＝15.8,7.9Hz,2H),3.50(dd,J＝9.0,4.7Hz,2H),3.31(t,J＝6.0Hz,2H),3.14(s,3H),2.95–2.85(m,1H),2.83–2.73(m,1H),2.53(td,J＝12.6,6.6Hz,1H),2.13–2.01(m,1H),1.56(td,J＝12.9,7.4Hz,1H).HRMS(ESI)m/z[M+Na] + C 34 H 33 Cl 2 F 6 N 9 O 12 S 3 Calculating the value: 1062.0682,1064.0663,1066.0663; found 1062.05854,1064.0579,1066.0557.
EXAMPLE 4 preparation of 2- (((((2- (((3-cyano-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1 h-pyrazol-5-yl) carbamoyl) oxa) ethyl) thia) (4,5-dimethoxy-2-nitrophenyl) methyl) thia) ethyl-3- ((6-chloropyridin-3-yl) -methyl) -2-nitroiminoimidazolidine-1-carboxylate (I-26)
Figure BDA0003066834160000221
Compound i-26 was synthesized in a similar manner to example 3, except that:
step (c) 1 ) The 1-methyl-2-nitro-3- ((tetrahydrofuran-3-yl) methyl) guanidine of (1), which was replaced with N- (1- ((6-chloropyridin-3-yl) -methyl) -imidazolidinone-2-ylidene) nitramide.
The characterization results were as follows: 1 H NMR(400MHz,CDCl 3 )δ8.45(s,1H),8.25(d，1H)，8.18(d,1H),7.45(s,1H),7.37(s，2H)，7.35(s,1H),6.01(s,1H),5.02(s,2H),4.28(t,J＝6.4Hz,4H),3.94(s,3H),3.87(s,3H),3.62(m,4H),3.21–2.86(m,4H),HRMS(ESI)m/z[M+Na] + C 36 H 29 Cl 3 F 6 N 10 O 11 S 3 calculating the value: 1115.0047,1117.0018,1119.9988,1120.9959; found 1115.0048,1117.0015,1119.9987,1120.9956.
EXAMPLE 5 preparation of 1- (4- (n-butyl) phenyl) -1-cyano-9- (4,5-dimethoxy-2-nitrophenyl) -4-oxo-2- (1,3,4-trimethyl-1H-pyrazol-5-yl-3,5-dioxa-8,10-dithiododec-1-en-12-yl (4- (2,5-dimethylphenyl) -8-methoxy-2-oxo-1-azaspiro [4.5] dec-3-en-3-yl) carbonate (I-34)
Figure BDA0003066834160000222
Compounds i-34 were synthesized in a similar manner to example 3, except that:
step (c) 1 ) And (c) 2 ) 1-methyl-2-nitro-3- ((tetrahydrofuran-3-yl) methyl) guanidine and 5-amino-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1 hydro-pyrazole-3-cyano as described in (1) above with 4- (2,5-dimethylphenyl) -3-hydroxy-8-methoxy-1-azaspiro [4.5] respectively]Decane-3-en-2-one and 2- (4- (n-butyl) phenyl) -3-hydroxy-3- (1,3,4-trimethyl-1H-pyrazol-5-yl) acrylonitrile.
The characterization results were as follows: 1 H NMR(400MHz,CDCl 3 )δ7.46(s,1H),7.35(s,1H),7.28(d,2H),7.20(d,2H),7.08(s,1H),7.02-6.90(d,2H),6.02(s,1H),4.29(t,J＝6.4Hz,4H),3.99(s,3H),3.93(s,3H),3.87(s,3H),3.69(s,3H),3.31(m,1H),3.19–2.86(m,4H),2.71(s,3H),2.52(s,3H),2.25(s,3H),2.01(s,3H),1.77–1.42(m,8H),1.05(s,9H),HRMS(ESI)m/z[M+Na] + C 52 H 61 N 5 O 12 S 2 calculating the value: 1011.3758; found 1011.3761.
EXAMPLE 6 preparation of bis (3- ((1H-1,2,4-triazol-1-yl) methyl) -1- (4-chlorophenyl) -2,4,4-trimethylpentan-3-yl) (((((4,5-dimethoxy-2-nitrophenyl) methylene) bis (sulfanediyl)) bis (ethane-2,1-diyl) dicarbonate (I-42)
Figure BDA0003066834160000231
Compounds i-42 were synthesized analogously to example 1, with the exception that:
the 5-amino-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1 hydro-pyrazole-3-cyano group described in step (c) was replaced with 3- ((1 hydro-1,2,4-triazol-1-yl) methyl) -1- (4-chlorophenyl) -2,4,4-trimethylpentan-3-ol.
The characterization results were as follows: 1 H NMR(400MHz,CDCl 3 )δ8.27(s,2H),8.05(s,2H),7.44(s,1H),7.35(s,1H),7.30(d,J＝8.2Hz,4H),7.02(d,J＝8.2Hz,4H),6.00(s,1H),4.35(d,J＝14.4Hz,2H),4.32(d,J＝14.4Hz,2H),4.29(t,J＝6.4Hz,4H),3.95(s,3H),3.89(s,3H),3.22–2.86(m,4H),2.44(m,2H),2.21(m,2H),1.76(m,2H),1.03(s,18H),0.92(d,6H),HRMS(ESI)m/z[M+Na] + C 49 H 63 Cl 2 N7 8 O 10 S 2 calculating the value: 1043.3455,1045.3425,1047.3396; found 1066.3353,1068.3323,1070.3294.
Example 7 preparation of- ((1H-1,2,4-triazol-1-yl) methyl) -11- (n-butyl) -13- (4-chlorophenyl) -4- (4,5-dimethoxy-2-nitrophenyl) -12-methyl-9-oxo-8,10-dioxa-3,5-dithidecyl (3-cyano-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1H-pyrazol-5-yl) carbamate (I-50)
Figure BDA0003066834160000241
Compounds i-50 were synthesized in a similar manner to example 3, except that:
step (c) 1 ) The 1-methyl-2-nitro-3- ((tetrahydrofuran-3-yl) methyl) guanidine described in (1), was replaced with 3- ((1-hydro-1,2,4-triazol-1-yl) methyl) -1- (4-chlorophenyl) -2,4,4-trimethylpentan-3-ol.
The characterization results were as follows: 1 H NMR(400MHz,CDCl 3 )δ8.27(s,1H),8.05(s,1H),7.46(s,1H),7.38(s,2H),7.35(s,1H),7.30(d,J＝8.2Hz,2H),7.02(d,J＝8.2Hz,2H),6.00(s,1H),4.35(d,J＝14.4Hz,1H),4.32(d,J＝14.4Hz,1H),4.29(t,J＝6.4Hz,4H),3.95(s,3H),3.89(s,3H),3.22–2.86(m,4H),2.44(m,1H),2.21(m,1H),1.76(m,1H),1.03(s,9H),0.92(d,3H),HRMS(ESI)m/z[M+Na] + C 44 H 43 Cl 3 F 6 N 8 O 10 S 3 calculating the value: 1181.1132,1183.1103,1185.1073,1187.1031; found 1181.1134,1183.1102,1185.1075,1187.1032.
Example 8 preparation of 1- (4-chlorophenoxy) -3,3-dimethyl-1- (1 hydro-1,2,4-triazol-1-yl) butan-2-yl (2- ((((2- (((2,3-dichloro-4- (1-methylcyclohexyl-1-carboxamido) phenoxy) carbonyl) oxa) ethyl) thia) (4,5-dimethoxy-2-nitrophenyl) methylthio) ethyl) carbonate (I-58)
Figure BDA0003066834160000242
Compounds i-58 were synthesized in a similar manner to example 3, except that:
step (c) 1 ) And (c) 2 ) 1-methyl-2-nitro-3- ((tetrahydrofuran-3-yl) methyl) guanidine and 5-amino-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1 hydro-pyrazole-3-cyano as described in (1), were replaced with N- (2,3-dichloro-4-hydroxyphenyl) -1-methylcyclohexyl-1-carboxamide and 1- (4-chlorophenoxy) -3,3-dimethyl-1- (1 hydro-1,2,4-triazol-1-yl) butan-2-ol, respectively.
The characterization results were as follows: 1 H NMR(400MHz,CDCl 3 )δ8.29(s,1H),8.08(s,1H),7.97(d,1H),7.70(s,1H),7.45(s,1H),7.37(s,1H),7.31(d,J＝8.2Hz,2H),7.20(d,1H),7.05(d,J＝8.2Hz,2H),6.02(s,1H),4.35(d,J＝14.0Hz,1H),4.30(t,J＝6.4Hz,4H),3.95(s,3H),3.89(s,3H),3.21–2.87(m,4H),2.44(d,J＝14.5Hz,1H),2.01(t,1H),1.65-1.41(m,9H),1.31(s,3H),1.01(s,9H),HRMS(ESI)m/z[M+Na] + C 43 H 50 Cl 3 N 5 O 12 S 2 calculating the value: 1020.1861,1022.1831,1024.1802,1026.1772; found 1020.1860,1022.1834,1024.1804,1026.1775.
Example 9 preparation of 2- ((((2- (((2,3-dichloro-4- (1-methylcyclohexyl-1-carboxamido) phenoxy) carbonyl) oxa) ethyl) thia) (4,5-dimethoxy-2-nitrophenyl) methyl) thia) ethyl 3- ((6-chloropyridin-3-yl) -methyl) -2-nitroiminoimidazolidine-1-carboxylate (I-66)
Figure BDA0003066834160000251
Compounds I-66 were synthesized in a similar manner to example 3, except that:
step (c) 1 ) And (c) 2 ) 1-methyl-2-nitro-3- ((tetrahydrofuran-3-yl) methyl) guanidine and 5-amino-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1 hydro-pyrazole-3-cyano as described in (1) were replaced with N- (2,3-dichloro-4-hydroxyphenyl) -1-methylcyclohexyl-1-carboxamide and N- (1- ((6-chloropyridin-3-yl) methyl) -imidazolidinone-2-ylidene) nitramide, respectively.
The characterization results were as follows: 1 H NMR(400MHz,CDCl 3 )δ8.43(s,1H),8.26(d，1H),8.19(d,1H),7.98(d,1H),7.72(s,1H),7.43(s,1H),7.38(s,1H),7.21(d,1H),6.01(s,1H),5.05(s,2H),4.30(t,J＝6.4Hz,4H),3.95(s,3H),3.89(s,3H),3.61(m,4H),3.21–2.87(m,4H),2.01(t,1H),1.66-1.42(m,9H),1.32(s,3H),HRMS(ESI)m/z[M+Na] + C 38 H 42 Cl 3 N 7 O 12 S 2 calculating the value: 980.1296,982.1267,984.1237,986.1208; found 980.1299,982.1268,984.1235,986.1204.
EXAMPLE 10 preparation of 4-phenoxybenzyl 2- ((11- ((2- ((but-3-en-1-ylsulfanyl) carbonyl) -1-isopropyl-5-oxo-4- (o-tolyl) -2,5-dihydro-1 hydro-pyrazol-3-yl) amino) -6- (4,5-dimethoxy-2-nitrophenyl) -11-oxo-2,10-dioxa-5,7-dithiaundecyl) amino) -6-methylnicotinate (I-74)
Figure BDA0003066834160000261
Compounds i-74 were synthesized in a similar manner to example 3, except that:
step (c) 1 ) And (c) 2 ) The 1-methyl-2-nitro-3- ((tetrahydrofuran-3-yl) methyl) guanidine and 5-amino-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1 hydro-pyrazole-3-cyano described in (1), were replaced with 4-phenoxybenzyl 2-amino-6-methylnicotinate and (but-3-en-1-yl) 5-amino-2-isopropyl-3-oxo-4- (o-tolyl) -2,3-dihydro-1 hydro-pyrazole-1-carboxylic acid thioester, respectively.
The characterization results were as follows: 1 H NMR(400MHz,CDCl 3 )δ7.53(d,1H),7.46(s,1H),7.34(s,1H),7.33-7.28(m,4H),7.17(t,1H),7.12-7.10(m,2H),7.08(d,2H),6.89(d,2H),6.85-6.70(m,2H),6.63(d,1H),6.01(s,1H),5.64(m,1H),5.13(s,2H),5.01(m,1H),4.75(m,1H),4.30(t,J＝6.4Hz,4H),3.97(s,3H),3.90(s,3H),3.52(m,1H),3.26–2.89(m,4H),2.83(t,2H),2.64(q,2H),2.54(s,3H),2.34(s,3H),1.03(d,6H),HRMS(ESI)m/z[M+Na] + C 53 H 56 N 6 O 13 S 3 calculating the value: 1103.2965; found 1103.2966.
EXAMPLE 11 preparation of 4-phenoxybenzyl 2- ((1- (2-dichlorothiazol-4-yl) -10- (4,5-dimethoxy-2-nitrophenyl) -4-methyl-3-nitroimino-5-oxo-6,14-dioxa-9,11-dith-2,4-diazepin-15-yl) amino) -6-methylnicotinate (I-82)
Figure BDA0003066834160000262
Compound i-82 was synthesized in a similar manner to example 3, except that:
step (c) 1 ) And (c) 2 ) The 1-methyl-2-nitro-3- ((tetrahydrofuran-3-yl) methyl) guanidine and 5-amino-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1 hydro-pyrazole-3-cyano described in (1) were replaced with 4-phenoxybenzyl 2-amino-6-methylnicotinate and 1- ((2-dichlorothiazol-4-yl) methyl) -3-methyl-2-nitroguanidine, respectively.
The characterization results were as follows: 1 H NMR(400MHz,CDCl 3 )δ7.52(d,1H),7.45(s,1H),7.33(s,1H),7.31-7.25(m,4H),7.18(t,1H),7.11-7.08(m,2H),6.89(d,2H),6.64(d,1H),6.53(s,1H),6.02(s,1H),5.13(s,2H),4.32(t,J＝6.4Hz,4H),4.11(d,2H),3.96(s,3H),3.91(s,3H),3.26–2.89(m,4H),2.73(s,3H),2.44(s,1H),2.34(s,3H),HRMS(ESI)m/z[M+Na] + C 41 H 41 ClN 8 O 13 S 3 calculating the value: 1007.1542,1009.1512; found 1007.1545,1009.1510.
EXAMPLE 12 preparation of ((((4,5-dimethoxy-2-nitrophenyl) methylene) bis (sulfanediyl)) bis (ethane-2,1-diyl) dicarbonate) bis (2E, 4E) -5- ((R) -1-hydroxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl) -3-methylpentane-2,4-dienoic dianhydride (I-90)
Figure BDA0003066834160000271
Compounds I-90 were synthesized in a similar manner to example 1, except that:
the 5-amino-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1 hydro-pyrazol-3-cyano described in step (c) was replaced with (2E, 4E) -5- ((R) -1-hydroxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl) -3-methylpentane-2,4-dienoic acid.
The characterization results were as follows: 1 H NMR(400MHz,CDCl 3 )δ7.44(s,1H),7.39(s,1H),6.41(d,2H),6.11(s,2H),6.01(s,1H),5.88(d,2H),5.50(s,2H),4.89(s,2H),4.32(t,J＝6.4Hz,4H),3.95(s,3H),3.91(s,3H),3.21–2.88(m,4H),2.41(s,6H),2.38-2.17(dd,4H),2.11(s,6H),1.01(s,12H),HRMS(ESI)m/z[M+Na] + C 45 H 55 NO 16 S 2 calculating the value: 952.2860, found 952.2862.
EXAMPLE 13 preparation of ((((4,5-dimethoxy-2-nitrophenyl) methylene) bis (sulfanediyl)) bis (ethane-2,1-diyl) dicarbonate) bis (1R, 2S) -3-oxo-2- ((E) -pent-2-en-1-yl) cyclopentane-1-carboxylic dianhydride (I-98)
Figure BDA0003066834160000281
Compounds i-98 were synthesized in a similar manner to example 1, except that:
the 5-amino-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1 hydro-pyrazole-3-cyano group described in step (c) was replaced with (1R, 2S) -3-oxo-2- ((E) -pent-2-en-1-yl) cyclopentane-1-carboxylic acid.
The characterization results were as follows: 1 H NMR(400MHz,CDCl 3 )δ7.45(s,1H),7.35(s,1H),6.01(s,1H),5.33(m,4H),4.29(t,J＝6.4Hz,4H),3.95(s,3H),3.87(s,3H),3.20–2.84(m,4H),2.66(m,2H),2.33–1.90(m,14H),1.82(m,4H),0.86(t,6H),HRMS(ESI)m/z[M+Na] + C 37 H 47 NO 14 S 2 calculating the value: 816.2336; found 816.2338.
Example 14 preparation of (1R, 2S) -3-oxo-2- ((E) -pent-2-en-1-yl) cyclopentane-1-carboxylic acid (((((4,5-dimethoxy-2-nitrophenyl) methylene) bis (sulfanediyl)) bis (ethane-2,1-diyl) dicarbonate) benzo [1,2,3] thiadiazole-7-carboxylic acid dianhydride (I-106)
Figure BDA0003066834160000282
Compounds i-106 were synthesized in a similar manner to example 3, except that:
step (c) 1 ) And (c) 2 ) 1-methyl-2-nitro-3- ((tetrahydrofuran-3-yl) methyl) guanidine and 5-amino-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1 hydro-pyrazol-3-cyano as described in (1R, 2S) -3-oxo-2- ((E) -pent-2-en-1-yl) cyclopentane-1-carboxylic acid and benzo [1,2,3, respectively]Thiadiazole-7-carboxylic acid substitution.
The characterization results were as follows: 1 H NMR(400MHz,CDCl 3 )δ8.56(d,1H),8.06(d,1H),7.76(t,1H),7.46(s,1H),7.35(s,1H),6.01(s,1H),5.30(m,2H),4.28(t,J＝6.4Hz,4H),3.98(s,3H),3.93(s,3H),3.25–2.88(m,4H),2.66(m,1H),2.35–1.94(m,7H),1.81(m,2H),0.82(t,3H),HRMS(ESI)m/z[M+Na] + C 33 H 35 N 3 O 13 S 2 calculating the value: 800.1230; found 800.1229.
Example 15 preparation of (9- (3- ((6-Chloropyridin-3-yl) methyl) -2-nitroiminoimidazolidin-1-yl) -4- (4,5-dimethoxy-2-nitrophenyl) -9-oxo-8-oxa-3,5-dithianonanylcarbonic acid) (2E, 4E) -5- ((R) -1-hydroxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl) -3-methylpentane-2,4-diene anhydride (I-114)
Figure BDA0003066834160000291
Compounds i-114 were synthesized in a similar manner to example 3, except that:
step (c) 1 ) And (c) 2 ) The 1-methyl-2-nitro-3- ((tetrahydrofuran-3-yl) methyl) guanidine and 5-amino-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1 hydro-pyrazol-3-cyano described in (2e, 4e) -5- ((R) -1-hydroxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl) -3-methylpentane-2,4-dienoic acid and N- (1- ((6-chloropyridin-3-yl) methyl) -imidazolidinone-2-ylidene) nitroamide, respectively.
1 H NMR(400MHz,CDCl 3 )δ8.42(s,1H),8.28(d，1H),8.17(d,1H),7.42(s,1H),7.38(s,1H),6.42(d,1H),6.11(s,1H),6.01(s,1H),5.89(d,1H),5.53(s,1H),5.09(s,2H),4.89(s,1H),4.32(t,J＝6.4Hz,4H),3.99(s,3H),3.90(s,3H),3.64(m,4H),3.22–2.91(m,4H),2.42(s,3H),2.38-2.17(dd,2H),2.12(s,3H),1.01(s,6H),HRMS(ESI)m/z[M+Na] + C 39 H 45 ClN 6 O 14 S 2 Calculating the value: 920.2124,922.2094, found 943.2022,945.1992.
Example 16 preparation of (2- ((((2- (((3-cyano-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1 hydro-pyrazol-5-yl) carbamoyl) oxy) ethylcarbonic acid) (1S, 2R) -3-oxo-2- ((E) -pent-2-en-1-yl) cyclopentane-1-carboxylic anhydride (I-122)
Figure BDA0003066834160000292
Compounds I-122 were synthesized in a similar manner to example 3, except that:
step (c) 1 ) The 1-methyl-2-nitro-3- ((tetrahydrofuran-3-yl) methyl) guanidine of (1R, 2S) -3-oxo-2- ((E) -pent-2-en-1-yl) cyclopentane-1-carboxylic acid.
The characterization results were as follows: 1 H NMR(400MHz,CDCl 3 )δ7.46(s,1H),7.38(s，2H),7.34(s,1H),6.01(s,1H),5.31(m,2H),4.29(t,J＝6.4Hz,4H),3.95(s,3H),3.89(s,3H),3.21–2.86(m,4H),2.66(m,1H),2.36–1.95(m,7H),1.82(m,2H),0.83(t,3H),HRMS(ESI)m/z[M+Na] + C 38 H 35 Cl 2 F 6 N 5 O 12 S 3 calculating the value: 1056.0624,1058.0594,1060.0565; found 1056.0626,1058.0595,1060.0568.
Example 17 preparation of benzo [1,2,3] thiadiazole-7-carboxylic acid (11- ((4-chlorophenoxy) (1H-1,2,4-triazol-1-yl) methyl) -4- (4,5-dimethoxy-2-nitrophenyl) -12,12-dimethyl-9-oxo-8,10-dioxa-3,5-dithianylalkyl carbonate) anhydride (I-130)
Figure BDA0003066834160000301
Compound i-130 was synthesized in a similar manner to example 3, except that:
step (c) 1 ) And (c) 2 ) The 1-methyl-2-nitro-3- ((tetrahydrofuran-3-yl) methyl) guanidine and 5-amino-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1H-pyrazol-3-cyano as described in (1- (4-chlorophenoxy) -3,3-dimethyl-1- (1H-1,2,4-triazol-1-yl) butan-2-ol and benzo [1,2,3]Thiadiazole-7-carboxylic acid substitution.
The characterization results were as follows: 1 H NMR(400MHz,CDCl 3 )δ8.54(d,1H),δ8.27(s,1H),8.14(s,1H),8.09(d,1H),7.74(t,1H),7.44(s,1H),7.38(s,1H),7.32(d,J＝8.2Hz,2H),7.09(d,J＝8.2Hz,2H),6.01(s,1H),4.36(d,J＝14.0Hz,1H),4.32(t,J＝6.4Hz,4H),3.98(s,3H),3.88(s,3H),3.20–2.88(m,4H),2.45(d,J＝14.5Hz,1H),1.00(s,9H),HRMS(ESI)m/z[M+Na] + C 36 H 37 ClN 6 O 12 S 3 calculating the value: 899.1218,1001.1189; found 899.1220,1001.1187.
Example 18 preparation of (2- ((((2- (((2,3-dichloro-4- (1-methylcyclohexyl-1-carboxamido) phenoxy) carbonyl) oxa) ethyl) thia) (4,5-dimethoxy-2-nitrophenyl) methyl) thia) ethylcarbonic acid) (2E, 4E) -5- ((S) -1-hydroxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl) -3-methylpentane-2,4-diene anhydride (I-138)
Figure BDA0003066834160000302
Compounds i-138 were synthesized in a similar manner to example 3, except that:
step (c) 1 ) And (c) 2 ) The 1-methyl-2-nitro-3- ((tetrahydrofuran-3-yl) methyl) guanidine and 5-amino-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1 hydro-pyrazole-3-cyano described in (2E, 4E) -5- ((R) -1-hydroxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl) -3-methylpentane-2,4-dienoic acid and N- (2,3-dichloro-4-hydroxyphenyl) -1-methylcyclohexyl-1-carboxamide, respectively.
The characterization results were as follows: 1 H NMR(400MHz,CDCl 3 )δ7.95(d,1H),7.70(s,1H),7.44(s,1H),7.36(s,1H),7.20(d,1H),6.43(d,1H),6.13(s,1H),6.03(s,1H),5.87(d,1H),5.51(s,1H),4.88(s,1H),4.31(t,J＝6.4Hz,4H),3.98(s,3H),3.93(s,3H),3.20–2.92(m,4H),2.41(s,3H),2.41-2.20(dd,2H),2.15(s,3H),2.00(t,1H),1.68-1.44(m,9H),1.34(s,3H),1.04(s,6H),HRMS(ESI)m/z[M+Na] + C 44 H 52 Cl 2 N 2 O 14 S 2 calculating the value: 966.2237,968.2208,970.2178, found 989.2035,991.2106,993.2076.
EXAMPLE 19 preparation of (10- (4-phenoxybenzyl 6-methylnicotin-2-yl) -4- (4,5-dimethoxy-2-nitrophenyl) -10-aza-9-oxo-8-oxa-3,5-dithiadecylcarbonic acid) (1R, 2S) -3-oxo-2- ((E) -pent-2-en-1-yl) cyclopentane-1-carboxylic acid anhydride (I-146)
Figure BDA0003066834160000311
Compounds I-146 were synthesized in a similar manner to example 3, except that:
step (c) 1 ) And (c) 2 ) 1-methyl-2-nitro-3- ((tetrahydrofuran-3-yl) methyl) guanidine and 5-Ammonia as described in (1)The radical-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4- ((trifluoromethyl) sulfinyl) -1 h-pyrazole-3-cyano, was replaced by (1R, 2S) -3-oxo-2- ((E) -pent-2-en-1-yl) cyclopentane-1-carboxylic acid and 4-phenoxybenzyl 2-amino-6-methylnicotinate, respectively.
The characterization results were as follows: 1 H NMR(400MHz,CDCl 3 )δ7.55(d,1H),7.45(s,1H),7.35(s,1H),7.31-7.26(m,4H),7.15(t,1H),7.08(d,2H),6.88(d,2H),6.62(d,1H),6.01(s,1H),5.30(m,2H),5.12(s,2H),4.28(t,J＝6.4Hz,4H),3.98(s,3H),3.93(s,3H),3.25–2.88(m,4H),2.66(m,1H),2.54(s,3H),2.37–1.92(m,7H),1.80(m,2H),0.84(t,3H),HRMS(ESI)m/z[M+Na] + C 46 H 49 N 3 O 14 S 2 calculating the value: 954.2554; found 954.2551.
Example 20: preparation of the other compounds in Table 1
The procedures of 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.
Example 21 biological Activity assay
(1) Insecticidal Activity test of Compounds of the present invention
a. Alfalfa aphid activity assay
The test object is adult alfalfa aphids, and the test method of the experiment is a leaf dipping method:
1) Early preparation work: the broad beans are potted with fine sand in advance for one week, watered and moistened, and water is added every other day; 2) Repelling adult aphids from broad bean plants, and starving for 1.5 hours in the dark; 3) Selecting seedlings with the tooth length of 3-4cm and without rottenness from broad bean seedlings planted seven days ago, cleaning the surfaces with clear water, removing roots, and inserting the seedlings into moistened sponge; 4) Respectively dissolving compounds to be tested in dimethyl sulfoxide (DMSO), taking a certain amount of dimethyl sulfoxide mother liquor, diluting with aqueous solution containing triton (2-3 drops of triton are added into 500mL of water, and performing ultrasonic treatment for half an hour) in a gradient manner to obtain a series of concentrations, ensuring that the volume concentration of dimethyl sulfoxide is less than 5%, performing test in three groups, and performing test on one group by using solutions with different concentrationsIrradiating the solution under ultraviolet for 0.5 hr, irradiating the solutions with different solubilities under sunlight for 0.5 hr in two groups, and storing the three groups in dark; 5) Selecting adults with black and bright whole bodies, uniformly repelling aphids around the sprouts inserted on the sponges by using a writing brush, and placing for 2 hours at the temperature of 25 ℃; 6) Inverting bean seedlings with stems firmly adsorbed by aphids, soaking in solutions with different concentrations for 4-5 seconds, taking out, pausing for 1 second, continuing for 2 times, and sucking the redundant liquid medicine with paper, wherein each concentration is 3 in parallel; 7) Vertically inserting bean seedlings into the wet sponge, covering a section of Ma Dengzhao covered by gauze, and standing for 48 hours at 25 ℃ in the dark at constant temperature; 8) After 48 hours, the brush touches and observes the death condition of aphids, and the mortality (%) is calculated according to the formula: mortality (%) = (number of control live insects-number of treated live insects)/number of control live insects × 100%. LC is calculated by using software SPSS 50 . ( Criteria for death: the body of the insect is dark black, and the body is touched slightly by a writing brush, so that the body is regarded as dead without any stress reaction. )
b. Aedes albopictus larva
The test subjects were 4-instar aedes albopictus larvae. The experimental test method is as follows:
1) Respectively dissolving compounds to be tested in dimethyl sulfoxide, taking a certain amount of dimethyl sulfoxide mother liquor, diluting the dimethyl sulfoxide mother liquor into a series of concentrations by using deionized water, ensuring that the volume concentration of the dimethyl sulfoxide is less than 5%, performing tests in three groups, wherein the first group is used for placing the solutions with different concentrations under ultraviolet radiation for 0.5 hour, the second group is used for placing the solutions with different solubilities under sunlight for 0.5 hour, and the third group is placed in a dark environment; 2) Selecting 4-instar larvae with 10 active and strong head worms, and sucking the larvae into a 5mL centrifuge tube by using a suction tube; 3) Adding three groups of prepared liquid medicines with different solubilities into a centrifugal tube, wherein three solubilities are parallel. Blank control and positive control are carried out on the experimental groups; 4) The larvae of aedes albopictus were observed and counted for mortality after 24 hours and the mortality (%) was calculated according to the formula: mortality (%) = (number of control live insects-number of treated live insects)/number of control live insects × 100%. Then, the software SPSS is utilized to calculate LC 50 。
c. Sticky insect
The test object is armyworm larvae of 3 th instar, and the test method of the experiment is a leaf soaking method:
the method comprises the following steps:
1) Catching 3-instar larvae from the maize seedling plant, and starving for 1.5 hours in the dark; 2) Selecting good-growing corn seedlings, cutting off roots, binding every ten corn seedlings together, and storing the corn seedlings in a dark place; 3) Dissolving the three target compounds in dimethyl sulfoxide respectively, taking a certain amount of dimethyl sulfoxide mother liquor, diluting the dimethyl sulfoxide mother liquor into a series of concentrations in a gradient manner by using an aqueous solution containing triton (2-3 drops of triton are added into 500mL of water, and performing ultrasonic treatment for half an hour), ensuring that the volume concentration of the dimethyl sulfoxide is less than 5%, and storing the dimethyl sulfoxide in the dark; 4) Soaking the tied maize seedlings in the prepared solution for 10 seconds for three times continuously, and naturally airing the maize seedlings in the dark, wherein the concentration of each maize seedling is three in parallel; 5) Selecting 3-year-old larvae with active and robust insects, driving the insects into a wide-mouth bottle padded with 100mL of filter paper by using a writing brush, placing the aired corn seedlings into the wide-mouth bottle, sealing the mouth of the wide-mouth bottle by using gauze, placing the wide-mouth bottle in a dark place for 24 hours, taking out the corn seedlings soaked with the pesticide, and carrying out testing in three groups, wherein the first group exposes the insects to ultraviolet for 0.5 hour, then places the insects into the wide-mouth bottle, places the fresh corn seedlings not stained with the pesticide, the second group exposes the insects to sunlight for 0.5 hour, then places the insects into the wide-mouth bottle, places the fresh corn seedlings not stained with the pesticide, and the third group does not carry out illumination treatment, places the insects into the wide-mouth bottle, and places the fresh corn seedlings not stained with the pesticide; 6) After 72 hours, the death conditions of the armyworms in the illuminated group and the non-illuminated group are observed and counted, and the armyworms are touched by a writing brush and are regarded as dead without stress response. Blank controls and positive controls were made for all experimental groups.
The second method comprises the following steps:
1) Catching 3-instar larvae from the maize seedling plant, and starving for 1.5 hours in the dark; 2) Selecting good-growing corn seedlings, cutting off roots, binding every ten corn seedlings together, and storing the corn seedlings in a dark place; 3) Dissolving three compounds to be tested in dimethyl sulfoxide respectively, taking a certain amount of dimethyl sulfoxide mother liquor, diluting the dimethyl sulfoxide mother liquor into a series of concentrations in a gradient manner by using an aqueous solution containing triton (2-3 drops of triton are added into 500mL of water, and performing ultrasonic treatment for half an hour), ensuring that the volume concentration of the dimethyl sulfoxide is less than 5%, performing tests in three groups, placing the solutions with different concentrations in a first group under ultraviolet irradiation for 0.5 hour, placing the solutions with different concentrations in a second group under sunlight for 0.5 hour, and placing the third group under dark for storage; 4) Soaking the tied maize seedlings in the prepared solution for 10 seconds for three times continuously, and naturally airing the maize seedlings in the dark, wherein the concentration of each maize seedling is three in parallel; 5) Selecting three-instar larvae with active and strong bodies, driving the sticky insects into a wide-mouth bottle filled with 100mL of filter paper by using a writing brush, putting the aired maize seedlings into the wide-mouth bottle, sealing the mouth of the wide-mouth bottle by using gauze, placing the wide-mouth bottle in a dark place, and standing for 72 hours; 6) After 72 hours, the death conditions of the armyworms in the illuminated group and the non-illuminated group are observed and counted, and the armyworms are touched by a writing brush and are regarded as dead without stress response. Blank control and positive control were performed for all experimental groups.
After 72 hours, myxoworm death was observed and counted, and the mortality (%) was calculated according to the formula: mortality (%) = (number of control live insects-number of treated live insects)/number of control live insects × 100%. Then, the software SPSS is utilized to calculate LC 50 。
The difference between the first method and the second method is that: applying the medicine after irradiating the liquid medicine, feeding the armyworm after applying the medicine, and irradiating.
(2) Fungicidal Activity test of Compounds of the present invention
1) Activated culture of test plant pathogenic fungi
Inoculating slant culture of plant pathogenic fungi pathogenic bacteria to potato glucose agar solid culture medium plate, activating, and culturing in a thermostat for 2-4 days.
Picking the slant culture of Sclerotinia sclerotiorum with inoculating needle, inoculating to potato glucose agar solid culture medium (PDA) plate, activating, and culturing in a thermostat for 2-4 days.
2) Determination of antibacterial activity by hypha growth rate method
Placing an aseptic triangular flask containing a PDA culture medium (49 mL) in a microwave oven to melt the PDA, placing the aseptic triangular flask in a constant-temperature oven to keep the temperature of the culture medium at 55-60 ℃, quickly pouring a pre-prepared drug-containing solution (1 mL) into an aseptic working table, fully and uniformly mixing, respectively pouring into 3 aseptic culture dishes with the diameter of 9cm to prepare drug-containing flat plates, and cooling and solidifying.
The pre-prepared drug-containing solution (1 mL) includes a drug-containing Dimethylsulfoxide (DMSO) solution (0.5 mL) and a 0.1% aqueous Tween 80 solution (0.5 mL), wherein DMSO (0.5 mL) + a 0.1% aqueous Tween 80 solution (0.5 mL) is used as a blank.
Selecting the plant pathogenic fungi with equivalent growth vigor (the growth diameter is within 1 cm) from the activated test plant pathogenic fungi, and punching holes along the outer edge of the colony growth by using a puncher to obtain a test plant pathogenic fungi cake (the diameter is 5 mm); transferring the fungus cake to the circle center position of a previously prepared PDA (personal digital assistant) plate by using an inoculation needle, enabling the hypha surface of the fungus cake to be attached to the surface of a PDA culture medium, and respectively placing the plates inoculated with different plant pathogenic fungi in a constant temperature box for culturing for 48-96 hours.
The colony growth diameter was measured by the cross method, and the inhibition rate was calculated by the following formula:
Figure BDA0003066834160000341
the list of compounds of formula (I) and their bacteriostatic activity (hyphal growth inhibition at 5ppm concentration against Gibberella tritici, sclerotinia sclerotiorum, or Botrytis cinerea) results are shown in Table 1:
(3) Plant growth regulating Activity test of the Compound of the present invention
a. Reducing plant water use in corn
Compounds were tested for their effect on reducing water use by plants as follows. These compounds were applied by foliar spray to 12-day-old corn 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% of the adjuvant rapeseed methyl ester. The drug-containing solution is divided into three groups for testing, wherein one group irradiates the solutions with different concentrations for 0.5 hour under ultraviolet light, the other group irradiates the solutions with different solubilities for 0.5 hour under sunlight, and the other group is stored in the dark; the blank was not treated. Plant water use during the day was assessed by repeatedly weighing pots in which plants were grown before and after application of the compounds at the indicated times, expressed in Days After Application (DAA). The pre-application moisture usage data is used to correct for any differences in moisture usage due to non-treatment effects (e.g., due to differences in plant size). Unconverted water use values were subjected to covariance analysis, the treatment effect was fitted, and baseline water use 1 day prior to application was used as a covariate.
The application of these chemicals (ODAA) was performed approximately between 08. During the day (room light on at 06 to 20: ODAA a.m. (10-12), ODAA p.m. (14.
Tables 1-2: the corn plants sprayed with a compound indicated at 500PM had an increased or decreased percentage of Water Use (WU) during the day compared to the negative control treatment (e.g., 0= same as negative control; -8.5= a-8.5% decrease in water use compared to negative control treatment).
Tables 1-2 show the average WU values for 6 pots (three plants in each) per treatment.
b. Reducing plant water use of soybeans
Compounds were tested for their effect on reducing water use by plants as follows. The compounds were 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 additional surfactant (extrivon lg/20L). The drug-containing solution is divided into three groups for testing, wherein one group irradiates the solutions with different concentrations for 0.5 hour under ultraviolet light, the other group irradiates the solutions with different solubilities for 0.5 hour under sunlight, and the other group is stored in the dark; the blank was not treated. Plant water use during the day was assessed by repeatedly weighing the pots in which the plants were grown before and after application of the compounds at the indicated times, expressed in Days After Application (DAA). The pre-application moisture usage data is used to correct for any differences in moisture usage due to non-treatment effects (e.g., due to differences in plant size). Unconverted water use values were subjected to covariance analysis, the treatment effect was fitted, and baseline water use 1 day prior to application was used as a covariate.
The application of these chemicals (0 DAA) was carried out approximately between 08. During the day (room light on at 06 to 20: moisture utilization (WU) was measured 0 daa.m. (10.
Table 1: a percentage increase or decrease in daytime Water Use (WU) of soybean plants sprayed with a compound indicated at 125PM compared to a negative control treatment (e.g., 0= same as negative control; -8.5= a-8.5% decrease in water use compared to negative control treatment).
Table 1 shows the average WU values for 6 pots (three plants in each) per treatment.
Figure BDA0003066834160000361
Figure BDA0003066834160000371
Figure BDA0003066834160000381
Figure BDA0003066834160000391
Figure BDA0003066834160000401
Figure BDA0003066834160000411
Figure BDA0003066834160000421
Figure BDA0003066834160000431
Figure BDA0003066834160000441
Figure BDA0003066834160000451
Figure BDA0003066834160000461
Figure BDA0003066834160000471
Figure BDA0003066834160000481
The lethal medium concentration of dinotefuran on alfalfa sprouts is 15-20 mu M, the lethal medium concentration of dinotefuran on armyworms is 60-80 mu M, and the lethal medium concentration of dinotefuran on aedes albopictus larvae is 2.0-3.0 mu M; the inhibition rate of fenhexamid (5 mu g/mL) on botrytis cinerea is 60-70%, the inhibition rate on fusarium graminearum is 55-60%, and the inhibition rate on sclerotinia sclerotiorum is 65-75%.
Therefore, the compound has insecticidal activity which is basically equivalent to or even better than dinotefuran or bacteriostatic activity which is basically equivalent to or even better than fenhexamid or has better regulation effect on the growth of plants. For example, the lethal middle concentration (LC) of most of the compounds in Table 1 (I-13-40) against armyworm 50 )<20 μ M, (I-1-132) lethal Medium concentration (LC) of all compounds against Aedes albopictus larvae 50 )<1 mu M; (I-133-144) inhibitory Rate of most Compounds against Gibberella cerealis>60%, (I-181-192) most of the compoundsInhibition rate of cucumber botrytis>60 percent; (I-205-276) Water Use (WU) of most of the compounds on corn or soybean plants is reduced and in a reduced amount>20。
All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Claims (10)

1. A compound represented by formula (I), an optical isomer, a cis-trans isomer or an agriculturally pharmaceutically acceptable salt thereof:
Figure FDA0003066834150000011
wherein W, X are each independently a pesticide molecule;
R 1 、R 2 、R 3 、R 4 each independently is: hydrogen, halogen, hydroxy, nitro, cyano, C 1 -C 8 Carboxylic acid group, C 1 -C 8 Alkyl radical, C 2 -C 6 Alkenyl radical, C 2 -C 6 Alkynyl, C 1 -C 6 Alkoxy radical, C 1 -C 8 Haloalkyl, C 2 -C 6 Haloalkenyl, C 2 -C 6 Halogenated alkynyl, C 1 -C 6 Haloalkoxy, C 3 -C 8 Cycloalkyl radical, C 5 -C 7 Cycloalkenyl, 3-8 membered heterocyclyl, C 6 -C 10 Aryl, 5-14 membered heteroaryl;
wherein, the C 1 -C 8 Carboxylic acid group, C 1 -C 8 Alkyl radical, C 2 -C 6 Alkenyl radical, C 2 -C 6 Alkynyl, C 1 -C 6 Alkoxy radical, C 3 ～C 8 Cycloalkyl, C 5 ～C 7 Cycloalkenyl, 3-8 membered heterocyclyl, C 6 -C 10 Aryl, 5-14 membered heteroaryl optionally substituted with one or more groups selected from: halogen, hydroxy, nitro, cyano;
wherein said heterocyclyl, heteroaryl, contains 1,2 or 3 heteroatoms selected from N, O or S.
2. The compound, its optical isomer, cis-trans isomer, or agriculturally pharmaceutically acceptable salt thereof of claim 1, wherein W or X are each independently selected from the group consisting of:
Figure FDA0003066834150000012
Figure FDA0003066834150000021
3. the compound, an optical isomer, a cis-trans isomer, or an agriculturally acceptable salt thereof of claim 1 wherein W or X are each independently selected from the group consisting of:
Figure FDA0003066834150000022
4. the compound, its optical isomer, cis-trans isomer, or agriculturally pharmaceutically acceptable salt thereof of claim 1, wherein: r 1 、R 2 、R 3 、R 4 Each independently selected from the group consisting of: hydrogen, halogen, C 1 -C 4 Alkyl radical, C 1 -C 4 Alkoxy radical, C 1 -C 4 Haloalkyl, C 1 -C 4 A haloalkoxy group.
5. The compound, an optical isomer, a cis-trans isomer, or an agriculturally pharmaceutically acceptable salt thereof of claim 1, wherein the compound is any one of the compounds set forth in table 1.
6. A process for the preparation of a compound of formula (i) as claimed in claim 1, comprising the steps of:
Figure FDA0003066834150000023
(i) In the presence of an inert solvent, the reaction mixture is,
Figure FDA0003066834150000024
reacting with 2-mercaptoethanol to obtain a compound II;
(ii) Reacting the compound II with p-nitrophenyl chloroformate in an inert solvent to obtain a compound III;
(iii) And reacting the compound III with pesticide molecules in an inert solvent to obtain a compound I.
7. An agricultural composition comprising:
(a) 0.001 to 99.99% by weight of a compound of any one of claims 1-5, an optical isomer, a cis-trans isomer, or an agriculturally pharmaceutically acceptable salt thereof, or a combination thereof; and
(b) An agriculturally pharmaceutically acceptable carrier and/or excipient.
8. Use of a compound according to any one of claims 1 to 5, an optical isomer, a cis-trans isomer, or an agriculturally pharmaceutically acceptable salt thereof, or an agricultural composition according to claim 7, for controlling an agricultural pest or regulating plant growth, or for the preparation of a pesticide, a fungicide, a plant growth regulator for controlling an agricultural pest or regulating plant growth.
9. A method of controlling an agricultural pest, which comprises applying a compound as claimed in any one of claims 1 to 5, an optical isomer, a cis-trans isomer or an agriculturally pharmaceutically acceptable salt thereof or an agricultural composition as claimed in claim 7 to a plant, animal, soil surrounding or likely to be subjected to a pest.
10. A method of regulating plant growth, comprising applying a compound of any one of claims 1-5, an optical isomer, a cis-trans isomer, or an agriculturally pharmaceutically acceptable salt thereof, or an agricultural composition of claim 7 to a plant, a part of a plant, a plant organ, a plant propagation material, or a plant growing locus.
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH05117112A (en) * 1990-06-15 1993-05-14 Takeda Chem Ind Ltd Sustained release agricultural chemical granule
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CN106577645A (en) * 2016-11-16 2017-04-26 武汉理工大学 GSH (glutathione) responsive controlled-release nano-pesticide formulation and preparation method and application thereof
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Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH05117112A (en) * 1990-06-15 1993-05-14 Takeda Chem Ind Ltd Sustained release agricultural chemical granule
CN103688928A (en) * 2014-01-06 2014-04-02 中国科学院长春应用化学研究所 Slow-release pesticide and preparation method thereof
CN106577645A (en) * 2016-11-16 2017-04-26 武汉理工大学 GSH (glutathione) responsive controlled-release nano-pesticide formulation and preparation method and application thereof
CN111567517A (en) * 2020-05-14 2020-08-25 河北威远生物化工有限公司 Novel aqueous pesticide suspending agent and preparation method thereof

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