WO2020001494A1 - Diarylethene compound and preparation and use thereof - Google Patents

Abstract

Disclosed are a diarylethene compound and a preparation and use thereof, wherein the structural formula of same is as shown in formula (A). Such compounds are a class of good photochromic compounds, and will perform a photoisomerization reaction under irradiation by light of a specific wavelength to generate a ring-closing compound; and the compounds and their ring-closing derivatives after photoisomerization have a high activity against agroforestry pest aphids, and larvae of Aedes albopictus, Nematocera, Culicidae, etc., and the activity of the ring-closing compound after illumination is higher than that of the ring-opening compound before illumination.

Description

Diaryl vinyl compounds and preparation and use thereof Technical field

The invention belongs to the fields of pesticides and medicine. Specifically, the present invention relates to a photochromic diaryl vinyl compound, and a preparation method and application thereof.

technical background

In 1952, Hirshberg first defined photochromism. Photoisomers can also be called photochromic compounds or light-controlled switches. There are two types of isomers in these compounds. They show different physical and chemical properties in terms of absorption spectrum, spatial geometry, and dipole moment. . Under different wavelengths of light, compounds can convert between two isomers and this conversion is reversible; they have different absorption spectra and can produce reversible color changes. So far, there have been many studies on photo-isomer materials, and these compounds have been widely used in optical information storage, liquid crystal materials, molecular switches, and biology. Due to the excellent photophysical and chemical properties of photoisomers, many new photoisomers are also being developed.

In photoisomers, diarylethylene plays a very important role. Heterocyclic substituted diarylethylene compounds have a hexatriene parent structure that conjugates six electrons, and its photochromism is based on an intramolecular cyclization reaction (pericyclic reaction). Under the excitation of ultraviolet light, the compound spins in a closed loop to form a chromophore. The chromophore can undergo opposite changes under visible light irradiation, and a thermal irreversible photochromic reaction occurs. The compound generally exhibits good thermal stability and fatigue resistance. It has received great attention from people. This structure has attracted much attention as the core unit of photochromic generation. It has become a hotspot to obtain new functional compounds through the optimization of its structure, so the synthesis and modification of this structure have also been repeatedly innovated and attracted much attention recently.

Based on the special photoisomerization properties of diarylethylene, people have developed a variety of photochromic functional materials and widely used them in ultra-high density optical information storage, molecular switches, molecular logic gates, molecular wires, optoelectronic materials, and more Photonic devices, surface / nano devices, liquid crystal materials, chemical sensing, biological imaging, self-assembly, aggregation-induced luminescence, light-controlled biological systems, and many other fields. Among them, diarylvinyl compounds are ideal photochromic materials due to their excellent thermal stability, excellent fatigue resistance, fast response rate, high conversion and quantum yield, and excellent solid-phase reactivity. one.

Most diarylvinyl compounds can change the end-to-end distance of the two ends of the molecule through photoisomerization, thereby causing the functional changes of the target biomolecules. If the target biomolecules are opened or closed, the target biomolecules can be completely Inactive or active states, diarylethylene optical switches will probably be the most effective. In a stable dark environment, diarylethylene compounds exist in a more stable ring-opening configuration. Irradiation with ultraviolet light can transform into a large number of closed-loop structures, and closed-loop structures can be transformed into open-loop structures under heat or blue light. Diaryl dilute compounds have been used in light-controlled coupling isomerization reactions, including peptides, proteins, and nucleic acids in vitro and ion channels and receptors in vivo.

γ-aminobutyric acid (GABA) receptors are widely present in the central nervous system of vertebrates and insects, and can be regulated by the neurotransmitter γ-aminobutyric acid and some exogenous drugs. Many human mental illnesses such as epilepsy, schizophrenia, insomnia, alcoholism, and Parkinson's syndrome are all related to GABA receptors.

In order to improve the selectivity of ligands acting on GABA receptors and the precise control of their activities, in recent years, researchers have introduced photoisomerized structures into GABA receptor ligands and designed photoisomerized GABA receptor ligands. Body, to achieve precise regulation of receptors in time and space.

Those skilled in the art are devoted to the research and development of a photoisomeric GABA receptor ligand with obvious photochromism, good thermal stability, good fatigue resistance, and high insecticidal activity.

Summary of the invention

One of the objectives of the present invention is to provide a class of photoisomer compounds that can be used as GABA receptor ligands and a method for preparing the same.

Another object of the present invention is to provide applications of the above compounds in controlling pests and the like.

A first aspect of the present invention provides a compound having a structure represented by formula (A), or an optical isomer, cis-trans isomer of the compound, or a salt thereof:

In formula (A):

R ₁ and R ₂ are each independently H, substituted or unsubstituted C _1-6 alkyl, allyl, benzyl, substituted or unsubstituted C _1-4 alkoxy-C _1-6 alkyl, Substituted or unsubstituted C _1-6 alkyl-carbonyl, substituted or unsubstituted C _1-4 alkoxy-carbonyl or phenoxycarbonyl; or R ₁ and R ₂ together form -CH ₂ -CH ₂ -or- CH ₂ -CH ₂ -CH _2- ;

Each R _{3 is} independently hydrogen, a substituted or unsubstituted C _1-4 alkyl group, a halogen atom, a substituted or unsubstituted 6 to 10 membered aromatic ring group, or a substituted or unsubstituted 5 to 6 membered heterocyclic ring;

R ₄ , R ₅ , R ₆ , R ₇ , R ₈ and R ₉ are each independently hydrogen, fluorine, C _1-4 alkyl, substituted or unsubstituted 6 to 10 membered aromatic ring group, or substituted or unsubstituted A 5- to 6-membered heterocyclic ring; or a combination of one of R ₄ , R ₅ , R ₈ and R ₉ and R ₆ or R ₇ constitutes a substituted or unsubstituted 6 to 10-membered aromatic ring group, or a substituted or unsubstituted Substituted 5-6 membered heterocyclic ring;

Each R _{10 is} independently C _1-4 alkyl or C _1-4 alkoxy;

Z is selected from S, O or NH;

Wherein, the above-mentioned substitution means that the hydrogen atom is replaced by a group selected from the group consisting of a halogen atom, a C _1-6 alkyl group or a halogenated C _1-6 alkyl group, a C _1-6 alkoxy group, or a halogenated C group. _1-6 alkoxy, C _2-6 alkenyl, C _2-6 alkynyl, halogenated C _2-6 alkenyl, halogenated C _2-6 alkynyl, C _1-4 alkoxy-C _1-6 alkyl, C _1-6 alkoxy-carbonyl, C _2-6 alkynyl-carbonyl, C _2-6 alkenyl-carbonyl.

In a preferred embodiment, R ₁ and R ₂ are each independently hydrogen or C _1-4 alkyl.

In a preferred embodiment, R ₁ and R ₂ are each independently hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, or tert-butyl.

In a preferred example, each R _{3 is} independently a hydrogen, a C _1-3 alkyl group or a halogen atom.

In a preferred example, each R _{3 is} independently hydrogen.

In a preferred example, R ₄ , R ₅ , R ₆ , R ₇ , R ₈ and R ₉ are each independently hydrogen, fluorine or C _1-4 alkyl;

In a preferred example, R ₄ , R ₅ , R ₆ , R ₇ , R ₈ and R ₉ are each independently hydrogen or fluorine.

In a preferred embodiment, each R _{10 is} independently a C _1-2 alkyl group or a C _1-2 alkoxy group.

In a preferred example, each R _{10 is} independently a methyl group.

In a preferred example, Z is S.

A second aspect of the present invention provides a compound having a structure represented by formula (B), or an optical isomer, cis-trans isomer of the compound, or a salt thereof:

In formula (B):

R ₁ and R ₂ are each independently H, substituted or unsubstituted C _1-6 alkyl, allyl, benzyl, substituted or unsubstituted C _1-4 alkoxy-C _1-6 alkyl, Substituted or unsubstituted C _1-6 alkyl-carbonyl, substituted or unsubstituted C _1-4 alkoxy-carbonyl or phenoxycarbonyl; or R ₁ and R ₂ together form -CH ₂ -CH ₂ -or- CH ₂ -CH ₂ -CH _2- ;

Each R _{3 is} independently hydrogen, a substituted or unsubstituted C _1-4 alkyl group, a halogen atom, a substituted or unsubstituted 6 to 10 membered aromatic ring group, or a substituted or unsubstituted 5 to 6 membered heterocyclic ring;

R ₄ , R ₅ , R ₆ , R ₇ , R ₈ and R ₉ are each independently hydrogen, fluorine, C _1-4 alkyl, substituted or unsubstituted 6 to 10 membered aromatic ring group, or substituted or unsubstituted A 5- to 6-membered heterocyclic ring; or a combination of one of R ₄ , R ₅ , R ₈ and R ₉ and R ₆ or R ₇ constitutes a substituted or unsubstituted 6 to 10-membered aromatic ring group, or a substituted or unsubstituted Substituted 5-6 membered heterocyclic ring;

Each R _{10 is} independently C _1-4 alkyl or C _1-4 alkoxy;

Z is selected from S, O or NH;

Wherein, the above-mentioned substitution means that the hydrogen atom is replaced by a group selected from the group consisting of a halogen atom, a C _1-6 alkyl group or a halogenated C _1-6 alkyl group, a C _1-6 alkoxy group, or a halogenated C group. _1-6 alkoxy, C _2-6 alkenyl, C _2-6 alkynyl, halogenated C _2-6 alkenyl, halogenated C _2-6 alkynyl, C _1-4 alkoxy-C _1-6 alkyl, C _1-6 alkoxy-carbonyl, C _2-6 alkynyl-carbonyl, C _2-6 alkenyl-carbonyl.

A third aspect of the present invention provides a pesticide composition comprising 0.001-99.99% by weight of the component (a) and the component (b); wherein,

Component (a) is a compound according to the first aspect, or an optical isomer, a cis-trans isomer, or a salt thereof; and / or a compound according to the second aspect, or an optical isomer of the compound Structure, cis-trans isomer or salt thereof;

Ingredient (b) is a pesticidely acceptable carrier and / or excipient.

In a preferred example, the component (a) accounts for 0.01-99.9% by weight, and preferably 0.05-90% by weight of the pesticide composition.

In a preferred example, the insecticide composition is used to kill or prevent a pest selected from the group consisting of Coleoptera, Lepidoptera, Hemiptera, Orthoptera, Isoptera, or Diptera insects.

In another preferred example, the pest is preferably an Isoptera or Lepidoptera insect.

In a preferred example, the pest has a mouth suction or file suction mouthpiece.

In another preferred example, the pests are aphids, maggots, planthoppers, whitefly, leafhoppers, thrips, cotton bollworm, cabbage worm, diamondback moth, Spodoptera litura, and armyworm.

In another preferred example, the insecticide further comprises other active substances selected from the group consisting of: insecticides, baits, fungicides, acaricides, nematicides, fungicides, or growth control Agents, and application of the pesticide composition to pests that endanger animal health.

A fourth aspect of the present invention provides an insecticidal and / or pest control method, which comprises applying one or more of the following to a plant body that has suffered or is likely to suffer from pests, the surrounding soil, or the environment:

The compound of the first aspect, or an optical isomer, cis-trans isomer of the compound, or a salt thereof;

The compound of the second aspect, or an optical isomer, cis-trans isomer of the compound, or a salt thereof;

The insecticide composition according to the third aspect;

The plant body, the surrounding soil, or the environment is optionally illuminated with light having a wavelength of 310-380 nm.

A fifth aspect of the present invention provides the compound according to the first aspect, or the optical isomer, cis-trans isomer, or a salt thereof; the compound according to the second aspect, or the optical isomerization of the compound Or a cis-trans isomer or a salt thereof; or the use of the insecticide composition according to the third aspect in the preparation of an insecticide composition.

A sixth aspect of the present invention provides the compound of the first aspect, or the use of an optical isomer, cis-trans isomer, or a salt of the compound, the compound, or the optical isomer, cis, The trans isomer or a salt thereof generates a compound according to the second aspect, or an optical isomer, a cis-trans isomer, or a salt thereof, after irradiation with light having a wavelength of 310-380 nm;

Of the various types:

R ₁ and R ₂ are each independently H, substituted or unsubstituted C _1-6 alkyl, allyl, benzyl, substituted or unsubstituted C _1-4 alkoxy-C _1-6 alkyl, Substituted or unsubstituted C _1-6 alkyl-carbonyl, substituted or unsubstituted C _1-4 alkoxy-carbonyl or phenoxycarbonyl; or R ₁ and R ₂ together form -CH ₂ -CH ₂ -or- CH ₂ -CH ₂ -CH _2- ;

Each R _{3 is} independently hydrogen, a substituted or unsubstituted C _1-4 alkyl group, a halogen atom, a substituted or unsubstituted 6 to 10 membered aromatic ring group, or a substituted or unsubstituted 5 to 6 membered heterocyclic ring;

R ₄ , R ₅ , R ₆ , R ₇ , R ₈ and R ₉ are each independently hydrogen, fluorine, C _1-4 alkyl, substituted or unsubstituted 6 to 10 membered aromatic ring group, or substituted or unsubstituted A 5- to 6-membered heterocyclic ring; or a combination of one of R ₄ , R ₅ , R ₈ and R ₉ and R ₆ or R ₇ constitutes a substituted or unsubstituted 6 to 10-membered aromatic ring group, or a substituted or unsubstituted Substituted 5-6 membered heterocyclic ring;

Each R _{10 is} independently C _1-4 alkyl or C _1-4 alkoxy;

Z is selected from S, O or NH;

Wherein, the above-mentioned substitution means that the hydrogen atom is replaced by a group selected from the group consisting of a halogen atom, a C _1-6 alkyl group or a halogenated C _1-6 alkyl group, a C _1-6 alkoxy group, or a halogenated C group. _1-6 alkoxy, C _2-6 alkenyl, C _2-6 alkynyl, halogenated C _2-6 alkenyl, halogenated C _2-6 alkynyl, C _1-4 alkoxy-C _1-6 alkyl, C _1-6 alkoxy-carbonyl, C _2-6 alkynyl-carbonyl, C _2-6 alkenyl-carbonyl.

A seventh aspect of the present invention provides the compound described in the second aspect, or the use of an optical isomer, cis-trans isomer, or a salt of the compound, the compound, or the optical isomer of the compound 1. The cis-trans isomer or salt thereof generates a compound described in the first aspect, or an optical isomer, cis-trans isomer or salt thereof, under light having a wavelength of more than 493 nm (preferably 493-760 nm). ;

Of the various types:

R ₁ and R ₂ are each independently H, substituted or unsubstituted C _1-6 alkyl, allyl, benzyl, substituted or unsubstituted C _1-4 alkoxy-C _1-6 alkyl, Substituted or unsubstituted C _1-6 alkyl-carbonyl, substituted or unsubstituted C _1-4 alkoxy-carbonyl or phenoxycarbonyl; or R ₁ and R ₂ together form -CH ₂ -CH ₂ -or- CH ₂ -CH ₂ -CH _2- ;

Each R _{3 is} independently hydrogen, a substituted or unsubstituted C _1-4 alkyl group, a halogen atom, a substituted or unsubstituted 6 to 10 membered aromatic ring group, or a substituted or unsubstituted 5 to 6 membered heterocyclic ring;

R ₄ , R ₅ , R ₆ , R ₇ , R ₈ and R ₉ are each independently hydrogen, fluorine, C _1-4 alkyl, substituted or unsubstituted 6 to 10 membered aromatic ring group, or substituted or unsubstituted A 5- to 6-membered heterocyclic ring; or a combination of one of R ₄ , R ₅ , R ₈ and R ₉ and R ₆ or R ₇ constitutes a substituted or unsubstituted 6 to 10-membered aromatic ring group, or a substituted or unsubstituted Substituted 5-6 membered heterocyclic ring;

Each R _{10 is} independently C _1-4 alkyl or C _1-4 alkoxy;

Z is selected from S, O or NH;

Wherein, the above-mentioned substitution means that the hydrogen atom is replaced by a group selected from the group consisting of a halogen atom, a C _1-6 alkyl group or a halogenated C _1-6 alkyl group, a C _1-6 alkoxy group, or a halogenated C group. _1-6 alkoxy, C _2-6 alkenyl, C _2-6 alkynyl, halogenated C _2-6 alkenyl, halogenated C _2-6 alkynyl, C _1-4 alkoxy-C _1-6 alkyl, C _1-6 alkoxy-carbonyl, C _2-6 alkynyl-carbonyl, C _2-6 alkenyl-carbonyl.

An eighth aspect of the present invention provides a method for preparing a compound according to the first aspect, or an optical isomer, a cis-trans isomer, or a salt thereof,

(a) When R1 is the same as R2, the method includes the step of: reacting a compound of formula (1g) with a compound of formula 01 or 01 'in an inert solvent to obtain a compound of formula (A);

In the above formulas, the definition of each group is the same as above and R1 and R2 are the same;

or

(b) when R1 and R2 are different, the method includes the steps of: reacting a compound of formula (1g) with a compound of formula 01 in an inert solvent to obtain a compound of formula (1h); and in an inert solvent, (1h) reacting a compound with a compound of formula 01 'to obtain a compound of formula (A);

In the above formulas, the definition of each group is the same as above and R1 and R2 are different;

or

(c) When R1 and R2 are different, the method includes the step of: reacting a compound of formula (1g) with a compound of formula 01 and a compound of formula 01 'in an inert solvent to obtain a compound of formula (A);

In the above formulae, the definition of each group is the same as above and R1 and R2 are different.

In another preferred example, the method for preparing the compound of formula (1g) includes steps:

(1) nucleophilic reaction of a compound of formula (1a) with bromine in an inert solvent to obtain a compound of formula (1b);

(2) protecting the compound of formula (1b) with ethylene glycol in an inert solvent to obtain a compound of formula (1c);

(3) In an inert solvent, extract the compound of formula (1c) with

Reaction to obtain a compound of formula (1d);

(4) deprotecting the compound of formula (1d) in an inert solvent to obtain a compound of formula (1e);

(5) reducing the compound of formula (1e) in an inert solvent to obtain a compound of formula (1f);

(6) The compound of formula (1f) is subjected to a chlorination reaction in an inert solvent to obtain a compound of formula (1g):

In the above formulas, the definitions of the respective groups are the same as above.

In another preferred example, the method for preparing the compound of formula (1g) includes steps:

(1) In an inert solvent, combine the compound of formula (2a) with

A Fuke acylation reaction is performed to obtain a compound of formula (2b):

(2) The compound of formula (2b) is subjected to a ring-closure reaction in an inert solvent to obtain a compound of formula (2c):

(3) The compound of the formula (2c) is extracted with n-butyllithium and then reacted with dimethylformamide in an inert solvent to obtain a compound of the formula (1e):

(4) The compound of formula (1e) is subjected to a reduction reaction in an inert solvent to obtain a compound of formula (1f):

(5) The compound of formula (1f) is subjected to a chlorination reaction in an inert solvent to obtain a compound of formula (1g):

In the above formulas, the definitions of the respective groups are the same as above.

It should be understood that, within the scope of the present invention, the above technical features of the present invention and the technical features specifically described in the following (such as the embodiments) can be combined with each other to form a new or preferred technical solution. Due to space limitations, I will not repeat them here.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an absorption spectrum chart of the compound 1 of the invention before and after irradiation with ultraviolet light in an acetonitrile solution.

Figure 2 shows the fatigue resistance of Compound 1 of the invention at specific wavelengths.

detailed description

Through long-term and in-depth research, the inventors discovered that a diarylethylene fragment was introduced into a commercial fipronil to synthesize a class of photochromic diarylethylene compounds containing a GABA receptor inhibitor unit. The compound Light-enclosed products have high insecticidal activity. On this basis, the inventors have completed the present invention.

Group definition

As used herein, the term "C _1-4 alkyl" refers to a straight or branched chain alkyl group having 1-4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl , Sec-butyl, tert-butyl, or similar groups.

The term "C _1-4 alkoxy" refers to a straight or branched chain alkoxy group having 1-4 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, Isobutoxy, sec-butoxy, t-butoxy, or similar groups.

As used herein, the term "C _2-6 alkenyl" refers to a straight or branched chain alkenyl group having 2 to 6 carbon atoms, such as vinyl, propenyl, isopropenyl, butenyl, isobutenyl, sec-butyl Alkenyl, or similar.

As used herein, the term "C _2-6 alkynyl" refers to a straight or branched chain alkynyl group having 2 to 6 carbon atoms, such as ethynyl, propynyl, isopropynyl, butynyl, isobutynyl Group, sec-butynyl, or similar group.

The term "halogen atom" refers to fluorine, chlorine, bromine, or iodine. The term "halo" refers to a group substituted with one or more of the above-mentioned halogen atoms, such as trifluoromethyl, pentafluoroethyl, or similar groups.

The term "heterocyclic" means that at least one of the atoms forming the heterocyclic skeleton is not carbon and is nitrogen, oxygen or sulfur. Generally, heterocycles contain no more than 4 nitrogens, no more than 2 oxygens, and / or no more than 2 sulfurs. Unless otherwise specified, heterocycles can be saturated, partially unsaturated, or fully unsaturated rings. For example, pyridyl, thiazolyl, triazolyl, pyrimidinyl, dihydrofuryl, tetrahydrofuryl, oxazolyl, piperidinyl, piperazinyl, pyrrolyl, morpholinyl, indolyl, and the like.

The term "5- to 6-membered heterocyclic ring" refers to a saturated, partially unsaturated or fully unsaturated heterocyclic ring having 5-6 ring atoms, such as pyridyl, thiazolyl, triazolyl, pyrimidinyl, dihydro Furyl, tetrahydrofuryl, oxazolyl, piperidinyl, piperazinyl, pyrrolyl, morpholinyl, and the like.

The term "5- to 6-membered aromatic heterocyclic group" refers to a completely unsaturated heterocyclic ring having 5 to 6 ring atoms, such as pyridyl, thiazolyl, pyrimidinyl, or oxazolyl, and the like.

The term "6- to 10-membered aromatic ring group" refers to an aryl group having 6 to 10 carbon atoms, such as phenyl, naphthyl, and the like.

The term "photochromic" refers to a compound (A), which can undergo a specific chemical reaction or physical effect when receiving a certain wavelength of light, to obtain the product (B), which is caused by the structural change (the visible part of the A significant change in the absorption spectrum occurred. Under the action of light of another wavelength or heat, the product (B) can return to its original form.

The term "ring-closing product" refers to a compound obtained after a diarylethene compound is irradiated with ultraviolet light of a specific wavelength, and a ring closure reaction occurs in the molecule.

The term "fatigue resistance" refers to an evaluation index based on the number of cycles between the coloration and decolorization of a compound undergoing photochromism.

The term "inert solvent" refers to a variety of solvents that do not react with the starting materials, including various linear, branched or cyclic alcohols, ethers or ketones, haloalkanes, 1,4-dioxane, acetonitrile, tetrahydrofuran , N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), etc.

As used herein, "composition" refers to any mixture. It can be a solution, a mixture, a liquid, a powder, an ointment, an aqueous, a non-aqueous, or any combination thereof.

The abbreviations of any protective groups, amino acids, and other compounds used herein are consistent with their common and recognized abbreviations or biochemical nomenclature issued by the IUPAC-IUB Committee, unless specifically stated otherwise.

The compounds of the invention may contain one or more asymmetric centers and therefore appear as racemates, racemic mixtures, single enantiomers, diastereomeric compounds and single diastereomers. The asymmetric center that can exist depends on the nature of the various substituents on the molecule. Each such asymmetric center will independently produce two optical isomers, and all possible optical isomers and diastereomeric mixtures and pure or partially pure compounds are included within the scope of the present invention. The invention includes all isomeric forms of the compounds.

Preparation method of the compound of the present invention

The compound represented by the general formula (A) of the present invention can be prepared by the following method, but the conditions of the method, such as reactants, solvents, acids and bases, the amount of the compound used, the reaction temperature, and the time required for the reaction are not limited to the following explanation of. The compound of the present invention can also optionally be conveniently prepared by combining various synthetic methods described in the present specification or known in the art, and such combination can be easily performed by those skilled in the art to which the present invention belongs.

The compound represented by the general formula (A) of the present invention can be synthesized by the following method:

(A) When R1 is the same as R2, the method includes steps:

(1) nucleophilic reaction of a compound of formula (1a) with bromine in an inert solvent to obtain a compound of formula (1b);

(2) protecting the compound of formula (1b) with ethylene glycol in an inert solvent to obtain a compound of formula (1c);

(3) In an inert solvent, extract the compound of formula (1c) with

Reaction to obtain a compound of formula (1d);

(4) deprotecting the compound of formula (1d) in an inert solvent to obtain a compound of formula (1e);

(5) reducing the compound of formula (1e) in an inert solvent to obtain a compound of formula (1f);

(6) The compound of formula (1f) is subjected to a chlorination reaction in an inert solvent to obtain a compound of formula (1g):

(7) reacting a compound of formula (1g) with a compound of formula 01 or 01 'in an inert solvent to obtain a compound of formula (A);

In the above formulas, the definition of each group is the same as above and R1 and R2 are the same;

Or (B) when R1 and R2 are the same, the method includes the steps:

(1) In an inert solvent, combine the compound of formula (2a) with

A Fuke acylation reaction is performed to obtain a compound of formula (2b):

(2) The compound of formula (2b) is subjected to a ring-closure reaction in an inert solvent to obtain a compound of formula (2c):

(3) The compound of formula (2c) is extracted with n-butyllithium in chlorine and reacted with dimethylformamide in an inert solvent to obtain a compound of formula (1e):

(4) The compound of formula (1e) is subjected to a reduction reaction in an inert solvent to obtain a compound of formula (1f):

(5) The compound of formula (1f) is subjected to a chlorination reaction in an inert solvent to obtain a compound of formula (1g):

(6) reacting a compound of formula (1g) with a compound of formula 01 or 01 'in an inert solvent to obtain a compound of formula (A);

In the above formulas, the definition of each group is the same as above and R1 and R2 are the same;

Or (C) when R1 and R2 are different, the method includes the steps:

(1) nucleophilic reaction of a compound of formula (1a) with bromine in an inert solvent to obtain a compound of formula (1b);

(2) protecting the compound of formula (1b) with ethylene glycol in an inert solvent to obtain a compound of formula (1c);

(3) In an inert solvent, extract the compound of formula (1c) with

Reaction to obtain a compound of formula (1d);

(4) deprotecting the compound of formula (1d) in an inert solvent to obtain a compound of formula (1e);

(5) reducing the compound of formula (1e) in an inert solvent to obtain a compound of formula (1f);

(6) The compound of formula (1f) is subjected to a chlorination reaction in an inert solvent to obtain a compound of formula (1g):

(7) reacting a compound of formula (1g) with a compound of formula 01 in an inert solvent to obtain a compound of formula (1h);

(8) reacting a compound of formula (1h) with a compound of formula 01 'in an inert solvent to obtain a compound of formula (A);

In the above formulas, the definition of each group is the same as above and R1 and R2 are different;

Or (C1) When R1 and R2 are different, the method includes the steps:

Steps (1)-(6) in method (C); and (7) reacting a compound of formula (1g) with a compound of formula 01 and a compound of formula 01 'in an inert solvent to obtain a compound of formula (A);

And in the above formulae, the definition of each group is the same as above and R1 and R2 are different.

Or (D) when R1 and R2 are different, the method includes the steps:

(1) In an inert solvent, combine the compound of formula (2a) with

A Fuke acylation reaction is performed to obtain a compound of formula (2b):

(2) The compound of formula (2b) is subjected to a ring-closure reaction in an inert solvent to obtain a compound of formula (2c):

(3) The compound of the formula (2c) is extracted with n-butyllithium and then reacted with dimethylformamide in an inert solvent to obtain a compound of the formula (1e):

(4) The compound of formula (1e) is subjected to a reduction reaction in an inert solvent to obtain a compound of formula (1f):

(5) The compound of formula (1f) is subjected to a chlorination reaction in an inert solvent to obtain a compound of formula (1g):

(6) reacting a compound of formula (1g) with a compound of formula 01 in an inert solvent to obtain a compound of formula (2g);

(7) reacting a compound of formula (2g) with a compound of formula 01 'in an inert solvent to obtain a compound of formula (A);

In the above formulae, the definition of each group is the same as above and R1 and R2 are different.

Or (D1) When R1 and R2 are different, the method includes the steps:

Steps (1)-(5) in method (D); and (6) reacting a compound of formula (1g) with a compound of formula 01 and a compound of formula 01 'in an inert solvent to obtain a compound of formula (A);

And in the above formulae, the definition of each group is the same as above and R1 and R2 are different.

Insecticidal activity of the active substance according to the invention

The term "active substance of the invention" or "active compound of the invention" refers to a compound of the invention, its optical isomers, cis-trans isomers, or agrochemically acceptable salts, which have significantly increased insecticidal activity , And an expanded insecticidal spectrum.

The term "pesticologically acceptable salt" means that the anion of the salt is known and acceptable when forming a pharmaceutically acceptable salt of a pesticide. The salt is preferably water-soluble. Suitable acid addition salts formed from compounds of formula (A) include salts formed from inorganic acids, such as hydrochloride, phosphate, sulfate, nitrate; and salts including organic acids, such as acetate, Benzoate.

The active substance of the present invention can be used to control and eliminate a wide range of agricultural and forestry plant pests, stored cereal pests, public health pests, pests endangering animal health, and the like. In this specification, "insecticide" is a collective term for a substance having an action to control all the pests mentioned above. Examples of pests include, but are not limited to: Coleoptera insects: Sitophilus zeamais, Tribolium castaneum, Henosepilachna vigintioctomaculata, Henosepilachna sparsa, fine-breasted hoe Insects (Agriotes fuscicollis), red-footed green beetle (Anomala cupripes), four-striped beetle (Popillia quadriguttata), potato leaf beetle (Monolepta hieroglyphica), monochamus (Monochamus alternatus), rice root elephant (Echinocnemus squameme) Basiprionota bisignata, Anoplophora chinensis, Apripera germari, Scolytus schevy, or Agriotes fuscicollis. Lepidoptera insects: Lymantria dispar, Malacosoma neustria testacea, Diaphania perspectalis, Clania variegata, Cnidocampa flaguescens, Dendrolimus punctatus), archaea moth (Orgyia gonostigma), poplar wing moth (Paranthrene tabaniformis), Spodoptera litura, Chilo suppressalis, corn borer (Ostrinia nunubilalis), Ephestia baccautella, Cotton roll moth (Adoxophyes ororana), chestnut small roll moth (laspyresia splendana), small ground tiger (Agrotis fucosa), great wax owl (Galleria mellonella), vegetable moth (Plutella xylostella), orange moth (Phyllocnistis citcitrella), or oriental Mythimna separata. Homoptera insects: Nephotettix cincticeps, Nilaparvata lugens, Pseudococcus comstocki, Unaspis yanonensis, Myzus persicae, Aphis gossydii ), Radish aphids (Lipaphis erysimi pseudobrassicae), Stephanitis nashi, or whitefly (Bemisia tabaci). Orthoptera insects: Blattella germanica, Periplaneta americana, Gryllotalpa africana, or Locus migratoria. Isoptera insects: Solenopsis invicta, or Coptotermes formosanus. Diptera insects: Musca domestica, Aedes aegypti, Delia platura, Culex sp., Or Anopheles sinensis.

The compounds involved in the present invention are particularly effective against agricultural and forestry pests such as aphids, leafhoppers, planthoppers, thrips, and whiteflies, as well as hygienic pest mosquito larvae.

Insecticide composition containing active substance of the present invention

The active substance of the present invention can be prepared into a pesticide composition by a conventional method. These active compounds can be formulated into conventional formulations, such as solutions, emulsions, suspensions, powders, foams, pastes, granules; aerosols, natural and synthetic materials impregnated with active substances, in polymer Microcapsules, seed coatings, and preparations for use with combustion devices, such as smoke cartridges, cans, and trays, as well as ULV Cold Mist and Hot Mist ( Warm).

These preparations can be produced by known methods, for example, by mixing an active compound with an extender, which is a liquid or liquefied gas or solid diluent or carrier, and optionally a surfactant such as an emulsifier and / or Dispersant and / or foam former. For example, when using water as an extender, organic solvents can also be used as auxiliaries.

Basically suitable when using liquid solvents as diluents or carriers, such as: aromatic hydrocarbons, such as xylene, toluene or alkyl naphthalene; chlorinated aromatic or chlorinated aliphatic hydrocarbons, such as chlorobenzene, vinyl chloride or Dichloromethane; aliphatic hydrocarbons, such as cyclohexane or paraffin, 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 Ketones or cyclohexanone; or polar solvents that are not commonly used, such as dimethylformamide and dimethylsulfoxide, and water. Liquefied gas diluent or carrier refers to a liquid that will become a gas at normal temperature and pressure, such as aerosol propellants, such as halogenated hydrocarbons, butane, propane, nitrogen and carbon dioxide.

The solid support can be ground minerals such as kaolin, clay, talc, quartz, activated clay, montmorillonite, or diatomaceous earth, and ground synthetic minerals such as highly dispersed silicic acid, alumina, and silicates. . The solid carriers for granules are crushed and graded natural spar, such as calcite, marble, pumice, sepiolite, and dolomite, as well as granules made from inorganic and organic meals, and organic materials such as sawdust, coconut shell, Corn on the cob and tobacco stems.

Non-ionic and anionic emulsifying columns can be used as emulsifiers and / or foam formers. For example polyoxyethylene-fatty acid esters, polyoxyethylene-fatty alcohol ethers, such as alkylaryl polyethylene glycol ethers, alkyl sulfonates, alkyl sulfates, aryl sulfonates and white Protein hydrolysate. Dispersants include, for example, lignin sulfite waste liquor and methyl cellulose.

Binders such as carboxymethyl cellulose and natural and synthetic polymers in the form of powders, granules or emulsions can be used in the formulations, such as gum arabic, polyvinyl alcohol and polyvinyl acetate. Colorants such as inorganic dyes, such as iron oxide, diamond oxide, and Prussian blue; organic dyes, such as organic dyes, such as chloro dyes or metal titanium cyanine dyes; and trace nutritional agents, such as iron, manganese, boron, copper , Cobalt, aluminum and zinc salts, etc.

These active compounds of the present invention may be present in a commercial formulation or in a dosage form prepared from these formulations in a mixture with other active compounds including, but not limited to, pesticides, bait, fungicides, Acaricides, thread killers, fungicides, growth control agents, etc. Insecticides include, for example, phosphates, carbamates, pyrethroids, chlorinated hydrocarbons, benzoylureas, wormworm toxins, and substances produced by microorganisms such as avermectin.

In addition, the active compounds of the present invention can also be formulated as a mixture with a synergist in their commercial formulations to be used in dosage forms prepared from these formulations. A synergist is a compound that enhances the action of an active compound. Since the active compound itself is active, it is not necessary to add a synergist.

These formulations usually contain the active compound of the invention in an amount of 0.001-99.99% by weight, preferably 0.01-99.9% by weight, and more preferably 0.05-90% by weight of the insecticide composition. The concentration of the active compound in a dosage form prepared from a commercial preparation can be varied within a wide range. The concentration of the active compound in the dosage form used may be from 0.0000001 to 100% (g / v), preferably between 0.0001 and 1%.

Based on the basic principles of photopharmachology, a class of photochromic diarylethylene compounds containing GABA receptor inhibitor units provided by the present invention has obvious photochromism, good thermal stability, and good fatigue resistance. The ring product has high insecticidal activity and can be used as an insecticide to control agricultural pests. At the same time, it provides a new method for the study of GABA receptors.

The present invention will be further described below with reference to specific embodiments. It should be understood that these examples are only used to illustrate the present invention and not to limit the scope of the present invention. The experimental methods without specific conditions in the following examples are generally based on conventional conditions or conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are by weight. Among them, r.t. represents room temperature.

Example 1 Synthesis of Compound 1

1.1 Preparation of 4-bromo-5-methyl-2-thienaldehyde

In a 100 mL round-bottomed flask, add 5-methyl-2-thiophene formaldehyde (6.3 g, 50.0 mmol) and 50 mL of acetic acid, and then weigh Br ₂ (8.78 g, 55.0 mmol) in a suitable amount of acetic acid using a constant pressure dropping funnel. Bromine acetic acid solution was slowly added dropwise at room temperature, and stirred at room temperature for 24 hours. After TLC followed the reaction, water was added to stop the reaction. The reaction mixture was neutralized to neutrality with anhydrous sodium carbonate. The product was extracted three times with ether, and the organic phase was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain a black liquid. Column chromatography was eluted with petroleum ether: ethyl acetate = 40: 3 (v: v). The solvent was evaporated to dryness to obtain 3.1 g of a white solid with a yield of 30.1%. ¹ H NMR (400MHz, CDCl ₃ ) δ 9.78 (s, 1H), 7.26 (s, 1H), 2.49 (s, 3H). ¹³ C NMR (101 MHz, CDCl ₃ ) δ 181.60, 145.84, 140.12, 138.73, 111.24 , 15.93.

1.2 Preparation of 4-bromo-5-methyl-2- (1,3-dioxolane) thiophene

In a 100 mL round-bottomed flask, 4-bromo-5-methyl-2-thiophenealdehyde (2.0 g, 9.75 mmol), ethylene glycol (Glycol) (1.23 g, 19.51 mmol), and p-toluenesulfonic acid (0.15 g, 97.53mmol), add 60mL Benzene (Benzene) to dissolve, install a water separator, stir and reflux (reflux) for 4h, after TLC tracking the reaction is completed, reduce the temperature of the reaction solution to room temperature, use 3.0mol / L sodium hydroxide It was washed three times and then three times with water. The organic phase was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain a yellow liquid. Column chromatography was eluted with petroleum ether: ethyl acetate = 20: 1 (v: v). The solvent was evaporated to obtain 2.4 g of a white oil with a yield of 90.8%. ¹ H NMR (400MHz, CDCl ₃ ) δ 6.96 (s, 1H), 6.00 (s, 1H), 4.18-3.88 (m, 4H), 2.38 (s, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ138.70, 135.35, 128.79, 108.45, 99.69, 65.19, 14.86.

1.3 Preparation of 1,2-bis [2-methyl-5- (1,3-dioxolane) -3-thienyl] octafluorocyclopentene

Under nitrogen and -78 ° C, add 4-bromo-5-methyl-2- (1,3-dioxolane) thiophene (2.4g, 9.63mmol) to a 50mL cryogenic reaction flask, and add 30mL of anhydrous Tetrahydrofuran, stir, slowly add 2.5mol / L n-BuLi / n-hexane (7.7mL, 19.27mmol) with a syringe, continue to stir the reaction at low temperature for 40min, and slowly add octafluorocyclopentene (1.23g, 5.78 mmol), continue to stir the reaction at low temperature for 2 h. After the completion of the TLC tracking reaction, the reaction solution was naturally warmed to room temperature, and the reaction was quenched with 2M hydrochloric acid (15 mL). The layers were separated. The aqueous layer was extracted three times with anhydrous ether and combined. There are several layers, and then washed three times with water. The organic layer is dried over anhydrous sodium sulfate, filtered, and the solvent is removed under reduced pressure to obtain 2.0 g of an oily liquid. This crude product is directly put into the next step of deprotection reaction without further separation.

1.4 Preparation of 1,2-bis (2-methyl-5-formyl-3-thienyl) octafluorocyclopentene

In a 250 mL round bottom flask, add the crude product 1,2-di [2-methyl-5- (1,3-dioxolane) -3-thienyl] octafluorocyclopentene (2.0 g, 3.90 mmol) And p-toluenesulfonic acid (0.4g, 2.22mmol), mixed solvents of water (30mL) and acetone (80mL) were added to dissolve, then 2.0mL of pyridine was added to the mixture, and the reaction was stirred at reflux for 24h. After the TLC tracking reaction was completed, the temperature of the reaction solution was lowered to room temperature. The reaction solution was washed with saturated sodium bicarbonate solution and water, and the layers were separated. The aqueous layer was extracted with dichloromethane. The organic phases were combined, dried over anhydrous sodium sulfate, and filtered. The solvent was removed under reduced pressure to give a yellow liquid, which was subjected to column chromatography and eluted with petroleum ether: ethyl acetate = 1: 5 (v: v). The solvent was evaporated to give 0.15 g of a blue solid with a yield of 8.7%. ¹ H NMR (400MHz, CDCl ₃ ) δ9.86 (s, 2H), 7.74 (s, 2H), 2.03 (s, 6H). ¹⁹ F NMR (376MHz, CDCl ₃ ) δ-110.30 (t, J = 5.1 Hz, 4F), -130.57--133.99 (m, 2F).

1.5 Preparation of 1,2-bis (2-methyl-5-hydroxymethyl-3-thienyl) octafluorocyclopentene

Under nitrogen and ice bath conditions, add 1,2-bis (2-methyl-5-formyl-3-thienyl) octafluorocyclopentene (0.45 g, 1.06 mmol) to a 50 mL round bottom flask and add 35 mL of methanol was dissolved, and sodium borohydride (0.16 g, 4.24 mmol) was added in portions. The reaction was continued to be stirred in the ice bath for 1 h. After TLC followed the reaction, an appropriate amount of water was added to quench the reaction, and then the reaction mixture was extracted with ether (30 mL × 2). The organic phases were combined and the organic phase was washed three times with saturated sodium chloride solution. It was dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain a yellow solid. Column chromatography was performed with petroleum ether: ethyl acetate = 1: 1 (v: v). The solvent was evaporated to dryness to obtain 0.45 g of a white solid with a yield of 99%. ¹ H NMR (400MHz, CDCl ₃ ) δ 6.95 (s, 2H), 4.76 (s, 4H), 1.88 (s, 8H). ¹⁹ F NMR (376MHz, CDCl ₃ ) δ-110.10 (t, J = 10.9 Hz, 4F), -131.48--134.27 (m, 2F).

1.6 Preparation of 1,2-bis (2-methyl-5-chloromethyl-3-thienyl) octafluorocyclopentene

Under nitrogen and ice bath conditions, in a 100 mL round-bottomed flask, add 1,2-bis (2-methyl-5-hydroxymethyl-3-thienyl) octafluorocyclopentene (0.25 g, 0.58 mmol) and Anhydrous pyridine (1.0 mL) was dissolved by adding 40 mL of anhydrous tetrahydrofuran and stirred. Thionyl chloride (0.28 g, 2.33 mmol) was weighed into a constant pressure dropping funnel, and slowly added dropwise to the reaction system, and the reaction was continued in an ice bath with stirring for 2 h. After the TLC tracking reaction was completed, the reaction solution was slowly poured into a 40 mL ice-water mixture and stirred. The reaction mixture was then extracted with ether (30 mL × 2), and the combined organic phases were washed with 30 mL of saturated sodium bicarbonate, dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to give 0.35 g of a pale yellow solid with a yield of 92%. Since the product was very unstable in air, it was immediately put into the next reaction without purification.

1.7 Preparation of Compound 1

Under nitrogen and 50 ° C oil bath conditions, put fipronil (0.421 g, 0.9 mmol) and cesium carbonate (0.949 g, 2.17 mmol) in a 50 mL round-bottomed flask, add 30 mL of dimethylformamide to dissolve, and keep the temperature at 50 ° C Stir the reaction for half an hour. Then slowly add 1,2-bis (2-methyl-5-chloromethyl-3-thienyl) octafluorocyclopentene dissolved in 5 mL of dimethylformamide, and continue the reaction at constant temperature for 4 h. After the completion of the TLC tracking reaction, the precipitate was removed by filtration, and the solvent was removed under reduced pressure to obtain a brown-red solid. Column chromatography was eluted with ethyl acetate: petroleum ether = 1: 5 (v: v). The solvent was evaporated to give a white solid 0.35. g, yield 28.3%. mp231.8-238.8 ℃. ¹ H NMR (400 MHz, DMSO) δ 8.40 (s, 2H), 8.39-8.33 (m, 4H), 7.04 (d, J = 5.2 Hz, 2H), 4.71 (dt, J = 17.2, 5.6 Hz, 2H), 4.45 (dd, J = 17.6, 6.4 Hz, 2H), 1.80 (d, J = 4.4 Hz, 6H). ¹³ C NMR (101 MHz, DMSO) δ 149.59, 141.85, 139.05, 136.05 , 135.84,134.18,133.91,133.58,127.01,125.53,124.35,123.47,120.81,111.31,95.38,94.48,42.66,14.01. ¹⁹ F NMR (376MHz, DMSO) δ-61.36--61.65 (m),-73.32 ( t, J = 8.3Hz), -108.91--109.89 (m), -131.04--131.49 (m). HRMS (ESI-TOF): m / z C ₄₁ H ₁₈ ³⁵ Cl ₄ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1286.8800, Measured value: 1286.8793; m / z C ₄₁ H ₁₈ ³⁵ Cl ₃ ³⁷ ClF ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1288.8770, Measured Value: 1288.8760; m / z C ₄₁ H ₁₈ ³⁵ Cl ₂ ³⁷ Cl ₂ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated value: 1290.8741, Found: 1290.8707; m / z C ₄₁ H ₁₈ ³⁵ Cl ³⁷ Cl ₃ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1292.8711, Found: 1292.8723.

Example 2 Synthesis of Compound 2

2.1 Preparation of 1,5-bis (5-chloro-2-methylthien-3-yl) pentane-1,5-dione

In a 50 mL round-bottomed flask, anhydrous aluminum trichloride (12.1 g, 90.49 mmol) and 150 mL of nitromethane were sequentially added. Under an ice-bath condition, a solution of nitrosyl chloride (6.37, 37.71 mmol) was first added dropwise. A solution of 2-chloro-5-methylthiophene (10 g, 75.41 mmol) in nitromethane was added dropwise. After the addition is complete, continue the reaction for 0.5h, then remove the ice bath, and continue to stir the reaction for 6h at room temperature. After the TLC has followed the reaction, carefully add 60mL of ice-water mixture slowly and continue stirring for 5min. The organic phase is separated and the aqueous layer is separated. Extract with anhydrous ether (50mL × 2), combine the organic phases, adjust to neutrality with saturated sodium bicarbonate solution, then wash with water, wash with saturated sodium chloride solution, dry over anhydrous magnesium sulfate overnight, and remove a large amount of solvent by rotary evaporation. The obtained viscous black crude product was passed through a silica gel column (7: 3, v / v) with petroleum ether and ethyl acetate, and the solvent was evaporated to obtain 16 g of a pale yellow solid powder with a yield of 59%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.19 (s, 2H), 2.93-2.78 (t, J = 18 Hz, 4H), 2.66 (s, 6H), 2.06 (m, 2H). ¹³ C NMR (101 MHz , CDCl ₃ ): δ 194.7, 147.6, 134.7, 126.7, 125.2, 40.4, 18.1, 16.0.

2.2 Preparation of 1,2-bis (5-chloro-2-methylthien-3-yl) cyclopentene

Under nitrogen protection, 100 mL of anhydrous tetrahydrofuran and zinc powder (7.24 g, 110.71 mmol) were added to a 250 mL three-necked flask, and the titanium tetrachloride solution (16.80 g, 88.57 mmol) was slowly added dropwise under an ice bath under vigorous stirring. After completion of the dropwise addition, the ice bath was stirred for 5 min, transferred to an oil bath, heated to 80 ° C., and heated under reflux for 1 hour. The color of the reaction solution gradually changed from yellow-green to dark black. Allow to cool to room temperature, and inject 40 mL of 1,5-bis (5-chloro-2-methylthien-3-yl) pentane-1,5-dione) (16g, 44.29mmol) with a syringe. Tetrahydrofuran solution. Continue heating and refluxing for 4 hours. Stop heating. After cooling, pour the reaction solution into a 10% potassium carbonate aqueous solution, precipitate a large amount of solid, suction filter, and repeatedly filter the cake with anhydrous ether. The aqueous layer was extracted, the organic phases were combined, dried over anhydrous sodium sulfate overnight, filtered, and the solvent was removed by rotary evaporation. The crude product was eluent with petroleum ether, passed through a silica gel column, and the solvent was evaporated to give 3.3 g of a colorless oily liquid. Set to a colorless waxy solid with a yield of 30%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.57 (s, 2H), 2.71 (t, J = 7.5 Hz, 4H), 2.07-1.96 (m, 2H), 1.88 (s, 6H). ¹³ C NMR ( 101MHz, CDCl ₃ ) δ134.82,134.41,133.28,126.67,125.18,38.32,22.81,14.16.

2.3 Preparation of 1,2-bis (5-formyl-2-methylthien-3-yl) cyclopentene

Under nitrogen and -78 ° C, add 1,2-bis (5-chloro-2-methylthiophen-3-yl) cyclopentene (1.50 g, 4.56 mmol) to a 50 mL low-temperature reaction flask, and add 10 mL of Water tetrahydrofuran, stir, slowly add 2.5mol / L n-BuLi / hexane (5.5mL) with a syringe, continue to stir the reaction at low temperature for 60min, then slowly add DMF (2.29mL) with a pre-cooled syringe, continue to stir at low temperature for 1h After the completion of the TLC tracking reaction, the reaction solution was naturally warmed to room temperature, and the reaction was quenched with 2M hydrochloric acid (15 mL), and the liquid was separated. The aqueous layer was extracted with anhydrous ether (20 mL × 2), and several layers were combined. It was washed three times with water, the organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure. The obtained crude product was passed through a silica gel column (5: 1, v / v) with petroleum ether and ethyl acetate, and the solvent was evaporated to give 1.5. g blue solid powder, yield 46%. ¹ H NMR (400MHz, CDCl ₃ ) δ9.74 (s, 2H), 7.43 (s, 2H), 2.84 (t, J = 7.5Hz, 4H), 2.17-2.07 (m, 2H), 2.05 (s, 6H). ¹³ C NMR (101MHz, CDCl3) δ 182.38, 146.38, 140.23, 137.42, 137.07, 134.98, 38.41,22.89, 15.38.

2.4 Preparation of 1,2-bis (5-hydroxymethyl-2-methylthien-3-yl) cyclopentene

Under nitrogen and ice bath conditions, in a 50 mL round-bottomed flask, add 1,2-bis (5-formyl-2-methylthiophen-3-yl) cyclopentene (0.87 g, 2.75 mmol), and 35 mL of methanol Dissolve, then add sodium borohydride (0.42 g, 11.0 mmol) in portions. The reaction was continued to be stirred in the ice bath for 1 h. After TLC followed the reaction, an appropriate amount of water was added to quench the reaction, and then the reaction mixture was extracted with diethyl ether (30 mL × 2). The organic phases were combined, and the organic phases were washed three times with saturated sodium chloride solution. It was dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain a yellow solid. Column chromatography was performed with petroleum ether: ethyl acetate = 6: 1 (v: v). The solvent was evaporated to dryness to obtain 0.86 g of a white solid with a yield of 98%. ¹ H NMR (400MHz, CDCl ₃ ) δ6.61 (s, 2H), 4.61 (s, 4H), 2.75 (t, J = 7.4Hz, 4H), 2.32 (s, 2H), 2.06-1.98 (m, 2H), 1.95 (s, 6H ). 13 C NMR (101MHz, CDCl 3) δ139.35,135.33,134.93,134.56,126.91,59.91,38.25,22.98,14.36.

2.5 Preparation of 1,2-bis (5-chloromethyl-2-methylthien-3-yl) cyclopentene

Under nitrogen and ice bath conditions, in a 100 mL round bottom flask, add 1,2-bis (5-hydroxymethyl-2-methylthiophen-3-yl) cyclopentene (0.86 g, 2.86 mmol) and anhydrous Pyridine (1.0 mL) was dissolved by adding 40 mL of anhydrous tetrahydrofuran and stirred. Thionyl chloride (1.28 g, 10.73 mmol) was weighed into a constant-pressure dropping funnel, slowly added to the reaction system, and the reaction was continued in an ice-bath with stirring for 2 h. After the TLC tracking reaction was completed, the reaction solution was slowly poured into a 40 mL ice-water mixture and stirred. The reaction mixture was then extracted with diethyl ether (30 mL x 2), and the combined organic phases were washed with 30 mL of saturated sodium bicarbonate, dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to give a brown solid. Since the product was very unstable in air, it was immediately put into the next reaction without purification.

2.6 Preparation of Compound 2

Under nitrogen and 50 ° C oil bath conditions, put fipronil (Fip, 0.378 g, 1.06 mmol) and cesium carbonate (1.11 g, 2.54 mmol) in a 50 mL round bottom flask, add 30 mL of dimethylformamide to dissolve, 50 The reaction was stirred at a constant temperature of ℃ for half an hour. Then slowly add 1,2-bis (5-chloromethyl-2-methylthien-3-yl) cyclopentene (0.80 g, 2.24 mmol) dissolved in 5 mL of dimethylformamide, and continue the reaction at constant temperature for 4 h . After the completion of the TLC tracking reaction, the precipitate was removed by filtration, and the solvent was removed under reduced pressure to obtain a brown-red solid. Column chromatography was eluted with ethyl acetate: petroleum ether = 1: 5 (v: v). The solvent was evaporated to give a white solid 0.2. g, yield 16.3%. mp113.4-118.5 ℃. ¹ H NMR (400MHz, DMSO) δ 8.38 (s, 2H), 8.36 (s, 2H), 8.30 (dd, J = 15.0, 6.4 Hz, 2H), 6.74 (d, J = 7.6Hz, 2H), 4.57 (dd, J = 17.2, 6.0Hz, 2H), 4.38-4.21 (m, 2H), 2.68 (t, J = 7.2Hz, 4H), 1.98 (dd, J = 14.4, 7.2Hz, 2H), 1.80 (d, J = 8.0Hz, 6H). ¹³ C NMR (101MHz, DMSO) δ149.68, 136.09, 135.91, 135.76, 134.98, 134.26, 133.71, 126.92, 126.10, 125.49, 123.55, 120.79, 111.37, 95.13, 90.7, 30.92, 22.04, 13.96. ¹⁹ F NMR (376MHz, CDCl ₃ ) δ-62.10--64.26 (m), -73.19--75.35 (m) .HRMS (ESI-TOF): m / z C ₄₁ H ₂₄ ³⁵ Cl ₄ F ₁₂ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1178.9365, Found: 1178.9355; m / z C ₄₁ H ₂₄ ³⁵ Cl ₃ ³⁷ ClF ₁₂ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1180.9336, Found: 1180.9349; m / z C ₄₁ H ₂₄ ³⁵ Cl ₂ ³⁷ Cl ₂ F ₁₂ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1182.9306 , Found: 1182.9320; m / z C ₄₁ H ₂₄ ³⁵ Cl ³⁷ Cl ₃ F ₁₂ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1184.9277, Found: 1184.9261; m / z C ₄₁ H ₂₄ ³⁷ Cl ₄ F ₁₂ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1186.9247, Found: 1186.9230.

Preparation of N-methyl fipronil

N- (3-cyano-1- (2,6-dichloro-4- (trifluoromethyl) phenyl) -4-((trifluoromethyl) sulfinyl) -1H-pyrazole- 5-yl) propionamide (4.91 g, 10 mmol), 20 mmol of dilute sulfuric acid was stirred in ethanol, and the reaction was carried out at 100 ° C. The reaction was followed by TLC to the end of the reaction. Wash with water, adjust the pH, and extract the reaction solution. Because the product obtained is relatively pure, it is directly sent to the next step without purification.

Preparation of compound 3

The synthesis method is the same as that of compound 2, step 2.6, except that the fipronil is replaced by N-methyl fipronil.

mp118.2-123.1 ℃. ¹ H NMR (400MHz, DMSO) δ 7.55 (s, 2H), 7.56 (s, 2H), 6.58 (d, J = 7.6 Hz, 2H), 4.58 (dd, J = 17.2 , 6.0Hz, 2H), 4.57-4.21 (m, 2H), 2.38 (t, J = 7.2Hz, 4H), 2.33 (s, 6H), 1.88 (dd, J = 14.4, 7.2Hz, 2H), 1.11 (t, J = 8.0Hz, 6H). ¹³ C NMR (101MHz, DMSO) δ 154.78,141.38,139.09,136.91,135.28,134.76,133.98,131.22,130.11,127.26,125.71,123.92,123.10,115.49,110.37, 55.13, 46.78, 30.92, 21.04, 12.78. HRMS (ESI-TOF): m / z C ₄₃ H ₂₈ ³⁵ Cl ₄ F ₁₂ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated value: 1206.9678, Found: 1206.9675C ₄₃ H ₂₈ ³⁵ Cl ₃ ³⁷ ClF ₁₂ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1208.9649, Found: 1208.9645; m / z C ₄₃ H ₂₈ ³⁵ Cl ₂ ³⁷ Cl ₂ F ₁₂ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1210.9619, Found: 1210.9616; m / z C ₄₃ H ₂₈ ³⁵ Cl ³⁷ Cl ₃ F ₁₂ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated Value: 1212.9590, Found: 1212.9577; m / z C ₄₃ H ₂₈ ³⁷ Cl ₄ F ₁₂ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1214.9548, Found: 1214.9553.

Preparation of compound 4

The synthetic method is the same as that of compound 1, step 1.7; the difference is that fipronil is replaced by N-methyl fipronil.

mp121.8-124.3 ℃. ¹ H NMR (400MHz, DMSO) δ 7.58 (s, 2H), 7.57 (s, 2H), 6.68 (d, J = 7.6 Hz, 2H), 4.88 (dd, J = 17.2 , 6.0Hz, 2H), 4.87-4.51 (m, 2H), 2.45 (s, 6H), 1.21 (t, J = 8.0Hz, 6H). ¹³ C NMR (101MHz, DMSO) δ 156.78, 143.38, 142.09, 139.12 , 136.71,135.10,134.16,133.98,131.02,127.56,125.88,123.16,122.49,114.23,109.03,107.11,58.88,55.13,47.78,12.28.HRMS (ESI-TOF): m / z C ₄₃ H ₂₂ ³⁵ Cl ₄ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated value: 1314.9113, Found: 1314.9110; C ₄₃ H ₂₂ ³⁵ Cl ₃ ³⁷ ClF ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated value : 1316.9083, found: 1316.9080; m / z C ₄₃ H ₂₂ ³⁵ Cl ₂ ³⁷ Cl ₂ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1318.9041. Found: 1318.9044; m / z C ₄₃ H ₂₂ ³⁵ Cl ³⁷ Cl ₃ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1320.9121, Found: 1320.9117; m / z C ₄₃ H ₂₂ ³⁷ Cl ₄ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1322.8982, Found: 1322.8985.

Preparation of N-butyl fipronil

Add 50ml N, N-dimethylformamide, 10.0g fipronil, 2g KOH to the ultrasonic sprayer (fixed power 150W), and then add 2.7g n-bromobutane. The ultrasonic vibration is performed at room temperature for one hour, and the spray is opened after shaking. The switch sends the mist to the top of the microwave reactor through the air pipe. The microwave reactor is turned on and the power is adjusted to 300W to start the heating reaction. When the solvent in the ultrasonic sprayer is about to be atomized and dried (the phenomenon is in the transparent tube connecting the ultrasonic sprayer and the microwave reactor The mist was significantly reduced), the atomization was stopped, the sample inlet of the microwave reactor was closed, and the reaction was continued for 120 minutes. After the reaction, the product was washed with water, and 11.6 g of the compound was obtained after filtering and drying. Yield ^{92.6%. 1 H NMR (400MHz} , CDCl 3) δ7.90 (s, 1H), 7.80 (s, 1H), 5.62 (s, 2H), 2.82 (s, 2H), 2.52 (s, 2H) , 2.02 (s, 2H), 1.52 (s, 1H).

Preparation of compound 5

The synthesis method is the same as that of compound 1, step 1.7; the difference is that fipronil is replaced with N-butyl fipronil.

mp151.4-154.7 ℃. ¹ H NMR (400MHz, DMSO) δ 7.85 (s, 2H), 7.87 (s, 2H), 6.69 (d, J = 7.6 Hz, 2H), 4.98 (dd, J = 17.2 , 6.0Hz, 2H), 4.87-4.41 (m, 2H), 3.51 (m, 4H), 3.40 (m, 4H), 3.21 (m, 4H) 2.45 (s, 6H), 1.01 (t, J = 8.0 Hz, 6H). ¹³ C NMR (101MHz, DMSO) δ165.88,142.38,141.09,139.82,136.11,135.29,135.00,134.78,131.32,127.59,125.69,123.66,123.06,122.21,115.23,108.03,107.61,61.22,57.88 , 30.87,27.21,21.78,15.06,11.28.HRMS (ESI-TOF): m / z C ₄₉ H ₃₄ ³⁵ Cl ₄ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated value: 1399.0052, found : 1399.0056; C ₄₉ H ₃₄ ³⁵ Cl ₃ ³⁷ ClF ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1401.0022, Found: 1401.0020; m / z C ₄₉ H ₃₄ ³⁵ Cl ₂ ³⁷ Cl ₂ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1403.0090, Found: 1403.0087; m / z C ₄₉ H ₃₄ ³⁵ Cl ³⁷ Cl ₃ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1405.0047, Found: 1405.0050; m / z C ₄₉ H ₃₄ ³⁷ Cl ₄ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1407.0031, Found: 1407.0030.

Preparation of compound 6

The synthesis method is the same as that of compound 1, step 1.7. Under nitrogen and 50 ° C oil bath conditions, a 50 mL round bottom flask was charged with N-methyl fipronil (0.202 g, 0.45 mmol) and N-butyl fipronil (0.221). g, 0.45 mmol) and cesium carbonate (0.949 g, 2.17 mmol), dissolved by adding 30 mL of dimethylformamide, and stirred at 50 ° C for half an hour under constant temperature stirring. Then slowly add 1,2-bis (2-methyl-5-chloromethyl-3-thienyl) octafluorocyclopentene dissolved in 5 mL of dimethylformamide, and continue the reaction at constant temperature for 4 h. After the completion of the TLC tracking reaction, the precipitate was removed by filtration, and the solvent was removed under reduced pressure to obtain a brown-red solid. Column chromatography was eluted with ethyl acetate: petroleum ether = 1: 5 (v: v). The solvent was evaporated to give a white solid 0.20 g, yield 16.2%.

mp181.1-189.5 ℃. ¹ H NMR (400MHz, DMSO) δ 7.57 (s, 2H), 7.45 (s, 2H), 6.58 (d, J = 7.6 Hz, 1H), 6.57 (d, J = 7.6 Hz, 1H), 4.58 (dd, J = 17.2, 6.0 Hz, 2H), 4.57-4.11 (m, 2H), 3.41 (m, 2H), 3.01 (s, 3H), 2.47 (s, 3H), 2.48 (s, 3H), 2.21 ( m, 2H), 2.11 (m, 2H), 1.11 (t, J = 8.0Hz, 3H). 13 C NMR (101MHz, DMSO) δ165.05,155.21,143.33,142.23,141.01, 139.88,138.88,136.71,137.14,135.33,134.34,133.99,132.01,131.46,128.87,127.86,126.54,125.88,124.33,123.56,123.01,122.11,120.98,120.03,117.21,115.74,114.49,112.45,111.94,111.94 109.52, 107.81, 62.31, 59.91, 48.76, 47.32, 39.21, 30.21, 27.34, 23.44, 15.23, 12.89. HRMS (ESI-TOF): m / z C ₄₆ H ₂₈ ³⁵ Cl ₄ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1356.9582, Found: 1356.9583; C ₄₆ H ₂₈ ³⁵ Cl ₃ ³⁷ ClF ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1358.9553, Found: 1358.9556; m / z C ₄₆ H ₂₈ ³⁵ Cl ₂ ³⁷ Cl ₂ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1360.9511, Found: 1360.9516; m / z C ₄₆ H ₂₈ ³⁵ Cl ³⁷ Cl ₃ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1362.9494, Found: 1362.9490; m / z C ₄₆ H ₂₈ ³⁷ Cl ₄ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated Value: 1364 .9452, Found: 1364.9450.

Preparation of compound 7

The synthetic method is the same as that of compound 6; the difference is that N-butyl fipronil is replaced with fipronil.

mp195.8-209.6 ℃. ¹ H NMR (400MHz, DMSO) δ 7.67 (s, 2H), 7.55 (s, 2H), 6.59 (d, J = 7.6 Hz, 1H), 6.61 (d, J = 7.6 Hz, 1H), 5.11 (d, J = 17.2, 1H), 4.68 (dd, J = 17.2, 6.0 Hz, 2H), 4.77-4.31 (m, 2H), 3.21 (s, 3H), 2.17 (s, 3H), 2.18 (s, 3H) ¹³ C NMR (101MHz, DMSO) δ158.78,155.34,145.65,144.21,142.56,141.31,139.80,138.87,137.21,136.77,135.26,135.11,134.21,133.87,131.29,129.87,128.66 , 127.61,127.06,126.34,125.78,124.11,123.54,123.07,122.43,122.06,120.87,114.21,112.87,110.98,109.33,108.64,107.26,62.34,47.87,40.26,39.11,15.23.HRMS (ESI-TOF): m / z C ₄₂ H ₂₀ ³⁵ Cl ₄ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1300.8956, Found: 1300.8954; C ₄₂ H ₂₀ ³⁵ Cl ₃ ³⁷ ClF ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1302.8927, Found: 1302.8931; m / z C ₄₂ H ₂₀ ³⁵ Cl ₂ ³⁷ Cl ₂ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1304.8897 , Found: 1304.8890; m / z C ₄₂ H ₂₀ ³⁵ Cl ³⁷ Cl ₃ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1306.8868, Found: 1306.8870; m / z C ₄₂ H ₂₀ ³⁷ Cl ₄ F ₁₈ N ₈ O ₂ S ₄ Na [M + Na] ⁺ Calculated: 1308.8826, Found: 1308.8823.

Example 3 Insecticide activity test of the compound of the present invention

(1) Insecticidal activity against aphids

Aphids are commonly known as greasy or honey bugs, belonging to the homoptera order, and are a common crop pest. Aphids are mainly distributed in temperate and subtropical regions of the northern hemisphere, and they are rarely distributed in tropical regions. Aphids are pests of stinging mouthparts, often clustering in leaves, tender stems, flower buds, and top buds, etc., sucking juice, causing the leaves to shrink, curl, and deform, causing severe withering or even death of the entire plant. Honeydew secreted by aphids can also cause coal pollution, virus disease and attract ants. Aphids have strong reproduction and adaptability, and various control methods are difficult to achieve a curative effect. For the control of aphids, it is important to control them to prevent aphids from occurring in large numbers. Bean aphid (Aphis craccivora) was used as a test object, and the test was performed by dipping method.

Operation process: Select robust bean aphid wingless adults (the worm body is black-green, shiny, and the abdomen is full. The fading, tibia, and pupa of each foot are dark black, and the rest are yellow-white). Protect from light and starve for 0.5 to 1 h in the dark. Select broad bean seedlings with a good growth, about 3cm in height, wash the sand (take care to keep the bean skin intact), remove the roots, insert them into a sponge with water, so that the bean seedlings maintain sufficient water supply. The starved bean aphids were shaken around the bean seedlings, and the aphids were allowed to climb the seedlings in the sun, and punctured the needles (which took about 2 to 3 hours), and finally each bean seedling was crawled with about 20 to 30 aphids. The compound solution with the required concentration was prepared and divided into two groups. The first group was not irradiated with ultraviolet light (unlighted group), and the second group was irradiated with 310nm ultraviolet light for a certain period of time (lighted group, placed in dark conditions). The content of DMSO in the solution does not exceed 5%, and the solution contains a small amount of the surfactant Tritraton (2 to 3 drops of Tritraton in 500ml of water). The aphids are treated by the seed soaking method, and the bean seedlings crawling with the bean aphids are immersed in the prepared two groups of solutions for 2 to 3 s for three consecutive times. Then use blotting paper to blot the excess solution from the bean sprouts, in triplicate for each concentration. Then insert the bean sprouts into a sponge with water, put on a horse light cover, protect from light, and leave it at 25 ° C for 48 hours. After 48 hours, observe and count the death of aphids in the light group and the non-light group, and calculate the mortality rate (%) according to the formula: mortality rate (%) = (control live insects-treated live insects) / control live insects × 100% . The results are shown in Table 1.

(2) Insecticidal activity against 4th instar larvae of Aedes albopictus

Aedes albopictus is commonly known as black mosquito, flower mosquito, spotted mosquito, flower foot mosquito, fierce and aggressive, also known as "Asian tiger mosquito", belonging to the family Aceridae, medium size Black mosquitoes with markings formed by white scales. Aedes albopictus originated from Southeast Asia and is a common mosquito species in Southeast Asia and China. Aedes albopictus larvae (pupa) invertebrates, insects, larvae of Diptera. It is hatched from eggs laid by female mosquitoes in fresh water. Its body is slender, its chest is wider than its head and abdomen, and its body flexes and stretches when swimming. Aedes albopictus likes to lay eggs on a small area of standing water, and its larvae are "quiet". The water environment is quiet and shady, and it is not easy to be disturbed.孑孓 The body is slender and dark brown, swimming vertically in the water, feeding on bacteria and unicellular algae in the water, and breathing air. Larvae mainly accumulate water in bamboo tubes, tree holes, stone caves, waste tires, and tanks, earthenware bowls, and pickle tanks near the human house. They are also found in the leaf axils of plants such as pineapples. The tadpoles develop into tadpoles after 4 molts. The tadpoles can still move in the early stage, but they are basically immobile when they emerge, and then become mosquitoes. Aedes albopictus is both a highly aggressive mosquito and an important viral vector. It can transmit many pathogens, including dengue, Ross River virus, and West Nile virus. Comprehensive mosquito control methods include environmental control, biological control, chemical control, regulatory control and genetic control. The chemical control is through the injection of the breeding ground, which has a good effect on the direct spraying of Aedes albopictus adult mosquitoes, but it has caused considerable pollution to the environment while investing a large amount of human, material and financial resources, and the application of chemical drugs It also makes mosquitoes resistant. Therefore, research on high-efficiency, low-toxic insecticides to kill mosquito larvae can effectively control the increase in the number of mosquitoes and inhibit the spread of human diseases.

Operation process: Select a few 4th instar Aedes albopictus larvae with the same size. Dilute the test compound with DMSO (the content of DMSO in the solution does not exceed 5%), dilute it with dechlorinated water, and accurately prepare 800, 400, 200, 100, 50, 25, 12.5, 6.25, 3.13, 1.57ppm solutions. Two sets of experiments were set up, the first group was not irradiated with ultraviolet light (unlighted group), and the second group was irradiated with 310nm ultraviolet light for a certain time (lighted group, placed in dark conditions). Then take 2 mL of the compound of each concentration and add it to a 4 mL centrifuge tube, and then transfer 30 maggots into the corresponding centrifuge tube. Finally, add 2 mL of dechlorinated water to make the solution volume 4 mL, and the final compound concentration is 400. , 200, 100, 50, 25, 12.5, 6.25, 3.13, 1.57, 0.79 ppm, and treated with a chlorine-free aqueous solution as a blank control, and imidacloprid as a positive control, each concentration was set up in triplicate. Both the light group and the non-light group were placed in a dark condition, and left at a constant temperature of 25 ° C for 24 hours. After 24 hours, observe and count the death of the maggots in the light group and the non-light group, and calculate the mortality rate (%) according to the formula: mortality rate (%) = (control live insects-treated live insects) / control live insects × 100% . The results are shown in Table 1.

Table 1. Insecticidal activity of compounds of formula (A)

Example 4 Photochromism of Compound 1

Photochromism refers to compound A, which can undergo a specific chemical reaction after being irradiated with light of a specific wavelength, thereby producing product B, and can be restored to the original under the action of light of another wavelength of light or heat. State of the phenomenon.

Diarylvinyl compounds are also a class of organic photochromic compounds based on pericyclic reactions. The parent structure of these compounds is a 6π electron-conjugated hexatriene. Under the excitation of ultraviolet light, molecules in antiparallel state undergo an intramolecular cyclotron ring-closing reaction to form a conjugated closed-loop molecule and appear colored. After irradiation with visible light, the closed-loop molecules return to the original state. After proper molecular structure modification, the closed-loop state of such compounds can show all colors from yellow to green.

Take Compound 1 as an example to illustrate: Compound 1 undergoes a photochromic reaction in a closed loop under the action of ultraviolet light. The reaction formula is as follows:

The acetonitrile solution of ring-opening compound 1 was irradiated with ultraviolet light at 310 nm. The ring-opening compound 1 slowly formed ring-closed compound 1. A broad absorption peak appeared at 520 nm in the visible light region. With the extension of the irradiation time, the ring-closed product As the concentration increases, the intensity of the absorption peak increases. After about 90s of irradiation, compound 1 reached the equilibrium state of open-loop and closed-loop (Figure 1). It can be observed that the color of the solution quickly changed from colorless to red, which indicates that compound 1 had closed-loop light under the action of ultraviolet light. Discoloration reaction. Then, the ring-closed compound 1 was irradiated with blue light at 493 nm, and the solution color was observed to change from red to colorless, indicating that the ring-closed compound 1 had a photochromic reaction of ring-opening under visible light.

Combining Example 3 and Example 4 shows that the insecticidal effect of the ring-closure compound is better.

Example 5 Fatigue Resistance of Compound 1

Fatigue resistance is an evaluation index based on the number of cycles between coloration and decolorization of a compound undergoing photochromism. Photochromic reactions are always accompanied by changes in chemical bonds. In this process, the occurrence of side reactions is inevitable. This will undoubtedly lead to partial degradation of the compound and reduce the fatigue resistance of the compound. Apart from the environmental factors, the fatigue resistance of diarylethylene compounds is also affected by the differences in their molecular structure. In terms of molecular structure, the type of substituents on aryl groups will greatly affect its fatigue resistance, and asymmetric structures can also improve the fatigue resistance of compounds.

Studies have shown that dibenzothiophene perfluorocyclopent-based compound has high general fatigue endurance, number of cycles in the air can be up to ¹⁰⁴ or more.

When the acetonitrile solution of Compound 1 was irradiated with ultraviolet light and visible light alternately, it exhibited good photochromic properties. When irradiated with 310 nm ultraviolet light, the acetonitrile solution of Compound 1 changed from colorless to red, and a new characteristic absorption peak appeared near 550 nm, which indicates that it forms a closed-loop compound. When the light is larger than 493nm, the red color of the solution disappears, and the ring-opened compound undergoes a ring-opening reaction to become a ring-opened compound.

Repeating the process of irradiating with different wavelengths of light, the results are shown in Figure 2. The entire color formation and bleaching process can be repeated more than 6 times without large attenuation, which indicates that Compound 1 has good fatigue resistance.

Example 6 Preparation of a Pesticide Composition Containing a Compound of the Invention

(a) Oily suspension

The following components were prepared in proportion: 25% (weight percent, the same below) of any one of compounds 1-7; 5% polyoxyethylene sorbitol hexaoleate; 70% higher aliphatic hydrocarbon oil. The components are ground together in a sand mill until the solid particles fall below about 5 microns. The obtained viscous suspension can be used directly, but it can also be used after emulsified in water.

(b) Water suspension

The following components were prepared in proportion: 25% of any one of compounds 1-7; 3% hydrated attapulgit; 10% calcium lignosulfonate; 0.5% sodium dihydrogen phosphate; and 61.5% water. The components are ground together in a ball mill until the solid particles fall below about 10 microns. This aqueous suspension can be used directly.

(c) Bait

Prepare the following components in proportion: 0.1-10% of any one of compounds 1-7; 80% wheat flour; 19.9-10% molasses. These components are thoroughly mixed to form a bait shape as required. Edible bait can be dispersed to places where sanitary pests infect, such as domestic or industrial places, such as kitchens, hospitals or shops or outdoor areas, to control the pests by oral ingestion.

All documents mentioned in the present invention are incorporated by reference in this application, as if each document was individually incorporated by reference. In addition, it should be understood that after reading the above teaching content of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of the present application.

Claims (14)

1. A compound having a structure represented by formula (A), or an optical isomer, cis-trans isomer of the compound, or a salt thereof:

   

   In formula (A):

   R ₁ and R ₂ are each independently H, substituted or unsubstituted C _1-6 alkyl, allyl, benzyl, substituted or unsubstituted C _1-4 alkoxy-C _1-6 alkyl, Substituted or unsubstituted C _1-6 alkyl-carbonyl, substituted or unsubstituted C _1-4 alkoxy-carbonyl or phenoxycarbonyl; or R ₁ and R ₂ together form -CH ₂ -CH ₂ -or- CH ₂ -CH ₂ -CH _2- ;

   Each R _{3 is} independently hydrogen, a substituted or unsubstituted C _1-4 alkyl group, a halogen atom, a substituted or unsubstituted 6 to 10 membered aromatic ring group, or a substituted or unsubstituted 5 to 6 membered heterocyclic ring;

   R ₄ , R ₅ , R ₆ , R ₇ , R ₈ and R ₉ are each independently hydrogen, fluorine, C _1-4 alkyl, substituted or unsubstituted 6 to 10 membered aromatic ring group, or substituted or unsubstituted A 5- to 6-membered heterocyclic ring; or a combination of one of R ₄ , R ₅ , R ₈ and R ₉ and R ₆ or R ₇ constitutes a substituted or unsubstituted 6 to 10-membered aromatic ring group, or a substituted or unsubstituted Substituted 5-6 membered heterocyclic ring;

   Each R _{10 is} independently C _1-4 alkyl or C _1-4 alkoxy;

   Z is selected from S, O or NH;

   Wherein, the above-mentioned substitution means that the hydrogen atom is replaced by a group selected from the group consisting of a halogen atom, a C _1-6 alkyl group or a halogenated C _1-6 alkyl group, a C _1-6 alkoxy group, or a halogenated C group. _1-6 alkoxy, C _2-6 alkenyl, C _2-6 alkynyl, halogenated C _2-6 alkenyl, halogenated C _2-6 alkynyl, C _1-4 alkoxy-C _1-6 alkyl, C _1-6 alkoxy-carbonyl, C _2-6 alkynyl-carbonyl, C _2-6 alkenyl-carbonyl.
2. The compound according to claim 1, or an optical isomer, cis-trans isomer, or a salt thereof, wherein R ₁ and R ₂ are each independently hydrogen or C _1-4 alkyl.
3. The compound according to claim 1, or an optical isomer, cis-trans isomer, or a salt thereof, wherein each R _{3 is} independently hydrogen, a C _1-3 alkyl group, or a halogen atom. .
4. The compound according to claim 1, or an optical isomer, cis-trans isomer or a salt thereof, wherein R ₄ , R ₅ , R ₆ , R ₇ , R ₈ and R ₉ are respectively Independently is hydrogen, fluorine or C _1-4 alkyl.
5. The compound according to claim 1, or an optical isomer, cis-trans isomer or a salt thereof, wherein each R _{10 is} independently a C _1-2 alkyl group or a C _1-2 Alkoxy.
6. The compound according to claim 1, wherein Z is S, or an optical isomer, cis-trans isomer of the compound, or a salt thereof.
7. A compound having a structure represented by formula (B), or an optical isomer, cis-trans isomer of the compound, or a salt thereof:

   

   In formula (B):

   R ₁ and R ₂ are each independently H, substituted or unsubstituted C _1-6 alkyl, allyl, benzyl, substituted or unsubstituted C _1-4 alkoxy-C _1-6 alkyl, Substituted or unsubstituted C _1-6 alkyl-carbonyl, substituted or unsubstituted C _1-4 alkoxy-carbonyl or phenoxycarbonyl; or R ₁ and R ₂ together form -CH ₂ -CH ₂ -or- CH ₂ -CH ₂ -CH _2- ;

   Each R _{3 is} independently hydrogen, a substituted or unsubstituted C _1-4 alkyl group, a halogen atom, a substituted or unsubstituted 6 to 10 membered aromatic ring group, or a substituted or unsubstituted 5 to 6 membered heterocyclic ring;

   R ₄ , R ₅ , R ₆ , R ₇ , R ₈ and R ₉ are each independently hydrogen, fluorine, C _1-4 alkyl, substituted or unsubstituted 6 to 10 membered aromatic ring group, or substituted or unsubstituted A 5- to 6-membered heterocyclic ring; or a combination of one of R ₄ , R ₅ , R ₈ and R ₉ and R ₆ or R ₇ constitutes a substituted or unsubstituted 6 to 10-membered aromatic ring group, or a substituted or unsubstituted Substituted 5-6 membered heterocyclic ring;

   Each R _{10 is} independently C _1-4 alkyl or C _1-4 alkoxy;

   Z is selected from S, O or NH;

   Wherein, the above-mentioned substitution means that the hydrogen atom is replaced by a group selected from the group consisting of a halogen atom, a C _1-6 alkyl group or a halogenated C _1-6 alkyl group, a C _1-6 alkoxy group, or a halogenated C group. _1-6 alkoxy, C _2-6 alkenyl, C _2-6 alkynyl, halogenated C _2-6 alkenyl, halogenated C _2-6 alkynyl, C _1-4 alkoxy-C _1-6 alkyl, C _1-6 alkoxy-carbonyl, C _2-6 alkynyl-carbonyl, C _2-6 alkenyl-carbonyl.
8. An insecticide composition comprising 0.001-99.99% by weight of component (a) and component (b); wherein,

   Component (a) is a compound according to any one of claims 1 to 6, or an optical isomer, cis-trans isomer or a salt thereof; and / or a compound according to claim 7, or Optical isomers, cis-trans isomers, or salts thereof of the compounds;

   Ingredient (b) is a pesticidely acceptable carrier and / or excipient.
9. The insecticide composition according to claim 8, wherein the insecticide composition is used to kill or prevent a pest selected from the group consisting of Coleoptera, Lepidoptera, Hemiptera, Orthoptera , Isoptera, or Diptera insects.
10. An insecticidal and / or pest control method comprising applying one or more of the following to a plant body that has suffered or is likely to be exposed to pests, the surrounding soil, or the environment:

    The compound according to any one of claims 1-6, or an optical isomer, a cis-trans isomer of the compound, or a salt thereof;

    The compound according to claim 7, or an optical isomer, cis-trans isomer of the compound, or a salt thereof;

    The insecticide composition of claim 8;

    The plant body, the surrounding soil, or the environment is optionally illuminated with light having a wavelength of 310-380 nm.
11. The compound according to any one of claims 1 to 6, or an optical isomer, cis-trans isomer, or a salt thereof; the compound according to claim 7, or an optical isomer of the compound , A cis-trans isomer or a salt thereof; or the use of the insecticide composition according to claim 8 in the preparation of an insecticide composition.
12. The compound according to any one of claims 1 to 6, or the use of an optical isomer, cis-trans isomer or a salt of the compound, wherein the compound, or the optical Isomers, cis-trans isomers, or salts thereof after irradiation with light at a wavelength of 310-380 nm generate the compound according to claim 7, or optical isomers, cis-trans isomers, or salts thereof;

    

    Of the various types:

    R ₁ and R ₂ are each independently H, substituted or unsubstituted C _1-6 alkyl, allyl, benzyl, substituted or unsubstituted C _1-4 alkoxy-C _1-6 alkyl, Substituted or unsubstituted C _1-6 alkyl-carbonyl, substituted or unsubstituted C _1-4 alkoxy-carbonyl or phenoxycarbonyl; or R ₁ and R ₂ together form -CH ₂ -CH ₂ -or- CH ₂ -CH ₂ -CH _2- ;

    Each R _{3 is} independently hydrogen, a substituted or unsubstituted C _1-4 alkyl group, a halogen atom, a substituted or unsubstituted 6 to 10 membered aromatic ring group, or a substituted or unsubstituted 5 to 6 membered heterocyclic ring;

    R ₄ , R ₅ , R ₆ , R ₇ , R ₈ and R ₉ are each independently hydrogen, fluorine, C _1-4 alkyl, substituted or unsubstituted 6 to 10 membered aromatic ring group, or substituted or unsubstituted A 5- to 6-membered heterocyclic ring; or a combination of one of R ₄ , R ₅ , R ₈ and R ₉ and R ₆ or R ₇ constitutes a substituted or unsubstituted 6 to 10-membered aromatic ring group, or a substituted or unsubstituted Substituted 5-6 membered heterocyclic ring;

    Each R _{10 is} independently C _1-4 alkyl or C _1-4 alkoxy;

    Z is selected from S, O or NH;

    Wherein, the above-mentioned substitution means that the hydrogen atom is replaced by a group selected from the group consisting of a halogen atom, a C _1-6 alkyl group or a halogenated C _1-6 alkyl group, a C _1-6 alkoxy group, or a halogenated C group. _1-6 alkoxy, C _2-6 alkenyl, C _2-6 alkynyl, halogenated C _2-6 alkenyl, halogenated C _2-6 alkynyl, C _1-4 alkoxy-C _1-6 alkyl, C _1-6 alkoxy-carbonyl, C _2-6 alkynyl-carbonyl, C _2-6 alkenyl-carbonyl.
13. The compound according to claim 7, or the use of an optical isomer, cis-trans isomer or a salt thereof, wherein the compound, or the optical isomer, cis The anti-isomer or salt thereof generates a compound according to any one of claims 1-6, or an optical isomer, cis-trans isomer of the compound under light having a wavelength of more than 493 nm (preferably 493-760 nm). Body or salt thereof;

    

    Of the various types:

    R ₁ and R ₂ are each independently H, substituted or unsubstituted C _1-6 alkyl, allyl, benzyl, substituted or unsubstituted C _1-4 alkoxy-C _1-6 alkyl, Substituted or unsubstituted C _1-6 alkyl-carbonyl, substituted or unsubstituted C _1-4 alkoxy-carbonyl or phenoxycarbonyl; or R ₁ and R ₂ together form -CH ₂ -CH ₂ -or- CH ₂ -CH ₂ -CH _2- ;

    Each R _{3 is} independently hydrogen, a substituted or unsubstituted C _1-4 alkyl group, a halogen atom, a substituted or unsubstituted 6 to 10 membered aromatic ring group, or a substituted or unsubstituted 5 to 6 membered heterocyclic ring;

    R ₄ , R ₅ , R ₆ , R ₇ , R ₈ and R ₉ are each independently hydrogen, fluorine, C _1-4 alkyl, substituted or unsubstituted 6 to 10 membered aromatic ring group, or substituted or unsubstituted A 5- to 6-membered heterocyclic ring; or a combination of one of R ₄ , R ₅ , R ₈ and R ₉ and R ₆ or R ₇ constitutes a substituted or unsubstituted 6 to 10-membered aromatic ring group, or a substituted or unsubstituted Substituted 5-6 membered heterocyclic ring;

    Each R _{10 is} independently C _1-4 alkyl or C _1-4 alkoxy;

    Z is selected from S, O or NH;

    Wherein, the above-mentioned substitution means that the hydrogen atom is replaced by a group selected from the group consisting of a halogen atom, a C _1-6 alkyl group or a halogenated C _1-6 alkyl group, a C _1-6 alkoxy group, or a halogenated C group. _1-6 alkoxy, C _2-6 alkenyl, C _2-6 alkynyl, halogenated C _2-6 alkenyl, halogenated C _2-6 alkynyl, C _1-4 alkoxy-C _1-6 alkyl, C _1-6 alkoxy-carbonyl, C _2-6 alkynyl-carbonyl, C _2-6 alkenyl-carbonyl.
14. The method for preparing a compound according to any one of claims 1-6, or an optical isomer, a cis-trans isomer of the compound, or a salt thereof, characterized in that:

    (a) When R1 is the same as R2, the method includes the step of: reacting a compound of formula (1g) with a compound of formula 01 or 01 'in an inert solvent to obtain a compound of formula (A);

    

    In the above formulas, the definition of each group is the same as above and R1 and R2 are the same;

    or

    (b) when R1 and R2 are different, the method includes the steps of: reacting a compound of formula (1g) with a compound of formula 01 in an inert solvent to obtain a compound of formula (1h); and in an inert solvent, (1h) reacting a compound with a compound of formula 01 'to obtain a compound of formula (A);

    

    In the above formulas, the definition of each group is the same as above and R1 and R2 are different;

    or

    (c) When R1 and R2 are different, the method includes the step of: reacting a compound of formula (1g) with a compound of formula 01 and a compound of formula 01 'in an inert solvent to obtain a compound of formula (A);

    

    In the above formulae, the definition of each group is the same as above and R1 and R2 are different.

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