Diphenyl ether ester compound, preparation method thereof and application of diphenyl ether ester compound in preparation of pesticide bactericide

Abstract

The invention discloses a diphenyl ether ester compound, a preparation method thereof and application of the diphenyl ether ester compound in preparation of pesticide bactericides, and belongs to the field of pesticide bactericides. The diphenyl ether ester compound has a structure as shown in a formula (I). The diphenyl ether ester compound disclosed by the invention has the advantages of novel action structure, low toxicity and efficient bactericidal activity, and has a great application prospect as a bactericide. # imgabs0 #

Description

Technical Field

[0001] The invention relates to the field of pesticide bactericides, and specifically designs a class of diphenyl ether ester compounds with bactericidal activity, a preparation method thereof, and an application thereof in the preparation of pesticide bactericides. Background Art

[0002] As the mainstream fungicide in the market, succinate dehydrogenase inhibitor (SDHI) fungicide has many advantages such as high efficiency, low toxicity and broad spectrum. The target site is specific, acting on succinate dehydrogenase (SDH) in the tricarboxylic acid cycle. As an inhibitor of pathogen respiration, it interferes with the normal function of mitochondria, thereby limiting the growth of the colony. However, the long-term use of a single type of fungicide has led to an increasing number of resistant strains, so it is of great significance to develop new varieties of efficient and broad-spectrum fungicides. The skeleton of SDHI fungicide is constantly optimized, guided by amide fragments, and many fragments such as hydrazides and hydrazones have been studied in large quantities. However, the toxicity of this type of fragment is relatively high, and as a green agent development era, this type of skeleton has some disadvantages. However, ester fragments are of great significance in the skeleton structure of herbicides, fungicides, insecticides, etc. due to their own easy degradation and metabolism properties. Therefore, the purpose of this patent is to provide a new type of SDH fungicide candidate with ester group as the pharmacological fragment.

[0003] In the previous work of our research group, a class of diphenyl ether phenyl propyl ester compounds for controlling rice blast fungi were designed and synthesized (CN113683509B; Nature Plants, 2024, 4 (10): 618-632.). This class of compounds is mainly used to control rice blast fungi, interfering with the interaction between MoErs1 of rice blast fungi and OsRD21 of rice, thereby controlling the infection of rice blast fungi, specifically taking FY21001 as an example. The main feature of this series of compounds is that they contain phenyl propyl ester fragments, while the structure of formula I shown in the patent contains methyl ester fragments, which are different from phenyl propyl esters. In addition, it is worth noting that the control spectrum of FY21001 is narrow and it is effective against rice blast. Based on this, we designed and synthesized the structure shown in formula I in order to obtain diphenyl ether ester compounds with a wider control spectrum and higher efficiency. Summary of the invention

[0004] The purpose of the present invention is to provide a diphenyl ether ester compound and a preparation method thereof and application thereof in the preparation of pesticide fungicides. The compound of the present invention has a very high control effect on fungal diseases on crops.

[0005] In order to achieve the above object, the present invention provides the following technical solutions:

[0006] In the first aspect, the present invention claims a diphenyl ether ester compound, a diphenyl ether ester compound, the compound having a structure shown in formula (I),

[0007]

[0008] Wherein, in formula (I),

[0009] R 1 is selected from H, halogen, hydroxy, amino, mercapto, cyano, nitro, C1-C8 alkyl, C1-C8 alkyl substituted by halogen, C1-C8 alkoxy, C1-C8 alkoxy substituted by halogen, phenyl substituted or unsubstituted by C1-C8 alkyl and / or halogen, benzyl, naphthyl, pyridyl, furyl, thienyl, pyrazolyl, imidazolyl, phenyl substituted by C1-C8 alkoxy, benzyl, naphthyl, pyridyl, furyl, thienyl, pyrazolyl, imidazolyl, C3-C8 heterocycle substituted or unsubstituted by C1-C8 alkyl and / or halogen;

[0010] R 2 is selected from H, halogen, hydroxy, amino, mercapto, cyano, nitro, C1-C8 alkyl, C1-C8 alkyl substituted by halogen, C1-C8 alkoxy, C1-C8 alkoxy substituted by halogen, phenyl substituted or unsubstituted by C1-C8 alkyl and / or halogen, benzyl, naphthyl, pyridyl, furyl, thienyl, pyrazolyl, imidazolyl, phenyl substituted by C1-C8 alkoxy, benzyl, naphthyl, pyridyl, furyl, thienyl, pyrazolyl, imidazolyl, C3-C8 heterocycle substituted or unsubstituted by C1-C8 alkyl and / or halogen;

[0011] Q is selected from phenyl, naphthyl, pyrrolyl, furanyl, tetrahydrofuranyl, thienyl, thiazolyl, imidazolyl, pyrazolyl, oxazolyl, valerolactamyl, pyridyl, pyranyl, piperidinyl, piperazinyl, pyridazinyl, pyrimidinyl, caprolactamyl, C3-C8 heterocycle;

[0012] R 3 is selected from H, halogen, hydroxy, amino, mercapto, cyano, nitro, C1-C8 alkyl, C1-C8 alkyl substituted by halogen, C1-C8 alkoxy, C1-C8 alkoxy substituted by halogen, phenyl substituted or unsubstituted by C1-C8 alkyl and / or halogen, benzyl, naphthyl, pyridyl, furyl, thienyl, pyrazolyl, imidazolyl, phenyl substituted by C1-C8 alkoxy, benzyl, naphthyl, pyridyl, furyl, thienyl, pyrazolyl, imidazolyl, C3-C8 heterocycle substituted or unsubstituted by C1-C8 alkyl and / or halogen;

[0013] R 1 ,R 2 ,R 3 It is located at any substitution position of the aromatic ring, either monosubstituted or polysubstituted.

[0014] Further, in formula (I),

[0015] R1 Selected from H, 4-OH, 4-NH2, 4-F, 4-CF 3、 3,5-di-F, 2,4-di-F, 4-CN;

[0016] R 2 Selected from H, 3-F, 3-Cl, 2-F, 2-Cl, 2-CF 3、 2-CHF2, 3-CF3;

[0017] Q is selected from benzene ring, 2-thiophene, cyclohexane, 2-pyridine;

[0018] R 3 Selected from H, 2-F, 2-Cl, 2-CH3, 2-CH2CH3, 3-F, 3-CN, 3-CH3, 4-F, 4-Cl, 4-CF3, 4-CN, 4-OCH3, 4-CH3, 2,5-di-CH3, 2,6-di-CH3, 3,4-di-CH3, 3,5-di-CH3, 5-F, 3-OH;

[0019] R 1 ,R 2 ,R 3 It is located at any substitution position of the aromatic ring, either monosubstituted or polysubstituted.

[0020] Furthermore, the compounds of the present invention are specifically, but not limited to, the following compounds:

[0021] Compound 1aa: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is H;

[0022] Compound 1ae: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 2-F;

[0023] Compound 1af: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 2-Cl;

[0024] Compound 1ag: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 2-CH3;

[0025] Compound 1ah:R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 2-CH2CH3;

[0026] Compound 1ai:R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 3-F;

[0027] Compound 1aj: R 1is 4-OH, R2 is H, Q is a benzene ring, and R3 is 3-CN;

[0028] Compound 1ak:R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 3-CH3;

[0029] Compound 1al:R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 4-F;

[0030] Compound 1am: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 4-Cl;

[0031] Compound 1an:R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 4-CF3;

[0032] Compound 1ao: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 4-CN;

[0033] Compound 1ap:R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 4-OCH3; Compound 1aq: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 4-CH3;

[0034] Compound 1ar:R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 2,5-di-CH3; Compound 1as: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 2,6-di-CH3; Compound 1at: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 3,4-di-CH3; Compound 1au: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 3,5-di-CH3; Compound 1av: R 1 is 4-OH, R2 is 3-F, Q is a benzene ring, and R3 is H;

[0035] Compound 1aw:R 1 is 4-OH, R2 is 3-F, Q is a benzene ring, and R3 is 2-F;

[0036] Compound 1ax: R 1 is 4-OH, R2 is 3-F, Q is a benzene ring, and R3 is 2-Cl;

[0037] Compound 1ay: R 1 is 4-OH, R2 is 3-F, Q is a benzene ring, and R3 is 4-F;

[0038] Compound 1az: R 1 is 4-OH, R2 is 3-Cl, Q is a benzene ring, and R3 is H;

[0039] Compound 1ba: R 1 is 4-OH, R2 is 3-Cl, Q is a benzene ring, and R3 is 2-F;

[0040] Compound 1bb: R 1 is 4-OH, R2 is 3-Cl, Q is a benzene ring, and R3 is 2-Cl;

[0041] Compound 1bc: R 1 is 4-NH2, R2 is 3-F, Q is a benzene ring, and R3 is 2-F;

[0042] Compound 1bd: R 1 is 4-NH2, R2 is 3-F, Q is a benzene ring, and R3 is 4-F;

[0043] Compound 1be:R 1 is H, R2 is 3-F, Q is a benzene ring, and R3 is 4-F;

[0044] Compound 1bf: R 1 is H, R2 is 3-F, Q is a benzene ring, and R3 is 2-F;

[0045] Compound 1bg: R 1 is H, R2 is 3-Cl, Q is a benzene ring, and R3 is 4-F;

[0046] Compound 1bh: R 1 is H, R2 is 3-Cl, Q is a benzene ring, and R3 is 2-F;

[0047] Compound 1bi: R 1 is H, R2 is 2-F, Q is a benzene ring, and R3 is 4-F;

[0048] Compound 1bj: R 1 is H, R2 is 2-F, Q is a benzene ring, and R3 is 2-F;

[0049] Compound 1bk: R 1 is H, R2 is 2-Cl, Q is a benzene ring, and R3 is 4-F;

[0050] Compound 1bl: R 1 is H, R2 is 2-Cl, Q is a benzene ring, and R3 is 2-F;

[0051] Compound 1bm: R 1 is H, R2 is 2-CF3, Q is a benzene ring, and R3 is 2-F;

[0052] Compound 1bn: R 1 is H, R2 is 2-CHF2, Q is a benzene ring, and R3 is 2-F;

[0053] Compound 1bo:R 1 is 4-F, R2 is 3-F, Q is a benzene ring, and R3 is 2-F;

[0054] Compound 1bp:R 1 is 4-F, R2 is 3-F, Q is 2-thiophene, and R3 is 2-F;

[0055] Compound 1bq: R 1 is 4-F, R2 is 3-F, Q is cyclohexane, and R3 is H;

[0056] Compound 1br:R 1 is 4-F, R2 is 3-F, Q is 2-pyridine, and R3 is 5-F;

[0057] Compound 1bs:R 1 is 4-F, R2 is 3-F, Q is 2-pyridine, and R3 is 3-F;

[0058] Compound 1bt:R 1 is 4-F, R2 is 3-F, Q is 2-pyridine, and R3 is 3-OH;

[0059] Compound 1bu:R 1 is 4-CF3, R2 is 3-F, Q is a benzene ring, and R3 is 2-F;

[0060] Compound 1bv: R 1 is 4-CF3, R2 is 3-F, Q is 2-thiophene, and R3 is 2-F;

[0061] Compound 1bw: R 1 is 4-CF3, R2 is 3-F, Q is cyclohexane, and R3 is H;

[0062] Compound 1bx: R 1 is 4-CF3, R2 is 3-F, Q is 2-pyridine, and R3 is 5-F;

[0063] Compound 1by: R 1 is 4-CF3, R2 is 3-F, Q is 2-pyridine, and R3 is 3-F;

[0064] Compound 1bz: R 1 is 4-CF3, R2 is 3-F, Q is 2-pyridine, and R3 is 3-OH; Compound 1ca: R 1 is 3,5-di-F, R2 is 3-F, Q is a benzene ring, and R3 is 2-F;

[0065] Compound 1cb: R 1 is 3,5-di-F, R2 is 3-F, Q is 2-thiophene, and R3 is 2-F; Compound 1cc: R 1 is 3,5-di-F, R2 is 3-F, Q is cyclohexane, and R3 is H;

[0066] Compound 1cd: R 1 is 3,5-di-F, R2 is 3-F, Q is 2-pyridine, and R3 is 5-F; Compound 1ce: R 1 is 3,5-di-F, R2 is 3-F, Q is 2-pyridine, and R3 is 3-F; Compound 1cf: R 1 is 3,5-di-F, R2 is 3-F, Q is 2-pyridine, and R3 is 3-OH; Compound 1cg: R 1 is 2,4-di-F, R2 is 3-F, Q is a benzene ring, and R3 is 2-F;

[0067] Compound 1ch: R 1 is 2,4-di-F, R2 is 3-F, Q is 2-thiophene, and R3 is 2-F; Compound 1ci: R 1 is 2,4-di-F, R2 is 3-F, Q is cyclohexane, and R3 is H;

[0068] Compound 1cj: R 1 is 2,4-di-F, R2 is 3-F, Q is 2-pyridine, and R3 is 5-F; Compound 1ck: R 1 is 2,4-di-F, R2 is 3-F, Q is 2-pyridine, and R3 is 3-F; Compound 1cl: R 1 is 2,4-di-F, R2 is 3-F, Q is 2-pyridine, and R3 is 3-OH; compound 1cm: R 1 is 4-OH, R2 is 3-F, Q is 2-thiophene, and R3 is 2-F;

[0069] Compound 1cn: R 1 is 4-OH, R2 is 3-F, Q is cyclohexane, and R3 is H;

[0070] Compound 1co:R 1 is 4-OH, R2 is 3-F, Q is 2-pyridine, and R3 is 5-F;

[0071] Compound 1cp:R 1 is 4-OH, R2 is 3-F, Q is 2-pyridine, and R3 is 3-F;

[0072] Compound 1cq: R 1 is 4-OH, R2 is 3-F, Q is 2-pyridine, and R3 is 3-OH;

[0073] Compound 1cr:R 1 is 4-CN, R2 is 3-F, Q is a benzene ring, and R3 is 2-F;

[0074] Compound 1cs:R 1 is 4-CN, R2 is 3-F, Q is 2-thiophene, and R3 is 2-F;

[0075] Compound 1ct: R 1 is 4-CN, R2 is 3-F, Q is cyclohexane, and R3 is H;

[0076] Compound 1cu:R 1 is 4-CN, R2 is 3-F, Q is 2-pyridine, and R3 is 5-F;

[0077] Compound 1cv: R 1 is 4-CN, R2 is 3-F, Q is 2-pyridine, and R3 is 3-F;

[0078] Compound 1cw: R 1 is 4-CN, R2 is 3-F, Q is 2-pyridine, and R3 is 3-OH;

[0079] Compound 1cx: R 1 is 4-F, R2 is 2-F, Q is a benzene ring, and R3 is 2-F;

[0080] Compound 1cy:R 1 is 4-CF3, R2 is 2-F, Q is a benzene ring, and R3 is 2-F;

[0081] Compound 1cz:R 1 is 3,5-di-F, R2 is 2-F, Q is a benzene ring, and R3 is 2-F;

[0082] Compound 1da:R 1 is 2,4-di-F, R2 is 2-F, Q is a benzene ring, and R3 is 2-F;

[0083] Compound 1db: R 1 is 4-CN, R2 is 2-F, Q is a benzene ring, and R3 is 2-F;

[0084] Compound 1dc: R 1 is 4-CF3, R2 is 3-CF3, Q is a benzene ring, and R3 is 2-F;

[0085] Compound 1dd: R 1 It is 4-CF3, R2 is 2-CF3, Q is a benzene ring, and R3 is 2-F.

[0086] The present invention will be described in detail below by way of examples. In the following examples, unless otherwise specified, all the raw materials used are commercially available.

[0087] The terms of the present invention are explained below.

[0088] “C1-C 12 The term "alkyl" refers to an alkyl group having 1 to 12 carbon atoms, including a straight-chain alkyl group, a branched alkyl group or a cycloalkyl group, for example, a straight-chain alkyl group, a branched alkyl group or a cycloalkyl group having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, for example, a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a tert-butyl group, a n-pentyl group, an isopentyl group, a n-hexyl group, a cyclopropyl group, a methylcyclopropyl group, an ethylcyclopropyl group, a cyclobutyl group, a methylcyclobutyl group, an ethylcyclobutyl group, a cyclopentyl group, a methylcyclopentyl group, an ethylcyclopentyl group, a cyclohexyl group, a methylcyclohexyl group, an ethylcyclohexyl group and the like.

[0089] In the present invention, "C1-C 12 The term "alkoxy" refers to an alkoxy group having 1 to 12 carbon atoms, for example, methyloxy, ethyloxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, tert-butyloxy, n-pentyloxy, isopentyloxy, n-hexyloxy, cyclopropyloxy, methylcyclopropyloxy, ethylcyclopropyloxy, cyclopentyloxy, methylcyclopentyloxy and cyclohexyloxy.

[0090] In the present invention, "C1-C 12 The term "alkylamino" refers to an amino group substituted by an alkyl group having 1 to 12 carbon atoms, which may be substituted by a single or double alkyl group, wherein when substituted by a double alkyl group, the alkyl groups may be the same and / or different.

[0091] In the present invention, "C1-C 12 The term "alkylmercapto" refers to an alkylmercapto group having 1 to 12 carbon atoms, for example, methylmercapto, ethylmercapto, n-propylmercapto, isopropylmercapto, n-butylmercapto, isobutylmercapto, tert-butylmercapto, n-pentylmercapto, isopentylmercapto, n-hexylmercapto, cyclopropylmercapto, methylcyclopropylmercapto, ethylcyclopropylmercapto, cyclopentylmercapto, methylcyclopentylmercapto, cyclohexylmercapto, and the like.

[0092] In the present invention, "C2-C6 alkenyl" means a monoalkenyl, diene or polyalkenyl group having 1 to 6 carbon atoms, for example, vinyl, n-propenyl, isopropenyl, n-butenyl, n-dibutenyl, isobutenyl, tert-butenyl, n-pentenyl, 1,3-pentadienyl, isopentenyl, n-hexenyl, 1,3-hexadienyl, cyclopropenyl, methylcyclopropenyl, ethylcyclopropenyl, cyclopentenyl, methylcyclopentenyl and cyclohexenyl.

[0093] In the present invention, "C2-C6 alkynyl" means a monoalkynyl, dialkynyl or polyalkynyl group having 1 to 6 carbon atoms, for example, ethynyl, n-propynyl, isopropynyl, n-butynyl, n-dibutynyl, isobutynyl, tert-butynyl, n-pentynyl, 1,3-pentadiynyl, isopentynyl, n-hexynyl, 1,3-hexadiynyl, cyclopropynyl, methylcyclopropynyl, ethylcyclopropynyl, cyclopentynyl, methylcyclopentynyl and cyclohexynyl.

[0094] In the present invention, the “substituted or unsubstituted C3-C8 heterocycle” refers to a heterocycle containing at least one element of N, O and S.

[0095] In the present invention, "halogen" means at least one element selected from the group consisting of fluorine, chlorine, bromine and iodine.

[0096] In a second aspect, the present invention claims a method for preparing the compound as described above, the method comprising steps AC in the following synthetic route:

[0097]

[0098] In the above synthetic route, the substituents in the compounds represented by formula II, formula III and formula IV have the same definitions as the corresponding groups in the compound represented by formula (I) of the present invention.

[0099] Furthermore, in the above-mentioned preparation method, in step A, the synthesis method of formula III is: dissolving raw material II and alkali in a solvent, adding a phenol derivative, and after the reaction is completed, extracting with an organic solvent, washing with saturated brine, combining the organic layers, drying and concentrating, and column chromatography to obtain intermediate III;

[0100] In step B, the synthesis method of formula IV is: dissolving intermediate III in a solvent, adding sodium hydroxide aqueous solution, adding dilute hydrochloric acid to the reaction system after the reaction is completed, and a large amount of precipitate can be observed, followed by suction filtration, washing with clean water, and drying to obtain intermediate IV;

[0101] In step C, the synthesis method of the target product is: dissolving intermediate IV in a solvent, adding substituted or unsubstituted heterocyclic benzyl alcohol and a condensing agent, after the reaction is completed, extracting with an organic solvent, washing with a saturated sodium bicarbonate aqueous solution, combining the organic layers, drying and concentrating, and column chromatography to obtain the target product.

[0102] Furthermore, the solvent described in reaction A is selected from one of N,N-dimethylformamide, acetonitrile, N,N-dimethylacetamide, N,N-diethylacetamide, 1,4-dioxane, toluene, and dimethyl sulfoxide; preferably, it is selected from one of N,N-dimethylformamide and N,N-dimethylacetamide; the reaction temperature is 25°C-120°C, preferably, the reaction temperature is 60°C-90°C; the base used is selected from one of potassium carbonate, sodium carbonate, sodium hydroxide, potassium tert-butoxide, sodium tert-butoxide, triethylamine, pyridine, sodium hydride, potassium hydroxide, and lithium hydroxide; preferably, it is selected from one of potassium carbonate and potassium tert-butoxide;

[0103] The solvent in reaction B is selected from one of methanol, ethanol, tetrahydrofuran, 1,4-dioxane, and acetonitrile; preferably, it is selected from one of methanol, ethanol or tetrahydrofuran; the reaction temperature is 25°C-120°C, preferably, the reaction temperature is 60°C-70°C;

[0104] The solvent in reaction C is selected from one of acetonitrile, 1,4-dioxane, dichloromethane, and tetrahydrofuran; preferably, it is selected from one of dichloromethane and tetrahydrofuran; the reaction temperature is 25°C-50°C, preferably, the reaction temperature is 30°C; the condensing agent used is selected from one of a combination of DMAP and EDCI, and a combination of DIAD and triphenylphosphine.

[0105] In addition to the above methods, those skilled in the art can obtain other suitable methods for preparing the derivatives represented by formula (I) based on the compound structures provided by the present invention in combination with synthesis methods in the field of chemistry, which are not described in detail herein.

[0106] In the third aspect, the present invention claims the use of the above-mentioned compounds in the preparation of pesticides and fungicides for preventing and controlling plant diseases. Studies have shown that the diphenyl ether ester compounds of the present invention have significant effects in inhibiting the function of the target succinate dehydrogenase (SDH) in pathogenic fungi; they can be used to prevent and control pathogenic fungi and / or pathogenic bacteria.

[0107] Further, in the above-mentioned application, the plant disease is selected from at least one of the bacterial diseases white leaf blight, bacterial base rot, bacterial brown streak, bacterial streak, bacterial brown spot, bacterial wilt, and bacterial stem rot; or at least one of the fungal diseases damping-off, root rot, downy mildew, white rust, blight, cotton blight, fusarium head blight, powdery mildew, anthracnose, leaf spot, black spot, smut, rust, sheath blight, damping-off, gray mold, and rapeseed sclerotinia.

[0108] In a fourth aspect, the present invention seeks protection for a pesticide fungicide, which consists of an active ingredient and excipients, wherein the active ingredient includes at least one of the above-mentioned diphenyl ether ester compounds; the content of the active ingredient is 1-99.9999 weight %; preferably, the content of the active ingredient is 1-50 weight %; preferably, the content of the active ingredient is 20-40 weight %.

[0109] Furthermore, the formulation of the pesticide fungicide is selected from one of emulsifiable concentrate, suspension, wettable powder, dust, granule, aqueous solution, poison bait, mother liquor and mother powder.

[0110] The room temperature described in the present invention is 25±10° C., but is not limited thereto.

[0111] The present invention has the following advantages:

[0112] First, the compounds of the present invention are brand-new molecular skeletons of targeted SDH inhibitors, which provide a new direction for the subsequent research and development of new drugs. This type of brand-new molecular skeleton has excellent inhibitory activity against the tested pathogens. The inhibitory activity of some compounds against rice sheath blight and tomato gray mold is better than that of the commercial agent boscalid. At the same time, since it is a brand-new molecular skeleton, it is expected to overcome the resistance problem of pathogens. The compounds of the present invention have a simple structure, are easy to prepare, have high activity, and show excellent commercial application potential. BRIEF DESCRIPTION OF THE DRAWINGS

[0113] Figure 1 The results show the effect of agent 1ae on the control of rice sheath blight in rice leaves; A: lesion image of rice leaves; B: lesion area (DLA) evaluated by Image J software; one-way ANOVA, data compared with the control group or data compared with boscalid, ****P<0.0001; "ns" represents P≥0.05.

[0114] Figure 2 The results of agent 1ae on controlling Botrytis cinerea on tomato fruits; A: picture of tomato fruits infected by Botrytis cinerea; B: relative control effect of the agent (%). DETAILED DESCRIPTION

[0115] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0116] Example 1: Synthesis of compounds 1aa-1au

[0117]

[0118] Synthesis of intermediate III-1: The initial raw materials hydroquinone (15 mmol) and potassium carbonate (12 mmol) were dissolved in DMF, stirred at room temperature for about 15 min, and then p-fluorobenzonitrile II-1 (10 mmol) was added and stirred at 80°C for about 6 h. The reaction was monitored by TLC. After the reaction was completed, water (200 ml) was added to the reaction system, and ethyl acetate (100 mL) was extracted three times. The organic layers were combined, and the organic phase was washed three times with saturated brine (200 ml). The organic phase was dried, concentrated, and column chromatography was performed to obtain intermediate III-1.

[0119] Synthesis of intermediate IV-1: Dissolve intermediate III-1 (10 mmol) in tetrahydrofuran, reflux and stir evenly, gradually add sodium hydroxide solution (4N), continue reflux reaction for 5 hours, and monitor the reaction by TLC until completion. After cooling to room temperature, gradually add dilute hydrochloric acid (2N) to the reaction system and stir until precipitation occurs, filter, wash with clean water 3 times, and dry to obtain the key intermediate IV-1.

[0120] Synthesis of target product 1aa:

[0121]

[0122] The key intermediate IV-1 (1 mmol), DIAD (diisopropyl azodicarboxylate) (1 mmol), and Ph3P (triphenylphosphine) (1 mmol) were weighed into a 10 mL Shrek tube. After nitrogen replacement, benzyl alcohol (1 mmol) was added, followed by tetrahydrofuran to dissolve. After reacting at room temperature for 12 h, TLC was monitored until the reaction was completed. Saturated aqueous sodium bicarbonate solution was added to the reaction system, and extracted with DCM (dichloromethane). The organic phase was collected, dried over anhydrous sodium sulfate, and concentrated by column chromatography to obtain the target product 1aa.

[0123] Synthesis of target product 1al:

[0124]

[0125] The key intermediate IV-1 (1 mmol), DIAD (1 mmol), and Ph3P (1 mmol) were weighed into a 10 mL Shrek tube. After nitrogen replacement, p-fluorobenzyl alcohol (1.2 mmol) was added, followed by tetrahydrofuran to dissolve. After reacting at room temperature for 15 h, TLC was used to monitor the completion of the reaction. Saturated aqueous sodium bicarbonate solution was added to the reaction system, extracted with DCM, and the organic phase was collected, dried over anhydrous sodium sulfate, and concentrated by column chromatography to obtain the target product 1al.

[0126] Synthesis of target product 1au:

[0127]

[0128] The key intermediate IV-1 (1 mmol), DIAD (1 mmol), and Ph3P (1 mmol) were weighed into a 10 mL Shrek tube. After nitrogen replacement, 3,5-dimethylbenzyl alcohol (1.1 mmol) was added, followed by tetrahydrofuran to dissolve. After reacting at room temperature for 12 h, TLC was used to monitor the completion of the reaction. Saturated aqueous sodium bicarbonate solution was added to the reaction system, extracted with DCM, and the organic phase was collected, dried over anhydrous sodium sulfate, and concentrated by column chromatography to obtain the target product 1au.

[0129] Referring to the above synthesis method, the 3 The target product 1aa-1au can be obtained by derivatives of the fragments.

[0130] Example 2: Synthesis of Compounds 1av-1ay

[0131]

[0132] Synthesis of intermediate III-2: The initial raw materials hydroquinone (15 mmol) and potassium carbonate (12 mmol) were dissolved in DMF, stirred at room temperature for about 15 min, and then 3,4-difluorobenzonitrile II-2 (10 mmol) was added and stirred at 80°C for about 6 h. The reaction was monitored by TLC. After the reaction was completed, water (200 ml) was added to the reaction system, and ethyl acetate (100 mL) was extracted three times. The organic layers were combined, and the organic phase was washed three times with saturated brine (200 ml). The organic phase was dried, concentrated, and column chromatography was performed to obtain intermediate III-2.

[0133] Synthesis of intermediate IV-2: Dissolve intermediate III-2 (10 mmol) in tetrahydrofuran, reflux and stir evenly, gradually add sodium hydroxide solution (4N), continue reflux reaction for 5 hours, and monitor the reaction by TLC until completion. After cooling to room temperature, gradually add dilute hydrochloric acid (2N) to the reaction system and stir until precipitation occurs, filter, wash with clean water 3 times, and dry to obtain key intermediate IV-2.

[0134] Synthesis of target product 1av:

[0135]

[0136] The key intermediate IV-2 (1 mmol), DIAD (1 mmol), and Ph3P (1 mmol) were weighed into a 10 mL Shrek tube. After nitrogen replacement, benzyl alcohol (1.0 mmol) was added, followed by tetrahydrofuran to dissolve. After reacting at room temperature for 12 h, TLC was monitored until the reaction was completed. Saturated aqueous sodium bicarbonate solution was added to the reaction system, extracted with DCM, and the organic phase was collected, dried over anhydrous sodium sulfate, and concentrated by column chromatography to obtain the target product 1av.

[0137] Synthesis of target product 1aw:

[0138]

[0139] The key intermediate IV-2 (1 mmol), DIAD (1 mmol), and Ph3P (1 mmol) were weighed into a 10 mL Shrek tube. After nitrogen replacement, o-fluorobenzyl alcohol (1.2 mmol) was added, followed by tetrahydrofuran dissolution. After reacting at room temperature for 15 h, TLC was monitored until the reaction was completed. Saturated sodium bicarbonate aqueous solution was added to the reaction system, extracted with DCM, and the organic phase was collected, dried over anhydrous sodium sulfate, and concentrated by column chromatography to obtain the target product 1aw.

[0140] Referring to the above synthesis method, the 3 The target products 1aa-1ay can be obtained by derivatives of the fragments.

[0141] Example 3: Synthesis of Compounds 1az-1bb

[0142]

[0143] Synthesis of intermediate III-3: The initial raw materials hydroquinone (15 mmol) and potassium carbonate (12 mmol) were dissolved in DMF, stirred at room temperature for about 15 min, and then 4-fluoro-5-chloro-benzonitrile II-3 (10 mmol) was added and stirred at 80°C for about 6 h. The reaction was monitored by TLC. After the reaction was completed, water (200 ml) was added to the reaction system, and ethyl acetate (100 mL) was extracted three times. The organic layers were combined, and the organic phase was washed three times with saturated brine (200 ml). The organic phase was dried, concentrated, and column chromatography was performed to obtain intermediate III-3.

[0144] Synthesis of intermediate IV-3: Dissolve intermediate III-3 (10 mmol) in tetrahydrofuran, reflux and stir evenly, gradually add sodium hydroxide solution (4N), continue reflux reaction for 5 hours, and monitor the reaction by TLC until completion. After cooling to room temperature, gradually add dilute hydrochloric acid (2N) to the reaction system and stir until precipitation occurs, filter, wash with clean water 3 times, and dry to obtain key intermediate IV-3.

[0145] Synthesis of target product 1az:

[0146]

[0147] The key intermediate IV-3 (1 mmol), DIAD (1 mmol), and Ph3P (1 mmol) were weighed into a 10 mL Shrek tube. After nitrogen replacement, benzyl alcohol (1 mmol) was added, followed by tetrahydrofuran to dissolve. After reacting at room temperature for 12 h, the reaction was monitored by TLC until the end. Saturated aqueous sodium bicarbonate solution was added to the reaction system, extracted with DCM, and the organic phase was collected, dried over anhydrous sodium sulfate, and concentrated by column chromatography to obtain the target product 1az.

[0148] Synthesis of target product 1bb:

[0149]

[0150] The key intermediate IV-3 (1 mmol), DIAD (1 mmol), and Ph3P (1 mmol) were weighed into a 10 mL Shrek tube. After nitrogen replacement, o-chlorobenzyl alcohol (1.2 mmol) was added, followed by tetrahydrofuran dissolution. After reacting at room temperature for 15 h, TLC was monitored until the reaction was completed. Saturated sodium bicarbonate aqueous solution was added to the reaction system, extracted with DCM, and the organic phase was collected, dried over anhydrous sodium sulfate, and concentrated by column chromatography to obtain the target product 1bb.

[0151] Referring to the above synthesis method, the 3 The target product 1az-1bb can be obtained by derivatives of the fragments.

[0152] Example 4: Synthesis of Compounds 1bc-1bd

[0153]

[0154] Synthesis of intermediate III-4: The initial raw materials p-hydroxyaniline (15 mmol) and potassium carbonate (12 mmol) were dissolved in DMF, stirred at room temperature for about 15 min, and then 3,4-difluorobenzonitrile II-4 (10 mmol) was added and stirred at 80°C for about 6 h. The reaction was monitored by TLC. After the reaction was completed, water (200 ml) was added to the reaction system, and ethyl acetate (100 mL) was extracted three times. The organic layers were combined, and the organic phase was washed three times with saturated brine (200 ml). The organic phase was dried, concentrated, and column chromatography was performed to obtain intermediate III-4.

[0155] Synthesis of intermediate IV-4: Dissolve intermediate III-4 (10 mmol) in tetrahydrofuran, reflux and stir evenly, gradually add sodium hydroxide solution (4N), continue reflux reaction for 5 hours, and monitor the reaction by TLC until completion. After cooling to room temperature, gradually add dilute hydrochloric acid (2N) to the reaction system and stir until precipitation occurs, filter, wash with clean water 3 times, and dry to obtain key intermediate IV-4.

[0156] Synthesis of target product 1bc:

[0157]

[0158] The key intermediate IV-4 (1 mmol), DIAD (1 mmol), and Ph3P (1 mmol) were weighed into a 10 mL Shrek tube. After nitrogen replacement, o-fluorobenzyl alcohol (1 mmol) was added, followed by tetrahydrofuran to dissolve. After reacting at room temperature for 12 h, TLC was used to monitor the completion of the reaction. Saturated aqueous sodium bicarbonate solution was added to the reaction system, extracted with DCM, and the organic phase was collected, dried over anhydrous sodium sulfate, and concentrated by column chromatography to obtain the target product 1bc.

[0159] Referring to the above synthesis method, the 3 The target products 1bc-1bd can be obtained by derivatives of the fragments.

[0160] Example 5: Synthesis of Compounds 1be-1bn

[0161]

[0162] Synthesis of intermediate III-5: The initial raw materials phenol (15 mmol) and potassium carbonate (12 mmol) were dissolved in DMF, stirred at room temperature for about 15 min, and then 2,4-difluorobenzonitrile II-5 (10 mmol) was added and stirred at 80°C for about 6 h. The reaction was monitored by TLC. After the reaction was completed, water (200 ml) was added to the reaction system, and ethyl acetate (100 mL) was extracted three times. The organic layers were combined, and the organic phase was washed three times with saturated brine (200 ml). The organic phase was dried, concentrated, and column chromatography was performed to obtain intermediate III-5.

[0163] Synthesis of intermediate IV-5: Dissolve intermediate III-5 (10 mmol) in tetrahydrofuran, reflux and stir evenly, gradually add sodium hydroxide solution (4N), continue reflux reaction for 5 hours, and monitor the reaction by TLC until completion. After cooling to room temperature, gradually add dilute hydrochloric acid (2N) to the reaction system and stir until precipitation occurs, filter, wash with clean water 3 times, and dry to obtain key intermediate IV-5.

[0164] The key intermediates of 1be-1bn can be obtained by referring to the above method.

[0165] Synthesis of target product 1bi:

[0166]

[0167] The key intermediate IV-5 (1 mmol), DIAD (1 mmol), and Ph3P (1 mmol) were weighed into a 10 mL Shrek tube. After nitrogen replacement, p-fluorobenzyl alcohol (1 mmol) was added, followed by tetrahydrofuran dissolution. After reacting at room temperature for 12 h, TLC was used to monitor the completion of the reaction. Saturated aqueous sodium bicarbonate solution was added to the reaction system, extracted with DCM, and the organic phase was collected, dried over anhydrous sodium sulfate, and concentrated by column chromatography to obtain the target product 1bi.

[0168] Referring to the above synthesis method, the 2 ,R 3 The target product 1be-1bn can be obtained by derivatives of the fragments.

[0169] Example 6: Synthesis of compounds 1bo-1cq, 1cx-1da, 1dc-1dd

[0170]

[0171] Synthesis of intermediate III-6: The initial raw materials 3,5-difluorophenol (15mmol) and potassium carbonate (12mmol) were dissolved in DMF, stirred at room temperature for about 15min, and then 3,4-difluorobenzonitrile II-6 (10mmol) was added and stirred at 80°C for about 6h. The reaction was monitored by TLC. After the reaction was completed, water (200ml) was added to the reaction system, and ethyl acetate (100mL) was extracted three times. The organic layers were combined, and the organic phase was washed three times with saturated brine (200ml). The organic phase was dried, concentrated, and column chromatography was performed to obtain intermediate III-6.

[0172] Synthesis of intermediate IV-6: Dissolve intermediate III-6 (10 mmol) in tetrahydrofuran, reflux and stir evenly, gradually add sodium hydroxide solution (4N), continue reflux reaction for 5 hours, and monitor the reaction by TLC until completion. After cooling to room temperature, gradually add dilute hydrochloric acid (2N) to the reaction system and stir until precipitation occurs, filter, wash with clean water 3 times, and dry to obtain key intermediate IV-6.

[0173] The key intermediates of 1bo-1cq, 1cx-1da, and 1dc-1dd can be obtained by referring to the above method.

[0174] Synthesis of target product 1cd:

[0175]

[0176] The key intermediate IV-6 (1 mmol), DIAD (1 mmol), and Ph3P (1 mmol) were weighed into a 10 mL Shrek tube. After nitrogen replacement, 5-fluoro-2-pyridinemethanol (1 mmol) was added, followed by tetrahydrofuran dissolution. After reacting at room temperature for 12 h, TLC was monitored until the reaction was completed. Saturated sodium bicarbonate aqueous solution was added to the reaction system, extracted with DCM, and the organic phase was collected, dried over anhydrous sodium sulfate, and concentrated by column chromatography to obtain the target product 1cd.

[0177] Referring to the above synthesis method, the 1 ,R 2 ,R 3 The target products 1bo-1cq, 1cx-1da, 1dc-1dd can be obtained by derivatives of the fragments.

[0178] Example 7: Synthesis of compounds 1cr-1cw, 1db

[0179]

[0180] Synthesis of intermediate III-7: The initial raw materials p-hydroxybenzonitrile (15 mmol) and potassium carbonate (12 mmol) were dissolved in DMF, stirred at room temperature for about 15 min, and then tert-butyl 2,4-difluorobenzoate II-7 (10 mmol) was added, and stirred at 80°C for about 6 h. The reaction was monitored by TLC. After the reaction was completed, water (200 ml) was added to the reaction system, and ethyl acetate (100 mL) was extracted three times. The organic layers were combined, and the organic phase was washed three times with saturated brine (200 ml). The organic phase was dried, concentrated, and column chromatography was performed to obtain intermediate III-7.

[0181] Synthesis of intermediate IV-7: Dissolve intermediate III-7 (10 mmol) in dichloromethane, stir evenly at room temperature, gradually add trifluoroacetic acid, continue stirring for 2 hours, and monitor the reaction by TLC until completion. Concentrate to remove TFA and DCM, and dry to obtain key intermediate IV-7. This synthetic method is used to protect the terminal cyano group.

[0182] Synthesis of target product 1db:

[0183]

[0184] The key intermediate IV-7 (1 mmol), DIAD (1 mmol), and Ph3P (1 mmol) were weighed into a 10 mL Shrek tube. After nitrogen replacement, 2-fluorobenzyl alcohol (1 mmol) was added, followed by tetrahydrofuran to dissolve. After reacting at room temperature for 12 h, TLC was used to monitor the completion of the reaction. Saturated aqueous sodium bicarbonate solution was added to the reaction system, extracted with DCM, and the organic phase was collected, dried over anhydrous sodium sulfate, and concentrated by column chromatography to obtain the target product 1db.

[0185] The key intermediates of 1cr-1cw and 1db can be obtained by referring to the above method.

[0186] The derivatives containing diphenyl ether ester structures of the present invention were synthesized according to the above method. The structural characterization data of some compounds of the present invention are listed in Table 1 below.

[0187] Table 1 Structural characterization data of compound (I)

[0188]

[0189]

[0190]

[0191]

[0192] Example 8: Antifungal Activity Screening (Growth Rate Inhibition Method)

[0193] The mycelial growth rate method was used to determine the effects of the target compounds on rice sheath blight, rapeseed sclerotinia, wheat fusarium and tomato gray mold. The compound was dissolved in DMSO and added to a quantitative PDA (glucose 20g, potato 200g, agar 20g, ultrapure water to 1L) medium to prepare drug-containing plates with a final concentration of 50μg / mL and 10μg / mL and plates without drug addition as blank controls. Boscalid was used as a positive control. The bacterial cakes were inoculated in the center of the drug-containing plates and blank control plates, respectively. The samples were cultured in a dark incubator at 25°C for 3-5 days. When the control colony diameter exceeded 5cm, the colony diameter of the sample was measured by the cross method. Inhibition rate (%) = [(control colony diameter-treated colony diameter) / (control colony diameter-0.5)]×100 (0.5 is the filter cake diameter (cm)).

[0194] The results are shown in Table 2. At a dose of 50 μg / mL, the inhibition rate of most compounds on rice sheath blight was greater than 80%, which was equivalent to the inhibitory activity of the positive control boscalid. In particular, compounds 1ae and 1aw had better inhibitory effects on rice sheath blight than boscalid. In addition, most compounds had good inhibitory effects on rapeseed sclerotinia, tomato gray mold, and wheat fusarium, especially compound 1aj had better inhibitory activity on tomato gray mold than boscalid.

[0195] In conclusion, this series of compounds can effectively inhibit the growth of four bacteria at lower concentrations, which is better than the inhibitory activity of the positive control commercial agent boscalid, and has great development potential.

[0196] Table 2 Inhibition rate (%) of antibacterial activity of some compounds (Ⅰ) (dose 50 μg / mL)

[0197]

[0198]

[0199] Example 9: Difference in in vitro antifungal activity between drug 1aa and control drug FY21001

[0200] The antifungal activity screening method is the same as in Example 8.

[0201] In the previous work of our research group, a class of diphenyl ether phenyl propyl ester compounds for controlling rice blast fungi were designed and synthesized (CN113683509B; Nature Plants, 2024, 4 (10): 618-632.). This class of compounds is mainly used to control rice blast fungi, interfering with the interaction between MoErs1 of rice blast fungi and OsRD21 of rice, thereby controlling the infection of rice blast fungi, specifically taking FY21001 as an example. In the work of the present invention, the related work of diphenyl ether methyl ester is presented, specifically taking 1aa as an example. Since FY21001 has a special effect on rice blast fungi, but the control effect on other pathogenic fungi is weak, we optimized the structure and obtained diphenyl ether methyl ester related derivatives, as shown in Formula I, this class of compounds has excellent control effects on rice sheath blight fungi, rapeseed sclerotinia fungi, wheat fusarium rust fungi, and tomato gray mold fungi. The specific data are shown in Table 3. Compared with FY21001, 1aa has a significantly improved control effect on rice sheath blight and tomato gray mold, among which the control effect on rice sheath blight increased from 68.8% to 87.9%, and the control effect on tomato gray mold increased from 37.6% to 80.0%. In addition, the control effect on rapeseed sclerotinia and wheat fusarium was also improved. Combined with the relevant diphenyl ether methyl ester derivatives in Table 2, we believe that the broad-spectrum control of the diphenyl ether methyl ester structure is better than FY21001, and has a good effect in controlling rice sheath blight and tomato gray mold. In addition, the target of the series of compounds shown in Formula I is succinate dehydrogenase (SDH), which is inconsistent with the target of the series of derivatives related to FY21001.

[0202] Table 3 Inhibition rate of antibacterial activity of some compounds (Ⅰ) (dose 50 μg / mL)

[0203]

[0204] Example 10: Determination of the activity of rice leaves treated with drugs to control rice sheath blight

[0205] Rice planting: Place the susceptible rice seeds in a culture dish at 37±1℃ for 2 days, then spread them evenly in culture soil (nutrient soil: vermiculite = 2:1, w:w), and culture them under the conditions of light: dark = 12h:12h and temperature of 28±1℃ for 3 weeks before use.

[0206] The disease resistance of rice leaves to rice sheath blight was detected by the 0.5% (g / 100mL) drug-containing water-agar method. 1ae was dissolved in DMSO and added to sterile water-agar to a final concentration of 100μg / mL and 200μg / mL, respectively. DMSO was used as a solvent control. Boscalid was used as a positive control. 6-8cm fresh rice leaves were cut, drug-containing agar was applied on the front, and rice sheath blight that had been activated three times was inoculated on the back. The leaves were placed at 25°C, with 16h of light / 8h of darkness, and cultured for 3d. The lesion area (DLA) of each leaf was calculated by Imagej, and the experiment was repeated 3 times.

[0207] The results are as follows Figure 1 As shown in the figure, in the rice leaves without drug treatment, the lesions on the leaf surface are serious, and the lesions extend from the fungus cake to both ends, and the leaves have almost no normal green color. After treatment with 100μg / mL of 1ae, the lesion area is reduced, but there are still lesions, and they extend to both ends of the rice leaves. The control effect is slightly weaker than that of boscalid. However, after treatment with 200μg / mL of 1ae, there are almost no lesions on the leaf surface. Compared with the positive control boscalid, the lesion area is almost the same, and the relative control effect is equivalent. In short, the agent 1ae at 200μg / mL can effectively prevent and control the rice sheath blight fungus from infecting rice leaves.

[0208] Example 11: Determination of the activity of drug-treated tomatoes against Botrytis cinerea

[0209] The in vivo inhibitory effect of compound 1aj on Botrytis cinerea was determined by inoculating tomato fruits with pathogens. Compound 1aj was prepared as 100μg / mL and 200μg / mL solutions. The 1aj solution was applied to tomato fruits 24h in advance and once every 6h. The Botrytis cinerea cake was inoculated on the top of the tomato and placed in the dark at 25℃ for 3d. The lesion diameter was measured by the cross method to calculate the relative control efficiency. Each treatment was repeated 3 times.

[0210] The results are as follows Figure 2As shown in the figure, at the top of the tomato fruit infected with gray mold without drug treatment, there are large lesions, the bacteria infect the inside of the tomato fruit, the surface rots, and the hyphae grow vigorously. However, after being treated with 100μg / mL of 1aj and boscalid, the lesion area is smaller, but there is still hyphae infection. When the concentration is increased to 200μg / mL, there are almost no lesions, the gray mold blocks do not spread, and the hyphae do not extend, and the relative control effect reaches 90%. This shows that the agent 1aj can effectively prevent and control the infection of tomato gray mold in living bodies.

[0211] Example 12: Determination of the activity of rice leaves treated with drugs to control rice blast fungus

[0212] The susceptible rice seeds CO39 were placed in a culture dish at 37±1℃ for germination for 2 days, and then evenly sown in culture soil (nutrient soil: vermiculite = 2:1), and cultured under the conditions of light:dark = 12h:12h and temperature of 28±1℃ for 14 days before use.

[0213] Method for inducing spores of wild-type Guy11 of rice blast pathogen: extract hyphae from PDA slant seed tubes and culture them on SDC solid medium in the dark for 4 days, pick the edge hyphae and transfer them to a new SDC solid medium plate, culture them in the dark at 28±1℃ for 7 days, then scrape off the aerial hyphae and culture them under black light for 3 days to induce spore production. Rinse the spores on the SDC plate with 2.5 ml sterile water, filter through a single layer of filter cloth, and collect them in a 2.0 mL centrifuge tube.

[0214] SDC medium, each liter of medium contains 100g rice straw, 40g corn flour, and 15g agar.

[0215] Weigh the rice straw in the above weight proportion, boil the juice, add agar and glucose, and dilute with water. Dispense into Erlenmeyer flasks and sterilize at 121℃ for 25 minutes to prepare the required culture medium.

[0216] The concentration of the spore solution was adjusted to 1×10 5 Each treatment was 5 ml of spore solution, and 0.2% (g / 100 mL) of gelatin was added, and the leaves of wild-type rice seedlings planted for 14 days were evenly sprayed with a sprayer (the drug spray treatment was carried out 24 hours in advance, and the method was the same as in Example 76). After spraying, the rice was placed in a dark box at 28±1°C and 80±10% humidity for 24 hours, and then cultured under 12 hours of light: 12 hours of dark alternation. Water was added twice a day with a spray bottle to maintain suitable humidity conditions. The pathogenicity results were observed and photographed after 7 days.

[0217] The results are shown in Table 4. Most of the rice treated with the agents had excellent control effects on rice blast fungi, and the control effects after the agents were all higher than 80%. It was better than the positive agent FY21001 and comparable to the flexibility of rice blast fungi. It is worth noting that the control effect of compound 1aw on rice blast fungi reached 98.38%, which was better than the positive agent rice blast (95.60%). In short, this series of agents has a very strong control effect on rice blast fungi and has the potential for commercialization.

[0218] Table 4 Effect of the treatment of rice with pesticides on the control of rice blast fungus (%)

[0219]

[0220] From the above antibacterial activity data, it can be seen that the antibacterial effect of some compounds is better than that of the control agent boscalid. The inhibitory activity of compounds 1ae, 1aw, and 1az against rice sheath blight is better than that of the positive control boscalid, and it is expected to be developed into a paddy field fungicide mainly for rice sheath blight. At the same time, it is difficult to control tomato gray mold, and the inhibition rate of compound 1aj against tomato gray mold is better than that of the positive control boscalid, which provides a new idea for the subsequent control of tomato gray mold. In addition, some compounds have a high control efficiency against rapeseed sclerotia and wheat gibberella, which is comparable to the positive control boscalid, and has great development potential. In the in vivo experiment, we found that this series of compounds has a strong control effect on rice blast fungus, especially 1aw, which has a control effect of nearly 100% on rice blast fungus, which is significantly better than the positive agent rice blast. In short, this series of compounds has high inhibitory activity against a variety of pathogenic fungi and has the potential to be industrialized as a candidate fungicide variety. Therefore, this type of compound has a good application prospect.

[0221] In summary, the diphenyl ether ester compounds described in the present invention have the characteristics of simple structure, convenient preparation, low toxicity, high activity, etc., and show good inhibitory effects on various pathogens, and are worthy of further research and development.

[0222] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.

Claims

1. A diphenyl ether ester compound having a structure shown in formula (I), in, In formula (I), R 1 is selected from H, halogen, hydroxy, amino, mercapto, cyano, nitro, C1-C8 alkyl, C1-C8 alkyl substituted by halogen, C1-C8 alkoxy, C1-C8 alkoxy substituted by halogen, phenyl substituted or unsubstituted by C1-C8 alkyl and / or halogen, benzyl, naphthyl, pyridyl, furyl, thienyl, pyrazolyl, imidazolyl, phenyl substituted by C1-C8 alkoxy, benzyl, naphthyl, pyridyl, furyl, thienyl, pyrazolyl, imidazolyl, C3-C8 heterocycle substituted or unsubstituted by C1-C8 alkyl and / or halogen; R 2 is selected from H, halogen, hydroxy, amino, mercapto, cyano, nitro, C1-C8 alkyl, C1-C8 alkyl substituted by halogen, C1-C8 alkoxy, C1-C8 alkoxy substituted by halogen, phenyl substituted or unsubstituted by C1-C8 alkyl and / or halogen, benzyl, naphthyl, pyridyl, furyl, thienyl, pyrazolyl, imidazolyl, phenyl substituted by C1-C8 alkoxy, benzyl, naphthyl, pyridyl, furyl, thienyl, pyrazolyl, imidazolyl, C3-C8 heterocycle substituted or unsubstituted by C1-C8 alkyl and / or halogen; Q is selected from phenyl, naphthyl, pyrrolyl, furanyl, tetrahydrofuranyl, thienyl, thiazolyl, imidazolyl, pyrazolyl, oxazolyl, valerolactamyl, pyridyl, pyranyl, piperidinyl, piperazinyl, pyridazinyl, pyrimidinyl, caprolactamyl, C3-C8 heterocycle; R 3 is selected from H, halogen, hydroxy, amino, mercapto, cyano, nitro, C1-C8 alkyl, C1-C8 alkyl substituted by halogen, C1-C8 alkoxy, C1-C8 alkoxy substituted by halogen, phenyl substituted or unsubstituted by C1-C8 alkyl and / or halogen, benzyl, naphthyl, pyridyl, furyl, thienyl, pyrazolyl, imidazolyl, phenyl substituted by C1-C8 alkoxy, benzyl, naphthyl, pyridyl, furyl, thienyl, pyrazolyl, imidazolyl, C3-C8 heterocycle substituted or unsubstituted by C1-C8 alkyl and / or halogen; R 1 ,R 2 ,R 3 It is located at any substitution position of the aromatic ring, either monosubstituted or polysubstituted.

2. The compound according to claim 1, characterized in that In formula (I), R 1 Selected from H, 4-OH, 4-NH2, 4-F, 4-CF 3、 3,5-di-F, 2,4-di-F, 4-CN; R 2 Selected from H, 3-F, 3-Cl, 2-F, 2-Cl, 2-CF 3、 2-CHF2, 3-CF3; Q is selected from benzene ring, 2-thiophene, cyclohexane, 2-pyridine; R 3 H、2-F、2-Cl、2-CH3、2-CH2CH3、3-F、3-CN、3-CH3、4-F、4-Cl、4-CF3、4-CN、4-OCH3、4-CH3、2,5-di-CH3、2,6-di-CH3、3,4-di-CH3、3,5-di-CH3、5-F、3-OH; R 1 ,R 2 ,R 3 It is located at any substitution position of the aromatic ring, either monosubstituted or polysubstituted.

3. The compound according to claim 1 or 2, characterized in that The compound is a compound in which each substituent is as follows: Compound 1aa: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is H; Compound 1ae: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 2-F; Compound 1af: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 2-Cl; Compound 1ag: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 2-CH3; Compound 1ah:R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 2-CH2CH3; Compound 1ai:R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 3-F; Compound 1aj: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 3-CN; Compound 1ak:R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 3-CH3; Compound 1al:R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 4-F; Compound 1am: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 4-Cl; Compound 1an:R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 4-CF3; Compound 1ao: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 4-CN; Compound 1ap:R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 4-OCH3; Compound 1aq: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 4-CH3; Compound 1ar:R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 2,5-di-CH3; Compound 1as:R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 2,6-di-CH3; Compound 1at: R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 3,4-di-CH3; Compound 1au:R 1 is 4-OH, R2 is H, Q is a benzene ring, and R3 is 3,5-di-CH3; Compound 1av:R 1 is 4-OH, R2 is 3-F, Q is a benzene ring, and R3 is H; Compound 1aw:R 1 is 4-OH, R2 is 3-F, Q is a benzene ring, and R3 is 2-F; Compound 1ax: R 1 is 4-OH, R2 is 3-F, Q is a benzene ring, and R3 is 2-Cl; Compound 1ay: R 1 is 4-OH, R2 is 3-F, Q is a benzene ring, and R3 is 4-F; Compound 1az: R 1 is 4-OH, R2 is 3-Cl, Q is a benzene ring, and R3 is H; Compound 1ba: R 1 is 4-OH, R2 is 3-Cl, Q is a benzene ring, and R3 is 2-F; Compound 1bb: R 1 is 4-OH, R2 is 3-Cl, Q is a benzene ring, and R3 is 2-Cl; Compound 1bc: R 1 is 4-NH2, R2 is 3-F, Q is a benzene ring, and R3 is 2-F; Compound 1bd: R 1 is 4-NH2, R2 is 3-F, Q is a benzene ring, and R3 is 4-F; Compound 1be:R 1 is H, R2 is 3-F, Q is a benzene ring, and R3 is 4-F; Compound 1bf: R 1 is H, R2 is 3-F, Q is a benzene ring, and R3 is 2-F; Compound 1bg: R 1 is H, R2 is 3-Cl, Q is a benzene ring, and R3 is 4-F; Compound 1bh: R 1 is H, R2 is 3-Cl, Q is a benzene ring, and R3 is 2-F; Compound 1bi: R 1 is H, R2 is 2-F, Q is a benzene ring, and R3 is 4-F; Compound 1bj: R 1 is H, R2 is 2-F, Q is a benzene ring, and R3 is 2-F; Compound 1bk: R 1 is H, R2 is 2-Cl, Q is a benzene ring, and R3 is 4-F; Compound 1bl: R 1 is H, R2 is 2-Cl, Q is a benzene ring, and R3 is 2-F; Compound 1bm: R 1 is H, R2 is 2-CF3, Q is a benzene ring, and R3 is 2-F; Compound 1bn: R 1 is H, R2 is 2-CHF2, Q is a benzene ring, and R3 is 2-F; Compound 1bo:R 1 is 4-F, R2 is 3-F, Q is a benzene ring, and R3 is 2-F; Compound 1bp:R 1 is 4-F, R2 is 3-F, Q is 2-thiophene, and R3 is 2-F; Compound 1bq: R 1 is 4-F, R2 is 3-F, Q is cyclohexane, and R3 is H; Compound 1br:R 1 is 4-F, R2 is 3-F, Q is 2-pyridine, and R3 is 5-F; Compound 1bs:R 1 is 4-F, R2 is 3-F, Q is 2-pyridine, and R3 is 3-F; Compound 1bt:R 1 is 4-F, R2 is 3-F, Q is 2-pyridine, and R3 is 3-OH; Compound 1bu:R 1 is 4-CF3, R2 is 3-F, Q is a benzene ring, and R3 is 2-F; Compound 1bv: R 1 is 4-CF3, R2 is 3-F, Q is 2-thiophene, and R3 is 2-F; Compound 1bw: R 1 is 4-CF3, R2 is 3-F, Q is cyclohexane, and R3 is H; Compound 1bx: R 1 is 4-CF3, R2 is 3-F, Q is 2-pyridine, and R3 is 5-F; Compound 1by: R 1 is 4-CF3, R2 is 3-F, Q is 2-pyridine, and R3 is 3-F; Compound 1bz: R 1 is 4-CF3, R2 is 3-F, Q is 2-pyridine, and R3 is 3-OH; Compound 1ca: R 1 is 3,5-di-F, R2 is 3-F, Q is a benzene ring, and R3 is 2-F; Compound 1cb: R 1 is 3,5-di-F, R2 is 3-F, Q is 2-thiophene, and R3 is 2-F; Compound 1cc: R 1 is 3,5-di-F, R2 is 3-F, Q is cyclohexane, and R3 is H; Compound 1cd: R 1 is 3,5-di-F, R2 is 3-F, Q is 2-pyridine, and R3 is 5-F; Compound 1ce: R 1 is 3,5-di-F, R2 is 3-F, Q is 2-pyridine, and R3 is 3-F; Compound 1cf:R 1 is 3,5-di-F, R2 is 3-F, Q is 2-pyridine, and R3 is 3-OH; Compound 1cg: R 1 is 2,4-di-F, R2 is 3-F, Q is a benzene ring, and R3 is 2-F; Compound 1ch: R 1 is 2,4-di-F, R2 is 3-F, Q is 2-thiophene, and R3 is 2-F; Compound 1ci: R 1 is 2,4-di-F, R2 is 3-F, Q is cyclohexane, and R3 is H; Compound 1cj: R 1 is 2,4-di-F, R2 is 3-F, Q is 2-pyridine, and R3 is 5-F; Compound 1ck: R 1 is 2,4-di-F, R2 is 3-F, Q is 2-pyridine, and R3 is 3-F; Compound 1cl:R 1 is 2,4-di-F, R2 is 3-F, Q is 2-pyridine, and R3 is 3-OH; Compound 1cm:R 1 is 4-OH, R2 is 3-F, Q is 2-thiophene, and R3 is 2-F; Compound 1cn: R 1 is 4-OH, R2 is 3-F, Q is cyclohexane, and R3 is H; Compound 1co:R 1 is 4-OH, R2 is 3-F, Q is 2-pyridine, and R3 is 5-F; Compound 1cp:R 1 is 4-OH, R2 is 3-F, Q is 2-pyridine, and R3 is 3-F; Compound 1cq: R 1 is 4-OH, R2 is 3-F, Q is 2-pyridine, and R3 is 3-OH; Compound 1cr:R 1 is 4-CN, R2 is 3-F, Q is a benzene ring, and R3 is 2-F; Compound 1cs:R 1 is 4-CN, R2 is 3-F, Q is 2-thiophene, and R3 is 2-F; Compound 1ct: R 1 is 4-CN, R2 is 3-F, Q is cyclohexane, and R3 is H; Compound 1cu:R 1 is 4-CN, R2 is 3-F, Q is 2-pyridine, and R3 is 5-F; Compound 1cv: R 1 is 4-CN, R2 is 3-F, Q is 2-pyridine, and R3 is 3-F; Compound 1cw: R 1 is 4-CN, R2 is 3-F, Q is 2-pyridine, and R3 is 3-OH; Compound 1cx: R 1 is 4-F, R2 is 2-F, Q is a benzene ring, and R3 is 2-F; Compound 1cy:R 1 is 4-CF3, R2 is 2-F, Q is a benzene ring, and R3 is 2-F; Compound 1cz:R 1 is 3,5-di-F, R2 is 2-F, Q is a benzene ring, and R3 is 2-F; Compound 1da:R 1 is 2,4-di-F, R2 is 2-F, Q is a benzene ring, and R3 is 2-F; Compound 1db: R 1 is 4-CN, R2 is 2-F, Q is a benzene ring, and R3 is 2-F; Compound 1dc: R 1 is 4-CF3, R2 is 3-CF3, Q is a benzene ring, and R3 is 2-F; Compound 1dd: R 1 It is 4-CF3, R2 is 2-CF3, Q is a benzene ring, and R3 is 2-F.

4. The method for preparing the compound according to any one of claims 1 to 3, characterized in that: The method comprises the following steps AC:

5. The preparation method according to claim 4, characterized in that: In step A, the synthesis method of formula III is: dissolving raw material II and alkali in a solvent, adding a phenol derivative, and after the reaction is completed, extracting with an organic solvent, washing with saturated brine, combining the organic layers, drying and concentrating, and column chromatography to obtain intermediate III; In step B, the synthesis method of formula IV is: dissolving intermediate III in a solvent, adding sodium hydroxide aqueous solution, adding dilute hydrochloric acid to the reaction system after the reaction is completed, and a large amount of precipitate can be observed, followed by suction filtration, washing with clean water, and drying to obtain intermediate IV; In step C, the synthesis method of the target product is: dissolving intermediate IV in a solvent, adding substituted or unsubstituted heterocyclic benzyl alcohol and a condensing agent, after the reaction is completed, extracting with an organic solvent, washing with a saturated sodium bicarbonate aqueous solution, combining the organic layers, drying and concentrating, and column chromatography to obtain the target product.

6. The preparation method according to claim 4 or 5, characterized in that: The solvent described in reaction A is selected from one of N,N-dimethylformamide, acetonitrile, N,N-dimethylacetamide, N,N-diethylacetamide, 1,4-dioxane, toluene, and dimethyl sulfoxide; preferably, it is selected from one of N,N-dimethylformamide and N,N-dimethylacetamide; the reaction temperature is 25°C-120°C, preferably, the reaction temperature is 60°C-90°C; the base used is selected from one of potassium carbonate, sodium carbonate, sodium hydroxide, potassium tert-butoxide, sodium tert-butoxide, triethylamine, pyridine, sodium hydride, potassium hydroxide, and lithium hydroxide; preferably, it is selected from one of potassium carbonate and potassium tert-butoxide; The solvent in reaction B is selected from one of methanol, ethanol, tetrahydrofuran, 1,4-dioxane, and acetonitrile; preferably, selected from one of methanol, ethanol and tetrahydrofuran; the reaction temperature is 25°C-120°C, preferably, the reaction temperature is 60°C-70°C; The solvent in reaction C is selected from one of acetonitrile, 1,4-dioxane, dichloromethane, and tetrahydrofuran; preferably, it is selected from one of dichloromethane and tetrahydrofuran; the reaction temperature is 25°C-50°C, preferably, the reaction temperature is 30°C; the condensing agent used is selected from one of a combination of DMAP and EDCI, and a combination of DIAD and triphenylphosphine.

7. Use of the compound according to any one of claims 1 to 3 in the preparation of pesticide fungicides for preventing and controlling plant diseases.

8. The use according to claim 7, characterized in that: The plant diseases are selected from at least one of the bacterial diseases white leaf blight, bacterial basal rot, bacterial brown streak, bacterial streak, bacterial brown spot, bacterial wilt, and bacterial stem rot; or at least one of the fungal diseases damping-off, root rot, downy mildew, white rust, blight, cotton blight, fusarium head blight, powdery mildew, anthracnose, leaf spot, black spot, smut, rust, sheath blight, damping-off, gray mold, and rapeseed sclerotinia.

9. A pesticide fungicide, characterized in that: The pesticide fungicide consists of an active ingredient and excipients, wherein the active ingredient includes at least one of the compounds described in any one of claims 1 to 3; the content of the active ingredient is 1-99.9999 weight %; preferably, the content of the active ingredient is 1-50 weight %; preferably, the content of the active ingredient is 20-40 weight %.

10. The pesticide fungicide according to claim 9, characterized in that: The formulation of the pesticide fungicide is selected from one of emulsifiable concentrate, suspension, wettable powder, dust, granule, aqueous solution, poison bait, mother liquor and mother powder.

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