Substituted 1,2,3-triazole compounds, processes for their preparation and their use in the control of plant diseases

Abstract

The present application relates to substituted 1,2,3-triazole compounds represented by formula (I) and methods for their preparation, to pesticidal compositions comprising them and to their use in the control of plant diseases; in particular to substituted 1,2,3-triazole compounds capable of inhibiting fungal and oomycete appressorium formation and methods for their preparation and use in the control of plant diseases caused by fungi and oomycetes.

Description

TECHNICAL FIELD

[0001] The present application relates to substituted 1,2,3-triazole compounds, methods for preparing the same, pesticidal compositions containing the same, and uses thereof in controlling plant diseases; in particular, the present application relates to substituted 1,2,3-triazole compounds capable of inhibiting the formation of fungal and oomycete appressoria, methods for preparing the same, and uses thereof in controlling plant diseases caused by fungi and oomycetes. BACKGROUND

[0002] 70-80% of plant diseases are caused by fungi and oomycetes, and several or even dozens of different fungi and oomycetes can occur on a plant. For example, sheath blight, rice blast, rice smut, hulless spot, and bunt of rice, scab, powdery mildew, stripe rust, leaf rust, root rot, and sheath blight of wheat, large spot, small spot, stalk rot, rust, sheath blight, curvularia leaf spot, smut, and smut of corn are all caused by fungi. These fungal diseases account for more than 90% of crop diseases in terms of the area affected and the losses caused. In addition to fungal diseases, diseases caused by oomycetes are also very harmful to many crops, such as potato late blight, soybean downy mildew, pepper downy mildew, grape downy mildew, and cucumber downy mildew.

[0003] For plant diseases caused by fungi and oomycetes, the application of chemical agents is generally the main control method. Currently, the fungicides commonly used in chemical control include Bordeaux mixture, chlorothalonil, chlorfenazole, thiophanate-methyl, carbendazim, azoxystrobin, pyraclostrobin, anilazine, and tricyclazole, among which, Bordeaux mixture, chlorfenazole, azoxystrobin, anilazine, and tricyclazole are used as protective agents, and chlorothalonil, thiophanate-methyl, carbendazim, and pyraclostrobin have both protective and curative effects. The molecular structures of protective agents and curative agents are diverse, but most of them include nitrogen-containing heterocyclic structures, among which, pyrimidine, imidazole, pyrazole, and 1,2,4-triazole are relatively common.

[0004] The commonly used structure of triazoles is 1,2,4-triazole. Compounds containing this structure include the representative systemic fungicides difenoconazole and tebuconazole, which complete disease control by inhibiting the demethylation of pathogenic fungal sterols. Currently, there are many reports on 1,2,4-triazole compounds, but there are few reports on fungicidal 1,2,3-triazole compounds. Compared with 1,2,4-triazole compounds, 1,2,3-triazole compounds have completely different synthesis methods and different modes of action with target proteins, and they cannot be replaced similarly; at the same time, there are few reports on the evaluation of substituted 1,2,3-triazole compounds and their derivatives in the control of plant diseases caused by fungi and oomycetes.

[0005] Most of the diseases caused by fungi and oomycetes are mainly spread in the field by asexual spores. Some of the asexual spores of fungi or oomycetes, such as Magnaporthe grisea and Colletotrichum gloeosporioides, germinate after landing on the surface of a plant, form an appressorium at the tip of the germination tube, and enter the plant tissue through the appressorium turgor, causing disease. The appressorium is a specific infection structure formed by many plant and animal pathogenic fungi, and therefore, there have been many studies to reveal the molecular mechanism of appressorium formation in order to provide a target for the development of green fungicides. Currently, tricyclazole, which is widely used in rice blast control, achieves the purpose of controlling disease by inhibiting the melanin formation of the appressorium of M. grisea. However, there are very few fungicides that inhibit appressorium formation, and therefore, the development of an inhibitor of appressorium formation is of great significance for the development of fungicides for plant fungal and oomycete diseases.

[0006] Currently, the general method for evaluating the fungicidal activity of a candidate compound includes determining the inhibition rate of the candidate compound on the growth of the vegetative hyphae of a pathogenic fungus, and then inferring the control effect on the pathogenic fungus. However, this method cannot objectively reflect the function of the candidate compound to a great extent, especially for pathogenic fungi and oomycetes that form appressorium. Taking the model pathogenic fungus M. grisea, which can form appressorium, as an example, according to the existing literature, the growth rate of the vegetative hyphae of M. grisea has no obvious correlation with its pathogenic ability, and the spore germination, germ tube growth, and appressorium formation and maturation directly determine the pathogenic ability of M. grisea. Therefore, based on the determination of the inhibition rate of a candidate compound on the spore germination and appressorium formation of a pathogenic fungus, the control effect on the disease is evaluated, and a new class of substituted 1,2,3-triazole compounds is developed.

[0007] Since pathogenic bacteria in nature will continuously develop resistance to a certain specific fungicide or some fungicides will have environmental problems during use, the development of fungicides with better application properties is a problem faced by the field. SUMMARY

[0008] In view of the disadvantages in the prior art, the purpose of the present application is to provide a 1,2,3-triazole compound for preventing and treating plant diseases caused by fungi and oomycetes.

[0009] Therefore, the first aspect of the present application provides a compound of formula (I), a stereoisomer, a racemate, a tautomer, an isotopically-labeled, a nitroxide, an agriculturally acceptable salt or ester, a solvate, or a solvate of an agriculturally acceptable salt thereof:

[0010]

[0011] wherein,

[0012] R1and R2independently of one another represent H, unsubstituted or independently of one another substituted by one, two or more RaC1-C 12 alkyl, C2-C 12 alkenyl, C2-C 12 alkynyl, C3-C 20 cycloalkyl, 3- to 20-membered heterocyclyl, C6-C 20 aryl or 5- to 20-membered heteroaryl; or R1and R2together with the N atom to which they are attached form an unsubstituted or independently of one another substituted by one, two or more Rb3- to 20-membered heterocyclyl,

[0013] Ra independently of one another represent H, C1-C 12 alkyl, C2-C 12 alkenyl, C2-C 12 alkynyl, C3-C 20 cycloalkyl, C1-C 12 alkyl C3-C 20 cycloalkyl, C1-C 12 alkyl C6-C 20 aryl, carboxyl, ester, hydroxyl, hydroxyl C1-C 12 alkyl, amino, -NH(C1-C 12 alkyl), -N(C1-C 12 alkyl)2, amido, nitro, CN, azido, azido C 1- C 12 alkyl, oxo (=0), halogen, thiol, hydroxyl, -CHO, wherein the carbon chain of the alkyl, alkenyl or alkynyl radical or the ring atoms of the cycloalkyl radical can optionally be interrupted by an oxygen atom, nitrogen atom or sulfur atom or can optionally be oxo,

[0014] Rb independently of one another represent H, C1-C 12 alkyl, C2-C 12 alkenyl, C2-C 12 alkynyl, C3-C 20 cycloalkyl, C1-C 12 alkylcarbonyl, C2-C 12 alkenylcarbonyl, C3-C 20 cycloalkylcarbonyl, C6-C 20 arylcarbonyl, wherein the carbon atoms of the alkyl, alkenyl or alkynyl radical or the ring atoms of the cycloalkyl radical can optionally be substituted by one, two or more hydroxyl, C1-C 12 alkylcarbonyloxy, C1-C 12 alkyloxycarbonyl, C2-C 12 alkynyloxy, azido-C1-C 12 alkyloxy-C1-C 12 alkyloxy, amino-C1-C 12alkyl, C2-C 12 alkyl, C2-C 12 alkyl, C2-C 12 alkyl, C2-C 12 alkyl, C2-C 12 alkyl, C2-C 12 alkyl, C2-C

[0015] R3, R4, R5, R6and R7independently of one another represent halogen, cyano, nitro, amino, C1-C 12 alkyl, C2-C 12 alkyl, C2-C 12 alkyl, C2-C 12 alkyl, C2-C 12 alkyl, C3-C 20 alkyl, C3-C 20 alkyl, C3-C 14 alkyl, C3-C 12 alkyl, C3-C 12 alkyl, C3-C 12 alkyl, C3-C 12 alkyl, C3-C 12 alkyl, C3-C

[0016] According to some embodiments of the application, the compound of formula (I) has the structure of formula (IA) or (IB) below:

[0017]

[0018] wherein R1, R2, R3, R4, R5, R6and R7are as defined in formula (I).

[0019] According to some embodiments of the application, R1and R2independently of one another represent H, C1-C6alkyl which is unsubstituted or substituted by one, two or more Ra, independently of one another, C2-C6alkenyl, C2-C6alkynyl, C3-C 12 cycloalkyl, 3-10 membered heterocyclyl, C6-C 10 aryl, 5-10 membered heteroaryl; or R1and R2together with the N atom to which they are attached form a 3-10 membered heterocyclyl which is unsubstituted or substituted by one, two or more Rb, independently of one another.

[0020] Preferably, R1and R2independently of one another represent H, C1-C6alkyl, haloC1-C6alkyl, C3-C 12 cycloalkyl, haloC3-C12 Cycloalkyl, 5-8 membered heteroaryl or 6-10 membered aryl; or R1and R2together with the N atom to which they are attached form a 3-6 membered heterocyclyl which is unsubstituted or substituted by one, two or more Rb, independently of one another.

[0021] More preferably, R1and R2independently of one another represent H, methyl, n-butyl, tert-butyl, cyclopentyl, pyranyl, imidazolyl, thiazolyl, phenyl, pyridyl, thienyl which is unsubstituted or substituted by one, two or more Ra, independently of one another; or R1and R2together with the N atom to which they are attached form pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, thiomorpholinyl or 1,3,5-triazinyl which is unsubstituted or substituted by one, two or more Rb, independently of one another.

[0022] Most preferably, R1and R2independently of one another represent H, methyl, n-butyl, cyclopentyl, phenyl, pyrid-3-yl, thiazol-2-yl or benzyl; or R1and R2together with the N atom to which they are attached form pyrrolidinyl, morpholin-4-yl or piperazinyl which is unsubstituted or substituted by one Rb. Preferably, the piperazinyl substituted by one Rb is piperazinyl substituted in the 4-position by Rb.

[0023] Preferably, Ra represents C1-C6 alkyl or C6-C 10 aryl; more preferably, Ra represents methyl, ethyl, n-propyl, i-propyl, phenyl.

[0024] Preferably, Rb represents C1-C6 alkyl, C1-C6 alkylcarbonyl, C5-C7 cycloalkylcarbonyl, C6-C 10 arylcarbonyl, C2-C6 alkenylcarbonyl, acetyloxycarbonyl, hydroxyC1-C6 alkylcarbonyl, C1-C6 alkylcarbonylC 1- C6 alkyl, C2-C6 alkynyl oxyC1-C6 alkyl, azidoethoxyethoxyC1-C6 alkyl, aminoethoxyethoxyC1-C6 alkyl, tert-butoxycarbonyl ethoxy ethoxyC1-C6 alkyl, tert-butoxycarbonyl ethoxyC1-C6 alkyl.

[0025] More preferably, Rb represents C1-C6 alkyl, C1-C6 alkylcarbonyl, C5-C7 cycloalkylcarbonyl, C6-C 10 arylcarbonyl, C2-C6 alkenylcarbonyl, acetyloxycarbonyl, hydroxyC1-C6 alkylcarbonyl, C1-C6 alkylcarbonyl ethyl, C2-C6 alkynyl oxyethyl, azidoethoxyethoxyethyl, aminoethoxyethoxyethyl, tert-butoxycarbonyl ethoxy ethoxy ethyl, tert-butoxycarbonyl ethoxy ethyl.

[0026] Most preferably, Rb represents methyl, acetyl, cyclopentylcarbonyl, benzoyl, propenoyl, 2-(acetyloxy)acetyl, 2-hydroxyacetyl, 2-(ethoxycarbonyl)ethyl, 2-(propyn-3- yloxy)ethyl, 2-(2-(2-azidoethoxy)ethoxy)ethyl, 2-(2-(2-aminoethoxy)ethoxy)ethyl, 2-(2-(2- tert-butoxycarbonylethoxy)ethoxy)ethyl, 2-(2-tert-butoxycarbonylethoxy)ethyl.

[0027] Preferably, R3, R4, R5, R6 and R7 represent, independently from each other, halogen, C1-C6 alkyl, C1-C6 alkyloxy, halogeno-C1-C6 alkyl, C1-C6 alkylcarbonyl, C1-C6 alkyloxycarbonyl, C3-C7 cycloalkyl, C3-C7 cycloalkyloxy, C6-C10 aryl, C6-C10 aryloxy, C1-C6 alkylcarbonyl, C1-C6 alkyloxycarbonyl, carboxyl, 5-7 membered heterocyclyl, -CON(C1-C6 alkyl)2, -CONH(C1-C6 alkyl), -N(C1-C6 alkyl)2, 5-7 membered heterocyclylcarbonyl; more preferably, R3, R4, R5, R6 and R7 represent, independently from each other, halogen, C1-C3 alkyl, C1-C3 alkyloxy, halogeno-C1-C3 alkyl, C1-C3 alkylcarbonyl, C1-C3 alkyloxycarbonyl, C3-C5 cycloalkyl, C3-C5 cycloalkyloxy, C6-C10 aryl, C6-C10 aryloxy, C1-C3 alkylcarbonyl, C1-C3 alkyloxycarbonyl, carboxyl, 5-7 membered heterocyclyl, -CON(C1-C3 alkyl)2, -CONH(C1-C3 alkyl), -N(C1-C3 alkyl)2, 5-7 membered heterocyclylcarbonyl; most preferably, R3, R4, R5, R6 and R7 represent, independently from each other, Cl, F, methyl, isopropyl, methoxy, trifluoromethyl, cyclohexyl, cyclohexyloxy, phenoxy, acetyl, carboxyl, pyrrolidin-1-yl, morpholin-4-yl, dimethylaminocarbonyl, n-butylaminocarbonyl, pyrrolidin-1-ylcarbonyl, methoxycarbonyl or dimethylamino. 1- C6 alkyl, C5-C7 cycloalkyl, C5-C7 cycloalkyloxy, C6-C 10 aryl, C6-C10 aryloxy, C1-C6 alkylcarbonyl, C1-C6 alkyloxycarbonyl, carboxyl, 5-7 membered heterocyclyl, -CON(C1-C6 alkyl)2, -CONH(C1-C6 alkyl), -N(C1-C6 alkyl)2, 5-7 membered heterocyclylcarbonyl; more preferably, R3, R4, R5, R6 and R7 represent, independently from each other, halogen, C1-C3 alkyl, C1-C3 alkyloxy, halogeno-C1-C3 alkyl, C1-C3 alkylcarbonyl, C1-C3 alkyloxycarbonyl, C3-C5 cycloalkyl, C3-C5 cycloalkyloxy, C6-C10 aryl, C6-C10 aryloxy, C1-C3 alkylcarbonyl, C1-C3 alkyloxycarbonyl, carboxyl, 5-7 membered heterocyclyl, -CON(C1-C3 alkyl)2, -CONH(C1-C3 alkyl), -N(C1-C3 alkyl)2, 5-7 membered heterocyclylcarbonyl; most preferably, R3, R4, R5, R6 and R7 represent, independently from each other, Cl, F, methyl, isopropyl, methoxy, trifluoromethyl, cyclohexyl, cyclohexyloxy, phenoxy, acetyl, carboxyl, pyrrolidin-1-yl, morpholin-4-yl, dimethylaminocarbonyl, n-butylaminocarbonyl, pyrrolidin-1-ylcarbonyl, methoxycarbonyl or dimethylamino. 1- C6 alkyl, C5-C7 cycloalkyl, C5-C7 cycloalkyloxy, C6-C 10 aryl, C6-C10 aryloxy, C1-C6 alkylcarbonyl, C1-C6 alkyloxycarbonyl, carboxyl, 5-7 membered heterocyclyl, -CON(C1-C6 alkyl)2, -CONH(C1-C6 alkyl), -N(C1-C6 alkyl)2, 5-7 membered heterocyclylcarbonyl; more preferably, R3, R4, R5, R6 and R7 represent, independently from each other, halogen, C1-C3 alkyl, C1-C3 alkyloxy, halogeno-C1-C3 alkyl, C1-C3 alkylcarbonyl, C1-C3 alkyloxycarbonyl, C3-C5 cycloalkyl, C3-C5 cycloalkyloxy, C6-C10 aryl, C6-C10 aryloxy, C1-C3 alkylcarbonyl, C1-C3 alkyloxycarbonyl, carboxyl, 5-7 membered heterocyclyl, -CON(C1-C3 alkyl)2, -CONH(C1-C3 alkyl), -N(C1-C3 alkyl)2, 5-7 membered heterocyclylcarbonyl; most preferably, R3, R4, R5, R6 and R7 represent, independently from each other, Cl, F, methyl, isopropyl, methoxy, trifluoromethyl, cyclohexyl, cyclohexyloxy, phenoxy, acetyl, carboxyl, pyrrolidin-1-yl, morpholin-4-yl, dimethylaminocarbonyl, n-butylaminocarbonyl, pyrrolidin-1-ylcarbonyl, methoxycarbonyl or dimethylamino.

[0028] Preferably, the compounds of formula (I) according to the present application have the structure as shown in Tables 1-8.

[0029] A third aspect of the present application provides a pesticidal composition, such as a fungicide, herbicide, plant protection agent composition, comprising one, two or more of the compounds of formula (I), stereoisomers, racemates, tautomers, isotopically-labeled, nitroxides, agriculturally acceptable salts or esters, solvates or solvates of agriculturally acceptable salts thereof, as active ingredients.

[0030] According to some embodiments of the present application, the pesticide composition is a fungicide comprising a compound of formula (I) and optionally an agriculturally acceptable adjuvant. Preferably, the pesticide composition is used as a plant protection agent for preventing or protecting a plant from a plant disease, including rice blast, anthracnose, downy mildew, late blight and / or powdery mildew. More preferably, the disease is selected from rice blast, pepper anthracnose, cucurbit downy mildew such as cucumber downy mildew, strawberry anthracnose, corn anthracnose, potato late blight, pepper late blight and / or wheat powdery mildew.

[0031] According to some embodiments of the present application, the weight percentage of the active ingredient, preferably the compound of formula (I), its stereoisomer, racemate, tautomer, isotopically-labeled, nitroxide, agriculturally acceptable salt or ester, solvate or solvate of agriculturally acceptable salt, in the composition is 0.1-99.9%, for example, 0.5-99%.

[0032] According to some embodiments of the present application, the composition further comprises one, two or more of agriculturally and / or forestry and / or animal husbandry and / or horticulture acceptable carriers.

[0033] According to some embodiments of the present application, the composition can be applied in the form of a formulation.

[0034] For example, the compound of formula (I) is dissolved or dispersed in a carrier or formulated into a formulation as an active ingredient for easier dispersion when used as a herbicide.

[0035] According to some embodiments of the present application, the formulation includes, but is not limited to, the following forms: granules, wettable powders, oil suspensions, aqueous suspensions, aqueous emulsions, water, emulsions or microcapsules, etc.

[0036] According to some embodiments of the present application, a liquid or solid carrier and optionally a surfactant can be further added to the composition.

[0037] A fourth aspect of the present application provides the use of one, two or more of the compound of formula (I), its stereoisomer, racemate, tautomer, isotopically-labeled, nitroxide, agriculturally acceptable salt or ester, solvate or solvate of agriculturally acceptable salt for controlling rice blast, pepper anthracnose, cucurbit downy mildew such as cucumber downy mildew, strawberry anthracnose, corn anthracnose, potato late blight, pepper late blight and / or wheat powdery mildew.

[0038] According to some embodiments of the present application, the effective amount of the compound of formula (I), stereoisomer, racemate, tautomer, isotopically-labeled, nitroxide, agriculturally acceptable salt or ester, solvate or solvate of agriculturally acceptable salt thereof according to the present application is from 10 grams to 1000 grams per hectare, preferably the effective amount is from 20 grams to 500 grams per hectare.

[0039] Advantages of the present application

[0040] The present application utilizes compounds with 1,2,3-triazole as the core for derivatization, which has the activity of inhibiting the formation of fungal and oomycete appressoria. Through research, it is found that the compound of formula (I) can effectively inhibit the conidial germination, germ tube growth or appressorium formation of fungi and oomycetes.

[0041] The present inventors have found that 1,2,3-triazole compounds can effectively prevent plant infection by pathogens by inhibiting conidial germination, germ tube growth or appressorium formation, thereby providing a new choice for plant protection drugs for controlling plant diseases that are harmful, including rice blast, anthracnose, downy mildew, late blight, powdery mildew.

[0042] The present inventors have found that some specific 1,2,3-triazole compounds with specific structures can effectively inhibit the formation of pathogenic fungi and oomycete appressoria at a concentration of 10-1000 ppm.

[0043] The present inventors have found that some specific 1,2,3-triazole compounds with specific structures can produce corresponding control effects in the field application of rice blast and potato late blight at a concentration of 10-1000 ppm. DETAILED DESCRIPTION

[0044] Terms and explanations

[0045] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Unless otherwise indicated, all patents and published patent applications or publications referred to herein are incorporated by reference in their entirety.

[0046] In the present text, when describing one, two or more, "more" shall mean a case of more than 2, for example representing a case of an integer greater than or equal to 3, for example 3, 4, 5, 6, 7, 8, 9 or 10.

[0047] In the present text, the term "optional" means both cases of presence or absence of the feature.

[0048] The term "halogen" means fluorine, chlorine, bromine and iodine.

[0049] The term "C1- C 12 "Alkyl" refers to a straight-chain and branched saturated hydrocarbon group having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 carbon atoms, including methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, n-hexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl, or 1,2-dimethylbutyl, or their isomers.

[0050] The term "alkoxy" refers to -O-alkyl, where alkyl is defined as described elsewhere in this document. Non-limiting examples of alkoxy groups include: methoxy, ethoxy, propoxy, butoxy, cyclopropoxy, cyclobutoxy, cyclopentoxy, and cyclohexoxy.

[0051] Term "C" 2- C 12 "Alkenyl" should be understood to preferably represent a straight-chain or branched monovalent hydrocarbon group containing one, two or more double bonds and having 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, for example, having 2 or 3 carbon atoms (i.e., C40, C50, C60, C7 ... 2-C3alkenyl). It is to be understood that in case the alkenyl group comprises more than one double bond, the double bonds can be separated from each other or conjugated. The alkenyl group is, for example, ethenyl, allyl, (E)-2-methylethenyl, (Z)-2-methylethenyl, (E)-but-2-enyl, (Z)-but-2-enyl, (E)-but-1-enyl, (Z)-but-1-enyl, pent-4-enyl, (E)-pent-3-enyl, (Z)-pent-3-enyl, (E)-pent-2-enyl, (Z)-pent-2-enyl, (E)-pent-1-enyl, (Z)-pent-1-enyl, hex-5-enyl, (E)-hex-4-enyl, (Z)-hex-4-enyl, (E)-hex-3-enyl, (Z)-hex-3-enyl, (E)-hex-2-enyl, (Z)-hex-2-enyl, (E)-hex-1-enyl, (Z)-hex-1-enyl, isopropenyl, 2-methylprop-2-enyl, 1-methylprop-2-enyl, 2-methylprop-1-enyl, (E)-1-methylprop-1-enyl, (Z)-1-methylprop-1-enyl, 3-methylbut-3-enyl, 2-methylbut-3-enyl, 1-methylbut-3-enyl, 3-methylbut-2-enyl, (E)-2-methylbut-2-enyl, (Z)-2-methylbut-2-enyl, (E)-1-methylbut-2-enyl, (Z)-1-methylbut-2-enyl, (E)-3-methylbut-1-enyl, (Z)-3-methylbut-1-enyl, (E)-2-methylbut-1-enyl, (Z)-2-methylbut-1-enyl, (E)-1-methylbut-1-enyl, (Z)-1-methylbut-1-enyl, 1,1-dimethylprop-2-enyl, 1-ethylprop-1-enyl, 1-propylvinyl, 1-isopropylvinyl.

[0052] The term "C 2- C 12 Alkynyl" is to be understood as preferably denoting a straight-chain or branched one- valent hydrocarbon group, which contains one or more triple bonds and which has 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, for example, 2 or 3 carbon atoms ("C2-C3-alkynyl"). 2-C3alkynyl") is intended. Said alkynyl is, for example, ethynyl, prop-1-ynyl, prop-2-ynyl, but-1-ynyl, but-2-ynyl, but-3-ynyl, pent-1-ynyl, pent-2-ynyl, pent-3-ynyl, pent-4-ynyl, hex-1-ynyl, hex-2-ynyl, hex-3-ynyl, hex-4-ynyl, hex-5-ynyl, 1-methylprop-2-ynyl, 2-methylbut-3-ynyl, 1-methylbut-3-ynyl, 1-methylbut-2-ynyl, 3-methylbut-1-ynyl, 1-ethylprop-2-ynyl, 3-methylpent-4-ynyl, 2-methylpent-4-ynyl, 1-methylpent-4-ynyl, 2-methylpent-3-ynyl, 1-methylpent-3-ynyl, 4-methylpent-2-ynyl, 1-methylpent-2-ynyl, 4-methylpent-1-ynyl, 3-methylpent-1-ynyl, 2-ethylbut-3-ynyl, 1-ethylbut-3-ynyl, 1-ethylbut-2-ynyl, 1-propylprop-2-ynyl, 1-isopropylprop-2-ynyl, 2,2-dimethylbut-3-ynyl, 1,1-dimethylbut-3-ynyl, 1,1-dimethylbut-2-ynyl or 3,3-dimethylbut-1-ynyl. In particular, the alkynyl group is ethynyl, prop-1-ynyl or prop-2-ynyl.

[0053] The term "C3-C 20 Cycloalkyl" is to be understood as meaning a saturated, monovalent, monocyclic, bicyclic or bridged cycloalkane having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms. The C 3-10 Cycloalkyl" is to be understood as meaning a saturated, monovalent, monocyclic, bicyclic or bridged cycloalkane having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms. The C 3-10 Cycloalkyl" is to be understood as meaning a saturated, monovalent, monocyclic, bicyclic or bridged cycloalkane having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms. The C 3-10 Cycloalkyl" is to be understood as meaning a saturated, monovalent, monocyclic, bicyclic or bridged cycloalkane having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms. The C

[0054] The term "3-20 membered heterocyclyl" means a saturated or unsaturated non-aromatic ring or ring system and contains at least one heteroatom selected from O, S and N. The heterocyclyl group can be attached to the rest of the molecule by any of the carbon atoms or the nitrogen atom, if present, or the oxygen or sulphur atom, especially in the case of the formation of onium salts. The heterocyclyl group can include fused or bridged rings as well as spirocyclic rings. In particular, the heterocyclyl group can include, but is not limited to: 4-membered rings such as azetidinyl, oxetanyl, thietanyl; 5-membered rings such as tetrahydrofuranyl, dioxolanyl, dioxolynyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, pyrrolinyl; or 6-membered rings such as tetrahydropyranyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl or trithianyl; or 7-membered rings such as diazepanyl, oxazepanyl. Optionally, the heterocyclyl group can be benzo and / or naphtho-fused. The heterocyclyl group can be bicyclic, for example, but not limited to, 5,5 membered rings such as hexahydrocyclopenta[c]pyrrol-2(lH)-yl ring, or 5,6 membered bicyclic rings such as hexahydropyrrolo[l,2-a]pyrazin-2(lH)-yl ring. The heterocyclyl group can be partially unsaturated, i.e. it can contain one, two or more double bonds, for example, but not limited to, dihydrofuranyl, dihydropyranyl, 2,5-dihydro-lH-pyrrolyl, 4H-[l,3,4]thiadiazinyl, 4,5-dihydrooxazolyl or 4H-[l,4]thiazinyl, or it can be benzo-fused, for example, but not limited to, dihydroisoquinolinyl.

[0055] The term "C6-C 20 aryl" is to be understood as preferably meaning a monovalent, aromatic or partially aromatic, monocyclic, bicyclic or tricyclic hydrocarbon ring having 6 to 20 carbon atoms, preferably "C 6-14 aryl". The term "C 6-14 aryl" is to be understood as preferably meaning a monovalent, aromatic or partially aromatic, monocyclic, bicyclic or tricyclic hydrocarbon ring having 6, 7, 8, 9, 10, 11, 12, 13 or 14 carbon atoms ("C 6-14 aryl"), in particular a ring having 6 carbon atoms ("C6aryl"), for example phenyl; or a ring having 9 carbon atoms ("C9aryl"), for example indanyl or indenyl; or a ring having 10 carbon atoms ("C 10 aryl"), for example tetrahydronaphthyl, dihydronaphthyl or naphthyl; or a ring having 13 carbon atoms ("C 13 aryl"), for example fluorenyl; or a ring having 14 carbon atoms ("C 14 aryl"), for example anthryl. When the C 6-20 aryl is substituted, it can be mono- or polysubstituted. Also, there is no limitation as to the substitution site, for example ortho, para or meta substitution.

[0056] The term "5-20 membered heteroaryl" is to be understood as including a monovalent monocyclic, bicyclic or tricyclic aromatic ring system having 5 to 20 ring atoms and comprising 1 to 5 heteroatoms independently selected from N, O and S, for example "5-14 membered heteroaryl". The term "5-14 membered heteroaryl" is to be understood as including a monovalent monocyclic, bicyclic or tricyclic aromatic ring system having 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 ring atoms, in particular 5 or 6 or 9 or 10 carbon atoms, and comprising 1 to 5, preferably 1 to 3, heteroatoms each independently selected from N, O and S and, in addition, in each case, can be benzo-fused. In particular, the heteroaryl group is selected from thienyl, furanyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, thia-4H-pyrazolyl and the like and their benzo derivatives, for example benzo furanyl, benzo thienyl, benzo oxazolyl, benzo isoxazolyl, benzo imidazolyl, benzo triazolyl, indazolyl, indolyl, isoindolyl and the like; or pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and the like and their benzo derivatives, for example quinolinyl, quinazolinyl, isoquinolinyl and the like; or azocinyl, indolizinyl, purinyl and the like and their benzo derivatives; or cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenoxazinyl, phenothiazinyl, phenoxazinyl and the like. When the 5-20 membered heteroaryl group is attached to another group to form a compound of the present application, it can be attached to a carbon atom of the 5-20 membered heteroaryl ring or to a heteroatom of the 5-20 membered heteroaryl ring. When the 5-20 membered heteroaryl group is substituted, it can be mono- or polysubstituted. Also, there is no limitation on the substitution site, for example, the hydrogen attached to a carbon atom of the heteroaryl ring can be substituted, or the hydrogen attached to a heteroatom of the heteroaryl ring can be substituted.

[0057] Unless otherwise indicated, a heterocyclyl, heteroaryl or heteroarylenyl group includes all possible isomeric forms thereof, for example, positional isomers. Thus, for some illustrative, non-limiting examples, forms which can be included are those substituted or bonded at one, two or more of the 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, 12-positions, etc. (if present) thereof, including pyrid-2-yl, pyrid-3-yl, pyrid-4-yl; thienyl or thiophenyl includes thien-2-yl, thien-3-yl; pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl.

[0058] The term "oxo" refers to an oxo substituent (=0) formed by oxidation of a carbon atom, a nitrogen atom or a sulfur atom in a substituent.

[0059] Unless otherwise indicated, the definitions herein apply equally to groups containing the term in question, e.g. C 1-6 The definition of alkyl also applies to C 1-6 alkoxy, -N(C 1-6 alkyl)2, -NHC 1-6 alkyl, -SO-C 1-6 alkyl or -S(O)2-C 1-6 alkyl, etc.

[0060] It should be appreciated that definitions of standard chemical terminology can be found in reference works including Carey and Sundberg, "ADVANCED ORGANIC CHEMISTRY 4 TH ED." Vols. A (2000) and B (2001), Plenum Press, New York. Unless otherwise indicated, conventional methods well known in the art of synthetic organic chemistry, as for example, mass spectrometry, NMR, IR and UV / Vis spectroscopy and pharmacological methods, were employed. Unless specifically defined, terms used in the description and appended claims of this application are to be construed in accordance with the principles of the art to which the description pertains. Standard techniques can be used for chemical synthesis, chemical analysis, pharmaceutical formulation, and delivery, and treatment of patients. For example, reactions and purification can be performed utilizing the instructions provided by manufacturers of reagents, or according to well known methods in the art or as described herein. The foregoing techniques and procedures can be readily implemented by the skilled artisan by following the teachings of the present specification and the examples given herein. In the present description, groups and substituents thereof can be selected by one skilled in the art to provide stable moieties and compounds.

[0061] The term "agriculturally acceptable salt" as used herein refers to salts that retain the biological effectiveness and none of the adverse effects of the free acids and free bases of the specified compounds and are biologically or otherwise

[0062] Agriculturally acceptable salts include, but are not limited to, inorganic or organic base salts derived from acidic groups such as carboxyl, sulfonyl, phenolic hydroxyl, etc. Agriculturally acceptable salts according to the invention can be synthesized from a parent compound, i.e., by reacting an acidic group in the parent compound with a suitable amount of base, for example, 1-4 equivalents of base, in a solvent system; or similarly, in the presence of a basic group such as an amino group in the parent compound, by forming salts with a suitable inorganic or organic acid; and in the case where the parent compound contains both an acidic center (e.g., a carboxyl group) and a basic center (e.g., an amino group), it can also form an inner salt. Suitable salts are listed in Remingtong's Pharmaceutical Sciences, 17. th See, for example, sodium salts, in Mack Publishing Company, Easton, Pa., 1985, p. 1418 and Journal of Pharmaceutical Science, 66, 2 (1977).

[0063] The compounds of the present invention may exist as solvates (such as hydrates), wherein the compounds of the present invention contain a polar solvent, particularly, for example, water, methanol, or ethanol, as a structural element of the lattice of the compound. The amount of the polar solvent, particularly water, may be stoichiometric or non-stoichiometric.

[0064] Depending on their molecular structure, the compounds of the present invention can be chiral, and therefore may exist in various enantiomeric forms. Thus, these compounds can exist in racemic or optically active forms. The compounds of the present invention or their intermediates can be isolated as enantiomers by chemical or physical methods known to those skilled in the art, or used in this form for synthesis. In the case of racemic amines, diastereomers are obtained from the mixture by reaction with an optically active resolving agent. Examples of suitable resolving agents are optically active acids, such as tartaric acid in R and S forms, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid, suitable N-protected amino acids (e.g., N-benzoylproline or N-benzenesulfonylproline), or various optically active camphorsulfonic acids. Chromatographic enantiomeric resolution can also be advantageously performed using optically active resolving agents (e.g., dinitrobenzoylphenylglycine immobilized on silica gel, cellulose triacetate, or other carbohydrate derivatives or chiral derivatized isobutylene ester polymers). Suitable eluents for this purpose are aqueous or alcoholic solvent mixtures, such as hexane / isopropanol / acetonitrile.

[0065] The term "tautomer" refers to isomers of a functional group that result from the rapid movement of an atom in a molecule between two positions. The compounds of the present application can exhibit tautomerism. Tautomeric compounds can exist in two or more interconvertible forms. Proton-shift tautomers result from the migration of a hydrogen atom covalently bonded between two atoms. Tautomers generally exist in equilibrium, and attempts to isolate a single tautomer usually result in a mixture whose physical properties are consistent with a mixture of compounds. The position of equilibrium depends on the chemical properties within the molecule. For example, in many aliphatic aldehydes and ketones such as acetaldehyde, the keto form predominates; in phenols, the enol form predominates. The present application encompasses all tautomeric forms of the compounds.

[0066] The corresponding stable isomers can be separated according to known methods, for example by extraction, filtration or column chromatography.

[0067] The term "substituted" means that one, two or more hydrogen atoms, preferably up to 5, more preferably 1 to 3, of the groups mentioned are replaced independently of each other by a corresponding number of substituents. The substituents are obviously only in their possible chemical positions, which can be determined (experimentally or theoretically) by the person skilled in the art without excessive effort, as possible or impossible substitutions. For example, an amino group with a free hydrogen or a hydroxyl group can be unstable in combination with a carbon atom having an unsaturated (e.g. olefinic) bond.

[0068] The term "fungicide" includes herein chemicals and / or formulations which are capable of controlling and / or killing pathogenic microorganisms such as bacteria, fungi, oomycetes, rickettsiae, mycoplasmas, viruses and / or algae and the like which are detrimental to plants.

[0069] The term "pesticide composition" denotes a mixture containing one, two or more compounds described herein or agriculturally acceptable salts or prodrugs thereof with other active or non-active ingredients such as adjuvants, in particular for example carriers and excipients.

[0070] Due to their positive properties, the compounds of formula (I) can be advantageously used for protecting important crops of arable land and non-arable land, and the environment frequented by humans, from harmful pathogenic organisms.

[0071] The amount of the compounds of formula (I) to be used varies depending on various factors such as the compound used, the crop to be protected, the type of harmful pathogenic organisms, the degree of infestation, the climatic conditions, the method of application and the formulation employed.

[0072] The choice of the formulation or composition ingredients described herein should be consistent with the physical properties of the active ingredient, the mode of application and the environmental factors such as the type of soil, humidity and temperature.

[0073] Useful formulations include liquids such as solutions (including emulsions), suspensions, emulsions (including microemulsions and / or suspensions), and the like, optionally thickened into gels. Useful formulations also include solids such as powders, dusts, granules, tablets, pellets, films, and the like, which can be water dispersible ("wettable") or water soluble. The active ingredient can be microencapsulated for delivery in a suspension or solid form; alternatively, the entire formulation can be encapsulated. Encapsulation can control or delay release of the active ingredient. Sprayable formulations can be diluted in appropriate media and applied at a volume of about one hundred to several hundred liters per hectare. High concentrations of the compositions are useful as intermediates for further processing.

[0074] Typical solid diluents are described in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents are described in Marsden, Solvents Guide and Chemicals Interscience, New York, 1950. McCutcheon's Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, and Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964, list surfactants and recommended applications. All formulations can contain minor amounts of additives to reduce foaming, corrosion, microbiological growth, or to enhance the presence or persistence of the formulations.

[0075] Surfactants include, for example, polyethoxylated alcohols, polyethoxylated alkyl phenols, polyethoxylated sorbitan fatty acid esters, sulfonated dialkyl succinates, alkyl sulfates, alkyl benzene sulfonates, organosilanes, N,N-dialkyl taurates, lignin sulfonates, naphthalene sulfonate formaldehyde condensates, polycarboxylates, and polyoxyethylene / polyoxypropylene block copolymers.

[0076] Solid diluents include, for example, clays such as bentonite, monmorillonite, attapulgite, kaolin, starch, sugars, silica, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate, sodium bicarbonate, and sodium sulfate; liquid diluents include, for example, water, N,N-dimethylformamide, dimethylsulfoxide, N-alkylpyrrolidinone, ethylene glycol, polypropylene glycol, paraffin, alkylbenzenes, alkylnaphthalenes, olive oil, castor oil, linseed oil, tung oil, sesame oil, corn oil, peanut oil, cottonseed oil, soybean oil, rapeseed oil, and cocoa butter, fatty acid esters; ketones such as cyclohexanone, 2-heptanone, isophorone, and 4-hydroxy-4-methyl-2-pentanone; and alcohols such as methanol, cyclohexanol, dodecanol, and tetrahydrofurfuryl alcohol.

[0077] Solutions, suspensions, emulsions, etc. can be prepared by simply mixing the components. Dusts and fine powders can be prepared by mixing and, usually, grinding in a hammer mill or fluid energy mill. Suspensions are generally prepared by wet milling.

[0078] Herein, for some applications of the composition, for example, in agriculture, one, two or more other fungicides, insecticides, acaricides, herbicides, plant growth regulators, plant protectants or fertilizers, etc. can be added to the composition of the present application, whereby additional advantages and effects can be produced.

[0079] The compounds of the formula (I) can be used as such or preferably together with the carriers and adjuvants customarily employed in the art of formulation.

[0080] The present application therefore also relates to compositions for controlling or protecting against phytopathogenic microorganisms, which comprise a compound of the formula (I) and an inert carrier, and to methods for controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein the composition comprising a compound of the formula (I) as active ingredient and an inert carrier is applied to the plants, to their parts or the locus thereof.

[0081] To this end, the compounds of the formula (I) and the inert carrier are conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granules, and also encapsulations in e.g. polymer substances. As with the type of the compositions, the methods of application, e.g. spraying, atomizing, dusting, spreading, coating and pouring, are likewise chosen in dependence of the target objects and the main environmental conditions. The compositions can also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders and spreaders, and also fertilizers, micronutrient donors or other formulating agents for obtaining special effects.

[0082] Suitable carriers and adjuvants can be solid or liquid and are substances useful in the art of formulation, such as natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers.

[0083] The formulations, that is to say the compositions comprising a compound of the formula (I) or (II) and, if desired, solid or liquid adjuvants, are prepared in known manner: generally by intimately mixing the compound with extenders, such as solvents, solid carriers and, optionally, surface-active compounds (surfactants) and / or grinding the mixture.

[0084] The agrochemical formulations generally comprise 0.1 to 99% by weight, preferably 0.1 to 95% by weight, of the compound of the formula (I), 99.9 to 1% by weight, preferably 99.8 to 5% by weight, of solid or liquid adjuvants, and 0 to 25% by weight, preferably 0.1 to 25% by weight, of surfactants.

[0085] The 1,2,3-triazole derivatives (I) can be combined with any one or two or more pesticidally active ingredients conventionally used in the art for the control of diseases of agricultural and horticultural plants.

[0086] The active ingredient of the pesticide may be selected from: benzothiadiazole, thiamethoxam, thiamethoxam, methyl thiamethoxam, 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, sodium 4-methyl-1,2,3-thiadiazole-5-carboxylate, ethyl 4-methyl-1,2,3-thiadiazole-5-carboxylate, DL-β-aminobutyric acid, isothiazamide, 3,4-dichloroisothiazolium-5-carboxylic acid, sodium 3,4-dichloroisothiazolium-5-carboxylate, ethyl 3,4-dichloroisothiazolium-5-carboxylate, ribavirin, antofenfen, ningnanmycin or salicylic acid, cymoxanil, thiram, zinc thiram, mancozeb, aluminum fosetyl-aluminum, thiophanate-methyl, chlorothalonil, dichlorvos, iprodione, benzyl benzoate, thiophanate-methyl, thiophanate-methyl, metalaxyl, flumorph, dimethomorph, high-efficiency metalaxyl. High-efficiency benzalkonium chloride, cyhalofop-butyl, sulfadiazine, mesotrione, thiabendazole, chlorothalonil, cyprothiophanate-methyl, cycloflufenoxam, cyclopyridamole, cyhalofop-butyl, silthiabendazole, carbendazim, oxychlorpyrifos, methyl thiophanate, fluopyram, furazolidone, thiabendazole, cyprothiophanate-methyl, pyraclostrobin, bifenthiophanate-methyl, fluopyram, fluoxastrobin Fluopyram, fluopyram aniline, benzyl-fluoroquinolone, isothiazamide, fluopyram hydroxylamine, fluopyram, fluopyram, diyrylamide, benzylamide, ethoxysulfuron, iprodione, pyraclostrobin, fenpyroxime, fluopyram, fenpyroxime, fenpyroxime, pyraclostrobin, fenpyroxime, fenpyroxime, oxadiazon, fenpyroxime, fenpyroxime, oxadiazon, fenpyroxime, oxadiazon, fenpyroxime, cyclophosphamide, ciprofloxacin Azoxystrobin, difenoconazole, tebuconazole, high-efficiency tebuconazole, fluconazole, cyproconazole, fluquinazole, flusilazole, fenbendazole, hexaconazole, imidacloprid, tebuconazole, tebuconazole, propiconazole, thiophanate-methyl, tebuconazole, tetraflufenazole, triazole, tebuconazole, bifenthrin, thiamethoxam, fenbendazole, imazalil, high-efficiency imazalil, prochloraz, fluconazole Cyazofamid, imidacloprid, oxadiazon, isoprothiolane, oxadiazon, pyraclostrobin, oxadiazon, oxadiazon, thiamethoxam, terbufos, oxadiazon, benzylthiocyanate, dodecyl morpholine, butyl morpholine, tridemorpholine, seed dressing agent, fluazinam, fluazinam, pyridaben, cyclopyridamole, fluazinam, pyridaben, pyrimethanil, fluazinam, pyrimethanil, chlorobenzyl Pyrimidinol, Fluoropyrimidinol, Acaricide, Dicyananthraquinone, Ethoxyquinoline, Hydroxyquinoline, Propoxyquinoline, Phenoxyquinoline, Ethoxycarb, Isopropylamine, Benzylamine, Cymoxanil, Sulfocarb, Dichlorvos, Isoprothiolane, Pyridaben, Methyl thiophanate, Miconazole, Kasugamycin, Polyoxin, Polyoxin, Validamycin, Jinggangmycin, Streptomycin, Metalaxyl, Furazolidone, Benzopyrazosulfan, Furazolidone, Carbendazim, Benomyl, Thiophanate-methyl, Triadimefon, Ethylpyrimethanil Sulfate, Dimethomorph, Ethylpyrimethanil, Captan, Captan, Ethylpyridinium Chloride, Fluorochlorothalonil, Isopyridaben, Chlorothalonil, Isoprothiolane, Isoprothiolane, Effluox, Pentachloronitrobenzene, Propineb, Aluminum Trisphosphonate, Sulfur, Bordeaux mixture, Copper sulfate, Copper oxychloride, Cuprous oxide, Copper hydroxideMetrafenone, pencycuron, pyridachlone, tecloftalam, queinoxyfen, spiroxamine, tricyclazole, oxycarboxin, dodine, iminoctad, fenhexamid, zoxamide, acypetacs, quinofumelin, probenazole, thiabendazole, fuberidazole, thiophanate-methyl, pyracarbolid, guazatine, guazatine-acetate, dichlofluanid, tolylfluanid, flusulfamide, ethaboxam, isoprothiolane, thiadenchlor, dichlofluanid, dichlofluanid, allyl-isothiazolone, etc.

[0087] Example

[0088] The preparation method of the present application will be further illustrated in detail below in connection with specific examples. It should be understood that the following examples are only illustratively used to explain and illustrate the present application, and should not be interpreted as limiting the scope of protection of the present application. Any technical solutions achieved based on the content of the present application are covered within the scope of protection intended by the present application.

[0089] Unless otherwise specified, the experimental methods used in the following examples are conventional methods in the art; the reagents, raw materials, instruments, equipment, etc. used in the following examples can be obtained from commercial channels.

[0090] Reagents used

[0091] Except for ethyl acetate, petroleum ether and dichloromethane, the rest of the reagents were used after being treated with anhydrous oxygen-free. The synthetic precursors used were purchased from Bide Pharmaceutical Group, and the metal catalysts used were purchased from Saen Chemical Group.

[0092] Instruments and equipment

[0093] Determined by Bruker DPX500 and Varian Mercury 400 nuclear magnetic resonance instruments 1 H, 13 C, 19 F NMR spectra, wherein 1 H NMR and 13 In the analysis of H NMR and C NMR, tetramethylsilane (TMS) was used as an internal standard, and the unit of chemical shift was ppm. High resolution mass spectrometry was determined by Bruker Apex IV FTMS spectrometer and Thermo Q-Exactive HRMS instrument. Infrared spectroscopy was determined by Nicolet AVATAR 330 FT-IR.

[0094] The synthesis, biological activity and related applications of representative 1,2,3-triazole compounds of Formula (I) according to the present application are illustratively explained by way of preparation examples and biological examples.

[0095] The various compounds in Tables 1-8 below can be synthesized and characterized by those skilled in the art using corresponding starting materials that are routine and known in the art according to the following general synthetic routes I-V.

[0096] General Synthetic Route I (applicable to preparation of compounds numbered in A or B or C series in Tables 1-3 below):

[0097]

[0098] Place p-substituted (applicable to synthesis of compounds numbered in A series) or m-substituted (applicable to synthesis of compounds numbered in B series) or o-substituted (applicable to synthesis of compounds numbered in C series) nitrophenol (20.0 mmol) in a reaction flask, add 30.0 mL of acetone, add potassium carbonate (40.0 mmol) under stirring, add 3-bromopropyne (21.0 mmol), and check the completion of the reaction by TLC. Filter, concentrate the filtrate under reduced pressure, separate the residue by column chromatography to obtain G-A-1.

[0099] Place compound G-A-1 (10.0 mmol) in a reaction flask, add 8.0 mL of N,N- dimethylformamide, add copper sulfate pentahydrate (2.0 mmol) under stirring, add azide compound (11.0 mmol), sodium ascorbate (20.0 mmol), and 2.0 mL of water, and check the completion of the reaction by TLC. Filter, concentrate the filtrate, extract with water and dichloromethane, wash with saturated brine, combine the organic layers, dry over anhydrous sodium sulfate, filter, concentrate the filtrate, separate the residue by column chromatography to obtain G-A-2.

[0100] Place compound G-A-2 (1.0 mmol) in a reaction flask, add 2.5 mL of ethanol and 2.5 mL of water, add reduced iron powder (5.0 mmol) and ammonium chloride (5.0 mmol) under stirring, and check the substantial disappearance of the starting material by TLC. Extract with water and dichloromethane, wash with saturated brine, combine the organic layers, dry over anhydrous sodium sulfate, filter, concentrate the filtrate, separate the residue by column chromatography to obtain G-A-3.

[0101] Place compound G-A-3 (0.5 mmol) in a reaction flask, add 3.0 mL of a solvent, then add a base and compound R1-X or R2-Y or X-R1-R2-Y (0.75 mmol) under stirring, and react at a corresponding temperature. Check the completion of the reaction by TLC, extract with water and dichloromethane, wash with saturated brine, combine the organic layers, separate by preparative thin layer chromatography to obtain compounds numbered in A or B or C series in Tables 1-3 below.

[0102] General Synthetic Route II (applicable to preparation of compounds numbered in A or B or C series in Tables 1-3 below):

[0103]

[0104] Place p-bromophenol (20.0 mmol) or m-bromophenol (20.0 mmol) or o-bromophenol (20.0 mmol) in a reaction flask, add 30.0 mL of acetone, add potassium carbonate (40.0 mmol) under stirring, add 3-bromopropyne (21.0 mmol), and check the completion of the reaction by TLC. Filter, concentrate the filtrate under reduced pressure, and separate the residue by column chromatography to obtain G-B-1.

[0105] Place compound G-B-1 (10.0 mmol) in a reaction flask, add 8.0 mL of N,N- dimethylformamide, add copper sulfate pentahydrate (2.0 mmol) under stirring, add azide compound G-B-0 (11.0 mmol), sodium ascorbate (20.0 mmol), and 2.0 mL of water, and check the completion of the reaction by TLC. Filter, concentrate, extract with water and dichloromethane, wash with saturated brine, combine the organic layers, dry over anhydrous sodium sulfate, filter, concentrate the filtrate, and separate the residue by column chromatography to obtain G-B-2.

[0106] Place compound G-B-2 (1.0 mmol) in a Schlenk flask, add 1.5 mL of 1,4- dioxane, and replace with N2. Add Pd2(dba)3 (0.05 mmol), XPhos (0.10 mmol), amino compound NHR1R2, and sodium tert-butoxide (1.6 mmol), and amine compound NHR1R2 in this order, and replace with N2 three times. Check the disappearance of the starting material by TLC, extract with water and dichloromethane, wash with saturated brine, combine the organic layers, dry over anhydrous sodium sulfate, filter, concentrate the filtrate, and separate the residue by column chromatography to obtain the compounds of the A or B or C series of numbers in Tables 1 to 3.

[0107] General synthetic route III (applicable to the preparation of the compounds of the D or E or F series of numbers in Tables 4 to 6):

[0108]

[0109] Place (hydroxyphenyl)piperazine-1-carboxylate tert-butyl ester substituted at the para position (applicable to the synthesis of the compounds of the D series of numbers) or the meta position (applicable to the synthesis of the compounds of the E series of numbers) or the ortho position (applicable to the synthesis of the compounds of the F series of numbers) relative to the hydroxyl group of the benzene ring (20.0 mmol) in a reaction flask, add 30.0 mL of acetone, add potassium carbonate (40.0 mmol) under stirring, and add 3-bromopropyne (21.0 mmol). Check the completion of the reaction by TLC, filter, concentrate the filtrate under reduced pressure, and separate the residue by column chromatography to obtain G-C-1.

[0110] Compound G-C-1 (10.0 mmol) was taken in a reaction flask to which was added 8.0 mL of N,N-dimethylformamide, copper sulfate pentahydrate (2.0 mmol), azide (11.0 mmol), sodium ascorbate (20.0 mmol) and 2.0 mL of water were added with stirring. The reaction was monitored by TLC and upon completion, the reaction mixture was filtered, concentrated and water and dichloromethane were added to the filtrate. The organic layer was separated, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated and the residue was purified by column chromatography to obtain G-C-2.

[0111] Compound G-C-2 (1.0 mmol) was taken in a reaction flask to which was added 1,4-dioxane solution of hydrochloric acid (4 M, 2.0 mL) and stirred at room temperature. The reaction was monitored by TLC and upon completion, water and dichloromethane were added to the reaction mixture. The organic layer was separated, washed with saturated brine and purified by column chromatography to obtain G-C-3.

[0112] Compound G-C-3 (0.5 mmol) was taken in a reaction flask to which was added 2.0 mL of dichloromethane, triethylamine (1.0 mmol) was added with stirring and the corresponding compound R 11 -LG (0.75 mmol, where LG is the corresponding leaving group) was added with stirring and the reaction was allowed to proceed at room temperature. The progress of the reaction was monitored by TLC and upon completion, water and dichloromethane were added to the reaction mixture. The organic layer was separated, washed with saturated brine, concentrated and the residue was purified by column chromatography to obtain the compounds numbered in series D or E or F in Tables 4 to 6 below.

[0113] General synthetic route IV (applicable for preparing the compounds numbered in series G in Table 7 below):

[0114]

[0115] p- (applicable for synthesizing the compounds numbered in series G) or m- or o-substituted nitrophenol (20.0 mmol) was taken in a reaction flask to which was added 30.0 mL of acetone, potassium carbonate (40.0 mmol) and 3-bromopropyne (21.0 mmol) were added with stirring. The progress of the reaction was monitored by TLC and upon completion, the reaction mixture was filtered, concentrated under reduced pressure and the residue was purified by column chromatography to obtain G-D-1.

[0116] Compound G-D-1 (10.0 mmol) was taken in a reaction flask, to this 8.0 mL of 1,4-dioxane was added, under stirring pentamethylcyclopentadienyl bis(triphenylphosphine) ruthenium(IV) chloride (0.5 mmol) and azide compound G-D-0 (11.0 mmol) was added, TLC monitoring of the reaction completion. The reaction mixture was filtered, the filtrate was concentrated, water and dichloromethane was added and extracted, washed with saturated brine, the organic layer was combined, dried over anhydrous sodium sulphate, concentrated and the residue was separated by column chromatography to obtain G-D-2.

[0117] Compound G-D-2 (1.0 mmol) was taken in a reaction flask, to this 2.5 mL of ethanol and 2.5 mL of water was added, under stirring iron powder (5.0 mmol) and ammonium chloride (5.0 mmol) was added, TLC monitoring of the starting material was consumed. Water and dichloromethane was added and extracted, washed with saturated brine, the organic layer was combined, dried over anhydrous sodium sulphate, filtered, the filtrate was concentrated and the residue was separated by column chromatography to obtain G-D-3.

[0118] Compound G-D-3 (0.5 mmol) was taken in a reaction flask, to this 3.0 mL of solvent was added, then under stirring base and compound R1-X and / or R2-Y or X-R1-R2-Y (0.75 mmol) was added, the reaction was carried out at respective temperature. TLC monitoring of the reaction completion, water and dichloromethane was added and extracted, washed with saturated brine, the organic layer was combined, purified by preparative thin layer chromatography to obtain compounds of series G as per Table 7 below.

[0119] General synthetic route V (applicable for preparing compounds of series H as per Table 8 below):

[0120]

[0121] Compound (hydroxyphenyl)piperazine-1-carboxylate tert-butyl ester (20.0 mmol) substituted para to the hydroxyl group with respect to the benzene ring (applicable for synthesis of compounds of series H) was taken in a reaction flask, to this 30.0 mL of acetone was added, under stirring potassium carbonate (40.0 mmol) and 3-bromopropyne (21.0 mmol) was added, TLC monitoring of the reaction completion. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure, the residue was separated by column chromatography to obtain G-E-1.

[0122] Compound G-E-1 (10.0 mmol) was taken in a reaction flask, to this 8.0 mL of 1,4-dioxane was added, under stirring pentamethylcyclopentadienyl bis(triphenylphosphine) ruthenium(IV) chloride (0.5 mmol) and azide compound G-E-0 (11.0 mmol) was added, TLC monitoring of the reaction completion. The reaction mixture was filtered, the filtrate was concentrated, water and dichloromethane was added and extracted, washed with saturated brine, the organic layer was combined, dried over anhydrous sodium sulphate, concentrated and the residue was separated by column chromatography to obtain G-E-2.

[0123] Compound G-E-2 (1.0 mmol) was taken in a reaction flask, to which 1.0 mL of 1,4-dioxane solution of hydrochloric acid (4 M) was added and stirred. The reaction was monitored by TLC. Upon completion of the reaction, water was added and extracted with dichloromethane, washed with saturated brine, combined the organic layer, concentrated and the residue was purified by column chromatography to obtain G-E-3.

[0124] Compound G-E-3 (0.5 mmol) was taken in a reaction flask, to which 2.0 mL of solvent was added, stirred and base (1.0 mmol) and corresponding R 11 -LG (0.75 mmol, where LG is corresponding leaving group) was added and stirred at room temperature. The progress of the reaction was monitored by TLC. Upon completion of the reaction, water was added and extracted with dichloromethane, washed with saturated brine, combined the organic layer, purified by column chromatography to obtain the compounds listed under series H in Table 8 below.

[0125] Compound Examples

[0126] Hereinafter, the compounds of the present application can be synthesized by following the general synthetic routes A to E described above on the basis of the preparation examples, wherein the series of compounds numbered starting with A, B, C, D, E, F, G and H correspond to the following general formulae, respectively:

[0127]

[0128] In the following Tables 1 to 8, "Me" represents methyl, "Et" represents ethyl, "iPr" represents isopropyl, "cPen" represents cyclopentyl, "nBu" represents n-butyl, "tBu" represents tert-butyl, "Phen" represents phenyl, "3-Py" represents pyridin-3-yl, "Bn" represents benzyl, "Ac" represents acetyl.

[0129] Synthesis of compound A-001 of Preparation Example 1

[0130]

[0131] First Step:

[0132]

[0133] To 2.3 g of a1-1 in a reaction flask, 15 mL of acetone was added, stirred and 4.56 g of potassium carbonate, 2.05 g of 3-bromopropyne was added and refluxed. The progress of the reaction was monitored by TLC. Upon completion of the reaction, filtered, concentrated under reduced pressure and purified by column chromatography to obtain a1-2 as yellow semi-solid semi-solid 2.3 g in 90% yield.

[0134] Second Step:

[0135]

[0136] Take 1.0 grams of a1-2 in a reaction bottle, add 8 milliliters of N, N- dimethylformamide, 282 milligrams of copper sulfate pentahydrate, 1.18 grams of 3,4- dichlorobenzyl azide, 2.24 grams of sodium ascorbate and 2 milliliters of water, 50 degrees Celsius reaction, TLC detection reaction is complete. After filtration, add water and dichloromethane extraction, saturated brine wash combined organic layer, anhydrous sodium sulfate drying, column chromatography separation of a1-3 light yellow solid 2.0 grams, yield 94%.

[0137] Third step:

[0138]

[0139] Take 250 milligrams of a1-3 in a reaction bottle, add 2.5 milliliters of ethanol and 2.5 milliliters of water, 198 milligrams of iron powder, 104 milligrams of ammonium chloride, 60 degrees Celsius reaction, TLC detection of raw materials largely disappear. Add water and dichloromethane extraction, saturated brine wash combined organic layer, anhydrous sodium sulfate drying, column chromatography separation of a1-4 yellow semi-oil solid 110 milligrams, yield 48%.

[0140] Fourth step:

[0141]

[0142] Take 100 milligrams of a1-4 in a reaction bottle, add 3 milliliters of tetrahydrofuran, 13.4 milligrams of sodium hydride, reaction 25 minutes. 30 microliters of iodomethane added to the reaction system, room temperature reaction. TLC detection reaction is complete, add water and dichloromethane extraction, saturated brine wash combined organic layer, preparative thin layer chromatography separation of 34 milligrams of compound A-001, yield 30%.

[0143] Synthesis of compound A-011 of preparation example 2

[0144]

[0145] First step:

[0146]

[0147] Into a dry 500 mL round bottom flask, add 3,4-dichlorobenzyl 10 g, add dimethyl sulfoxide 100 mL, start stirring, add sodium azide 3.35 g in batches under ice water bath. Stir at room temperature for 8 h. TLC detection reaction is complete, add 200 mL water, then use dichloromethane 200 mL extraction three times, combined organic layer, using 300 mL saturated sodium chloride solution to wash the organic layer, using anhydrous sodium sulfate drying. The organic layer is concentrated, separated by column chromatography, 3,4-dichlorobenzyl azide 9.2 g, yield 89%.

[0148] Second step:

[0149]

[0150] Into a 100 mL round bottom flask, add 4-bromophenyl propargyl ether 1.12 g and N,N-dimethylformamide 15 mL, with stirring add copper sulfate pentahydrate 340 mg and 3,4-dichlorobenzyl azide 1.05 g, followed by sodium ascorbate solution (1.78 g sodium ascorbate dissolved in 2.5 mL water), reaction at 50 degree Celsius. TLC test after 8 h reaction, reaction is complete, concentrate, add 40 mL water, extract with 60 mL dichloromethane three times, combine the organic layer and wash with saturated sodium chloride solution, dry the organic layer with anhydrous sodium sulfate. Column chromatography separation, get the second step product 1.85 g, yield 84%.

[0151] Third step:

[0152]

[0153] Into a 100 mL round bottom flask, add third step product 51.0 mg, 1,4-dioxane 1.5 mL, 3-aminopyridine 19 mg, tris-dibenzylideneacetone palladium 5.4 mg, 2-dicyclohexylphosphino-2',4',6'-triisopropyl biphenyl 8.0 mg and sodium tert-butoxide 19.0 mg, replace with nitrogen three times, reaction at 110 degree Celsius. TLC test after 12 h reaction, product is generated, add 5 mL water, extract with 10 mL dichloromethane three times, combine the organic layer and wash with saturated sodium chloride solution, dry with anhydrous sodium sulfate. Column chromatography separation, get 21 mg compound A-011, yield 40%.

[0154] In a similar manner to that described in Preparation Example 1 or Preparation Example 2, and with reference to General Synthetic Route I, by making the appropriate substitutions to the starting materials, the compounds numbered A, B, C, etc. in Tables 1 to 3 below can be obtained.

[0155] Table 1 Compounds of the formula A according to the application

[0156]

[0157]

[0158]

[0159] Table 2 Compounds of the formula B according to the application

[0160]

[0161]

[0162] Table 3 Compounds of formula C according to the application

[0163]

[0164]

[0165] Synthesis of compound D-037 of Preparation Example 3

[0166]

[0167] First step:

[0168]

[0169] Into a 100 mL round bottom flask, dry, was added 4-chlorobenzyl 1.0 g, dimethyl sulfoxide 10 mL, start stirring, sodium azide 430 mg was added in batches under ice water bath. Stirring at room temperature for 8 h. TLC detection reaction was complete, added 20 mL water, extracted with dichloromethane 20 mL three times, combined organic layer, using 30 mL saturated sodium chloride solution to wash the organic layer, using anhydrous sodium sulfate drying. The organic layer was concentrated, separated using column chromatography, 4-chlorobenzyl azide 970 mg, yield 93%.

[0170] Second step:

[0171]

[0172] Into a 100 mL round bottom flask, added 4-(4-(prop-2-yn-1-yloxy)phenyl)piperazine-1- carboxylate 200 mg and N,N-dimethylformamide 8 mL, stirring, added copper sulfate 85 mg and the first step obtained 4-chlorobenzyl azide 117 mg, followed by sodium ascorbate solution (250 mg of ascorbic acid sodium dissolved in 2.0 mL of water), 50 degrees Celsius reaction. After 8 h of reaction, TLC detection reaction was complete, concentrated, added 20 mL water, extracted with 30 mL dichloromethane three times, combined organic layer and washed with saturated sodium chloride solution, the organic layer was dried with anhydrous sodium sulfate. Separated using column chromatography, the second step product 250 mg, yield 82%.

[0173] Third step:

[0174]

[0175] Into a 50 mL round bottom flask, was placed 248 mg of the product from Step 2 and 5.0 mL of 1,4-dioxane, 1.0 mL of concentrated hydrochloric acid was added with stirring and the reaction was allowed to proceed at room temperature. After 3 h, the reaction was complete as determined by TLC. The reaction mixture was concentrated, the pH was adjusted to 9.0 using saturated sodium carbonate solution, 10 mL of water was added, and the mixture was extracted three times with 10 mL of dichloromethane. The organic layers were combined and washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 210 mg of the crude product from Step 3.

[0176] Step 4:

[0177]

[0178] Into a 100 mL round bottom flask, was placed 90 mg of the crude product from Step 3 and 4.0 mL of acetonitrile, 98 mg of potassium carbonate and 42 μL of methyl-p-toluenesulfonate were added with stirring and the reaction was allowed to proceed at reflux. After 5 h, the product was formed as determined by TLC. The reaction mixture was cooled to room temperature, 10 mL of water was added, and the mixture was extracted three times with 15 mL of dichloromethane. The organic layers were combined, washed with saturated sodium chloride solution, and dried over anhydrous sodium sulfate. Column chromatography gave 39 mg of Compound D-037 in 42% yield.

[0179] In a similar manner to that described in Preparation Example 3, and with reference to General Synthetic Route III, by making appropriate substitutions of starting materials, the compounds numbered D, E, F in Tables 4 to 6 below can be obtained.

[0180] Table 4 Compounds of the formula D according to the application

[0181]

[0182]

[0183]

[0184]

[0185] Table 5 Compounds of the formula E according to the application

[0186]

[0187]

[0188]

[0189]

[0190]

[0191] Table 6 Compounds of the formula F according to the application

[0192]

[0193]

[0194]

[0195]

[0196]

[0197] Synthesis of compound G-005 of Preparation Example 4

[0198]

[0199] First step:

[0200]

[0201] Into a 100 mL round bottom flask, 4-methoxybenzyl chloride 1.0 g was added, dimethyl sulfoxide 10 mL was added, stirring was started, sodium azide 498 mg was added slowly under ice water bath. The reaction was stirred at room temperature for 8 h. TLC test showed the reaction was completed, 30 mL water was added, the reaction mixture was extracted with dichloromethane 30 mL for three times, the organic layers were combined, the organic layer was washed with 100 mL saturated sodium chloride solution, dried with anhydrous sodium sulfate. The organic layer was concentrated, separated by column chromatography, 4-methoxybenzyl azide 901 mg was obtained, the yield was 86%.

[0202] Second step:

[0203]

[0204] Into a 100 mL Schlenk flask, 400 mg 1-nitro-4-(prop-2-yn-1-yloxy)benzene and 25 mg pentamethylcyclopentadienyl bis(triphenylphosphine) ruthenium chloride were added, 10 mL 1,4-dioxane and 4-methoxybenzyl azide 335 mg were added under nitrogen protection, the reaction was carried out by heating to 80 degrees Celsius. The reaction was detected by TLC after 4 h, concentrated, 30 mL water was added, extracted with 40 mL dichloromethane for three times, the organic layers were combined and washed with saturated sodium chloride solution, the organic layer was dried with anhydrous sodium sulfate. Column chromatography separation obtained the second step product 634 mg, the yield was 84%.

[0205] Third step:

[0206]

[0207] To a 100 mL round bottom flask, 350 mg of the product from Step 2 was added along with 3.0 mL of ethanol and 3.0 mL of water. While stirring, 240 mg of iron powder and 156 mg of ammonium chloride were added and the reaction was allowed to proceed at 60 °C. TLC indicated that the starting material was consumed. Water was added and the reaction mixture was extracted with dichloromethane. The organic layers were combined, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate and chromatographed to give 110 mg of the product from Step 3 in 27% yield.

[0208] Step 4:

[0209]

[0210] To a 100 mL round bottom flask, 110 mg of the product from Step 3 was added along with 2 mL of dichloromethane. While stirring, 270 μL of triethylamine and 120 μL of dimethyl sulfate were added and the reaction was allowed to proceed at room temperature. After 12 h, TLC indicated that the product was formed. The reaction mixture was diluted with 10 mL of water and extracted with 15 mL of dichloromethane three times. The organic layers were combined, washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate. Chromatography gave 12 mg of Compound G-005 in 10% yield.

[0211] In a similar manner to that described in Preparation Example 4, and with reference to General Synthetic Route III, the compounds listed in Tables 4 to 6 below can be obtained by replacing the starting materials with the compounds listed in Tables 4 to 6.

[0212] Table 7 Compounds of Formula G according to the application

[0213]

[0214]

[0215]

[0216] Synthesis of Compound H-037 of Preparation Example 5

[0217]

[0218] Step 1:

[0219]

[0220] To a 250 mL round bottom flask, 1.0 g of 4-chlorobenzyl chloride was added along with 10 mL of dimethyl sulfoxide. While stirring, 380 mg of sodium azide was added slowly under an ice water bath. The reaction was allowed to proceed at room temperature for 8 h. TLC indicated that the reaction was complete. The reaction mixture was diluted with 30 mL of water and extracted with 30 mL of dichloromethane three times. The organic layers were combined, washed with 100 mL of saturated sodium chloride solution and dried over anhydrous sodium sulfate. The organic layer was concentrated and chromatographed to give 346 mg of 4-chlorobenzyl azide in 85% yield.

[0221]

[0222] Second step: To 100 mL Schlenk flask was added tert-butyl 4-(4-(prop-2-yn-1-yloxy)phenyl)piperazine-1-carboxylate 500 mg and pentamethylcyclopentadienyl bis(triphenylphosphine) ruthenium chloride 25 mg, 10 mL of 1,4-dioxane and 4-chlorobenzyl azide 345 mg was added under nitrogen protection, the reaction was heated to 80 degree Celsius. TLC test after 4 h reaction, the reaction was completed, concentrated, 30 mL of water was added, extracted with 30 mL of dichloromethane three times, combined the organic layer and washed with saturated sodium chloride solution, the organic layer was dried with anhydrous sodium sulfate. Column chromatography separation to get the second step product 500 mg, yield 65%.

[0223]

[0224] Third step: To 100 mL round bottom flask was added the second step product 500 mg and 1,4-dioxane 10.0 mL, 2.0 mL of concentrated hydrochloric acid was added under stirring, the reaction was carried out at room temperature. TLC test after 3 h reaction, the reaction was completed, concentrated, the pH was adjusted to 10.0 with sodium hydroxide solution (6M), 25 mL of water was added, extracted with 25 mL of dichloromethane three times, combined the organic layer and washed with saturated sodium chloride solution, the organic layer was dried with anhydrous sodium sulfate. Third step crude product 300 mg was obtained by distillation under reduced pressure.

[0225]

[0226] Fourth step: To 100 mL round bottom flask was added the third step crude product 300 mg and dichloromethane 5 mL, 272 μL of triethylamine and 109 μL of methyl iodide was added under stirring, the reaction was carried out at room temperature. TLC test after 6 h reaction, the product was generated, 10 mL of water was added, extracted with 15 mL of dichloromethane three times, combined the organic layer and washed with saturated sodium chloride solution, and dried with anhydrous sodium sulfate. Column chromatography separation to get 60 mg of compound H-037, yield 17%.

[0227] In a similar manner to that described in Preparation Example 4, and with reference to General Synthetic Route V, the compounds listed in Tables 4 to 6 below can be obtained by replacing the starting materials with the H-numbered compounds.

[0228] Table 8 Compounds of formula H according to the application

[0229]

[0230]

[0231]

[0232]

[0233] Table 9, 10 and 11: Compound structure characterization data

[0234] Table 9 shows the mass spectrometry data or1H-NMR data of representative compounds listed in Table 1, Table 2 and Table 3. 1 H-NMR data, Table 10 shows the mass spectrometry data or1H-NMR data of representative compounds listed in Table 4, Table 5 and Table 6. 1 H-NMR data, Table 11 shows the mass spectrometry data or1H-NMR data of representative compounds listed in Table 7 and Table 8. 1 H-NMR data. Deuterated chloroform (Chloroform-d, CDCl3) or deuterated dimethyl sulfoxide DMSO-d6 were used as test solvents, unless otherwise stated.

[0235] In all the description of Tables 9, 10 and 11 and hereinafter, "NMR" means nuclear magnetic resonance spectrum, MS stands for mass spectrometry. The following abbreviations are used:

[0236] s = singlet, br = broad, d = doublet, dd = double doublet, t = triplet, td = triple doublet, q = quartet, m = multiplet

[0237] Table 9:

[0238]

[0239]

[0240]

[0241] Table 10:

[0242]

[0243]

[0244]

[0245]

[0246]

[0247]

[0248]

[0249]

[0250] Table 11:

[0251]

[0252]

[0253] Formulation Example 1

[0254] Examples F1.1 to F1.2: Emulsifiable concentrate

[0255]

[0256] An emulsion of the desired concentration for use can be prepared by diluting this concentrate with water or other dispersing agent.

[0257] Example F2: Wettable powder

[0258]

[0259]

[0260] All components are mixed and the mixture is thoroughly ground in a suitable mill to give a wettable powder which can be diluted with water or other dispersing agent to the desired concentration for use.

[0261] Example F3: Suspension concentrate

[0262]

[0263] A suspension concentrate of the desired concentration for use can be prepared by diluting this concentrate with water or other dispersing agent.

[0264] Example F4: Dispersible oil suspension

[0265]

[0266] An oil suspension of the desired concentration for use can be prepared by diluting this concentrate with water or other dispersing agent.

[0267] Example F5: Water dispersible granules

[0268]

[0269]

[0270] All components are mixed and the mixture is extrusion granulated with a suitable amount of water and then dried to give water dispersible granules. These can be diluted with water or other dispersing agent to the desired concentration for use.

[0271] Example F6: Granules

[0272]

[0273] The compound is ground in a stream of air and mixed with a ball of bentonite clay. A polyvinyl alcohol binder is sprayed in during the mixing. After the mixture is uniform, it is dried to obtain granules. The granules can be diluted with water or other dispersing agent to the desired concentration of the dispersion for use.

[0274] Biological Examples

[0275] In view of the fact that Magnaporthe grisea usually invades plants via appressorium-mediated mode and can be artificially cultured in the laboratory, Magnaporthe grisea can be used as a model pathogenic fungus to test the inhibition of Magnaporthe grisea conidial germination, germ tube growth or appressorium formation by the compounds according to the present application. The relevant activity of the compounds according to the present application is exemplified by the following examples.

[0276] Biological Example G1. Inhibition of Magnaporthe grisea conidial germination and appressorium formation by substituted 1,2,3-triazole compounds

[0277] a. Test pathogenic fungus: Magnaporthe grisea strain P131

[0278] b. Test method:

[0279] 1) Production of Magnaporthe grisea conidia: The Magnaporthe grisea strain P131 to be tested is inoculated on a tomato oat agar (OTA) plate and incubated in a constant temperature and light incubator at 28°C. After 3-5 days, the Magnaporthe grisea colonies on the OTA are broken up thoroughly and then evenly spread on a new OTA plate and incubated in a constant temperature and light incubator at 28°C. When the newly grown hyphae can be seen on the surface of the medium (usually 1-2 days), the hyphae are broken up gently with a cotton swab and washed clean with sterile water and then air dried. A single layer of gauze is placed on the culture plate and incubated at 28°C under light for 48 hours to produce a large number of conidia on the surface of the OTA.

[0280] 2) Preparation of Magnaporthe grisea conidial suspension: The culture on the OTA is washed off with sterile water and filtered through three layers of lens paper. The filtrate is the conidial suspension. The concentration of the conidia in the suspension is adjusted to 2 x 10 5

[0281] 3) The test compound is added to the conidial suspension at different concentration gradients to prepare solutions with working concentrations of 200 ppm and 50 ppm and then spotted on hydrophobic glass slides. Four spots are spotted on each glass slide and treated in the dark with moisture. After 12 hours of inoculation, the conidial germination rate and appressorium formation rate are observed and counted under a microscope.

[0282] ​4) Statistics and Analysis: Count 100 conidia in the center of each of the three inoculation points on each hydrophobic slide. Calculate the average number of germinated conidia and the number of appressoria formed. Calculate the percent germination and the percent appressoria formation. Calculate the IC50 value.

[0283] Table 12 shows the data of biological example Gl for some of the compounds of Tables 1-8, where "-" means no inhibition at 200 ppm, "+" means less than 40% inhibition at 200 ppm, "++" means more than 40% inhibition at 50 ppm, and "+++" means more than 80% inhibition at 50 ppm.

[0284] Table 12

[0285]

[0286]

[0287]

[0288]

[0289] Biological Example G2: Control of Magnaporthe grisea by substituted 1,2,3-triazole compounds - Rice pot experiment

[0290] Preparation of rice: Take four-leafed rice seedlings of susceptible varieties CO39 and Xiangwanxian 11 and place them in an inoculation box for use.

[0291] Production of Magnaporthe grisea conidia: Place Magnaporthe grisea strain P131 on a tomato oatmeal agar (OTA) plate and incubate in a 28°C constant temperature light incubator. After 3-5 days, break the Magnaporthe grisea colonies on the OTA plate and evenly spread them on a new OTA plate. Incubate in a 28°C constant temperature light incubator. When new hyphae grow out of the surface of the medium (usually 1-2 days), break the hyphae with a cotton swab and rinse with sterile water. Dry the plate and cover it with a single layer of gauze. Incubate for 48 hours at 28°C under light to produce a large number of conidia on the surface of the OTA plate.

[0292] Preparation of Magnaporthe grisea conidia suspension: Wash the culture on the OTA plate with sterile water and filter it through three layers of lens paper. Centrifuge the filtrate at 5000 rpm for 5 minutes at room temperature. Resuspend the precipitated conidia in gelatin and adjust the concentration of the conidia to 5 x 10 4

[0293] Preparation of test compound solution: Add the test compound stock solution to the prepared Magnaporthe grisea conidia suspension and dilute it to a working concentration of 200 ppm.​

[0294] Spray inoculation: The mixture of Magnaporthe grisea conidia and small molecule agents was sprayed on rice susceptible varieties Xiangwanxian 11 and CO39, 15 mL of mixture was sprayed for each treatment. Dark and moist culture for 36 hours, then normal culture. After 7 days of inoculation, the control effect of the test compound on rice blast was evaluated.

[0295] Table 13 shows the data of biological example G2 of some compounds in Tables 1-8.

[0296] The rice blast leaf blight disease investigation was carried out according to the agricultural industry standard “Technical Regulation for Field Monitoring of Rice Blast Resistance” (NYT3685-2020), and the specific standards are as follows: 0 level: no disease on the whole leaf; 1 level: pinhead-sized brown necrotic spots on the leaf; 2 level: larger (1-2 mm in diameter) brown necrotic spots on the leaf, but no typical disease spots; 3 level: typical rice blast disease spots, spot area < 2%; 4 level: typical rice blast disease spots, 2% ≤ spot area < 5%; 5 level: typical rice blast disease spots, 5% ≤ spot area < 10%; 6 level: typical rice blast disease spots, 10% ≤ spot area < 25%; 7 level: typical rice blast disease spots, 25% ≤ spot area < 50%; 8 level: typical rice blast disease spots, 50% ≤ spot area < 75%; 9 level: typical rice blast disease spots, spot area ≥ 75%.

[0297] Table 13

[0298]

[0299]

[0300] Biological example G3: control effect of substituted 1,2,3-triazole compounds on potato late blight - potato pot experiment

[0301] Preparation of potato: after normal culture of potato late blight susceptible variety “Desiree” seedlings, they were placed in an inoculation box for use

[0302] Preparation of potato late blight sporangia: the medium-strength strain “MZ” was selected for culture on a suitable medium, and after the sporangia were produced, they were washed off with sterile water, filtered with double-layer gauze to prepare a sporangia suspension, which was treated with darkness for 3 h at 4°C and stored for standby use.

[0303] Preparation of sporangia suspension: the standby sporangia solution treated with 4°C sterile water was adjusted to a concentration of 4×10 3 / mL of suspension.

[0304] Preparation of spray working solution: dilute the mother liquor of the test compound with water to a working concentration of 200 ppm.

[0305] Spray inoculation: before inoculation, the plants to be treated were acclimated in a 20°C artificial climate greenhouse for 4 hours, after which the treated plants were sprayed evenly on both sides of the leaves with the working solution, 2 plants per treatment, 60 mL per plant, and after the working solution was allowed to dry naturally, the plants were cultured normally for 24 hours. Subsequently, the plants were spray inoculated with the prepared sporangia suspension, and after 24 hours of dark treatment, the plants were cultured under normal light (20°C, 18 hours of light / 6 hours of darkness), and the disease condition was observed in real time, and the control effect of the test compound on potato late blight was evaluated after 7 days.

[0306] Table 14 shows the data of biological example G3 of some of the compounds in Tables 1-8, and the potato late blight disease condition was investigated according to the grading standard, and the specific standard is as follows: 0 level: no disease spot; 1 level: the disease spot area accounts for less than 5% of the whole leaf area; 3 level: the disease spot area accounts for 6%-10% of the whole leaf area; 5 level: the disease spot area accounts for 11%-20% of the whole leaf area; 7 level: the disease spot area accounts for 21%-50% of the whole leaf area; 9 level: the disease spot area accounts for more than 50% of the whole leaf area.

[0307] Table 14

[0308]

[0309]

[0310] Biological example G4: control effect of substituted 1,2,3-triazole compounds on corn anthracnose - corn pot experiment

[0311] Preparation of corn: corn Mo17 seedlings were cultured to the three-leaf-one-heart stage and placed in an inoculation box for use.

[0312] Preparation of anthracnose conidia: the M2 strain of Colletotrichum graminicola was selected, and the isolated anthracnose was picked up and transferred to a new PDA+0.1% YE plate culture medium for further culture for 4 days. The mycelium grown on the plate was scraped off with a sterile cotton swab to promote sporulation. The conidia were picked up in sterile water and shaken with a vortex shaker. Then 50 μL of the spore suspension was added dropwise to the WA plate culture medium, which was dried with a spreader and cultured at 28°C in the dark. After the conidia germinated, the germinated conidia were picked up one by one under a body lens and cultured with a new PDA culture medium at 28°C in the dark.

[0313] Preparation of anthracnose conidia suspension: the culture on PDA was eluted with sterile water, filtered with three layers of lens paper, and the filtrate was the conidia solution. The concentration of the conidia was adjusted to 1 x 10 5 individual / mL with a hemocytometer.

[0314] Preparation of spray inoculation working solution: the mother liquor of the test compound was diluted with water to a working concentration of 200 ppm.

[0315] Spray inoculation: the spray inoculation working solution was evenly sprayed onto the leaf surface until the leaf was covered with mist droplets, 3 plants per treatment, and the test compound was allowed to dry naturally, and the conidial suspension was inoculated. After inoculation, the plants were moved to a humidity chamber for dark incubation for 24 h, and then incubated at 25°C, light, and 80% humidity. The control effect of the test compound was evaluated 5 days after inoculation.

[0316] Table 15 shows the data of biological example G4 of some of the compounds in Tables 1-8, and the disease investigation of the corn anthracnose disease was conducted according to the grading standard, and the specific standard is as follows: 0 level: no symptoms; 1 level: a brown spot or brown spot with a needle tip size, and the area of the spot accounts for less than 5% of the leaf area; 3 level: a brown spot in a nearly round or spindle shape, and the area of the spot accounts for 5%-10% of the leaf area; 5 level: a black necrotic spot, or local spots are connected, and the area of the spot accounts for 11%-25% of the leaf area; 7 level: the black necrotic spot is enlarged, or the leaf edge is dead, and the area of the spot accounts for 26%-50% of the leaf area; 9 level: the area of the spot accounts for more than 50% of the leaf area, or the leaf is dead.

[0317] Table 15

[0318]

[0319]

[0320] Biological example G5: control effect of substituted 1,2,3-triazole compounds on strawberry anthracnose—strawberry pot experiment

[0321] Preparation of strawberry: after normal culture, the strawberry seedlings of “Red Beauty” were placed in an inoculation box for use.

[0322] Production of conidium of Colletotrichum gloeosporioides: the strain C28 was selected, and the isolated C. gloeosporioides was picked to a new PDA+0.1% YE plate medium for continuous culture for 4 days. The mycelium growing on the plate was scraped off with a sterile cotton swab to promote sporulation. The conidium was picked into sterile water and shaken with a vortex oscillator. Then, 50 μL of the spore suspension was dropped on a WA plate medium, which was dried with a spreader and cultured at 28°C in the dark. After the conidium germinated, the germinated conidium was picked one by one under a body lens, and a new PDA medium was used for culture at 28°C in the dark for use.

[0323] Preparation of conidium suspension of C. gloeosporioides: the culture on PDA was eluted with sterile water, filtered with three layers of lens paper, and the filtrate was a conidium solution. The concentration of the conidium was adjusted to 1×105 0.1 mL.

[0324] Preparation of spray inoculation working solution: the mother liquor of the test compound was added to the prepared anthrax conidiospore solution and diluted to a working concentration of 200 ppm.

[0325] Spray inoculation: the spray inoculation working solution was evenly sprayed onto the leaf surface until the leaf was covered with mist droplets, 3 plants per treatment. The subsequently inoculated treatments were transferred to 12h / 12h light-dark alternating conditions after being cultured at 28°C in the dark for 36h. Whether or not to be sick was observed every day, and the control effect of the test compound was evaluated after 7 days of inoculation.

[0326] Table 16 shows the data of biological example G5 of part of the compounds in Tables 1-8, and the disease investigation of strawberry anthracnose disease was carried out according to the grading standard, and the specific standard is as follows: 0 level: no symptoms; 1 level: brown spots or brown spots of needle size appear, and the area of the disease spot accounts for less than 5% of the leaf area; 3 level: brown spots of near-circular or spindle shape appear, and the area of the disease spot accounts for 5%-10% of the leaf area; 5 level: black necrotic spots appear, or local disease spots are connected, and the area of the disease spot accounts for 11%-25% of the leaf area; 7 level: black necrotic spots expand, or the leaf edge dies, and the area of the disease spot accounts for 26%-50% of the leaf area; 9 level: the area of the disease spot accounts for more than 50% of the leaf area, or the leaf dies.

[0327] Table 16

[0328] Compound No. Disease Rating A-003 7 A-013 5 B-010 7 D-010 0 D-011 3 D-012 0 D-013 0 D-014 1 D-037 5 E-013 0 E-020 5 E-037 0 F-005 9 G-011 7 H-016 1 H-017 1 H-037 1

[0329] Biological example G6: control effect of substituted 1,2,3-triazole compounds on wheat powdery mildew-wheat pot experiment

[0330] Preparation of wheat: the wheat seedlings of powdery mildew susceptible variety Xiaoyan No. 6 were normally cultured to the 2-leaf stage and then placed in an inoculation box for use. At the same time, the wheat seedlings of Xiaoyan No. 6 infected with powdery mildew strain No. 63 were prepared and continued to be cultured.

[0331] Preparation of spray working solution: the mother liquor of the test compound was added to water and diluted to a working concentration of 200 ppm.

[0332] Spray inoculation: the spray working solution was sprayed on the wheat seedlings, and after spraying, the seedlings were placed in a cool place to dry naturally. Fresh spores produced within 24h on the diseased wheat leaves were evenly shaken and inoculated on the treated pot seedlings, 3 pots per treatment, 10 plants per pot. Then, the seedlings were placed in suitable conditions for further culture. The control effect of the test compound was evaluated after 6 days of inoculation.

[0333] Table 17 shows the data of biological example G6 of some compounds in Tables 1-8, the disease investigation of wheat powdery mildew disease was carried out according to the grading standard, and the specific standard was as follows: 0 level: no disease; 1 level: the area of disease spot was less than 5% of the whole leaf area; 3 level: the area of disease spot was 6%-15% of the whole leaf area; 5 level: the area of disease spot was 16%-25% of the whole leaf area; 7 level: the area of disease spot was 26%-50% of the whole leaf area; 9 level: the area of disease spot was more than 50% of the whole leaf area.

[0334] Table 17

[0335]

[0336]

[0337] Biological example G7: control effect of substituted 1,2,3-triazole compounds on cucumber downy mildew - cucumber pot experiment

[0338] Preparation of cucumber: long spring thorn, commercially available, cucumber seeds were planted in a seedling pot and cultivated in a greenhouse, and after the plants grew to 3-4 leaf stage, suitable plants were selected for use.

[0339] Preparation of cucumber downy mildew spore sac: collect cucumber downy mildew leaves, wash off the impurities and old spore sacs on the diseased leaves with sterile water, then place in a culture dish and keep moist, place in a growth room with 19°C, RH>80%, light and dark alternation, after 24 hours, a large number of new spore sacs are produced on the test leaves, then wash off the new spore sacs produced on the single lesion with sterile water, inoculate on the collected healthy detached leaves, cultivate in a growth room with 19°C, RH>80%, 12h light and dark alternation, and store and propagate the strain for use.

[0340] Preparation of spore sac suspension: wash off the new spore sacs propagated on the detached leaves after treatment with 4°C sterile water, and prepare a suspension with a concentration of 1x10 5 individual / mL.

[0341] Preparation of spray working solution: add the test compound stock solution to the prepared cucumber downy mildew spore sac suspension, and dilute to a working concentration of 200ppm.

[0342] Spray inoculation: spray the spray working solution on cucumber seedlings, 3 plants per treatment, and cultivate in a dark growth environment at 19°C for 48h, then continue to cultivate in suitable conditions. Evaluate the control effect of the test compound after 7d of inoculation.

[0343] Table 18 shows the data of biological example G7 of some compounds in Tables 1-8, and the disease investigation of cucumber downy mildew was carried out according to the grading standard, and the specific standard was as follows: 0 grade: no disease; 1 grade: the area of disease spot accounted for less than 5% of the whole leaf area; 3 grade: the area of disease spot accounted for 6%-10% of the whole leaf area; 5 grade: the area of disease spot accounted for 11%-25% of the whole leaf area; 7 grade: the area of disease spot accounted for 26%-50% of the whole leaf area; 9 grade: the area of disease spot accounted for more than 50% of the whole leaf area.

[0344] Table 18

[0345] Compound No. Disease Rating A-005 5 A-013 7 A-017 5 B-011 9 C-001 9 D-010 1 D-011 3 D-012 1 D-013 0 D-014 5 D-027 7 E-013 0 E-037 5 F-013 5 G-011 9 H-016 1 H-017 3 H-037 3

[0346] The embodiments of the present application are described above. However, the present application is not limited to the above-described embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. The compound represented by formula (IA), its racemate, tautomer, or agriculturally acceptable salt: ， in, R1 and R2 are selected from C1-C6 alkyl groups; R3, R4, R5, R6, and R7 represent halogens independently of each other.

2. The compound according to claim 1, its racemate, tautomer, or agriculturally acceptable salt, wherein, R1 and R2 are selected from C1-C3 alkyl groups.

3. The compound according to claim 1 or 2, its racemate, tautomer, or agriculturally acceptable salt, wherein, R1 and R2 are selected from methyl, ethyl, or n-propyl.

4. The compound according to claim 1 or 2, its racemate, tautomer, or agriculturally acceptable salt, wherein, R3, R4, R5, R6, and R7 represent Cl or F independently.

5. The following compounds, their racemic mixtures, tautomers, or agriculturally acceptable salts: A B C D E F G H 。 6. A pesticide composition comprising one, two or more of the compound of any one of claims 1 to 5, its racemic form, tautomer, or agriculturally acceptable salt as an active ingredient.

7. The pesticide composition according to claim 6, wherein, The pesticide composition is a fungicide or an ovicide.

8. The pesticide composition according to claim 6 or 7, wherein, The pesticide composition is a fungicide or ovicide containing a compound according to any one of claims 1 to 5 and optionally an agriculturally acceptable adjuvant.

9. The pesticide composition according to claim 6 or 7, wherein, Pesticide compositions are used as plant protectants to prevent or protect plants from plant diseases.

10. The pesticide composition according to claim 9, wherein, The plant diseases mentioned include rice blast, anthracnose, downy mildew, Phytophthora blight, and / or powdery mildew.

11. The pesticide composition according to claim 10, wherein, The diseases mentioned are selected from rice blast, pepper anthracnose, cucurbit downy mildew, strawberry anthracnose, potato late blight, pepper phytosis and / or wheat powdery mildew.

12. Use of one, two or more of the compounds, racemates, tautomers or agriculturally acceptable salts of any one of claims 1 to 5 for the prevention and control of rice blast, pepper anthracnose, cucurbit downy mildew, strawberry anthracnose, potato late blight, pepper phytosis and / or wheat powdery mildew.

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