CN112624988B - New triazole compound and application thereof in agriculture - Google Patents

Abstract

The invention provides a novel triazole compound and application thereof in agriculture; specifically, the invention relates to a triazole compound shown as a formula (IV) and a preparation method thereof; r in formula (IV) ^a And R is ^b Is hydrogen, C _1‑6 Alkyl, etc., X is-CH ₂ ‑、‑CH(CH ₃ ) -etc., R ¹ 、R ² 、R ³ 、R ⁴ And R is ⁵ Is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, C _1‑6 Alkyl groups, etc.; the compound, the composition and/or the preparation containing the compound have better bactericidal activity and are applied as bactericides in agriculture.

Description

New triazole compound and application thereof in agriculture

Technical Field

The invention provides a novel triazole compound and a preparation method thereof; triazole compounds and application of compositions and/or preparations containing the compounds as bactericides in agriculture.

Background

In order to obtain high crop yields, it is extremely important to control plant diseases caused by phytopathogenic fungi. Plant diseases that damage ornamental, vegetable, field, cereal and fruit crops can result in significant yield loss, leading to increased consumption costs. For this purpose, there are a number of products commercially available, but there is a continuing need for new compounds that are more effective, more economical, less toxic, safer to the environment or have different sites of action.

The invention provides a novel triazole compound with bactericidal activity.

Disclosure of Invention

The invention aims to provide a novel bactericidal compound with remarkable effect on preventing and controlling plant diseases, a bactericidal composition and a preparation containing the bactericidal compound and application thereof.

In one aspect, the present invention provides a compound which is a compound having the formula (IV) or a stereoisomer, oxynitride or salt thereof of the compound of formula (IV):

wherein:

R ^a and R is ^b Each independently is hydrogen, C _1-6 Alkyl, C _2-6 Alkenyl, C _2-6 Alkynyl, C _3-8 Cycloalkyl, C _3-8 cycloalkyl-C _1-3 Alkyl-, phenyl optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halogen or phenyl-C optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halogen _1-3 Alkyl-; or R is ^a 、R ^b And the N atom to which it is attached form a 3-8 membered heterocyclyl or a 5-10 membered heteroaryl;

x is-CR ^c R ^d -(CR ^e R ^f ) _n -；

R ^c And R is ^d Each independently is hydrogen or C _1-4 An alkyl group;

each R is ^e And R is ^f Independently hydrogen or C _1-4 An alkyl group;

or R is ^e 、R ^f And the C atom attached thereto form c=o;

n is 0 or 1;

R ¹ 、R ² 、R ³ 、R ⁴ and R is ⁵ Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, C _1-6 Alkyl, C _2-6 Alkenyl, C _2-6 Alkynyl, halo C _2-6 Alkenyl, halo C _2-6 Alkynyl, C _2-6 Alkenyloxy, C _2-6 Alkynyloxy, C _1-6 Alkoxy, C _1-6 Alkylthio, halo C _1-6 Alkyl, halogenated C _1-6 Alkoxy, halo C _1-6 Alkylthio group,C _1-6 Alkyl NH-, (C) _1-6 Alkyl group ₂ N-、C _1-6 alkyl-C (=o) -, C _1-6 alkoxy-C (=o) -or optionally substituted with 1, 2, 3, 4 or 5 groups selected from fluoro, chloro, bromo, iodo, hydroxy, cyano, nitro, C _1-6 Alkyl, C _1-6 Alkoxy, halo C _1-6 Alkyl, halogenated C _1-6 Alkoxy or C _1-6 Phenyl substituted by a substituent of alkoxy-C (=o) -;

or R is ¹ 、R ² And the carbon atoms to which they are attached form a benzene ring;

or R is ² 、R ³ And the carbon atoms to which they are attached form a benzene ring;

or R is ³ 、R ⁴ And the carbon atoms to which they are attached form a benzene ring;

or R is ⁴ 、R ⁵ And the carbon atoms to which they are attached form a benzene ring;

the conditions are as follows: r is R ¹ 、R ² 、R ³ 、R ⁴ And R is ⁵ And cannot be hydrogen at the same time.

In some embodiments, the present invention provides a compound that is a compound having the formula (IV) or a stereoisomer, nitroxide, or salt thereof of a compound of formula (IV), wherein:

R ^a and R is ^b Each independently is hydrogen, C _1-4 Alkyl, C _2-4 Alkenyl, C _2-4 Alkynyl, C _3-6 Cycloalkyl, C _3-6 cycloalkyl-C _1-3 Alkyl-, phenyl optionally substituted with 1, 2, 3, 4 or 5 substituents selected from fluorine, chlorine, bromine or iodine, or phenyl-C optionally substituted with 1, 2, 3, 4 or 5 substituents selected from fluorine, chlorine, bromine or iodine _1-3 Alkyl-.

In other embodiments, the present invention provides a compound that is a compound having the formula (IV) or a stereoisomer, nitroxide, or salt thereof of a compound of formula (IV), wherein:

R ^a and R is ^b Each independently is hydrogen, methyl, ethyl, n-propyl, isopropyl, ethenyl, propenyl, allyl, cyclopropylCyclobutyl, cyclopentyl, cyclohexyl, phenyl or benzyl.

In some embodiments, the present invention provides a compound that is a compound having the formula (IV) or a stereoisomer, nitroxide, or salt thereof of a compound of formula (IV), wherein:

x is-CH ₂ -、-CH(CH ₃ )-、-C(CH ₃ ) ₂ -or-CH ₂ -C(＝O)-。

In other embodiments, the present invention provides a compound that is a compound having the formula (IV) or a stereoisomer, nitroxide, or salt thereof of a compound of formula (IV), wherein:

x is-CH ₂ -or-CH ₂ -C(＝O)-。

In some embodiments, the present invention provides a compound that is a compound having the formula (IV) or a stereoisomer, nitroxide, or salt thereof of a compound of formula (IV), wherein:

R ¹ 、R ² 、R ³ 、R ⁴ and R is ⁵ Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, C _1-4 Alkyl, C _2-4 Alkenyl, C _2-4 Alkynyl, C _1-4 Alkoxy, C _1-4 Alkylthio, halo C _1-4 Alkyl, halogenated C _1-4 Alkoxy, halo C _1-4 Alkylthio, C _1-4 Alkyl NH-, (C) _1-4 Alkyl group ₂ N-、C _1-4 alkyl-C (=o) -, C _1-4 alkoxy-C (=o) -or optionally substituted with 1, 2, 3, 4 or 5 groups selected from fluorine, chlorine, bromine, iodine, hydroxy, cyano, nitro or C _1-4 Phenyl substituted by substituent of alkoxy-C (=o) -.

In still other embodiments, the present invention provides a compound that is a compound having the formula (IV) or a stereoisomer, nitroxide, or salt thereof of a compound of formula (IV), wherein:

R ¹ 、R ² 、R ³ 、R ⁴ and R is ⁵ Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, -CH ₃ 、-CH ₂ CH ₃ 、-CH ₂ CH ₂ CH ₃ 、-CH(CH ₃ ) ₂ 、-C(CH ₃ ) ₃ 、CH ₂ ＝CH-、-OCH ₃ 、-OCH ₂ CH ₃ 、-OCH ₂ CH ₂ CH ₃ 、-OCH(CH ₃ ) ₂ 、-OC(CH ₃ ) ₃ 、-SCH ₃ 、-SCH ₂ CH ₃ 、-CH ₂ F、-CHF ₂ 、-CF ₃ 、-OCH ₂ F、-OCHF ₂ 、-OCF ₃ 、-SCF ₃ 、CH ₃ O-C (=o) -or optionally is substituted with 1, 2, 3, 4 or 5 groups selected from fluorine, chlorine, bromine, iodine, hydroxy, cyano, nitro, CH ₃ O-C (=O) -or C (CH) ₃ ) ₃ Phenyl substituted by O-C (=o) -substituents.

In still other embodiments, the present invention provides a compound that is a compound having the formula (IV) or a stereoisomer, nitroxide, or salt thereof of a compound of formula (IV), wherein:

the following sub-structural formula is shown as follows:

in another aspect, the present invention provides a compound that is a stereoisomer, nitroxide, or salt thereof, of a compound having one of the following structures:

In another aspect, the invention provides a composition comprising a compound of the invention. Unless otherwise indicated, all tautomers, racemates, hydrates, solvates, metabolites, metabolic precursors and prodrugs of the compounds of the invention are intended to be within the scope of the invention.

In some embodiments, the compositions according to the present invention further comprise an agropharmaceutically acceptable surfactant and/or carrier.

In another aspect, the invention provides the use of a compound according to the invention or a composition according to the invention for controlling plant diseases, in particular as a fungicide.

In some embodiments, the plant disease is caused by a phytopathogenic fungus.

In other embodiments, the plant disease is cucumber downy mildew.

In another aspect, the present invention provides a method for controlling plant diseases comprising applying to a plant or locus thereof an effective amount of a compound of the present invention or a composition comprising a compound of the present invention.

Isotopically enriched compounds have the structures given herein except that one or more atoms are replaced by an atom having a selected atomic or mass number. Exemplary isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chlorine, such as ² H， ³ H， ¹¹ C， ¹³ C， ¹⁴ C， ¹⁵ N， ¹⁷ O， ¹⁸ O， ¹⁸ F， ³¹ P， ³² P， ³⁵ S， ³⁶ Cl and Cl ¹²⁵ I。

Any asymmetric atom (e.g., carbon, etc.) of the disclosed compounds may exist in racemic or enantiomerically enriched form, such as in the (R) -, (S) -or (R, S) -configuration.

The foregoing merely outlines certain aspects of the invention and is not limited to these and other aspects, which are described more fully below.

Salts of the compounds of the present invention include those derived from alkali metals or alkaline earth metals, as well as those derived from ammonia and amines. Preferred cations include sodium, potassium, magnesium and have the formula N ⁺ (R ¹⁹ R ²⁰ R ²¹ R ²² ) Wherein R is an ammonium cation of ¹⁹ 、R ²⁰ 、R ²¹ And R is ²² Independently selected from hydrogen, C ₁ -C ₆ Alkyl and C ₁ -C ₆ A hydroxyalkyl group. Salts of the compound of formula (IV) may be prepared by treating the compound of formula (IV) with a metal hydroxide (e.g., sodium hydroxide) or an amine (e.g., ammonia, trimethylamine, diethanolamine, 2-methylthiopropylamine, bisallylamine, 2-butoxyethylamine, morpholine, cyclododecamine, or benzylamine).

When the compounds of the present invention contain a base moiety, acceptable salts may be formed with organic and inorganic acids, such as acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic, naphthalenesulfonic, benzenesulfonic, toluenesulfonic, camphorsulfonic, and similarly known acceptable acids.

Definitions and general terms

Reference will now be made in detail to certain embodiments of the invention, examples of which are illustrated in the accompanying structural and chemical formulas. The invention is intended to cover all alternatives, modifications and equivalents, which may be included within the scope of the invention as defined by the appended claims. Those skilled in the art will recognize that many methods and materials similar or equivalent to those described herein can be used in the practice of the present invention. The present invention is in no way limited to the methods and materials described herein. In the event of one or more of the incorporated references, patents and similar materials differing from or contradictory to the present application (including but not limited to defined terms, term application, described techniques, etc.), the present application controls.

It should further be appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents and publications referred to herein are incorporated by reference in their entirety.

The following definitions as used herein should be applied unless otherwise indicated. For the purposes of the present invention, chemical elements are in accordance with CAS version of the periodic Table of the elements, and handbook of chemistry and physics, 75 th edition, 1994. In addition, general principles of organic chemistry may be referenced to the descriptions in "Organic Chemistry", thomas Sorrell, university Science Books, sausalato:1999, and "March's Advanced Organic Chemistry" by Michael b.smith and Jerry March, john Wiley & Sons, new york:2007, the entire contents of which are incorporated herein by reference.

The articles "a," "an," and "the" are intended to include "at least one" or "one or more" unless the context clearly dictates otherwise or otherwise. Thus, as used herein, the articles refer to articles of manufacture that include one or more than one (i.e., at least one) object. For example, "a component" refers to one or more components, i.e., more than one component is contemplated as being employed or used in embodiments of the described embodiments.

The term "comprising" is an open-ended expression, i.e., including what is indicated by the invention, but not excluding other aspects.

The term "stereoisomer" refers to a compound having the same chemical structure but different arrangements of atoms or groups in space. Stereoisomers include enantiomers, diastereomers, conformational isomers (rotamers), geometric isomers (cis/trans), atropisomers, and the like.

"enantiomer" refers to two isomers of a compound that do not overlap but are in mirror image relationship to each other.

"diastereoisomers" refers to stereoisomers which have two or more chiralities and whose molecules are not mirror images of each other. Diastereomers have different physical properties, such as melting point, boiling point, spectral properties, and reactivity. The diastereomeric mixture may be separated by high resolution analytical procedures such as electrophoresis and chromatography, e.g., HPLC.

The stereochemical definitions and rules used in the present invention generally follow S.P. Parker, ed., mcGraw-Hill Dictionary of Chemical Terms (1984) McGraw-Hill Book Company, new York; and Eliel, e.and Wilen, s., "Stereochemistry of Organic Compounds", john Wiley & Sons, inc., new York, 1994.

Many organic compounds exist in optically active form, i.e., they have the ability to rotate the plane of plane polarized light. In describing optically active compounds, the prefixes D and L or R and S are used to represent the absolute configuration of the molecule with respect to one or more of its chiral centers. The prefixes d and l or (+) and (-) are symbols for specifying the rotation of plane polarized light by a compound, where (-) or l indicates that the compound is left-handed. The compound prefixed with (+) or d is dextrorotatory. One particular stereoisomer is an enantiomer, and a mixture of such isomers is referred to as an enantiomeric mixture. A50:50 mixture of enantiomers is referred to as a racemic mixture or racemate, which can occur when there is no stereoselectivity or stereospecificity in a chemical reaction or process.

Any asymmetric atom (e.g., carbon, etc.) of the disclosed compounds may exist in racemic or enantiomerically enriched form, such as in the (R) -, (S) -or (R, S) -configuration. In certain embodiments, each asymmetric atom has at least 50% enantiomeric excess, at least 60% enantiomeric excess, at least 70% enantiomeric excess, at least 80% enantiomeric excess, at least 90% enantiomeric excess, at least 95% enantiomeric excess, or at least 99% enantiomeric excess in the (R) -or (S) -configuration.

Depending on the choice of starting materials and methods, the compounds of the invention may be present in the form of one of the possible isomers or mixtures thereof, for example racemates and non-corresponding isomer mixtures, depending on the number of asymmetric carbon atoms. Optically active (R) -or (S) -isomers can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. If the compound contains a double bond, the substituent may be in the E or Z configuration; if the compound contains a disubstituted cycloalkyl group, the substituents of the cycloalkyl group may have cis or trans configuration.

The resulting mixture of any stereoisomers may be separated into pure or substantially pure geometric isomers, enantiomers, diastereomers, e.g., by chromatography and/or fractional crystallization, depending on the differences in the physicochemical properties of the components.

Any of the resulting racemates of the end products or intermediates can be resolved into the optical enantiomers by methods familiar to those skilled in the art, e.g., by separation of the diastereoisomeric salts thereof obtained, using known methods. The racemic product can also be separated by chiral chromatography, e.g., high Performance Liquid Chromatography (HPLC) using chiral adsorbents. In particular, enantiomers may be prepared by asymmetric synthesis.

In addition, unless explicitly indicated otherwise, the descriptions used in this disclosure of the manner in which each … is independently "and" … is independently "and" … is independently "are to be construed broadly as meaning that particular items expressed between the same symbols in different groups do not affect each other, or that particular items expressed between the same symbols in the same groups do not affect each other.

In the various parts of the present specification, substituents of the presently disclosed compounds are disclosed in terms of the type or scope of groups. It is specifically noted that the present invention includes each individual subcombination of the individual members of these group classes and ranges. For example, the term "C ₁ -C ₆ Alkyl "or" C _1-6 Alkyl "means in particular methyl, ethyl, C independently disclosed ₃ Alkyl, C ₄ Alkyl group、C ₅ Alkyl and C ₆ An alkyl group.

The term "alkyl" or "alkyl group" as used herein means a saturated straight or branched monovalent hydrocarbon group containing from 1 to 20 carbon atoms. Unless otherwise specified, alkyl groups contain 1 to 20 carbon atoms. In one embodiment, the alkyl group contains 1 to 12 carbon atoms; in one embodiment, the alkyl group contains 1 to 8 carbon atoms; in another embodiment, the alkyl group contains 1 to 6 carbon atoms; in yet another embodiment, the alkyl group contains 1 to 4 carbon atoms; in yet another embodiment, the alkyl group contains 1 to 3 carbon atoms.

Examples of alkyl groups include, but are not limited to, methyl (Me, -CH ₃ ) Ethyl (Et, -CH) ₂ CH ₃ ) N-propyl (n-Pr, -CH) ₂ CH ₂ CH ₃ ) Isopropyl (i-Pr, -CH (CH) ₃ ) ₂ ) N-butyl (n-Bu, -CH) ₂ CH ₂ CH ₂ CH ₃ ) Isobutyl (i-Bu, -CH) ₂ CH(CH ₃ ) ₂ ) Sec-butyl (s-Bu, -CH (CH) ₃ )CH ₂ CH ₃ ) Tert-butyl (t-Bu, -C (CH) ₃ ) ₃ ) N-pentyl (-CH) ₂ CH ₂ CH ₂ CH ₂ CH ₃ ) 2-pentyl (-CH (CH) ₃ )CH ₂ CH ₂ CH ₃ ) 3-pentyl (-CH (CH) ₂ CH ₃ ) ₂ ) 2-methyl-2-butyl (-C (CH) ₃ ) ₂ CH ₂ CH ₃ ) 3-methyl-2-butyl (-CH (CH) ₃ )CH(CH ₃ ) ₂ ) 3-methyl-1-butyl (-CH) ₂ CH ₂ CH(CH ₃ ) ₂ ) 2-methyl-1-butyl (-CH) ₂ CH(CH ₃ )CH ₂ CH ₃ ) And so on.

The term "alkenyl" denotes a straight-chain or branched monovalent hydrocarbon radical containing 2 to 12 carbon atoms, in which there is at least one site of unsaturation, i.e. one carbon-carbon sp ² Double bonds, wherein the alkenyl groups may be optionally substituted with one or more substituents described herein, including the positioning of "cis" and "tans", or the positioning of "E" and "Z. In one embodiment, the alkenyl group contains 2 to 8 carbon atoms; in another embodiment, the alkenyl group comprises 2 to 6 carbon atoms; in yet another embodiment, the alkenyl group contains 2 to 4 carbon atoms. Examples of alkenyl groups include, but are not limited to, vinyl (-ch=ch) ₂ ) Allyl (-CH) ₂ CH＝CH ₂ ) Propenyl (CH) ₃ -ch=ch-), oxo-butenyl (CH ₃ -C (=o) -ch=ch-), and so on.

The term "alkynyl" denotes a straight or branched monovalent hydrocarbon radical containing 2 to 12 carbon atoms, wherein there is at least one carbon-carbon sp triple bond.

The term "alkoxy" means that the alkyl group is attached to the remainder of the molecule through an oxygen atom, wherein the alkyl group has the meaning as described herein. Examples of alkoxy groups include, but are not limited to, methoxy (MeO, -OCH) ₃ ) Ethoxy (EtO, -OCH) ₂ CH ₃ ) 1-propoxy (n-PrO, n-propoxy, -OCH) ₂ CH ₂ CH ₃ ) Isopropoxy (i-PrO, i-propoxy, -OCH (CH) ₃ ) ₂ ) Isobutoxy (i-BuO, i-butoxy, CH (CH) ₃ ) ₂ CH ₂ O-), isopentyloxy (CH) ₃ ) ₂ CH ₂ CH ₂ O-) and the like.

The term "alkenyloxy" means that the alkenyl group is attached to the remainder of the molecule through an oxygen atom, wherein the alkenyl group has the meaning as described herein. Examples of alkenyloxy groups include, but are not limited to, CH ₂ ＝CH-O-、CH ₂ ＝CHCH ₂ -O-, etc.

The term "alkynyloxy" means an alkynyl group attached to the remainder of the molecule through an oxygen atom, wherein the alkynyl group has the meaning as described herein.

The term "alkylthio" means that the alkyl group is attached to the remainder of the molecule through a sulfur atom, wherein the alkyl group has the meaning as described herein. Examples of alkylthio groups include, but are not limited to, -SCH ₃ 、-SCH ₂ CH ₃ 、-SCH ₂ CH ₂ CH ₃ 、-SCH(CH ₃ ) ₂ Etc.

The term "cycloalkyl" denotes a monovalent or polyvalent saturated monocyclic, bicyclic or tricyclic ring system containing 3 to 12 carbon atoms. In one embodiment, cycloalkyl groups contain 3 to 10 carbon atoms; in another embodiment, cycloalkyl groups contain 3 to 8 carbon atoms; in yet another embodiment, cycloalkyl groups contain 3 to 6 carbon atoms. The cycloalkyl group is optionally substituted with one or more substituents described herein. Examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, and the like.

The term "haloalkyl" means an alkyl group substituted with one or more halogen atoms, wherein the alkyl group has the meaning as described herein. Examples of haloalkyl groups include, but are not limited to, -CH ₂ F，-CHF ₂ ，-CH ₂ Cl，-CH ₂ Br，-CF ₃ ，-CH ₂ CF ₃ ，-CH ₂ CH ₂ F，-CH ₂ CH ₂ Cl，-CH ₂ CH ₂ Br，-CH ₂ CHF ₂ ，-CH ₂ CH ₂ CF ₃ ，-CH ₂ CH ₂ CH ₂ F，-CH ₂ CH ₂ CH ₂ Cl，-CH ₂ CH ₂ CH ₂ Br，-CHFCH ₂ CH ₃ ，-CHClCH ₂ CH ₃ And so on.

The term "haloalkoxy" means that the alkoxy group is substituted with one or more halogen atoms, wherein the alkoxy group has the meaning as described herein. Examples of haloalkoxy groups include, but are not limited to, -OCH ₂ F，-OCHF ₂ ，-OCH ₂ Cl，-OCH ₂ Br，-OCF ₃ ，-OCH ₂ CF ₃ ，-OCH ₂ CH ₂ F，-OCH ₂ CH ₂ Cl，-OCH ₂ CH ₂ Br，-OCH ₂ CHF ₂ ，-OCH ₂ CH ₂ CF ₃ ，-OCH ₂ CH ₂ CH ₂ F，-OCH ₂ CH ₂ CH ₂ Cl，-OCH ₂ CH ₂ CH ₂ Br，-OCHFCH ₂ CH ₃ ，-OCHClCH ₂ CH ₃ And so on.

The term "haloalkylthio" means that the alkylthio group is substituted with one or more halogen atoms, wherein the alkylthio group has the meaning as described herein.

The terms "heterocyclyl" and "heterocycle" are used interchangeably herein to refer to a saturated or partially unsaturated monocyclic, bicyclic or tricyclic ring containing 3 to 15 ring atoms, wherein the monocyclic, bicyclic or tricyclic ring contains no aromatic rings and at least one ring atom is selected from the group consisting of nitrogen, sulfur and oxygen atoms. Unless otherwise indicated, a heterocyclic group may be a carbon or nitrogen group, and-CH ₂ The group may optionally be replaced by-C (=o) -. The sulfur atom of the ring may optionally be oxidized to an S-oxide. The nitrogen atom of the ring may optionally be oxidized to an N-oxide. Examples of heterocyclyl groups include, but are not limited to, oxiranyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl (e.g., 2-pyrrolidinyl), 2-pyrrolinyl, 3-pyrrolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, dihydrothienyl, 1, 3-dioxacyclopentyl, dithiocyclopentyl, tetrahydropyranyl, dihydropyranyl, 2H-pyranyl, 4H-pyranyl, tetrahydrothiopyranyl, piperidinyl (2-piperidinyl, 3-piperidinyl, 4-piperidinyl), morpholinyl, thiomorpholinyl, (1-oxo) -thiomorpholinyl, (1, 1-dioxo) -thiomorpholinyl, piperazinyl, dioxanyl, dithianyl, thiazalkyl, homopiperazinyl, homopiperidinyl, oxepinyl, thietanyl, 2-oxa-5-azabicyclo [2.2.1 ]Hept-5-yl, tetrahydropyridinyl. In heterocyclic groups-CH ₂ Examples of the substitution of the-group by-C (=o) -include, but are not limited to, 2-oxopyrrolidinyl, oxo-1, 3-thiazolidinyl, 2-piperidonyl, 3, 5-dioxopiperidyl. Examples of sulfur atoms in the heterocyclic group that are oxidized include, but are not limited to, sulfolane, 1-dioxothiomorpholino. The heterocyclyl group is optionally substituted with one or more substituents described herein.

The terms "3-12 membered heterocyclyl", "3-10 membered heterocyclyl", "3-8 membered heterocyclyl" or "3-6 membered heterocyclyl", wherein "3-12 membered", "3-10 membered", "3-8 membered" or "3-6 membered" typically describes the number of ring forming atoms in the molecule. For example, piperidinyl is 6 membered heterocyclyl.

The term "unsaturated" as used in the present invention means that the group contains one or more unsaturations.

The term "heteroatom" refers to O, S, N, P and Si, including N, S and any oxidation state forms of P; primary, secondary, tertiary and quaternary ammonium salt forms; or a form in which the hydrogen on the nitrogen atom in the heterocycle is substituted, for example, N (like N in 3, 4-dihydro-2H-pyrrolyl), NH (like NH in pyrrolidinyl) or NR (like NR in N-substituted pyrrolidinyl).

The term "phenylalkyl" means an alkyl group substituted with one or more phenyl groups, wherein the alkyl group has the meaning as described herein. Examples of phenylalkyl groups include, but are not limited to, benzyl, phenethyl, and the like.

The term "heteroaryl" means monocyclic, bicyclic and tricyclic ring systems containing 5 to 12 ring atoms, or 5 to 10 ring atoms, or 5 to 6 ring atoms, wherein at least one ring system is aromatic and at least one ring system contains one or more heteroatoms, wherein each ring system contains a ring of 5 to 7 atoms and has one or more attachment points attached to the remainder of the molecule. The term "heteroaryl" may be used interchangeably with the term "heteroaromatic ring" or "heteroaromatic compound". The heteroaryl group is optionally substituted with one or more substituents described herein.

In one embodiment, the heteroaryl group of 5 to 10 atoms comprises 1,2,3 or 4 heteroatoms independently selected from O, S and N.

In another embodiment, the ring atoms of the heteroaryl group comprise 1 to 9 carbon atoms and 1 to 4 heteroatoms selected from N, O or S; in another embodiment, the ring atoms of the heteroaryl group comprise 1 to 5 carbon atoms and 1 to 4 heteroatoms selected from N, O or S.

In yet another embodiment, heteroaryl represents a 5-or 6-membered heteroaryl group containing 1-4N heteroatoms; in yet another embodiment, heteroaryl represents a 5 membered heteroaryl containing 1-3 heteroatoms selected from N, O or S; in yet another embodiment, heteroaryl represents a 5 membered heteroaryl containing 1-3 heteroatoms selected from N or O; in yet another embodiment, heteroaryl represents a 5 membered heteroaryl containing 1-3 heteroatoms selected from N or S.

Examples of heteroaryl groups include, but are not limited to, 2-furyl, 3-furyl, N-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, N-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, pyridazinyl (e.g., 3-pyridazinyl), 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, tetrazolyl (e.g., 5-tetrazolyl), triazolyl (e.g., 2-triazolyl and 5-triazolyl), 2-thienyl, 3-thienyl, pyrazolyl, isothiazolyl, 1,2, 3-oxadiazolyl, 1,2, 5-oxadiazolyl, 1,2, 4-oxadiazolyl, 1, 2-triazolyl, 3-triazolyl, 1, 3-triazolyl, 3-thiotriazinyl, 1, 2-thiotriazinyl, 1-thiotriazinyl; the following bicyclic rings are also included, but are in no way limited to: benzimidazolyl, benzofuranyl, benzothienyl, indolyl (e.g., 2-indolyl), benzopiperidinyl, and the like.

The term "halogen" refers to fluorine (F), chlorine (Cl), bromine (Br) or iodine (I).

The term "haloalkenyl" means an alkenyl group substituted with one or more halogen atoms, wherein the alkenyl group has the meaning as described herein.

The term "haloalkynyl" means that the alkynyl group is substituted with one or more halogen atoms, wherein the alkynyl group has the meaning as described herein.

Compositions and formulations of the compounds of the invention

The compounds of the present invention are generally useful as fungicide active ingredients in compositions or formulations which typically also comprise an agropharmaceutically acceptable surfactant and/or carrier.

The surfactant may be any of various surfactants known in the art of agricultural chemical formulation, and the present invention is preferably one or more of an emulsifier, a dispersant and a wetting agent.

Other carriers besides the above surfactants may be various carriers well known in the art of agricultural chemical formulation, including various silicates, carbonates, sulfates, oxides, phosphates, plant carriers, synthetic carriers. Specifically, for example: white carbon black, kaolin, diatomaceous earth, clay, talc, organic bentonite, pumice, titanium dioxide, dextrin, cellulose powder, light calcium carbonate, soluble starch, corn starch, sawdust powder, urea, an amine fertilizer, a mixture of urea and an amine fertilizer, glucose, maltose, sucrose, anhydrous potassium carbonate, anhydrous sodium carbonate, anhydrous potassium bicarbonate, anhydrous sodium bicarbonate, attapulgite, a mixture of anhydrous potassium carbonate and anhydrous potassium bicarbonate, and a mixture of anhydrous sodium carbonate and anhydrous sodium bicarbonate.

The emulsifier may be various emulsifiers known in the field of pesticide formulation, and specifically, the emulsifier may be one or more of calcium dodecyl benzene sulfonate, triphenyl ethyl phenol polyoxyethylene ether phosphate, fatty alcohol polyoxyethylene ether, alkylphenol polyoxyethylene polyoxypropylene ether, fatty amine, ethylene oxide adduct of fatty amide, fatty acid polyoxyethylene ester, rosin acid ethylene oxide adduct, polyol fatty acid ester and ethylene oxide adduct thereof, styrylphenyl polyoxyethylene ether, alkylphenol formaldehyde resin polyoxyethylene ether, hydroxyl-terminated polyoxyethylene polyoxypropylene ether, styrylphenol formaldehyde resin polyoxyethylene polyoxypropylene ether and castor oil polyoxyethylene ether.

The dispersing agent can be various dispersing agents known in the pesticide formulation field, and specifically, the dispersing agent is one or more of acrylic acid homopolymer sodium salt, maleic acid disodium salt, naphthalene sulfonic acid formaldehyde condensate sodium salt, rosin block polyoxyethylene ether polyoxypropylene ether sulfonate, hydroxyl-terminated polyoxyethylene polyoxypropylene ether block copolymer, triphenyl ethyl phenol polyoxyethylene ether phosphate, fatty alcohol polyoxyethylene ether phosphate and p-hydroxyphenyl lignin sulfonic acid sodium salt.

The wetting agent can be various wetting agents known in the pesticide formulation field, and concretely, the wetting agent can be one or more of sodium dodecyl sulfate, secondary sodium alkyl sulfate, sodium dodecyl benzene sulfonate, fatty alcohol polyoxyethylene ether, alkyl naphthalene sulfonate and alkylphenol polyoxyethylene ether sulfate.

The bactericide composition according to the present invention may further contain various adjuvants for formulation commonly used in the field of agricultural chemical formulation, and specifically, the adjuvants for formulation may be one or more of solvents, co-solvents, thickeners, antifreezes, encapsulating materials, protective agents, antifoaming agents, disintegrants, stabilizers, preservatives and binders.

The above solvent may be various solvents well known in the field of agricultural chemical formulation, and specifically, the solvent may be one or more of organic solvents, vegetable oils, mineral oils, solvent oils and water.

Wherein the organic solvent comprises one or more of N-methylpyrrolidone, tetrahydrofuran, dimethyl sulfoxide, N-dimethyl capramide, N-dimethylformamide, trimethylbenzene, tetramethylbenzene, xylene, toluene, octane, heptane, methanol, isopropanol, N-butanol, tetrahydrofurfuryl alcohol, tributyl phosphate, 1, 4-dioxane and cyclohexanone.

The vegetable oil comprises one or more of methylated vegetable oil, turpentine-based vegetable oil, turpentine, epoxidized soybean oil, peanut oil, rapeseed oil, castor oil, corn oil and pine seed oil.

The mineral oil includes one or more of liquid wax, engine oil, kerosene, and lubricating oil.

Meanwhile, the solvent can also be used as a cosolvent.

The above antifreezing agent may be various antifreezing agents known in the field of agricultural chemical formulation, and the present invention is preferably one or more of ethylene glycol, propylene glycol, glycerin and urea.

The thickener may be various thickeners known in the field of pesticide dosage forms, and specifically, the thickener may be one or more of xanthan gum, polyvinyl alcohol, polyacrylate alcohol, polyethylene glycol, white carbon black, diatomaceous earth, kaolin, clay, sodium alginate, aluminum magnesium silicate, aluminum sodium silicate, carboxymethyl cellulose, hydroxypropyl cellulose sodium, and organic bentonite.

The capsule wall material can be various capsule wall materials known in the pesticide formulation field, and the invention is preferably one or more of polyurethane, polyurea and urea-formaldehyde resin.

The protective agent may be any of various protective agents known in the field of agricultural chemical formulations, and the present invention is preferably polyvinyl alcohol and/or polyethylene glycol.

The above defoamer may be various defoamers known in the field of pesticide formulation, and the present invention is preferably one or more of organosiloxane, tributyl phosphate and silicone.

The stabilizer is one or more selected from triphenyl phosphite, epichlorohydrin and acetic anhydride.

The preservative is selected from one or more of benzoic acid, sodium benzoate, 1, 2-benzisothiazolin-3-one (BIT for short), pinocembrane and potassium sorbate.

The invention also provides a preparation prepared from the bactericide composition, wherein the preparation formulation of the preparation is emulsifiable concentrate, aqueous emulsion, microemulsion, soluble liquid, aqueous suspension, suspension emulsion, ultra-low volume spray, oil suspension, microcapsule suspension, water surface spreading oil, wettable powder, water dispersible granules, dry suspension, soluble powder, soluble granules, emulsifiable powder, emulsifiable granules, solid microcapsule preparation, effervescent tablets, effervescent granules, water floating dispersible granules or seed coating. The above dosage forms can be prepared by methods conventional in the art.

The preparation method of the emulsifiable concentrate preparation can comprise, for example, mixing and stirring the active components, the solvent, the cosolvent and the emulsifier to form a uniform transparent oil phase, thus obtaining the emulsifiable concentrate preparation.

The above aqueous emulsion preparation method may include, for example, mixing the active ingredient, the emulsifier, the cosolvent and the solvent to form a homogeneous oil phase; water, thickener, antifreeze, etc. are mixed to make it into a uniform aqueous phase. Under high-speed shearing, adding the water phase into the oil phase or adding the oil phase into the water phase to form the aqueous emulsion with good dispersibility.

The microemulsion may be prepared by mixing and stirring the active ingredient, the emulsifier and the solvent into a uniform transparent oil phase. Under stirring, water was gradually added to form a uniform transparent microemulsion.

The preparation method of the water/oil suspending agent comprises the following steps: for example, water or oil is used as a medium, and additives such as active components, surfactants and the like are added into a sanding kettle, ground to a certain particle size, and filtered. And adding the metered thickener into the ground mother solution, and shearing and dispersing uniformly. Making into oil suspension or water suspension.

The preparation method of the water-dispersible granule and the soluble granule comprises the following steps: for example, the water-dispersible granule or soluble granule can be obtained by uniformly mixing the active components, the dispersing agent, the wetting agent, the carrier and the like, then crushing the mixture to a certain particle size by air flow, adding water for kneading, finally adding the mixture into a granulator for granulating, and drying the mixture.

The preparation method of the soluble powder and the wettable powder comprises the following steps: for example, the active ingredients, various auxiliary agents, and other fillers such as carriers may be thoroughly mixed and pulverized by a pulverizer.

The fungicide composition of the present invention may be provided in the form of a finished formulation, i.e. the materials of the composition have been mixed; or in the form of separate preparations which are self-mixed in a tank or can before use and optionally diluted with water depending on the desired concentration of active substance.

Use of the compounds and compositions of the invention

The compounds of the present invention are useful as plant disease controlling agents. Thus, the present invention may also include a method for controlling plant diseases caused by phytopathogenic fungi, said method comprising applying to the plant to be protected or to a part thereof or to the seed of the plant to be protected an effective amount of a compound of the invention or a fungicidal composition comprising said compound. The compounds and/or compositions of the present invention provide control of diseases caused by broad-spectrum plant pathogenic fungi of basidiomycetes, ascomycetes, oomycetes and deuteromycetes. They are effective in controlling a broad spectrum of plant diseases, especially foliar pathogens in ornamental, lawn, vegetable, field, cereal and fruit crops. These pathogens include: oomycetes, including Phytophthora (Phytophthora) diseases such as Phytophthora infestans (Phytophthora infestans), phytophthora sojae (Phytophthora megasperma), citrus foot rot (Phytophthora parasitica), phytophthora camphorata (Phytophthora cinnamomi) and Phytophthora cucurbitae (Phytophthora capsici), pythium (Pythium) species diseases such as Pythium triclopyr (Pythium aphanidermatum), and Peronospora species diseases such as downy mildew (Plasmopara viticola), peronospora diseases (Peronospora spp.) (including Peronospora tabacia (Peronospora tabacina) and Peronospora parasitica (Peronospora parasitica)), pseudoperonospora (Pseudoperonospora spp.) (including Peronospora cucumeria (Pseudoperonospora cubensis) and scentis discriminan (bria tucae)); ascomycetes (including Alternaria species (Alternaria) such as tomato early blight (Alternaria solani) and cabbage black spot (Alternaria brassicae), ball seat species (guilnarria) such as grape black spot (Guignardia bidwell), cladosporium species (Venturia) such as apple black spot (Venturia inaequalis), septoria species (Septoria) such as Septoria glume (Septoria nodorum) and leaf blight (Septoria tritica), powdery mildew (powdery mill) such as powdery mildew (erygium spp.) (including wheat powdery mildew (erygium) and radio white spot (Erysiphe polygoni)), grape powdery mildew (Uncinula necator), cucumber powdery mildew (Sphaerotheca fuligena) and apple powdery mildew (Podosphaera leucotricha), wheat middlingia (Pseudocercosporella herpotrichoides), botrytis (Botrytis) such as strawberry gray mold (Botrytis), peach kernel (49), and corn mildew (Sclerotinia such as Scutellaria anthracis), and corn (Colletotrichum orbiculare), wheat mildew (37 such as corn anthracnose (Colletotrichum orbiculare), corn anthracnose (37) or corn (Colletotrichum orbiculare), corn (37) such as corn anthracnose (Colletotrichum orbiculare), corn (37) and corn (37) such as corn (37) or wheat mildew (37, corn (37) such as corn (37) and wheat mildew (37). The basidiomycete is used as a seed, including rust diseases caused by rust (Puccinia spp.) (such as Puccinia recondita (Puccinia recondita), puccinia striolata (Puccinia striiformis), puccinia phyllanthus (Puccinia hordei), puccinia striolata (Puccinia graminis) and Puccinia pedunculata (Puccinia arachidis)), puccinia caffei (Hemileia vastatrix) and soybean rust (Phakopsora pachyrhizi); other pathogens include Rhizoctonia species (Rhizoctonia spp.) (e.g., rhizoctonia solani (Rhizoctonia solani)); fusarium (Fusarium) species diseases such as Fusarium roseum, fusarium graminearum (Fusarium graminearum), and Fusarium oxysporum (Fusarium oxysporum); verticillium dahliae (Verticillium dahliae); southern blight (Sclerotium rolfsii); the fungus (Rynchosporium secalis); black spot bacteria (Cercosporidium personatum), black spot bacteria (Cercospora arachidicola) and brown spot bacteria (Cercospora beticola); and other classes and species closely related to these pathogens. In addition to their fungicidal activity, the compositions or combinations also have resistant activity against bacteria such as Pyricularia pyrifolia (Erwinia amylovora), xanthomonas campestris (Xanthomonas campestris), pseudomonas syringae (Pseudomonas syringae), and other species.

The bactericide composition provided by the invention is simple in use method, is applied to crops and the sites where the crops grow before or after germination of plant diseases according to a conventional method, such as soil mixing, spraying, pouring and the like, and the application amount of the bactericide composition is generally 10-5000g per mu according to climatic conditions or crop states, and is diluted to 10-400mg/L (preferably 100-300 mg/L). The diluent is preferably water.

The bactericidal composition of the present invention has a bactericidal effect generally related to external factors such as climate, but the influence of climate can be alleviated by using a proper dosage form.

The composition of the present invention may be used in combination with other compounds having bactericidal, insecticidal or herbicidal properties, or may be used in combination with nematicides, acaricides, protectants, herbicide safeners, growth regulators, plant nutrients or soil conditioners, etc.

General synthetic procedure

The following schemes describe the preparation of the compounds of the present invention which, unless otherwise indicated, may be prepared by the methods described herein. The raw materials, reagents, and the like used in preparing the compounds of the invention are all commercially available, and suppliers are Annaiji chemistry, aladine, carbofuran, and the like; or the starting materials, reagents, etc. used in the preparation of the compounds of the present invention may be prepared by methods conventional in the art. In this specification, a structure is dominant if there is any difference between a chemical name and a chemical structure.

The testing conditions of the nuclear magnetic resonance hydrogen spectrum of the invention are as follows: nuclear magnetic instrument of 400MHz or 600MHz of Bruker (Bruker) under room temperature condition, CDC1 ₃ ，d ⁶ -DMSO，CD ₃ OD or d ⁶ Acetone as solvent (reported in ppm) with TMS (0 ppm) or chloroform (7.26 ppm) as reference standard. When multiple peaks occur, the following abbreviations will be used: s (single, singlet), d (doublet ), t (triplet, quartet), q (quartet), m (multiplet ), br (broadened, broad), dd (doublet of doublets, doublet), dt (doublet of triplets, doublet). Coupling constants are expressed in hertz (Hz).

The conditions for measuring the low-resolution Mass Spectrum (MS) data of the invention are as follows: agilent 6120 Quadragole HPLC-MS (column model: zorbax SB-C18, 2.1X30 mm,3.5 μm,6min, flow rate 0.6mL/min, mobile phase 5% -95% (CH containing 0.1% formic acid) ₃ CN) in (H containing 0.1% formic acid) ₂ Ratio in O)) was detected with UV at 210/254nm using electrospray ionization mode (ESI).

Synthesis scheme one

The target compound represented by the formula (IV-1) can be prepared by the first synthesis scheme. Compound a and formula%b) The compound is subjected to nucleophilic substitution reaction under alkaline conditions (such as sodium hydroxide, sodium hydride, potassium carbonate and the like) to obtain a target compound shown in a formula (IV-1); r is R ¹ 、R ² 、R ³ 、R ⁴ 、R ⁵ And X has the meaning described in the present invention; hal is bromine, chlorine or iodine.

The following abbreviations are used throughout the present invention:

g; mg; mol; mmol millimoles; h, the time is h; min; l liter; mL, mL milliliters; m mol/L; PE petroleum ether; etOAc ethyl acetate; DMF N, N-dimethylformamide; THF tetrahydrofuran

Examples

EXAMPLE A Synthesis of intermediate 1, 2-bis (1H-1, 2, 4-triazol-3-yl) disulfane

3-mercapto-1, 2, 4-triazole (101.0 g,1.00 mol) was dissolved in dichloromethane (500 mL) and pyridine (79.0 g,1.00 mol) was added. Benzenesulfonyl chloride (88.30 g,0.50 mol) was slowly added dropwise with stirring at 0℃over a period of 2 hours. After the addition was completed, the mixture was stirred at 25℃for 18 hours. The dichloromethane was distilled off under reduced pressure using a rotary evaporator, and water (500 mL) was added to the residue under mechanical stirring, followed by stirring for 1h. Filtration, washing the filter residue with water (800 mL) and ethyl acetate (300 mL), respectively, and air drying gave 95.2g of yellow powder in 95.2% yield.

LC-MS:(M+1)m/z＝201.1.

EXAMPLE B Synthesis of intermediate 3,3' -disulfide (N, N-dimethyl-1H-1, 2, 4-triazole-1-sulfonamide)

1, 2-bis (1H-1, 2, 4-triazol-3-yl) dithiolane (60.0 g,0.30 mol) was dissolved in N, N-dimethylformamide (300 mL) under nitrogen, and potassium carbonate (69.0 g,0.50 mol) was added thereto and mixed under stirring at 0 ℃. N, N-dimethylaminosulfonyl chloride (93.34 g,0.65 mol) was slowly added dropwise, and the reaction was continued for 6 hours after the completion of the addition for 2 hours. After the reaction was completed, the reaction solution was slowly poured into water and stirred for 1h. Filtration and air drying of the solid gave 107.2g of white powder in 86.3% yield.

LC-MS:(M+1)m/z＝415.0.

EXAMPLE C Synthesis of intermediate 1- (N, N-dimethylaminosulfonyl) -1H-1,2, 4-triazole-3-sulfonyl chloride

3,3' -Disulfanediylbis (N, N-dimethyl-1H-1, 2, 4-triazole-1-sulfonamide) (41.40 g,0.10 mol) was dissolved in 1, 2-dichloroethane (150 mL), water (300 mL) was added, cooled to 0℃and acetic acid (150 mL) was added, the temperature was controlled at 10℃to 25℃for 2 hours, chlorine gas (35.50 g,0.50 mol) was introduced, and the reaction was continued for half an hour. After the completion of the reaction, the solution was transferred to a separating funnel, left to stand for separation, and the organic phase was washed three times with water (30 mL), and the solvent was distilled off under reduced pressure using a rotary evaporator to give 48.11g of a white powder, yield 87.8%.

LC-MS:(M+1)m/z＝274.8.

Example D intermediate N ³ -cyclohexyl-N ¹ ,N ¹ Synthesis of-dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide

Cyclohexylamine (1.98 g,0.02 mol), triethylamine (2.22 g,0.02 mol) and tetrahydrofuran (30 mL) were added to a 100mL three-necked flask under nitrogen, stirred at 0℃and 1- (N, N-dimethylaminosulfonyl) -1H-1,2, 4-triazole-3-sulfonyl chloride (5.48 g,0.02 mol) in tetrahydrofuran (20 mL) was added dropwise over 10min with the appearance of white smoke and a white solid gradually precipitated. After the addition was completed, the solid was removed by filtration at room temperature, and the solvent was removed from the filtrate under reduced pressure using a rotary evaporator to give a pale yellow solid, which was recrystallized (EtOAc/PE (v/v) =5/1) to give 5.58g of a white solid, yield: 60.4%.

¹ H NMR(400MHz,DMSO-d ₆ ):δ(ppm)9.30(s,1H),7.72(s,1H),3.90-3.85(m,1H),2.96(s,6H),1.78-1.54(m,4H),1.32-1.25(m,5H),0.99-0.92(m,1H).

LC-MS:(M+1)m/z＝338.3.

Example (IV-70): n (N) ³ -cyclohexyl-N ³ - (4-fluorobenzyl) -N ¹ ,N ¹ Synthesis of-dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide

Will N ³ -cyclohexyl-N ¹ ,N ¹ dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide (0.34 g,1.0 mmol), potassium carbonate (0.28 g,2.0 mmol) and DMF (10 mL) were added to a 100mL three-necked flask, and 1- (bromomethyl) -4-fluorobenzene (0.28 g,1.5 mmol) was slowly added to the reaction system and reacted at 25℃for 8 hours; quench with water (20 mL), extract with ethyl acetate (15 mL. Times.3), wash the organic phase with saturated brine, dry over anhydrous magnesium sulfate, filter, and remove the solvent under reduced pressure using a rotary evaporator to give 0.26g of a colorless oily liquid, yield: 60%.

¹ H NMR(400MHz,CDCl ₃ ):δ(ppm)8.63(s,1H),7.42(dd,J＝8.2,5.5Hz,2H),7.03(t,J＝8.6Hz,2H),4.55(s,2H),3.88(dd,J＝15.3,7.2Hz,1H),3.08(s,6H),1.75–1.64(m,4H),1.30(dd,J＝20.3,9.4Hz,4H),1.11–0.76(m,2H).

¹⁹ F NMR(376MHz,CDCl ₃ )δ-115.03.

LC-MS:(M+1)m/z＝446.0.

Example D (intermediate N) was prepared in a similar manner to example (IV-70) ³ -cyclohexyl-N ¹ ,N ¹ -dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide) with the corresponding starting material to give the target compounds of table 1.

TABLE 1

Biological examples of the invention

Test target: cucumber downy mildew fungus

Test treatment: the compound was dissolved in DMF to 1% ec for use. The bactericidal activity of these compounds against cucumber downy mildew bacteria at different doses was evaluated by the living potting method.

Selecting 1 pot cucumber seedling with consistent growth condition in true leaf period (removing growing point), spraying, naturally drying, inoculating 24 hr after treatment, collecting fresh cucumber downy mildew disease leaf, dipping with brush pen, washing sporangium on the back of the disease leaf with distilled water, and preparing into sporangium suspension (2-3 x 10) ⁵ and/mL). Uniformly spraying and inoculating on cucumber seedlings by using an inoculating sprayer (with the pressure of 0.1 MPa), transferring the inoculated test material to a climatic chamber, keeping the relative humidity at about 100%, keeping the temperature at about 21 ℃ after 24 hours, keeping the relative humidity at about 21%, carrying out moisture preservation and induction, and carrying out grading investigation according to the disease condition of blank control after 5 days, wherein the control effect is calculated according to the disease index.

The test results are shown in tables A-C.

TABLE A control of the compounds of the invention on cucumber downy mildew at 200ppm

Examples	Control effect (%)	Examples	Control effect (%)
				Example (IV-70)	100	Example (IV-71)	100
Example (IV-72)	100	Example (IV-73)	100
				Example (IV-74)	100	Example (IV-75)	100
Example (IV-76)	100	Example (IV-77)	100
				Example (IV-78)	100	Example (IV-79)	100
Example (IV-80)	100	Example (IV-81)	100
				Example (IV-82)	100	Example (IV-83)	100
Example (IV-84)	100	Example (IV-85)	100
				Example (IV-86)	100	Examples(IV-87)	100
Example (IV-88)	100	Example (IV-89)	100
				Example (IV-90)	100	Example (IV-91)	100
Example (IV-92)	100	Example (IV-93)	100
				Example (IV-94)	100	Example (IV-95)	100
Example (IV-96)	100	Example (IV-97)	100
				Example (IV-98)	80	Example (IV-99)	100
Example (IV-100)	100	Example (IV-102)	90
				Example (IV-103)	100	Example (IV-104)	100
Example (IV-105)	100	Example (IV-106)	100
				Example (IV-107)	100	Example (IV-108)	100
Example (IV-109)	80	Example (IV-110)	80
				Example (IV-111)	100

TABLE B control of the compounds of the invention at 100ppm against cucumber downy mildew

Table C control of the compounds of the invention against cucumber downy mildew at 50ppm

The results in tables A to C show that the compound has remarkable control effect on cucumber downy mildew at different concentrations, and has good development prospect.

The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the specific details of the above embodiments, and various simple modifications can be made to the technical solution of the present invention within the scope of the technical concept of the present invention, and all the simple modifications belong to the protection scope of the present invention.

Claims (7)

1. A compound which is a compound having the formula (IV):

wherein:

R ^a and R is ^b Each independently is methyl;

x is-CH ₂ -or-CH ₂ -C(＝O)-；

R ¹ 、R ² 、R ³ 、R ⁴ And R is ⁵ Each independently is hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, C _1-4 Alkyl, C _2-4 Alkenyl, C _1-4 Alkoxy, C _1-4 Alkylthio, halo C _1-4 Alkyl, halogenated C _1-4 Alkoxy, C _1-4 alkoxy-C (=o) -or optionally substituted with 1 member selected from C _1-4 Phenyl substituted by a substituent of alkoxy-C (=o) -;

the conditions are as follows: r is R ¹ 、R ² 、R ³ 、R ⁴ And R is ⁵ And cannot be hydrogen at the same time.

2. A compound according to claim 1, wherein:

R ¹ 、R ² 、R ³ 、R ⁴ and R is ⁵ Each independently is hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, -CH ₃ 、-CH ₂ CH ₃ 、-CH ₂ CH ₂ CH ₃ 、-CH(CH ₃ ) ₂ 、-C(CH ₃ ) ₃ 、CH ₂ ＝CH-、-OCH ₃ 、-OCH ₂ CH ₃ 、-OCH ₂ CH ₂ CH ₃ 、-OCH(CH ₃ ) ₂ 、-OC(CH ₃ ) ₃ 、-SCH ₃ 、-SCH ₂ CH ₃ 、-CH ₂ F、-CHF ₂ 、-CF ₃ 、-OCH ₂ F、-OCHF ₂ 、-OCF ₃ 、CH ₃ O-C (=o) -or optionally is substituted with 1 selected from CH ₃ O-C (=O) -or C (CH) ₃ ) ₃ Phenyl substituted by O-C (=o) -substituents.

3. A compound which is a compound having one of the following structures or a salt thereof:

4. a composition comprising a compound of any one of claims 1-3.

5. The composition of claim 4, further comprising an agropharmaceutically acceptable surfactant and/or carrier.

6. Use of the compound according to any one of claims 1 to 3 or the composition according to claim 4 or 5 as a plant disease control agent in agriculture, wherein the plant disease is cucumber downy mildew.

7. A method for controlling plant diseases which comprises applying to a plant or locus thereof an effective amount of a compound as claimed in any one of claims 1 to 3 or a composition as claimed in claim 4 or 5.