CN110734433B - Triazole compound and application thereof in agriculture - Google Patents

Abstract

The invention provides a triazole compound; specifically, the invention relates to a triazole compound shown in formula (I) or a stereoisomer, a nitrogen oxide and a salt of the triazole compound shown in formula (I), a preparation method of the triazole compound, application of the triazole compound as a fungicide, a form of a fungicide composition of the triazole compound, and a method for preventing and treating diseases by using the triazole compound or the triazole compound; wherein R is¹、R²、Y、n、X、R³、R⁴M and Het have the meanings indicated in the description.

Description

Triazole compound and application thereof in agriculture

Technical Field

The invention relates to the field of pesticides, in particular to a triazole compound and a pesticide containing the triazole compound as an active ingredient, and particularly relates to a plant pathogen preventing and treating agent.

Background

In modern agricultural production, various pesticides are required to be frequently used for ensuring the healthy growth of crops, and as the pesticides are frequently used for a long time, part of diseases on the crops generate drug resistance to the existing pesticides, so that the control effect of the existing pesticides is reduced; in order to solve the problem of drug resistance, new compounds for controlling crop diseases are continuously developed.

Disclosure of Invention

The invention provides a triazole compound and a composition containing the compound, wherein the triazole compound and the composition are used for preventing and treating plant diseases.

Specifically, the method comprises the following steps:

in one aspect, the invention provides compounds of formula (I) or stereoisomers, nitroxides and salts thereof:

wherein,

R¹and R²Each independently is hydrogen, C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-8Cycloalkyl, 3-10 membered heterocyclyl, C_6-10Aryl, 5-10 membered heteroaryl, C_3-8Cycloalkyl radical C_1-6Alkyl, 3-10 membered heterocyclyl C_1-6Alkyl radical, C_6-10Aryl radical C_1-6Alkyl or 5-10 membered heteroaryl C_1-6An alkyl group; or R¹、R²And the N atom to which they are attached, form a 3-10 membered heterocyclic group or a 5-10 membered heteroaryl group; wherein, said C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-8Cycloalkyl, 3-10 membered heterocyclyl, C_6-10Aryl, 5-10 membered heteroaryl, C_3-8Cycloalkyl radical C_1-6Alkyl, 3-10 membered heterocyclyl C_1-6Alkyl radical, C_6-10Aryl radical C_1-6Alkyl and 5-10 membered heteroaryl C_1-6Alkyl is optionally substituted by 1,2,3,4 or 5R^mSubstitution;

each R^mIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro,Amino, carboxyl, C_1-6Alkyl, halo C_1-6Alkyl radical, C_1-6Alkoxy or halo C_1-6An alkoxy group;

y is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, halo C_1-6Alkyl, halo C_2-6Alkenyl, halo C_2-6Alkynyl, C_6-10Aryl, halo C_6-10Aryl radical, C_6-10Aryl radical C_1-6Alkyl or halo C_6-10Aryl radical C_1-6An alkyl group;

n is 0, 1 or 2;

-X-is-S-or-NR⁵-；

R⁵Is hydrogen, C_1-6Alkyl, -C (═ O) -C_1-6Alkyl, -C (═ O) -O-C_1-6Alkyl radical, C_1-6Alkoxy radical, C_1-6Alkoxy radical C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-8Cycloalkyl, 3-10 membered heterocyclyl, C_6-10Aryl radical, C_6-10Aryl radical C_1-6Alkyl radical, C_3-8Cycloalkyl radical C_1-6Alkyl or 3-10 membered heterocyclyl C_1-6An alkyl group;

m is 0 or 1;

R³and R⁴Independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, halo C_1-6Alkyl, halo C_2-6Alkenyl, halo C_2-6Alkynyl or C_3-8A cycloalkyl group;

or R³And R⁴The carbon atom to which it is attached forms C ═ O;

het is 5-10 membered heteroaryl; wherein said 5-10 membered heteroaryl is optionally substituted with 1,2,3,4, 5 or 6R^ASubstitution;

wherein each R is^AIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, -NHC_1-6Alkyl, -N (C)_1-6Alkyl radical)₂、-NR^BC(＝O)OC_1-6Alkyl, -NR^B1C(＝O)C_1-6Alkyl, -NR^B1C(＝O)C_3-8Cycloalkyl, -C (═ O) OC_1-6Alkyl, -C (═ O) OC_3-8Cycloalkyl, -OC (═ O) C_1-6Alkyl, -OC (═ O) C_3-8Cycloalkyl, -OC (═ O) NR^B2R^B3、C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy, halo C_1-6Alkyl, halo C_2-6Alkenyl, halo C_2-6Alkynyl, halo C_1-6Alkoxy radical, C_3-8Cycloalkyl radical, C_3-8Cycloalkyl radical C_1-6Alkyl radical, C_6-10Aryl radical, C_6-10Aryl radical C_1-6Alkyl or C_6-10An aryloxy group; wherein each R is^AOptionally substituted by 1,2,3,4 or 5R^CSubstitution;

wherein R is^B、R^B1、R^B2And R^B3Each independently is hydrogen or C_1-6An alkyl group;

each R^CIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, C_1-6Alkyl radical, C_1-6Alkoxy, halo C_1-6Alkyl or halo C_1-6An alkoxy group.

In some embodiments, R¹And R²Each independently is hydrogen, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_3-6Cycloalkyl radical, C_6-10Aryl radical, C_3-6Cycloalkyl radical C_1-4Alkyl or C_6-10Aryl radical C_1-4An alkyl group; or R¹、R²And the N atom to which they are attached, form a 3-6 membered heterocyclyl or 5-10 membered heteroaryl; wherein, said C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_3-6Cycloalkyl radical, C_6-10Aryl radical, C_3-6Cycloalkyl radical C_1-4Alkyl radical, C_6-10Aryl radical C_1-4Alkyl 3-6 membered heterocyclyl and 5-10 membered heteroaryl optionally substituted with 1,2,3,4 or 5R^mSubstitution;

each R^mIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino,Carboxy, C_1-4Alkyl, halo C_1-4Alkyl radical, C_1-4Alkoxy or halo C_1-4An alkoxy group;

y is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, C_1-4Alkyl, halo C_1-4Alkyl radical, C_6-10Aryl, halo C_6-10Aryl radical, C_6-10Aryl radical C_1-4Alkyl or halo C_6-10Aryl radical C_1-4An alkyl group.

In other embodiments, R¹And R²Each independently is hydrogen, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-CH(CH₃)CH₂CH₃、-CH₂CH(CH₃)CH₃、-C(CH₃)₃、-CH＝CH₂、-CH₂CH＝CH₂、-CH＝CHCH₃、-C≡CH、-CH₂-C≡CH、-CH₂CH₂-C ≡ CH, phenyl or benzyl;

or R¹、R²And the N atom to which it is attached form the following subformula:

y is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂Cl、-CHF₂or-CF₃。

In some embodiments, R³And R⁴Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl or halo C_1-4An alkyl group;

R⁵is hydrogen, C_1-4Alkyl, -C (═ O) -C_1-4Alkyl, -C (═ O) -O-C_1-4Alkyl radical, C_1-4Alkoxy radical, C_1-3Alkoxy radical C_1-3Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_3-6Cycloalkyl radical, C_6-10Aryl radical, C_6-10Aryl radical C_1-4Alkyl or C_3-6Cycloalkyl radical C_1-4An alkyl group.

In other embodiments, R³And R⁴Independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, -CH₃or-CH₂CH₃；

R⁵Is hydrogen, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-CH(CH₃)CH₂CH₃、-CH₂CH(CH₃)CH₃、-C(CH₃)₃Cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;

or R⁵Is of the sub-structure:

in some embodiments, Het is 5-10 membered heteroaryl; wherein said 5-10 membered heteroaryl is optionally substituted with 1,2,3,4, 5 or 6R^ASubstitution;

wherein each R is^AIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, -NHC_1-6Alkyl, -N (C)_1-6Alkyl radical)₂、-NR^BC(＝O)OC_1-4Alkyl, -NR^B1C(＝O)C_1-6Alkyl, -C (═ O) OC_1-4Alkyl, -OC (═ O) C_1-6Alkyl, -OC (═ O) NR^B2R^B3、C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_1-4Alkoxy, halo C_1-4Alkyl, halo C_1-4Alkoxy radical, C_6-10Aryl radical, C_6-10Aryl radical C_1-4Alkyl or C_6-10An aryloxy group; wherein each R is^AOptionally substituted by 1,2,3,4 or 5R^CSubstitution;

wherein R is^B、R^B1、R^B2And R^B3Each independently is hydrogen or C_1-4An alkyl group;

each R^CIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, C_1-4Alkyl radical, C_1-4Alkoxy, halo C_1-4Alkyl or halo C_1-4An alkoxy group.

In other embodiments, Het is 5-10 membered heteroaryl; wherein said 5-10 membered heteroaryl is optionally substituted with 1,2,3,4, 5 or 6R^ASubstitution;

wherein each R is^AIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, -NHC (═ O) OCH₃、-NHC(＝O)OCH₂CH₃、-NHC(＝O)OCH₂CH₂CH₃、-NHC(＝O)OCH(CH₃)₂、-NHC(＝O)OC(CH₃)₃、-NHCH₃、-NHCH₂CH₃、-N(CH₃)₂、-N(CH₂CH₃)₂、-C(＝O)OCH₃、-C(＝O)OCH₂CH₃、-OC(＝O)CH₃、-OC(＝O)CH₂CH₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-CH(CH₃)CH₂CH₃、-CH₂CH(CH₃)CH₃、-C(CH₃)₃、-OCH₃、-OCH₂CH₃、-OCH₂CH₂CH₃、-OCH(CH₃)₂、-OC(CH₃)₃、-CH₂Cl、-CH₂Br、-CHF₂、-CF₃、-OCF₃Phenyl, benzyl or phenoxy; wherein each R is^AOptionally substituted by 1,2,3,4 or 5R^CSubstitution;

each R^CIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-C(CH₃)₃、-OCH₃、-OCH₂CH₃、-OCH₂CH₂CH₃、-OCH(CH₃)₂、-OC(CH₃)₃、-CH₂Cl、-CHF₂、-CF₃or-OCF₃。

In still other embodiments, Het is of the subformula:

in another aspect, the present invention provides a composition comprising a compound of the present invention, wherein the composition further comprises an agriculturally pharmaceutically acceptable surfactant and/or carrier.

In another aspect, the invention discloses the use of a compound of the invention or a composition of the invention for the control of plant diseases.

Detailed description of the invention

Definitions and general terms

Reference will now be made in detail to certain embodiments of the invention, examples of which are illustrated by the accompanying structural and chemical formulas. The invention is intended to cover alternatives, modifications and equivalents, which may be included within the scope of the invention as defined by the appended claims. One 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 that one or more of the incorporated documents, patents, and similar materials differ or contradict this application (including but not limited to defined terminology, application of terminology, described techniques, and the like), this application controls.

It will be further 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 subcombination.

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, the chemical elements are in accordance with the CAS version of the periodic Table of the elements, and the handbook of chemistry and Physics, 75 th edition, 1994. In addition, general principles of Organic Chemistry can be found in the descriptions of "Organic Chemistry", Thomas Sorrell, University Science Books, Sausaltito: 1999, and "March's Advanced Organic Chemistry" by Michael B.Smith and JerryMarch, John Wiley & Sons, New York:2007, the entire contents of which are incorporated herein by reference.

The articles "a," "an," and "the" as used herein are intended to include "at least one" or "one or more" unless otherwise indicated or clearly contradicted by context. Thus, as used herein, the articles refer to one or to more than one (i.e., to at least one) of the objects. For example, "a component" refers to one or more components, i.e., there may be more than one component contemplated for use or use in embodiments of the described embodiments.

The term "comprising" is open-ended, i.e. includes the elements indicated in the present invention, but does not exclude other elements.

"stereoisomers" refers to compounds having the same chemical structure but differing in the arrangement of atoms or groups in space. Stereoisomers include enantiomers, diastereomers, conformers (rotamers), geometric isomers (cis/trans), atropisomers, and the like.

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

"diastereomer" refers to a stereoisomer that has two or more chiral neutrals and whose molecules are not mirror images of each other. Diastereomers have different physical properties, such as melting points, boiling points, spectral properties, and reactivities. Mixtures of diastereomers 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 the general definitions of S.P. Parker, Ed., McGraw-Hilldictionary 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 an 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 denote the absolute configuration of a molecule with respect to one or more of its chiral centers. The prefixes d and l or (+) and (-) are the symbols used to specify the rotation of plane polarized light by the compound, where (-) or l indicates that the compound is left-handed. Compounds prefixed with (+) or d are dextrorotatory. A 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 may occur when there is no stereoselectivity or stereospecificity in the chemical reaction or process.

Any asymmetric atom (e.g., carbon, etc.) of a compound disclosed herein can exist in racemic or enantiomerically enriched forms, such as 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 exist as one of the possible isomers or as mixtures thereof, for example as racemates and mixtures of non-corresponding isomers (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 substituents 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.

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

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

The compounds of the invention may be optionally substituted with one or more substituents, as described herein, in compounds of the general formula above, or as specifically exemplified, sub-classes, and classes of compounds encompassed by the invention. It is understood that the term "optionally substituted" may be used interchangeably with the term "substituted or unsubstituted". In general, the term "substituted" means that one or more hydrogen atoms in a given structure are replaced with a particular substituent. Unless otherwise indicated, an optional substituent group may be substituted at each substitutable position of the group. When more than one position in a given formula can be substituted with one or more substituents selected from a particular group, the substituents may be substituted at each position, identically or differently. Specifically, examples of "one or more" refer to 1,2,3,4, 5, 6, 7, 8, 9, or 10. Wherein said substituent may be, but is not limited to, deuterium, fluorine, chlorine, bromine, iodine, cyano, hydroxyl, nitro, amino, carboxyl, alkyl, alkoxy, alkoxyalkyl, alkoxyalkoxy, alkoxyalkylamino, aryloxy, heteroaryloxy, heterocyclyloxy, arylalkoxy, heteroarylalkoxy, heterocyclylalkoxy, cycloalkylalkoxy, alkylamino, alkylaminoalkyl, alkylaminoalkylamino, cycloalkylamino, cycloalkylalkylamino, alkylthio, haloalkyl, haloalkoxy, hydroxyl-substituted alkyl, hydroxyl-substituted alkylamino, cyano-substituted alkyl, cyano-substituted alkoxy, cyano-substituted alkylamino, amino-substituted alkyl, alkanoyl, heteroalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, arylamino, heteroaryl, heteroarylalkyl, heteroarylamino, amido, sulfonyl, aminosulfonyl, and the like.

In addition, unless otherwise explicitly indicated, the descriptions of the terms "… independently" and "… independently" and "… independently" used in the present invention are interchangeable and should be understood in a broad sense to mean that the specific items expressed between the same symbols do not affect each other in different groups or that the specific items expressed between the same symbols in the same groups do not affect each other.

In the various parts of this specification, substituents of the disclosed compounds are disclosed in terms of group type or range. It is specifically intended that the invention includes each and every independent subcombination of the various members of these groups and ranges. For example, the term "C₁-C₆Alkyl "or" C_1-6Alkyl "means in particular independently disclosed methyl, ethyl, C₃Alkyl radical, C₄Alkyl radical, C₅Alkyl and C₆An alkyl group.

The term "alkyl" or "alkyl group" as used herein, denotes a saturated, straight or branched chain, monovalent hydrocarbon group containing from 1 to 20 carbon atoms; wherein the alkyl group is optionally substituted with one or more substituents described herein. Unless otherwise specified, alkyl groups contain 1-20 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 group (Et, -CH)₂CH₃) N-propyl (n-Pr, -CH)₂CH₂CH₃) Isopropyl group (i-Pr, -CH (CH)₃)₂) N-butyl (n-Bu, -CH)₂CH₂CH₂CH₃) Isobutyl (i-Bu, -CH)₂CH(CH₃)₂) Sec-butyl (s-Bu, -CH (CH)₃)CH₂CH₃) Tert-butyl (t-Bu, -C (CH)₃)₃) N-pentyl (-CH)₂CH₂CH₂CH₂CH₃) 2-pentyl (-CH (CH)₃)CH₂CH₂CH₃) 3-pentyl (-CH (CH)₂CH₃)₂) 2-methyl-2-butyl (-C (CH)₃)₂CH₂CH₃) 3-methyl-2-butyl (-CH (CH)₃)CH(CH₃)₂) 3-methyl-1-butyl (-CH)₂CH₂CH(CH₃)₂) 2-methyl-1-butyl (-CH)₂CH(CH₃)CH₂CH₃) And so on.

The term "alkoxy" means an alkyl group attached to the rest 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)₂CH₃) 1-propoxy (n-PrO, n-propoxy, -OCH)₂CH₂CH₃) 2-propoxy (i-PrO, i-propoxy, -OCH (CH)₃)₂) And so on.

The term "alkoxyalkyl" denotes an alkyl group wherein the hydrogen atom is replaced by one or more alkoxy groups, wherein alkyl and alkoxy groups have the meaning as described herein.

The term "alkenyl" denotes a straight or branched chain monovalent hydrocarbon radical containing 2 to 12 carbon atoms, wherein there is at least one site of unsaturation, i.e. one carbon-carbon sp²A double bond, wherein the alkenyl group 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 contains 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)₂CH＝CH₂) Allyl (CH)₃-CH ═ CH-), oxo butenyl (CH)₃-C (═ O) -CH ═ CH-) and the like.

The term "alkynyl" denotes a straight or branched chain monovalent hydrocarbon radical containing 2 to 12 carbon atoms, wherein there is at least one carbon-carbon sp triple bond. In one embodiment, alkynyl groups contain 2-8 carbon atoms; in another embodiment, alkynyl groups contain 2-6 carbon atoms; in yet another embodiment, alkynyl groups contain 2-4 carbon atoms. Examples of alkynyl groups include, but are not limited to, -C.ident.CH, -CH₂-C≡CH、-CH₂-C≡CCH₃、-CH₂CH₂-C≡CH、-CH₂-C≡CCH₂CH₃And so on.

The term "cycloalkyl" denotes a monovalent or polyvalent saturated monocyclic, bicyclic or tricyclic ring system containing from 3 to 12 carbon atoms. In one embodiment, the cycloalkyl group contains 3 to 10 carbon atoms; in another embodiment, cycloalkyl contains 3 to 8 carbon atoms; in yet another embodiment, the cycloalkyl group contains 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 "cycloalkylalkyl" denotes an alkyl group wherein the hydrogen atom is replaced by one or more cycloalkyl groups, wherein alkyl and cycloalkyl groups have the meaning as described herein.

The term "heterocyclyl" the terms "heterocyclyl" and "heterocycle" are used interchangeably herein and refer to a saturated or partially unsaturated monocyclic, bicyclic or tricyclic ring containing 3 to 15 ring atoms, wherein no aromatic ring is included in the monocyclic, bicyclic or tricyclic ring, and at least one ring atom is selected from the group consisting of nitrogen, sulfur and oxygen atoms. Unless otherwise specified, heterocyclyl may be carbon-or nitrogen-based, and-CH₂-the group may optionally be replaced by-C (═ O) -. The sulfur atom of the ring may optionally be oxidized to the S-oxide. The nitrogen atom of the ring may optionally be oxidized to an N-oxygen compound.

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 describe the number of ring-forming atoms in the molecule. For example, piperidinyl is 6-membered heterocyclyl.

The term "heterocyclylalkyl" means that a hydrogen atom in an alkyl group is replaced by one or more heterocyclyl groups, wherein the alkyl and heterocyclyl groups have the meanings as described herein.

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

The term "aryl" denotes monocyclic, bicyclic and tricyclic carbon ring systems containing 6 to 14 ring atoms, or 6 to 12 ring atoms, or 6 to 10 ring atoms, wherein at least one ring system is aromatic, wherein each ring system comprises a ring of 3 to 7 atoms with one or more attachment points to the rest of the molecule. The term "aryl" may be used interchangeably with the term "aromatic ring". Examples of the aryl group may include phenyl, indenyl, naphthyl and anthryl. The aryl group is optionally substituted with one or more substituents described herein.

The term "aryloxy" means that the aryl group is attached to the rest of the molecule through an oxygen atom, wherein the aryl group has the meaning as described herein.

The term "arylalkyl" means that the hydrogen atoms in the alkyl group are replaced by one or more aryl groups, wherein the alkyl and aryl groups have the meaning as described herein. Examples include, but are not limited to, benzyl, phenethyl, and the like.

The term "heteroaryl" denotes 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 with one or more attachment points to the rest of the molecule. The term "heteroaryl" may be used interchangeably with the terms "heteroaromatic ring" or "heteroaromatic compound". The heteroaryl group is optionally substituted with one or more substituents described herein. In one embodiment, a heteroaryl group of 5-10 atoms contains 1,2,3, or 4 heteroatoms independently selected from O, S, and N.

The term "heteroarylalkyl" denotes an alkyl group wherein the hydrogen atom is replaced by one or more heteroaryl groups, wherein the alkyl and heteroaryl groups have the meaning as described herein.

The term "haloalkyl" denotes an alkyl group substituted with one or more halogen atoms, examples of which include, but are not limited to, -CF₃，-CHF₂，-CH₂Cl，-CH₂CF₃，-CH₂CHF₂，-CH₂CH₂CF₃And the like.

The term "haloalkoxy" denotes an alkoxy group substituted with one or more halogen atoms, examples of which include, but are not limited to, -OCF₃，-OCHF₂，-OCHCl₂，-OCH₂CHF₂，-OCH₂CHCl₂，-OCH(CH₃)CHF₂And the like.

The term "haloalkenyl" denotes an alkenyl group substituted with one or more halogen atoms.

The term "haloalkynyl" denotes an alkynyl group substituted by one or more halogen atoms.

The term "haloaryl" denotes an aryl group substituted with one or more halogen atoms, examples of which include, but are not limited to, 4-fluorophenyl, 2, 4-difluorophenyl and the like.

The term "haloarylalkyl" denotes an arylalkyl group substituted with one or more halogen atoms.

Salts of the compounds of the present invention include those derived from alkali or alkaline earth metals as well as those derived from ammonia and amines. Preferred cations include sodium, potassium, magnesium and those of formula N⁺(R³¹R³²R³³R³⁴) Ammonium cation of (2), wherein R is³¹、R³²、R³³And R³⁴Independently selected from hydrogen, C₁-C₆Alkyl and C₁-C₆A hydroxyalkyl group. Salts of compounds of formula (I) may be prepared by treating a compound of formula (I) with a metal hydroxide (e.g., sodium hydroxide) or an amine (e.g., ammonia, trimethylamine, diethanolamine, 2-methylthiopropylamine, diallylamine, 2-butoxyethylamine, morpholine, cyclododecylamine or benzylamine).

When a compound of the invention comprises a base moiety, acceptable salts can be formed from organic and inorganic acids, such as acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic, napthalenesulfonic, benzenesulfonic, toluenesulfonic, camphorsulfonic, and similarly known acceptable acids.

Detailed description of the Compounds of the invention

The present invention aims to provide a compound having a remarkable effect of controlling plant diseases, a composition and a preparation containing the compound, and an application thereof as a fungicide.

In one aspect, the invention provides compounds of formula (I) or stereoisomers, nitroxides and salts thereof:

wherein R is¹And R²Each independently is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, or heteroarylalkyl; or R¹、R²And the N atom to which they are attached, together form a heterocyclic or heteroaryl group; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, and heteroarylalkyl are optionally substituted with 1,2,3,4, or 5R^mSubstitution;

each R^mIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, alkyl, haloalkyl, alkoxy or haloalkoxy;

y is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, aryl, haloaryl, arylalkyl or haloarylalkyl;

n is 0, 1 or 2;

-X-is-S-or-NR⁵-；

R⁵Is hydrogen, alkyl, -C (═ O) -O-alkyl, alkoxy, alkoxyalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, cycloalkylalkyl, or heterocyclylalkyl;

m is 0 or 1;

R³and R⁴Independently hydrogen, fluoro, chloro, bromo, iodo, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, or cycloalkyl;

or R³And R⁴The carbon atom to which it is attached forms C ═ O;

het is heteroaryl; wherein said heteroaryl is optionally substituted with 1,2,3,4, 5 or 6R^ASubstitution;

wherein each R is^AIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, -NH alkyl, -N (alkyl)₂、-NR^BC (═ O) Oalkyl, -NR^B1C (═ O) alkyl, -NR^B1C (═ O) cycloalkyl, -C (═ O) oalkyl, -C (═ O) oxocycloalkyl, -OC (═ O) alkyl, -OC (═ O) cycloalkyl, -OC (═ O) NR^B2R^B3Alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkenyl, haloalkynyl, haloalkoxy, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl or aryloxy; wherein each R is^AOptionally substituted by 1,2,3,4 or 5R^CSubstitution;

wherein R is^B、R^B1、R^B2And R^B3Each independently is hydrogen or alkyl;

each R^CIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, alkyl, alkoxy, haloalkyl or haloalkoxy.

In some embodiments, R¹And R²Each independently is hydrogen, C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-8Cycloalkyl, 3-10 membered heterocyclyl, C_6-10Aryl, 5-10 membered heteroaryl, C_3-8Cycloalkyl radical C_1-6Alkyl, 3-10 membered heterocyclyl C_1-6Alkyl radical, C_6-10Aryl radical C_1-6Alkyl or 5-10 membered heteroaryl C_1-6An alkyl group; or R¹、R²And the N atom to which they are attached, form a 3-10 membered heterocyclic group or a 5-10 membered heteroaryl group; wherein, said C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-8Cycloalkyl, 3-10 membered heterocyclyl, C_6-10Aryl, 5-10 membered heteroaryl, C_3-8Cycloalkyl radical C_1-6Alkyl, 3-10 membered heterocyclyl C_1-6Alkyl radical, C_6-10Aryl radical C_1-6Alkyl and 5-10 membered heteroaryl C_1-6Alkyl is optionally substituted by 1,2,3,4 or 5R^mSubstitution;

each R^mIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, C_1-6Alkyl, halo C_1-6Alkyl radical, C_1-6Alkoxy or halo C_1-6An alkoxy group.

In yet other embodiments of the present invention, the substrate is,R¹and R²Each independently is hydrogen, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_3-6Cycloalkyl radical, C_6-10Aryl radical, C_3-6Cycloalkyl radical C_1-4Alkyl or C_6-10Aryl radical C_1-4An alkyl group; or R¹、R²And the N atom to which they are attached, form a 3-6 membered heterocyclyl or 5-10 membered heteroaryl; wherein, said C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_3-6Cycloalkyl radical, C_6-10Aryl radical, C_3-6Cycloalkyl radical C_1-4Alkyl radical, C_6-10Aryl radical C_1-4Alkyl 3-6 membered heterocyclyl and 5-10 membered heteroaryl optionally substituted with 1,2,3,4 or 5R^mSubstitution;

each R^mIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, C_1-4Alkyl, halo C_1-4Alkyl radical, C_1-4Alkoxy or halo C_1-4An alkoxy group.

In still other embodiments, R¹And R²Each independently is hydrogen, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-CH(CH₃)CH₂CH₃、-CH₂CH(CH₃)CH₃、-C(CH₃)₃、-CH＝CH₂、-CH₂CH＝CH₂、-CH＝CHCH₃、-C≡CH、-CH₂-C≡CH、-CH₂CH₂-C ≡ CH, phenyl or benzyl.

In still other embodiments, or R¹、R²And the N atom to which it is attached form the following subformula:

in some embodiments, Y is hydrogen, fluoro, chloro, bromo, iodo, hydroxy, cyano, nitro, amino, carboxy, C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, halo C_1-6Alkyl, halo C_2-6Alkenyl, halo C_2-6Alkynyl, C_6-10Aryl, halo C_6-10Aryl radical, C_6-10Aryl radical C_1-6Alkyl or halo C_6-10Aryl radical C_1-6An alkyl group.

In other embodiments, Y is hydrogen, fluoro, chloro, bromo, iodo, hydroxy, cyano, nitro, amino, carboxy, C_1-4Alkyl, halo C_1-4Alkyl radical, C_6-10Aryl, halo C_6-10Aryl radical, C_6-10Aryl radical C_1-4Alkyl or halo C_6-10Aryl radical C_1-4An alkyl group.

In still other embodiments, Y is hydrogen, fluoro, chloro, bromo, iodo, hydroxy, cyano, nitro, amino, carboxy, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂Cl、-CHF₂or-CF₃。

In some embodiments, R³And R⁴Independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, halo C_1-6Alkyl, halo C_2-6Alkenyl, halo C_2-6Alkynyl or C_3-8A cycloalkyl group.

In other embodiments, R³And R⁴Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl or halo C_1-4An alkyl group.

In still other embodiments, R³And R⁴Independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, -CH₃or-CH₂CH₃。

In other embodiments, R³And R⁴The carbon atom to which it is attached forms C ═ O.

In some embodiments, R⁵Is hydrogen, C_1-6Alkyl, -C (═ O) -C_1-6Alkyl, -C (═ O) -O-C_1-6Alkyl radical, C_1-6Alkoxy radical, C_1-6Alkoxy radical C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-8Cycloalkyl, 3-10 membered heterocyclyl, C_6-10Aryl radical, C_6-10Aryl radical C_1-6Alkyl radical, C_3-8Cycloalkyl radical C_1-6Alkyl or 3-10 membered heterocyclyl C_1-6An alkyl group.

In other embodiments, R⁵Is hydrogen, C_1-4Alkyl, -C (═ O) -C_1-4Alkyl, -C (═ O) -O-C_1-4Alkyl radical, C_1-4Alkoxy radical, C_1-3Alkoxy radical C_1-3Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_3-6Cycloalkyl radical, C_6-10Aryl radical, C_6-10Aryl radical C_1-4Alkyl or C_3-6Cycloalkyl radical C_1-4An alkyl group.

In still other embodiments, R⁵Is hydrogen, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-CH(CH₃)CH₂CH₃、-CH₂CH(CH₃)CH₃、-C(CH₃)₃Cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

In still other embodiments, R⁵Is of the sub-structure:

in some embodiments, Het is 5-10 membered heteroaryl; wherein said 5-10 membered heteroaryl is optionally substituted with 1,2,3,4, 5 or 6R^ASubstitution;

wherein each R is^AIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, -NHC_1-6Alkyl, -N (C)_1-6Alkyl radical)₂、-NR^BC(＝O)OC_1-6Alkyl, -NR^B1C(＝O)C_1-6Alkyl, -NR^B1C(＝O)C_3-8Cycloalkyl, -C (═ O) OC_1-6Alkyl, -C (═ O) OC_3-8Cycloalkyl, -OC (═ O) C_1-6Alkyl, -OC (═ O) C_3-8Cycloalkyl, -OC (═ O) NR^B2R^B3、C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_1-6Alkoxy, halo C_1-6Alkyl, halo C_2-6Alkenyl, halo C_2-6Alkynyl, halo C_1-6Alkoxy radical, C_3-8Cycloalkyl radical, C_3-8Cycloalkyl radical C_1-6Alkyl radical, C_6-10Aryl radical, C_6-10Aryl radical C_1-6Alkyl or C_6-10An aryloxy group; wherein each R is^AOptionally substituted by 1,2,3,4 or 5R^CSubstitution;

wherein R is^B、R^B1、R^B2And R^B3Each independently is hydrogen or C_1-6An alkyl group;

each R^CIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, C_1-6Alkyl radical, C_1-6Alkoxy, halo C_1-6Alkyl or halo C_1-6An alkoxy group.

In other embodiments, Het is pyrrolyl, thienyl, furyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, 1,2,3, 4-tetrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzopyrolyl, benzothienyl, benzofuranyl, benzopyrazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzopyridyl, benzopyrimidinyl, benzopyrazinyl, pyridazolyl, pyridoimidazolyl, or pyridopyridyl; wherein, the pyrrolyl, the thienyl, the furyl, the pyrazolyl, the imidazolyl, the 1,2, 4-triazolyl, the 1,2, 3-triazolyl, the 1,2, 5-triazolyl, the 1,3, 4-triazolyl, the oxazolyl, the isoxazolyl, the thiazolyl, the isothiazolyl, the 1,3, 4-oxadiazolyl, the 1,3, 4-thiadiazolylOxadiazolyl, 1,2,3, 4-tetrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzopyrolyl, benzothienyl, benzofuranyl, benzopyrazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzopyridyl, benzopyrimidinyl, benzopyrazinyl, pyridazinyl, pyridopyrrolyl, pyridopyrazolyl, pyridoimidazolyl and pyridopyridyl optionally substituted with 1,2,3,4, 5 or 6R^ASubstituted, wherein each R^AHaving the definitions set out in the present invention.

In still other embodiments, Het is pyrrolyl, thienyl, furyl, pyrazolyl, imidazolyl, 1,2, 4-triazolyl, 1,2, 3-triazolyl, 1,2, 5-triazolyl, 1,3, 4-triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,3, 4-oxadiazolyl, 1,2, 5-oxadiazolyl, 1,3, 4-thiadiazolyl, 1,2, 5-thiadiazolyl, 1,2,3, 4-tetrazolyl, pyridyl, pyrimidinyl, benzopyrolyl, benzothienyl, benzofuranyl, benzopyrazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, or benzopyridyl; wherein said pyrrolyl, thienyl, furyl, pyrazolyl, imidazolyl, 1,2, 4-triazolyl, 1,2, 3-triazolyl, 1,2, 5-triazolyl, 1,3, 4-triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,3, 4-oxadiazolyl, 1,3, 4-thiadiazolyl, 1,2,3, 4-tetrazolyl, pyridyl, pyrimidinyl, benzopyrolyl, benzothienyl, benzofuryl, benzopyrazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl and benzopyridyl are optionally substituted with 1,2,3,4, 5 or 6R^ASubstituted, wherein each R^AHaving the definitions set out in the present invention.

In still other embodiments, Het is of the subformula:

wherein the above sub-formulae are optionally substituted by 1,2,3,4, 5 or 6R^ASubstituted, wherein each R^AHaving the definitions set out in the present invention.

In some embodiments, each R is^AIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, -NHC_1-6Alkyl, -N (C)_1-6Alkyl radical)₂、-NR^BC(＝O)OC_1-4Alkyl, -NR^B1C(＝O)C_1-6Alkyl, -C (═ O) OC_1-4Alkyl, -OC (═ O) C_1-6Alkyl, -OC (═ O) NR^B2R^B3、C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_1-4Alkoxy, halo C_1-4Alkyl, halo C_1-4Alkoxy radical, C_6-10Aryl radical, C_6-10Aryl radical C_1-4Alkyl or C_6-10An aryloxy group; wherein each R is^AOptionally substituted by 1,2,3,4 or 5R^CAnd (4) substitution.

In some embodiments, R^B、R^B1、R^B2And R^B3Each independently is hydrogen or C_1-4An alkyl group.

In other embodiments, each R is^AIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, -NHC (═ O) OCH₃、-NHC(＝O)OCH₂CH₃、-NHC(＝O)OCH₂CH₂CH₃、-NHC(＝O)OCH(CH₃)₂、-NHC(＝O)OC(CH₃)₃、-NHCH₃、-NHCH₂CH₃、-N(CH₃)₂、-N(CH₂CH₃)₂、-C(＝O)OCH₃、-C(＝O)OCH₂CH₃、-OC(＝O)CH₃、-OC(＝O)CH₂CH₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-CH(CH₃)CH₂CH₃、-CH₂CH(CH₃)CH₃、-C(CH₃)₃、-OCH₃、-OCH₂CH₃、-OCH₂CH₂CH₃、-OCH(CH₃)₂、-OC(CH₃)₃、-CH₂Cl、-CH₂Br、-CHF₂、-CF₃、-OCF₃Phenyl, benzyl or phenoxy; wherein each R is^AOptionally substituted by 1,2,3,4 or 5R^CAnd (4) substitution.

In some embodiments, each R is^CIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, C_1-4Alkyl radical, C_1-4Alkoxy, halo C_1-4Alkyl or halo C_1-4An alkoxy group.

In other embodiments, each R is^CIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-C(CH₃)₃、-OCH₃、-OCH₂CH₃、-OCH₂CH₂CH₃、-OCH(CH₃)₂、-OC(CH₃)₃、-CH₂Cl、-CHF₂、-CF₃or-OCF₃。

In still other embodiments, Het is of the subformula:

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

in another aspect, the invention provides a composition comprising a compound of the invention.

In some embodiments, the compositions of the present invention further comprise at least one additional component that acts as a carrier.

In another aspect, the invention provides the use of a compound or composition comprising the invention in agriculture.

Further, the invention provides application of the compound or the composition in plant disease control.

In another aspect, the present invention provides a method for controlling plant diseases, characterized in that an effective amount of the compound or the composition according to the present invention is applied to a plant, a plant seed, soil where a plant is grown, or a plant cultivation area.

Compositions and formulations of the compounds of the invention

The compounds of the present invention are generally useful as fungicide active ingredients in compositions, i.e., formulations, typically further comprising an agriculturally acceptable surfactant and/or carrier.

The surfactant may be any of various surfactants known in the art of pesticide formulation, such as anionic, cationic, nonionic and amphoteric surfactants, block polymers, polyelectrolytes, and mixtures thereof. Such surfactants may be used as emulsifiers, dispersants, wetting agents, penetration enhancers or adjuvants.

Suitable anionic surfactants are alkali metal, alkaline earth metal or ammonium salts of sulfonic acids, sulfuric acids, phosphoric acids, carboxylic acids and mixtures thereof. Examples of sulfonates are alkylarylsulfonates, diphenylsulfonates, alpha-olefin sulfonates, lignosulfonates, sulfonates of fatty acids and oils, sulfonates of ethoxylated alkylphenols, sulfonates of alkoxylated arylphenols, sulfonates of condensed naphthalenes, sulfonates of dodecyl-and tridecylbenzenes, sulfonates of naphthalenes and alkylnaphthalenes, sulfosuccinates or sulfosuccinamates. Examples of sulfates are sulfates of fatty acids and oils, sulfates of ethoxylated alkylphenols, sulfates of alcohols, sulfates of ethoxylated alcohols or sulfates of fatty acid esters. An example of a phosphate is a phosphate ester. Examples of carboxylates are alkyl carboxylates and also carboxylated alcohol or alkylphenol ethoxylates.

Suitable nonionic surfactants are alkoxylates, N-substituted fatty acid amides, amine oxides, esters, sugar-based surfactants, polymeric surfactants and mixtures thereof. Examples of alkoxylates are compounds such as alcohols, alkylphenols, amines, amides, arylphenols, fatty acids or fatty acid esters which have been alkoxylated by 1 to 50 equivalents. Ethylene oxide and/or propylene oxide may be used for the alkoxylation, preferably ethylene oxide. Examples of N-substituted fatty acid amides are fatty acid glucamides or fatty acid alkanolamides. Examples of esters are fatty acid esters, glycerol esters or monoglycerides. Examples of sugar-based surfactants are sorbitan, ethoxylated sorbitan, sucrose and glucose esters or alkyl polyglucosides. Examples of polymeric surfactants are homopolymers or copolymers of vinylpyrrolidone, vinyl alcohol or vinyl acetate.

Suitable cationic surfactants are quaternary ammonium type surfactants, such as quaternary ammonium compounds having 1 or 2 hydrophobic groups, or salts of long chain primary amines. Suitable amphoteric surfactants are alkyl betaines and imidazolines. Suitable block polymers are block polymers of the A-B or A-B-A type comprising blocks of polyoxyethylene and polyoxypropylene, or block polymers of the A-B-C type comprising alkanols, polyoxyethylene and polyoxypropylene. Suitable polyelectrolytes are polyacids or polybases. Examples of polyacids are alkali metal salts of polyacrylic acid or polyacid comb polymers. Examples of polybases are polyvinylamine or polyvinylamine.

The carrier may be any of various carriers known in the field of agricultural chemical preparations, including various silicates, carbonates, sulfates, oxides, phosphates, plant carriers, and synthetic carriers. Specifically, for example: white carbon black, kaolin, diatomite, 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 fungicide composition according to the present invention may further contain various formulation auxiliaries commonly used in the field of pesticide formulation, and specifically, the formulation auxiliaries may be one or more of a solvent, a cosolvent, a thickener, an antifreeze, a capsule material, a protectant, an antifoaming agent, a disintegrant, a stabilizer, a preservative, a binder, and a chelating agent.

Suitable solvents are water and organic solvents, such as mineral oil fractions of medium to high boiling point, e.g. kerosene, diesel oil; oils of vegetable or animal origin; aliphatic, cyclic and aromatic hydrocarbons, such as toluene, paraffins, tetrahydronaphthalene, alkylated naphthalenes; alcohols, such as ethanol, propanol, butanol, benzyl alcohol, cyclohexanol; glycols; DMSO; ketones, such as cyclohexanone; esters, such as lactate, carbonate, fatty acid ester, γ -butyrolactone; a fatty acid; a phosphonate ester; amines; amides, such as N-methylpyrrolidone, fatty acid dimethylamide; and mixtures thereof.

The solvents mentioned above can also be used as cosolvents.

Suitable thickeners are selected from polysaccharides (e.g. xanthan gum, carboxymethyl cellulose), inorganic clays (organically modified or unmodified), polycarboxylates and silicates.

Suitable antifreeze agents are selected from the group consisting of ethylene glycol, propylene glycol, glycerol, urea, glycerol and mixtures thereof.

Suitable capsule materials are selected from the group consisting of polyurethanes, polyureas, urea-formaldehyde resins and mixtures thereof.

Suitable protective agents are selected from polyvinyl alcohol and/or polyethylene glycol.

Suitable antifoaming agents are selected from the group consisting of polysiloxanes, silicone emulsions, long chain alcohols, fatty acids and salts thereof, and fluoro-organics and mixtures thereof.

Suitable disintegrants are selected from bentonite, urea, ammonium sulfate, aluminum chloride, citric acid, succinic acid, sodium bicarbonate and mixtures thereof

Suitable stabilizers are selected from the group consisting of triphenyl phosphite, epichlorohydrin, acetic anhydride and mixtures thereof.

Suitable preservatives are selected from benzoic acid, sodium benzoate, 1, 2-benzisothiazolin-3-one (BIT for short), carbazone, potassium sorbate and mixtures thereof.

Suitable binders are selected from polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol, polyacrylates, biological or synthetic waxes and cellulose ethers.

The fungicides according to the invention can be applied in their formulated form or in the use forms prepared therefrom, such as aerosols, capsule suspensions, cold-fogging concentrates, hot-fogging concentrates, encapsulated granules, fine granules, flowable concentrates for seed treatment (flowable concentrates), ready-to-use solutions, dustable powders, emulsifiable concentrates, oil-in-water emulsions, water-in-oil emulsions, macrogranules, microgranules, oil-dispersible powders, oil-miscible flowable concentrates, oil-miscible liquids, gas agents (under pressure), gas-generating products, foams, pastes, suspension concentrates, soluble concentrates, suspensions, wettable powders, soluble powders, dusts and granules, water-soluble and water-dispersible granules or tablets, water-soluble or water-dispersible powders for seed treatment, wettable powders, natural and synthetic substances impregnated with active substances, and microcapsules in polymers and seed coatings, and ULV (ultra low volume) cold and hot fog formulations. The above forms of use can be prepared by conventional means in the art.

Application of the inventive compounds and compositions

The compounds or compositions according to the invention are useful as plant disease control agents, in crop protection and in the protection of materials for controlling unwanted fungal and bacterial diseases, for example:

diseases caused by powdery mildew pathogens, e.g., the genus Blumeria, such as Blumeria graminis (Blumeria graminis); the genus aphelenchoides (podosphaea), such as the aphelenchoides leucotricha (podosphaea leucotricha); genus mono-vesicular shell (Sphaerotheca), such as balsamine mono-vesicular shell (Sphaerotheca fuliginea); devil's claw (Uncinula) genera, such as grapevine's claw (Uncinula necator);

diseases caused by rust pathogens, for example, the genus, e.g., brown rust (Gymnosphaerella sabinae); camelina rust (hemieia) genus, such as camelina coffea (hemiaviastatrix); phakopsora (Phakopsora) genera, such as Phakopsora pachyrhizi (Phakopsora purpurizi) and Phakopsora meibomiae (Phakopsora meibomiae); puccinia (Puccinia) genera, such as Puccinia recondite (Puccinia recondite), Puccinia triticina (P.triticina), Puccinia graminis (Puccinia graminis) or Puccinia striiformis (Puccinia striiformis); genus unicellular rust (Uromyces), such as, for example, Ruscus verrucosa (Uromyces apendiculus);

diseases caused by Oomycete (oomycin) pathogens, e.g. white rust (Albugo) genera, such as white rust (Albugo Candida); peronospora species (Bremia), for example, Peronospora lactucae (Bremia lactucae); peronospora species, for example Peronospora pisi (Peronospora pisi) or Peronospora cruciferae (Peronospora brassicae); phytophthora (Phytophthora) species, such as Phytophthora infestans; plasmopara species, such as Plasmopara viticola (Plasmopara viticola); pseudoperonospora (Pseudoperonospora), for example Pseudoperonospora praecox (Pseudoperonospora humuli) or Pseudoperonospora cubensis; pythium (Pythium) genera, such as Pythium ultimum;

leaf blight (Leaf patch) and Leaf wilting (Leaf wilt) diseases caused by the following pathogens: for example, the genus Alternaria (Alternaria), such as Alternaria alternata (Alternaria solani); a genus of Asperula beta (Cercospora), for example, Asperuma beta (Cercospora beta); cladosporium species, such as Cladosporium cucumerinum; the genus Cochliobolus (Cochliobolus) such as Cochliobolus graminis (Cochliobolus sativus) (conidia form: Helminthosporium (Drechslera), Syn: Helminthosporium (Helminthosporium)), and Thielavia gondii (Cochliobolus miyabenus); anthrax (Colletotrichum) genus, such as Phaseolus vulgaris (Colletotrichum lindemuthanum); the genus Puccinia (Cycloconium), such as malachite leaf spot (Cycloconium oleginum); intercalary shell (Diaporthe) genera, such as citrus intercalary shell (Diaporthe citri); elsinoe spp (Elsinoe) such as Elsinoe citroideus (Elsinoefawcettii); discodermospora (Gloeosporium), e.g. discodermospora roseticolor; plexi-shell (glomeriella) genus, such as plexi-shell (glomeriella cingulata); the genus of coccobacillus (Guignardia), such as coccobacillus viticola (Guignardia bidwelli); the genus Leptosphaeria (Leptosphaeria), such as Leptosphaeria maculans (Leptosphaeria maculans), Leptosphaeria nodorum (Leptosphaeria nodorum); large destructed shells (Magnaporthe) genera, such as gray large destructed shells (Magnaporthe grisea); aschersonia (Microdochium), e.g.Aschersonia (Microdochium nivale); the genus sphacelella (Mycosphaerella), such as Mycosphaerella graminicola (Mycosphaerella graminicola), Mycosphaerella arachidicola (m.arachidacola), and Mycosphaerella fijiensis (m.fijiensis); septoria (phaesperaria) genus, such as septoria nodorum (phaesperaria nodorum); pyrenophora (Pyrenophora) genus, such as Pyrenophora teres (Pyrenophora teres), Pyrenophora tritici-repentis (Pyrenophora tritici-epentais); the genus Bectona (Ramularia), for example, Ramularia sincalifornica (Ramularia collo-cygni), Ramularia leucotricha (Ramularia areola); rhynchophorium genus, such as Rhynchophorium secalii (Rhynchophorium secalis); conidia (Septoria) genera, such as Septoria apiacea (Septoria apiacea), Septoria lycopersici (Septoria lycopersici); corallina (Typhula) genus, such as Corallina carnea (Typhulaincarnata); genus Venturia (Venturia), such as apple scab (Venturia inaqualis);

root and stem diseases caused by the following pathogens: for example, the genus of the species of the genus of the species of; fusarium (Fusarium) genus, such as Fusarium oxysporum (Fusarium oxysporum); the genus Gaeumannomyces, such as Gaeumannomyces graminis (Gaeumannomyces graminis); rhizoctonia (Rhizoctonia) genus, such as Rhizoctonia solani (Rhizoctonia solani); for example, diseases of the genus cladosporium (Sarocladium) caused by cladosporium oryzae (Sarocladium oryzae); sclerotium (Sclerotium) disease caused by Sclerotium rot (Sclerotium oryzae); tapesia species, such as Tapesia acuformis; genus Rhinocerotis (Thielavirosis), such as Rhinocerotis (Thielavirosis basicola);

panicle or panicle diseases (including corn cobs) caused by the following pathogens: for example, the genus Alternaria (Alternaria), such as the genus Alternaria (Alternaria spp.); aspergillus (Aspergillus) genus, such as Aspergillus flavus; cladosporium (Cladosporium), such as Cladosporium cladosporioides (Cladosporium cladosporioides); claviceps (Claviceps) genus, such as Claviceps (Claviceps purpurea); fusarium (Fusarium) genus, such as Fusarium flavum (Fusarium culmorum); gibberella species, such as Gibberella zeae (Gibberella zeae); small picture shells (monograms) belong to the genus, e.g., snow rot small picture shells (monograms); genus chitin (Stagonospora), such as chitin glumae (Stagonosporanodosum);

diseases caused by smut, for example, of the genus leptospirillum (Sphacelotheca), such as leptospirillum seriana (Sphacelotheca reiliana); tilletia species (Tilletia), such as Tilletia grisea (Tilletia), Tilletia controversa (T.contrivarsa); ustilago virens (Urocystis) genus, such as Ustilago virens (Urocystis occulta); smut (Ustilago) genera, such as, for example, Ustilago nuda (Ustilago nuda), Ustilago tritici (U.nuda tritici);

fruit decay caused by the following pathogens: for example, Aspergillus (Aspergillus) genus, such as Aspergillus flavus (Aspergillus flavus); botrytis (Botrytis) genera, such as Botrytis cinerea (Botrytis cinerea); penicillium (Penicillium) genera, such as Penicillium expansum (Penicillium expansum) and Penicillium purpurogenum (p.purpurogenum); sclerotinia species, such as Sclerotinia sclerotiorum (Sclerotinia sclerotiorum); verticillium species, such as Verticillium alboatrum (Verticillium alboatrum);

rotting and soil-borne rot, mildew, wilting, rot and damping-off of seeds caused by the following pathogens: for example, the genus Alternaria (Alternaria), such as Alternaria brassicae (Alternaria brassicola); the genus Saccharomycosis (Aphanomyces), such as, for example, Rhizoctonia solani (Aphanomyces euteiches); ascochyta (Ascochyta) genus, such as, for example, Bisporum lentinus (Ascochyta lentis); aspergillus (Aspergillus) such as Aspergillus flavus; cladosporium (Cladosporium) genus, such as Cladosporium herbarum (Cladosporium herbarum); the genus Cochliobolus (Cochliobolus) such as Cochliobolus graminis (Cochliobolus sativus) (conidia form: Helminthosporium endocordalis, Helminthosporium (Bipolaris) Syn: Helminthosporium); anthrax (Colletotrichum) genus, such as Colletotrichum fuliginosum (Colletotrichum coccodes); fusarium (Fusarium) genus, such as Fusarium flavum (Fusarium culmorum); gibberella species, such as Gibberella zeae (Gibberella zeae); the genus ascochyta (macrophostoma), such as ascochyta phaseoloides (macrophostoma phaseolina); small picture shells (monograms) belong to the genus, e.g., snow rot small picture shells (monograms nivalis); penicillium (Penicillium) genus, such as Penicillium expansum (Penicillium expandasum); phoma (Phoma) genus, such as Phoma nigricans (Phomalignam); phomopsis species, such as Phomopsis sojae; phytophthora (Phytophtora) species, such as Phytophthora infestans (Phytophtora cacorum); pyrenophora (Pyrenophora) genus, such as Pyrenophora graminea (Pyrenophora graminea); pyricularia (Pyricularia) genus, such as Pyricularia oryzae (Pyricularia oryzae); pythium (Pythium) genera, such as Pythium ultimum; rhizoctonia (Rhizoctonia) genus, such as Rhizoctonia solani (Rhizoctonia solani); rhizopus (Rhizopus) genus, such as Rhizopus oryzae (Rhizopus oryzae); sclerotinia species (Sclerotium), such as Sclerotinia sclerotiorum (Sclerotium rolfsii); septoria (Septoria) genus, such as Septoria nodorum (Septoria nodorum); corallina (Typhula) genus, such as Corallina carnea (Typhula incarnata); verticillium species, such as Verticillium dahliae (Verticillium dahliae);

cancerous diseases, galls and broom diseases (witches' brooms) caused by the following pathogens: for example, genus Haematoloma (Nectria), such as Haematoloma manshuriensis (Nectria galligena);

atrophy diseases caused by the following pathogens: for example, the genus Sclerotinia (Monilinia), such as Sclerotinia drus (Monilinia laxa);

leaf wheal or leaf curl caused by the following pathogens: for example, the genus Exobasidium (Exobasidium), such as the genus Exobasidium putida (Exobasidium vexans); exocystis (Taphrina), such as exocystis malformation (taphridaeformans);

degenerative diseases of woody plants caused by the following pathogens: for example, diseases according to the discipline (Esca) caused by, for example, Rhizopus oryzae (Phaeomoniella chlamydospora), Phaeoacremonium aleophilum and Histoplasma geotrichum (Fomitipidia media); such as grape blight disease (Eutypa dieback) caused by grape vine blight (Eutypa latica); diseases of the genus Ganoderma (Ganoderma), for example, caused by Ganoderma boninense (Ganoderma boninense); for example, a scleroderma (Rigidoporus) disease caused by scleroderma (Rigidoporus lignosus);

flower and seed diseases caused by the following pathogens: for example, the genus Botrytis (Botrytis), such as Botrytis cinerea (Botrytis cinerea);

diseases of plant tubers caused by the following pathogens: for example, the genus Rhizoctonia (Rhizoctonia), such as Rhizoctonia solani (Rhizoctonia solani); helminthosporium species, such as Helminthosporium solani (Helminthosporium solani);

clubroot diseases caused by the following pathogens: for example, Plasmodiophora, such as Plasmodiophora yunnanensis (Plasmodiophora brassicae);

diseases caused by the following bacterial pathogens: for example, the genus Xanthomonas (Xanthomonas), such as Xanthomonas oryzae var alba (Xanthomonas campestris pv. oryzae); pseudomonas, such as Pseudomonas syringae Cucumaria var syringae (Pseudomonas syringae pv. lachrymans); erwinia (Erwinia) genus, such as Erwinia amylovora (Erwinia amylovora).

In addition, they are suitable for combating fungi which infect wood or plant roots.

Fungicides can be used in crop protection for controlling Pseudomonas (Pseudomonas), Rhizobiaceae (Rhizobiaceae), Enterobacter (Enterobacteriaceae), Corynebacterium (Corynebacterium), and Streptomyces (Streptomyces).

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

The fungicidal compositions of the present invention have a fungicidal effect which is usually associated with external factors such as climate, but the effect of climate can be alleviated by using appropriate formulations.

The compositions of the present invention may also be used in admixture with other compounds having fungicidal, insecticidal or herbicidal properties, as well as with nematicides, acaricides, protectants, herbicidal safeners, growth regulators, plant nutrients or soil conditioners, and the like.

General synthetic procedure

In this specification, a structure is dominant if there is any difference between the chemical name and the chemical structure. In general, the compounds of the present invention may be prepared by the methods described herein, wherein the substituents are as defined in (I), unless otherwise indicated.

Those skilled in the art will recognize that: the chemical reactions described herein may be used to suitably prepare a number of other compounds of the invention, and other methods for preparing the compounds of the invention are considered to be within the scope of the invention. For example, the synthesis of those non-exemplified compounds according to the present invention can be successfully accomplished by those skilled in the art by modification, such as appropriate protection of interfering groups, by the use of other known reagents (other than those described herein), or by some routine modification of reaction conditions. In addition, the reactions disclosed herein or known reaction conditions are also recognized as being applicable to the preparation of other compounds of the present invention.

The following synthetic schemes describe the steps for preparing the compounds disclosed herein. Wherein R is¹、R²And Het has the meaning described in the present invention.

Synthetic schemes

Synthesis scheme I

The target compound I-1 can be prepared by the first synthesis scheme. And reacting the compound a with the compound b under an alkaline condition to obtain the target compound I-1.

Synthesis scheme two

The target compound I-2 can be prepared by the second synthesis scheme. And reacting the compound a with the compound c under an alkaline condition to obtain the target compound I-2.

Synthesis scheme three

The target compound I-3 can be prepared by the third synthesis scheme. And reacting the compound a with the compound d under an alkaline condition to obtain the target compound I-3.

Synthesis scheme four

The target compound I-3 can also be prepared by the fourth synthesis scheme. Reacting the compound e with the compound f under an alkaline condition to obtain a target compound I-3;

wherein, X¹Is fluorine, chlorine, bromine or iodine.

Synthesis scheme five

The target compound I-4 can also be prepared by synthesis scheme five. Reacting the compound g with the compound h under an alkaline condition to obtain a target compound I-4;

wherein, X¹Is fluorine, chlorine, bromine or iodine.

Detailed Description

The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention.

Examples

An intermediate A: synthesis of 1, 2-di (1H-1,2, 4-triazole-3-yl) dithioane

3-mercapto-1, 2, 4-triazole (101.0g,1.00mol) is dissolved in dichloromethane (500mL), pyridine (79.0g,1.00mol) is added, stirring is carried out at 0 ℃, benzenesulfonyl chloride (88.30g,0.50mol) is slowly added dropwise, and the dropwise addition is completed within 2 hours. After the addition was complete, the mixture was stirred at 25 ℃ for 18 hours. The methylene chloride was evaporated under reduced pressure using a rotary evaporator, and the residue was stirred for 1 hour with water (500mL) added under mechanical stirring. Filtration and washing of the residue with water (800mL) and ethyl acetate (300mL) respectively followed by air drying gave 95.2g of a yellow powder in the following yield: 95.2 percent.

LC-MS:(M+1)m/z＝201.1。

An intermediate B: synthesis of 3, 3' -disulfanediylbis (N, N-dimethyl-1H-1, 2, 4-triazole-1-sulfonamide)

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

LC-MS:(M+1)m/z＝415.0。

An intermediate C: synthesis of 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) (41.40g,0.10mol) is dissolved in 1, 2-dichloroethane (300mL), water (300mL) is added, the mixture is cooled to 0 ℃, acetic acid (100mL) is added, the temperature is controlled between 10 ℃ and 25 ℃, chlorine gas (35.50g,0.50mol) is introduced after 2 hours, and the reaction is continued for half an hour. After completion of the reaction, the solution was transferred to a separatory funnel, allowed to stand for separation, the organic phase was washed three times with water (30mL), and the solvent was evaporated under reduced pressure using a rotary evaporator to obtain 48.11g of a white powder with a yield of: 87.8 percent.

LC-MS:(M+1)m/z＝274.8。

An intermediate D: n is a radical of³-cyclopropyl-N¹,N¹Synthesis of (dimethyl) -1H-1,2, 4-triazole-1, 3-disulfonamide

Under the protection of nitrogen, cyclopropylamine (1.14g,0.02mol), triethylamine (2.22g,0.022mol) and tetrahydrofuran (30mL) were added to a 100mL three-necked flask, stirred at 0 ℃ and a solution of 1- (N, N-dimethylaminosulfonyl) -1H-1,2, 4-triazole-3-sulfonyl chloride (6.04g,0.02mol) in tetrahydrofuran (20mL) was added dropwise over 10 minutes, and then reacted at 25 ℃ for 2 hours. The solid was removed by filtration, and the filtrate was freed of the solvent under reduced pressure using a rotary evaporator to give a pale yellow solid, which was recrystallized [ EtOAc/PE (v/v) ═ 5/1] to give 4.42g of a white solid in the following yield: 75.0 percent.

¹H NMR(400MHz,DMSO-d₆)(ppm):9.30(s,1H),7.49(s,1H),2.96(s,6H),2.48(m,1H),0.63-0.56(m,2H),0.50-0.43(m,2H)；

LC-MS:(M+1)m/z＝296.3。

Intermediate E: n is a radical of³-cyclopentyl-N¹,N¹-dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide synthesis:

under the protection of nitrogen, cyclopentylamine (1.70g,0.02mol), triethylamine (2.22g,0.022mol) and tetrahydrofuran (30mL) were added to a 100mL three-necked flask, stirred at 0 ℃ and added dropwise with a solution of 1- (N, N-dimethylaminosulfonyl) -1H-1,2, 4-triazole-3-sulfonyl chloride (6.04g,0.02mol) in tetrahydrofuran (20mL) over 10 minutes, and reacted at 25 ℃ for 2 hours after the addition. The solid was removed by filtration, and the filtrate was freed of solvent under reduced pressure using a rotary evaporator to give a pale yellow solid, which was recrystallized [ EtOAc/PE (v/v) ═ 5/1] to give 4.72g of a white solid in the following yield: 73.0 percent.

¹H NMR(400MHz,DMSO-d₆)(ppm):9.30(s,1H),7.66(s,1H),4.38(dt,1H),2.96(s,6H),1.70(d,2H),1.44(ddd,4H),1.29(s,2H)；

LC-MS:(M+1)m/z＝324.1。

An intermediate F: synthesis of N- ((2-fluoropyridin-3-yl) methyl) cyclopropylamine

Cyclopropylamine (1.71g,30.0mmol), 2-fluoro-3-formylpyridine (1.25g,10.0mmol), anhydrous magnesium sulfate (3.60g,30.0mmol) and methylene chloride (30mL) were added to a 100mL three-necked flask and reacted at 25 ℃ for 12 hours. Filtering, and removing the solvent from the filtrate under reduced pressure by using a rotary evaporator to obtain the imine intermediate. The imine intermediate was dissolved in methanol (20mL), sodium borohydride (0.38g,10.0mmol) was slowly added to the reaction, reacted at room temperature at 25 ℃ for 5 hours, spun dry, and purified by column chromatography [ EtOAc/PE (v/v) ═ 1/5] to give 1.34g of a colorless liquid in the following yield: 81.0 percent.

LC-MS:(M+1)m/z＝167.1。

The intermediates in table 1 were obtained by a similar synthesis of intermediate F, replacing the 2-fluoro-3-formylpyridine with the corresponding material.

TABLE 1

Example 1: n is a radical of¹,N¹-dimethyl-N³Synthesis of- (1,3, 4-thiadiazole-2-yl) -1H-1,2, 4-triazole-1, 3-disulfonamide

2-amino-1, 3, 4-thiadiazole (0.20g,2.0mmol), pyridine (0.32g,4.0mol), tetrahydrofuran (10mL) were added to a 50mL single vial, stirred uniformly at room temperature, 1- (N, N-dimethylaminosulfonyl) -1H-1,2, 4-triazole-3-sulfonyl chloride (0.82g,3.0mmol) was slowly added to the reaction system, reacted at 25 ℃ for 12 hours, quenched with water (20mL), extracted with ethyl acetate (15mL × 3), dried over anhydrous magnesium sulfate, filtered, the filtrate was subjected to reduced pressure using a rotary evaporator to remove the solvent, and purified by column chromatography [ EtOAc/PE (v/v) ═ 1/3] to give 0.53g of a white solid in a yield: 78.0 percent.

¹H NMR(400MHz,DMSO-d₆)(ppm):9.17(s,1H),8.62(s,1H),4.72(s,1H),2.99(s,6H)；

LC-MS:(M+1)m/z＝340.1。

By a similar synthesis method of example 1, the target compounds in table 2 can be obtained by reacting the corresponding materials with the intermediate 1- (N, N-dimethylaminosulfonyl) -1H-1,2, 4-triazole-3-sulfonyl chloride.

TABLE 2

Example 12: n is a radical of³-cyclopropyl-N³- ((6-Fluoropyridin-3-yl) methyl) -N¹,N¹Synthesis of (dimethyl) -1H-1,2, 4-triazole-1, 3-disulfonamide

Will N³-cyclopropyl-N¹,N¹-dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide (0.30g,1.0mmol), potassium carbonate (0.28g,2.0mmol) and N, N-dimethylformamide (10mL) were added to a 50mL one-neck flask, 5- (chloromethyl) -2-fluoropyridine (0.29g,2.0mmol) was slowly added to the reaction system, reacted at 25 ℃ for 8 hours, quenched with water (20mL), extracted with ethyl acetate (15mL x 3), the organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, the filtrate was decompressed by a rotary evaporator to remove the solvent, and column chromatography was performed to purify [ EtOAc/PE (v/v) ═ 1/3]0.32g of white solid is obtained in yield: 78.0 percent.

¹H NMR(400MHz,DMSO-d₆)(ppm):9.43(s,1H),8.20-8.17(d,1H),7.98-7.92(m,1H),7.21-7.16(m,1H),4.56(s,2H),2.99(s,6H),2.60-2.55(m,1H),0.75-0.70(m,4H)；

LC-MS:(M+1)m/z＝405.0。

By analogy with the synthesis of example 12, starting from the corresponding material and intermediate N³-cyclopropyl-N¹,N¹And (3) reacting the dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide to obtain the target compounds in the table 3.

TABLE 3

Example 24: n is a radical of³- ((5-chlorothien-2-yl) methyl) -N³-cyclopentyl-N¹,N¹Synthesis of (dimethyl) -1H-1,2, 4-triazole-1, 3-disulfonamide

Will N³-cyclopentyl-N¹,N¹-dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide (0.32g,1.0mmol), potassium carbonate (0.28g,2.0mmol) and N, N-dimethylformamide (10mL) were added to a 50mL single-neck flask, 2-chloro-5- (chloromethyl) thiophene (0.33g,2.0mmol) was slowly added to the reaction system, reacted at 25 ℃ for 8 hours, quenched with water (20mL), extracted with ethyl acetate (15mL x 3), the organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, the filtrate was subjected to reduced pressure using a rotary evaporator to remove the solvent, and purified by column chromatography [ EtOAc/PE (v/v) ═ 1/3]0.35g of a white solid is obtained in a yield of: 76.0 percent.

¹H NMR(400MHz,CDCl₃)(ppm):8.62(s,1H),6.83(d,J＝3.7Hz,1H),6.76(d,J＝3.7Hz,1H),4.62(s,2H),4.42-4.31(m,1H),3.08(s,6H),1.82-1.28(m,8H)；

LC-MS:(M+1)m/z＝454.0。

By analogy with the synthesis of example 24, starting from the corresponding material and intermediate N³-cyclopentyl-N¹,N¹And (3) reacting the dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide to obtain the target compounds in the table 4.

TABLE 4

Activity assay

In the following test examples, the inventors examined the control efficacy of the compounds of the present invention against harmful fungi by taking some of the compounds of the present invention as examples. Test example 1

Test targets: rhizoctonia solani, botrytis cinerea, peronospora cubensis and erysiphe necator

And (3) test treatment: the compound was dissolved in DMF to 1% EC for use. The bactericidal activity of these compounds at different doses against 4 test targets was evaluated using the in vivo potting method.

1) Pseudoperonospora cubensis test (Pseudoperonospora cubensis)

Selecting 1 potted cucumber seedling with consistent growth vigor in true leaf period (removing growing point), spraying, air drying, inoculating 24 hr later, taking fresh cucumber downy mildew diseased leaf, washing off sporocyst on back of diseased leaf with distilled water, and making into sporangium suspension (2-3X 10)⁵one/mL). Uniformly spraying and inoculating on cucumber seedlings by using an inoculation sprayer (the pressure is 0.1MPa), transferring inoculated test materials to an artificial climate chamber, keeping the relative humidity at 100% and the temperature at about 21 ℃, keeping the temperature at about 21 ℃ after 24 hours, keeping the relative humidity at about 95% for moisture induction, carrying out grading investigation according to blank control disease occurrence conditions after 5 days, and calculating the control effect according to disease indexes.

2) Cucumber powdery mildew test (Sphaerothecafeuliginea)

Selecting a cucumber seedling with a true leaf period and consistent growth vigor, and drying in the shade for 24 hours after spraying treatment. Washing fresh powdery mildew spores on cucumber leaves, filtering the fresh powdery mildew spores by using double-layer gauze to prepare suspension with the spore concentration of about 10 ten thousand/mL, and spraying for inoculation. And (3) transferring the inoculated test material into an artificial climate, keeping the relative humidity between 60 and 70 percent, keeping the temperature between 21 and 23 ℃, carrying out grading investigation according to blank control disease occurrence conditions after about 10 days, and calculating the control effect according to disease indexes.

3) Cucumber gray mold (Botrytis cinerea)

The method adopts a leaf inoculation method. Two potted cucumber seedlings with the same growth vigor of the true leaf period are selected, and after the agent is sprayed and dried, a fungus cake is inoculated on the leaves. And (3) after 24-26 ℃ dark light moisture preservation is carried out for 24 hours, natural illumination moisture preservation culture is carried out for about 3 days. After the contrast is fully developed, the diameter of the lesion spot of each inoculation point is measured by a caliper, and the control effect is calculated.

4) Rhizoctonia solani (Rhizoctonia)

Selecting potted corn seedlings with two leaves and one heart and consistent growth vigor, naturally drying after spraying treatment, inoculating for about 24 hours, and inoculating a fungus cake on leaves after the medicament is sprayed and dried. And (3) after the dark light is moisturized for 24 hours at the temperature of 25-26 ℃, natural illumination is recovered for moisturizing and culturing for about 3 days. After the disease is sufficiently distributed in contrast, the length of the lesion spot of each inoculation point is measured by a caliper, and the control effect is calculated.

And (3) test results: the test results are shown in tables 5 to 7.

Table 5200 mg/L dose test results for the Compounds of the invention

Test results for Compounds of the invention at Table 6100 mg/L dose

TABLE 750 mg/L dosage test results for the compounds of the invention

From the above test results, it is understood that the compounds of the present invention have excellent controlling effects on diseases on plants, particularly cucumber downy mildew.

Claims (8)

1. A compound having formula (I) or a salt of a compound of formula (I):

wherein,

R¹and R²Each independently is C_1-4An alkyl group;

y is hydrogen;

n is 2;

-X-is-NR⁵-；

R⁵Is C_3-6A cycloalkyl group;

m is 1;

R³and R⁴Independently is hydrogen;

het is

Wherein, the

Optionally substituted by 1 or 2R^ASubstitution;

wherein each R is^AIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, -NHC (═ O) OC_1-4Alkyl or C_1-4An alkyl group.

2. The compound of claim 1, wherein,

R¹and R²Each independently is-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-CH(CH₃)CH₂CH₃、-CH₂CH(CH₃)CH₃or-C (CH)₃)₃。

3. The compound of claim 1, wherein,

R⁵is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

4. The compound of claim 1, wherein,

het is

Wherein, the

Optionally substituted by 1 or 2R^ASubstitution;

wherein each R is^AIndependently fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, -NHC (═ O) OCH₃、-NHC(＝O)OCH₂CH₃、-NHC(＝O)OCH₂CH₂CH₃、-NHC(＝O)OCH(CH₃)₂、-NHC(＝O)OC(CH₃)₃、-CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-CH(CH₃)CH₂CH₃、-CH₂CH(CH₃)CH₃or-C (CH)₃)₃。

5. The compound of claim 1, wherein,

het is the following subformula:

6. a compound which is a compound having one of the following structures or a salt of a compound having one of the following structures:

7. a composition comprising a compound according to any one of claims 1 to 6 and an agriculturally pharmaceutically acceptable surfactant and/or carrier.

8. Use of the compound according to any one of claims 1 to 6 or the composition according to claim 7 for controlling plant diseases.