CN110950810B

CN110950810B - Triazole compound and application thereof in agriculture

Info

Publication number: CN110950810B
Application number: CN201910915530.1A
Authority: CN
Inventors: 李义涛; 林健; 李法霖; 姚文强; 王传伟; 刘新烁; 刘杨润琦
Original assignee: Dongguan Hec Pesticides R&d Co ltd
Current assignee: Dongguan Hec Pesticides R&d Co ltd
Priority date: 2018-09-27
Filing date: 2019-09-26
Publication date: 2021-12-03
Anticipated expiration: 2039-09-26
Also published as: CN110950811B; CN110950812A; CN110950810A; CN110950811A; CN110950812B; WO2020063756A1

Abstract

The invention provides a triazole compound and application thereof in agriculture; specifically, the invention provides a compound shown as a formula (I) and a preparation method thereof; compositions and formulations containing these compounds and their use as fungicides; wherein R is¹、R²、R³、w、R⁴、R⁵、R⁶、R⁷、R⁸、R⁹、R^a、R^bAnd X has the meaning as given in the present invention.

Description

Triazole compound and application thereof in agriculture

Technical Field

The invention provides a novel triazole compound and a preparation method thereof; compositions containing these compounds and their use in agriculture.

Background

To achieve 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 cause significant reductions in yield, leading to increased costs of consumption. For this purpose, there are many products commercially available, but there is a continuing need for new compounds that are more effective, more economical, less toxic, environmentally safer 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 control effect on plant diseases, a bactericidal composition containing the bactericidal compound, a preparation and application of the bactericidal composition.

In one aspect, the invention provides a compound of formula (I) or a stereoisomer, a nitroxide or a salt thereof:

wherein:

R¹and R²Each independently is hydrogen, alkyl, alkoxyalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, halo-substituted arylalkyl, or heteroarylalkyl; or R¹、R²And the N atom to which they are attached, together form a heterocyclic or heteroaryl group;

R³is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, aryl or haloaryl;

w is 0, 1 or 2;

R⁴is hydrogen, alkyl, -C (═ O) -alkyl, -alkylene-C (═ O) -alkyl, -C (═ O) -O-alkyl, -alkylene-C (═ O) -O-alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, cycloalkylalkyl, or heterocyclylalkyl;

R⁵、R⁶、R⁷、R⁸and R⁹Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, alkyl, hydroxyl, carboxyl, amino, carboxyl, amino,alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, alkylamino, haloalkoxy, haloalkenyloxy, haloalkynyloxy, haloalkylthio, haloalkylamino, aryl, heteroaryl, cycloalkyl, heterocyclyl, aryloxy, heteroaryloxy, cycloalkyloxy or heterocyclyloxy;

wherein R is⁵、R⁶Optionally together with the carbon atoms to which they are attached form a benzene ring;

wherein R is⁶、R⁷Optionally together with the carbon atoms to which they are attached form a benzene ring;

wherein R is⁷、R⁸Optionally together with the carbon atoms to which they are attached form a benzene ring;

wherein R is⁸、R⁹Optionally together with the carbon atoms to which they are attached form a benzene ring;

x is- (CR)^cR^d) x or-O- (CR)^cR^d)v-；

Each R^cAnd R^dIndependently hydrogen, fluoro, chloro, bromo, iodo, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, or cycloalkyl;

or R^c、R^dAnd the carbon atom to which it is attached form C ═ O;

x and v are each independently 0, 1,2,3,4, 5 or 6;

wherein

1)R^aAnd R^bTogether form oxo (═ O); or

2)R^a、R⁵And the atoms to which they are attached, optionally form a 4-8 membered ring; each R^bIndependently hydrogen, fluoro, chloro, bromo, iodo, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, or cycloalkyl; or

3)R^a、R⁹And the atoms to which they are attached, optionally form a 4-8 membered ring; each R^bIndependently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, aminoA carboxyl group, an alkyl group, an alkenyl group, an alkynyl group, a haloalkyl group, a haloalkenyl group, a haloalkynyl group, or a cycloalkyl group.

In some of these embodiments, R¹And R²Each independently is hydrogen, C_1-3Alkyl radical, C_1-4Alkoxy radical C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_3-6Cycloalkyl, phenyl, C_3-6Cycloalkyl radical C_1-3Alkyl, phenyl C_1-3Alkyl or halogen substituted phenyl C_1-3An alkyl group; or R¹、R²And the N atom to which they are attached, together form a 3-6 membered heterocyclic group;

R³is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, halo C_1-4Alkyl, halo C_2-4Alkenyl, halo C_2-4Alkynyl, phenyl or halophenyl;

R⁴is hydrogen, C_1-4Alkyl, -C (═ O) -C_1-4Alkyl, -C_1-4alkylene-C (═ O) -C_1-4Alkyl, -C (═ O) -O-C_1-4Alkyl, -C_1-4alkylene-C (═ O) -O-C_1-4Alkyl radical, C_1-4Alkoxy radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_3-6Cycloalkyl, phenyl C_1-3Alkyl or C_3-6Cycloalkyl radical C_1-3An alkyl group.

In some of these embodiments, R¹And R²Each independently is hydrogen, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂Cyclopropyl, cyclopentyl, cyclohexyl, phenyl or benzyl;

R³is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂Or phenyl;

R⁴is hydrogen, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-C(CH₃)₃Cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

In some of these embodiments, the present invention provides a compound of formula (Ia) or a stereoisomer, a nitroxide or a salt thereof:

wherein: r¹、R²、R³、w、R⁴、R⁵、R⁶、R⁷、R⁸And R⁹Have the meaning as indicated for the corresponding substituents in formula (I) of the invention.

In some of these embodiments, the present invention provides compounds of formula (I) or formula (Ia), stereoisomers, nitroxides, and salts thereof, of compounds of formula (Ia), wherein

R¹And R²Each independently is hydrogen, C_1-6Alkyl radical, C_1-6Alkoxy radical C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-8Cycloalkyl, 3-12 membered heterocyclyl, C_6-10Aryl radical, C_1-9Heteroaryl group, C_3-8Cycloalkyl radical C_1-6Alkyl, 3-12 membered heterocyclyl C_1-6Alkyl radical, C_6-10Aryl radical C_1-6Alkyl, halogen substituted C_6-10Aryl radical C_1-6Alkyl or C_1-9Heteroaryl C_1-6An alkyl group; or R¹、R²Together with the N atom to which they are attached form a 3-8 membered heterocyclic group or C_1-9A heteroaryl group;

R³is 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 or halo C_6-10An aryl group;

R⁴is hydrogen, C_1-6Alkyl, -C (═ O) -C_1-6Alkyl, -C_1-6alkylene-C (═ O) -C_1-6Alkyl, -C (═ O) -O-C_1-6Alkyl, -C_1-6alkylene-C (═ O) -O-C_1-6Alkyl radical, C_1-6Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-8Cycloalkyl, 3-12 membered heterocyclyl, C_6-10Aryl radical, C_6-10Aryl radical C_1-6Alkyl radical, C_3-8Cycloalkyl radical C_1-6Alkyl or 3-12 membered heterocyclyl C_1-6An alkyl group;

R⁵、R⁶、R⁷、R⁸and R⁹Each independently 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_1-6Alkoxy radical, C_2-6Alkenyloxy radical, C_2-6Alkynyloxy, C_1-6Alkylthio radical, C_1-6Alkylamino, halogeno C_1-6Alkoxy, halo C_2-6Alkenyloxy, halogeno C_2-6Alkynyloxy, halo C_1-6Alkylthio, halo C_1-6Alkylamino radical, C_6-10Aryl radical, C_1-9Heteroaryl group, C_3-8Cycloalkyl, 3-12 membered heterocyclyl, C_6-10Aryloxy radical, C_1-9Heteroaryloxy radical, C_3-8Cycloalkyloxy or 3-12 membered heterocyclyloxy;

wherein R is⁸、R⁹Optionally together with the carbon atoms to which they are attached, form a benzene ring.

In still other embodiments, the invention provides a compound of formula (Ib), or a stereoisomer, a nitroxide, or a salt thereof:

wherein: r⁵、R⁶、R⁷、R⁸And R⁹Have the meaning as indicated for the corresponding substituents in formula (I) of the invention.

In still other embodiments, the invention provides a compound of formula (Ic) or a stereoisomer, nitroxide or salt thereof of a compound of formula (Ic):

In still other embodiments, the invention provides compounds of formula (Id), or stereoisomers, nitroxides, and salts of compounds of formula (Id):

wherein: z is 0, 1,2 or 3; r⁶、R⁷、R⁸And R⁹Have the meaning as indicated for the corresponding substituents in formula (I) of the invention.

In still other embodiments, the invention provides a compound of formula (I), formula (Ia), formula (Ib), formula (Ic) or formula (Id), a stereoisomer, nitroxide or salt of a compound of formula (I), a stereoisomer, nitroxide or salt of a compound of formula (Ia), a stereoisomer, nitroxide or salt of a compound of formula (Ib), a stereoisomer, nitroxide or salt of a compound of formula (Ic), or a stereoisomer, nitroxide or salt of a compound of formula (Id), wherein

R⁵、R⁶、R⁷、R⁸And R⁹Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, halo C_1-4Alkyl, halo C_2-4Alkenyl, halo C_2-4Alkynyl, C_1-4Alkoxy radical, C_2-4Alkenyloxy radical, C_2-4Alkynyloxy, C_1-4Alkylthio radical, C_1-4Alkylamino, halogeno C_1-4Alkoxy, halo C_2-4Alkenyloxy, halogeno C_2-4Alkynyloxy, halo C_1-4Alkylthio, halo C_1-4Alkylamino radical, C_6-10Aryl radical, C_1-5Heteroaryl group, C_3-6Cycloalkyl, 3-8 membered heterocyclyl, C_6-10Aryloxy radical, C_1-5Heteroaryloxy radical, C_3-6Cycloalkyloxy or 3-8 membered heterocyclyloxy.

R⁵、R⁶、R⁷、R⁸And R⁹Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-C(CH₃)₃、-CH₂F、-CHF₂、-CF₃、-CH₂CH₂F、-CH₂CHF₂、-CH₂CF₃、-CH＝CH₂、-CH₂-CH＝CH₂、-OCH₃、-OCH₂CH₃、-OCH₂CH₂CH₃、-OCH(CH₃)₂、-OCF₃、-OCH₂CF₃、-SCH₃、-SCH₂CH₃、-SCH₂CH₂CH₃、-SCH(CH₃)₂、-SCF₃、-SCH₂CF₃、-NH(CH₃)、-N(CH₃)₂、-NH(CH₂CH₃)、-N(CH₂CH₃)₂Or phenyl.

In another aspect, the invention provides a compound of formula (III) or a stereoisomer, a nitroxide or a salt thereof:

wherein:

R⁵³and R⁹³Each independently is hydrogen, fluorine, chlorine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, alkylamino, haloalkoxy, haloalkenyloxy, haloalkynyloxy, haloalkylthio, haloalkylamino, aryl, heteroaryl, cycloalkyl, heterocyclyl, aryloxy, heteroaryloxy, cycloalkyloxy, heterocyclyloxy, arylalkoxy, heteroarylalkoxy, cycloalkylalkoxy, or heterocyclylalkoxy;

R⁶³、R⁷³and R⁸³Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, alkylamino, haloalkoxy, haloalkenyloxy, haloalkynyloxy, haloalkylthio, haloalkylamino, aryl, heteroaryl, cycloalkyl, heterocyclyl, aryloxy, heteroaryloxy, cycloalkyloxy, heterocyclyloxy, arylalkoxy, heteroarylalkoxy, cycloalkylalkoxy or heterocyclylalkoxy;

R⁵³、R⁶³、R⁷³、R⁸³and R⁹³Each independently optionally substituted by 1,2,3,4 or 5 substituents selected from fluoro, chloro, bromo, iodo, hydroxy, cyano, nitro, amino, carboxy, C_1-6Alkyl, halo C_1-6Alkyl radical, C_1-6Alkoxy or halo C_1-6Substituted by a substituent of alkoxy.

In some of these embodiments, the invention provides a compound of formula (III) or a stereoisomer, a nitroxide, or a salt thereof, of a compound of formula (III)

R⁵³And R⁹³Each independently is hydrogen, fluorine, chlorine, 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_1-6Alkoxy radical, C_2-6Alkenyloxy radical, C_2-6Alkynyloxy, C_1-6Alkylthio radical, C_1-6Alkylamino, halogeno C_1-6Alkoxy, halo C_2-6Alkenyloxy, halogeno C_2-6Alkynyloxy, halo C_1-6Alkylthio, halo C_1-6Alkylamino radical, C_6-10Aryl radical, C_1-9Heteroaryl group, C_3-8Cycloalkyl, 3-12 membered heterocyclyl, C_6-10Aryloxy radical, C_1-9Heteroaryloxy radical, C_3-8Cycloalkyloxy, 3-12 membered heterocyclyloxy, C_6-10Aryl radical C_1-6Alkoxy radical, C_1-9Heteroaryl C_1-6Alkoxy radical, C_3-8Cycloalkyl radical C_1-6Alkoxy or 3-12 membered heterocyclyl C_1-6An alkoxy group;

R⁶³、R⁷³and R⁸³Each independently 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_1-6Alkoxy radical, C_2-6Alkenyloxy radical, C_2-6Alkynyloxy, C_1-6Alkylthio radical, C_1-6Alkylamino, halogeno C_1-6Alkoxy, halo C_2-6Alkenyloxy, halogeno C_2-6Alkynyloxy, alkynyloxy,Halogen substituted C_1-6Alkylthio, halo C_1-6Alkylamino radical, C_6-10Aryl radical, C_1-9Heteroaryl group, C_3-8Cycloalkyl, 3-12 membered heterocyclyl, C_6-10Aryloxy radical, C_1-9Heteroaryloxy radical, C_3-8Cycloalkyloxy, 3-12 membered heterocyclyloxy, C_6-10Aryl radical C_1-6Alkoxy radical, C_1-9Heteroaryl C_1-6Alkoxy radical, C_3-8Cycloalkyl radical C_1-6Alkoxy or 3-12 membered heterocyclyl C_1-6An alkoxy group;

R⁵³、R⁶³、R⁷³、R⁸³and R⁹³Each independently optionally substituted by 1,2,3,4 or 5 substituents selected from fluoro, chloro, bromo, iodo, hydroxy, cyano, nitro, amino, carboxy, C_1-4Alkyl, halo C_1-4Alkyl radical, C_1-4Alkoxy or halo C_1-4Substituted by a substituent of alkoxy.

In still other embodiments, the invention provides a compound of formula (III) or a stereoisomer, a nitroxide, or a salt thereof, of a compound of formula (III)

R⁵³And R⁹³Each independently is hydrogen, fluorine, chlorine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-C(CH₃)₃、-OCH₃、-OCH₂CH₃、-OCH₂CH₂CH₃、-OCH(CH₃)₂A halogen-substituted phenoxy group or a 2-chloro-4- (trifluoromethyl) phenoxy group;

R⁶³、R⁷³and R⁸³Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-C(CH₃)₃、-CH₂F、-CHF₂、-CF₃、-CH₂CH₂F、-CH₂CHF₂、-CH₂CF₃、-CF(CF₃)₂、-OCH₃、-OCH₂CH₃、-OCH₂CH₂CH₃、-OCH(CH₃)₂、-C(CF₃)₂-OCH₃Halogen-substituted phenoxy or 2-chloro-4- (trifluoromethyl) phenoxy.

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

In some embodiments, the composition further comprises an agriculturally acceptable surfactant and/or carrier.

In another aspect, the present invention provides the use of a compound according to the present invention or a composition according to the present invention for the control of plant diseases.

In some of these embodiments, the plant disease is caused by a plant pathogenic fungus.

The compounds of formula (I), formula (Ia), formula (Ib), formula (Ic), formula (Id) or formula (III) may exist in different stereoisomers or optical isomers or tautomeric forms. The invention encompasses all such isomers and tautomers and mixtures thereof in various ratios, as well as isotopic forms such as heavy hydrogen-containing compounds.

Isotopically enriched compounds have the structure depicted by the formulae given herein, except that one or more atoms are replaced by an atom having a selected atomic mass 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 as²H，³H，¹¹C，¹³C，¹⁴C，¹⁵N，¹⁷O，¹⁸O，¹⁸F，³¹P，³²P，³⁵S，³⁶Cl and¹²⁵I。

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.

The foregoing has outlined only certain aspects of the present invention and is not intended to be limited in these or other respects to the details described herein.

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 referred to as described in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausaltito: 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" 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-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 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 "alkylene" denotes a saturated divalent hydrocarbon radical resulting from the removal of two hydrogen atoms from a saturated straight or branched chain hydrocarbon. Unless otherwise specified, the alkylene group contains 1 to 12 carbon atoms. In one embodiment, the alkylene group contains 1 to 8 carbon atoms; in one embodiment, the alkylene group contains 1 to 6 carbon atoms; in another embodiment, the alkylene group contains 1 to 4 carbon atoms; in yet another embodiment, the alkylene group contains 1 to 3 carbon atoms; in yet another embodiment, the alkylene group contains 1 to 2 carbon atoms. Examples of this include methylene (-CH)₂-, ethylene (-CH)₂CH₂-, propylene (-CH)₂CH₂CH₂-)，-CH(CH₃)CH₂-，-C(CH₃)₂-，-CH₂CH₂CH(CH₃)-，-CH₂CH₂C(CH₃)₂-, and the like.

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.

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 "alkenyloxy" means an alkenyl group attached to the rest of the molecule through an oxygen atom, wherein the alkenyl group has the meaning as described herein.

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

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

The term "alkylthio" means an alkyl group attached to the rest 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, -SCH₃、-SCH₂CH₃、-SCH₂CH₂CH₃、-SCH(CH₃)₂And so on.

The term "alkylamino" or "alkylamino" includes "N-alkylamino" and "N, N-dialkylamino" in which the amino groups are each independently substituted with one or two alkyl groups. In some of these embodiments, the alkylamino group is one or two C_1-6Lower alkylamino groups in which the alkyl group is attached to the nitrogen atom. In other embodiments, the alkylamino group is C_1-3Lower alkylamino groups of (a). Suitable alkylamino groups can be monoalkylamino or dialkylamino, examples of which include, but are not limited to, N-methylamino, N-ethylamino, N, N-dimethylaminoAmino, N, N-diethylamino, and the like.

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 substituted by one or more cycloalkyl groups, wherein the alkyl group and the cycloalkyl group have the meaning as described herein.

The term "cycloalkyloxy" includes optionally substituted cycloalkyl groups, as defined herein, attached to and linked from the oxygen atom to the rest of the molecule, wherein the cycloalkyl group has the meaning as described herein.

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. 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-dioxocyclopentyl, dithiocyclopentyl, tetrahydropyranyl, dihydropyranyl, 2H-pyranyl, 4H-pyranyl, tetrahydrothiopyranyl, piperidinyl (2-piperazinyl)Pyridyl, 3-piperidyl, 4-piperidyl), morpholinyl, thiomorpholinyl, (1-oxo) -thiomorpholinyl, (1, 1-dioxo) -thiomorpholinyl, piperazinyl, dioxanyl, dithianyl, thiaxanyl, homopiperazinyl, homopiperidinyl, oxepanyl, thiacycloheptyl, 2-oxa-5-azabicyclo [2.2.1]Hept-5-yl, tetrahydropyridinyl. In heterocyclic radicals of-CH₂Examples of-groups substituted by-C (═ O) -include, but are not limited to, 2-oxopyrrolidinyl, oxo-1, 3-thiazolidinyl, 2-piperidinonyl, 3, 5-dioxopiperidinyl. Examples of sulfur atoms in heterocyclic groups that are oxidized include, but are not limited to, sulfolane, 1, 1-dioxothiomorpholinyl. 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 describe the number of ring-forming atoms in the molecule. For example, piperidinyl is 6-membered heterocyclyl.

The term "heterocyclylalkyl" means that an alkyl group is substituted with one or more heterocyclyl groups, wherein the alkyl group and the heterocyclyl group have the meanings as described herein.

The term "heterocyclyloxy" includes optionally substituted heterocyclyl groups, as defined herein, attached to an oxygen atom and linked to the rest of the molecule by an oxygen atom, wherein the heterocyclyl group has the meaning as described herein.

The term "unsaturated" as used herein 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 form of P; primary, secondary, tertiary amines and quaternary ammonium salt forms; or a form in which a hydrogen on a 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 "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 "arylalkyl" or "aralkyl" means that an alkyl group is substituted with one or more aryl groups, wherein the alkyl and aryl groups have the meaning as described herein.

The term "aryloxy" or "aryloxy" includes optionally substituted aryl groups, as defined herein, attached to and linked from an oxygen atom to the rest of the molecule, wherein the aryl group has the meaning as described herein.

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.

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 group containing 1-3 heteroatoms selected from N, O or S; in yet another embodiment, heteroaryl represents a 5 membered heteroaryl group containing 1-3 heteroatoms selected from N or O; in yet another embodiment, heteroaryl represents a 5 membered heteroaryl group 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, 3-triazolyl, 1,2, 3-thiadiazolyl, 1,3, 4-thiadiazolyl, 1,2, 5-thiadiazolyl, pyrazinyl, 1,3, 5-triazinyl, pyrimidinonyl, pyridonyl; the following bicyclic rings are also included, but are in no way limited to these: benzimidazolyl, benzofuranyl, benzotetrahydrofuranyl, benzothienyl, indolyl (e.g., 2-indolyl), benzopiperidinyl, and the like.

The term "heteroarylalkyl" or "heteroaralkyl" means that an alkyl group is substituted with one or more heteroaryl groups, wherein the alkyl group and heteroaryl groups have the meaning as set forth herein.

The term "heteroaryloxy" or "heteroaryloxy" includes optionally substituted heteroaryl groups, as defined herein, attached to and linked by an oxygen atom to the rest of the molecule, wherein the heteroaryl group has the meaning as set forth herein.

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

The term "haloalkyl" denotes an alkyl group substituted with one or more halogen atoms, wherein the alkyl group has the meaning as described herein. Examples of haloalkyl include, but are not limited to, -CH₂F，-CHF₂，-CH₂Cl，-CH₂Br，-CF₃，-CH₂CF₃，-CH₂CH₂F，-CH₂CH₂Cl，-CH₂CH₂Br，-CH₂CHF₂，-CH₂CH₂CF₃，-CH₂CH₂CH₂F，-CH₂CH₂CH₂Cl，-CH₂CH₂CH₂Br，-CHFCH₂CH₃，-CHClCH₂CH₃And so on.

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

The term "haloalkynyl" denotes an alkynyl group substituted by one or more halogen atoms, wherein the alkynyl group has the meaning as described herein.

The term "haloaryl" denotes an aryl group substituted with one or more halogen atoms, wherein the aryl group has the meaning as described herein.

The term "haloalkoxy" denotes an alkoxy group substituted by one or more halogen atoms, wherein the alkoxy group has the meaning as described herein. Examples of haloalkoxy include, but are not limited to, -OCH₂F，-OCHF₂，-OCH₂Cl，-OCH₂Br，-OCF₃，-OCH₂CF₃，-OCH₂CH₂F，-OCH₂CH₂Cl，-OCH₂CH₂Br，-OCH₂CHF₂，-OCH₂CH₂CF₃，-OCH₂CH₂CH₂F，-OCH₂CH₂CH₂Cl，-OCH₂CH₂CH₂Br，-OCHFCH₂CH₃，-OCHClCH₂CH₃And so on.

The term "haloalkenyloxy" denotes an alkenyloxy group substituted by one or more halogen atoms, wherein the alkenyloxy group has the meaning as described herein.

The term "haloalkynyloxy" denotes an alkynyloxy group substituted with one or more halogen atoms, wherein the alkynyloxy group has the meaning as described herein.

The term "haloalkylthio" denotes an alkylthio group substituted by one or more halogen atoms, wherein the alkylthio group has the meaning as described herein.

The term "haloalkylamino" denotes an alkylamino group substituted by one or more halogen atoms, wherein the alkylamino group has the meaning as described herein.

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⁺(R¹⁹R²⁰R²¹R²²) Ammonium cation of (2), wherein R is¹⁹、R²⁰、R²¹And R²²Independently selected from hydrogen, C₁-C₆Alkyl and C₁-C₆A hydroxyalkyl group. Salts of compounds having formula (I), formula (Ia), formula (Ib), formula (Ic), formula (Id) or formula (III) may be prepared by treating a compound having formula (I), formula (Ia), formula (Ib), formula (Ic), formula (Id) or formula (III) with a metal hydroxide, such as sodium hydroxide, or an amine, such as 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

wherein:

w is 0, 1 or 2;

R⁵、R⁶、R⁷、R⁸and R⁹Each independently is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, alkylamino, haloalkoxy, haloalkenyloxy, haloalkynyloxy, haloalkylthio, haloalkylamino, aryl, heteroaryl, cycloalkyl, heterocyclyl, aryloxy, heteroaryloxy, cycloalkyloxy or heterocyclyloxy;

wherein R is⁶、R⁷Optionally and withThe carbon atoms to which they are attached together form a benzene ring;

x is- (CR)^cR^d) x or-O- (CR)^cR^d)v-；

or R^c、R^dAnd the carbon atom to which it is attached form C ═ O;

x and v are each independently 0, 1,2,3,4, 5 or 6;

wherein

1)R^aAnd R^bTogether form oxo (═ O); or

3)R^a、R⁹And the atoms to which they are attached, optionally form a 4-8 membered ring; each R^bIndependently hydrogen, fluoro, chloro, bromo, iodo, hydroxy, cyano, nitro, amino, carboxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, or cycloalkyl.

In some of these embodiments, R¹And R²Each independently is hydrogen, C_1-4Alkyl radical, C_1-4Alkoxy radical C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_3-6Cycloalkyl, phenyl, C_3-6Cycloalkyl radical C_1-3Alkyl, phenyl C_1-3Alkyl or halogen substituted phenyl C_1-3An alkyl group; or R¹、R²And therewithThe attached N atoms together form a 3-6 membered heterocyclic group.

In other embodiments, R¹And R²Each independently is hydrogen, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-C(CH₃)₃、-CH＝CH₂、-CH₂-CH＝CH₂Cyclopropyl, cyclopentyl, cyclohexyl, phenyl or benzyl.

In some of these embodiments, R³Is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, halo C_1-4Alkyl, halo C_2-4Alkenyl, halo C_2-4Alkynyl, phenyl or halophenyl.

In other embodiments, R³Is hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂Or a phenyl group.

In some of these embodiments, R⁴Is hydrogen, C_1-4Alkyl, -C (═ O) -C_1-4Alkyl, -C_1-4alkylene-C (═ O) -C_1-4Alkyl, -C (═ O) -O-C_1-4Alkyl, -C_1-4alkylene-C (═ O) -O-C_1-4Alkyl radical, C_1-4Alkoxy radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_3-6Cycloalkyl, phenyl C_1-3Alkyl or C_3-6Cycloalkyl radical C_1-3An alkyl group.

In other embodiments, R⁴Is hydrogen, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-C(CH₃)₃Cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

R¹And R²Each independently is hydrogen, C_1-6Alkyl radical, C_1-6Alkoxy radical C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-8Cycloalkyl, 3-12 membered heterocyclyl, C_6-10Aryl radical, C_1-9Heteroaryl group, C_3-8Cycloalkyl radical C_1-6Alkyl, 3-12 membered heterocyclyl C_1-6Alkyl radical, C_6-10Aryl radical C_1-6Alkyl, halogen substituted C_6-10Aryl radical C_1-6Alkyl or C_1-9Heteroaryl C_1-6An alkyl group; or R¹、R²Together with the N atom to which they are attached form a 3-8 membered heterocyclic group or C_1-9A heteroaryl group.

R³Is 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 or halo C_6-10And (4) an aryl group.

R⁴Is hydrogen, C_1-6Alkyl, -C (═ O) -C_1-6Alkyl, -C_1-6alkylene-C (═ O) -C_1-6Alkyl, -C (═ O) -O-C_1-6Alkyl, -C_1-6alkylene-C (═ O) -O-C_1-6Alkyl radical, C_1-6Alkoxy radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-8Cycloalkyl, 3-12 membered heterocyclyl, C_6-10Aryl radical, C_6-10Aryl radical C_1-6Alkyl radical, C_3-8Cycloalkyl radical C_1-6Alkyl or 3-12 membered heterocyclyl C_1-6An alkyl group.

In still other embodiments, the invention provides a compound of formula (Id), or a stereoisomer, nitroxide, or salt thereof, of a compound of formula (Id):

In still other embodiments, the present invention provides a compound of formula (I), formula (Ia), formula (Ib), formula (Ic), or formula (Id), a stereoisomer, a nitroxide, or a salt thereof, or a stereoisomer, a nitroxide, or a salt thereof, a compound of formula (Id), wherein

Each one of

Independently the sub-formulae:

wherein:

R⁵³And R⁹³Each independently is hydrogen, fluorine, chlorine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, halo C_1-6Alkyl, haloC_2-6Alkenyl, halo C_2-6Alkynyl, C_1-6Alkoxy radical, C_2-6Alkenyloxy radical, C_2-6Alkynyloxy, C_1-6Alkylthio radical, C_1-6Alkylamino, halogeno C_1-6Alkoxy, halo C_2-6Alkenyloxy, halogeno C_2-6Alkynyloxy, halo C_1-6Alkylthio, halo C_1-6Alkylamino radical, C_6-10Aryl radical, C_1-9Heteroaryl group, C_3-8Cycloalkyl, 3-12 membered heterocyclyl, C_6-10Aryloxy radical, C_1-9Heteroaryloxy radical, C_3-8Cycloalkyloxy, 3-12 membered heterocyclyloxy, C_6-10Aryl radical C_1-6Alkoxy radical, C_1-9Heteroaryl C_1-6Alkoxy radical, C_3-8Cycloalkyl radical C_1-6Alkoxy or 3-12 membered heterocyclyl C_1-6An alkoxy group.

R⁶³、R⁷³And R⁸³Each independently 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_1-6Alkoxy radical, C_2-6Alkenyloxy radical, C_2-6Alkynyloxy, C_1-6Alkylthio radical, C_1-6Alkylamino, halogeno C_1-6Alkoxy, halo C_2-6Alkenyloxy, halogeno C_2-6Alkynyloxy, halo C_1-6Alkylthio, halo C_1-6Alkylamino radical, C_6-10Aryl radical, C_1-9Heteroaryl group, C_3-8Cycloalkyl, 3-12 membered heterocyclyl, C_6-10Aryloxy radical, C_1-9Heteroaryloxy radical, C_3-8Cycloalkyloxy, 3-12 membered heterocyclyloxy, C_6-10Aryl radical C_1-6Alkoxy radical, C_1-9Heteroaryl C_1-6Alkoxy radical, C_3-8Cycloalkyl radical C_1-6Alkoxy or 3-12 membered heterocyclyl C_1-6An alkoxy group.

R⁵³And R⁹³Each independently is hydrogen, fluorine, chlorine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-C(CH₃)₃、-OCH₃、-OCH₂CH₃、-OCH₂CH₂CH₃、-OCH(CH₃)₂Halogen-substituted phenoxy or 2-chloro-4- (trifluoromethyl) phenoxy.

In another aspect, the present invention provides a compound which 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. Unless otherwise indicated, all tautomers, racemates, hydrates, solvates, metabolites, metabolic precursors and prodrugs of the compounds of formula (I), formula (Ia), formula (Ib), formula (Ic), formula (Id) or formula (III) of the present invention are also within the scope of the present invention.

In some embodiments, the composition according to the present invention further comprises an agriculturally pharmaceutically acceptable surfactant and/or carrier.

In another aspect, the invention provides the use of a compound of the invention or a composition of the invention for the control of plant diseases, particularly as a fungicide. In some of these embodiments, the plant disease is caused by a plant pathogenic fungus.

Compositions and formulations of the compounds of the invention

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

The surfactant may be any of various surfactants known in the field of pesticide formulation, and one or more of an emulsifier, a dispersant and a wetting agent are preferred in the present invention.

The carrier other than the surfactant may be any of various carriers known in the field of pesticide formulation, 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 emulsifier may be any emulsifier known in the field of pesticide formulation, and specifically, the emulsifier may be one or more of calcium dodecylbenzenesulfonate, trisethylphenol 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 field of pesticide formulation, and specifically, the dispersing agent is one or more of acrylic acid homopolymer sodium salt, maleic acid disodium salt, naphthalene sulfonic acid formaldehyde condensation product sodium salt, rosin block polyoxyethylene ether polyoxypropylene ether sulfonate, hydroxyl-terminated polyoxyethylene polyoxypropylene ether block copolymer, triphenyl polyoxyethylene phenol phosphate, fatty alcohol polyoxyethylene ether phosphate and p-hydroxyphenyl lignosulfonate sodium salt.

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

According to the bactericide composition, various preparation auxiliaries commonly used in the field of pesticide formulation can be further contained, and specifically, the preparation auxiliaries can be one or more of a solvent, a cosolvent, a thickening agent, an antifreezing agent, a capsule wall material, a protective agent, an antifoaming agent, a disintegrating agent, a stabilizing agent, a preservative and a binder.

The solvent may be any of various solvents known in the field of pesticide formulation, and specifically, the solvent may be one or more of an organic solvent, a vegetable oil, a mineral oil, a solvent oil and water.

Wherein the organic solvent comprises one or more of N-methylpyrrolidone, tetrahydrofuran, dimethyl sulfoxide, N-dimethyldecanamide, N-dimethylformamide, trimethylbenzene, tetramethylbenzene, dimethylbenzene, methylbenzene, 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, rosin-based vegetable oil, turpentine oil, epoxidized soybean oil, peanut oil, rapeseed oil, castor oil, corn oil and pine seed oil.

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

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

The antifreeze can be various antifreeze agents known in the field of pesticide formulation, and the invention is preferably one or more of ethylene glycol, propylene glycol, glycerol and urea.

The thickener can be various thickeners known in the field of pesticide formulation, and specifically can be one or more of xanthan gum, polyvinyl alcohol, polypropylene alcohol, polyethylene glycol, white carbon black, diatomite, kaolin, clay, sodium alginate, magnesium aluminum silicate, sodium aluminum silicate, carboxymethyl cellulose, sodium hydroxypropyl cellulose and organic bentonite.

The capsule material can be various capsule materials known in the field of pesticide formulation, 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 pesticide formulation, and polyvinyl alcohol and/or polyethylene glycol is preferred in the present invention.

The defoaming agent may be any of those known in the field of agricultural agent formulation, and in the present invention, one or more of organosiloxane, tributyl phosphate and silicone are preferable.

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

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

The invention also provides a preparation prepared from the bactericide composition, and the preparation is in the form of missible oil, aqueous emulsion, microemulsion, soluble liquid, aqueous suspension, suspoemulsion, ultra-low volume spray, oil suspension, microcapsule suspension, water surface spreading oil, wettable powder, water dispersible granule, dry suspension, soluble powder, soluble granule, emulsifiable powder, emulsifiable granule, solid microcapsule preparation, effervescent tablet, effervescent granule, water floating dispersion granule or seed coating. The above formulations 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, so as to obtain the emulsifiable concentrate preparation.

The preparation method of the aqueous emulsion can comprise, for example, mixing the active ingredient, the emulsifier, the cosolvent and the solvent to form a uniform oil phase; mixing water, thickener, antifreeze, etc. to obtain uniform water 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, for example, by mixing and stirring the active ingredient, emulsifier, and solvent to form a uniform transparent oil phase. Under stirring, water is gradually added to form a uniform and transparent microemulsion.

The preparation method of the water/oil suspending agent comprises the following steps: for example, water or oil can be used as a medium, and an auxiliary agent such as an active component and a surfactant is added into a sanding kettle, and after grinding to a certain particle size, filtration is performed. And adding the weighed thickening agent into the ground mother liquor, and uniformly shearing and dispersing. 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 active ingredients, the dispersing agent, the wetting agent, the carrier and the like are uniformly mixed, then are pulverized into a certain particle size through air flow, are added with water for kneading, are finally added into a granulator for granulation, and are dried to obtain the water dispersible granules or the soluble granules.

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

The germicide composition of the present invention may be provided in the form of a finished formulation, i.e., the components of the composition have been mixed; or in separate formulations which are self-mixing in a tub or tank prior to use and optionally diluted by mixing with water depending on the concentration of active desired.

Application of the inventive compounds and compositions

The compound of the present invention is useful as a plant disease control agent. The present invention therefore also comprises a method for controlling plant diseases caused by phytopathogenic fungi, which comprises applying to the plants to be protected or to parts thereof or to the seeds of the plants to be protected an effective amount of a compound according to the invention or of a fungicidal composition comprising said compound. The compounds and/or compositions of the present invention provide control of diseases caused by a broad spectrum of phytopathogenic fungi of the classes Basidiomycetes, Ascomycetes, Oomycetes and Deuteromycetes. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, turf, vegetable, field, cereal and fruit crops. These pathogens include: oomycetes, including Phytophthora (Phytophthora) diseases such as Phytophthora infestans, Phytophthora sojae (Phytophthora megasporum), Phytophthora citri (Phytophthora parasitica), Phytophthora citrullus (Phytophthora parasiti), Phytophthora cinnamomi (Phytophthora cinnamomi) and Phytophthora cucurbitae (Phytophthora capsici), Pythium graminum (Pythium) species diseases such as Pythium turtium (Pythium aphanidermatum) diseases, and Peronosporaceae (Peronospora) species diseases such as Plasmopara viticola (Plasmopara viticola), Peronospora (Peronospora spp.) (including P. nicotianae (Peronospora tabacina) and P. parasitica (Pseudoperonospora Pseudoperonospora), including P. nicotianae (Pseudoperonospora cinerea) and P. Pseudoperonospora (Pseudoperonospora Pseudoperonospora) diseases including P); ascomycetes (including Alternaria (Alternaria) such as Alternaria solani and Phytophthora brassicae (Alternaria solani), Mycoporia globosa (Guignardia) diseases such as Staphylococcus viticola (Guignardia bidwell), Venturia (Venturia) diseases such as Venturia mali (Venturia inaequalis), Sphaerotheca (Sepia) diseases such as Microchaeta (Septoria nodorum) and Phytophthora parasitica (Septorii), Powderzia (Powderi) diseases such as Erysiphe graminis (Erysiphe spp.) and Sphaerotheca (Septoria), Powderiana graminis (Erysiphe sp.) diseases such as Microchaeta oryzae (Erysiphe graminis) and Pseudoperonospora rosea (Botrytis), Staphylococcus viticola (Uncinula necator), Pseudomonas cucumerina (Sphaerothecoides) and Pseudoperonospora cinerea (Botrytis), Scleroticola (Botrytis cinerea) diseases such as Microchaetobacter sphaera, Scleroticola (Botrytis cinerea), Scleroti cinerea), Scleroticola (Potentilla) diseases such as Microchaetotrichia cinerea), Scleroti cinerea (Potentilla cinerea), Scleroti cinerea) diseases such as Microchaetotrichia cinerea (Scleroti cinerea), Scleroticola (Scleroti (Scleroticola (Scleroti cinerea) diseases (Scleroti cinerea), Scleroti cinerea) diseases (Scleroti cinerea), Scleroti cinerea) diseases (Scleroticola (Scleroti cinerea), and Scleroti cinerea) diseases (Scedo cinerea (Scleroti cinerea), and Scleroti cinerea) diseases (Scleroti cinerea) diseases (Scleroti cinerea), and Scedo cinerea (Scedo cinerea), and Scedo cinerea (Scleroti cinerea) diseases (Scedo cinerea), and Scedo cinerea (Scedo cinerea), and Scedo cinerea) diseases (Scedodes (Scedo cinerea) diseases (Scedo cinerea), and Scedodes (Sci (Scedodes (Gray (Gra, Pyricularia oryzae (Magnaporthe grisea), Rhizoctonia solani (Phomopsis viticola), Helminthosporium (Helminthosporium) diseases such as northern leaf blight (Helminthosporium tritici reptilis), Moss reticulata (Pyrenophora teres), anthrax bacteria such as Hedychium nigrum (Glomerella) or Anthrax (Colletochium spp.) diseases (such as Colletotrichum graminicum (Colestochium graminicum) and watermelon anthrax (Colletochium orbiculosum)), and wheat holothrix graminis (Gaeumannomyces graminis); basidiomycetes, including rust diseases caused by the genus Puccinia (Puccinia spp.), such as Puccinia recondita (Puccinia recondita), Puccinia striiformis (Puccinia striiformis), Puccinia purpurea (Puccinia hordei), Puccinia graminis (Puccinia graminis) and Puccinia arachidis (Puccinia arachidis), coffee rust (hemix) and soybean rust (Phakopsora pachyrhizi); other pathogens include Rhizoctonia species (Rhizoctonia spp.) (such as Rhizoctonia solani); fusarium species diseases such as Fusarium roseum (Fusarium roseum), Fusarium graminearum (Fusarium graminearum), and Fusarium oxysporum (Fusarium oxysporum); verticillium dahliae (Verticillium dahliae); sclerotium rolfsii (sclerotiotium rolfsii); physalospora piricola (Rynchosporium secalis); black acerola (Cercosporium personatum), Episra nigrella (Cercospora arachidicola), and Episra fuscospora (Cercospora betacola); and other classes and species closely related to these pathogens. In addition to their fungicidal activity, the compositions or combinations also have a resistant activity against bacteria such as Erwinia amylovora (Erwinia amylovora), Xanthomonas campestris (Xanthomonas campestris), Pseudomonas syringae (Pseudomonas syringae) and other species.

The bactericide composition of the invention is simple in use method, and can be applied to crops and places where the crops grow by a conventional method such as soil mixing, spraying, pouring and the like before or after the germination of plant diseases, wherein the application amount is determined according to climatic conditions or crop states, 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 bactericidal effect of the bactericide composition of the present invention is generally related to external factors such as climate, but the influence of climate can be alleviated by using appropriate dosage forms.

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

The following scheme describes the preparation of compounds of the present invention, wherein R¹、R²、R³、R⁵、R⁶、R⁷、R⁸、R⁹、R⁵³、R⁶³、R⁷³、R⁸³、R⁹³And z has the meaning as described in the present invention. Unless otherwise indicated, the compounds of the invention may be prepared by the methods described herein. The starting materials, reagents and the like used in the preparation of the compounds of the present invention are commercially available or can be prepared by methods conventional in the art. In this specification, a structure is dominant if there is any difference between the chemical name and the chemical structure.

The test conditions of the nuclear magnetic resonance hydrogen spectrum of the invention are as follows: brookfield (Bruker) nuclear magnetic instrument at 400MHz or 600MHz in CDC1 at room temperature₃，d⁶-DMSO，CD₃OD or d⁶Acetone as solvent (reported in ppm) with TMS (0ppm) or chloroform (7.26ppm) as reference standard. When multiple peaks occur, the following abbreviations will be used: s (singleton), d (doublet), t (triplet), q (quatet, quartet), m (multiplet ), br (broadpeded, broad), dd (doublet of doublets), dt (doublet of triplets). Coupling constants are expressed in hertz (Hz).

Synthesis scheme I

The compounds of formula (k) may be prepared by synthetic scheme one. A compound of formula (a) at a certain temperatureUnder the temperature (such as-10 ℃ to 40 ℃), carrying out oxidation coupling reaction with acyl chloride (such as benzene sulfonyl chloride and p-toluene sulfonyl chloride) under the alkaline condition (such as pyridine, triethylamine, potassium carbonate and the like) to obtain a compound in a formula (f); a compound of formula (f) and R¹R²N-SO₂Cl is subjected to substitution reaction at a certain temperature (such as-10-40 ℃) under an alkaline condition (such as pyridine, triethylamine, potassium carbonate and the like) to obtain a compound shown in a formula (g); the compound of the formula (g) and chlorine gas are subjected to oxidation reaction at a certain temperature (such as-10 ℃ to 10 ℃) under an acidic condition (such as hydrochloric acid, dilute sulfuric acid, acetic acid and the like) to obtain a compound of a formula (h); carrying out condensation reaction on the compound of the formula (h) and the compound of the formula (i) at a certain temperature (such as-10-40 ℃) under an alkaline condition (such as pyridine, triethylamine, potassium carbonate and the like) to obtain a compound of a formula (j); the compound of formula (j) reacts with bromocyclopropane at a certain temperature (such as-10 ℃ to 40 ℃) under an alkaline condition (such as pyridine, triethylamine, potassium carbonate and the like) to obtain the compound of formula (k).

Synthesis scheme two

The compounds of formula (o) may be prepared by synthesis scheme two. The compound of the formula (h) and cyclopropylamine are subjected to condensation reaction at a certain temperature (such as-10-40 ℃) under an alkaline condition (such as pyridine, triethylamine, potassium carbonate and the like) to obtain a compound of a formula (m); the compound of formula (m) is reacted with optionally substituted benzoyl chloride (n) at a temperature (e.g., -10 ℃ to 40 ℃) under basic conditions (e.g., pyridine, triethylamine, potassium carbonate, etc.) to obtain the compound of formula (o).

Synthesis scheme three

The compound of formula (r) may be prepared according to scheme three. Carrying out condensation reaction on the compound of the formula (h) and the compound of the formula (p) at a certain temperature (such as-10-40 ℃) under an alkaline condition (such as pyridine, triethylamine, potassium carbonate and the like) to obtain a compound of the formula (q); the compound of formula (q) reacts with bromomethylcyclopropane at a certain temperature (e.g., -10 ℃ to 40 ℃) under an alkaline condition (e.g., pyridine, triethylamine, potassium carbonate, etc.) to obtain the compound of formula (r).

The following acronyms are used throughout the invention:

g, g; mg; mol; mmol millimole; h hours; min; l liter; mL, mL; 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 (101.0g,1.00mol) was dissolved in dichloromethane (500mL), and pyridine (79.0g,1.00mol) was added. Benzenesulfonyl chloride (88.30g,0.50mol) was slowly added dropwise with stirring at 0 ℃ over 2 h. After the addition was complete, the mixture was stirred at 25 ℃ for 18 h. The dichloromethane was evaporated under reduced pressure using a rotary evaporator and the residue was stirred for 1h with water (500mL) added under mechanical stirring. Filtration was carried out, and the residue was washed with water (800mL) and ethyl acetate (300mL), respectively, and air-dried to give 95.2g of a yellow powder in 95.2% yield.

LC-MS:(M+1)m/z＝201.1.

EXAMPLE B Synthesis of intermediate 3, 3' -Dithio (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) is slowly dropped into the mixture, and after the dropping is finished for 2 hours, the reaction is 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 a white powder with a yield of 86.3%.

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) (41.40g,0.10mol) was dissolved in 1, 2-dichloroethane (150mL), water (300mL) was added, cooling to 0 deg.C, acetic acid (150mL) was added, the temperature was controlled at 10 deg.C to 25 deg.C, chlorine (35.50g,0.50mol) was introduced for 2 hours, and the reaction was 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%.

LC-MS:(M+1)m/z＝274.8.

EXAMPLE D intermediate N¹,N¹-dimethyl-N³Synthesis of (1,2,3, 4-tetrahydronaphthalene-1-yl) -1H-1,2, 4-triazole-1, 3-disulfonamide

1,2,3, 4-tetrahydronaphthalen-1-amine (0.74g,5.0mmol), pyridine (0.79g,10.0mol), and tetrahydrofuran (20mL) were added to a 100mL single-neck vial; after stirring uniformly at room temperature, 1- (N, N-dimethylaminosulfonyl) -1H-1,2, 4-triazole-3-sulfonyl chloride (1.37g,5.0mmol) was slowly added to the reaction system, and after reaction at room temperature of 25 ℃ for 12 hours, water (30mL) was added to quench, extraction was performed with ethyl acetate (20mL × 3), anhydrous magnesium sulfate was dried, filtration was performed, the filtrate was subjected to reduced pressure using a rotary evaporator to remove the solvent, and column chromatography purification (EtOAc/PE (v/v) ═ 1/3) was performed to obtain 1.10g of a white solid, yield: 52 percent.

LC-MS:(M+1)m/z＝426.1.

The intermediate compounds of table 1 were obtained by following the procedure of example D using the corresponding starting materials.

TABLE 1

EXAMPLE E intermediate N¹,N¹-dimethyl-N³Synthesis of- (3- (trifluoromethyl) phenyl) -1H-1,2, 4-triazole-1, 3-disulfonamide

3- (trifluoromethyl) aniline (0.80g,5.0mmol), pyridine (0.79g,10.0mol), and tetrahydrofuran (20mL) were added to a 100mL single-neck bottle; after stirring uniformly at room temperature, 1- (N, N-dimethylaminosulfonyl) -1H-1,2, 4-triazole-3-sulfonyl chloride (1.37g,5.0mmol) was slowly added to the reaction system, and after reaction at room temperature of 25 ℃ for 12 hours, water (30mL) was added to quench, extraction was performed with ethyl acetate (20mL × 3), anhydrous magnesium sulfate was dried, filtration was performed, the filtrate was subjected to reduced pressure using a rotary evaporator to remove the solvent, and column chromatography purification (EtOAc/PE (v/v) ═ 1/3) was performed to obtain 1.20g of a white solid, yield: 60 percent.

LC-MS:(M+1)m/z＝400.1.

Referring to the preparation method of example E, the intermediate compound shown in table 2 can be obtained by reacting the corresponding material with the intermediate compound 1- (N, N-dimethylaminosulfonyl) -1H-1,2, 4-triazole-3-sulfonyl chloride.

TABLE 2

EXAMPLE EE intermediate N³-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 10min, with white smoke appearing and a white solid gradually precipitated. After the addition was complete, the reaction was carried out at room temperature for 2 hours, the solid was removed by filtration, and the filtrate was freed from 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, yield: 75.1 percent.

¹H NMR(400MHz,DMSO-d₆):δ(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.

EXAMPLE 1 Compound N³-cyclopropyl-N¹,N¹-dimethyl-N³Synthesis of (1,2,3, 4-tetrahydronaphthalene-1-yl) -1H-1,2, 4-triazole-1, 3-disulfonamide

Will N³- (1,2,3, 4-tetrahydronaphthalen-1-yl) -N¹,N¹-dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide (0.39g,1.0mmol), potassium carbonate (0.28g,2.0mmol) and DMF (10mL) are added into a 100mL three-necked bottle, cyclopropyl bromide (0.24g,2.0mmol) is slowly added into the reaction system, and the reaction is carried out for 8 hours at room temperature of 25 ℃; quenching with water (20mL), extraction with ethyl acetate (15mL × 3), washing of the organic phase with saturated brine, drying over anhydrous magnesium sulfate, filtration, removal of the solvent from the filtrate under reduced pressure with a rotary evaporator, and purification by column chromatography (EtOAc/PE (v/v) ═ 1/3) gave 0.15g of a white solid in yield: 35 percent.

¹H NMR(400MHz,CDCl₃):δ(ppm)8.78(s,1H),7.72-6.92(s,4H),3.94(m,1H),3.82(m,2H),2.98(s,6H),1.82(m,1H),1.73-1.65(m,2H),1.43-1.35(m,2H),0.55-0.39(m,2H),0.17-0.15(m,2H).

LC-MS:(M+1)m/z＝426.1.

Referring to the preparation method of example 1, the intermediate compounds in table 1 were reacted with cyclopropyl bromide, respectively, to obtain the target compounds in table 3.

TABLE 3

EXAMPLE 4 Synthesis of Compound 4-chloro-N-cyclopropyl-N- ((1- (N, N-dimethylsulfonyl) -1H-1,2, 4-triazol-3-yl) sulfonyl) benzamide

Will N³-cyclopropyl-N¹,N¹-dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide (0.30g,1.0mmol), triethylamine (0.30g,3.0mmol), 4-dimethylaminopyridine (0.02g,0.2mmol) and dichloromethane (10mL) are added into a 50mL single-neck bottle, 4-chlorobenzoyl chloride (0.35g,2.0mmol) is slowly added into the reaction system, and the reaction is carried out for 8 hours at room temperature of 25 ℃; quenching with water (20mL), extraction with dichloromethane (15mL × 3), washing of the organic phase with saturated brine, drying over anhydrous magnesium sulfate, filtration, removal of the solvent from the filtrate under reduced pressure using a rotary evaporator, and purification by column chromatography (EtOAc/PE (v/v) ═ 1/3) gave 0.30g of a white solid in yield: 70 percent.

¹H NMR(400MHz,CDCl₃):δ(ppm)8.65(s,1H),7.70(d,J＝8.5Hz,2H),7.45(d,J＝8.5Hz,2H),3.07(s,7H),1.00-0.95(m,4H).

LC-MS:(M+1)m/z＝434.0.

Preparation of reference example 4, N³-cyclopropyl-N¹,N¹the-dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide respectively reacts with corresponding raw materials to obtain the target compounds in the table 4.

TABLE 4

EXAMPLE 32 Compound N³- (cyclopropylmethyl) -N¹,N¹-dimethyl-N³Synthesis of- (3- (trifluoromethyl) phenyl) -1H-1,2, 4-triazole-1, 3-disulfonamide

Will N¹,N¹-dimethyl-N³- (3- (trifluoromethyl) phenyl) -1H-1,2, 4-triazole-1, 3-disulfonamide (0.40g,1.0mmol), potassium carbonate (0.28g,2.0mmol) and DMF (10mL) are added into a 100mL three-necked flask, bromomethyl cyclopropane (0.27g,2.0mmol) is slowly added into the reaction system, and the reaction is carried out for 8 hours at the room temperature of 25 ℃; quenching with water (20mL), extraction with ethyl acetate (15 mL. times.3), washing the organic phase with saturated brine, drying over anhydrous magnesium sulfate, filtering, and evaporating the filtrate with a rotary evaporatorThe solvent was removed under reduced pressure and purified by column chromatography (EtOAc/PE (v/v) ═ 1/3) to give 0.36g of a white solid in yield: 79 percent.

¹H NMR(400MHz,CDCl₃):δ(ppm)8.67(s,1H),7.65-7.62(m,3H),7.56-7.52(m,1H),3.73(d,J＝7.2Hz,2H),3.04(s,6H),1.02-0.90(m,1H),0.51-0.47(m,2H),0.19-0.15(m,2H).

LC-MS:(M+1)m/z＝454.1.

Referring to the preparation method of example 32, the intermediate compounds in table 2 were reacted with bromomethylcyclopropane, respectively, to obtain the target compounds in table 4.

TABLE 4

Biological examples of the present invention

Test targets: cucumber downy mildew

And (3) test treatment: the compound was dissolved in DMF to 1% EC for use. The bactericidal activity of the compounds on cucumber downy mildew is evaluated by using a living pot culture method under different dosages.

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.

The test results are shown in tables A-C.

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

TABLE B controlling effect of the compounds of the invention on cucumber downy mildew at 100ppm

Examples	Control effect (%)
		Example 1	100
Example 2	100
		Example 3	100
Example 4	100
		Example 6	80
Example 8	100
		Example 9	100
Example 10	80
		Example 11	100
Example 12	100
		Example 13	85
Example 14	80
		Example 15	80
Example 16	87
		Example 27	80

TABLE C control of cucumber downy mildew at 50ppm of the compounds of the invention and of the comparative compounds

The results in tables A to C show that the compound has obvious control effect on cucumber downy mildew under different concentrations. Particularly, the control effect of the compound of the present invention, for example, example 12, on cucumber downy mildew can be more than 50% at 6.25 ppm.

The preferred embodiments of the present invention have been described in detail, however, the present invention is not limited to the specific details of the above embodiments, and various simple modifications may be made to the technical solution of the present invention within the technical idea of the present invention, and these simple modifications are within the protective scope of the present invention.

Claims

1. A compound which is a compound of formula (I) or a stereoisomer of a compound of formula (I) or a salt thereof:

(I)；

wherein:

R¹and R²Each independently is methyl;

R³is hydrogen;

w is 2;

R⁴is cyclopropyl;

R⁵、R⁶、R⁷、R⁸and R⁹Each independently is hydrogen, fluorine, chlorine, bromine, iodine, nitro, C_1-4Alkyl, halo C_1-4Alkyl radical, C_1-4Alkoxy radical, C_1-4Alkylamino, halogeno C_1-4Alkylthio or phenyl;

x is- (CR)^cR^d) x or-O- (CR)^cR^d)v-；

Each R^cAnd R^dIndependently is hydrogen or C_1-4An alkyl group;

x and v are each independently 0 or 1;

wherein

1）R^aAnd R^bTogether form oxo (= O); or

2）R^a、R⁵And the atoms to which they are attached, optionally form a 4-8 membered ring; each R^bIndependently is hydrogen; or

3）R^a、R⁹And the atoms to which they are attached, optionally form a 4-8 membered ring; each R^bIndependently hydrogen.

2. The compound of claim 1, which is a compound of formula (Ib) or a stereoisomer of a compound of formula (Ib) or a salt thereof:

(Ib)。

3. the compound of claim 1, which is a compound of formula (Ic) or a stereoisomer of a compound of formula (Ic) or a salt thereof:

(Ic)。

4. the compound of claim 1, which is a compound of formula (Id) or a stereoisomer of a compound of formula (Id), or a salt thereof:

(Id)；

wherein: z is 1 or 2.

5. The compound according to any one of claims 1 to 4, wherein

R⁵、R⁶、R⁷、R⁸And R⁹Each independently is hydrogen, fluorine, chlorine, bromine, iodine, nitro, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-C(CH₃)₃、-CH₂F、-CHF₂、-CF₃、-CH₂CH₂F、-CH₂CHF₂、-CH₂CF₃、-OCH₃、-OCH₂CH₃、-OCH₂CH₂CH₃、-OCH(CH₃)₂、-SCF₃、-SCH₂CF₃、-NH(CH₃)、-N(CH₃)₂、-NH(CH₂CH₃)、-N(CH₂CH₃)₂Or a phenyl group.

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

(I-1)、

(I-2)、

(I-3)、

(I-4)、

(I-5)、

(I-6)、

(I-7)、

(I-8)、

(I-9)、

(I-10)、

(I-11)、

(I-12)、

(I-13)、

(I-14)、

(I-15)、

(I-16)、

(I-17)、

(I-18)、

(I-19)、

(I-20)、

(I-21)、

(I-22)、

(I-23)、

(I-24)、

(I-25) or

(I-26)。

7. A composition comprising a compound of any one of claims 1-6.

8. The composition of claim 7, further comprising an agriculturally pharmaceutically acceptable surfactant and/or carrier.

9. Use of a compound according to any one of claims 1 to 6 or a composition according to claim 7 or 8 for controlling cucumber downy mildew.

10. Use of a compound according to any one of claims 1 to 6 or a composition according to claim 7 or 8 for controlling plant diseases caused by cucumber downy mildew.

11. Use of a compound according to any one of claims 1 to 6 or a composition according to claim 7 or 8 as fungicide for the control of cucumber downy mildew.