CN114380761A

CN114380761A - Novel isoxazole derivative and application thereof in agriculture

Info

Publication number: CN114380761A
Application number: CN202011139016.2A
Authority: CN
Inventors: 李义涛; 林健; 吴双志; 曾水明; 池伟林
Original assignee: Ningxia Sulongda Chemical Co ltd
Current assignee: Ningxia Sulongda Chemical Co ltd
Priority date: 2020-10-22
Filing date: 2020-10-22
Publication date: 2022-04-22

Abstract

The invention provides a novel isoxazole derivative and application thereof in agriculture; specifically, the invention provides a compound shown as a formula (I) and a preparation method thereof, a composition containing the compound, a preparation and application thereof in agriculture, in particular to application of the compound as a herbicide for controlling unwanted plants; wherein R is¹、R²、R³、R⁴、n、R⁵、R⁶、R⁷、R⁸、R⁹、R¹⁰And R¹¹Have the meaning as described in the present invention.

Description

Novel isoxazole derivative and application thereof in agriculture

Technical Field

The invention relates to the field of agriculture, in particular to a novel isoxazole derivative, a preparation method thereof and application thereof as a herbicide in agriculture.

Background

Herbicides are applied, and it is desired that they exhibit a sufficient herbicidal effect at a low dose after application to soil or stems and leaves of plants, have a high selectivity for weeds in useful crops, have a high safety for useful crops, or have a drug for promoting the growth of useful plants.

Herbicidal activity of isoxazole derivatives is described in WO2002062770, WO2003000686, WO 2003010165 and WO 2001012613, and the properties of isoxazole derivatives to which the present invention relates are not known.

Disclosure of Invention

The present invention relates to a novel isoxazole derivative which has excellent activity against weeds at a low dose.

Specifically, the method comprises the following steps:

in one aspect, the invention relates to a compound that is a compound of formula (I) or a stereoisomer, a nitroxide, or a salt thereof of the compound of formula (I):

wherein:

R¹and R²Each independently hydrogen, halogen, cyano, nitro, hydroxy, carboxy, C_1-6Alkyl, halo C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-8Cycloalkyl radical, C_3-8cycloalkyl-C_1-3Alkylene-, C_1-6alkoxy-C_1-3Alkylene-or C_1-6alkylthio-C_1-3Alkylene-;

or R¹、R²And the carbon atom to which they are attached form C_3-8A cycloalkyl group;

R³and R⁴Each independently hydrogen, halogen, cyano, nitro, hydroxy, carboxy, C_1-6Alkyl, halo C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-8Cycloalkyl radical, C_3-8cycloalkyl-C_1-3Alkylene-, C_1-6alkoxy-C_1-3Alkylene-or C_1-6alkylthio-C_1-3Alkylene-;

or R³、R⁴And the carbon atom to which they are attached form C_3-8A cycloalkyl group;

or R²、R⁴And the carbon atom to which they are attached form C_3-8A cycloalkyl group;

n is 0, 1 or 2;

R⁵and R⁶Each independently hydrogen, halogen, cyano, nitro, hydroxy, carboxy, C_1-6Alkyl radical, C_2-6Alkenyl or C_2-6An alkynyl group;

R⁷、R⁸、R⁹and R¹⁰Each independently is fluorine, chlorine, bromine or iodine;

R¹¹is hydrogen, C_1-6Alkyl, halo C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, halo C_2-6Alkenyl, halo C_2-6Alkynyl, C_3-8Cycloalkyl radical, C_3-8cycloalkyl-C_1-3Alkylene-, optionally substituted by 1, 2,3, 4 or 5 groups selected from halogen, hydroxy, cyano, nitro, C_1-4Alkyl, halo C_1-4Alkyl radical, C_1-4Alkoxy or halo C_1-4Alkoxy-substituted C_6-10Aryl or optionally substituted by 1, 2,3, 4 or 5 substituents selected from halogen, hydroxy, cyano, nitro, C_1-4Alkyl, halo C_1-4Alkyl radical, C_1-4Alkoxy or halo C_1-4Alkoxy-substituted C_6-10aryl-C_1-3Alkylene-.

In some embodiments, R¹And R²Each independently hydrogen, halogen, cyano, nitro, hydroxy, carboxy, C_1-4Alkyl, halo C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_3-6Cycloalkyl radical, C_3-6cycloalkyl-C_1-3Alkylene-, C_1-4alkoxy-C_1-3Alkylene-or C_1-4alkylthio-C_1-3Alkylene-;

or R¹、R²And a carbon atom attached theretoSub-formation C_3-6A cycloalkyl group;

R³and R⁴Each independently hydrogen, halogen, cyano, nitro, hydroxy, carboxy, C_1-4Alkyl, halo C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_3-6Cycloalkyl radical, C_3-6cycloalkyl-C_1-3Alkylene-, C_1-4alkoxy-C_1-3Alkylene-or C_1-4alkylthio-C_1-3Alkylene-;

or R³、R⁴And the carbon atom to which they are attached form C_3-6A cycloalkyl group.

In other embodiments, R¹And R²Each independently is hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, carboxyl, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂Cl、-CH₂F、-CHF₂、-CF₃、-CH₂CHF₂、-CH＝CH₂、-CH₂CH＝CH₂、-CH₂CH₂CH＝CH₂、-CH₂CH＝CHCH₃、-C≡CH、-CH₂-C≡CH、-CH₂-C≡CCH₃、-CH₂CH₂-C ≡ CH, cyclopropyl or cyclopropyl-CH₂-；

Or R¹、R²And the carbon atom to which it is attached form a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group;

R³and R⁴Each independently is hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, carboxyl, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂Cl、-CH₂F、-CHF₂、-CF₃、-CH₂CHF₂、-CH＝CH₂、-CH₂CH＝CH₂、-CH₂CH₂CH＝CH₂、-CH₂CH＝CHCH₃、-C≡CH、-CH₂-C≡CH、-CH₂-C≡CCH₃、-CH₂CH₂-C ≡ CH, cyclopropyl or cyclopropyl-CH₂-；

Or R³、R⁴And the carbon atom to which it is attached form a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group.

In some embodiments, R⁵And R⁶Each independently hydrogen, halogen, cyano, nitro, hydroxy, carboxy, C_1-4Alkyl radical, C_2-4Alkenyl or C_2-4Alkynyl.

In other embodiments, R⁵And R⁶Each independently is hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, carboxyl, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH＝CH₂、-CH₂CH＝CH₂-C.ident.CH or-CH₂-C≡CH。

In some embodiments, R¹¹Is hydrogen, C_1-4Alkyl, halo C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, halo C_2-4Alkenyl, halo C_2-4Alkynyl, C_3-6Cycloalkyl radical, C_3-6cycloalkyl-C_1-3Alkylene-, optionally substituted by 1, 2,3, 4 or 5 groups selected from halogen, hydroxy, cyano, nitro, C_1-4Alkyl, halo C_1-4Alkyl radical, C_1-4Alkoxy or halo C_1-4Phenyl substituted by alkoxy or optionally substituted by 1, 2,3, 4 or 5 substituents selected from halogen, hydroxy, cyano, nitro, C_1-4Alkyl, halo C_1-4Alkyl radical, C_1-4Alkoxy or halo C_1-4Alkoxy-substituted benzyl.

In other embodiments, R¹¹Is hydrogen, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-CH₂Cl、-CH₂F、-CHF₂、-CF₃、-CH₂CF₃、-CH₂CH₂CF₃、-CH＝CH₂、-CH₂CH＝CH₂、-CH₂CH₂CH＝CH₂、-CH₂CH＝CHCH₃、-C≡CH、-CH₂-C≡CH、-CH₂-C≡CCH₃、-CH₂CH₂-C ≡ CH, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropyl-CH₂-, cyclobutyl-CH₂-, cyclopentyl-CH₂-, cyclohexyl-CH₂-, optionally substituted by 1, 2,3, 4 or 5 substituents selected from fluorine, chlorine, bromine, iodine, hydroxy, cyano, nitro, -CH₃、-CF₃、-OCH₃or-OCF₃Substituted phenyl or optionally substituted by 1, 2,3, 4 or 5 substituents selected from fluoro, chloro, bromo, iodo, hydroxy, cyano, nitro, -CH₃、-CF₃、-OCH₃or-OCF₃A substituted benzyl group.

In another aspect, the present invention provides a composition comprising at least one compound according to the invention and at least one agriculturally pharmaceutically customary auxiliary.

In yet another aspect, the compound of the invention or the composition of the invention is used as a herbicide in agriculture.

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 articles of one or more than one (i.e., at least one) object. 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; stereochemical definitions and rules as described in 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.

By "room temperature" is meant a temperature of about 15 ℃ to 35 ℃ or about 20 ℃ to 30 ℃ or about 23 ℃ to 28 ℃ or about 25 ℃. In the context of the present invention, all numbers disclosed herein are approximate values, regardless of whether the word "about" or "approximately" is used. The numerical value of each number may vary by 1%, 2%, 3%, 4% or 5%.

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. 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 include each and every independent member of each of these groups classes and rangesAnd (4) secondary combination. 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 10 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) N-hexyl (-CH)₂CH₂CH₂CH₂CH₂CH₃) 2-hexyl (-CH (CH)₃)CH₂CH₂CH₂CH₃) 3-hexyl (-CH (CH)₂CH₃)(CH₂CH₂CH₃) 2-methyl-2-pentyl (-C (CH))₃)₂CH₂CH₂CH₃) 3-methyl-2-pentyl (-CH (CH)₃)CH(CH₃)CH₂CH₃) 4-methyl-2-pentyl (-CH (CH)₃)CH₂CH(CH₃)₂) 3-methyl-3-pentyl (-C (CH)₃)(CH₂CH₃)₂) 2-methyl-3-pentyl (-CH (CH)₂CH₃)CH(CH₃)₂) 2, 3-dimethyl-2-butyl (-C (CH)₃)₂CH(CH₃)₂) 3, 3-dimethyl-2-butyl (-CH (CH)₃)C(CH₃)₃) N-heptyl, n-octyl, 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 10 carbon atoms; 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-)，-CH₂CH₂CH＝CH₂、-CH₂CH＝CHCH₃、-CH₂CH₂CH₂CH＝CH₂、-CH₂CH₂CH＝CHCH₃、-CH₂CH₂CH₂CH＝CHCH₃And so on.

The term "alkynyl" denotes a straight or branched chain monovalent hydrocarbon radical containing 2 to 12 carbon atoms, whereinHaving at least one carbon-carbon sp triple bond, wherein said alkynyl group may be optionally substituted with one or more substituents as described herein. In one embodiment, alkynyl groups contain 2-10 carbon atoms; 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, -C.ident.CCH₃、-CH₂-C≡CH、-CH₂-C≡CCH₃、-CH₂CH₂-C≡CH、-CH₂-C≡CCH₂CH₃、-CH₂CH₂-C≡CCH₃And 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. Unless otherwise specified, the alkoxy group contains 1 to 12 carbon atoms. In one embodiment, the alkoxy group contains 1 to 10 carbon atoms; in one embodiment, the alkoxy group contains 1 to 8 carbon atoms; in one embodiment, the alkoxy group contains 1 to 6 carbon atoms; in another embodiment, the alkoxy group contains 1 to 4 carbon atoms; in yet another embodiment, the alkoxy group contains 1 to 3 carbon atoms. The alkoxy group may be optionally substituted with one or more substituents 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) 1-butoxy (n-BuO, n-butoxy, -OCH)₂CH₂CH₂CH₃) 2-methyl-l-propoxy (i-BuO, i-butoxy, -OCH)₂CH(CH₃)₂) 2-butoxy (s-BuO, s-butoxy, -OCH (CH)₃)CH₂CH₃) 2-methyl-2-propoxy (t-BuO, t-butoxy, -OC (CH)₃)₃) 1-pentyloxy (n-pentyloxy, -OCH)₂CH₂CH₂CH₂CH₃) 2-pentyloxy (-OCH (CH)₃)CH₂CH₂CH₃) 3-pentyloxy (-OCH (CH))₂CH₃)₂) 2-methyl-2-butoxy (-OC (CH))₃)₂CH₂CH₃) 3-methyl-2-butoxy (-OCH (CH)₃)CH(CH₃)₂) 3-methyl-l-butoxy (-OCH)₂CH₂CH(CH₃)₂) 2-methyl-l-butoxy (-OCH)₂CH(CH₃)CH₂CH₃) And so on.

The term "alkylthio" refers to a straight or branched chain alkyl group attached to a divalent sulfur atom, wherein the alkyl group has the meaning as described herein. Examples of alkylthio groups include, but are not limited to, -SCH₃、-SCH₂CH₃、-SCH₂CH₂CH₃And so on.

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. 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 "haloalkoxy" denotes an alkoxy group substituted with one or more halogen atoms. 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 "haloalkylthio" denotes an alkylthio group substituted by one or more halogen atoms.

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 "cycloalkyl" denotes a monovalent or polyvalent saturated monocyclic, bicyclic or tricyclic ring system containing from 3 to 15 carbon atoms. In one embodiment, the cycloalkyl group contains 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, adamantyl, and the like.

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 "alkylene" denotes a saturated straight or branched chain hydrocarbonSaturated divalent hydrocarbyl groups derived by dropping two hydrogen atoms. 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 "alkoxy-alkylene" means that the alkoxy group is attached to the rest of the molecule through an alkylene group, wherein the alkylene and alkoxy groups have the meaning described herein. Examples include, but are not limited to, CH₃O-CH₂-，CH₃O-CH₂CH₂-, and the like.

The term "alkylthio-alkylene" means that the alkylthio group is attached to the rest of the molecule through an alkylene group, wherein the alkylene and alkylthio groups have the meaning described herein.

The term "cycloalkyl-alkylene" means that the cycloalkyl group is attached to the rest of the molecule through an alkylene group, wherein alkylene and cycloalkyl groups have the meaning as described herein. Examples include, but are not limited to, cyclopropyl-CH₂-, cyclobutyl-CH₂-, cyclopentyl-CH₂-, cyclohexyl-CH₂-, and the like.

The term "aryl-alkylene" means that the aryl group is attached to the rest of the molecule through an alkylene group, wherein alkylene and aryl groups have the meaning as described herein. Examples include, but are not limited to, benzyl (phenyl-CH)₂-, phenethyl (benzene-CH)₂CH₂-) and so on。

The term "cyano" refers to — CN.

The term "hydroxy" refers to-OH.

The term "nitro" means-NO₂。

The term "carboxy" refers to-COOH.

When the compounds of the present invention contain an acid moiety, 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) may be prepared by treating a compound having 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 invention provides a novel isoxazole derivative, a preparation method thereof, a composition containing the isoxazole derivative and application of the isoxazole derivative and/or the composition as a herbicide in agriculture.

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

wherein:

R¹and R²Each independently hydrogen, halogen, cyano, nitro, hydroxy, carboxy, C_1-8Alkyl, halo C_1-8Alkyl radical, C_2-8Alkenyl radical, C_2-8Alkynyl, C_3-8Cycloalkyl radical, C_3-8cycloalkyl-C_1-3Alkylene-, C_1-8alkoxy-C_1-3Alkylene-or C_1-8alkylthio-C_1-3Alkylene-;

R³and R⁴Each independently hydrogen, halogen, cyano, nitro, hydroxy, carboxy, C_1-8Alkyl, halo C_1-8Alkyl radical, C_2-8Alkenyl radical, C_2-8Alkynyl, C_3-8Cycloalkyl radical, C_3-8cycloalkyl-C_1-3Alkylene-, C_1-8alkoxy-C_1-3Alkylene-or C_1-8alkylthio-C_1-3Alkylene-;

n is 0, 1 or 2;

R⁵and R⁶Each independently hydrogen, halogen, cyano, nitro, hydroxy, carboxy, C_1-8Alkyl radical, C_2-8Alkenyl or C_2-8An alkynyl group;

R¹¹is hydrogen, C_1-8Alkyl, halo C_1-8Alkyl radical, C_2-8Alkenyl radical, C_2-8Alkynyl, halo C_2-8Alkenyl, halo C_2-8Alkynyl, C_3-8CycloalkanesBase, C_3-8cycloalkyl-C_1-3Alkylene-, optionally substituted by 1, 2,3, 4 or 5 groups selected from halogen, hydroxy, cyano, nitro, C_1-6Alkyl, halo C_1-6Alkyl radical, C_1-6Alkoxy or halo C_1-6Alkoxy-substituted C_6-14Aryl or optionally substituted by 1, 2,3, 4 or 5 substituents selected from halogen, hydroxy, cyano, nitro, C_1-6Alkyl, halo C_1-6Alkyl radical, C_1-6Alkoxy or halo C_1-6Alkoxy-substituted C_6-14aryl-C_1-3Alkylene-.

In some embodiments, R¹And R²Each independently hydrogen, halogen, cyano, nitro, hydroxy, carboxy, C_1-6Alkyl, halo C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-8Cycloalkyl radical, C_3-8cycloalkyl-C_1-3Alkylene-, C_1-6alkoxy-C_1-3Alkylene-or C_1-6alkylthio-C_1-3Alkylene-.

In other embodiments, R¹And R²Each independently hydrogen, halogen, cyano, nitro, hydroxy, carboxy, C_1-4Alkyl, halo C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_3-6Cycloalkyl radical, C_3-6cycloalkyl-C_1-3Alkylene-, C_1-4alkoxy-C_1-3Alkylene-or C_1-4alkylthio-C_1-3Alkylene-.

In still other embodiments, R¹And R²Each independently is hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, carboxyl, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂Cl、-CH₂F、-CHF₂、-CF₃、-CH₂CHF₂、-CH＝CH₂、-CH₂CH＝CH₂、-CH₂CH₂CH＝CH₂、-CH₂CH＝CHCH₃、-C≡CH、-CH₂-C≡CH、-CH₂-C≡CCH₃、-CH₂CH₂-C ≡ CH, cyclopropyl or cyclopropyl-CH₂-。

Preferably, in some embodiments, R¹And R²Each independently is C_1-6Alkyl or halo C_1-6An alkyl group.

More preferably, in some embodiments, R¹And R²Each independently is C_1-4Alkyl or halo C_1-4An alkyl group.

Specifically, in some embodiments, R¹And R²Each independently is-CH₃、-CH₂CH₃or-CH₂Cl。

Particularly preferably, in some embodiments, R¹is-CH₃；R²is-CH₃、-CH₂CH₃or-CH₂Cl。

In some embodiments, R¹、R²And the carbon atom to which they are attached form C_3-6A cycloalkyl group.

Specifically, in some embodiments, R¹、R²And the carbon atom to which it is attached form a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group.

In some embodiments, R³And R⁴Each independently hydrogen, halogen, cyano, nitro, hydroxy, carboxy, C_1-6Alkyl, halo C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, C_3-8Cycloalkyl radical, C_3-8cycloalkyl-C_1-3Alkylene-, C_1-6alkoxy-C_1-3Alkylene-or C_1-6alkylthio-C_1-3Alkylene-.

In other embodiments, R³And R⁴Each independently hydrogen, halogen, cyano, nitro, hydroxy, carboxy, C_1-4Alkyl, halo C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_3-6Cycloalkyl radical, C_3-6cycloalkyl-C_1-3Alkylene-, C_1-4alkoxy-C_1-3Alkylene-or C_1-4alkylthio-C_1-3Alkylene-.

In still other embodiments, R³And R⁴Each independently is hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, carboxyl, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂Cl、-CH₂F、-CHF₂、-CF₃、-CH₂CHF₂、-CH＝CH₂、-CH₂CH＝CH₂、-CH₂CH₂CH＝CH₂、-CH₂CH＝CHCH₃、-C≡CH、-CH₂-C≡CH、-CH₂-C≡CCH₃、-CH₂CH₂-C ≡ CH, cyclopropyl or cyclopropyl-CH₂-。

Preferably, in some embodiments, R³And R⁴Each independently hydrogen or halogen.

Specifically, in some embodiments, R³And R⁴Each independently hydrogen, fluorine or bromine.

Particularly preferably, in some embodiments, R³Is hydrogen; r⁴Is hydrogen, fluorine or bromine.

In some embodiments, R³、R⁴And the carbon atom to which they are attached form C_3-6A cycloalkyl group.

Specifically, in some embodiments, R³、R⁴And the carbon atom to which it is attached form a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group.

In some embodiments, R⁵And R⁶Each independently hydrogen, halogen, cyano, nitro, hydroxy, carboxy, C_1-6Alkyl radical, C_2-6Alkenyl or C_2-6Alkynyl.

In other embodiments, R⁵And R⁶Each independently hydrogen, halogen, cyano, nitro, hydroxy, carboxy, C_1-4Alkyl radical, C_2-4Alkenyl or C_2-4Alkynyl.

In still other embodiments, R⁵And R⁶Each independentlyIs hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, carboxyl, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH＝CH₂、-CH₂CH＝CH₂-C.ident.CH or-CH₂-C≡CH。

Preferably, in some embodiments, R⁵And R⁶Each independently hydrogen or halogen.

More preferably, in some embodiments, R⁵And R⁶Each independently hydrogen or fluorine.

Preferably, in some embodiments, n is 2.

Preferably, in some embodiments, R⁷、R⁸、R⁹And R¹⁰Each independently being fluorine.

In some embodiments, R¹¹Is hydrogen, C_1-6Alkyl, halo C_1-6Alkyl radical, C_2-6Alkenyl radical, C_2-6Alkynyl, halo C_2-6Alkenyl, halo C_2-6Alkynyl, C_3-8Cycloalkyl radical, C_3-8cycloalkyl-C_1-3Alkylene-, optionally substituted by 1, 2,3, 4 or 5 groups selected from halogen, hydroxy, cyano, nitro, C_1-4Alkyl, halo C_1-4Alkyl radical, C_1-4Alkoxy or halo C_1-4Alkoxy-substituted C_6-10Aryl or optionally substituted by 1, 2,3, 4 or 5 substituents selected from halogen, hydroxy, cyano, nitro, C_1-4Alkyl, halo C_1-4Alkyl radical, C_1-4Alkoxy or halo C_1-4Alkoxy-substituted C_6-10aryl-C_1-3Alkylene-.

In other embodiments, R¹¹Is hydrogen, C_1-4Alkyl, halo C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, halo C_2-4Alkenyl, halo C_2-4Alkynyl, C_3-6Cycloalkyl radical, C_3-6cycloalkyl-C_1-3Alkylene-, optionally substituted by 1, 2,3, 4 or 5 groups selected from halogen, hydroxy, cyano, nitro, C_1-4Alkyl, halo C_1-4Alkyl radical, C_1-4Alkoxy or halo C_1-4Phenyl substituted by alkoxy or optionally substituted by 1, 2,3, 4 or 5 substituents selected from halogen, hydroxy, cyano, nitro, C_1-4Alkyl, halo C_1-4Alkyl radical, C_1-4Alkoxy or halo C_1-4Alkoxy-substituted benzyl.

In still other embodiments, R¹¹Is hydrogen, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-CH₂Cl、-CH₂F、-CHF₂、-CF₃、-CH₂CF₃、-CH₂CH₂CF₃、-CH＝CH₂、-CH₂CH＝CH₂、-CH₂CH₂CH＝CH₂、-CH₂CH＝CHCH₃、-C≡CH、-CH₂-C≡CH、-CH₂-C≡CCH₃、-CH₂CH₂-C ≡ CH, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropyl-CH₂-, cyclobutyl-CH₂-, cyclopentyl-CH₂-, cyclohexyl-CH₂-, optionally substituted by 1, 2,3, 4 or 5 substituents selected from fluorine, chlorine, bromine, iodine, hydroxy, cyano, nitro, -CH₃、-CF₃、-OCH₃or-OCF₃Substituted phenyl or optionally substituted by 1, 2,3, 4 or 5 substituents selected from fluoro, chloro, bromo, iodo, hydroxy, cyano, nitro, -CH₃、-CF₃、-OCH₃or-OCF₃A substituted benzyl group.

Preferably, in some embodiments, R¹¹Is hydrogen, C_1-4Alkyl, halo C_1-4Alkyl or C_3-6A cycloalkyl group.

Particularly preferably, in some embodiments, R¹¹Is hydrogen, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-CH₂CF₃Cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

In particular toMore preferably, in some embodiments, R¹¹Is hydrogen, -CH₃Or a cyclopentyl group.

In some 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 a compound having one of the following structures:

In yet another aspect, the invention provides the use of a compound according to the invention or a composition according to the invention as a herbicide in agriculture.

In some embodiments, the present invention provides the use of a compound of the present invention or a composition of the present invention as a pre-emergent herbicide in agriculture.

In other embodiments, the present invention provides the use of a compound of the present invention or a composition of the present invention as a post-emergence herbicide in agriculture.

In yet another aspect, the present invention provides a method of controlling the growth of weeds in useful plants, comprising applying to the locus of the weeds an effective amount of a compound of the present invention or a composition comprising a compound of the present invention.

In some embodiments, the weeds comprise broadleaf weeds and/or grass weeds.

Further, the broadleaf weeds comprise at least one selected from abutilon, amaranthus retroflexus and snakehead intestine; the grassy weeds include at least one selected from the group consisting of large crabgrass, barnyard grass, moleplant seed, and green bristlegrass.

In some embodiments, the useful plant is rice, wheat, soybean, peanut, canola and/or sunflower.

Compositions and formulations of the compounds of the invention

The compounds of the present invention are generally useful as herbicidal active ingredients in compositions or formulations comprising at least one agriculturally pharmaceutically customary adjuvant selected from the group consisting of surfactants, solid diluents and liquid diluents, and the like, all of which meet the requirements of use as a pesticide. The formulation or composition ingredients are selected to be compatible with the physical characteristics of the active ingredient, the mode of application, and environmental factors such as soil type, moisture and temperature.

Useful formulations include liquid compositions and solid compositions. Liquid compositions include solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions), and the like, which may optionally be thickened into gels. Common types of aqueous liquid compositions are soluble concentrates, suspension concentrates, capsule suspensions, concentrated emulsions, microemulsions and suspoemulsions. Common types of non-aqueous liquid compositions are emulsifiable concentrates, microemulsifiable concentrates, dispersible concentrates and oil dispersions.

The general types of solid compositions are powders, granules, pellets, prills, lozenges, tablets, filled films (including seed coatings), and the like, which may be water dispersible ("wettable") or water soluble. Films and coatings formed from film-forming solutions or flowable suspensions are particularly useful for seed treatment. The active ingredient may be (micro) encapsulated and further formed into a suspension or solid formulation; alternatively, the entire active ingredient formulation may be encapsulated (or "coated"). Encapsulation may control or delay the release of the active ingredient. Emulsifiable granules combine the advantages of both emulsifiable concentrate formulations and dry granular formulations. The high concentration compositions are mainly used as intermediates for other formulations.

Sprayable formulations are typically dispersed in a suitable medium prior to spraying. Such liquid and solid formulations are formulated to be readily diluted in a spray medium, typically water. The spray volume may be in the range of about one to several thousand liters per hectare, but more typically in the range of about ten to several hundred liters per hectare. The sprayable formulation may be mixed with water or another suitable medium in a water tank for treatment of the foliage by air or ground application, or applied to the growing medium of the plant. The liquid and dry formulations can be dosed directly into the drip irrigation system or into the furrow during planting.

The formulation will typically comprise effective amounts of active ingredient, diluent and surfactant, the sum being 100% by weight.

Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starches, dextrins, sugars (e.g., lactose, sucrose), silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate and sodium sulfate. Typical solid Diluents are described in Handbook of Instrument Dust Diluents and Cariers, 2 nd edition, Dorland Books, Caldwell, N.J. by Watkins et al.

Liquid diluents include, for example, water, N-dimethyl alkanamides (e.g., N-dimethylformamide), limonene, dimethyl sulfoxide, N-alkylpyrrolidones (e.g., N-methylpyrrolidone), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oil, N-paraffins, isoparaffins), alkylbenzenes, alkylnaphthalenes, glycerol, triacetin, sorbitol, aromatic hydrocarbons, dealkylated aliphatics, alkylbenzenes, alkylnaphthalenes, ketones (e.g., cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone), acetates (e.g., isoamyl acetate, hexyl acetate, heptyl acetate, octyl acetate, nonyl acetate, tridecyl acetate, and isobornyl acetate), Other esters (such as alkylated lactates, dibasic esters and gamma-butyrolactones) and may be straight chain, branched chain, saturated or unsaturated alcohols (such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, n-hexanol, 2-ethylhexanol, n-octanol, decanol, isodecanol, isostearyl alcohol, cetyl alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol and benzyl alcohol). Liquid diluents also include glycerol esters of saturated and unsaturated fatty acids (typically C6-C22), such as vegetable seed and fruit oils (e.g., olive oil, castor oil, linseed oil, sesame oil, corn oil, peanut oil, sunflower oil, grapeseed oil, safflower oil, cottonseed oil, soybean oil, rapeseed oil, coconut oil, and palm kernel oil), animal derived fats (e.g., tallow, lard, cod liver oil, fish oil), and mixtures thereof. Liquid diluents also include alkylated (e.g., methylated, ethylated, butylated) fatty acids, which can be obtained by hydrolysis of vegetable and animal derived glycerides and can be purified by distillation. Typical liquid diluents are described in Marsden's Solvents Guide, 2 nd edition, Interscience, New York, 1950.

The solid and liquid compositions of the present invention typically comprise one or more surfactants. Surfactants (also known as "surface active agents") generally change when added to a liquid, most often lowering the surface tension of the liquid. Surfactants can be used as wetting agents, dispersing agents, emulsifying agents, or defoaming agents, depending on the nature of the hydrophilic and lipophilic groups in the surfactant molecule.

Surfactants can be classified as nonionic, anionic, or cationic surfactants. Nonionic surfactants useful as compositions of the present invention include, but are not limited to: alcohol alkoxylates, such as alcohol alkoxylates based on natural and synthetic alcohols (which are branched or linear) and prepared from alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylation, alkanolamides, and ethoxylated alkanolamides; alkoxylated triglycerides, such as ethoxylated soybean, castor and rapeseed oil; alkylphenol alkoxylates such as octylphenol ethoxylate, nonylphenol ethoxylate, dinonylphenol ethoxylate and dodecylphenol ethoxylate (prepared from phenol and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); a block polymer prepared from ethylene oxide or propylene oxide and a reverse block polymer, wherein the end block is prepared from propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenols (including those prepared from ethylene oxide, propylene oxide, butylene oxide, or mixtures thereof); fatty acid esters, glycerides, lanolin-based derivatives, polyethoxylated esters, such as polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitol fatty acid esters, and polyethoxylated glycerol fatty acid esters; other sorbitan derivatives, such as sorbitan esters; polymeric surfactants such as random copolymers, block copolymers, alkyd PEG (polyethylene glycol) resins, graft or comb polymers, and star polymers; polyethylene glycol (PEG); polyethylene glycol fatty acid esters; a silicone-based surfactant; and sugar derivatives such as sucrose esters, alkyl polyglucosides, and alkyl polysaccharides.

Useful anionic surfactants include, but are not limited to: alkyl aryl sulfonic acids and their salts; carboxylated alcohols or alkylphenol ethoxylates; a diphenyl sulfonate derivative; lignin and lignin derivatives, such as lignosulfonates; maleic or succinic acid or anhydrides thereof; olefin sulfonates; phosphate esters such as phosphate esters of alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates, and phosphate esters of styrylphenol ethoxylates; a protein-based surfactant; a sarcosine derivative; styrylphenol ether sulfate; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of ethoxylated alcohols; amine and amide sulfonates, such as N, N-alkyl taurates; benzene, cumene, toluene, xylene, and sulfonates of dodecylbenzene and tridecylbenzene; a sulfonate of condensed polynaphthalene; sulfonates of naphthalene and alkylnaphthalenes; sulfonates of petroleum fractions; sulfosuccinamates; and sulfosuccinates and their derivatives, such as dialkyl sulfosuccinates.

Useful cationic surfactants include, but are not limited to: amides and ethoxylated amides; amines such as N-alkyl propylene diamine, tripropylene triamine and dipropylene tetramine, and ethoxylated, ethoxylated and propoxylated amines (prepared from amines and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); amine salts, such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary salts, ethoxylated quaternary salts and diquaternary salts; and amine oxides such as alkyldimethylamine oxide and bis- (2-hydroxyethyl) -alkylamine oxide.

Also useful in the compositions of the present invention are mixtures of nonionic and anionic surfactants or mixtures of nonionic and cationic surfactants. Nonionic, anionic and cationic surfactants and their proposed uses are disclosed in a number of published references, including McCutcheon's Emulsifiers and Detergents, north american and international yearbook versions, published by McCutcheon's Division, The Manufacturing conditioner Publishing co; the Encyclopdia of Surface Active Agents by Sisely and Wood, Chemical Publ.Co., Inc., New York, 1964; and Synthetic Detergents, seventh edition, John Wiley and Sons, New York, 1987, by a.s.davidson and b.milwidsky.

The compositions of the present invention may also contain formulation adjuvants and additives known to those skilled in the art as co-formulations (some of which may also be considered to act as solid diluents, liquid diluents or surfactants). Such formulation aids and additives may control: pH (buffer), foaming during processing (antifoam such as polyorganosiloxane), sedimentation of the active ingredient (suspending agent), viscosity (thixotropic thickener), microbial growth in the container (biocide), product freezing (antifreeze), color (dye/pigment dispersion), elution (film former or binder), evaporation (anti-evaporation agent), and other formulation attributes. Film formers include, for example, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymers, polyvinyl alcohol copolymers, and waxes. Examples of formulation aids and additives include McCutcheon's Volume 2 published by McCutcheon's Division, The Manufacturing conditioner Publishing co: functional Materials, north american and international yearbook versions; and those listed in PCT publication WO 03/024222.

The compounds of the present invention and any other active ingredients are typically incorporated into the compositions of the present invention by dissolving the active ingredient in a solvent or by grinding the active ingredient in a liquid diluent or a dry diluent. Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. If the solvent of the liquid composition used as an emulsifiable concentrate is water-immiscible, an emulsifier is usually added to emulsify the solvent containing the active ingredient upon dilution with water. A media mill may be used to wet grind an active ingredient slurry having a particle size of up to 2,000 μm to obtain particles having an average diameter of less than 3 μm. The aqueous slurry can be prepared as a finished suspension concentrate (see, e.g., U.S.3,060,084) or further processed by spray drying to form water-dispersible granules. Dry formulations typically require a dry milling step, which results in an average particle size in the range of 2 to 10 μm. Powders and dusts can be prepared by mixing, and usually by grinding (e.g., with a hammer mill or fluid energy mill). Particles and granules can be prepared by spraying the active substance onto preformed particle carriers or by agglomeration techniques. See Browning "agglomerization" (Chemical Engineering, 12.4.1967, pages 147-48; Perry's Chemical Engineering' Handbook, 4 th edition, McGraw-Hill, New York, 1963, pages 8-57 and later and WO 91/13546. the pellets can be prepared as described in u.s.4,172,714. the water dispersible and water soluble particles can be prepared as set forth in u.s.4,144,050, u.s.3,920,442 and de.3,246,493. the tablets can be prepared as set forth in u.s.5,180,587, u.s.5,232,701 and u.s.5,208,030. the films can be prepared as set forth in GB2,095,558 and u.s.3,299,566.

For additional information regarding The formulation art, see "The formulations's Toolbox-Product for model agricultural", Pesticide Chemistry and Bioscience, The Food-environmental Challenge, T.Brooks and T.R.Roberts eds., Proceedings of The 9th International conformation on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, p.120-133. See also U.S.3,235,361, column 6, line 16 to column 7, line 19 and examples 10-41; U.S. Pat. No. 3,309,192, column 5, column 43 to column 7, column 62 and examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138, 162, 164, 166, 167 and 169, 182; U.S.2,891,855 at column 3, line 66 to column 5, line 17 and examples 1-4; wed Control as a Science by Klingman, John Wiley and Sons, Inc., New York, 1961, pages 81-96; weed Control Handbook, 8 th edition, Blackwell Scientific Publications, Oxford, 1989, by Hance et al; and Developments in simulation technology, PJB Publications, Richmond, UK, 2000.

Application of the inventive compounds and compositions

The herbicides of the present invention can be used by spraying plants, applying to soil, applying to the surface of water. The amount of the active ingredient is appropriately determined to meet the purpose of use. The content of the active ingredient is appropriately determined depending on the purpose.

The amount of the compound of the present invention to be used is determined depending on the kind of the compound to be used, the target weed, the tendency of weed to appear, environmental conditions, the kind of herbicide, and the like. When the herbicides of the invention are used as such, for example in the form of powders or granules, the amount is suitably selected to be from 1g to 50kg per hectare of active ingredient, preferably from 10g to 10kg per hectare. When the herbicide of the present invention is used in a liquid form, for example, in the form of an emulsifiable concentrate, a wettable powder or a flowable formulation, the amount thereof is suitably selected from 0.1 to 50,000ppm, preferably from 10 to 10,000 ppm.

The present invention provides a method for controlling weeds in a crop of useful plants, comprising applying to said weeds or to the locus of said weeds, or to said useful plants or to the locus of said useful plants, a compound or composition of the invention.

The present invention also provides a method of selectively controlling grasses and/or weeds in crops of useful plants, which comprises applying to the useful plants or the locus thereof or to the area of cultivation a herbicidally effective amount of a compound of formula (I).

The term "herbicide" means a compound that controls or modifies the growth of plants. The term "effective amount" means the amount of such a compound or composition of such compounds that is capable of producing an effect of controlling or modifying the growth of a plant. The effects of control or modification include all deviations from natural development, e.g., kills, delays, leaf burns, albinism, dwarfing, etc. The term "plant" refers to all tangible parts of a plant, including seeds, seedlings, plantlets, roots, tubers, stems, stalks, leaves, and fruits. The term "locus" is intended to include soil, seeds and seedlings, as well as established plants (grassed habitat) and includes not only areas where weeds may have grown, but also areas where weeds have not yet emerged, and also areas for the planting of crops of useful plants. "planted area" includes the land on which crop plants have grown, as well as the land intended for planting such crop plants. The term "weeds" as used herein means any undesirable vegetation and thus includes not only important agronomic weeds as described below, but also volunteer crop plants.

Crops of useful plants in which the compositions according to the invention may be used include, but are not limited to, perennial crops such as citrus fruits, grapevines, nuts, oil palms, olives, pome fruits, stone fruits and rubber, and annual arable crops such as cereals (such as barley and wheat), cotton, oilseed rape, maize, rice, soya, sugar beet, sugar cane, sunflowers, ornamentals, switchgrass, turf and vegetables, especially cereals, maize and soya.

The grasses and weeds to be controlled can be both monocotyledonous species, such as agrostis, alopecurus, avena, brachiaria, bromus, tribulus, cyperus, digitaria, barnyard grass, kojima, lolium, monocrotonia, panicum, poa, cylindron, arrowhead, scirpus, setaria, sida and sorghum, and dicotyledonous species, such as kenaf, amaranthus, chenopodium, chrysanthemum, euphorbia, labra, ipomoea, kochia, eclipta, polygonum, rhodomyrtus, sinapis, solanum, chickweed, veronica, viola and xanthium.

The compounds of the invention may show tolerance to important crops including, but not limited to, alfalfa, barley, cotton, wheat, canola, sugar beet, corn (maize), sorghum, soybean, rice, oats, peanut, vegetables, tomato, potato, perennial plant crops including coffee, cocoa, oil palm, rubber, sugar cane, citrus, grapes, fruit trees, nut trees, bananas, plantains, pineapple, hops, tea and forests such as eucalyptus and conifer (e.g., loblolly pine), and turf varieties (e.g., prairie grass, san augustine grass (st. augustine grass), Kentucky grass and bermudagrass).

If desired, the compounds of the formula (I) according to the invention can also be used in combination with other active ingredients, for example other herbicides and/or insecticides and/or acaricides and/or nematicides and/or molluscicides and/or fungicides and/or plant growth regulators. These mixtures, and the use of these mixtures for controlling the growth of weeds and/or undesired vegetation, form yet further aspects of the invention. For the avoidance of doubt, inventive mixtures also include mixtures of two or more different compounds of formula (I). In particular, the present invention also relates to a composition according to the invention comprising, in addition to the compound of formula (I), at least one further herbicide.

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 invention may be prepared by the methods described herein, unless otherwise indicated. 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.

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, singlet), d (doublet ), t (triplet, triplet), q (quatet, quartet), m (multiplet ), br (broadpede, broad), dd (doublet of doublets, doublet), dt (doublet of triplets ). Coupling constants are expressed in hertz (Hz).

The mass spectrometry method used in the invention comprises the following steps: agilent 1260HPLC was used; agilent 6120 ESI.

Phase A: water (0.1% formic acid); phase B: acetonitrile (0.1% formic acid).

Gradient elution: 0-3min, 5-100% B; 3-6min, 100% B.

Flow rate: 0.6 mL/min.

Detection wavelength: 254 nm.

MS parameters: ESI positive scan, collision induced ionization: 70V.

Drying nitrogen gas: 12L/min, atomizing gas pressure: 40psi, gas temperature: at 350 ℃.

Taking a proper amount of sample, dissolving in 0.5mL of methanol, injecting a sample, and performing primary MS full scanning in a positive ESI mode to obtain an excimer peak [ M + H ]]⁺And (6) reading.

The following abbreviations are used throughout the present invention:

DMF: dimethylformamide, N-dimethylformamide; petroleum ether, PE: petroleum ether; NBS: n-bromosuccinimide; CCl₄: carbon tetrachloride; m-CPBA: m-chloroperoxybenzoic acid; EtOAc: ethyl acetate; AgF: silver fluoride.

Synthetic schemes

Synthesis scheme I

The compound of formula (II-1) can be prepared by the first synthetic scheme. The compound shown in the formula (a) is subjected to oxidation reaction under the action of an oxidant (such as m-CPBA) to obtain the compound shown in the formula (II-1).

Synthesis scheme two

The compound represented by the formula (II-2) can be prepared by the second synthesis scheme. Carrying out substitution reaction on the compound shown in the formula (b) to obtain a compound shown in a formula (c); the compound shown in the formula (c) is subjected to oxidation reaction under the action of an oxidant (such as m-CPBA and the like) to obtain the compound shown in the formula (II-2).

Synthesis scheme three

The compound represented by the formula (II-3) can be prepared by the third synthesis scheme. The compound shown in the formula (II-2) undergoes a substitution reaction to obtain a compound shown in a formula (II-3).

In the first to fourth synthesis schemes, R¹、R²、R³、R⁴And R¹¹Have the meaning as described in the present invention; r¹²Is C_1-4Alkyl, halo C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, halo C_2-4Alkenyl, halo C_2-4Alkynyl, C_3-6Cycloalkyl radical, C_3-6cycloalkyl-C_1-3Alkylene-, optionally substituted by 1, 2,3, 4 or 5 groups selected from halogen, hydroxy, cyano, nitro, C_1-4Alkyl, halo C_1-4Alkyl radical, C_1-4Alkoxy or halo C_1-4Phenyl substituted by alkoxy or optionally substituted by 1, 2,3, 4 or 5 substituents selected from halogen, hydroxy, cyano, nitro, C_1-4Alkyl, halo C_1-4Alkyl radical, C_1-4Alkoxy or halo C_1-4Alkoxy-substituted benzyl; r¹³And R¹⁴Each independently is halogen, cyano, nitro, hydroxy, carboxy, C_1-4Alkyl radical, C_2-4Alkenyl or C_2-4Alkynyl.

Examples

Intermediate 1: synthesis of 4-bromo-5, 5-dimethyl-3- (methylsulfonyl) -4, 5-dihydroisoxazole

Step 1: synthesis of 5, 5-dimethyl-3- (methylthio) -4, 5-dihydroisoxazole

3-chloro-5, 5-dimethyl-4, 5-dihydroisoxazole (50.00g,0.37mol) was dissolved in 100mL of DMF, and the mixture was stirred at 0 ℃ for 0.5 hour, and a 20% aqueous solution of sodium methanethiol (144.20g,0.41mol) was added dropwise to the above mixture, and after completion of the addition, the reaction was stirred at room temperature for 12 hours. To the reaction mixture was added 500mL of water and stirred, 200mL of ethyl acetate was extracted three times, the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, the filtrate was concentrated under reduced pressure, and the residue was separated by column chromatography (eluent: Petroleum ether) to give 34.90g of a yellow liquid, yield: 65.0 percent.

MS-ESI:m/z 146.0[M+H]⁺。

Step 2: synthesis of 4-bromo-5, 5-dimethyl-3- (methylthio) -4, 5-dihydroisoxazole

5, 5-dimethyl-3- (methylthio) -4, 5-dihydroisoxazole (15.20g,104.70mmol) and NBS (22.36g,126.00mmol) were dissolved in CCl₄To the mixture (100mL), the temperature was raised to 80 ℃ under nitrogen, azobisisobutyronitrile (1.72g,10.50mmol) was added to the mixture, and the reaction was continued for 4 hours. After the reaction solution was cooled to room temperature, it was filtered, the filter cake was washed with 30mL of CCl4 in three portions, the combined organic phases were freed of the solvent under reduced pressure, and the residue was separated by column chromatography (eluent: Petroleum ether) to give 14.80g of a yellow liquid, yield: and (3.5).

MS-ESI:m/z 224.0[M+H]⁺。

And step 3: synthesis of 4-bromo-5, 5-dimethyl-3- (methylsulfonyl) -4, 5-dihydroisoxazole

4-bromo-5, 5-dimethyl-3- (methylthio) -4, 5-dihydroisoxazole (6.40g,28.60mmol) was dissolved in dichloromethane (100mL), stirred at room temperature for 0.5h, m-CPBA (13.20g,57.36mmol) was added to the mixture at a mass content of 75%, and the reaction was continued for 5 h. Washed with 200mL of saturated aqueous sodium bisulfite and sodium bicarbonate, respectively, extracted with 100mL of dichloromethane, dried over anhydrous sodium sulfate, filtered, the filtrate concentrated under reduced pressure, and the residue separated by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 5/1) to give 4.80g of a white solid in yield: 65.7 percent.

MS-ESI:m/z 256.0[M+H]⁺。

Intermediate 2: synthesis of 4-fluoro-5, 5-dimethyl-3- (methylsulfonyl) -4, 5-dihydroisoxazole

Step 1: synthesis of 4-fluoro-5, 5-dimethyl-3- (methylthio) -4, 5-dihydroisoxazole

4-bromo-5, 5-dimethyl-3- (methylthio) -4, 5-dihydroisoxazole (9.40g,42.00mmol) was dissolved in acetonitrile (150mL), stirred at room temperature for 0.5h, AgF (10.66g,84.00mmol) was added to the above mixture, and the mixture was refluxed at 90 ℃ for 8h while being shielded from light. The reaction was cooled to room temperature, filtered through silica gel and the filtrate was spin dried to give the crude product 6.71g of a yellow solid, yield: 98.0 percent.

MS-ESI:m/z 164.0[M+H]⁺。

Step 2: synthesis of 4-fluoro-5, 5-dimethyl-3- (methylsulfonyl) -4, 5-dihydroisoxazole

4-fluoro-5, 5-dimethyl-3- (methylthio) -4, 5-dihydroisoxazole (6.71g,41.00mmol) was dissolved in dichloromethane (150mL), stirred at room temperature for 0.5h, m-CPBA (18.66g,81.08mmol) was added to the above mixture at a mass content of 75%, and the reaction was continued for 5 h. Washed with 200mL of saturated aqueous sodium bisulfite and sodium bicarbonate, respectively, extracted with 60mL of dichloromethane, the organic phase dried over anhydrous sodium sulfate, filtered, the filtrate concentrated under reduced pressure, and the residue separated by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 5/1) to give 3.00g of a white solid in yield: 37.5 percent.

MS-ESI:m/z 196.0[M+H]⁺。

Intermediate 3: synthesis of 5-ethyl-5-methyl-3- (methylsulfonyl) -4, 5-dihydroisoxazole

Step 1: synthesis of 5-ethyl-5-methyl-3- (methylthio) -4, 5-dihydroisoxazole

3-chloro-5-ethyl-5-methyl-4, 5-dihydroisoxazole (10.00g,67.80mmol) was dissolved in 50mL of DMF, and the mixture was stirred at 0 ℃ for 0.5h, and 20% aqueous sodium methanethiol (28.50g,81.30mmol) was added dropwise to the mixture, after which the reaction was stirred at room temperature for 12 h. Adding 100mL of water and 50mL of ethyl acetate into the reaction mixture, extracting for three times, combining organic phases, drying by anhydrous sodium sulfate, filtering, and spin-drying the filtrate to obtain 10.00g of yellow liquid, wherein the yield is as follows: 92.7 percent.

MS-ESI:m/z 160.3[M+H]⁺。

Step 2: synthesis of 5-ethyl-5-methyl-3- (methylsulfonyl) -4, 5-dihydroisoxazole

5-Ethyl-5-methyl-3- (methylthio) -4, 5-dihydroisoxazole (10.00g,62.80mmol) was dissolved in dichloromethane (100mL), stirred at room temperature for 0.5h, m-CPBA (28.90g,125.60mmol) was added to the above mixture at a mass content of 75% and the reaction was continued for 5 h. Filtration, washing of the filtrate with 100mL of saturated aqueous sodium bisulfite and sodium bicarbonate, extraction with 100mL of dichloromethane, combining the organic phases, drying over anhydrous sodium sulfate, filtration, concentration of the filtrate under reduced pressure, and separation of the residue by column chromatography (eluent: petroleumer/EtOAc (v/v) ═ 5/1) gave 8.00g of a yellow solid, yield: 66.6 percent.

MS-ESI:m/z 192.3[M+H]⁺。

Intermediate 4: synthesis of 5- (chloromethyl) -5-methyl-4, 5-dihydroisoxazol-3-ylisothiourea hydrobromide

Thiourea (6.00g,79.00mmol) was dissolved in acetonitrile (120mL) at room temperature, hydrobromic acid (47% by mass, 40.70g) was added dropwise thereto, and after stirring at room temperature for 2 hours, 3-chloro-5- (chloromethyl) -5-methyl-4, 5-dihydroisoxazole (23.80g,142.00mmol) was added dropwise to the above mixed solution, and the mixture was heated to 40 ℃ and stirred for 12 hours. The solvent was evaporated under reduced pressure and the resulting solid was recrystallized from acetonitrile to give 20.00g of a grey solid, yield: 87.9 percent.

Intermediate 5: synthesis of 5, 5-dimethyl-4, 5-dihydroisoxazol-3-ylisothiourea hydrobromide

Thiourea (6.00g,79.00mmol) was dissolved in acetonitrile (65mL) at room temperature, hydrobromic acid (48%, 10mL) was added dropwise thereto, and after stirring at room temperature for 1 hour, 3-chloro-5, 5-dimethyl-4, 5-dihydroisoxazole (12.60g,95.00mmol) was added dropwise to the above mixed solution, and the mixture was heated to 40 ℃ and stirred overnight. The solvent was evaporated under reduced pressure and the resulting solid was recrystallized from ethyl acetate to give 19.20g of a white solid, yield: 96.0 percent.

Example 1: synthesis of (4- (((5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl) sulfonyl) methyl) -2,3,5, 6-tetrafluorophenyl) methanol

Step 1: synthesis of (4- (bromomethyl) -2,3,5, 6-tetrafluorophenyl) methanol

2,3,5, 6-tetrafluoroterephthalyl alcohol (10.00g,47.60mmol) was dissolved in toluene (100mL) and stirred at room temperature, and hydrobromic acid (47.90g,0.59mol) was added to the above mixture, and then the mixture was heated to 110 ℃ and stirred for 1 hour. The solvent was removed under reduced pressure, quenched with 150mL of ice water, extracted three times with 200mL of ethyl acetate, the combined organic phases were freed of solvent under reduced pressure, and the residue was separated by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 10/1) to give 9.60g of a white solid in yield: 73.88 percent.

MS-ESI:m/z 272.9[M+H]⁺。

Step 2: synthesis of (4- (((5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl) thio) methyl) -2,3,5, 6-tetrafluorophenyl) methanol

(4- (bromomethyl) -2,3,5, 6-tetrafluorophenyl) methanol (0.40g,1.47mmol) and 5, 5-dimethyl-4, 5-dihydroisoxazol-3-ylisothiourea hydrobromide (0.45g,1.46mmol) were dissolved in acetonitrile (20mL), and after stirring at room temperature for 10min, potassium carbonate (0.81g,5.86mmol) was added to the above mixture, followed by further reaction for 12 h. Acetonitrile was removed, washed with 20mL water, extracted three times with 40mL ethyl acetate, the combined organic phases were freed of solvent under reduced pressure to give the crude product 0.47g of a pale yellow solid in yield: 99.2 percent.

MS-ESI:m/z 324.0[M+H]⁺。

And step 3: synthesis of (4- (((5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl) sulfonyl) methyl) -2,3,5, 6-tetrafluorophenyl) methanol

(4- (((5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl) thio) methyl) -2,3,5, 6-tetrafluorophenyl) methanol (0.47g,1.45mmol) was dissolved in dichloromethane (20mL), stirred at room temperature for 0.5h, and 75% m-CPBA (0.84g,3.63mmol) was added to the mixture and the reaction was continued for 6 h. Washed with 20mL of saturated aqueous sodium bisulfite and sodium bicarbonate, respectively, extracted with 30mL of dichloromethane, the combined organic phases are dried over anhydrous sodium sulfate, filtered, the filtrate is concentrated under reduced pressure, and the residue is separated by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 5/1) to give 0.25g of a white solid, yield: 48.4 percent.

MS-ESI:m/z 356.0[M+H]⁺；

¹H NMR(400MHz,CDCl₃)δ4.86(d,J＝6.4Hz,2H),4.77(s,2H),3.11(s,2H),2.03(t,J＝6.4Hz,1H),1.53(s,6H)。

Example 2: synthesis of (4- (((5- (chloromethyl) -5-methyl-4, 5-dihydroisoxazol-3-yl) sulfonyl) methyl) -2,3,5, 6-tetrafluorophenyl) methanol

Step 1: synthesis of (4- (((5- (chloromethyl) -5-methyl-4, 5-dihydroisoxazol-3-yl) thio) methyl) -2,3,5, 6-tetrafluorophenyl) methanol

(4- (bromomethyl) -2,3,5, 6-tetrafluorophenyl) methanol (0.40g,1.47mmol) and 5- (chloromethyl) -5-methyl-4, 5-dihydroisoxazol-3-ylisothiourea hydrobromide (0.51g,1.76mmol) were dissolved in acetonitrile (20mL) and after stirring at room temperature for 10min, potassium carbonate (0.81g,5.86mmol) was added to the above mixture and the reaction was continued for 12 h. The acetonitrile is removed, the residue is washed with 20mL of water, extracted three times with 40mL of ethyl acetate, the organic phases are combined and the solvent is removed under reduced pressure to give the crude product 0.52g of a pale yellow solid, yield: 99.3 percent.

MS-ESI:m/z 358.0[M+H]⁺。

Step 2: synthesis of (4- (((5- (chloromethyl) -5-methyl-4, 5-dihydroisoxazol-3-yl) sulfonyl) methyl) -2,3,5, 6-tetrafluorophenyl) methanol

(4- (((5- (chloromethyl) -5-methyl-4, 5-dihydroisoxazol-3-yl) thio) methyl) -2,3,5, 6-tetrafluorophenyl) methanol (0.52g,1.45mmol) was dissolved in dichloromethane (20mL), stirred at room temperature for 0.5h, 75% m-CPBA (0.84g,3.63mmol) was added to the mixture, and the reaction was stirred for an additional 6 h. Washed with 20mL of saturated aqueous sodium bisulfite and sodium bicarbonate, respectively, extracted with 30mL of dichloromethane, the combined organic phases are dried over anhydrous sodium sulfate, filtered, the filtrate is concentrated under reduced pressure, and the residue is separated by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 5/1) to give 0.37g of a white solid in yield: 65.0 percent.

MS-ESI:m/z 390.0[M+H]⁺；

¹H NMR(400MHz,CDCl₃)δ4.86(d,J＝6.2Hz,2H),4.78(s,2H),3.63(dd,J＝27.7,11.7Hz,2H),3.53(d,J＝17.8Hz,1H),3.12(d,J＝17.8Hz,1H),2.04(t,J＝6.6Hz,1H),1.64(s,3H)。

Example 3: synthesis of (4- (((4-bromo-5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl) sulfonyl) methyl) -2,3,5, 6-tetrafluorophenyl) methanol

Step 1: synthesis of (4- (((4-bromo-5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl) thio) methyl) -2,3,5, 6-tetrafluorophenyl) methanol

(4- (bromomethyl) -2,3,5, 6-tetrafluorophenyl) methanol (0.50g,1.83mmol) and thiourea (0.14g,1.83mmol) were dissolved in methanol (30mL) and stirred at room temperature for 5 hours, and then potassium carbonate (0.51g,3.66mmol) and 4-bromo-5, 5-dimethyl-3- (methylsulfonyl) -4, 5-dihydroisoxazole (0.47g,1.83mmol) were added to the mixture and the reaction was stirred for an additional 12 hours. The methanol was removed, the residue was washed with 30mL of water, extracted three times with 50mL of ethyl acetate, and the combined organic phases were freed of solvent under reduced pressure to give the crude product 0.44g of a white solid in yield: 60.0 percent.

MS-ESI:m/z 401.9[M+H]⁺。

Step 2: synthesis of (4- (((4-bromo-5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl) sulfonyl) methyl) -2,3,5, 6-tetrafluorophenyl) methanol

(4- (((4-bromo-5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl) thio) methyl) -2,3,5, 6-tetrafluorophenyl) methanol (0.44g,1.09mmol) was dissolved in dichloromethane (30mL), stirred at room temperature for 0.5h, and 75% m-CPBA (0.63g,2.73mmol) was added to the mixture and the reaction was continued for 5 h. Washed with 20mL of saturated aqueous sodium bisulfite and sodium bicarbonate, respectively, extracted with 50mL of dichloromethane, the organic phases are combined, dried over anhydrous sodium sulfate, filtered, the filtrate is concentrated under reduced pressure, and the residue is separated by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 5/1) to give 0.37g of a white solid in yield: 77.9 percent.

MS-ESI:m/z 433.9[M+H]⁺；

¹H NMR(400MHz,CDCl₃)δ5.14(s,1H),4.86(d,J＝5.8Hz,4H),2.04(t,J＝6.5Hz,1H),1.76(s,3H),1.48(s,3H)。

Example 4: synthesis of (2,3,5, 6-tetrafluoro-4- (((4-fluoro-5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl) sulfonyl) methyl) phenyl) methanol

Step 1: synthesis of (2,3,5, 6-tetrafluoro-4- (((4-fluoro-5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl) thio) methyl) phenyl) methanol

(4- (bromomethyl) -2,3,5, 6-tetrafluorophenyl) methanol (0.50g,1.83mmol) and thiourea (0.14g,1.83mmol) were dissolved in methanol (30mL), and after stirring at room temperature for 5 hours, potassium carbonate (0.51g,3.66mmol) and 4-fluoro-5, 5-dimethyl-3- (methylsulfonyl) -4, 5-dihydroisoxazole (0.36g,1.83mmol) were added to the above mixture, followed by further reaction for 12 hours. Methanol was distilled off under reduced pressure, the residue was washed with 30mL of water, extracted three times with 50mL of ethyl acetate, the organic phases were combined and the solvent was removed under reduced pressure to give the crude product 0.32g of a pale yellow liquid, yield: 51.6 percent.

MS-ESI:m/z 342.0[M+H]⁺。

Step 2: synthesis of (2,3,5, 6-tetrafluoro-4- (((4-fluoro-5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl) sulfonyl) methyl) phenyl) methanol

(2,3,5, 6-tetrafluoro-4- (((4-fluoro-5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl) thio) methyl) phenyl) methanol (0.30g,0.88mmol) was dissolved in dichloromethane (30mL), stirred at room temperature for 0.5h, and 75% m-CPBA (0.51g,2.20mmol) was added to the above mixture and the reaction was continued for 5 h. Washed with 20mL of saturated aqueous sodium bisulfite and sodium bicarbonate, respectively, extracted with 40mL of dichloromethane, the organic phases are combined, dried over anhydrous sodium sulfate, filtered, the filtrate is concentrated under reduced pressure, and the residue is separated by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 5/1) to give 0.20g of a white solid in yield: 60.9 percent.

MS-ESI:m/z 374.0[M+H]⁺；

¹H NMR(400MHz,CDCl₃)δ5.53(d,J＝56.7Hz,1H),4.85(d,J＝6.6Hz,2H),4.73(s,2H),2.02(t,J＝6.7Hz,1H),1.61(d,J＝3.5Hz,3H),1.42(s,3H)。

Example 5: synthesis of (4- (((5-ethyl-5-methyl-4, 5-dihydroisoxazol-3-yl) sulfonyl) methyl) -2,3,5, 6-tetrafluorophenyl) methanol

Step 1: synthesis of (4- (((5-ethyl-5-methyl-4, 5-dihydroisoxazol-3-yl) thio) methyl) -2,3,5, 6-tetrafluorophenyl) methanol

(4- (bromomethyl) -2,3,5, 6-tetrafluorophenyl) methanol (0.35g,1.28mmol) and thiourea (0.10g,1.28mmol) were dissolved in methanol (20mL) and stirred at room temperature for 5 hours, and then potassium carbonate (0.35g,2.56mmol) and 5-ethyl-5-methyl-3- (methylsulfonyl) -4, 5-dihydroisoxazole (0.25g,1.28mmol) were added to the above mixture to continue the reaction for 12 hours. The methanol was removed, the residue was washed with 30mL of water, extracted three times with 40mL of ethyl acetate, the organic phases were combined and the solvent was removed under reduced pressure to give the crude product 0.27g of a pale yellow liquid, yield: 62.4 percent.

MS-ESI:m/z 338.0[M+H]⁺。

Step 2: synthesis of (4- (((5-ethyl-5-methyl-4, 5-dihydroisoxazol-3-yl) sulfonyl) methyl) -2,3,5, 6-tetrafluorophenyl) methanol

(4- (((5-ethyl-5-methyl-4, 5-dihydroisoxazol-3-yl) thio) methyl) -2,3,5, 6-tetrafluorophenyl) methanol (0.27g,0.80mmol) was dissolved in dichloromethane (30mL), stirred at room temperature for 0.5h, and 75% m-CPBA (0.46g,2.00mmol) was added to the mixture and the reaction was continued for 5 h. Washed with 20mL of saturated aqueous sodium bisulfite and sodium bicarbonate, respectively, extracted with 40mL of dichloromethane, the organic phases are combined, dried over anhydrous sodium sulfate, filtered, the filtrate is concentrated under reduced pressure, and the residue is separated by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 5/1) to give 0.24g of a white solid in yield: 81.9 percent.

MS-ESI:m/z 370.0[M+H]⁺。

¹H NMR(400MHz,CDCl₃)δ4.85(d,J＝6.6Hz,2H),4.77(s,2H),3.16(d,J＝17.3Hz,1H),3.01(d,J＝17.3Hz,1H),2.08(t,J＝6.7Hz,1H),1.79(q,J＝7.4Hz,2H),1.48(s,3H),0.98(t,J＝7.5Hz,3H)。

Example 6: synthesis of 5, 5-dimethyl-3- ((2,3,5, 6-tetrafluoro-4- ((2,2, 2-trifluoroethoxy) methyl) benzyl) sulfonyl) -4, 5-dihydroisoxazole

Step 1: synthesis of 3- ((4- (bromomethyl) -2,3,5, 6-benzyl) thio) -5, 5-dimethyl-4, 5-dihydroisoxazole

(4- (((5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl) thio) methyl) -2,3,5, 6-tetrafluorophenyl) methanol (2.00g,6.19mmol) was dissolved in dichloromethane (60mL) at 0 ℃ and a solution of phosphorus tribromide (1.84g,6.80mmol) in dichloromethane (15mL) was slowly added dropwise to the mixture at a temperature of not higher than 5 ℃ and after the addition, the mixture was heated to room temperature and stirred for reaction for 2 hours. Quenching with 40mL of ice water, three extractions with 80mL of ethyl acetate, combining the organic phases and removing the solvent under reduced pressure, and separating the residue by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 10/1) to give 1.50g of a pale yellow liquid, yield: 62.9 percent.

MS-ESI:m/z 385.9[M+H]⁺。

Step 2: synthesis of 5, 5-dimethyl-3- ((2,3,5, 6-tetrafluoro-4- ((2,2, 2-trifluoroethoxy) methyl) benzyl) thio) -4, 5-dihydroisoxazole

3- ((4- (bromomethyl) -2,3,5, 6-benzyl) thio) -5, 5-dimethyl-4, 5-dihydroisoxazole (0.36g,0.93mmol) and cesium carbonate (0.61g,1.86mmol) were dissolved in acetonitrile (30mL), and after stirring at room temperature for 10min, trifluoroethanol (0.19g,1.86mmol) was added to the above mixture, followed by further reaction for 12 h. The acetonitrile is removed, the residue is washed with 20mL of water, extracted three times with 40mL of ethyl acetate, the organic phases are combined and the solvent is removed under reduced pressure, and the residue is separated by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 10/1) to give 0.18g of a pale yellow oil in yield: 47.3 percent.

MS-ESI:m/z 406.0[M+H]⁺。

And step 3: synthesis of 5, 5-dimethyl-3- ((2,3,5, 6-tetrafluoro-4- ((2,2, 2-trifluoroethoxy) methyl) benzyl) sulfonyl) -4, 5-dihydroisoxazole

5, 5-dimethyl-3- ((2,3,5, 6-tetrafluoro-4- ((2,2, 2-trifluoroethoxy) methyl) benzyl) thio) -4, 5-dihydroisoxazole (0.18g,0.44mmol) was dissolved in dichloromethane (20mL) at room temperature, and after adding 75% m-CPBA (0.26g,1.11mmol) to the above mixture, the reaction was continued for 6 h. Washed with 20mL of saturated aqueous sodium bisulfite and sodium bicarbonate, respectively, extracted with 30mL of dichloromethane, the organic phases are combined, dried over anhydrous sodium sulfate, filtered, the filtrate is concentrated under reduced pressure, and the residue is separated by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 5/1) to give 0.10g of a white solid in yield: 51.4 percent.

MS-ESI:m/z 438.0[M+H]⁺；

¹H NMR(400MHz,CDCl₃)δ4.82(s,2H),4.79(s,2H),3.93(q,J＝8.5Hz,2H),3.11(s,2H),1.53(s,6H)。

Example 7: synthesis of 3- ((4- (butoxymethyl) -2,3,5, 6-tetrafluorobenzyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

Step 1: synthesis of 3- ((4- (bromomethyl) -2,3,5, 6-tetrafluorobenzyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

(4- (((5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl) sulfonyl) methyl) -2,3,5, 6-tetrafluorophenyl) methanol (1.00g,2.81mmol) was dissolved in dichloromethane (40mL), and the mixture was stirred at 0 ℃ to slowly drop a solution of phosphorus tribromide (0.84g,3.10mmol) in dichloromethane (15mL), the temperature was controlled to 5 ℃ or lower, and after dropping, the mixture was warmed to room temperature and stirred for 2 hours. Quenching with 40mL of ice water, three extractions with 60mL of ethyl acetate, combining the organic phases, removing the solvent under reduced pressure, and separating the residue by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 10/1) to give 0.81g of a pale yellow liquid, yield: 68.0 percent.

MS-ESI:m/z 417.9[M+H]⁺。

Step 2: synthesis of 3- ((4- (butoxymethyl) -2,3,5, 6-tetrafluorobenzyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

3- ((4- (bromomethyl) -2,3,5, 6-tetrafluorobenzyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole (0.30g,0.71mmol) was dissolved in n-butanol (20mL), stirred at room temperature, and after adding iron sulfate heptahydrate (2.01g,7.10mmol) to the above mixture, the mixture was heated to reflux and allowed to react for 12 h. Washed with 40mL of water, extracted three times with 60mL of ethyl acetate, the organic phases are combined, the solvent is removed under reduced pressure, and the residue is separated by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 5/1) to give 0.10g of a white solid in yield: 33.8 percent.

MS-ESI:m/z 412.1[M+H]⁺。

¹H NMR(400MHz,CDCl₃)δ4.77(s,2H),4.62(s,2H),3.52(t,J＝6.5Hz,2H),3.11(s,2H),1.59(dd,J＝8.3,5.3Hz,2H),1.53(s,6H),1.37(dq,J＝14.7,7.3Hz,2H),0.91(t,J＝7.4Hz,3H)。

Example 8: synthesis of 3- ((4- ((cycloalkyloxy) methyl) -2,3,5, 6-tetrafluorobenzyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

3- ((4- (bromomethyl) -2,3,5, 6-tetrafluorobenzyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole (0.43g,1.03mmol) was dissolved in cyclopentanol (20mL), stirred at room temperature for 0.5h, and after adding iron sulfate heptahydrate (2.88g,10.3mmol) to the above mixture, the reaction was continued for 12h by warming to reflux. Washed with 40mL of water and extracted three times with 60mL of ethyl acetate, the combined organic phases are freed of solvent under reduced pressure, and the residue is separated by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 5/1) to give 0.16g of a white solid in yield: 36.7 percent.

MS-ESI:m/z 424.1[M+H]⁺；

¹H NMR(400MHz,CDCl₃)δ4.76(s,2H),4.57(s,2H),4.06–4.01(m,1H),3.11(s,2H),1.76–1.69(m,6H),1.58–1.51(m,2H),1.52(s,6H)。

Example 9: synthesis of 5, 5-dimethyl-3- ((2,3,5, 6-tetrafluoro-4- (methoxymethyl) benzyl) sulfonyl) -4, 5-dihydroisoxazole

Step 1: synthesis of 1- (bromomethyl) -2,3,5, 6-tetrafluoro-4- (methoxymethyl) benzene

Dissolving 4-methoxymethyl-2, 3,5, 6-tetrafluorobenzyl alcohol (2.00g,8.92mmol) in dichloromethane (60mL), stirring at 0 ℃, then slowly dripping a solution of phosphorus tribromide (2.66g,9.81mmol) in dichloromethane (25mL) into the mixed solution, controlling the temperature to be not higher than 5 ℃, after finishing dripping, heating to room temperature, and stirring for reaction for 2 hours. Quenching with 60mL of ice water, three extractions with 80mL of ethyl acetate, combining the organic phases and removing the solvent under reduced pressure, and separating the residue by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 10/1) to yield 1.97g of a pale yellow solid, yield: 76.2 percent.

MS-ESI:m/z 286.9[M+H]⁺。

Step 2: synthesis of 5, 5-dimethyl-3- ((2,3,5, 6-tetrafluoro-4- (methoxymethyl) benzyl) thio) -4, 5-dihydroisoxazole

1- (bromomethyl) -2,3,5, 6-tetrafluoro-4- (methoxymethyl) benzene (0.50g,1.74mmol) and 5, 5-dimethyl-4, 5-dihydroisoxazol-3-ylisothiourea hydrobromide (0.53g,2.09mmol) were dissolved in acetonitrile (30mL), and after stirring at room temperature for 10min, potassium carbonate (0.96g,6.97mmol) was added to the above mixture, followed by further reaction for 12 h. Acetonitrile was removed, washed with 20mL water, extracted three times with 40mL ethyl acetate, the combined organic phases were freed of solvent under reduced pressure to give the crude product 0.46g of a yellow solid, yield: 78.9 percent.

MS-ESI:m/z 338.0[M+H]⁺。

And step 3: synthesis of 5, 5-dimethyl-3- ((2,3,5, 6-tetrafluoro-4- (methoxymethyl) benzyl) sulfonyl) -4, 5-dihydroisoxazole

5, 5-dimethyl-3- ((2,3,5, 6-tetrafluoro-4- (methoxymethyl) benzyl) thio) -4, 5-dihydroisoxazole (0.46g,1.36mmol) was dissolved in dichloromethane (30mL), stirred at room temperature for 0.5h, and 75% m-CPBA (0.78g,3.41mmol) was added to the above mixture and the reaction was continued for 6 h. Washed with 20mL of saturated aqueous sodium bisulfite and sodium bicarbonate, respectively, extracted with 40mL of dichloromethane, the organic phase dried over anhydrous sodium sulfate, filtered, the filtrate concentrated under reduced pressure to remove the solvent, and the residue separated by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 5/1) to give 0.30g of a white solid, yield: and 59.5 percent.

MS-ESI:m/z 370.0[M+H]⁺；

¹H NMR(400MHz,CDCl₃)δ4.77(s,2H),4.60(s,2H),3.42(s,3H),3.11(s,2H),1.53(s,6H)。

Example 10: synthesis of 5- (chloromethyl) -5-methyl-3- ((2,3,5, 6-tetrafluoro-4- (methoxymethyl) benzyl) sulfonyl) -4, 5-dihydroisoxazole

Step 1: synthesis of 5- (chloromethyl) -5-methyl-3- ((2,3,5, 6-tetrafluoro-4- (methoxymethyl) benzyl) thio) -4, 5-dihydroisoxazole

1- (bromomethyl) -2,3,5, 6-tetrafluoro-4- (methoxymethyl) benzene (0.50g,1.74mmol) and 5- (chloromethyl) -5-methyl-4, 5-dihydroisoxazol-3-ylisothiourea hydrobromide (0.60g,2.09mmol) were dissolved in acetonitrile (30mL), and after stirring at room temperature for 10min, potassium carbonate (0.96g,6.97mmol) was added to the above mixture, followed by further reaction for 12 h. The acetonitrile was removed, washed with 20mL of water, extracted three times with 40mL of ethyl acetate, and the combined organic phases were freed of solvent under reduced pressure to give the crude product 0.48g of a yellow oil, yield: 74.1 percent.

MS-ESI:m/z 372.0[M+H]⁺。

Step 2: synthesis of 5- (chloromethyl) -5-methyl-3- ((2,3,5, 6-tetrafluoro-4- (methoxymethyl) benzyl) sulfonyl) -4, 5-dihydroisoxazole

5- (chloromethyl) -5-methyl-3- ((2,3,5, 6-tetrafluoro-4- (methoxymethyl) benzyl) thio) -4, 5-dihydroisoxazole (0.48g,1.29mmol) was dissolved in dichloromethane (40mL), stirred at room temperature for 0.5h, to the above mixture 75% m-CPBA (0.74g,3.23mmol) was added and the reaction was continued for 6 h. Washed with 20mL of saturated aqueous sodium bisulfite and sodium bicarbonate, respectively, extracted with 40mL of dichloromethane, the organic phase dried over anhydrous sodium sulfate, filtered, the filtrate concentrated under reduced pressure to remove the solvent, and the residue separated by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 5/1) to give 0.40g of a white solid, yield: 76.6 percent.

MS-ESI:m/z 404.0[M+H]⁺；

¹H NMR(400MHz,CDCl₃)δ4.79(s,2H),4.60(s,2H),3.63(dd,J＝27.7,11.7Hz,2H),3.53(d,J＝17.8Hz,1H),3.42(s,3H),3.11(d,J＝17.8Hz,1H),1.64(s,3H)。

Example 11: synthesis of 4-bromo-5, 5-dimethyl-3- ((2,3,5, 6-tetrafluoro-4- (methoxymethyl) benzyl) sulfonyl) -4, 5-dihydroisoxazole

Step 1: synthesis of 4-bromo-5, 5-dimethyl-3- ((2,3,5, 6-tetrafluoro-4- (methoxymethyl) benzyl) thio) -4, 5-dihydroisoxazole

After 1- (bromomethyl) -2,3,5, 6-tetrafluoro-4- (methoxymethyl) benzene (0.26g,0.90mmol) and thiourea (70mg,0.90mmol) were dissolved in methanol (30mL) and stirred at room temperature for 5 hours, potassium carbonate (0.25g,1.81mmol) and 4-bromo-5, 5-dimethyl-3- (methylsulfonyl) -4, 5-dihydroisoxazole (0.23g,0.95mmol) were added to the above mixture, and the reaction was continued for 12 hours. Methanol was removed, washed with 30mL water, extracted three times with 50mL ethyl acetate, the organic phases were combined and the solvent was removed under reduced pressure to give a crude 0.18g of a pale yellow oil in yield: 49.4 percent.

MS-ESI:m/z 415.9[M+H]⁺。

Step 2: synthesis of 4-bromo-5, 5-dimethyl-3- ((2,3,5, 6-tetrafluoro-4- (methoxymethyl) benzyl) sulfonyl) -4, 5-dihydroisoxazole

4-bromo-5, 5-dimethyl-3- ((2,3,5, 6-tetrafluoro-4- (methoxymethyl) benzyl) thio) -4, 5-dihydroisoxazole (0.18g,0.43mmol) was dissolved in dichloromethane (30mL), stirred at room temperature for 0.5h, and 75% m-CPBA (0.25g,1.08mmol) was added to the above mixture and the reaction was continued for 5 h. Washed with 20mL of saturated aqueous sodium bisulfite and sodium bicarbonate, respectively, extracted with 50mL of dichloromethane, the organic phase dried over anhydrous sodium sulfate, filtered, the filtrate concentrated under reduced pressure, and the residue separated by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 5/1) to give 0.10g of a white solid in yield: 51.5 percent.

MS-ESI:m/z 447.9[M+H]⁺；

¹H NMR(400MHz,CDCl₃)δ5.14(s,1H),4.87(s,2H),4.60(s,2H),3.41(s,3H),1.76(s,3H),1.48(s,3H).

Example 12: synthesis of 3- ((difluoro (2,3,5, 6-tetrafluoro-4- (methoxymethyl) phenyl) methyl) sulfonyl) -5, 5-dimethyl-4, 5-dihydroisoxazole

5, 5-dimethyl-3- ((2,3,5, 6-tetrafluoro-4- (methoxymethyl) benzyl) sulfonyl) -4, 5-dihydroisoxazole (0.42g,1.14mmol) was dissolved in tetrahydrofuran (20mL), and the mixture was stirred at-78 ℃ for 0.5h, a solution of sodium bis (trimethylsilyl) amide in tetrahydrofuran (2.27mL,2.27mmol) was added dropwise to the above mixture, and after stirring for 10min, N-fluorobisbenzenesulfonamide (0.89g,2.84mmol) was added to continue the reaction for 1.5 h. The reaction mixture was quenched by adding saturated aqueous ammonium chloride solution, washed with 30mL of water, extracted with 50mL of ethyl acetate, dried over anhydrous sodium sulfate, filtered, the filtrate was concentrated under reduced pressure, and the residue was separated by column chromatography (eluent: Petroleum ether/EtOAc (v/v) ═ 4/1) to give 0.20g of a white solid, yield: 43.4 percent.

MS-ESI:m/z 406.0[M+H]⁺；

¹H NMR(400MHz,CDCl₃)δ4.62(s,2H),3.43(s,3H),3.20(s,2H),1.57(s,6H)。

Examples of Activity test

Compound preparation: weighing a certain mass of original drug by an analytical balance (0.0001g), dissolving by DMF containing 1 wt% of Tween-80 emulsifier to prepare 1.0 wt% of mother liquor, and then diluting by distilled water for later use.

The test method comprises the following steps: the test target of the potting method is barnyard grass. A flowerpot with the inner diameter of 7.5cm is taken, composite soil (vegetable garden soil: seedling raising matrix, 1:2, v/v) is filled to 3/4 positions, the weed target is directly sown (the bud ratio is more than or equal to 85 percent), soil is covered by 0.2cm, and water is added to keep the soil moist for 24 hours for later use. The compounds prepared in examples were applied to an automatic spray tower (model: 3WPSH-700E) at a predetermined dose (e.g., 200g a.i./ha, 100g a.i./ha, etc.), respectively, and after the soil surface solution was dried, the soil was transferred to a greenhouse for cultivation, and the preemergence herbicidal activity (%) against weeds was investigated 25 days later.

Activity evaluation: the inhibition (%) of the emergence of weeds by the compounds was investigated visually and recorded.

Evaluation criteria:

rate of emergence inhibition (%)	Evaluation of herbicidal Activity
		0-40	Difference (D)
41-70	In general
		71-90	Is preferably used
91-100	Is very good

The test results are shown in table 1:

TABLE 1 Pre-emergence herbicidal Activity of the compounds according to the invention at a dose of 200g a.i./ha

Examples	Barnyard grass
		Example 1	95
Example 8	85
		Example 9	100
Example 10	100
		Example 11	85
Example 12	100

The test results show that under the dosage of 200g of a.i./ha, the weeding activities of the example 1, the example 8, the example 9, the example 10, the example 11 and the example 12 on the barnyard grass are 95, 85, 100, 85 and 100 in sequence, and the weeding composition has better emergence inhibition rate on the barnyard grass; the pre-emergence herbicidal activity of example 6 and example 7 on barnyard grass at a dose of 200g of a.i./ha is 60 and 50 in sequence, and the emergence inhibition rate of the compound on barnyard grass is general; while example 9, example 10, example 12 still had excellent activity on barnyard grass at low doses, as shown in table 2:

TABLE 2 Pre-emergence herbicidal Activity of the compounds according to the invention at a dose of 100g a.i./ha

Examples	Barnyard grass
		Example 9	100
Example 10	90
		Example 12	100
Fenoxasulfone	50

Wherein the Fenoxasulfone is compound 47 shown in Table 1 in JP2004002324A, and is prepared according to the method described in the specification, and the structure of the Fenoxasulfone is as follows:

crop safety testing

The test method comprises the following steps: the test target of the potting method is rice. A flowerpot with the inner diameter of 7.5cm is taken, composite soil (vegetable garden soil: seedling raising matrix, 1:2, v/v) is filled to 3/4, a crop target is directly sown (the bud rate is more than or equal to 85%), soil is covered by 0.2cm, and water is added to keep the soil moist for 24 hours for later use. After the compounds are applied to an automatic spray tower (model: 3WPSH-700E) according to the specified dosage, transferring the liquid medicine on the soil surface to a greenhouse for culture after the liquid medicine is dried, and checking the phytotoxicity (%) of crops after 25 days; where 0 means no damage or normal growth process and 100 means no emergence or at least complete death of the aerial parts.

The test results are shown in table 3.

TABLE 3 safety of the compounds of the invention on rice at a dose of 200g a.i./ha

The results in Table 3 show that the compounds of the present invention are very safe for rice at 200g a.i./ha.

The compound has good control effect on weeds, the control effect of partial compounds on weeds is superior to that of commercial medicaments, and in addition, the compound is safe to crops and has good application prospect.

Claims

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

wherein:

n is 0, 1 or 2;

2. The compound of claim 1, wherein:

R¹and R²Each independently hydrogen, halogen, cyano, nitro, hydroxy, carboxy, C_1-4Alkyl, halo C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, C_3-6Cycloalkyl radical, C_3-6cycloalkyl-C_1-3Alkylene-, C_1-4alkoxy-C_1-3Alkylene-or C_1-4alkylthio-C_1-3Alkylene-;

or R¹、R²And the carbon atom to which they are attached form C_3-6A cycloalkyl group;

3. The compound of claim 2, wherein:

R¹and R²Each independently is hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, carboxyl, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂Cl、-CH₂F、-CHF₂、-CF₃、-CH₂CHF₂、-CH＝CH₂、-CH₂CH＝CH₂、-CH₂CH₂CH＝CH₂、-CH₂CH＝CHCH₃、-C≡CH、-CH₂-C≡CH、-CH₂-C≡CCH₃、-CH₂CH₂-C ≡ CH, cyclopropyl or cyclopropyl-CH₂-；

4. The compound of claim 1, wherein:

R⁵and R⁶Each independently hydrogen, halogen, cyano, nitro, hydroxy, carboxy, C_1-4Alkyl radical, C_2-4Alkenyl or C_2-4Alkynyl.

5. The compound of claim 4, wherein:

R⁵and R⁶Each independently is hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, hydroxyl, carboxyl, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH＝CH₂、-CH₂CH＝CH₂-C.ident.CH or-CH₂-C≡CH。

6. The compound of claim 1, wherein:

R¹¹is hydrogen, C_1-4Alkyl, halo C_1-4Alkyl radical, C_2-4Alkenyl radical, C_2-4Alkynyl, halo C_2-4Alkenyl, halo C_2-4Alkynyl, C_3-6Cycloalkyl radical, C_3-6cycloalkyl-C_1-3Alkylene-, optionally substituted by 1, 2,3, 4 or 5 groups selected from halogen, hydroxy, cyano, nitro, C_1-4Alkyl, halo C_1-4Alkyl radical, C_1-4Alkoxy or halo C_1-4Phenyl substituted by alkoxy or optionally substituted by 1, 2,3, 4 or 5 substituents selected from halogen, hydroxy, cyano, nitro, C_1-4Alkyl, halo C_1-4Alkyl radical, C_1-4Alkoxy or halo C_1-4Alkoxy-substituted benzyl.

7. The compound of claim 6, wherein:

R¹¹is hydrogen, -CH₃、-CH₂CH₃、-CH₂CH₂CH₃、-CH(CH₃)₂、-CH₂CH₂CH₂CH₃、-CH₂Cl、-CH₂F、-CHF₂、-CF₃、-CH₂CF₃、-CH₂CH₂CF₃、-CH＝CH₂、-CH₂CH＝CH₂、-CH₂CH₂CH＝CH₂、-CH₂CH＝CHCH₃、-C≡CH、-CH₂-C≡CH、-CH₂-C≡CCH₃、-CH₂CH₂-C ≡ CH, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropyl-CH₂-, cyclobutyl-CH₂-, cyclopentyl-CH₂-, cyclohexyl-CH₂-, optionally substituted by 1, 2,3, 4 or 5 substituents selected from fluorine, chlorine, bromine, iodine, hydroxy, cyano, nitro, -CH₃、-CF₃、-OCH₃or-OCF₃Substituted phenyl or optionally substituted by 1, 2,3, 4 or 5 substituents selected from fluoro, chloro, bromo, iodo, hydroxy, cyano, nitro, -CH₃、-CF₃、-OCH₃or-OCF₃A substituted benzyl group.

8. The compound according to any one of claims 1 to 7, which is a compound having one of the following structures or a stereoisomer, a nitroxide or a salt thereof of a compound having one of the following structures:

9. a composition comprising a compound according to any one of claims 1 to 8 and at least one agriculturally suitable auxiliary.

10. A compound according to any one of claims 1 to 8 or a composition according to claim 9 for use as a herbicide in agriculture.