WO2025223400A1 - Picolinamide compound and use thereof - Google Patents

Abstract

The present invention relates to the technical field of pesticides, and specifically relates to a picolinamide compound and a use thereof. The compound is as shown in formula (I), wherein W₁ is O or S; R₁ is hydrogen, alkyl, alkenyl, or alkynyl, etc.; R₂ is hydrogen, alkyl, alkenyl, or alkynyl, etc.; R₃ is hydrogen, halogen, alkyl, alkenyl, or alkynyl, etc.; R₄ is alkyl; X₁, X₂, X₃, and X₄ are independently hydrogen, halogen, etc. The compound has an excellent bactericidal effect.

Description

Pyridine amide compounds and their applications Technical Field

This invention belongs to the field of pesticide technology, specifically relating to a pyridine amide compound and its application.

Background Technology

In recent years, due to the long-term use of pest control agents, such as insecticides or fungicides, pests have acquired resistance, becoming difficult to control with existing pesticides or fungicides. Furthermore, some known pest control agents are highly toxic, or some damage ecosystems through their long-term persistence. In this context, despite the existence of numerous known fungicides, such as WO2016109302A1 which discloses pyridine amide compounds and their applications as fungicides, there is still a need to develop new pest control agents with low toxicity and low residue.

Summary of the Invention

To address the aforementioned problems in the prior art, this invention provides a pyridine amide compound and its applications. The compound exhibits excellent bactericidal activity.

The technical solution adopted in this invention is as follows:

A pyridine amide compound as shown in Formula I:

Where _W1 is O or S;

R ₁ is hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, or cycloalkylalkyl;

R ₂ is hydrogen, alkyl, alkenyl, _{alkynyl , cycloalkyl, cycloalkylalkyl} , _alkyl , alkenyl, alkenyl, alkenyl, alkenyl, alkenyl, alkenyl, alkenyl, alkenyl, alkenyl, _alkenyl , _alkenyl , alkenyl, _alkenyl , alkenyl _{, alkenyl , alkenyl , alkenyl , alkenyl , alkenyl} , _alkenyl , _alkenyl , _{trialkylsilyl} , aryl, _{alkenyl ...}

R ₃ is hydrogen, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, alkyl, alkenyl, alkenyl, or alkynyl, alkenyl, aryl, -O(CO)R ₁₁ , -N(R ₁₁ ) ₂ , -OR ₁₁ , -S(O) _n R ₁₁ , -O(CO)R ₁₁ or -O(CO)OR ₁₁ , alkyl, alkenyl or alkynyl, aryl, heterocyclic, -OR ₁₁ , -O(CO)R ₁₁ , -S(O) _n R ₁₁ or -N(R ₁₁ ) ₂ ...alkyl, alkenyl or alkynyl, alkyl, alkenyl or alkynyl, alkyl, alkenyl or alkynyl, alkyl, alkenyl or

_R4 is an alkyl group;

R ₁₁ is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclic, or an alkyl, alkenyl, or alkynyl group substituted by at least one group selected from halogen, -OR, -O(CO)R, -(CO)OR, -(CO)O-alkylene-OR, -S(O) _nR , -ON=C(R) ₂ , cycloalkyl, aryl, or heterocyclic.

n is 0, 1, or 2;

_X1 , _X2 , _X3 , and _X4 are, independently, hydrogen, halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cyano, nitro, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, -OR, -SR, -SOR, -( _SO2 )R, -N(R) ₂ , -(CO)R, or -(CO)N(R) ₂ ;

The aforementioned "cycloalkyl", "heterocyclic" or "aryl" may optionally be replaced by at least one group selected from oxo, halogen, cyano, nitro, alkyl, alkenyl, ynyl, cycloalkyl, haloalkyl, haloalkenyl, haloynyl, -OR, -SR, -(CO)R, -(CO)OR, N(R) ₂ , -(CO)N(R) ₂ , -(CS)N(R) ₂ , -(SO)R or -( _SO2 )R;

R independently represents hydrogen, alkyl, alkenyl, alkynyl, alkyl, alkenyl or alkynyl substituted with at least one group selected from halogen, hydroxyl, alkoxy, cyano or alkoxycarbonyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, phenyl or phenyl substituted with at least one group selected from halogen, cyano, nitro, alkyl, haloalkyl, alkoxycarbonyl, alkylthio, alkylsulfonyl, alkoxy or haloalkoxy.

In one specific embodiment, _R1 is hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, halo-C1-C8 alkyl, halo-C2-C8 alkenyl, halo-C2-C8 alkynyl, C3-C8 cycloalkyl or C3-C8 cycloalkyl-C1-C8 alkyl.

_R2 is hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 ynyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl, C1-C8 alkyl, and is a _C1 -C8 alkyl, _C2 - _C8 alkenyl, or C2- _C8 ynyl group substituted with at least _one of the following substituents: halogen, tri-C1-C8 alkylsilyl, aryl, aryl, -O(CO) _R11 , -N( _R11 ), -OR11, -S(O) _nR11 , _-COR11 , -(CO) _OR11 , -O(CO)N( _{R11 ) 2} , or -O(CO) _{OR11 .} ) ₂ , -(CO)N(R ₁₁ )(OR ₁₁ ), -S(O) _n R ₁₁ or -SO ₂ N(R ₁₁ ) ₂ ;

R ₃ is a C1-C8 alkyl, C2-C8 alkenyl, C2-C8 ynyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl-C1-C8 alkyl, substituted with at least one of the following: halogen, tri-C1-C8 alkylsilyl, heterocyclic, aryl, -O(CO)R ₁₁ , -N(R _{11 ) 2} , _{-OR 11} , -S(O _{) n} R ₁₁ , -O(CO) _{R 11} or -O(CO) _{OR 11 ;}

_R4 is a C1-C8 alkyl group;

R ₁₁ is, independently, hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 ynyl, C3-C8 cycloalkyl, aryl, heterocyclic, or a C1-C8 alkyl, C2-C8 alkenyl, or C2-C8 ynyl group substituted with at least one group selected from halogen, -OR, -O(CO)R, -(CO)OR, -(CO)O-(C1-C8 alkylene)-OR, -S(O) _nR , -ON=C(R) ₂ , C3-C8 cycloalkyl, aryl, or heterocyclic.

_X1 , _X2 , _X3 , and _X4 are, independently, hydrogen, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, halo-C1-C8 alkyl, halo-C2-C8 alkenyl, halo-C2-C8 alkynyl, cyano, nitro, C3-C8 cycloalkyl, C3-C8 cycloalkyl-C1-C8 alkyl, aryl, aryl-C1-C8 alkyl, heterocyclic, heterocyclic-C1-C8 alkyl, -OR, -SR, -SOR, -( _SO2 )R, -N(R) ₂ , -(CO)R, or -(CO)N(R) ₂ ;

The aforementioned “C3-C8 cycloalkyl”, “heterocyclic” or “aryl” may optionally be replaced by at least one group selected from oxo, halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 ynyl, C3-C8 cycloalkyl, halo-C1-C8 alkyl, halo-C2-C8 alkenyl, halo-C2-C8 ynyl, -OR, -SR, -(CO)R, -(CO)OR, -N(R) ₂ , -(CO)N(R) ₂ , -(CS)N(R) ₂ , -(SO)R or -( _SO2 )R;

R independently represents hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 alkyl, C2-C8 alkenyl or C2-C8 alkynyl substituted with at least one group selected from halogen, hydroxyl, C1-C8 alkoxy, cyano or C1-C8 alkoxycarbonyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl C1-C8 alkyl, C3-C8 cycloalkenyl, C3-C8 cycloalkenyl C1-C8 alkyl, phenyl or phenyl substituted with at least one group selected from halogen, cyano, nitro, C1-C8 alkyl, halo-C1-C8 alkyl, C1-C8 alkoxycarbonyl, C1-C8 alkylthio, C1-C8 alkylsulfonyl, C1-C8 alkoxy or halo-C1-C8 alkoxy.

In another specific embodiment, _R1 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo-C1-C6 alkyl, halo-C2-C6 alkenyl, halo-C2-C6 alkynyl, C3-C6 cycloalkyl or C3-C6 cycloalkyl-C1-C6 alkyl.

_R2 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl, C1-C6 alkyl, and is a _C1 -C6 alkyl, _C2 - _C6 alkenyl, or C2- _C6 ynyl group substituted with at least _one of the following substituents: halogen, tri-C1-C6 alkylsilyl, aryl, aryl, -O(CO) _R11 , -N( _R11 ), -OR11, -S(O) _nR11 , _-COR11 , -(CO) _OR11 , -O(CO)N( _{R11 ) 2} , or -O(CO) _{OR11 .} ) ₂ , -(CO)N(R ₁₁ )(OR ₁₁ ), -S(O) _n R ₁₁ or -SO ₂ N(R ₁₁ ) ₂ ;

R ₃ is a C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl-C1-C6 alkyl group substituted with at least one of the following: halogen, tri-C1-C6 alkylsilyl, heterocyclic, aryl, -O(CO)R ₁₁ , -N(R _{11 ) 2} , _{-OR 11} , -S(O _{) n} R ₁₁ , -O(CO) _{R 11} or -O(CO) _{OR 11 ;}

_R4 is a C1-C6 alkyl group;

R ₁₁ is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C6 cycloalkyl, aryl, heterocyclic, or a C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 ynyl group substituted with at least one group selected from halogen, -OR, -O(CO)R, -(CO)OR, -(CO)O-(C1-C6 alkylene)-OR, -S(O) _nR , -ON=C(R) ₂ , C3-C6 cycloalkyl, aryl, or heterocyclic.

_X1 , _X2 , _X3 , and _X4 are, independently, hydrogen, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogenated C1-C6 alkyl, halogenated C2-C6 alkenyl, halogenated C2-C6 alkynyl, cyano, nitro, C3-C6 cycloalkyl, C3-C6 cycloalkyl C1-C6 alkyl, aryl, aryl C1-C6 alkyl, heterocyclic, heterocyclic C1-C6 alkyl, -OR, -SR, -SOR, -( _SO2 )R, -N(R) ₂ , -(CO)R, or -(CO)N(R) ₂ ;

The aforementioned “C3-C6 cycloalkyl”, “heterocyclic” or “aryl” may optionally be replaced by at least one group selected from oxo, halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C6 cycloalkyl, halo-C1-C6 alkyl, halo-C2-C6 alkenyl, halo-C2-C6 ynyl, -OR, -SR, -(CO)R, -(CO)OR, -N(R) ₂ , -(CO)N(R) ₂ , -(CS)N(R) ₂ , -(SO)R or -( _SO2 )R;

R independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl substituted with at least one group selected from halogen, hydroxyl, C1-C6 alkoxy, cyano or C1-C6 alkoxycarbonyl, C3-C6 cycloalkyl, C3-C6 cycloalkylC1-C6 alkyl, C3-C6 cycloalkenyl, C3-C6 cycloalkenylC1-C6 alkyl, phenyl or phenyl substituted with at least one group selected from halogen, cyano, nitro, C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxycarbonyl, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 alkoxy or halo-C1-C6 alkoxy.

In another specific embodiment, R ₁₁ is independently hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, aryl, heterocyclic, arylalkyl or heterocyclic alkyl.

In another specific embodiment, R ₁₁ is independently hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, halo-C1-C8 alkyl, halo-C2-C8 alkenyl, halo-C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl-C1-C8 alkyl, aryl, heterocyclic, aryl-C1-C8 alkyl, or heterocyclic-C1-C8 alkyl.

In another specific embodiment, R ₁₁ is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo-C1-C6 alkyl, halo-C2-C6 alkenyl, halo-C2-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl-C1-C6 alkyl, aryl, heterocyclic, aryl-C1-C6 alkyl, or heterocyclic-C1-C6 alkyl.

In the definitions of compounds shown in the above general formulas and in all the following structural formulas, the technical terms used, whether alone or in compound terms, represent the following substituents: alkyl groups having more than two carbon atoms can be straight-chain or branched. For example, in the compound term "arylalkyl," the alkyl group can be _-CH₂- , _-CH₂CH₂- , -CH( _CH₃ )-, -C( _CH₃ ) _{₂- ,} etc. Alkyl groups are, for example, C1 alkyl-methyl; C2 alkyl-ethyl; C3 alkyl-propyl such as n-propyl or isopropyl; C4 alkyl-butyl such as n-butyl, isobutyl, tert-butyl, or 2-butyl; C5 alkyl-pentyl such as n-pentyl; C6 alkyl-hexyl such as n-hexyl, isohexyl, and 1,3-dimethylbutyl. Similarly, alkenyl groups are, for example, vinyl, allyl, 1-methylprop-2-en-1-yl, 2-methylprop-2-en-1-yl, but-2-en-1-yl, but-3-en-1-yl, 1-methylbut-3-en-1-yl, and 1-methylbut-2-en-1-yl. Alkynyl groups are, for example, ethynyl, propynyl, but-2-yn-1-yl, but-3-yn-1-yl, and 1-methylbut-3-yn-1-yl. Multiple bonds can be in any position in each unsaturated group. Cycloalkyl groups are carbocyclic saturated ring systems having, for example, three to six carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. Similarly, cycloalkenyl groups are monocyclic alkenyl groups having, for example, three to six carbon ring members, such as cyclopropenyl, cyclobutenyl, cyclopentenyl, and cyclohexenyl, wherein double bonds can be in any position. Halogens are fluorine, chlorine, bromine, or iodine.

Unless otherwise specified, the term "aryl" in this invention includes, but is not limited to, phenyl, naphthyl, and... The "heterocyclic group" includes, but is not limited to, saturated or unsaturated non-aromatic cyclic groups. And, including but not limited to, heteroaryl groups, i.e., aromatic cyclic groups containing, for example, 3 to 6 ring atoms and optionally fused with benzo[a] rings, wherein 1 to 4 (e.g., 1, 2, 3, or 4) heteroatoms are selected from oxygen, nitrogen, and sulfur, for example

If a group is substituted by another group, this should be understood to mean that the group is substituted by one or more identical or different groups selected from those groups mentioned. Furthermore, the identical or different substitution characters contained in the identical or different substituents are chosen independently and may be identical or different. This also applies to ring systems formed from different atoms and units. Meanwhile, the scope of the claims excludes compounds that are chemically unstable under standard conditions, as known to those skilled in the art.

Furthermore, unless otherwise specified, the phrase "replaced by at least one group" in this invention refers to being replaced by, for example, 1, 2, 3, 4, or 5 groups; groups without specific attachment positions (including heterocyclic groups, aryl groups, etc.) can be attached at any position, including positions attached to C or N; if it is substituted, the substituent can also be substituted at any position, as long as it conforms to the rules of chemical bond attachment. For example, a heteroaryl group substituted by one methyl group. Can represent wait.

The present invention also provides a pyridine amide compound having a chiral center as shown in Formula I':

Wherein, the substituents _R1 , _R2 , _R3 , _R4 , _X1 , _X2 , _X3 , _X4 and _W1 are defined as described above, and _R3 is not hydrogen; *at least one (1, 2 or 3) chiral centers are present at the carbon atom position, and based on the content of stereoisomers with R and S configurations at position 1, it has a stereochemical purity of 60-100% (S), preferably 70-100% (S), more preferably 80-100% (S), further preferably 90-100% (S), and even more preferably 95-100% (S); and/or

Based on the content of stereoisomers having R and S configurations at position 2, it has a stereochemical purity of 60-100% (S), preferably 70-100% (S), more preferably 80-100% (S), further preferably 90-100% (S), and even more preferably 95-100% (S); and/or

Based on the content of stereoisomers having R and S configurations at position 3, it has a stereochemical purity of 60-100% (S), preferably 70-100% (S), more preferably 80-100% (S), further preferably 90-100% (S), and even more preferably 95-100% (S).

"Stereochemical purity" refers to the percentage of the amount of the stereoisomer relative to the total amount of stereoisomers that generate chiral centers.

Compounds of Formula I, in their respective free or salt forms, and where appropriate, their tautomers, may exist as one of the possible isomers or as mixtures thereof, for example, as pure isomers, such as enantiomers and/or diastereomers, or as mixtures of isomers, such as mixtures of enantiomers, such as racemic mixtures, diastereomer mixtures, or racemic mixtures, depending on the number of asymmetric carbon atoms present in the molecule, their absolute and relative configurations, and/or on the configuration of the non-aromatic double bonds present in the molecule; the present invention relates to these pure isomers and also to all possible mixtures of isomers and should be understood in this sense in each of the above and below, even if stereochemical details are not specifically mentioned in each case. The present invention therefore covers all such isomers and tautomers and mixtures thereof in all proportions, together with isotopic forms, such as deuterated compounds.

In another embodiment, Formula I is also understood to include their salts or hydrates. Exemplary salts include, but are not limited to, hydrochlorides, hydrobroms, and hydroiodates.

Those skilled in the art will also understand that, unless otherwise stated, additional substitutions are permitted, provided that the rules of chemical bonding and strain energy are satisfied and the product still exhibits antifungal activity.

Another embodiment of this application is a method for preparing the pyridine amide compound, comprising the following steps:

(1) Compound I is prepared by a condensation reaction of compound II and compound III. The chemical reaction equation is as follows:

(2) Compound I is prepared by condensation reaction of compound IV with compound V or its salt (such as hydrochloride), and the chemical reaction equation is as follows:

(3) Alternatively, when _R2 does not represent H, from compound I' Prepared via a substitution reaction;

Wherein, L and L' independently represent OH or halogen _{, respectively; the definitions of substituents R1, R2, R3, R4, X1 , X2 , X3 , X4 and W1} are as described above.

In one specific embodiment, the reactions in steps (1) and (2) are carried out in the presence of a solvent.

In another specific embodiment, a condensing agent and/or a base are added during the reaction process of steps (1) and (2).

In one embodiment, the solvent is selected from at least one of DMF, DMA, acetonitrile, dichloroethane, DMSO, dioxane, dichloromethane, or ethyl acetate.

In one specific embodiment, the base is selected from at least one of inorganic bases (such as _K₂CO₃ , _{Na₂CO₃ , Cs₂CO₃ , NaHCO₃} , _KF , CsF, KOAc, AcONa, _K₃PO₄ , t-BuONa, EtONa, NaOH, KOH, NaOMe, etc.) or organic bases (such as 4-PPy, 4 _- methylmorpholine, pyrazole, triethylamine, DIEA/DIPEA, etc.).

In one specific embodiment, the condensing agent is selected from at least one of Py-BOP, Py-AOP, EDCI, HOBT, DCC, HBTU, or HATU.

Another embodiment of this application is an intermediate, as shown in Formula II, Formula V, or a salt thereof.

In addition, another embodiment of this application is a bactericidal composition comprising a biologically effective amount of a compound of formula I or I'; preferably, in one embodiment, it further comprises a formulation adjuvant; in another embodiment, it further comprises other active ingredients.

Another embodiment of this application is the use of the compound of formula I or I’ or the above-described fungicidal composition in the control of plant pathogenic fungi. This use is for protecting plants from plant pathogenic microorganisms or for treating plants infected by plant pathogenic microorganisms, including applying the compound of formula I or I’ or a composition containing said compound to soil, plants, parts of plants, leaves, and/or roots.

The compounds of this application can be applied as compounds or as formulations containing said compounds using any of the various known techniques. For example, said compounds can be applied to the roots or leaves of plants to control various fungi without compromising the commercial value of the plants. The substances can be applied in any commonly used formulation type, such as as solutions, powders, wetting powders, flowable concentrates, or emulsifiable concentrates.

Preferably, the compounds of this application are applied in formulation form, said formulation comprising one or more compounds of formula I or I' and a botanically acceptable carrier. The concentrated formulation may be dispersed in water or other liquids for application, or the formulation may be a dust or granules that can be applied immediately without further processing. The formulation may be prepared according to methods common in the field of agricultural chemistry.

This application contemplates the use of all media through which the one or more compounds can be formulated for delivery and use as fungicides. Typically, the formulation is applied as an aqueous suspension or emulsion. The suspension or emulsion can be prepared from water-soluble, water-suspendable, or emulsifiable formulations, which are generally referred to as wettable powders when the water-soluble, water-suspendable, or emulsifiable formulation is a solid; or as emulsifiable oils, aqueous suspensions, or suspension concentrates when the water-soluble, water-suspendable, or emulsifiable formulation is a liquid. It is readily understood that any substance capable of incorporating these compounds can be used, provided that the desired use is achieved without significantly impairing the activity of these compounds as antifungal agents.

Wettable powders that can be pressed into water-dispersible particles comprise an intimate mixture of one or more compounds of formula I or I', an inert carrier, and a surfactant. The concentration of the compounds in the wettable powder, by weight of the total wettable powder, can range from about 10 wt% to about 90 wt%, more preferably from about 25 wt% to about 75 wt%. In the preparation of wettable powder formulations, the compounds can be mixed with any finely pulverized solids, such as prophyllite, talc, chalk, gypsum, Fuller's earth, bentonite, attapulgite, starch, casein, gluten, montmorillonite, diatomaceous earth, refined silicates, etc. In this operation, the finely pulverized carrier and surfactant are typically blended with and ground with the compounds.

Based on the total weight of the emulsifiable concentrate, the compound of formula I or I' can be contained in a suitable liquid at a conventional concentration, for example, from about 1 wt% to about 50 wt%. The compound can be dissolved in an inert support, which is a mixture of a water-miscible solvent or a water-immiscible organic solvent and an emulsifier. The emulsifiable concentrate can be diluted with water and oil to form a spray mixture in the form of an oil-in-water emulsion. Useful organic solvents include the aromatic fractions of petroleum, particularly the high-boiling cycloalkane and alkene fractions, such as heavy aromatic naphtha. Other organic solvents may also be used, such as terpene solvents including rosin derivatives, aliphatic ketones such as cyclohexanone, and complex alcohols such as 2-ethoxyethanol.

The emulsifiers that can be advantageously used in this application can be readily determined by those skilled in the art and include a variety of nonionic emulsifiers, anionic emulsifiers, cationic emulsifiers, and amphoteric emulsifiers, or blends of two or more emulsifiers. Examples of nonionic emulsifiers used to prepare the emulsifiable concentrates include polyalkylene glycol ethers, and condensation products of alkyl and aryl phenols, aliphatic alcohols, aliphatic amines, or fatty acids with ethylene oxide or propylene oxide, such as ethoxylated alkylphenols and carboxylic acid esters dissolved in polyols or polyoxyethylenes. Cationic emulsifiers include quaternary ammonium compounds and fatty amine salts. Anionic emulsifiers include oil-soluble salts of alkyl aryl sulfonic acids (e.g., calcium salts), oil-soluble salts of sulfated polyglycol ethers, and suitable salts of phosphorylated polyglycol ethers.

Representative organic liquids that can be used in the preparation of the emulsifiable concentrates of the compounds of this application are aromatic liquids such as xylene and propylbenzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkylamides of various fatty acids, especially dimethylamides and diol derivatives of fatty glycols such as n-butyl ether, ethyl ether or methyl ether of diethylene glycol, methyl ether of triethylene glycol, petroleum fractions or hydrocarbons such as mineral oils, aromatic solvents, paraffin oils, etc.; vegetable oils such as soybean oil, rapeseed oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil, etc.; esters of the above vegetable oils; etc. Mixtures of two or more organic liquids can also be used in the preparation of the emulsifiable concentrate. Organic liquids include xylene and propylbenzene fractions, with xylene being the most preferred in some cases. Surfactant dispersants are typically used in liquid formulations, and the amount of the surfactant dispersant is from 0.1 to 20 wt% based on the total weight of the dispersant and one or more compounds. The formulation may also contain other compatible additives, such as plant growth regulators and other bioactive compounds used in agriculture.

Aqueous suspensions comprise suspensions of one or more water-insoluble compounds of formula I or I' dispersed in an aqueous medium, with a concentration of about 1 wt% to about 50 wt% by weight of the total aqueous suspension. The suspension is prepared by finely grinding one or more of the compounds and vigorously mixing the ground compounds into a medium composed of water and surfactants selected from the same type described above. Other components, such as inorganic salts and synthetic or natural gums, may also be added to increase the density and viscosity of the aqueous medium.

Compounds of Formula I or I' can also be applied in granular form, particularly for application to soil. By total weight, the granular formulation typically contains about 0.5 wt% to about 10 wt% of the compound dispersed in an inert carrier, which is wholly or mostly composed of coarsely pulverized inert material, such as attapulgite, bentonite, diatomaceous earth, clay, or similar inexpensive materials. The formulation is typically prepared by dissolving the compound in a suitable solvent and applying it to a granular carrier pre-formed to a suitable particle size (ranging from about 0.5 to about 3 mm). The suitable solvent is one in which the compound is substantially or completely soluble. The formulation can also be prepared by forming the carrier, compound, and solvent into a paste or ointment, then crushing and drying to obtain the desired granular particles.

Powders containing compounds of formula I or I' can be prepared by homogenizing one or more of the compounds in powder form with a suitable powdery agricultural carrier, such as kaolin clay, crushed volcanic rock, etc. The powder may suitably contain about 1% to about 10% of the compounds by weight.

The formulation may additionally contain co-active surfactants to enhance the deposition, wetting, and penetration of the compound onto target crops and microorganisms. These co-active surfactants may optionally be used as a component of the formulation or as a tank mixture. The amount of the co-active surfactant is typically from 0.01 to 1.0% by volume of water spray, preferably from 0.05 to 0.5% by volume. Suitable auxiliary surfactants include, but are not limited to, ethoxylated nonylphenol, ethoxylated synthetic alcohols or ethoxylated natural alcohols, sulfosuccinates or sulfosuccinates, ethoxylated organosiloxanes, ethoxylated fatty amines, blends of surfactants with mineral oils or vegetable oils, crop oil concentrates (mineral oil (85%) + emulsifier (15%)); nonylphenol ethoxylates; benzyl cocoyl dimethyl quaternary ammonium salts; blends of petroleum hydrocarbons, alkyl esters, organic acids and anionic surfactants; _C9 - _C11 alkyl polyglycosides; phosphorylated alcohol ethoxylates; natural primary alcohols ( _C12 - _C16 ) ethoxylates; di-sec-butylphenol EO-PO block copolymers; polysiloxane-methyl-terminated compounds; nonylphenol ethoxylates + urea ammonium nitrate; emulsified methylated seed oils; tridecyl alcohol (synthetic) ethoxylates (8EO); tallow amine ethoxylates (15EO); PEG (400) dioleate-99. The formulation may also include oil-in-water emulsions, such as those disclosed in U.S. Patent Application Serial No. 11/495,228, the disclosure of which is incorporated herein by reference.

The formulation may optionally include a combination containing other pesticide compounds. These additional pesticide compounds may be fungicides, insecticides, herbicides, nematicides, acaricides, arthropodicides, fungicides, or combinations thereof, which are compatible with the compounds of this application in the chosen application medium and do not antagonize the activity of the compounds of this application. Therefore, in the described embodiments, the other pesticide compounds are used as supplementary toxins for the same or different pesticide uses. The compounds of formula I or I’ and pesticide compounds are typically present in combination in a weight ratio of 1:100 to 100:1.

The compounds of this application can also be combined with other fungicides to form fungicidal mixtures and synergistic mixtures thereof. The fungicidal compounds of this application are typically applied in combination with other fungicides to control a wider range of undesirable diseases. When applied in combination with other fungicides, the compounds claimed in this application can be formulated together with other fungicides, mixed with other fungicide canisters, or applied sequentially with other fungicides. These other fungicides may include: 2-(thiocyanatomethylthio)-benzothiazole, 2-phenylphenol, 8-hydroxyquinoline sulfate, ametoctradin, amisulbrom, antimycin, Ampelomyces quisqualis, azaconazole, and azoxystrobin. n), Bacillus subtilis, Bacillus subtilis strain QST713, benalaxyl, benomyl, benthiavalicarb-isopropyl, benzylaminobenzene-sulfonate (BABS) salt, bicarbonates, biphenyl compounds, bismerthiazol, bifenthazole Bittertanol, bixafen, blasticidin-S, borax, Bordeaux mixture, boscalid, bromuconazole, bupirimate, calcium polysulfide, captafol, captan, carbendazim, carboxin, carpropamid, carvone, chlorfenapyr. Afenone, chloroneb, chlorothalonil, chlozolinate, Coniothyrium mintans, copper hydroxide, copper tanoate, copper oxychloride, copper sulfate, copper sulfate (tribasic), cuprous oxide, cyazofamid, cyclofluorobenzamide Flufenamid, Cymoxanil, Cyproconazole, Cyprodinil, Dazomet, Debacarb, Diammonium ethylenebis(dithiocarbamate), Dichlofluanid, Dichlorophen, Dicloymet, Diclomezine, Dichloran, Diethofencarb arb), difenoconazole, difenzoquat ion, diflumetorim, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinobuton, dinitrocrotonate, diphenylamine, dithianon, dodemorph, dodemorph acetate cetate, dodine, dodine freebase, edifenphos, enestrobin, enestroburin, epoxiconazole, ethaboxam, ethoxyquin, etridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fenfuram, cyclophosphamide ( fenhexamid, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumorph, fluopicolide, fluorine Fluopyram, fluoroimide, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil, flutolanil, flutriafol, fluxapyroxad, folpet, formaldehyde, fosetyl, fosetyl-aluminum, fuber idazole), furaxyl, furamepyr, guazatine, guazatine acetate, sodium tetrasulfide (GY-81), hexachlorobenzene, hexaconazole, hymexazol, imazalil, imazalil sulfate, imibenconazole, iminoctadine, iminoctadine triacetate Acetate), Biguanide octylamine tris (p-dodecylbenzene sulfonate) [iminoctadine tris (albesilate)], iodocarb, ipconazole, ipfenpyrazolone, iprobenfos, iprodione, iprovalicarb, isoprothiolane, isopyrazam, isothiazine, kasugamycin, kasugamycin hydrochloride hydrate Hloride hydrate), Kresoxim-methyl, Laminarin, Mancopper, Mancozeb, Mandipropamid, Maneb, Mefenoxam, Mepanipyrim, Mepronil, Meptyl-dinocap, Mercuric chloride, Mercuric oxide, Mercurous chloride Metalaxyl, Metalaxyl-M, Metam, Metam-ammonium, Metam-potassium, Metam-sodium, Metconazole, Methasulfocarb, Methyl iodide, Methyl isothiocyanate, Metiram, Metominostrobin, Metrafenone, Mildiomycin Cin), Myclobutanil, Nabam, Nitrothal-isopropyl, Nuarimol, Octilinone, Ofuronamide, Oleic acid (fatty acid), Orysastrobin, Oxadixyl, Oxine-copper, Oxpoconazole fumarate, Oxycarboxin, Pefuraz oate), penconazole, pencycuron, penflufen, pentachlorophenol, pentachlorophenyl laurate, penthiopyrad, phenylmercuryacetate, phosphonic acid, phthalide, picoxystrobin, polyoxin B, polyoxins Polyoxorim, potassium bicarbonate, potassium hydroquinoline sulfate, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, proquinazid, prothioconazole hioconazole, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, quinoclamine, quinoxyfen, quintozene, Reynodolene extract Utriasachalinensis extract), sedaxane, silthiofam, simeconazole, sodium 2-phenyl phenoxide, sodium bicarbonate, sodium pentachlorophenoxide, spiroxamine, sulfur, SYP-Z048, wood tar, tebuconazole, isobutylethoxyquinoline ( Tebufloquin, Tetraconazole, Thiabendazole, Thifluzamide, Thiophanate-methyl, Thiram, Tiadinil, Tolclofos-methyl, Tolylfluanid, Triadimefon, Triadimenol, Triazoxide, Tricyclazole Tridemorph, trifloxystrobin, triflumizole, triforine, triticonazole, validamycin, valifenalate, valiphenal, vinclozolin, zineb, ziram, zoxamide, Candida oleophila, Fusarium oxysporum, and other fungicides (Gl). *Isocladium spp.*, *Phlebiopsis gigantea*, *Streptomyces griseoviridis*, *Trichoderma spp.*, (RS)-N-(3,5-dichlorophenyl)-2-(methoxymethyl)-succinimide, 1,2-dichloropropane, 1,3-dichloro-1,1,3,3-tetrafluoroacetone hydrate (1,3-d... ichloro-1,1,3,3-tetrafluoroacetone hydrate), 1-chloro-2,4-dinitronaphthalene, 1-chloro-2-nitropropane, 2-(2-heptadecyl-2-imidazolin-1-yl)ethanol, 2,3-dihydro-5-phenyl-1,4-dithione-1,1,4,4-tetraoxide 1,4-dithi-ine 1,1,4,4-tetraoxide, 2-methoxyethylmercury acetate, 2-methoxyethylmercury chloride, 2-methoxyethylmercury silicate, 3-(4-chlorophenyl)-5-methylrhodanine, 4-(2-nitroprop-1-enyl)phenyl thiocyanate rop-1-enyl)phenylthiocyanate, ampropylfos, anilazine, azithiram, barium polysulfide, Bayer 32394, benodanil, benquinox, bentaluron, benzamacril; benzamacril-isobutyl, benzamorf, binapacryl, sulfuric acid Bis(methylmercury)sulfate, bis(tributyltin)oxide, buthiobate, cadmium calcium copper zinc chromate sulfate, carbamorph, CECA, chlobenthiazone, chloraniformethan, chlorfenazole, chlorquinox, clidiclofen mbazole), copper bis(3-phenylsalicylate), copper zinc chromate, cufraneb, copper hydrazinium sulfate, cuprobam, cyclafuramid, cypendazole, cyprofuram, decafentin, dichloronaphthoquinone, dichlozoline, benzyltriazole iclobutrazol, dimethirimol, dinosulfon, dinoterbon, dipyrithione, ditalimfos, dodicin, drazoxolon, EBP, ESBP, etaconazole, etem, ethirim, fenaminosulfonium, fenapanil, finitropan. Fluotrimazole, Furcarbanil, Furconazole, Furconazole-cis, Furmecyclox, Furophanate, Glyodine, Griseofulvin, Halacrinate, Hercules 3944, Hexylthiofos, Propiconazole (ICIA0858), Isopamphos, Isovaledio ne), mebenil, mecarbinzid, metazoxolon, methfuroxam, methylmercury dicyandiamide, metsulfovax, milneb, mucochloric anhydride, myclozolin, N-3,5-dichlorophenylsuccinimide, N-3-nitr ophenylitaconimide, natamycin, N-ethylmercurio-4-toluenesulfonanilide, nickel bis(dimethyldithiocarbamate), octachlorophenone (OCH), phenylmercurydimethyldithiocarbamate, phenylmercury nitrate, phosdiphen, thiobacterium Prothiocarb; prothiocarb hydrochloride, pyracarbolid, pyridinitril, pyroxychlor, pyroxyfur, quinacetol; quinacetol sulfate, quinazamid, quinconazole, rabenzazole, salicylanilide ), azoxystrobin (SSF-109), sulforium sulfide (sultropen), tecoram, thiadifluor, thicyofen, thiochlorfenphim, thiophanate, thioquinox, tioxymid, triamiphos, triarimol, triazbutil, trihlamide, urethane, zarilamid, and any combination thereof.

Furthermore, the compounds described in this application can be combined with other insecticides, including insecticides, nematicides, acaricides, arthropod icides, fungicides, or combinations thereof, wherein the other insecticides are compatible with the compounds of this application in the chosen application medium and do not antagonize the activity of the compounds of this application to form insecticidal mixtures and synergistic mixtures thereof. The fungicidal compounds of this application can be applied in combination with one or more other insecticides to control a wider range of undesirable pests. When applied in combination with other insecticides, the compounds claimed in this application can be formulated together with other insecticides, mixed with other insecticide canisters, or applied sequentially with other insecticides. Common insecticides include, but are not limited to: 1,2-dichloropropane, abamectin, acephate, acetamiprid, acethion, acetoprole, acrinathrin, acrylonitrile, alanycarb, aldicarb, aldoxycarb, aldrin, allethrin, allosamidin, and allyx. ycarb), alpha-cypermethrin, alpha-ecdysone, alpha-endosulfan, amiditthion, aminocarb, amiton, amiton oxalate, amitraz, anabasine, athidathion, azadirachtin, azamethiphos, azinphos-ethyl, azinphos-meth Yl), azothoate, barium hexafluorosilicate, barthrin, bendiocarb, benfuracarb, bensultap, beta-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bistrifluron Borax, Boric acid, Bromfenvinfos, Bromocyclen, Bromo-DDT, Bromophos, Bromophos-ethyl, Bufencarb, Buprofezin, Butacarb, Butathiofos, Butocarboxim, Butonate, Butoxycarboxim, Cadusafos, Calcium arsenate Arsenate, lime sulfur, camphechlor, carbanolate, carbaryl, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, cartap, cartap hydrochloride, chlorantraniliprole, borneol orbicyclen), chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorethoxyfos, chlorfenapyr, chlorfenvinphos, chlorfluazuron, chlormephos, chloroform, chloropicrin, chlorphoxim, chlorprazoph os), chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, chromafenozide, cinerin I, cinerin II, cinerins, cismethrin, cloethocarb, closantel, clothianidin, copper acetoarsenite, copper arsenate, copper naphthenate Copper oleate, Coumaphos, Coumithoate, Crotamiton, Crotoxyphos, Crufomate, Cryolite, Cyanofenphos, Cyanophos, Cyanthoate, Cyantraniliprole, Cycyclethrin, Cycloprothrin, Cyfluthrin ), cyhalothrin, cypermethrin, cyphenothrin, cyromazine, cythioate, DDT, decarbofuran, deltamethrin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl thyl), demeton-S, demeton-S-methyl, demeton-S-methylsulphon, diafenthiuron, dialifos, diatomaceous earth, diazinon, dicapthon, dichlofenthion, dichlorvos, dicresyl, dicrotophos, dicyclofenac lanil), dieldrin, diflubenzuron, dilor, dimefluthrin, dimefox, dimetan, dimethoate, dimethrin, dimethylvinphos, dimetilan, dinex, dinex-diclexine, dinoprop, dinosam, dinotefuran, diofenolan, dioxon abenzofos, dioxacarb, dioxathion, disulfoton, dithicrofos, d-limonene, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, doramectin, ecdysterone, emamectin, emamectinbenzoate, EMPC ), empenthrin, endosulfan, endothion, endrin, EPN, epofenonane, eprinomectin, esdepalléthrine, esfenvalerate, etaphos, ethiofencarb, ethion, ethiprole, ethoate-methyl, ethoprophos, ethyl formate e), Ethyl-DDD, 1,2-dibromoethane, 1,2-dichloroethane, ethylene oxide, etofenprox, etrimfos, EXD, famphur, fenamiphos, fenazaflor, fenchlorphos, fenethacarb, fenfluthrin, fenitrothion, fenocarb Bucarb, fenoxacrim, fenoxycarb, fenpirithrin, fenpropathrin, fensulfothion, fenthion, fenthion-ethyl, fenvalerate, fipronil, flonicamid, flubendiamide, flucofuron, flucycloxuron, flucythrinate, pyrimethanil Flufenerim, flufenoxuron, flufenprox, fluvalinate, fonofos, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosmethilan, fospirate, fosthietan, furathiocarb b) Furethrin, gamma-cyhalothrin, gamma-HCH, halfenprox, halofenozide, HCH, HEOD, heptachlor, heptenophos, thermophos, hexaflumuron, HHDN, hydramethylnon, hydrogen cyanide, hydroprene, hyquincarb Imidacloprid, imiprothrin, indoxacarb, iodomethane, IPSP, isazofos, isobenzan, isocarbophos, isodrin, isofenphos, isofenphos-methyl, isoprocarb, isoprothiolane, isothioate, isoxathion, iverm Jasmolin I, Jasmolin II, Jodfenphos, Juvenile Hormone I, Juvenile Hormone II, Juvenile Hormone III, Kelevan, Kinoprene, Lambda-cyhalothrin, Lead Arsenate, Lepimectin, Leptophos, Lindane, Acetaminophen Phosphorus (lirimfos), Lufenuron, Lythidathion, Malathion, Malonoben, Mazidox, Mecarbam, Mecarphon, Menazon, Mephosfolan, Mercurous chloride, Mesulfenfos, Metaflumizone, Methacrifos, Methamidophos, Methamidophos thion), methiocarb, methocrotophos, methomyl, methoprene, emthoxychlor, methoxyfenozide, methyl bromide, methyl isothiocyanate, methyl chloroform, methylenechloride, metofluthrin, metolcarb, metoxa Diazone), Mevinphos, Mexacarbate, Milbemectin, Milbemycinoxime, Mipafox, Mirex, Molosultap, Monocrotophos, Monomehypo, Monosultap, Morphothion, Moxidectin, Naftalofos, Naled, Naphthalene, Nicotine, Nifenpyram Fluridide, nitenpyram, nithiazine, nitrilacarb, novaluron, noviflumuron, omethoate, oxamyl, oxydemeton-methyl, oxydeprofos, oxydisulfoton, para-dichlorobenzene, parathion, parathion-methyl, penfluro n), pentachlorophenol, permethrin, phenkapton, phenothrin, phenthoate, phorate, phosalone, phosfolan, phosmet, phosnichlor, phosphamidon, phosphine, phoxim, phoxim-methyl, pirimetaphos, pirimic arb), pyrimiphos-ethyl, pyrimiphos-methyl, potassium arsenite, potassium thiocyanate, pp'-DDT, prallethrin, precocene I, precocene II, precocene III, primidophos, profenofos, profluralin, promacyl, and cypermethrin. Promecarb, propaphos, propetamphos, propoxur, prothidathion, prothiofos, prothoate, protrifenbute, piraclofos, pirafluprole, pyrazophos, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyridaben ), pyridalyl, pyridaphenthion, pyrifluquinazon, pyrimidifen, pyrimitate, pyriprole, pyriproxyfen, quassia, quinalphos, quinalphos-methyl, quinothion, rafoxanide, resmethrin, rotenone, ryania, sabadil LA), Schradan, Selamectin, Silafluofen, Silica Gel, Sodium Arsenite, Sodium Fluoride, Sodium Hexafluorosilicate, Sodium Thiocyanate, Sophamide, Spintoram, Spinosad, Spiromesifen, Spiotetramat, Sulfodioxanone ofuron), sulcofuron-sodium, sulfluramid, sulfotep, sulfoxaflor, sulfurylfluoride, sulprofos, tau-fluvalinate, tazimcarb, TDE, tebufenozide, tebufenpyrad, tebupirimfos, teflubenzuron, tefluthrin, and more. Temephos, TEPP, terallethrin, terbufos, tetrachloroethane, tetrachlorvinphos, tetramethrin, tetramethylfluthrin, theta-cypermethrin, thiacloprid, thiamethoxam, thicrofos, thiocarboxime, thiocyclam, thiocyclam oxalate iocyclam oxalate, thiodicarb, thiofanox, thiometon, thiosultap, thiosultap-disodium, thiosultap-monosodium, thuringiensin, tolfenpyrad, tralomethrin, transfluthrin, transpermethrin, triarathene, bensulfuron-methyl Triazamate, triazophos, trichlorfon, trichlormetaphos-3, trichloronat, trifenofos, triflumuron, trimethacarb, triprene, vamidothion, vaniliprole, XMC, xylylcarb, zeta-cypermethrin, zolaprofos, and any combination thereof.

Furthermore, the compounds described in this application can be combined with herbicides that are compatible with and do not antagonize the activity of the compounds in the chosen application medium to form insecticidal mixtures and synergistic mixtures thereof. The fungicidal compounds of this application are typically applied in combination with one or more herbicides to control a wider range of undesirable plants. When applied in combination with a herbicide, the claimed compounds can be formulated together with the herbicide, mixed with a herbicide container, or applied sequentially with the herbicide. Common herbicides include, but are not limited to: 4-CPA; 4-CPB; 4-CPP; 2,4-D; 3,4-DA; 2,4-DB; 3,4-DB; 2,4-DEB; 2,4-DEP; 3,4-DP; 2,3,6-TBA; 2,4,5-T; 2,4,5-TB; acetochlor; acifluorfen; aclofen; acrolein; alachlor; allidochlor; alloxydim; and allyl alcohol. Alcohol), pentachloropentanolic acid (alorac), ametridone, ametryn, amibuzin, amicarazone, amidosulfuron, aminocyclopyrachlor, aminopyralid, amiprofos-methyl, amitrol, ammonium sulfate Sulfamate, Anilofos, Anisuron, Asulam, Atrazine, Azafenidin, Azimsulfuron, Aziprotryne, Barban, BCPC, Beflubutamid, Benazolin, Bencarbazone, Benfluralin, Benfuresate, Bensulfuron, Bensulide, Bentazone, Benzadox, Benzfendizone, Benzipram, Benbicyclon, Benfenap, Bensulfuron Benzoylprop, benzthiazuron, bicyclopyrone, bifenox, bilanafos, bispyribac, borax, bromacil, bromobonil, bromobutide, bromofenoxim, bromoxynil ), brompyrazon, butachlor, butafenacil, butamifos, butenachlor, buthidazole, buthiuron, butralin, butroxydim, buturon, butylate, cacodylic acid acid), cafenstrole, calcium chlorate, calcium cyanamide, cambendichlor, carbasulam, carbetamide, carboxazole, chlorprocarb, carfentrazone, CDEA, CEPC, chlomethoxyfen, chloramben, chloranocryl, chlorazifop, chlorazine, chlorbromuron, chlorbufam, chloreturon, chlorfenac, chlorfenprop, chlorflurazole, chlorflurenol, chloridazon, chlorpyrifos. Chlorimuron, chlornitrofen, chloropon, chlorotoluron, chloroxuron, chloroxynil, chlorpropham, chlorsulfuron, chlorthal, chlorthiamid, cinidon-ethyl, cinmethyli n), cinosulfuron, cisanilide, clethodim, cliodinate, clodinafop, clofop, clonazol, clonazol, clonprop, cloprop, cloproxydim, clopyralid, cloransulam, CMA, copper sulfate sulfate), CPMF, CPPC, credazine, cresol, cumyluron, cyanatryn, cyanazine, cycloate, cyclosulfamuron, cycloxydim, cycluron, cyhalofop, cyperquat, cyprazine, cyprazole, cypromid, daimuron, dalapon, dazomet, delachlor, desmedipham, desmetryn, di-allate, dicamba mba), dichlobenil, dichloralurea, dichlormate, dichlorprop, dichlorprop-P, diclofop, diclosulam, diethamquat, diethatyl, difenopenten, difenoxuron, difenzoquat, diflufenican, diflufenzopyr, dimefuron, dimepiperate, dimethachlor, dimethametryn, dimethachlor enamid), dimethenamid-P, dimexano, dimidazon, diinitramine, dinofenate, dinoprop, dinosam, dioseb, dinoterb, diphenamid, dipropetryn, diquat, 2,4-D sulfuric acid, dithiopyr, diuron, DMPA, DNOC, DSMA, EBEP, eglinazine, endothal, epronaz, EPTC, erbon, esprocarb, ethalflu ralin), ethametsulfuron, ethidimuron, ethiolate, ethofumesate, ethoxyfen, ethoxysulfuron, etinofen, etnipromid, etobenzanid, EXD, fenasulam, fenoprop, fenoxaprop, fenoxaprop-P, fenoxasulfone, fenteracol, fenthiaprop, fentrazamide, fenuron, ferrous sulfate sulfate), flamprop, flamprop-M, flazasulfuron, florasulam, fluazifop, fluazifop-P, fluazolate, flucarbazone, flucetosulfuron, fluchloralin, flufenacet, flufenican, flufenpyr, flumetsulam, flumezin, flumiclorac, propargite, etc. Flumioxazin, flumipropyn, fluometuron, fluorodifen, fluoroglycofen, fluoromidine, fluoronitrofen, fluothiuron, flupoxam, flupropacil, flupropanate, flupyrsulfuron, fluridone, flurochloridone, fluroxypyr, flurtamone, fluth... iacet), fomesafen, foramsulfuron, fosamine, furyloxyfen, glufosinate, glufosinate-P, glyphosate, halosafen, halosulfuron, haloxydine, haloxyfop, haloxyfop-P, hexachloroacetone, hexaflurate, hexazinone, imazalazine, Imazalcifen, Imazapic, Imazapyr, Imazaquin, Imazethapyr, Imazosulfuron, Indanofan, Indaziflam, Iodobonil, Iodomethane, Iodosulfuron, Ioxynil, Ipazine, Ipfencarbazone, Iprymidam, Isocarbamid, Isocillin, Isomethiozin, Isoruron, Nitrogen Herbicides include: isopolinate, isopropalin, isoproturon, isouron, isoxaben, isoxachlortole, isoxaflutole, isoxapyrifop, karbutilate, ketospiradox, lactoferrin, lenacil, linuron, methylarsine (MAA), monoammonium methylarsine (MAMA), MCPA, MCPA-thioethyl, MCPB, mecoprop, mecoprop-P, medinoterb, and mefenoxam. Fenacet), mefluidide, mesoprazine, mesosulfuron, mesotrione, metam, metamifop, metamitron, metazachlor, metazosulfuron, metflurazon, methabenzthiazuron, metalpropalin, methazole, methiobencarb, methiozolin, methiuron, methometon, methoprotryne, methyl bromide bromide, methyl isothiocyanate, methyl dymron, metobenzuron, metobromuron, metolachlor, metosulam, metoxuron, metribuzin, metsulfuron, molinate, monalide, monisouron, monochloroacetic acid (acid), monolinuron, monouron, morfamquat, MSMA, naproanilide, napropamide, naptalam, neburon, nicosulfuron, nipyraclofen, nitralin, nitrofen, nitrofluorfen, norflurazon, noruron, octachlor (OCH), orbencarb, ortho-dichlorobenzene, orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxapyrazon, oxasulfuron, oxaziclomefone, oxyfluorfen, parafluron, paraquat, pebulate, pelargonic acid acid), pendimethalin, penoxsulam, pentachlorophenol, pentanochlor, pentoxazone, perfluidone, pethoxamid, phenisopham, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenylmercury acetate, picloram, picolinafen, pinoxaden, piperophos, potassium arsenite, potassium azide, potassium cyanate cyanate), pretilachlor, primisulfuron, procyazine, prodiamine, profluazol, profluralin, profoxydim, proglinazine, prometon, prometryn, propachlor, propanil, propaquizafop, propazine, propham Proisochlor, propoxycarbazone, propyrisulfuron, propyzamide, prosulfalin, prosulfocarb, prosulfuron, proxan, prynachlor, pydanon, pyraclonil, piraflufen, pyrasulfotole, pyrazolynate, pyrimisulfuron azosulfuron, pyrazoxyfen, pyribenzoxim, pyributicarb, pyriclor, pyridafol, pyridate, pyriftalid, pyriminobac, pyrimisulfan, pyrithiobac, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quinoclamine Quinonamid, quizalofop, quizalofop-P, rhodethanil, rimsulfuron, saflufenacil, S-metolachlor, sebuthylazine, secbumeton, sethoxydim, siduron, simazine, simeton, simetryn, SMA, sodium arsenite Arsenite, sodium azide, sodium chlorate, sulcotrione, sulfallate, sulfentrazone, sulfometuron, sulfosulfuron, sulfuric acid, sulglycapin, swep, TCA, tebutam, tebuthiuron, tefuryltrione, tembotrione, tepraloxydim, terbacil, terbucarb, terbuchlor, terbumeton, terbuthylazine, and more. Terbutryn, tetrafluron, thenylchlor, thiazafluron, thiazopyr, thidiazimin, thidiazuron, thiencarbazone-methyl, thifensulfuron, thiobencarb, tiocarbazil, pyrimimetholone Tioclorim, toramezone, tralkoxydim, triafamone, tri-allate, triasulfuron, triaziflam, tribenuron, tricamba, trilopyr, tridiphane, trietazine, trifloxysulphuron The following herbicides are listed: furon, trifluralin, triflusulfuron, trifop, trifopsime, trihydroxytriazine, trimeturon, tripropindan, tritac, tritosulfuron, vernolate, and xylachlor.

Another embodiment of this application is a method for preventing and controlling harmful fungi. It involves treating fungi, or materials, plants, soil, or seeds to be protected against fungal invasion, with a compound of formula I or I' or the aforementioned fungicidal composition.

The compounds have been found to have significant antifungal activity, particularly for agricultural applications. Many of these compounds are especially effective for agricultural crops and horticultural plants.

Those skilled in the art will understand that the efficacy of the compound against the aforementioned fungi establishes the compound's general utility as a fungicide.

The compound exhibits broad-spectrum activity against fungal pathogens. Exemplary pathogens may include, but are not limited to, the following disease-causing agents: wheat leaf blight (Zymoseptoria tritici), wheat brown rust (Puccinia triticina), wheat stripe rust (Puccinia striiformis), and apple scab (Venturia ina). Equalis), Powdery mildew of grape (Uncinula necator), Barley scald (Rhynchosporium secalis), Rice blast (Pyricularia oryzae), Soybean rust (Phakopsorapachyrhizi), Wheat glume blotch Wheat (Leptosphaerianodorum), wheat powdery mildew (Blumeria graminis f.sp. tritici), barley powdery mildew (Blumeria graminis f.sp. hordei), cucumber powdery mildew (Erysiphe cichoracearu) Anthracnose of cucumbers (Colletotrichum lagenarium), leaf spot of beet (Cercospora beticola), early blight of tomato (Alternaria solani), and spot blotch of barley (Cochliobolus sativus). The exact amount of active substance applied depends not only on the specific active substance applied but also on the desired action, the species of fungus being controlled and its growth stage, and the plant part or other product that will come into contact with the compound. Therefore, all compounds and formulations containing the compound may not be equally effective or ineffective against the same species of fungi at similar concentrations.

The compound is applied to plants in a disease-inhibiting and botany-acceptable amount. The term "disease-inhibiting and botany-acceptable amount" refers to the amount of a compound that kills or inhibits plant diseases (to which control is desired) but is not obviously toxic to the plant. This amount is typically from about 0.1 to about 1000 ppm (parts per million), preferably 1 to 500 ppm. The exact concentration of the desired compound varies depending on the fungal disease being controlled, the type of formulation used, the method of application, the specific plant species, climatic conditions, etc. Suitable application rates are typically in the range of about 0.10 to about 4 pounds per acre (about 0.01 to 0.45 grams per square meter, g/ ^m² ).

It will be apparent to those skilled in the art that any range or desired value given herein can be extended or modified without losing the desired effect.

Detailed Implementation

The following examples are for illustrative purposes only and should not be construed as limiting the invention in any way. The scope of protection of this invention is defined by the claims.

Given the economic efficiency and diversity of the compounds, we preferentially synthesized a number of compounds, some of which are listed in Table 1 below. The specific compound structures and corresponding compound information are shown in Table 1. The compounds in Table 1 are only for better illustration of the present invention and do not limit the invention. Those skilled in the art should not interpret this as limiting the scope of the above-mentioned subject matter of the invention to the following compounds.

Table 1. Compound structures and their ^¹H NMR values.

Table AC is constructed in the same way as Table 1 above, except that the general formula I is replaced with the general formula I' which has a chiral center at the * position. (At least one chiral center exists at the stated position, and _R3 is not hydrogen). In Table A, the entries under the "Serial Number" column heading are sequentially described as 1(1S)-20(1S), 22(1S)-163(1S). For example, 1(1S) corresponds to the compound 1 in Table 1 where the chiral carbon at position * is in the S configuration. In Table B, the entries under the "Serial Number" column heading are sequentially described as 1(1S,2S)-20(1S,2S), 22(1S,2S)-163(1S,2S). For example, 1(1S,2S) corresponds to the compound 1 in Table 1 where both chiral carbons at positions 1 and 2 are in the S configuration. In Table C, the entries under the "Serial Number" column heading are sequentially described as 1(1S,2S,3S)-20(1S,2S,3S), 22(1S,2S,3S)-163(1S,2S,3S). For example, 1(1S,2S,3S) corresponds to the compound in Table 1 where the chiral carbons at positions 1, 2, and 3 are all in the S configuration.

Several methods for preparing the compounds of the present invention are described in detail in the following schemes and examples. The raw materials can be commercially available or prepared by methods known in the literature or as detailed in the description. Those skilled in the art will understand that other synthetic routes can also be used to synthesize the compounds of the present invention. Although specific raw materials and conditions in the synthetic routes have been described below, they can be easily replaced with other similar raw materials and conditions. Such variations or modifications to the preparation methods of the present invention, such as various isomers of the compounds, are all included within the scope of the present invention. Furthermore, the preparation methods described below can be further modified according to the disclosure of the present invention using conventional chemical methods well known to those skilled in the art. For example, protecting appropriate groups during the reaction process, etc.

The following method examples are provided to further illustrate the preparation methods of the present invention. The specific substances, types, and conditions used are intended to further explain the invention and are not intended to limit its reasonable scope. The reagents used in the synthetic compounds shown in the table below are either commercially available or can be easily prepared by those skilled in the art.

Examples of representative compounds are given below. The synthesis methods of other compounds are similar and will not be described in detail here.

1. Synthesis of compound 5 (1S)

(1) Compound 5-1 (24.0 g, 106.20 mmol) was dissolved in 300 mL of tetrahydrofuran. 3M methylmagnesium chloride (53.1 mL, 159.3 mmol) was added dropwise under a nitrogen atmosphere at 0 °C. After the addition was complete, the mixture was stirred at room temperature for 2 h, and the reaction was monitored by TLC until complete. The reaction solution was quenched with ammonium chloride aqueous solution, diluted with ethyl acetate, and the organic phase was washed with water and saturated brine. The solution was dried and concentrated, and the residue was purified by column chromatography (EA/PE = 1/5) to give a white solid compound 5-2 (13.5 g, 38.5%).

(2) Compound 5-3 (185 mg, 0.8 mmol), 4-pyrrolylpyridine (114 mg, 0.8 mmol), EDCI (295 mg, 15.4 mmol), and compound 5-2 (150 mg, 0.6 mmol) were dissolved in 5 mL of dichloromethane and stirred at room temperature for 48 h. The reaction was monitored by LCMS until complete. The reaction solution was diluted with dichloromethane, and the organic phase was washed with ammonium chloride aqueous solution and saturated brine. The solution was dried and concentrated, and the residue was purified by column chromatography (EA/PE = 1/1) to give a light yellow oily compound 5(1S) (60 mg, 20.86%).

2. Synthesis of compound 5 (1S, 2S, 3S)

(1) Compound 5-4 (2.4 g, 10 mmol) was dissolved in 30 ml of DCM, and HOBT (2 g, 15.4 mmol), EDCI (2.9 g, 15 mmol), N,O-dimethylhydroxylamine hydrochloride (1.5 g, 15 mmol) and triethylamine (3 g, 30 mmol) were added sequentially. The reaction was carried out for 2 hours and the reaction was monitored by LCMS to ensure complete reaction. The reaction solution was concentrated, diluted with ethyl acetate, and the organic phase was washed with water and saturated brine. The solution was dried and concentrated, and the residue was purified by column chromatography (EA/PE = 1/3) to obtain compound 5-5 (2.4 g, 85%).

(2) Compound 5-5 (2.4 g, 8.4 mmol) was dissolved in 30 ml THF, and methyl magnesium chloride (3 M in THF, 8.4 ml) was added dropwise in an ice bath. The reaction was allowed to rise naturally to room temperature. The reaction was monitored by LCMS until it was complete. The reaction was quenched with saturated ammonium chloride. The reaction solution was concentrated and diluted with ethyl acetate. The organic phase was washed with water and saturated brine, dried and concentrated. The residue was purified by column chromatography (EA/PE = 1/4) to obtain compound 5-6 (1.4 g, 70%).

(3) Compound 5-6 (0.7 g, 2.9 mmol) was dissolved in 10 ml THF, and compound 5-7 (160 mg, 0.58 mmol) was added. Borane tetrahydrofuran complex (1 M in THF, 3 ml) was added dropwise in an ice bath. The reaction was allowed to rise naturally to room temperature. The reaction was monitored by LCMS until it was complete. The reaction was quenched with water. The reaction solution was concentrated and diluted with ethyl acetate. The organic phase was washed with water and saturated brine, dried and concentrated. The residue was purified by column chromatography (EA/PE = 1/4) to obtain compound 5-8 (0.4 g, 56%).

(4) Compound 5-9 (650 mg, 3.4 mmol) was dissolved in 10 ml THF. Triethylamine (694 mg, 6.8 mmol), pentanoyl chloride (408 mg, 3.4 mmol), compound 5-8 (592 mg, 2.4 mmol), and a catalytic amount of DMAP were added sequentially in an ice bath. The reaction was carried out overnight at room temperature. The reaction was monitored by LCMS until complete. The reaction was quenched with saturated ammonium chloride. The reaction solution was concentrated and diluted with ethyl acetate. The organic phase was washed with water and saturated brine. The solution was dried and concentrated. The residue was purified by column chromatography (EA/PE = 1/3) to obtain compound 5-10 (760 mg, 53%).

(5) Dissolve compound 5-10 (760 mg, 1.8 mmol) in 5 ml DCM, add 10 ml hydrochloric acid-dioxane solution, react for 1 hour, monitor the reaction to ensure complete reaction by LCMS, and evaporate the solvent in the reaction solution to obtain crude compound 5-11 (0.6 g).

(6) Compound 5-11 (0.6 g, 1.9 mmol) was dissolved in 10 ml DMF, and triethylamine (387 mg, 3.8 mmol) was added and reacted for 1 hour. Compound 5-12 (334 mg, 1.9 mmol), 4-methylmorpholine (767 mg, 7.6 mmol), HOBT (360 mg, 2.6 mmol) and EDCI (474 mg, 2.5 mmol) were added sequentially and reacted overnight at room temperature. The reaction was monitored by LCMS until complete. The reaction solution was concentrated and diluted with ethyl acetate. The organic phase was washed with water and saturated brine, dried and concentrated. The residue was purified by column chromatography (EA/PE = 1/2) and chiral resolution was used to obtain compound 5 (1S, 2S, 3S) (58 mg, 7%).

3. Synthesis of compound 3 (1S)

Compound 3-1 (300 mg, 1.2 mmol) was weighed and dissolved in dichloromethane, then compound 5-3 (233 mg, 0.97 mmol) was added, followed by EDCI (372 mg, 2.4 mmol) and 4-ppy (266 mg, 1.8 mmol). The mixture was reacted overnight at room temperature. The next day, the reaction was monitored by LCMS until complete. A large amount of water was added, and the mixture was extracted with ethyl acetate. The organic phase was collected, concentrated, and the residue was purified by column chromatography to give 3(1S) (white oil, 110 mg, 19%).

4. Synthesis of compound 73(1S)

(1) Compound 73-2 (978 mg, 3.18 mmol) was weighed and dissolved in tetrahydrofuran. Under nitrogen protection, potassium tert-butoxide (668 mg, 2.7 mmol) was added dropwise in an ice bath. The reaction was carried out in an ice bath for half an hour, and then the temperature was raised to room temperature for another half hour. Then, compound 73-1 (490 mg, 2.2 mmol) was added dropwise in an ice bath, and the reaction was carried out overnight at room temperature. The next day, the reaction was monitored by LCMS until it was complete. The mixture was dried, extracted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain compound 73-3 (yellow oil, 420 mg, 76%).

(2) Weigh out compound 73-3 (420 mg, 1.6 mmol) and dissolve it in dioxane hydrochloride. React at room temperature for half an hour. Monitor the reaction as complete by LCMS. Dry the solvent to obtain compound 73-4 (yellow oil, 350 mg, 88%).

(3) Compound 73-4 (350 mg, 1.43 mmol) was weighed and dissolved in tetrahydrofuran under nitrogen protection. Then, methyl magnesium bromide (340 mg, 2.86 mmol) was added dropwise under ice bath. The reaction was allowed to proceed at room temperature for 2 hours. The reaction was monitored by LCMS until it was complete. The reaction was quenched with saturated ammonium chloride solution, extracted with ethyl acetate, and concentrated to obtain compound 73-5 (white oil, 290 mg, 78%).

(4) Compound 73-5 (290 mg, 1.1 mmol) was weighed and dissolved in dichloromethane, then compound 5-3 (213 mg, 0.9 mmol) was added, followed by EDCI (370 mg, 2.2 mmol) and 4-ppy (260 mg, 1.65 mmol). The mixture was reacted overnight at room temperature. The next day, the reaction was monitored by LCMS until it was complete. A large amount of water was added, and the mixture was extracted with ethyl acetate. The organic phase was collected, concentrated, and the residue was purified by column chromatography to obtain 73(1S) (white oil, 125 mg, 23%).

5. Synthesis of Compound 78

(1) Substrate 73-2 (3.8 g, 12.5 mmol) was dissolved in THF, and potassium tert-butoxide in tetrahydrofuran solution (1.2 g, 10.8 mmol) was added under ice bath. After 1 h, substrate 78-1 (2 g, 8.3 mmol) was dissolved in THF and added dropwise to the reaction system under ice bath. The reaction was allowed to proceed overnight at room temperature. After the reaction was complete, the reaction was quenched with water, extracted with ethyl acetate, and purified by silica gel column chromatography to give intermediate 78-2, a white oil (1.2 g, 4.5 mmol, 53.8%).

(2) Substrate 78-2 (1.2 g, 4.5 mmol) was dissolved in 10 mL of 1,4-dioxane hydrochloric acid solution and reacted at room temperature for 1 h. After the reaction was complete, the solvent was removed by rotary evaporation and the mixture was extracted with ethyl acetate/water to give intermediate 78-3, a white oil (1.1 g, 4.3 mmol, 95.0%).

(3) Substrate 78-3 (1.1 g, 4.3 mmol) was dissolved in THF, and methyl magnesium bromide (6.5 mmol) was added under ice bath. The reaction was carried out at room temperature for 3 h. After the reaction was completed, saturated ammonium chloride was added to quench the reaction, and the mixture was extracted with ethyl acetate/water to give intermediate 78-4, a white oil (500 mg, 1.8 mmol, 42.8%).

(4) Compound 78-5 (222 mg, 0.9 mmol) was dissolved in dichloromethane. 4-PPY (137 mg, 0.9 mmol), EDCI (354 mg, 1.8 mmol), and substrate 78-4 (250 mg, 0.9 mmol) were added under ice bath conditions, and the reaction was carried out overnight at room temperature. After the reaction was complete, the mixture was extracted with dichloromethane/water and purified by silica gel column chromatography to give 78 (180 mg, 0.34 mmol, 39.5%).

6. Synthesis of compound 88(1S)

Compound 5(1S) (150 mg, 0.32 mmol) was dissolved in 5 mL of acetone at room temperature. Sodium iodide (9.6 mg, 0.064 mmol), sodium carbonate (102.5 mg, 0.97 mmol), and compound 88-1 (66.0 mg, 0.48 mmol) were added, and the mixture was refluxed for 3 h. The reaction was monitored by LCMS to ensure complete reaction. After the reaction solution was evaporated to dryness, the residue was purified by column chromatography (EA/PE = 1/1) to give compound 88(1S) (128 mg, 68.8%), a pale yellow oil.

7. Synthesis of compound 109(1S)

Compound 5(1S) (150 mg, 0.32 mmol) was dissolved in 5 mL of dichloromethane. Triethylamine (34 mg, 0.34 mmol) and 4-dimethylaminopyridine (2 mg, 0.02 mmol) were added sequentially to the reaction solution. Starting material 109-1 (53 mg, 0.38 mmol) was added under ice bath conditions, and the mixture was allowed to rise naturally to room temperature. The reaction was monitored for completeness. Post-treatment: The mixture was washed once with water, extracted three times with dichloromethane, dried, concentrated, loaded onto a wet plate, purified in normal phase, and the fraction was evaporated to dryness to obtain product 109(1S) (100 mg, 55% yield), a colorless oil.

8. Synthesis of compound 111(1S)

Compound 109(1S) (100 mg, 0.18 mmol) was weighed and dissolved in dichloromethane. Under ice bath conditions, m-chloroperoxybenzoic acid (93 mg, 0.54 mmol) was added dropwise. The mixture was brought to room temperature and reacted for 1 hour under intermediate control. The reaction was monitored by LC-MS until complete. The mixture was washed 3-4 times with saturated sodium thiosulfate solution, followed by 3-4 times with sodium bicarbonate solution. The organic phase was collected, concentrated, and purified under normal phase to give a white oily substance 111(1S) (white oily substance, 70 mg, 66%).

9. Synthesis of Compound 153

Compound 5 was synthesized following the synthetic procedure of 5(1S). Compound 5 (0.2 g, 1 eq, 0.43 mmol) was dissolved in 5 mL of dichloromethane, and triethylamine (0.13 g, 3 eq, 1.29 mmol) was added. Furan-2-carboxyl chloride (68 mg, 1.2 eq, 0.52 mmol) was added dropwise, followed by a catalytic amount of DMAP (5 mg, 0.1 eq, 0.04 mmol). The reaction was carried out at room temperature for 0.5 h, and the reaction was monitored until the starting material disappeared. The reaction solution was directly mixed, and the organic phase was purified by column chromatography to obtain product 153 (0.17 g, purity 92%, yield 71%), a white oily substance.

10. Synthesis of compound 154(1S)

Compound 154-1 (50 mg, 0.4 mmol) was weighed and dissolved in dichloromethane. Then, oxalyl chloride (91 mg, 0.79 mmol) and a few drops of DMF were added dropwise under ice bath conditions. The reaction was allowed to proceed for 15 minutes at room temperature, and LCMS was used to monitor completeness. The solvent was then evaporated to dryness. Compound 5(1S) (221 mg, 0.48 mmol) was weighed and dissolved in dichloromethane. Then, triethylamine (39 mg, 0.39 mmol) and DMAP (39 mg, 0.39 mmol) were added. Acyl chloride was added dropwise under ice bath conditions, and the reaction was allowed to proceed for half an hour at room temperature. LCMS was used to monitor completeness. Water was added to the system, and the mixture was extracted with dichloromethane. The organic phase was washed 2-3 times with dilute hydrochloric acid, concentrated, loaded onto a wet plate, and purified under normal phase to obtain compound 154(1S) (white solid, 65 mg, 29%).

11. Synthesis of compound 163(1S)

Compound 5(1S) (170 mg, 0.37 mmol) was weighed and dissolved in dichloromethane. Then, triethylamine (39 mg, 0.39 mmol) and DMAP (2.5 mg, 0.02 mmol) were added. Compound 163-1 (66 mg, 0.44 mmol) was added dropwise under ice bath conditions, and the reaction was carried out at room temperature for half an hour. The reaction was monitored by LCMS until complete. Water was added to the system, and the mixture was extracted with dichloromethane. The organic phase was washed 2-3 times with dilute hydrochloric acid, concentrated, loaded onto the wet plate, and purified by normal phase to give compound 163(1S) (white solid, 70 mg, 33%).

Bioactivity evaluation (bactericidal activity test - pot method):

The agent was dissolved in dimethyl sulfoxide and diluted with 0.1% Tween 80 aqueous solution to different concentrations. Each concentration treatment was repeated three times. The experiment included a solvent control without the agent and a water treatment as blank controls. The solution was sprayed evenly onto the leaf surface until completely wetted, and then allowed to air dry before use.

For Asian rust of soybean, anthracnose of cucumber, gray mold of tomato, and blast of rice: The experimental targets were selected from *Phakopsora pachyrhizi* Syd., *Colletotrichum orbiculare* Arx., *Botrytis cinerea* Pers. Fr., and *Magnaporthe oryza*, all cultured in live pots. Spores were collected from the leaves of soybean, cucumber, and rice, respectively, using a 0.1% Tween 80 aqueous solution and prepared into suspensions (concentration of ⁴ x 10⁵ to ¹ x 10⁶ spores per ml), stored at 4°C for later use. The fresh spore suspensions were sprayed onto the leaf surface for inoculation. For protective testing, inoculation was performed 24 hours after treatment. After inoculation, the plants were placed in dark conditions with relative humidity above 90% and a temperature of approximately 25°C. After 24 hours, the plants were cultured alternately under light/dark conditions for 12 hours each.

Cucumber powdery mildew: The experimental target should be cucurbit monothecia [Sphaerotheca cucurbitae (Jacz.) Z.Y.Zhao] cultured on live potted plants or detached leaves. Remove diseased and spore-producing pumpkin leaves, shake off excess powder, and gently tap the leaves with a glass rod to evenly distribute the powdery mildew spores onto the test material. For protective experiments, inoculation should be performed 24 hours after pesticide treatment. After inoculation, the plants should be placed at approximately 25°C and cultured under alternating light and dark conditions for 12 hours each.

Sunflower sclerotinia stem rot: Holes are punched in culture dishes covered with mycelium to create 5mm mycelial cakes. These cakes are then inoculated onto sunflower host material. For protective testing, inoculation is performed 24 hours after pesticide treatment. Inoculated material is then transferred to an incubator or artificial climate chamber for incubation in complete darkness.

Based on the disease incidence in the blank control group (disease level 9), the inoculated leaves were graded. The following grading method was used:

Level 0: No disease;

Grade 1: The area of lesions accounts for less than 5% of the total leaf area;

Grade 3: The lesion area accounts for 6% to 10% of the total leaf area;

Level 5: The lesion area accounts for 11% to 25% of the total leaf area;

Level 7: The lesion area accounts for 26% to 50% of the total leaf area;

Level 9: The lesion area accounts for more than 50% of the total leaf area.

Based on the survey data, the disease index and prevention and control effects of each treatment were calculated.

The disease index is calculated using formula (1), and the result is rounded to two decimal places:
X＝{(∑(Ni x i))/(N x 9)}x 100……………………………………(1)

In the formula: X—disease index; Ni—number of diseased leaves at each level; i—relative level value; N—total number of leaves surveyed.

The prevention and control effect is calculated according to formula (2):
P＝{(CK-PT)/CK}x 100……………………………………(2)

In the formula: P—prevention and control effect, in percentage (%); CK—disease index of blank control; PT—disease index of drug treatment.

Table 2. Results of control using representative compounds

Table 3 Comparison of Compound Control Results

Note: N represents no data; control compound A: Reference compound B:

Furthermore, numerous tests have revealed that the compounds and their compositions described in this invention exhibit good control activity against various fungi, including those belonging to the Ascomycetes, Basidiomycetes, Deuteromycetes, and Oomycetes, and thus possess certain commercial value.

Claims (10)

A pyridine amide compound as shown in Formula I:
Where _W1 is O or S; R ₁ is hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, or cycloalkylalkyl; R ₂ is hydrogen, alkyl, alkenyl, _{alkynyl , cycloalkyl, cycloalkylalkyl} , _alkyl , alkenyl, alkenyl, alkenyl, alkenyl, alkenyl, alkenyl, alkenyl, alkenyl, alkenyl, _alkenyl , _alkenyl , alkenyl, _alkenyl , alkenyl _{, alkenyl , alkenyl , alkenyl , alkenyl , alkenyl} , _alkenyl , _alkenyl , _{trialkylsilyl} , aryl, _{alkenyl ...} R ₃ is hydrogen, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, alkyl, alkenyl, alkenyl, or alkynyl, alkenyl, aryl, -O(CO)R ₁₁ , -N(R ₁₁ ) ₂ , -OR ₁₁ , -S(O) _n R ₁₁ , -O(CO)R ₁₁ or -O(CO)OR ₁₁ , alkyl, alkenyl or alkynyl, aryl, heterocyclic, -OR ₁₁ , -O(CO)R ₁₁ , -S(O) _n R ₁₁ or -N(R ₁₁ ) ₂ ...alkyl, alkenyl or alkynyl, alkyl, alkenyl or alkynyl, alkyl, alkenyl or alkynyl, alkyl, alkenyl or _R4 is an alkyl group; R ₁₁ is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclic, or an alkyl, alkenyl, or alkynyl group substituted by at least one group selected from halogen, -OR, -O(CO)R, -(CO)OR, -(CO)O-alkylene-OR, -S(O) _nR , -ON=C(R) ₂ , cycloalkyl, aryl, or heterocyclic. n is 0, 1, or 2; _X1 , _X2 , _X3 , and _X4 are, independently, hydrogen, halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cyano, nitro, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclic, heterocyclic alkyl, -OR, -SR, -SOR, -( _SO2 )R, -N(R) ₂ , -(CO)R, or -(CO)N(R) ₂ ; The aforementioned "cycloalkyl", "heterocyclic" or "aryl" may optionally be replaced by at least one group selected from oxo, halogen, cyano, nitro, alkyl, alkenyl, ynyl, cycloalkyl, haloalkyl, haloalkenyl, haloynyl, -OR, -SR, -(CO)R, -(CO)OR, -N(R) ₂ , -(CO)N(R) ₂ , -(CS)N(R) ₂ , -(SO)R or -( _SO2 )R; R independently represents hydrogen, alkyl, alkenyl, alkynyl, alkyl, alkenyl or alkynyl substituted with at least one group selected from halogen, hydroxyl, alkoxy, cyano or alkoxycarbonyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, phenyl or phenyl substituted with at least one group selected from halogen, cyano, nitro, alkyl, haloalkyl, alkoxycarbonyl, alkylthio, alkylsulfonyl, alkoxy or haloalkoxy. The pyridine amide compound according to claim 1 is characterized in that, R ₁ is hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, halo-C1-C8 alkyl, halo-C2-C8 alkenyl, halo-C2-C8 alkynyl, C3-C8 cycloalkyl or C3-C8 cycloalkyl-C1-C8 alkyl. _R2 is hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 ynyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl, C1-C8 alkyl, and is a _C1 -C8 alkyl, _C2 - _C8 alkenyl, or C2- _C8 ynyl group substituted with at least _one of the following substituents: halogen, tri-C1-C8 alkylsilyl, aryl, aryl, -O(CO) _R11 , -N( _R11 ), -OR11, -S(O) _nR11 , _-COR11 , -(CO) _OR11 , -O(CO)N( _{R11 ) 2} , or -O(CO) _{OR11 .} ) ₂ , -(CO)N(R ₁₁ )(OR ₁₁ ), -S(O) _n R ₁₁ or -SO ₂ N(R ₁₁ ) ₂ ; R ₃ is a C1-C8 alkyl, C2-C8 alkenyl, C2-C8 ynyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl-C1-C8 alkyl, substituted with at least one of the following: halogen, tri-C1-C8 alkylsilyl, heterocyclic, aryl, -O(CO)R ₁₁ , -N(R _{11 ) 2} , _{-OR 11} , -S(O _{) n} R ₁₁ , -O(CO) _{R 11} or -O(CO) _{OR 11 ; R4} is a C1-C8 alkyl group; R ₁₁ is, independently, hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 ynyl, C3-C8 cycloalkyl, aryl, heterocyclic, or a C1-C8 alkyl, C2-C8 alkenyl, or C2-C8 ynyl group substituted with at least one group selected from halogen, -OR, -O(CO)R, -(CO)OR, -(CO)O-(C1-C8 alkylene)-OR, -S(O) _nR , -ON=C(R) ₂ , C3-C8 cycloalkyl, aryl, or heterocyclic. _X1 , _X2 , _X3 , and _X4 are, independently, hydrogen, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, halo-C1-C8 alkyl, halo-C2-C8 alkenyl, halo-C2-C8 alkynyl, cyano, nitro, C3-C8 cycloalkyl, C3-C8 cycloalkyl-C1-C8 alkyl, aryl, aryl-C1-C8 alkyl, heterocyclic, heterocyclic-C1-C8 alkyl, -OR, -SR, -SOR, -( _SO2 )R, -N(R) ₂ , -(CO)R, or -(CO)N(R) ₂ ; The aforementioned “C3-C8 cycloalkyl”, “heterocyclic” or “aryl” may optionally be replaced by at least one group selected from oxo, halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 ynyl, C3-C8 cycloalkyl, halo-C1-C8 alkyl, halo-C2-C8 alkenyl, halo-C2-C8 ynyl, -OR, -SR, -(CO)R, -(CO)OR, -N(R) ₂ , -(CO)N(R) ₂ , -(CS)N(R) ₂ , -(SO)R or -( _SO2 )R; R independently represents hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 alkyl, C2-C8 alkenyl or C2-C8 alkynyl substituted with at least one group selected from halogen, hydroxyl, C1-C8 alkoxy, cyano or C1-C8 alkoxycarbonyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl C1-C8 alkyl, C3-C8 cycloalkenyl, C3-C8 cycloalkenyl C1-C8 alkyl, phenyl or phenyl substituted with at least one group selected from halogen, cyano, nitro, C1-C8 alkyl, halo-C1-C8 alkyl, C1-C8 alkoxycarbonyl, C1-C8 alkylthio, C1-C8 alkylsulfonyl, C1-C8 alkoxy or halo-C1-C8 alkoxy. The pyridine amide compound according to claim 1 or 2 is characterized in that, R ₁ is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo-C1-C6 alkyl, halo-C2-C6 alkenyl, halo-C2-C6 alkynyl, C3-C6 cycloalkyl or C3-C6 cycloalkyl-C1-C6 alkyl. _R2 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl, C1-C6 alkyl, and is a _C1 -C6 alkyl, _C2 - _C6 alkenyl, or C2- _C6 ynyl group substituted with at least _one of the following substituents: halogen, tri-C1-C6 alkylsilyl, aryl, aryl, -O(CO) _R11 , -N( _R11 ), -OR11, -S(O) _nR11 , _-COR11 , -(CO) _OR11 , -O(CO)N( _{R11 ) 2} , or -O(CO) _{OR11 .} ) ₂ , -(CO)N(R ₁₁ )(OR ₁₁ ), -S(O) _n R ₁₁ or -SO ₂ N(R ₁₁ ) ₂ ; R ₃ is a C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl-C1-C6 alkyl group substituted with at least one of the following: halogen, tri-C1-C6 alkylsilyl, heterocyclic, aryl, -O(CO)R ₁₁ , -N(R _{11 ) 2} , _{-OR 11} , -S(O _{) n} R ₁₁ , -O(CO) _{R 11} or -O(CO) _{OR 11 ; R4} is a C1-C6 alkyl group; R ₁₁ is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C6 cycloalkyl, aryl, heterocyclic, or a C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 ynyl group substituted with at least one group selected from halogen, -OR, -O(CO)R, -(CO)OR, -(CO)O-(C1-C6 alkylene)-OR, -S(O) _nR , -ON=C(R) ₂ , C3-C6 cycloalkyl, aryl, or heterocyclic. _X1 , _X2 , _X3 , and _X4 are, independently, hydrogen, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogenated C1-C6 alkyl, halogenated C2-C6 alkenyl, halogenated C2-C6 alkynyl, cyano, nitro, C3-C6 cycloalkyl, C3-C6 cycloalkyl C1-C6 alkyl, aryl, aryl C1-C6 alkyl, heterocyclic, heterocyclic C1-C6 alkyl, -OR, -SR, -SOR, -( _SO2 )R, -N(R) ₂ , -(CO)R, or -(CO)N(R) ₂ ; The aforementioned “C3-C6 cycloalkyl”, “heterocyclic” or “aryl” may optionally be replaced by at least one group selected from oxo, halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C6 cycloalkyl, halo-C1-C6 alkyl, halo-C2-C6 alkenyl, halo-C2-C6 ynyl, -OR, -SR, -(CO)R, -(CO)OR, -N(R) ₂ , -(CO)N(R) ₂ , -(CS)N(R) ₂ , -(SO)R or -( _SO2 )R; R independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl substituted with at least one group selected from halogen, hydroxyl, C1-C6 alkoxy, cyano or C1-C6 alkoxycarbonyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl C1-C6 alkyl, C3-C6 cycloalkenyl, C3-C6 cycloalkenyl C1-C6 alkyl, phenyl or phenyl substituted with at least one group selected from halogen, cyano, nitro, C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxycarbonyl, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 alkoxy or halo-C1-C6 alkoxy; Preferably, the compound is selected from any one of Table 1, A-C in the specification. A pyridine amide compound with a chiral center, as shown in Formula I':
Wherein, the substituents _R1 , _R2 , _R3 , _R4 , _X1 , _X2 , _X3 , _X4 and _W1 are defined as described in any one of claims 1-3, and _R3 is not hydrogen; *the carbon atom position has at least one chiral center, and based on the content of stereoisomers with R and S configurations at position 1, it has a stereochemical purity of 60-100% (S), preferably 70-100% (S), more preferably 80-100% (S), further preferably 90-100% (S), and even more preferably 95-100% (S); and/or Based on the content of stereoisomers having R and S configurations at position 2, it has a stereochemical purity of 60-100% (S), preferably 70-100% (S), more preferably 80-100% (S), further preferably 90-100% (S), and even more preferably 95-100% (S); and/or Based on the content of stereoisomers having R and S configurations at position 3, it has a stereochemical purity of 60-100% (S), preferably 70-100% (S), more preferably 80-100% (S), further preferably 90-100% (S), and even more preferably 95-100% (S). The method for preparing the pyridine amide compound according to any one of claims 1-4 comprises the following steps: (1) Compound I is prepared by a condensation reaction of compound II and compound III. The chemical reaction equation is as follows:
(2) Compound I is prepared by condensation reaction of compound IV with compound V or its salt (such as hydrochloride), and the chemical reaction equation is as follows:
(3) Alternatively, when _R2 does not represent H, from compound I' Prepared via a substitution reaction; Wherein, L and L' independently represent OH or halogen, respectively; the definitions of substituents _R1 , _R2 , _R3 , _R4 , _X1 , _X2 , _X3 , _X4 and _W1 are as described in any one of claims 1-4. The method for preparing pyridine amide compounds according to claim 5 is characterized in that, The reactions in steps (1) and (2) are carried out in the presence of a solvent. Preferably, a condensing agent and/or a base are added during the reaction in steps (1) and (2). More preferably, the solvent is selected from at least one of DMF, DMA, acetonitrile, dichloroethane, DMSO, dioxane, dichloromethane, or ethyl acetate, the base is selected from at least one of inorganic or organic bases, and the condensing agent is selected from at least one of Py-BOP, Py-AOP, EDCI, HOBT, DCC, HBTU, or HATU. An intermediate as described in formula II, formula V, or a salt thereof as claimed in claim 5. A bactericidal composition, characterized in that it comprises a biologically effective amount of at least one of the pyridine amide compounds according to any one of claims 1-4; preferably, it further comprises a formulation adjuvant; more preferably, it further comprises other active ingredients. The use of the pyridine amide compound as described in any one of claims 1-4, or the fungicidal composition as described in claim 8, in the control of plant pathogenic fungi. A method for controlling harmful fungi comprises treating fungi or materials, plants, soil or seeds to be protected against fungal invasion with an effective amount of a pyridine amide compound as described in any one of claims 1-4, or a fungicidal composition as described in claim 8.