KR20030059315A - Aryl and heteroarylcyclopropyl oxime ethers and their use as fungicides - Google Patents

Abstract

The present invention relates to certain cyclopropyl oxime ether compounds with substituted aryl and heterocyclic substituents, compositions containing such compounds and methods of inhibiting fungi by using fungal toxicologically effective amounts of such compounds. The compound has a wide range of fungicidal properties.

Description

Aryl and heteroarylcyclopropyl oxime ethers and their use as fungicides

This application claims the priority of US Provisional Application No. 60 / 254,120, filed Dec. 8, 2000.

The present invention relates to certain aryl cyclopropyl oxime ether compounds, compositions containing the compounds and methods of inhibiting fungi using fungal toxicologically effective amounts of such compounds.

Compounds having specific oxime ether structures are described in US Pat. No. 5,824,705. We have found cyclopropyl oxime ether groups with substituted aryl and heterocyclic moieties having a wide range of fungicidal properties.

Cyclopropyloxime ethers of the present invention are compounds of formula (I), salts, complexes, enantiomorphs, stereoisomers and mixtures thereof.

In Formula I,

A is hydrogen, halo, cyano, (C ₁ -C ₁₂ ) alkyl or (C ₁ -C ₁₂ ) alkoxy,

R ₁ is (C ₁ -C ₁₂ ) alkyl or halo (C ₁ -C ₁₂ ) alkyl,

R ₂ is hydrogen, (C ₁ -C ₁₂ ) alkyl, halo (C ₁ -C ₁₂ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, halo (C ₃ -C ₇ ) cycloalkyl, (C ₂ -C ₈ ) alkenyl, halo (C ₂ -C ₈ ) alkenyl, (C ₂ -C ₈ ) alkynyl, halo (C ₂ -C ₈ ) alkynyl or cyano,

R ₃ is hydrogen,

R ₄ and R ₅ are independently hydrogen, (C ₁ -C ₁₂ ) alkyl, halo (C ₁ -C ₁₂ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, halo (C ₃ -C ₇ ) cycloalkyl, (C ₂ -C ₈ ) alkenyl, halo (C ₂ -C ₈ ) alkenyl, (C ₂ -C ₈ ) alkynyl, halo (C ₂ -C ₈ ) alkynyl, halo, cyano or (C ₁ -C ₄ ) alkoxycarbonyl,

[A] R ₇ is aryl, arylalkyl, heterocyclic or heterocyclic (C ₁ -C ₄ ) alkyl wherein the aryl or heterocyclic ring is substituted by 2 to 5 substituents and is bonded to a cyclopropyl ring Positions on the aryl or heterocyclic ring adjacent to are both substituted), and R ₆ is hydrogen, (C ₁ -C ₁₂ ) alkyl, halo (C ₁ -C ₁₂ ) alkyl, (C ₃ -C ₇ ) cyclo Alkyl, halo (C ₃ -C ₇ ) cycloalkyl, (C ₂ -C ₈ ) alkenyl, halo (C ₂ -C ₈ ) alkenyl, (C ₂ -C ₈ ) alkynyl, halo (C ₂ -C ₈ ) alkynyl, halo, cyano, or (C ₁ -C ₄ ) alkoxycarbonyl; or

[B] R ₇ is aryl, arylalkyl, heterocyclic or heterocyclic (C ₁ -C ₄ ) alkyl wherein the aryl or heterocyclic ring is unsubstituted or substituted by 1 to 4 substituents and is cyclo At least one position on the aryl or heterocyclic ring adjacent to the bond with the propyl ring is hydrogen), and R ₆ is hydrogen, (C ₁ -C ₁₂ ) alkyl, halo (C ₁ -C ₁₂ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, halo (C ₃ -C ₇ ) cycloalkyl, (C ₂ -C ₈ ) alkenyl, halo (C ₂ -C ₈ ) alkenyl, (C ₂ -C ₈ ) alkynyl, halo (C ₂ -C ₈ ) alkynyl, halo, cyano or (C ₁ -C ₄ ) alkoxycarbonyl.

The above-mentioned (C ₁ -C ₁₂ ) alkyl, (C ₂ -C ₈ ) alkenyl, (C ₂ -C ₈ ) alkynyl and (C ₃ -C ₇ ) cycloalkyl groups include nitro, halomethyl, (C ₁ -C ₄ ) may be optionally and independently substituted with up to 3 substituents selected from alkoxycarbonyl and cyano.

The term alkyl includes both branched and straight chain alkyl groups having 1 to 12 carbon atoms. Typical alkyl groups are methyl, ethyl, n-propyl, iso-propyl, n-butyl, secondary-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, n-heptyl, isooctyl , Nonyl, decyl, undecyl, and dodecyl. The term haloalkyl refers to an alkyl group substituted with 1 to 3 halogens.

The term alkenyl means an ethylenically unsaturated hydrocarbon group having a chain length of 2 to 8 carbon atoms, which is a straight or branched chain having 1 or 2 ethylene bonds. The term haloalkenyl means an alkenyl group substituted by one to three halogen atoms. The term alkynyl refers to an unsaturated hydrocarbon group having a chain length of 2 to 8 carbon atoms, which is a straight or branched chain having 1 or 2 acetylene bonds.

The term aryl is halogen, cyano, nitro, trihalomethyl, trihalomethoxy, phenyl, phenoxy, (C ₁ -C ₄ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, (C ₂ -C ₈ ) Alkenyl, (C ₁ -C ₄ ) alkoxy, (C ₁ -C ₄ ) alkylthio, (C ₁ -C ₄ ) alkylsulfoxide, halo (C ₁ -C ₄ ) alkyl, halo (C ₁ -C ₄ ) up to 5 substituents independently selected from the group consisting of alkoxy, halo (C ₃ -C ₇ ) cycloalkyl, halo (C ₂ -C ₈ ) alkenyl, or (C ₁ -C ₄ ) alkoxycarbonyl Phenyl and naphthyl which may be substituted by.

Typical phenyl substituents in which hydrogen is substituted at one or more positions on the phenyl ring adjacent to the bond with the cyclopropyl ring include, but are not limited to, 2-chloro, 3-chloro, 4-chloro, 2-fluoro, 3- Fluoro, 4-fluoro, 2-bromo, 3-bromo, 4-bromo, 2-methyl, 3-methyl, 4-methyl, 2-trifluoromethyl, 3-trifluoromethyl, 4 -Trifluoromethyl, 2-methoxy, 3-methoxy, 4-methoxy, 2-trifluoromethoxy, 3-trifluoromethoxy, 4-trifluoromethoxy, 2-cyano, 3-cya Furnace, 4-cyano, 2,3-dichloro, 2,3-difluoro, 2,3-dibromo, 2,3-dimethyl, 2,3-dimethoxy, 2,3-bis- (tri Fluoromethyl), 2,3-bis- (trifluoromethoxy), 2,4-difluoro, 2,4-dichloro, 2,4-dibromo, 2,4-dimethyl, 2,4- Dimethoxy, 2,4-bis- (trifluoromethyl), 2,4-bis- (trifluoromethoxy), 2,5-difluoro, 2,5-dichloro, 2,5-dibromo, 2,5-dimethyl, 2,5-dimethoxy, 2,5-bis- (trifluoromethyl), 2,5-bis- (trifluoromethoxy), 3,4 -Difluoro, 3,4-dichloro, 3,4-dibromo, 3,4-dimethyl, 3,4-dimethoxy, 3,4-bis- (trifluoromethyl), 3,4-bis -(Trifluoromethoxy), 3,5-difluoro, 3,5-dichloro, 3,5-dibromo, 3,5-dimethyl, 3,5-bis- (trifluoromethyl), 3 , 5-bis- (trifluoro-methoxy), 2,3,4-trifluoro, 2,3,4-trichloro, 2,3,4-tribromo, 2,3,4-trimethyl , 2,3,4-trimethoxy, 2,3,4-tris (trifluoromethyl), 2,3,4-tris (trifluoromethoxy), 2,3,5-trifluoro, 2 , 3,5-trichloro, 2,3,5-tribromo, 2,3,5-trimethyl, 2,3,5-tris (trifluoromethyl), 2,3,5-tris (trifluoro Lomethoxy), 2,4,5-trifluoro, 2,4,5-trichloro, 2,4,5-tribromo, 2,4,5-trimethyl, 2,4,5-trimethoxy , 2,4,5-tris (trifluoromethyl), 2,4,5-tris (trifluoromethoxy), 3,4,5-trifluoro, 3,4,5-trichloro, 3,4,5-tribromo, 3,4,5-trimethyl , 3,4,5-trimethoxy, 3,4,5-tris (trifluoromethyl), 3,4,5-tris (trifluoromethoxy), 2,3,4,5-tetrafluoro , 2,3,4,5-tetrachloro, 2,3,4,5-tetrabromo, 2,3,4,5-tetramethyl, 2,3,4,5-tetramethoxy, 2,3 , 4,5-tetra (trifluoromethyl) and 2,3,4,5-tetra (tetrafluoromethoxy).

Typical phenyl substituents in which both positions on the phenyl ring adjacent to the cyclopropyl ring are substituted are, but are not limited to, 2,6-dichloro, 2,3,6-trichloro, 2,4,6-trichloro 2,6-difluoro, 2,3,6-trifluoro, 2,4,6-trifluoro, 2,6-dibromo, 2,3,6-tribromo, 2, 4,6-tribromo 2,3,4,6-tetrachloro, 2,3,5,6-tetrachloro, 2,3,4,5,6-pentachloro, 2,3,4,6- Tetrabromo, 2,3,5,6-tetrabromo, 2,3,4,5,6-pentabromo, 2,3,4,6-tetrafluoro, 2,3,5,6- Tetrafluoro, 2,3,4,5,6-pentafluoro, 2,6-dimethyl, 2,3,6-trimethyl, 2,4,6-trimethyl, 2,6-dimethoxy, 2,3 , 6-trimethoxy, 2,4,6-trimethoxy, 2,6-diethoxy, 2,3,6-triethoxy, 2,4,6-triethoxy, 2,3,4, 6-tetramethyl, 2,3,5,6-tetramethyl, 2,3,4,5,6-pentamethyl, 2,3,4,6-tetramethoxy, 2,3,5,6-tetra Methoxy, 2,3,4,5,6- pentamethoxy, 2,3,4,6- Triethoxy, 2,3,5,6-tetraethoxy, 2,3,4,5,6-pentaethoxy, 2,6-dicyano, 2,3,6-tricyano, 2,4, 6-tricyano, 2,6-dinitro, 2,6-diphenyl, 2,6-diphenoxy, 2,6-dibenzyl, 2,6-bis- (trifluoromethyl), 2,3 , 6-tris- (trifluoromethyl), 2,4,6-tris- (trifluoro-methyl), 2,3,4,6-tetra- (trifluoromethyl), 2,3,5 , 6-tetra- (trifluoromethyl), 2,3, 4,5,6- penta- (trifluoromethyl), 2,6-bis- (trifluoromethoxy), 2,3,6- Tris (trifluoromethoxy), 2,4,6-tris- (trifluoromethoxy), 2,3,4,5-tetra (trifluoromethoxy), 2,3,4,6-tetra- ( Trifluoro-methoxy), 2,3,5,6-tetra- (trifluoromethoxy), 2,3,4,5,6-penta- (trifluoromethoxy), 2-bromo-6 -Chloro, 2-bromo-6-fluoro, 2-bromo-6- (trifluoromethyl), 2-bromo-6-methyl, 2-bromo-6-methoxy, 2-bromo -6- (trifluoromethoxy), 2-bro -6-cyano, 2-chloro-6-fluoro, 2-chloro-6- (trifluoromethyl), 2-chloro-6-methyl, 2-chloro-6-methoxy, 2-chloro-6 -Trifluoromethoxy, 2-chloro-6-cyano, 2-fluoro-6- (trifluoromethyl), 2-fluoro-6-methyl, 2-fluoro-6-methoxy, 2- Fluoro-6- (trifluoromethoxy), 6-cyano-2-fluoro, 2-methyl-6- (trifluoromethyl), 6-methoxy-2-methyl, 2-methyl-6- (Trifluoromethoxy), 6-cyano-2-methyl, 3,6-dichloro-2-fluoro, 3-chloro-2,6-difluoro, 4-chloro-2,6-difluoro , 2-bromo-3,6-dichloro, 2,3-dibromo-6-chloro, 3-chloro-2,6-dibromo, 2,6-dichloro-3-fluoro, 2,3 -Dichloro-6-fluoro, 2-chloro-3,6-difluoro, 3-bromo-2,6-dichloro, 3-bromo-2,6-fluoro, 3-bromo-6- Chloro-2-fluoro, 2-bromo-5-chloro-6-fluoro, 2,6-dibromo-3-fluoro, 2,5-dibromo-6-fluoro, 2,4 - Chloro-6-fluoro, 2,6-chloro-4-fluoro, 2,4-dichloro-6-bromo, 2,6-dichloro-4-bromo, 2,4-difluoro-6- Chloro, 2,4-difluoro-6-bromo, 2,6-difluoro-4-bromo, 2,4-dibromo-6-fluoro, 2,4-dibromo-6 -Chloro, 2,6-dibromo-4-chloro, 2,6-dibromo-4-fluoro, 2,4-dichloro-6-methyl, 2,6-dichloro-4-methyl, 2- Chloro-4,6-dimethyl, 4-chloro-2,6-dimethyl, 2,4-difluoro-6-methyl, 2,6-difluoro-4-methyl, 2-fluoro-4,6 -Dimethyl, 4-fluoro-2,6-dimethyl, 2,4-dibromo-6-methyl, 2,6-dibromo-4-methyl, 2-bromo-4,6-dimethyl, 4 -Bromo-2,6-dimethyl, 2,4-dichloro-6-methoxy, 2,6-dichloro-4-methoxy, 2-chloro-4,6-dimethoxy, 4-chloro-2,6 -Dimethoxy, 2,4-difluoro-6-methoxy, 2,6-difluoro-4-methoxy-, 2-fluoro-4,6-dimethoxy, 4-fluoro-2, 6-dimethoxy, 2,4-dibromo-6-methoxy, 2,6-dibromo-4-methoxy, 4-bro -2,6-dimethoxy, 4-bromo-2,6-dimethoxy, 2,4-dichloro-6- (trifluoromethyl), 2,6-dichloro-4- (trifluoromethyl), 2-chloro-4,6-bis- (trifluoromethyl), 4-chloro-2,6-bis- (trifluoromethyl), 2,4-difluoro-6- (trifluoromethyl) , 2,6-difluoro-4- (trifluoromethyl), 2-fluoro-4,6-bis- (trifluoromethyl), 4-fluoro-2,6-bis- (trifluoro Romethyl), 2,4-dibromo-6- (trifluoromethyl), 2,6-dibromo-4- (trifluoromethyl), 2-bromo-4,6-bis- ( Trifluoromethyl), 4-bromo-2,6-bis- (trifluoromethyl), 2-chloro-4,6-bis- (trifluoromethoxy), 4-chloro-2,6-bis -(Trifluoromethoxy), 2,4-difluoro-6- (trifluoromethoxy), 2,6-difluoro-4- (trifluoromethoxy), 2-fluoro-4,6 -Bis- (trifluoro-methoxy), 4-fluoro-2,6-bis- (trifluoromethoxy), 2,4-dibromo-6- ( Trifluoromethoxy), 2,6-dibromo-4- (trifluoromethoxy), 2-bromo-4,6-bis- (trifluoromethoxy), 4-bromo-2,6- Bis- (trifluoromethoxy), 4,6-dichloro-2-nitro, 4,6-dibromo-2-nitro, 4,6-difluoro-2-nitro, 2,6-dichloro-4 -Nitro, 2-bromo-3,4,6-trichloro, 6-fluoro-2,4,5-trichloro, 6-chloro-2,4,5-tribromo, 6-fluoro- 2,4,5-tribromo, 2-bromo-3,4,6-trifluoro, 2-chloro-3,4,6-trifluoro, 6-methyl-2,4,5-trichloro 6-methyl-2,4,5-tribromo, 6-methyl-2,4,5-trifluoro, 6- (trifluoromethyl) -2,4,5-trichloro, 6- (Trifluoromethyl) -2,4,5-tribromo, 2- (trifluoro-methyl) -3,4,6-trifluoro, 6- (trifluoromethoxy) -2,4, 5-tribromo, 2- (trifluoromethoxy) -3,4,6-trifluoro, 6- (trifluoromethoxy) -2,4,5-trichloro, 2-bromo-3, 5,6-trichloro, 6- Luoro-2,3,5-trichloro, 6-chloro-2,3,5-tribromo, 6-fluoro-2,3,5-tribromo, 2-bromo-3,5, 6-trifluoro, 2-chloro-3,5,6-trifluoro, 6-methyl-2,3,5-trichloro, 6-methyl-2,3,5-tribromo, 2-methyl -3,5,6-trifluoro, 2,3,5-trichloro-6-trifluoromethyl, 2,3,5-tribromo-6-trifluoromethyl), 3,5,6 -Trifluoro-2- (trifluoromethyl), 3,5,6-trichloro-2-trifluoro-methoxy, 2,3,5-tribromo-6-trifluoromethoxy, 3 , 5,6-trifluoro-2-trifluoromethoxy, 4-bromo-2,3,5,6-tetrachloro, 4-fluoro-2,3,5,6-tetrachloro, 4- Chloro-2,3,5,6-tetrabromo-, 4-fluoro-2,3,5,6-tetrabromo, 4-chloro-2,3,5,6-tetrafluoro, 4- Bromo-2,3,5,6-tetrafluoro, 2-bromo-3,4,5,6-tetrachloro, 6-fluoro-2,3,4,5-tetrachloro, 2-chloro -3,4,5,6-tetrafluoro, 2-bromo-3,4,5,6- Tetrafluoro, 2-chloro-3,4,5,6-tetrabromo, 2-fluoro-3,4,5,6-tetrabromo, 4-methyl-2,3,5,6-tetra Chloro, 4-methyl-2,3,5,6-tetrabromo, 4-methyl-2,3,5,6-tetrafluoro, 2,3,5,6-tetrachloro-4- (trifluoro Romethyl), 2,3,5,6-tetrabromo-4- (trifluoromethyl), 2,3,5,6-tetrafluoro-4- (trifluoromethyl), 2,3, 5,6-tetrachloro-4- (trifluoromethoxy), 2,3,5,6-tetrabromo-4- (trifluoromethoxy, 2,3,5,6-tetrafluoro-4- (Trifluoromethoxy), 6-methyl-2,3,4,5-tetrachloro, 6-methyl-2,3,4,5-tetrabromo, 2-methyl-3,4,5,6- Tetrafluoro, 2,3,4,5-tetrachloro-6- (trifluoromethyl), 2,3,4,5-tetrabromo-6- (trifluoromethyl), 3,4,5 , 6-tetrafluoro-2- (trifluoromethyl), 2,3,4,5-tetrachloro-6- (trifluoromethoxy), 2,3,4,5-tetrabromo-6- (Trifluoromethoxy) and 3,4,5,6-te A la-fluoro-a (trifluoromethoxy).

The term heterocyclic is a substituted 6-membered unsaturated ring selected from the group consisting of 3- or 4-pyridinyl, 5-pyrimidinyl and 3-pyridazinyl or 3-thienyl, 3-furyl, 3-pyrrolyl , 4-isoxazolyl, 4-isothiazolyl and 4-pyrazolyl, means a 5-membered unsaturated ring, wherein both positions on a heterocyclic ring adjacent to a bond with a cyclopropyl ring are substituted Wherein the ring is (C ₁ -C ₄ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, trihalomethyl, trihalomethoxy, halogen, cyano, (C ₁ -C ₄ ) alkoxycarbonyl, Substituted by 2 to 4 substituents independently selected from the group consisting of nitro, phenyl and phenoxy. The term heterocyclic is also a substituted or unsubstituted 6-membered unsaturated ring containing 1, 2 or 3 heteroatoms, preferably 1, 2 or 3 heteroatoms independently selected from oxygen, nitrogen and sulfur or 5-membered unsaturated rings containing 1, 2 or 3 heteroatoms independently selected from 2, 3 or 3 heteroatoms, preferably oxygen, nitrogen and sulfur, wherein the heterocyclic ring is unsubstituted or bonded to a cyclopropyl ring At least one position of the heterocyclic ring adjacent to is substituted by 1 to 3 substituents which are hydrogen substituents. Examples of heterocycles include, but are not limited to, 2-, 3- or 4-pyridinyl, pyrazinyl, 4- or 5-pyrimidinyl, pyridazinyl, pyrazole, imidazolyl, 2 or 3-thier Nil, 2 or 3-furyl, 3-pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl and thiadiazolyl. These rings are independent from (C ₁ -C ₄ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, trihalomethyl, halogen, cyano, (C ₁ -C ₄ ) alkoxycarbonyl, nitro, phenyl and phenoxy And optionally substituted with one to three substituents.

The term arylalkyl is used to denote a group having an aryl moiety as described above, wherein the alkyl chain is from 1 to 10 carbon atoms and is branched or straight chain, preferably straight chain. Typical arylalkyl moieties are optionally substituted benzyl, phenethyl, phenpropyl and phenbutyl moieties.

Typical benzyl residues in which one or more positions on the phenyl ring adjacent to the methylene bound to the cyclopropyl ring are replaced by hydrogen include, but are not limited to, 2-chlorobenzyl, 3-chlorobenzyl, 4-chloro-benzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2-bromobenzyl, 3-bromobenzyl, 4-bromobenzyl, 2-trifluoromethylbenzyl, 3-trifluoromethyl Benzyl, 4-trifluoromethylbenzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl 2,3-difluorobenzyl, 2,3-dichlorobenzyl, 2,3-dibromobenzyl, 2 , 3-dimethylbenzyl, 2,4-difluorobenzyl, 2,4-dichlorobenzyl, 2,4-dibromobenzyl, 2,4-dimethylbenzyl, 2,5-difluorobenzyl, 2,5 -Dichlorobenzyl, 2,5-dibromobenzyl, 2,5-dimethylbenzyl, 3,4-difluorobenzyl, 3,4-dichlorobenzyl, 3,4-dibromobenzyl, 3,4-dimethyl Benzyl, 3,5-difluorobenzyl, 3,5-dichlorobenzyl, 3,5-dibro Benzyl, 3,5-dimethylbenzyl, 2,3,4-trifluorobenzyl, 2,3,4-trichlorobenzyl, 2,3,4-tribromobenzyl, and 3,4,5-trichloro There is benzyl. Typical benzyl residues in which both positions on the phenyl ring are substituted adjacent to the methylene bound to the cyclopropyl ring are, but are not limited to, 2,6-dichlorobenzyl, 2,3,6-trichlorobenzyl, 2 , 4,6-trichlorobenzyl, 2,6-difluorobenzyl, 2,3,6-fluorobenzyl, 2,4,6-trifluorobenzyl, 2,6-bis- (trifluoromethyl ) Benzyl, 2,3,6-tris- (trifluoromethyl) benzyl, 2,4,6-tris- (trifluoromethyl) benzyl, 2,3,4,6-tetrachlorobenzyl, 2,3 , 5,6-tetrachlorobenzyl, 2,3,4,5,6-pentachlorobenzyl, 2,3,4,6-tetrabromobenzyl, 2,3,5,6-tetrabromobenzyl, 2 , 3,4,5,6-pentabromobenzyl, 2,3,4,6-tetrafluorobenzyl, 2,3,5,6-tetrafluorobenzyl and 2,3,4,5,6- Pentafluorobenzyl. Examples of typical phenethyl moieties wherein one or more positions on the phenyl ring adjacent to the ethyl moiety bound to the cyclopropyl ring are replaced by hydrogen include, but are not limited to, 2- (2-chlorophenyl) ethyl, 2- (3-chlorophenyl) ethyl, 2- (4-chlorophenyl) ethyl, 2- (2-fluorophenyl) ethyl, 2- (3-fluorophenyl) ethyl, 2- (4-fluoro-phenyl) Ethyl, 2- (2-methylphenyl) ethyl, 2- (3-methylphenyl) ethyl, 2- (4-methylphenyl) ethyl, 2- (4-trifluoroethylphenyl) ethyl, 2- (2,4-dichloro Phenyl) ethyl and 2- (3,5-dimethoxyphenyl) ethyl. Typical phenethyl moieties in which both positions on the phenyl ring are substituted adjacent to the ethyl moiety bound to the cyclopropyl ring, include, but are not limited to, 2- (2,6-dichlorophenyl) ethyl, 2- ( 2,3,6-trichlorophenyl) ethyl, 2- (2,4,6-trichlorophenyl) ethyl, 2- (2,6-difluorophenyl) ethyl, 2- (2,3,6- Trifluorophenyl) ethyl, 2- (2,4,6-trifluorophenyl) ethyl, 2- (2,6-dimethylphenyl) ethyl, 2- (2,3,6-trimethylphenyl) ethyl, 2 -(2,4,6-trimethylphenyl) ethyl, 2- (2,6-bis- (trifluoromethyl) phenyl) ethyl, 2- (2,3,6-tris (trifluoromethyl) phenyl) Ethyl, 2- (2,4,6-tris- (trifluoromethyl) phenyl) ethyl, 2- (2,6-dimethoxyphenyl) ethyl, 2- (2,3,6-trimethoxy-phenyl ) Ethyl and 2- (2,4,6-trimethoxyphenyl) ethyl. Typical phenpropyl residues in which one or more positions on the phenyl ring adjacent to the propyl moiety bound to the cyclopropyl ring are substituted by hydrogen include, but are not limited to, 3-phenylpropyl, 3- (2-chlorophenyl) Propyl, 3- (3-chlorophenyl) propyl, 3- (4-chlorophenyl) propyl, 3- (2,4-dichlorophenyl) propyl, 3- (2-fluorophenyl) propyl, 3- (3- Fluorophenyl) propyl, 3- (4-fluorophenyl) propyl, 3- (2-methylphenyl) propyl, 3- (3-methylphenyl) propyl, 3- (4-methylphenyl) propyl, 3- (4-tri Fluoromethyl-phenyl) propyl, 3- (2,4-dichlorophenyl) propyl and 3- (3,5-dimethylphenyl) propyl. Typical penpropyl residues in which both positions on the phenyl ring adjacent to the propyl moiety bound to the cyclopropyl ring are substituted include, but are not limited to, 3- (2,6-dichlorophenyl) propyl, 3- ( 2,3,6-trichlorophenyl) propyl, 3- (2,4,6-trichlorophenyl) propyl, 3- (2,6-difluorophenyl) propyl, 3- (2,3,6- Trifluorophenyl) propyl, 3- (2,4,6-trifluorophenyl) propyl, 3- (2,6-dimethylphenyl) propyl, 3- (2,3,6-trimethyl-phenyl) propyl, 3- (2,4,6-trimethylphenyl) propyl and 3- (2,6-bis (trifluoromethyl) phenyl) propyl. Typical phenbutyl moieties wherein one or more positions on the phenyl ring adjacent to the butyl moiety bound to the cyclopropyl ring are substituted by hydrogen, include but are not limited to 4-phenylbutyl, 4- (2-chloro-phenyl ) Butyl, 4- (3-chlorophenyl) butyl, 4- (4-chlorophenyl) butyl, 4- (2-fluorophenyl) -butyl, 4- (3-fluorophenyl) butyl, 4- (4 -Fluorophenyl) butyl, 4- (2-methylphenyl) butyl, 4- (3-methylphenyl) butyl, 4- (4-methylphenyl) butyl and 4- (2,4-dichlorophenyl) butyl. Typical phenbutyl moieties in which both positions on the phenyl ring are substituted adjacent to the butyl moiety bound to the cyclopropyl ring are not limited thereto, but are not limited to 4- (2,6-di-chlorophenyl) butyl, 4 -(2,3,6-trichlorophenyl) butyl, 4- (2,4,6-trichlorophenyl) butyl, 4- (2,6-difluorophenyl) butyl, 4- (2,3, 6-trifluorophenyl) butyl, 4- (2,4,6-trifluorophenyl) -butyl, 4- (2,6-dimethylphenyl) butyl, 4- (2,3,6-trimethyl-phenyl ) Butyl, 4- (2,4,6-trimethylphenyl) butyl and 4- (2,6-bis (trifluoromethyl) -phenyl) butyl.

Halogen or halo includes iodo, fluoro, bromo and chloro.

Compounds of formula (I) can be obtained as preparation E / Z isomer mixtures. These isomers can be separated into individual components by conventional methods. Substituted cyclopropanes of formula (I) can be obtained as a mixture of cis and trans isomers which can be separated into individual components by conventional means in the preparation. Both individual isomeric compounds and mixtures thereof constitute the subject of the present invention and can be used as fungicides and pesticides.

One preferred embodiment of the invention is a compound of formula I, enantiomeric forms, salts and complexes wherein A, R ₄ and R ₅ are hydrogen and R ₁ and R ₂ are independently (C ₁ -C ₄ ) Alkyl, R ₇ is phenyl ring adjacent to the bond with the cyclopropyl ring and phenyl, phenylalkyl or heterocyclic, substituted at the position on the heterocyclic ring, R ₆ is hydrogen, (C ₁ -C ₁₂ ) alkyl , Halo (C ₁ -C ₁₂ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, halo (C ₃ -C ₇ ) cycloalkyl, (C ₂ -C ₈ ) alkenyl, halo (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ ) alkynyl and halo (C ₂ -C ₈ ) alkynyl.

More preferred embodiments of the present invention are compounds of formula I, enantiomeric forms, salts and complexes wherein A, R ₄ and R ₅ are hydrogen, and R ₁ and R ₂ are independently (C ₁ -C ₄ ) alkyl R ₆ is hydrogen or (C ₁ -C ₁₂ ) alkyl, and R ₇ is 2,6-disubstitutedphenyl, 2,3,6-trisubstitutedphenyl or 2,4,6-trisubstitutedphenyl.

Even more preferred embodiments of the invention are compounds of formula I, enantiomeric forms, salts and complexes wherein A, R ₄ and R ₅ are hydrogen, R ₁ and R ₂ are CH ₃ , and R ₆ is hydrogen or (C ₁ -C ₄ ) alkyl, R ₇ is 2,6-dihalophenyl, 2,3,6-trihalophenyl or 2,4,6-trihalophenyl.

A second preferred embodiment of the invention is a compound of formula I, enantiomeric forms, salts and complexes wherein A, R ₄ and R ₅ are hydrogen and R ₁ and R ₂ are independently (C ₁ -C ₄ Is alkyl, R ₇ is phenyl, phenylalkyl or heterocyclic, bonded to cyclopropyl and at least one position on an adjacent phenyl ring or heterocyclic ring is a hydrogen substituent, R ₆ is hydrogen, (C ₁ -C ₁₂ ) alkyl, halo (C ₁ -C ₁₂ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, halo (C ₃ -C ₇ ) cycloalkyl, (C ₂ -C ₈ ) alkenyl, halo (C ₂ -C ₈ ) alkenyl, (C ₂ -C ₈ ) alkynyl and halo (C ₂ -C ₈ ) alkynyl.

A second more preferred aspect of the invention is a compound of formula (I), enantiomeric forms, salts and complexes wherein A, R ₄ and R ₅ are hydrogen, R ₁ and R ₂ are CH ₃ , and R ₇ is Phenyl, 2-substituted phenyl, 3-substituted phenyl, 4-substituted phenyl, 3,4-disubstituted phenyl, 3,5-disubstituted phenyl, 2,3,4-trisubstituted phenyl, 2,3, 5-trisubstituted phenyl, 2,4,5-trisubstituted phenyl, 3,4,5-trisubstituted phenyl and 2,3,4,5- tetrasubstituted phenyl, R ₆ Is hydrogen, C ₁ (C ₁ -C ₄ ) alkyl or halo (C ₁ -C ₄ ) alkyl.

A second more preferred embodiment of the invention is a compound of formula I, enantiomeric forms, salts and complexes wherein A, R ₄ and R ₅ are hydrogen, R ₁ and R ₂ are CH ₃ , and R ₇ Silver phenyl, 2-halophenyl, 3-halophenyl, 4-halophenyl, 2,3-dihalophenyl, 2,4-dihalophenyl, 2,5-dihalophenyl, 3,4-dihalophenyl, 3,5-dihalophenyl, 2,3,4-trihalophenyl, 2,3,5-trihalophenyl, 2,4,5-trihalophenyl or 3,4,5-trihalo Phenyl and R ₆ is hydrogen or (C ₁ -C ₄ ) alkyl.

Most preferred embodiments of the invention are compounds of formula II, enantiomeric forms, salts and complexes wherein R ₇ is 2,6-dichlorophenyl, 2,3,6-trichlorophenyl or 2,4,6-trichloro Rophenyl.

Another most preferred embodiment of the invention is a compound of formula II ', enantiomeric forms, salts and complexes wherein R ₇ is phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluoro Phenyl, 3-fluorophenyl and 4-fluorophenyl, R ₆ is CH ₃ .

Typical compounds of formula I included in the present invention, wherein A, R ₄ and R ₅ are hydrogen and R ₁ is methyl, are those of formula III shown in Table 1 wherein R ₂ , R ₆ and R ₇ Is as defined in Table 1).

Typical compounds of formula I included in the present invention, wherein A, R ₄ and R ₅ are hydrogen and R ₁ is methyl, are compounds of formula III shown in Table 2 wherein R ₂ , R ₆ and R ₇ Is as defined in Table 2).

Formula III

Typical compounds of formula I included in the present invention, wherein A, R ₄ and R ₅ are hydrogen and R ₁ is methyl, are compounds of formula III shown in Table 3 wherein R ₂ , R ₆ and R ₇ Is as defined in Table 3).

Formula III

Typical compounds of formula I included in the present invention, wherein A, R ₄ and R ₅ are hydrogen, R ₅ is hydrogen, X is CH, Z is O and R ₁ is methyl Included are the compounds of formula III shown wherein R ₂ , R ₆ and R ₇ are as defined in Table 4.

Formula III

As used in Tables 1 to 4, Ph can be understood as phenyl.

Compounds of the present invention are prepared according to the following synthetic procedures. Scheme A depicts the preparation of compounds of Formula I 'wherein A and R ₁ to R ₇ are defined in Tables 1-4. Cyclopropyl oxime (V) is reacted with a suitably substituted benzyl derivative (IV), where Z is a halogen such as bromo, chloro or iodo, preferably benzyl bromide. The cyclopropyl substituted oxime represented by formula (V) is treated with a suitable base at room temperature to form anions, followed by the addition of benzyl bromide (IV). Typical bases used are metal hydrides such as sodium hydride, alkoxides such as sodium methoxide and hydroxide bases such as sodium or potassium hydroxide and hydride bases such as sodium or potassium carbonate. Typical solvents used with hydride bases are N, N-dimethylformamide (DMF) and tetrahydrofuran (THF), and typical solvents used with hydroxide bases are DMF, THF, methyl ethyl ketone (MEK) And acetone, and typical solvents used with alkali bases are solvents such as DMF, acetone and MEK.

As shown in Scheme A, NO bonds in C (R ₂ ) = NO—appear at the E position ( Is assumed to be a greater substituent). It should be recognized that the Z isomer may be prepared as a mixture. When isomers are prepared, they are referred to as Isomer A (higher R _f over thin layer chromatography) and Isomer B (lower R _f over thin layer chromatography). Whether isomer A or B is either E or Z geometry can be determined by conventional techniques such as X-ray crystallography or by spectroscopic means such as nuclear magnetic resonance spectroscopy. In the compounds of the present invention, Isomer A was identified in the E iminoxi configuration, and Isomer B was identified in the Z iminoxy configuration.

Compounds of formula (I) are prepared by alkylating methyl N- (2-bromomethylphenyl) -N-alkoxycarbamate in a solvent, preferably acetone or methyl ethyl ketone, in the presence of a base, preferably NaOH or KOH. Specifically, as shown in Scheme A (Z is bromo), methyl N- (2-bromomethylphenyl) -N-methoxycarbamate (IV) is reacted with oxime (V) to give a compound of formula (I '). To prepare. Methyl N- (2-bromomethylphenyl) -N-alkoxycarbamate and specifically methyl N- (2-bromomethylphenyl) -N-methoxycarbamate (IV wherein Z is bromo) is a US patent. Prepare as shown in Scheme B in a four step sequence as described in US Pat. No. 5,650,434. As described in the above-mentioned European patent application, o-nitrotoluene is reacted in the presence of ammonium chloride and zinc to give N-2-methylhydroxyamine (XI) as described in the literature. Organic Synthesis Collective Volume III, p.668). The hydroxylamine is acylated with methyl chloroformate to give methyl N-hydroxycarbamate (XII), for example alkylated with dimethylsulfate, where R is methyl to give the compound of formula XIII And bromination in the presence of a catalyst such as benzoyl peroxide under standard conditions such as N-bromosuccinimide in carbon tetrachloride to afford the intermediate benzyl bromide (XIV).

Oximes of Formula (V) are suitable, such as methanol or ethanol, in the presence of a suitable cyclopropyl aldehyde or ketone (X) and hydroxylamine hydrochloride, such as sodium hydroxide, potassium carbonate or pyridine, as shown in Scheme C. It can be obtained by reacting at room temperature to reflux temperature, preferably at room temperature in a solvent. General procedures for the synthesis of oximes and hydroxyamines are described in the literature, which is incorporated herein by reference (March, Advanced Organic Chemistry , 4th Ed, pp. 906-907). When obtained in a mixture of similar or opposite oxime isomers, the oxime of formula III can be separated into individual isomers and alkylated as described in Schemes A and B. When a mixture of oximes of formula III is used in Schemes A and B, the compounds of formulas VI, VII and IX can be separated into their individual isomers by conventional chromatography techniques.

Cyclopropyl aldehyde or ketone (X) is prepared by conventional techniques. Reaction of the unsaturated intermediate, Formula XI (Scheme D), with sulfur illide, prepared from the dimethylsulfonium salt in the presence of a base, yields a substituted acyl cyclopropane, Formula X, as shown in Scheme D. The chemistry of sulfur illides is described in the literature: Trost and Melvin, Sulfur Ylids , Academic Press, New York, NY 1975 and in Block, Reactions of Organosulfur Compounds , pp. 91-123, Academic Press, New York, NY 1978). Typical reaction conditions for the formation of sulfur illides from dimethyl sulfoxium salts are used in solvents such as dimethoxyethane, dimethyl sulfoxide and water, depending on which base is used, such as hydroxides, metal hydroxides and alkoxides. . The reaction is carried out at an alkali metal hydroxide in dimethylsulfoxide, preferably at 0 to 20 ° C, preferably at 10 to 15 ° C. Typically, dimethyl sulfoxium methylide is prepared from trimethylsulfonium iodide in dimethyl sulfoxide in the presence of powdered sodium hydroxide at room temperature. Unsaturated aldehyde or ketone (XI) is added dropwise to the illide and stirred at room temperature.

α, β-unsaturated aldehydes or ketones (XI) may be prepared by conventional condensation techniques. An extensive description of the synthesis of α, β-unsaturated aldehydes or ketones (enones) is described in the literature cited herein by March, Advanced Organic Chemistry , 4th Ed. pp. 937-955). For example, the literature describes aldol condensation reactions of ketones and aldehydes ( Organic Reactions , Volume 16). In the intermediate of the general formula (XI) of the present invention, ketones and aldehydes are generally R ₇ COR ₆ (XII) and R ₂ COCH ₂ R ₃ (XIII), wherein R ₂ , R ₃ , R ₆ and R ₇ are described above. As shown in FIG. When R ₆ is hydrogen, aldehyde R ₇ CHO (XIV) is, for example, benzaldehyde (arylCHO) or heterocyclic aldehyde substituted by 2 to 5 substituents, wherein, in formula (I), Positions on the aryl and heterocyclic rings adjacent to the bond are both substituted. Such substituted benzaldehydes or heterocyclic aldehydes are commercially available or prepared by conventional techniques. Aldehyde R ₇ CHO (XIV) is reacted with ketone R ₂ COCH ₂ R ₃ (Formula XIII) (as shown in Scheme E) to give intermediate Enone Formula XV. Typically, ketone R ₂ COCH ₂ R ₃ is dissolved in a hydroxy solvent such as methanol or ethanol, and aldehyde R ₇ CHO is added dropwise followed by the dropwise addition of the base or the aldehyde solution in aqueous base solution. Conventional bases used may be alkali metal hydroxides such as barium, potassium or sodium hydroxide, and the dropwise addition is carried out at 0 ° C to 35 ° C, preferably at ambient temperature. If enone is derived from acetone, where R ₂ is methyl and R ₃ is hydrogen, the solvent may be acetone, followed by R ₇ COR ₆ , followed by the dropwise addition of aqueous hydroxide solution. Preferably the aldehyde is dissolved in a solvent mixture of acetone: water (1: 5), to which base is added with stirring at room temperature.

When R ₆ is not hydrogen, R ₇ COR ₆ (XII) is a ketone arylCOR ₆ or heterocyclic ketone, substituted by 2 to 5 substituents, wherein the bond is adjacent to the cyclopropyl ring in formula (I) Positions on the aryl and heterocyclic rings are both substituted or the aryl or heterocyclic ring is unsubstituted or substituted by 1 to 4 substituents, wherein aryl or is bonded adjacent to the cyclopropyl ring in formula (I) At least one position on the heterocyclic ring is hydrogen. For compounds of formula (I), wherein R ₆ is not hydrogen, the intermediate unsaturated aldehydes and ketones (XI) are prepared and purified as shown in Scheme F, following the procedure described in line 20 of column 17 of US Pat. No. 3,950,427. The lower surface E diastereomer, wherein R ₇ is trans with respect to R ₂ CO in XI, is obtained. In conventional preparations, ketones such as R ₇ COR ₆ are reacted in dimethylformamide in the presence of ethyl trans 3-ethoxycrotonate and potassium tert-butoxide, followed by acid hydrolysis and decarboxylation to give the general formula (XI). To obtain. Formula XVI, a crotonate, is prepared from substituted ethyl acetoketones by conventional techniques.

Or α, β-unsaturated cyclopropyl ketone (X) may be prepared from cyclopropyl nitrile (XIV) prepared by cyclopropaneation of acrylonitrile (XVIII) as described in Scheme G. Acrylonitrile (XVIII) starting materials, shown in Scheme G, can be prepared by conventional synthetic methods as described in the literature cited herein by March, Advanced Organic Chemistry, 4th Ed, pp.937. -955). For example, the nitrile derivative R ₃ CH ₂ CN is condensed in the presence of a ketone or an aldehyde R ₇ COR ₆ base with acrylonitrile (XIII). Typically, the nitrile is dissolved in a solvent such as ethanol and water, to which aldehyde or ketone and then base are added. Conventional bases used may be alkali metal hydroxides such as barium, potassium or sodium hydrosides and the mixture is typically stirred at ambient temperature.

Acrylonitrile (XVIII) is treated with sulfur illide as shown in Scheme D to yield cyclopropyl nitrile (XVII). Cyclopropyl nitrile (XVII) is transformed into cyclopropyl ketone by adding an organometallic to the nitrile and then hydrolyzing it. For example, standard Grignard reagent R ₂ MgX or organolithium reagent R ₂ Li is added to the nitrile functional group to obtain ketone (X). Addition reactions to nitriles are described in the literature cited herein by March, Advanced Organic Chemistry, 4th Ed, pp. 935-936. Cyclopropyl nitrile (XVII) can be transformed into cyclopropyl aldehyde (X ') by standard reduction methods using such as diisobutylaluminum hydride (DiBAL). The preparation of aldehydes from the reduction of nitriles is described in the literature cited herein by March, Advanced Organic Chemistry, 4th Ed, pp. 919-920.

Direct synthesis of the compound of formula VII or IX is shown in Scheme H. Compounds of formula (VII) or (IX) can be prepared directly by condensation with aminoxy intermediates (XIX) from functionalized cyclopropyl ketones or aldehydes (X). The preparation of the aminooxy intermediate (XIX) is described in US Pat. No. 5,194,662. Aminoxy intermediates (XIX) are prepared in a two step sequence by alkylation of IV with N-hydroxyphthalimide, where X is N. Aminoxy intermediate (XIX) is condensed with ketone or aldehyde (X) to afford VII and treated as shown in Scheme B to give IX.

Compounds of the invention can be prepared according to the following steps

Example 1

Preparation of E and Z Aminoxy Isomers: Methyl N-methoxy-N- [2-((E) and (Z)-(1- (trans-2-phenylcyclopropyl) ethylidene) aminooxymethyl) phenyl ] Carbamate

Compounds 1.11A and 1.11B of Table 1

Preparation of Trans-2-phenylcyclopropylmethyl Ketone

A 2000 ml round bottom flask equipped with a magnetic stirrer was charged with 150 g (0.685 mol, 1.0 equivalent) of trimethylsulfonium iodide, 28 g (0.685 mol, 1.0 equivalent) of powdered sodium hydroxide and 1000 ml of DMSO. After adding 100 g of trans-4-phenyl-3-buten-2-one (0.685 mol) in one portion, the flask was clogged and stirred at ambient temperature for 15 minutes. After the reaction was stirred for 5 minutes at ambient temperature, 500 ml of water was injected and extracted three times with 200 ml of ethyl ether. The ether extract was washed twice with 200 ml of water, dried over anhydrous MgSO ₄ , filtered and stripped to separate 94 g of yellow liquid (yield 86%), which was prepared by fractionation by 300 MHz ¹ H NMR. It is consistent with the product, trans-2-cyclopropylmethyl ketone.

300 MHz, ¹ H, CDCl ₃ , TMS = 0 ppm): 1.3 (m, 1H), 1.7 (m, 1H), 2.2 (m, 1H), 2.3 (s, 3H), 2.6 (m, 1H), 7.1 ( d, 2H), 7.2-7.4 (m, 3H)

E and Z imine isomers: (E) and (Z) -methyl N-methoxy-N- [2-((trans-1- (2-phenylcyclopropyl) ethylidene) aminooxymethyl) phenyl] carbamate

In a 20 ml glass vial, methyl N-methoxy-N- [2- (aminooxymethyl) phenyl] carbamate (600 mg, 2.65 mmol), trans-2-cyclopropylmethyl ketone (400 mg, 2.4 mmol) and MeOH (15 ml) is added. The resulting mixture is stirred overnight at ambient temperature. The progress of the reaction is observed by GC and TLC. When the reaction is complete, water is added, followed by extraction with ether. The crude product was purified by silica column with 70:30 hexanes / ethyl acetate solvent mixture to afford (methyl-N-methoxy-TT- [2-((E)-(1- (trans-2-petylcyclopropyl) 300 mg of isomer A as ethylethylen) aminooxymethyl) phenyl] carbamate and methyl N-methoxy-N- [2- (Z)-(1- (trans-2-phenylcyclopropyl) -ethylidene) aminooxy 270 mg of isomer B are obtained as methyl) phenyl] carbamate with a total separation yield of 65%.

NMR isomer A: (E) -isomer: 300 MHz, ¹ H, CDCl ₃ , TMS = 0 ppm): 1.1-1.2 (m, 1H), 1.35-1.45 (m, 1H), 1.75-1.80 (m, 1H) , 1.84 (s, 3H), 3.74 (s, 3H), 3.77 (s, 3H), 5.12 (s, 2H), 7.05-7.6 (m, 9H).

NMR isomer B: (Z) -isomer: 300 MHz, ¹ H, CDCl ₃ , TMS = 0 ppm): 1.2-1.4 (m, 2H), 1.68 (s, 3H), 2.2-2.3 (m, 1H), 1.65 -1.75 (m, 1H), 3.65 (s, 3H), 3.72 (s, 3H), 5.11 (s, 2H), 7.0-7.5 (m, 9H), 3.72 (s, 3H), 5.11 (s, 2H ), 7.0-7.5 (m, 9H).

Preparation of Methyl N-methoxy-N- [2- (aminooxymethyl) phenyl] carbamate as Intermediate Used in Examples of the Present Invention

Methyl N-methoxy-N- [2- (O-phthalimidoxymethyl) phenylcarbamate

Anhydrous 1000 ml round bottom flask equipped with a magnetic stirrer and nitrogen inlet was charged with 8.4 g (0.0512 mol) of N-hydroxyphthalimide, 2.1 g (0.0521 mol) of powdered sodium hydroxide and 500 ml of DMF. . The dark red solution is stirred at ambient temperature for 20 minutes, then 20 g (0.0512 mol) of 70% purity methyl N- (2-bromomethylphenyl) -N-methoxycarbamate are added in one portion. The reaction is stirred overnight at ambient temperature, poured into 500 ml of water and stirred for 1 hour to give a white solid collected by vacuum filtration and washed with water and hexane. The tan solid is dried overnight at 40 ° C. under vacuum. 17.1 g of N-methoxy-N-methyl [2- (O-phthalimidoxymethyl) -phenyl} carbamate are isolated as a light brown solid in 94% separation yield.

300 MHz, ¹ H NMR (CDCl ₃ , tms = 0 ppm) 3.76 (s, 3H); 3.78 (s, 3 H); 5.25 (s, 2 H); 7.4 (m, 3H), 7.8 (m, 5H)

Preparation of Methyl N-methoxy-N- [2- (aminooxymethyl) phenyl] carbamate

In a 250 ml round bottom flask equipped with a magnetic stirrer, 5 g (0.0195 mol) of N-methoxy-N-methyl [2- (O-phthalimidoxymethyl) phenyl] carbamate, 100 ml of anhydrous methanol and 1.08 hydrazine monohydrate Charge g (0.0215 moles). The flask is closed and the reaction is carried out with stirring at ambient temperature for 2 hours. The resulting solid is separated by filtration and the filtrate is stripped with rotavap. The residue was slurried in 150 mL of anhydrous ether, filtered and stripped to yield 4.1 g of methyl N-methoxy-N- [2- (aminooxymethyl) phenyl] carbamate as a dark yellow liquid which was subsequently Store at -20 ° C until needed for synthesis.

300 MHz, ¹ H NMR (CDCl ₃ , tms = 0 ppm) 3.75 (s, 3H); 3.78 (s, 3 H), 4.75 (s, 2 H); 5.2 (bs, 2H), 7.35 (m, 3H); 7.4 (m, 1 H)

Preparation of Methyl N- (2-bromomethylphenyl) -N-methoxycarbamate

Preparation of N-2-methylphenylhydroxylamine

A 1 L three-neck round bottom flask was charged with 28.6 g (1.0 equivalent, 0.21 mol) of o-nitrotoluene and 28.7 g (2.1 equivalent, 0.44 mol) of pure zinc powder in 200 ml of ethyl alcohol. The reaction solution is heated to 45 ° C. and 13.5 g (1.2 equivalents, 0.25 mole) of ammonium chloride in 120 ml of water are added using an addition funnel, adjusting the exotherm to 50 ° C. to 55 ° C. with an ice bath. The reaction was observed by GLC analysis and after 30 minutes additional 7.2 g (0.11 mol) of zinc was added, followed by 3.3 g (0.06 mol) of ammonium chloride in 10 ml of water. After 45 minutes the reaction mixture is vacuum filtered through celite, the wet cake is washed with 50 ml of ethyl alcohol and the solvent is removed in a rotary evaporator at 30 ° C. to complete the reaction to complete the orange oil. 300 ml of ether and 200 ml of water are added to the oil. The organic phase was separated, washed three times with 200 ml of water using NaCl, triturated into an emulsion, dried over anhydrous MgSO 4 and the ether removed at 30 ° C. on a rotary evaporator to give 16.1 g (62.3% yield) of an orange oil product. Obtained and used directly in the next step.

Preparation of Methyl N-hydroxy-N-2-methylphenylcarbamate

In a 250 ml three necked round bottom flask stirred under nitrogen atmosphere, 16.1 g (1.0 equiv, 0.13 mole) of N-2-methylphenylhydroxyamine in 40 ml methylene chloride and 16.8 g (1.5 equiv, 0.20 mole) of pure sodium bicarbonate ). 13.1 g (1.05 equiv, 0.37 mole) of methyl chloroformate is added to the mixture at −5 ° C. to + 5 ° C. using a pipette. The reaction mixture is stirred at 0 ° C. for 30 minutes, then the addition and reaction are observed by GC. After 45 minutes, while cooling in an ice bath, 100 ml of methylene chloride and 100 ml of water are added to quench the reaction. Further reaction is completed with methylene chloride and 100 ml of water. The organic phase is separated, washed three times with 200 ml of water and the solvent is removed on a rotary evaporator at 30 ° C. to give 21.3 g of crude product as an orange rubbery solid. Titrate with 40 mL of hexane, triturate with mortar and pestle, and wash the resulting solid three times with 20 mL of hexane to give 15.35 g (yield 65.3%) of the product as a cloudy white solid.

300 MHz, ¹ H, CDCl ₃ , TMS = 0 ppm): 2.31 (s, 3H), 3.76 (s, 3H), 7.25-7.26 (m, 4H), and 7.78-7.81 (br, 1H)

Preparation of Methyl N-methoxy-2-methyl Phenylcarbamate

In a 250 mL three-neck round bottom flask with agitation under a nitrogen atmosphere, 15.25 g (1.0 equiv, 84.25 mmol) of methyl N-hydroxy-N-2-methyl phenylcarbamate in 30 ml of methylene chloride and 17.4 g of pure potassium carbonate Filling (1.5 equiv, 0.126 mole) gives a solid cake almost immediately. At least 150 ml of methylene chloride is added to the reaction mixture, and the large cake is crushed into chunks using a spatula. To the reaction mixture is added 12.74 g (1.2 equiv, 0.101 mole) of pure dimethyl sulfate and the mixture is heated to 40 ° C. Reactions were observed after 1 hour and after 3 hours using TLC, and after 1 hour 1.2 g (9.5 mmol) of pure dimethylsulfate were added. After 3 hours, the reaction mixture is quenched by adding the reaction to 250 ml of water. The reaction is terminated by adding 150 ml of methylene chloride, the organic phase is partitioned, washed with 250 ml of water and dried over anhydrous magnesium sulfate. The solvent is removed at 45 ° C. on a rotary evaporator to give 20.8 g of crude product as a light brown oil containing dimethyl sulfate. 1.5 g of crude product are washed with 10% ammonium hydroxide and dimethyl sulfate is removed to give 0.9 g of product. 19.3 g of residual crude product containing dimethyl sulfate are obtained in 250 ml ether, washed three times with 200 ml of 10% ammonium hydroxide, three times with 200 ml of water and dried over anhydrous magnesium sulfate. The solvent is removed at 45 ° C. on a rotary evaporator to give 13.3 g of 12.4 g and 0.9 g of methyl N-methoxy-N-2-methyl phenylcarbamate as a brown / orange oil (yield 81.1%).

300 MHz, ¹ H, CDCl ₃ , TMS = 0 ppm): 2.29 (s, 3H), 3.73 (s, 3H), 3.78 (s, 3H), 7.26 (m, 4H)

Methyl N-2-bromomethylphenyl-N-methoxycarbamate

12.0 g (1.0 equivalent, 61.5 mmol) of methyl N-methoxy-N-2-methyl phenylcarbamate in 70 ml of CCl ₄ in a 500 ml three-neck round bottom flask under N ₂ atmosphere, pure N-bromosuccinimide (NBS) 12.0 g (1.1 equiv, 67.7 mmol), 36 mg 2,2-azobis (2-methylpropionitrile) (AIBN) were charged and heated at reflux at 77 ° C. for 10 hours using a high intensity lamp. . During this time add 300 mg of AIBN and 3 g of additional NBS. The reaction mixture is completed by vacuum filtration, the filtrate is washed twice with 200 ml of 2.5% sodium bisulfite, 200 ml of 2.5% sodium bicarbonate, 200 ml of water and dried over anhydrous magnesium sulfate. The solvent is removed by rotary evaporator at 40 ° C. to give 16.0 g (71% purity, 68.0% yield) of orange oil.

300 MHz, ¹ H, CDCl ₃ , TMS = 0 ppm): 3.79 (s, 3H), 3.80 (s, 3H), 4.5 (s, 2H), 7.2-7.4 (m, 4H)

Example 2

Preparation of E Aminoxy Isomers: Methyl N-methoxy-N- [2- (E- (1- (trans- (2- (4'-fluorophenyl) -2-methyl) cyclopropyl) ethylidene) Aminoxyoxymethyl) phenyl carbamate, compound 1.58A in Table 1

Preparation of 4- (4-fluorophenyl) -3-penten-2-one

(A) Preparation of ethyl-trans-3-ethoxycrotonate

A 500 mL volume round bottom flask equipped with a magnetic stirrer and a nitrogen inlet was charged with 81.5 g (0.626 mol) of ethyl acetoacetate, 95 g (0.64 mol) of triethyl orthoformate and 20 drops of concentrated sulfuric acid (catalyst). The reaction is stirred overnight at ambient temperature. GC analysis of aliquots reveals the final reaction with one main product. A slight excess of quinoline (about 40 drops) is added to neutralize the sulfuric acid. The reaction is then distilled at 15 mm Hg (85-90 ° C.) to yield 94 g of ethyl-trans-3-ethoxycrotonate as a clear colorless liquid which is crystallized when left (separation yield 95%).

300 MHz ¹ H NMR (CDCl ₃ , tms = 0 ppm) 1.3 (t, 3H); 1.33 (t, 3 H); 2.3 (s, 3 H); 3.8 (q, 2 H); 4.14 (q, 2H), 5.0 (s, 1H)

(B) Preparation of 4- (4-fluorophenyl) -3-penten-2-one

100 g (0.72 mol) of 4'-fluoroacetophenone, 115 g (0.72 mol) of ethyl-trans-3-ethoxycrotonate and dimethyl anhydride in a 3000 ml round bottom flask equipped with a mechanical stirrer, a nitrogen inlet and an addition funnel 500 ml of formamide is charged. Next, 89 g (0.79 mol) of potassium tert-butoxide are added to the solution in one portion, and 250 ml of DMF is added. The reaction is then stirred at room temperature under nitrogen for a full 2 days. The reaction mixture is then poured into 1000 ml of water and the aqueous solution is extracted three times with 200 ml of ethyl ether to remove any unreacted starting material. The aqueous fraction is then acidified to pH 2 with 6N aqueous HCl, collected by filtration, washed with water, hexanes and air dried to give a yellow solid. The solid is poured into 500 ml of 6N aqueous HCl and warmed at 50 ° C. for 1 hour. Analysis of the fractions by TLC and GC shows that no starting material remains, and that one new product is formed. The aliquot mixture is cooled to room temperature and then poured into 500 ml of water and extracted three times with 200 ml of ethyl ether. The ether extract was washed twice with 200 ml of water, 100 ml of brine, dried over anhydrous sulfuric acid, filtered and stripped to give 82 g of 4- (4-fluorophenyl) -3-penten-2-one as pale yellow liquid. As a mixture of 95% trans and 5% cis isomer (yield 65%).

300 MHz ¹ H NMR (CDCl ₃ , tms = 0 ppm) 2.3 (s, 3H); 2.5 (s, 3 H); 6.5 (s, 1H0; 7.1 (t, 2H), 7.5 (m, 2H)

Preparation of trans-1-methyl-1- (4-fluorophenyl) -2-acetyl-cyclopropane

A 2000 ml volume round bottom flask equipped with a mechanical stirrer, nitrogen inlet and addition funnel was charged with 112 g (0.51 mol) of trimethyl sulfoxonium iodide, 20.4 g (0.51 mol) of powdered sodium hydroxide and 500 ml of anhydrous DMSO. . The mixture is stirred at room temperature for 1 hour, then 82 g (0.0461 mol) of 4- (4-fluorophenyl) -3-penten-2-one in 100 ml DMSO are added quickly. The reaction is stirred at ambient temperature for 3 days, then poured into 200 ml of ice water and extracted three times with 200 ml of ethyl ether. The ether extract was washed twice with 100 ml of water, 100 ml of brine, dried over anhydrous magnesium sulfate, filtered through 2 "silica gel and stripped to give 97 g of a dark pale yellow oil, which was fractionated at 0.2 mm Hg. The pureest fractions were combined to give 74 g of a pale yellow liquid with a purity of about 88% by GC analysis, with a few impurities remaining. Chromatography on silica gel using the combined pure fractions yielded 37 g of trans-1-methyl-1- (4-fluorophenyl) -2-acetyl-cyclopropane as a clear colorless liquid (42% yield). .

300 MHz ¹ H NMR (CDCl ₃ , tms = 0 ppm) 1.4 (m, 1H); 1.45 (s, 3 H); 1.6 (m, 1 H), 2.25 (m, 1 H), 2.35 (s, 3 H); 7.0 (t, 2 H); 7.35 (m, 2H)

Methyl N-methoxy-N- [2- (E- (1- (trans- (2- (4'-fluorophenyl) -2-methyl) cyclopropyl) ethylidene) aminooxymethyl) phenyl] carbamate Manufacture

0.6 g (0.0031 mol) of trans-1-methyl-1- (4-fluorophenyl) -2-acetyl-cyclopropane and methyl N-methoxy-N in a 50 ml round bottom flask equipped with a magnetic stirrer and nitrogen inlet Charge 0.82 g (0.0035 mol) of [2- (aminooxymethyl) phenyl] carbamate. The mixture is dissolved in 20 ml of anhydrous methanol and two drops of glacial acetic acid are added as catalyst. The flask is stirred overnight at ambient temperature, then poured into 100 ml of water and extracted three times with 100 ml of ethyl ether. The ether extract was washed twice with 100 ml of water, 100 ml of brine, dried over anhydrous magnesium sulfate, filtered and stripped, 1.3 g of a dark brown oil chromatographed on silica with 20% ethyl acetate and 80% hexane. To obtain. Pure fractions were combined and stripped to form methyl N-methoxy-N- [2- (E- (1- (trans- (2- (4'-fluorophenyl) -2-methyl) cyclopropyl) ethylidene 0.72 g)) aminooxymethyl) phenyl] carbamate are obtained as a clear pale yellow liquid (58% yield isolated).

300 MHz ¹ H NMR (CDCl ₃ , tms = 0 ppm) 1.1 (m, 1H); 1.2 (s, 3 H); 1.35 (m, 1 H); 1.85 (m, 1 H); 2.1 (s, 3 H); 3.75 (s, 3 H); 3.8 (s, 3 H); 5.15 (s, 2 H); 7.1 (t, 2 H), 7.35 (m, 2 H); 7.4 (m, 3 H); 7.5 (m, 1H)

Example 3

Preparation of E Aminoxy Isomers: Methyl N-methoxy-N- [2- (E- (1- (trans-2- (2 ', 6'-dichlorophenyl) cyclopropyl) ethylidene) aminooxymethyl) Phenyl Carbamate, Compound 3.16A of Table 1

Preparation of 4- (2,6-dichlorophenyl) -3-buten-2-one

A 1000 ml round bottom flask equipped with a mechanical stirrer and a nitrogen inlet was charged with 26.5 g (0.15 mol) of 2,6-dichlorobenzaldehyde, 125 ml of acetone, 600 ml of water and 9.3 g (0.23 mol) of sodium hydroxide. The mixture is stirred at rt for 12 h. Analysis of the aliquots by GC showed completion of the reaction. The resulting solid is collected by vacuum filtration, washed with 100 ml of water, 100 ml of hexane and dried at 40 ° C. for 3 hours under vacuum. 31.4 g of the title compound, 4- (2,6-dichlorophenyl) -3-buten-2-one, are isolated as a pale yellow solid (98% yield isolated).

300 MHz, ¹ H, CDCl ₃ TMS = 0 ppm): 2.43 (s, 3H); 6.80 (d, 1 H); 7.18-7. 38 (m, 1 H); 7.4 (d, 2 H); 7.6 (d, 1 H)

Preparation of trans-1- (2,6-dichlorophenyl) -2-acetyl-cyclopropane

In a 1000 ml round bottom flask equipped with a magnetic stirrer, a nitrogen inlet and an addition funnel, 33.2 g of trimethyl sulfoxonium iodide 33.2 g, 6.1 g (0.151 mol) of powdered sodium hydroxide and 300 ml of DMSO Charge it. The mixture is stirred at room temperature for 1 hour, then 4- (2,6-dichlorophenyl) -3-buten-2-one (32.3 g, 0.151 mol) is added rapidly at once. The reaction is then stirred at ambient temperature for 10 minutes, then poured into 200 ml of water and extracted three times with 100 ml of ethyl ether. The ether extract was washed twice with 100 ml of water, 100 ml of brine, dried over anhydrous MgSO ₄ , filtered through 2 "silica gel, concentrated in vacuo on a rotary evaporator to 90% hexane, 10% ethyl Chromatography on silica gel using acetate yields 31.7 g of a dark pale yellow oil, combining the pure fractions and concentrating on a rotary evaporator under vacuum to trans-1- (2,6-dichlorophenyl) -2-acetyl- 27.9 g of cyclopropane are obtained as a free flowing pale yellow liquid (yield 81%).

300 MHz, ¹ H, CDCl ₃ , TMS = 0 ppm): 1.4-1.48 (m, 1H); 1.78-1.86 (m, 1 H); 2.21-2.30 (m, 1 H); 2.34-2.4 (m, 1 H); 2.41 (s, 3H), 7.2 (m, 1H), 7.3 (d, 2H)

Preparation of E Aminoxy Isomers: Methyl N-methoxy-N- [2- (E- (1- (trans-2- (2 ', 6'-dichlorophenyl) cyclopropyl) ethylidene) aminooxymethyl) Phenyl] carbamate

0.6 g (0.00262 mole) of trans-1- (2,6-dichlorophenyl) -2-acetylcyclopropane and methyl N-methoxy-N- [2- (aminooxymethyl) phenyl, according to the procedure of Example 2 ] Carbomate 0.7 g (0.00288 mole) gives methyl N-methoxy-N- [2- (E- (1- (trans-2- (2 ', 6'-dichlorophenyl) cyclopropyl) ethylidene) 0.6 g of aminooxymethyl) phenyl] carbamate are obtained (53% yield isolated).

300 MHz ¹ H NMR (CDCl ₃ , tms = 0 ppm) 1.2 (m, 1H); 1.6 (m, 1 H); 1.85 (m, 1 H); 1.9 (s, 3 H); 2.2 (m, 1 H); 3.75 (s, 3 H); 3.8 (s, 3 H); 5.15 (s, 2 H); 7.1 (t, 2 H), 7.35 (d, 2 H); 7.4 (m, 2 H); 7.55 (m, 1 H)

Example 4

Preparation of E and Z Aminooxy Isomers: Methyl N-methoxy-N- [2- (E and Z- (1- (trans-2- (4'-chlorophenyl) cyclopropyl) ethylidene) aminooxymethyl ) Phenyl carbamate, compounds 1.14A and 1.14B of Table 1

Preparation of 4- (4-chlorophenyl) -3-buten-2-one

A 250 ml round bottom flask was charged with 2 g (0.0142 mol) of 4-chlorobenzaldehyde, 10.5 ml (0.142 mol) of acetone, 50 ml of ethanol and 10 ml of water. After stirring for about 1 minute, 0.27 g (0.00142 mol) of barium hydroxide is added and the resulting mixture is stirred overnight at ambient temperature. When the reaction is complete, water is added and extracted with ether. The ether solvent is removed in vacuo to give 4- (4-chlorophenyl) -3-buten-2-one as a brown oil.

Preparation of trans-1- (4-chlorophenyl) -2-acetyl-cyclopropane

A 250 ml round bottom flask was charged with 100 ml of DMSO, 3.10 g (0.014 mol) of trimethyl sulfoxium iodide and 0.56 g (0.014 mol) NaOH. The resulting mixture is stirred at room temperature for 1 hour. The mixture is stirred at room temperature for 1 hour, and then 2.3 g (0.0128 mol) of 4- (4-chlorophenyl) -3-buten-2-one are added rapidly at once. The resulting mixture is stirred for another 5 minutes at ambient temperature and the reaction is observed by GLC. When the reaction is complete, water is added, followed by extraction with ether. The ether solvent is removed in vacuo to yield 1.8 g of trans-1- (4-chlorophenyl) -2-acetyl-cyclopropane as a brown oil.

Preparation of E and Z Aminooxy Isomers: Methyl N-methoxy-N- [2- (E and Z- (1- (trans-2- (4'-chlorophenyl) cyclopropyl) ethylidene) aminooxymethyl ) Phenyl] carbamate

According to the procedure of Example 2, 0.96 g (0.0049 mol) of trans-1- (4-chlorophenyl) -2-acetylcyclopropane and methyl N-methoxy-N- [2- (aminooxymethyl) phenyl] carba Using 1.3 g (0.0055 mol) of mate, isomer A {methyl N-methoxy-N- [2- (E- (1) was followed by elution sequence from silica gel chromatography column (20% ethyl acetate, 80% hexane). 0.42 g of-(trans-2- (4'-chlorophenyl) cyclopropyl) ethylidene) aminooxymethyl) phenyl] carbamate} and isomer B {methyl N-methoxy-N- [2- (Z- (1 0.34 g of-(trans-2- (4'-chlorophenyl) cyclopropyl) ethylidene) aminooxymethyl) phenyl] -carbamate} is obtained. Separate yields are 21% and 17%, respectively.

NMR: Isomer A (E aminooxy isomer) 300 MHz ¹ H NMR (CDCl ₃ , tms = 0ppm) 1.1 (m, 1H); 1.5 (m, 1 H); 1.8 (m, 1 H); 1.85 (s, 3 H); 2.2 (m, 1 H); 3.7 (s, 3 H); 3.75 (s, 3 H); 5.1 (s, 2 H); 7.0 (d, 2H), 7.2 (d, 2H); 7.4 (m, 3 H); 7.5 (m, 1H)

NMR: Isomer B (Z Aminooxy Isomer) 300 MHz ¹ H NMR (CDCl ₃ , tms = 0 ppm) 1.1 (m, 1H); 1.3 (m, 1 H); 1.65 (s, 3 H); 2.2 (m, 1 H); 2.7 (m, 1H; 3.65 (s, 3H); 3.7 (s, 3H); 5.1 (s, 2H); 7.0 (d, 2H), 7.3 (d, 2H); 7.4 (m, 3H); 7.5 ( m, 1H)

Example 5

Numerous compounds of the invention have been tested for in vivo fungicidal activity against the diseases described below. The compound is dissolved in a mixture of acetone and methanol 1: 1, and then diluted with a mixture of water, acetone and methanol (volume) 2: 1: 1 to obtain a suitable concentration. The solution is sprayed onto the plants and dried for 2 hours. The plant is then inoculated with fungal cells. In this protective test, the plants are inoculated for one day after treatment with the compounds of the present invention. The remainder of the description of each test is shown below with the results of administering 150 g per hectare of the various compounds described herein by various compound numbers to various fungi. This result is the disease inhibition rate compared to the unchecked check, where 100 represents complete disease inhibition and 0 means no disease inhibition. Application of test fungal cells to test plants is as follows:

Wheat Leaf Rust (WLR)

Puccinia recondita (f.sp. tritici) is incubated in a greenhouse for 12 days on 7-day wheat plants (cv. Fielder). Cells are collected from the leaves by fixing onto aluminum foil. The dried cells are used for one month. Cell suspensions are prepared from anhydrous uredia by adding 20 mg (9.5 million cells) per ml of salt oil. The suspension is dispensed into gelatin capsules (0.7 ml volume) attached to the oil sprayer. One capsule is used per 20 flats of 2in ² pots of 7 day old plants. Wait at least 15 minutes for the oil to evaporate from the wheat leaves, then store the plants in the dew chamber for 24 hours. The plants are then placed in the greenhouse and evaluated for disease after 12 days.

Wheat Leaf Spot (SNW)

Cezopek-Dox V-8 juice medium in a culture medium of Septoria nodorum in the incubator at 20 ° C. by a period of 12 hours of light and 12 hours of dark for 2 weeks. Keep on board. A portion of the plant is stirred with fungal material in deionized water and filtered through a cheesecloth to prepare a water suspension of cells. Dilute the cell containing water suspension to a cell concentration of 3.0 x 10 ⁶ cells per ml. The inoculum is dispersed on a weekly wheat plant (cv. Fielder) previously sprayed with the fungicide compound by a DeVilbiss sprayer. Inoculated seedlings are then stored for 2 days in a room controlled at 20 ° C. at 80% humidity. Record the disease inhibition value as% inhibition.

Wheat Powder Bottle (WPM)

Erysiphe graminis (f.sp. Tritici) is incubated on a wheat seedling (cv. Fielder) in a controlled temperature room at 18 ° C. Percentage cells from the culture plate are dropped into 7-day wheat seedlings pre-sprayed with the fungicide compound. Inoculated seedlings are kept in a controlled room at 18 ° C. and underground irrigated. Percent disease inhibition is measured 7 days after inoculation. Disease inhibition values were recorded as percent inhibition.

Cucumber White Powder (CPM)

Spaerotheca fulginea is maintained on cucumber plants in the greenhouse (cv. Bush Champion hybrid). Inoculum is prepared by placing five to ten leaves of severely white powder in a glass container with 500 ml of water containing one drop of Tween 80 (polyoxyethylene monooleate) per 100 ml. After stirring the liquid and leaves, the inoculum is filtered through cheesecloth and sprayed onto the plants using a spray vessel sprayer. The cell number is 100,000 cells per ml. The plant is then placed in a greenhouse for infection and cultivation. The plants are observed for 7 days after inoculation. Disease inhibition values are reported as percent inhibition.

Tomato blight (TLB)

A fertilizer of Phytophthora infestans is maintained for 2 to 3 weeks in agar modified with green peas. Cells are washed from agar with water and distributed to the leaves of three weekly patio hybrid tomato plants previously treated with a compound of the present invention using a DeVilbis sprayer. The inoculated plants are stored for 24 hours in an inoculum phase at 20 ° C. to infect them. The plant is then transferred to a controlled room at 20 ° C. and 90% humidity. Plants are assessed for disease inhibition after 5 days.

Rice Death Disease (RB)

Cultures of Pyricularia oyrzae are maintained on tomato dextrose agar for 2-3 weeks. The cells are washed from agar with water containing one drop of Tween 80 per 100 ml. The cell suspension is filtered through two layers of cheesecloth and the cell number is adjusted to 5 x 10 ⁵ per ml of water. The cell suspension is sprayed onto 12 day old rice plants using a DeVilvis sprayer. Store for 36 hours in a completely dark inoculation phase at 20 ° C. to infect the inoculated plants. After the infection period, the plants are stored in the greenhouse. After 6 days, the plants are evaluated for disease inhibition. Disease inhibition values are reported as percent inhibition.

Cucumber Anthrax (CA)

The fungal pathogen Colletotrichum lagenarium is incubated on potato textaros agar (PDA) for 8-14 days in the dark at 22 ° C. The surface of the plate was washed with distilled water modified with yeast extract 0.5% v / w to remove seeds from the PDA plate. Remove the cells of lagenariaum. The fungal colonies are scratched with a blunt plastic instrument until most of the cells are released from the aqueous environment. The cell suspension is filtered through cheesecloth and the cell number is adjusted by adding more water containing yeast extract until 3.0 x 10 6 cells per ml of water are achieved. Chemically treated cucumber plants are sprayed into the cell suspension using a hand pump sprayer until deteriorated. The plants are stored for 48 hours in a fluorescent spray room (12 hours light, 12 hours dark). After the infection period, the plants are stored in the growth chamber for 3 days at 25 ° C. and 80% humidity. The treated plants are then evaluated for disease inhibition. Disease inhibition values are reported as percent inhibition.

Tomato Early Blight (TEB)

Cultures of Alternaria solani are grown on a V-8 juice agar plate under fluorescent light (12 hours light, 12 hours dark) for 2 weeks at room temperature. The surface of the agar plate is washed with an aqueous 0.5% yeast extract solution to obtain a cell suspension. The surface of the agar plate is scratched with a blunt plastic instrument to escape the cells into the liquid. The cell suspension is filtered through cheesecloth and the cell concentration is adjusted to about 80,000 cells per ml. Tomato plants (cv. Patio hybrid) 18 days after treatment with the experimental compound. After treatment, the plants are stored in the greenhouse for 1 day. After this period, the plants are inoculated with the cell suspension just prepared using a DeVilvis sprayer. This cell suspension is applied to the upper surface of the leaves. After inoculation, the plants are stored for 24 hours in the inoculation phase at 20 ° C. for infection. The plants are then transferred to a growth chamber at 22 ° C. and 80% humidity for 3 days. Disease inhibition values are reported as percent inhibition.

When tested against wheat rust, Compound 1.11A exhibited 95% inhibition at 150 g per hectare, and Compound 1.11B, 1.14A, 1.58A and 3.16A showed at least 95% inhibition when tested at 100 g per hectare. It was.

When tested for wheat leaf spots, compounds 1.14A, 1.58A and 3.16A at 100 g per hectare show at least 95% inhibition.

When tested against wheat powder, compound 1.11A showed 95% inhibition at 150 g per hectare, and compound 1.11B, 1.14A, 1.58A and 3.16A showed at least 80% inhibition at 100 g per hectare.

When tested against cucumber powder bottle, compound 1.11A at 85 g per hectare shows 85% inhibition, and compound 1.14A, 1.58A and 3.16A at 100 g per hectare show at least 80% inhibition.

When tested for terminal blight, Compound 1.11A showed at least 100% inhibition at 150 g per hectare.

When tested against rice mortality, compound 1.11ASMS showed 95% inhibition at 150 g per hectare, and compound 1.14A, 1.58A and 3.16A at 100 g per hectare showed at least 95% inhibition.

When tested for cucumber anthrax, compound 1.11A exhibited 90% inhibition at 150 g per hectare, and compound 1.14A, 1.58A and 3.16A at 100 g per hectare showed at least 80% inhibition.

When tested for tomato early blight, Compound 1.11A exhibited 80% inhibition at 150 g per hectare, and Compound 1.14A, 1.58A and 3.16A at 100 g per hectare showed at least 95% inhibition.

The compounds of the present invention are useful as agricultural fungicides and can likewise be applied to a variety of habitats such as seeds, soil or plant leaves.

The compounds of the present invention can be applied as fungicide sprays by commonly used methods such as conventional high pressure hydraulic sprays, low pressure sprays, compressed air sprays, atmospheric sprays and dusts. Dilution and rate of application will depend on the type of equipment used, the method of application, the plant to be treated and the disease to be suppressed. Typically the compounds of the present invention are applied in an amount of about 0.005 kg to about 50 kg of active ingredient per hectare, preferably in an amount of about 0.025 to about 25 kg per hectare.

As a seed protectant, the amount of poison coated on the seeds is usually in a dosage of about 0.05 to about 20 g, preferably about 0.05 to about 4 g and more preferably about 0.1 to about 1 g per 100 kg of seed. As soil fungicides, the chemical may be incorporated into the soil or applied to the surface in an amount of about 0.02 to about 20 kg, preferably about 0.05 to about 10 kg, more preferably about 0.1 to about 5 kg per hectare. As fungicide of the leaves, the poison is applied to plants growing in an amount of about 0.01 to about 10 kg, preferably about 0.02 to 5 kg, more preferably about 0.25 to about 1 kg per hectare.

As long as the compounds of the present invention exhibit fungicidal activity, these compounds can be combined with other known fungicides to obtain a wide range of activities. Suitable fungicides include, but are not limited to, the compounds described in US Pat. No. 5,252,594 (see especially columns 14 and 15). Other known fungicides combined with the compounds of the present invention are dimethomorph, cymoxanyl, tifusamide, furlaxyl, opras, benalaxil, oxadixyl, propamocarb, ciprofuram, fenpiclo Neil, Fludioxonyl, Pyrmetanyl, Ciprodinyl, Triticazole, Fluquinconazole, Metaconazole, Spiroxamine, Carpropamide, Azoxystrobin, Cresoxime-methyl, Metomynost Robin and tripleoxytropin.

The compounds of the present invention can be advantageously used in various ways. Since these compounds have a wide range of fungicidal activity, they can be used for the storage of cereals. In addition, these compounds can be used as fungicides in cereals, rice, peanuts, green beans and grapes, grass, fruits, nuts and vegetable orchards and golf courses including wheat, barley and rye.

Examples of diseases in which the compounds of the present invention are useful include parasites of corn and barley, powdery mildew of wheat and barley, rust of wheat and stem, rust of barley and leaves, early tomato blight, late tomato blight, early peanut leaf spot, grapes White powder, grape black rot, apple spot, apple white powder, cucumber white powder, fruit brown rot, mold disease, pea white powder, cucumber anthrax, wheat septoria nodallium, rice stripe blight, and rice alopecia.

In addition, the compositions and formulations according to the invention may comprise known pesticidal compounds. This extends the range of activity of the formulation and can be synergistic. Suitable pesticides known in the art include those described in US Pat. No. 5,075,471 (see especially columns 14 and 15).

The compounds of the present invention can be used in the form of compositions or formulations. Examples of the preparation of compositions and formulations can be found in the literature, see the American Chemical Society publication "Pesticidal Formulation Research", (1969), Advances in Chemistry Series No. 86, written by Wade Van Valkenburg; and the Marcel Dekker, Inc. publication "Pesticide Formulations", (1973) edited by Wade Van Valkenburg. In such compositions and formulations, the active materials are conventionally inert, agriculturally acceptable (ie, seedling miscible and / or bactericidally inert) in a form useful for conventional fungicide compositions or formulations, such as solid carrier materials or liquid carrier materials. Mix with fungicide diluent or extender. A "crophysically acceptable carrier" can be used to dissolve, disperse or disperse an active ingredient without inhibiting the effect of the active ingredient in the composition, which in itself has no significant adverse effect on soil, equipment, the desired crop or crop environment. Does not mean any substance. If desired, auxiliaries such as surfactants, stabilizers, antifoams and anti-drift agents can be combined.

Examples of compositions and formulations according to the invention include aqueous solutions and dispersions, oily solutions and oily dispersions, pastes, dust powders, wettable powders, emulsion concentrates, effluents, granules, bites, conversion emulsions, aerosol compositions and fumigation candles. . Wettable powders, pastes, effluents, and emulsion concentrates are concentrated formulations that are diluted with water before or during use. In such formulations, the compounds are extended by liquid or solid carriers and optionally incorporate suitable surfactants. Bites are preparations that normally contain food or other substances that attract insects and include one or more compounds of the present invention.

In particular, in the case of leaf spray formulations, it is usually desirable to include auxiliaries such as wetting agents, spreading agents, dispersants, stickers, adhesives and the like, depending on the agricultural practice. A listing of these adjuvants and discussion of auxiliaries commonly used in the art can be found in the literature. John W. McCutcheon, Inc. publication "Detergents and Emulsifiers, Annual"].

The active compounds of the present invention may be used alone or in a mixture with each other and / or solid and / or liquid dispersion carrier vehicles and / or other known miscible actives, in particular other pesticides, arthropod removers, linear animal removers, fungicides, bacteria It can be used in the form of a mixture with crop protection agents such as scavengers, rodent scavengers, herbicides, fertilizers, growth regulators, synergists.

In the compositions of the present invention, the active compound is used in an amount of 0.0001% to 99% by weight. For compositions suitable for storage and transportation, the amount of active ingredient is preferably in the range of 0.5 to 90% by weight of the mixture, more preferably 1 to 75% by weight of the mixture. Compositions suitable for direct application or in situ application usually contain the active compound in an amount of 0.0001 to 95% by weight, preferably 0.0005 to 90% by weight, more preferably 0.001 to 75% by weight of the mixture. The composition can also be expressed in the ratio of compound to carrier. In the present invention, the weight ratio of such materials may vary from 99: 1 to 1: 4, more preferably 10: 1 to 1: 3.

In general, the compounds of the present invention can be dissolved in certain solvents such as acetone, methanol, ethanol, dimethylformamide, pyridine or dimethyl sulfoxide and these solutions can be diluted with water. The concentration of the solution can vary from 1% to 90%, with a preferred range of 5% to 50%.

For emulsifiable concentrate formulations, the present compounds may be dissolved with an emulsifier in a suitable organic solvent or mixture of solvents to enhance the solubility of the compounds in water. The concentration of the active ingredient in the emulsion concentrate is usually 10% to 90%, and can be up to 75% in the flowable emulsion concentrate.

Wettable powders suitable for spraying can be prepared by mixing the present compounds with finely divided solids such as clays, inorganic silicates and carbonates, and silica and incorporating wetting agents, thickeners and / or dispersants into the mixture. The concentration of active ingredient in such formulations is usually in the range of 20% to 99%, preferably 40% to 75%. Typical wettable powders are prepared by blending 50 parts of a compound of formula (I), 45 parts of synthetic precipitated hydrated silicon dioxide and 5 parts of sodium lignosulfonate. In another formulation, kaolin clay (Barden) clay is used in the wettable powders described above in place of synthetic precipitated hydrated silicon dioxide, and in another formulation 25% of silicon dioxide is used in place of synthetic sodium silicone aluminate.

Dust is prepared by mixing the present compound with a finely divided inert solid which may be organic or inorganic in nature. Materials useful for this purpose include vegetable flour, silica, silicates, carbonates and clays. One common method for preparing dust is to dilute the wettable powder using a finely divided carrier. Dust concentrates containing 20% to 80% of the active ingredient are normally prepared and then diluted to a use concentration of 1% to 10%.

In addition to the components mentioned above, the preparations according to the invention may contain other substances customarily used in this kind of preparation. For example, a lubricant such as calcium stearate or magnesium stearate may be added to the wettable powder or mixture to be granulated. Also, for example, an "adhesive" (eg polyvinyl alcohol-cellulose derivative) or other colloidal material (eg casein) may be added to improve the adhesion of the pesticide to the surface to be protected.

Claims (10)

Compounds of formula (I), salts, complexes, enantiomorphs, stereoisomers and mixtures thereof. Formula I In Formula I, A is hydrogen, halo, cyano, (C ₁ -C ₁₂ ) alkyl or (C ₁ -C ₁₂ ) alkoxy, R ₁ is (C ₁ -C ₁₂ ) alkyl or halo (C ₁ -C ₁₂ ) alkyl, R ₂ is hydrogen, (C ₁ -C ₁₂ ) alkyl, halo (C ₁ -C ₁₂ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, halo (C ₃ -C ₇ ) cycloalkyl, (C ₂ -C ₈ ) alkenyl, halo (C ₂ -C ₈ ) alkenyl, (C ₂ -C ₈ ) alkynyl, halo (C ₂ -C ₈ ) alkynyl or cyano, R ₃ is hydrogen, R ₄ and R ₅ are independently hydrogen, (C ₁ -C ₁₂ ) alkyl, halo (C ₁ -C ₁₂ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, halo (C ₃ -C ₇ ) cycloalkyl, (C ₂ -C ₈ ) alkenyl, halo (C ₂ -C ₈ ) alkenyl, (C ₂ -C ₈ ) alkynyl, halo (C ₂ -C ₈ ) alkynyl, halo, cyano or (C ₁ -C ₄ ) alkoxycarbonyl, [A] R ₇ is aryl, arylalkyl, heterocyclic or heterocyclic (C ₁ -C ₄ ) alkyl wherein the aryl or heterocyclic ring is substituted by 2 to 5 substituents and is bonded to a cyclopropyl ring Positions on the aryl or heterocyclic ring adjacent to are both substituted), and R ₆ is hydrogen, (C ₁ -C ₁₂ ) alkyl, halo (C ₁ -C ₁₂ ) alkyl, (C ₃ -C ₇ ) Cycloalkyl, halo (C ₃ -C ₇ ) cycloalkyl, (C ₂ -C ₈ ) alkenyl, halo (C ₂ -C ₈ ) alkenyl, (C ₂ -C ₈ ) alkynyl, halo (C _2- C ₈₎ alkynyl, halo, cyano, or (C _l -C ₄₎ alkoxycarbonyl; or [B] R ₇ is aryl, arylalkyl, heterocyclic or heterocyclic (C ₁ -C ₄ ) alkyl wherein the aryl or heterocyclic ring is unsubstituted or substituted by 1 to 4 substituents and is cyclo At least one position on the aryl or heterocyclic ring adjacent to the bond with the propyl ring is hydrogen), and R ₆ is hydrogen, (C ₁ -C ₁₂ ) alkyl, halo (C ₁ -C ₁₂ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, halo (C ₃ -C ₇ ) cycloalkyl, (C ₂ -C ₈ ) alkenyl, halo (C ₂ -C ₈ ) alkenyl, (C ₂ -C ₈ ) alkynyl, halo (C ₂ -C ₈ ) alkynyl, halo, cyano or (C ₁ -C ₄ ) alkoxycarbonyl. The compound of claim 1, wherein R ₁ and R ₂ are CH ₃ and R ₆ is hydrogen or (C ₁ -C ₁₂ ) alkyl. The compound of claim 1, wherein R ₁ and R ₂ are CH ₃ , R ₆ is hydrogen or (C ₁ -C ₁₂ ) alkyl, R ₇ is 2,6-dichlorophenyl, 2,6-difluorophenyl, 2,6-dibromophenyl, 2,6-bis (trifluoromethyl) phenyl, 2,3,6-trichlorophenyl, 2,3,6-trifluorophenyl, 2,3,6-tri Ribomophenyl, 2,3,6-tris (trifluoromethyl) phenyl 2,4,6-trichlorophenyl, 2,4,6-trifluorophenyl, 2,4,6-tribromophenyl or 2,4,6-tris (trifluoromethyl) phenyl, wherein R ₆ is hydrogen. The compound of claim 1, wherein N-methyl-2- [2-((trans-1- (2-N-methoxy-N-methyl-N- [2-((trans- (2- (2 ', 6) '-Dichlorophenyl) cyclopropyl) -ethylidene) aminooxymethyl) phenyl] carbamate. The compound of claim 1, wherein R ₁ and R ₂ are CH ₃ , R ₆ is hydrogen or (C ₁ -C ₁₂ ) alkyl, and R ₇ is phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl , 4-fluorophenyl, 4-bromophenyl, 2- (trifluoromethyl) -phenyl, 2,4-dichlorophenyl, 2,4-difluorophenyl, 2,4-dibromophenyl or 2 , 4-bis (trifluoromethyl) phenyl, wherein R ₆ is (C ₁ -C ₁₂ ) alkyl. The compound of claim 5, wherein R ₇ is phenyl, 4-chlorophenyl or 4-fluorophenyl and R ₆ is CH ₃ . The compound of claim 1, wherein N-methoxy-N-methyl-N- [2-((trans-1- (2- (4'-fluorophenyl-2-methyl) cyclopropyl) ethylidene) aminooxymethyl ) Phenyl] carbamate. N-methoxy-N-methyl (E) -2- (aminooxymethyl) -phenyl carbamate 1-aryl-1- (C ₁ -C ₁₂ ) alkyl-2- (C (= O) (CH ₃ )) cyclopropane-1-or heteroaryl -1- (C ₁ -C ₁₂₎ alkyl -2- (C (= O) ( CH 3)) comprising the step of cyclo propane and reaction, R ₆ is (C ₁ -C ₁₂ ) A process for the preparation of a compound according to claim 4, which is an alkyl. A fungicidal composition for inhibiting phytopathogenic fungi comprising a crop acceptable carrier and the compound according to claim 1 wherein the ratio of carrier to compound is from 99: 1 to 1: 2. A method of inhibiting phytopathogenic fungi, comprising applying the compound according to claim 1 in a locus to be inhibited at a rate of 0.005 to 50 kg per hectare.