CN1222301A - Process for preparation of fungicidal compositions - Google Patents

Process for preparation of fungicidal compositions Download PDF

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CN1222301A
CN1222301A CN98119131A CN98119131A CN1222301A CN 1222301 A CN1222301 A CN 1222301A CN 98119131 A CN98119131 A CN 98119131A CN 98119131 A CN98119131 A CN 98119131A CN 1222301 A CN1222301 A CN 1222301A
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base
alkyl
methyl
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CN100358877C (en
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B·W·克卢格
P·格迪斯
L·阿什曼
U·海尼曼
H·盖耶
D·库特
U·菲利浦
T·塞兹
J·施泰特
R·泰曼
H·W·迪尼
S·杜茨曼
G·汉斯勒
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Bayer AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D273/00—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/88—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with three ring hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

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  • Pest Control & Pesticides (AREA)
  • Agronomy & Crop Science (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

New azadioxacycloalkenes have the formula (I), in which A stands for optionally substituted alkane diyl (alkylene); Ar stands for optionally substituted arylene or heteroarylene; E stands for one of the following groupings (a), (b), (c), (d), (e) where Y is oxygen, sulphur, methylene (CH2) or alkylimino (N-R); and Z - G stand for various substituents. Also disclosed are a process for preparing the same and their use as fungicides.

Description

The method for preparing Fungicidal composition
The application is that application number is 94193669.4, and the applying date is on July 29th, 1994, and denomination of invention is divided an application for the application for a patent for invention of " the azepine dioxane alkene of replacement and as the application of fungicide ".
The present invention relates to new substituted nitrogen heterocyclic dioxane alkene, its preparation method with and as the purposes of fungicide.
5 of some replacement was disclosed already, 6-dihydro-1,4,2-dioxazine have fungicidal properties (referring to, JP-A01221371-quotes from the 112:98566t in Chem.Abstracts; JP-A 02001484-quotes from the 113:6381y in Chem.Abstracts).
Yet these compounds are not paid attention to especially.
Have now found that the azepine dioxane alkene of the new replacement of general formula (I)
Figure A9811913100041
Wherein alkane two bases (alkylidene) that replace are chosen in the A representative wantonly, optional separately arlydene or the inferior heteroaryl that replaces of Ar; The E representative is with R on 2 1The 1-alkene-1 of base, 1-two bases, or on 2, be with
R 22-azepine-1-the alkene-1 of base, 1-two bases, or on 1, be with R 1Base
3-oxa-or 3-thia-1-propylene-2,3-two bases, or the representative at 3
Last band R is basic and be with R on 1 13-azepine-1-the propylene-2 of base, 3-two
Base, or representative is with R on 1 21-azepine-1-the propylene-2 of base, 3-two
Base, or representative is with R on 1 2The 3-oxa-or the 3-thia-1-azepine of base
-propylene-2,3-two bases, or representative is being with the R base and is being with R on 1 on 3 2
1 of base, 3-diaza-1-propylene-2,3-two bases, or the optional replacement of representative
Imino group (" aza-methylene ", N-R 3),
Wherein
R represents alkyl,
R 1Represent hydrogen, halogen, cyano group or optional separately alkyl, alkoxyl, the alkane sulphur that replaces
Base, alkylamino or dialkyl amido,
R 2Represent hydrogen, amino, cyano group or optional separately alkyl, alkoxyl, the alkane ammonia that replaces
Base or dialkyl amido; With
R 3Represent hydrogen, cyano group or optional separately alkyl, alkenyl, alkynyl, the cycloalkanes that replaces
Base or cycloalkyl-alkyl, G represent a singly-bound, oxygen or representative optional separately by halogen, hydroxyl, alkyl, halo
Alkane two bases, olefin 2 base, oxa-olefin 2 base, alkynes two bases that alkyl or cycloalkyl replaces,
Or represent one of following groups:
-Q-CQ-,-CQ-Q-,-CH 2-Q-,-Q-CH 2-,-CQ-Q-CH 2-,
-CH 2-Q-CQ-,-Q-CQ-CH 2-,-Q-CQ-Q-CH 2-,-N=N-,-S(O) n-,
-CH 2-S(O) n-,-CQ-,-S(O) n-CH 2-,-C(R 4)=N-O-,
-C(R 4)=N-O-CH 2-,-N(R 5)-,-CQ-N(R 5)-,-N(R 5)-CQ-,
-Q-CO-N(R 5)-,-N=C(R 4)-Q-CH 2-,-CH 2-O-N=C(R 4)-,
-N(R 5)-CQ-Q-,-CQ-N(R 5)-CQ-Q-,-N(R 5)-CQ-Q-CH 2-,
-CQ-CH 2-or-N=N-C (R 4)=N-O-,
Wherein
N represents 0,1 or 2 numeral;
Q represents oxygen or sulphur;
R 4Represent the optional separately alkyl that replaces of hydrogen, cyano group or representative, alkoxyl, alkylthio group,
Alkylamino, dialkyl amido or cycloalkyl and
R 5Represent the optional separately alkyl that replaces of hydrogen, hydroxyl, cyano group or representative, alkoxyl or
The optional separately alkyl that replaces of cycloalkyl and Z representative, alkenyl, alkynyl, cycloalkyl, aryl or assorted
Cyclic group.
Also have found that the azepine dioxane alkene of new replacement that can following acquisition general formula (I): (a) first step, when suitable, in the presence of acid acceptor when suitable, in the presence of thinner,
Make the carboxylic acid derivates of general formula (II) and hydroxylamine or with its halogenation hydride reaction,
Figure A9811913100061
Wherein
Ar, E, G and Z have above-mentioned connotation and
R represents alkyl;
And the product of the first step is in position, promptly need not intermediate section from, in second step, when suitable,
In the presence of acid acceptor and when suitable, in the presence of thinner, with general formula (III)
Two replace the alkane reaction,
X-A-X (Ⅲ)
Wherein
A has above-mentioned connotation, and
X represents halogen, alkylsulfonyloxy or aryl-sulfonyl oxygen, or (b) in formula (I), G represent oxygen or-CH 2-O-group, and A, Ar, E and
When Z has above-mentioned connotation;
When suitable, in the presence of acid acceptor, and when suitable, in the presence of thinner, make general formula
The compound reaction of the hydroxy aryl compound of (IV) and general formula (V),
Figure A9811913100071
Wherein
A, Ar and E have above-mentioned connotation;
Z-(CH 2) m-X (Ⅴ)
Wherein
X and Z have above-mentioned connotation, and
M represents numeral 0 or 1
And when suitable, subsequently the Z group is carried out substitution reaction by conventional method, or (c) in formula (I), G representative-Q-CH 2When-group and A, Ar, E and Z group have above-mentioned connotation, when suitable in the presence of acid acceptor, and when suitable in the presence of thinner, the halogenated methyl compound of general formula (VI) and the compound of general formula (VII) are reacted,
Figure A9811913100072
Wherein
A, Ar and E have above-mentioned connotation, and
X 1Represent halogen,
Z-Q-H (Ⅶ)
Wherein
Q and Z have above-mentioned connotation, or when (d) suitable in the presence of thinner, make the hydroxy alkoxy base acid amides of general formula (VIII) and dehydrating agent carry out cyclization,
Wherein
A, Ar, E, G and Z have above-mentioned connotation.
Find also that at last the azepine dioxane alkene of the new replacement of general formula (I) has very high Fungicidally active.
When suitable, compound of the present invention can exist with various possible isomer, particularly E and Z mixture of isomers form.Required for protection is any mixture of E and Z isomer and isomer thereof.
Preferred such formula (I) compound of the present invention, wherein the A representative has alkane two bases of 1 to 3 carbon atom, and it is optional by halogen or 1 to 4 carbon
The alkyl of atom or haloalkyl replace; Optional separately phenylene or the naphthylene that replaces of Ar representative, or represent 5 or 6 annular atomses,
And wherein at least one annular atoms is represented oxygen, sulphur or nitrogen, when suitable other one or two
Annular atoms is represented the inferior heteroaryl of nitrogen, and wherein possible substituting group is preferably selected from:
Halogen, cyano group, nitro, amino, hydroxyl, formoxyl, carboxyl, carbamoyl,
Thiocarbamoyl, respectively do for oneself straight or branched alkyl, alkoxyl, alkylthio group,
Alkyl sulphinyl or alkyl sulphonyl, they respectively have 1 to 6 carbon atom, respectively do for oneself
The alkenyl of straight or branched, alkenyloxy or alkynyloxy group, they respectively have 2 to 6 carbon
Atom, the haloalkyl of the straight or branched of respectively doing for oneself, halogenated alkoxy, halogenated alkylthio,
Haloalkyl sulfinyl or halogenated alkyl sulfonyl, they respectively have 1 to 6 carbon atom
With 1 to 13 identical or different halogen atom, the halo chain of the straight or branched of respectively doing for oneself
Thiazolinyl or halo alkenyloxy, they respectively have 2 to 6 carbon atoms with 1 to 13 mutually
With or different halogen atoms, the alkyl amino of the straight or branched of respectively doing for oneself, dialkyl amido,
Alkyl-carbonyl, alkyl carbonyl oxy, alkoxy carbonyl group, alkylsulfonyloxy, oxyimino
Alkyl or Alkoximino alkyl, they each at moieties separately 1 to 6 carbon is arranged
Atom, or representative respectively the do for oneself alkylidene or two oxyalkylenes of divalence, they respectively have 1 to
6 carbon atoms and optionally separately be selected from halogen and/or 1 to 4 by identical or different
The straight or branched alkyl of carbon atom and/or contain 1 to 4 carbon atom with 1 to 9 mutually
With or the substituting group list of the straight or branched haloalkyl of different halogen atoms replace or polysubstituted; E represents one of following groups:
Figure A9811913100091
Wherein Y represents oxygen, sulphur, methylene (CH 2) or alkyl imino (N-R), the R representative has the alkyl of 1 to 6 carbon atom, R 1Represent hydrogen, halogen, cyano group or represent alkyl, alkoxyl, alkylthio group, alkane ammonia
Base or dialkyl amido, they each 1 to 6 carbon atom and separately arranged on alkyl
Optional by halogen, cyano group or C 1-C 4Alkoxyl replaces, R 2Represent hydrogen, amino, cyano group, or represent alkyl, alkoxyl, alkylamino or dioxane
Base is amino, 1 to 6 carbon atom is arranged on their each comfortable moieties and appoints separately
Choosing ground is by halogen, cyano group or C 1-C 4Alkoxyl replaces, and R 3Represent hydrogen, cyano group, or represent alkyl, alkenyl or alkynyl, they have maximum 6
Individual carbon atom is also optional by halogen, cyano group or C 1-C 4Alkoxyl replaces, or
If representative has 3 to 6 carbon atoms and suits at moieties at cycloalkyl moiety
Cycloalkyl or cycloalkyl-alkyl that 1 to 4 carbon atom is arranged, they optional separately by
Halogen, cyano group, carboxyl, C 1-C 4Alkyl or C 1-C 4Alkoxy carbonyl group
Replace, G represents singly-bound, oxygen, or represents alkane three bases, olefin 2 base, oxa-alkene two bases, alkynes two bases,
They each have maximum 4 carbon atoms and optional separately by halogen, hydroxyl, C 1-C 4
Alkyl, C 1-C 4Haloalkyl or C 3-C 6Cycloalkyl substituted, or representative is down
One of row group:
-Q-CQ-,-CQ-Q-,-CH 2-Q-,-Q-CH 2-,-CQ-Q-CH 2-,
-CH 2-Q-CQ-,-Q-CQ-CH 2-,-Q-CQ-Q-CH 2-,-N=N-,-S(O) n-,
-CH 2-S(O) n-,-CQ-,-S(O) n-CH 2-,-C(R 4)=N-O-,
-C(R 4)=N-O-CH 2-,-N(R 5)-,-CQ-N(R 5)-,-N(R 5)-CQ-,
-Q-CQ-N(R 5)-,-N=C(R 4)-Q-CH 2-,-CH 2-O-N=C(R 4)-,
-N(R 5)-CQ-Q-,-CQ-N(R 5)-CQ-Q-,-N(R 5)-CQ-Q-CH 2-,
-CQ-CH 2-or-N=N-C (R 4)=N-O-,
Wherein
N represents numeral 0,1 and 2,
Q represents oxygen or sulphur,
R 4Represent hydrogen, cyano group, or represent alkyl, alkoxyl, alkylthio group, alkylamino or two
Alkyl amino, they each on alkyl, have 1 to 6 carbon atom and optional separately by
Halogen, cyano group or C 1-C 4Alkoxyl replaces, or representative has 3 to 6 carbon
The cycloalkyl of atom, they are optional by halogen, cyano group, carboxyl, C 1-C 4
Alkyl or C 1-C 4Alkoxy carbonyl group replace and
R 5Represent hydrogen, hydroxyl, cyano group, or representative is optional by halogen, cyano group or C 1-C 4
The alkyl of 1 to 6 broken atom that alkoxyl replaces, or representative optional by halogen,
Cyano group, carboxyl, C 1-C 4Alkyl or C 1-C 4Alkoxy carbonyl group replaces
The cycloalkyl of 3 to 6 carbon atoms and Z represent the alkyl of 1 to 8 carbon atom, it optional by halogen, cyano group, hydroxyl, amino,
C 1-C 4Alkoxyl, C 1-C 4Alkylthio group, C 1-C 4Alkyl sulfenyl
Base or C 1-C 4Alkyl sulphonyl (can choose wantonly separately by halogen and replace) replaces, or
Represent alkenyl or alkynyl, they contain maximum 8 carbon atoms and choose wantonly separately and got by halogen
Generation, or represent the cycloalkyl of 3 to 6 carbon atoms, they optional by halogen, cyano group,
Carboxyl, phenyl (are chosen wantonly by halogen, cyano group, C 1-C 4Alkyl, C 1-C 4
Haloalkyl, C 1-C 4Alkoxyl or C 1-C 4Halogenated alkoxy replaces),
C 1-C 4Alkyl or C 1-C 4Alkoxy carbonyl group replaces, or represents optional separately getting
The heterocyclic radical of the phenyl in generation, naphthyl or (optional benzene condenses) tool 5 or 6 annular atomses,
At least one represents oxygen, sulphur or nitrogen in the annular atoms, and if suitable, other has one or two
Individual annular atoms is represented nitrogen, and wherein possible substituting group is preferably selected from:
Oxygen (replacing two geminal hydrogen atoms), halogen, cyano group, nitro, amino, hydroxyl,
Formoxyl, carboxyl, carbamoyl, thiocarbamoyl, respectively do for oneself straight chain or
The alkyl of chain, alkoxyl, alkylthio group, alkyl sulphinyl or alkyl sulphonyl, they
1 to 6 carbon atom is respectively arranged, the alkenyl or the alkenyloxy of the straight or branched of respectively doing for oneself,
They respectively have 2 to 6 carbon atoms, haloalkyl, the halo of the straight or branched of respectively doing for oneself
Alkoxyl, halogenated alkylthio, haloalkyl sulfinyl or halogenated alkyl sulfonyl, it
1 to 6 carbon atom and 1 to 13 identical or different halogen atom are respectively arranged, separately
Be halogenated alkenyl, the halo alkenyloxy of straight or branched, they respectively have 2 to 6
Carbon atom and 1 to 13 identical or different halogen atom, the straight or branched of respectively doing for oneself
Alkylamino, dialkyl amido, alkyl carboxyl, alkyl carbonyl oxy, alkoxy carbonyl group, alkyl
Sulfonyloxy, oximino alkyl or Alkoximino alkyl, they are at alkyl separately
Part has 1 to 6 carbon atom, the alkylidene of the divalence of respectively doing for oneself or two oxyalkylenes, it
1 to 6 carbon atom and optional separately by being selected from halogen and/or 1 to 4 carbon respectively arranged
The straight or branched alkyl of atom and/or contain 1 to 4 carbon atom with 1 to 9 mutually
The identical or different substituting group of the straight or branched haloalkyl of same or different halogen atoms
Single replacement or polysubstituted, or the cycloalkyl of 3 to 6 carbon, heterocyclic radical or heterocyclyl methyl,
They respectively have 3 to 7 annular atomses, and it is identical or not that 1 to 3 annular atoms is wherein respectively arranged
With hetero atom---particularly ammonia, oxygen and/or sulphur and phenyl, phenoxy group, benzyl,
Benzyloxy, phenethyl or benzene ethyoxyl, they are optional by being selected from halogen, cyanogen at phenyl moiety
The straight chain of base, nitro, carboxyl, carbamoyl and/or 1 to 4 carbon atom or
Alkyl group and/or contain 1 to 4 carbon atom and 1 to 9 identical or different halogen atom
The straight or branched haloalkyl and/or contain the straight or branched alkane of 1 to 4 carbon atom
Oxygen base and/or contain 1 to 4 carbon atom and 1 to 9 identical or different halogen atom
The alkyl-carbonyl of straight or branched halogenated alkoxy and/or each self-contained maximum 5 carbon atom
Or the identical or different substituting group list replacement of alkoxy carbonyl group or polysubstituted.
In definition, saturated or aliphatic unsaturated hydrocarbon as alkyl, alkane two bases, alkenyl or alkynyl, and is connected with heteroatomic situation, as at alkoxyl, and in alkylthio group or the alkylamino, each straight or branched naturally in all cases.
Halogen is represented fluorine, chlorine, bromine or iodine usually, preferred fluorine, chlorine or bromine, particularly fluorine or chlorine.
Specifically, the present invention relates to the compound of formula (I), wherein A represents methylene or dimethylene (second-1,2-two bases), they can choose wantonly by fluorine,
Chlorine, methyl, ethyl or trifluoromethyl replace, the optional separately neighbour who replaces of Ar representative, or to phenylene, or represent furans two bases, thiophene
Two bases, pyrroles's two bases, pyrazoles two bases, triazole two Ji, oxazoles two basic, isoxazole two bases,
Thiazole two bases, isothiazole two Ji, oxadiazoles two bases, thiadiazoles two bases, pyridine two bases,
Pyrimidine two bases, pyridazine two bases, pyrazine two bases, 1,3,4-triazine two bases or 1,2,3
-triazine two bases, wherein possible substituting group particularly is selected from:
Fluorine, chlorine, cyano group, methyl, ethyl, trifluoromethyl, methoxyl group, ethyoxyl, first sulphur
Base, methylsulfinyl or methyl sulphonyl, E represents one of following groups:
Figure A9811913100131
Wherein
Y represents oxygen, sulphur, methylene (CH 2) or alkyl imino (N-R),
R represent methylidene, ethyl, just or isopropyl, or just, the XOR tert-butyl group,
R 1Represent hydrogen, fluorine, chlorine, bromine, cyano group or represent methylidene, ethyl, propyl group, first
Oxygen base, ethyoxyl, methyl mercapto, ethylmercapto group, methylamino, ethylamino or dimethyl
Amino, they are optional by fluorine, chlorine, cyano group, methoxy or ethoxy replacement;
R 2Represent hydrogen, amino, cyano group, or represent methylidene, ethyl, methoxyl group, ethyoxyl,
Methylamino, ethylamino or dimethylamino, they are optional separately by fluorine, chlorine, cyanogen
Base, methoxy or ethoxy replace and
R 3Represent hydrogen, cyano group, or represent methylidene, ethyl, just or isopropyl, just, XOR
The tert-butyl group, they are optional separately by fluorine, cyano group, methoxy or ethoxy replacement,
Or represent pi-allyl or propargyl, or represent cyclopropyl, cyclobutyl, cyclopenta,
Cyclohexyl, cyclopropyl methyl, cyclobutylmethyl, cyclopentyl-methyl or cyclohexyl
Methyl, they optional separately by fluorine, chlorine, cyano group, carboxyl, methyl, ethyl,
Just or isopropyl, methoxycarbonyl group or carbethoxyl group replace, G represents singly-bound, oxygen or represents methylene, dimethylene (second-1,2-two bases), ethene-1,2-two bases, acetylene-1,2-two bases, they optional separately by fluorine, chlorine, hydroxyl, methyl, ethyl, just or isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopenta or cyclohexyl replace, or represent one of following groups :-Q-CQ-,-CQ-Q-,-CH 2-Q-,-Q-CH 2-,-CQ-Q-CH 2-,-CH 2-Q-CQ-,-Q-CQ-CH 2-,-Q-CQ-Q-CH 2-,-N=N-,-S (O) n-,
-CH 2-S(O) n-,-CQ-,-S(O) n-CH 2-,-C(R 4)=N-O-,
-C(R 4)=N-O-CH 2-,-N(R 5)-,-CQ-N(R 5)-,-N(R 5)-CQ-,
-Q-CQ-N(R 5)-,-N=C(R 4)-Q-CH 2-,-CH 2-O-N=C(R 4)-,
-N (R 5)-CQ-Q-,-CQ-N (R 5)-CQ-Q-or-N (R 5)-CQ-Q-CH 2-,
Wherein
N represents numeral 0,1 or 2,
Q represents oxygen or sulphur,
R 4Represent hydrogen, cyano group or represent methylidene, ethyl, just or isopropyl, just, XOR
The tert-butyl group, methoxyl group, ethyoxyl, propoxyl group, butoxy, methyl mercapto, second sulphur
Base, rosickyite base, butylthio, methylamino, ethylamino, third amino, dimethylamino
Base or diethylamino, they optional separately by fluorine, chlorine, cyano group, methoxyl group or
Ethyoxyl replaces, or represents cyclopropyl, cyclobutyl, cyclopenta or cyclohexyl, it
Optional separately by fluorine, chlorine, cyano group, carboxyl, methyl, ethyl, just or different third
Base, methoxycarbonyl group or carbethoxyl group replace and
R 5Represent hydrogen, hydroxyl, cyano group or represent methylidene, ethyl, just or isopropyl, just,
Different, the second month in a season or the tert-butyl group, they optional separately by fluorine, chlorine, cyano group, methoxyl group or
Ethyoxyl replaces, or represents cyclopropyl, cyclobutyl, cyclopenta or cyclohexyl, it
Optional separately by fluorine, chlorine, cyano group, carboxyl, methyl, ethyl, just or different third
Base, methoxycarbonyl group or carbethoxyl group replace, with the Z represent methylidene, ethyl, just or isopropyl, or just, different, secondary, or the tert-butyl group, they are optional separately by fluorine, chlorine, bromine, cyano group, hydroxyl, amino, methoxyl group, ethyoxyl, methyl mercapto, ethylmercapto group, methylsulfinyl, the ethyl sulfinyl, methyl sulphonyl or ethylsulfonyl (they are optional separately by fluorine and/or chlorine replacement) replace, or representative pi-allyl, cyclobutenyl, 1-methyl-pi-allyl, propargyl or 1-methyl-propargyl, they are optional separately by fluorine, chlorine or bromine replaces, or representative cyclopropyl, cyclobutyl, cyclopenta or cyclohexyl, they are optional separately by fluorine, chlorine, bromine, cyano group, carboxyl, phenyl is (optional by fluorine, chlorine, bromine, cyano group, methyl, ethyl, just or isopropyl, just, different, the second month in a season or the tert-butyl group, trifluoromethyl, methoxyl group, ethyoxyl, just or isopropoxy, difluoro-methoxy or trifluoromethoxy replace), methyl, ethyl, just or isopropyl, methoxycarbonyl group or carbethoxyl group replace, or the optional separately substituted phenyl of representative, naphthyl, furyl, tetrahydrofuran base, benzofuranyl, THP trtrahydropyranyl, thienyl, benzothienyl, pyrrole radicals, the pyrrolin base, the nafoxidine base, the benzopyrrole base, benzo pyrrolin base oxazolyl benzoxazolyl isoxazolyl, thiazolyl, benzothienyl, isothiazolyl, imidazole radicals, benzimidazolyl oxadiazole base, thiadiazolyl group, pyridine radicals, pyrimidine radicals, pyridazinyl, pyrazinyl, 1,2, the 3-triazinyl, 1,2,4-triazinyl or 1,3, the 5-triazinyl, wherein possible substituting group is preferably selected from: oxygen (substituting two geminal hydrogen atoms), fluorine, chlorine, bromine, cyano group, nitro, amino, hydroxyl, formoxyl, carboxyl, carbamoyl, thiocarbamoyl, methyl, ethyl, just or isopropyl, just, different, the second month in a season or the tert-butyl group, methoxyl group, ethyoxyl, just or isopropoxy, methyl mercapto, ethylmercapto group, just or different rosickyite base, methylsulfinyl, the ethyl sulfinyl, methyl sulphonyl or ethylsulfonyl, trifluoromethyl, difluoro-methoxy, trifluoromethoxy, the difluoro methyl mercapto, trifluoromethylthio, trifluoromethyl sulphinyl base or trifluoromethyl sulfonyl, methylamino, ethylamino, just or isopropylamino, dimethylamino, diethylamino, acetyl group, propiono, acetoxyl group, methoxycarbonyl group, carbethoxyl group, mesyloxy, ethanesulfonyloxy group, the oximino methyl, the oximino ethyl, the methoxyimino methyl, the ethoxy imino methyl, methoxyimino ethyl or ethoxy imino ethyl; Or trimethylene (the third-1; 3-two bases); methylene-dioxy or ethylenedioxy; cyclopropyl; cyclobutyl; cyclopenta or cyclohexyl; their optional separately fluorine that is selected from; chlorine; methyl; ethyl or just or the identical or different substituting group list of isopropyl replace or polysubstituted; and phenyl; phenoxy group; benzyl or benzyloxy, they are respectively at the optional fluorine that is selected from of phenyl moiety; chlorine; bromine; cyano group; nitro; carboxyl; carbamoyl; methyl; ethyl; just or isopropyl; just; different; the second month in a season or the tert-butyl group; trifluoromethyl; methoxyl group; ethyoxyl; just or isopropoxy; difluoro-methoxy; trifluoromethoxy; acetyl group; the identical or different substituting group list of methoxycarbonyl group or carbethoxyl group replaces or is polysubstituted.Most preferred one group of The compounds of this invention is such formula (I) compound, and wherein A represents dimethylene (second-1,2-two bases), and Ar represents neighbour-phenylene, pyridine-2, and 3-two bases or thiophene-2,3-two bases, E represents one of following groups:
Wherein
R 1And R 2Representation methoxy separately, G represents oxygen, one of methylene or following groups:
-CE 2-O-,-O-CH 2-,-S(O) n-,-CH 2-S(O) n-,-S(O) n-CH 2-,
-C (R 4)=N-O-,-O-N=C (R 4)-,-C (R 4)=N-O-CH 2-,-N (R 5)-or
-CH 2-O-N=C(R 4)-，
Wherein
N represents numeral 0,1 or 2,
R 4Represent hydrogen, methyl or ethyl and
R 5Represent hydrogen, the optional separately substituted phenyl of methyl or ethyl and Z representative, pyridine radicals, pyrimidine radicals, pyridazinyl, pyrazinyl,
1,2,3-triazinyl, 1,2,4-triazinyl or 1,3,5-triazines base, wherein
Possible substituting group is preferably selected from:
Fluorine, chlorine, bromine, cyano group, methyl, ethyl, just or isopropyl, just, different, second month in a season or uncle
Butyl, methoxyl group, ethyoxyl, just or isopropoxy, methyl mercapto, ethylmercapto group, just or
Different rosickyite base, methylsulfinyl, ethyl sulfinyl, mesyl or ethylsulfonyl,
Trifluoromethyl, difluoro-methoxy, trifluoromethoxy, difluoro methyl mercapto, trifluoromethylthio,
Trifluoromethyl sulphinyl base or trifluoromethyl sulfonyl, methoxycarbonyl group, carbethoxyl group, first
Oxygen base imino group ethyl, ethoxy imino ethyl, methoxyimino ethyl or ethoxy
Base imino group ethyl, or methylene-dioxy or ethylenedioxy, they are optional separately by choosing
Identical or different substituting group list from fluorine, chlorine, methyl or ethyl replaces or two replacement,
And phenyl, phenoxy group, benzyl or benzyloxy, their each comfortable phenyl moieties optional by
Be selected from fluorine, chlorine, bromine, cyano group, methyl, ethyl, just or isopropyl, just, different, secondary
Or the tert-butyl group, trifluoromethyl, methoxyl group, ethyoxyl, just or isopropoxy, difluoro first
The identical or different substituting group list of oxygen base or trifluoromethoxy replaces or is polysubstituted.
The above-mentioned general group definition or the group definition of preferable range are applicable to the end-product of formula (I), and are applicable to and prepare required raw material or intermediate in all cases.
If desired, the definition of these groups can be made up mutually, and in other words, the combination between specified preferred compound scope also is possible.
For example, if make raw material with α-methoxyimino-α-(2-Phenoxyphenyl)-methyl acetate, hydroxylamine hydrochloride and glycol dibromide, the reaction path among the preparation method of the present invention (a) can be summarized with following reaction equation:
For example, if with 3-[α-methoxyimino-α-(2-hydroxyl-phenyl)-methyl]-5,6-dihydro-1,4,2-dioxazine and benzyl chlorine are made raw material, and the reaction path among the preparation method of the present invention (b) can be with following reaction equation general introduction:
For example, if with 3-[α-methoxyimino-α-(2-chloromethyl-phenyl)-methyl]-5,6-dihydro-1,4,2-dioxazine and 2-methylphenol are made raw material, and the reaction path among the preparation method of the present invention (c) can be with following reaction equation general introduction:
Figure A9811913100182
For example, if make raw material with N-(2-hydroxyl-ethyoxyl)-α-methoxyimino-α-(2-phenoxy group-phenyl)-acetamide, the reaction path among the preparation method of the present invention can be summarized with following reaction equation:
Figure A9811913100191
Formula (II) provides the General Definition that needs as the carboxylic acid derivates of the raw material that carries out the inventive method (a).In formula (II), Ar, E, G preferably or particularly have with formula of the present invention (I) compound with Z and describe the relevant preferred or particularly preferred Ar that had mentioned already, E, G and Z implication; R preferably represents the alkyl of 1 to 4 carbon atom; Particularly methyl or ethyl.
The raw material of formula (II) be known and/or can by known method preparation itself (referring to, EP-A 178826, EP-A 242081, EP-A 382375, EP-A 493711).
Formula (III) provides the general definition of other the two replacement alkane that are used as raw material in the inventive method (a).In the formula (III), A preferably or particularly has the implication of describing the relevant preferred or particularly preferred A that had mentioned already with formula of the present invention (I) compound; X preferably represents chlorine, bromine, mesyloxy, phenylsulfonyloxy or tosyloxy.
The raw material of formula (III) is known organic synthesis compound.
Formula (IV) is provided at the general definition that is used as the hydroxy aryl compound of raw material in the inventive method (a) for preparing general formula (I) compound.In the formula (IV), A, Ar preferably or particularly has the preferred or particularly preferred A that already provided relevant with the description of formula (I) compound, those connotations of Ar and E with E.
The raw material of formula (IV) does not see document so far as yet, and as novel substance, it is the application's a part.
The new hydroxy-aryl compound of formula (IV) can be by following acquisition: when suitable, in the presence of thinner, for example at water, methyl alcohol, ethanol or ethyl acetate exist down, between 0 ℃ to 100 ℃, make the tetrahydropyran oxygen based compound and the acid reaction of general formula (IX), hydrochloric acid for example, sulfuric acid, methanesulfonic acid, benzene sulfonic acid, p-methyl benzenesulfonic acid, or with acid ion exchangers reaction (referring to preparation embodiment).
Figure A9811913100201
Wherein
A, Ar and E have above-mentioned connotation.
The tetrahydropyran oxygen based compound of formula (IX) does not see document so far as yet, and as novel substance, it is the application's a part.
The new tetrahydropyran oxygen based compound of formula (IX) can be by following acquisition: when suitable, in the presence of acid acceptor such as potassium hydroxide, and when suitable, in the presence of thinner such as first alcohol and water, make the reaction of the ester of general formula (X) and hydroxylamine (if or suitable, with its hydrochloride reaction), and when suitable, at acid acceptor for example in the presence of the potash, the intermediate that forms at 0 ℃ of-100 ℃ of chien shih saturated dihalide of original position and above-mentioned general formula (III) again reacts, (referring to, according to the description of the inventive method (a) and preparation embodiment)
Wherein
Ar, E and R have above-mentioned connotation.
The ester of formula (X) does not see document so far as yet, and as novel substance, it is the application's a part.
The new ester of formula (X) can followingly obtain: with the THP trtrahydropyranyl oxygen base of general formula (XI)-phenylacetic acid ester with conventional method derivation (referring to preparation embodiment):
Figure A9811913100211
Wherein
Ar and R have above-mentioned connotation.
The THP trtrahydropyranyl oxygen base-phenylacetic acid ester of formula (XI) does not see document so far as yet, and as novel substance, it is the application's a part.
New tetrahydro-pyran oxy-phenylacetic acid the ester of formula (XI) can followingly obtain: when suitable, at catalyzer as in the presence of to the methylene benzene sulfonic acid, when suitable in the presence of thinner such as oxolane, in the hydroxyphenyl acetic acid ester and the dihydropyran reaction of 0 ℃ to 100 ℃ chien shih general formula (XII)
Figure A9811913100212
Wherein
Ar and R have above-mentioned connotation; (referring to preparation embodiment).
The raw material of formula (XII) is known synthetic compound.
Formula (V) provides the other general definition that is used as the compound of raw material in the inventive method (b) of preparation general formula (I) compound that is used as.In the formula (V), Z preferably or particularly has the implication of describing the relevant preferred or particularly preferred Z that had mentioned already with formula (I) compound; X preferably represents chlorine, bromine, mesyloxy, phenylsulfonyloxy or tosyloxy.
The raw material of formula (V) is known synthetic compound.
Formula (VI) is provided at the general definition that is used as the halogenated methyl compound of raw material in the inventive method (c) for preparing general formula (I) compound.In the formula (VI), A, Ar and E preferably or particularly have with formula (I) compound describe relevant mentioned already preferably, or particularly preferred A, those connotations of Ar and E; X 1Preferably represent fluorine, chlorine, bromine or iodine, particularly chlorine or bromine.
The raw material of formula (VI) does not see document so far as yet, and as novel substance, it is the application's a part.
The new halogenated methyl compound of formula (VI) can followingly obtain: when suitable, at catalyzer as 2,2 '-the azo isobutyronitrile existence is down, if and suit in the presence of thinner such as tetrachloromethane, 0～150 ℃ of methyl compound and for example N-bromine or N-chloro-succinimide reaction (referring to preparation embodiment) of halogenating agent that makes general formula (X III)
Figure A9811913100221
In the formula
A, Ar and E have above-mentioned connotation.
Need not see document so far as yet as formula (X III) methyl compound of precursor; As novel substance, it is the application's a part.
The new methyl compound of formula (X III) can followingly obtain: when suitable, and in the presence of acid acceptor such as potassium hydroxide, and if suitable, in the presence of thinner such as methyl alcohol, make ester and the azanol or the hydroxylamine hydrochloride reaction of formula (X IV),
Figure A9811913100222
In the formula
A, E and R have above-mentioned connotation; And when suitable, in the presence of acid acceptor such as potash, make two of product and above-mentioned general formula (III) replace alkane reaction (referring to preparation embodiment) at 0～150 ℃ by the mode that is similar to the inventive method (a).
The precursor of formula (X IV) is known and/or can be by aforementioned known method preparation (referring to EP-A 386561, EP-A 498188, preparation embodiment).
Formula (VII) provides the general definition that is used as the compound of raw material in the inventive method (c) of other preparation general formula (I) compound.In the formula (VII), Q preferably or particularly has with formula (I) compound with Z and describes the relevant above-mentioned preferred or particularly preferred Q that had provided already and those connotations of Z.
The raw material of formula (VII) is known organic synthesis compound.
Formula (VIII) is provided at the general definition that is used as the hydroxy alkoxy base acid amides of raw material in the inventive method (d) for preparing general formula (I) compound.In the formula (VIII), A, Ar, E, G and Z are preferred, or particularly, have with formula (I) compound and describe relevant above-mentioned preferred or particularly preferred A, Ar, E, G and the Z implication that had provided already.
The raw material of formula (X III) does not see document so far as yet, and as novel substance, it is the application's a part.
The new hydroxy alkoxy base acid amides of formula (VIII) can followingly obtain: make the carboxylic acid derivates of general formula (X V) and the azanol reaction of general formula (X VI):
Figure A9811913100231
Wherein
Ar, E, G and Z have above-mentioned connotation, and
Y represents halogen, hydroxyl or alkoxyl,
H 2N-O-A-OH (ⅩⅥ)
In the formula
A has above-mentioned connotation; Reaction condition is: 0 ℃ to 150 ℃ temperature, when suitable, if in the presence of acid acceptor such as triethylamine, pyridine or 4-dimethylamino-pyridine and suitable, at thinner such as carrene, toluene or oxolane exist down, (referring to preparing embodiment).
To need formula (X V) carboxylic acid derivates as precursor be known and/or can be by aforementioned known method preparation (referring to EP-A 178826, EP-A 242081, EP-A382375, EP-A 493711).
Need in addition also to be known and/or can to prepare (referring to J.Chem.Soc.Perkin Trans.I 1987,2829-2832) by aforementioned known method as formula (X VI) azanol of precursor.
Method (a) and (b) of the present invention and (c) preferably in the presence of the acid acceptor that is fit to, carry out.The acid acceptor that is fit to is all conventional inorganic or organic bases, comprises, for example, the hydride of alkali metal or alkaline earth metal, hydroxide, hydride, alcoholates, acetate, carbonate or bicarbonate, for example, sodium hydride, sodium amide, sodium methoxide, caustic alcohol, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate, calcium acetate, ammonium acetate, sodium carbonate, potash, saleratus, sodium bicarbonate or ammonium carbonate, and also comprise tertiary amine, as trimethylamine, triethylamine, tri-n-butylamine, N, accelerine, N, N-dimethyl-benzylamine, pyridine, the N-methyl piperidine, N, N-dimethyl aminopyridine, diazabicyclooctane (DABCO), Diazabicyclononene (DBN) or diazabicylo hendecene (DBU).
Enforcement the inventive method (a) and (b) and the thinner that is fit to (c) are water and organic solvent.Comprise, particularly, the hydro carbons of the optional halo of aliphatic, alicyclic or aromatics, as, gasoline, benzene, toluene, dimethylbenzene, chlorobenzene, dichloro-benzenes, benzinum, hexane, cyclohexane, carrene, chloroform, carbon tetrachloride; Ethers, as ether, diisopropyl ether ， diox, oxolane or glycol dimethyl ether or ethylene glycol diethyl ether; Ketone, as acetone, butanone or methylisobutylketone; Nitrile, as acetonitrile, propionitrile or phenylcyanide; Amide-type, as N, dinethylformamide, N,N-dimethylacetamide, N-methyl-formanilide, N-Methyl pyrrolidone or HMPA; The ester class is as methyl acetate or ethyl acetate; The sulfoxide class is as dimethyl sulfoxide (DMSO); Alcohols, as methyl alcohol, ethanol, just or isopropyl alcohol, glycol monoethyl ether, ethylene glycol monoethyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether; The mixture of they and water, or pure water.
Method of the present invention (d) is preferably carried out in the presence of dehydrating agent.The dehydrating agent that is fit to is conventional anhydro compounds, particularly acid anhydrides, as, phosphorous oxide (V) (phosphorus pentoxide).
The suitable thinner of implementing the inventive method (d) is conventional inert organic solvents.Comprise that particularly aliphatic, alicyclic or aromatics is chosen the hydro carbons of halo wantonly, for example, gasoline, benzene, toluene, dimethylbenzene, chlorobenzene, dichloro-benzenes, benzinum, hexane, cyclohexane, carrene, chloroform, carbon tetrachloride; Ethers, as ether, diisopropyl ether ， diox, oxolane or glycol dimethyl ether or ethylene glycol diethyl ether; Ketone, as acetone, butanone or methyl iso-butyl ketone (MIBK); Nitrile, as acetonitrile, propionitrile or benzonitrile; Amide-type, as N, dinethylformamide, N,N-dimethylacetamide, N-methyl-formanilide, N-Methyl pyrrolidone or HMPA; The ester class is as methyl acetate or ethyl acetate; The sulfoxide class is as dimethyl sulfoxide (DMSO).
Implement method (a) and (b) of the present invention, (c) and (d) time, reaction temperature can change in wide range.Usually, these methods can be carried out between-20 ℃ to+200 ℃, preferably the temperature between 0 ℃ and 150 ℃.
When implementing the inventive method (a), every mole formula (II) carboxylic acid derivates adopts 1 to 5 mole usually, preferred 1.0 to 2.5 moles azanol or hydroxylamine hydrochloride and common 1 to 10 mole, and preferred 1.0 to 5.0ml formula (III) two replaces alkane.
When implementing the inventive method (b), every mole formula (IV) hydroxy aryl compound adopts 0.5 to 2.0 mole usually, preferred 0.9 to 1.2 mole formula (V) compound.
When implementing the inventive method (c), every mole formula (VI) halogenated compound adopts 1 to 5 mole usually, preferred 1.5 to 3 moles formula (VII) compound.
When implementing the inventive method (d), every mole formula (VIII) hydroxy alkoxy base acid amides adopts 1 to 5 mole usually, preferred 1.5 to 4 moles dehydrating agent.
In all cases, by known method react, processing and reaction product isolated (referring to preparation embodiment).
Reactive compound of the present invention has strong microbiocidal activity and can actually be used for preventing and treating harmful microorganism.Reactive compound is suitable as plant protection product, particularly as fungicide.
Fungicide in the plant protection is applicable to control Plasmodiophoromycetes (Plasmodiophoromycetes); oomycetes subclass (Domycetes); Chytridiomycetes (Chytridiomycetes); Zygomycetes (Zygomycetes); Ascomycetes (Ascomycetes), Basidiomycetes (Basidiomycetes) and Fungi Imperfecti (Deuteromycetes).
Having that the pathogenic organisms body of above-mentioned some fungal disease of listing can be mentioned is for example following, but never is limited to this: pythium, as sweet potato white rot germ; Phytophthora is as the potato phytophthora; False Peronospora is as Pseudoperonospora humuli or downy mildew of cucurbits bacterium; Plasmopara is as the downy mildew of garpe bacterium; Peronospora is as Peronospora pisi or rape frost bacterium; Erysiphe is as the powdery mildew of wheat and barley bacterium; Sphaerotheca is as powdery mildew of cucumber spherical shell bacterium; Podosphaera is as the apple mildew bacterium; Venturia is as apple black star bacteria; Caryosphere shell Pseudomonas is as barley reticulate pattern germ or stripe disease of barley (conidial form: Drechslera, sexual propagation: Helminthosporium); Cochliobolus belongs to, as standing grain cochliobolus (conidial form: Drechslera, sexual propagation: Helminthosporium); The monospore rust belongs to, as Kidney bean monospore rest fungus; The handle rust belongs to, as the wheat leaf rust bacterium; Tilletia is as wheat net bunt bacterium; Ustilago is as naked bloom bacterium or black loose smut of oat bacterium; The film lead fungi belongs to, as Rhizoctonia solani Kuhn; Magnaporthe grisea belongs to, as piricularia oryzae; Fusarium is as yellow Fusarium; Botrytis is as grayish green botrytis; Septoria is as wheat class grain husk spot blight septoria musiva bacterium; Leptosphaeria is as Leptosphaeria nodorum; Cercospora is as Cercospora canescens; Alternaria belongs to, as black spot of cabbage Alternariaspp and false little cercospora, as Pseudocercosporella herpotrichoides.
Plant makes its acrial part that can handle plant, vegetative propagation rhizome and seed and soil to the good drug-resistant of this reactive compound of the desired concn of controlling plant diseases.
In this article, reactive compound of the present invention can be used for successfully preventing and treating the disease of fruit tree and crop especially, for example prevents and treats the Phytophthora germ, or control wheat class disease, as caryosphere shell Pseudomonas germ.
In addition, reactive compound of the present invention has the activity of the good following disease of control: for example powdery mildew of wheat and barley bacterium, standing grain cochliobolus, ball cavity bacteria (Leptosphaeria nodorum), Fusarium germ on false little tail spore bacterium (Pseudocercosporella herpotrichoides) and the cereal class, prevent and treat piricularia oryzae and Rhizoctonia solani Kuhn, and have the external activity of wide spectrum.
According to its concrete physics and/or chemical property, reactive compound can change into regular dosage form, as solution, and emulsion, suspending agent, pulvis, foaming agent, paste, granule, aerosol is used for polymer and the trickle capsule of application composition and the ULV cold-peace thermal fog of seed.
These type agent can be produced in known manner, for example, reactive compound and filler (being liquid flux, the liquid gas under the pressure) are mixed, and/or mix, and the optional surfactant (being emulsifier and/or dispersant and/or foaming agent) that uses with solid carrier.Use water as under the situation of filler, organic solvent also can be used as cosolvent.As liquid flux, suitable mainly contains: aromatic compounds, and as dimethylbenzene, toluene or Fluhyzon, chloro aromatic compounds or chlorinated aliphatic hydrocarbon, as the chlorobenzene class, polyvinyl chloride-base or carrene, aliphatic hydrocarbon, as cyclohexane or paraffin, mineral oil fraction for example, alcohols, as butanols or ethylene glycol with and ether and ester, ketone, as acetone, MEK, methyl isopropyl Ketone or cyclohexanone, intensive polar solvent, as dimethyl formamide or dimethyl sulfoxide (DMSO), and water; Liquefied gas filler or carrier are meant under environmental temperature and the atmospheric pressure it is the liquid of gas, aerosol propellant for example, and as halogenated hydrocarbons and butane, propane, nitrogen and carbonic acid gas; What solid carrier was fit to has: clay, and talcum, chalk, quartz, Attagel, montmorillonite or diatomite and the synthetic mineral matter that grinds, as high dispersive silica, alumina and silicate; Be used for suitable the having of solid carrier of granule: for example crushing and broken natural mineral matter such as calcite, marble, float stone, sepiolite and dolomite, and the synthetic particle of organic and inorganic powder and following organic particle: wood sawdust, coconut husk, corncob and tobacco stem; What emulsifier and/or foaming agent were fit to has: for example nonionic and anion emulsifier, and as polyoxyethylene fatty acid ester, polyoxyethylene aliphatic alcohol ether, for example, alkaryl polyglycol ether, alkylsulfonate, alkyl sulfate, arylsulphonate and albumin hydrolysate; What dispersant was fit to has: for example, and lignin sulfite waste liquor and methylcellulose.
Can use the carboxymethyl cellulose and the natural and synthetic polymer of adhesive such as powdery, particle or latex form in the preparation, as gum Arabic, polyvinyl alcohol and polyvinyl acetate, and natural phospholipid, as cephalin and lecithin, and synthetic phospholipid.Other adhesive can be mineral oil and vegetable oil.
Also may use dyestuff, as inorganic pigment, iron oxide for example, titanium oxide and Prussian blue, and organic dyestuff, as alizarin dyes, azo dyes and metal phthalocyanine dyestuff and micronutrient such as iron, manganese, boron, copper, cobalt, molybdenum and zinc salt.
Usually the reactive compound that contains weight ratio 0.1 to 95% in the preparation, preferred 0.5 to 90%.
Reactive compound of the present invention can itself or with its dosage form, use with the form of the mixture of known fungicide, bactericide, miticide, nematocide or insecticide, enlarging action spectrum, or for preventing the progressively foundation of resistance.In many cases, can obtain synergistic effect, in other words, the activity of mixture exceeds the activity of single component.
Particularly advantageous component is a following compounds for example in the mixture: fungicide:
The 2-butylamine, 2-phenylamino-4-methyl-6-cyclopropyl-pyrimidine; 2 ', 6 '-two bromo-2-methyl-4 '-trifluoromethoxy-4 '-Trifluoromethyl-1,3-thiazole-5-formailide; 2,6-two chloro-N-(4-trifluoromethyl benzyl) benzamide; (E)-2-methoxyimino-N-methyl-2-(2-phenoxy phenyl) acetamide; Oxine sulphate; (E)-and and 2-{2-[6-(2-cyano group-phenoxy group) pyrimidine-4-oxygen base] phenyl }-the 3-methoxy-methyl acrylate; (E)-and methoxyimino [α-(oxy-o-cresyl)-o-tolyl] methyl acetate; 2-phenylphenol (OPP), Aldimorph, Ampropylfos, anilazine; Penta ring azoles, the spirit of withering of M 9834, iodine, benomyl; Binapacryl, biphenyl, Bitertanol, blasticidin-S; Bromuconazole, bupirimate, fourth Saite, lime sulfur; Difoltan, captan, carbendazim, carboxin; Chinomethionate, chloroneb, chloropicrin, Bravo; Chlozolinate, cufraneb, white urea cyanogen, cyproconazole; Cyprofuram, mildew-resistant phenol, diclobutrazol, Euparen; Diclomezine, botran, the mould prestige of second, Difenoconazole; The phonetic alcohol of first, dimethomorph, alkene azoles alcohol, clear mite is general; Diphenylamines, dipyrithion, Plondrel, Delan; Dodine, drazoxolon, the gram bacterium looses epoxy azoles (epoxyconazole); Pyrimethamine, kobam, two chlorobenzene pyrimidines, benzene cyanogen azoles; The spirit of withering of one first furan is planted the clothing ester, fenpiclonil, fenpropidin; Butadiene morpholine, triphenyltin acetate, triphen hydroxyl tin, fervam; Ferimzone, fluazinam, Fludioxonil; Fluoromide, fluquinconazole, fluorine azoles; Flusulfamide, flutolanil, Flutriafol; Folpet, aliette, Rabcide; Furidazol, furalaxyl, seed dressing amine; The biguanides suffering, hexachloro-benzene, own azoles alcohol; First Qiang isoxazole, imazalil, acid amides azoles; Biguanide spicy acid salt, IBP, iprodione; Isoprothiolane, kasugarnycin, copper agent such as Kocide SD; Copper naphthenate, basic copper chloride, copper sulphate; Cupric oxide, quinolinone and Bordeaux mixture, two for mixture; Mancozeb, maneb, mepanipyrim; Mebenil, metalaxyl, mefconazole; Methasulfocarb, load bacterium amine, Carbatene; Metsulfovax, nitrile bacterium azoles, Sankel; Nitrothal-isopropyl, nuarimol, fenfuram; Dislike acid amides, oxamocarb, oxycarboxin; Perfurazoat, penconazole, Pencycuron; Pimaricin, piperidines is peaceful, Polyoxin; Allyl isothiazole, prochloraz, SP 751011; Propamocarb, propiconazole, propineb; Ppyrazophos, pyrifenox, pyrimethanil; Pyroquilon, pentachloronitrobenzene, sulphur and sulphur preparation; Tebuconazole, phthalein cumfrey, tecnazene; Fluorine ether azoles, probenazole, thicyofen; Thiophanate methyl, thiram, methyl stands withered spirit; Tolyfluanid, triazolone, Triadimenol; Azoles bacterium piperazine, poplar bacterium amine, tricyclazole; Cyclomorpholine, fluorine bacterium azoles, triforine; Triticonazole, zineb, ziram. Bactericide:
Mix gossypol, mildew-resistant phenol, N-Serve, Sankel, kasugarnycin, octhilinone, furancarboxylic acid, terramycin, allyl isothiazole, streptomycin, phthalein cumfrey, copper sulphate and other copper agent.Insecticide/miticide/nematocide:
Olivomitecidin, orthene, fluorine ester chrysanthemum ester, alanycarb, Aldicarb, nail body cypermethrin, Amitraz, Olivomitecidin (avermectin), AZ60541, azadirachtin, triazotion, gusathion m, azacyclotin, bacillus thuringiensis, 4-bromo-2-(4-chlorphenyl)-1-(ethoxymethyl)-5-(trifluoromethyl)-1H-pyrazoles-3-formonitrile HCN Ben Evil prestige, Benfuracard micro, desinsection mite, second body cyfloxylate, bifenthrin, Osbac, bromo-ether chrysanthemum ester (brofenprox), bromophos mixes penta prestige, Buprofezin, butocarboxim, butyl pyridaben, cadusafos, sevin, carbofuran, trithion, carbosulfan, Padan, cloethocarb, chlorethoxyfos, chlorfenviphos, UC 62644, chlormephos, N-[(6-chloro-3-pyridine radicals)-methyl]-N '-cyano group-N-methyl-second imino group acid amides, chlopyrifos, chlorpyrifos-methyl, cis resmethrin, Cyhalothrin, four mite piperazines, cynock, cycloprothrin, cyfloxylate, cyhalothrin, plictran, cypermethrin, fly eradication amine, decis, demeton-methyl, different one zero five nine II, different suction phosphorus II, methamidophos, diazinon, chloro line phosphorus, dichlorvos, dicliphos, Carbicron, ethion, diflubenzuron, Rogor, dimethylvinphos ， delnav, disulfoton, Hinosan, emamectin, esfenvalerate removes the aphid prestige, ethion, ether chrysanthemum ester, ethoprop, ether chrysanthemum ester, etrimfos, Nemacur, fenazaquin, mite is finished tin, sumithion, fenobucarb, fenothiocarb, ABG-6215, fenpropathrin, fenpyrad, azoles mite ester, fenthion, sumicidin, fipronil, fluazinam, fluazuron, flucycloxuron, flucythrinate, flufenoxuron, fluorine ether chrysanthemum ester (flufenprox), taufluvalinate, Fonofos, peace fruit, colophonate, fubfenprox, furathiocarb, hexachlorcyclohexane, heptenophos, fluorine bell urea, Hexythiazox, imidacloprid, iprobenfos, isazofos, isofenphos, Mobucin ， oxazole phosphorus, ivermectin is gone into-Cyhalothrin lufenuron, the malathion, menazon, Menite, the fenthion sulfoxide, Halizan, methacrifos, acephatemet, first thiophene sulphur phosphorus, methiocarb, Methomyl, metolcarb, Mil's times rhzomorph, nuvacron, moxidectin, 2-dichloroethylk dimethyl phosphate, NC184, nitenpyram, omethoate, grass oxime prestige, sulfone is inhaled sulphur phosphorus, oxydeprofos, the malathion, methyl malathion, permethrin, phenthoate dimephenthoate cidial, thimet, Phosalone, phosmet, phosphamidon, phoxim, Aphox, methylpyrimidine sulphur phosphorus, pirimiphos-ethyl, Profenofos, Fac, pymefrozin, pyrachlophos, pyraclofos, pyridaphenthione, pyresmethrin, Dalmatian chrysanthemum, pyridaben, pyrimidifen, pyriproxyfen, quinalphos, salithion, cadusafos, silafluofen, sulfotep, first Toyodan, tebufenozide, tebufenpyrad, special fourth pirimiphos-ethyl, Teflubenzuron, tefluthrin, Swebate, terbam, special fourth thimet, Ravap, thiafenox, UC-51762, hexanone oxime prestige, thiometon, quinoline line phosphorus, thuricin, tralomethrin, triarathen, Hostathion, triazuron, chlorophos, desinsection is grand, trimethacarb, the intact sulphur phosphorus that goes out, Cosban, dimethylbenzene prestige, YI 5301/5302, zetamethrin.
Also can with other known activity compound such as weed killer herbicide or with the mixing of chemical fertilizer and growth regulator.
Reactive compound can use with the type of service of its preparation or its preparation, and described preparation type of service is as can directly using solution, suspending agent, " Spritz " (wettable) pulvis, paste, soluble powder, pulvis and granule.They use with conventional method, for example pour, and spraying, atomizing spreads fertilizer over the fields, and dusts, and bubbles brushing or the like.Available in addition ultra low volume method is used compound, or active agent preparations or reactive compound itself are injected soil.Also can handle the seed of plant.
When handling plant part, the activity compound concentration in the type of service can change on a large scale;
Usually, between weight ratio 1 and 0.0001%, preferably in weight ratio 0.5 and 0.001% use.
Handle kind of a period of the day from 11 p.m. to 1 a.m, per kilogram seed demand 0.001 is to 50g usually, the reactive compound of preferred 0.01 to 10g amount.
When handling soil, needing the concentration of reactive compound at application point is weight ratio 0.00001 to 0.1%, preferred weight ratio 0.0001 to 0.02%.
Preparation EXAMPLE Example 1
Under 20 ℃, 1.8g (25mmol) hydroxylamine salt acidulants is imported in the 20ml methyl alcohol, and slowly add the 20ml methanol solution of 3.3g potassium hydroxide (86%).Add 4.0g (12.8mmol) α-methoxyimino-α-[2-(2-methyl-phenoxy group-methyl)-phenyl]-methyl acetate subsequently in batches, then reactant mixture is stirred down at 40 ℃, finish (thin layer chromatography) until reaction.At first, then 10.8g (59mmol) glycol dibromide is added this reactant mixture with 1.7g (12.8mmol) potash.This mixture was stirred 12 hours down at 65 ℃, be cooled to 20 ℃ subsequently, and filter.Filtrate concentrates under pump vacuum, and with residue through silica gel chromatography (toluene/acetone, 9: 1 volume ratios).
Obtain 1.4g (theoretical value 33%) 3-{ α-methoxyimino-α-[2-(2-methyl-phenoxy group-methyl)-phenyl]-methyl }-5,6-dihydro-1,4,2-dioxazine.
Refraction index: n D 20=1.5705.
Can similar embodiment 1 and list in down according to other example of formula (I) compound of preparation method's of the present invention general description preparation and to tabulate in 1.
Figure A9811913100351
(1) with being marked on CDCl in the tetramethylsilane work 3Middle record 1The H-NMR spectrum, the data that provide are normally made the δ value with chemical shift.Shifts as δ values table 1: the embodiment of formula (I) compound
Figure A9811913100352
Figure A9811913100361
Figure A9811913100371
Figure A9811913100381
Figure A9811913100421
Figure A9811913100431
Figure A9811913100451
Figure A9811913100461
Figure A9811913100481
Figure A9811913100501
Figure A9811913100511
Figure A9811913100521
Figure A9811913100531
Figure A9811913100541
Figure A9811913100551
Figure A9811913100561
Figure A9811913100571
Figure A9811913100581
Figure A9811913100591
Figure A9811913100601
Figure A9811913100611
Figure A9811913100631
Figure A9811913100651
Figure A9811913100691
Figure A9811913100701
Figure A9811913100711
Figure A9811913100721
Figure A9811913100731
Figure A9811913100751
Figure A9811913100771
Figure A9811913100781
Figure A9811913100791
Figure A9811913100801
Figure A9811913100811
Figure A9811913100831
Figure A9811913100841
Figure A9811913100871
Figure A9811913100881
Figure A9811913100901
Figure A9811913100921
Figure A9811913100941
Figure A9811913100951
The compound that provides with embodiment 60 in the table 1 can for example be prepared as follows:
Figure A9811913100971
The oil white oil suspension of 60% concentration of 0.3g (6mmol) sodium hydride is added to 1.5g (6mmol) 3-[α-methoxyimino-α-(2-hydroxyl-phenyl) methyl under ice bath]-5,6-dihydro-1,4,2-dioxazine, 0.9g (6mmol) 4,6-two chloro-pyrimidines and 30ml N are in the mixture of dinethylformamide.After removing ice bath, reactant mixture was stirred 15 hours at 20 ℃.Concentrate under the oil pump vacuum then, residue is handled with ethyl acetate, washes with water, uses dried over sodium sulfate, and filters.Pump vacuum is distillation down, carefully solvent is removed from filtrate.
Obtain 1.9g (theoretical value 86%) 3-{ α-methoxyimino-α-[2-(6-chloro-pyrimidine-4-oxygen base)-phenyl]-methyl }-5,6-dihydro-1,4, the 2-dioxazine is the oily residue.
The compound that provides with embodiment 61 in the table 1 can for example be prepared as follows:
Figure A9811913100981
With 0.3g (0.9mmol) 3-{ α-methoxyimino-α-[2-(6-chloro-pyrimidine-4-oxygen base)-phenyl]-methyl }-5,6-dihydro-1,4,2-dioxazine, 0.1g (0.9mmol) 2-hydroxy benzonitrile, 0.1g (0.9mmol) potash, one little spoonful of copper chloride (I) and 5ml N, the mixture of N-dimethyl-formamide stirred 15 hours at 100 ℃, concentrated under the oil pump vacuum then, residue is handled with ethyl acetate, wash with water, use dried over sodium sulfate, and filter.Filtrate is concentrated residue silica gel chromatography (adopting hexane/acetone, 7: 3 volume ratios).
Obtain 0.3g (theoretical value 81%) 3-{ α-methoxyimino-α-[2-(6-(2-cyano group-phenoxy group)-pyrimidine-4-oxygen base)-phenyl]-methyl }-5,6-dihydro-1,4,2-dioxazine, 82 ℃ of fusing points.
The compound that provides with embodiment 58 in the table 1 can for example be prepared as follows:
Figure A9811913100991
With 0.5g (2mmol) 3-[α-methoxyimino-α-(2-hydroxyl-phenyl)-methyl]-5,6-dihydro-1,4, the mixture of 2-dioxazine, 0.3g (2.2mmol) 2-methyl-benzyl chloride, 0.4g (2.5mmol) potash and 10ml acetonitrile refluxed 15 hours, concentrate then, residue is handled with carrene, washes with water, use dried over sodium sulfate, and filter.Under pump vacuum, distill, carefully solvent is removed from filtrate.
Obtain 0.4g (theoretical value 59%) 3-{ α-methoxyimino-α-[2-(2-methyl-benzyloxy)-phenyl]-methyl }-5,6-dihydro-1,4,2-dioxazine, 142 ℃ of fusing points.
In addition, the compound according to embodiment 1 can obtain can for example be prepared as follows:
Figure A9811913100992
With 0.75g (2.4mmol) 3-[α-methoxyimino-α-(2-bromomethyl-phenyl)-methyl]-5,6-dihydro-1,4,2-dioxazine and 0.70g (6.4mmol) 2-methyl-phenol is dissolved in the 15ml dimethyl formamide, and after this mixture is cooled to-10 ℃, slowly add 0.21g (7.0mmol) sodium hydride (80% concentration).After removing cryostat, reactant mixture was stirred 14 hours not being higher than under 25 ℃ the temperature, pour into subsequently in the long-pending water of general dliploid.After rocking with ethyl acetate, isolate organic facies,, use dried over sodium sulfate with the washing of 2N sodium hydroxide solution, and filtration.Under reduced pressure distillation is carefully removed solution from filtrate.
Obtain 0.40g (theoretical value 49%) 3-{ α-methoxyimino-α-[2-(2-methyl-phenoxy group-methyl)-phenyl]-methyl }-5,6-dihydro-1,4,2-dioxazine (refraction index: n D 20=1.5705).
The compound that provides with embodiment 19 in the table 1 can for example be prepared as follows:
Figure A9811913101001
0.20g (0.56mmol) N-(2-hydroxyl-ethyoxyl)-α-methoxyimino-α-[2-(2,4-dimethyl-phenoxy group-methyl)-phenyl]-acetamide is dissolved in the 3ml chloroform, and adds 0.25g (1.76mmol) phosphorous oxide (V) down at 0 ℃.This reactant mixture was stirred 1 hour at 20 ℃, reflux then and stirred 4 hours down, pour into subsequently in the long-pending water of general dliploid, and rock.After organic facies was isolated, water extracted three times with chloroform again.Merge organic extract liquid, use dried over mgso, concentrated then, and with column chromatography purifying (silica gel; Toluene/acetone, 10: 1).
Obtain 84mg (theoretical value 42%) 3-{ α-methoxyimino-α-[2-(2,4-dimethyl-phenoxy group-methyl)-phenyl]-methyl }-5,6-dihydro-1,4,2-dioxazine.
1H?NMR(D 6-DMSO,δ):4.87,3.84,4.38,4.10ppm。The raw material embodiment of formula (IV) (IV-1)
Figure A9811913101011
With 9.0g (28mmol) 3-[α-methoxyimino-α-(2-oxinane-2-oxygen base)-benzyl]-5,6-dihydro-1,4, the 90ml methanol solution of 2-dioxazine and 1.8g ion-exchanger " Lewatit SPC 108 " stirred 15 hours down at 20 ℃, then this mixture is concentrated under pump vacuum, residue is handled with carrene, and filters.Filtrate concentrates under pump vacuum, residue silica gel chromatography (adopting hexane/acetone, 7: 3 volume ratios).
First fraction that obtains is 0.6g (theoretical value 9%) Z-{3-[α-methoxyimino-α-(2-hydroxyl-phenyl)-methyl]-5,6-dihydro-1,4,2-dioxazine }, be amorphous products; Second fraction is 3.3g (theoretical value 50%) E-{3-[α-methoxyimino-α-(2-hydroxyl-phenyl)-methyl]-5,6-dihydro-1,4,2-dioxazine }, 153 ℃ of fusing points.The raw material embodiment of formula (IX) (IX-1)
Figure A9811913101021
The potassium hydroxide aqueous solution and 17g (58mmol) α-methoxyimino-α-(2-oxinane-2-oxygen base-phenyl)-methyl acetate of 13.9g (211mmol) 85% concentration are added in the 290ml methanol solution of 6.8g (98mmol) hydroxylamine salt acidulants, and this mixture was stirred one hour down at 40 ℃.Add 7.7g (56mmol) potash, and be added dropwise to 42.5g (226mmol) glycol dibromide.Then mixture was refluxed 15 hours, under pump vacuum, concentrate subsequently.Residue is handled with carrene, washes with water, uses dried over sodium sulfate, and filters.Filtrate is concentrated, and with residue through silica gel chromatography (adopting hexane/acetone, 7: 3 volume ratios).
Obtain 9.0g (theoretical value 49%) 3-[α-methoxyimino-α-(2-oxinane-2-oxygen base)-benzyl]-5,6-dihydro-1,4, the 2-dioxazine is the oily product.The raw material embodiment of formula (X) (X-1)
Figure A9811913101031
203g (1.81mol) potassium tert-butoxide is imported in 2 liters of tert-butyl alcohols, and to the 500ml t-butanol solution that wherein adds 564g (4.93mol) uncle's butyronitrile and 411g (1.64mol) 2-tetrahydro-pyran oxy-phenylacetic acid methyl esters.After 90 minutes, 350g (2.47mol) methyl iodide is added dropwise to, and mixture was stirred 15 hours at 20 ℃.Under pump vacuum, concentrate then, and residue is handled with methyl tertiary butyl ether(MTBE), use dried over sodium sulfate, and filter.Residue produces crystallization with ether digestion, and this product is emanated through suction filtration.
Obtain 69.3g (theoretical value 15%) α-methoxyimino-α-(2-oxinane)-2-oxygen base-phenyl)-methyl acetate, 79 ℃ of fusing points.The raw material embodiment of formula (XI) (XI-1)
Figure A9811913101032
With 500g (3.0mol) 2-hydroxyl-phenyl-acetic acid methyl esters 506g (6.0mol) 3, the 4-dihydropyran, one little spoonful of p-methyl benzenesulfonic acid and 2.5 liters of oxolanes stirred 15 hours at 20 ℃, stirred with 10% ice-cold concentration potassium hydroxide aqueous solution then, add sodium sulphate, and mixture is filtered.Under pump vacuum, distill, carefully solvent is removed from filtrate.
Obtain 698g (theoretical value 99%) 2-tetrahydro-pyran oxy-phenyl-acetic acid methyl esters, be the oily residue.The raw material embodiment of formula (VI) (VI-1)
With 0.50g (2.13mmol) 3-[α-methoxyimino-α-(2-methyl-phenyl)-methyl]-5,6-dihydro-1,4,2-dioxazine and 0.57g (3.2mmol) N-bromo-succinimide imports the 10ml carbon tetrachloride, and add after the 200mg azo isobutyronitrile, mixture was refluxed 4 hours.After adding 0.57g (3.2mmol) N-bromo-succinimide again, mixture was refluxed one hour again.Cool off subsequently and filter, filtrate is concentrated, and residue is carried out chromatogram (silica gel; Toluene/acetone, 10: 1) handle.
Obtain 20mg (theoretical value 30%) 3-[α-methoxyimino-α-(2-bromo-methyl-phenyl)-methyl]-5,6-dihydro-1,4,2-dioxazine. 1H?NMR(CDCl 3,δ):4.4ppm。The raw material embodiment (X III-1) of formula (X III)
Figure A9811913101051
19.6g (0.283mol) hydroxylamine salt acidulants is imported 150ml methyl alcohol, and slowly add the 150ml methanol solution of 36.9g (0.565mol) potassium hydroxide (86% concentration).Add 30g (0.145mol) α-methoxyimino-α-(2-methyl-phenyl)-methyl acetate then in batches.Under 50 ℃, mixture was stirred 3 hours.Add 20g (0.145mol) potash and 122g (0.65mol) glycol dibromide at 20 ℃ subsequently, and this mixture was stirred 17 hours down at 65 ℃.After the mixture cooling, filter with suction, filtrate is concentrated, and residue is carried out chromatogram (silica gel; Toluene/acetone, 15: 1) handle.
Obtain 15.2g (theoretical value 45%) 3-[α-methoxyimino-α-(2-methyl-phenyl)-methyl]-5,6-dihydro-1,4,2-dioxazine. 1H?NMR(CDCl 3,δ):2.2ppm。The raw material embodiment (X IV-1) of formula (X IV)
Figure A9811913101052
187.5g (1.673mol) potassium tert-butoxide is dissolved in the 1875ml tert-butyl alcohol.The 500ml t-butanol solution of 471.5g (4.57mol) nitrite tert-butyl and 250g (1.525mol) 2-methyl-phenyl-acetic acid methyl esters is metered into, medium temperature is not risen to be higher than 50 ℃.Mixture was stirred 90 minutes, rise to 30 ℃ from 20 ℃.Be added dropwise to 326.5g (2.3mol) methyl iodide then, and reactant mixture was stirred 14 hours at 20 ℃.Solution is removed in distillation under pump vacuum subsequently, and residue is handled with 2 premium on currency, and with mixture ethyl acetate extraction three times.Merge organic facies, use dried over sodium sulfate, and filter.Filtrate is concentrated, and residue is handled with the 250ml isopropyl alcohol, and adds entry under refluxing, until the mixture feculence.
With mixture be cooled to 0 ℃ and stirred 60 minutes after, with the crystalline product isolated by filtration under suction that obtains.
Obtain 84.5g (theoretical value 27%) α-methoxyimino-α-(2-methyl-phenyl)-methyl acetate, 53 ℃ of fusing points. 1H?NMR(CDCl 3,δ):2.19ppm。The raw material embodiment of formula (VIII) (VIII-1)
Figure A9811913101061
0.8g (2.36mmol) α-methoxyimino-α-[2-(2,4-dimethyl-phenoxy group-methyl)-phenyl]-chloroacetic chloride is dissolved in the 10ml oxolane, and adds 0.26g (2.6mmol) triethylamine.0.25g (2.6mmol) O-(2-the ethoxy)-azanol that will be dissolved in the 10ml oxolane then is added dropwise under 0 ℃.Reactant mixture was stirred 2 hours at 20 ℃, pour in the water then, and use ethyl acetate extraction.The extraction solution dried over mgso concentrates the circumstances in which people get things ready for a trip spectrum (silica gel of going forward side by side; Toluene/acetone, 10: 1) handle.
Obtain 0.4g (theoretical value 50%) N-(2-hydroxyl-ethyoxyl)-α-methoxyimino-α-[2-(2,4-dimethyl-phenoxy group-methyl)-phenyl]-acetamide. 1H?NMR(CDCl 3,δ):3.65；3.90；9.15ppm。The raw material embodiment (X V-1) of formula (X V)
0.93g (2.95mmol) α-methoxyimino-α-[2-(2,4-dimethyl-phenoxy group-methyl)-phenyl]-acetate is mixed with 4.0g (2.9mmol) thionyl chloride and 50mg dimethyl formamide, and mixture was stirred 30 minutes under refluxing.Distillation under reduced pressure, carefully the component that will more volatilize is removed.
Obtain that 0.95g α-methoxyimino-α-[2-(2,4-dimethyl-phenoxy group-methyl)-phenyl-chloroacetic chloride is the oily residue.Embodiment (X V-2)
2.0g (6.1mmol) α-methoxyimino-α-[2-(2,4-dimethyl-phenoxy group-methyl)-phenyl]-methyl acetate is dissolved in the 20ml isopropyl alcohol, and adds 30ml 1N sodium hydroxide solution.Mixture was stirred 14 hours at 40 ℃, pour in the water then.With 2N hydrochloric acid its pH is transferred to 6, and the crystalline product that obtains is emanated by suction filtration.
Obtain 1.5g (theoretical value 78%) α-methoxyimino-α-[2-(2,4-dimethyl-phenoxy group-methyl)-phenyl]-acetate.
1H?NMR(CDCl 3,δ):3.9；4.85ppm。Purposes EXAMPLE Example A net blotch of barley (Pyrenophora teres) protectiveness control test solvent: the N-Methyl pyrrolidone emulsifier of 10 parts of weight: the alkaryl polyglycol ether of 0.6 part of replacement
During the appropriate formulation of preparation reactive compound,, and this missible oil is diluted with water to desired concn with the reactive compound of 1 part of weight and the solvent and the emulsifier of described amount.
Be test protectiveness activity, be sprayed onto as the dew shoot moistening with active agent preparations.After the hydrojet layer becomes dry, plant is inoculated with net blotch of barley bacterium conidial suspension.Allow plant stay in the incubator of 20 ℃ and 100 relative moisture 48 hours.
Plant is placed in the greenhouse of general 20 ℃ and relative air humidity general 80% of temperature.
Inoculating post-evaluation in 7 days should test.
In this test, for example, the compound of preparation embodiment 1 demonstrates 100% control efficiency level when the amount of application of 400g/ha..The interior absorption control of Embodiment B potato late blight (Phytophthora) test solvent: the acetone emulsifier of 4.7 parts of weight: the alkaryl polyglycol ether of 0.3 part of weight
During the appropriate formulation of preparation reactive compound,, and this missible oil is diluted with water to desired concn with the reactive compound of 1 part of weight and the solvent and the emulsifier of described amount.
Be absorption energy in testing, active agent preparations poured into contained in the standard soil of preparing as the shoot of testing.Handle after 3 days, with the spore fluid suspension inoculation of phytophthora infestans.
Plant is stayed in the incubator of general 20 ℃ and 100% relative air humidity.
Inoculate after 3 days, estimate this test.
In this test, the compound that for example prepares embodiment 1 demonstrates 58% control efficiency level when activity compound concentration 100ppm.The interior absorption control of Embodiment C rice blast (Pyricularia) test solvent: the acetone emulsifier of 12.5 parts of weight: the alkaryl polyglycol ether of 0.3 part of weight
During the appropriate formulation of preparation reactive compound,, and the emulsifier of this concentrate water and described amount is diluted to desired concn with the reactive compound of 1 part of weight and the solvent of described amount.
For absorption energy in testing, the 40ml active agent preparations is poured in the standard soil of the rice seedlings of growing, handles after 7 days, the spore fluid suspension inoculation rice strain of usefulness Pyricularia oryzae, and it is stayed in 25 ℃ of greenhouses with relative air themperature 100%, until evaluation.
Inoculate 4 days post-evaluation incidences of disease.
In this test, for example, the compound of preparation embodiment 1 demonstrates 80% control efficiency level when the amount of application of 100mg/100ml.

Claims (1)

1. method for preparing Fungicidal composition is characterized in that the azepine dioxane alkene of formula (I) is mixed with filler and/or surfactant:
Figure A9811913100021
Wherein alkane two bases that replace are chosen in the A representative wantonly, optional separately arlydene or the inferior heteroaryl that replaces of Ar; The E representative is with R on 2 1The 1-alkene-1 of base, 1-two bases, or on 2, be with
R 22-azepine-1-the alkene-1 of base, 1-two bases, or on 1, be with R 1Base
3-oxa-or 3-thia-1-propylene-2,3-two bases, or the representative at 3
Last band R is basic and be with R on 1 13-azepine-1-the propylene-2 of base, 3-two
Base, or representative is with R on 1 21-azepine-1-the propylene-2 of base, 3-two
Base, or representative is with R on 1 2The 3-oxa-or the 3-thia-1-azepine of base
-propylene-2,3-two bases, or representative is being with the R base and is being with R on 1 on 3 2
1 of base, 3-diaza-1-propylene-2,3-two bases, or the optional replacement of representative
Imino group,
Wherein
R represents alkyl,
R 1Represent hydrogen, halogen, cyano group or optional separately alkyl, alkoxyl, the alkane sulphur that replaces
Base, alkylamino or dialkyl amido,
R 2Represent hydrogen, amino, cyano group or optional separately alkyl, alkoxyl, the alkane ammonia that replaces
Base or dialkyl amido; With
R 3Represent hydrogen, cyano group or optional separately alkyl, alkenyl, alkynyl, the cycloalkanes that replaces
Base or cycloalkyl-alkyl, G represent a singly-bound, oxygen or representative optional separately by halogen, hydroxyl, alkyl, halo
Alkane two bases, olefin 2 base, oxa-olefin 2 base, alkynes two bases that alkyl or cycloalkyl replaces,
Or represent one of following groups:
-Q-CQ-,-CQ-Q-,-CH 2-Q-,-Q-CH 2-,-CQ-Q-CH 2-,
-CH 2-Q-CQ-,-Q-CQ-CH 2-,-Q-CQ-Q-CH 2-,-N=N-,
-S(O) n-,-CH 2-S(O) n-,-CQ-,-S(O) n-CH 2-,
-C(R 4)=N-O-,-C(R 4)=N-O-CH 2-,-N(R 5)-,
-CQ-N(R 5)-,-N(R 5)-CQ-,-Q-CQ-N(R 5)-,
-N=C(R 4)-Q-CH 2-,-CH 2-O-N=C(R 4)-,-N(R 5)-CQ-Q-,
-CQ-N (R 5)-CQ-Q-,-N (R 5)-CQ-Q-CH 2-,-CQ-CH 2-or
-N=N-C(R 4)=N-O-,
Wherein
N represents 0,1 or 2 numeral;
Q represents oxygen or sulphur;
R 4Represent the optional separately alkyl that replaces of hydrogen, cyano group or representative, alkoxyl, alkylthio group,
Alkylamino, dialkyl amido or cycloalkyl and
R 5Represent the optional separately alkyl that replaces of hydrogen, hydroxyl, cyano group or representative, alkoxyl or
Cycloalkyl and Z representative are at alkyl, alkenyl, alkynyl, cycloalkyl, aryl or the heterocyclic radical of optional replacement separately.
CNB981191312A 1993-08-11 1994-07-29 Process for preparation of fungicidal compositions Expired - Lifetime CN100358877C (en)

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DEP4326908.7 1993-08-11
DEP4408005.0 1994-03-10

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US6268312B1 (en) 1994-04-01 2001-07-31 Shionogi & Co., Ltd. Oxime derivative and bactericide containing the same as active ingredient
WO1995026956A1 (en) 1994-04-01 1995-10-12 Shionogi & Co., Ltd. Oxime derivative and bactericide containing the same as active ingredient
TR199700790T1 (en) * 1995-02-13 1998-02-21 Bayer Aktiengesellschaft Substituted heterocycloalkenes.
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US7521473B2 (en) 2004-02-25 2009-04-21 Wyeth Inhibitors of protein tyrosine phosphatase 1B
US9193698B2 (en) 2013-07-08 2015-11-24 Advinus Therapeutics, Ltd. Process for preparing fluoxastrobin
BR112017025678B1 (en) * 2015-05-29 2021-12-28 Arysta Lifescience Corporation IMPROVED PROCESS FOR PREPARATION OF (E)-(5,6-DI-HYDRO1,4,2-DIOXAZINE-3-YL)(2-HYDROXYPHENYL) METHANONE O-METHYL OXIMA

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DE3789683T2 (en) * 1986-04-17 1994-08-25 Zeneca Ltd Fungicides.
JP3188286B2 (en) * 1991-08-20 2001-07-16 塩野義製薬株式会社 Phenylmethoxyimino compound and agricultural fungicide using the same

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CN101239955B (en) 2011-11-23
DE59407240D1 (en) 1998-12-10

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