Oxime ether compound and application thereof
阅读说明：本技术 一种肟醚类化合物及其用途 (Oxime ether compound and application thereof ) 是由 程学明 于海波 陈亮 吴鸿飞 孙庚� 郭春晓 徐利保 徐靖博 孙宁宁 于 2020-11-02 设计创作，主要内容包括：本发明公开了一种结构新颖的肟醚类化合物,结构如通式I所示,式中各取代基的定义见说明书。通式I化合物具有优异的杀菌活性,对植物细菌病害和真菌病害具有良好的防治效果,本发明包括通式I化合物在农业和其它领域中用作杀菌剂的用途。(The invention discloses an oxime ether compound with a novel structure, which has a structure shown as a general formula I, wherein the definition of each substituent group is shown in the specification.)
1. An oxime ether compound, which is characterized in that: the compound is shown as a general formula I:
in the formula:
x is selected from sulfur or oxygen;
z is selected from hydrogen, C unsubstituted or substituted by any of the following groups1-C6Linear or branched alkyl of (a): halogen, cyano, trifluoromethyl, trifluoromethoxy, hydroxy, nitro, amino;
a is selected from CN, (C ═ O) OR1、(C＝O)NHR2Or (C ═ O) NHNH2；
R1Is selected from C1-C8An alkyl group;
R2selected from hydrogen or C1-C8An alkyl group;
w is selected from hydrogen, acetonitrile, C1-C8Alkyl radical, C1-C8Haloalkyl, C3-C6Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C1-C8Alkoxy radical C1-C8Alkyl, C (═ O) R3、C(＝O)CH2R3、C(＝O)CH2OR3、NO2、OR4、S(O)2R5、N(R6)R7Or N ═ C (R)8)R9；
Q is selected from hydrogen, acetonitrile, C1-C8Alkyl radical, C1-C8Haloalkyl, C3-C6Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C1-C8Alkoxy radical C1-C8Alkyl or C (═ O) R3；
Or Q, N and the N-linked W form a 3-6 membered saturated or unsaturated ring containing 0-2N-R10O, S or oxidized S, and the ring may also be substituted by R11Substituted or fused with a benzene ring;
R3selected from hydrogen, C1-C8Alkyl radical, C1-C8Haloalkyl, C3-C6Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C1-C8Alkoxy radical C1-C8Alkyl, N (R)12)R13Optionally substituted aryl or optionally substituted heteroaryl;
R4selected from hydrogen, C1-C8Alkyl radical, C1-C8Haloalkyl or C3-C6A cycloalkyl group;
R5is selected from C1-C2Alkyl radical, C1-C2Haloalkyl, C3-C6Cycloalkyl radical, C1-C4Alkoxy radical, C1-C4Alkyl-substituted phenyl or N (R)12)R13；
R6Selected from hydrogen or C1-C8An alkyl group;
R7selected from hydrogen or C1-C8An alkyl group;
R8selected from hydrogen, C1-C8Alkyl radical, C1-C8Haloalkyl, phenyl which is unsubstituted or optionally substituted by hydrogen, halogen, cyano, nitro, C1-C4Alkyl or C1-C4A haloalkyl group;
R9is selected from C1-C8Alkyl radical, C1-C8Haloalkyl, phenyl which is unsubstituted or optionally substituted by hydrogen, halogen, cyano, nitro, C1-C4Alkyl or C1-C4A haloalkyl group;
R10is hydrogen, C1-C2Alkyl radical, C1-C2Haloalkyl, C1-C2Alkylcarbonyl or C1-C2An alkoxycarbonyl group;
R11is H, halogen, CN, NO2、C1-C2Alkyl radical, C1-C2Haloalkyl, C1-C4Alkoxy radical, C1-C2Haloalkoxy, optionally substituted aryl or S (O) nR14Wherein n is 0, 1 or 2;
R12is selected from C1-C8An alkyl group;
R13is selected from C1-C8An alkyl group;
R14is hydrogen, C1-C2Alkyl radical, C1-C2Haloalkyl, C3-C6Cycloalkyl or C1-C4An alkoxy group;
or a salt of a compound of formula I.
2. The compound of claim 1, wherein in formula I,
x is selected from sulfur or oxygen;
z is selected from hydrogen, unsubstitutedOr C substituted by any of the following groups1-C3Linear or branched alkyl of (a): halogen, cyano, trifluoromethyl, trifluoromethoxy, hydroxy, nitro, amino;
a is selected from CN, (C ═ O) OR1、(C＝O)NHR2Or (C ═ O) NHNH2；
R1Is selected from C1-C4An alkyl group;
R2selected from hydrogen or C1-C4An alkyl group;
w is selected from hydrogen, acetonitrile, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C4Alkenyl radical, C2-C4Haloalkenyl, C2-C4Alkynyl, C2-C4Halogenated alkynyl, C1-C4Alkoxy radical C1-C4Alkyl, C (═ O) R3、C(＝O)CH2R3、C(＝O)CH2OR3、NO2、OR4、S(O)2R5、N(R6)R7Or N ═ C (R)8)R9；
Q is selected from hydrogen, acetonitrile, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C4Alkenyl radical, C2-C4Haloalkenyl, C2-C4Alkynyl, C2-C4Halogenated alkynyl, C1-C4Alkoxy radical C1-C4Alkyl or C (═ O) R3；
Or Q, N and the N-linked W form a 3-6 membered saturated or unsaturated ring containing 0-2N-R10O, S or oxidized S, and the ring may also be substituted by R11Substituted or fused with a benzene ring;
R3selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C4Alkenyl radical, C2-C4Haloalkenyl, C2-C4Alkynyl, C2-C4Halogenated alkynyl, C1-C4Alkoxy radical C1-C4Alkyl, N (R)12)R13Or phenyl, pyridyl, pyrazolyl, thiazolyl, isothiazolyl or thiadiazolyl which are unsubstituted or optionally substituted by hydrogen, halogen, cyano, nitro, hydroxyl, mercapto, amino, aldehyde, C (═ O) NH2、C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C1-C3Alkoxy radical, C1-C3Haloalkoxy, C1-C3Alkylthio radical, C1-C3Haloalkylthio, C1-C3Alkylamino radical, C1-C3Dialkylamino radical, C3-C6Cycloalkylamino, C1-C3Alkoxycarbonyl group, C1-C3Alkylsulfonyl radical, C1-C3Alkylaminocarbonyl radical, C1-C3Alkylaminosulfonyl, phenyl or pyridyl, unsubstituted or optionally substituted by hydrogen, halogen, cyano, nitro, C1-C4Alkyl or C1-C4A haloalkyl group;
R4selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6A cycloalkyl group;
R5is selected from C1-C2Alkyl radical, C1-C2Haloalkyl, C3-C6Cycloalkyl radical, C1-C4Alkoxy radical, C1-C4Alkyl-substituted phenyl or N (R)12)R13；
R6Selected from hydrogen or C1-C4An alkyl group;
R7selected from hydrogen or C1-C4An alkyl group;
R8selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, phenyl which is unsubstituted or optionally substituted byWherein, the following groups are hydrogen, halogen, cyano and nitro;
R9is selected from C1-C4Alkyl radical, C1-C4Haloalkyl, phenyl unsubstituted or optionally substituted by hydrogen, halogen, cyano, nitro;
R10is hydrogen, C1-C2Alkyl radical, C1-C2Haloalkyl, C1-C2Alkylcarbonyl or C1-C2An alkoxycarbonyl group;
R11is H, halogen, CN, NO2、C1-C2Alkyl radical, C1-C2Haloalkyl, C1-C4Alkoxy radical, C1-C2Haloalkoxy, optionally substituted aryl or S (O) nR14Wherein n is 0, 1 or 2;
R12is selected from C1-C4An alkyl group;
R13is selected from C1-C4An alkyl group;
R14is hydrogen, C1-C2Alkyl radical, C1-C2Haloalkyl, C3-C6Cycloalkyl or C1-C4An alkoxy group;
or a salt of a compound of formula I.
3. The compound of claim 2, wherein in formula I,
x is selected from oxygen or sulfur;
z is selected from hydrogen, methyl or ethyl;
a is selected from CN, (C ═ O) OR1、(C＝O)NHR2Or (C ═ O) NHNH2；
R1Selected from methyl or ethyl;
R2selected from hydrogen, methyl or ethyl;
w is selected from hydrogen and C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl, C (═ O) R3、OR4、S(O)2R5、N(R6)R7Or N ═ C (R)8)R9；
Q is selected from hydrogen and C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl or C (═ O) R3；
Or Q, N and the N-linked W form a 3-6 membered saturated or unsaturated ring containing 0-2N-R10O, S or oxidized S, and the ring may form a ring with a benzene ring;
R3is selected from C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl, N (R)12)R13Phenyl, pyridyl, pyrazolyl, thiazolyl, isothiazolyl or thiadiazolyl, unsubstituted or optionally substituted with: the following groups are hydrogen, halogen, cyano, nitro, C (═ O) NH2、C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C1-C3Alkoxy radical, C1-C3Haloalkoxy, C1-C3Alkylthio radical, C1-C3Haloalkylthio, C1-C3Alkylamino radical, C1-C3Dialkylamino radical, C3-C6Cycloalkylamino, C1-C3Alkoxycarbonyl group, C1-C3Alkylsulfonyl radical, C1-C3Alkylaminocarbonyl radical, C1-C3Alkylaminosulfonyl, phenyl unsubstituted or optionally substituted with: the following groups are hydrogen, halogen, cyano, nitro, C1-C4Alkyl or C1-C4A haloalkyl group;
R4selected from hydrogen, C1-C4Alkyl or C1-C4A haloalkyl group;
R5is selected from C1-C2Alkyl radical, C1-C2Haloalkyl, methyl-substituted phenyl or N (R)11)R12；
R6Selected from hydrogen, methyl or ethyl;
R7selected from hydrogen, methyl or ethyl;
R8selected from methyl, ethyl, trifluoromethyl, phenyl unsubstituted or optionally substituted by: the following groups are hydrogen, halogen, cyano and nitro;
R9selected from methyl, ethyl, trifluoromethyl, phenyl unsubstituted or optionally substituted by: the following groups are hydrogen, halogen, cyano and nitro;
R12selected from methyl or ethyl;
R13selected from methyl or ethyl.
Or a salt of a compound of formula I.
4. A compound according to claim 3, characterized in that, in formula I,
x is selected from oxygen or sulfur;
z is selected from hydrogen;
a is selected from CN, (C ═ O) OR1Or (C ═ O) NH2；
R1Selected from methyl or ethyl;
w is selected from hydrogen and C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl, C (═ O) R3、S(O)2R5、N(R6)R7Or N ═ C (R)8)R9；
Q is selected from hydrogen and C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl or C (═ O) R3；
R3Is selected from C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl, N (R)12)R13Phenyl, pyridyl, pyrazolyl, thiazolyl, isothiazolyl or thiadiazolyl, unsubstituted or optionally substituted with: the following groups are hydrogen, halogen, cyano, nitro, C1-C4Alkyl radical, C1-C4Alkyl halidesBase, C1-C4Alkoxy radical, C1-C4Haloalkoxy, C1-C4Alkylthio or C1-C4A haloalkylthio group;
R5is selected from C1-C2Alkyl radical, C1-C2Haloalkyl, p-methylphenyl or N (R)12)R13；
R6Selected from hydrogen, methyl or ethyl;
R7selected from hydrogen, methyl or ethyl;
R8selected from methyl, ethyl, trifluoromethyl, phenyl unsubstituted or optionally substituted by: the following groups are hydrogen, halogen, cyano and nitro;
R9selected from methyl, ethyl, trifluoromethyl, phenyl unsubstituted or optionally substituted by: the following groups are hydrogen, halogen, cyano and nitro;
R12selected from methyl or ethyl;
R13selected from methyl or ethyl;
or a salt of a compound of formula I.
5. The compound of claim 4, wherein in formula I,
x is selected from sulfur;
z is selected from hydrogen;
a is selected from CN or (C ═ O) NH2；
W is selected from hydrogen and C1-C4Alkyl radical, C3-C6Cycloalkyl, C (═ O) R3Or N ═ C (R)8)R9；
Q is selected from hydrogen and C1-C4Alkyl radical, C3-C6Cycloalkyl or C (═ O) R3；
R3Is selected from C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl, phenyl, pyridyl, pyrazolyl, thiazolyl, isothiazolyl or thiadiazolyl, unsubstituted or optionally substituted with: the following groups are hydrogen and halogenElement, cyano, nitro, C1-C4Alkyl radical, C1-C4Haloalkyl, C1-C4Alkoxy radical, C1-C4Haloalkoxy, C1-C4Alkylthio or C1-C4A haloalkylthio group;
R8selected from methyl, ethyl, trifluoromethyl, phenyl unsubstituted or optionally substituted by: the following groups are hydrogen, halogen, cyano and nitro;
R9selected from methyl, ethyl, trifluoromethyl, phenyl unsubstituted or optionally substituted by: the following groups are hydrogen, halogen, cyano and nitro;
or a salt of a compound of formula I.
6. The compound of claim 5, wherein in formula I,
x is selected from sulfur;
z is selected from hydrogen;
a is selected from CN or (C ═ O) NH2；
W is selected from hydrogen and C1-C4Alkyl or C (═ O) R3；
Q is selected from hydrogen and C1-C4Alkyl or C (═ O) R3；
R3Is selected from C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, K1-K10Any one of the groups shown, phenyl or pyridyl, unsubstituted or optionally substituted with: the following groups are halogen, cyano, nitro, C1-C4Alkyl radical, C1-C4Haloalkyl, C1-C4Alkoxy radical, C1-C4Haloalkoxy, C1-C4Alkylthio or C1-C4A haloalkylthio group;
K1-K10is represented as follows:
or salts of the compounds of the general formula I with hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulphonic acid, 4-toluenesulphonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.
7. Use of the oxime ether compound or a salt thereof according to claim 1 as a fungicide in agriculture, forestry or hygiene.
8. A germicidal composition, characterized by: the oxime ether compound or the salt thereof shown in claim 1 is used as an active component in the composition, and the weight percentage of the active component in the composition is 0.1-99%.
9. A method of controlling a pathogen, comprising: applying to a crop or to a growing medium or locus of a crop a germicidally effective amount of the fungicidal composition of claim 8.
Technical Field
The present invention belongs to the field of agricultural bactericide. In particular to an oxime ether compound and application thereof.
Background
The oxime ether derivatives are compounds with broad spectrum bioactivity and are widely applied to pesticides, herbicides and bactericides. Since the first commercial oxime ether fungicide cymoxanil (Cymoxan) developed by dupont in 1974, new commercial varieties continue to emerge.
Patent CN106916084A discloses compounds CK1, CK2 and CK3 (compound numbers: 107, 115 and 116 in table 1 of CN106916084A, respectively) which have good activity against bacterial diseases and fungal diseases.
In the prior art, the oxime ether compounds and the bactericidal activity thereof shown in the invention are not reported.
Disclosure of Invention
The invention aims to provide an oxime ether compound with a novel structure, which can be used for preparing medicines for preventing and treating germs in agriculture and other fields.
In order to achieve the purpose, the technical scheme of the invention is as follows:
an oxime ether compound, which is characterized in that: the compound is shown as a general formula I:
in the formula:
x is selected from sulfur or oxygen;
z is selected from hydrogen, C unsubstituted or substituted by any of the following groups1-C6Linear or branched alkyl of (a): halogen, cyano, trifluoromethyl, trifluoromethoxy, hydroxy, nitro, amino;
a is selected from CN, (C ═ O) OR1、(C＝O)NHR2Or (C ═ O) NHNH2；
R1Is selected from C1-C8An alkyl group;
R2selected from hydrogen or C1-C8An alkyl group;
w is selected from hydrogen, acetonitrile, C1-C8Alkyl radical, C1-C8Haloalkyl, C3-C6Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C1-C8Alkoxy radical C1-C8Alkyl, C (═ O) R3、C(＝O)CH2R3、C(＝O)CH2OR3、NO2、OR4、S(O)2R5、N(R6)R7Or N ═ C (R)8)R9；
Q is selected from hydrogen, acetonitrile, C1-C8Alkyl radical, C1-C8Haloalkyl, C3-C6Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C1-C8Alkoxy radical C1-C8Alkyl or C (═ O) R3；
Or Q, N and the N-linked W form a 3-6 membered saturated or unsaturated ring containing 0-2N-R10O, S or oxidized S, and the ring may also be substituted by R11Substituted or fused with a benzene ring;
R3selected from hydrogen, C1-C8Alkyl radical, C1-C8Haloalkyl, C3-C6Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Haloalkenyl, C2-C8Alkynyl, C2-C8Halogenated alkynyl, C1-C8Alkoxy radical C1-C8Alkyl, N (R)12)R13Optionally substituted aryl or optionally substituted heteroaryl;
R4selected from hydrogen, C1-C8Alkyl radical, C1-C8Haloalkyl or C3-C6A cycloalkyl group;
R5is selected from C1-C2Alkyl radical, C1-C2Haloalkyl, C3-C6Cycloalkyl radical, C1-C4Alkoxy radical, C1-C4Alkyl-substituted phenyl or N (R)12)R13；
R6Selected from hydrogen or C1-C8An alkyl group;
R7selected from hydrogen or C1-C8An alkyl group;
R8selected from hydrogen, C1-C8Alkyl radical, C1-C8Haloalkyl, phenyl which is unsubstituted or optionally substituted by hydrogen, halogen, cyano, nitro, C1-C4Alkyl or C1-C4A haloalkyl group;
R9is selected fromC1-C8Alkyl radical, C1-C8Haloalkyl, phenyl which is unsubstituted or optionally substituted by hydrogen, halogen, cyano, nitro, C1-C4Alkyl or C1-C4A haloalkyl group;
R10is hydrogen, C1-C2Alkyl radical, C1-C2Haloalkyl, C1-C2Alkylcarbonyl or C1-C2An alkoxycarbonyl group;
R11is H, halogen, CN, NO2、C1-C2Alkyl radical, C1-C2Haloalkyl, C1-C4Alkoxy radical, C1-C2Haloalkoxy, optionally substituted aryl or S (O) nR14Wherein n is 0, 1 or 2;
R12is selected from C1-C8An alkyl group;
R13is selected from C1-C8An alkyl group;
R14is hydrogen, C1-C2Alkyl radical, C1-C2Haloalkyl, C3-C6Cycloalkyl or C1-C4An alkoxy group;
or a salt of a compound of formula I.
Preferred compounds of the invention are: in the general formula I
X is selected from sulfur or oxygen;
z is selected from hydrogen, C unsubstituted or substituted by any of the following groups1-C3Linear or branched alkyl of (a): halogen, cyano, trifluoromethyl, trifluoromethoxy, hydroxy, nitro, amino;
a is selected from CN, (C ═ O) OR1、(C＝O)NHR2Or (C ═ O) NHNH2；
R1Is selected from C1-C4An alkyl group;
R2selected from hydrogen or C1-C4An alkyl group;
w is selected from hydrogen, acetonitrile, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C4Alkenyl radical, C2-C4Haloalkenyl, C2-C4Alkynyl, C2-C4Halogenated alkynyl, C1-C4Alkoxy radical C1-C4Alkyl, C (═ O) R3、C(＝O)CH2R3、C(＝O)CH2OR3、NO2、OR4、S(O)2R5、N(R6)R7Or N ═ C (R)8)R9；
Q is selected from hydrogen, acetonitrile, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C4Alkenyl radical, C2-C4Haloalkenyl, C2-C4Alkynyl, C2-C4Halogenated alkynyl, C1-C4Alkoxy radical C1-C4Alkyl or C (═ O) R3；
Or Q, N and the N-linked W form a 3-6 membered saturated or unsaturated ring containing 0-2N-R10O, S or oxidized S, and the ring may also be substituted by R11Substituted or fused with a benzene ring;
R3selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C4Alkenyl radical, C2-C4Haloalkenyl, C2-C4Alkynyl, C2-C4Halogenated alkynyl, C1-C4Alkoxy radical C1-C4Alkyl, N (R)12)R13Or phenyl, pyridyl, pyrazolyl, thiazolyl, isothiazolyl or thiadiazolyl which are unsubstituted or optionally substituted by hydrogen, halogen, cyano, nitro, hydroxyl, mercapto, amino, aldehyde, C (═ O) NH2、C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C1-C3Alkoxy radical,C1-C3Haloalkoxy, C1-C3Alkylthio radical, C1-C3Haloalkylthio, C1-C3Alkylamino radical, C1-C3Dialkylamino radical, C3-C6Cycloalkylamino, C1-C3Alkoxycarbonyl group, C1-C3Alkylsulfonyl radical, C1-C3Alkylaminocarbonyl radical, C1-C3Alkylaminosulfonyl, phenyl or pyridyl, unsubstituted or optionally substituted by hydrogen, halogen, cyano, nitro, C1-C4Alkyl or C1-C4A haloalkyl group;
R4selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6A cycloalkyl group;
R5is selected from C1-C2Alkyl radical, C1-C2Haloalkyl, C3-C6Cycloalkyl radical, C1-C4Alkoxy radical, C1-C4Alkyl-substituted phenyl or N (R)12)R13；
R6Selected from hydrogen or C1-C4An alkyl group;
R7selected from hydrogen or C1-C4An alkyl group;
R8selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, phenyl unsubstituted or optionally substituted by hydrogen, halogen, cyano, nitro;
R9is selected from C1-C4Alkyl radical, C1-C4Haloalkyl, phenyl unsubstituted or optionally substituted by hydrogen, halogen, cyano, nitro;
R10is hydrogen, C1-C2Alkyl radical, C1-C2Haloalkyl, C1-C2Alkylcarbonyl or C1-C2An alkoxycarbonyl group;
R11is H, halogen, CN, NO2、C1-C2Alkyl radical, C1-C2Haloalkyl, C1-C4Alkoxy radical, C1-C2Haloalkoxy, optionally substituted aryl or S (O) nR14Wherein n is 0, 1 or 2;
R12is selected from C1-C4An alkyl group;
R13is selected from C1-C4An alkyl group;
R14is hydrogen, C1-C2Alkyl radical, C1-C2Haloalkyl, C3-C6Cycloalkyl or C1-C4An alkoxy group;
or a salt of a compound of formula I.
Further optional compounds in the present invention are: in the general formula I
X is selected from oxygen or sulfur;
z is selected from hydrogen, methyl or ethyl;
a is selected from CN, (C ═ O) OR1、(C＝O)NHR2Or (C ═ O) NHNH2；
R1Selected from methyl or ethyl;
R2selected from hydrogen, methyl or ethyl;
w is selected from hydrogen and C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl, C (═ O) R3、OR4、S(O)2R5、N(R6)R7Or N ═ C (R)8)R9；
Q is selected from hydrogen and C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl or C (═ O) R3；
Or Q, N and the N-linked W form a 3-6 membered saturated or unsaturated ring containing 0-2N-R10O, S or oxidized S, and the ring may form a ring with a benzene ring;
R3is selected from C1-C4Alkyl, aryl, heteroaryl, and heteroaryl,C1-C4Haloalkyl, C3-C6Cycloalkyl, N (R)12)R13Phenyl, pyridyl, pyrazolyl, thiazolyl, isothiazolyl or thiadiazolyl, unsubstituted or optionally substituted with: the following groups are hydrogen, halogen, cyano, nitro, C (═ O) NH2、C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C1-C3Alkoxy radical, C1-C3Haloalkoxy, C1-C3Alkylthio radical, C1-C3Haloalkylthio, C1-C3Alkylamino radical, C1-C3Dialkylamino radical, C3-C6Cycloalkylamino, C1-C3Alkoxycarbonyl group, C1-C3Alkylsulfonyl radical, C1-C3Alkylaminocarbonyl radical, C1-C3Alkylaminosulfonyl, phenyl unsubstituted or optionally substituted with: the following groups are hydrogen, halogen, cyano, nitro, C1-C4Alkyl or C1-C4A haloalkyl group;
R4selected from hydrogen, C1-C4Alkyl or C1-C4A haloalkyl group;
R5is selected from C1-C2Alkyl radical, C1-C2Haloalkyl, methyl-substituted phenyl or N (R)11)R12；
R6Selected from hydrogen, methyl or ethyl;
R7selected from hydrogen, methyl or ethyl;
R8selected from methyl, ethyl, trifluoromethyl, phenyl unsubstituted or optionally substituted by: the following groups are hydrogen, halogen, cyano and nitro;
R9selected from methyl, ethyl, trifluoromethyl, phenyl unsubstituted or optionally substituted by: the following groups are hydrogen, halogen, cyano and nitro;
R12selected from methyl or ethyl;
R13selected from methyl or ethyl.
Or a salt of a compound of formula I.
Further optional compounds in the present invention are: in the general formula I
X is selected from oxygen or sulfur;
z is selected from hydrogen;
a is selected from CN, (C ═ O) OR1Or (C ═ O) NH2；
R1Selected from methyl or ethyl;
w is selected from hydrogen and C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl, C (═ O) R3、S(O)2R5、N(R6)R7Or N ═ C (R)8)R9；
Q is selected from hydrogen and C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl or C (═ O) R3；
R3Is selected from C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl, N (R)12)R13Phenyl, pyridyl, pyrazolyl, thiazolyl, isothiazolyl or thiadiazolyl, unsubstituted or optionally substituted with: the following groups are hydrogen, halogen, cyano, nitro, C1-C4Alkyl radical, C1-C4Haloalkyl, C1-C4Alkoxy radical, C1-C4Haloalkoxy, C1-C4Alkylthio or C1-C4A haloalkylthio group;
R5is selected from C1-C2Alkyl radical, C1-C2Haloalkyl, p-methylphenyl or N (R)12)R13；
R6Selected from hydrogen, methyl or ethyl;
R7selected from hydrogen, methyl or ethyl;
R8selected from methyl, ethyl, trifluoromethyl, unsubstituted or substituted byOptionally substituted phenyl: the following groups are hydrogen, halogen, cyano and nitro;
R9selected from methyl, ethyl, trifluoromethyl, phenyl unsubstituted or optionally substituted by: the following groups are hydrogen, halogen, cyano and nitro;
R12selected from methyl or ethyl;
R13selected from methyl or ethyl;
or a salt of a compound of formula I.
Still further optional compounds of the invention are: in the general formula I
X is selected from sulfur;
z is selected from hydrogen;
a is selected from CN or (C ═ O) NH2；
W is selected from hydrogen and C1-C4Alkyl radical, C3-C6Cycloalkyl, C (═ O) R3Or N ═ C (R)8)R9；
Q is selected from hydrogen and C1-C4Alkyl radical, C3-C6Cycloalkyl or C (═ O) R3；
R3Is selected from C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl, phenyl, pyridyl, pyrazolyl, thiazolyl, isothiazolyl or thiadiazolyl, unsubstituted or optionally substituted with: the following groups are hydrogen, halogen, cyano, nitro, C1-C4Alkyl radical, C1-C4Haloalkyl, C1-C4Alkoxy radical, C1-C4Haloalkoxy, C1-C4Alkylthio or C1-C4A haloalkylthio group;
R8selected from methyl, ethyl, trifluoromethyl, phenyl unsubstituted or optionally substituted by: the following groups are hydrogen, halogen, cyano and nitro;
R9selected from methyl, ethyl, trifluoromethyl, phenyl unsubstituted or optionally substituted by: the following groups are hydrogen, halogen, cyano and nitro;
or a salt of a compound of formula I.
Yet further optional compounds of the invention are: in the general formula I
X is selected from sulfur;
z is selected from hydrogen;
a is selected from CN or (C ═ O) NH2；
W is selected from hydrogen and C1-C4Alkyl or C (═ O) R3；
Q is selected from hydrogen and C1-C4Alkyl or C (═ O) R3；
R3Is selected from C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, K1-K10Any one of the groups shown, phenyl or pyridyl, unsubstituted or optionally substituted with: the following groups are halogen, cyano, nitro, C1-C4Alkyl radical, C1-C4Haloalkyl, C1-C4Alkoxy radical, C1-C4Haloalkoxy, C1-C4Alkylthio or C1-C4A haloalkylthio group;
K1-K10is represented as follows:
or salts of the compounds of the general formula I with hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulphonic acid, 4-toluenesulphonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.
In the definitions of the compounds of the general formula given above, the terms used in the collection generally represent the following substituents:
unsubstituted means that all substituents are hydrogen.
Halogen: refers to fluorine, chlorine, bromine or iodine.
Alkyl groups: straight-chain or branched alkyl radicals, such as the methyl, ethyl, n-propyl, isopropyl or the different butyl, pentyl or hexyl isomers.
Halogenated alkyl groups: straight-chain or branched alkyl groups, the hydrogen atoms on which may be partially or fully substituted by halogen, such as chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, heptafluoroisopropyl, and the like.
Cycloalkyl groups: substituted or unsubstituted cyclic alkyl groups such as cyclopropyl, cyclopentyl or cyclohexyl; substituents such as methyl, halogen, and the like.
Alkenyl: including straight or branched chain alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the different butenyl, pentenyl and hexenyl isomers; alkenyl also includes polyenes such as 1, 2-allenyl and 2, 4-hexadienyl.
Halogenated alkenyl groups: alkenyl groups in which at least one or more hydrogen atoms may be substituted with halogen atoms.
Alkynyl: including straight or branched alkynes such as ethynyl, 1-propynyl, and the different butynyl, pentynyl, and hexynyl isomers; alkynyl also includes groups consisting of multiple triple bonds, such as 2, 5-hexadiynyl.
Halogenated alkynyl group: an alkynyl group which may have at least one or more hydrogen atoms substituted with a halogen atom.
Alkoxy groups: straight or branched chain alkyl groups attached to the structure via an oxygen atom, such as methoxy, ethoxy, t-butoxy, and the like.
Haloalkoxy groups: straight-chain or branched alkoxy groups, in which the hydrogen atoms may be partially or completely replaced by halogen, such as chloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, trifluoroethoxy and the like.
Alkylthio group: straight or branched chain alkyl groups attached to the structure via a sulfur atom, such as methylthio, ethylthio, and the like.
Haloalkylthio: straight-chain or branched alkylthio groups in which the hydrogen atoms may be partially or fully substituted by halogen, such as difluoromethylthio, trifluoroethylthio, and the like.
Alkylamino group: straight or branched chain alkyl groups attached to the structure via a nitrogen atom, such as methylamino, ethylamino, n-propylamino, isopropylamino, or the isomeric butylamines.
Dialkylamino group: two identical or different linear or branched alkyl groups are attached to the structure via a nitrogen atom, such as dimethylamino, methylethylamino, and the like.
Cycloalkylamino group: cycloalkyl-NH-, such as cyclopropylamino.
Alkyl amino carbonyl: alkyl-NH-CO-, e.g. CH3NHCO-。
Alkylaminosulfonyl: alkyl-NH-S (O)2-, e.g. CH3NH S(O)2-。
Alkoxyalkyl groups: alkyl-O-alkyl-, e.g. CH3OCH2-。
Haloalkoxyalkyl groups: straight-chain or branched alkoxyalkyl groups in which the hydrogen atoms may be partially or fully substituted by halogen, for example chloromethoxymethyl, dichloromethoxymethyl, trichloromethoxymethyl, fluoromethoxymethyl, difluoromethoxymethyl, trifluoromethoxy methyl, chlorofluoromethoxymethyl, trifluoroethoxymethyl and the like.
Alkoxyalkoxy group: alkyl-O-, e.g. CH3OCH2O-。
Alkoxycarbonyl group: alkyl-O- (C ═ O) -, e.g. CH3O(C＝O)-。
An alkylsulfonyl group: alkyl-S (O)2-, for example methylsulfonyl.
Aryl: monocyclic or polycyclic aromatic radicals having 6 to 20 carbon atoms, e.g. phenyl, naphthyl.
Heteroaryl group: monocyclic or polycyclic heteroaromatic groups having 1 to 20 carbon atoms, 1 to 4 heteroatoms selected from N, S, O, such as pyrrolyl, furyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyridazinonyl, indolyl, benzofuryl, benzoxazolyl, benzothienyl, benzothiazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolyl, benzopyrazolyl, quinoxalinyl and the like.
C1-C4Alkyl-substituted phenyl: meaning that the phenyl groups may be substituted by 1 to 5 different or identical C1-C4Alkyl substituents, such as 4-methylphenyl, 2-methyl-3 ethylphenyl.
Optionally substituted aryl: the aryl group may be substituted with any number of substituents at any position.
Optionally substituted C1-C6Linear or branched alkyl of (a): c1-C6Each C atom on the linear or branched alkyl group of (a) may be substituted with any number of substituents.
Some of the compounds of general formula I of the present invention are shown in Table 1, but the present invention is by no means limited to these compounds.
TABLE 1
Of partial compounds1H NMR and physico-chemical properties were as follows:
TABLE 2
The compounds of the general formula I according to the invention can be prepared by the following processes, in which the radicals are as defined above, unless otherwise indicated.
The method comprises the following steps:
the compound of the general formula I is prepared by reacting the compound of the general formula II with the compound of the general formula III in a proper solvent at the temperature of between 10 ℃ below zero and the boiling point of the solvent for 0.5 to 48 hours.
Reacting the compound of formula IV containing amino with W and Q in a suitable solvent at a temperature of from-10 ℃ to the boiling point of the solvent for 0.5 to 48 hours to obtain the compound of formula II, wherein the reaction can be carried out in the presence or absence of a base.
The second method comprises the following steps:
the compound V containing amino group is reacted with W and Q in proper solvent at-10 deg.c to solvent boiling point for 0.5-48 hr to obtain the compound of the general formula I, and the reaction may be carried out in the presence or absence of alkali.
The compound of the general formula V is prepared by reacting the compound of the general formula IV with the compound of the general formula III in a proper solvent at the temperature of between 10 ℃ below zero and the boiling point of the solvent for 0.5 to 48 hours.
The preparation method comprises the following steps: LG represents a leaving group and suitable leaving groups may be selected from halogens or other conventional nucleofugic groups such as mesylate or tosylate groups and the like. M represents a cation, e.g. Na+、K+、CS+、Ag+Or NH4 +And the like. Suitable solvents include aromatic hydrocarbons such as benzene, toluene and xylene, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, and chlorineHalogenated aromatic hydrocarbons such as chloroform and dichloromethane, esters such as methyl acetate and ethyl acetate, ethers such as tetrahydrofuran, dioxane, diethyl ether and 1, 2-dimethoxyethane, polar solvents such as water, acetonitrile, N-dimethylformamide, N-methylpyrrolidone and dimethyl sulfoxide, or mixed solvents thereof; the base may be organic base such as triethylamine, pyridine, DBU, DMAP, etc., alkali metal hydride such as sodium hydride, potassium hydride, etc., alkali metal hydroxide such as sodium hydroxide, potassium hydroxide, etc., alkali earth metal hydroxide such as calcium hydroxide, alkali metal carbonate such as sodium carbonate, potassium carbonate, etc., alkali metal bicarbonate such as sodium bicarbonate, etc., metal alkoxide such as sodium methoxide, potassium ethoxide, etc.
The compounds of formula III may be purchased or prepared according to known methods (e.g., CN103804321, WO2008139481, US20130096098 or Journal of the Chemical Society of Pakistan,33(3),324, 332,2011, etc.).
The compounds of formula IV can be purchased or prepared by known methods (e.g., CN 101885708A or Journal of Medicinal Chemistry 59(21), 9686-9720; 2016).
The compound or the salt thereof can be used for controlling plant diseases, can be used for controlling diseases caused by various fungi such as oomycetes, basidiomycetes, ascomycetes, adelomycetes and the like on various crops, and has good control effect on diseases such as cucumber downy mildew, cucumber gray mold, cucumber anthracnose, cucumber powdery mildew, tomato early blight, tomato late blight, pepper epidemic disease, grape downy mildew, grape white rot, apple ring rot, apple alternaria leaf spot, rice sheath blight, rice blast, wheat rust, wheat leaf spot, wheat powdery mildew, rape sclerotinia rot, corn microsporum and the like at lower dose.
The compound also has good bactericidal activity, and can be used for preventing and treating various plant bacterial diseases, such as bacterial wilt, bacterial blight, canker, soft rot, bacterial angular leaf spot, bacterial leaf streak, leaf blight, wildfire and bacterial scab, and the like, and specifically comprises rice bacterial streak, rice bacterial leaf blight, rice basal rot, rice bacterial brown streak, rice bacterial brown patch, potato bacterial wilt, potato soft rot, potato black shank, potato ring rot, citrus canker, pear root canker, pear fire blight, peach bacterial perforation, kiwi canker, walnut black spot, fruit tree bacterial root canker, bacterial watermelon bacterial wilt, watermelon bacterial fruit rot, solanaceae vegetable bacterial wilt, cucumber bacterial angular leaf spot, melon bacterial angular leaf spot, cruciferous vegetable soft rot, bacterial black rot, and the like, Bacterial black spot, flower bacterial diseases, and the like.
The invention also provides a bactericidal composition, which contains the compound shown in the general formula I or the salt thereof and an agriculturally acceptable carrier, wherein the compound shown in the general formula I or the salt thereof is used as an active component, and the weight percentage of the active component in the composition is 0.1-99%.
Detailed Description
The following specific examples are intended to further illustrate the invention, but are not intended to limit the invention.
Synthetic examples
Example 1: preparation of Compound 34
In a 50 ml reaction flask were charged ((2-aminothiazol-4-yl) methoxy) imidoimide dicyanide (0.5 g, 2.41 mmol), triethylamine (0.37 g, 3.66 mmol), DMAP (0.3 g, 2.46 mmol) and 20 ml of dichloromethane, then stirring was started, then 2.4-dichlorobenzoyl chloride (0.5 g, 2.39 mmol) was dissolved in 10 ml of dichloromethane, under ice bath conditions, the acid chloride solution was dropped into the reaction flask, the reaction was continued to stir at room temperature after completion of the dropping, TLC (ethyl acetate: petroleum ether ═ 1:5) was monitored, after completion of the reaction, the solvent was evaporated under reduced pressure, and the residue column chromatography (ethyl acetate: petroleum ether ═ 1:5 as eluent, 100-mesh 140 mesh silica gel produced by the Qingdao ocean Biochemical plant division) was purified to obtain 0.42 g of yellow solid with a yield of 46%.
Example 2: preparation of Compound 47
Preparation of intermediate 4- (chloromethyl) thiazole-2-amino hydrochloride
Thiourea (6.49 g, 85.26 mmol) and 40 ml methanol were added to a 100 ml reaction flask, then 1, 3-dichloroacetone (10.83 g, 85.26 mmol) was dissolved in 30 ml acetone, the 1, 3-dichloroacetone solution was slowly added dropwise to the thiourea solution under ice bath conditions, the ice bath was removed after the dropwise addition, the stirring was continued overnight at room temperature, the solvent was removed by spinning, then 20 ml acetone was added to the residue, the mixture was stirred vigorously until a solid precipitated, and then the mixture was suction-filtered and air-dried to obtain 13.5 g white solid with 86% yield.
In a 50 ml reaction flask were added 4- (chloromethyl) thiazole-2-amino hydrochloride (0.5 g, 2.7 mmol), malononitrile oxime ether sodium salt (0.32 g, 2.7 mmol), triethylamine (0.28 g, 2.77 mmol) and 15 ml acetonitrile, the reaction was stirred at 60 ℃ and monitored by TLC (ethyl acetate: petroleum ether ═ 1: 1), after completion of the reaction, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (ethyl acetate: petroleum ether ═ 1:2 as eluent, 100-mesh 140-mesh silica gel produced by Qingdao ocean biochemistry factory division) to obtain 0.21 g of a yellow solid with a yield of 37%.
Example 3: preparation of Compound 97
In a 50 ml reaction flask were charged ((2-aminothiazol-4-yl) methoxy) imidoimide dicyanide (0.27 g, 1.30 mmol), triethylamine (0.19 g, 1.88 mmol), DMAP (0.16 g, 1.31 mmol) and 20 ml of dichloromethane, then stirring was started, then 4-tert-butylbenzoyl chloride (0.25 g, 1.27 mmol) was dissolved in 10 ml of dichloromethane, under ice bath conditions, the acid chloride solution was dropped into the reaction flask, the reaction was continued to stir at room temperature after dropping, monitored by TLC (ethyl acetate: petroleum ether ═ 1:5), after completion of the reaction, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (ethyl acetate: petroleum ether ═ 1:5 as eluent, 100-mesh 140-mesh silica gel produced by the Qingdao Marine Biochemical plant division) to give 0.22 g of black oil in 47% yield.
Example 4: preparation of Compound 179
In a 50 ml reaction flask were added 4- (chloromethyl) thiazole-2-amino hydrochloride (0.45 g, 2.43 mmol), cyanoacetamide oxime ether (0.28 g, 2.48 mmol), potassium carbonate (1.01 g, 7.29 mmol) and 25 ml acetonitrile, stirred at 65 ℃ for 8 hours, after the reaction solution was cooled, filtered through celite to give a clear solution, then the solvent was removed under reduced pressure, and the residue was washed with dichloromethane to give 0.22 g of a yellow solid in 40% yield.
Example 5: preparation of compound 361
4-fluoroacetophenone (2 g, 14.48 mmol), thiosemicarbazide (1.32 g, 14.48 mmol), acetic acid 0.2 ml and 35 ml of ethanol were added to a 50 ml reaction flask, and the mixture was heated under reflux for 8 hours, after the reaction solution was cooled, a white solid was precipitated, and then the mixture was filtered to obtain 2.2 g of the target compound with a yield of 72%.
The condensation product obtained in the previous step (1.2 g, 5.68 mmol) and 1, 3-dichloroacetone (0.72 g, 5.68 mmol) were added to a single-neck flask, 50 ml of ethanol was then added, the mixture was heated to 60 ℃ for reaction for 8 hours, monitored by TLC (ethyl acetate: petroleum ether: 1:5), after completion of the reaction, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (ethyl acetate: petroleum ether: 1:5 as eluent, 100-grade 140-mesh silica gel produced by Qingdao ocean Biochemical plant division) to obtain 0.66 g of black oil with a yield of 41%.
The chloride (0.4 g, 1.41 mmol) obtained in the previous step, malononitrile oxime ether sodium salt (0.17 g, 1.41 mmol) and 15 ml acetonitrile were charged into a 50 ml reaction flask, heated to 60 ℃ and stirred for reaction, monitored by TLC (ethyl acetate: petroleum ether: 1:3), after completion of the reaction, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (ethyl acetate: petroleum ether: 1:3 as eluent, 100-140 mesh silica gel produced by Qingdao ocean Biochemical plant division) to obtain 0.18 g of black oil in 37% yield.
Example 6: preparation of Compound 363
In a 50 ml reaction flask were charged ((2-aminothiazol-4-yl) methoxy) imidoimide dicyanide (0.21 g, 1.01 mmol), triethylamine (0.16 g, 1.58 mmol), DMAP (0.13 g, 1.06 mmol) and 20 ml of dichloromethane, then stirring was started, then methyl 4-carboxylate benzoyl chloride (0.20 g, 1.01 mmol) was dissolved in 10 ml of dichloromethane, under ice bath conditions, the acid chloride solution was added dropwise to the reaction flask, stirring was continued at room temperature after completion of the reaction, TLC (ethyl acetate: petroleum ether ═ 1:5) was monitored, after completion of the reaction, the solvent was evaporated under reduced pressure, and the residue column chromatography (ethyl acetate: petroleum ether ═ 1:5 as eluent, 100-mesh 140 mesh silica gel produced by the Qingdao ocean Biochemical plant division) was purified to obtain 0.18 g of yellow solid in 48% yield.
Example 7: preparation of Compound 364
To a 50 ml reaction flask were added 4- (chloromethyl) thiazole-2-amino hydrochloride (0.4 g, 2.16 mmol), triethylamine (0.54 g, 5.34 mmol), DMAP (0.26 g, 2.13 mmol), and 20 ml of dichloromethane, followed by stirring. O-ethoxybenzoyl chloride (0.39 g, 2.11 mmol) is dissolved in 10 ml of dichloromethane, then under the condition of ice bath, acyl chloride is dripped into a reaction bottle, the reaction is continued to be stirred at room temperature after the dripping is finished, TLC (ethyl acetate: petroleum ether ═ 1:5) monitoring is carried out, after the reaction is finished, the solvent is removed under reduced pressure, and the residue is purified by column chromatography (ethyl acetate: petroleum ether ═ 1:5 is used as eluent, 100-mesh 140-mesh silica gel produced by Qingdao ocean biochemical factories and factories) to obtain 0.46 g of white solid with 73 percent yield.
In a 50 ml reaction flask were added N- (4- (chloromethyl) thiazol-2-yl) -2-ethoxybenzamide (0.45 g, 1.52 mmol), malononitrile oxime ether sodium salt (0.18 g, 1.54 mmol) and 15 ml acetonitrile, the reaction was stirred at 60 ℃ and monitored by TLC (ethyl acetate: petroleum ether 1:3), after completion of the reaction, the acetonitrile was evaporated under reduced pressure and the residue was purified by column chromatography (ethyl acetate: petroleum ether 1:3 as eluent, 100-140 mesh silica gel produced by Qingdao Seiko) to obtain 0.25 g of a yellow solid with a yield of 46%.
Other compounds represented by the general formula I can be obtained by substituting the starting materials according to the descriptions of the above examples and the synthetic route of the general formula I in the summary of the invention.
Biological activity assay
Example 8: measurement of controlling Effect on plant bacterial diseases
The compound of the invention is used for carrying out prevention and treatment determination on various plant bacterial diseases, and aiming at different bacterial diseases, the test procedures are as follows:
and (3) dissolving the compound to be tested in a small amount of N, N dimethylformamide, and diluting the solution to the required concentration by using water. Uniformly mixing pathogenic bacteria cultured to a stable growth period with a quantitative compound solution, soaking the melon seeds subjected to germination acceleration in a mixed solution of a bacterial liquid and a compound for half an hour, sowing the seeds in an earthworm soil culture cup, putting the earthworm soil culture cup into a greenhouse for wet culture, culturing for two weeks generally, and performing control effect investigation after full control disease attack.
Cutting 2 cm square leaf of Chinese cabbage, and placing into a glass culture dish filled with double-layer filter paper. The method comprises the steps of dissolving N, N-dimethylformamide, spraying a compound diluted by water to a required concentration on the surface of a Chinese cabbage leaf, airing the liquid medicine on the surface of the Chinese cabbage leaf in a fume hood, carrying out needle-punching on the surface of the Chinese cabbage leaf by using an inoculating needle to cause a wound, taking 5 microliters of Chinese cabbage soft rot bacteria cultured to a stable growth period, adding the Chinese cabbage soft rot bacteria into the wound, and inoculating. And finally, placing the test material into an incubator to be cultured for 48 hours in a dark place, and carrying out control effect investigation after the control is fully developed.
The test results were as follows:
at 400mg/L, the control effect of the compounds 4, 5, 6, 20, 22, 23, 34, 36, 45, 47, 65, 74, 86, 87, 95, 97, 99, 104, 117, 118, 119, 123, 134, 179, 228, 253, 361, 366 and 367 on the soft rot of the Chinese cabbage is 100 percent.
At 400mg/L, the control effect of the compounds 4, 5, 6, 20, 22, 23, 34, 36, 45, 47, 65, 74, 86, 87, 95, 97, 99, 104, 117, 118, 119, 123, 134, 179, 228, 253, 361, 366 and 367 on the muskmelon fruit blotch is 100 percent.
Example 9: measurement of controlling Effect on plant fungal diseases
The living pot culture determination method is adopted, namely a compound sample to be tested is dissolved by a small amount of solvent (the type of the solvent is acetone, methanol, DMF, and the like, is selected according to the dissolving capacity of the solvent to the sample, and the volume ratio of the solvent amount to the liquid spraying amount is equal to or less than 0.05.), diluted by water containing 0.1 percent of Tween 80, and prepared into the liquid to be tested with the required concentration. Foliar spray treatments were carried out with the compounds of the present invention at the designed concentrations. Additionally setting blank control of spraying clear water, repeating for 3 times, inoculating disease the next day after treatment, and culturing the plant in artificial climate chamber for moisture (temperature: 25 deg.C day, 20 deg.C night, relative humidity 95-99%). After the test material is cultured for 24 hours, the test material is transferred to a greenhouse for culture, and plants which do not need to be subjected to moisture-retention culture are directly inoculated and cultured in the greenhouse. After the control was well established (usually one week), the control effect of the compound was evaluated, and the results were investigated with reference to A Manual of Association Keys for Plant Diseases, written by the American society of Plant, as 100-0, with "100" grade representing no disease and "0" grade representing the most severe degree of disease.
Preventing soybean rust:
when the concentration of part of tested compounds is 400ppm, for example, the compounds 10, 16, 19, 20, 22, 23, 34, 36, 47, 57, 65, 86, 87, 95, 98, 100, 117, 179, 363, 364 and 365 have good control effect on soybean rust, and the control effect is more than or equal to 80%.
According to the method, the compounds 10, 23, 47, 179 and 365 are selected to be compared with the known compound CK1 in parallel for preventing and controlling the soybean rust, and the test results are shown in Table 3
TABLE 3
Preventing effect on cucumber downy mildew:
some tested compounds, such as compounds 10, 16, 19, 20, 22, 23, 36, 45, 47, 57, 65, 86, 87, 95, 97, 98, 100, 117, 123, 134, 179 and 365 have good control effect on cucumber downy mildew at a concentration of 400ppm, and the control effect is more than or equal to 80 percent,
according to the method, compounds 20, 45, 97 and 117 are selected to be compared with known compounds CK1, CK2 and CK3 in parallel for controlling cucumber downy mildew, and the test results are shown in Table 4
TABLE 4
Example 10: cucumber bacterial angular leaf spot field test
Selecting compound 47 and97 field verification test, wherein the control object is cucumber bacterial angular leaf spot (Pseudomonas syringae pv. lachrymans), the treatment dose of the test agent is 400mg/L, the treatment dose of the contrast agent CK2 is 700mg/L, the test agent and the contrast agent are arranged in random blocks, and the area of each cell is as follows: 15m2And 3 repetitions. The application method is spray treatment of the whole plant, three times of application are carried out at intervals of 7 days, and the control effect investigation is carried out 7 days after the last application. During investigation, sampling is carried out at 5 points in each cell, all leaves are investigated, the lesion area of each leaf accounts for the whole leaf area, and the disease index and the prevention effect are calculated by grading. The results are shown in Table 5
TABLE 5
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