Amide compound and preparation method and application thereof
阅读说明：本技术 酰胺类化合物及其制备方法和应用 (Amide compound and preparation method and application thereof ) 是由 徐靖博 吴鸿飞 孙芹 徐利保 李志念 程学明 孙宁宁 郭春晓 于海波 于 2018-07-17 设计创作，主要内容包括：本发明提供了一种酰胺类化合物及其制备方法和应用。该酰胺类化合物具有式I所示结构,较高的杀菌活性,尤其是对多种作物上由卵菌纲、担子菌纲、子囊菌和半知菌类等多种真菌引起的病害具有良好的防治作用,例如在较低剂量下对黄瓜霜霉病、黄瓜灰霉病、黄瓜炭疽病、黄瓜白粉病、番茄早疫病、番茄晚疫病、辣椒疫病、葡萄霜霉病、葡萄白腐病、苹果轮纹病、苹果斑点落叶病、水稻纹枯病、水稻稻瘟病、小麦锈病、小麦叶斑病、小麦白粉病、油菜菌核病、玉米小斑病等病害都有着很好的防效。<Image he="359" wi="494" file="DDA0001733292440000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(The invention provides an amide compound and a preparation method and application thereof. The amide compound has a structure shown in a formula I, has high bactericidal activity, and particularly has good control effect on diseases of various crops caused by various fungi such as oomycetes, basidiomycetes, ascomycetes, deuteromycetes and the like, such as cucumber downy mildew, cucumber gray mold, cucumber anthracnose, cucumber powdery mildew, tomato early blight, tomato late blight, pepper blight, 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 a low dose.)
1. An amide compound, wherein the amide compound has a structure represented by formula I:
in the formula I:
R1selected from hydrogen, halogen, hydroxy, -NH2、-NHNH2、C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Alkynyl, -OR7、-NR7R8Unsubstituted or optionally substituted aryl, or aryl-substituted C1-C6An alkyl group; wherein R is7And R8Each independently selected from hydrogen and C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Alkynyl, C1-C6Alkoxy radical C1-C6Alkyl, unsubstituted or optionally substituted aryl, or aryl-substituted C1-C6Alkyl, and said R7And said R8Not hydrogen at the same time;
R2selected from hydrogen, C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Alkynyl, unsubstituted or optionally substituted aryl, unsubstituted or optionally substituted heteroaryl;
R3selected from hydrogen, C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl radical, C2-C8Alkenyl or C2-C8An alkynyl group;
R4selected from hydrogen, C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Alkynyl, unsubstituted or optionally substituted aryl, unsubstituted or optionally substituted heteroaryl;
R5and R6Each independently selected from halogen, cyano, nitro, hydroxy, mercapto, -NH2、-NHNH2、C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl radical, C1-C6Alkoxy radical, C1-C6Haloalkoxy, C1-C6Alkylthio radical, C1-C6Haloalkylthio, C2-C8Alkenyl radical, C2-C8Alkynyl, C1-C6Alkylamino radical, C1-C6Haloalkylamino, C1-C6Dialkylamino radical, C3-C8Cycloalkylamino, C1-C6Alkyl hydrazino, C1-C6Haloalkyl hydrazino, C1-C6Dialkylhydrazino group, C3-C8Cycloalkylhydrazino, unsubstituted or optionally substituted aryl, unsubstituted or optionally substituted heteroaryl.
2. The amide-based compound according to claim 1, wherein in the formula I, R is5And said R6Each independently selected from halogen, cyano, nitro, hydroxy, mercapto, -NH2、-NHNH2、C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C1-C4Alkoxy radical, C1-C4Haloalkoxy, C1-C4Alkylthio radical, C1-C4Haloalkylthio, C2-C6Alkenyl radical, C2-C6Alkynyl, C1-C4Alkylamino radical, C1-C4Haloalkylamino, C1-C4Dialkylamino radical, C3-C6Cycloalkylamino, C1-C4Alkyl hydrazino, C1-C4Haloalkyl hydrazino, C1-C4Dialkylhydrazino group, C3-C6Cycloalkylhydrazino, unsubstituted or optionally substituted aryl, unsubstituted or optionally substitutedThe heteroaryl group of (a);
preferably, said R is5And said R6Each independently selected from halogen, cyano, nitro, hydroxy, mercapto, -NH2、-NHNH2、C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C1-C4Alkoxy radical, C1-C4Alkylthio or C1-C4An alkylamino group;
more preferably, said R5And said R6Each independently selected from halogen, cyano, nitro, hydroxy, mercapto, -NH2、-NHNH2、C1-C4Haloalkyl, C1-C4Alkoxy radical, C1-C4Alkylthio or C1-C4An alkylamino group;
further preferably, said R5And said R6Each independently selected from halogen, cyano, nitro, hydroxy, mercapto, -NH2、-NHNH2Trifluoromethyl, methoxy, methylthio or methylamino.
3. The amide-based compound according to claim 1 or 2, wherein in the formula I, R is1Selected from hydrogen, halogen, hydroxy, -NH2、-NHNH2、C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl, -OR7、-NR7R8Unsubstituted or optionally substituted aryl, or aryl-substituted C1-C4An alkyl group; wherein said R7And said R8Each independently selected from hydrogen and C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl, C1-C4Alkoxy radical C1-C4Alkyl, unsubstituted or optionally substituted aryl, or aryl-substituted C1-C4An alkyl group;
preferably, said R is1Selected from hydrogen, halogen, hydroxy, -NH2、-NHNH2、-OR7or-NR7R8(ii) a Wherein said R7And said R8Each independently selected from hydrogen and C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl, C1-C4Alkoxy radical C1-C4Alkyl, unsubstituted or optionally substituted phenyl, or benzyl-;
more preferably, said R1Is selected from-OR7or-NR7R8(ii) a Wherein said R7And said R8Each independently selected from hydrogen and C1-C4Alkyl, trifluoroethyl, cyclopropyl, 1-propenyl, propynyl, methoxyethyl, phenyl or benzyl.
4. Amide-based compound according to any one of claims 1 to 3, characterized in that in formula I, R is2Selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl, unsubstituted or optionally substituted aryl, unsubstituted or optionally substituted heteroaryl; the R is3Selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl or C2-C6An alkynyl group; the R is4Selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl, unsubstituted or optionally substituted aryl, unsubstituted or optionally substituted heteroaryl;
preferably, said R is2Selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl, unsubstituted or optionally substituted phenyl; the R is3Selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl or C2-C6An alkynyl group; the R is4Selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl, unsubstituted or optionally substituted phenyl;
more preferably, said R2Is selected from C1-C4An alkyl group; the R is3Selected from hydrogen or methyl; the R is4Selected from hydrogen, methyl, difluoromethyl or trifluoromethyl.
5. A process for producing the amide-based compound according to any one of claims 1 to 4, wherein the amide-based compound is synthesized by the following route:
wherein R is1、R2、R3、R4、R5、R6Is as defined in any one of claims 1 to 4.
6. The method of manufacturing according to claim 5, comprising the steps of: reacting the compound with the structure of the formula II and the compound with the structure of the formula III in a solvent to obtain the amide compound;
preferably, the solvent is selected from one or more of dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, dioxane, THF, DMF and DMSO;
preferably, the reaction is carried out in the presence of a base, more preferably the base is selected from one or more of triethylamine, N-diisopropylethylamine, pyridine, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium methoxide and potassium tert-butoxide;
preferably, the reaction temperature in the reaction process is-10 ℃ to the boiling point temperature of the solvent, and the reaction time is 0.5-48 hours.
7. Use of the amide-based compound according to any one of claims 1 to 4 as a fungicide in the fields of agriculture, forestry and hygiene.
8. A fungicidal composition, characterized by comprising the amide-based compound according to any one of claims 1 to 4 and an agriculturally acceptable carrier.
9. The bactericidal composition of claim 8, wherein the compound of formula I is an active ingredient, and the active ingredient is present in the bactericidal composition in an amount of 0.1 to 99% by weight.
10. A method of controlling plant disease, comprising: the fungicidal composition of claim 8 or 9 is applied to a disease or its growth medium to be controlled at a dose of 10 to 1000 g per hectare.
Technical Field
The invention relates to the field of agricultural bactericides, and particularly relates to an amide compound and a preparation method and application thereof.
Background
In recent years, the control work has become extremely difficult due to severe resistance against harmful fungi by the use of conventional fungicides throughout the years in the agricultural and horticultural fields. In addition, the use of highly toxic pesticides also has many problems, and therefore, new bactericides with unique action mechanisms need to be continuously developed.
The fungicidal compound KC is disclosed in US5747518A1(the patent number is compound 3.13) has the control effect on the gray mold of kidney beans and the brown rust of wheat which are both more than or equal to 80 percent at the concentration of 200 ppm.
WO2005044008A2 discloses the fungicidal compound KC2(patent No. 14-495) shows an inhibition ratio of 90% or more against the ocular spot disease at a concentration of 10 ppm.
Bioorganic&The compound KC is disclosed in Medicinal Chemistry Letters (2013),23(8),2306-3And KC4As a BRAFV600EEnzyme inhibitors are useful for the treatment of cancer.
However, the amide compound provided by the invention and the bactericidal activity thereof are not reported.
Disclosure of Invention
The invention mainly aims to provide an amide compound, a preparation method and application thereof, which can be used for preventing and treating germs in agriculture and other fields.
In order to achieve the above object, according to one aspect of the present invention, there is provided an amide-based compound having a structure represented by formula I:
in formula I:
R1selected from hydrogen, halogen, hydroxy, -NH2、-NHNH2、C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Alkynyl, -OR7、-NR7R8Unsubstituted or optionally substituted aryl, or aryl-substituted C1-C6An alkyl group; wherein R is7And R8Each independently selected from hydrogen and C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Alkynyl, C1-C6Alkoxy radical C1-C6Alkyl, unsubstituted or optionally substituted aryl, or aryl-substituted C1-C6Alkyl, and R7And R8Not hydrogen at the same time;
R2selected from hydrogen, C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Alkynyl, unsubstituted or optionally substituted aryl, unsubstitutedSubstituted or optionally substituted heteroaryl;
R3selected from hydrogen, C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl radical, C2-C8Alkenyl or C2-C8An alkynyl group;
R4selected from hydrogen, C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Alkynyl, unsubstituted or optionally substituted aryl, unsubstituted or optionally substituted heteroaryl;
R5and R6Each independently selected from halogen, cyano, nitro, hydroxy, mercapto, -NH2、-NHNH2、C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl radical, C1-C6Alkoxy radical, C1-C6Haloalkoxy, C1-C6Alkylthio radical, C1-C6Haloalkylthio, C2-C8Alkenyl radical, C2-C8Alkynyl, C1-C6Alkylamino radical, C1-C6Haloalkylamino, C1-C6Dialkylamino radical, C3-C8Cycloalkylamino, C1-C6Alkyl hydrazino, C1-C6Haloalkyl hydrazino, C1-C6Dialkylhydrazino group, C3-C8Cycloalkylhydrazino, unsubstituted or optionally substituted aryl, unsubstituted or optionally substituted heteroaryl.
Further, in the formula I, R5And R6Each independently selected from halogen, cyano, nitro, hydroxy, mercapto, -NH2、-NHNH2、C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C1-C4Alkoxy radical, C1-C4Haloalkoxy, C1-C4Alkylthio radical, C1-C4A haloalkylthio group,C2-C6Alkenyl radical, C2-C6Alkynyl, C1-C4Alkylamino radical, C1-C4Haloalkylamino, C1-C4Dialkylamino radical, C3-C6Cycloalkylamino, C1-C4Alkyl hydrazino, C1-C4Haloalkyl hydrazino, C1-C4Dialkylhydrazino group, C3-C6Cycloalkylhydrazino, unsubstituted or optionally substituted aryl, unsubstituted or optionally substituted heteroaryl; preferably, R5And R6Each independently selected from halogen, cyano, nitro, hydroxy, mercapto, -NH2、-NHNH2、C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C1-C4Alkoxy radical, C1-C4Alkylthio or C1-C4An alkylamino group; more preferably, R5And R6Each independently selected from halogen, cyano, nitro, hydroxy, mercapto, -NH2、-NHNH2、C1-C4Haloalkyl, C1-C4Alkoxy radical, C1-C4Alkylthio or C1-C4An alkylamino group; further preferably, R5And R6Each independently selected from halogen, cyano, nitro, hydroxy, mercapto, -NH2、-NHNH2Trifluoromethyl, methoxy, methylthio or methylamino.
Further, in the formula I, R1Selected from hydrogen, halogen, hydroxy, -NH2、-NHNH2、C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl, -OR7、-NR7R8Unsubstituted or optionally substituted aryl, or aryl-substituted C1-C4An alkyl group; wherein R is7And R8Each independently selected from hydrogen and C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radicals、C2-C6Alkenyl radical, C2-C6Alkynyl, C1-C4Alkoxy radical C1-C4Alkyl, unsubstituted or optionally substituted aryl, or aryl-substituted C1-C4An alkyl group; preferably, R1Selected from hydrogen, halogen, hydroxy, -NH2、-NHNH2、-OR7or-NR7R8(ii) a Wherein R is7And R8Each independently selected from hydrogen and C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl, C1-C4Alkoxy radical C1-C4Alkyl, unsubstituted or optionally substituted phenyl, or benzyl-; more preferably, R1Is selected from-OR7or-NR7R8(ii) a Wherein R is7And R8Each independently selected from hydrogen and C1-C4Alkyl, trifluoroethyl, cyclopropyl, 1-propenyl, propynyl, methoxyethyl, phenyl or benzyl.
Further, in the formula I, R2Selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl, unsubstituted or optionally substituted aryl, unsubstituted or optionally substituted heteroaryl; r3Selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl or C2-C6An alkynyl group; r4Selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl, unsubstituted or optionally substituted aryl, unsubstituted or optionally substituted heteroaryl; preferably, R2Selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl, unsubstituted or substitutedAn optionally substituted phenyl group; r3Selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl or C2-C6An alkynyl group; r4Selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl, unsubstituted or optionally substituted phenyl; more preferably, R2Is selected from C1-C4An alkyl group; r3Selected from hydrogen or methyl; r4Selected from hydrogen, methyl, difluoromethyl or trifluoromethyl.
According to another aspect of the present invention, there is also provided a preparation method of the above amide compound, which synthesizes the amide compound according to the following route:
wherein R is1、R2、R3、R4、R5、R6Is as defined in any one of claims 1 to 4.
Further, the preparation method comprises the following steps: reacting a compound with a structure shown in a formula II with a compound with a structure shown in a formula III in a solvent to obtain an amide compound; preferably, the solvent is selected from one or more of dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, dioxane, THF, DMF and DMSO; preferably, the reaction is carried out in the presence of a base, more preferably a base selected from one or more of triethylamine, N-diisopropylethylamine, pyridine, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium methoxide and potassium tert-butoxide; preferably, the reaction temperature during the reaction is from-10 ℃ to the boiling point temperature of the solvent, and the reaction time is from 0.5 to 48 hours.
According to another aspect of the invention, the application of the amide compound as a bactericide in the fields of agriculture, forestry and sanitation is also provided.
According to another aspect of the invention, a bactericidal composition is also provided, which comprises the amide compound and an agriculturally acceptable carrier.
Further, the compound shown in the general formula I is used as an active component, and the weight percentage of the active component in the bactericidal composition is 0.1-99%.
According to another aspect of the present invention, there is also provided a method of controlling plant diseases, comprising: the bactericidal composition is applied to the disease or the growth medium of the disease to be controlled at a dosage of 10 g to 1000 g per hectare.
The invention provides an amide compound. The amide compound has high bactericidal activity, and particularly has good control effect on diseases of various crops caused by various fungi such as oomycetes, basidiomycetes, ascomycetes, deuteromycetes and the like, for example, 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 small leaf spot and the like under low dosage.
Detailed Description
It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict. The present invention will be described in detail with reference to examples.
The substituents are defined as follows:
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.
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.
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 hydrazine group: alkyl-NH-NH-, such as methylhydrazino, ethylhydrazino, n-propylhydrazino, isopropylhydrazino or the isomeric butylhydrazines.
A dialkylhydrazino group: two identical or different linear or branched alkyl radicals linked to the structure via a nitrogen atom, e.g. (CH)3)2N-NH-。
Cycloalkyl hydrazine group: cycloalkyl-NH-NH-, such as cyclopropylhydrazino.
Alkoxyalkyl groups: alkyl-O-alkyl-, e.g. CH3OCH2-。
Aryl: including phenyl and naphthyl.
Aryl-substituted alkyl groups: aryl-alkyl-, e.g. PhCH2-。
Heteroaryl group: refers to a five or six membered ring containing 1 or more heteroatoms of N, O, S. For example, pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyridazinonyl, indolyl, benzofuranyl, benzoxazolyl, benzothienyl, benzothiazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolyl, benzopyrazolyl, quinoxalinyl, and the like.
The present application is described in further detail below with reference to specific examples, which should not be construed as limiting the scope of the invention as claimed.
The invention provides an amide compound, which is characterized by having a structure shown in a formula I:
in formula I:
R1selected from hydrogen, halogen, hydroxy, -NH2、-NHNH2、C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Alkynyl, -OR7、-NR7R8Unsubstituted or optionally substituted aryl, or aryl-substituted C1-C6An alkyl group; wherein R is7And R8Each independently selected from hydrogen and C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Alkynyl, C1-C6Alkoxy radical C1-C6Alkyl, unsubstituted or optionally substituted aryl, or aryl-substituted C1-C6Alkyl, and R7And R8Not hydrogen at the same time; r2Selected from hydrogen, C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Alkynyl, unsubstituted or optionally substituted aryl, unsubstituted or optionally substituted heteroaryl; r3Selected from hydrogen, C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl radical, C2-C8Alkenyl or C2-C8An alkynyl group; r4Selected from hydrogen, C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Alkynyl, unsubstituted or optionally substituted aryl, unsubstituted or optionally substituted heteroaryl; r5And R6Each independently selected from halogen, cyano, nitro, hydroxy, mercapto, -NH2、-NHNH2、C1-C6Alkyl radical, C1-C6Haloalkyl, C3-C8Cycloalkyl radical, C1-C6Alkoxy radical, C1-C6Haloalkoxy, C1-C6Alkylthio radical, C1-C6Haloalkylthio, C2-C8Alkenyl radical, C2-C8Alkynyl, C1-C6Alkylamino radical, C1-C6Haloalkylamino, C1-C6Dialkylamino radical, C3-C8Cycloalkylamino, C1-C6Alkyl hydrazino, C1-C6Haloalkyl hydrazino, C1-C6Dialkylhydrazino group, C3-C8Cycloalkylhydrazino, unsubstituted or optionally substituted aryl, unsubstituted or optionally substituted heteroaryl.
The amide compound has high bactericidal activity, and particularly has good control effect on diseases of various crops caused by various fungi such as oomycetes, basidiomycetes, ascomycetes, deuteromycetes and the like, for example, 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 small leaf spot and the like under low dosage.
In order to further enhance the bactericidal activity of the above amide-based compounds, in a preferred embodiment, R5And R6Each independently selected from halogen, cyano, nitro, hydroxy, mercapto, -NH2、-NHNH2、C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C1-C4Alkoxy radical, C1-C4Haloalkoxy, C1-C4Alkylthio radical, C1-C4Haloalkylthio, C2-C6Alkenyl radical, C2-C6Alkynyl, C1-C4Alkylamino radical, C1-C4Haloalkylamino, C1-C4Dialkylamino radical, C3-C6Cycloalkylamino, C1-C4Alkyl hydrazino, C1-C4Haloalkyl hydrazino, C1-C4Dialkylhydrazino group, C3-C6Cycloalkylhydrazino, unsubstituted or optionally substituted aryl, unsubstituted or optionally substituted heteroaryl.
The preparation cost and the bactericidal activity are combined, so that the large-scale use of the amide compound in the bactericidal field is further improved, preferably, R5And R6Each independently selected from halogenElements, cyano, nitro, hydroxy, mercapto, -NH2、-NHNH2、C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C1-C4Alkoxy radical, C1-C4Alkylthio or C1-C4An alkylamino group; more preferably, R5And R6Each independently selected from halogen, cyano, nitro, hydroxy, mercapto, -NH2、-NHNH2、C1-C4Haloalkyl, C1-C4Alkoxy radical, C1-C4Alkylthio or C1-C4An alkylamino group; further preferably, R5And R6Each independently selected from halogen, cyano, nitro, hydroxy, mercapto, -NH2、-NHNH2Trifluoromethyl, methoxy, methylthio or methylamino.
In a preferred embodiment, R1Selected from hydrogen, halogen, hydroxy, -NH2、-NHNH2、C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl, -OR7、-NR7R8Unsubstituted or optionally substituted aryl, or aryl-substituted C1-C4An alkyl group; wherein R is7And R8Each independently selected from hydrogen and C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl, C1-C4Alkoxy radical C1-C4Alkyl, unsubstituted or optionally substituted aryl, or aryl-substituted C1-C4An alkyl group. Selecting the above R1The structure and the bactericidal effect of the amide compound are better. Preferably, R1Selected from hydrogen, halogen, hydroxy, -NH2、-NHNH2、-OR7or-NR7R8(ii) a Wherein R is7And R8Each independently selected from hydrogen and C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl, C1-C4Alkoxy radical C1-C4Alkyl, unsubstituted or optionally substituted phenyl, or benzyl-; more preferably, R1Is selected from-OR7or-NR7R8(ii) a Wherein R is7And R8Each independently selected from hydrogen and C1-C4Alkyl, trifluoroethyl, cyclopropyl, 1-propenyl, propynyl, methoxyethyl, phenyl or benzyl.
To further enhance the fungicidal activity of the compounds and to reduce production costs, in a preferred embodiment, in formula I, R2Selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl, unsubstituted or optionally substituted aryl, unsubstituted or optionally substituted heteroaryl; r3Selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl or C2-C6An alkynyl group; r4Selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl radical, C2-C6Alkynyl, unsubstituted or optionally substituted aryl, unsubstituted or optionally substituted heteroaryl; preferably, R2Selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl, unsubstituted or optionally substituted phenyl; r3Selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl radical, C2-C6Alkenyl or C2-C6An alkynyl group; r4Selected from hydrogen, C1-C4Alkyl radical, C1-C4Haloalkyl, C3-C6Cycloalkyl, unsubstituted or substitutedOptionally substituted phenyl; more preferably, R2Is selected from C1-C4An alkyl group; r3Selected from hydrogen or methyl; r4Selected from hydrogen, methyl, difluoromethyl or trifluoromethyl.
According to another aspect of the present invention, there is also provided a method for preparing the amide compound, which comprises synthesizing the amide compound according to the following route:
wherein R is1、R2、R3、R4、R5、R6The definition of (A) is the same as that of the amide-based compound described above.
The compounds of formula II above can be prepared by the following procedures, wherein the groups are as defined above, unless otherwise indicated.
Specifically, the compound of formula IV is reacted with the compound of formula V in a suitable solvent in the presence or absence of a suitable base at a temperature of-10 ℃ to the boiling point of the suitable solvent for 0.5-48 hours to obtain the compound of formula II. Wherein the suitable solvent is selected from dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, dioxane, THF, DMF or DMSO, etc. Suitable bases are selected from triethylamine, N-diisopropylethylamine, pyridine, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium methoxide, potassium t-butoxide, and the like. The base here acts as an acid-binding agent.
The preparation method comprises the following steps: LG represents a leaving group, and suitable leaving groups may be selected from halogens or other conventional leaving groups, such as chlorine, bromine, iodine, methane sulfonic acid or methyl benzene sulfonic acid.
Compounds of formula IV may be purchased or prepared by known methods (e.g., WO2015136557, Advances in color Science and Technology (2003),6(3),63-72 or American Journal of organic chemistry (2015),5(2),73-77, etc.); the compounds of formula V are commercially available.
The compounds of the formula III used in the present invention can be obtained commercially or prepared by known methods (for example, WO2014184234, WO2012158844, WO2008085118 or Journal of Medicinal Chemistry (2014),57(14),5949-5964, etc.).
In a preferred embodiment, the above preparation method comprises the steps of: reacting a compound with a structure shown in a formula II with a compound with a structure shown in a formula III in a solvent to obtain an amide compound; preferably, the solvent is selected from one or more of dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, dioxane, THF, DMF and DMSO; preferably, the reaction is carried out in the presence of a base, more preferably a base selected from one or more of triethylamine, N-diisopropylethylamine, pyridine, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium methoxide and potassium tert-butoxide; preferably, the reaction temperature during the reaction is from-10 ℃ to the boiling point temperature of the solvent, and the reaction time is from 0.5 to 48 hours.
The preparation method provided by the invention is used for preparing the amide compound, and has the advantages of short reaction route, mild conditions and high yield.
In addition, the invention also provides application of the amide compound as a bactericide in the fields of agriculture, forestry and sanitation. The compound has good control effect on diseases of various crops caused by various fungi such as oomycetes, basidiomycetes, ascomycetes, deuteromycetes and the like, 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 blight, grape downy mildew, grape white rot, apple ring spot, apple alternaria leaf spot, rice sheath blight, rice blast, wheat rust, wheat leaf spot, wheat powdery mildew, rape sclerotinia rot, corn small spot and the like at a low dose. Can also be used as a bactericide in the hygiene field.
According to another aspect of the invention, the invention also provides a bactericidal composition which comprises the amide compound and an agriculturally acceptable carrier.
The "agriculturally acceptable carrier" described above may specifically be a substance satisfying the following conditions: it is formulated with an active ingredient (an active ingredient having a bactericidal action, such as the above-mentioned amide compounds) and applied to the site to be treated, which may be, for example, a plant, a seed or soil; or to facilitate storage, transport or handling. The carrier may be a solid or a liquid, including materials which are normally gaseous but which have been compressed to form a liquid, and carriers which are normally used in formulating insecticidal and fungicidal compositions may be used.
Suitable solid carriers include natural or synthetic clays or silicates, such as diatomaceous earth, talc, attapulgite, aluminum silicate (kaolin), montmorillonite, mica; calcium carbonate; calcium sulfate; ammonium sulfate; synthetic silica, synthetic calcium silicate or aluminum silicate; elements such as carbon, sulfur; natural or synthetic resins such as benzofuran resins, polyvinyl chloride, styrene polymers or copolymers; solid polychlorophenol; asphalt; waxes such as beeswax, paraffin wax.
Suitable liquid carriers include water; alcohols such as isopropanol, ethanol; ketones such as acetone, methyl ethyl ketone, methyl isopropyl ketone, cyclohexyl ketone; an ether; aromatic hydrocarbons such as benzene, toluene, xylene; petroleum fractions such as kerosene, mineral oil; chlorinated hydrocarbons such as carbon tetrachloride, perchloroethylene, trichloroethylene. In general, mixtures of these liquids are also suitable.
In the above fungicidal composition, the amide-based compound may be a single compound or a mixture of a plurality of compounds.
In a preferred embodiment, the compound shown in the general formula I is used as an active component, and the weight percentage of the active component in the bactericide composition is 0.1-99%.
According to still another aspect of the present invention, there is also provided a method of controlling plant diseases, comprising: the bactericidal composition is applied to the disease or the growth medium of the disease to be controlled at a dosage of 10 g to 1000 g per hectare.
For certain applications, for example in agriculture, one or more other insecticides, fungicides, herbicides, plant growth regulators or fertilizers and the like may be added to the fungicidal compositions of the present invention, thereby providing additional advantages and effects.
The beneficial effects of the present invention are further illustrated by the following examples:
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