CN113480541A - Process for producing imidazopyridine compound and intermediate thereof - Google Patents
Process for producing imidazopyridine compound and intermediate thereof Download PDFInfo
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- CN113480541A CN113480541A CN202110753038.6A CN202110753038A CN113480541A CN 113480541 A CN113480541 A CN 113480541A CN 202110753038 A CN202110753038 A CN 202110753038A CN 113480541 A CN113480541 A CN 113480541A
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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract
The invention discloses a preparation method of an imidazopyridine compound shown in formula (I) and an intermediate compound shown in formula (II), wherein each substituent group has the definition given in the specification. The compound of formula (I) has insecticidal and bactericidal biological activity, especially has high activity on pests such as aphids, plant hoppers and the like, and can be used for preventing and treating pests and diseases such as aphids, plant hoppers, sclerotinia sclerotiorum and the like.
Description
This application is a divisional application
The application date of the original application is as follows: year 2019, 03 month 07
The application numbers of the original applications are: 201910172079.9
The invention name of the original application is: imidazopyridine compound and intermediate, preparation method and application thereof
Technical Field
The invention belongs to the field of pesticides and bactericides, and particularly relates to imidazopyridine compounds with pesticidal and bactericidal biological activities and intermediates thereof, preparation methods of the imidazopyridine compounds and the intermediates, pesticidal and bactericidal compositions containing the imidazopyridine compounds, and application and methods for controlling pests and harmful bacteria by using the imidazopyridine compounds.
Background
The prevention and control of pests and harmful germs are very important in the process of realizing high-efficiency agriculture. The control of pests and harmful germs is also important in forests, herds, paraphernalia, fisheries, and public health. Although many pest and harmful germ control agents are available in the market, due to the continuous expansion of the market and the problems of the resistance of the external pests, harmful germs, pests and harmful germs, the service life of the drugs, the economic efficiency of the drugs and the like, and the increasing attention of people to the environment, the requirements on the pest and harmful germ control agents are increasingly strict, so that scientists are required to continuously research, and then new varieties of the pest and bactericide with high efficiency, safety, economy, environmental compatibility and different action modes are developed.
The neonicotinoid compounds have insecticidal activity, and neonicotinoid insecticides represented by imidacloprid (D1) are excellent in activity and successful in sale, and make a prominent contribution to pest control. Unfortunately neonicotinoid insecticides such as imidacloprid (D1) have undesirable acute toxicity to bees and have a sub-lethal effect, and for that reason, many countries and organizations reevaluate or limit the environmental risk of neonicotinoid insecticides such as imidacloprid (D1), and even ban their use. Under the circumstances, bayer and Meiji Seika Pharma have developed new neonicotinoid insecticides, namely, fluoropyrafuranone and flupyrminin (D2), respectively, in recent years, and although the insecticidal activities of fluoropyrafuranone and flupyrminin (D2) against pests such as aphids do not match those of imidacloprid (D1), they have solved to some extent the disadvantages of neonicotinoid insecticides such as imidacloprid (D1) in terms of high bee toxicity, and the like.
The imidazopyridine compounds with biological activity and intermediates thereof are rare in the literature and even difficult to see. Although the information of imidazopyridine compounds is also given in EP0296453a2, the structures of the compounds in EP0296453a2 are not confirmed by nuclear magnetic resonance, mass spectrometry and the like, and the melting point data are not verified.
In order to obtain bioactive compounds with better environmental compatibility, safety, high efficiency and economy, based on previous results, the imidazopyridine compounds with activities of pests and harmful bacteria shown in a formula (I) which are not reported in documents are designed and synthesized, wherein some compounds have excellent insecticidal activity, some compounds have remarkable bactericidal activity, and compared with neonicotinoid insecticides such as imidacloprid (D1), the imidazopyridine compound is safe for bees.
Disclosure of Invention
The invention provides an imidazopyridine compound with biological activities of pests, harmful bacteria and the like and an isomer thereof, which are shown in a formula (I):
wherein:
I.B is selected from O, S or C1-C12An alkylimino group;
r is selected from hydrogen, halogen, C1-C12Alkyl radical, C2-C12Alkenyl radical, C2-C12Alkynyl, C3-C8Cycloalkyl radical, C3-C8Heterocyclic group, C6-C12Aryl or heteroaryl;
III.R1selected from hydrogen, nitro, cyano, C1-C12Alkyl radical, C1-C12Alkoxycarbonyl, C1-C12Alkyl thiocarbonyl, C1-C12Alkoxycarbonyl thiocarbonyl or C1-C12An alkylthio carbonyl group;
R2selected from hydrogen, halogen, C1-C12Alkyl or C1-C12An alkoxy group;
R3selected from hydrogen, halogen, nitro, cyano, C1-C12Alkyl radical, C1-C12Alkoxycarbonyl, C1-C12Alkyl thiocarbonyl, C1-C12Alkoxycarbonyl thiocarbonyl or C1-C12An alkylthio carbonyl group;
IV.R4、R5、R6And R7Are identical or different and represent hydrogen, halogen, C1-C12Alkyl radical, C2-C12Alkenyl radical, C2-C12Alkynyl, C1-C12Alkoxy radical, C1-C12Alkylthio or C1-C12An alkylamino group;
and 1) hydrogen atoms in I, II, III and IV may be partially or totally substituted by the same or different substituents selected from the group consisting of: halogen, C1-C6Alkyl radical, C1-C6Alkoxy radical, C1-C6Alkylthio radical, C1-C6Alkylamino radical, di (C)1-C6) Alkylamino radical, C2-C6Alkenyl radical, C2-C6Alkenoxy group, C2-C6Alkenylthio radical, C2-C6Alkenamino, di-C2-C6Alkenylamino group, C2-C6Alkynyl, C2-C6Alkynyloxy, C2-C6Alkynylthio, C2-C6Alkynylamino, di-C2-C6Alkynylamino, C3-C8Cycloalkyl radical, C3-C8Cycloalkoxy, C3-C8Cycloalkylthio radical, C3-C8Cycloalkylamino, di-C3-C8Cycloalkylamino, phenyl, phenoxy, anilino, heteroaryl, heteroaryloxy, heteroarylamino; 1) wherein the hydrogen atoms may be partially or wholly substituted by the same or different substituents selected from the group consisting of: halogen, C1-C6Alkyl radical, C1-C6Haloalkyl, C1-C6Alkoxy radical, C1-C6Haloalkoxy, C1-C6Alkylthio radical, C1-C6Haloalkylthio, C1-C6Alkylamino radical or C1-C6A halogenated alkylamino group;
in the definitions of the compounds (I) given above, the terms used, whether used alone or in compound words, represent the following substituents:
halogen: fluorine, chlorine, bromine, iodine;
Alkyl groups: refers to straight or branched chain alkyl;
cycloalkyl groups: refers to saturated and unsaturated cycloalkyl groups;
alkenyl: means straight or branched and may have a double bond present at any position;
alkynyl: refers to a straight or branched chain and may have a triple bond at any position;
C6-C12aryl: phenyl, naphthyl, anthryl or phenanthryl;
heteroaryl group: refers to thiazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, quinolinyl, furanyl, thienyl, pyrrolyl or to varying degrees hydride of the above heteroaryl;
halogenation: means that the hydrogen atoms are partially or completely substituted by halogen atoms.
Preferred compounds of the invention are compounds of formula (I) wherein:
I.B is selected from O, S or C1-C12An alkylimino group;
r is selected from thiazolyl or pyridyl;
III.R1selected from nitro, cyano or trifluoromethyl;
R2selected from hydrogen, halogen or C1-C12An alkyl group;
R3selected from hydrogen, halogen or C1-C12An alkyl group;
IV.R4、R5、R6and R7Are identical or different and represent hydrogen, halogen or C1-C12An alkyl group;
and the hydrogen atoms in I, II, III and IV may be partially or wholly substituted by the same or different substituents selected from the group consisting of: halogen, C1-C6Alkyl radical, C1-C6Haloalkyl, C1-C6Alkoxy radical, C1-C6Haloalkoxy, C1-C6Alkylthio or C1-C6A haloalkylthio group.
Further preferred compounds of the invention are compounds of formula (I) wherein:
I.B is selected from O;
r is selected from 2-chlorothiazol-5-yl, 2-chloropyridin-5-yl or 2-trifluoromethylpyridin-5-yl;
III.R1is selected from nitro;
R2selected from hydrogen, halogen or C1-C6An alkyl group;
R3selected from hydrogen, halogen or C1-C6An alkyl group;
IV.R4、R5、R6and R7Are identical or different and represent hydrogen, halogen or C1-C6An alkyl group.
Particularly preferred compounds of the invention are compounds of formula (I) wherein:
I.B is selected from O;
r is selected from 2-chlorothiazol-5-yl, 2-chloropyridin-5-yl or 2-trifluoromethylpyridin-5-yl;
III.R1is selected from nitro;
R2selected from hydrogen, methyl or ethyl;
R3selected from hydrogen, methyl or ethyl;
IV.R4、R5、R6and R7Are the same or different and are substitutedEpi-hydrogen or C1-C3An alkyl group.
Particularly preferred compounds of formula (I) according to the invention are the following compounds:
1- ((2-chlorothiazol-5-yl) methyl) -8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
1- ((2-chlorothiazol-5-yl) methyl) -3-methyl-8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
1- ((2-chlorothiazol-5-yl) methyl) -2-methyl-8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
(S) -1- ((2-chlorothiazol-5-yl) methyl) -2-methyl-8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
1- ((2-chlorothiazol-5-yl) methyl) -2-ethyl-8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
1- ((2-chlorothiazol-5-yl) methyl) -7-methyl-8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
1- ((2-phenylthiazol-4-yl) methyl) -8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
1- ((2- (4-methylphenyl) thiazol-4-yl) methyl) -8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
1- ((2-chloropyridin-5-yl) methyl) -8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
1- ((2-chloropyridin-5-yl) methyl) -3-methyl-8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
1- ((2-chloropyridin-5-yl) methyl) -2-methyl-8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
1- ((2-chloropyridin-5-yl) methyl) -2-ethyl-8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
1- ((2-chloropyridin-5-yl) methyl) -7-methyl-8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
1- ((tetrahydrofuran-3-yl) methyl) -8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
1-ethyl-8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
1- (2-chloroethyl) -8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
1- ((2-chloropyridin-5-yl) methyl) -8-cyano-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
1- ((2-chloropyridin-5-yl) methyl) -8-trifluoromethyl-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
1- ((2-chlorophenyl) methyl) -8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one;
n-ethyl-1- ((2-chloropyridin-5-yl) methyl) -8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -imine;
1- ((2-trifluoromethylpyridin-5-yl) methyl) -8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one.
The compound of formula (II) is an important intermediate for preparing the compound of formula (I) of the invention, and the structure and physicochemical properties of the compound are not reported. Therefore, the technical scheme of the invention also comprises an intermediate compound shown as a formula (II) for preparing the compound shown as the formula (I), and a preparation method and application of the compound shown as the formula (II), wherein the structural formula of the intermediate shown as the formula (II) is as follows:
in the formula:
l is selected from halogen or C1-C6An alkoxy group;
r is selected from hydrogen, halogen and C1-C12Alkyl radical, C2-C12Alkenyl radical, C2-C12Alkynyl, C3-C8Cycloalkyl radical, C3-C8Heterocyclic group, C6-C12Aryl or heteroaryl;
R1selected from hydrogen, nitro, cyano, C1-C12Alkyl radical, C1-C12Alkoxycarbonyl, C1-C12Alkyl thiocarbonyl, C1-C12Alkoxycarbonyl thiocarbonyl or C1-C12An alkylthio carbonyl group; r 2Selected from hydrogen, halogen, C1-C12Alkyl or C1-C12An alkoxy group; r3Selected from hydrogen, halogen, nitro, cyano, C1-C12Alkyl radical, C1-C12Alkoxycarbonyl, C1-C12Alkyl thiocarbonyl, C1-C12Alkoxycarbonyl thiocarbonyl or C1-C12An alkylthio carbonyl group;
R4、R5、R6and R7Are identical or different and represent hydrogen, halogen, C1-C12Alkyl radical, C2-C12Alkenyl radical, C2-C12Alkynyl, C1-C12Alkoxy radical, C1-C12Alkylthio or C1-C12An alkylamino group;
and R, R1、R2、R3、R4、R5、R6And R7Wherein the hydrogen atoms may be partially or wholly substituted by the same or different substituents selected from the group consisting of: halogen, C1-C6Alkyl radical, C1-C6Haloalkyl, C1-C6Alkoxy radical, C1-C6Haloalkoxy, C1-C6Alkylthio radical, C1-C6Haloalkylthio, C1-C6Alkylamino radical or C1-C6A halogenated alkylamino group;
in the definitions of the compounds of formula (II) given above, the terms used, whether used alone or in compound words, represent the following substituents:
halogen: fluorine, chlorine, bromine, iodine;
alkyl groups: refers to straight or branched chain alkyl;
cycloalkyl groups: refers to saturated and unsaturated cycloalkyl groups;
alkenyl: means straight or branched and may have a double bond present at any position;
alkynyl: refers to a straight or branched chain and may have a triple bond at any position;
C6-C12aryl: phenyl, naphthyl, anthryl or phenanthryl;
heteroaryl group: refers to thiazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, quinolinyl, furanyl, thienyl, pyrrolyl or to varying degrees hydride of the above heteroaryl;
Halogenation: means that the hydrogen atoms are partially or completely substituted by halogen atoms.
Preferred compounds of formula (II) according to the invention are the following compounds:
n- ((2-chlorothiazol-5-yl) methyl) -N- (2-hydroxyethyl) -6-methoxy-3-nitropyridin-2-amine;
n- ((2-chlorothiazol-5-yl) methyl) -N- (2-hydroxyethyl) -6-chloro-3-nitropyridin-2-amine;
n- ((2-chlorothiazol-5-yl) methyl) -N- (2-hydroxypropyl) -6-methoxy-3-nitropyridin-2-amine;
n- ((2-chlorothiazol-5-yl) methyl) -N- (2-hydroxypropyl) -6-chloro-3-nitropyridin-2-amine;
n- ((2-chlorothiazol-5-yl) methyl) -N- (1-hydroxypropan-2-yl) -6-methoxy-3-nitropyridin-2-amine;
n- ((2-chlorothiazol-5-yl) methyl) -N- (1-hydroxypropan-2-yl) -6-chloro-3-nitropyridin-2-amine;
(S) -N- ((2-chlorothiazol-5-yl) methyl) -N- (1-hydroxypropan-2-yl) -6-methoxy-3-nitropyridin-2-amine;
(S) -N- ((2-chlorothiazol-5-yl) methyl) -N- (1-hydroxypropan-2-yl) -6-chloro-3-nitropyridin-2-amine;
n- ((2-chlorothiazol-5-yl) methyl) -N- (1-hydroxybutan-2-yl) -6-methoxy-3-nitropyridin-2-amine;
n- ((2-chlorothiazol-5-yl) methyl) -N- (1-hydroxybutan-2-yl) -6-chloro-3-nitropyridin-2-amine;
n- ((2-chlorothiazol-5-yl) methyl) -N- (2-hydroxyethyl) -4-methyl-6-methoxy-3-nitropyridin-2-amine;
N- ((2-chlorothiazol-5-yl) methyl) -N- (2-hydroxyethyl) -4-methyl-6-chloro-3-nitropyridin-2-amine;
n- ((2-phenylthiazol-4-yl) methyl) -N- (2-hydroxyethyl) -6-methoxy-3-nitropyridin-2-amine;
n- ((2-phenylthiazol-4-yl) methyl) -N- (2-hydroxyethyl) -6-chloro-3-nitropyridin-2-amine;
n- ((2- (4-methylphenyl) thiazol-4-yl) methyl) -N- (2-hydroxyethyl) -6-methoxy-3-nitropyridin-2-amine;
n- ((2- (4-methylphenyl) thiazol-4-yl) methyl) -N- (2-hydroxyethyl) -6-chloro-3-nitropyridin-2-amine;
n- ((2-chloropyridin-5-yl) methyl) -N- (2-hydroxyethyl) -6-methoxy-3-nitropyridin-2-amine;
n- ((2-chloropyridin-5-yl) methyl) -N- (2-hydroxyethyl) -6-chloro-3-nitropyridin-2-amine;
n- ((2-chloropyridin-5-yl) methyl) -N- (2-hydroxypropyl) -6-methoxy-3-nitropyridin-2-amine;
n- ((2-chloropyridin-5-yl) methyl) -N- (2-hydroxypropyl) -6-chloro-3-nitropyridin-2-amine;
n- ((2-chloropyridin-5-yl) methyl) -N- (1-hydroxypropan-2-yl) -6-methoxy-3-nitropyridin-2-amine;
n- ((2-chloropyridin-5-yl) methyl) -N- (1-hydroxypropan-2-yl) -6-chloro-3-nitropyridin-2-amine;
n- ((2-chloropyridin-5-yl) methyl) -N- (1-hydroxybutan-2-yl) -6-methoxy-3-nitropyridin-2-amine;
N- ((2-chloropyridin-5-yl) methyl) -N- (1-hydroxybutan-2-yl) -6-chloro-3-nitropyridin-2-amine;
n- ((2-chloropyridin-5-yl) methyl) -N- (2-hydroxyethyl) -4-methyl-6-methoxy-3-nitropyridin-2-amine;
n- ((2-chloropyridin-5-yl) methyl) -N- (2-hydroxyethyl) -6-chloro-4-methyl-3-nitropyridin-2-amine;
n- ((tetrahydrofuran-3-yl) methyl) -N- (2-hydroxyethyl) -6-methoxy-3-nitropyridin-2-amine;
n- ((tetrahydrofuran-3-yl) methyl) -N- (2-hydroxyethyl) -6-chloro-3-nitropyridin-2-amine;
N-ethyl-N- (2-hydroxyethyl) -6-methoxy-3-nitropyridin-2-amine;
N-ethyl-N- (2-hydroxyethyl) -6-chloro-3-nitropyridin-2-amine;
n- (2-chloroethyl) -N- (2-hydroxyethyl) -6-methoxy-3-nitropyridin-2-amine;
n- (2-chloroethyl) -N- (2-hydroxyethyl) -6-chloro-3-nitropyridin-2-amine;
n- ((2-chloropyridin-5-yl) methyl) -N- (2-hydroxyethyl) -6-methoxy-3-cyanopyridin-2-amine;
n- ((2-chloropyridin-5-yl) methyl) -N- (2-hydroxyethyl) -6-chloro-3-cyanopyridin-2-amine;
n- ((2-chloropyridin-5-yl) methyl) -N- (2-hydroxyethyl) -6-methoxy-3-trifluoromethylpyridin-2-amine;
n- ((2-chloropyridin-5-yl) methyl) -N- (2-hydroxyethyl) -6-chloro-3-trifluoromethylpyridin-2-amine;
N- ((2-chlorophenyl) methyl) -N- (2-hydroxyethyl) -6-methoxy-3-nitropyridin-2-amine;
n- ((2-chlorophenyl) methyl) -N- (2-hydroxyethyl) -6-chloro-3-nitropyridin-2-amine;
n- ((2-trifluoromethylpyridin-5-yl) methyl) -N- (2-hydroxyethyl) -6-methoxy-3-nitropyridin-2-amine;
n- ((2-trifluoromethylpyridin-5-yl) methyl) -N- (2-hydroxyethyl) -6-chloro-3-nitropyridin-2-amine.
The compounds of the present invention may exist in the form of one or more isomers. Isomers of the compound of formula (I) or formula (II) include enantiomers, diastereomers, geometric isomers, rotamers, and tautomers; the compound of formula (I) or the compound of formula (II) of the present invention can form geometrical isomers due to different substituents connected to the carbon-carbon double bond or the carbon-nitrogen double bond, and Z and E represent different configurations respectively, and the present invention includes Z-type isomers and E-type isomers and mixtures thereof in any proportion; the invention relates to a compound of formula (I) or a compound of formula (II), which forms stereoisomers by connecting four different substituents on the same carbon atom or three different substituents on the same nitrogen atom, wherein R and S respectively represent different configurations, and the invention comprises R-type isomers and S-type isomers and mixtures thereof in any proportion; the invention relates to a compound of formula (I: B ═ O)) which forms isomers due to the fact that carbonyl group C ═ O is located at 2-of pyridine ring, different isomers are respectively represented by I and I ', and the invention comprises I type isomers and I' type isomers and mixtures thereof in any proportion. When B in formula (I) represents oxygen, one of the I' isomers may be represented as follows:
In the formula (I'), B represents O, R, R1、R2、R3、R4、R5、R6And R7As defined in claim 1.
Particularly preferred compounds of formula (I') according to the invention are:
1- ((2-chlorothiazol-5-yl) methyl) -8-nitro-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
1- ((2-chlorothiazol-5-yl) methyl) -3-methyl-8-nitro-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
1- ((2-chlorothiazol-5-yl) methyl) -2-methyl-8-nitro-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
(S) -1- ((2-chlorothiazol-5-yl) methyl) -2-methyl-8-nitro-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
1- ((2-chlorothiazol-5-yl) methyl) -2-ethyl-8-nitro-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
1- ((2-chlorothiazol-5-yl) methyl) -7-methyl-8-nitro-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
1- ((2-phenylthiazol-4-yl) methyl) -8-nitro-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
1- ((2- (4-methylphenyl) thiazol-4-yl) methyl) -8-nitro-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
1- ((2-chloropyridin-5-yl) methyl) -8-nitro-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
1- ((2-chloropyridin-5-yl) methyl) -3-methyl-8-nitro-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
1- ((2-chloropyridin-5-yl) methyl) -2-methyl-8-nitro-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
1- ((2-chloropyridin-5-yl) methyl) -2-ethyl-8-nitro-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
1- ((2-chloropyridin-5-yl) methyl) -7-methyl-8-nitro-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
1- ((tetrahydrofuran-3-yl) methyl) -8-nitro-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
1-ethyl-8-nitro-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
1- (2-chloroethyl) -8-nitro-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
1- ((2-chloropyridin-5-yl) methyl) -8-cyano-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
1- ((2-chloropyridin-5-yl) methyl) -8-trifluoromethyl-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
1- ((2-chlorophenyl) methyl) -8-nitro-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt;
1- ((2-trifluoromethylpyridin-5-yl) methyl) -8-nitro-2, 3-dihydro-1H-imidazo [1,2-a ] pyridin-4-ium-5-salt.
The invention also relates to a composition for controlling pests or harmful bacteria, comprising a biologically effective amount of a compound of formula (I) and at least one further diluent selected from the group consisting of surfactants, solid diluents and liquid diluents.
The invention also relates to a composition for controlling pests or harmful bacteria, comprising a biologically effective amount of a compound of formula (I) and an effective amount of at least one further biologically active compound or agent.
The invention also relates to a method for controlling pests or harmful bacteria, which comprises contacting the pests, harmful bacteria or their environment with a biologically effective amount of a compound of formula (I). Also disclosed is a method for controlling pests or harmful bacteria by contacting the pests, harmful bacteria or their environment with a biologically effective amount of a compound of formula (I) or a mixture containing a compound of formula (I) and a biologically effective amount of at least one additional compound or agent.
The compounds of formula (I) of the present invention have a broad spectrum of activity: these compounds are useful for controlling pests or harmful germs. And some compounds have high biological activity to some pests or harmful germs, so that good effect can be obtained at low dosage.
Preferred compositions of the invention are those containing the preferred compounds described above. Preferred methods are those using the preferred compounds described above.
The present invention is further illustrated, but not limited, by the following tables 1-2, which list some of the compounds of formula (I) and tables 3-4, which list some of the compounds of formula (II). The melting points given in the present invention are not corrected; when the compound of formula (I) and the compound of formula (II) synthesized by the invention are viscous liquid or viscous solid, some viscous liquid or viscous solid can be solidified into non-viscous solid after being placed; molecular ion peak M of all compounds in Table 1 was observed in LC-MS (APCI, Pos) (Agilent 1260/6120Series LC/MSD) ++ 1; the molecular ion peak M of the compound in Table 3 can be observed in LC-MS (APCI, Pos) (Agilent 1260/6120Series LC/MSD)++1, its molecular ion peak M is typically observed in GC-MS (EI, 70Ev M/z) (Agilent 7890-+(ii) a Of the compounds in tables 1 and 31H NMR (Varian INOVA-300spectrometer or Varian INOVA-500spectrometer) with Tetramethylsilane (TMS) as internal standard, deuterated chloroform (CDCl)3) Or deuterated dimethyl sulfoxide (DMSO) and the like as solvents,13c NMR (Varian INOVA-125spectrometer) with Tetramethylsilane (TMS) as internal standard, deuterated chloroform (CDCl)3) Or deuterated dimethyl sulfoxide (DMSO), etc. as a solvent.
The structure of the compound of formula (I) can be confirmed by combining the HPLC analysis result, mass spectrum data, nuclear magnetic information and single crystal data of the derivative of the compound of formula (I). The structures of the compounds in table 3 are confirmed by MS, most of the compounds in table 3 are confirmed by nuclear magnetism, and for the sake of convenience, table 4 lists only part of the nuclear magnetism data and physical property data of the compounds of formula (II).
TABLE 1
TABLE 2
TABLE 3
TABLE 4
The compound represented by formula (I) of the present invention can be obtained by reaction formula 1 shown below; the (II) in the reaction formula 1 can be obtained by the reaction formula 2 shown below; the compounds (III), (IV) and (VI) in the reaction scheme 2 can be obtained by purchase or prepared according to the relevant reference methods. The invention relates to compounds of formula (I) Can also be obtained by the reaction formula 3 shown below; (VII) and (VIII) in equation 3 can be obtained commercially or prepared by methods of the relevant references; l in the reaction formula is C1-C3Alkoxy, fluorine, chlorine, bromine or iodine, etc., L 'is fluorine, chlorine, bromine or iodine, etc., R' is methyl, ethyl or propyl, etc.; the other substituents are as defined above unless otherwise indicated.
Reaction formula 1:
reaction formula 2:
reaction formula 3:
the compounds of formula (I) may be prepared by: the compound of formula (I) (reaction formula 1) can be prepared from the compound of formula (II) in a suitable solvent such as tetrahydrofuran, 1, 4-dioxane, acetone, benzene, toluene, xylene, methanol, ethanol, dichloromethane, dichloroethane, chloroform, tetrachloromethane, hexane, ethyl acetate, acetonitrile, dimethyl sulfoxide or N, N-dimethylformamide, singly or in a mixture of any two thereof, at a temperature of-10 ℃ to the reflux temperature of the system, in the presence of a suitable halogenating agent such as thionyl chloride, thionyl bromide, phosphorus trichloride or phosphorus pentachloride.
The compounds of formula (II) may be prepared by: reacting the compound shown in the formula (III) with the compound shown in the formula (IV) in a single or a mixed solvent of any two of a proper solvent such as water, tetrahydrofuran, 1, 4-dioxane, acetone, benzene, toluene, xylene, methanol, ethanol, dichloromethane, dichloroethane, chloroform, tetrachloromethane, hexane, ethyl acetate, acetonitrile, dimethyl sulfoxide or N, N-dimethylformamide at a temperature of-15 ℃ to system reflux temperature to obtain the compound shown in the formula (V), and adding a proper base such as triethylamine, N-dimethylaniline, pyridine, picoline, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydride, sodium methoxide, sodium tert-butoxide, potassium tert-butoxide or sodium hydrogen carbonate to promote or facilitate the reaction when necessary; in a suitable solvent such as water, tetrahydrofuran, 1, 4-dioxane, benzene, toluene, xylene, methanol, ethanol, dichloromethane, dichloroethane, chloroform, tetrachloromethane, hexane, ethyl acetate, acetonitrile, dimethyl sulfoxide or N, N-dimethylformamide or a mixture of any two of them, at a temperature of-15 ℃ to system reflux temperature, in the presence of a suitable base such as triethylamine, N-dimethylaniline, pyridine, picoline, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydride, sodium methoxide, sodium tert-butoxide, potassium tert-butoxide or sodium bicarbonate, the compound represented by formula (V) and the compound represented by formula (VI) are reacted to obtain the compound represented by formula (II) (reaction formula 2).
The compounds of formula (I) may also be prepared by: the compound of formula (VII) is reacted with the compound of formula (VIII) in a suitable solvent such as tetrahydrofuran, 1, 4-dioxane, acetone, benzene, toluene, xylene, methanol, ethanol, dichloromethane, dichloroethane, chloroform, tetrachloromethane, hexane, ethyl acetate, acetonitrile, dimethyl sulfoxide or a mixture of any two of them at a temperature of-10 deg.C to reflux the system to obtain the compound of formula (I: B ═ O, R ═ N-dimethylformamide3H) compound, followed by a compound of formula (I: b ═ O, R3H) compound to give a compound of formula (I) (reaction formula 3).
Specific synthetic methods are set forth in more detail in the examples below.
The present invention is further illustrated by the following examples, which are not intended to limit the scope of the invention, but the yields in the examples are not optimized.
The compound of formula (I) provided by the invention has broad-spectrum bioactivity at the dosage of 15-2250 g of active ingredient per hectare, and can be used for preventing and treating harmful insects and harmful germs. Some compounds have good pest control effect and can obtain good effect at very low dosage.
The compound of the formula (I) has bioactivity, and the compound has good bioactivity, and particularly shows activity in the aspects of preventing and controlling agricultural, horticultural, flower and sanitary pests and germs. Pests as used herein include, but are not limited to:
Harmful insects: orthoptera such as Blatta seu periplaneta, Thysanoptera such as thrips gossypii, thrips oryzae, thrips citrulli, Homoptera such as leafhopper, plant hopper, aphid, mealybug, Hemiptera such as whitefly, Lepidoptera such as Oriental armyworm, Spodoptera litura, diamond back moth, beet armyworm, cabbage looper, Hymenoptera such as Apidae larvae, Diptera such as Aedes aegypti, Culex, fly; acarina such as Panonychus citri, Tetranychus gossypii, Tetranychus urticae;
harmful pathogenic bacteria: phytophthora species, erysiphe species, gibberella species, venturia species, sclerotinia species, rhizoctonia species, botrytis species, pyricularia species, fusarium species. Such as rice blast (Pyricularia oryzae); wheat stripe rust (Puccinia striiformis), leaf rust (Puccinia recondita) and other rust diseases; barley stripe rust (Puccinia striiformis), leaf rust (Puccinia recondita) and other rust; barley and wheat powdery mildew (Erysiphe graminis), cucumber powdery mildew (Sphaerotheca fuligena), apple powdery mildew (podosphaea leucotricha) and grape powdery mildew (podosphaea leucotricha); sheath and glume blight of wheat (Septoria nodorum). Helminthosporium, Mortierella, Sclerotiella, Pseudocercospora herpotrichoides, and wheat take-all (Gaeumannomyces graminis) on cereals. Cercospora arachidicola (Cercospora arachidicola) and Cercospora black spot (Cercospora personata); apple ring rot pathogen (Botryosphaeria berenggiana f.sp. piricola), apple rot pathogen (cytopora sp.); urospora disease on beet, soybean and rice. Tomato, cucumber, grape gray mold (Botrytis cinerea). Geobacillus disease in vegetables (e.g., cucumber). Anthracnose in cucumber, apple scab, cucumber downy mildew, grape downy mildew, blight in potato and tomato, the monad Thanatephorus cupmeris on rice and other rhizoctonia species on other hosts such as wheat and barley, vegetables; sclerotinia sclerotiorum (sclerotiorum); wheat scab (Gibberella zeae); phytophthora capsici (Phytophythora capsicii).
The compounds of formula (I) of the present invention are effective against pests, harmful bacteria, alone, and they may also be used together with other biochemical substances including other insecticides, nematocides, acaricides and bactericides.
The agricultural preparation using the compound of formula (I) provided by the invention as an effective ingredient can be made into any desired dosage forms such as dry compressed particles, flowable compositions, granules, wettable powders, water dispersible granules, emulsifiable concentrates, powders, powdery concentrates, microemulsions, suspensions, emulsifiable concentrates, aqueous emulsions, soluble liquid agents, aqueous solutions, dispersible liquid agents, and suitable auxiliaries including carriers (diluents) and other adjuvants such as spreaders, emulsifiers, wetting agents, dispersants, stickers and decomposers. These formulations comprise the compounds of the present invention in admixture with an inert, pharmacologically acceptable solid or liquid diluent.
Examples of the compositions of the present invention may also be formulated into any desired dosage form such as dry compressed granules, flowable compositions, granules, wettable powders, water dispersible granules, emulsifiable concentrates, dusts, powdered concentrates, microemulsions, suspensions, emulsifiable concentrates, emulsions in water, soluble liquids, mists, dispersible liquids, suitable adjuvants including carriers (diluents) and other adjuvants such as spreaders, emulsifiers, wetting agents, dispersants, stickers and disintegrants. These formulations comprise the compounds of the present invention in admixture with an inert, pharmacologically acceptable solid or liquid diluent.
The invention is further illustrated by the following examples, all without optimization of the yields.
Detailed Description
Synthetic examples
EXAMPLE 1 this example illustrates the preparation of compound 1 of Table 1 and compound II-1 of Table 3
To a solution of 2-aminoethanol (0.25mol) in N, N-dimethylformamide (DMF, 50mL) was slowly added dropwise a mixed solution of 2-chloro-5-chloromethylthiazole (0.10mol) and DMF (10mL) with cooling in an ice-water bath and stirring. After the dropwise addition is finished, stirring and reacting at the temperature of 0-35 ℃ until the reaction is completed. The reaction mixture is worked up conventionally: adding ice brine, extracting with ethyl acetate, washing the organic phase with water, drying the organic phase with anhydrous sodium sulfate, removing the solvent under reduced pressure to obtain the crude product of the title compound, and purifying the crude product by column chromatography to obtain the title compound of light yellow viscous liquid with the yield of more than 80%. The structure is confirmed by MS.
N- (2-Chlorothiazol-5-yl) methyl-N- (2-hydroxyethyl) -6-methoxy-3-nitropyridine-2-amine 2- (((2-Chlorothiazol-5-yl) methyl) amino) ethanol (0.13mol), 2-chloro-3-nitro-6-methoxypyridine (0.10mol) and anhydrous potassium carbonate (0.13mol) were dissolved in acetonitrile (150mL) and the reaction was stirred at 0-35 ℃ until complete. The reaction mixture is worked up conventionally: adding ice brine, extracting with ethyl acetate, washing the organic phase with water, drying the organic phase with anhydrous sodium sulfate, removing the solvent under reduced pressure to obtain the crude product of the title compound, and purifying the crude product by column chromatography to obtain the title compound of light yellow solid with the yield of more than 80%. The structure is confirmed by MS.
To a solution of N- (2-chlorothiazol-5-yl) methyl-N- (2-hydroxyethyl) -6-methoxy-3-nitropyridin-2-amine (0.01mol) in dichloromethane (20mL) was slowly added dropwise a mixture of thionyl chloride (0.015mol) and dichloromethane (5mL) with cooling in an ice-water bath of 1- ((2-chlorothiazol-5-yl) methyl) -8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one and stirring. After the dropwise addition is finished, stirring and reacting at the temperature of 0-35 ℃ until the reaction is completed. Filtering, washing filter cake with petroleum ether, and recrystallizing with ethanol and/or water to obtain the title compound as yellow solid. The yield thereof was found to be 80%.
Example 2 this example illustrates the preparation of compound 1 of table 1
1- ((2-chlorothiazol-5-yl) methyl) -8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one 2-chloro-5- ((2- (nitromethylene) imidazolin-1-yl) methyl) thiazole (0.01mol) and ethyl propargionate (0.01mol) were reacted in ethanol (20mL) under reflux with stirring for 10-20H until the reaction was complete. The reaction mixture was concentrated and purified by column chromatography to give the title compound as a yellow solid. The yield thereof was found to be 55%.
Example 3 this example illustrates the preparation of compound 2 in Table 1 and II-3 in Table 3
To a solution of 1-amino-2-propanol (0.25mol) in N, N-dimethylformamide (DMF, 50mL) was slowly added dropwise a mixed solution of 2-chloro-5-chloromethylthiazole (0.10mol) and DMF (10mL) with cooling in an ice-water bath and stirring. After the dropwise addition is finished, the reaction is carried out at the temperature of 0-35 ℃ until the reaction is completed. The reaction mixture is worked up conventionally: adding ice brine, extracting with ethyl acetate, washing the organic phase with water, drying the organic phase with anhydrous sodium sulfate, removing the solvent under reduced pressure to obtain the crude product of the title compound, and purifying the crude product by column chromatography to obtain the title compound of light yellow viscous liquid with the yield of more than 70%. The structure is confirmed by MS.
N- ((2-Chlorothiazol-5-yl) methyl) -N- (2-hydroxypropyl) -6-methoxy-3-nitropyridin-2-amine 1- (((2-Chlorothiazol-5-yl) methyl) amino) propan-2-ol (0.13mol), 2-chloro-6-methoxy-3-nitropyridine (0.10mol) and anhydrous potassium carbonate (0.13mol) in acetonitrile (150mL) reacted to completion at 0-35 ℃. The reaction mixture is worked up conventionally: adding ice brine, extracting with ethyl acetate, washing the organic phase with water, drying the organic phase with anhydrous sodium sulfate, removing the solvent under reduced pressure to obtain the crude product of the title compound, and purifying the crude product by column chromatography to obtain the title compound of light yellow solid with the yield of 70%. The structure is confirmed by MS.
To a solution of N- ((2-chlorothiazol-5-yl) methyl) -N- (2-hydroxypropyl) -6-methoxy-3-nitropyridin-2-amine (0.01mol) in chloroform (20mL) under cooling in an ice-water bath and stirring 1- ((2-chlorothiazol-5-yl) methyl) -3-methyl-8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one was slowly added dropwise a mixed solution of thionyl chloride (0.015mol) and chloroform (5 mL). After the dropwise addition is finished, the reaction is carried out at the temperature of 0-35 ℃ until the reaction is completed. Filtering, washing filter cake with petroleum ether, and recrystallizing with ethanol and/or water to obtain the title compound as yellow solid. The yield thereof was found to be 70%.
Example 4 this example illustrates the preparation of compound 6 in Table 1 and compounds II-12 in Table 3
N- ((2-Chlorothiazol-5-yl) methyl) -N- (2-hydroxyethyl) -4-methyl-6-chloro-3-nitropyridin-2-amine 2- (((2-chlorothiazol-5-yl) methyl) amino) ethanol (0.13mol), 2, 6-dichloro-4-methyl-3-nitropyridine (0.10mol) and anhydrous potassium carbonate (0.13mol) were in acetonitrile (150mL) and the reaction was stirred to completion at 0-35 ℃. The reaction mixture is worked up conventionally: adding ice brine, extracting with ethyl acetate, washing the organic phase with water, drying the organic phase with anhydrous sodium sulfate, removing the solvent under reduced pressure to obtain the crude product of the title compound, and purifying the crude product by column chromatography to obtain the title compound of light yellow solid with the yield of more than 80%.
To a solution of N- ((2-chlorothiazol-5-yl) methyl) -N- (2-hydroxyethyl) -4-methyl-6-chloro-3-nitropyridin-2-amine (0.01mol) in dichloromethane (20mL) under cooling in an ice-water bath and stirring conditions of 1- ((2-chlorothiazol-5-yl) methyl) -7-methyl-8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one, a mixed solution of thionyl chloride (0.015mol) and dichloromethane (5mL) was slowly added dropwise. After the dropwise addition is finished, stirring and reacting at the temperature of 0-35 ℃ until the reaction is completed. Filtering, washing filter cake with petroleum ether, and recrystallizing with ethanol and/or water to obtain the title compound as yellow solid. The yield thereof was found to be 80%.
Example 5 this example illustrates the preparation of compound 9 in Table 1 and II-17 in Table 3
To a solution of 2-aminoethanol (0.25mol) in N, N-dimethylformamide (DMF, 50mL) was slowly added dropwise a mixed solution of 2-chloro-5-chloromethylpyridine (0.10mol) and DMF (10mL) with cooling in an ice-water bath and stirring. After the dropwise addition is finished, the reaction is carried out at the temperature of 0-35 ℃ until the reaction is completed. The reaction mixture is worked up conventionally: adding ice brine, extracting with ethyl acetate, washing the organic phase with water, drying the organic phase with anhydrous sodium sulfate, removing the solvent under reduced pressure to obtain the crude product of the title compound, and purifying the crude product by column chromatography to obtain the title compound of light yellow viscous liquid with the yield of more than 80%.
N- (2-Chloropyridin-5-yl) methyl-N- (2-hydroxyethyl) -6-methoxy-3-nitropyridin-2-amine 2- (((2-Chloropyridin-5-yl) methyl) amino) ethanol (0.13mol), 2-chloro-6-methoxy-3-nitropyridine (0.10mol) and anhydrous potassium carbonate (0.13mol) in acetonitrile (150mL) at 0-35 ℃ to completion. The reaction mixture is worked up conventionally: adding ice brine, extracting with ethyl acetate, washing the organic phase with water, drying the organic phase with anhydrous sodium sulfate, removing the solvent under reduced pressure to obtain the crude product of the title compound, and purifying the crude product by column chromatography to obtain the title compound of light yellow solid with the yield of 80%. The structure is confirmed by MS.
To a solution of N- (2-chloropyridin-5-yl) methyl-N- (2-hydroxyethyl) -6-methoxy-3-nitropyridin-2-amine (0.01mol) in chloroform (20mL) was slowly added dropwise a mixed solution of thionyl chloride (0.015mol) and chloroform (5mL) with cooling in an ice-water bath of 1- ((2-chloropyridin-5-yl) methyl) -8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one and stirring. After the dropwise addition is finished, the reaction is carried out at the temperature of 0-35 ℃ until the reaction is completed. Filtering, washing filter cake with petroleum ether, and recrystallizing with ethanol and/or water to obtain the title compound as yellow solid. The yield thereof was found to be 80%.
Example 6 this example illustrates the preparation of compound 13 in Table 1 and compounds II-25 in Table 3
N- (2-Chloropyridin-5-yl) methyl-N- (2-hydroxyethyl) -6-methoxy-4-methyl-3-nitropyridin-2-amine 2- (((2-chloropyridin-5-yl) methyl) amino) ethanol (0.13mol), 2-chloro-4-methyl-6-methoxy-3-nitropyridine (0.10mol) and anhydrous potassium carbonate (0.13mol) in acetonitrile (150mL) were stirred to completion at 0-35 ℃. The reaction mixture is worked up conventionally: adding ice brine, extracting with ethyl acetate, washing the organic phase with water, drying the organic phase with anhydrous sodium sulfate, removing the solvent under reduced pressure to obtain the crude product of the title compound, and purifying the crude product by column chromatography to obtain the title compound of light yellow solid with the yield of 80%. The structure is confirmed by MS.
To a solution of N- (2-chloropyridin-5-yl) methyl-N- (2-hydroxyethyl) -6-methoxy-4-methyl-3-nitropyridin-2-amine (0.01mol) in chloroform (20mL) was slowly added dropwise a mixed solution of thionyl chloride (0.015mol) and chloroform (5mL) with 1- ((2-chloropyridin-5-yl) methyl) -7-methyl-8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one cooled in an ice-water bath and with stirring. After the dropwise addition is finished, stirring and reacting at the temperature of 0-35 ℃ until the reaction is completed. Filtering, washing filter cake with petroleum ether, and recrystallizing with ethanol and/or water to obtain the title compound as yellow solid. The yield thereof was found to be 80%.
Other compounds of the invention may be prepared by reference to the procedures of examples 1 to 6 or by reference to examples 1 to 6 in combination with relevant references.
Bioassay examples
The compounds of the present invention were tested for insecticidal and fungicidal activity, and the samples for activity testing were synthesized by the reaction formula (1), and some of the results are as follows.
Example 7 evaluation of biological Activity of armyworm (Mythimna separata)
Potter spray method: weighing a proper amount of the compound of the invention, dissolving the compound in N, N-Dimethylformamide (DMF), adding a small amount of Tween 80 emulsifier, uniformly stirring, adding a certain amount of clear water to prepare the required concentration, and taking the clear water as a reference. Fresh and tender corn leaves are cut into segments with basically consistent sizes and placed into a culture dish (phi 90mm) in which filter paper is placed in advance. Then 10 heads of armyworm larvae of 3 years old are inoculated into the dish, the dish is put under a Potter spray tower for quantitative spraying, the amount of the sprayed liquid medicine is 1ml, and each time, the amount of the sprayed liquid medicine is 1ml Concentration was repeated 3 times. After the treatment, the dish cover is covered, the dish cover is placed in a recovery room for culture, the culture is regularly observed, the death condition of the test insects is checked and recorded after 72 hours, the death rate (%) is calculated, and the results are averaged. The activity of the composition is classified into A, B, C, D grades, wherein the A grade is 100% or more and 90% or more of mortality, the B grade is 90% or more and 70% or more of mortality, the C grade is 70% or more and 50% or more of mortality, and the D grade is 50% or more and 0% or more of mortality. The results show that the compound of the invention has activity on armyworms, for example, at the concentration of 500mg/L, the compounds 1, 6, 9, 15 and the like and D2(Flupyrimin) have 100 percent of A-grade activity on armyworms, and the compound 13 and the like have B-grade activity on armyworms; d1 (Imidacloprid) has class C activity against armyworm.
Example 8 evaluation of insecticidal Activity against aphids (Aphis spp.)
In order to evaluate the activity of the compound on homoptera pests, aphids are selected as targets, and the activity of the compound on the aphids is measured by an immersion method.
The dipping method comprises the following steps: weighing a proper amount of the compound, dissolving the compound by using N, N-Dimethylformamide (DMF), diluting the solution to a required concentration by using clear water containing 0.2 percent of Tween80 emulsifier, and taking a blank without the compound as a control. Each treatment was repeated 3 times. Shearing broad bean seedlings with 3-day-old broad bean aphids, wherein more than 20 broad bean seedlings are cut per plant. Soaking broad bean seedlings and test insects in the liquid medicine of the compound shown in the formula (I), taking out after 5 seconds, sucking redundant liquid medicine, inserting the liquid medicine into absorbent sponge, covering the sponge with a glass tube, checking the number of the living insects and the dead insects after 24 hours, and averaging the results. The activity (mortality) is classified into A, B, C, D grades according to percentage relative to a blank control, wherein 100% and 90% of mortality are A grades, 90% and 70% of mortality are B grades, 70% and 50% of mortality are C grades, and 50% and 0% of mortality are D grades. The results show that the compounds of the invention have activity on broad bean aphids, and some of the compounds have good activity, and the following results are listed:
Compounds 1, 2, 4, 6, 9, 10, 11, 12, 13 and 14 etc. as well as D1 (imidacloprid) and D2(Flupyrimin) had class a activity on aphids at a concentration of 500 mg/L; 3. 5, 16 and the like have B-level activity on aphids;
compounds of the invention were active against aphids at concentrations of 200mg/L, 50mg/L and 12.5mg/L, with some results as given in Table 5.
Compounds of the present invention have insecticidal activity against aphids at concentrations of 20mg/L, 5mg/L and 1.25mg/L, with some results as shown in Table 6.
TABLE 5 partial results of aphid Activity (%)
| Compound (I) | 200mg/L | 50mg/L | 12.5mg/L |
| 1 | 100 | 100 | 90.52 |
| 2 | 100 | 90.28 | 24.39 |
| 4 | 100 | 57.45 | 16.68 |
| 6 | 100 | 92.01 | 34.27 |
| 9 | 100 | 95.95 | 96.34 |
| 10 | 100 | 100 | 100 |
| 11 | 100 | 100 | 100 |
| 13 | 100 | 94.94 | 94.59 |
| D1 | 100 | 100 | 100 |
| D2 | 100 | 100 | 94.85 |
TABLE 6 partial results of aphid Activity (%)
| Compound (I) | 20mg/L | 5mg/L | 1.25mg/L |
| 1 | 100 | 33.16 | 16.70 |
| 9 | 100 | 79.92 | 16.12 |
Example 9 evaluation of insecticidal Activity against Rice planthoppers (Nilaparvata lugens)
In order to evaluate the activity of the compound on homoptera pests, rice planthoppers are selected as objects, and the insecticidal activity of the compound on the rice planthoppers is measured by a rice stem soaking method.
The rice stem dipping method comprises the following steps: weighing a proper amount of the compound, dissolving the compound by using N, N-Dimethylformamide (DMF), diluting the solution to a required concentration by using clear water containing 0.2 percent of Tween80 emulsifier, and taking a blank without the compound as a control. Each treatment was repeated 3 times. 15 rice seedlings with two leaves and one core are selected, soaked in the compound reagent solution for 30 seconds, taken out and naturally dried, wrapped with wet absorbent cotton at the root for moisturizing, wrapped with a preservative film and placed in a glass test tube (200 multiplied by 30 mm). Then inoculating 3-year-old nymphs of rice planthoppers by using a brush pen, wherein the number of each tube is not less than 15, and the tube openings are tightened by using white gauze. After the treatment, the patient is placed in an observation room, the death condition is checked and recorded after 72 hours, the death rate is calculated, and the result is averaged. The activity (mortality) is classified into A, B, C, D grades according to percentage relative to a blank control, wherein 100% and 90% of mortality are A grades, 90% and 70% of mortality are B grades, 70% and 50% of mortality are C grades, and 50% and 0% of mortality are D grades. The results show that the compounds of the invention are active against rice planthopper. At the test concentration of 500mg/L, the compounds 1, 9 and the like of the invention show 100% of insecticidal activity on rice planthopper.
In order to research the effectiveness of the compounds of the invention on rice planthoppers, the compounds 1 and 9 and the like of the invention are selected for deep screening research, and the results show that the compounds of the invention have activity on the rice planthoppers, and the following test results are listed in part:
under the test concentration of 20mg/L, the insecticidal activity of the compound 1 of the invention on rice planthoppers is 40.95 percent, and the insecticidal activity of the compound 9 on the rice planthoppers is 34.31 percent;
at the test concentration of 10mg/L, the insecticidal activity of the compound 1 of the invention on rice planthopper is 24.67%, and the insecticidal activity of the compound 9 on rice planthopper is 18.01%.
Example 10 fungicidal Activity against Sclerotinia sclerotiorum (Sclerotinia sclerotiorum)
The method comprises the following steps: dissolving the compound to be tested in a suitable solvent such as N, N-Dimethylformamide (DMF), and diluting with sterile water containing 0.1% Tween80 emulsifier to desired concentration; 3mL of the liquid medicine is taken by a pipette and added into 27mL of potato agar medium (PDA) which is cooled to 45 ℃, and the liquid medicine is poured into a culture dish after being fully shaken up; cooling, taking 6mm diameter mycelium block from the edge of the bacteria colony cultured for 7 days by using an inoculating needle, transferring to the center of a culture dish, making the mycelium face downwards, setting a blank containing no compound to be detected as a control, and repeating for 4 times each treatment; after the treatment, the culture dish is placed in a constant-temperature biochemical incubator at 28 ℃ for culture, the growth diameter of hyphae is measured after 4 days, and the analysis is carried out by using EXCEL statistical software and the hypha growth inhibition rate (%) is calculated. The activity of the composition is classified into A, B, C, D grades, wherein 100% inhibition rate and 90% are A grade, 90% inhibition rate and 70% are B grade, 70% inhibition rate and 50% inhibition rate are C grade, and 50% inhibition rate and 0% inhibition rate are D grade.
The fungicidal activity of the compounds of the present invention against Phytophthora capsici (Phytophthora capsici), Alternaria alternata (Alternaria alternata) and Botrytis cucumeri (Botrytis cinerea) was determined, respectively, with reference to the above-described method for determining the fungicidal activity against Sclerotinia sclerotiorum (Sclerotinia sclerotiorum).
The results show that the compound has bactericidal activity on sclerotinia sclerotiorum, phytophthora capsici, alternaria alternata and botrytis cinerea. Some of the results are as follows:
under the test concentration of 25mg/L, the compounds 1, 19, II-12 and the like have B-grade activity on sclerotinia sclerotiorum, the compound 18 and the like have C-grade activity on sclerotinia sclerotiorum, and the compound 9 and the like, D1 (imidacloprid) and D2(Flupyrimin) do not show obvious bactericidal activity on sclerotinia sclerotiorum;
under the test concentration of 25mg/L, the compound 6 and the like have A-grade activity on phytophthora capsici, the compound 2 and the like have C-grade activity on phytophthora capsici, and the compound 9 and the like, D1 (imidacloprid) and D2(Flupyrimin) do not show obvious bactericidal activity on phytophthora capsici;
under the test concentration of 25mg/L, the compounds 1, 2, 3, 4, 14, II-23 and the like have C-grade activity on alternaria alternata, and the compounds 9 and the like, D1 (imidacloprid) and D2(Flupyrimin) do not show obvious bactericidal activity on alternaria alternata;
At the test concentration of 25mg/L, the compounds 1, 3, 18 and 19 and the like have C-grade activity on cucumber botrytis cinerea, and the compounds 9 and the like, D1 (imidacloprid) and D2(Flupyrimin) do not show obvious bactericidal activity on cucumber botrytis cinerea.
Example 11 controlling Effect on wheat powdery mildew (Erisiphe grimmins) (potting method)
The method comprises the following steps: dissolving the compound to be tested in a suitable solvent such as N, N-Dimethylformamide (DMF), diluting with sterile water containing 0.2% Tween80 emulsifier to desired concentration, setting blank containing no compound to be tested as control, and repeating the treatment for 3 times; taking pots with the diameter of about 15cm, sowing 20 plump and robust seeds of wheat in each pot, and supplying the seeds for testing after 2 leaves and 1 heart grow out; spraying the prepared wheat seedling plants with a medicament with a certain concentration, inoculating germs after one day, culturing in a moisturizing and proper temperature manner until blank control is encountered, checking the area of lesion spots, and calculating the medicament control effect. The activity of the active relative blank control is classified into A, B, C, D grades, wherein 100% and 90% of the control effect are A grades, 90% and 70% of the control effect are B grades, 70% and 50% of the control effect are C grades, and 50% and 0% of the control effect are D grades. .
The control effects of the compounds of the present invention on corn rust (Puccinia Polysora) and rice sheath blight (Rhizoctonia solani) were evaluated by pot culture with reference to the above-described evaluation method of bactericidal activity against wheat powdery mildew (Erisiphe grimminis).
The results show that the compound has control effects on wheat powdery mildew, corn rust and rice sheath blight. Some of the results are as follows:
at a dose of 500mg/L, the compound 4 and the like have A-grade control effects on wheat powdery mildew, the compounds 16, 18 and 20 and the like have B-grade control effects on wheat powdery mildew, the compounds 9, 12, 15, II-23 and the like have C-grade control effects on wheat powdery mildew, and the control effects of D1 (imidacloprid) and D2(Flupyrimin) on wheat powdery mildew are D-grade.
Under the dosage of 500mg/L, the compounds 16, II-7 and the like have A-grade control effect on the corn rust, the compounds 6, 18, II-23 and the like have C-grade control effect on the corn rust, and the compounds 9 and the like, D1 (imidacloprid) and D2(Flupyrimin) have D-grade control effect on the corn rust.
Under the dosage of 500mg/L, the compounds II-7 and the like have B-grade control effect on rice sheath blight disease, the compounds 3, 6, 7, 13, 18, 20 and the like have C-grade control effect on rice sheath blight disease, and the compounds 9 and the like, D1 (imidacloprid) and D2(Flupyrimin) have D-grade control effect on rice sheath blight disease.
In order to research the influence of the compound on bees, the acute contact toxicity research on the bees is carried out according to the method for testing the acute contact toxicity of the bee in the 10 th part of GB/T31270.10-2014' test criteria for evaluating environmental safety of chemical pesticides, and the result shows that the toxicity of the compound on the bees is lower than that of D1 (imidacloprid) on the bees, and the compound is safe to the bees.
Claims (3)
1. The imidazopyridines represented by the general formula (I) are 1- ((2-chloropyridin-5-yl) methyl) -8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one,
characterized in that 1- ((2-chloropyridin-5-yl) methyl) -8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one is prepared by the reaction shown below:
in a single solvent or a mixed solvent of any two of water, tetrahydrofuran, 1, 4-dioxane, acetone, benzene, toluene, xylene, methanol, ethanol, dichloromethane, dichloroethane, chloroform, tetrachloromethane, hexane, ethyl acetate, acetonitrile, dimethyl sulfoxide or N, N-dimethylformamide, 2-aminoethanol and 2-chloro-5-chloromethylpyridine are reacted at a temperature of-15 ℃ to obtain 2- (((2-chloropyridin-5-yl) methyl) amino) ethanol, and if necessary, triethylamine, N-dimethylaniline, pyridine, picoline, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydride, sodium methoxide, sodium tert-butoxide, potassium tert-butoxide or sodium hydrogen carbonate is added to promote the reaction, or facilitate the reaction; reacting 2- ((2-chloropyridin-5-yl) methyl) amino) ethanol and 2-chloro-6-methoxy-3-nitropyridine or 2, 6-dichloro-3-nitropyridine with a solvent selected from the group consisting of water, tetrahydrofuran, 1, 4-dioxane, benzene, toluene, xylene, methanol, ethanol, dichloromethane, dichloroethane, chloroform, tetrachloromethane, hexane, ethyl acetate, acetonitrile, dimethyl sulfoxide and N, N-dimethylformamide, in the presence of triethylamine, N-dimethylaniline, pyridine, picoline, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydride, sodium methoxide, sodium tert-butoxide, potassium tert-butoxide and sodium hydrogencarbonate at a temperature of-15 ℃ to system reflux temperature, obtaining N- (2-chloropyridine-5-yl) methyl-N- (2-hydroxyethyl) -6-methoxyl-3-nitropyridine-2-amine or N- (2-chloropyridine-5-yl) methyl-N- (2-hydroxyethyl) -6-chlorine-3-nitropyridine-2-amine;
In the solvent of tetrahydrofuran, 1, 4-dioxane, acetone, benzene, toluene, xylene, methanol, ethanol, dichloromethane, dichloroethane, trichloromethane, tetrachloromethane, hexane, ethyl acetate, acetonitrile, dimethyl sulfoxide or N, N-dimethylformamide or a mixture of any two of them, at a temperature of-10 ℃ to system reflux temperature, in the presence of halogenating agent of thionyl chloride, thionyl bromide, phosphorus trichloride or phosphorus pentachloride, N- (2-chloropyridin-5-yl) methyl-N- (2-hydroxyethyl) -6-methoxy-3-nitropyridine-2-amine or N- (2-chloropyridin-5-yl) methyl-N- (2-hydroxyethyl) -6-chloro-3-nitropyridine-2-amine can be prepared to obtain the 1- ((2-chloropyridin-5-yl) methyl) -8-nitro-2, 3-dihydro-imidazo [1,2-a ] pyridin-5 (1H) -one.
2. An intermediate for the preparation of a compound of formula (I) according to claim 1, represented by general formula (II):
characterized in that the compound of formula (II) is:
n- ((2-chloropyridin-5-yl) methyl) -N- (2-hydroxyethyl) -6-chloro-3-nitropyridin-2-amine;
n- ((2-Chloropyridin-5-yl) methyl) -N- (2-hydroxypropyl) -6-methoxy-3-nitropyridin-2-amine.
3. A process for the preparation of an intermediate of imidazopyridines according to claim 2, characterized in that N- ((2-chloropyridin-5-yl) methyl) -N- (2-hydroxyethyl) -6-methoxy-3-nitropyridin-2-amine or N- ((2-chloropyridin-5-yl) methyl) -N- (2-hydroxyethyl) -6-chloro-3-nitropyridin-2-amine is prepared by the reaction shown below:
In a single solvent or a mixed solvent of any two of water, tetrahydrofuran, 1, 4-dioxane, acetone, benzene, toluene, xylene, methanol, ethanol, dichloromethane, dichloroethane, chloroform, tetrachloromethane, hexane, ethyl acetate, acetonitrile, dimethyl sulfoxide or N, N-dimethylformamide, 2-aminoethanol and 2-chloro-5-chloromethylpyridine are reacted at a temperature of-15 ℃ to obtain 2- (((2-chloropyridin-5-yl) methyl) amino) ethanol, and if necessary, triethylamine, N-dimethylaniline, pyridine, picoline, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydride, sodium methoxide, sodium tert-butoxide, potassium tert-butoxide or sodium hydrogen carbonate is added to promote the reaction, or facilitate the reaction; reacting 2- ((2-chloropyridin-5-yl) methyl) amino) ethanol and 2-chloro-6-methoxy-3-nitropyridine or 2, 6-dichloro-3-nitropyridine with a solvent selected from the group consisting of water, tetrahydrofuran, 1, 4-dioxane, benzene, toluene, xylene, methanol, ethanol, dichloromethane, dichloroethane, chloroform, tetrachloromethane, hexane, ethyl acetate, acetonitrile, dimethyl sulfoxide and N, N-dimethylformamide, in the presence of triethylamine, N-dimethylaniline, pyridine, picoline, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydride, sodium methoxide, sodium tert-butoxide, potassium tert-butoxide and sodium hydrogencarbonate at a temperature of-15 ℃ to system reflux temperature, to obtain N- (2-chloropyridin-5-yl) methyl-N- (2-hydroxyethyl) -6-methoxy-3-nitropyridine-2-amine or N- (2-chloropyridin-5-yl) methyl-N- (2-hydroxyethyl) -6-chloro-3-nitropyridine-2-amine.
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