CN110563645B - Quinolone compound and preparation method and application thereof - Google Patents
Quinolone compound and preparation method and application thereof Download PDFInfo
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- CN110563645B CN110563645B CN201910931912.3A CN201910931912A CN110563645B CN 110563645 B CN110563645 B CN 110563645B CN 201910931912 A CN201910931912 A CN 201910931912A CN 110563645 B CN110563645 B CN 110563645B
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
Abstract
The invention discloses a novel quinolone compound and a preparation method and application thereof, wherein the structural formula of the compound is shown as (I); the novel quinolone compound has a novel structure, shows good activity on various bacterial germs in the agricultural field due to the fact that the novel quinolone compound contains a quinolone mother ring and a specific substituent group, can obtain good control effect under a very low dosage, can be used for preparing bactericides, particularly bactericides for crops or plants, and has good activity on the aspect of improving the growth and development of the crops; the novel quinolone compound has a wide bactericidal spectrum, and has very good inhibitory or bactericidal activity on gram-negative bacteria, gram-positive bacteria and other bacteria; the compounds can obtain good control effect at very low dosage, and are safe and harmless to crops. In addition, the compound has simple preparation steps and high yield, thereby having good application prospect.
Description
Technical Field
The invention relates to the technical field of agricultural fungicides, in particular to a novel quinolone compound and a preparation method and application thereof.
Background
In recent years, with the common influence of climate change, change of crop varieties, rapid development of facility agriculture and other factors, the loss caused by crop bacterial diseases is increased year by year, and meanwhile, the effective chemical control agent is lacked, so that once the crop diseases occur on a large scale, the crop diseases are difficult to be effectively controlled in a short time.
Quinolone antibiotics have been developed for 4 generations at present, are general drugs for human and livestock, have the advantages of wide antibacterial spectrum, strong antibacterial activity, no cross drug resistance with other antibacterial drugs, small toxic and side effects and the like, and are widely applied to livestock breeding, aquatic product breeding and the like for preventing and treating animal diseases. However, medical antibiotics are rarely used in agricultural fungicides due to limitations in the type of sterilization, resistance, control, and production costs.
At present, the medicaments for preventing and treating bacterial diseases in agricultural production mainly comprise two main products, and the maximum using amount of the medicaments is copper preparations, including organic or inorganic copper preparations. Another class is antibiotic products, including agricultural or medical antibiotics. The copper preparation has low control effect, and a large amount of heavy metal is sprayed into the environment to pollute soil, water and food and cause the risk of environment and food safety; the use of a large amount of antibiotics can cause pathogenic bacteria of human bodies to generate drug resistance to medical antibiotics, and the use is often limited. Therefore, the development of novel green chemical pesticides with low toxicity, low residue, safety and broad bactericidal spectrum is urgently needed to meet the requirement of agricultural sterilization.
Disclosure of Invention
In order to solve the above problems, the present invention aims to provide a novel quinolone compound, and a preparation method and application thereof.
In order to achieve the purpose, the invention is realized by the following technical scheme:
a novel quinolone compound has a structural formula (I);
in the formula (I), R1Selected from ethyl, cyclopropyl, 2-fluoroethyl or 2-fluorocyclopropyl;
R2selected from hydrogen, - (CH)2)2OH or- (CH)2)2OCH3；
R3Is selected from C1-C4Alkoxy, halo C1-C4Alkoxy, NRmRnOr a 6-membered heterocyclic group;
Rm、Rneach independently selected from hydrogen and C1-C4Alkyl or C3-C6A cycloalkyl group.
Preferably, R2Selected from hydrogen.
Preferably, R1Selected from ethyl or cyclopropyl.
Preferably, R3Selected from NRmRn、
Rm、RnEach independently selected from hydrogen and C1-C4Alkyl or C3-C6A cycloalkyl group.
Preferably, R1Selected from cyclopropyl.
Preferably, R3Selected from NH (CH)3)、NH(CH2CH2CH3)、NH(CH2CH2CH2CH3)、 N(CH2CH2CH3)2、N(CH3)(CH2CH3)、N(CH3)(CH2CH2CH3)、N(CH3)(CH2CH2CH2CH3)、 N(CH2CH3)(CH2CH2CH3)、N(CH2CH3)(CH2CH2CH2CH3)、
The invention also comprises the application of the novel quinolone compound in agricultural bactericides.
The invention also discloses a composition which takes at least one of the compounds of any one of claims 1 to 6 as an active ingredient.
A method for controlling bacteria, comprising applying an effective amount of at least one compound according to any one of claims 1 to 6 to a growth medium for the bacteria.
By way of example, the compounds of formula (I) are illustrated by the specific compounds listed in Table 1, but do not limit the invention.
In the general formula (I), R1、R2、R3See table 1.
To reduce the space of the specification, exemplary groups and/or compounds of the present invention are described in the form of the above tables.
According to an embodiment of the invention, the compounds of formula (I) are commercially available or can be prepared by known methods.
In the formula I, R2When selected from H, Compound (I-1) is prepared according to the following procedure. When R is3When the compound is selected from alkoxy or substituted amino, the compound shown in the formula (I-1) can be prepared by the substitution reaction of the compound shown in the formula (I-1-1) and the compound shown in the formula (VII),
according to an embodiment of the invention, the reaction may be carried out in the presence (or not) of a base; the base can be one, two or more of organic bases such as triethylamine, pyridine, sodium methoxide, sodium ethoxide, potassium tert-butoxide and the like, or inorganic bases such as sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium hydride, sodium or potassium and the like.
According to the production method of the present invention, the reaction may be carried out in a solvent; the solvent may be selected from one, two or more of aromatic hydrocarbon solvents, amide solvents, sulfone solvents, etc., for example, one, two or more selected from toluene, N-methylpyrrolidone, N-dimethylformamide, N-dimethylacetamide, dimethylsulfoxide, etc.
According to an embodiment of the present invention, the temperature of the reaction is preferably 50 to 150 ℃.
According to an embodiment of the present invention, the reaction can be carried out by a method described in patent document CA 1218067 or other similar methods.
Or a compound represented by the formula (I-1), or a compound represented by the formula (I-1-1) with a metal salt (VIII) of a compound represented by the formula (VII),
wherein R is1、R3Having the definition of any one of claims 1 to 5; l' is selected from a leaving group, for example a halogen atom, such as fluorine, chlorine, bromine or iodine; m is selected from alkali metals, such as sodium or potassium.
According to the production method of the present invention, the reaction may be carried out in a solvent; the solvent may be selected from one, two or more of aromatic hydrocarbon solvents, amide solvents, sulfone solvents, etc., for example, one, two or more selected from toluene, N-methylpyrrolidone, N-dimethylformamide, N-dimethylacetamide, dimethylsulfoxide, etc.
According to an embodiment of the present invention, the temperature of the reaction is preferably 50 to 150 ℃.
According to an embodiment of the invention, the compounds of formula (I) are commercially available or can be prepared by known methods, R1When cyclopropyl, ethyl, 2-fluoroethyl and 2-fluorocyclopropyl are used, the following concrete points are included:
the intermediates (I-1) mentioned in the examples are commercially available, so that no specific details are given for their preparation and the process for preparing the final target is provided.
In the formula I, R2Is selected from- (CH)2)2OH or- (CH)2)2OCH3When the compound I-3 is prepared according to the following steps, the compound I-3 comprises the following steps of preparing acyl chloride (I-2) from the compound shown in the formula (I-1), and reacting the acyl chloride shown in the formula (I-2) with the compound shown in the formula (I-4) to obtain the compound shown in the formula (I-3), wherein the formula is as follows:
l is selected from a leaving group, for example a halogen atom, such as chlorine or bromine; r' is selected from H or CH3。
According to an embodiment of the present invention, the halogenation reagent used in the reaction for preparing the acid chloride (I-2) from the compound represented by the formula (I-1) may be selected from acid halides of inorganic acids, such as phosphorus trichloride, phosphorus pentachloride, thionyl chloride, oxalyl chloride, phosphorus oxychloride, phosphorus tribromide, and the like.
According to an embodiment of the present invention, the halogenation reaction may be carried out in a solvent; the solvent may be selected from one, two or more of aromatic hydrocarbon solvents, halogenated alkane solvents, for example, one, two or more selected from toluene, 1, 2-dichloroethane, petroleum ether, or the like.
According to an embodiment of the present invention, the temperature of the halogenation reaction may be 20 to 120 ℃.
According to an embodiment of the present invention, the halogenation reaction can be carried out by referring to the method described in handbook of organic compound synthesis 2011 edition or other similar methods.
According to an embodiment of the present invention, the reaction for preparing the compound represented by the formula (I-3) from the formula (I-2) may be carried out in the presence of a base; the base can be one, two or more of organic bases such as triethylamine and pyridine, or inorganic bases such as sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium hydride and potassium tert-butoxide.
According to an embodiment of the present invention, the reaction may be carried out in a solvent; the solvent may be selected from one, two or more of aromatic hydrocarbon solvents, haloalkane solvents, ether solvents, and the like, for example, one, two or more selected from toluene, dichloromethane, 1, 2-dichloroethane, tetrahydrofuran, t-butyl methyl ether, ethyl acetate, and the like.
According to an embodiment of the present invention, the temperature of the reaction is preferably-10 to 50 ℃.
According to an embodiment of the present invention, the reaction can be carried out by a method described in patent documents CN200680004480 or CN95194436 or other similar methods.
Or when in formula I, R2Is selected from- (CH)2)2OH or- (CH)2)2OCH3When this is the case, a compound (R) represented by the formula (I-1)2For H) preparation of the carboxylate compound of formula (I-6), reacting the compound of formula (I-6) with the compound of formula (I-5)The compound of (a) to obtain a compound represented by I-3, specifically, as shown in the following reaction formula:
R1、R3and R' substituent is the same as above.
According to an embodiment of the present invention, the compound (R) represented by the formula (I-1)2As H) the reaction for preparing the carboxylate compound represented by the formula (I-6) may be carried out in the presence of a base; the alkali can be one or two of sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, etc.
According to the production method of the present invention, the reaction may be carried out in water or an organic solvent, for example, one or two selected from water, methanol, ethanol, tetrahydrofuran, and the like.
According to an embodiment of the present invention, the temperature of the reaction is preferably 20 to 90 ℃.
According to an embodiment of the present invention, the reaction of the compound of formula (I-6) with the compound represented by formula (I-5) may be carried out in a solvent, for example, one, two or more selected from toluene, 1, 2-dichloroethane, acetonitrile, butanone, or dimethyl sulfoxide, or the like.
According to an embodiment of the present invention, the temperature of the reaction is preferably 20 to 120 ℃.
According to an embodiment of the invention, the reaction can be carried out according to the methods described in Tetrahedron Lett.1975:4095 or Tetrahedron Lett.1974:2417, etc.
Compared with the prior art, the invention has the following advantages:
the novel quinolone compound has a novel structure, shows good activity on various bacterial germs in the agricultural field due to the fact that the novel quinolone compound contains a quinolone mother ring and a specific substituent, can obtain good control effect at a low dosage, can be used for preparing bactericides, particularly bactericides for crops or plants, and has good activity on the aspect of improving the growth and development of the crops.
The quinolone compound has a wide bactericidal spectrum, and has very good inhibitory or bactericidal activity on gram-negative bacteria, gram-positive bacteria and other bacteria; the compounds can obtain good control effect at very low dosage, are safe and harmless to crops, and can be used for preparing bactericides. In addition, the compound has simple preparation steps and high yield, thereby having good application prospect.
Detailed Description
The invention is further described with reference to specific examples.
The following examples are merely illustrative and explanatory of the present invention and should not be construed as limiting the scope of the invention. All the technologies realized based on the above-mentioned contents of the present invention are covered in the protection scope of the present invention.
Unless otherwise indicated, the raw materials and reagents used in the following examples are all commercially available products or can be prepared by known methods.
The following method was used for LC-MS analysis:
a chromatographic column: agilent ZORBAX SB-C18150 mm X4.6 mm, 5 μm (inside diameter);
detection wavelength: 254 nm;
flow rate: 0.8 mL/min;
column temperature: 30 ℃;
gradient elution conditions:
| time (min) | Acetonitrile (%) | 0.1% aqueous formic acid (%) |
| 0.00 | 50 | 50 |
| 5.00 | 50 | 50 |
| 15.00 | 90 | 10 |
| 20.00 | 90 | 10 |
Example 17-ethoxy-1-ethyl-6-fluoro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (Compound 1)
Sodium wool (0.46g, 20mmol) was added portionwise to ethanol (2.30g, 50mmol) at room temperature, heated and refluxed for 3 h. To the above solution were added dimethyl sulfoxide (15mL) and 7-chloro-1-ethyl-6-fluoro-4-oxo-1, 4-dihydro-quinoline-3-carboxylic acid (2.70g, 10mmol) in this order, and the mixture was gradually heated to 90 ℃ for reaction for 6 hours. After cooling to room temperature, water (20mL) and ethyl acetate (3 × 15mL) were added to the reaction system to conduct extraction. The organic layers were combined, washed with water (2 × 15mL), saturated brine (15mL), and dried over anhydrous magnesium sulfate. The mixture was desolventized under reduced pressure and column chromatography (eluent: mixture of dichloromethane and methanol (6:1)) was carried out to obtain 1.43g of a product with a yield of 51%.
LC/MS[M+H]+＝280.1、[M+Na]+＝302.08、[M+K]+＝318.05。
Example 21-Ethyl-6-fluoro-4-oxo-7- (2,2, 2-trifluoroethoxy) -1, 4-dihydroquinoline-3-carboxylic acid (Compound 11)
Sodium wool (0.46g, 20mmol) was added portionwise to trifluoroethanol (5.00g, 50mmol) at room temperature, heated and refluxed for 3 h. To the above solution were added dimethyl sulfoxide (20mL) and 7-chloro-1-ethyl-6-fluoro-4-oxo-1, 4-dihydro-quinoline-3-carboxylic acid (2.70g, 10mmol) in this order, and the mixture was gradually heated to 90 ℃ for reaction for 6 hours. After cooling to room temperature, water (20mL) and ethyl acetate (3 × 20mL) were added to the reaction system to conduct extraction. The organic layers were combined, washed with water (2 × 15mL), saturated brine (15mL), and dried over anhydrous magnesium sulfate. The mixture was desolventized under reduced pressure and column chromatography (eluent: mixed solution of dichloromethane and methanol (6:1)) was carried out to obtain 1.86g of a 56% yield product.
LC/MS[M+H]+＝334.07、[M+Na]+＝356.05、[M+K]+＝372.02。
Example 3: 1-Ethyl-6-fluoro-4-oxo-7- (propylamino) -1, 4-dihydroquinoline-3-carboxylic acid (Compound 13)
Propylamine (1.18g, 20mmol) and 7-chloro-1-ethyl-6-fluoro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (2.69g, 10mmol) were dissolved in this order in 15mL of dimethyl sulfoxide at room temperature, and the reaction was carried out for 4 hours while gradually heating to 110 ℃. After cooling to room temperature, water (20mL) and ethyl acetate (3 × 15mL) were added to the reaction system to conduct extraction. The organic layers were combined, washed with water (2 × 15mL), saturated brine (15mL), and dried over anhydrous magnesium sulfate. Vacuum desolventizing, and performing column chromatography (eluent: mixed solution of ethyl acetate, petroleum ether and formic acid (1.5:1:0.01)) to obtain 1.81g of product with yield of 62%.
LC/MS[M+H]+＝293.13、[M+Na]+＝315.11、[M+K]+＝331.08。
Example 4: 7- (diethylamino) -1-ethyl-6-fluoro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (Compound 15)
Diethylamine (1.46g, 20mmol), 7-chloro-1-ethyl-6-fluoro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (2.69g, 10mmol) were dissolved in 15mL of dimethyl sulfoxide in this order at room temperature, gradually heated to 110 ℃ and reacted for 4 h. After cooling to room temperature, water (20mL) and ethyl acetate (3 × 15mL) were added to the reaction system to conduct extraction. The organic layers were combined, washed with water (2 × 15mL), saturated brine (15mL), and dried over anhydrous magnesium sulfate. Vacuum desolventizing, and performing column chromatography (eluent: mixed solution of ethyl acetate, petroleum ether and formic acid (1.5:1:0.01)) to obtain 1.83g of product with yield of 60%.
LC/MS[M+H]+＝307.15、[M+Na]+＝329.13、[M+K]+＝345.1。
Example 5: 7- (diethylamino) -1-ethyl-6-fluoro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (Compound 31)
Piperidine (1.70g, 20mmol), 7-chloro-1-ethyl-6-fluoro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (2.69g, 10mmol) were dissolved in 15mL of dimethyl sulfoxide in this order at room temperature, gradually heated to 110 ℃ and reacted for 6 h. After cooling to room temperature, water (20mL) and ethyl acetate (3 × 15mL) were added to the reaction system to conduct extraction. The organic layers were combined, washed with water (2 × 15mL), saturated brine (15mL), and dried over anhydrous magnesium sulfate. Vacuum desolventizing, and performing column chromatography (eluent: mixed solution of ethyl acetate, petroleum ether and formic acid (1.5:1:0.02)) to obtain 1.65g of product with yield of 52%.
LC/MS[M+H]+＝319.15、[M+Na]+＝341.13、[M+K]+＝357.1。
Example 6: 7- (4-tert-Butylpiperazin-1-yl) -1-ethyl-6-fluoro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (Compound 33)
1-tert-butylpiperazine (2.84g, 20mmol) and 7-chloro-1-ethyl-6-fluoro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (2.69g, 10mmol) were dissolved in this order in 15mL of dimethyl sulfoxide at room temperature, and the reaction was carried out for 6 hours while gradually heating to 110 ℃. After cooling to room temperature, water (20mL) and ethyl acetate (3 × 15mL) were added to the reaction system to conduct extraction. The organic layers were combined, washed with water (2 × 15mL), saturated brine (15mL), and dried over anhydrous magnesium sulfate. Vacuum desolventizing, and performing column chromatography (eluent: mixed solution of ethyl acetate, petroleum ether and formic acid (1.5:1:0.02)) to obtain 1.50g of product with yield of 40%.
LC/MS[M+H]+＝376.21、[M+Na]+＝398.19、[M+K]+＝414.16。
Example 7: 1-cyclopropyl-7- (methylamino) -6-fluoro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (compound 36)
Methylamine (0.62g, 20mmol) and 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (2.82g, 10mmol) were dissolved in 15mL of dimethyl sulfoxide in this order at room temperature, and the reaction was carried out for 4h while gradually heating to 110 ℃. After cooling to room temperature, water (20mL) and ethyl acetate (3 × 15mL) were added to the reaction system to conduct extraction. The organic layers were combined, washed with water (2 × 15mL), saturated brine (15mL), and dried over anhydrous magnesium sulfate. Vacuum desolventizing, and performing column chromatography (eluent: mixed solution of ethyl acetate, petroleum ether and formic acid (1.5:1:0.01)) to obtain 1.55g of product with yield of 56%.
LC/MS[M+H]+＝277.1、[M+Na]+＝299.08、[M+K]+＝315.05。
Example 8: 1-cyclopropyl-7- (ethyl (methyl) amino) -6-fluoro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (Compound 40)
Methylethylamine (1.18g, 20mmol), 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (2.82g, 10mmol) were dissolved in 15mL of dimethyl sulfoxide in this order at room temperature, gradually heated to 110 ℃ and reacted for 4 h. After cooling to room temperature, water (20mL) and ethyl acetate (3 × 15mL) were added to the reaction system to conduct extraction. The organic layers were combined, washed with water (2 × 15mL), saturated brine (15mL), and dried over anhydrous magnesium sulfate. Vacuum desolventizing, and performing column chromatography (eluent: mixed solution of ethyl acetate, petroleum ether and formic acid (1.5:1:0.01)) to obtain 1.46g of product with yield of 48%.
LC/MS[M+H]+＝305.13、[M+Na]+＝327.11、[M+K]+＝343.08。
Example 9: 1-cyclopropyl-7- (cyclopropyl (methyl) amino) -6-fluoro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (Compound 45)
N-methylcyclopropylamine (1.42g, 20mmol) and 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (2.82g, 10mmol) were dissolved in 20mL of dimethyl sulfoxide in this order at room temperature, and the reaction was carried out for 4 hours while gradually heating to 110 ℃. After cooling to room temperature, water (25mL) and ethyl acetate (3 × 20mL) were added to the reaction system to conduct extraction. The organic layers were combined, washed with water (2 × 15mL), saturated brine (15mL), and dried over anhydrous magnesium sulfate. Vacuum desolventizing, and performing column chromatography (eluent: mixed solution of ethyl acetate, petroleum ether and formic acid (1.5:1:0.01)) to obtain 1.23g of product with yield of 39%.
LC/MS[M+H]+＝317.13、[M+Na]+＝339.11、[M+K]+＝355.08。
Example 10: 7-ethoxy-6-fluoro-1- (2-fluoroethyl) -4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (Compound 52)
Sodium wool (0.46g, 20mmol) was added portionwise to ethanol (2.30g, 50mmol) at room temperature, heated and refluxed for 3 h. To the above solution were added dimethyl sulfoxide (15mL) and 7-chloro-6-fluoro-1- (2-fluoroethyl) -4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (2.87g, 10mmol) in this order, and the mixture was gradually heated to 100 ℃ for 5 hours. After cooling to room temperature, water (20mL) and ethyl acetate (3 × 15mL) were added to the reaction system to conduct extraction. The organic layers were combined, washed with water (2 × 15mL), saturated brine (15mL), and dried over anhydrous magnesium sulfate. Vacuum desolventizing, and performing column chromatography (eluent: mixed solution of ethyl acetate, petroleum ether and formic acid (1:1.5:0.01)) to obtain 1.96g of product with 66% yield.
LC/MS[M+H]+＝298.09、[M+Na]+＝320.07、[M+K]+＝336.04。
Example 11: 6-fluoro-1- (2-fluoroethyl) -4-oxo-7- (2,2, 2-trifluoroethoxy) -1, 4-dihydroquinoline-3-carboxylic acid (Compound 62)
Sodium wool (0.46g, 20mmol) was added portionwise to trifluoroethanol (5.00g, 50mmol) at room temperature, heated and refluxed for 3 h. To the above solution were added dimethyl sulfoxide (15mL) and 7-chloro-6-fluoro-1- (2-fluoroethyl) -4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (2.87g, 10mmol) in this order, and the mixture was gradually heated to 100 ℃ for 6 hours. After cooling to room temperature, water (20mL) and ethyl acetate (3 × 15mL) were added to the reaction system to conduct extraction. The organic layers were combined, washed with water (2 × 15mL), saturated brine (15mL), and dried over anhydrous magnesium sulfate. Vacuum desolventizing, and performing column chromatography (eluent: mixed solution of ethyl acetate, petroleum ether and formic acid (1:1.5:0.01)) to obtain 2.03g of product with yield of 58%.
LC/MS[M+H]+＝352.06、[M+Na]+＝374.04、[M+K]+＝390.01。
Example 12: 7- (ethylamino) -6-fluoro-1- (2-fluoroethyl) -4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (Compound 65)
Ethylamine (0.90g, 20mmol) and 7-chloro-6-fluoro-1- (2-fluoroethyl) -4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (2.87g, 10mmol) were dissolved in this order in 15mL of dimethyl sulfoxide at room temperature, and the reaction was carried out for 5 hours while gradually heating to 110 ℃. After cooling to room temperature, water (20mL) and ethyl acetate (3 × 15mL) were added to the reaction system to conduct extraction. The organic layers were combined, washed with water (2 × 15mL), saturated brine (15mL), and dried over anhydrous magnesium sulfate. Vacuum desolventizing, and performing column chromatography (eluent: mixed solution of ethyl acetate, petroleum ether and formic acid (1.5:1:0.02)) to obtain 1.80g of product with yield of 61%.
LC/MS[M+H]+＝297.11、[M+Na]+＝319.09、[M+K]+＝335.06。
Example 13: 7- (dimethylamino) -6-fluoro-1- (2-fluoroethyl) -4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (Compound 68)
Dimethylamine (0.90g, 20mmol) and 7-chloro-6-fluoro-1- (2-fluoroethyl) -4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (2.87g, 10mmol) were dissolved in this order in 15mL of dimethyl sulfoxide at room temperature, and the reaction was carried out for 6 hours while gradually heating to 110 ℃. After cooling to room temperature, water (20mL) and ethyl acetate (3 × 15mL) were added to the reaction system to conduct extraction. The organic layers were combined, washed with water (2 × 15mL), saturated brine (15mL), and dried over anhydrous magnesium sulfate. Vacuum desolventizing, and performing column chromatography (eluent: mixed solution of ethyl acetate, petroleum ether and formic acid (1.5:1:0.02)) to obtain 1.66g of product with yield of 56%.
LC/MS[M+H]+＝297.11、[M+Na]+＝319.09、[M+K]+＝335.06。
Example 14: 6-fluoro-1- (2-fluoroethyl) -7-morpholine-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (Compound 87)
Morpholine (1.75g, 20mmol) and 7-chloro-6-fluoro-1- (2-fluoroethyl) -4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (2.87g, 10mmol) were dissolved in 15mL of dimethyl sulfoxide in this order at room temperature, gradually heated to 110 ℃ and reacted for 8 h. After cooling to room temperature, water (20mL) and ethyl acetate (3 × 15mL) were added to the reaction system to conduct extraction. The organic layers were combined, washed with water (2 × 15mL), saturated brine (15mL), and dried over anhydrous magnesium sulfate. Vacuum desolventizing, and performing column chromatography (eluent: mixed solution of ethyl acetate, petroleum ether and formic acid (1.5:1:0.02)) to obtain 1.56g of product with yield of 46%.
LC/MS[M+H]+＝339.12、[M+Na]+＝361.1、[M+K]+＝377.07。
Example 15: 7-ethoxy-6-fluoro-1- ((2S) -2-fluorocyclopropyl) -4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (Compound 92)
Sodium wool (0.46g, 20mmol) was added portionwise to ethanol (2.30g, 50mmol) at room temperature, heated and refluxed for 3 h. To the above solution were added dimethyl sulfoxide (15mL) and 7-chloro-6-fluoro-1- ((2S) -2-fluorocyclopropyl) -4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (2.99g, 10mmol) in this order, and the mixture was gradually heated to 100 ℃ for 5 hours. After cooling to room temperature, water (20mL) and ethyl acetate (3 × 15mL) were added to the reaction system to conduct extraction. The organic layers were combined, washed with water (2 × 15mL), saturated brine (15mL), and dried over anhydrous magnesium sulfate. Vacuum desolventizing, and performing column chromatography (eluent: mixed solution of ethyl acetate, petroleum ether and formic acid (1:1.5:0.01)) to obtain 1.92g of product with yield of 62%.
LC/MS[M+H]+＝310.09、[M+Na]+＝332.07、[M+K]+＝348.04。
Example 16: 7-ethoxy-6-fluoro-1- ((2S) -2-fluorocyclopropyl) -4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (Compound 93)
Morpholine (1.75g, 20mmol) and 7-chloro-6-fluoro-1- ((2S) -2-fluorocyclopropyl) -4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (2.99g, 10mmol) were dissolved in 15mL of dimethyl sulfoxide in this order at room temperature, gradually heated to 110 ℃ and reacted for 8 h. After cooling to room temperature, water (20mL) and ethyl acetate (3 × 15mL) were added to the reaction system to conduct extraction. The organic layers were combined, washed with water (2 × 15mL), saturated brine (15mL), and dried over anhydrous magnesium sulfate. Vacuum desolventizing, and performing column chromatography (eluent: mixed solution of ethyl acetate, petroleum ether and formic acid (1.5:1:0.02)) to obtain 1.82g of product with yield of 52%.
LC/MS[M+H]+＝351.12、[M+Na]+＝373.1、[M+K]+＝389.07。
Other compounds of the invention were synthesized according to the methods described above.
Other part structural characterization data for the compounds of formula (I) are shown in table 2:
TABLE 2 structural characterization data for other parts of the compounds of formula (I)
Formulation examples
In the following examples, all percentages are by weight and all dosage forms are prepared by conventional methods.
Example 17:
in this example, the compound obtained in the above example is used to prepare a wettable powder, which is specifically prepared by using the following raw material compositions in mass ratio:
3660.0% of compound, 4.0% of dodecylphenol polyethoxy glycol ether, 5.0% of calcium lignosulfonate, 6.0% of sodium aluminosilicate and 25.0% of montmorillonite (calcined)
Example 18:
in this example, granules were prepared using the compounds obtained in the above examples, specifically using the following raw material compositions in mass ratio:
4010.0% of compound, 2% of polyethoxylated alkylphenol, 5% of calcium lignosulfonate, 8% of potassium chloride, 1% of polydimethylsiloxane and 100% of soluble starch.
Example 19:
in this example, the compounds obtained in the above examples were used to prepare extruded pellets, specifically using the following raw material compositions in mass ratio:
4525.0% of compound, 10.0% of anhydrous calcium sulfate, 5.0% of crude calcium lignosulfonate, 5.0% of sodium alkyl naphthalene sulfonate and 55.0% of calcium/magnesium bentonite.
Example 20:
in this example, the compounds obtained in the above examples are used to prepare emulsifiable concentrates, and specifically, the emulsifiable concentrates are prepared by using the following raw materials in mass ratio:
5225.0% of compound, 15060% of solvent, PEG 4005% of Rhodacal 70/B3% of Rhodameen RAM/77%.
Example 21:
in this example, the compounds obtained in the above examples were used to prepare an aqueous suspension, specifically using the following raw material compositions in mass ratio:
6530.0% of compound, 5.0% of POE polystyrene phenyl ether sulfate, 0.5% of xanthan gum, 5% of polyethylene glycol, 1% of triethanolamine, 0.5% of sorbitol and water to make up to 100.0%.
Biological activity assay
The compound of the invention has good activity on various bacterial germs in the agricultural field.
Example 22:
1. measurement of fungicidal Activity
The compound of the invention performs in vitro bacteriostatic activity or in vivo protection effect tests on various bacterial diseases of plants and performs a test on the effect of improving the growth and development of crops. The results of the bactericidal activity measurement and the effect of improving the growth and development of crops are shown in the following examples.
1.1 in vitro bactericidal Activity assay
The test method is as follows: the agent is formulated and diluted to a range of concentrations with a suitable solvent (the kind of solvent is, for example, acetone, methanol, N-dimethylformamide, dimethylsulfoxide, etc., and is selected according to its dissolving power for the sample). Under aseptic condition, packaging NB culture solution into test tubes in equal amount, sequentially and quantitatively sucking medicinal liquid from low concentration to high concentration, respectively adding into the test tubes, shaking, respectively adding bacterial suspension in logarithmic phase in equal amount, and repeating for 4 times. After mixing, placing the mixture in a shaking incubator at 25 ℃ for dark culture, and measuring the OD value in the logarithmic growth phase.
(1) The in vitro bacteriostatic activity (expressed as inhibition rate) of some compounds on cucumber bacterial angular leaf spot pathogenic bacteria is as follows:
at the dose of 5ppm, the compounds with the inhibition rate of more than 90 percent on cucumber bacterial angular leaf spot pathogenic bacteria comprise: 1. 15, 31, 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 136, 143, 144, 149. Under the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on cucumber bacterial angular leaf spot pathogenic bacteria are respectively 2% and 48%.
The compounds with the inhibition rate of more than 90 percent on cucumber bacterial angular leaf spot pathogenic bacteria under the dosage of 1ppm comprise: 1. 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 143, 144, 149. Under the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on cucumber bacterial angular leaf spot pathogenic bacteria are 0 and 21 percent respectively.
(2) The in vitro bacteriostatic activity (expressed as inhibition rate) of part of compounds on tobacco bacterial wilt pathogenic bacteria is as follows:
under the dosage of 5ppm, the compounds with the inhibition rate of more than 90 percent on pathogenic bacteria of tobacco bacterial wilt comprise: 1. 15, 31, 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 136, 143, 144, 149. Under the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on tobacco bacterial wilt pathogenic bacteria are 5% and 51% respectively.
Under the dosage of 1ppm, the compounds with the inhibition rate of more than 90 percent on the tobacco bacterial wilt pathogenic bacteria comprise: 1. 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 143, 144, 149. Under the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on tobacco bacterial wilt pathogenic bacteria are 0 and 28 percent respectively.
(3) The in vitro bacteriostatic activity (expressed as inhibition rate) of part of compounds on the potato phytophthora parasitica pathogen has the following test results:
at a dose of 5ppm, the compounds with the inhibition rate of more than 90 percent on potato phytophthora parasitica comprise: 1. 15, 31, 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 136, 143, 144, 149. At the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on the phytophthora parasitica of the potato phytophthora parasitica are 3% and 55%, respectively.
At a dosage of 1ppm, the compounds with the inhibition rate of more than 90 percent on potato phytophthora parasitica have the following components: 1. 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 143, 144, 149. Under the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on the phytophthora parasitica of the potato phytophthora parasitica are 0 and 38 respectively.
(4) The in vitro bacteriostatic activity (expressed by inhibition rate) of part of compounds on the pathogenic bacteria of the sweet potato stem rot disease is as follows:
under the dosage of 5ppm, the compounds with the inhibition rate of more than 90 percent on the pathogenic bacteria of the stem rot of the sweet potato comprise: 1. 15, 31, 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 136, 143, 144, 149. Under the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on the pathogenic bacteria of the stem rot of the sweet potato are 7 percent and 46 percent respectively.
Under the dosage of 1ppm, the compounds with the inhibition rate of more than 90 percent on the pathogenic bacteria of the stem rot of the sweet potato comprise: 1. 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 143, 144, 149. Under the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on the pathogenic bacteria of the stem rot of the sweet potato are respectively 2% and 25%.
(5) The in vitro bacteriostatic activity (expressed by inhibition rate) of part of compounds on pathogenic bacteria of bacterial blight of rice is as follows:
under the dosage of 5ppm, the compounds with the inhibition rate of more than 90 percent on pathogenic bacteria of bacterial blight of rice comprise: 1. 15, 31, 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 136, 143, 144, 149. Under the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on pathogenic bacteria of the bacterial leaf blight of the rice are 16 percent and 48 percent respectively.
Under the dosage of 1ppm, the compounds with the inhibition rate of more than 90 percent on pathogenic bacteria of bacterial blight of rice comprise: 1. 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 143, 144, 149. Under the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on pathogenic bacteria of the bacterial leaf blight of the rice are respectively 9% and 30%.
(6) The in vitro bacteriostatic activity (expressed as inhibition rate) of part of compounds on pathogenic bacteria of watermelon fruit blotch is as follows:
at the dosage of 5ppm, the compounds with the inhibition rate of more than 90 percent on the pathogenic bacteria of the watermelon fruit blotch comprise: 1. 15, 31, 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 136, 143, 144, 149. Under the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on the pathogenic bacteria of the watermelon fruit blotch are 3 percent and 52 percent respectively.
Under the dosage of 1ppm, the compounds with the inhibition rate of more than 90 percent on the pathogenic bacteria of the watermelon fruit blotch comprise: 1. 32, 35, 45, 50, 696, 52, 68, 86, 91, 108, 118, 124, 130, 133, 143, 144, 149. Under the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on the pathogenic bacteria of the watermelon fruit blotch are 0 and 29 percent respectively.
(7) The in vitro bacteriostatic activity (expressed by inhibition rate) of part of compounds on pathogenic bacteria of the cabbage black rot disease is as follows:
under the dosage of 5ppm, the compounds with the inhibition rate of more than 90 percent on the pathogenic bacteria of the Chinese cabbage black rot disease comprise: 1. 15, 31, 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 136, 143, 144, 149. Under the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on the pathogenic bacteria of the Chinese cabbage black rot disease are 5% and 46% respectively.
Under the dosage of 1ppm, the compounds with the inhibition rate of more than 90 percent on the pathogenic bacteria of the Chinese cabbage black rot disease comprise: 1. 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 143, 144, 149. Under the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on the Chinese cabbage black rot pathogenic bacteria are 0 and 19 respectively.
(8) The in vitro bacteriostatic activity (expressed as inhibition rate) of part of the compounds on pathogenic bacteria of the cassava bacterial wilt disease is as follows:
under the dosage of 5ppm, the compounds with the inhibition rate of more than 90 percent on the pathogenic bacteria of the cassava bacterial wilt disease comprise: 1. 15, 31, 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 136, 143, 144, 149. Under the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on the pathogenic bacteria of the cassava bacterial wilt are 15% and 51% respectively.
Under the dosage of 1ppm, the compounds with the inhibition rate of more than 90 percent on the pathogenic bacteria of the cassava bacterial wilt disease comprise: 1. 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 143, 144, 149. Under the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on the pathogenic bacteria of the cassava bacterial wilt are 7 percent and 32 percent respectively.
(9) The in vitro bacteriostatic activity (expressed by inhibition rate) of part of compounds on pathogenic bacteria of the pear fire blight is as follows:
under the dosage of 5ppm, the compounds with the inhibition rate of more than 90 percent on the pathogenic bacteria of the pear fire blight have the following components: 1. 15, 31, 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 136, 143, 144, 149. Under the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on the pathogenic bacteria of the pear fire blight are 3% and 43% respectively.
Under the dosage of 1ppm, the compounds with the inhibition rate of more than 90 percent on the pathogenic bacteria of the pear fire blight have the following components: 1. 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 143, 144, 149. Under the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on the pathogenic bacteria of the pear fire blight are 0 and 23 percent respectively.
1.2 Activity assay for Living body protection
The compound to be tested is dissolved by a small amount of appropriate solvent (the types of the solvent are acetone, methanol, N-dimethylformamide, dimethyl sulfoxide and the like, and are selected according to the dissolving capacity of the solvent on a sample), and then the compound to be tested is diluted by 0.1 percent of Tween 80 to the test concentration. Uniformly mixing pathogenic bacteria cultured to a stable growth period with a quantitative compound solution, putting the melon seeds, the tomato seeds, the tobacco seeds and the potato seeds subjected to germination acceleration into a mixed solution of a bacterial liquid and a compound for soaking for half an hour, sowing the seeds into an earthworm soil culture cup, putting the earthworm soil culture cup into a greenhouse for moisture preservation and culture, and performing control effect investigation after full control and disease attack.
Cutting 2 cm square leaf of Chinese cabbage, and placing into a glass culture dish filled with double-layer filter paper. Dissolving a compound to be tested by using a small amount of proper solvent (the types of the solvent are acetone, methanol, N-dimethylformamide, dimethyl sulfoxide and the like, and are selected according to the dissolving capacity of the solvent on a sample), spraying the compound diluted to a required concentration by using water on the surface of a Chinese cabbage leaf, airing the liquid medicine on the surface of the Chinese cabbage leaf in a fume hood, needling the surface of the Chinese cabbage leaf by using an inoculating needle to cause a wound, taking 5 microliters of Chinese cabbage soft rot bacteria cultured to a stable growth period, adding the Chinese cabbage soft rot bacteria into the wound, and inoculating. And finally, placing the test material into an incubator to be cultured for 48 hours in a dark place, and carrying out control effect investigation after the control is fully developed.
The compound to be tested is dissolved by a small amount of proper solvent (the types of the solvent are acetone, methanol, N-dimethylformamide, dimethyl sulfoxide and the like, and are selected according to the dissolving capacity of the solvent on a sample), and then the compound to be tested is diluted by water to the required concentration. Spraying the compound water solution on the surface of a plant test material, air-drying the surface liquid medicine in a shade, spraying and inoculating the pathogenic bacterium liquid cultured to a stable growth period on the surface of the plant test material, and then putting the plant test material into a greenhouse for moisture preservation and culture. Usually, the culture is carried out for about ten days, and after the control is fully ill, the control effect investigation is carried out.
Potato black shank, the compound to be tested is dissolved in a small amount of a suitable solvent (the kind of solvent is acetone, methanol, N-dimethylformamide, dimethyl sulfoxide, etc., and is selected according to its dissolving ability for the sample), and then diluted with water to the desired concentration. Root irrigation is carried out on the test potatoes according to the designed medicament concentration, the dosage of each plant is 200mL, and the dosage of each plant is kept consistent (including control treatment). The inoculation of the phytophthora parasitica was performed on day 2 after the application. The results were investigated according to the disease onset.
(1) The test results of the control effect of part of the compounds on cucumber bacterial angular leaf spot are as follows:
at the dose of 10ppm, the compounds with the control effect on cucumber bacterial angular leaf spot higher than 90 percent comprise: 1. 15, 31, 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 136, 143, 144, 149. At the dosage, the control medicaments of the oxine-copper and the zhongshengmycin have 15 percent and 20 percent of control effects on the cucumber bacterial angular leaf spot respectively.
At a dose of 5ppm, the compounds with the control effect on cucumber bacterial angular leaf spot higher than 90 percent comprise: 1. 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 143, 144, 149. At the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on the control effect of the cucumber bacterial angular leaf spot are 10% and 12% respectively.
(2) The results of the control effect test of part of compounds on tobacco bacterial wilt are as follows:
at a dose of 10ppm, the compounds with the control effect on tobacco bacterial wilt being more than 90 percent comprise: 1. 15, 31, 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 136, 143, 144, 149. Under the dosage, the control medicaments of the oxine-copper and the zhongshengmycin have the control effects on tobacco bacterial wilt of 11 percent and 35 percent respectively.
At the dose of 5ppm, the compounds with the control effect on tobacco bacterial wilt being more than 90 percent comprise: 1. 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 143, 144, 149. Under the dosage, the control medicaments of the oxine-copper and the zhongshengmycin have the control effects of 5 percent and 24 percent on the tobacco bacterial wilt respectively.
(3) The results of the test on the control effect of partial compounds on the potato black shank are as follows:
at a dose of 10ppm, the compounds with the control effect on potato black shank being more than 90 percent comprise: 1. 15, 31, 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 136, 143, 144, 149. At the dosage, the inhibition rates of the control medicaments of the oxine-copper and the zhongshengmycin on the control effect of the potato phytophthora parasitica are 22% and 25%, respectively.
At the dose of 5ppm, the compounds with the control effect on potato black shank more than 90 percent comprise: 1. 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 143, 144, 149. At the dosage, the control medicaments of oxine-copper and zhongshengmycin have the control effects on the potato black shank of 11 percent and 17 percent respectively.
(4) The results of the test on the control effect of partial compounds on the stem rot of the sweet potatoes are as follows:
at the dose of 10ppm, the compounds with the control effect on the stem rot of the sweet potato of more than 90 percent comprise: 1. 15, 31, 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 136, 143, 144, 149. Under the dosage, the control medicaments of the oxine-copper and the zhongshengmycin have the control effects of 20 percent and 38 percent on the stem rot of the sweet potato respectively.
At the dose of 5ppm, the compounds with the control effect on the stem rot of the sweet potato of more than 90 percent comprise: 1. 32, 35, 45, 50, 696, 52, 68, 86, 91, 108, 118, 124, 130, 133, 143, 144, 149. Under the dosage, the control medicaments of the oxine-copper and the zhongshengmycin have the control effects of 13 percent and 23 percent on the stem rot of the sweet potato respectively.
(5) The results of the test on the control effect of part of compounds on bacterial blight of rice are as follows:
at a dose of 10ppm, the compounds with the control effect on the bacterial blight of rice more than 90 percent comprise: 1. 15, 31, 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 136, 143, 144, 149. Under the dosage, the control medicaments of the oxine-copper and the zhongshengmycin have 10 percent and 35 percent of control effects on the bacterial blight of rice respectively.
At 5ppm dose, the compounds with the control effect on the bacterial blight of rice more than 90 percent comprise: 1. 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 143, 144, 149. Under the dosage, the control medicaments of the oxine-copper and the zhongshengmycin have 6 percent and 24 percent of control effects on the bacterial blight of rice respectively.
(6) The test results of the prevention effect of part of compounds on the watermelon fruit blotch are as follows:
at the dose of 10ppm, the compounds with the prevention effect on the watermelon fruit blotch of more than 90 percent comprise: 1. 15, 31, 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 136, 143, 144, 149. Under the dosage, the control medicaments of the oxine-copper and the zhongshengmycin have the control effects on the watermelon fruit blotch of 22 percent and 33 percent respectively.
At the dose of 5ppm, the compounds with the prevention effect on the watermelon fruit blotch of more than 90 percent have the following components: 1. 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 143, 144, 149. Under the dosage, the control medicaments of the oxine-copper and the zhongshengmycin have the control effects on the watermelon fruit blotch of 15 percent and 19 percent respectively.
(7) The results of the test on the prevention effect of part of compounds on the soft rot of Chinese cabbage are as follows:
under the dosage of 10ppm, the compound with the prevention effect on the soft rot of the Chinese cabbage of more than 90 percent has the following components: 1. 15, 31, 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 136, 143, 144, 149. Under the dosage, the control medicaments of the oxine-copper and the zhongshengmycin have 16 percent and 39 percent of control effects on the soft rot of the Chinese cabbage respectively.
At the dose of 5ppm, the compound with the prevention effect on the soft rot of the Chinese cabbage of more than 90 percent has the following components: 1. 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 143, 144, 149. Under the dosage, the control medicaments of the oxine-copper and the zhongshengmycin have 6 percent and 23 percent of control effects on the soft rot of the Chinese cabbage respectively.
3. Safety of crops
At a dose of 200ppm, the compounds 1, 15, 31, 32, 35, 45, 50, 52, 68, 86, 91, 108, 118, 124, 130, 133, 136, 143, 144 and 149 are safe for cucumber plant growth, and no discoloration, necrosis, wilting, deformity, etc. appear after administration. Namely, the compound has no adverse effect on test crops, has good safety and meets the safety requirement of green pesticide.
The compound of the invention has positive physiological effects on crops as follows: compared with a blank control, the method has the advantages that the plant height growth of the plants is promoted, the synthesis of chlorophyll is stimulated, the leaf area of the plants is increased, the leaves of the plants are greener and thicker, the photosynthetic efficiency is improved, the plant immunity and the capability of resisting the external adverse environment are indirectly improved, and the plants are stronger.
Claims (7)
1. A quinolone compound characterized by: the structural formula is (I);
（I）
a compound of formula (I) selected from
2. The use of the quinolone compound according to claim 1, wherein: the quinolone compound is used for plants in the agricultural field.
3. The use of the quinolone compound according to claim 1, wherein: the quinolone compound is used for crops in the agricultural field.
4. A crop bacterium-killing composition characterized by comprising at least one carbostyril compound as set forth in claim 1 as an active ingredient.
5. A phytocidal composition comprising as an active ingredient at least one of the quinolone compound set forth in claim 1.
6. A method for controlling bacteria in crops, which comprises applying an effective amount of at least one of the quinolone compound set forth in claim 1 to a crop having bacteria.
7. A method for controlling plant bacteria, which comprises applying an effective amount of at least one of the quinolone compound set forth in claim 1 to a plant having bacteria.
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| CN110551124B (en) | 2021-01-08 |
| CN111320581A (en) | 2020-06-23 |
| CN110563645A (en) | 2019-12-13 |
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