CN116253727A - Piperidine amide compound containing trifluoromethyl oxadiazole biphenyl, preparation method and application thereof - Google Patents
Piperidine amide compound containing trifluoromethyl oxadiazole biphenyl, preparation method and application thereof Download PDFInfo
- Publication number
- CN116253727A CN116253727A CN202111494598.0A CN202111494598A CN116253727A CN 116253727 A CN116253727 A CN 116253727A CN 202111494598 A CN202111494598 A CN 202111494598A CN 116253727 A CN116253727 A CN 116253727A
- Authority
- CN
- China
- Prior art keywords
- alkyl
- hydrogen
- amide compound
- piperidine amide
- biphenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three ring hetero atoms
Abstract
The invention discloses piperidine amide compounds containing trifluoromethyl oxadiazole biphenyl, which are shown in the following formula (T):
Description
Technical Field
The invention belongs to the field of agricultural bactericides, and particularly relates to piperidine amide compounds containing trifluoromethyl oxadiazole biphenyl, a preparation method and application thereof.
Background
In agriculture, long-term use of the same pesticide variety is likely to cause disease resistance, and therefore, new varieties with different mechanisms of action are required to be developed continuously.
WO2015185485A, WO2019101511A, WO2019052932A, WO2018158365A, WO2018162643A, WO2018202487A, WO2020007658A, WO2020016180A discloses a class of trifluoromethyl oxadiazole-containing benzidine compounds, but similar compounds with piperidine structures are not reported, and further reports that similar compounds with piperidine structures have bactericidal activity are not disclosed.
Disclosure of Invention
In order to solve the technical problems, the invention provides a piperidine amide compound containing trifluoromethyl oxadiazole biphenyl, which is shown in a general formula (T):
wherein:
R 1 selected from hydrogen, halogen, C 1 -C 6 Alkyl or C 1 -C 6 A haloalkyl group;
R 2 、R 3 independently selected from hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 1 -C 6 Haloalkyl, C 1 -C 6 Haloalkoxy, cyano-substituted C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy substituted C 1 -C 6 Alkyl, C 3 -C 6 Cycloalkyl or C 1 -C 6 Alkyl substituted C 3 -C 6 Cycloalkyl, or substituted by hydrogen, cyano, halogen, nitro, phenoxy, hydroxy, formyl, carboxyl, C 1 -C 6 Alkyl, C 1 -C 6 Alkenyl, C 1 -C 6 Alkynyl, C 1 -C 6 Haloalkyl, C 1 -C 6 Haloalkoxy, C 1 -C 6 Alkoxycarbonyl or C 1 -C 6 At least one substituted phenyl or 5 membered heteroaryl ring group or 6 membered heteroaryl ring group in haloalkoxycarbonyl, or a structure represented by the following formula (1):
wherein X is selected from the group consisting of-CH 2 -or-CHR 8 -, wherein:
R 8 selected from C 1 -C 6 Alkyl, halogenated C 1 -C 6 Alkyl, and with R 8 The connected carbon atoms are chiral carbon atoms, and the chiral carbon atoms are in a left-handed configuration and/or a right-handed configuration;
R 9 、R 10 、R 11 independently selected from hydrogen, cyano, halo, nitro, phenoxy, hydroxy, formyl, carboxy, C 1 -C 6 Alkyl, C 1 -C 6 Alkenyl, C 1 -C 6 Alkynyl, C 1 -C 6 Haloalkyl, C 1 -C 6 Haloalkoxy, C 1 -C 6 Alkoxycarbonyl or C 1 -C 6 Haloalkoxy carbonyl;
-NR 2 R 3 can also exist in the form of the following ring closure:
wherein R is 12 、R 13 Independently selected from hydrogen, halogen, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 1 -C 6 Haloalkyl、C 1 -C 6 Haloalkoxy groups; when R is 12 And R is 13 When not being hydrogen, with R 12 And/or R 13 The connected carbon atoms are chiral carbon atoms, and the chiral carbon atoms are in a left-handed configuration and/or a right-handed configuration; a is selected from carbon or oxygen.
Preferably, R 1 Selected from hydrogen, halogen, C 1 -C 3 Alkyl, halogenated C 1 -C 3 A haloalkyl group;
R 2 、R 3 independently selected from hydrogen, C 1 -C 3 Alkyl, C 1 -C 3 Alkoxy, C 1 -C 3 Haloalkyl, C 1 -C 3 Haloalkoxy, cyano-substituted C 1 -C 3 Alkyl, C 1 -C 3 Alkoxy substituted C 1 -C 3 Alkyl, C 3 -C 6 Cycloalkyl or C 1 -C 3 Alkyl substituted C 3 -C 6 Cycloalkyl, or by hydrogen, cyano, halogen, nitro, phenoxy, formyl, C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Haloalkoxy, C 1 -C 3 Alkoxycarbonyl or C 1 -C 3 At least one substituted phenyl or pyridyl or thiazolyl group in haloalkoxy carbonyl, or a structure represented by the following formula (1):
x is selected from-CH 2 -or-CHR 8 -, wherein: r is R 8 Selected from C 1 -C 3 An alkyl group; r is R 9 、R 10 、R 11 Independently selected from hydrogen, cyano, halogen, nitro, phenoxy, formyl, C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Haloalkoxy, C 1 -C 3 Alkoxycarbonyl, C 1 -C 3 Haloalkoxy carbonyl;
-NR 2 R 3 can also exist in the form of the following ring closure:
R 12 and R is 13 Independently selected from hydrogen, halogen, C 1 -C 3 Alkyl, C 1 -C 3 Alkoxy, halo C 1 -C 3 Alkyl, halogenated C 1 -C 3 An alkoxy group; a is selected from carbon or oxygen.
Further preferably, R 1 Selected from hydrogen, halogen, methyl or trifluoromethyl;
R 2 、R 3 independently selected from hydrogen, methyl, ethyl, methoxy, ethoxy, 2-trifluoroethyl, cyanomethyl or C 3 -C 6 Cycloalkyl, or phenyl or pyridyl or thiazolyl substituted with at least one of hydrogen, cyano, halogen, nitro, phenoxy, methyl, ethyl, trifluoromethyl, trifluoromethoxy, methoxycarbonyl, or a structure represented by the following formula (1):
x is selected from-CHR 8 -, wherein: r is R 8 Is methyl, R 9 、R 10 、R 11 Independently selected from hydrogen, halogen or methyl;
-NR 2 R 3 can also exist in the form of the following ring closure:
R 12 、R 13 independently selected from hydrogen, halogen, methyl, ethyl; a is selected from carbon or oxygen.
More preferably, the piperidine amide compound containing trifluoromethyl oxadiazole biphenyl is selected from the following structures:
among the substituents described in the present invention: alkyl refers to straight or branched chain forms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl and the like; cycloalkyl is meant to include groups in the form of cyclic chains, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like; haloalkyl refers to a group in which the alkyl group is substituted with one or more halogen atoms; alkoxy means a group having an oxygen atom attached to the end of an alkyl group, such as methoxy, ethoxy, n-propoxy, isopropoxy, t-butoxy and the like; haloalkoxy refers to a group in which an alkyl group is substituted with one or more halogen atoms and an oxygen atom is attached at the end; halogen means fluorine, chlorine, bromine, iodine; by 5-or 6-membered heteroaryl ring group is meant a 5-or 6-membered conjugated ring containing 1 to 3 heteroatoms, the remainder being carbon atoms, wherein the heteroatoms are oxygen, nitrogen, sulfur, e.g., pyridyl, pyrimidinyl, thiazolyl, pyrazolyl, triazolyl, and the like.
The piperidine amide compounds containing trifluoromethyl oxadiazole biphenyl and shown in the general formula (T) provided by the invention are shown in Table 1. The typical compounds shown in Table 1 do not limit the scope of the piperidine amide compound represented by the general formula (T) according to the present invention.
TABLE 1 partial typical Compounds and Nuclear magnetic Hydrogen Spectrometry data
In table 1: s is singlet, b is broad singlet, d is doublet, dd is doublet, t is triplet, q is quartet, and m is multiplet.
The invention also provides a preparation method of the piperidine amide compound containing trifluoromethyl oxadiazole biphenyl, which is shown in the general formula (T), and the preparation method comprises the following steps:
wherein: substituent R 1 、R 2 、R 3 The definition of (a) is as described above, and the acyl chloride reagent is selected from thionyl chloride and/or oxalyl chloride.
Specifically, the preparation method comprises the following steps:
(1) Reacting the intermediates (I), (II) with a base in a first solvent to form an intermediate (III);
(2) The intermediate (III) is hydrolyzed and acidized to generate an Intermediate (IV);
(3) Reacting the Intermediate (IV) with an acid chloride reagent in a second solvent to form an intermediate acid chloride;
(4) In a third solvent, in the presence of a base, an intermediate acid chloride and R 2 R 3 The substituted amine reacts to generate the piperidine amide compound containing trifluoromethyl oxadiazole biphenyl.
In step (1), the first solvent may be an organic solvent commonly used in the art. Preferably, the first solvent is selected from at least one of N, N-dimethylformamide, toluene, dichloromethane, chloroform, carbon tetrachloride, tetrahydrofuran, acetonitrile or dimethylsulfoxide. More preferably, the first solvent is selected from at least one of N, N-dimethylformamide, acetonitrile or tetrahydrofuran. The base is selected from potassium carbonate, sodium carbonate or sodium bicarbonate, preferably potassium carbonate. The reaction temperature in the step (1) is 0-100 ℃, and the preferable reaction temperature is 25-100 ℃.
In step (2), the hydrolysis is carried out in a sodium hydroxide-water soluble organic solvent system, the water soluble organic solvent being selected from ethanol or tetrahydrofuran; acidifying with hydrochloric acid after hydrolysis to obtain Intermediate (IV).
In step (3), the second solvent may be an organic solvent commonly used in the art. Preferably, the second solvent is selected from at least one of N, N-dimethylformamide, toluene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane, tetrahydrofuran, or dimethylsulfoxide. More preferably, the second solvent is selected from at least one of dichloromethane, chloroform or carbon tetrachloride. The reaction temperature of the step (3) is 0-100 ℃, and the reaction temperature is preferably 25-solvent reflux temperature.
In the step (4), the third solvent is selected from at least one of N, N-dimethylformamide, toluene, methylene chloride, chloroform, carbon tetrachloride, tetrahydrofuran or dimethylsulfoxide; more preferably, the third solvent is selected from at least one of toluene, methylene chloride or tetrahydrofuran. The base may be an organic base or an inorganic base, preferably at least one selected from triethylamine, sodium acetate, sodium carbonate or potassium carbonate. The reaction temperature in the step (4) is 0-100 ℃, preferably 0-25 ℃.
The invention also provides application of the piperidine amide compound containing trifluoromethyl oxadiazole biphenyl shown in any one of the general formulas (T) in agricultural sterilization.
As a preferred embodiment, the piperidine amide compound containing trifluoromethyl oxadiazole phenyl group represented by the general formula (T) is suitable for controlling at least one disease selected from Rhizoctonia solani, rhizoctonia brassicae, rhizoctonia apple, pyricularia oryzae, corn rust, soybean rust or wheat leaf rust.
As another preferred embodiment, the piperidine amide compound containing trifluoromethyl oxadiazole phenyl group shown in the general formula (T) is particularly suitable for sterilization of crops such as rice, wheat, cotton, corn, soybean, vegetables and rape.
The invention also provides a pesticide preparation, which contains 0.001-99.99% by weight of piperidine amide compounds containing trifluoromethyl oxadiazole biphenyl, which are shown in the general formula (T). The pesticide preparation can be prepared into emulsifiable concentrates, suspending agents, aqueous suspension agents, microemulsions, (aqueous) emulsions, powders, wettable powders, soluble powders, (water dispersible) granules or capsules and the like.
The pesticide preparation provided by the invention can further contain an agriculturally acceptable carrier besides 0.001-99.99% by weight of piperidine amide compound containing trifluoromethyl oxadiazole biphenyl shown in the general formula (T).
The carrier may be solid or liquid. Suitable solid carriers include natural or synthetic clays and silicates, such as natural silica and diatomaceous earth; magnesium silicate such as talc; magnesium aluminum silicate such as kaolinite, kaolin, montmorillonite and mica; white carbon black, calcium carbonate and light calcium carbonate; calcium sulfate; limestone; sodium sulfate; amine salts such as ammonium sulfate, hexamethylenediamine. The liquid carrier includes water and an organic solvent, which can also be used as an adjuvant or an anti-freezing additive when water is used as a solvent or diluent. Suitable organic solvents include aromatic hydrocarbons such as benzene, xylene, toluene, and the like; chlorinated hydrocarbons such as chlorobenzene, vinyl chloride, chloroform, methylene chloride, etc.; aliphatic hydrocarbons such as petroleum fractions, cyclohexane, light mineral oils; alcohols such as isopropanol, butanol, ethylene glycol, propylene glycol, cyclohexanol, and the like; and their ethers and esters; also ketones, such as acetone, cyclohexanone, dimethylformamide and N-methyl-pyrrolidone.
The carrier may also be a surfactant. Suitable surfactants may be emulsifiers, dispersants or wetting agents; may be ionic or nonionic. Nonionic emulsifiers such as polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, polyoxyethylene fatty amines, and commercially available emulsifiers: agricultural milk 2201B, agricultural milk 0203B, agricultural milk 100#, agricultural milk 500#, agricultural milk 600#, agricultural milk 600-2#, agricultural milk 1601, agricultural milk 2201, agricultural milk NP-10, agricultural milk NP-15, agricultural milk 507#, agricultural milk OX-635, agricultural milk OX-622, agricultural milk OX-653, agricultural milk OX-667, and Ning milk 36#. The dispersing agent comprises sodium lignin sulfonate, nekal, calcium lignin sulfonate, methyl naphthalene sulfonic acid formaldehyde condensate and the like. The wetting agent is as follows: sodium lauryl sulfate, sodium dodecyl benzene sulfonate, sodium alkyl naphthalene sulfonate, and the like.
The invention also provides a sterilization method, which comprises the following steps: the piperidine amide compound containing trifluoromethyl oxadiazole biphenyl shown in the general formula (T) is applied to bacteria needing to be controlled or a medium for growth of the bacteria. When the piperidine amide compound containing trifluoromethyl oxadiazole biphenyl shown in the general formula (T) is applied to bacteria needing to be controlled or a medium for growth of the bacteria, the application amount of the piperidine amide compound is 10-1000 per hectare.
Compared with the prior art, the piperidine amide compound containing trifluoromethyl oxadiazole biphenyl, which is shown in the general formula (T), has the following advantages:
(1) The compound has a novel structure;
(2) The compound has higher bactericidal activity on sheath blight of rice, sclerotinia rot of rape, apple ring rot of apple, rice blast, corn rust, soybean rust, wheat leaf rust and the like, and has higher bactericidal activity at low concentration, in particular to soybean rust and corn rust.
Detailed Description
The invention will be further illustrated with reference to the following specific examples, without limiting the invention to these specific embodiments. It will be appreciated by those skilled in the art that the invention encompasses all alternatives, modifications and equivalents as may be included within the scope of the claims.
1. Synthesis of Compounds
EXAMPLE 1 Synthesis of target Compound T001
(1) Synthesis of intermediate (III) (r1=h)
Intermediate (I) (r1=h) (24.56 g,0.08 mol) was added to a 500mL round bottom flask, 200mL acetonitrile was added, anhydrous potassium carbonate (13.80 g,0.10 mol) and intermediate (II) (15.70 g,0.10 mol) were added, stirred at 40 ℃, monitored by TLC followed by 6H after completion of the reaction, dried over a small amount of anhydrous magnesium sulfate, filtered, concentrated and separated by column chromatography to give intermediate (III) (r1=h). The nuclear magnetic hydrogen spectrum is as follows:
1 H NMR(CDCl3,400MHz)δ:7.96(d,2H,J＝8.4Hz,Ph-H),7.40(d,2H,J＝8.4Hz,Ph-H),4.06(q,2H,J＝6.8Hz,CH2),3.47(s,2H,CH2),2.75～2.80(m,2H,peridine-H),2.19～2.26(m,1H,peridine-H),1.95～2.03(m,2H,peridine-H),1.79～1.85(m,2H,peridine-H),1.67～1.76(m,2H,peridine-H),1.17(t,3H,J＝7.2Hz,CH3).
when R1 is other substituents, the synthesis method of the intermediate (III) is the same as that of the intermediate (III).
(2) Synthesis of Intermediate (IV) (r1=h)
Intermediate (III) (r1=h) (19.15 g,0.05 mol) was added to a 500mL round bottom flask, 200mL of tetrahydrofuran was added and stirred until complete dissolution, 100mL of water and sodium hydroxide (4.00 g,0.10 mol) were added, stirred at room temperature, monitored by TLC followed by 12H and the reaction was complete and stopped. Neutralizing with concentrated hydrochloric acid, adjusting pH to 1-2, precipitating white solid, filtering, and oven drying to obtain Intermediate (IV) (R1=H).
The nuclear magnetic data are as follows: 1 H NMR(DMSO-d 6 ,400MHz)δ:7.99(d,2H,J＝8.4Hz,Ph-H),7.51(d,2H,J＝8.4Hz,Ph-H),3.51(s,2H,CH 2 ),2.70～2.75(m,2H,peridine-H),2.13～2.21(m,1H,peridine-H),1.96～2.03(m,2H,peridine-H),1.74～1.78(m,2H,peridine-H),1.49～1.58(m,2H,peridine-H).
when R1 is other substituents, the synthesis method of the Intermediate (IV) is the same as that described above.
(3) Synthesis of target Compound T001
Intermediate (IV) (r1=h) (0.1 g,0.30 mmol) was taken and added to a 50mL round bottom flask, 15mL of dichloromethane was added, after stirring well, 1 drop of DMF was added, 1mL of oxalyl chloride was slowly added dropwise, and the mixture was heated to reflux at 50 ℃, and after completion of the reaction, all solvents were dried by spinning. 15mL of methylene chloride was added, 0.70mmol of triethylamine and 0.35mmol of 2-methylaniline were added thereto with stirring, and the mixture was stirred at room temperature for 1 hour, and after concentration, TLC separation was performed to obtain the objective compound.
The nuclear magnetic data are as follows: 1 H NMR(400MHZ,CDCl 3 /TMS):δ:8.05(d,2H,J＝8.4Hz,Ph-H),7.81(d,1H,J＝8.4Hz,Ph-H),7.48(d,2H,J＝8.0Hz,Ph-H),7.12(t,2H,J＝8.0Hz,Ph-H),7.07(d,1H,J＝8.0Hz,Ph-H),6.99(s,1H,NH),3.58(s,2H,CH 2 ),2.96～3.00(m,2H,peridine-H),2.25～2.34(m,1H,Piperidine-H),2.24(s,3H,CH 3 ),2.07～2.12(m,2H,Piperidine-H),1.87～1.96(m,4H,Piperidine-H).
other compounds described in table 1 can be synthesized by referring to the same method.
2. Preparation
The following examples show the preparation of the piperidine amide compound containing trifluoromethyl oxadiazole phenyl group as the active ingredient. In the examples below, all "%" refer to weight percent.
EXAMPLE 2 wettable powder
15% of compound (I) (Table 1), 5% of lignosulfonate (M q ) Uniformly mixing 1% of laurinol polyoxyethylene ether (JFC), 40% of diatomite and 44% of light calcium carbonate, and crushing to obtain wettable powder.
Example 3 emulsifiable concentrate
Heating and stirring 10% of compound (I) (shown in Table 1), 5% of pesticide emulsion No. 500 (calcium salt), 5% of pesticide emulsion No. 602, 5% of N-methyl-2-pyrrolidone and 75% of xylene uniformly to obtain the emulsifiable concentrate.
Example 4, granules
Uniformly mixing 5% of compound (I) (table 1), 1% of polyvinyl alcohol (PVA), 4% of sodium naphthalene sulfonate formaldehyde condensate (NMO) and 90% of clay, crushing, adding 20 parts of water into 100 parts of the mixture, kneading, preparing into particles with 14-32 meshes by using an extrusion granulator, and drying to obtain granules.
Example 5 Water-dispersible granules
20% of compound (I) (Table 1), 4% of naphthalene sulfonate formaldehyde condensate, 1% of naphthalene sulfonate, 2% of white carbon black and 73% of kaolin are mixed and crushed, and then water is added for kneading, and the mixture is added into a granulator provided with a screen of a certain specification for granulation. And then drying and sieving (according to the screen range) to obtain the granular product.
Example 6 aqueous suspension
Uniformly mixing 20% of compound (I) (table 1), 1% of fatty alcohol polyoxyethylene ether, 3% of rosin block polyoxyethylene ether polyoxypropylene ether sulfonate, 1% of magnesium aluminum silicate, 0.4% of organosilicon defoamer, 5% of propylene glycol and deionized water (69.5%), adding into a sand mill for sand milling, filtering to obtain suspension mother liquor, and adding the prepared xanthan gum (0.1%) aqueous solution for shearing and uniformly mixing.
3. Biological Activity test
Examples of biological activity assays using the compounds of the invention are given below, it being noted that the invention is not limited to the following examples.
Example 7 determination of Bactericidal Activity
(1) In vivo bactericidal activity test:
the sterilization test target is Puccinia sorghi (Puccinia sorghi).
The test method adopts a leaf inoculation method. Selecting two pots of potted corn seedlings with consistent growth vigor in the true leaf period, dissolving a sample with a proper amount of DMF solvent to prepare liquid medicine with the concentration of 200mg/L, 100 mg/L, 50mg/L and 25mg/L, spraying the liquid medicine on leaf surfaces, and inoculating fungus cakes on the leaf surfaces after the liquid medicine is sprayed and dried. After 24-26 ℃ dark light moisturizing for 24 hours, natural light moisturizing culture is restored for about 3 days. After the control is fully ill, the diameter of the disease spot of each inoculation point is measured by a caliper, and the control effect is calculated.
After test treatment, the disease condition and hypha growth condition of the leaves and plants are observed and recorded, and according to the disease index and the hypha diameter, the relative prevention effect is calculated according to the disease index by referring to the bactericide volume of "created pesticide biological Activity evaluation SOP".
Formula for calculating bactericidal efficacy
Disease index = 100×Σ (number of leaves at each stage x representative value at each stage)/(total leaves investigated x representative value at highest stage);
control effect (%) =100× (control disease index-treated disease index)/control disease index.
The results of the evaluation of the bactericidal activity are as follows.
At the concentration of 200mg/L, the prevention effect of the compounds T006, T038, T042, T044, T047, T049, T053, T065 and T071 on corn rust is more than 70%;
at the concentration of 200mg/L, the prevention effect of the compounds T001, T002, T003, T011, T012, T016, T019, T035, T039, T040, T051, T066, T068, T069, T070 and T076 on corn rust is more than 50%.
(2) In vitro bactericidal activity test
Test treatment: each test compound was dissolved in DMSO to 1% ec stock solution for use. The indoor bactericidal activity of the compound to be tested on the test target at the dose of 50ppm is evaluated by adopting a bacteriostasis circle method, and a water control (QCK) is additionally arranged. Test object: tomato early blight (Alternaria solani), wheat scab (Gibberella zeae), rice blast (Pyricularia oryae), pepper phytophthora capsici (Phytophthora capsici), sclerotinia sclerotiorum (Sclerotinia sclerotiorum), cucumber Botrytis cinerea (Botrytis cinerea), rhizoctonia solani (Riziocotinia solani), cucumber fusarium wilt (Fusarium oxysporum), peanut brown spot (Cercospora arachidicola) and apple ring rot (Physalospora piricola).
The test method comprises the following steps: a pipetting gun was used to aspirate 0.15mL of the EC mother solution prepared as described above, and the resultant was dissolved in 2.85mL of distilled water to prepare a drug solution having an effective concentration of the test compound of 500 ppm. 1mL of the liquid medicine is sucked by a pipette, placed in a sterilized culture dish, placed in 9mL of PDA culture medium, shaken well and cooled. After taking out the circular fungus cake by a puncher, picking up the circular fungus cake to the center of a culture dish by an inoculating needle, then placing the culture dish in an incubator at 27 ℃ for culturing, and measuring the colony diameter after 48-72 hours. The pure growth amount of the bacterial colony is the difference value between the average diameter of the bacterial colony and the diameter of a bacterial cake, and the calculation method of the fungi inhibition rate is referred to the following formula.
The control colony pure growth in the above calculation formula refers to the colony pure growth under the clear water control (QCK) test.
In vitro sterilization results at 50mg/L concentration:
A. rice sheath blight germ: the inhibition rate of the compounds T006, T019, T038, T042, T044, T047, T049, T051, T053, T065, T069, T071 and T073 to the rice sheath blight bacteria is above 80%;
B. sclerotinia sclerotiorum: the inhibition rate of the compounds T006, T019, T038, T042, T044, T047, T049, T051, T053, T065, T069 and T071 on the sclerotinia rot of rape is above 80%;
C. apple ring rot germ: the inhibition rate of the compounds T006, T042, T053 and T065 to the apple ring rot is above 80%, and the inhibition rate of the compounds T019, T038, T044, T047, T049, T051, T069, T071 and T073 to the apple ring rot is above 50%;
D. rice blast fungus: the inhibition rate of the compound T053 to the rice blast fungus is more than 80 percent, and the inhibition rate of the compounds T038, T042, T044 and T073 to the rice blast fungus is more than 50 percent.
Claims (13)
1. Piperidine amide compounds containing trifluoromethyl oxadiazole biphenyl and shown in the following formula (T):
wherein:
R 1 selected from hydrogen, halogen, C 1 -C 6 Alkyl or C 1 -C 6 A haloalkyl group;
R 2 、R 3 independently selected from hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 1 -C 6 Haloalkyl, C 1 -C 6 Haloalkoxy, cyano-substituted C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy substituted C 1 -C 6 Alkyl, C 3 -C 6 Cycloalkyl or C 1 -C 6 Alkyl substituted C 3 -C 6 Cycloalkyl, or substituted by hydrogen, cyano, halogen, nitro, phenoxy, hydroxy, formyl, carboxyl, C 1 -C 6 Alkyl, C 1 -C 6 Alkenyl, C 1 -C 6 Alkynyl, C 1 -C 6 Haloalkyl, C 1 -C 6 Haloalkoxy, C 1 -C 6 Alkoxycarbonyl or C 1 -C 6 At least one substituted phenyl or 5 membered heteroaryl ring group or 6 membered heteroaryl ring group in haloalkoxycarbonyl, or a structure represented by the following formula (1):
wherein X is selected from the group consisting of-CH 2 -or-CHR 8 -, wherein:
R 8 selected from C 1 -C 6 Alkyl, halogenated C 1 -C 6 Alkyl, and with R 8 The connected carbon atoms are chiral carbon atoms, and the chiral carbon atoms are in a left-handed configuration and/or a right-handed configuration;
R 9 、R 10 、R 11 independently selected from hydrogen, cyano, halo, nitro, phenoxy, hydroxy, formyl, carboxy, C 1 -C 6 Alkyl, C 1 -C 6 Alkenyl, C 1 -C 6 Alkynyl, C 1 -C 6 Haloalkyl, C 1 -C 6 Haloalkoxy, C 1 -C 6 Alkoxycarbonyl or C 1 -C 6 Haloalkoxy carbonyl;
-NR 2 R 3 can also exist in the form of the following ring closure:
wherein R is 12 、R 13 Independently selected from hydrogen, halogen, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 1 -C 6 Haloalkyl, C 1 -C 6 Haloalkoxy groups; when R is 12 And R is 13 When not being hydrogen, with R 12 And/or R 13 The connected carbon atoms are chiral carbon atoms, and the chiral carbon atoms are in a left-handed configuration and/or a right-handed configuration; a is selected from carbon or oxygen.
2. The piperidine amide compound having a trifluoromethyl oxadiazole phenyl group according to claim 1, wherein:
R 1 selected from hydrogen, halogen, C 1 -C 3 Alkyl, halogenated C 1 -C 3 A haloalkyl group;
R 2 、R 3 independently selected from hydrogen, C 1 -C 3 Alkyl, C 1 -C 3 Alkoxy, C 1 -C 3 Haloalkyl, C 1 -C 3 Haloalkoxy, cyano-substituted C 1 -C 3 Alkyl, C 1 -C 3 Alkoxy substituted C 1 -C 3 Alkyl, C 3 -C 6 Cycloalkyl or C 1 -C 3 Alkyl substituted C 3 -C 6 Cycloalkyl, or by hydrogen, cyano, halogen, nitro, phenoxy, formyl, C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Haloalkoxy, C 1 -C 3 Alkoxycarbonyl or C 1 -C 3 At least one substituted phenyl or pyridyl or thiazolyl group in haloalkoxy carbonyl, or a structure represented by the following formula (1):
x is selected from-CH 2 -or-CHR 8 -, wherein: r is R 8 Selected from C 1 -C 3 An alkyl group; r is R 9 、R 10 、R 11 Independent and independentSelected from hydrogen, cyano, halogen, nitro, phenoxy, formyl, C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Haloalkoxy, C 1 -C 3 Alkoxycarbonyl, C 1 -C 3 Haloalkoxy carbonyl;
-NR 2 R 3 can also exist in the form of the following ring closure:
R 12 and R is 13 Independently selected from hydrogen, halogen, C 1 -C 3 Alkyl, C 1 -C 3 Alkoxy, halo C 1 -C 3 Alkyl, halogenated C 1 -C 3 An alkoxy group; a is selected from carbon or oxygen.
3. The piperidine amide compound having a trifluoromethyl oxadiazole phenyl group according to claim 2, wherein: in the general formula (T):
R 1 selected from hydrogen, halogen, methyl or trifluoromethyl;
R 2 、R 3 independently selected from hydrogen, methyl, ethyl, methoxy, ethoxy, 2-trifluoroethyl, cyanomethyl or C 3 -C 6 Cycloalkyl, or phenyl or pyridyl or thiazolyl substituted with at least one of hydrogen, cyano, halogen, nitro, phenoxy, methyl, ethyl, trifluoromethyl, trifluoromethoxy, methoxycarbonyl, or a structure represented by the following formula (1):
x is selected from-CHR 8 -, wherein: r is R 8 Is methyl, R 9 、R 10 、R 11 Independently selected from hydrogen, halogen or methyl;
-NR 2 R 3 also can be a ring as followsThe combined form exists:
R 12 、R 13 independently selected from hydrogen, halogen, methyl, ethyl; a is selected from carbon or oxygen.
4. A piperidine amide compound having a trifluoromethyl oxadiazole phenyl group according to claim 3, characterized in that: the piperidine amide compound containing trifluoromethyl oxadiazole biphenyl is selected from the following structures:
5. a process for producing a piperidine amide compound having a trifluoromethyl oxadiazole phenyl group represented by any one of the general formulas (T) according to claims 1 to 4, characterized in that: the preparation method comprises the following steps:
wherein: substituent R 1 、R 2、 R 3 The definition of (c) is as in claim 1, the acyl chloride reagent is selected from thionyl chloride and/or oxalyl chloride.
6. The process for producing a piperidine amide compound having a trifluoromethyl oxadiazole phenyl group represented by the general formula (T) according to claim 5, characterized by: the preparation method comprises the following steps:
(1) Reacting the intermediates (I), (II) with a base in a first solvent to form an intermediate (III);
(2) The intermediate (III) is hydrolyzed and acidized to generate an Intermediate (IV);
(3) Reacting the Intermediate (IV) with an acid chloride reagent in a second solvent to form an intermediate acid chloride;
(4) In a third solvent, in the presence of a base, an intermediate acid chloride and R 2 R 3 The substituted amine reacts to generate the piperidine amide compound containing trifluoromethyl oxadiazole biphenyl.
7. The process for producing a piperidine amide compound having a trifluoromethyl oxadiazole phenyl group represented by the general formula (T) according to claim 6, characterized by:
in the step (1), the reaction temperature is 0-100 ℃, and the first solvent is at least one selected from N, N-dimethylformamide, toluene, methylene dichloride, chloroform, carbon tetrachloride, tetrahydrofuran, acetonitrile and dimethyl sulfoxide; the base is selected from potassium carbonate or triethylamine;
in the step (2), hydrolysis and acidification reactions are carried out in a sodium hydroxide-water-soluble organic solvent system, wherein the water-soluble organic solvent is at least one selected from ethanol, methanol, 1, 4-dioxane or tetrahydrofuran;
in the step (3), the second solvent is selected from at least one of N, N-dimethylformamide, toluene, methylene chloride, chloroform, carbon tetrachloride, dichloroethane, tetrahydrofuran, or dimethylsulfoxide;
in the step (4), the third solvent is selected from at least one of N, N-dimethylformamide, toluene, methylene chloride, chloroform, carbon tetrachloride, tetrahydrofuran or dimethylsulfoxide; the base is selected from at least one of an organic base and an inorganic base.
8. The process for producing a piperidine amide compound having a trifluoromethyl oxadiazole phenyl group represented by the general formula (T) according to claim 7, characterized by:
in the step (1), the reaction temperature is 25-100 ℃, the first solvent is at least one of N, N-dimethylformamide, acetonitrile or tetrahydrofuran, and the alkali is potassium carbonate;
in step (2), the water-soluble organic solvent is selected from ethanol or tetrahydrofuran;
in the step (3), the second solvent is selected from at least one of dichloromethane, chloroform or carbon tetrachloride;
in the step (4), the third solvent is selected from at least one of toluene, methylene chloride or tetrahydrofuran, and the base is selected from triethylamine or potassium carbonate.
9. Use of piperidine amides containing trifluoromethyl oxadiazole biphenyl according to any one of claims 1-4, characterized in that: the piperidine amide compound containing trifluoromethyl oxadiazole biphenyl is used for sterilization.
10. Use of piperidine amides containing trifluoromethyl oxadiazole biphenyl according to claim 9, characterized in that: the piperidine amide compound containing trifluoromethyl oxadiazole biphenyl is used for preventing and controlling at least one disease of Rhizoctonia solani, sclerotinia brassicae, apple ring rot, rice blast, corn rust, soybean rust or wheat leaf rust.
11. A pesticide formulation characterized in that: the pesticide preparation contains 0.001-99.99% by weight of piperidine amide compound containing trifluoromethyl oxadiazole biphenyl represented by any one of the general formulas (T) in claims 1-4, and the balance of agriculturally acceptable carriers.
12. A method of controlling disease, characterized by: applying the piperidine amide compound having a trifluoromethyl oxadiazole phenyl group represented by the general formula (T) according to any one of claims 1 to 4 to a disease to be controlled or a medium in which the disease grows.
13. A method of controlling disease according to claim 12, wherein: the effective amount of the piperidine amide compound containing trifluoromethyl oxadiazole biphenyl applied to the diseases to be controlled or the medium on which the piperidine amide compound grows is 10-1000 g per hectare.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111494598.0A CN116253727A (en) | 2021-12-09 | 2021-12-09 | Piperidine amide compound containing trifluoromethyl oxadiazole biphenyl, preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111494598.0A CN116253727A (en) | 2021-12-09 | 2021-12-09 | Piperidine amide compound containing trifluoromethyl oxadiazole biphenyl, preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116253727A true CN116253727A (en) | 2023-06-13 |
Family
ID=86677907
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111494598.0A Pending CN116253727A (en) | 2021-12-09 | 2021-12-09 | Piperidine amide compound containing trifluoromethyl oxadiazole biphenyl, preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116253727A (en) |
-
2021
- 2021-12-09 CN CN202111494598.0A patent/CN116253727A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2751642C1 (en) | M-diamide based compound, method of synthesis and application thereof | |
| JP5089581B2 (en) | 1,2-Benzisothiazole derivatives and plant disease control agents for agriculture and horticulture | |
| KR101693375B1 (en) | Halogen-substituted compounds used as pesticides | |
| WO2013064079A1 (en) | Use of compound of pyrazole amides as agricultural fungicide | |
| WO2008145052A1 (en) | Substituted pyrimidine ether compounds and their use | |
| WO2014187298A1 (en) | N-pyridine amide compound, preparation method therefor, and application thereof | |
| WO2014187297A1 (en) | N-pyridine(hetero)aromatic amide compound and preparation method and use thereof | |
| CN108570018B (en) | Amide compound and preparation method and application thereof | |
| CA3134907A1 (en) | Amide compounds and preparation method therefor and use thereof | |
| JP4706482B2 (en) | Pyridylmethyl derivative of 2,6-dichloroisonicotinic acid, method for producing the same, and agricultural and horticultural disease control agent | |
| CN113045561B (en) | Diarylamine derivatives as fungicides | |
| CN116253727A (en) | Piperidine amide compound containing trifluoromethyl oxadiazole biphenyl, preparation method and application thereof | |
| CN116253728A (en) | Piperidine amide compound containing trifluoromethyl oxadiazole dithiophene, and preparation method and application thereof | |
| CN110804019B (en) | Amide compound and preparation method and application thereof | |
| TW201737B (en) | ||
| JPH10505075A (en) | Imidic acid derivatives and their use as pesticides | |
| JP4406155B2 (en) | Benzoxazole derivatives, process for producing them and herbicides | |
| JP2000159610A (en) | Plant disease control agent for agriculture and horticulture and new isooxazole carboxylic acid derivative | |
| JP4484308B2 (en) | Benzoxazole derivative, process for producing the same and herbicide | |
| JP3366715B2 (en) | Aminopyrimidine derivatives, their production method and intermediates for production, and agricultural fungicides, insecticides and acaricides containing the same | |
| JP4561068B2 (en) | 2-Chloro-1,3-thiazole-5-methanol derivative, process for producing the same and agricultural and horticultural disease control agent | |
| CN108610283B (en) | Secondary amine compound and preparation and application thereof | |
| JP5016760B2 (en) | Benzoxazole derivatives, process for producing them and herbicides | |
| JPWO2006004215A1 (en) | Benzoxazole compounds | |
| CN116924952A (en) | Sulfur-containing amide compound and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |