Pyrazole ether compound as well as preparation method and application thereofTechnical Field
The invention belongs to the field of pesticides and bactericides, and in particular relates to a pyrazole ether compound with insecticidal and bactericidal biological activity, a preparation method thereof, an insecticidal and bactericidal composition containing the compound, and application and a method for controlling pests and harmful bacteria by using the compound.
Background
Pest control and control of harmful pathogens are important in achieving efficient agriculture. The control of pests and harmful pathogens is also important in the fields of forests, pastures, auxiliary, fishing and public health. Although many pesticides for pest and harmful bacteria exist in the market, due to the continuous expansion of the market, the external pests and harmful bacteria, the drug resistance of the pests and harmful bacteria, the service life of the drugs, the economy of the drugs and the like, and the increasing importance of people on the environment, scientists are required to continuously research and develop new varieties of pesticides with high efficiency, safety, economy, environmental compatibility and unique action modes.
The pyrazole ether compound has broad-spectrum bioactivity, and the broad-spectrum bactericide pyraclostrobin D1 (CAS 175013-18-0) is disclosed in patents such as US5869517, US6054592, CN1154692, CN1308065 and the like, and the English generic name is pyraclostrobin.
Related derivatives D2 (CAS 512165-96-7) of pyraclostrobin with OCH3 as H are also reported in the relevant literature.
In order to obtain novel pyrazole ether compounds with biological activity, based on related literature and our earlier work, we designed and synthesized pyrazole ether compounds with insecticidal and bactericidal activity shown in formula (I) which are not reported. The synthesis of the compound is simpler and more convenient than D1, and the compound of the invention such as 03, 135 and the like shows higher bactericidal activity on diseases such as wheat gibberella, phytophthora capsici and the like than D1 and D2, and the activity of 135 and the like on diseases such as corn rust and the like is at the same level as D1.
Disclosure of Invention
The invention provides a pyrazole ether compound with biological activity for preventing and controlling pests, harmful bacteria and the like, which is shown in a formula (I):
Wherein:
I.R represents C1-C12 alkoxy, C3-C8 cycloalkoxy, C3-C8 heterocycloalkoxy, C2-C12 alkenyloxy, C2-C12 alkynyloxy, C1-C12 alkylthio, C2-C12 alkenylthio, C2-C12 alkynylthio, C1-C12 alkylamino, C1-C12 dialkylamino, C2-C12 alkenylamino, C2-C12 alkynylamino, C2-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl;
r1、R2、R3 are identical or different and represent hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkinyl, C3-C8 cycloalkyl, C3-C8 heterocycloalkyl;
R4、R5 are identical or different and represent hydrogen, halogen, C1-C12 alkyl, C1-C12 alkoxy;
W represents oxygen or sulfur;
V.m, n are identical or different, m represents an integer of 1, 2,3 or 4, n represents an integer of 1, 2,3, 4 or 5;
I. The hydrogen atoms in the alkyl, alkenyl, alkynyl, cycloalkyl or heterocyclyl groups in II or III may be partially or fully substituted by identical or different substituents selected from the group consisting of: halogen, C1-C6 alkyl, C1-C6 alkoxy, phenyl, substituted phenyl;
In the definition of compound (I) above, the terms used, whether used alone or in compound words, represent the following substituents:
halogen: fluorine, chlorine, bromine, iodine;
Alkyl: refers to straight or branched chain alkyl groups;
alkenyl groups; refers to straight or branched alkyl groups and may have double bonds at any position;
alkynyl; refers to straight or branched alkyl groups and may have triple bonds at any position;
halogenating: means that hydrogen atoms are partially or completely substituted with halogen atoms;
cycloalkyl: refers to saturated or unsaturated cycloalkyl;
Heterocycloalkyl group: refers to saturated or unsaturated heterocycloalkyl groups of which there are at least 1N, O or S.
Preferred compounds of the invention are: in formula (I):
I.R represents a C1-C6 alkoxy group, a C1-C6 alkylamino group;
R1、R2、R3 are identical or different and represent hydrogen, C1-C3 alkyl;
R4、R5 are identical or different and represent hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy;
W represents oxygen or sulfur;
V.m, n are identical or different, m represents an integer of 1, 2,3 or 4, n represents an integer of 1, 2,3, 4 or 5.
Further preferred compounds of the invention are: in formula (I):
I.R represents a C1-C3 alkoxy group;
R1、R2、R3 are identical or different and represent hydrogen, methyl, monofluoromethyl, difluoromethyl, trifluoromethyl, ethyl, pentafluoroethyl, propyl, heptafluoropropyl;
R4、R5 are identical or different and represent hydrogen, halogen, methyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, pentafluoroethyl, propyl, heptafluoropropyl;
w represents oxygen;
V.m, n are identical or different, m represents an integer of 1, 2,3 or 4, n represents an integer of 1, 2,3, 4 or 5.
Particularly preferred compounds of the invention are: in formula (I):
I.R represents methoxy;
R1、R2、R3 are identical or different and represent hydrogen, methyl, monofluoromethyl, difluoromethyl, trifluoromethyl;
r4、R5 are identical or different and represent hydrogen, halogen, methyl, trifluoromethyl, methoxy, trifluoromethoxy;
w represents oxygen;
V.m, n are identical or different, m represents an integer of 1, 2,3 or 4, n represents an integer of 1, 2,3, 4 or 5.
Further particularly preferred compounds of formula (I) according to the invention are those shown below:
The compounds of the present invention may exist in one or more isomeric forms. Isomers include enantiomers, diastereomers, geometric isomers and cis-trans isomers. The compounds of formula (I) of the present invention, which may form geometric isomers (Z and E represent different configurations, respectively) due to the different substituents attached to the carbon-carbon double bond, include Z-type isomers and E-type isomers and mixtures thereof in any ratio. The compound shown in the formula (I) forms stereoisomers (respectively represented by R and S in different configurations) due to the fact that four different substituents are connected to one carbon atom, and the invention comprises R-type isomers and S-type isomers and mixtures thereof in any proportion. The compound shown in the formula (I) forms cis-trans isomers (respectively expressed by cis and trans) due to the fact that more than 2 substituents are connected on cycloalkyl or heterocycloalkyl, and the cis-isomer, trans-isomer and the mixture of cis-isomer and trans-isomer in any proportion are included in the invention.
The invention also relates to a composition for controlling pests, harmful bacteria, comprising a biologically effective amount of a compound of formula (I) and at least one additional diluent selected from the group consisting of surfactants, solid diluents and liquid diluents.
The invention also relates to a composition for controlling pests, harmful bacteria, comprising a biologically effective amount of a compound of formula (I) and an effective amount of at least one further biologically active compound or formulation.
The invention also relates to a method for controlling pests, harmful pathogens, comprising contacting the pests, harmful pathogens, or the environment thereof with a biologically effective amount of a compound of formula (I). Also disclosed is a method for controlling pests, harmful pathogens, or their environment by contacting the pests, harmful pathogens, or their environment with a biologically effective amount of a compound of formula (I) or a mixture comprising a compound of formula (I) and a biologically effective amount of at least one additional compound or formulation.
The compounds of formula (I) of the present invention have broad spectrum activity: some compounds are useful for controlling harmful pathogens, and also for controlling pests; and some compounds have high biological activity on certain harmful pathogens, so that good effects can be obtained at low doses.
Preferred compositions of the present invention are compositions containing the preferred compounds described above. Preferred methods are those using the preferred compounds described above.
The invention is further illustrated, but not limited, by the following description of some of the compounds of formula (I) listed in Table 1. The melting points given in the present invention are not corrected, and when the compound of formula (I) synthesized in the present invention is a viscous solid, some of the viscous solid solidifies to a non-viscous solid after being left to stand, and when the compound of formula (I) synthesized in the present invention is a viscous liquid, some of the viscous liquid solidifies after being left to stand, and molecular ion peaks are observed in LC-MS (APCI, pos or Neg) (Agilent 1100Series LC/MSD) of the compounds in Table 1. Table 2 shows the NMR and MS data for a portion of the compounds, compound1 H NMR (Varian INOVA-300 spectrometer) in Table 2 using TETRAMETHYLSILANE (TMS) as an internal standard, deuterated chloroform (CDCl3) or deuterated dimethyl sulfoxide (DMSO) as solvents.
Table 1:
TABLE 2
The compound represented by the formula (I) of the present invention can be obtained by the following reaction formula 1; (II) in the reaction scheme 1 can be obtained by the following reaction scheme 2; (IV) in the reaction scheme 1 can be obtained by the following reaction scheme 3; (VI) in the reaction scheme 2 can be obtained by the following scheme 4; the compounds (III), (V), (VII) and (IX) in the reaction formula can be synthesized by purchasing or referring to relevant documents; l in the formula is a leaving group such as chlorine, bromine, iodine, sulfonate, etc., and the other substituents are as defined above unless otherwise indicated.
Reaction formula 1-1:
Reaction formula 1-2:
Reaction formula 2:
Reaction formula 3-1:
reaction formula 3-2:
Reaction formula 4:
The compounds of formula (I) can be prepared as such (reaction formula 1): in ethyl acetate, dichloromethane, dichloroethane, acetonitrile, toluene, N-Dimethylformamide (DMF), methanol, ethanol, tetrahydrofuran or dioxane, or a mixed solvent of any two, in the presence of a proper base such as triethylamine, pyridine, sodium hydride, potassium hydroxide, potassium carbonate, sodium hydroxide or sodium carbonate, or the like, at a temperature of between-10 and 60 ℃, the compound of formula (II) is reacted with the compound of formula (III), or the compound of formula (IV) is reacted with the compound of formula (V), so as to obtain the compound of formula (I).
The compound of formula (II) can be prepared as follows (reaction formula 2): the compound of formula (II) is obtained by reacting the compound of formula (VI) with the compound of formula (V) in the presence of a suitable base such as triethylamine, pyridine, sodium hydride, potassium hydroxide, potassium carbonate, sodium hydroxide or sodium carbonate in a single solvent or a mixed solvent of any two of ethyl acetate, dichloromethane, dichloroethane, acetonitrile, toluene, N-Dimethylformamide (DMF), methanol, ethanol, tetrahydrofuran or dioxane.
The compound of formula (IV) can be prepared as follows (scheme 3): reacting a compound of formula (VI) with a compound of formula (III) in the presence of a suitable base such as triethylamine, pyridine, sodium hydride, potassium hydroxide, potassium carbonate, sodium hydroxide or sodium carbonate in ethyl acetate, dichloromethane, dichloroethane, acetonitrile, toluene, N-Dimethylformamide (DMF), methanol, ethanol, tetrahydrofuran or dioxane or a mixed solvent of any two at-10 to 60 ℃ to obtain a compound of formula (IV);
Or in ethyl acetate, dichloromethane, dichloroethane, acetonitrile, toluene, N-Dimethylformamide (DMF), methanol, ethanol, isopropanol, tetrahydrofuran or dioxane, or a mixed solvent of any two, in the presence of a proper base such as triethylamine, pyridine, sodium hydride, potassium hydroxide, potassium carbonate, sodium hydroxide or sodium carbonate, and the like at a temperature of 25 ℃ to a reflux temperature of the system, the compound of the formula (VI) and the compound of the formula (VII) react to obtain the compound of the formula (VIII), and the compound of the formula (VIII) is reduced in a single solvent or a mixed solvent of any two of ethyl acetate, methanol, ethanol, propanol, isopropanol, tetrahydrofuran or acetic acid, and the like at a reflux temperature of 25 ℃ to a reflux temperature of the system, in the absence of a catalyst or in the presence of a proper catalyst such as palladium carbon, raney nickel or hydrochloric acid, and the like, with a proper reducing agent such as sodium borohydride, lithium aluminum hydride, hydrazine hydrate, zinc powder or hydrogen.
The compound of formula (VI) can be prepared as follows (scheme 4): reducing the compound of formula (IX) with a suitable reducing agent such as sodium borohydride, lithium aluminum hydride, hydrazine hydrate, zinc powder or hydrogen in the presence of a suitable catalyst such as palladium on charcoal, raney nickel, hydrochloric acid or sulfuric acid in ethyl acetate, dichloromethane, dichloroethane, acetonitrile, toluene, N-Dimethylformamide (DMF), methanol, ethanol, isopropanol, tetrahydrofuran or dioxane or a mixed solvent of any two at a temperature of 25 ℃ to the reflux temperature of the system to obtain the compound of formula (VI).
Specific synthetic methods are set forth in more detail in the examples below.
The compound of the formula (I) provided by the invention has broad-spectrum biological activity under the dosage of 15-2250 g of active ingredient per hectare, and can be used for preventing and treating harmful bacteria and harmful insects. Some compounds have good harmful bacteria preventing and treating effect, and good effect can be obtained at low dosage.
The compound of the formula (I) provided by the invention has biological activity and some compounds have good biological activity, and particularly has activity in the aspect of controlling agricultural, horticultural, flower and sanitary pests and harmful bacteria. The pests described herein include, but are not limited to:
Harmful pathogenic bacteria: phytophthora species, erysiphe species, gibberella species, ceripomoea species, rhizoctonia species, botrytis species, pyricularia species, fusarium species. Such as rice blast (Pyricularia oryzae); wheat stripe rust (Puccinia striiformis), leaf rust (Puccinia recondita) and other rust; barley stripe rust (Puccinia striiformis), leaf rust (Puccinia recondita), and other rust; barley and wheat powdery mildew (ERYSIPHE GRAMINIS), cucumber powdery mildew (Sphaerotheca fuligenea), apple powdery mildew (Podosphaera leucotrichar) and grape powdery mildew (Podosphaera leucotrichar); sheath blight and glume blight (Septoria nodorum) of wheat. Vermicular, muzzle, aschersonia, nucleocapsid, pseudocercosporella herpotrichoides and wheat take-all on cereals (Gaeumannomyces graminis). Brown spot (Cercospora arachidicola) and black spot (Cercosporidium personata) of peanuts; alternaria alternata (Botryosphaeria berengriana f.sp piricola), and alternaria alternata (Cytospora sp.); its cercospora disease on beet, soybean and rice. Tomato, cucumber, grape gray mold (Botrytis cinerea). Gemini disease on vegetables such as cucumber. Anthracnose on cucumber, apple scab, cucumber downy mildew, grape downy mildew, epidemic disease on potato and tomato, monocotyledonous Thanatephorus cucumeris on rice and other hosts such as wheat and barley, other rhizoctonia on vegetables; sclerotinia rot of colza (Sclerotonia sclerotiorum); wheat scab (Gibberella zeae); phytophthora capsici (Phytophythora capsici).
Insect pest: lepidoptera pests such as Oriental armyworm, spodoptera litura, plutella xylostella, spodoptera exigua, cabbage caterpillar, orientials such as Blatta seu Blatta, thysanoptera such as Fragilt, rice thrips, and melon thrips, homoptera such as leafhopper, plant hopper, and aphid, hymenoptera such as larva of Apis, diptera such as Aedes, culex, and fly; acarina pest mites such as panonychus citri, tetranychus gossypii, tetranychus urticae, etc.
The compounds of formula (I) of the present invention, when used alone, are effective in controlling pests, harmful pathogens, and may also be used with other biochemical substances including other insecticides, nematocides, acaricides and fungicides.
The agricultural preparation taking the compound (I) as the effective component can be prepared into any desired dosage form such as dry compressed particles, flowable mixture, granules, wettable powder, water dispersible granules, emulsifiable concentrate, powder, powdery concentrate, microemulsion, suspending agent, emulsifiable concentrate, aqueous emulsion, soluble liquid, aqueous solution and dispersible agent, and suitable auxiliary agents comprise carriers (diluents) and other auxiliary agents such as spreading agents, emulsifying agents, wetting agents, dispersing agents, adhesion agents and decomposing agents. These formulations contain the compounds of the present invention in admixture with an inert, pharmacologically acceptable solid or liquid diluent.
Examples of compositions of the invention may also be formulated into any desired dosage form such as dry compressed granules, flowable mixtures, granules, wettable powders, water dispersible granules, emulsifiable concentrates, powders, powdered concentrates, microemulsions, suspensions, emulsifiable concentrates, aqueous solutions, dispersible solutions, suitable adjuvants include carriers (diluents) and other adjuvants such as spreaders, emulsifiers, wetting agents, dispersants, adhesives and disintegrants. These formulations contain the compounds of the present invention in admixture with an inert, pharmacologically acceptable solid or liquid diluent.
The invention is further illustrated by the following examples, in which the yields are not optimised, and in which other compounds of the invention can be prepared by reference to the following examples and the relevant literature.
Detailed Description
Synthetic examples
Example 1 this example illustrates a process for the preparation of compound 03 of Table 1 (Process A)
O-nitrobenzyl bromide to a mixture of 40% hydrobromic acid (0.10 mol) and methylene chloride (200 mL) was added dropwise, with stirring, at 50-80℃O-nitrobenzyl bromide, O-nitrotoluene (0.10 mol), azobisisobutyronitrile (0.80 g) and 15% hydrogen peroxide (0.09 mol). After the dropping, the reaction is continued for 2to 5 hours until the reaction is complete, and the separated organic layer is washed by 10 percent of sodium sulfite solution and layered to obtain the methylene dichloride solution of o-nitrobenzyl bromide which is directly used for the next reaction.
To a reaction mixture of 2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) nitrobenzene, 1- (4-chlorophenyl) -3-hydroxy-1H-pyrazole (0.05 mol), o-nitrobenzyl bromide (0.06 mol) obtained in the above step, tetrabutylammonium bromide (0.80 g), water (15 g) and methylene chloride (50 mL) at 10-25℃under stirring was added dropwise a 10% aqueous solution of sodium hydroxide (0.08 mol). After the dripping is finished, the reaction is carried out for 1 to 3 hours at the temperature of 50 to 80 ℃ until the reaction is complete. The mixture was separated by adding dilute hydrochloric acid, extracting the aqueous layer with dichloromethane, mixing the organic phases, drying over anhydrous sodium sulfate, and concentrating under reduced pressure to obtain the title compound, which was used directly in the next reaction.
To a reaction mixture of 2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) aniline, 2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) nitrobenzene (0.02 mol), methanol (25 mL) and methylene chloride (20 mL) at 15-35℃with stirring was added Rany Ni (0.02 mol) in portions. Stirring for 10-15min, heating to 45-65deg.C, dropwise adding hydrazine hydrate (10 mL), continuing to react for 2.5-5.0 hr until the reaction is complete, and removing Rany Ni from the reaction mixture while it is hot. The organic layer was separated, the aqueous layer was extracted with dichloromethane, the organic phases were combined and washed with water, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give the title compound as a yellow solid, 5.12g, which was used directly in the next reaction.
Methyl N- (2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) phenyl) carbamate to a reaction mixture of 2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) aniline (0.01 mol), potassium carbonate (0.015 mol) and acetonitrile (15 mL) was added dropwise methyl chloroformate (0.012 mol) with cooling in an ice bath and stirring. After the dripping is finished, stirring is continued for 0.5 to 2.0 hours, and then the mixture is naturally warmed to room temperature to react completely. The reaction mixture was added to ice water, extracted with ethyl acetate, and the organic phase was washed with water, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give the title crude product, which was recrystallized from ethyl acetate and petroleum ether to give 3.16g of the title compound as an off-white solid.
Methyl N- (2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) phenyl) -N-methylcarbamate to a solution of methyl N- (2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) phenyl) carbamate (5.0 mmol) in N, N-dimethylformamide (15 mL) was added in portions with stirring under cooling in an ice water bath, naH (6.5 mmol) was added after stirring for 15min, methyl iodide (7.5 mmol) was added, and the reaction was allowed to spontaneously warm to room temperature for 0.5 to 2.5H with stirring to complete the reaction. The reaction mixture was added to ice water, extracted with ethyl acetate, and the organic phase was washed with water, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give the title crude product, which was recrystallized from ethyl acetate and petroleum ether to give 1.25g of the title compound as an off-white solid.
Example 2 this example illustrates a process for the preparation of compound 03 of Table 1 (Process B)
A reaction mixture of 2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) -N-methyleneanilino 2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) aniline (0.02 mol), paraformaldehyde (0.022 mol), triethylamine (0.5 g), toluene (20 mL) and ethanol (4 mL) was reacted at 80-95℃for 2-3 hours, heated to 100-115℃for 2-3 hours, and concentrated under reduced pressure to give the title compound, which was directly used for the next reaction.
2- (((1- (4-Chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) -N-methylaniline NaBH4 (0.015 mol), 2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) -N-methyleneaniline (10 mmol) and ethanol (15 mL) were reacted under reflux with stirring to completion, concentrated under reduced pressure to remove most of the ethanol, cooled, dichloromethane was added, washed with water, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give the title compound as a yellow solid which was used directly in the next reaction.
To a solution of methyl N- (2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) phenyl) -N-methylcarbamate in dichloroethane (15 mL) was added potassium carbonate (7.5 mmol) in portions with stirring under cooling in an ice-water bath, and methyl chloroformate (6.0 mmol) was added dropwise after stirring for 15 min. After the dripping is finished, stirring and reacting for 0.5-2.0h, and naturally heating to room temperature to react completely. The reaction mixture was added to ice water, extracted with ethyl acetate, the organic phase was washed with water, dried over anhydrous sodium sulfate, and the solvent was removed to give the title crude product, which was recrystallized from ethyl acetate and petroleum ether to give 1.55g of the title compound as an off-white solid.
Example 3 this example illustrates a process for the preparation of compound 19 of Table 1 (Process A)
Referring to example 1, 2-bromomethyl-4-heptafluoroisopropylaniline, 2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) -4-heptafluoroisopropylaniline, and methyl N- (2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) -4- (heptafluoroisopropyl) phenyl) carbamate were synthesized from 2-methyl-4-heptafluoroisopropylaniline.
Methyl N- (2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) -4- (heptafluoroisopropyl) phenyl) -N-methylcarbamate to a solution of methyl N- (2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) -4- (heptafluoroisopropyl) phenyl) carbamate (5.0 mmol) in N, N-dimethylformamide (15 mL) was added in portions with stirring for 15min, methyl iodide (7.5 mmol) was added, and after stirring for 0.5 to 2.5 hours, the reaction was allowed to spontaneously warm to room temperature to completion. The reaction mixture was added to ice water, extracted with ethyl acetate, the organic phase was washed with water, dried over anhydrous sodium sulfate, and the solvent was removed to give a crude product, which was subjected to column chromatography with ethyl acetate and petroleum ether to give the title 1.15g.
Example 4 this example illustrates a method for the preparation of compound 135 of Table 1 (method A)
Methyl N- (2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) phenyl) -N-ethylcarbamate was cooled in an ice-water bath and stirred, and then NaH (6.0 mmol) was added in portions to a solution of methyl N, N-dimethylformamide (15 mL) in methyl N- (2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) phenyl) carbamate (5.0 mmol) at room temperature under stirring, followed by addition of ethyl iodide (7.5 mmol) after stirring for 0.5 to 2.5 hours, and then allowed to spontaneously warm to room temperature to completion. The reaction mixture was added to ice water, extracted with ethyl acetate, and the organic phase was washed with water, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give the title crude product, which was recrystallized from ethyl acetate and petroleum ether to give 1.36g of the title compound as a yellow solid.
Other compounds of the invention can be synthesized by reference to examples 1-4 and, if necessary, the relevant references.
Formulation examples
EXAMPLE 5 preparation of 10% oil slick
Weighing a proper amount (10% by weight) of a compound shown in the formula (I) provided by the invention, such as N- (2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) phenyl) -N-ethylcarbamate (compound 135 in table 1), a proper amount of a cosolvent (such as ethyl acetate or acetone), a proper amount of an auxiliary agent for pesticides, a proper amount of a solvent (such as toluene) and the like, putting the mixture into a reaction kettle, adding a proper amount of the solvent (such as toluene) and an antifoaming agent, stirring for 10-30 min, adding a proper amount of a stabilizer, a synergist, a penetrating agent and the like, continuously stirring for 10-30 min, adjusting the pH value, putting an effective amount of the solvent into the kettle, stirring uniformly, and discharging to obtain 10% emulsifiable concentrate of the compound shown in the invention, such as N- (2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) phenyl) -N-ethylcarbamate (compound 135 in table 1).
EXAMPLE 6 preparation of 20% wettable powder
Weighing a proper amount (20% by weight) of a compound shown in the formula (I) provided by the invention, such as N- (2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) phenyl) -N-ethylcarbamate (compound 03 in table 1), sodium dodecyl sulfate (2% by weight), sodium lignin sulfonate (10% by weight) and kaolin which is complemented to 100% by weight, mixing together, and crushing in a crusher until the particles reach the standard, thus obtaining the compound shown in the invention, such as N- (2- (((1- (4-chlorophenyl) -1H-pyrazol-3-yl) oxy) methyl) phenyl) -N-ethylcarbamate (compound 03 in table 1) 20% wettable powder.
Example of biological measurement
The compounds of the present invention were tested for bactericidal and insecticidal activity, D1 and D2 as controls, and some of the results are shown below.
Example 7 bactericidal Activity against pathogens such as Gibberella zeae
The method comprises the following steps: dissolving the compound to be tested in a proper solvent such as N, N-dimethylformamide, diluting to the required concentration by using sterile water containing 0.1% of Tween80 emulsifier, and taking a blank without the compound to be tested as a control, wherein each treatment is repeated for 4 times; 3mL of the liquid medicine is taken by a pipette, added into 27mL of potato agar medium (PDA) cooled to 45 ℃ and poured into a culture dish after being fully shaken; after cooling, 6mm diameter mycelium blocks are taken from the edge of a germ colony cultivated for 7 days by an inoculating needle, and the mycelium blocks are moved to the center of a culture dish with the mycelium faces downwards; after the treatment, placing the culture dish in a constant temperature biochemical incubator at 28 ℃ for culture, measuring the growth diameter of hypha after 4 days, analyzing by adopting EXCEL statistical software, and calculating the growth inhibition rate of hypha. The activity was divided into A, B, C, D four stages in percentage relative to the blank, with 100% > inhibition rate ≡90% being stage A, 90% > inhibition rate ≡70% being stage B, 70% > inhibition rate ≡50% being stage C, 50% > inhibition rate ≡0% being stage D.
The bactericidal activity of the compound of the present invention against phytophthora capsici (phytophythora capsici), fusarium graminearum (ALTERNARIA ALTERNATA), botrytis cinerea (Botrytis cinerea) and sclerotium bacteria (Sclerotonia sclerotiorum) was measured by the above-mentioned method for measuring bactericidal activity against Gibberella wheat germ (Gibberella zeae).
The results show that the compounds of the invention are active against the above pathogens at a test concentration of 25mg/L, the following are partial results:
At a concentration of 25mg/L, the compound 135 and the like of the invention have B-class activity of more than 80% on wheat scab; under the same conditions, D1 had 71.13% of B-stage activity against wheat scab and D2 had 43.08% of D-stage activity.
At a concentration of 25mg/L, the compound 03 and the like have B-level activity of 88.68 percent on phytophthora capsici, and 10, 135, 139 and the like have C-level activity; under the same conditions, D1 has C-level activity on phytophthora capsici and D2 has D-level activity. At a concentration of 5mg/L, compound 03 and the like of the present invention still have B-stage activity against phytophthora capsici.
At the concentration of 25mg/L, the compound 03 and the like have B-level activity of 84.44 percent on Alternaria tabaci and C-level activity of 275 and the like; under the same conditions, D1 and D2 have C-level activity on Alternaria alternata.
At a concentration of 25mg/L, the compound 03 and the like have A-level activity on the gray mold bacteria of cucumber, and 135, 136, 139 and the like have C-level activity; under the same conditions, the activity of D1 on the botrytis cinerea is C level, and the activity of D2 on the botrytis cinerea is B level. At the concentration of 10mg/L, the compound 03 and the like still have B-level activity on the gray mold bacteria of the cucumber; under the same conditions, the activity of D2 on the botrytis cinerea is C level.
At the concentration of 25mg/L, the compound 03 and the like have B-level activity of 82.35 percent on Sclerotinia sclerotiorum, and 135, 139, 275 and the like have C-level activity; under the same conditions, the activity of D1 to Sclerotinia sclerotiorum is C level, and the activity of D2 to Sclerotinia sclerotiorum is 70.59% B level.
Example 8 bactericidal Activity against corn rust (Puccinia Polysora)
Potting method: dissolving the compound to be tested in a proper solvent such as N, N-dimethylformamide, diluting to the required concentration by using sterile water containing 0.1% of Tween80 emulsifier, and taking blank without the compound to be tested as a control; 4 replicates per treatment; cutting diseased corn leaves, washing spores with 0.05% Tween80 or other suitable surfactant aqueous solution, and filtering with 2-4 layers of gauze to obtain suspension with concentration of 1×105 spores/mL; spraying the liquid medicine of the compound to be tested on the corn until the corn grows to 2 leaves and 1 core, spraying and inoculating spore suspension after 1 day, transferring to a moisturizing cabinet (the relative humidity is above 95 percent, the temperature is between 20 and 22 ℃), and culturing for 15 to 24 hours under the condition of weak light (the illumination intensity is between 5 000 and 10000 Lux); and when the leaf disease rate of the blank control reaches more than 50%, the disease conditions of each treatment are investigated, and the drug control effect is calculated. The activity is divided into A, B, C, D stages according to the percentage relative to a blank control, 100 percent is larger than or equal to 90 percent and is A stage, 90 percent is larger than or equal to 70 percent and is B stage, 70 percent is larger than or equal to 50 percent and is C stage, and 50 percent is larger than or equal to 0 percent and is D stage. The results show that the compound has a control effect on corn rust, and some compounds still have a good control effect at low concentration. The partial results are listed below:
at the concentration of 500mg/L, the compounds 03, 05, 19, 135, 136, 139, 145 and the like have A-level prevention and treatment effects on corn rust; under the same condition, D1 has a class A control effect on corn rust, and D2 has a class D control effect;
at the concentration of 100mg/L, the compounds 03, 05, 135, 136, 145 and the like have A-level control effects on corn rust, and 19, 139 and the like have B-level control effects; under the same condition, D1 has a class A control effect on corn rust;
At the concentration of 20mg/L, the compound 135 and the like have a class A prevention and treatment effect on corn rust; under the same condition, D1 has a class A control effect on corn rust;
at the concentration of 5mg/L, the compound 135 and the like have B-level prevention and treatment effects on corn rust; under the same condition, D1 has B-level prevention and treatment effects on corn rust;
in order to further study the control effect of the compound of the invention on corn rust, the compound 135 and the like of the invention are selected as objects, tebuconazole is used as commodity control, and the control effect of the compound on corn rust is compared. The results show that the compound of the invention such as 135 and the like has better prevention and treatment effects on corn rust than tebuconazole.
Example 9 bactericidal Activity against wheat powdery mildew (ERISIPHE GRIMINIS)
Potting method: dissolving the compound to be tested in a proper solvent such as N, N-dimethylformamide, and diluting to the required concentration by using sterile water containing 0.1% of Tween80 emulsifier; taking pot with straight stem about 15cm, sowing 20 seeds of wheat with full and strong seeds in each pot, and growing two leaves and one core for test; spraying the prepared wheat seedling plant with a certain concentration of agent, and inoculating bacteria after one day. Repeating for 3 times, and setting blank without compound to be tested as blank control; after the control is subjected to moisturizing and temperature-adaptive culture until blank control is sick, the area of the disease spots is checked, and the control effect of the medicament is calculated. The activity is divided into A, B, C, D stages according to the percentage relative to a blank control, 100 percent is larger than or equal to 90 percent and is A stage, 90 percent is larger than or equal to 70 percent and is B stage, 70 percent is larger than or equal to 50 percent and is C stage, and 50 percent is larger than or equal to 0 percent and is D stage. The results show that the compound provided by the invention has a control effect on wheat powdery mildew, and some compounds still have a good effect at low concentration. The partial results were as follows:
At the concentration of 500mg/L, the compounds 03, 14, 135, 136 and the like have A-level control effects on wheat powdery mildew, and 05, 19, 139, 145 and the like have B-level control effects; under the same condition, D1 has a grade A control effect on wheat powdery mildew, and D2 has a grade D control effect;
At the concentration of 100mg/L, the compounds 03, 135, 136 and the like have A-level control effects on wheat powdery mildew, 145 and the like have B-level control effects; under the same condition, D1 has a class A control effect on wheat powdery mildew;
at the concentration of 50mg/L, the compounds 135, 136 and the like have A-level prevention and treatment effects on wheat powdery mildew; under the same condition, D1 has a class A control effect on wheat powdery mildew;
In order to further study the control effect of the compound of the invention on the wheat powdery mildew, the compound 135 and the like of the invention are selected as objects, and the flusilazole is used as commodity contrast, so that the control effect of the compound of the invention on the wheat powdery mildew is compared. The result shows that the prevention and treatment effect of the compound of the invention such as 135 and the like on wheat powdery mildew can be compared favorably with that of flusilazole.
Example 10 bactericidal Activity against Rhizoctonia solani (Rhizoctonia solani)
Potting method: dissolving the compound to be tested in a proper solvent such as N, N-dimethylformamide, diluting to the required concentration by using sterile water containing 0.1% of Tween80 emulsifier, and taking a blank without the compound to be tested as a control, wherein each treatment is repeated for 4 times; transferring the rice sheath blight pathogen to a PDA plate for activation culture, transferring the rice sheath blight pathogen to a PD culture medium, and culturing the rice sheath blight pathogen in a constant-temperature water bath for 4 days. Pulverizing the cultured mycelium pellet with a refiner and blending with clear water to obtain bacterial suspension with a certain concentration. The cucumber was used for the experiment when it was grown to flatten two cotyledons. Spraying the liquid medicine, spraying the bacterial suspension to the surface of the seedling after 24 hours, and carrying out moisturizing culture. Observing the disease condition of seedlings, and when the disease condition of control treatment is obvious, starting to investigate the disease condition of each treatment, and calculating the drug control effect. The activity is divided into A, B, C, D stages according to the percentage relative to a blank control, 100 percent is larger than or equal to 90 percent and is A stage, 90 percent is larger than or equal to 70 percent and is B stage, 70 percent is larger than or equal to 50 percent and is C stage, and 50 percent is larger than or equal to 0 percent and is D stage. The results show that the compound has control effect on rice sheath blight. The partial results are listed below:
at the concentration of 500mg/L, the compounds 03, 135, 136 and the like have A-level prevention and treatment effects on rice sheath blight diseases; under the same conditions, D1 has a class A control effect on rice sheath blight and D2 has a class B control effect.
At 200mg/L concentration, the compounds 03, 135 and the like have B-stage control effects on rice sheath blight diseases, and under the same conditions, D1 has B-stage control effects on rice sheath blight diseases.
EXAMPLE 11 insecticidal Activity against aphids (Aphis fabae)
To evaluate the activity of the compounds of the invention against sucking pests, aphids were selected as targets and the activity of the compounds of the invention against aphids was determined in a laboratory using a dipping method.
Dipping method: the test compound is dissolved in a suitable solvent such as acetone or N, N-dimethylformamide, diluted to the desired concentration with clear water containing 0.1% Tween80 emulsifier, and a blank without test compound is used as a control, and each treatment is repeated 3 times. The method comprises the steps of inoculating the broad bean aphids on the bean seedlings which are just unearthed, inoculating more than 20 bean seedlings on each plant, immersing the bean seedlings together with test insects in the liquid medicine of the formula (I) provided by the invention, taking out after 5 seconds, sucking the excessive liquid medicine, inserting the liquid medicine into water-absorbing sponge, covering the sponge with a glass tube, checking the number of surviving and dead insects after 24 hours, and taking the average value of the results. The activity (mortality) is divided into A, B, C, D grades in percentage relative to a blank control, wherein the mortality rate is more than or equal to 100 percent and is more than or equal to 90 percent and is grade A, the mortality rate is more than or equal to 90 percent and is grade B, the mortality rate is more than or equal to 70 percent, the mortality rate is more than or equal to 50 percent and is grade C, and the mortality rate is more than or equal to 50 percent and is more than or equal to 0 and is grade D. The results show that the compounds of the invention are active against aphids. At a concentration of 500mg/L, compounds 03, 135, 136, 139 and the like of the present invention have class A activities on aphids, and 19 and the like have class B activities; under the same conditions, the activity of D1 on aphids is A grade, and the activity of D2 on aphids is D grade.
EXAMPLE 12 biological Activity against armyworm (MYTHIMNA SEPARATA)
Potter spray method: weighing a proper amount of the compound, dissolving the compound by using N, N-dimethylformamide, adding a small amount of Tween 80 emulsifier, uniformly stirring, adding quantitative clear water, preparing the compound into the required concentration, and taking the clear water as a contrast. Fresh and tender corn leaves are cut into segments with basically consistent sizes, and placed in a culture dish (phi 90 mm) which is pre-filled with filter paper. Then, 10 larvae of myxoplasma 3 years old are inoculated in a dish, and the larvae are put under a Potter spray tower for quantitative spraying, the spraying liquid amount is 1ml, and the repetition is carried out for 3 times per concentration. After the treatment, the dish cover is covered, the dish cover is placed in a recovery room for culture, periodic observation is carried out, the death condition of the test insects is checked and recorded after 72 hours, the death rate (%) is calculated, and the result is averaged. The activity is in percent relative to the blank. The results indicate that the compounds of the present invention are active against armyworm. At a concentration of 500mg/L, the activity against armyworm of compound 145 or the like of the present invention is 85%, the activity against armyworm of 136 or the like is 55%,
135, Etc. is 45%; under the same conditions, the activity of D1 on armyworm is 20% and the activity of D2 is 0.