CN108530407A - The preparation and its application of loop coil amides compound - Google Patents
The preparation and its application of loop coil amides compound Download PDFInfo
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- CN108530407A CN108530407A CN201710117145.3A CN201710117145A CN108530407A CN 108530407 A CN108530407 A CN 108530407A CN 201710117145 A CN201710117145 A CN 201710117145A CN 108530407 A CN108530407 A CN 108530407A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/94—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom spiro-condensed with carbocyclic rings or ring systems, e.g. griseofulvins
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- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
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- 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
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
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- A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
- A01N47/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having no bond to a nitrogen atom
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- C07—ORGANIC CHEMISTRY
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- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
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Abstract
The invention belongs to agricultural bactericidal, Insecticidal and acaricidal agent field, the preparation of two kinds of loop coil amides compounds and the application as pesticide are specifically disclosed.Shown in the loop coil amides compound such as general formula (I) and general formula (II) of the present invention, its biological activity determination shows, such compound has such compound of the bactericidal activity of wide spectrum to various crop (rice, wheat, corn, beans, vegetables, fruit) on disease have good preventive effect, especially to powdery mildew have excellent activity.The compound of the present invention has good insecticidal activity simultaneously, especially has special efficacy to Jie-Li enzyme-SQ.The compound of the present invention is suitable for the integrated control of the disease and insect pest on various crops.
Description
Technical field
The invention belongs to disinfectant use in agriculture, insecticide and acaricide technical field, and in particular to loop coil amides compound
And its preparation method and application.
Background technology
Acid amide fungicides are a kind of ancient fungicide, have semicentennial history away from the present, now still in agricultural
On play huge effect.Numerous results of study show that most acid amide fungicides are the suppressions based on mitochondrial respiratory system
Preparation.In recent years, as a collection of activity is high and the exploitation of the SDHIs series bactericidal agents of wide sterilization spectrum, acid amide fungicides again at
For the hot spot direction of novel pesticide development.
Spiro-compound structure novel, two plane of a loops are mutually perpendicular in three-dimensional structure.Wherein heterocyclic ring spiroring compounds can
The special nature that can not have with the general heterocyclic compound such as spiral shell conjugation, spiral shell hyperconjugation or different head effect also.In certain item
Under part, due to the presence of chiral axis, asymmetric molecult or chiral molecular can be constituted, machine is acted on containing heteroatomic spiro-compound
Reason is unique, is not likely to produce drug resistance.Currently, spirane structure is in natural product chemistry, combinatorial chemistry, medical chemistry and chemistry of pesticide
Etc. related fields be widely used it is general.
Insecticidal/acaricidal agent Envidor, Spiromesifen and the spiral shell worm second for the commercialization spirane structure that Beyer Co., Ltd successfully develops
Ester.The original research of such product starts from 1993, Beyer Co., Ltd when studying dione herbicides, compound is carried out
Insecticidal activity is screened, it is found that it can destroy the balance of acetyl-CoA carboxylase in insect bodies, so that the growth of regulation and control insect,
So that pest can not normal growth and development and it is dead.Then pass through a series of correlative studys.It is wide that Beyer Co., Ltd releases first energy
The general insecticidal/acaricidal agent Envidor for field.
In existing technology, the pesticide containing spirane structure is relatively fewer.A kind of loop coil amides as representative of the present invention
Derivative and its preparation have no that pertinent literature is reported.
Invention content
It is this kind of present invention aims at the related compound and preparation method thereof for providing completely new loop coil amide structure skeleton
Compound can be used for the agricultural prevention and control of plant diseases, pest control, and preparation method high income, step is few, easy to operate.
Technical scheme is as follows：
Loop coil amides compound provided by the invention, such as general formula I and general formula II and shown：
In formula：R1Selected from H or CH3；
R2、R3、R4、R5、R6Can be identical or different, it is respectively selected from hydrogen, halogen, cyano, nitro, C1-C6Alkyl, C1-C6Halogen
Substituted alkyl, C3-C6Naphthenic base, C2-C6Alkenyl, C2-C6Alkynyl, C1-C6Alkoxy, C2-C6Alkoxyalkyl, C1-C6Alkyl groups in the halogenalkoxy,
C2-C6Alkyl acyl, C2-C6Alkoxy acyl, C1-C6Alkylthio group, C1-C6Alkyl sulphinyl or C1-C6Alkyl sulphonyl, substitution
Or unsubstituted amino；R2-R6Cannot be H simultaneously；
R7Selected from hydrogen, C1-C3Alkyl, C1-C3Alkoxy or C3-C6Naphthenic base；
R8Selected from hydrogen, C1-C6Alkyl, C1-C6Halogenated alkyl, C3-C6Naphthenic base, C2-C6Alkenyl, C2-C6Alkynyl, C1-C6Alkane
Oxygroup, C2-C6Alkoxyalkyl, C1-C6Alkyl groups in the halogenalkoxy, C2-C6Alkyl acyl, C2-C6Alkoxy acyl, C1-C6Alkylthio group；
M=0,1,2,3；
Meanwhile the present invention also provides the preparation methods of a kind of loop coil amide derivatives：
General formula compound I of the present invention can be prepared by following method, and each group definition is the same in reaction equation.
Its I synthetic method of general formula compound is as follows：After general formula compound IV is prepared into acyl chlorides with thionyl chloride, with compound
III in suitable solvent, to select alkali as a catalyst appropriate, temperature be to react 0.5-6h under -10 DEG C to solvent boiling point mesh is made
Mark chemical compounds I.Its reaction equation is：
Wherein, the reaction dissolvent selection dichloromethane, chloroform, tetrahydrofuran, toluene, acetonitrile, N, N- dimethyl formyls
Amine, dimethyl sulfoxide (DMSO).
Suitable alkali is added and is chosen as sodium hydroxide, potassium hydroxide, triethylamine, N, N- dimethyl-ethylenediamines or pyridine etc..
General formula compound IV prepares reaction equation:
By cyclanone (commercially available) in suitable solvent with diethyl maleate zinc powder and elemental iodine catalysis under, occur
Reformatsky reacts, and certain temperature stirs 6-18 hours obtained compounds VI.The optional benzene of solvent, toluene, acetonitrile, DMF, THF
Or 1,4- dioxane etc..Zinc powder and elemental iodine are commercially available.
General formula compound V is dissolved in suitable solvent, lithium hydrate is added, reacts 2-8 hours obtained chemical combination
Object IV.The optional methanol of solvent, ethyl alcohol or tetrahydrofuran etc..
The preparation method of its general formula compound II is as follows：After general formula compound VI is prepared into acyl chlorides with thionyl chloride, with change
Close object III in suitable solvent, select suitable alkali to be 0 DEG C for catalyst, temperature to obtain to reacting 0.5-6h under solvent boiling point
Target compound II.Its reaction equation is：
Wherein, the reaction dissolvent selection dichloromethane, chloroform, tetrahydrofuran, toluene, acetonitrile, N, N- dimethyl formyls
Amine, dimethyl sulfoxide (DMSO).
Suitable alkali is added and is chosen as sodium hydroxide, potassium hydroxide, triethylamine, N, N- dimethyl-ethylenediamines or pyridine etc..
General formula compound VIII prepares reaction equation:
By cycloalkanes formonitrile HCN (commercially available) and diethyl maleate under suitable solvent, in sodium ethoxide, sodium hydride or tertiary fourth
Under potassium alcoholate catalysis, Michael addition reactions occur, certain temperature stirs 6-18 hours obtained compounds Ⅸ.The optional benzene of solvent, first
Benzene, acetonitrile, DMF, THF or 1,4- dioxane etc..
General formula compound Ⅸ flows back under the conditions of the concentrated sulfuric acid, is reduced into general formula compound VIII.
The reaction equation for preparing of general formula compound VI is：
General formula compound VIII is dissolved in suitable solvent, occurs under sodium hypochlorite or the effect of sodium hypobromite alcoholic solution
Hofmann rearrangement reactions, heating reaction 1-12h obtain target compound VII.
Suitable solvent selection dichloromethane, chloroform, tetrahydrofuran, toluene, acetonitrile or benzene.
General formula compound VII is dissolved in suitable solvent, lithium hydroxide, 2-12 hours obtainedization of normal-temperature reaction is added
Close object VI.The optional methanol of solvent, ethyl alcohol or tetrahydrofuran etc..
Purposes the present invention also provides the loop coil amide compound as fungicide and insecticide.
As pesticide, its weight percent containing the loop coil amide compound is 1-99%.
Specific implementation mode
It is following in conjunction with specific embodiments to the present invention related compound, and its preparation method and application make further it is detailed
Explanation.
The structural formula and property of the part representative compound of the loop coil amide of the present invention are as shown in table 1：
The structure of 1 part of compounds of table
Embodiment 1:
The preparation of chemical compounds I -7 in table 1；Its reaction step is as follows：
The elemental iodine of the zinc powder of 18.6mmol and 0.78mmol is added into anhydrous tetrahydro furan, nitrogen protection, is heated up
It is stirred 30 minutes to 50 DEG C.Cyclohexanone and the diethyl maleate mixing tetrahydrofuran that equivalent (15.5mmol) is slowly added dropwise are molten
In liquid to reaction bulb, it is warming up to 70 DEG C and flows back 2 hours, a small amount of 1N hydrochloric acid solutions are added after being cooled to room temperature.It is stirred at room temperature to zinc
Powder disappears, ethyl acetate extraction, washing, anhydrous sodium sulfate drying.Last column chromatography is up to product V -7, yield 87%.
Obtained product V-7 is added into the mixed solution (v/v=3/1) of tetrahydrofuran and water, the hydrogen of 2 equivalents is added
Lithia solid reacts at room temperature 4 hours.After reaction, reaction solution is modulated to acid, ethyl acetate extraction with 1N hydrochloric acid solutions
It takes, is concentrated under reduced pressure, crystallizes to obtain product IV -7, yield 91%.
The compounds Ⅳ -7 of 9.8mmol is added into the round-bottomed flask of 50Ml, 15.6mmol thionyl chlorides are slowly added dropwise,
Extra thionyl chloride is removed in back flow reaction 4h, reduced pressure, and the acid chloride product for obtaining compounds Ⅳ -7 is spare.
The compound III -7 of 10.7mmol and 11.8mmol triethylamines are added to the round bottom equipped with dichloromethane solution and burnt
In bottle, it is cooled to 0 DEG C, the dichloromethane solution of the acid chloride product of compounds Ⅳ -7 is slowly added dropwise, reaction is slowly increased to room temperature
Stirring 4 hours.After reaction, it washes 2 times, ethyl acetate extraction.Column chromatography obtains chemical compounds I -7, yield 85%.1H NMR
δ=9.85 (600MHz, Chloroform-d) (s, 1H), 7.59 (dd, 1H), 7.42 (dd, 1H), 6.80 (dd, 1H), 3.88
(s,3H),3.01(t,1H),2.78(m,1H),2.52(m,1H),1.88-1.40(m,10H).MS(m/z):
calc.for337.1；found,337.1
Embodiment 2:
The preparation of chemical compounds I -18 in table 1：Its reaction step is as follows：
The elemental iodine of the zinc powder of 22.4mmol and 0.94mmol is added into anhydrous tetrahydro furan, nitrogen protection, is heated up
It is stirred 30 minutes to 50 DEG C.4- methoxycyclohexyls ketone and the diethyl maleate mixing four of equivalent (18.7mmol) is slowly added dropwise
In hydrogen tetrahydrofuran solution to reaction bulb, it is warming up to 70 DEG C and flows back 4.5 hours, a small amount of 1N hydrochloric acid solutions are added after being cooled to room temperature.Room
Temperature stirring to zinc powder disappears, ethyl acetate extraction, washing, anhydrous sodium sulfate drying.Last column chromatography is received up to product V -28
Rate 80%.
Obtained product V-28 is added into the mixed solution (v/v=3/1) of tetrahydrofuran and water, 2 equivalents are added
Lithium hydroxide solid reacts at room temperature 5 hours.After reaction, reaction solution is modulated to acid, ethyl acetate extraction with 1N hydrochloric acid solutions
It takes, is concentrated under reduced pressure, crystallizes to obtain product IV -28, yield 84%.
The compounds Ⅳ -28 of 15.2mmol is added into the round-bottomed flask of 50mL, it is sub- that 24.8mmol dichloros are slowly added dropwise
Extra thionyl chloride is removed in sulfone, back flow reaction 4h, reduced pressure, and the acid chloride product for obtaining compounds Ⅳ -28 is spare.
The compound III -28 of 17.8mmol and 18.1mmol triethylamines are added to the round bottom equipped with dichloromethane solution and burnt
In bottle, it is cooled to 0 DEG C, the dichloromethane solution of the acid chloride product of compounds Ⅳ -28 is slowly added dropwise, reaction is slowly increased to room temperature
Stirring 4 hours.After reaction, it washes 2 times, ethyl acetate extraction.Column chromatography obtains chemical compounds I -28, yield 87%.1H
δ=9.87 (s, 1H) NMR (600MHz, Chloroform-d), 7.63 (dd, 1H), 7.23 (dd, 1H), 6.70 (dd, 1H),
3.82(s,3H),3.41(s,3H),3.24(m,1H),3.02(t,1H),2.77(m,1H),2.52(m,1H),1.81-1.45
(m,8H).MS(m/z):calc.for 351.1；found,351.1
Embodiment 3:
The preparation of chemical compounds I -28 in table 1：Its reaction step is as follows：
The elemental iodine of the zinc powder of 20.2mmol and 0.85mmol is added into anhydrous tetrahydro furan, nitrogen protection, is heated up
It is stirred 30 minutes to 50 DEG C.4- methoxycyclohexyls ketone and the diethyl maleate mixing four of equivalent (16.8mmol) is slowly added dropwise
In hydrogen tetrahydrofuran solution to reaction bulb, it is warming up to 70 DEG C and flows back 4 hours, a small amount of 1N hydrochloric acid solutions are added after being cooled to room temperature.Room temperature
Stirring to zinc powder disappears, ethyl acetate extraction, washing, anhydrous sodium sulfate drying.Last column chromatography is up to product V -28, yield
82%.
Obtained product V-28 is added into the mixed solution (v/v=3/1) of tetrahydrofuran and water, 2 equivalents are added
Lithium hydroxide solid reacts at room temperature 6 hours.After reaction, reaction solution is modulated to acid, ethyl acetate extraction with 1N hydrochloric acid solutions
It takes, is concentrated under reduced pressure, crystallizes to obtain product IV -28, yield 86%.
The compounds Ⅳ -28 of 15.2mmol is added into the round-bottomed flask of 50mL, it is sub- that 24.8mmol dichloros are slowly added dropwise
Extra thionyl chloride is removed in sulfone, back flow reaction 4h, reduced pressure, and the acid chloride product for obtaining compounds Ⅳ -28 is spare.
The compound III -28 of 17.8mmol and 18.1mmol triethylamines are added to the round bottom equipped with dichloromethane solution and burnt
In bottle, it is cooled to 0 DEG C, the dichloromethane solution of the acid chloride product of compounds Ⅳ -28 is slowly added dropwise, reaction is slowly increased to room temperature
Stirring 4 hours.After reaction, it washes 2 times, ethyl acetate extraction.Column chromatography obtains chemical compounds I -28, yield 87%1H NMR
δ=9.87 (600MHz, Chloroform-d) (s, 1H), 7.28 (dd, 1H), 7.27 (dd, 1H), 3.41 (s, 3H), 3.24 (m,
1H),3.00(t,1H),2.78(m,1H),2.53(m,1H),1.82-1.43(m,8H).MS(m/z):calc.for 455.1；
found,455.1
Embodiment 4:
The preparation of compound ii -4 in table 1：Its reaction step is as follows：
The sodium block of 12.6mmol is added into absolute ethyl alcohol, after return stirring 1h, waits for that sodium block is completely dissolved, is cooled to room
Warm standby is used.
In the round-bottomed flask of 50mL, the diethyl maleate of 12.6mmol is dissolved in the absolute ethyl alcohol of 10mL, it is cooling
It is stirred 10 minutes to 0 DEG C.It is slowly dropped into the alcohol sodium solution prepared, 0 DEG C is stirred 30 minutes, and 10.5mmol hexamethylenes are eventually adding
The ethanol solution of formonitrile HCN after 0 degree Celsius is stirred 1 hour, moves to be stirred at room temperature to react for 6 hours and terminate.It is extra that removing is concentrated under reduced pressure
Methanol.Water and saturated common salt is used to wash successively, ethyl acetate extraction, conventional treatment.Column chromatography obtains compound Ⅸ -4, yield
78%.
Obtained product Ⅸ -4 is added into the concentrated hydrochloric acid of 6mL, is warming up to 50 DEG C, is stirred 2 hours.It is cold after reaction
But to room temperature, careful is added hydrochloric acid in saturated sodium bicarbonate saturated solution and extra, ethyl acetate extraction, saturated salt solution
Washing.It is dry to concentrate up to compound VIII -4.Yield 88%.
The bromine of 8.26mmol is slowly dropped at 0 DEG C in the 0.5M sodium ethoxide alcoholic solutions prepared.Stirring 15 minutes
Afterwards, it is added the tetrahydrofuran solution of 6.88mmol compounds VIII -4,0 DEG C after the reaction was continued 1 hour, removes ice bath, then heats up
Reflux 1 hour.After reaction, unnecessary alcohol is removed.Last column chromatography obtains compound VII -4, yield 78%.
Obtained product VII -4 is added into the mixed solution (v/v=3/1) of tetrahydrofuran and water, 2 equivalents are added
Lithium hydroxide solid reacts at room temperature 2 hours.After reaction, reaction solution is modulated to acid, ethyl acetate extraction with 1N hydrochloric acid solutions
It takes, is concentrated under reduced pressure, crystallizes to obtain product VI -4, yield 92%.
The compound VI -4 of 5.4mmol is added into the round-bottomed flask of 50mL, 10.8mmol thionyl chlorides are slowly added dropwise,
Extra thionyl chloride is removed in back flow reaction 4h, reduced pressure, and the acid chloride product for obtaining compound VI -4 is spare.
The compound III -4 of 6.5mmol and 6.8mmol triethylamines are added to the round-bottomed flask equipped with dichloromethane solution
In, it is cooled to 0 DEG C, the dichloromethane solution of the acid chloride product of compound VI -4 is slowly added dropwise, reaction, which is slowly increased to room temperature, stirs
It mixes 3 hours.After reaction, it washes 2 times, ethyl acetate extraction.Column chromatography obtains compound ii -4, yield 88%.1H NMR
δ=9.85 (600MHz, Chloroform-d) (s, 1H), 7.75 (s, 1H), 7.63 (dd, 1H), 7.24 (dd, 1H), 6.71
(dd,1H),3.83(s,3H),3.08(t,1H),2.88(m,1H),2.63(m,1H),1.73-1.43(m,10H).MS(m/z):
calc.for 320.2；found,320.2
Embodiment 5:
The preparation of compound ii -12 in table 1：Its reaction step is as follows：
The sodium block of 11.8mmol is added into absolute ethyl alcohol, after return stirring 1h, waits for that sodium block is completely dissolved, is cooled to room
Warm standby is used.
In the round-bottomed flask of 50mL, the diethyl maleate of 11.8mmol is dissolved in the absolute ethyl alcohol of 10mL, it is cooling
It is stirred 10 minutes to 0 DEG C.It is slowly dropped into the alcohol sodium solution prepared, 0 DEG C is stirred 30 minutes, and 9.8mmol hexamethylenes are eventually adding
The ethanol solution of formonitrile HCN after 0 degree Celsius is stirred 1 hour, moves to be stirred at room temperature to react for 6 hours and terminate.It is extra that removing is concentrated under reduced pressure
Methanol.Water and saturated common salt is used to wash successively, ethyl acetate extraction, conventional treatment.Column chromatography obtains compound Ⅸ -12, yield
81%.
Obtained product Ⅸ -12 is added into the concentrated hydrochloric acid of 6mL, is warming up to 50 DEG C, is stirred 2 hours.After reaction
It is cooled to room temperature, careful is added hydrochloric acid in saturated sodium bicarbonate saturated solution and extra, ethyl acetate extraction, saturated common salt
Water washing.It is dry to concentrate up to compound VIII -12.Yield 86%.
The bromine of 8.22mmol is slowly dropped at 0 DEG C in the 0.5M sodium ethoxide alcoholic solutions prepared.Stirring 15 minutes
Afterwards, it is added the tetrahydrofuran solution of 6.81mmol compounds VIII -12,0 DEG C after the reaction was continued 1 hour, removes ice bath, then heats up
Reflux 1 hour.After reaction, unnecessary alcohol is removed.Last column chromatography obtains compound VII -12, yield 84%.
Obtained product VII -12 is added into the mixed solution (v/v=3/1) of tetrahydrofuran and water, 2 equivalents are added
Lithium hydroxide solid reacts at room temperature 2 hours.After reaction, reaction solution is modulated to acid, ethyl acetate extraction with 1N hydrochloric acid solutions
It takes, is concentrated under reduced pressure, crystallizes to obtain product VI -12, yield 89%.
The compound VI -12 of 5.8mmol is added into the round-bottomed flask of 50mL, it is sub- that 11.6mmol dichloros are slowly added dropwise
Extra thionyl chloride is removed in sulfone, back flow reaction 4h, reduced pressure, and the acid chloride product for obtaining compound VI -12 is spare.
The compound III -12 of 7mmol and 7.2mmol triethylamines are added to the round-bottomed flask equipped with dichloromethane solution
In, it is cooled to 0 DEG C, the dichloromethane solution of the acid chloride product of compound VI -12 is slowly added dropwise, reaction, which is slowly increased to room temperature, stirs
It mixes 4 hours.After reaction, it washes 2 times, ethyl acetate extraction.Column chromatography obtains compound ii -12, yield 87%.1H NMR
δ=9.84 (600MHz, Chloroform-d) (s, 1H), 7.76 (s, 1H), 7.63 (dd, 1H), 7.27 (dd, 1H), 7.26
(dd,1H),3.05(t,1H),2.87(m,1H),2.62(m,1H),1.75-1.42(m,10H).MS(m/z):
calc.for424.1；found,424.1
Embodiment 6:
The preparation of compound ii -28 in table 1：Its reaction step is as follows：
The sodium block of 14.4mmol is added into absolute ethyl alcohol, after return stirring 1h, waits for that sodium block is completely dissolved, is cooled to room
Warm standby is used.
In the round-bottomed flask of 50mL, the diethyl maleate of 14.4mmol is dissolved in the absolute ethyl alcohol of 10mL, it is cooling
It is stirred 10 minutes to 0 DEG C.It is slowly dropped into the alcohol sodium solution prepared, 0 DEG C is stirred 30 minutes, and 12mmol hexamethylene first is eventually adding
The ethanol solution of nitrile after 0 degree Celsius is stirred 1 hour, moves to be stirred at room temperature to react for 5 hours and terminate.It is concentrated under reduced pressure and removes extra first
Alcohol.Water and saturated common salt is used to wash successively, ethyl acetate extraction, conventional treatment.Column chromatography obtains compound Ⅸ -28, yield 79%.
Obtained product Ⅸ -28 is added into the concentrated hydrochloric acid of 6mL, is warming up to 50 DEG C, is stirred 2 hours.After reaction
It is cooled to room temperature, careful is added hydrochloric acid in saturated sodium bicarbonate saturated solution and extra, ethyl acetate extraction, saturated common salt
Water washing.It is dry to concentrate up to compound VIII -28.Yield 83%.
The bromine of 10.2mmol is slowly dropped at 0 DEG C in the 0.5M sodium ethoxide alcoholic solutions prepared.Stirring 15 minutes
Afterwards, it is added the tetrahydrofuran solution of 8.5mmol compounds VIII -28,0 DEG C after the reaction was continued 1 hour, removes ice bath, then heats up
Reflux 1.5 hours.After reaction, unnecessary alcohol is removed.Last column chromatography obtains compound VII -28, yield 88%.
Obtained product VII -28 is added into the mixed solution (v/v=3/1) of tetrahydrofuran and water, 2 equivalents are added
Lithium hydroxide solid reacts at room temperature 2 hours.After reaction, reaction solution is modulated to acid, ethyl acetate extraction with 1N hydrochloric acid solutions
It takes, is concentrated under reduced pressure, crystallizes to obtain product VI -28, yield 85%.
The compound VI -28 of 7.2mmol is added into the round-bottomed flask of 50mL, it is sub- that 14.4mmol dichloros are slowly added dropwise
Extra thionyl chloride is removed in sulfone, back flow reaction 4h, reduced pressure, and the acid chloride product for obtaining compound VI -28 is spare.
The compound III -28 of 8.64mmol and 8.8mmol triethylamines are added to the round bottom equipped with dichloromethane solution and burnt
In bottle, it is cooled to 0 DEG C, the dichloromethane solution of the acid chloride product of compound VI -28 is slowly added dropwise, reaction is slowly increased to room temperature
Stirring 4 hours.After reaction, it washes 2 times, ethyl acetate extraction.Column chromatography obtains compound ii -28, yield 91%.1H
δ=9.86 (s, 1H) NMR (600MHz, Chloroform-d), 7.78 (s, 1H), 7.75 (dd, 1H), 7.74 (dd, 1H), 3.42
(s,3H),3.24(m,1H),3.05(t,1H),2.88(m,1H),2.63(m,1H),1.73-1.42(m,8H).MS(m/z):
calc.for 454.1；found,454.1
Embodiment 7:Toxicity test of the compound to powdery mildew of cucumber
For studying object and bacterial strain：Cucumber, potting seedling grow spare to 4~6 leaves.Cucumber powdery mildew's pathogen (Sphaeotheca
), fuliginea Agricultural University Of South China's natural pesticide is provided with key lab of the chemical biology Ministry of Education.
Experiment uses pot-culture method.The Powdery Mildew Fresh spores generated in for 24 hours that will fall ill on cucumber leaves uniformly are shaken off to connect
Kind is on for examination cucumber seedling.According to agent activity, 5-7 series mass concentration is set.After inoculation 24 hours, liquid is uniformly sprayed
Blade face is imposed on to whole wettings, waits for that liquid natural air drying is spare.3 basins, 4 repetitions are often handled, and is set containing only solvent and surface work
Property agent and without containing effect ingredient processing make blank control.After inoculation, in 20 ± 2 DEG C of temperature, the item of 90% or more relative humidity
It is cultivated 7 days under part.Statistics is per the lesion area on basin cucumber leaves, investigation prevention effect.Control drug is Fluoxastrobin (content
96%).
Embodiment 8:Toxicity test of the compound to Jie-Li enzyme-SQ
For trying acarid：Jie-Li enzyme-SQ, Agricultural University Of South China's natural pesticide are carried with key lab of the chemical biology Ministry of Education
For.
Experiment uses slide infusion process.Double faced adhesive tape is cut into 1.5cm × 4cm sizes, is pasted onto one end of glass slide, is used
Tweezers throw off paper layer to expose glue surface, to be used for fixing test worm.Select the healthy tangerine that in the same size, body colour is bright-coloured, action is active
Panonychus citri its back is sticked on adhesive tape, and makes its mouthpart and appendage etc. can freely activity, every 80.Before processing, binocular is used
Stereoscopic dissection sem observation, removes abnormal individual.Test compound and Spiromesifen are diluted on the basis of preliminary experiment
5-7 concentration gradient, each concentration are repeated 3 times.Investigate 24-48 hours test results.Control drug is Spiromesifen (content
95%).
Embodiment 9:Compound insecticidal activity assay
For trying insect：Beet armyworm
Experiment uses leaf dipping method.Compound is dissolved in dimethyl sulfoxide (DMSO) (DMSO), mother liquor is made, and is diluted to needed for measurement
Concentration is spare.Fresh dish leaf dish is impregnated into 10 seconds, each one, 3, each sample in liquid.Successively by sample flag sequence
It is placed on processing paper.After liquid dries, it is put into in culture dish, accesses Nature enemy 12h beet armyworm instar larvaes, use yarn
Cloth covers nozzle.Each processing repeats three times, each to repeat 40 cephalonts.For 24 hours, 48h, 72h are dead for examination insect mortality for record
Rate.Control drug is ethiprole (content 96%).
Selected compounds are to 2 instar larvae insecticidal activity of beet armyworm.
Claims (10)
1. two kinds of loop coil amides compounds, the structure as shown in general formula (I) and general formula (II)：
In formula：
R1Selected from hydrogen or methyl；
R2、R3、R4、R5、R6Can be identical or different, it is respectively selected from hydrogen, halogen, cyano, nitro, C1-C6Alkyl, C1-C6Alkyl halide
Base, C3-C6Naphthenic base, C2-C6Alkenyl, C2-C6Alkynyl, C1-C6Alkoxy, C2-C6Alkoxyalkyl, C1-C6Alkyl groups in the halogenalkoxy, C2-C6Alkane
Base acyl group, C2-C6Alkoxy acyl, C1-C6Alkylthio group, C1-C6Alkyl sulphinyl or C1-C6Alkyl sulphonyl, substitution or unsubstituted
Amino；R2-R6Cannot be H simultaneously；
R7Selected from hydrogen, C1-C3Alkyl, C1-C3Alkoxy or C3-C6Naphthenic base；
R8Selected from hydrogen, C1-C6Alkyl, C1-C6Halogenated alkyl, C3-C6Naphthenic base, C2-C6Alkenyl, C2-C6Alkynyl, C1-C6Alkoxy,
C2-C6Alkoxyalkyl, C1-C6Alkyl groups in the halogenalkoxy, C2-C6Alkyl acyl, C2-C6Alkoxy acyl, C1-C6Alkylthio group；M=0,1,2,3.
2. the preparation method of loop coil amides compound I described in a kind of claim 1, which is characterized in that it includes the following steps：
After general formula compound IV is prepared into acyl chlorides with thionyl chloride, urged with alkali of the compound III in suitable solvent, suitable
Agent, temperature are 0.5-6 hours obtained target compounds I of -10 DEG C~80 DEG C reactions.Its reaction equation is：
Wherein, the reaction dissolvent selection dichloromethane, chloroform, tetrahydrofuran, toluene, acetonitrile, n,N-Dimethylformamide, two
Methyl sulfoxide.Suitable alkali is added and is selected from potassium hydroxide, sodium hydroxide, triethylamine, N, N- dimethyl-ethylenediamines or pyridine etc..
3. the preparation method of loop coil amides compound I according to claim 2, it is characterised in that：Structural formula is IV institute
The molar ratio of the intermediate shown and structural formula intermediate as shown in III is 1：0.8-1.2, structural formula are intermediate shown in IV
Molar ratio with alkali is 1:1.0-1.5.
4. according to the preparation method of loop coil amides compound I described in Claims 2 or 3, it is characterised in that：General formula compound institute
The intermediate synthetic method shown is as follows：By cyclanone (commercially available) in suitable solvent with diethyl maleate in zinc powder and iodine
Under simple substance catalysis, temperature is that 20 DEG C~80 DEG C reactions obtain target compound V in 6-18 hours.Then, general formula compound V is molten
Lithium hydroxide is added in suitable solvent in solution, and temperature is 2-12 hours obtained chemical combination IV of 20 DEG C~80 DEG C reactions.
Wherein, the optional methanol of solvent, ethyl alcohol, benzene, toluene, acetonitrile, DMF, THF or Isosorbide-5-Nitrae-dioxane etc..Zinc powder and elemental iodine
It is commercially available.The molar ratio of raw material and reaction reagent described in structural formula is 1：0.8-3.
5. the preparation method of loop coil amides compound II described in a kind of claim 1, which is characterized in that it includes following step
Suddenly：
After general formula compound VI is prepared into acyl chlorides with thionyl chloride, with compound III in suitable solvent, select suitable alkali
It is that -10 DEG C~80 DEG C reaction 0.5-6h obtain target compound II for catalyst, temperature.Its reaction equation is：
Wherein, the reaction dissolvent selection dichloromethane, chloroform, tetrahydrofuran, toluene, acetonitrile, n,N-Dimethylformamide, two
Methyl sulfoxide.Suitable alkali is added and is chosen as potassium hydroxide, sodium hydroxide, triethylamine, N, N- dimethyl-ethylenediamines or pyridine etc..
6. the preparation method of loop coil amides compound II according to claim 5, it is characterised in that：Structural formula is VI institute
The molar ratio of the intermediate shown and structural formula intermediate as shown in III is 1：0.8-1.2, structural formula are intermediate shown in VI
Molar ratio with alkali is 1:1.0-1.5.
7. according to the preparation method of the loop coil amides compound of claim 5 or 6 II, it is characterised in that：General formula compound
Shown in intermediate synthetic method it is as follows：By commercially available cycloalkanes formonitrile HCN and diethyl maleate under suitable solvent, suitable
Under the catalysis of suitable alkali, 20 DEG C~100 DEG C reaction 6-18 obtain compound Ⅸ.Then general formula compound Ⅸ is under the conditions of the concentrated sulfuric acid
Reflux, reduction obtain general formula compound VIII.Its reaction equation is：
Wherein, the optional benzene of solvent, toluene, acetonitrile, n,N-Dimethylformamide, tetrahydrofuran or Isosorbide-5-Nitrae-dioxane etc..Alkali selects
For sodium ethoxide, one kind in sodium hydride or potassium tert-butoxide.The molar ratio of raw material and reaction reagent described in structural formula is 1：0.8-3.
General formula compound VIII is dissolved in suitable solvent, reacts under sodium hypochlorite or the effect of sodium hypobromite alcoholic solution,
Heating reaction 1-12h obtains target compound VII.Then, obtained general formula compound VII is dissolved in suitable solvent, is added
Enter lithium hydroxide, reacts 2-12 hours obtained compounds VI.The reaction equation for preparing of general formula compound VI is：
Wherein, the optional methanol of solvent, ethyl alcohol, benzene, toluene, acetonitrile, n,N-Dimethylformamide, tetrahydrofuran or Isosorbide-5-Nitrae-dioxy six
Ring etc..Other reagents are commercially available.The molar ratio of raw material and reaction reagent described in structural formula is 1：0.8-3.
8. two kinds of general formulas (I) described in accordance with the claim 1 and general formula (II) compound be as disinfectant use in agriculture, insecticide and kill
The purposes of mite agent.
9. two kinds of Pesticidal combinations containing the active component of compound as shown in general formula (I) and general formula (II) and can agriculturally connect
The carrier received, the weight percentage of active component is 1-99% in composition.
10. the method for two kinds of control insect pests, it is characterised in that：Composition described in claim 3 is arrived for 10 grams with per hectare
1000 grams of effective dose imposes on the pest for needing to control or growth medium.
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|---|---|---|---|---|
| CN102898354A (en) * | 2011-07-28 | 2013-01-30 | 华南农业大学 | Oxime ether derivatives of spirocyclic tetronic acid, the preparation thereof, and insecticidal, acaricidal, bactericidal and herbicidal usages thereof |
| CN103467380A (en) * | 2013-09-29 | 2013-12-25 | 南开大学 | Substituted phenyl pyrazole amide derivative and preparation method and application thereof |
-
2017
- 2017-03-04 CN CN201710117145.3A patent/CN108530407A/en active Pending
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|---|---|---|---|---|
| CN102898354A (en) * | 2011-07-28 | 2013-01-30 | 华南农业大学 | Oxime ether derivatives of spirocyclic tetronic acid, the preparation thereof, and insecticidal, acaricidal, bactericidal and herbicidal usages thereof |
| CN103467380A (en) * | 2013-09-29 | 2013-12-25 | 南开大学 | Substituted phenyl pyrazole amide derivative and preparation method and application thereof |
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