CN106632132B - High activity N- oxyl anabasine analog and its preparation method and application - Google Patents

High activity N- oxyl anabasine analog and its preparation method and application Download PDF

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CN106632132B
CN106632132B CN201710005006.1A CN201710005006A CN106632132B CN 106632132 B CN106632132 B CN 106632132B CN 201710005006 A CN201710005006 A CN 201710005006A CN 106632132 B CN106632132 B CN 106632132B
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insecticide
nicotinoids
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CN106632132A (en
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覃兆海
杨冬燕
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China Agricultural University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • 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
    • A01N51/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds having the sequences of atoms O—N—S, X—O—S, N—N—S, O—N—N or O-halogen, regardless of the number of bonds each atom has and with no atom of these sequences forming part of a heterocyclic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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    • C07C291/02—Compounds containing carbon and nitrogen and having functional groups not covered by groups C07C201/00 - C07C281/00 containing nitrogen-oxide bonds
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/61—Halogen atoms or nitro radicals
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/30—Halogen atoms or nitro radicals
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Abstract

The invention belongs to field of pesticides, and in particular to high activity N- oxyl anabasine analog and its preparation method and application.The present invention provides a kind of structure novel, insecticidal activity and pyrrole worm forest form and works as, to the high activity N- oxyl anabasine analogue pesticide of honeybee safety by introducing flexible side-chains.The insecticide solves the problems, such as the drug resistance of imidacloprid and to toxicity to honeybees; it can advantageous protection crops, gardening plant, fruits and vegetables etc.; its yield is increased in the generation for preventing pest and disease damage, while being high activity and the road development and exploration Liao Yitiaoxin to the insecticide of beneficial organism low toxicity.

Description

High activity N- oxyl anabasine analog and its preparation method and application
Technical field
The invention belongs to field of pesticides, and in particular to high activity N- oxyl anabasine analog and preparation method thereof and Using.
Background technique
Pest to the drug resistance of pesticide and pesticide to the safety of ecological environment be in modern pesticides development field most by Two aspects of concern, this requires the new varieties of pesticides that we develop should have efficient, less toxic, low-residual, to environment friend It the features such as good, will also be with existing insecticide variety no interactions resistance.
Anabasine insecticide is derived from botanical pesticide nicotine, and imidacloprid is the nicotinoids desinsection that first success is developed Agent.Due to the insecticides have unique mechanism of action, there is no cross resistance with common insecticides, not only have efficiently, Wide spectrum and good root absorbability are tagged and stomach poison function, and low to mammalian toxicity, environmentally safe, can be effective The pests such as Semiptera, coleoptera, Diptera and Lepidoptera are prevented and treated, are also had to the pest to be developed drug resistance with conventional pesticides prevention and treatment Good activity can be not only used for cauline leaf process, can also be used for soil, seed treatment, causes the extensive concern of people.In recent years by In outstanding day by day resistance problems and to the safety issue of honeybee, anabasine is faced with huge challenge.
Summary of the invention
The purpose of the present invention is to propose to high activity N- oxyl anabasine analog and its preparation method and application, specific skills Art scheme is as follows:
High activity N- oxyl anabasine analog is N- oxyl nitroguanidine compounds shown in Formulas I；
Wherein, R1For hydrogen, C1-C10 saturation or unsaturated fatty hydrocarbons base, furans, benzene, substituted-phenyl, benzyl, replace benzyl Base, pyridine, imidazoles, oxazole, thiazole, C1~C5 alkoxy or aryloxy group；
R2For C1-C10 saturation or unsaturated fatty hydrocarbons base, substituted benzyl, substituted-phenyl, haloperidid methyl, halogenated Thiazole methyl, tetrahydrofuran methyl, pyrimidine -2-base or substituted pyrimidines -2- base.
The R1And R2The substituent group number of middle substituted-phenyl is 1-5, substituent part or all by halogen, hydroxyl, ammonia Base or substituted-amino replace；The substituted-amino is methylamino, nitro or amino；
The R1The substituent group number of middle substituted benzyl is 1-5, and substituent group is halogen, amino, hydroxyl, C1~C5 alkyl Or C1~C5 alkoxy, wherein C1~C5 alkyl and hydrogen partial in C1~C5 alkoxy or all it is optionally substituted by halogen；
The R2The substituent group number of middle substituted benzyl is 1-5, substituent group be halogen, nitro, amino, hydroxyl, cyano, C1~C5 alkyl, C1~C5 alkylthio group or C1~C5 alkoxy, wherein C1~C5 alkyl, C1~C5 alkylthio group or C1~C5 alcoxyl Hydrogen partial or whole in base are optionally substituted by halogen；
The substituent group number of -2 base of substituted pyrimidines is 1-3, and substituent group is halogen, C1~C5 alkyl, C1~C5 alkane Sulfenyl or C1~C5 alkoxy, wherein C1~C5 alkyl, C1~C5 alkylthio group or hydrogen partial or whole in C1~C5 alkoxy It is optionally substituted by halogen；
The R1Middle aryloxy group is phenoxy group or pyridine oxygroup.
The preparation method of high activity N- oxyl anabasine analog, includes the following steps:
1) by compound shown in Formula II and R1X reaction, obtains compound shown in formula III；
2) compound shown in formula III and hydration hydrazine reaction, obtain compound shown in formula IV；
3) compound shown in formula IV is reacted with N- nitro S- methyl isothiourea, obtains compound shown in Formula V；
4) compound and R shown in Formula V2X reaction, obtains compound shown in Formulas I；
Wherein, X indicates halogen.
High activity N- oxyl anabasine analog is preparing the application in insecticide.
The insecticide is used to murder one kind or more of Semiptera, coleoptera, Diptera or lepidoptera pest, described to kill Worm agent is to honeybee safety.
The active constituent of the insecticide is the high activity N- oxyl anabasine analog.
A kind of insecticide wettable powder, as the material composition of following mass percentages: high activity N- described in 50% Oxyl anabasine analog, 2% lauryl sodium sulfate, 3% sodium lignin sulfonate, 5% naphthalenesulfonateformaldehyde formaldehyde condensation Object, 40% precipitated calcium carbonate.
A kind of insecticide suspending agent, as the material composition of following mass percentages: high activity N- hydrocarbon oxygen described in 35% Base anabasine analog, 10% ethylene glycol, 6% Nonoxynol-9,10% sodium lignin sulfonate, 1% Carboxymethyl cellulose, 0.2% 37% formalin, 0.8% 75% silicone oil aqueous emulsion, 37% water.
A kind of pesticide water dispersible granule, as the material composition of following mass percentages: high activity N- described in 60% Oxyl anabasine analog, 12% naphthalene sulfonic acid-formaldehyde condensation product, 8% N- Nmethyl-N-oleoyl base-sodium taurocholate, 2% Polyvinylpyrrolidone, 3% kaolin.
A kind of insecticide composition, by a) and b) forming, it is described a) for the high activity N- oxyl anabasine seemingly Object；Described b) is agriculturally acceptable carrier；Mass percentage a) is 10~99%.
The invention has the benefit that the present invention provides a kind of structure novel, insecticidal activity by introducing flexible side-chains Work as with pyrrole worm forest form, to the high activity N- oxyl anabasine analogue pesticide of honeybee safety.The insecticide solves pyrrole worm The drug resistance of quinoline and the problem of to toxicity to honeybees, can advantageous protection crops, gardening plant, fruits and vegetables etc., prevent disease pest Its yield is increased in harmful generation, while being high activity and the road development and exploration Liao Yitiaoxin to the insecticide of beneficial organism low toxicity.
Detailed description of the invention
Fig. 1 is compound Ia hydrogen nuclear magnetic resonance spectrogram.
Fig. 2 is compound Ia carbon-13 nmr spectra figure.
Fig. 3 is compound Ib hydrogen nuclear magnetic resonance spectrogram.
Fig. 4 is compound Ib carbon-13 nmr spectra figure.
Specific embodiment
The invention proposes high activity N- oxyl anabasine analogs and its preparation method and application, below with reference to implementation Example is described further the present invention.
R1 and R2 substituent group citing such as table 1 in formula Compound I, but it is not limited only to this.
R1 and R2 substituent group in 1 compound of formula I of table
High activity N- oxyl anabasine analog provided by the present invention is N- oxyl nitroguanidine compounds, synthesizes road Line is as follows:
It reacts and is carried out in suitable solvent, the optional tetrahydrofuran of suitable solvent, acetonitrile, toluene, dimethylbenzene, benzene, N, Dinethylformamide, dimethyl sulfoxide, acetone etc..
The optional sodium hydroxide of suitable alkali, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, triethylamine, pyridine, methanol Sodium, sodium ethoxide, potassium tert-butoxide, sodium tert-butoxide etc..
Reaction temperature is between ice bath and solvent boiling point temperature, and usually 0~100 DEG C.
Reaction time is 0.5~20h, usual 4~8h.
Experimental method described in following embodiments is unless otherwise specified conventional method；The reagent and material, such as Without specified otherwise, commercially obtain.
Embodiment 1: the synthesis of compound Ia
(1) preparation of N- ethyoxyl phthalimide
Stirrer and condenser pipe are loaded onto dry 250ml three-necked flask, solvent DMF 100ml is added, and N- hydroxyl is added Phthalimide 16.3g (0.1mol), heating, solid all dissolve, then corresponding halogenated by the mass ratio of the material 1:1 investment Alkane (iodoethane) is to slowly warm up to 60 DEG C, and triethylamine is added in the amount 1:1.1 that substance is pressed after reaction 5min, adds under stirring condition For heat to 60 DEG C of reactions, whether contact plate detection reaction is complete, after reaction, is slowly cooled to room temperature, and pours ice water into, is precipitated solid Body filters drying, obtains N- ethyoxyl phthalimide.Structure confirmation data are as follows:1H NMR(300MHz,CDCl3,25 DEG C) δ 7.99-7.82 (m, 2H), 7.85-7.71 (m, 2H), 4.31 (q, J=7.1Hz, 2H), 1.45 (t, J=7.1Hz, 3H).
(2) preparation of amine ethoxylate
Stirrer is loaded onto 250mL single port bottle, solvent methanol 100ml is added, and it is sub- that N- ethyoxyl phthalyl is added Hydrazine hydrate solid is added dropwise by the mass ratio of the material 1:1 in amine (0.1mol), stirring, and all dissolution, reappears muddiness for a moment, after 2h Contact plate detects raw material end of reaction, filters, and the methanol solution of product is directly used in next step.
(3) preparation of N- nitro S- methyl isothiourea
Stirrer is loaded onto 500ml there-necked flask, the concentrated sulfuric acid 120ml of 65% concentrated nitric acid 60ml and 98%, ice is added Salt bath is cooled to -10 DEG C or so, several times be added S- methyl-isourea 20g (0.144mol), after adding, under ice bath after Continuous stirring 1h, reaction solution is poured into ice (about 1000g), and white solid, filtering is precipitated, and solid is tied again with (ethyl alcohol: water=1:2) Crystalline substance, obtains white needles intermediate 214.5g, yield 75%, and 156-157 DEG C of fusing point.
(4) preparation of N- ethyoxyl guanidine
Stirrer is loaded onto 250ml three-necked flask, the methanol solution (0.1mol) of ethoxy amine is added, and phase is added in stirring The N- nitro S- methyl isothiourea for answering the amount of substance, is stirred at room temperature, and whether contact plate detection reaction is complete, and reaction terminates, and filters Filtrate is rotated, and is dissolved with a small amount of ethyl alcohol, is filtered, is obtained N- ethyoxyl guanidine.Structure confirmation data are as follows:1H NMR (300MHz, DMSO, 25 DEG C) δ 11.29 (s, 1H), 8.31 (s, 2H), 3.88 (q, J=7.0Hz, 2H), 1.22 (t, J= 7.0Hz,3H)。
(5) synthesis of N- ethyoxyl diuril azoles nitroguanidine
In dry 100mL there-necked flask, N- ethyoxyl guanidine is added, is placed in corresponding flask while being reacted, with N- ethyoxyl guanidine: NaH: halogenated hydrocarbons=1:1.5:1.1 ratio carries out final step reaction.By calculating, N- ethyoxyl guanidine is answered This takes 0.005mol；Sodium hydride takes 0.0075mol, is 60% in view of its purity, therefore takes 0.3g；The chloro- methylthiazol of 2- chlorine 5- takes 0.0055mol, i.e. 0.92g；In the flask that N- ethyoxyl guanidine is added, 5~10ml DMF solvent is added, stirring is cooled to 0 DEG C, adds Entering sodium hydride, halogenated hydrocarbons is added in ice bath 1h, removes ice bath, reacts at room temperature 22h, about 40ml ice water next is added to flask is interior, Continue to stir, get out extraction equipment, extracted with separatory funnel, ethyl acetate is as extractant, and each 30ml, extraction is three times.
Structure confirmation data are as follows:1H NMR(300MHz,CDCl3,25℃)δ9.10(s,1H),7.51(s,1H),7.01(s, 1H), 4.91 (s, 2H), 4.06 (q, J=7.1Hz, 2H), 1.34 (t, J=7.1Hz, 3H)13C NMR(75MHz,CDCl3,25 ℃)δδ161.08,152.86,141.29,132.20,70.74,45.44,13.06.Hydrogen nuclear magnetic resonance spectrogram and carbon spectrogram are as schemed 1 and Fig. 2.
HRMS (ESI) m/z calculated value C7H11ClN5O3S(M+H)+280.0266 measured value 280.0265.
Embodiment 2: the synthesis of general formula compound Ib
(1) preparation of N- benzyloxy phthalimide
Stirrer and condenser pipe are loaded onto dry 250ml three-necked flask, solvent DMF 100ml is added, and N- hydroxyl is added Phthalimide 16.3g (0.1mol), heating, solid all dissolve, then corresponding halogenated by the mass ratio of the material 1:1 investment Alkane (benzyl bromine) is to slowly warm up to 60 DEG C, and triethylamine is added in the amount 1:1.1 that substance is pressed after reaction 5min, heats under stirring condition It is reacted to 60 DEG C, contact plate detects fully reacting, is slowly cooled to room temperature, and pours ice water into, and solid is precipitated, and filters drying, obtains N- Benzyloxy phthalimide.
Structure confirmation data are as follows:1H NMR(300MHz,CDCl3, 25 DEG C) and δ 7.84 (dt, J=7.3,3.7Hz, 2H), 7.81-7.72 (m, 2H), 7.58 (dd, J=6.6,2.9Hz, 2H), 7.48-7.36 (m, 3H), 5.25 (s, 2H).
(2) preparation of benzyloxy amine
Stirrer is loaded onto 250mL single port bottle, solvent methanol 100ml is added, and it is sub- that N- benzyloxy phthalyl is added Hydrazine hydrate solid is added dropwise by the mass ratio of the material 1:1 in amine (0.1mol), stirring, and all dissolution, reappears muddiness for a moment, after 2h Contact plate detects raw material end of reaction, filters, and the methanol solution of product is directly used in next step.
(3) preparation of N- nitro S- methyl isothiourea
Stirrer is loaded onto 500ml there-necked flask, the concentrated sulfuric acid 120ml of 65% concentrated nitric acid 60ml and 98%, ice is added Salt bath is cooled to -10 DEG C or so, several times be added S- methyl-isourea 20g (0.144mol), after adding, under ice bath after Continuous stirring 1h, reaction solution is poured into ice (about 1000g), and white solid, filtering is precipitated, and solid is tied again with (ethyl alcohol: water=1:2) Crystalline substance, obtains white needles intermediate 214.5g, yield 75%, and 156-157 DEG C of fusing point.
(4) preparation of N- benzyloxy nitroguanidine
Stirrer is loaded onto 250ml three-necked flask, the methanol solution (0.1mol) of benzyloxy amine is added, and phase is added in stirring The N- nitro S- methyl isothiourea for answering the amount of substance, is stirred at room temperature, and whether contact plate detection reaction is complete, and reaction terminates, and filters Filtrate is rotated, and is dissolved with a small amount of ethyl alcohol, is filtered, is obtained N- ethyoxyl guanidine.Structure confirmation data are as follows:1H NMR (300MHz, DMSO, 25 DEG C) δ 11.40 (s, 1H), 8.29 (s, 2H), 7.45 (ddd, J=7.0,6.3,2.5Hz, 5H), 4.89 (s,2H)。
(5) synthesis of N- benzyloxy chloropyridine nitroguanidine
In dry 100mL there-necked flask, N- benzyloxy guanidine is added, is placed in corresponding flask while being reacted, with N- benzyloxy guanidine: NaH: halogenated hydrocarbons=1:1.5:1.1 ratio carries out final step reaction, and by calculating, N- benzyloxy guanidine is answered This takes 0.005mol；Sodium hydride takes 0.0075mol, is 60% in view of its purity, therefore takes 0.3g；The chloro- picoline of 2- chlorine 5- takes 0.0055mol, i.e. 0.92g；In the flask that N- benzyloxy guanidine is added, 5~10ml DMF solvent is added, stirring is cooled to 0 DEG C, adds Entering sodium hydride, halogenated hydrocarbons is added in ice bath 1h, removes ice bath, reacts at room temperature 22h, about 40ml ice water next is added to flask is interior, Continue to stir, get out extraction equipment, extracted with separatory funnel, ethyl acetate is as extractant, and each 30ml, extraction is three times.
Structure confirmation data are as follows:1H NMR(300MHz,CDCl3,25℃)δ9.04(s,1H),8.33(s,1H),7.70(d, J=6.1Hz, 1H), 7.57-7.25 (m, 6H), 6.76 (s, 1H), 4.90 (s, 2H), 4.77 (s, 2H)13C NMR(75MHz, CDCl3)δ161.26,151.14,149.70,139.22,132.90,129.55,129.26,128.99,128.85,124.06, 77.52,50.15.Hydrogen nuclear magnetic resonance spectrogram and carbon spectrogram such as Fig. 3 and Fig. 4.
HRMS (ESI) m/z calculated value C14H15ClN5O3(M+H)+336.0858 measured value 336.0857.
Other general formulas are that series compound shown in Formulas I is prepared according to the method described above.
The biological activity determination of embodiment 3:N- oxyl anabasine analog
1. the insecticidal activity of pair aphid
(1) for trying insect
Black peach aphid (Myzus persicae) larva, picks up from Haidian District, Beijing City peach.
(2) comparison medicament
Imidacloprid raw medicine (95%), Jiangsu Changlong Chemical Co,
The synthesis of guadipyr raw medicine laboratory.
(3) experimental method
Medicament is prepared；
Preliminary biological activity determination: weighing 20mg compound sample with a ten thousandth balance, with 1mL dimethylformamide (DMF) dissolution obtains 2% mother liquor.Pipette partial mother liquid with containing 0.05% triton x-100 aqueous solution be configured to 400mg/L and The measurement liquid of 40mg/L.The preparation method of comparison medicament is same, the test dose set according to preliminary experiment are as follows: imidacloprid 40mg/L, guadipyr 40mg/L and 400mg/L.(dose double 400mg/L and 40mg/L, single repetition, and set by pest target Set comparison medicament and blank control).
Processing method:
Insecticidal activity assay is carried out using infusion process, the peach leaves with black peach aphid is selected, will be impregnated in medical fluid with aphid blade 10s records borer population and is put into the culture dish added with moisturizing filter paper, is put into (25 ± 1) DEG C illumination box after capping after drying. Each chemicals treatment 30 or more, inspection result after 48 hours.Dead judgment criteria are as follows: touch polypide, cannot normally creep Pest individual is considered as dead individuals.
(4) data statistics and analysis
According to survey data, the corrected mortality of each processing is calculated, unit is percentage (%).Based on formula (1) and (2) It calculates, calculated result remains into 2 significant digits:
In formula:
P1--- the death rate；K--- death borer population；The total borer population of N---- processing；P2--- corrected mortality；
Pt--- the processing death rate；P0--- the blank control death rate.
If compareing the death rate less than 5%, without correction；The death rate is compareed between 5%-20%, should be carried out by formula (2) Correction；It compares the death rate and is greater than 20%, test need to be done again.
Part of detecting compound is to the indoor biometrics toxicity of black peach aphid, as a result such as table 2.From table 2 it can be seen that part of compounds Excellent insecticidal activity is all shown in high concentration and low concentration, such as the compound that number is 3,8,9,25 and 26 in table.
Indoor biometrics toxicity of 2 part of compounds of table to black peach aphid
2. the toxotest of pair honeybee
(1) test organism
Take apis mellifera apis mellifera.L adult worker bee for examination, total Test is derived from same tool king bee with bee Group selects health, individual of the same size to be tested.
(2) tube method is fed
It is carried out referring to OECD chemicals test philosophy.Test is respectively 12cm × 10.5cm × 9cm, with net in length It is carried out in the bee cage of yarn lining.A feeding pipe is installed in cage bottom portion, and beak can be protruded into pipe interior suction taking liquid for examination honeybee.Use quality The aqueous sucrose solution that concentration is 50% is mixed with medicament mother liquor by different proportion, is configured to by geometric sequence (interval is than being 2.00) The medical fluid of various concentration.
The 100 μ L medical fluid prepared is put into feeding pipe for honeybee feeding, is taken out the feeding pipe containing medical fluid after 4h, record Medical fluid consumption, while the sucrose solution for using no medicine instead continues to feed.9~11 adult workers bee are disposably moved into every cage. Every processing (including blank control) sets 3 repetitions.Test (25 ± 2) DEG C, relative humidity 50%~70% dark surrounds in It carries out.The 24th and 48h investigates each concentration group honeybee poisoning and death condition after on-test.
(3) data processing
Using SPSS data processing software, regression analysis is done, establishes " docs-effect " linear equation, and record LD50Value and Its 95% confidence limit.
(4) honeybee safety
Division to " feeding tube method " test result, referring to the classification being arranged in " chemical pesticide Safety Evaluation Experiment criterion " Standard: LD for 24 hours50Being worth≤0.001 μ g/bee is highly toxic pesticide；0.001μg/bee<24h LD50≤ 2.0 μ g/bee are height Malicious pesticide；2.0μg/bee<24h LD50≤ 11 μ g/bee are moderate toxicity；24h LD50> 11 μ g/bee are low-toxin farm chemicals.It surveys Test result is shown in Table 3.
The bioactivity comparison of 3 compound of table and commercialization insecticide
IMI- imidacloprid, FPF- fluorine pyrrole furanone, TFM-triflumezopyrim.
Experiment is also tested for compound 3,9,14 and 25, finds to find no in five concentration of setting lower than 1000mg/L Bee death, in high concentration 2000mg/L, the death rate is also below 10%.
From the test result of table 2 and table 3 it is found that compound shown in Formulas I is suitable with imidacloprid in biological activity test, together When to the toxicity of honeybee well below imidacloprid and similar commercialization medicament.Due to its positive characteristic, above-mentioned noval chemical compound can Advantageous protection crops, gardening plant, fruits and vegetables etc. prevent the generation of pest and disease damage, it are made to increase yield.
Embodiment 4: the preparation of 8 wettable powder of compound
8 wettable powder of compound by following mass percentages material composition:
Compound and each component are sufficiently mixed, after ultra-fine pulverizer disintegrating, obtain 50% wettable powder product.
Embodiment 5: the preparation of 26 suspending agent of compound
26 suspending agent of compound by following mass percentages material composition:
Compound 26 and each component are sufficiently mixed, the suspending agent product of 35% compound 26 is obtained.
Embodiment 6: the preparation of 12 water dispersible granules of compound
12 water dispersible granules of compound by following mass percentages material composition:
Compound 12 and each component are sufficiently mixed crushing, after adding water kneading, the pelletizer of 10-100 mesh screen is added In be granulated, then again through drying, screening.
Embodiment 7: the preparation of the water dispersible granules of compound 9 and monosultap composition
The water dispersible granules of compound 9 and monosultap composition by following mass percentages material composition:
Compound 9 and Cupric sulfate and each component are sufficiently mixed crushing, after adding water kneading, 10-100 mesh screen is added It is granulated in pelletizer, then again through drying, screening.

Claims (9)

1. the N- oxyl nicotinoids that one kind is used to prepare insecticide, which is characterized in that the insecticide is safe to honeybee, The N- oxyl nicotinoids are N- oxyl nitroguanidine compounds shown in Formulas I；
Wherein, R1For C1-C10 saturation or unsaturated fatty hydrocarbons base, R2For substituted benzyl, haloperidid methyl, halo thiazole first Base, the substituent group of the substituted benzyl are halogen, nitro, cyano, C1~C5 alkyl.
2. the preparation method of N- oxyl nicotinoids described in claim 1, which comprises the steps of:
1) by compound shown in Formula II and R1X reaction, obtains compound shown in formula III；
2) compound shown in formula III and hydration hydrazine reaction, obtain compound shown in formula IV；
3) compound shown in formula IV is reacted with N- nitro S- methyl isothiourea, obtains compound shown in Formula V；
4) compound and R shown in Formula V2X reaction, obtains compound shown in Formulas I；
Wherein, X indicates halogen；
3. N- oxyl nicotinoids described in claim 1 are preparing the application in insecticide.
4. application according to claim 3, which is characterized in that the insecticide is for murdering Semiptera, coleoptera, dipteron Mesh or one kind of lepidoptera pest or more, the insecticide is to honeybee safety.
5. application according to claim 3, which is characterized in that the active constituent of the insecticide is described in claim 1 N- oxyl nicotinoids.
6. a kind of insecticide wettable powder, which is characterized in that by the material composition of following mass percentages: 50% right It is required that N- oxyl nicotinoids described in 1,2% lauryl sodium sulfate, 3% sodium lignin sulfonate, 5% naphthalene sulphur Sour formaldehyde condensation products, 40% precipitated calcium carbonate.
7. a kind of insecticide suspending agent, which is characterized in that by the material composition of following mass percentages: 35% claim N- oxyl nicotinoids described in 1,10% ethylene glycol, 6% Nonoxynol-9,10% sulfomethylated lignin Sour sodium, 1% carboxymethyl cellulose, 0.2% 37% formalin, 0.8% 75% silicone oil aqueous emulsion, 37% water.
8. a kind of pesticide water dispersible granule, which is characterized in that by the material composition of following mass percentages: 60% right It is required that N- oxyl nicotinoids described in 1,12% naphthalene sulfonic acid-formaldehyde condensation product, 8% N- Nmethyl-N-oleoyl Ji-ox Sodium sulfonate, 2% polyvinylpyrrolidone, 3% kaolin.
9. a kind of insecticide composition, which is characterized in that by a) and b) forming, described a) is N- hydrocarbon oxygen described in claim 1 Base nicotinoids；Described b) is agriculturally acceptable carrier；Mass percentage a) is 10~99%.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101065368A (en) * 2004-11-24 2007-10-31 拜尔农作物科学股份公司 Substituted oxyguanidines
CN101821232B (en) * 2008-11-25 2012-09-05 覃兆海 Condensed amino nitroguanidine compounds, preparation method and use as botanical insecticides thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101065368A (en) * 2004-11-24 2007-10-31 拜尔农作物科学股份公司 Substituted oxyguanidines
CN101821232B (en) * 2008-11-25 2012-09-05 覃兆海 Condensed amino nitroguanidine compounds, preparation method and use as botanical insecticides thereof

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Kyotorphin analogues containing unnatural amino acids: synthesis,analgesic activity and computer modeling of their interactions with μ-receptor;Dzimbova, Tatyana et al.;《Medicinal Chemistry Research》;20140226;第23卷(第8期);3694-3704 *
Photochemical formation of nitroxide radicals from carcinogenic N-methyl-N"-nitro-N-nitrosoguanidine and related compounds;Y.IOKI et al.;《Photochemistry Photobiology》;19750630;第21卷;387-91 *
含肟醚的新型三唑并嘧啶衍生物的合成及除草活性研究;江黎黎等;《有机化学》;20090930;第29卷(第9期);1392-1404 *

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