CN1501917A - Compounds useful as insecticides, compounds useful as acaricides, and processes to use and make same - Google Patents
Compounds useful as insecticides, compounds useful as acaricides, and processes to use and make same Download PDFInfo
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- CN1501917A CN1501917A CNA018149138A CN01814913A CN1501917A CN 1501917 A CN1501917 A CN 1501917A CN A018149138 A CNA018149138 A CN A018149138A CN 01814913 A CN01814913 A CN 01814913A CN 1501917 A CN1501917 A CN 1501917A
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having 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
- C07D237/14—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
- 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
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/34—One oxygen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- Pest Control & Pesticides (AREA)
- Agronomy & Crop Science (AREA)
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Abstract
A compound according to Formula One is provided and a process to use such compound to control insects is provided.A compound according to Formula (One) is provided and a process to used such compound to control insects is provided wherein A represents a five or six membered heterocyclic ring containing at least one heteroatom selected from the group consisting of an oxygen, sulfur, or nitrogen, where said heterocyclic ring may be substituted by one or more substituents; E is selected from the group consisting of O, SOn where n is o-2, NH, and NX, where X is selected from the group consisting of C1-10 alkyl or halo C1-10 alkyl; J and R are independently selected from the group consisting of H, C1-10 alkyl, C1-10 alkenyl, C1-10 alkynyl, halo C1-10 alkyl, and C1-10 alkoxyalkyl; M is selected from the group consisting of N and Cz, where Z is selected from the group consisting of H and C(=O)H; Q is selected from the group consisting of NO2, CN, and C(=O)CF3; G and T are independently selected from the group consisting of H, C1-10 alkyl, C1-10 alkenyl, C1-10 alkynyl, halo C1-10 alkyl, and C1-10 alkoxyalkyl; optionally, G and T can also be joined together by a single bond, or through a connecting bridge, where such connecting bridge is selected from the group consisting of CH2, CHCH3, C(CH3)2, CH(halo C1-10 alkyl), C(halo C1-10 alkyl)2, CHF, CF2, O, SOn where n is o-2, NH, and NX where X is selected from the group consisting of C1-10 alkyl or halo C1-10 alkyl.A compound according to Formula (One) is provided and a process to used such compound to control insects is provided wherein A represents a five or six membered heterocyclic ring containing at least one heteroatom selected from the group consisting of an oxygen, sulfur, or nitrogen, where said heterocyclic ring may be substituted by one or more substituents; E is selected from the group consisting of O, SOn where n is o-2, NH, and NX, where X is selected from the group consisting of C1-10 alkyl or halo C1-10 alkyl.
Description
Right of priority
This application requires the right of priority from the U.S. Provisional Application 60/229,110 of submission on August 30th, 2000.
Invention field
The invention provides sterilant compound, miticide compound and use and preparation method.
Background of invention
Novel pesticide and miticide are badly in need of.Insect and acarid have had resistibility to the sterilant and the miticide of current use gradually.At least 400 kinds of arthropodss have resistibility to one or more sterilants.It is to some older sterilants, as DDT, carbamate, and organophosphate, the development of resistibility be well-known.And resistibility even developed into pyrethroid insectide and miticide at some renewals.Therefore, novel pesticide and miticide especially have compound novel or the atypia mode of action and are necessary.
Summary of the invention
The purpose of this invention is to provide sterilant with compound, miticide with compound and the method for using and prepare these compounds.According to the present invention, the compound as general formula one is provided, its preparation and using method also are provided.
General formula one
Invention is described
In general formula one, A represents one five yuan or hexa-member heterocycle, and this heterocycle contains a heteroatoms that is selected from oxygen, sulphur or nitrogen at least.Usually, preferably use hexa-member heterocycle.More preferably use the hexa-member heterocycle that contains one or two nitrogen heteroatom.
This heterocycle can be replaced by one or more substituting groups, and this substituting group is selected from: fluorine, chlorine, bromine, iodine, C
1-10Alkyl, halo C
1-10Alkyl, nitro, cyano group, C
1-10Alkoxyl group, C
1-10Alkylthio, C
1-10The alkyl sulfinyl, C
1-10Alkyl sulphonyl, C
1-10Alkenyl, halo C
1-10Alkoxyl group, halo C
1-10Alkylthio, halo C
1-10Alkenyl, amido, halo amido, C
1-10Alkoxy carbonyl, C
1-10Alkynyl, amino, C
1-10Alkylamino, C
1-10Dialkyl amido, C
3-12Cycloalkyl, C
1-10Alkoxyalkyl, acyl group, formyl radical, C
6-12Aryl, single or polysubstituted C
6-12Aryl, heteroaryl, and single or polysubstituted heteroaryl (heteroaryl described herein has 5-12 atom on ring, and in the ring described herein, 1-3 described atom is selected from nitrogen, oxygen and sulphur, and remaining atom is a carbon atom in the described ring, and substituting group is selected from halogen herein, C
1-10Alkyl, halo C
1-10Alkyl, C
1-10Alkoxyl group, nitro, cyano group, and C
6-12Aryloxy).
Described in the above symbol, and in the entire chapter document, preferred C
1-10Be C
1-6, more preferably C
1-10Be C
1-4
Usually, if heterocycle is substituted, preferably it is by methyl, ethyl, and fluorine, chlorine, or the bromine list replaces.Usually, preferably this substituting group and heteroatoms are adjacent.
E is selected from O, SO
n(wherein n is 0-2), NH, and NX (wherein X is selected from C
1-10Alkyl, halo C
1-10Alkyl).Usually, preferred E is O.
J and R are independently selected from H, C
1-10Alkyl, C
1-10Alkenyl, C
1-10Alkynyl, halo C
1-10Alkyl and C
1-10Alkoxyalkyl.Usually, preferred J and R are H.
M is selected from N and CZ, and wherein Z is selected from H and C (=O) H.Usually, preferably use CH.
Q is selected from NO
2, CN, and C (=O) CF
3Usually, preferred Q is NO
2
G and T are independently selected from H, C1-10 alkyl, C
1-10Alkenyl, C
1-10Alkynyl, halo C
1-10Alkyl, and C
1-10Alkoxyalkyl.Usually, preferred G and T are methyl or ethyl.
G and T also can pass through a singly-bound, or a cross structure is joined together, and at this, this cross structure is selected from CH
2, CHCH
3, C (CH
3)
2, CH (halo C
1-10Alkyl), C (halo C
1-10Alkyl)
2, CHF, CF
2, O, SO
n(wherein n is 0-2), NH, and NX (wherein X is selected from C
1-10Alkyl or halo C
1-10Alkyl).Usually preferred cross structure is a singly-bound or a CH
2
All salt of these compounds and ester and all optically active isomers thereof all are considered to a part of the present invention.
For whole document, unless specifically stated otherwise, all temperature are degree centigrade providing, and all per-cent refers to weight percent.
Unless specifically stated otherwise, when group of regulation can be selected from a class and determine that the substituting group of compound replaces by one or more, this will mean that substituting group can be independently selected from this compounds.
Compound of the present invention is for insect, and the control of acarid and aphid is useful.Therefore, the present invention also instructs and is used to suppress insect, acarid, or the method for aphid, and it comprises the location that general formula one compound of insect or acarid amount of suppression is applied to insect or acarid.Specifically, these compound control Homoptera insects comprise Aphidiadae (aphid), Aleyrodidae (aleyrodid), Delphacidae (plant hopper), Cicadellidae (leafhopper).They also control coleopteron (beetle), comprise Chrysomelidae (chrysomelid worm).
These compounds are useful and can be used for suppressing insect for the quantity that reduces insect and acarid, acarid, or the method for aphid, and it comprises that general formula one compound that will make the significant quantity of insect or acarid inactivation is applied to the location of insect or acarid.
" location " of insect or acarid is term as used herein, refers to environment that insect or acarid are lived or their ovum where, comprises their ambient airs, the food that they are eaten, or the object or the material of their contacts.For example, by active compound being applied to the plant part that insect or acarid are eaten, especially leaf, can controlling and draw plant class insect or acarid.By active compound being applied to control the insect that inhabits soil, as termite in the soil that insect creeps.By active compound being applied to be controlled the insect that parasitizes animal, as flea by the animal of parasitism.
By active compound being applied to this material, can think this compound for the protection textiles, paper, the cereal of storage, or seed also is useful.
Term " suppresses insect or acarid " and refers to reduce the quantity of survival insect or acarid, or reduces the quantity of can survive insect or acarid ovum.The reduction degree of using compound and obtaining depends on the rate of application of compound, employed particular compound, and the kind of targeted insect or acarid certainly.At least should use the amount of its inactivation.
Term " makes the amount of insect inactivation " and " making the amount of acarid inactivation " is used to be described in and handles insect or acarid mesopodium so that the amount that its quantity is obviously reduced.The general use at about 1 active compound to the amount of about 1000ppm weight range.In a preferred embodiment, the present invention instructs the method that is used to suppress acarid or aphid, and it comprises and will general formula one compound of the significant quantity of acarid or aphid inactivation is applied on the plant.
Compound of the present invention is employed with the form of composition, and said composition comprises compound of the present invention and plant-acceptable inert support.Said composition can be to be scattered in the concentration components that uses in the water, or does not do the dust-like or the granular composition of further processing.Said composition prepares according to program traditional in agrochemical field and prescription, but because wherein have compound of the present invention, so it is novel and important.
Wherein used the dispersion of this compound the most frequently used be aq suspension or emulsion by the concentration components preparation of this compound.This is water-soluble, but aqueous suspension or emulsified component can be the solids that is commonly referred to be wet powder, or is commonly referred to be the liquid of emulsifiable concentrate or aq suspension.The wettable powder that can be pressed into water-dispersible granular material comprises active compound, the intimate mixture of inert support and tensio-active agent.The normally about 10wt% to 90wt% of the concentration of this active compound.Inert support is selected from attapulgite clay usually, montmorillonitic clay, diatomite, or purified silicate.
But comprise about 0.5% effective surface promoting agent, be selected from sulfonated lignin, concentrate naphthalenesulfonate to about 10% wet powder, naphthalenesulfonate, alkylbenzene sulfonate, alkyl-sulphate, and nonionogenic tenside are as the ethylene oxide adduct of alkylphenol.
The emulsifiable concentrate of this compound comprises a compound that is dissolved in the simplification concentration in the inert support, as every liter of liquid about 50 to about 500 the gram, be equivalent to about 10% to about 50%, this inert support can be the mixture of water-miscible solvent or water-insoluble organic solvents and emulsifying agent.Useful organic solvent comprises aromatic substance, and the high boiling point naphthalene class of especially dimethylbenzene, and petroleum fractions, especially oil and olefinic part are as heavy aromatic petroleum naphtha.Can use other organic solvent, as comprise the terpenes solvent of rosin derivative, aliphatic ketone, as pimelinketone, and compound alcohol, as cellosolvo.Preparation emulsifiable concentrate suitable emulsifying agent is selected from traditional nonionogenic tenside, as discussed above those.
Aq suspension comprises the suspension of water-insoluble compound of the present invention, and its concentration with the extremely about 50wt% of about 5wt% is scattered in the aqueous carrier.By pulverizing this compound imperceptibly, and fully it is sneaked into prepare suspension in the carrier that comprises water and be selected from tensio-active agent of the same type discussed above.Inert component also can be added into as inorganic salt and synthetic or natural gum, to improve the density and the viscosity of aqueous carrier.By the preparation aqueous mixture, and as sand mill, ball mill, or it evenly to be pulverized and mix this compound simultaneously usually be the most effective.
This compound also can be used as granular composition and is employed, and is particularly advantageous in to be applied to soil.Granular composition comprises about 0.5wt% usually to the about compound of 10wt%, and it is scattered in one fully or most of by clay or in the inert support that similarly not expensive material is formed.Usually by with this compound dissolution in suitable solvent and the bead-type substrate that is applied to be prefabricated into about suitable particle size of 0.5 to 3mm prepare said composition.Dough that also can be by making carrier and compound or paste and crushing and dryly prepare said composition to obtain the ideal grain graininess.
The pulvis that contains this compound can be only by with this compound powder and suitable Powdered agricultural carrier, and as kaolin, pulverized volcanics etc. closely mix and prepare.Pulvis can suitably contain about 1% to about 10% this compound.
Active composition can contain the auxiliary agent tensio-active agent to improve the said composition deposition on target crops and organism, wettability and perviousness.These auxiliary agent tensio-active agents can optionally be used as system component or as the oil tank mixture.The amount of auxiliary agent tensio-active agent is 0.01% to 1.0% (V/V) of the spray volume of water, preferred 0.05% to 0.5%.The proper auxiliary agent tensio-active agent comprises ethoxylized nonylphenol, synthetic or the natural alcohol of ethoxylation, the salt of sulfosuccinic ester, the ethoxylation organo-siloxane, ethoxylated fatty amine contains the crops oil concentrate of high molecular paraffin oil and the mixture of tensio-active agent and mineral oil and vegetable oil.
Equally practicably, when because any reason when needing, with in appropriate organic solvent, normally Wen He petroleum oil is used this compound as the form of the solution in the spray oil, and it is widely used in agrochemistry.
Sterilant and miticide are generally used with the form of the dispersion of activeconstituents in liquid vehicle.Traditionally, decide rate of application according to the concentration of activeconstituents in carrier.The most widely used carrier is a water.
Compound of the present invention also can be used with the form of aerosol composition.In said composition, activeconstituents is dissolved or be scattered in in the inert support of produce pressing propellant mixture.This aerosol composition is put in the container, and this mixture distributes by an atomization valve from this container.Propellant mixture comprise can with organic solvent blended lower boiling halocarbon, perhaps by the aq suspension of rare gas element or gaseous state halocarbon pressurization.
Be applied to insect, the actual amount of acarid and the on-site compound of aphid is not vital and according to above-mentioned example, this amount is easy to be determined by those skilled in the art.Generally, the control that can provide is provided the compound of 10ppm to 5000ppm weight concentration.For many these compounds, 100 to 1500ppm concentration will be enough.
The place of using this compound can be the place that any insect or Araneae arthropods live, for example, and vegetables, fruit and nutwood, grape vine, and ornamental plant.
Because the toxin immunity ability of acarid ovum uniqueness need be used repeatedly to control emerging larva, as other known miticide.
When being applied to plant, except antimite effectively, outside aphid and the insect, general formula one compound also has interior assimilating activity.Therefore, other one side of the present invention is the infringement that protective plant is avoided insect, and it comprises with general formula one compound of significant quantity handled seed before sowing, handle the soil of sowing, or handle the soil of plant root after plantation.
By adding other for example desinsection, kill mite, and/or the composition of eelworm-killing activity, the effect that can widen The compounds of this invention.For example, one or more following materials are fit to be used in combination with compound of the present invention:
Organo phosphorous compounds, as acephate, R-1582, cadusafos, earth worm chlorine phosphorus, Chlorpyrifos 94, Coumaphos, Systox (dematon), methyl 1, diazinon, SD-1750, Rogor, EPN, Erthoate, ethoprop, the oxygen Pyrimithate, Nemacur, Sumithion, fensulfothion, Tiguvon, Dyfonate, peace fruit, thiazolone phosphorus, heptan worm phosphorus, the Malathion, acephatemet, parathion-methyl, Phosdrin, monocrotophos, thiophos, phorate, zolone, R-1504, phosphamidon, the second third phosphorus prestige, phoxim, Profenofos, Kayaphos, propetamphos, Toyodan, the methyl pirimiphosmethyl, pirimiphos ethyl, Resitox, second Toyodan; Close third phosphorus, temephos, Terbufos, tetrachlorvinphos, Thiafenox, thiometon, triazophos, and Trichlorphon.
Carbamate is as aldicarb ， Evil worm prestige, benfuracarb, bensultap, BPMC, oxygen fourth fork prestige (Butoxycarbocim), carbaryl, the furans pellet, carbosulfan, cloethocarb, benzene worm prestige; Osbac, furathiocarb, metmercapturon, isoprocarb; methomyl, thioxamyl, Aphox, promecarb; Propoxur, the two prestige of sulphur, and Thiofurox.
Pyrethroid, as fluorine ester chrysanthemum ester, Pynamin, β-cyfloxylate, bifenthrin, bioresmethrin, cyfloxylate, (RS)-and cyfloxylate, λ-(RS)-cyfloxylate; γ-(RS)-cyfloxylate, Cypermethrin; The nail body Cypermethrin; Own body Cypermethrin; Deltamethrin, esfenvalerate is killed the chrysanthemum ester, fenfluthrin, Fenvalerate, flucythrinate, flumethrin, taufluvalinate, hot body taufluvalinate, halogen ether chrysanthemum ester, permethrin, Protrifenbute, resmethrin, deinsectization silicon ether, tefluthrin, Tetramethrin, tralomethrin, fish security pyrethroid, ether chrysanthemum ester for example, pyrethrum, Tetramethrin, s-anti-third rare pyrethrum, fenfluthrin and the prallethrin.
Acylurea, other type insect growth regulator(IGR) and insect hormone analogue such as Buprofezin, Chromfenozide, UC 62644, TH-6040, ABG-6215, flufenoxuron, RH 0345, fluorine bell urea, Entocon ZR 512, Leufenuron, Entocon ZR 515, Runner, Rimon, pyriproxyfen, Teflubenzuron and RH-5992, N-[3,5-two chloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoro propoxy-) phenyl]-N ' (2, the 6-difluoro benzoyl) urea; Neonicotine (Neonicotnioids) and other nicotine, clear as the pyrrole worm, AKD-1022, cartap, TI-435, Clothiamidin, MTI-446, Dinotefuran, imidacloprid, Nicotine, nitenpyram, Thiamethoxam, Thiacloprid;
Macrolide, as avermectin, milbemycin (Milbemycins), or Spinosyns, for example, and Avrmectin, ivermectin, milbemycin is according to mark's butylbenzene manthanoate and SPINOSAD 105; And
Other desinsection, kill mite, kill mollusk and nematicidal compound or active substance, as aldrin, U-36059, Ai Zhading, azoles ring tin, Bifenazate, bromopropylate, chlordimeform, fluorine azoles worm is clear, Chlofentezine, G-23922, Niran, cyhexatin kills fly amine, DDT, Mitigan, Dieldrin-attapulgite mixture, DNOC, 5a,6,9,9a-hexahydro-6,9-methano-2,4, Ethoxazole, fenazaquin, fenbutatin oxide, azoles mite ester, β-azoles mite ester, sharp strength spy, thiazole mite, hexythiazox, IKI-220 oxadiazole worm, lindane, metmercapturon, Halizan, methoxychlor, Vepacide-Tech, oil and vegetable oil, pyridaben, pymetrozine, pyramine phenylate, tubatoxin, S-1812, S-9539, Spirodiclofen, sulphur, tebufenpyrad, tetradifon, triaxamate, a kind of plant extract of insect active; A kind of preparation that contains the threadworms insect active, a kind of available from Bacillus subtills, the preparation of Bacillusthuringiensis, a kind of nuclear polyhedral virus, or other similarly has genetic engineering or natural organism, and synergistic agent, as Piperonyl Butoxide, sesoxane (Sesamax), Safroxan and dodecyl imidazoles, and the phage stimulator, as cucurbitacin, sugar and Cox (Coax).
Embodiment
Provide following examples further to illustrate the present invention.They are not considered to limit the present invention.
(2Z)-preparation of 3-bromo-2-(Nitromethylene) tetramethyleneimine (allyl group bromination thing I)
(2Z)-2-(Nitromethylene) tetramethyleneimine
The solution of 4.00g (40.3mmo1) imido acid methyl esters (methyl imidate) (referring to Chem.Ber. in 1971,104,924) and 1.23g (20.1mmol) Nitromethane 99Min. was allowed to be cooled 100 ℃ of heating in 40 hours then.Under vacuum, concentrate this mixture to remove volatile matter and residuum is dissolved in the methylene dichloride and with silica gel (230-400 order) chromatographic separation, obtains the nitroethylene of 2.1g (42%) with dichloromethane/ethyl acetate mixture wash-out.
(2E)-and 2-[bromine (nitro) methylene radical] tetramethyleneimine
At room temperature, to the N-bromo-succinimide that just in the mixture of well-beaten 328mg (2.56mmol) nitroethylene, adds a 478mg (2.68mmol).This mixture is stirred to spend the night to be filtered subsequently and obtains 711mg, and it separates with silica gel chromatography, as eluent, obtains the vinyl bromide of 420mg (79%) with methylene dichloride.
(2Z)-3-bromo-2-(Nitromethylene) tetramethyleneimine
(allyl group bromination thing I)
The vinyl bromide that in batches adds 2.0g (9.7mmol) in the dimethylbenzene that 130ml is refluxing, the joining day was above 5-10 minute.Backflow was proceeded 8 hours and this mixture is allowed to cooling.Concentrate under vacuum and obtain a solid, this solid is by pack into silicagel column and obtained the allyl group bromination thing I of 1.10g (55%) by ethylene dichloride/ethyl acetate mixture wash-out of dry method.
(1Z)-3-bromo-N-methyl isophthalic acid-nitro but-1-ene-2-amine
The preparation of (allyl group bromination thing II)
(1Z)-N-methyl isophthalic acid-nitro but-1-ene-2-amine
(35.4g, 0.58mol) solution of Nitromethane 99Min. was allowed to cooling in 17 hours then 90-95 ℃ of heating with 29.3g (0.290mol) imido acid methyl esters (referring to Chem.Ber. in 1971,104,924) and 31.4mL.Concentrate this solution and obtain residuum, it is separated by silica gel chromatography, obtains the nitroethylene of 22.5g (60%) with dichloromethane/ethyl acetate mixture wash-out.
(1E)-1-bromo-N-methyl isophthalic acid-nitro but-1-ene-2-amine
Under 20-23 ℃, add the N-bromo-succinimide of 10.3g (57.8mmol) in the nitroethylene solution of the 6.95g in being dissolved in the 430ml tetracol phenixin (53.4mmol), the joining day was above 5-10 minute.This mixture is stirred to spend the night and is filtered subsequently.This filtrate being concentrated obtains the vinyl bromide of 10.5g (94%), fusing point: 79-81 ℃.
(1Z)-3-bromo-N-methyl isophthalic acid-nitro but-1-ene-2-amine
(allyl group bromination thing II)
To the vinyl bromide that adds 3.07g (14.7mmol) in 48-52 ℃ of well-beaten 200ml tetracol phenixin, the joining day was above 2-3 minute.This mixture is stirred 25 minutes, uses ice-cooled to 10 ℃ then.The collecting precipitation thing obtains the allyl group bromination thing II of 1.35g (44%).
Compd A
3-[(6-chloro-3-pyridyl) oxygen]-2-(Nitromethylene) piperidines
The preparation of (compd A)
The solution of 329mg (25.5mmol) compound 3 in the 10ml dry THF is at nitrogen and use the 60%NaH-oil dispersion of 109mg (27.3mmol) to handle at ambient temperature.After gaseous volatilization weakened, 65 ℃ are handled and be heated to this gray suspension with the 3-bromo-2-Nitromethylene piperidines [Ger.Offen.2,321,523 (1973)] of 500mg (22.6mmol).After 1.5 hours, this brown reaction mixture is separated between 1M HCl and methylene dichloride.Organic layer is with rare solution of potassium carbonate washing and use dried over sodium sulfate.Solvent is removed by vacuum, and residuum is purified by the flash distillation silica gel column chromatography, and 50% mixture that uses the EtOAc/ sherwood oil is as eluent.The yellow solid that obtains further extracts to remove byproduct with ether, obtains the target product of the white solid of 244mg (40%).
Compound 2
The preparation of 5-bromo-2-chloropyridine (compound 2)
Drip the sodium nitrite solution that is dissolved in the 51.8g (0.751mol) in the 100ml water in the 100.0g in the 600ml concentrated hydrochloric acid (0.578mol) 2-amino-5-bromopyridine solution of-4 ℃ to being cooled under agitation, the dropping time surpasses 50 minutes to keep temperature to be lower than 8 ℃.These slurries are allowed to be warmed to 15 ℃ and by in the frozen water of impouring more than 1800ml.Throw out is collected and is washed with water by filtering.This product is dissolved in the methylene dichloride, washes and use Na with water
2SO
4Dry.This solvent is removed the white crystalline solid that obtains 53.0g (47.6%) by vacuum.
Compound 3
The preparation of 6-chloro-3-pyridol (compound 3)
The solution that is dissolved in 48.2g (0.250mol) compound 2 in the 500ml dry ether is cooled to-76 ℃ and dropwise handle so that temperature keeps below-71 ℃ with the hexane solution of the 2.5M n-Butyl Lithium of 107.2ml (0.268mol) under nitrogen.The slurries that obtain were allowed to restir 30 minutes, used the trimethyl borate processing of 29.3ml (0.268mol) then and kept temperature to be lower than-100 ℃.These orange slurries are allowed to be warmed to 0 ℃, and the acetic acid solution that is cooled to 32% peracetic acid of-75 ℃ and 54.4ml is then dropwise added above 15 minutes.These xanchromatic slurries are allowed to be warmed to room temperature.In this mixture, add 150ml water and 150ml ether.Separated and the organic layer of each layer washs with saturated aqueous solution of sodium bisulfite.Organic layer concentrates under vacuum and this thick product is dissolved among the 2N NaOH of 150ml.This alkali layer is with extracted with diethyl ether and with the NaHSO of 41.4g (0.300mol)
4H
2The O acidifying obtains the precipitation of target product.This product is extracted into ether and organic layer dried over mgso.Solvent is removed under vacuum and obtains the creamy product of 23.6g (86%).
Compound 4
The preparation of 2-chloro-N-methyl propanamide (compound 4)
25.0g the solution of 2-chlorpromazine chloride in 100ml THF (0.197mol) dropwise adds the 2M methylamine THF solution of 197ml (0.394mol) at-45 ℃ to-25 ℃ quilts.These slurries are stirred 1 hour and are allowed to be warmed to room temperature at-45 ℃ to-65 ℃.Solvent is removed by vacuum and residuum is dissolved in the methylene dichloride and washes with water.The organic layer dried over sodium sulfate, and solvent is removed the target product that obtains 16.8g (70.1%) under vacuum.Obtain the colorless product of 12.6g (52.6%) by distillation method.
Compound 5
2-[(6-chloro-3-pyridyl) oxygen]-preparation of N-methyl propanamide (compound 5)
In the slurries of the compound 3 of 8.21g (0.0634mol) and the compound 4 that is dissolved in the 8.09g (0.0665mol) in the 100ml acetonitrile, add the salt of wormwood of 9.20g (0.0665mol) and the potassiumiodide powder of 1.0g (6.02mmol).These slurries are heated under nitrogen and refluxed 64 hours and be cooled subsequently.Solvent is removed by vacuum and residuum is separated in ethylene dichloride and water.Organic layer 1N sodium hydroxide, water washing, and use dried over sodium sulfate.Remove the target product that solvent obtains 7.43g (54.6%) in a vacuum.With hot methylcyclohexane it is ground, cooling afterwards obtains the white crystals product of 7.05g (51.8%).
Compound 6
2-[(6-chloro-3-pyridyl) oxygen]-preparation of N-methyl-prop thioamides (compound 6)
Lawesson ' the s reagent that in the slurries of the 6.78g in 100ml toluene (0.0316mol) compound 5, adds 6.39g (0.0158mol).These slurries are heated to reflux and were cooled then in 2 hours.This solvent is removed under vacuum and residuum is dissolved in the methylene dichloride and is loaded into silicagel column.Earlier obtain Lawesson ' s reagent by product with the methylene dichloride wash-out.Obtain the white crystals product of 6.23g (85.4%) with 35%EtOAc/ hexane wash-out.
Compound 7
Methyl (1E/Z)-2-[(6-chloro-3-pyridyl) oxygen]-N-[(E/Z)-and methyl] the third imido acid sulfo-methyl esters
The preparation of (compound 7)
Sodium hydride (1.14g, 0.0286mol, 60% oil dispersion) is used hexane wash and is transferred under nitrogen in the flask and with the dry DMF of 15ml and covered.At room temperature, in these slurries, dropwise be added in the solution that contains 6.0g (0.0260mol) compound 6 among the 50ml DMF.The gaseous volatilization phenomenon occurs and this pale yellow solution is stirred 1 hour in room temperature.In this mixture, add in the solution that contains 4.06g (0.0286mol) methyl iodide that is dissolved among the 5ml DMF.This solution is stirred in room temperature and spends the night and afterwards in the impouring 300ml frozen water.The mixture extracted with diethyl ether that obtains.Organic layer washes and uses dried over mgso with water.Solvent is removed the target product that obtains the light yellow oily of 5.57g (87.6%) under vacuum.
Compd B
(1E/Z)-and 3-[(6-chloro-3-pyridyl) oxygen]-N-methyl isophthalic acid-nitro-1-butylene-2-amine
The preparation of (compd B)
The solution that will contain 2.85g (0.0116mol) compound 7 in the 50ml Nitromethane 99Min. heated 4 days at 100 ℃ under nitrogen.This solvent is removed under vacuum and residuum passes through the column chromatography purifying, at first uses ethylene dichloride and uses the 50%EtOAc/ hexane as eluent then.The cut that contains product is merged and solvent is removed the target product that obtains 0.69g under vacuum, and its ethyl acetate with heat is ground, and obtains cream-colored product 0.57g (19%).
Compound C
(1E)-and 3-[(6-chloro-3-pyridyl) oxygen]-N, N-dimethyl-1-nitro-1-butylene-2-amine
The preparation of (Compound C)
Be added in the solution that contains 1.0g (3.88mmol) compd B among the 10ml DMF in the slurries of the 60%NaH-oil dispersion of 0.22g (5.50mmol) and the dry DMF of 5ml, the joining day was above 10 minutes.Gaseous volatilization takes place and temperature is risen to 31 ℃.After stirring 30 minutes, add the 0.35mL methyl iodide.This mixture is stirred 1.5 hours and by in the impouring 20ml frozen water.This white crystals product is collected by filtration, water and hexane wash.Obtain the target product of 0.641g (61%).
Compound D
2-[(6-chloro-3-pyridyl) oxygen]-N '-cyano group-N-methyl-prop imino-acid amides
The preparation of (Compound D)
In the solution that in 10ml ethanol, contains 2.44g (10.0mmol) compound 7, be added in the solution that contains 1.65g (39.4mmol) cyanamide in the 15ml ethanol.This solution at room temperature stirred 45 minutes, refluxed 30 minutes again, was cooled afterwards.This solvent is removed under vacuum and obtains an oily matter, this oily matter in the 35ml methylene dichloride by pulp.Separate out the white crystals by product and filter collection.This filtrate is installed on the silicagel column and pillar is used the methylene dichloride wash-out earlier, uses 50%EtOAc/ hexane wash-out again.The cut that contains this product is merged and solvent is removed the white crystals product that obtains 2.10g (88.2%) under vacuum.
Compound 11
2-[(6-chloro-3-pyridyl) oxygen]-preparation of N-methylacetamide (compound 11)
The potassium carbonate powder that in 8.35g (0.0637mol) compound 3 and 7.19g (0.0669mol) the commodity N-methyl-slurries of 2-chlor(o)acetamide in the 100ml acetonitrile, adds 9.24g (0.0669mol).These slurries are heated to reflux and were cooled afterwards in 2.5 hours.This solvent is removed under vacuum and obtains the brown solid residue, its in water by pulp.By filter collecting cream-colored product, washing with water and be dried.Obtain the product of 8.49g (66.9%).
Compound 12
2-[(6-chloro-3-pyridyl) oxygen]-preparation of N-methyl thioacetamide (compound 12)
Lawesson ' the s reagent that in the slurries that in 100ml toluene, contain 8.43g (0.0420mol) compound 11, adds 8.50g (0.0210mol).These slurries are heated to reflux and were cooled afterwards in 2 hours.The residuum that this solvent is removed and obtains under vacuum is dissolved in the methylene dichloride and is installed on the silicagel column.Earlier obtain Lawesson ' s reagent by product with the methylene dichloride wash-out.Obtain the white crystals product of 8.17g (90%) with 25%EtOAc/ hexane wash-out.
Compound 13
Methyl (1E/Z)-2-[(6-chloro-3-pyridyl) oxygen]-N-[(E/Z)-and methyl] (the change of second imido acid sulfo-methyl esters
Compound 13) preparation
Sodium hydride (1.62g, 0.0406mol, 60% oil dispersion) is used hexane wash and is transferred under nitrogen in the flask and with the dry DMF of 15ml and covered.In these slurries, dropwise be added in the solution that contains 8.0g (0.0369mol) compound 12 among the 50ml DMF.The gaseous volatilization phenomenon occurs and this light brown solution is stirred 30 minutes in room temperature.The methyl iodide that in this mixture, adds 5.76g (0.0406mol).This solution is stirred in room temperature and spends the night and surpassed in the 500ml frozen water by impouring afterwards.When stirring, this product crystallization and be filtered collection.This product is dissolved in the methylene dichloride, washes and use dried over sodium sulfate with water.Solvent is removed the white crystals product that obtains 5.84g (68.7%) under vacuum.
Compd E
(1E/Z)-and 3-[(6-chloro-3-pyridyl) oxygen]-N-methyl isophthalic acid-nitro-1-propylene-2-amine
The preparation of (compd E)
The solution that will contain 2.57g (11.1mmol) compound 13 in the 40ml Nitromethane 99Min. heated 4 days at 100 ℃ under nitrogen.This solvent is removed under vacuum and residuum is dissolved in the methylene dichloride and is loaded into silicagel column.At first use methylene dichloride and use this post of 40%EtOAc/ hexane wash-out then.The cut that contains product is merged and solvent is removed the cream-colored product that obtains 0.67g (24.8%) under vacuum.
Compound F 17-hydroxy-corticosterone
2-[(6-chloro-3-pyridyl) oxygen]-N '-cyano group-N-methyl second imino-acid amides
The preparation of (compound F 17-hydroxy-corticosterone)
The cyanamide that in the slurries that in 30ml ethanol, contain 3g (13.0mmol) compound 13, adds 2.15g (51.2mmol).These slurries at room temperature stirred 30 minutes, refluxed 25 minutes again.After at room temperature stirring is spent the night, collect crystalline product and use washing with alcohol by filtering.Obtain the white crystals product of 2.20g (75.9%).
Compound 16
The preparation of 2-chloro-N-ethyl propionic acid amide (compound 16)
The solution of 12.5g (0.0984mol) 2-chlorpromazine chloride in the 50mL tetrahydrofuran (THF) is dropwise added the 2.0M ethamine tetrahydrofuran solution of the 98.5ml (0.197mol) that is cooled to-45 ℃ to-25 ℃, and the dropping time was above 10 minutes.This mixture was stirred 1 hour in this temperature range, stirred 1 hour at-45 ℃ to-65 ℃ then.This mixture is allowed to be warmed to room temperature and stirred 2 hours afterwards.Tetrahydrofuran (THF) is removed by vacuum and residuum is dissolved in the 75ml methylene dichloride, with 75ml water washing twice, and uses dried over sodium sulfate.Concentrate the limpid colourless liquid acid amides product that obtains 11.1g (83%).
Compound 17
2-[(6-chloro-3-pyridyl) oxygen]-preparation of N-ethyl propionic acid amide (compound 17)
Will be at the 9.41g in the 100mL acetonitrile (72.6mmol) compound 3,10.0g (72.6mmol) Anhydrous potassium carbonate, 9.85g (72.6mmol) compound 16, and the mixture heating up of 1.1g (6.6mmol) potassiumiodide refluxed 48 hours.After cooling, mixture is filtered, and filtrate being concentrated obtains brown oil, and this oily matter is separated between 300ml ether and 36ml (72mmol) 2.0N sodium hydroxide and 75ml water.Each layer is separated, contains water with 200ml extracted with diethyl ether and merged organic phase dried over mgso.Under vacuum, concentrate and obtain the 13.2g solid, it is ground, collect and obtain 10.7g (64%) brown solid acid amides target product with hexane.
Compound 18
2-[(6-chloro-3-pyridyl) oxygen]-N-ethyl rosickyite is for the preparation of acid amides (compound 18)
The solution of Lawesson ' the s reagent that contains 6.80g (29.7mmol) compound 17 and 6.06g (15.0mmol) in 100ml exsiccant toluene is heated to reflux and was cooled afterwards in 3 hours.The solid that this solvent is removed and obtains under vacuum is dissolved in the methylene dichloride (40-50ml) and with silica gel (230-400 order) chromatographic separation, obtains 6.8g (93%) thioamides.
Compound 19
Methyl (1E/Z)-2-[(6-chloro-3-pyridyl) oxygen]-N-[(E/Z)-and ethyl] the third imido acid sulfo-methyl esters
The preparation of (compound 19)
The compound 18 that in the mixture of 60% sodium hydride that contain 1.11g (the 27.8mmol)-mineral oil dispersion of refrigerative in frozen water in the dry DMF of 10ml, in batches adds 6.80g (27.8mmol), joining day surpasses 10-15 minute, adds 15ml DMF subsequently.This dark brown mixture be allowed to be warmed to room temperature and after 1 hour again in ice cooling and the solution that contains 4.34g (30.6mmol) methyl iodide that is used among the 10mlDMF dropwise handle.This mixture is in stirred overnight at room temperature and be added in the 300ml frozen water.This mixture by the 350ml extracted with diethyl ether once.This extraction liquid washes twice and uses dried over mgso with water subsequently.Concentrate and obtain 6.56 (91%) the liquid target product of dark-brown.
Compound G
(1E/Z)-and 3-[(6-chloro-3-pyridyl) oxygen]-N-ethyl-1-nitro-1-butylene-2-amine
The preparation of (compound G)
The solution that contains 2.93g (11.3mmol) compound 19 in the 30ml Nitromethane 99Min. is heated to 100 ℃ of reactions and allowed to be cooled afterwards in 70 hours.This solution is condensed to oily matter, and this oily matter is obtained the 600mg solid by silica gel (230-400 order) chromatographic separation with the methylene dichloride wash-out.This material recrystallization from hexane/EtOAc (1: 1) obtains the target product of 473mg (15%).
Compound 21
The preparation of 6-fluoro-3-pyridol (compound 21)
To-70 ℃ by the solution that contains 17.6g (0.10mol) 5-bromo-2-fluorine pyridine in the churned mechanically 150ml of the being dissolved in ether in add the 2.5M n-Butyl Lithium (joining day be above 24 minutes for 44ml, 0.11mol) hexane solution.The orange slurries that obtain stirred 25 minutes under this temperature, and (11.4g, 0.10mol), the joining day was above 5-10 minute to add trimethyl borate by syringe then.After 15 minutes, cryostat is withdrawn, and these white slurries are stirred 1 hour and are warmed to 5 ℃ simultaneously.This reaction be cooled to again-70 ℃ and add the 32wt% peracetic acid (23ml), the joining day surpasses 15 minutes for 26.1g, 0.11mol, the result by heat release to-40 ℃.Cryostat is withdrawn and this reaction system is stirred at ambient temperature and spends the night.In this mixture, add 100ml water and stir this mixture up to all solid dissolvings.Add the solid sodium bisulfite then in batches and provide negative starch-iodide test paper test up to the waterbearing stratum.Separated and waterbearing stratum ethyl acetate (2 * 100ml) extraction of each layer.Merged organic layer concentrates under vacuum, and creamy residuum is dissolved in the toluene (75ml) and by gas and carries four times to remove residual acetic acid and water.So this product is suspended in the toluene (40ml), filtration and air dried overnight obtain the ivory white powder-product of 9.9g (87%).
Compound 22
2-[(6-fluoro-3-pyridyl) oxygen]-preparation of N-methyl propanamide (compound 22)
In 350ml Hastelloy autoclave, add compound 21 (6.80g, 60.1mmol), compound 4 (8.8g, 72.2mmol), salt of wormwood (10.0g, 72.2mmol) and acetonitrile (100ml).This still is charged into nitrogen, heats 12 hours to 50psi and at 150 ℃ with nitrogen pressure then.After the cooling, solvent is removed by vacuum, and the light brown residuum is dissolved in methylene dichloride (200ml) and (main coloring matter is removed in 2 * 100ml) washings with dilute sodium hydroxide aqueous solution.Organic layer washs with salt solution (100ml), and dried over sodium sulfate and vacuum concentration obtain the target product of the cream-coloured powder shape of 10.2g (86%).
Compound 23
2-[(6-fluoro-3-pyridyl) oxygen]-preparation of N-methyl-prop thioamides (compound 23)
Compound 22 (10.2g, 51.5mmol) and Lawesson ' s reagent (10.4g, 25.7mmol) solution in toluene (125ml) is heated and refluxed 1.5 hours.This solvent is removed under vacuum and residuum is dissolved in the minimum methylene dichloride.It is loaded into silicagel column (250g) and with methylene dichloride (ca.1L) wash-out to remove Lawesson ' s reagent by product and main yellow substance.Elutriant is replaced by 2: 1 hexane/EtOAc afterwards.The cut that contains product is merged and is concentrated the buff powder that obtains 9.2g (84%).
Compound 24
(1E/Z)-and 2-[(6-fluoro-3-pyridyl) oxygen]-N-[(E/Z)-and methyl] the third imino-sulfo-methyl esters
The preparation of (compound 24)
(0.84g, (4.3g is in solution 20.0mmol) by once adding the compound 23 that contains in the 100ml dry THF that is stirring for 60wt% oil dispersion 21.0mmol) for sodium hydride.After 30 minutes, dropwise add methyl iodide (3.0g, 21mmol) and stirring reaction spend the night.This reaction mixture by in the impouring water (50ml) and vacuum remove tetrahydrofuran (THF).(3 * 50ml) extract residuum with ether.Merged organic layer is with the salt water washing and use dried over mgso, concentrates under vacuum and obtains the 5g resistates, and it contains product and oily matter.Half this material uses in next step, and half uses chromatogram purification (3: 1 hexane/ethyl acetate).The cut that contains product is merged and concentrates obtains the light yellow oily product of 1.1g.
Compound H
(1E/Z)-and 3-[(6-fluoro-3-pyridyl) oxygen]-N-methyl isophthalic acid-nitro-1-butylene-2-amine
The preparation of (compound H)
The solution that contains 2.5g compound 24 crude products in the 35ml Nitromethane 99Min. is stirred backflow and monitors with proton magnetic resonance (PMR) simultaneously.After 40 hours, this solvent under vacuum, be removed and residuum (2.8g) (3 * 5ml) grind to remove oil, unreacted thioimides thing (thioimidate) and small amount of polar impurity with hexane.Residuum (2.6g) uses 1: 1 hexane/EtOAc by the silica gel chromatography purifying.The cut that contains product is merged and concentrates obtains light brown oily thing, and it is cured at leisure.Obtain cream-colored powdery product 590mg (2.4mmol) with hexane/ethyl acetate solution grinding in a spot of warm 3: 1 to remove main coloring matter.
Compound 26
2-[(6-chloro-3-pyridyl) oxygen]-N, the preparation of 2-dimethyl propylene acid amides (compound 26)
Compound 3 in acetonitrile (250ml) (6.5g, 50mmol), N-methyl-2-bromine isobutyl-acid amides (9.0g, 50mmol), and silver suboxide (11.6g, slurries 50mmol) are stirred under nitrogen and refluxed 2 hours.After cooling, this solid is filtered removal by the C salt hopper and mother liquor is concentrated under vacuum.This pinkish residuum is dissolved in the methylene dichloride (200ml) and with dilute sodium hydroxide aqueous solution (100ml) vibration to be mixed.This system allows to be placed before separation to spend the night.Organic layer obtains the cream-coloured powdery target product of 9.6g (84%) with dried over sodium sulfate and vacuum concentration.
Compound 27
2-[(6-chloro-3-pyridyl) oxygen]-N, the preparation of 2-dimethyl propylene thioamides (compound 27)
Compound 26 in 90ml toluene (9.3g, 40.7mmol) and Lawesson ' s reagent (8.3g, solution 20.6mmol) are heated and refluxed 1 hour.This solvent is removed under vacuum and residuum is dissolved in the methylene dichloride of minimum.It is loaded into silicagel column (250g) and with methylene dichloride (ca.1L) wash-out to remove Lawesson ' s reagent by product and main yellow substance.Eluent is used 2: 1 hexane/EtOAc instead.The cut that contains product is merged and the concentrated target product that obtains 8.0g (80%) yellow powder powder.
Compound 28
Methyl (1E/Z)-2-[(6-chloro-3-pyridyl) oxygen]-N-[(E/Z) 2-dimethyl]
The preparation of the third imido acid sulfo-methyl esters (compound 28)
(0.10g, (512mg is in dry DMF (14mL) solution 2.1mmol) by once adding the compound 27 that is stirring for 60wt% oil dispersion 2.5mmol) for sodium hydride.After 30 minutes, add methyl iodide (355mg, 2.5mmol) and stirring reaction spend the night.Water (10ml) makes this reaction terminating and (3 * 30ml) extract with ether.Merged organic layer water (50ml), salt solution (50ml) washing and use dried over mgso, and under vacuum, be concentrated and obtain the 0.5g residuum, it contains product and oily matter.(hexane/EtOAc) purifying obtained the oily target product in 3: 1 by chromatogram.
Compound I
(1E/Z)-and 3-[(6-chloro-3-pyridyl) oxygen]-N, 3-dimethyl-1-nitro-1-butylene-2-amine
The preparation of (Compound I)
The solution of compound 28 (272mg) and Nitromethane 99Min. (10ml) was heated 12 hours at 150 ℃ in Pa Er (Parr) container of sealing.This solvent is removed under vacuum and residuum passes through the silica gel chromatography purifying, uses 5vol%CH
3The dichloromethane solution of CN.The cut that contains product is merged and is concentrated the target product that obtains 50mg light brown oily.
Compound 30
The preparation of 6-bromo-3-pyridol (compound 30)
23.4g (99mmol) 2, the solution of 5-dibromo pyridine in the 1L dry ether under nitrogen, be cooled to-70 ℃ and with the 2.5M n-Butyl Lithium (45ml, 113mmol) hexane solution is dropwise handled so that it remains on below-65 ℃.The slurries that obtain were allowed to restir 20 minutes, used 14ml (125mmol) trimethyl borate dropwise to handle then, and temperature is remained on below-105 ℃.These slurries, it became orange, by restir 20 minutes.Use acetic acid solution (24ml, 125mmol) processing of 32wt% peracetic acid then.This yellow mixture is warmed to 0 ℃ and add sodium bisulfite and the water termination reaction, with extracted with diethyl ether and use dried over sodium sulfate.This solvent is removed by vacuum and is obtained 16.5g brown solid.Recrystallization obtains the target product of the yellow solid shape of 13.2g (77%) from ethyl acetate.
Compound 31
2-[(6-bromo-3-pyridyl) oxygen]-preparation of N-methyl propanamide (compound 31)
The solution that contains 4.0g (23mmol) compound 30 in the dry DMF of 50ml is used the salt of wormwood of 3.2g (23mmol) under nitrogen, the potassiumiodide of the compound 4 of 3.1g (25mmol) and 0.38g (2.3mmol) is handled and is heated to 100 ℃.After 24 hours, this mixture is with 1M HCl dilution, with dichloromethane extraction and use dried over sodium sulfate.This solvent is removed the brown solid that obtains 4.8g by vacuum.Obtain the target product of the taupe brown solid state of 2.50g (42%) with re-crystallizing in ethyl acetate.
Compound 32
2-[(6-bromo-3-pyridyl) oxygen]-preparation of N-methyl-prop thioamides (compound 32)
((1.9g 4.7mmol) handles and is heated to 110 ℃ of reactions 2.5 hours to 2.3g, suspension 8.9mmol) Lawesson ' s reagent to contain compound 31 in the toluene of 40ml.The liquid that floats over the upper strata is transferred in other container and solvent is removed by vacuum and obtained gentle brown solid.Then, this residuum is purifying and elder generation's methylene dichloride flush away by product on silica gel, uses 35%EtOAc/ sherwood oil mixture wash-out target product afterwards.This solvent is removed the target product of the white solid that obtains 1.68g (69%) by vacuum once more.
Compound 33
Methyl (1E/Z)-2-[(6-bromo-3-pyridyl) oxygen]-N-[(Z)-methyl]
The preparation of the third imido acid sulfo-methyl esters (compound 33)
At nitrogen, under the room temperature condition, handle the solution that in the dry DMF of 15ml, contains 1.57g compound 32 (5.43mmol) with 60% oil dispersion of 245mg sodium hydride (6.12mmol).After gaseous volatilization weakened, this green blue mixture was handled with 0.50ml (8.0mmol) MeI.The yellow mixture that obtains between water and ether separated and organic layer by dried over sodium sulfate.This solvent under vacuum, be removed and this residuum separated between acetonitrile and sherwood oil.This solvent is removed the target product that obtains 1.00g (64%) yellow liquid shape under vacuum.
Compound J
(1E/Z)-and 3-[(6-bromo-3-pyridyl) oxygen]-N-methyl isophthalic acid-nitro-1-butylene-2-amine
The preparation of (compound J)
950mg (3.29mmol) compound 33 solution that contain in the 10ml Nitromethane 99Min. stirred 3.5 days at 100 ℃.This solvent is removed and obtains with a spot of ether washing residuum the quite pure brown solid of 496mg under vacuum.Further extract the target product of the light brown solid state that obtains 258mg (26%) with minor amounts of acetonitrile.
Compound 35
1-dimethylamino-3-methyl-imino-1-nitro-4-[(2-chloropyridine-5-yl) oxygen]-the 1-amylene
The preparation of (compound 35)
Solution in the 5ml dry toluene was 100 ℃ of heating 4 hours and allow afterwards to be cooled with 315mg (1.22mmol) compd B and 291mg (2.44mmol) dimethylformamide dimethyl acetal.This solution is condensed to solid, and it grinds with ether.Obtain the light brown solid of 204mg after the collection, this solid is found to contain and mixes up the raw-material target product of 22wt%.This after filtration filtrate being concentrated of material obtain the 200mg residuum, it is by silica gel (230-400 order) chromatographic separation, uses ethyl acetate to obtain the nitro amylene of 24mg (6%) as elutriant.
Compound K
3-methylamino-1-nitro-4-[(2-chloropyridine-5-yl) oxygen]-preparation of 2-pentenals (compound K)
The mixture of compound 35 crude products (78wt%) of 202mg (0.504mmol) in the 3ml methyl alcohol 2.0N sodium-hydroxide treatment of 0.279ml (0.559mmol).This mixture at room temperature is stirred 3 hours, uses the 1.0N salt acid treatment of 0.56ml (0.56mmol) then.This mixture is concentrated to remove volatile matter and residuum and is dissolved in the 150ml methylene dichloride and uses dried over mgso.Concentrate the oily matter that obtains 3 10mg, this oily matter separates with the silica gel look, uses chloroform as eluent and raising polarity to 95/5 chloroform/methanol.This pentenals is obtained with 69% productive rate (100mg).
Compound 37
2-[(6-chloro-3-pyridyl) oxygen] preparation of methyl-butyrate (compound 37)
Add 17.6g (0.127mol) potassium carbonate powder and 1.0g (6.02mmol) potassiumiodide to 15.0g (0.116mol) compound 3 and 14.7ml (0.127mol) 2-bromo-butyric acid methyl esters in the slurries in the 150ml acetonitrile.These slurries are heated to reflux under nitrogen and are cooled after 4 hours.This solvent under vacuum, be removed and residuum separated between methylene dichloride and water.Organic layer 1N NaOH, saturated common salt water washing and use dried over sodium sulfate.Go down to desolventize to obtain the brown oily target product of 24.2g (91.0%) in vacuum.
Compound 38
2-[(6-chloro-3-pyridyl) oxygen] preparation of butyric acid (compound 38)
In the slurries of 85%KOH grain in 100ml ethanol of 20.8g (0.316mol), add the solution of 24.2g (0.105mol) compound 37 in 150ml ethanol.It is dissolved that heat release makes temperature rise to 50 ℃ and this KOH.Adding 50ml water and this solution are stirred 3 hours at ambient temperature in this solution.The hydration sodium pyrosulfate that in this solution, adds 150ml water and 43.6g (0.316mol) afterwards.A kind of white solid sucking-off and be filtered collection.Contain filter liquor by methylene dichloride (2 * 100ml) extractions.Merged organic layer is by dried over sodium sulfate.Go down to desolventize the cream-colored product that obtains 20.2g (89.2%) in vacuum.
Compound 39
2-[(6-chloro-3-pyridyl) oxygen]-preparation of N-methylbutyryl amine (compound 39)
In the slurries of 19.7g (0.0912mol) compound 38 in 150ml benzene, add 7.32ml (0.100mol) thionyl chloride and four DMF.These slurries are heated 1 hour under nitrogen starting material dissolving simultaneously.Go down to desolventize the target chloride of acid that obtains 23.3g in vacuum, it is dissolved in the 50ml methylene dichloride.Then with this solution in 0 ℃ of 2M methylamine tetrahydrofuran solution that dropwise adds to 137ml (0.274mol).Add 300ml methylene dichloride and this slurries again and be allowed to temperature to room temperature.The reaction mixture water, 0.50M NaOH washs and uses dried over sodium sulfate.Solvent is removed the target product that obtains 19.4g (93.0%) under vacuum.Methylcyclohexane with heat grinds it, and cooling obtains the cream-coloured crystalline product of 18.5g (88.7%).
Compound 40
2-[(6-chloro-3-pyridyl) oxygen]-preparation of N-methyl fourth thioamides (compound 40)
Lawesson ' the s reagent that in the slurries of 18.2g (0.0796mol) compound 39 in 100ml toluene, adds 16.6g (0.0398mol).These slurries are heated to reflux under nitrogen and are cooled after 2 hours.This solvent is removed under vacuum and residuum is dissolved in the methylene dichloride and is loaded into silicagel column.Earlier obtain Lawesson ' s reagent by product with the methylene dichloride wash-out.Obtain 19.0g (98.0%) white crystals product with 35%EtOAc/ hexane wash-out.
Compound 41
(1E/Z)-and 2-[(6-chloro-3-pyridyl) oxygen]-N-[(E/Z)-and methyl] fourth imino-sulfo-methyl esters
The preparation of (compound 41)
Sodium hydride (1.53g, 0.0382mol, 60% oil dispersion) is transferred to hexane wash and under nitrogen in the flask and with the dry DMF of 15ml and covers.At room temperature, in these slurries, dropwise be added in the solution that contains 8.50g (0.0347mol) compound 40 among the 75ml DMF.The gaseous volatilization phenomenon occurs and this solution is stirred 15 minutes in room temperature.The methyl iodide that in this mixture, adds 5.42g (0.0382mol).This solution room temperature be stirred spend the night and afterwards by impouring 200mL frozen water in.The mixture extracted with diethyl ether that obtains.Organic layer washes and uses dried over sodium sulfate with water.Solvent is removed the target product of the light yellow oily that obtains 7.77g (86.3%) under vacuum, it exists with crystal form.
Compound L
(1E/Z)-and 3-[(6-chloro-3-pyridyl) oxygen]-N-methyl isophthalic acid-nitro-1-amylene-2-amine
The preparation of (compound L)
The solution that will contain 3.0g (0.0116mol) compound 41 in the 30ml Nitromethane 99Min. heated 3 days at 100 ℃ under nitrogen.This solvent is removed under vacuum and residuum column chromatography purifying, and elder generation is with methylene dichloride and use the 40%EtOAc/ hexane as eluent afterwards.The target product that cut is merged and solvent is removed the crystalline solid shape that obtains 0.488g (15.5%) under vacuum after grinding with the 40%EtOAc/ hexane that contains product.
Compound 43
2-[(6-chloro-3-pyridyl) oxygen]-1-amino-1-methyl-imino propane
The preparation of (compound 43)
3.0g (0.0123mol) oil bath at 80 ℃ in the pipe of a sealing of the methanol solution of compound 7 and 31ml (0.0615mol) 2M methylamine was heated 8 hours.This solution is cooled and goes down to desolventize the target product that obtains 2.58g (98.5%) in vacuum.Grind with hot ethyl acetate, cooling obtains the white crystals product of 2.26g (86.3%).
Compound M
1-trifluoroacetyl imino--2-methylamino-3-[(6-chloro-3-pyridyl) oxygen] propane
The preparation of (compound M)
The DMAP and 0.35mL (2.46mmol) trifluoroacetic anhydride that in the slurries of compound 43 in the 15ml methylene dichloride of 0.50g (2.34mmol), add catalytic amount.This solution stirred 48 hours under nitrogen and is separated between methylene dichloride and water.Organic layer is with the saturated sodium bicarbonate washing and use dried over sodium sulfate.Under vacuum, remove to desolvate and obtain the target product of 0.59g (81.9%).Obtain the target product of 0.074g (10.3%) with ethyl alcohol recrystallization.
Compound N
2-chloro-5-{[(2Z)-and 2-(Nitromethylene) tetramethyleneimine-3-yl] oxygen } pyridine
The preparation of (compound N)
To 60% sodium hydride/mineral oil dispersion of 33mg (0.82mmol) in 2ml exsiccant dimethyl formamide (DMF) by ice-cooled suspension in add 75mg (0.58mmol) compound 3 in batches, the joining day was above 5 minutes.After stirring 15-20 minute, the solution of 120mg (0.57mmol) allyl group bromination thing I in 2ml DMF is dropwise added by syringe.This mixture at room temperature is stirred and spends the night and by in the impouring 20ml frozen water, and with twice of dichloromethane extraction.Merged extraction liquid is with dried over mgso and concentrate and to obtain the 120mg residuum, and this residuum is separated by silica gel chromatography, uses 4/1 dichloromethane/ethyl acetate wash-out, obtains the nitroethylene of 30mg (20%).
Compound O
2-chloro-5-{[(2Z)-and 2-(Nitromethylene) tetramethyleneimine-3-yl] oxygen } pyrimidine
The preparation of (compound O)
To 60% sodium hydride/mineral oil dispersion of 104mg (2.59mmol) in 2ml exsiccant dimethyl formamide (DMF) by ice-cooled suspension in add 338mg (2.59mmol) 2-chloro-5-hydroxy pyrimidine (referring to nineteen sixty-five J.Chem.Soc. in batches, 7116), the joining day was above 5 minutes.After stirring 30 minutes, I adds in batches with 536mg (2.59mmol) allyl group bromination thing, adds 1ml DMF subsequently.This mixture at room temperature is stirred to spend the night and be filtered afterwards and concentrate in the impouring 100ml methylene dichloride and obtains residuum, and it is separated by silica gel chromatography, uses 4/1 dichloromethane/ethyl acetate, obtains the nitroethylene of 91mg (14%).
Compound P
2-chloro-5-{[(2Z)-and 2-(Nitromethylene) piperidines-3-yl] oxygen } pyrimidine
The preparation of (Compound P)
2-chloro-5-hydroxy pyrimidine (70mg, 0.54mmol is referring to nineteen sixty-five J.Chem.Soc., 7116) is dissolved in the 2ml exsiccant dimethyl formamide (DMF) and with 60% sodium hydride/mineral oil dispersion of 23mg (0.57mmol) and handles.After stirring 30 minutes, the solution of 118mg (0.534mmol) 3-bromo-2-Nitromethylene piperidines [Ger.Offen.2,321,523 (1973)] in 2ml DMF is dropwise added by syringe.This mixture at room temperature is stirred and spends the night and usefulness 35ml frozen water processing then.This mixture is with extracted with diethyl ether three times and with twice of dichloromethane extraction and merged extraction liquid dried over mgso.Concentrate and obtain residuum, this residuum is separated by silica gel chromatography, uses dichloromethane/ethyl acetate mixture wash-out, obtains the nitroethylene of 69mg (48%).
Compound Q
(1Z)-N-methyl isophthalic acid-nitro-3-(pyrimidine-5-base oxygen) but-1-ene-2-amine
The preparation of (compound Q)
To 60% sodium hydride/mineral oil dispersion of 91.4mg (2.28mmol) in 1ml exsiccant dimethyl formamide (DMF) by ice-cooled suspension in dropwise add 219mg (2.28mmol) 5-hydroxy pyrimidine [Ger.Offen.3 by syringe, 423,622 (1986)] solution in 2ml DMF.After 10-15 minute, the solution of 478mg (2.28mmol) allyl group bromination thing II in 2ml dry tetrahydrofuran and 1ml DMF is dropwise added.This mixture at room temperature is stirred and spends the night and be filtered with after the 100ml methylene dichloride dilution.Filtrate is with dried over mgso and be concentrated and obtain the 510mg residuum, and it is separated by silica gel chromatography, uses 95/5 methylene chloride wash-out, obtains the nitroethylene of 115mg (22%).
Compound R
5-{[(2Z)-and 2-(Nitromethylene) tetramethyleneimine-3-yl] oxygen } pyrimidine
The preparation of (compound R)
To 60% sodium hydride/mineral oil dispersion of 101mg (2.52mmol) in 1ml exsiccant THF by ice-cooled suspension in add 183mg (1.91mmol) 5-hydroxy pyrimidine [Ger.Offen.3,423,622 (1986)] in batches, add 1ml THF subsequently.After 10-15 minute, II once adds with 434mg (2.10mmol) allyl group bromination thing.This mixture dilutes and at room temperature is stirred with 1ml DMF and spends the night.This mixture is used dried over mgso afterwards three times with the frozen water dilution and with dichloromethane extraction.Concentrate and obtain the 230mg residuum, it is separated by silica gel chromatography, uses 9/1 methylene chloride wash-out, obtains the nitroethylene of 85mg (20%).
Compound S
(1Z)-and 3-[(2-chloropyrimide-5-yl) oxygen]-N-methyl isophthalic acid-nitro but-1-ene-2-amine
The preparation of (compound S)
To 60% sodium hydride/mineral oil dispersion of 91.3mg (2.28mmol) in 1ml exsiccant dimethyl formamide (DMF) by ice-cooled suspension in add 298mg (2.28mmol) 2-chloro-5-hydroxy pyrimidine (referring to nineteen sixty-five J.Chem.Soc. in batches, 7116), add 1ml DMF subsequently.After 10-15 minute, II once adds with 478mg (2.28mmol) allyl group bromination thing.This mixture at room temperature is stirred and spends the night and handle with frozen water, uses dichloromethane extraction afterwards three times.Merged extraction liquid is with dried over mgso and be concentrated and obtain the 540mg residuum, and it is separated by silica gel chromatography, uses 97/3 methylene chloride wash-out, obtains the nitroethylene of 101mg (17%).
Compound T
The 2-methyl-5-{[(2Z)-2-(Nitromethylene) tetramethyleneimine-3-yl] oxygen } pyridine
The preparation of (compound T)
To 60% sodium hydride/mineral oil dispersion of 93mg (2.3mmol) in 1ml exsiccant THF by ice-cooled suspension in add 208mg (1.91mmol) 5-hydroxy-2-methyl pyridine in batches.After 10-15 minute, I once adds with 400mg (1.93mmol) allyl group bromination thing.This mixture at room temperature be stirred spend the night and handle with frozen water after with dichloromethane extraction three times.Merged extraction liquid is with dried over mgso and be concentrated and obtain oily matter, and it is separated by silica gel chromatography, uses 95/5 methylene chloride wash-out, obtains the nitroethylene of 50mg (11%).
Compound U
(1Z)-N-methyl isophthalic acid-nitro-3-(pyridin-3-yl oxygen) but-1-ene-2-amine
The preparation of (compound U)
To 60% sodium hydride/mineral oil dispersion of 99mg (2.5mmol) in 1ml exsiccant dimethyl formamide (DMF) by ice-cooled suspension in add 235mg (2.5mmol) 3-pyridone in batches.After 10-15 minute, II once adds with 517mg (2.5mmol) allyl group bromination thing.This mixture at room temperature is stirred and spends the night and handle with frozen water, uses dichloromethane extraction afterwards three times.Merged extraction liquid is with dried over mgso and be concentrated and obtain 400mg oily matter, and it is separated by silica gel chromatography, uses 95/5 methylene chloride wash-out, obtains the nitroethylene of 25mg (4%).
Compound V
(1Z)-and 3-[(5-bromo-6-chloropyridine-3-yl) oxygen]-N-methyl isophthalic acid-nitro but-1-ene-2-amine
The preparation of (compound V)
To 60% sodium hydride/mineral oil dispersion of 93mg (2.3mmol) in 1ml exsiccant dimethyl formamide (DMF) by ice-cooled suspension in add 485mg (2.32mmol) 3-bromo-2-chloro-5-pyridone (referring to nineteen ninety Synthesis, 499) in batches.After 10-15 minute, II once adds with 486mg (2.32mmol) allyl group bromination thing.This mixture at room temperature is stirred and spends the night and handle with frozen water, uses dichloromethane extraction afterwards three times.Merged extraction liquid is with dried over mgso and be concentrated and obtain residuum, and it is separated by silica gel chromatography, uses 95/5 methylene chloride wash-out, obtains the nitroethylene of 113mg (14%).
Compound W
3-{[(2Z)-and 2-(Nitromethylene) tetramethyleneimine-3-yl] oxygen } pyridine
The preparation of (compound W)
To 60% sodium hydride/mineral oil dispersion of 73mg (1.8mmol) in 1ml exsiccant DMF by ice-cooled suspension in add 174mg (1.83mmol) 3-pyridone in batches.This mixture allows to be warmed to room temperature and after 10-15 minute, this mixture is cooled in the ice and with 380mg (1.83mmol) allyl group bromination thing I again once to add.This mixture at room temperature is stirred and spends the night, and handles with frozen water afterwards, uses dichloromethane extraction then three times.Merged extraction liquid is with dried over mgso and be concentrated and obtain the 230mg residuum, and it is separated by silica gel chromatography, uses 95/5 methylene chloride wash-out, obtains the nitroethylene of 20mg (5%).
Compounds X
The 2-methyl-5-{[(2Z)-2-(Nitromethylene) piperidines-3-yl] oxygen } pyridine
The preparation of (compounds X)
Sodium hydride (0.220g, 0.0055mol, 60% oil dispersion) is added under nitrogen atmosphere in the flask that the 3ml dry DMF is housed.This flask is chilled to 0 ℃.(0.620g, 0.0057mol) solution in 4mlDMF is under agitation dropwise added 5-hydroxyl 2-picoline.Gaseous volatilization occurs.This mixture stirred 30 minutes at 0 ℃, and the solution of 3-bromo-2-Nitromethylene piperidines (1.01g, 0.0046mol, Ger.Offen.2,321,523 (1973)) in 4mlDMF is under agitation dropwise added afterwards.This flask allows to be warmed to room temperature and this mixture and is stirred and spends the night.This mixture is by in the impouring 40ml frozen water, and batch extraction with the 4-75ml methylene dichloride.Extraction liquid is concentrated with dried over mgso and under vacuum.Residuum passes through the column chromatography purifying with 4% ethanol/methylene as eluent.The cut that contains target product is merged, and removes this solvent under vacuum.Its grinding is obtained the target product of 0.57g (50.2%) yellow powder shape with ether.
Compound Z
The 2-methoxyl group-5-{[(2Z)-2-(Nitromethylene) piperidines-3-yl] oxygen } pyrimidine
The preparation of (compound Z)
Sodium hydride (0.158g, 0.0040mol, 60% oil dispersion) is added under nitrogen atmosphere in the flask that the anhydrous THF of 3ml is housed.This flask is chilled to 0 ℃.The solution of 5-hydroxyl 2-methoxy pyrimidine (0.500g, 0.0040mol, referring to Can.J.Chem., 62,1176 (1984)) in 20mlTHF is under agitation dropwise added.Gaseous volatilization occurs.This mixture stirred 30 minutes at 0 ℃, and the solution of 3-bromo-2-Nitromethylene piperidines (0.875g, 0.0040mol, Ger.Offen.2,321,523 (1973)) in 4ml THF is under agitation dropwise added afterwards.This flask is heated to 65 ℃ and be stirred 4 hours gradually with oil bath.So being chilled to room temperature and being stirred, this mixture spends the night.This mixture is by in the frozen water of impouring 40ml, and batch extraction with the 4-100ml methylene dichloride.Extraction liquid is concentrated with dried over mgso and under vacuum.Obtain 0.480g (45%) light orange powdery product with the ether grinding.
Compd A A
3-{[(2Z)-and 2-(Nitromethylene) piperidines-3-yl] oxygen } pyridine
The preparation of (compd A A)
Sodium hydride (0.105g, 0.0026mol, 60% oil dispersion) is added under nitrogen atmosphere in the flask that the 3ml dry DMF is housed.This flask is chilled to 0 ℃.(0.250g, 0.0026mol) solution in 3ml DMF is under agitation dropwise added the 3-pyridone.Gaseous volatilization occurs.This mixture stirred 30 minutes at 0 ℃, and the solution of 3-bromo-2-Nitromethylene piperidines (0.580g, 0.0026mol, Ger.Offen.2,321,523 (1973)) in 4ml DMF is under agitation dropwise added afterwards.This flask allows to be warmed to room temperature and this mixture and is stirred and spends the night.This mixture is by in the impouring 40ml frozen water, and batch extraction with the 4-75ml methylene dichloride.Extraction liquid is concentrated with dried over mgso and under vacuum.Residuum column chromatography purifying, with 4% ethanol/methylene as eluent.The cut that contains target product is merged, and solvent is removed under vacuum.Residuum grinds with ether, obtains the pulverous target product of 0.074g (12.1%) rust.
Compd A B
5-{[(2Z)-and 2-(Nitromethylene) piperidines-3-yl] oxygen } pyrimidine
The preparation of (compd A R)
Sodium hydride (0.104g, 0.0026mol, 60% oil dispersion) is added under nitrogen atmosphere in the flask that the 3ml dry DMF is housed.This flask is chilled to 0 ℃.The solution of 5-hydroxy pyrimidine (0.250g, 0.0026mol, referring to Ger.Offen., 3,423,622 (1986)) in 3ml DMF is under agitation dropwise added.Gaseous volatilization occurs.This mixture stirred 30 minutes at 0 ℃, and the solution of 3-bromo-2-Nitromethylene piperidines (0.575g, 0.0026mol, Ger.Offen.2,321,523 (1973)) in 4ml DMF is under agitation dropwise added afterwards.This flask allows to be warmed to room temperature and this mixture and is stirred and spends the night.This mixture is by in the impouring 40ml frozen water, and batch extraction with the 4-75ml methylene dichloride.Extraction liquid is concentrated with dried over mgso and under vacuum.Residuum is dissolved in the ebullient 50% ethyl acetate/methanol solution, and insoluble material is filtered out.Filtrate is concentrated under vacuum, obtains the target product of 0.240g (39.1%) brown ceramic powder shape.
Compd A C
3-chloro-6-{[(2Z)-and 2-(Nitromethylene) piperidines-3-yl] oxygen } pyridazine
The preparation of (compd A C)
3-bromo-2-Nitromethylene piperidines (0.369g, 0.0028mol, Ger.Offen.2,321,523 (1973)), and silver carbonate (1.560g, 0.0057mol), (0.625g, 0.0028mol) slurries in the 45ml methylcyclohexane stirred 12 hours at 100 ℃ in the dark with 3-chloro-6-hydroxyl pyridazine.This mixture is filtered by the C salt hopper.This C salt hopper becomes colourless up to elutant with ethyl acetate rinse, and this washings is concentrated under vacuum.Residuum column chromatography purifying uses 15% ethyl acetate/hexane as eluent.The cut that contains thick product is merged and is concentrated under vacuum.The TLC purifying that this thick product further is prepared uses 50% ethyl acetate/dichloromethane as eluent.The silica that contains target product is collected, and this material is removed from silica as eluent with ethyl acetate.This material is filtered, and is concentrated with dried over mgso and under vacuum, obtains the target product of 0.040mg (5.2%).
Compd A E
5-{[(2Z)-and 2-(Nitromethylene) piperidines-3-yl] oxygen } pyridine-2-methyl-formiate
The preparation of (compd A E)
Sodium hydride (0.131g, 0.0033mol, 60% oil dispersion) is added under nitrogen atmosphere in the flask that the 3.5ml dry DMF is housed.This flask is chilled to 0 ℃.The solution of 5-hydroxyl-2-pyridine carboxylic acid methyl esters (0.500g, 0.0033mol, Aust.J.Chem., 24,385 (1971)) in 3ml DMF is under agitation dropwise added.Gaseous volatilization occurs.This mixture stirred 30 minutes at 0 ℃, and the solution of 3-bromo-2-Nitromethylene piperidines (0.722g, 0.0033mol, Ger.Offen.2,321,523 (1973)) in 7ml DMF is under agitation dropwise added afterwards.This flask allows to be warmed to room temperature and this mixture and is stirred and spends the night.This mixture is by in the impouring 40ml frozen water, and batch extraction with the 3-75ml methylene dichloride.Extraction liquid is concentrated with dried over mgso and under vacuum.Residuum grinds with ether, obtains 0.312mg brown ceramic powder shape product.This powder recrystallization from boiling methyl alcohol obtains 0.113mg (11.9%) chocolate brown powder.
Compd A F
(1Z)-and N-methyl-3-[(6-picoline-3-yl) oxygen] 1-nitro but-1-ene-2-amine
The preparation of (compd A F)
Sodium hydride (0.092g, 0.0023mol, 60% oil dispersion) is added under nitrogen atmosphere in the flask that the 3ml dry DMF is housed.This flask is chilled to 0 ℃.(0.250g, 0.0023mol) solution in 3ml DMF is under agitation dropwise added 5-hydroxy-2-methyl pyridine.Gaseous volatilization occurs.This mixture stirred 30 minutes at 0 ℃, and (0.478g 0.0023mol) is added in this pure reaction flask allyl group bromination thing II afterwards.This flask allows to be warmed to room temperature and this mixture and is stirred and spends the night.This mixture is by in the impouring 40ml frozen water, and with 1N HCl the pH value transferred to 7.This mixture is batch extraction with the 2-75ml methylene dichloride.Extraction liquid is concentrated with dried over mgso and under vacuum.Residuum column chromatography purifying uses 5% ethanol/methylene as eluent.The cut that contains target product is merged, and solvent is removed under vacuum, obtains the light yellow crystalloid target product of 0.010g (1.8%).
Compound P AG
The preparation of 6-chloro-5-(5-chlorothiophene-2-yl) pyridine-3-phenol
3-bromo-2-chloro-5 pyridones (0.560g, 0.0027mol, Synthesis, 499,1990), and 5-chlorothiophene-2-boric acid (0.581g, 0.0036mol), Pd (PPh
3)
2Cl
2(0.094g, 0.0001mol), three (o-tolyl) phosphine (0.082g, 0.0003mol), and yellow soda ash (0.427g, 0.0040mol) the mixed flask that contains 26.5mL DME and 7ml water of putting into.This mixture is heated and refluxed 9 hours, is cooled to room temperature afterwards.This mixture dilutes with the 100ml methylene dichloride.This solution washs with 2-100ml salt solution in batches, criticizes washing with 2-100ml moisture more afterwards.Organic phase is concentrated with dried over mgso and under vacuum.Residuum column chromatography purifying uses 100% methylene dichloride earlier, re-uses 5% ethanol/methylene as eluent.The cut that contains target product is merged, and goes down to desolventize to obtain thick product in vacuum afterwards.This material is further used preprepared HPLC (40% water/acetonitrile, flow rate are 8ml/ minute) purifying.The cut that contains product is collected and is concentrated target product with the beige solid shape that obtains 0.055g in vacuum.
Compd A G
2-chloro-3-(5-chlorothiophene-2-yl)-5-{[(2Z)-2-(Nitromethylene) piperidines-3-yl] oxygen } pyridine
The preparation of (compd A G)
Sodium hydride (0.009g, 0.0002mol, 60% oil dispersion) is added under nitrogen atmosphere in the flask that the 1ml dry DMF is housed.This flask is chilled to 0 ℃.(0.055g, 0.0002mol) solution in 0.5ml DMF is under agitation dropwise added in this solution Compound P AG.Gaseous volatilization occurs.This mixture stirred 30 minutes at 0 ℃, and the solution of 3-bromo-2-Nitromethylene piperidines (0.123g, 0.0006mol, Ger.Offen.2,321,523 (1973)) in 0.5ml DMF is under agitation dropwise added afterwards.This flask allows to be warmed to room temperature and this mixture is stirred 2 days.This mixture is by in the impouring 40ml frozen water, and batch extraction with the 4-10mL methylene dichloride.Extraction liquid is concentrated with dried over mgso and under vacuum.Residuum column chromatography purifying uses 100% methylene dichloride earlier, re-uses 2% ethanol/methylene as eluent.The cut that contains target product is collected, and concentrates under vacuum afterwards, and this material is further used preprepared HPLC (20% water/acetonitrile, flow rate are 9ml/ minute) purifying afterwards.The cut that contains product is collected and is concentrated in vacuum, uses the 3-10ml dichloromethane extraction afterwards.This material concentrates with dried over mgso and under vacuum, obtains the target product of the yellow oily of 0.023g (25.9%).
Compd A H
3-bromo-2-chloro-5-{[(2Z)-and 2-(Nitromethylene) piperidines-3-yl] oxygen } pyridine
The preparation of (compd A H)
Sodium hydride (0.056g, 0.0014mol, 60% oil dispersion) is added under nitrogen atmosphere in the flask that the 5ml dry DMF is housed.This flask is chilled to 0 ℃.The solution of 3-bromo-2-chloro-5-pyridone (0.294g, 0.0014mol, Synthesis, 499, nineteen ninety) in 6ml DMF is under agitation dropwise added in this solution.Gaseous volatilization occurs.This mixture stirred 30 minutes at 0 ℃, and the solution of 3-bromo-2-Nitromethylene piperidines (0.780g, 0.0035mol, Ger.Offen.2,321,523 (1973)) in 7ml DMF is under agitation dropwise added afterwards.This flask allows to be warmed to room temperature and this mixture and is stirred and spends the night.This mixture is by in the impouring 40ml frozen water, and batch extraction with the 3-75ml methylene dichloride.Extraction liquid is concentrated with dried over mgso and under vacuum.Residuum column chromatography purifying uses earlier 1% ethanol/methylene, uses 10% ethyl acetate/dichloromethane as eluent again.The cut that contains target product is merged, and is concentrated under vacuum, obtains 0.150g colorless oil target product.This oily matter grinds the product that obtains 0.110g (22.4%) white solid with ether.
Bioassay
Cotten aphid (Cotton Aphid) (Aphis gossypil)-pumpkin spraying
Yellow crookneck squash, Cucurbita pepo is planted in 3 inches the flowerpot and is placed in the greenhouse.Plant is regularly watered 5 to 7 days up to there being leaf to occur.Plant is trimmed to single cotyledon then.This pumpkin is tested each processing and is all comprised four pumpkin plant, and every plant cotyledon all can carry out duplicate sampling.Four plants in addition are used to contrast treatment (only accepting to use blank solvent).Twenty four hours before using is placed on the Folium Cucurbitae subdivision that seriously is subjected to attacked by aphids on each cotyledon, allows the population mixture of cotton aphid larva and adult to move to and infects this test plants.The upper surface of the squash cotyledons that is infected in advance and lower surface are all sprayed, and applying pressure is the air-blast atomizer of 2psi.Prescription is that the aqueous solution that contains 5% solvent and 0.025%Tween 20 tensio-active agents is the test compounds of 50ppm to produce concentration.This plant is sprayed to reach run-off.Test is placed 3 days under the laboratory environment temperature.Add up by dissecting microscope in the aphid quantity that application (DAA) lived after three days.The quantity of aphid of will living in the plant of having handled compares and calculates per cent death loss with the aphid quantity of handling in the contrast in blank solvent alive.
T.urticae Koch (Two-spotted Spider Mite) (Tetranychus urticae)
-pumpkin spraying
It is the pumpkin plant that 5-7 days quilt is accomplished single cotyledon that the removable acarid of mixed age or acarid pupa are moved to the age.Solution with the 50ppm of a test compounds is sprayed to run-off with four plant of being infected by acarid, uses the hand gun that has nozzle.Eight plant of handling with blank solvent are as negative contrast.Plant is being placed under the laboratory environment temperature and humidity and is testing after 4 days in application.Will be in each processed plant the quantity of dead acarid and the dead quantity in contrast compare and calculate per cent death loss.
Sweet potato trialeurodes vaporariorum (Sweetpotato Whitefly) (Bemisia tabaci)-cotton spraying
Industrial materials are dissolved into 90: 10 acetone: in the alcoholic acid mixture; Its aqueous solution dilution that is contained 0.05%v/v Tween 20 tensio-active agents afterwards contains the solution spraying pearl of 200ppm test compounds with generation on plant, and keeps 2-3 days.Age is trimmed to preceding two true leaves and allows the tobacco adult whitefly to lay eggs on its leaf above 48 hours for cotton (Gossypiumhirsutum) plant all around.The solution of test compounds is applied to the two sides of each cotton leaf, uses the hand gun that nozzle is housed.Four whole tested compound treatment of blade, eight blades contrast with blank solvent.After 12 to 14 days, the quantity of the white powder nit of on processed plant, living added up and and contrast in quantity compare and calculate per cent death loss.
To brown paddy plant hopper (Brown Planthopper) (Nilaparvata lugens) and
The systemic insecticide method of greenery cicada (Nephotettix cincticeps)
Tested compound is dissolved into acetone, makes 10,000ppm solution.10, take out 0.1ml in the 000ppm solution, add the test soln of making the 10ppm of 100ml in the 99.9ml water.25 milliliters 10ppm test soln is added respectively in four glass cylinder boxes.In each right cylinder, several ages are dipped in the solution of test compounds for paddy rice (Oryza sativa) shoot root all around.The brown paddy plant hopper of five laboratory culture or greenery cicada the 3rd age pupa be placed in the glass cylinder shape box.Right cylinder (each handle repeat four times) is placed in the growth room of 28 ℃ and 75% relative humidity, and uses 14 hours photoperiod.After using six days, per cent death loss is added up and calculated to the quantity of dead insects.
To brown paddy plant hopper (Nilaparvata lugens) and greenery cicada (Nephotettix cincticeps)
The foliar insecticide method
This test compounds is dissolved into acetone and further dilute with water is made 200ppm solution.Several ages are placed in the glass cylinder box for paddy rice seedling all around, support with plastic wire, and 4 glass cylinder are used to each processing.Use a little spraying plant, 0.5ml test compounds solution is sprayed on the paddy rice seedling in each glass cylinder.After plant becomes dry, the brown paddy plant hopper of five laboratory culture or greenery cicada the 3rd age pupa be placed in the glass cylinder shape box.These right cylinders are placed in the growth room of 28 ℃ and 75% relative humidity, and use 14 hours photoperiod.After using six days, per cent death loss is added up and calculated to the quantity of dead insects.
Anti-state of Colorado colorado potato bug (Leptinotarsa decemlineata)
The typical method of biocidal activity
Test compounds is dissolved advances acetone to obtain the concentration of every microlitre 5 micrograms.This solution of one microlitre by suction move to the 3rd age the colorado potato bug larva back, each larva obtains 5 milligrams dosage.Six larvas are respectively by solution-treated.These larvas are placed on potato (Solanumtubersum) leaf and placed two days under the laboratory environment temperature and humidity.Two days later, per cent death loss is added up and calculated to the quantity of dead larva.
The black peach aphid biological assay
Plant preparation and infection: in the 2-4 leaf stage, during about 12 days age, before 4 days, the blade-section that infects by serious vibration above the wild cabbage seedling infects wild cabbage seedling (Brassica oleracea capitat) with the black peach aphid (Myzus persicae) in each stage at the application testing material.This aphid is moved to below sappy plant and the mainly edible leaf.This plant is tested before experimental compound is used is fully infected.
The plant of spray solution: the industrial material of each experimental compound is dissolved in 90: 10 acetone with 1mg/ml: ethanol, and afterwards with the tap water dilution that contains 0.05%Tween 20.A series of dilutions in addition are produced, and obtain 50,12.5,3.13,0.78,0.195 and the back solution of 0.049ppm.
Use the manual pneumatic atomizer to use.Upper surface and lower surface sprinkling to brassica specie young plant leaf are exhausted by even the sprinkling up to the residue spray solution up to the plant that reaches run-off and all processing afterwards.The each test with four plants.Only handle in order to correlated 8 plants with the diluent of blank solution preparation.
Test was carried out in the holding room of about 74 and 40 ° relative humidity 72 hours, and 24 hours photoperiod is arranged before test.After being employed 3 days, test is carried out, by using the aphid amount alive (all being in the no wing stage) that binocular microscope is estimated every leaf downside of dissecting.The aphid amount alive that obtains is used for calculating and the relative percentage of comparing in the aphid amount of blank solvent contrast.
Compd B, C, the preparation route of D:
Compound 2 compounds 3 compounds 4 compounds 5
Compound 6 compounds 7 compd B Compound C
The preparation route of compd E and F:
Compound 3 compounds 11 compounds 12 compounds 13
The compd E compound F 17-hydroxy-corticosterone
Preparation compound G, H, the route of I and J utilizes these chemical route.
| The per cent death loss scope of table 1 following compounds | |||||||||||
| The name of popular name science | Method minute concentration | F | E | D | B | ?G | H | C | A | J | ?K |
| Cotten aphid APHIS GOSSYPIL | Pumpkin sprays 3DAA 50ppm | ＜30 | ＞80 | ＞80 | ＞80 | ＞80 | ＞80 | ＞80 | ＞80 | ＞80 | ＞80 |
| Sweet potato trialeurodes vaporariorum BEMISIA TABACI | Cotton is sprayed 13DAA 200ppm | 30-50 | 30-50 | ＜30 | ＞80 | 50-80 | 50-80 | ＜30 | ＜30 | 50-80 | --- |
| Green rice leafhopper (GREEN RICE LEAFHOPPER) NEPHOTETTIX CINCTICEPS | Rice leaf sprays 6DAA 200ppm | --- | 50-80 | ＜30 | 30-50 | ＞80 | ＞80 | ＜30 | ＞80 | ＞80 | --- |
| Absorption 6DAA 10ppm in the paddy rice | --- | ＜30 | 50-80 | 30-50 | 50-89 | ＞80 | 50-80 | 50-80 | 50-80 | --- | |
| Brown paddy plant hopper NILAPARVATA LUGENS | Rice leaf sprays 6DAA 200ppm | --- | ＜30 | 50-80 | 50-80 | ＜30 | 50-80 | ＜30 | ＞80 | 50-80 | --- |
| Absorption 6DAA 10ppm in the paddy rice | --- | ＜30 | ＜30 | 30-50 | 50-80 | 50-80 | 30-50 | 50-80 | 50-80 | --- | |
| Colorado colorado potato bug LEPTINOTARSA DECEMLINEATA | Every larva of typical application 2DAA 5 micrograms | ＜30 | ＞80 | ＜30 | ＞80 | ＞80 | ＞80 | ＞80 | ＞80 | ＞80 | |
| T.urticae Koch TETRANYCHUS URTICAE | Pumpkin sprays 4DAA 50ppm | ＜30 | ＜30 | 30-50 | 50-80 | 30-50 | ＜30 | ＜30 | ＜30 | 30-50 | 30-50 |
| Table 2 per cent death loss scope | |||||||
| Compound | Cotten aphid | Black peach aphid (Myzus persicae) 50ppm | The sweet potato trialeurodes vaporariorum | Brown paddy plant hopper (blade sprinkling) | Brown paddy plant hopper (interior absorption) | Greenery cicada (blade sprinkling) | Greenery cicada (interior absorption) |
| M | ＜30 | 50-80 | |||||
| X | ＞80 | ＞80 | ＜30 | 30-50 | 30-50 | 50-80 | 50-80 |
| N | ＞80 | ＜30 | ＞80 | ||||
| Z | 30-50 | ＜30 | ＜30 | 30-50 | ＜30 | 30-50 | |
| L | ＞80 | ＜30 | ＞80 | ＜30 | ＞80 | 30-50 | 50-80 |
| P | ＞80 | ＞80 | ＞80 | ＞80 | 30-50 | ＞80 | |
| AA | ＞80 | ＜30 | 50-80 | ＜30 | ＞80 | ＞80 | |
| Q | ＞80 | ＜30 | ＞80 | 50-80 | ＞80 | 50-80 | 50-80 |
| AB | ＞80 | ＜30 | ＜30 | ＜30 | 50-80 | ＞80 | |
| AC | ＞80 | ＜30 | 50-80 | 50-80 | |||
| AE | ＜30 | ＜30 | ＜30 | 30-50 | ＜30 | 50-80 | |
| AF | ＞80 | ＜30 | ＜30 | ||||
| AG | ＜30 | ＜30 | ＜30 | ||||
| O | ＞80 | ＞80 | ＞80 | ＞80 | ＜30 | 30-50 | |
| R | ＞80 | ＜30 | ＜30 | ＞80 | ＞80 | ||
| S | ＞80 | ＞80 | ＞80 | 50-80 | 50-80 | ||
| T | ＞80 | ＜30 | ＜30 | 50-80 | 50-80 | ||
| AH | ＞80 | ＜30 | ＜30 | ＜30 | 50-80 | ||
| U | ＞80 | ＜30 | ＜30 | ||||
| V | ＞80 | 50-80 | |||||
| W | ＞80 | ||||||
Claims (23)
1. compound as general formula one
General formula one
Wherein
A represents one five yuan or hexa-member heterocycle, and this heterocycle contains a heteroatoms that is selected from oxygen, sulphur or nitrogen at least, and wherein said heterocycle can be replaced by one or more substituting groups, and this substituting group is selected from: fluorine, chlorine, bromine, iodine, C
1-10Alkyl, halo C
1-10Alkyl, nitro, cyano group, C
1-10Alkoxyl group, C
1-10Alkylthio, C
1-10The alkyl sulfinyl, C
1-10Alkyl sulphonyl, C
1-10Alkenyl, halo C
1-10Alkoxyl group, halo C
1-10Alkylthio, halo C
1-10Alkenyl, amido, halo amido, C
1-10Alkoxy carbonyl, C
1-10Alkynyl, amino, C
1-10Alkylamino, C
1-10Dialkyl amido, C
3-12Cycloalkyl, C
1-10Alkoxyalkyl, acyl group, formyl radical, C
6-12Aryl, single or polysubstituted C
6-12Aryl, heteroaryl, and single or polysubstituted heteroaryl (heteroaryl described herein has 5-12 atom on ring, and in the ring described herein, 1-3 described atom is selected from nitrogen, oxygen and sulphur, and remaining atom is a carbon atom in the described ring, and substituting group is selected from halogen herein, C
1-10Alkyl, halo C
1-10Alkyl, C
1-10Alkoxyl group, nitro, cyano group, and C
6-12Aryloxy);
E is selected from O, SO
n(wherein n is 0-2), NH, and NX (wherein X is selected from C
1-10Alkyl, halo C
1-10Alkyl);
J and R are independently selected from H, C
1-10Alkyl, C
1-10Alkenyl, C
1-10Alkynyl, halo C
1-10Alkyl and C
1-10Alkoxyalkyl;
M is selected from N and CZ, and wherein Z is selected from H and C (=O) H;
Q is selected from NO
2, CN, and C (=O) CF
3
G and T are independently selected from H, C
1-10Alkyl, C
1-10Alkenyl, C
1-10Alkynyl, halo C
1-10Alkyl, and C
1-10Alkoxyalkyl; Optionally, G and T also can pass through a singly-bound, or a cross structure is joined together, and at this, this cross structure is selected from CH
2, CHCH
3, C (CH
3)
2, CH (halo C
1-10Alkyl), C (halo C
1-10Alkyl)
2, CHF, CF
2, O, SO
n(wherein n is 0-2), NH, and NX (wherein X is selected from C
1-10Alkyl or halo C
1-10Alkyl).
2. as claim 1 described compound, wherein said heterocycle is a hexa-member heterocycle.
3. as claim 2 described compounds, wherein said heterocycle contains one or two nitrogen heteroatom.
4. as claim 3 described compounds, wherein said heterocycle is by methyl, ethyl, and fluorine, chlorine, or the bromine list replaces.
5. as claim 4 described compounds, wherein said substituting group and heteroatoms are the ortho positions.
6. as claim 1 described compound, wherein E is O.
7. as claim 1 described compound, wherein J and R are H.
8. as claim 1 described compound, wherein M is CH.
9. as claim 1 described compound, wherein Q is NO
2
10. as claim 1 described compound, wherein G and T are methyl or ethyl.
11. as claim 1 described compound, wherein G is connected by cross structure with T, this cross structure is a singly-bound or a CH
2
12. one kind comprises by being applied to the method that insect or acarid location suppress insect or acarid as the compound of general formula one.
Wherein
A represents one five yuan or hexa-member heterocycle, and this heterocycle contains a heteroatoms that is selected from oxygen, sulphur or nitrogen at least, and wherein said heterocycle can be replaced by one or more substituting groups, and this substituting group is selected from: fluorine, chlorine, bromine, iodine, C
1-10Alkyl, halo C
1-10Alkyl, nitro, cyano group, C
1-10Alkoxyl group, C
1-10Alkylthio, C
1-10The alkyl sulfinyl, C
1-10Alkyl sulphonyl, C
1-10Alkenyl, halo C
1-10Alkoxyl group, halo C
1-10Alkylthio, halo C
1-10Alkenyl, amido, halo amido, C
1-10Alkoxy carbonyl, C
1-10Alkynyl, amino, C
1-10Alkylamino, C
1-10Dialkyl amido, C
3-12Cycloalkyl, C
1-10Alkoxyalkyl, acyl group, formyl radical, C
6-12Aryl, single or polysubstituted C
6-12Aryl, heteroaryl, and single or polysubstituted heteroaryl (heteroaryl described herein has 5-12 atom on ring, and in the ring described herein, 1-3 described atom is selected from nitrogen, oxygen and sulphur, and remaining atom is a carbon atom in the described ring, and substituting group is selected from halogen herein, C
1-10Alkyl, halo C
1-10Alkyl, C
1-10Alkoxyl group, nitro, cyano group, and C
6-12Aryloxy);
E is selected from O, SO
n(wherein n is 0-2), NH, and NX (wherein X is selected from C
1-10Alkyl, halo C
1-10Alkyl);
J and R are independently selected from H, C
1-10Alkyl, C
1-10Alkenyl, C
1-10Alkynyl, halo C
1-10Alkyl and C
1-10Alkoxyalkyl;
M is selected from N and CZ, and wherein Z is selected from H and C (=O) H;
Q is selected from NO
2, CN, and C (=O) CF
3
G and T are independently selected from H, C
1-10Alkyl, C
1-10Alkenyl, C
1-10Alkynyl, halo C
1-10Alkyl, and C
1-10Alkoxyalkyl; Optionally, G and T also can pass through a singly-bound, or a cross structure is joined together, and at this, this cross structure is selected from CH
2, CHCH
3, C (CH
3)
2, CH (halo C
1-10Alkyl), C (halo C
1-10Alkyl)
2, CHF, CF
2, O, SO
n(wherein n is 0-2), NH, and NX (wherein X is selected from C
1-10Alkyl or halo C
1-10Alkyl).
13. as claim 12 described methods, wherein said heterocycle is a hexa-member heterocycle.
14. as claim 13 described methods, wherein said heterocycle contains one or two nitrogen heteroatom.
15. as claim 14 described methods, wherein said heterocycle is by methyl, ethyl, and fluorine, chlorine, or the bromine list replaces.
16. as claim 15 described methods, wherein said substituting group and heteroatoms are the ortho positions.
17. as claim 12 described methods, wherein E is O.
18. as claim 12 described methods, wherein J and R are H.
19. as claim 12 described methods, wherein M is CH.
20. as claim 12 described methods, wherein Q is NO
2
21. as claim 12 described methods, wherein G and T are methyl or ethyl.
22. as claim 12 described methods, wherein G is connected by cross structure with T, this cross structure is a singly-bound or a CH
2
23. one kind contains just like claim 1 described compound and at least a sterilant that is selected from miticide, other compound of nematocides and the composition of auxiliary agent tensio-active agent.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22911000P | 2000-08-30 | 2000-08-30 | |
| US60/229,110 | 2000-08-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1501917A true CN1501917A (en) | 2004-06-02 |
Family
ID=22859873
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA018149138A Pending CN1501917A (en) | 2000-08-30 | 2001-08-28 | Compounds useful as insecticides, compounds useful as acaricides, and processes to use and make same |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP1313704A2 (en) |
| JP (1) | JP2004521077A (en) |
| KR (1) | KR20030029878A (en) |
| CN (1) | CN1501917A (en) |
| AU (1) | AU2001286839A1 (en) |
| BR (1) | BR0113633A (en) |
| WO (1) | WO2002018339A2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108473443A (en) * | 2015-11-17 | 2018-08-31 | 美国陶氏益农公司 | 4- ((6- (two fluoro- 2- hydroxyls -3- (1H-1,2,4- triazol-1-yls) propyl of 2- (2,4 difluorobenzene base) -1,1-) pyridin-3-yl) oxygroup) benzonitriles and preparation method |
| CN108882708A (en) * | 2015-11-17 | 2018-11-23 | 美国陶氏益农公司 | 4- ((6- (fluoro- 2- hydroxyl -3- (1H-1,2,4- triazol-1-yl) propyl of 2- (2,4 difluorobenzene base) -1,1- two) pyridin-3-yl) oxygroup) benzonitrile and preparation method |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MXPA04011472A (en) | 2002-05-22 | 2005-02-14 | Amgen Inc | Amino-pyridine, -pyridine and pyridazine derivatives for use as vanilloid receptor ligands for the treatment of pain. |
| JP4555082B2 (en) | 2002-08-08 | 2010-09-29 | アムジエン・インコーポレーテツド | Vanilloid receptor ligands and their use in therapy |
| MY139645A (en) | 2004-02-11 | 2009-10-30 | Amgen Inc | Vanilloid receptor ligands and their use in treatments |
| WO2005077938A1 (en) | 2004-02-11 | 2005-08-25 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
| US7301022B2 (en) | 2005-02-15 | 2007-11-27 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
| TWI636045B (en) * | 2015-11-17 | 2018-09-21 | 美商維愛美製藥公司 | 4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-oxoethyl)pyridin-3-yl)oxy)benzonitrile and processes of preparation |
| KR102467497B1 (en) * | 2020-11-20 | 2022-11-15 | 주식회사 엘피엔 | Method for synthesis of ligand for preparation of organometallic compounds |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA978964A (en) * | 1972-05-04 | 1975-12-02 | Steven A. Roman | 2-(nitromethylene)piperidines and their use as insecticides |
| DE2321522C2 (en) * | 1972-05-04 | 1983-11-03 | Shell Internationale Research Maatschappij B.V., 2501 Den Haag | Insecticidal agent for combating caterpillar feeding on leaves |
| JPS59161347A (en) * | 1983-03-07 | 1984-09-12 | Sagami Chem Res Center | 3-amino-2-alkenenitrile and its preparation |
| JP2779403B2 (en) * | 1988-11-29 | 1998-07-23 | 日本バイエルアグロケム株式会社 | Insecticidal nitro compounds |
| IE960441L (en) * | 1988-12-27 | 1990-06-27 | Takeda Chemical Industries Ltd | Guanidine derivatives, their production and insecticides |
| US6048824A (en) * | 1993-04-08 | 2000-04-11 | Novartis Corporation | 2-nitromethylidene/2-cyanimino/2-nitro-imino-pyrrolidines and piperidines, intermediates, and their use as pesticides |
-
2001
- 2001-08-28 BR BR0113633-0A patent/BR0113633A/en not_active Application Discontinuation
- 2001-08-28 EP EP01966314A patent/EP1313704A2/en not_active Withdrawn
- 2001-08-28 KR KR10-2003-7002946A patent/KR20030029878A/en not_active Application Discontinuation
- 2001-08-28 AU AU2001286839A patent/AU2001286839A1/en not_active Abandoned
- 2001-08-28 WO PCT/US2001/026777 patent/WO2002018339A2/en not_active Application Discontinuation
- 2001-08-28 JP JP2002523457A patent/JP2004521077A/en active Pending
- 2001-08-28 CN CNA018149138A patent/CN1501917A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108473443A (en) * | 2015-11-17 | 2018-08-31 | 美国陶氏益农公司 | 4- ((6- (two fluoro- 2- hydroxyls -3- (1H-1,2,4- triazol-1-yls) propyl of 2- (2,4 difluorobenzene base) -1,1-) pyridin-3-yl) oxygroup) benzonitriles and preparation method |
| CN108882708A (en) * | 2015-11-17 | 2018-11-23 | 美国陶氏益农公司 | 4- ((6- (fluoro- 2- hydroxyl -3- (1H-1,2,4- triazol-1-yl) propyl of 2- (2,4 difluorobenzene base) -1,1- two) pyridin-3-yl) oxygroup) benzonitrile and preparation method |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1313704A2 (en) | 2003-05-28 |
| KR20030029878A (en) | 2003-04-16 |
| BR0113633A (en) | 2005-06-07 |
| AU2001286839A1 (en) | 2002-03-13 |
| WO2002018339A3 (en) | 2002-05-16 |
| JP2004521077A (en) | 2004-07-15 |
| WO2002018339A2 (en) | 2002-03-07 |
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