CN103242225B - Picolinate amino pyridine compound and preparation method thereof - Google Patents
Picolinate amino pyridine compound and preparation method thereof Download PDFInfo
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Abstract
The invention discloses there is sterilization, desinsection/mite, the bioactive Picolinate amino pyridine compound of weeding and preparation method thereof, sterilization containing described compound, desinsection/mite, herbicidal composition and control fungi, worm/mite, the purposes of weeds and method with these compounds shown in formula (I).
Description
Technical field
The present invention relates to and there is desinsection, sterilization, the bioactive Picolinate amino pyridine compound of weeding and preparation method thereof, desinsection containing described compound, sterilization, herbicidal composition and by the purposes of these compound Control pests, fungi, weeds and method.
Background technology
Heterogeneous ring compound particularly pyridine-heterocyclic compound is a class important compound in pharmaceutical chemistry, and they have the biological activity of wide spectrum.Although about the report of heterogeneous ring compound particularly pyridine-heterocyclic compound is a lot.But relevant Picolinate amino pyridine compound, except Shiokawa EP0398084A2 about shown in general formula (A) nitro replace heterogeneous ring compound in, report outside four compounds shown in formula (B) ~ formula (E), fail to find other bibliographical information.And from EP0398084A2, any biologically active data about formula (B) ~ shown four compounds of formula (E) can not be found.
The control of insect, germ, weeds is extremely important in the process realizing high-efficiency agriculture.The simultaneously control of insect, germ, weeds woods, herd, also very important in secondary, fishing and public health.Although existing a lot of insect, germ, control of weeds agent on market, but because the problem such as economy of the continuous expansion in market and insect, germ, the resistance of weeds, the work-ing life of medicine and medicine and people are to the pay attention to day by day of environment, need scientists constantly to study, so exploitation efficient, safety, economy, the Environmental compatibility that make new advances and the desinsection with the different mode of action, sterilization, weedicide new variety.
For obtaining efficient, the broad-spectrum biological activity material with unique mechanism of action, we have designed and synthesized the Picolinate amino pyridine compound with desinsection, sterilization, weeding activity, with four Compound Phase ratios shown in the formula reported in EP0398084A2 (B) ~ formula (E), not only there is different constructional features, and there is biological activity that is more excellent and more wide spectrum, some compound demonstrates the biological activity suitable with commercialization pesticide imidacloprid as 08 etc.
Summary of the invention
The invention provides, shown in general formula (I), there is bioactive Picolinate amino pyridine compound and isomer thereof:
Wherein:
I.R is hydrogen, halogen, nitro, cyano group, C
1~ C
3haloalkyl;
II.p is the integer of 0 to 3;
III.R
1and R
2be identical or different, and represent
(a) hydrogen, halogen;
(b) alkyl, alkoxyl group, alkylthio, alkyl sulphonyl, alkyl sulphinyl, alkoxy carbonyl, alkenyl, alkenyl oxy, alkenyl thio, alkenylsufonyl, alkenylsulfinyl, alkynyl, alkynyloxy base, alkynyl sulfenyl, alkynylsulfonyl, alkynylsulfinyl, cycloalkyl, cycloalkyl oxy, cycloalkylsulfanyl, naphthene sulfamide base, cycloalkylsulfinyl, alkyl-carbonyl, aryl, aryloxy, artyl sulfo, aryloxycarbonyl, aryl sulfonyl, aryl sulfonyl kia, heteroaryl, heteroaryl oxygen base, Heteroarylthio, heteroaryloxycarbonyl, heteroarylsulfonyl, heteroarylsulfinyl,
(c) NR
3r
4(R
3and R
4identical or different, and represent hydrogen, alkyl, alkoxyl group, alkylthio, alkyl sulphonyl, alkyl sulphinyl, alkoxy carbonyl, alkenyl, alkenyl oxy, alkenyl thio, alkenylsufonyl, alkenylsulfinyl, alkynyl, alkynyloxy base, alkynyl sulfenyl, alkynylsulfonyl, alkynylsulfinyl, cycloalkyl, cycloalkyl oxy, cycloalkylsulfanyl, naphthene sulfamide base, cycloalkylsulfinyl, alkyl-carbonyl, aryl, aryloxy, artyl sulfo, aryloxycarbonyl, aryl sulfonyl, aryl sulfonyl kia, heteroaryl, heteroaryl oxygen base, Heteroarylthio, heteroaryloxycarbonyl, heteroarylsulfonyl, heteroarylsulfinyl),
(d) as implication determined in III. (a), III. (b) or III. (c), R if desired
1or R
2in hydrogen atom can partly or entirely be selected from following in identical or different substituting group replace:
Halogen, nitro, cyano group, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, alkoxyl group, alkylthio, amino, alkylamino, dialkyl amido, haloalkyl, alkenyl oxy, alkenyl thio, alkenyl amino, alkenyl alkyl, halogenated alkenyl, alkynyloxy base, alkynyl sulfenyl, alkynylamino, alkynylalkyl, halo alkynyl, cycloalkyl oxy, cycloalkylsulfanyl, cycloalkyl amino, cycloalkylalkyl, halogenated cycloalkyl, aryloxy, artyl sulfo, arylamino, arylalkyl, halogenated aryl, heteroaryl oxygen base, Heteroarylthio, heteroaryl amino, heteroarylalkyl, haloheteroaryl,
E () aryl and heteroaryl as determined implication in III. (a), III. (b), III. (c) or III. (d) can partly or entirely hydrogenation, wherein 1 or 2 CH
2group can be replaced by CO;
IV.R
3halogen, C
1~ C
3alkyl, C
1~ C
3haloalkyl;
V.R=3-NO
2, R
2=CH
3time, R
p 1≠ 6-Cl, 6-H;
VI.R=3-NO
2, R
2=CH (CH
3)
2time, R
p 1≠ 6-H;
In the definition of the compound (I) provided, no matter term used is used alone or is used in compound word, represent following substituting group above:
Halogen: refer to fluorine, chlorine, bromine and iodine;
Alkyl: refer to the straight or branched alkyl with 1-6 carbon atom;
Alkoxyl group: refer to the straight or branched alkoxyl group with 1-6 carbon atom, be connected in structure through Sauerstoffatom key;
Alkylthio: refer to the straight or branched alkylthio with 1-6 carbon atom, be connected in structure through sulphur atom key;
Alkenyl: refer to the straight or branched thiazolinyl with 2-6 carbon atom;
Alkynyl: refer to the straight or branched alkynyl with 2-6 carbon atom;
Aryl: refer to there is the phenyl of 6 carbon atoms and there is the naphthyl of 12 carbon atoms;
Heteroaryl: the heteroaryl referring to as many as 10 carbon atoms;
Halo: refer to 1, multiple or all hydrogen atoms are optionally substituted by halogen, as having the straight or branched alkyl of 1-6 carbon atom, the hydrogen atom on these alkyl can partly or entirely be replaced by halogen atom.
Compound shown in (I) of the present invention, geometrical isomer (respectively with Z and E to represent different configurations) can be formed because carbon-to-carbon double bond, carbon-to-carbon three key or carbon-nitrogen double bond connect different substituents, the present invention includes the mixture of any ratio of Z-type isomer and E-isomer and they.
Compound of the present invention, steric isomer (respectively with R and S to represent different configurations) can be formed due to carbon or nitrogen-atoms connecting different substituting groups, the present invention includes the mixture of R type isomer and S type isomer and their any ratios.
Compound of the present invention, not only relates to geometrical isomer (Z/E formula) and steric isomer (R/S formula), also relates to the mixture of geometrical isomer and any ratio of steric isomer.
What inventors of the present invention synthesized have the Picolinate amino pyridine compound shown in general formula (I) has broad spectrum of activity: the compound had can be used for preventing and treating the various harmful insects of such as aphid etc.; Some compounds can be used for control by multiple fungus-caused diseases such as Haplomycetes, Phycomycetes, Oomycete, Ascomycetes and deuteromycetes; Some compounds not only can be used for preventing and treating the various harmful insects of such as aphid on various crop, also can be used for preventing and treating simultaneously on various crop by multiple fungus-caused diseases such as Haplomycetes, Phycomycetes, Oomycete, Ascomycetes and deuteromycetes, and the compound had has very high biological activity and makes just can obtain good effect under very low dosage.Specifically, part of compounds of the present invention is to the activity as excellent in aphid etc. has of harmful insect.
With the compound that table 1 ~ table 2 the following is listed, the present invention can be described, but not limit the present invention.The present invention give fusing point all not calibrated.Also the formula (B) and two compounds shown in formula (C) reported in the EP0398084A2 synthesized by the present invention is listed in table 1 and table 2, the fusing point of the formula (B) reported in EP0398084A2 is 123 ~ 124 DEG C, the fusing point of formula (C) is 71 ~ 74 DEG C, formula (B) synthesized by the present invention is liquid of vicidity, after fixing placed by refrigerator, and the fusing point of formula (C) is 71.4 ~ 72.7 DEG C.
Table 1
Table 2
* PyH represents H on pyridine ring
Compound shown in formula of the present invention (I) can be prepared by reaction formula 1, reaction formula 2 and reaction formula 3 shown below.Substituting group is wherein outer unless specified otherwise all to be limited as front, X, and X is that leavings group is as halogen (fluorine, chlorine, bromine), sulphonate etc.
Reaction formula 1-1:
Reaction formula 1-2:
Reaction formula 2-1:
Reaction formula 2-2:
Reaction formula 3:
The compound of formula (I) can be prepared (reaction formula 1-1) like this: at N, in dinethylformamide or benzene, toluene, tetrahydrofuran (THF) equal solvent, under sodium hydride or the alkali such as potassium hydroxide, salt of wormwood exist, in 25 ~ 80 DEG C or height under solvent reflux temperature, react to obtain the compound of formula (I) with the compound shown in the compound shown in formula (II) and formula (III).
The compound of formula (I) also can be prepared (reaction formula 1-2) like this: at N, dinethylformamide or tetrahydrofuran (THF), water, methylene dichloride, benzene, in the single solvents such as toluene or their mixed solvent, at sodium hydride or potassium hydroxide, under the alkali such as salt of wormwood exist, in room temperature or height under solvent reflux temperature, the compound of formula (V) is reacted to obtain with the compound of the compound shown in formula (II) and formula (IV), in alcohol or water equal solvent, add alkali metallic sodium or sodium alkoxide if desired, sodium hydride etc., in room temperature or height under solvent reflux temperature, the compound of formula (V) and R
p 1h reacts, and obtains the compound of formula (I).
The compound of formula (II) can be prepared (reaction formula 2-1) like this: in the mixed solvent of the single solvents such as trichloromethane or methylene dichloride, benzene, toluene or they and water or alcohol, under sodium hydride or the alkali such as sodium hydroxide, salt of wormwood exist, in room temperature or height under solvent reflux temperature, compound shown in formula (VI) reacts with the compound of (VII), obtain the compound of formula (II), add phase-transfer catalyst benzyltriethylammoinium chloride or Tetrabutyl amonium bromide etc. and reaction can be impelled to carry out or can accelerated reaction carry out.
Formula (II:R
2=H) compound also can prepare like this (reaction formula 2-2): at N, in dinethylformamide or ethanol equal solvent, in room temperature or height under solvent reflux temperature, the compound of the compound shown in formula (VI) and formula (VIII) is obtained by reacting the compound of formula (IX), in methyl alcohol or ethanol equal solvent, in room temperature or height under solvent reflux temperature, the compound hydrazine of formula (IX) or the reduction such as hydrazine hydrate, shortening, obtain formula (II:R
2=H) compound.
The compound of formula (III) can be prepared (reaction formula 3) like this: at solvent R
p 1in H, in subzero 15 DEG C or height under solvent reflux temperature, use R
p 1the compound of the alkaline purification general formulas (IV) such as ONa or sodium hydride, sodium hydroxide, salt of wormwood, obtains the compound of formula (III).
The compound of formula (III) also can be prepared (reaction formula 3) like this: in water or DMF equal solvent, in subzero 15 DEG C or height under solvent reflux temperature, uses R
p 1the compound of H and formula (IV) reacts, and obtains the compound of formula (III), adds suitable alkali such as triethylamine or sodium hydride, sodium hydroxide, salt of wormwood etc. and reaction can be impelled to carry out or can accelerated reaction carry out.
The compound of formula (III) can also be prepared (reaction formula 3) like this: in benzene or toluene, sherwood oil equal solvent, in subzero 15 DEG C or height under solvent reflux temperature, at alkali as under sodium hydride or sodium hydroxide, salt of wormwood exists, uses R
p 1the compound of H and formula (IV) reacts to obtain the compound of formula (III).
Picolinate amino pyridine compound provided by the invention, has biological activity and some compounds have good biological activity. particularly in the preventing and treating of disease of agricultural, gardening and flowers, show high reactivity.Harmful organism described here include but not limited to this:
Harmful pathogenic bacteria: phytophthora kind, white powder belongs to kind, Gibberella kind, Venturia kind, species of Monilinia fructicola, Rhizoctonia kind, Staphlosporonites kind, Pyricularia Sacc. kind, fusarium kind, as rice blast (Pyriculariaoryzae); Stripe rust of wheat (Pucciniastriiformis), leaf rust (Pucciniarecondita) and other rust; Large wheat yellow rust (Pucciniastriiformis), leaf rust (Pucciniarecondita) and other rust; Barley and wheat powdery mildew (Erysiphegraminis), powdery mildew of cucumber (Sphaerothecafuligenea), apple mildew (Podosphaeraleucotrichar) and uncinula necator (Podosphaeraleucotrichar); Wheat hypochnus and glume blight (Septorianodorum).The compacted spore of length on cereal, mouth spore is mould, Septoria is sick, caryosphere shell Pseudomonas is sick, Pseudocercosporellaherpotrichoides and take-all (Gaeumannomycesgraminis).The cercospora brown spot of peanut (Cercosporaarachidicola) and the cercospora black spot of peanut (Cercosporidiumpersonata); The mould genus of its tail spore on beet, soybean and paddy is sick.Tomato, cucumber, grape grey mould (Botrytiscinerea).Hinge spore on vegetables (as cucumber) belongs to sick.Anthrax on cucumber, scab of apple, cucumber downy mildew, downy mildew of garpe, the epidemic disease on potato and tomato, the list bacterium Thanatephoruscucumeris on paddy and other hosts are as other rhizoctonia on Wheat and barley, vegetables; Sclerotinia rot of colza (Sclerotoniasclerotiorum); Wheat scab (Gibberellazeae); Phytophthora capsici disease (Phytophythoracapsici).
Harmful insect: Orthoptera is as blattaria, Thysanoptera is as cotton thrips, rice thrips, melon thrips, Homoptera is as leafhopper, plant hopper, aphid, lepidopteran is as oriental armyworm, prodenia litura, small cabbage moth, cabbage caterpillar, Hymenoptera is as sawfly larva, Diptera is as yellow-fever mosquito, culex, fly, and acarina is as Jie-Li enzyme-SQ, cotton spider mites.
Injurious weed: monocotyledon weed lady's-grass, barnyard grass, Herba Setariae Viridis, hard Cao, Wang grass, bromegrass, amur foxtail, Triticum tauschii, alkali thatch, flower of Stinkgrass, wild avena sativa, rye grass; Broadleaf weed piemarker, chickweed, black nightshade, lamb's-quarters, recessed head amaranth, Amaranthus retroflexus etc.
With Picolinate amino pyridine compound provided by the invention, as the Agrotechnical formulation of effective ingredient, can make desired any one formulation as missible oil, wettable powder, suspension agent, granula, suitable auxiliary agent comprises carrier (thinner) and other auxiliary as spreader-sticker, emulsifying agent, wetting agent, dispersion agent, the agent of tackiness agent Sum decomposition.
Present invention also offers the preparation method of composition as defined above, method is by the compound of general formula (I) and the mixing of at least one carrier.This composition can contain the mixture of single compound of the present invention or several compound.
According to composition of the present invention, preferably containing the activeconstituents of 1-99% weight.Carrier system of the present invention meets the material of following condition: it and activeconstituents are convenient to be applied to pending site after preparing, as plant, seed or soil; Or be conducive to storage, transport or operation.Carrier can be solid or liquid, comprises and is generally gas but has been compressed into liquid bead material, and can use any usually at preparation desinsection, kill carrier used in mite and fungicidal composition.
Suitable solid carrier comprises clay that is natural and that synthesize and silicate, such as diatomite, talcum, attapulgite, pure aluminium silicate (kaolin), montmorillonite and mica; Calcium carbonate; Calcium sulfate; Ammonium sulfate; Synthetic silica and synthetic calcium silicate or pure aluminium silicate; Element is as carbon and sulphur; Resin that is natural and synthesis as coumarone resin, polyvinyl chloride and styrene polymer and multipolymer; Solid polystream phenol; Pitch; Wax as beeswax, paraffin.
Suitable liquid vehicle comprises water; Alcohol as Virahol, ethanol; Ketone is as acetone, methyl ethyl ketone, cyclohexyl ketone; Ether; Aromatic hydrocarbons is as benzene, toluene and dimethylbenzene; Petroleum fractions is as kerosene and mineral oil; Hydrochloric ether, as tetracol phenixin, tetrachloroethylene, also comprises the mixture of these liquid.
Sterilization, desinsection/acaricidal composition are usually processed into the form of enriched material and with this for transport, are diluted before administration by user.Having of a small amount of supporting surfactant helps dilution.Therefore, according in composition of the present invention, has a kind of carrier preferred surfactant at least.As composition contains at least two kinds of carriers, wherein at least one is tensio-active agent.
Tensio-active agent can be emulsifying agent, dispersion agent or wetting agent; It can be tensio-active agent that is non-ionic or ion.As sodium salt or the calcium salt of polyacrylic acid and lignosulfonic acid; Containing the lipid acid of at least 12 carbon atoms or the condenses of aliphatic amide or acid amides and oxyethane and/or propylene oxide in molecule; Glycol, sorbyl alcohol, the condenses of sucrose or pentaerythritol fatty ester and these esters and oxyethane and/or propylene oxide; The vitriol of these condensess or sulfonate; Sulfuric acid in the molecule containing at least 10 carbon atoms can the basic metal of sulphonate or alkaline earth salt.
The example of composition of the present invention is wettable powder, pulvis, granule and solution, emulsible enriching agent, emulsion, suspension enriching agent, aerosol and smoke substance.Wettable powder is usually containing 15,25, and 50% wt. Active ingredient, and usually except solid inert carrier, also containing 3-10% weight fraction powder, adds 0-10% weight stablizer and/or other additive if desired as permeate agent and tackiness agent.Pulvis may be molded to usually has the composition similar to wettable powder but the pulvis enriching agent not having dispersion agent.Granula is made usually has 10-100 order (1.676-0.152mm) size, and available agglomerating or implantttion technique preparation.Usually, granula containing the activeconstituents of 0.5-50% weight and 0-10% weight additive as stablizer, tensio-active agent, slowly-releasing modifying agent.Can emulsion concentrate in addition to the solvents, cosolvent can be contained if desired, 1-50%W/V activeconstituents, 2-20%W/V emulsifying agent and other additive of 0-20%W/V are as stablizer, permeate agent and corrosion inhibitor, and the dispersion agent of the activeconstituents of suspension enriching agent usually containing 10-75% weight, 0.5-15% weight, other additive of 0.1-10% weight are as defoamer, corrosion inhibitor, stablizer, permeate agent and tackiness agent.
Water dispersant and emulsion, such as, by the composition that dilute with water obtains according to wettable powder of the present invention or enriched material, also list scope of the present invention in.Indication emulsion comprises water-in-oil and oil-in-water two kinds.
By adding other one or more mycocides in the composition, more broad spectrum of activity can be had than independent general formula (I) compound.In addition, other mycocide the Fungicidally active of mutual-through type (I) compound can have synergism.The example that can comprise acaricide compound in the compositions of the present invention has: strobilurin fungicide, F-1991, derosal, m-tetrachlorophthalodinitrile, dimethomorph, triadimefon, cyanogen bacterium azoles, zinc manganese ethylenebisdithiocarbamate etc.
By adding other one or more sterilants in the composition, more broad spectrum of activity can be had than independent general formula (I) compound.In addition, other sterilant the insecticidal activity of mutual-through type (I) compound can have synergism.The suitable sterilant that can form composition with compound of the present invention comprises organophosphorus insecticides as acephatemet, Volaton, monocrotophos, Provado, triaxamate, indoxacarb and pyrethroid insecticides are as fenvalerate, cyfloxylate, bifenthrin, chlorantraniliprole, Flubendiamide etc.
Embodiment
Below in conjunction with embodiment, the invention will be further described, and the yield in embodiment is all without optimization, and fusing point is not calibrated.
The preparation of compound (02) in embodiment 1 the present embodiment instruction card 1
CCMP (16.10g) and trichloromethane (60mL) is added in the 250mL there-necked flask being furnished with magnetic stirring apparatus and drying tube, after stirring at room temperature 0.5-1.0hr, drip the ethylamine solution (18.0mL) of 60-70% and the NaOH aqueous solution (40.0mL) of 20% respectively, drip after finishing, add benzyltriethylammoinium chloride (0.1g), stirring at room temperature reaction is spent the night.Regulate pH value to weakly alkaline, separate organic layer, water layer dichloromethane extraction secondary, merge organic phase and wash after twice with cryosel, anhydrous sodium sulfate drying.Concentrating under reduced pressure obtains salmon liquid 2-chloro-5-ethamine picoline 15.9g, content 98.5%.GC-MS(M
+)(EI,70eV,m/z)(relativeintensity％)calc:170；found:170.
The chloro-3-nitropyridine (1.60g) of 2-and 15mLN is added in 100mL single port bottle, dinethylformamide (DMF), salt of wormwood (2.63g), under stirring at room temperature, drip the 10.0mLDMF solution of 2-chloro-5-ethamine picoline (1.72g), drip after finishing and be warming up to 50-80 DEG C of reaction 3-5hr, reaction solution is poured in 100mL water after cooling, extraction into ethyl acetate, washing, anhydrous sodium sulfate drying, concentrating under reduced pressure obtains the thick product of 2.62g.Be that eluent carries out column chromatography and obtains yellow viscous liquid N-((2-chloropyridine-5-base) methyl)-N-ethyl-3-nitropyridine-2-amine 1.49g, content 99.8%, yield 50.3% with the ethyl acetate of 1:5 and sherwood oil mixed solution.GC-MS(M
+)(EI,70eV,m/z)(relativeintensity％)calc:292；found:292；
1HNMR(CDCl
3/TMS,300MHz)δ(ppm):1.172(t,J＝6.9Hz,3H,CH
3),3.252(q,J＝6.9Hz,2H,CH
2),4.751(s,2H,CH
2),6.776(m,1H,PyH),7.259(d,J＝8.4Hz,1H,PyH),7.680(d,J＝5.7Hz,1H,PyH),8.058(d,J＝8.4Hz,1H,PyH),8.299(d,J＝8,4Hz,1H,PyH),8.364(s,1H,PyH).
The preparation of compound (08) in embodiment 2 the present embodiment instruction card 1
2-chloro-5-methylamine picoline is prepared with reference to the synthetic method of 2-chloro-5-ethamine picoline in embodiment 1.
2 are added in 100mL single port bottle, 6-dichloro-3-nitropyridine (2.00g) and N, dinethylformamide (DMF15mL), salt of wormwood (2.87g), under stirring at room temperature, drip DMF (8.0mL) solution of 2-chloro-5-methylamine picoline (1.60g), drip after finishing and be warming up to 50-80 DEG C of reaction 3-5hr, reaction solution is poured in 100mL water after cooling, extraction into ethyl acetate, anhydrous sodium sulfate drying, concentrating under reduced pressure obtains the chloro-N-of 6-((2-chloropyridine-5-base) methyl)-N-Methyl-3-nitropyridine-2-amine brown colored viscous solid 3.07g, content 67.3%.GC-MS(M
+)(EI,70eV,m/z)(relativeintensity％)calc:312；found:312。Without purification process, be directly used in next step synthesis.
Sodium Metal 99.5 (0.23g) and methyl alcohol (30mL) is added in the 100mL there-necked flask being furnished with magnetic stirring apparatus and drying tube, under water-bath, reaction is to producing without gas, drip methyl alcohol (10mL) solution of 6-chloro-N-((2-chloropyridine-5-base) methyl)-N-Methyl-3-nitropyridine-2-amine (3.07g), drip normal-temperature reaction 3-5hr after finishing, reaction solution is poured in 100mL water, extraction into ethyl acetate, washing, anhydrous sodium sulfate drying, concentrating under reduced pressure obtains thick product 2.57g.Be that eluent carries out column chromatography and obtains bright yellow solid 6-methoxyl group-N-((2-chloropyridine-5-base) methyl)-N-Methyl-3-nitropyridine-2-amine 1.18g with the ethyl acetate of 1:10 and sherwood oil mixed solution, content 99.0%, fusing point: 87.9-89.0 DEG C, two step total recoverys 38.9%.GC-MS(M
+)(EI,70eV,m/z)(relativeintensity％)calc:308；found:308；
1HNMR(CDCl
3/TMS,300MHz)δ(ppm):2.876(s,3H,NCH
3),3.827(s,3H,OCH
3),4.895(s,2H,CH
2),6.174(d,J＝9.0Hz,1H,PyH),7.315(d,J＝8.4Hz,1H,PyH),7.628-7.663(m,1H,PyH),8.175(d,J＝9.0Hz,1H,PyH),8.359(d,J＝2.4Hz,1H,PyH).
The preparation of compound (11) in embodiment 3 the present embodiment instruction card 1
2 are added in the there-necked flask of 250mL being furnished with magnetic agitation, constant pressure funnel and drying tube, 6-dichloro-3-nitropyridine (9.6g) and ethanol (60mL), after stirring at room temperature 15-30min, drip ethanol (30mL) solution of sodium ethylate (3.4g), 30-45min drips off, and reacts during 2-3h falls back under room temperature, filter, dry the chloro-6-oxyethyl group of faint yellow solid 2--3-nitropyridine 9.7g, content 80.0%, GC-MS (M
+) (EI, 70eV, m/z) (relativeintensity%) calc:202; Found:202.
The chloro-6-oxyethyl group of above-mentioned 2--3-nitropyridine (2.10g) and 15mLN is added in 100mL single port bottle, dinethylformamide (DMF), salt of wormwood (2.87g), under stirring at room temperature, drip DMF (10.0mL) solution of 2-chloro-5-methylamine picoline (1.60g), drip after finishing and be warming up to 50-80 DEG C of reaction 3-5hr, reaction solution is poured in 100mL water after cooling, extraction into ethyl acetate, washing, anhydrous sodium sulfate drying, concentrating under reduced pressure obtains thick product 2.89g.Be that eluent carries out column chromatography and obtains tacky yellowish solid 6-oxyethyl group-N-((2-chloropyridine-5-base) methyl)-N-Methyl-3-nitropyridine-2-amine 1.41g with the mixed solution of 1:10 ethyl acetate and sherwood oil, content 97.0%, yield 51.1%.GC-MS(M
+)(EI,70eV,m/z)(relativeintensity％)calc:322；found:322；
1HNMR(CDCl
3/TMS,300MHz)δ(ppm):1.289(t,J＝7.2,3H,CH
3),2.863(s,3H,CH
3),4.198(q,J＝7.2Hz,2H,CH
2),4.862(s,2H,CH
2),6.148(d,J＝8.7Hz,1H,PyH),7.301(d,J＝8.7Hz,1H,PyH),7.609(d,J＝8.7Hz,1H,PyH),8.169(d,J＝8.7Hz,1H,PyH),8.341(s,1H,PyH).
The preparation of compound (33) in embodiment 4 the present embodiment instruction card 1
The chloro-N-of 6-((2-chloropyridine-5-base) methyl)-N-ethyl-3-nitropyridine-2-amine (2.50g) and N is added in 100mL single port bottle, dinethylformamide (DMF15mL), salt of wormwood (1.60g), under stirring at room temperature, drip 33% dimethylamine agueous solution (10.0mL), reaction 3-5hr, reaction solution is poured in 100mL water, extraction into ethyl acetate, anhydrous sodium sulfate drying, concentrating under reduced pressure obtains thick product 2.31g.Be that eluent carries out column chromatography and obtains bright yellow solid 2-[N-((2-chloropyridine-5-base) methyl)-N-ethyl]-6-dimethylin-3-nitropyridine-2-amine 0.91g with the mixed solution of 1:10 ethyl acetate and sherwood oil, content 92.0%, fusing point: 93.7-95.1 DEG C, yield 32.6%.GC-MS(M
+)(EI,70eV,m/z)(relativeintensity％)calc:335；found:335；
1HNMR(CDCl
3/TMS,300MHz)δ(ppm):(CDCl
3):1.200(t,J＝7.2Hz,3H,CH
3),3.074(s,6H,2CH
3),3.296(q,J＝7.2Hz,2H,CH
2),4.487(s,2H,CH
2),5.980(d,J＝9.0Hz,1H,PyH),7.266(d,J＝6.6Hz,1H,PyH),7.076(d,J＝10.8Hz,1H,PyH),8.149(d,J＝9.0Hz,1H,PyH),8.531(s,1H,PyH).
The preparation of compound (44) in embodiment 5 the present embodiment instruction card 1
Phthalic acid imide (18.50g) and N is added in the 250mL there-necked flask being furnished with magnetic stirring apparatus and drying tube, dinethylformamide (DMF100mL), after stirring at room temperature 10-15min, drip DMF (40.0mL) solution of CCMP (16.20g), drip after finishing, stirring at room temperature reaction 6-8hr.Reaction solution is poured into water, filters, dry N-(the chloro-5-pyridyl of 2-) methylphthalic acid imines 19.05g, content 97.5%.GC-MS(M
+)(EI,70eV,m/z)(relativeintensity％)calc:272；found:272.
Above-mentioned gained solid is dissolved in ethanol (150mL), after mechanical stirring 15-30min, drip 8-10mL hydrazine hydrate, backflow 2-6hr, filters, and the aqueous sodium hydroxide solution with 20% regulates pH value to alkalescence, dichloromethane extraction, washing, anhydrous sodium sulfate drying, decompression precipitation obtain weak yellow liquid 2-chloro-5-aminomethyl-pyridine 9.50g, content 99.0%, GC-MS (M
+) (EI, 70eV, m/z) (relativeintensity%) calc:142; Found:142.
2 are added in 100mL single port bottle, 3-bis-chloro-5-trifluoromethylpyridine (1.22g) and N, dinethylformamide (DMF15mL), salt of wormwood (1.80g), under stirring at room temperature, drip DMF (8.0mL) solution of 2-chloro-5-aminomethyl-pyridine (0.85g), drip after finishing and be warming up to 50-80 DEG C of reaction 3-5hr, reaction solution is poured in 100mL water after cooling, extraction into ethyl acetate, washing, anhydrous sodium sulfate drying, concentrating under reduced pressure obtains thick product 1.67g.Be that eluent carries out column chromatography and obtains faint yellow solid N-((2-chloropyridine-5-base) methyl)-3-chloro-5-trifluoromethylpyridine-2-amine 0.66g with the ethyl acetate of 1:10 and sherwood oil mixed solution, content 98.1%, fusing point: 99.2-100.5.Yield 35.6%.GC-MS(M
+)(EI,70eV,m/z)(relativeintensity％)calc:321；found:321；
1HNMR(CDCl
3/TMS,300MHz)δ(ppm):4.738(d,J＝5.7Hz,2H,CH
2),7.290(d,J＝8.4Hz,1H,PyH),7.657-7.692(m,2H,PyH),8.279-8.289(m,1H,PyH),8.404(d,J＝2.4Hz,1H,PyH).
The preparation of compound (46 and 47) in embodiment 6 the present embodiment instruction card 1
Embodiment 1 is shown in the preparation of 2-chloro-5-ethamine picoline.
2 are added in 100mL single port bottle, the chloro-nicotinonitrile of 6-bis-(1.72g) and N, dinethylformamide (DMF15mL), salt of wormwood (2.00g), under stirring at room temperature, drip DMF (10.0mL) solution of 2-chloro-5-ethamine picoline (1.70g), drip after finishing and be warming up to 60-80 DEG C of reaction 3-5hr, reaction solution is poured in 100mL water after cooling, extraction into ethyl acetate, washing, anhydrous sodium sulfate drying, concentrating under reduced pressure obtains the thick product of 2.54g.Be that eluent carries out column chromatography and obtains buff white solid N-((2-chloropyridine-5-base) methyl)-N-ethyl-5-cyanopyridine-2-amine 0.59g with the ethyl acetate of 1:10 and sherwood oil mixed solution, content 98.0%, fusing point: 87.3-87.7, yield 18.9%.GC-MS(M
+)(EI,70eV,m/z)(relativeintensity％)calc:306；found:306；
1HNMR(CDCl
3/TMS,300MHz)δ(ppm):1.194(t,J＝7.2Hz,3H,CH
3),3.515(q,J＝7.2Hz,2H,CH
2),4.795(s,2H,CH
2),6.413(d,J＝8.7Hz,1H,PyH),7.296(d,J＝8.7Hz,1H,PyH),7.591(m,2H,PyH),8.324(d,J＝2.4Hz,1H,PyH)。
Also obtain off-white color solid N-((2-chloropyridine-5-base) methyl)-N-ethyl-nicotinonitrile-2-amine 0.26g, content 98.0%, yield 8.5% simultaneously.GC-MS(M
+)(EI,70eV,m/z)(relativeintensity％)calc:306；found:306；
1HNMR(CDCl
3/TMS,300MHz)δ(ppm):1.353(t,J＝7.2Hz,3H,CH
3),3.763(t,J＝7.2Hz,2H,CH
2),4.821(s,2H,CH
2),6.676(d,J＝8.1Hz,1H,PyH),7.305(d,J＝8.4Hz,1H,PyH),7.696-7.734(m,2H,PyH),8.375(d,J＝2.4Hz,1H,PyH).
Embodiment 7 prepares missible oil: by provided by the invention to 20 parts (weighing scale) containing Picolinate amino pyridine compound, 73 parts of thinners such as dimethylbenzene and 7 parts of suitable auxiliaries Homogeneous phase mixing can prepare missible oil, and dilute with water can be used (active compound content is 20%).
The preparation of embodiment 8 compound 08 (6-methoxyl group-N-((2-chloropyridine-5-base) methyl)-N-Methyl-3-nitropyridine-2-amine) 20% missible oil: by 20 parts of compounds 05 (weighing scale), 73 parts of thinners such as dimethylbenzene and 7 parts of suitable auxiliaries Homogeneous phase mixing can prepare missible oil, and dilute with water can be used (active compound content is 20%).
Embodiment 9 prepares wettable powder: by 20 parts of (by weight) Picolinate amino pyridine compound provided by the invention, 53 parts of clays, 20 parts of white carbon blacks, 5 parts of lignin silicate and 2 parts of polyoxyethanyl alkyl oxide mixing are worn into fine powder and can be obtained wettable powder (active compound content is 20%).
Raw survey embodiment
Sterilization, desinsection are carried out to synthesized compound, has killed mite and weeding activity test, listed the experimental result of part of compounds below.
The Insecticidal Activity of embodiment 10 pairs of bean aphids (Aphisfabae)
Method is as follows: take appropriate formula provided by the invention (I) compound, with suitable solvent as DMF dissolves, then add a small amount of tween 80 emulsifying agent, stir, add quantitative clear water, be mixed with desired concn, if clear water is contrast.Bean aphid is connected on just unearthed bean seedlings, every strain connects more than 20, then bean seedlings are dipped in formula provided by the invention (I) liquid liquid together with examination worm, take out after 5 seconds, suck unnecessary liquid, insert in the sponge of water suction, cover with glass-tube, after 24 hours, check survival and dead borer population.Experiment repetition 3 times.Results averaged.Activity is relative to blank with percentages, and be divided into A, B, C, D level Four, mortality ratio 100%-90% is A level, and mortality ratio 90%-70% is B level, and mortality ratio 70%-50% is C level, and mortality ratio 0%-50% is D level.Partial results is as following table 3 ~ table 4.
Table 3 part of compounds and Compound C under 500mg/L concentration to the activity (%) of aphid
| Compound | 02 | 03 | 04 | 08 | 10 | 11 | 12 | 13 | 14 | 16 | 17 |
| Active rank | A | A | C | A | A | A | B | A | A | A | B |
| Compound | 18 | 19 | 20 | 21 | 23 | 33 | 39 | 40 | 43 | 44 | Compound C |
| Active rank | B | A | B | A | C | B | C | C | B | C | D |
Table 4 part of compounds and compd B, C and Provado under 500 ~ 6.25mg/L concentration to the activity (%) of aphid
| Compound | 500mg/L | 100mg/L | 25mg/L | 6.25mg/L |
| 02 | 100 | 98.7 | 46.2 | 21.1 |
| 08 | 100 | 100 | 100 | 96.0 |
| 11 | 100 | 87.5 | 46.5 | 12.7 |
| 13 | 91.5 | 68.1 | 63.5 | 29.8 |
| 14 | 99.3 | 88.0 | 77.0 | 12.3 |
| 21 | 94.1 | 43.3 | 43.0 | 13.6 |
| Compd B | 100 | 96.8 | 57.0 | 5.10 |
| Compound C | 19.6 | / | / | / |
| Provado | 100 | 100 | 100 | 94.5 |
/: represent undetermined
The Insecticidal Activity of embodiment 11 pairs of Nilaparvata lugen (brown planthopper)s (Nilaparvatalugens)
Take appropriate formula provided by the invention (I) compound, with suitable solvent as DMF dissolves, then add a small amount of tween 80 emulsifying agent, stir, add quantitative clear water, be mixed with desired concn, if clear water is contrast.Choose two core rice seedling leachings into the liquid, take out after 5 seconds and dry, be placed in Boiling tube, often pipe 20 strain, then Nilaparvata lugen (brown planthopper) 3 ~ 5 nymph in age of introducing 20 or more, the mouth of pipe checks survival and dead borer population after 72 hours under being placed on greenhouse experiment with white gauze wrapping.Experiment repetition 3 times.Results averaged.Active relative to blank with percentages, result shows that formula (I) compound has insecticidal activity to Nilaparvata lugen (brown planthopper): under 40mg/L concentration, the activity that compound 08 kills Nilaparvata lugen (brown planthopper) reaches more than 80%, and the activity that compound 11 kills Nilaparvata lugen (brown planthopper) reaches more than 60%.
The fungicidal activity of embodiment 12 pairs of Sclerotinia sclerotiorums (Sclerotoniasclerotiorum)
Method is as follows: testing compound is dissolved in suitable solvent as in DMF (DMF), then is diluted to desired concn with the sterilized water containing 0.1%Tween80 emulsifying agent; Get 3mL liquid with transfer pipet to add in the potato agar substratum (PDA) of the 27mL being cooled to 45 DEG C and to pour culture dish into after fully shaking up; Cool rear inoculating needle and get 6mm diameter mycelia block from the cultivation germ colony edge of 7 days, move to culture dish central authorities, mycelia faces down, and sets thinner as contrast simultaneously, often processes 4 times and repeats; Constant temperature biochemical cultivation case culture dish being placed in 28 DEG C after being disposed is cultivated, and within 4 days, measures mycelial growth diameter afterwards, adopts EXCEL statistical software carry out analyzing and calculate mycelial growth inhibition rate (%).Active relative to blank with percentages, be divided into A, B, C, D level Four, 90 < inhibiting rate≤100 are A level, 70 < inhibiting rate≤90 are B level, 50 < inhibiting rate≤70 are C level, and inhibiting rate 0 < inhibiting rate≤50 are D level.Partial test the results are shown in Table 5.
Table 5 part of compounds and compd B, C and Provado under 25mg/L concentration to the activity (%) of Sclerotinia sclerotiorum
| Compound | 17 | 18 | 27 | 33 | Compd B | Compound C | Provado |
| Active (%) | 76.9 | 54.7 | 41.2 | 90.8 | 0 | 0 | 0 |
| Active rank | B | C | C | A | D | D | D |
The fungicidal activity of embodiment 13 pairs of botrytis cinerea pers (Botrytiscinerea)
Adopt the measuring method of the fungicidal activity of embodiment 12 pairs of Sclerotinia sclerotiorums, determine the fungicidal activity to botrytis cinerea pers of synthesized chemical combination.Partial test the results are shown in Table 6.
Table 6 part of compounds and compd B, C, Provado under 25mg/L concentration to the activity (%) of botrytis cinerea pers
| Compound | 28 | 30 | 33 | 40 | 44 | 47 | Compd B | Compound C | Provado |
| Active (%) | 43.8 | 43.8 | 72.0 | 51.0 | 43.8 | 50.3 | 0 | 0 | 10 |
| Active rank | D | D | B | C | D | C | D | D | D |
The evaluation of embodiment 14 weeding activity
Method is as follows: (1) is at sectional area 64cm
2plastic tub alms bowl in quantitatively dress soil pressure put down, be placed in Stainless steel basin, choose full seed, seed of the same size, divide monocotyledon weed (lady's-grass Digitariasanguinalis, barnyard grass Echinochloacrus-galli, Herba Setariae Viridis Setariaviridis) and broadleaf weed (piemarker Abutilontheophrasti (or chickweed Stelleriamedia or black nightshade Solanumnigrum), lamb's-quarters Chenopodiumalbum, recessed head amaranth Amaranthusascedense or Amaranthus retroflexus Amaranthusretroflexus) point alms bowl sowing, respectively account for 1/3 of alms bowl area, cover the thick fine earth of 1cm, bottom plastic tub alms bowl, add water to upper layer of soil infiltrate, be placed in hot-house culture, treat that examination material grows to required leaf age and carries out test process, (2) the N-oxygen base virtue phenoxy carboxylic acid amide compounds with weeding, insecticidal bioactivity provided by the invention is in right amount taken, with N, dinethylformamide dissolves, add a small amount of tween 80 emulsifying agent again, stir, add quantitative clear water, be mixed with desired concn, if coordinative solvent and clear water are contrast, (3) processing mode: next day is carried out soil treatment before seedling in the sowing of examination material, unifacial leaf examination material grew to for 1 leaf 1 heart stage, dicotyledonous examination material grows to 2 leaf periods and carries out cauline leaf process after seedling, (4) quantitatively pipette liquid carry out cauline leaf spraying or soil spraying process by arranging dosage, respectively with spray solvent and clear water for contrast, while with the clodinafop-propargyl shown in formula (P-i) for standard control, (5) process examination material is placed in hot-house culture, (6) to process after 15-25 days visually upper grown situation, according to investigation result, calculate the preventive effect of each compound to weeds as follows: preventive effect (%)=(contrast plant height-process plant height)/contrast plant height.Partial results is in table 7.
The weeding activity (%) of table 7 part of compounds and compd B, C, Provado cauline leaf/soil treatment under 150ga.i./mu dosage
Claims (7)
1. a Picolinate amino pyridine compound, is characterized in that representing with general formula (I):
Wherein:
I.R is nitro, cyano group, C
1~ C
3haloalkyl;
II.p is 0 or 1;
III.R
1represent a. hydrogen, halogen; B. alkyl, alkoxyl group, alkylthio, aryloxy; C.NR
4r
5r
4and R
5be identical or different, and represent hydrogen, alkyl; D. determined implication in III.a, III.b or III.c, R
1in hydrogen moiety or be all selected from following identical or different substituting group replace: halogen, aryl, heteroaryl, halogenated aryl or haloheteroaryl; E. in III.a, III.b, III.c or III.d, determine implication aryl and heteroaryl can partly or entirely hydrogenation, wherein 1 or 2 CH
2group can be replaced by CO;
R
2represent hydrogen or alkyl;
IV.R
3halogen, C
1~ C
3alkyl, C
1~ C
3haloalkyl;
V.R=3-NO
2, R
2=CH
3time, R
p 1≠ 6-Cl, 6-H;
VI.R=3-NO
2, R
2=CH (CH
3)
2time, R
p 1≠ 6-H;
In the definition of the compound (I) provided, no matter term used is used alone or is used in compound word, represent following substituting group above:
Halogen: refer to fluorine, chlorine, bromine and iodine;
Alkyl: refer to the straight or branched alkyl with 1-6 carbon atom;
Alkoxyl group: refer to the straight or branched alkoxyl group with 1-6 carbon atom, be connected in structure through Sauerstoffatom key;
Alkylthio: refer to the straight or branched alkylthio with 1-6 carbon atom, be connected in structure through sulphur atom key;
Aryl: refer to there is the phenyl of 6 carbon atoms and there is the naphthyl of 12 carbon atoms;
Heteroaryl: the heteroaryl referring to as many as 10 carbon atoms;
Halo: refer to 1, multiple or all hydrogen atoms are optionally substituted by halogen.
2. Picolinate amino pyridine compound according to claim 1, is characterized in that in the compound shown in general formula (I): R is nitro; P is 1; R
1represent hydrogen, halogen, C
1~ C
3alkyl, C
1~ C
3alkoxyl group, C
1~ C
3alkylthio, aryloxy, NR
4r
5: R
4and R
5be identical or different, and represent C
1~ C
3alkyl; R
2represent hydrogen, C
1~ C
3alkyl; R
3represent halogen, C
1~ C
3alkyl; R
1, R
2or R
3in hydrogen moiety or be all selected from following in identical or different substituting group replace: halogen; And R=3-NO
2, R
2=CH
3time, R
1≠ 6-Cl, 6-H; R=3-NO
2, R
2=CH (CH
3)
2time, R
1≠ 6-H.
3. Picolinate amino pyridine compound according to claim 1, is characterized in that in the compound shown in general formula (I): R is nitro; P is 1; R
1c
1~ C
3alkoxyl group, NR
4r
5: R
4and R
5be identical or different, and represent C
1~ C
3alkyl; R
2c
1~ C
3alkyl, C
1~ C
3haloalkyl; R
3halogen, C
1~ C
3alkyl, C
1~ C
3haloalkyl.
4. Picolinate amino pyridine compound according to claim 1, is characterized in that in the compound shown in general formula (I): R is nitro; P is 1; R
1methoxyl group, oxyethyl group, propoxy-, N (CH
3)
2; R
2methyl, ethyl; R
3chlorine, trifluoromethyl.
5. Picolinate amino pyridine compound according to claim 1, is characterized in that the compound shown in general formula (I) is:
N-((2-chloropyridine-5-base) methyl)-N-ethyl-3-nitropyridine-2-amine;
N-((2-chloropyridine-5-base) methyl)-N-butyl-3-nitropyridine-2-amine;
The chloro-N-of 6-((2-chloropyridine-5-base) methyl)-3-nitropyridine-2-amine;
6-methoxyl group-N-((2-chloropyridine-5-base) methyl)-N-Methyl-3-nitropyridine-2-amine;
6-oxyethyl group-N-((2-chloropyridine-5-base) methyl)-N-ethyl-3-nitropyridine-2-amine;
6-oxyethyl group-N-((2-chloropyridine-5-base) methyl)-N-Methyl-3-nitropyridine-2-amine;
6-methoxyl group-N-((2-chloropyridine-5-base) methyl)-N-ethyl-3-nitropyridine-2-amine;
6-propoxy--N-((2-chloropyridine-5-base) methyl)-N-ethyl-3-nitropyridine-2-amine;
6-propoxy--N-((2-chloropyridine-5-base) methyl)-N-Methyl-3-nitropyridine-2-amine;
6-methoxyl group-N-((2-chloropyridine-5-base) methyl)-N-butyl-3-nitropyridine-2-amine;
6-phenoxy group-N-((2-chloropyridine-5-base) methyl)-N-ethyl-3-nitropyridine-2-amine;
6-phenoxy group-N-((2-chloropyridine-5-base) methyl)-N-Methyl-3-nitropyridine-2-amine;
6-oxyethyl group-N-((2-chloropyridine-5-base) methyl)-N-propyl group-3-nitropyridine-2-amine;
6-methoxyl group-N-((2-chloropyridine-5-base) methyl)-N-propyl group-3-nitropyridine-2-amine;
6-propoxy--N-((2-chloropyridine-5-base) methyl)-N-propyl group-3-nitropyridine-2-amine;
6-phenoxy group-N-((2-chloropyridine-5-base) methyl)-N-sec.-propyl-3-nitropyridine-2-amine;
6-methylamino-N-((2-chloropyridine-5-base) methyl)-N-Methyl-3-nitropyridine-2-amine;
6-ethylamino--N-((2-chloropyridine-5-base) methyl)-N-Methyl-3-nitropyridine-2-amine;
6-(Pyrrolidine-1-base)-N-((2-chloropyridine-5-base) methyl)-N-Methyl-3-nitropyridine-2-amine;
6-dimethylin-N-((2-chloropyridine-5-base) methyl)-N-ethyl-3-nitropyridine-2-amine;
6-dimethylin-N-((2-chloropyridine-5-base) methyl)-N-Methyl-3-nitropyridine-2-amine;
6-methylthio group-N-((2-chloropyridine-5-base) methyl)-N-Methyl-3-nitropyridine-2-amine;
N-((2-chloropyridine-5-base) methyl)-5-5-flumethiazine-2-amine;
N-((2-chloropyridine-5-base) methyl)-3-chloro-5-trifluoromethylpyridine-2-amine;
The chloro-N-of 6-((2-chloropyridine-5-base) methyl)-N-ethyl-5-cyanopyridine-2-amine;
The chloro-N-of 6-((2-chloropyridine-5-base) methyl)-N-ethyl-nicotinonitrile-2-amine.
6. the preparation method of Picolinate amino pyridine compound according to claim 1, is characterized in that the compound shown in formula (I) is prepared by the reaction below,
Reaction formula 1-1: at solvent N, in dinethylformamide or benzene, toluene, tetrahydrofuran (THF), under alkali sodium hydride or potassium hydroxide, salt of wormwood exist, in 25 ~ 80 DEG C or height under solvent reflux temperature, react to obtain the compound of formula (I) with the compound shown in the compound shown in formula (II) and formula (III);
Reaction formula 1-2: at N, in dinethylformamide or tetrahydrofuran (THF), water, methylene dichloride, benzene, toluene single solvent or their mixed solvent, under alkali sodium hydride or potassium hydroxide, salt of wormwood exist, in room temperature or height under solvent reflux temperature, the compound of formula (V) is reacted to obtain with the compound of the compound shown in formula (II) and formula (IV), in alcohol or water solvent, there is no alkali or adding alkali metallic sodium or sodium alkoxide, sodium hydride, in room temperature or height under solvent reflux temperature, the compound of formula (V) and R
p 1h reacts, and obtains the compound of formula (I);
Reaction formula 2-1: in the mixed solvent of trichloromethane or methylene dichloride, benzene, toluene single solvent or they and water or alcohol, under alkali sodium hydride or sodium hydroxide, salt of wormwood exist, in room temperature or height under solvent reflux temperature, compound shown in formula (VI) reacts with the compound of (VII), the compound of formula (II), add phase-transfer catalyst benzyltriethylammoinium chloride or Tetrabutyl amonium bromide can impel reaction to carry out or accelerated reaction is carried out;
Reaction formula 2-2: at solvent N, in dinethylformamide or ethanol, in room temperature or height under solvent reflux temperature, the compound of the compound shown in formula (VI) and formula (VIII) is obtained by reacting the compound of formula (IX), in solvent methanol or ethanol, in room temperature or height under solvent reflux temperature, the compound hydrazine of formula (IX) or hydrazine hydrate, catalytic hydrogenating reduction, obtain formula (II:R
2=H) compound;
Reaction formula 3: at solvent R
p 1in H, in subzero 15 DEG C or height under solvent reflux temperature, use alkali R
p 1the compound of ONa or sodium hydride, sodium hydroxide, salt of wormwood process general formula (IV), obtains the compound of formula (III);
Reaction formula 3: in aqueous solvent or DMF, in subzero 15 DEG C or height under solvent reflux temperature, uses R
p 1the compound of H and formula (IV) reacts, and obtains the compound of formula (III), adds suitable alkali triethylamine or sodium hydride, sodium hydroxide, reaction can be impelled to carry out for salt of wormwood or accelerated reaction is carried out;
Reaction formula 3: in solvent benzol or toluene, sherwood oil, in subzero 15 DEG C or height under solvent reflux temperature, under alkali sodium hydride or sodium hydroxide, salt of wormwood exist, uses R
p 1the compound of H and formula (IV) reacts to obtain the compound of formula (III);
R, p, R in formula
1, R
2and R
3to have in claim 1 to definition, X ' and X is leavings group fluorine, chlorine, bromine, sulphonate.
7. the Picolinate amino pyridine compound according to any one of Claims 1 to 5 to have the purposes in the medicine of prevention effect to germ or insect, evil mite, weeds in preparation.
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| 吡啶甲胺类化合物的合成及杀虫活性研究进展;冯丽娟;《济宁学院学报》;20090620;第30卷(第3期);第19-21页 * |
| 四类吡啶化合物的合成与生物活性研究;吕兆萍;《中国博士学位论文全文数据库 工程科技I辑》;20090115(第1期);B016-7 * |
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