CN103539778A - Pyridine-pyrazole heterocyclic dihydrazide derivatives as well as preparation method and application thereof - Google Patents

Pyridine-pyrazole heterocyclic dihydrazide derivatives as well as preparation method and application thereof Download PDF

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CN103539778A
CN103539778A CN201310500628.3A CN201310500628A CN103539778A CN 103539778 A CN103539778 A CN 103539778A CN 201310500628 A CN201310500628 A CN 201310500628A CN 103539778 A CN103539778 A CN 103539778A
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chloropyridine
pyrazoles
hydrazine compound
chloro
benzoyl
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宋宝安
骆礼军
薛伟
吴剑
胡德禹
杨松
金林红
袁勤坤
吕明明
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Guizhou University
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Guizhou University
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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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/24—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof containing the groups, or; Thio analogues thereof
    • 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
    • C07D401/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings

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  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
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Abstract

The invention relates to pyridine-pyrazole heterocyclic dihydrazide derivatives as well as a preparation method and application thereof. Specifically, based on the pyrazole amide compounds, the framework bridge amide is transformed into a dihydrazide group, and the obtained derivatives are shown by the general formula I and general formula II, wherein the definition of each substituent group in the general formulas is shown in the specification. The compounds and derivatives thereof have excellent insecticidal activity and can be used for preparing an agricultural pest control medicine.

Description

Pyridine connects pyrazole heterocycle two hydrazide derivatives and its preparation method and application
Technical field
The invention belongs to agricultural insecticidal field.Be specifically related to a kind of new pyridine and connect preparation method and the application thereof of pyrazole heterocycle two hydrazide derivatives.
Background technology
Agricultural insect pests control is the focus of pesticide science research all the time, and the generally use of sterilant, also makes most insects obtain effectively preventing.Yet, application scale due to sterilant in global range constantly expands in recent years, cause the resistance problem that the sterilant of organic synthesis in use produces more to highlight, cause the Pests Damage in agriculture production day by day to increase the weight of, lasting, healthy, orderly development to industries such as Grain Development, vegetables industry and cash crop constitute a serious threat, and Agro-ecology faces severe situation.Therefore, find and to act on the inexorable trend that brand-new target spot, safety, low toxicity are efficient, become novel pesticide research without the micromolecular compound of cross resistance.
In recent years, agricultural chemicals containing heterocycle is more and more, the adjacent formamido-benzamide insecticides that the chlorantraniliprole of wherein take is representative, it is effective sterilant of the control lepidoptera pest developed in recent years, there is insecticidal activity high, insecticidal spectrum is wide, to Mammals and the low and good environmental resistance of hydrocoles toxicity etc., becomes the hot fields of novel pesticide initiative exploitation.In addition, du pont company, Japan agricultural chemicals company, Beyer Co., Ltd and more domestic scholars have also reported to have in a large number bioactive compound to this field, (for example applied for the patent of a large amount of association areas, US 2004242645A1, US 2008275065A1, US 2009181956A1, US 2010137314A1, US 2011071291A1, WO 2004033468A1, WO 03016283A1, WO 2005085234A2, WO 2006040113A2, WO 2006061200A1, WO 2006102025A1, WO 2008072745A1, WO 03016300A1, EP 2143721A1, CN 101298451A, CN 101298435A, CN 101659655A, CN 101570535A, CN 101845043A, CN 101333213A, CN 102260245A, CN 102276580A, CN 101735199A etc.).But compound and insecticidal activity thereof related in the present invention do not have patent literature.
Summary of the invention
The object of the invention is to synthesize a class insect is had to good preventive effect, and the new pyridine with features such as efficient, safety low-poison, environmental friendliness connects pyrazole heterocycle two hydrazide kind compounds, for the sterilant of control crop pest.
The invention provides a class new pyridine and connect pyrazole heterocycle two hydrazide derivatives, it has following general formula iand general formula iIshown structural formula:
Figure 842449DEST_PATH_IMAGE001
In formula:
R 1for the monosubstituted base on phenyl or the aromatic ring of multi-substituent, substituting group is hydrogen, methyl and chlorine;
R 2for containing singly getting or the heteroaryl acid of multi-substituent, as 2-chloro-3-pyridyl formic acid, acidum nicotinicum and the bromo-acidum nicotinicum of 5-;
R 3for adjacent on phenyl,, the monosubstituted base of contraposition, a plurality of substituting groups or not substituent aromatic ring, its substituting group be respectively methyl, methoxyl group, n,N-dimethyl, trifluoromethyl, trifluoromethoxy, nitro, halogen atom and benzo-heterocycle are as Ben Bing Evil dioxane etc., and its halogen atom is respectively fluorine, chlorine, bromine;
R 4for Cl and Br.
With the compound of listing in table 1, further illustrate general formula I of the present invention and general formula I I compound, but do not limit the present invention.
Table 1
Figure 323372DEST_PATH_IMAGE002
Figure 103109DEST_PATH_IMAGE003
General formula of the present invention iand general formula iIshown derivative preparation method:
1, synthetic route and the Method and process condition of preparing target compound I are:
With 3-bromine/chloro-1-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formic acid, oxalyl chloride and the different phenylformic acid replacing are raw material, and synthetic through four-step reactions such as esterification, hydrazinolysis, amidations, its synthetic route is:
Figure 2013105006283100002DEST_PATH_IMAGE004
Its preparation method and processing condition are as follows:
The first step: preparation is containing the methyl benzoate of different substituents 2reference literature ( j. Agric.Food Chem. 2012. 60,1036-1041.)
Second step: preparation is containing the benzoyl hydrazine of different substituents 3reference literature ( j. Agric.Food Chem. 2012. 60,1036-1041.)
The 3rd step: prepare target compound i
Take 1-(3-chloropyridine-2-yl)-3-bromine/chloro-1 h-pyrazoles-5-formic acid 0.86 mmol puts into in thermometer, prolong, drying tube, 50 mL there-necked flasks, measures 20 dry mL CH 2cl 2in system, then take 2.58 mmol oxalyl chlorides and be added drop-wise to system, stir, and drip 3 DMF in system, at room temperature stirring reaction 3 h, by reaction system concentrating under reduced pressure, obtain yellowish/brown solid, are directly used in the next step; Take 0.73 mmol containing different substituents benzoyl hydrazine 3put in the 50 mL there-necked flasks with ice bath with 0.95 mmol triethylamine, measure 20 dry mL THF in system, after stirring reaction 10 min, again yellowish/brown solid be dissolved in to 5 dry mL THF and be slowly added drop-wise in above-mentioned system, 10 min dropwise and remove ice bath, and TLC follows the tracks of reaction, at room temperature react 0.5 h, after TLC shows that raw material reaction is completely, stopped reaction.System is proceeded in the beaker that fills 30 mL water, use 1% NaHCO 3solution regulates pH of mixed to 9 ~ 10, dichloromethane extraction (3 * 20 mL), and combined dichloromethane layer with saturated NaCl solution washing, then use anhydrous Na 2sO 4dried overnight, filters, and solvent is sloughed in decompression, then uses dehydrated alcohol recrystallization, obtains corresponding target compound.
2, synthetic route and the Method and process condition of preparing target compound II are:
With 3-bromine/chloro-1-(3-chloropyridine-2-yl)-1 hthe phenylformic acid that-pyrazoles-5-formic acid, oxalyl chloride, difference replace and the heterocyclic acids that contains different substituents are raw material, and synthetic through four-step reactions such as cyclocondensation, hydrazinolysis, amidations, its synthetic route is:
Figure 560635DEST_PATH_IMAGE005
Its preparation method and processing condition are as follows:
The first step: preparation is containing different substituents oxazinone 5reference literature ( chemistry Central Journal. 2013. 7,64-70.)
Second step: preparation is containing the adjacent formamido-benzoyl hydrazine of different substituents 6reference literature ( chemistry Central Journal.2013. 7,64-70.)
The 3rd step: prepare target compound iI
Take 1-(3-chloropyridine-2-yl)-3-bromine/chloro-1 h-pyrazoles-5-formic acid 0.86 mmol puts into in thermometer, prolong, drying tube, 50 mL there-necked flasks, measures 20 dry mL CH 2cl 2in system, then take 2.58 mmol oxalyl chlorides and be added drop-wise to system, stir, and drip 3 DMF in system, at room temperature stirring reaction 3 h, by reaction system concentrating under reduced pressure, obtain yellowish/brown solid, are directly used in the next step; Take 0.84 mmol containing the adjacent formamido-benzoyl hydrazine of different substituents 6put in the 50 mL there-necked flasks with ice bath with 0.95 mmol triethylamine, measure 20 dry mL THF in system, after stirring reaction 10 min, again yellowish/brown solid be dissolved in to 5 dry mL THF and be slowly added drop-wise in above-mentioned system, 10 min dropwise and remove ice bath, and TLC follows the tracks of reaction, at room temperature react 0.5 h, after TLC shows that raw material reaction is completely, stopped reaction.System is proceeded in the beaker that fills 30 mL water, use 1% NaHCO 3solution regulates pH of mixed to 9 ~ 10, dichloromethane extraction (3 * 20 mL), and combined dichloromethane layer with saturated NaCl solution washing, then use anhydrous Na 2sO 4dried overnight, filters, and solvent is sloughed in decompression, then uses dehydrated alcohol recrystallization, obtains corresponding target compound.
Above-mentioned preparation connects the Method and process condition of pyrazole heterocycle two hydrazide derivatives containing pyridine, when 1-(3-chloropyridine-2-yl)-3-bromine/chloro-1 hwhen the input amount of-pyrazoles-5-formic acid changes, all the other reagent dosages are done respective change in proportion.
According to invention route and preparation method, be applicable to above-mentionedly containing pyridine, connect the synthetic of pyrazole heterocycle two hydrazide derivatives.
According to invention route and preparation method, synthesized and proved that the compound of insecticidal activity is as follows:
Compound I-01:
nthe bromo-1-of-(4-chlorobenzene formacyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-02:
nthe bromo-1-of-(4-fluoro benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-03:
nthe bromo-1-of-(benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I I-04:
n-[2-(the bromo-5-pyridine carboxamide of 3-) benzoyl] the bromo-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I I-05:
n-[2-(2-chloro-3-pyridyl methane amide)-3-methyl-5-chloro benzoyl] the bromo-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I I-06:
n-[2-(2-chloro-3-pyridyl methane amide)-3-methyl-benzoyl] the bromo-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-07:
nthe bromo-1-of-(2,6-difluoro benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-08:
nthe bromo-1-of-(2-methyl benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-09:
nthe chloro-1-of-(4-fluoro benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-10:
nthe chloro-1-of-(4-chlorobenzene formacyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-11:
nthe bromo-1-of-methyl-formiate-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-12:
nthe bromo-1-of-(3-fluoro benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-13:
nthe chloro-1-of-(2-fluoro benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-14:
nthe chloro-1-of-(2-methyl benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-15:
n-(3,4-dimethoxy benzoyl) the bromo-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound 16:
nthe bromo-1-of-(3,5-dimethylbenzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-17:
n-(3,4-dimethoxy benzoyl) the chloro-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-18:
n-(3-methyl-4-nitro benzoyl) the bromo-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-19:
nthe chloro-1-of-(benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-20:
nthe chloro-1-of-(3,5-dimethylbenzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-21:
n-(3,5-dichloro-benzoyl base) the bromo-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-22:
n-(3-trifluoromethyl benzoyl) the bromo-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-23:
nthe chloro-1-of-(2,6-difluoro benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-24:
n-(Isosorbide-5-Nitrae-benzodioxan-6-formyl radical) the chloro-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-25:
n-(Isosorbide-5-Nitrae-benzodioxan-6-formyl radical) the bromo-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-26:
n-(Isosorbide-5-Nitrae-benzodioxan-5-formyl radical) the bromo-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-27:
n-(3-( n,N-dimethyl) the bromo-1-of benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-28:
n-(3-( n,N-dimethyl) the chloro-1-of benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-29:
nthe bromo-1-of-(3-anisoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-30:
nthe chloro-1-of-(3-anisoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-31:
n-(Isosorbide-5-Nitrae-benzodioxan-5-formyl radical) the chloro-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-32:
nthe chloro-1-of-(3-fluoro benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-33:
n-(3-methyl-4-nitro benzoyl) the chloro-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-34:
n-(3,5-dichloro-benzoyl base) the chloro-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-35:
n-(4-trifluoromethyl benzoyl) the chloro-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
General formula of the present invention iand general formula iIcompound there is higher insecticidal activity, mainly the insects such as small cabbage moth, water rice hopper are had to good prevention effect.Therefore, general formula of the present invention iand general formula iIcompound can be used for candidate's insecticidal materials of preparation control agricultural insect pest.
Embodiment
Below in conjunction with embodiment, further illustrate the present invention, its object is to understand better content of the present invention and substantive distinguishing features of the present invention, so the cited case should not be considered as the restriction of protection scope of the present invention.
embodiment 1: the preparation of Compound I
The preparation of Compound I-01:
Figure 2013105006283100002DEST_PATH_IMAGE006
Take 0.26 g(0.86 mmol) 1-(3-chloropyridine-2-yl)-3-bromo-1 h-pyrazoles-5-formic acid is put into in thermometer, prolong, drying tube, 50 mL there-necked flasks, measures 20 dry mL CH 2cl 2in system, then taking 0.33 g(2.58 mmol) oxalyl chloride is added drop-wise to system, stirs, and drip 3 DMF in system, at room temperature, after stirring reaction 3 h, system is proceeded in single port bottle, precipitation under underpressure distillation, obtains faint yellow solid (being directly used in the next step).Take 0.12 g(0.73 mmol) 4-chlorobenzoyl hydrazine and 0.10 g(0.95 mmol) triethylamine puts in the 50 mL there-necked flasks with ice bath, measures 20 dry mL THF in system, after stirring reaction 10 min; After brown solid being dissolved in to 5 mL THF, be also slowly added drop-wise in above-mentioned system, 10 min dropwise and remove ice bath again, and TLC follows the tracks of reaction, at room temperature reacts 0.5 h, after TLC shows that raw material reaction is completely, and stopped reaction.System is proceeded in the beaker that fills 30 mL water, use 1% NaHCO 3solution regulates pH of mixed to 9 ~ 10, dichloromethane extraction (3 * 20 mL), and combined dichloromethane layer with saturated NaCl solution washing, then use anhydrous Na 2sO 4dried overnight, filters, and solvent is sloughed in decompression, then uses dehydrated alcohol recrystallization, obtains white solid, quality m=0.29 g, yield 90.6 %, m.p.:235 ~ 236 ℃.
Compound I-02, I-03, I-07～I-35 are except different substituted benzoic acids, and all the other conditions and synthetic method are as the preparation of embodiment mono-Compound I-01.
embodiment bis-: the preparation of Compound I I
The preparation of Compound I I-04:
Figure 375007DEST_PATH_IMAGE007
Take 0.26 g(0.86 mmol) 1-(3-chloropyridine-2-yl)-3-bromo-1 h-pyrazoles-5-formic acid is put into in thermometer, prolong, drying tube, 50 mL there-necked flasks, measures 20 dry mL CH 2cl 2in system, then taking 0.33 g(2.58 mmol) oxalyl chloride is added drop-wise to system, stirs, and drip 3 DMF in system, at room temperature, after stirring reaction 3 h, system is proceeded in single port bottle, precipitation under underpressure distillation, obtains faint yellow solid (being directly used in the next step).Take 0.12 g(0.73 mmol) 4-chlorobenzoyl hydrazine and 0.10 g(0.95 mmol) triethylamine puts in the 50 mL there-necked flasks with ice bath, measures 20 dry mL THF in system, after stirring reaction 10 min; After brown solid being dissolved in to 5 mL THF, be also slowly added drop-wise in above-mentioned system, 10 min dropwise and remove ice bath again, and TLC follows the tracks of reaction, at room temperature reacts 0.5 h, after TLC shows that raw material reaction is completely, and stopped reaction.System is proceeded in the beaker that fills 30 mL water, use 1% NaHCO 3solution regulates pH of mixed to 9 ~ 10, dichloromethane extraction (3 * 20 mL), and combined dichloromethane layer with saturated NaCl solution washing, then use anhydrous Na 2sO 4dried overnight, filters, and solvent is sloughed in decompression, then uses dehydrated alcohol recrystallization, obtains white solid, quality m=0.29 g, yield 90.6 %, m.p.:235 ~ 236 ℃.
Compound I I-05, II-06 are except the substituted benzoic acid with different with containing different substituent heterocyclic acids, and all the other conditions and synthetic method are with the preparation of embodiment bis-Compound I I-04.
Table 2: list part general formula iand general formula iIcompound number and compound structure:
Figure 259786DEST_PATH_IMAGE008
Figure 526820DEST_PATH_IMAGE009
Figure 725720DEST_PATH_IMAGE010
Table 3: list general formula iand general formula iIcompound 1h-NMR, 13c-NMR, IR and ultimate analysis data:
Figure 2013105006283100002DEST_PATH_IMAGE011
Figure 456916DEST_PATH_IMAGE012
Figure 2013105006283100002DEST_PATH_IMAGE013
Figure 34569DEST_PATH_IMAGE014
Figure 788898DEST_PATH_IMAGE016
Figure 2013105006283100002DEST_PATH_IMAGE017
Figure 588227DEST_PATH_IMAGE018
biological activity test example
embodiment tri-:
Biological activity determination to Brown Planthopper :take respectively 5.0 mg testing compounds with 200 μl DMSO is 500 mg/L with containing 0.1 % tween-80 solution dilution to concentration after dissolving.Employing is soaked leaf feeding method and is measured: fresh water rice plants is flooded to 10 s aftertreatment examination worms in liquid.Each medicine is processed 3 times and is repeated, and each repeats 10 examination worms, take immersion solvent as contrast, and the examination worm after processing is put into the culture dish of filter paper moisturizing, and is placed in thermostat container and raises.The dead borer population of investigation 3d, statistics insect population mortality ratio.Under 500 mg/L mass concentrations, part of compounds is as shown in table 4 below to the lethality rate of Brown Planthopper.
Table 4: under 500 mg/L mass concentrations, the lethality rate of part of compounds to Brown Planthopper
Figure 2013105006283100002DEST_PATH_IMAGE021
embodiment tetra-:
Biological activity determination to small cabbage moth: take respectively 5.0 mg testing compounds with 300 μl DMSO is 500 mg/L with containing 0.1 % tween-80 solution dilution to concentration after dissolving.Employing is soaked leaf feeding method and is measured: fresh cabbage leaves is placed on and in liquid, floods 10 s aftertreatments examination worms.Each medicine is processed 3 times and is repeated, and each repeats 10 examination worms, take immersion solvent as contrast, and the examination worm after processing is put into the culture dish of filter paper moisturizing, and is placed in thermostat container and raises.The dead borer population of investigation 3d, statistics insect population mortality ratio.Under different concns, part of compounds is as shown in table 5 below to the lethality rate of small cabbage moth.
Table 5: the lethality rate of part of compounds to small cabbage moth under different concns
Figure DEST_PATH_IMAGE022
Figure 2013105006283100002DEST_PATH_IMAGE023

Claims (6)

1. pyridine connects pyrazole heterocycle two hydrazide derivatives, and its main feature is as general formula iand general formula iIshown in:
In formula:
R 1for the monosubstituted base on phenyl or the aromatic ring of multi-substituent, substituting group is hydrogen, methyl and chlorine;
R 2for containing singly getting or the heterocyclic acids of multi-substituent, as 2-chloro-3-pyridyl formic acid, acidum nicotinicum and the bromo-acidum nicotinicum of 5-;
R 3for adjacent on phenyl,, the monosubstituted base of contraposition, a plurality of substituting groups or not substituent aromatic ring, these substituting groups are respectively methyl, methoxyl group, N, N-dimethyl, trifluoromethyl, trifluoromethoxy, nitro, halogen atom and benzo-heterocycle are as Ben Bing Evil dioxane etc., and its halogen atom is respectively fluorine, chlorine, bromine;
R 4for Cl and Br.
2. a kind of pyridine according to claim 2 connects pyrazole heterocycle two hydrazide kind compounds, it is characterized in that described compound is as follows:
Compound I-01:
nthe bromo-1-of-(4-chlorobenzene formacyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-02:
nthe bromo-1-of-(4-fluoro benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-03:
nthe bromo-1-of-(benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I I-04:
n-[2-(the bromo-5-pyridine carboxamide of 3-) benzoyl] the bromo-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I I-05:
n-[2-(2-chloro-3-pyridyl methane amide)-3-methyl-5-chloro benzoyl] the bromo-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I I-06:
n-[2-(2-chloro-3-pyridyl methane amide)-3-methyl-benzoyl] the bromo-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-07:
nthe bromo-1-of-(2,6-difluoro benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-08:
nthe bromo-1-of-(2-methyl benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-09:
nthe chloro-1-of-(4-fluoro benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-10:
nthe chloro-1-of-(4-chlorobenzene formacyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-11:
nthe bromo-1-of-methyl-formiate-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-12:
nthe bromo-1-of-(3-fluoro benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-13:
nthe chloro-1-of-(2-fluoro benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-14:
nthe chloro-1-of-(2-methyl benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-15:
n-(3,4-dimethoxy benzoyl) the bromo-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-16:
nthe bromo-1-of-(3,5-dimethylbenzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-17:
n-(3,4-dimethoxy benzoyl) the chloro-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-18:
n-(3-methyl-4-nitro benzoyl) the bromo-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-19:
nthe chloro-1-of-(benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-20:
nthe chloro-1-of-(3,5-dimethylbenzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-21:
n-(3,5-dichloro-benzoyl base) the bromo-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-22:
n-(3-trifluoromethyl benzoyl) the bromo-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-23:
nthe chloro-1-of-(2,6-difluoro benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-24:
n-(Isosorbide-5-Nitrae-benzodioxan-6-formyl radical) the chloro-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-25:
n-(Isosorbide-5-Nitrae-benzodioxan-6-formyl radical) the bromo-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-26:
n-(Isosorbide-5-Nitrae-benzodioxan-5-formyl radical) the bromo-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-27:
n-(3-( n,N-dimethyl) the bromo-1-of benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-28:
n-(3-( n,N-dimethyl) the chloro-1-of benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-29:
nthe bromo-1-of-(3-anisoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-30:
nthe chloro-1-of-(3-anisoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-31:
n-(Isosorbide-5-Nitrae-benzodioxan-5-formyl radical) the chloro-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-32:
nthe chloro-1-of-(3-fluoro benzoyl)-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-33:
n-(3-methyl-4-nitro benzoyl) the chloro-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-34:
n-(3,5-dichloro-benzoyl base) the chloro-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine
Compound I-35:
n-(4-trifluoromethyl benzoyl) the chloro-1-of-3-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formyl hydrazine.
3. according to pyridine claimed in claim 1, connect the preparation method of pyrazole heterocycle two hydrazide derivatives, it is characterized in that synthetic route is:
(1) synthetic route of Compound I:
With 3-bromine/chloro-1-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formic acid, oxalyl chloride and the phenylformic acid that replace containing difference are raw material, through four-step reactions such as esterification, hydrazinolysis, amidations, synthesize, and its synthetic route is:
(2) synthetic route of Compound I I:
With 3-bromine/chloro-1-(3-chloropyridine-2-yl)-1 h-pyrazoles-5-formic acid, oxalyl chloride and containing Bu Tong monosubstituted, two replace or without the anthranilic acid replacing and be raw material containing the heterocyclic acids of different replacements, through four-step reactions such as cyclocondensation, hydrazinolysis, amidations, synthesize, its synthetic route is:
Figure 2013105006283100001DEST_PATH_IMAGE005
?。
4. preparation connects the method for pyrazole heterocycle two hydrazide derivatives containing pyridine according to claim 3, comprise the intermediate 2 of Compound I and 3 existing preparation method and processing condition, comprise the intermediate 5 of Compound I I and 6 existing preparation method and processing condition, it is characterized in that:
(1) preparation contains the Method and process condition of the target compound I of different substituents:
Take 1-(3-chloropyridine-2-yl)-3-bromine/chloro-1 h-pyrazoles-5-formic acid 0.86 mmol puts into in thermometer, prolong, drying tube, 50 mL there-necked flasks, measures 20 dry mL CH 2cl 2in system, then take 2.58 mmol oxalyl chlorides and be added drop-wise to system, stir, and drip 3 DMF in system, at room temperature stirring reaction 3 h, by reaction system concentrating under reduced pressure, obtain yellowish/brown solid, are directly used in the next step; Take 0.73 mmol containing different substituents benzoyl hydrazine 3put in the 50 mL there-necked flasks with ice bath with 0.95 mmol triethylamine, measure 20 dry mL THF in system, after stirring reaction 10 min, more yellowish/brown solid is dissolved in to 5 dry mL THF and is slowly added drop-wise in above-mentioned system, 10 min dropwise and remove ice bath, TLC follows the tracks of reaction, at room temperature react 0.5 h, after TLC shows that raw material reaction is completely, stopped reaction, system is proceeded in the beaker that fills 30 mL water, use 1% NaHCO 3solution regulates pH of mixed to 9～10, dichloromethane extraction (3 * 20 mL), and combined dichloromethane layer with saturated NaCl solution washing, then use anhydrous Na 2sO 4dried overnight, filters, and solvent is sloughed in decompression, then uses dehydrated alcohol recrystallization, obtains corresponding target compound;
(2) preparation is containing the target compound of different substituents iImethod and process condition:
Take 1-(3-chloropyridine-2-yl)-3-bromine/chloro-1 h-pyrazoles-5-formic acid 0.86 mmol puts into in thermometer, prolong, drying tube, 50 mL there-necked flasks, measures 20 dry mL CH 2cl 2in system, then take 2.58 mmol oxalyl chlorides and be added drop-wise to system, stir, and drip 3 DMF in system, at room temperature stirring reaction 3 h, by reaction system concentrating under reduced pressure, obtain yellowish/brown solid, are directly used in the next step; Take 0.84 mmol containing the adjacent formamido-benzoyl hydrazine of different substituents 6put in the 50 mL there-necked flasks with ice bath with 0.95 mmol triethylamine, measure 20 dry mL THF in system, after stirring reaction 10 min, more yellowish/brown solid is dissolved in to 5 dry mL THF and is slowly added drop-wise in above-mentioned system, 10 min dropwise and remove ice bath, TLC follows the tracks of reaction, at room temperature react 0.5 h, after TLC shows that raw material reaction is completely, stopped reaction, system is proceeded in the beaker that fills 30 mL water, use 1% NaHCO 3solution regulates pH of mixed to 9 ~ 10, dichloromethane extraction (3 * 20 mL), and combined dichloromethane layer with saturated NaCl solution washing, then use anhydrous Na 2sO 4dried overnight, filters, and solvent is sloughed in decompression, then uses dehydrated alcohol recrystallization, obtains corresponding target compound.
5. preparation according to claim 4 connects the method for pyrazole heterocycle two hydrazide derivatives containing pyridine, it is characterized in that 1-(3-chloropyridine-2-yl)-3-bromine/chloro-1 hwhen the input amount of-pyrazoles-5-formic acid changes, all the other reagent dosages are done respective change in proportion.
6. according to connecting pyrazole heterocycle two hydrazide derivatives and there is excellent insecticidal activity containing pyridine described in claim 1 ~ 2, small cabbage moth and brown paddy plant hopper etc. is had to good prevention effect, can be used for candidate's insecticidal materials of preparation control agriculture and forestry injurious insect.
CN201310500628.3A 2013-10-23 2013-10-23 Pyridine-pyrazole heterocyclic dihydrazide derivatives as well as preparation method and application thereof Pending CN103539778A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105777639A (en) * 2016-01-26 2016-07-20 浙江博仕达作物科技有限公司 Pyrazole hydrazide compound and use thereof
CN111187214A (en) * 2020-01-14 2020-05-22 青岛科技大学 Fluorobenzene bishydrazide azole compound and application thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
谭成侠等: "1-吡唑甲酰基-2-芳基酰肼类化合物的合成及生物活性", 《农药学学报》 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105777639A (en) * 2016-01-26 2016-07-20 浙江博仕达作物科技有限公司 Pyrazole hydrazide compound and use thereof
WO2017128942A1 (en) * 2016-01-26 2017-08-03 浙江博仕达作物科技有限公司 Pyrazole hydrazide compound and use thereof
CN111187214A (en) * 2020-01-14 2020-05-22 青岛科技大学 Fluorobenzene bishydrazide azole compound and application thereof
CN111187214B (en) * 2020-01-14 2022-09-16 青岛科技大学 Fluorobenzene bishydrazide azole compound and application thereof

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