CN1062071A - Contain the Pesticidal combination and the application thereof of new azole derivatives - Google Patents

Contain the Pesticidal combination and the application thereof of new azole derivatives Download PDF

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Publication number
CN1062071A
CN1062071A CN91111112A CN91111112A CN1062071A CN 1062071 A CN1062071 A CN 1062071A CN 91111112 A CN91111112 A CN 91111112A CN 91111112 A CN91111112 A CN 91111112A CN 1062071 A CN1062071 A CN 1062071A
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China
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represent
pyrroles
base
formula
propinyl
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Inventor
琼·特斯尔
琼-皮埃尔·德穆特
布伦特·塔利安尼
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Sanofi Aventis France
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Roussel Uclaf SA
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Priority claimed from FR8506134A external-priority patent/FR2580637B2/en
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Abstract

The invention provides a kind of azole derivatives that contains chemical formula (I) is the Pesticidal combination of active component, R in the chemical formula 1, R 2, R 3, R 4And R 5Be defined in the specification and claims.This Pesticidal combination can be used as miticide, nematocide and insecticide.

Description

Contain the Pesticidal combination and the application thereof of new azole derivatives
The purpose of this invention is to provide the Pesticidal combination and the application thereof that contain new azole derivatives.The general formula of this derivative is:
Figure 911111123_IMG19
（Ⅰ）
Wherein:
-R 2Or R 3One of represent group
(wherein A is analogy chrysanthemic acid (pyrethrinoid acid) ACO 2The residue of H, Z are represented H, C ≡ N, C ≡ CH, CF 3, or the alkyl of 1-3 carbon.）
-another does not represent the R of above-mentioned group 2Or R 3, and R 4And R 5(being same to each other or different to each other) but hydrogen atom, fontanelle atom, up to the alkyl of 18 carbon, up to the aryl of 14 carbon, up to the aralkyl of 18 carbon, cyano group, CF 3, up to the CO of 8 carbon 2-alkyl, NO 2, up to the alkoxyl of 8 carbon, and group ; Or
Figure 911111123_IMG22
(n=0 wherein, 1 or 2; R ', R ' 1, R ' 2Represent the alkyl of 1-8 carbon atom), R 4And R 5Can form saturated or undersaturated, up to the carbocyclic ring of 8 carbon atoms.
-R 1Representative:
-
Figure 911111123_IMG23
≡ C-Y wherein X and Y(is same to each other or different to each other) represent hydrogen atom, fontanelle atom, the alkyl of 1-8 carbon atom, or up to the aryl of 14 carbon;
-or Wherein " (being same to each other or different to each other) represents a group in top X and the Y definition, and dotted line is illustrated in two keys that may form between 1 carbon and 2 carbon for X ', Y ', Y;
-or
Figure 911111123_IMG25
The wherein definition of γ ' and top R 4And R 5The definition unanimity, but do not comprise halogen, cyano group, NO 2,
Figure 911111123_IMG26
(n=1 or 2), and
Figure 911111123_IMG27
Group;
-or
Figure 911111123_IMG28
Wherein R " and R ' " (identical or different) represents hydrogen atom, and the alkyl of 1-18 carbon is up to the aryl of 14 carbon, up to the aralkyl of 18 carbon, CF 3, up to the CO of 8 carbon 2-alkyl is up to the alkoxyl of 8 carbon.
Said analogy chrysanthemic acid (pyrethrinoid acid) promptly is ACO 2H can be used as the intermediate of pyrethroid (pyrethrinoid) derivative of preparation biologically active.
When Z represents alkyl, methyl preferably.
When a substituting group of mentioning in general formula (1) definition is alkyl, preferably methyl, ethyl, n-pro-pyl, isopropyl, butyl, isobutyl group or n-pentyl.
When a substituting group of mentioning in general formula (1) definition is represented halogen atom, preferably fluorine, bromine or chlorine atom.
When a substituting group of mentioning in general formula (1) definition was represented aryl, it is phenyl preferably, and this aryl can be substituted, particularly by the alkyl of 1-8 carbon or alkoxyl, NO 2, CF 2, OH, halogen, the amino replacement.
When a substituting group of mentioning in general formula (1) definition is represented aralkyl, benzyl preferably.
A substituting group of mentioning in general formula (I) definition is represented CO 2When-alkyl or alkoxyl, " alkyl " be methyl preferably, ethyl, propyl group or isopropyl; " alkoxyl " be methoxyl group, ethyoxyl, propoxyl group or isopropoxy preferably.
Work as R 4And R 5When forming carbocyclic ring, the ring of 4 or 5 carbon atoms is arranged preferably.
The present invention provides preparation to have R in general formula (I) and (I) especially 1Representative-CH 2The method of the compound of-C ≡ CH group.
In the compound according to qualifications that obtains by the inventive method, can list group:
Figure 911111123_IMG29
Middle substituting group Z is those compounds of hydrogen atom or cyano group.
Those substituent R 2For
Figure 911111123_IMG30
The compound of group also can be classified the compound according to qualifications that obtains by the inventive method as.
The present invention also provides preparation to have general formula (I) especially, and substituent R in (I) 2, R 4, and R 5Respectively be the compound of hydrogen atom, and R 2, R 4And R 5Method for the compound of nitro or trifluoromethyl.
The present invention especially provides preparation to have the method for the compound of general formula (I), it is characterized in that:
-A represents group:
Figure 911111123_IMG31
Wherein:
-Z 1And Z 2Be respectively methyl,
-or Z 1Be hydrogen atom, and
-Z 2Represent group
Figure 911111123_IMG32
Z wherein 3Be hydrogen or halogen atom, T 1And T 2(identical or different) represents the alkoxyl or the alkyl of hydrogen atom, halogen atom, a 1-8 carbon, CF 3, or CN, or the phenyl ring that can be replaced by halogen, perhaps T 1And T 2Form the cycloalkyl of 3-6 carbon, or group:
Wherein B is oxygen or sulphur atom;
-or Z 2Represent group
Figure 911111123_IMG34
A wherein, b, c, d, (identical or different) respectively is halogen atom;
-or Z 2Represent group
Figure 911111123_IMG35
Wherein D represents hydrogen or halogen atom, the alkoxyl of 1-8 carbon; G is oxygen or sulphur atom; J or be the saturated or unsaturated alkyl of 1-8 carbon straight chain, side chain or ring-type, this alkyl can be replaced by one or more identical or different functional groups; Or be aryl 6-14 carbon, that can be replaced by one or more identical or different functional groups; Or be can be by the heterocyclic radical of one or more identical or different functional groups replacement;
-or A represent group
Figure 911111123_IMG36
Wherein U can represent halogen atom, the alkyl of 1-8 carbon or alkoxyl, m=0,1 or 2 on any position of phenyl ring.
Work as T 1, T 2, Z 3When being halogen atom, preferably fluorine, chlorine, bromine atoms.
Work as T 1Or T 2When expression alkyl or alkoxyl, preferably methyl, ethyl, n-pro-pyl, methoxyl group, ethyoxyl or positive propoxy.
A, b, c, d, be preferably the chlorine or bromine atom.
When D represents halogen atom, preferably fluorine, chlorine or bromine atom.
When alkyl that J represents to be replaced by one or more functional groups, alkyl is the alkyl of 1-8 carbon preferably, as methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, or tertiary butyl.A kind of functional group that functional group lists in disclosed european patent application (No. 50534).
J also can represent by aryl, especially the alkyl that may be replaced by phenyl.
When alkyl that J represents to be replaced by one or more functional groups, following groups is the best substituted alkyl of J;
--(CH 2) N1-CH al 3N wherein 1Be the integer of 1-8, Hal is a halogen atom, as :-CH 2-CCl 3,-CH 2-CF 3,-CH 2-CH 2-CCl 3, or-CH 2-CH 2-CF 3;
--(CH 2) N2-CHHal 2Wherein the Hal definition is the same, n 2Be the integer of 0-8, as :-CH 2-CHcl 2,-CH 2-CHF 2, or-CHF 3;
--(CH 2) N1-CH 2Hal is n wherein 1The same with the Hal definition, as :-CH 2-CH 2Cl, or-CH 2-CH 2F;
--C-(CHal 3) 3, wherein the Hal definition is the same, as :-C-(CF 3) 3,
Figure 911111123_IMG37
Or-(CH 2) wherein the definition of n is the same for n-CN;
Figure 911111123_IMG38
Wherein the Hal definition is the same, as:
Figure 911111123_IMG39
;
--(CH 2) n 1-ORa, wherein n 1Define the samely, Ra represents hydrogen atom, or 1-8 carbon straight or branched alkyl, as :-CH 2-OCH 3,-CH 2-CH 2-O-CH 3,-CH 2-CH 2-O-CH 2-CH 3, or-CH 2-CH 2-OH;
Figure 911111123_IMG40
Figure 911111123_IMG41
N wherein 1Define the same, as
Figure 911111123_IMG42
; When J representative-can substituted aryl, preferably can substituted phenyl.
When J represents heterocyclic radical, pyridine radicals preferably, furyl, thienyl, oxazolyl or thiazolyl.
In the according to qualifications compound that obtains with the inventive method, can list A and represent group
Figure 911111123_IMG43
Compound, Hal represents halogen atom in the formula, as chlorine, or bromine atoms.
Also can list A and represent group
Figure 911111123_IMG44
Compound, J represents straight chain, side chain or the cyclic alkyl of 1-8 carbon in the formula, two key geometric configurations are cis (Z).In these compounds, the best represent methylidene of J, ethyl, n-pro-pyl, isopropyl or the tert-butyl group.
Also can enumerate and have general formula (I), and A represents group
Figure 911111123_IMG45
Compound.Hal represents halogen atom in this formula, and J represents the alkyl of 1-8 carbon, and two key geometric configurations are trans (E).
In these compounds, the best represent methylidene of J, ethyl, n-pro-pyl, isopropyl or the tert-butyl group.
The present invention provides especially that A represents group in the preparation general formula
The method of compound.In the according to qualifications compound that obtains by the inventive method, can list general formula with following title compound for (I):
-1R, along (△ E) 2,2-dimethyl-3-(3-ethyoxyl-3-oxo-2-fluoro-1-acrylic) cyclopropane-carboxylic acid (1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters;
-1R, along (△ Z) 2,2-dimethyl-3-(3-methoxyl group-3-oxo-1-acrylic) cyclopropane-carboxylic acid (1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters;
-1R, along (△ E) 2,2-dimethyl-3-(3-ethyoxyl-3-oxo-2-fluoro-1-acrylic) cyclopropane-carboxylic acid (1-(2-propinyl)-2-Trifluoromethyl-1 H-pyrroles-3-yl) methyl esters;
-1R, along (△ E) 2,2-dimethyl-uncle 3-(3--butoxy-3-oxo-2-fluoro-1-acrylic)-cyclopropane-carboxylic acid (1-(2-propinyl)-2-Trifluoromethyl-1 H-pyrroles-3-yl) methyl esters.
General formula is the preparation method of the compound of (I), it is characterized in that general formula is (II)
Figure 911111123_IMG47
（Ⅱ）
Alcohol be subjected to general formula and be
Figure 911111123_IMG48
Acid of (III) (definition of A is consistent with the front) or functional group derivant's that should acid effect.In general formula (II), R 3" and R 3" one of represent group
Figure 911111123_IMG49
（Ⅲ）
Wherein the definition of Z is consistent with the front, another R 2" or R 3" and R 4And R 5Keep the front and give a definition R 1Definition and front consistent.
The most handy acid chloride of functional group derivant of acid.
When general formula is the acid and when reaction alcohol of (III), is preferably in dicyclohexyl carbodiimide and carries out under existing.
R in the preparation general formula (I) 1The method that comprises the compound of carbon-carbon double bond, its special card are to handle the corresponding derivative that contains three key-carry out in the presence of as year palladium barium sulfate and quinoline at catalyzer with a moles of hydrogen.
Product with general formula (II) is a novel substance.R in the formula 1, R 2",
Figure 911111123_IMG50
（Ⅱ）
R 3", R 4And R 5Keep former definition.On pyrrole ring, introduce one or more groups, or all synthetic this heterocycle, on synthetic pyrrole ring, introduce one or more functional groups subsequently, can obtain the product of general formula for (II).
Having described the general formula that obtains by following synthetic route in an embodiment is the various products of (II).
Figure 911111123_IMG54
Figure 911111123_IMG55
Figure 911111123_IMG56
Figure 911111123_IMG57
Figure 911111123_IMG58
Compound with general formula (II) can adopt the method for as above signal to produce, and is also available similar, is that conspicuous method obtains to the professional and technical personnel.
The product that has general formula (II) described in the embodiment obviously all is the compound of selecting the superior.
Produce if desired and have general formula (I), and the Z in (I) is-compound of CN base also can adopt the existing method of different so-called phase transfer methods, method described in belgian patent 851900.Phase transfer method comprises that order and corresponding aldehyde of the alcohol of general formula (II) and general formula react in the presence of water for the acid of (III), and alkaline cyanide is eluted in the water, adopts the aprotic solvent and the phase transfer catalyst that are immiscible in water to a certain extent.
Produce if desired and have general formula (II), and substituent R in (II) 2" or R 3", R 4; R 5In three the expression hydrogen atoms alcohol, preferably according to R 3" or R 2" expression group
Figure 911111123_IMG59
And employing is corresponding to the method for synthetic route 1 or 2.
Have-alcohol of CN group if produce on two of the pyrrole rings that has general formula in (II) and (II), according to-CN and methylol position separately, preferably select method for use corresponding to synthetic route 3 or 4.
Have pyrrole ring two bit strip NO in general formula (II) and (II) as producing 2The alcohol of group is preferably selected synthetic route 5 for use.
Have pyrrole ring three bit strip NO in general formula (II) and (II) as producing 2The alcohol of group is preferably selected synthetic route 6 for use.
Have general formula (II) as producing, and pyrrole ring two bit strip CF in (II) 2The alcohol of base is preferably selected the method corresponding to synthetic route 7 for use.
General formula has some key property for the compound of (I), therefore can be used to eliminate parasite, as the parasite on killing off plant, the indoor and warm-blooded animal.Based on this effect, product of the present invention can be used to killing off plant and animal insect, nematode on one's body, and parasitic mite.
Product with general formula (I) is used in particular for eliminating pest, as lice, Lepidoptera and the coleoptera larva of a tapeworm or the cercaria of a schistosome.The consumption of per hectare active constituent is 10～300g.
Product with general formula (I) also can be used to eliminate insect, especially fly, mosquito and the cockroach in the house.
Compound insecticidal properties among the embodiment 1,2,15,40 is very remarkable, and the fabulous performance of knocking down is especially arranged.
Product with general formula (I) also can be used to post the worm mite on the killing off plant.
Compound acaricidal properties among the embodiment 40 is especially remarkable, and the result is as follows for its biologic test.
Compound with general formula (I) also can be used to the parasitic nematode of killing off plant.
Compound with general formula (I) also can be used to eliminate the parasitic mite on the animal body, as various ticks, particularly in the tick that belongs to kind of tick, the tick that glass eye tick belongs to kind, the tick of Amblyomma kind, and the tick of Rh.Or various mite classes, particularly itch mite, itch mite and skin mite.
Can be mixed with composition with the compound of general formula (I) as effective ingredient, eliminate the warm-blooded animal body with these compositions again, in the dwelling house and the parasite on the plant.
Compound with general formula (I) is particularly useful for preparing insecticides.
The preparation of composition is according to the universal method in agrochemical industry, animal doctor's industry or the industry of animal foodstuff among the present invention.
Composition can be made into pulvis, particle, suspension, emulsion, solution, aerosol solution, inflammable band, bait or other compound methods of using these compounds to adopt usually.
Except that effective ingredient, generally to add excipient and/or surfactant in these compositions, but requiring is nonionic, each material of composition mixture can evenly be disperseed, but excipient liquid such as water, alcohol, hydrocarbons or other organic solvents, mineral, animal or plant oil, powdery such as talcum, clay, silicate, diatomite or inflammable solid.
The active constituent that preferably contains 0.005～95Wt% in the insecticides of the present invention.
For ease of using in the house, the present composition can be mixed with stifling composition.
Consider non-active portion, the present composition can be made into inflammable spiral insecticide, also can be made of the fibrous matrix that does not fire.Under latter event, the fumigant for preparing with active constituent can be placed on heating element heater such as the electric mosquito killer.
If use the spirality insecticide, inert carrier can be by the Dalmatian chrysanthemum residue, Tabu powder (or Machilus Thumbergii leaf powder), Dalmatian chrysanthemum stem powder, cedar leaf powder, wood powder (as pine powder), formations such as starch and coconut shell powder, the consumption of active constituent is 0.03～1Wt%.
As using the fiber carrier that does not fire, the active constituent consumption is 0.03～95wt%.
As using in doors, composition of the present invention can be made into the diffusible oil based on active constituent, with this oil immersion bubble wick, makes its burning again.
The concentration of active constituent is preferably 0.03～95wt% in the oil.
Compound with general formula (I) also can be prepared acaricide composition.
Have in the product of general formula (I) structure, the product among the embodiment 38 and 40 is particularly suited for doing miticide.
Compound with general formula (I) also can be prepared nematicidal agent composition.
All can add one or more other insecticide in insecticides of the present invention and miticide and the nematicidal agent composition.Miticide and nematicidal agent composition can be made pulvis, particle, suspension, emulsion and solution especially.
Do the miticide time spent, the most handy wetting powder carries out foliage spray, includes the active constituent of 1-80%.Also available every liter of liquid that contains 1～500g active constituent carries out foliage spray, and the also available pulvis that contains 0.05～3% active constituent carries out foliage spray.
Do the nematocide time spent, the most handy liquid handling soil that contains the 300-500g/l effective ingredient.
The consumption of miticide and nematocide compound per hectare 1-100 gram active constituent preferably among the present invention.
Compound with general formula (I) also can be prepared the parasitic acariasis that is used for eliminating on the warm-blooded animal body, particularly eliminates the acaricide composition of tick class and mite class.
In order to improve the biologically active of the product that obtains with the inventive method, can add synergist general under the analogue, as: 1-(2,5,8-trioxa dodecyl)-2-propyl group-4,5-(methylenedioxy) benzene (or piperonyl butoxide) or N-(2-ethyl heptyl) two rings (2,2-1)-5-heptene-2,3-two carbimides, or 3,4-(methylenedioxy) benzyl-two-2-(2 '-n-butoxy ethyoxyl) ethyl acetal (or tropi-tal)
If be used for eliminating parasitic mite class on the animal body, the nutrients dubbed feed mixture that product is often used among the present invention in the animal foodstuff.Nutrients apparent motion species is different and different, can comprise cereal, sugar and grain, soybean, peanut, sunflower cake, animal flesh, as the flesh of fish, synthesizing amino acid, mineral salt, vitamin and antioxidant.
So the compound with general formula (I) also can be used to the preparing animal fodder mixture.
Product also can be used as biocide or growth regulator among the present invention.
Compound with general formula (I) can be used to prepare have insecticide, the composition of miticide and nematocide activity, its special card is, active constituent in the composition, promptly comprise the compound of at least a general formula, comprise at least a pyrethroid (pyrethrinoicl) compound of from one group of ester that following ester constitutes, selecting again for (I).These compounds are: by allethrin alcohol ketone, 3,4,5, the ester that 6-tetrahydrochysene phthaloyl imino methyl alcohol, 5-benzyl-3-furfuralcohol, 3-phenoxy group benzylalcohol, α-Qing Ji-3-Ben Yangjibianchun class and chrysanthemumic acid class form; 5-benzyl-3-furfuralcohol and 2,2-dimethyl-3-(2-oxo-3-tetrahydrochysene sulfo-cyclohexadienylene methyl) ester that forms of cyclopropane-1-carboxylic acids; 3-phenoxy group benzylalcohol and α-Qing Ji-3-Ben Yangjibianchun class and 2,2-dimethyl-3-(2,2-dichloroethylene) ester that forms of cyclopropane-1-carboxylic acids; α-Qing Ji-3-Ben Yangjibianchun class and 2,2-dimethyl-3-(2,2-dibromo vinyl) ester that forms of cyclopropane-1-carboxylic acids; The ester that 3-phenoxy group benzylalcohol and 2-rubigan-2-isopropyl acetate class forms, allethrin alcohol ketone, 3,4,5,6-tetrahydrochysene phthaloyl imino methyl alcohol, 5-benzyl-3-furfuralcohol, 3-phenoxy group benzylalcohol, α-Qing Ji-3-Ben Yangjibianchun class and 2,2-dimethyl-3-(1,2,2,2-four haloethyls) ester that forms of cyclopropane-1-carboxylic acids, (wherein " halogen " expression fluorine, chlorine or bromine atom).The compound of general formula (I) can its various possible stereoisomeric forms in any ratio exist, and also can be the acid of above-mentioned pyrethroid compound, pure link (oopulas).
The outstanding advantage of above-mentioned composition of the present invention is: by its multiple action, can eliminate the parasitosis of wide range, in addition, show synergistic effect in some aspects.
According to the present invention, also can add the pyrethroid synergist in the different insecticides.
Following compounds is the conventional synergist of selecting for use under the analogue: 1-(2,5,8-trioxa dodecyl)-2-propyl group-4,5-(methylenedioxy) benzene (or pepper butyl ether), or N-(2-ethyl heptyl) two ring (2,2-1)-5-heptene-2,3-two carbimides, or 3,4-(methylenedioxy) benzyl-two-2-(2 '-n-butoxy ethyoxyl) ethyl acetal (or tropital).
Following embodiment illustrates the present invention, but does not limit the present invention.
Embodiment 1:
1R is along (△ Z) 3-(3-methoxyl group-3-oxo-1-acrylic)-2,2-dinethyl cyclopropane carboxylic acid (1-(2-propinyl)-1H pyrroles-3-yl) methyl esters.
The 542mg3-(1-(2-propinyl) pyrrole radicals) methyl alcohol is dissolved in 10cm 3In the carrene, be cooled to 0 °-5 ℃ then, add 795mg(1R, suitable) 2,2-dimethyl-3-(3-oxo-3-methoxyl group-1(△ Z) acrylic) cyclopropane-carboxylic acid, stirred 10 minutes.At 7 ℃, one after another drop of splashing into contained 8cm 3Carrene, the solution of 835 milligrams of dicyclohexyl carbodiimides and 5 milligrams of dimethylamino pyridines.After above-mentioned being added dropwise to complete, allowing the mixture of reaction return to room temperature and stirred 16 hours.Filter then, filtrate is concentrated into dried; Residue dissolves with ether and filters to remove insoluble matter.Concentrated filtrate obtains the 1.112g coarse products, and the product that obtains is done used in chromatograph hexane-isopropyl ether (55-45) and 2% triethylamine mixture elution in silicagel column.The product that obtains so just obtains 700 milligrams of desired products with isopropyl ether purifying once more.
(α) D=+23 °+2 ° (C=0.3% toluene)
According to the operating procedure among the embodiment 1, and, obtain following product according to the specified synthetic route in back.
Embodiment 2:1R, along (△ E) 2,2-dimethyl-3-(3-ethyoxyl-3-oxo-2-fluoro-1 acrylic)-cyclopropane-carboxylic acid (1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters.
Embodiment 3:1R, along (△ Z) 2,2-dimethyl 3-(3-tert-butoxy-3-oxo-acrylic) cyclopropane-carboxylic acid (1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters.
Embodiment 4:1R, along (△ E) 2,2-dimethyl-3-(3-methoxyl group-3-oxo-2-fluoro-1-acrylic) cyclopropane-carboxylic acid (1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters.
Embodiment 5:1R, along (△ E) 2,2-dimethyl-3-(3-tert-butoxy-3-oxo-2-fluoro-1-acrylic) cyclopropane-carboxylic acid (1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters.
Embodiment 6:1R, along 2,2-dimethyl-3-(dibromo vinyl) cyclopropane-carboxylic acid (1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters.
Embodiment 7:1R, along (△ Z) 2,2-dimethyl-3-(3-ethyoxyl-3-oxo-1-acrylic) cyclopropane-carboxylic acid (1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters.
Embodiment 8:1R, trans 2,2-dimethyl-3-(2,2-difluoroethylene base) cyclopropane-carboxylic acid 1-(1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters.
Embodiment 9:1R, along 2,2-dimethyl-3-(2,2-difluoroethylene base) cyclopropane-carboxylic acid 1-(1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters.
Embodiment 10:2,2-dimethyl-3,3-dimethyl-cyclopropane-carboxylic acid (1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters.
Embodiment 11: methyl esters (2S) 2-(4-difluoro-methoxy phenyl-3 Methylbutanoic acid (1-(2-propinyl)-1H-pyrroles-3-yl).
Embodiment 12:1R, trans (△ Z) and △ E2,2-dimethyl-3-(3,3,3-three fluoro-2-chloro-1-acrylic) cyclopropane-carboxylic acid (1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters.
Figure 911111123_IMG60
Figure 911111123_IMG61
Figure 911111123_IMG62
Figure 911111123_IMG63
Figure 911111123_IMG64
Embodiment 12:
Figure 911111123_IMG65
Preparation 1: the raw material 1-(2-propinyl that is used for producing product 1～12)-preparation method of 1H-pyrroles-3-methyl alcohol is as follows:
Steps A: the 1-(2-propinyl)-1H-pyrroles-3-carboxylic formaldehyde.
2.924 gram pyrroles-3-carboxylic formaldehyde (J.ORG.CHEM.1981,46,839) is dissolved in 45cm 3In the oxolane, the 1.488 gram sodium hydrides of adding 50% in oil stirred 10 minutes, at room temperature cooled off then 40 minutes.After the cooling, add 2.5cm 3Propargyl bromide, stirred 1 hour 30 minutes at 5 ℃, add 2 milliliters of propargyl bromides again, stirred 1 hour at 5 ℃, all pour in the water then and use dichloromethane extraction, at normal pressure solvent is distilled.In silicagel column, purify,, obtain the desired product of 2.868g like this with the elution of hexane-ethyl acetate (65-35) mixture with chromatography.
Step B:1-(2-propinyl)-1H-pyrroles-3-methyl alcohol.
3.1 gram products in A step preparation are dissolved in 90cm 3Oxolane and 19cm 3In the solution of water, this solution at room temperature stirred 15 minutes, added 2.517 gram potassium borohydrids then, at room temperature, stirred and after 5 hours 30 minutes reactant mixture was poured in the saturated sodium-chloride water solution, extracted with chloromethane then.Extract is dry and concentrated dried at 20 ℃.Obtain the coarse products that 3.4 grams can be used.
According to the step operation of embodiment 1, and, obtain following product according to indicated synthetic route.
Embodiment 13:1R, along 2,2-dimethyl-3-(2,2-dibromo vinyl) cyclopropane-carboxylic acid (R, S)-cyano group-(1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters, be separated into two isomer A and B.
Embodiment 14:1R, along (△ Z) 2,2-dimethyl-3-(3-methoxyl group-3-oxo-1-acrylic) cyclopropane-carboxylic acid (R, S)-cyano group-(1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters.
Embodiment 15:1R, along (△ E) 2,2-dimethyl-3-(3-ethyoxyl-3-oxo-2 fluoro-1-acrylic)-2,2-dinethyl cyclopropane carboxylic acid cyano group-(1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters, (A and B are isomer).
Embodiment 16: and isopropyl-4-chlorphenyl acetic acid (R, S)-cyano group-(1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters.
Embodiment 13:
Figure 911111123_IMG67
Figure 911111123_IMG68
Preparation 2: as the Alpha-hydroxy-1-(2-propinyl of the raw material of embodiment 12 to 16)-1H-pyrroles-3-acetonitrile is prepared as follows:
With 0.44cm 3Acetate add the product contain B step preparation in the 510mg preparation 1,7cm 3Methyl alcohol and 2cm 3The solution of water in.Add 0.44cm again 3Acetate, and complete soln is cooled to 20 ℃.Then, add the Cymag of 2.82mg, mixture was stirred 1 hour 30 minutes, be cooled to then+10 ℃ at 20 ℃.The Cymag and the 2.2cm that add 1.4g again 3Acetate.Stir after 4 hours, with in the reactant mixture impouring water and use ethyl acetate extraction.Wash organic facies with water, dry again, be concentrated into dried then.Obtain the expectation product of 590mg.
With the operating procedure among the embodiment 1,, obtain following product according to the synthetic route of pointing out:
(1R, suitable) 2,2-dimethyl-3-(2,2-dibromo vinyl) cyclopropane-carboxylic acid (1-(2-propinyl)-1H-pyrroles-2-yl) methyl esters.
Embodiment 17:
Figure 911111123_IMG69
(α) D=-12 ° ± 1 ° (C=1% toluene)
Preparation 3: as raw material 2-(1-(2-propinyl)-pyrrole radicals of embodiment 17) being prepared as follows of methyl alcohol:
Steps A: 1, the 2-propynyl pyrroles
10.32g propargyl amine and 24.76g2,5-dimethoxy hydrogenation furans is at 38cm 3Be mixed together in the acetate, be warming up to 110 ℃, continue to stir for 3 quarters with heating bath.Mixture is poured 250cm into 3In the water, and add 345cm 32N sodium hydroxide, after extracted with diethyl ether, drying also is concentrated into the dried 15g of obtaining product, carries out chromatographic isolation in silicagel column, with the mixture wash-out of hexane-ethyl acetate (8～2), concentrating under reduced pressure in the time of 30 ℃, obtains the expectation product of 10g.
Step B:2-(1-(2-propinyl) pyrrole radicals) formaldehyde.
The 16g phosphoryl chloride phosphorus oxychloride is added in the dimethyl formamide of 7.64g, add 50cm again 3Carrene stirs half an hour at 0 ℃, will contain the 11g1-(2-propinyl at 0 ℃ then) 40cm of pyrrole aldehyde 3Dichloromethane solution add wherein, reaction mixture refluxed half an hour be cooled to 20 ℃ then, and the aqueous solution that adds sodium acetate is (at 117cm 3The 58.6g sodium acetate is arranged) in the water.Complete soln refluxes a quarter of an hour under fully stirring again, and is dry and concentrated with washing with water behind the dichloromethane extraction, obtains product and carries out chromatographic isolation with silicagel column, with hexane-ethyl acetate (6～4) mixture wash-out, obtains the expectation product of 9.3g.
Step C:2-(1-(2-propinyl)-pyrrole radicals) methyl alcohol.
Prepared product in containing 1.75g step B, 50cm 3Oxolane and 10cm 3The solution of water in add the potassium borohydrid of 0.7g.After 1 hour, add the 0.35g potassium borohydrid 20 ℃ of stirrings again, and continue to stir 30 minutes at 20 ℃, this solution is saturated with sodium chloride then, and uses ethyl acetate extraction.Organic facies is merged dry.Under reduced pressure, make the expectation product of isolating 1.78g 40 ℃ of solvent evaporated.
With the operating procedure of embodiment 1,, obtain following product according to the synthetic route of pointing out below:
Embodiment 18:1R, along (△ E) 2,2-dimethyl-3-(3-ethyoxyl-3-oxo-2-fluoro-1-acrylic) cyclopropane-carboxylic acid 2-cyano group (1-(2-propinyl)-1H-pyrroles-4-yl) methyl esters.
Embodiment 19:1R, along 2,2-dimethyl-3-(2,2-dibromo vinyl) cyclopropane-carboxylic acid 2-cyano group (1-(2-propinyl)-1H-pyrroles-4-yl) methyl esters.
Embodiment 20:1R, along 2,2-dimethyl-3-(3-methoxyl group-3-oxo-1-acrylic)-2,2-dinethyl cyclopropane carboxylic acid 2-cyano group (1-(2-propinyl)-1H-pyrroles-4-yl) methyl esters.
Embodiment 21:1R, along (△ E) 2,2-dimethyl-3-(3-tert-butoxy-3-oxo-2-fluoro-1-acrylic) cyclopropane-carboxylic acid 2-cyano group (1-(2-propinyl)-1H-pyrroles-4-yl) methyl esters.
Embodiment 18:
Figure 911111123_IMG70
Figure 911111123_IMG71
α D=+35 ° ± 2 ° (C=0.5% toluene)
Preparation 4: as the 4-methylol-1-(2-propinyl of raw material)-1H-pyrroles-2-nitrile is prepared as follows:
Steps A: the 1-(2-propinyl)-1H-pyrroles-2-nitrile.
The 2-cyanopyrrole of 51.57g (it prepares according to the chemical engineering magazine of Canada (Can.J.chem.) 59, the method for pointing out in 2763(1981)), the triphenyl phasphine of 146.9g and the propargyl alcohol of 43.95g mix, and add 420cm 3Oxolane, complete soln be cooled to+and 5 ℃, in the time of 0～5 ℃, in half an hour, add the azo connection carboxylic acid, ethyl ester of 97.5g.Make temperature be raised to room temperature, continue to stir 18 hours.Vapourisation under reduced pressure falls solvent, and the residue that obtains crystallization also filters with ether dissolution.After filtrate concentrates, obtain a kind of grease, separate in the enterprising circumstances in which people get things ready for a trip spectrum of silicagel column, with hexane-ethyl acetate (7～3) mixture wash-out, obtain 34g expectation product.
Step B:4-formyl-((2-propynyl)-1H-pyrroles-2-nitrile.
At 6cm 3Anhydrous methylene chloride in contain 2.36g aluminium chloride mixture be cooled to-78 ℃.In this mixture, be added in 8cm 3The solution and the 0.5cm of the product for preparing in the 1.3g steps A in the carrene 3Nitromethane is dissolved in 15cm-55 ℃ of addings then 3The 1.49g dichlormetbylether of carrene.Reactant mixture was kept 1 hour at-60 ℃, made it be warmed up to 20 ℃ then, kept 18 hours in this temperature.Then reactant mixture is poured in the water, stirred, use 33cm 3The 2N sodium hydroxide pH value that neutralizes is 7.Use dichloromethane extraction, extract is with the potassium bicarbonate solution washing of 1M, and is dry then, is concentrated into dried.Obtain the product of 1.5g, with dupentane washing, drying.Obtain the expectation product of 1.1g, fusing point is 97 ℃.
Step C:4-(methylol)-the 1-(2-propinyl)-1H-pyrroles-2-nitrile.
The potassium borohydrid of 372mg is added at 40cm 3Oxolane and 5.5cm 3Water contains in the solution of the 546mg product for preparing among the B in steps.At room temperature continue to stir after 15 minutes, add 50cm 3Saturated aqueous sodium chloride, use ethyl acetate extraction, drying, concentrated extract obtains the expectation product of 600mg to doing.
Embodiment 22:1R, along 2,2-dimethyl-3-(2,2-dibromo vinyl) cyclopropane-carboxylic acid (R, S)-cyano group-(2-cyano group-1-(2-propinyl)-1H-pyrroles-4-yl) methyl esters.
The 4-of 447mg formyl-1-(2-propinyl)-1H-pyrroles-2-nitrile pours 13cm into 3Toluene in, add then: the Cymag of 173mg, the bromination tetrabutylammonium of 38mg, the 1R of 894mg, cis 2,2-dimethyl-3-(2,2-dibromo vinyl) cyclopropanecarbonyl chloride and 0.13cm 3Water.After stirring 18 hours under 20 ℃, add 100cm 3Benzene, dry and be concentrated into dried complete soln thereafter.Obtain the expectation product of 1017mg.
(α) D=+9 ° ± 2 ° (C=0.3% toluene)
With the operating procedure of embodiment 1, and, obtain following product according to the following synthetic route of pointing out:
Embodiment 23:1R, along (△ Z) 2,2-dimethyl-3-(3-methoxyl group-3-oxo-1-acrylic) cyclopropane-carboxylic acid cyano group-(2-cyano group-1-(2-propinyl)-1H-pyrroles-4-yl) methyl esters.
Embodiment 24:1R, along (△ E) 2,2-dimethyl-3-(3-ethyoxyl-3-oxo-2-fluoro-1-acrylic) cyclopropane-carboxylic acid cyano group-(2-cyano group-1-(2-propinyl)-1H-pyrroles-4-yl) methyl esters.
Embodiment 25:1R, along (△ E) 2,2-dimethyl-3-(3-tert-butoxy-3-oxo-2-fluoro-1-acrylic) cyclopropane-carboxylic acid cyano group-(2-cyano group-1-(2-propinyl)-1H-pyrroles-4-yl) methyl esters.
Figure 911111123_IMG73
With the operation of embodiment 1,, obtain following product according to the synthetic route of pointing out below:
Embodiment 26:1R, along 2,2-dimethyl-3-(2,2-dibromo vinyl) cyclopropane-carboxylic acid (1-(2-propinyl)-2-cyano group-1H-pyrroles-3-yl) methyl esters.
Embodiment 26:
Figure 911111123_IMG75
Preparation 5: the 3-methylol-1-(2-propinyl that in embodiment 25 to 28, is used as raw material)-1H-pyrroles-2-nitrile is prepared as follows:
Steps A: 2-formyl-1-(2-propinyl)-1H-pyrroles-3-methyl formate.
1 of 7.05g, the propargyl amine of 1-dimethoxy-2-oxo-methyl butyrate and 4.4g is at 20cm 3Solution in the water is cooled to 20 ℃, stirs 10 minutes.Acetate 1.2-two bromo-ethyl esters with 0.9 gram dropwise add then, keep stirring at 20 ℃ reaching 24 hours, then complete reaction mixture are poured in the water, use ethyl acetate extraction, and extract washs with sodium bicarbonate solution, drying, and be concentrated into dried.Obtain the 10g product, carry out chromatographic isolation in the silicon post, with cyclohexane-ethyl acetate (75～25) mixture wash-out, obtain the expectation product of 1.9g, its fusing point is 76 ℃.
Step B:1-(2-propinyl)-2-oximido methyl-3-pyrrole methyl formate.
The product 2g of steps A preparation, hydroxyl hydrochloride 725mg and 11cm 3Anhydrous pyridine at room temperature stirred 3 hours, under reduced pressure concentrate pyridine.Residue is with acetic acid ethyl dissolution and wash with water, and is dry then and concentrate, and obtains 2.3g expectation product, and its fusing point is 88～98 ℃.
Step C:2-cyano group-1-(2-propinyl)-1H-pyrroles-3-methyl formate.
To be dissolved in 2cm 33.54g thionyl chloride in the carrene and be dissolved in 15cm 3The 2.2g product that previous step in the carrene obtains mixes, the solution that obtains is cooled to 20 ℃, at room temperature stirred reaction mixture is 24 hours, concentrate then, thereby obtain the 1.8g product, it is carried out chromatographic isolation in silicagel column, and with cyclohexane-ethyl acetate (7～3) mixture wash-out, obtain 1.430g expectation product, fusing point is 112 ℃.
Step D:3-(methylol)-the 1-(2-propinyl)-1H-pyrroles-2-nitrile.
The product 830mg that contains the previous step preparation, 8cm 3Oxolane and 2cm 3The mixture of water stirred 24 hours at 20 ℃, added the 280mg lithium borohydride then, was adding 30cm 3Ethyl acetate after, dry and be concentrated into driedly, obtain the product of 750mg, it is carried out chromatographic isolation in the silicon post, and, obtains the expectation product of 138mg by the mixture wash-out of cyclohexane and ethyl acetate (6-4), fusing point is 65 ℃.
With the operating procedure of embodiment 1,, obtain following product according to the synthetic route of pointing out below:
Embodiment 27:1R, along (△ E) 2,2-dimethyl-3-(3-ethyoxyl-3-oxo-2-fluoro-1-acrylic) cyclopropane-carboxylic acid (1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters.
Embodiment 28:1R, along 2,2-dimethyl 3-(2,2-dibromo vinyl) cyclopropane-carboxylic acid (1-(2-propinyl)-2-nitro-1H-pyrroles-4-yl) methyl esters.
Embodiment 29:1R, along (△ Z) 2,2-dimethyl-3-(3-methoxyl group-3-oxo-1-acrylic) cyclopropane-carboxylic acid [2-nitro-1-(2-propinyl)-1H-pyrroles-4-yl) methyl esters.
Embodiment 30:1R, along (△ E) 2,2-dimethyl-3-(3-tert-butoxy-3-oxo-2-fluoro-1-acrylic) cyclopropane-carboxylic acid [2-nitro-1-(2-propynyl)-1H-pyrroles-4-yl) methyl esters.
Figure 911111123_IMG77
Preparation 6: as the 2-nitro-1-(2-propinyl of the raw material among the embodiment 29 to 32)-1H-pyrroles-4-methyl alcohol is prepared as follows:
The A step: 2-nitro-1-(2-propinyl)-1H-pyrroles-4-formaldehyde.
In the time of+5 ℃, the oil that contains the 310mg sodium hydride with 50% is added to the 15Cm of the 2-nitro-1H-pyrroles-4-formaldehyde that contains 0.9g 3The solution of oxolane in.2-nitro-1H-pyrroles-4-formaldehyde wherein is according to (Bull.Soc.Chim.France) (1972) the 283rd～291 pages of upward described method preparations of France's " chemical association circular ".After making temperature of charge rise to room temperature, add 0.53Cm 3Propargyl bromide.At 60 ℃ reactant mixture was stirred 6 hours, then, stirred 18 hours at 20 ℃.After filtration, be concentrated into do after, obtain the product of 1g.This product carries out chromatographic isolation in silicagel column, with the mixed liquor wash-out of heptane and ethyl acetate (1-1), obtain the expection product of 450mg.
Fusing point: 128 ℃
The B step: 2-nitro-1-(2-propinyl)-1H-pyrroles-4-methyl alcohol.
The 270mg potassium borohydride is added to the product that is prepared by the 450mgA step, 30Cm 3Oxolane and 4Cm 3In the solution that water is formed, continue to stir after 15 minutes, in the saturated solution with total overall reaction thing impouring sodium chloride, use ethyl acetate extraction, the extract drying is also concentrated, obtain the expection product of 455mg.
With the operating procedure of embodiment 1,, obtain following product according to the synthetic route of pointing out below.
Embodiment 31:1R, along 2,2-dimethyl-3-(2,2-dibromo vinyl) cyclopropane-carboxylic acid (R, S)-cyano group-(2-nitro-1-(2-propinyl)-1H-pyrroles-4-yl) methyl esters.
Embodiment 32:1R, along (△ E) 2,2-dimethyl-3-(3-ethyoxyl-3-oxo-2-fluoro-1-acrylic) cyclopropane-carboxylic acid (R, S)-cyano group-(2-nitro-1-(2-propinyl)-1H-pyrroles-4-yl) methyl esters.
Figure 911111123_IMG79
Preparation 7: the Alpha-hydroxy-1-(2 propinyl that is used as raw material among the embodiment in front)-1H-pyrroles-5-nitro-3-acetonitrile is prepared as follows:
2-nitro-1-(2-propinyl with 801mg)-and 1H-pyrroles-4-formaldehyde, 15Cm 3Methyl alcohol and 3Cm 3Water mix, add 3.6Cm then 3Acetate, the total overall reaction thing is cooled to+5 ℃, add the Cymag of 2.2g, allow temperature rise to 20 ℃, held dimension 4 hours, with in the reactant mixture impouring frozen water, use extracted with diethyl ether then, ether washes with water mutually, drying, concentrated after, obtain the expection product of 920mg.
With the operating procedure of embodiment 1,, obtain following product according to the synthetic route of pointing out below.
Embodiment 33:1R, along 2,2-dimethyl-3-(2,2-dibromo vinyl) cyclopropane-carboxylic acid (3-nitro-1-(2-propinyl)-1H-pyrroles-4-yl) methyl esters.
Figure 911111123_IMG80
Preparation 8: as the 3-nitro-2-(2-propinyl of raw material)-1H-pyrroles-4-methyl alcohol is prepared as follows:
The A step: 3-nitro-1-(2-propinyl)-1H-pyrroles-4-formaldehyde.
Pour 3-nitro-1H-pyrroles-4-formaldehyde of 826mg (according to " chemical association circular " (Bull.Soc.Chim) the method preparation in (1972) the 283rd～291 pages) into 40Cm 3Oxolane in, then at+5 ℃, add 50% the oil that contains the 280mg sodium hydride, with temperature 20 ℃ keep 1 hour after, add the propargyl bromide of 1.19g.Reactant was stirred 18 hours at 20 ℃, filter then, concentrate, in silicagel column, carry out chromatographic isolation,, obtain the product of 800mg, fusing point: 120 ℃ with the mixed liquor wash-out of hexane and ethyl acetate (1-1).
The B step: 3-nitro-1-(2-propinyl)-1H-pyrroles-4-methyl alcohol.
At 20 ℃, the potassium borohydride of 242mg is added to product by the preparation of 400mgA step, 30Cm 3Oxolane and 4Cm 3In the solution that water is formed, at room temperature, mixture was stirred 15 minutes, in the time of 20 ℃, add 10Cm 3The saturated solution of sodium chloride also stirred 5 minutes, and is dry, concentrated behind ethyl acetate extraction, obtains the expection product of 410mg.Fusing point: 60 ℃.
With the operating procedure of embodiment 1,, obtain following product according to the synthetic route of pointing out below.
Embodiment 34:1R, along 2,2-dimethyl-3-(2,2-dibromo vinyl) cyclopropane-carboxylic acid (R, S)-cyano group-(3-nitro-1-(2-propinyl)-1H-pyrroles-4-yl) methyl esters.
Figure 911111123_IMG82
With the operating procedure of embodiment 1,, obtain following product according to the synthetic route of pointing out below.
Embodiment 35:1R, along (△ E) 2,2-dimethyl-3-(3-ethyoxyl-3-oxo-2-fluoro-1-acrylic) cyclopropane-carboxylic acid ((1-allene base-1H-pyrroles-3-yl) methyl esters.
Embodiment 36:1R, along 2,2-dimethyl-3-(2,2-dibromo vinyl) cyclopropane-carboxylic acid ((1-allene base)-1H-pyrroles-3-yl) methyl esters.
Figure 911111123_IMG83
Figure 911111123_IMG84
Preparation 9: as the 3-(1-(allene base of raw material) pyrrole radicals) methyl alcohol is prepared as follows:
A step: 1-allene base-1H-pyrroles-3-formaldehyde.
1g pyrroles-3-formaldehyde is dissolved in 25Cm 3Oxolane in, at room temperature stirred 15 minutes, be cooled to 0 °～5 ℃ then, add 50% the oil that contains the 528mg sodium hydride, and under cooling, stirred 10 minutes, make temperature rise to room temperature then, under nitrogen, stirred again 40 minutes, add 1Cm 3Propargyl bromide, stirred 2 hours at 40 °～50 ℃, then with reactant mixture impouring 15Cm 3In the water, use dichloromethane extraction.With the extract drying, desolventize concentratedly by steaming, in silicagel column, carry out chromatographic isolation, with the mixed liquor wash-out of hexane and ethyl acetate (7-3), obtain the expection product of 1.166g.
B step: methyl alcohol pyrrole radicals 3-(1-(allene base)).
The product of the A step of 1.009g preparation is dissolved in 35Cm 3Oxolane and 6.7Cm 3The solution of water in, 20 ℃ stir 15 minutes after, add the potassium borohydride of 523mg, and stirred 2 hours 15 minutes at 20 ℃.Then, in the saturated aqueous solution with complete reaction mixture impouring sodium chloride, use dichloromethane extraction, drying, concentrate after, obtain the product of 0.899g, this product directly uses.
With the operating procedure of embodiment 1,, obtain following product according to the synthetic route of pointing out below.
Embodiment 37:1R, along 2,2-dimethyl-3-(2,2-dibromo vinyl) cyclopropane-carboxylic acid (1-(2-propinyl)-2-Trifluoromethyl-1 H-pyrroles-3-yl) methyl esters.
Embodiment 38:1R, along (△ E) 2,2-dimethyl-3-(3-ethyoxyl-3-oxo-2-fluoro-1-acrylic) cyclopropane-carboxylic acid (1-(2-propinyl)-2-Trifluoromethyl-1 H-pyrroles-3-yl) methyl esters.
Figure 911111123_IMG86
Preparation 10:1-(2-propinyl)-2-trifluoromethyl-3-pyrroles's methyl alcohol.
The A step: the 1-(2-propinyl)-2-trifluoromethyl-3-pyrrole carboxylic acid ethyl ester.
At 10 ℃, with 1.8Cm 33-oxo-4,4,4-trifluoroacetic acid ethyl ester adds 3.15Cm 32-propargylamine and 10Cm 3In the solution of water, stirred 10 minutes, add 1.65Cm then 3Acetate 1,2-dibromo ethyl ester.Mixture is heated to 70 ℃ and continues 45 minutes, uses ethyl acetate extraction then, after the extract drying concentrates, obtains the grease of 6g, and this grease carries out chromatographic isolation in silicagel column, obtain the expection product of 360mg.
The B step: the 1-(2-propinyl)-2-trifluoromethyl-3-pyrroles's methyl alcohol.
At 5 ℃, will contain the 10Cm of product of the A step preparation of 1.74g 3The lithium aluminium hydride reduction of tetrahydrofuran solution and 270mg mixes, and this mixture at room temperature stirred 3 hours, and cooling then adds 10Cm 3Ethyl acetate, the saturated solution of several sodium potassium tartrate tetrahydrates is wherein arranged.
Separate and concentrate the back and cool off, obtain the grease of 2.4g, this grease carries out chromatographic isolation in silicagel column, with the mixture wash-out of cyclohexane-ethyl acetate (8-2), obtains the expection product of 40mg, fusing point: 63 ℃.
According to the operating procedure of front, can prepare following product.
Figure 911111123_IMG87
Embodiment 40:1R, along (△ E) 2,2-dimethyl-3-(3-tert-butoxy-3-oxo-2-fluorine acrylic)-cyclopropane-carboxylic acid (2-Trifluoromethyl-1-(2-propynyl)-1H-pyrroles-3-yl) methyl esters.
With the dicyclohexylcarbodiimide of 455mg, the dimethylamino naphthyridine of 3mg and 5Cm 3The solution formed of anhydrous methylene chloride dropwise join in the mixture that in ice bath, cools off, this mixture contains the 1-(2-propinyl of 450mg)-2-trifluoromethyl-3-pyrroles's methyl alcohol, the 1R of 570mg, along (△ E) 2,2-dimethyl-3-(3-tert-butoxy-3-oxo-2-fluoro-1-acrylic) cyclopropane-carboxylic acid and 4Cm 3Anhydrous methylene chloride, allow the temperature of reactant mixture rise to room temperature and stirred 5 hours, remove by filter the precipitation of generation.Dissolve filtrate with isopropyl ether, concentrate, then insoluble material is removed by filter, filtrate is carried out chromatographic isolation after concentrating in silicagel column, with the mixed liquor wash-out of hexane and ethyl acetate (9-1), obtains the expection product of 518mg.
Embodiment 41:1R, along 2,2-dimethyl-3-vinyl cyclopropane-carboxylic acid (2-Trifluoromethyl-1-(2-propynyl)-1H-pyrroles-3-yl) methyl esters.
According to the operating procedure of embodiment 1,,, the 1-(2-propinyl of 2-dimethyl-3-vinyl cyclopropane-carboxylic acid and 800mg) along 2 with the 1R of 610mg-2-trifluoromethyl-3-pyrroles's methyl alcohol makes raw material, obtains the expection product of 1.28g.
(α) D=+9 ° (0.2% toluene)
Embodiment 42:1R, along () 2,2-dimethyl-3-(3-methoxyl group-(3-oxo-1-acrylic)) cyclopropane-carboxylic acid (2-Trifluoromethyl-1-(2-propynyl)-1H-pyrroles-3-yl) methyl esters.
Operating procedure according to embodiment 1,1R with 860mg, along (△ Z) 2,2-dimethyl-3-(3-methoxyl group)-the 3-oxo)-the 1-(2-propinyl of 1-acrylic cyclopropane-carboxylic acid and 800mg)-2-trifluoromethyl-3-pyrroles's methyl alcohol makes raw material, obtains the expection product of 1.18g.
(α) D=+17.5 ° (0.7% toluene)
Embodiment 43:1R, along (Z) 2,2-dimethyl-3-((2-chloro-3,3,3-trifluoro)-1-acrylic) cyclopropane-carboxylic acid (2-cyano group-1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters.
(2-cyano group-1-(2-propinyl)-1H-pyrroles with 430mg)-and the 1R of 3-methyl alcohol and 600mg, along (Z) 2,2-dimethyl-3-(2-chloro-3,3,3-trifluoro)-1-acrylic) cyclopropane-carboxylic acid adds 12Cm 3Carrene in, at 0 ℃, the dimethylamino naphthyridine that dropwise adds the dicyclohexylcarbodiimide of 509mg and 3mg in the solution that obtains is in 2Cm 3The solution that forms in the carrene.In the time of 20 ℃, reactant was stirred 5 hours, filter then, filtrate is concentrated into drying, adds isopropyl ether, removes by filter insoluble by product, filtrate is concentrated into drying, add the mixed liquor of hexane and isopropyl ether (1-1), refilter, and filtrate is concentrated into drying, residue carries out chromatographic isolation in silicagel column, mixed liquor wash-out with hexane and isopropyl ether (1-1) still contains a spot of urea in the product that obtains, to wherein adding 2Cm 3Isopropyl ether, by removing by filter the insoluble matter of generation, under reduced pressure distill then filtrate be concentrated into drying, obtain the expection product of 896mg.
(α) D=+7 ° (toluene of C=0.4%)
Elementary analysis: C 18H 16ClF 2N 2O 2: 884.789
Calculated value: C%56.19 H%4.19 cl%9.21 F%14.8 N%7.28
Enforcement value: 56.3 4.4 9.0 14.9 7.2
Embodiment 44:1R, along (E) 2,2-dimethyl-3-(3-ethyoxyl-2-fluoro-3-oxo-1-acrylic) cyclopropane-carboxylic acid cyano group-(1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters.
With (R, S) alpha-cyano (2-cyano group-1-(2-propinyl)-1H-pyrroles-3-yl)-4-methyl alcohol of 2g and the 1R of 2.48g, along (E) 2,2-dimethyl-3-(3-ethyoxyl-2-fluoro-3-oxo-1-acrylic) cyclopropane-carboxylic acid is dissolved in 30Cm 3Carrene in, then under 10 ℃, in about 30 minutes, add the dicyclohexylcarbodiimide of 2.22g and the 4-dimethylamino naphthyridine of 13mg be dissolved in 30Cm 3Carrene in solution.Stirred 18 hours at 20 ℃, be concentrated into drying after the filtration.Add ether, refilter, be concentrated into drying.The product that obtains at last carries out chromatographic isolation in silicagel column, with the mixed liquor wash-out of hexane and ethyl acetate (7-3), obtain the acid of 3.14g expection.
(α) D=+40 ° (C=1% toluene)
Elementary analysis: C 21H 20FN 3O 4: 397.409
Calculated value: C%63.47 H%5.07 F%4.78 N%10.57
Experimental value: 63.4 5.1 4.8 10.3
Preparation 11: the used 4-hydroxyl-1-(2-propinyl of raw material in embodiment 44)-1H-pyrroles-5-cyano group-3-acetonitrile can be prepared as follows:
1-(2-propinyl with 6g)-and 1H-pyrroles-2-nitrile, 125Cm 3Methyl alcohol and 25Cm 3Water mix, be cooled to then+5 ℃, and add 15.2Cm 3Acetate, then the Cymag with 9.3g divides several parts of addings, in 4 hours, the temperature of reactant is risen to 20 ℃, in the water with 1 liter of complete reaction mixture impouring, uses extracted with diethyl ether then, with the organic facies drying, and is concentrated into driedly, obtains the expection product of 7g.Fusing point: 60 ℃.
Embodiment 45:1R, along (E) 2,2-dimethyl-3-(2-fluoro-3-oxo-3-tert-butoxy-acrylic) cyclopropane-carboxylic acid (1-(2-propinyl)-3-trifluoromethyl)-1H-pyrroles-4-yl) methyl esters.
With the 1g1-(2-acrylic)-3-Trifluoromethyl-1 H-pyrroles-4-methyl alcohol and 1.5g1R, along (E) 2,2-dimethyl-3-(2-fluoro-3-oxo-3-tert-butoxy-acrylic) cyclopropane-carboxylic acid is dissolved in 25Cm 3Carrene in, then,, little by little add, and stirred 15 minutes at 0 ℃ by the dicyclohexylcarbodiimide of 1.3g and the mixture of 4-dimethylamino naphthyridine in carrene of 150mg at 0 ℃, in the time of 20 ℃, stirred 2 hours then.Reactant mixture is filtered, and filtrate is concentrated into dried.Add isopropyl ether, its temperature is fallen 0 ℃, and then filter, under reduced pressure distillation is concentrated into filtrate dried.The product that obtains carries out chromatographic isolation twice in silicagel column, with the mixed liquor wash-out of hexane and ethyl acetate (35～15), obtain the expection product of 1.7g.
(α) D=40.5 ° (C=0.7% chloroform)
Elementary analysis: C 22H 25F 4NO 4: 443.443
Calculated value: C%59.6 H%5.68 F%17.14 N%3.16
Experimental value: 59.2 5.7 17.1 3.2
Preparation 12: as at the 1-(2-propinyl of embodiment 45 raw materials)-3-Trifluoromethyl-1 H-pyrroles-4-methyl alcohol can prepare with following method:
A step: 3-Trifluoromethyl-1 H-pyrroles-4-Ethyl formate.
With 7.4g4,4,4-three fluoro-(E)-butenoic acid ethyl (E.T.McBEE, " U.S. association magazine " be the 76th volume (J.Am.Soc), 3724 pages (1954)) and 8.6g tosyl methyl carbylamine are added to 200Cm 3Methyl-sulfoxide and ether (1-2) mixture in, little by little add 50% the vaseline oil that contains the 2.9g sodium hydride then, have hydrogen to generate, in the time of 20 ℃, stir after 30 minutes, add several acetate.Then, in complete reaction mixture impouring frozen water, use extracted with diethyl ether.Extract is concentrated into dried by distillation under reduced pressure.Residue carries out chromatographic isolation in silicagel column, with the mixed liquor wash-out of hexane and ethyl acetate (7-3), obtain the expection product of 6.6g.Fusing point: 165 ℃.
Elementary analysis: C 8H 8F 2NO 2: 207.154
Calculated value: C%46.39 H%3.85 F%27.51 N%6.76
Experimental value: 46.5 3.9 27.1 6.8
The B step: the 1-(2-propinyl)-3-Trifluoromethyl-1 H-pyrroles-4-Ethyl formate.
3-Trifluoromethyl-1 H-pyrroles-4-Ethyl formate that 1g is obtained in the A step is added to 10Cm 3Oxolane in, in the time of 0 ℃, little by little add 50% the vaseline oil that contains the 240mg sodium hydride, in the time of 20 ℃, stir after 30 minutes, be cooled to 0 ℃, with 0.45Cm 3Propargyl bromide be dissolved in 1Cm 3The solution of oxolane be added in the reactant, stirred 30 minutes at 0 ℃, stirred 1 hour at 20 ℃ then, be cooled to 0 ℃ again, add some sodium hydrides, under this temperature, stirring adding 0.45Cm 3Propargyl bromide be dissolved in 1Cm 3The solution of oxolane.With in the whole impouring water of reactant, use dichloromethane extraction then, under reduced pressure distillation is concentrated into extract dried.Residue carries out chromatographic isolation in silicagel column, with the mixed liquor wash-out of hexane and ethyl acetate (8-2), obtain the expection product of 0.950mg.Fusing point=58 ℃.
The C step: the 1-(2-propinyl)-3-Trifluoromethyl-1 H-pyrroles-4-methyl alcohol.
At 0 ℃, the lithium aluminium hydride reduction of 1.95g little by little is added to the 1-(2-propinyl that 12.6g is obtained by the B step)-3-Trifluoromethyl-1 H-pyrroles-4-Ethyl formate is in 65Cm 3The solution of oxolane in, stirred 2 hours at 20 ℃, add 10Cm 3Ethyl acetate with remove may be excessive hydride, then in the saturated solution with reactant mixture impouring sodium potassium tartrate tetrahydrate, behind ethyl acetate extraction, under reduced pressure distill extract is concentrated into dried.Residue separates in the enterprising circumstances in which people get things ready for a trip spectrum of silicagel column, with the mixed liquor wash-out of hexane and ethyl acetate (7～3), obtains the expection product of 5.7g.Fusing point=45 ℃.
With the operating procedure of embodiment 43, or method (II) or (III), according to the synthetic route of pointing out below, obtain following product.
Embodiment 46:1R, along 2,2-dimethyl-3-(2,2-dibromo vinyl) cyclopropane-carboxylic acid (R, S)-cyano group ((1-benzoyl)-1H-pyrroles-3-yl) methyl esters.
Embodiment 47:1R, along 2,2-dimethyl-3-(2,2-dibromo vinyl) cyclopropane-carboxylic acid (1-(2-propinyl-2-methoxyl group-2-oxo-1H-pyrroles-3-yl) methyl esters.
Embodiment 48:1R, along 2,2-dimethyl-3-(2,2-dibromo vinyl) cyclopropane-carboxylic acid (R or S)-cyano group-(1-(2-propinyl-2-carbomethoxy)-1H-pyrroles-3-yl) methyl esters.
Embodiment 49:1R, anti-(E, 1/3) (Z, 2/3), 2,2-dimethyl-3-(2-chloro-2-trifluoromethyl vinyl) cyclopropane-carboxylic acid (1-(2-propinyl)-2-cyano group-1H-pyrroles-3-yl) methyl esters.
Embodiment 50:1R, along 2,2-dimethyl-3-(2,2-dibromo vinyl) cyclopropane-carboxylic acid (R, S)-cyano group (1 ,-(2-acrylic)-1H-pyrroles-3-yl) methyl esters.
Embodiment 51:1R, along 2,2-dimethyl-3-(3-methoxyl group-3-oxo-1-acrylic) cyclopropane-carboxylic acid (1-(2-propinyl)-2-cyano group-1H-pyrroles-3-yl) methyl esters.
Embodiment 52:1R, along 2,2-dimethyl-3-(2-fluoro-2-oxygen base-2-oxo-1-acrylic) cyclopropane-carboxylic acid (1-(2-propinyl)-2-cyano group-1H-pyrroles-3-yl) formicester.
Figure 911111123_IMG88
Figure 911111123_IMG89
Preparation 13:
Embodiment 46 used raw material alpha-cyano-3 ((1-benzoyl)-pyrroles) methyl alcohol can be made by following method.
Steps A: 1-benzoyl-3-formoxyl pyrroles,
500mg3-formoxyl pyrroles is dissolved in 10Cm 3Oxolane in, then at 20 ℃, disposable adding is dispersed in sodium hydride 227mg in the vaseline oil with 55% amount.Have gas to emit this moment, after stirring 15 minutes, at 5 ℃, dropwise adds 0.58Cm 3Chlorobenzoyl chloride is at 2Cm 3Solution in the oxolane stirred 2 hours at 20 ℃, and dilute with water is used extracted with diethyl ether, and decompression distillation is concentrated into drying, and residue separates in the enterprising circumstances in which people get things ready for a trip spectrum of silica gel, with 7: 3 hexanes and ethyl acetate mixture wash-out, obtains 558mg purpose product.
Nuclear magnetic resoance spectrum (tri-chlorination deuterium)
Represent hydrogen on 4 of the pyrroles with 6.8 to 6.9ppm peak.
Represent the hydrogen on 5 of the pyrroles at the peak at 7.4ppm place.
The hydrogen on the phenyl is represented at from 7.5 to 8.0 peak.
Represent the hydrogen on 2 of the pyrroles at the peak at 7.93ppm place.
Represent the hydrogen on the formyl at the peak at 10.0ppm place.
Step B: alpha-cyano-3-((1-benzoyl)-1-pyrroles) methyl alcohol.
1-benzoyl-3-formoxyl pyrroles and 12Cm with 0.9g 3Methyl alcohol, 4Cm 3Water, 1Cm 3Acetate and 0.47g Cymag mix, stirred 4 hours down at 20 ℃, the reactant mixture example is gone in the brine ice, use ethyl acetate extraction, extract is concentrated into dried with decompression distillation, residue separates in the enterprising circumstances in which people get things ready for a trip spectrum of silica gel, obtains 0.57g purpose product with 1: 1 hexane and eluent ethyl acetate, fusing point: 85 ℃.
Nuclear magnetic resoance spectrum (tri-chlorination deuterium)
Peak at the 5.5ppm place is represented
Figure 911111123_IMG90
Hydrogen
Represent the hydrogen on 4 of the pyrroles at the peak at 6.5ppm place.
The hydrogen of having represented phenyl from 7.3 to 7.9ppm peak.
Figure 911111123_IMG91
Preparation 14:
Be used as the 4-(hydroxymethyl of the raw material of embodiment 47)-the 1-(2-acrylic)-1H-pyrroles-2-methyl formate can be prepared as follows.
Steps A: 1H-pyrroles-2-methyl formate
With cold concentration is the solution 40Cm of 45nmoles/l2-chloroformyl base-1H-pyrroles in carrene 3Under cooling, dropwise join 4.3Cm 3Pyridine and 3.5Cm 3In the methanol mixture, reactant mixture is water and 6Cm successively 3Dichloromethane extraction is used in the sodium hydroxide washing of 1N.Organic facies is carried out drying, is concentrated into driedly, and residue separates in the enterprising circumstances in which people get things ready for a trip of silica gel spectrum.With the mixture wash-out of 8: 2 hexanes and ethyl acetate, obtain the expection product of 4.014g, 74 ℃ of fusing point: ≌.
Step B:
The 1-(2-propinyl)-1H-pyrroles-2-methyl formate.
With 3.302g1H-pyrroles-2-methyl formate, be dissolved in 40Cm 3Oxolane in, be dispersed in sodium hydride suspension 1.422g in the vaseline oil 0 ℃ of adding with 50% amount then, stirred 1 hour down at 20 ℃, dropwise add 2Cm 3Propargyl bromide at 10Cm 3Solution in the oxolane stirred 1 hour down at 50 ℃, was adding 5Cm 3Propargyl bromide after, reactant mixture is poured in the water, and uses dichloromethane extraction, the extract decompression distillation is concentrated into dried.Residue separates in the enterprising circumstances in which people get things ready for a trip spectrum of silica gel, obtains 2.993g purpose product with 9: 1 hexanes and ethyl acetate mixture wash-out.
Nuclear magnetic resoance spectrum (tri-chlorination deuterium)
Peak at the 2.37-2.42-2.46ppm place represents-hydrogen of H-C ≡ CH.
Peak at 3.8ppm is represented-OCH 3Hydrogen.
Peak at the 5.16-5.20ppm place is represented-CH 2The hydrogen of-C ≡ CH-C.
Represent the hydrogen on 4 of the pyrroles from 6.1 to 6.2ppm peak.
Represent the hydrogen on 3 and 5 of the pyrroles from 6.9 to 7.0ppm and 7.1 to 7.2ppm peak.
Step C:4-formoxyl-1-(2-propinyl)-1H-pyrroles-2-methyl formate.
1-(2-propinyl with 2.981g)-1H-pyrroles-2-methyl formate is at 11Cm 3Solution in the carrene and 1Cm 3Nitromethane is at 4Cm 3Solution in the carrene mix solution A.The alchlor of 4.312g is suspended in 11Cm 3In the carrene, suspension is cooled to-62 ℃, dropwise adds solution A, adds then and contains 2.3Cm 3Dichloromethyl ether and 19Cm 3The solution of carrene.Stirred 2 hours down at-60 ℃, stirred at ambient temperature again 1 hour.Add 200Cm 3Carrene and 300Cm 3Water, using 11Cm 310N sodium hydroxide in and after, stir and decant, organic facies is washed with potassium bicarbonate solution, and is dry and be concentrated into driedly, residue separates in the enterprising circumstances in which people get things ready for a trip spectrum of silica gel, with 7: 3 hexanes and ethyl acetate elution, obtains 2.734g and expects product.
Step D:4-(hydroxymethyl)-the 1-(2-propinyl)-1H-pyrroles-2-methyl formate.
With 747mg4-formoxyl-1-(2-propinyl)-1H-pyrroles-2-methyl formate is dissolved in 12Cm 3Oxolane and 3.3Cm 3Water in, add the potassium borohydrid of 426mg, stirred 5 hours down at 20 ℃.Reactant is poured in the saturated sodium-chloride water solution, uses dichloromethane extraction, and extract is concentrated into dried with decompression distillation, obtains the purpose product of 758mg, fusing point: 77 ℃.
Infrared spectrum (chloroform)
At 3609Cm -1The place absorbs expression-OH.
At 3307Cm -1The place absorbs expression-C ≡ CH.
At 2110Cm -1The place absorbs expression-C ≡ C
At 1702Cm -1The place absorbs expression-C=O
At 1445Cm -1The place absorbs expression-CH 3
1564,1476Cm -1The place absorbs the expression heterocycle.
Figure 911111123_IMG92
Embodiment 50:1R, along 2,2-dimethyl-3-(2,2-two bromo vinyl) cyclopropane-carboxylic acid (R, S)-cyano group (1-(2-acrylic)-1H-pyrroles-3-yl) methyl esters.
With 1R, along 2,2-dimethyl-3-(2,2-two bromo vinyl) cyclopropane-carboxylic acid (R, S)-cyano group (1-(2-propinyl)-1H-pyrroles-3-yl) methyl esters 682mg and 25Cm 3The De diox mixes in hydrogenation plant, adds then with 5% amount to be attached to palladium 167mg and 1/10Cm on the barium sulfate 3Quinoline.After the hydrogen cleaning and stirring, when having absorbed 35Cm 3During hydrogen, stop hydrogenation.Reactant filters, and the filtrate decompression distillation is concentrated into dried, and residue with the mixture of 85: 15 hexanes and ethyl acetate and 2% triethylamine wash-out, obtains the purpose product of 535mg, 60 ℃ of fusing points after the enterprising circumstances in which people get things ready for a trip spectrum of silica gel is separated.(α) D=-54 ° (C=0.6% toluene).
Figure 911111123_IMG93
Figure 911111123_IMG94
According to the step of embodiment 43 or according to process (II), the synthetic route that (III) or (IV) pointed out below can obtain following product:
Embodiment 53:1R, suitable, (E) 2,2-dimethyl-3-(2-fluoro-2-ethyoxyl-2-oxo-1-acrylic) cyclopropane-carboxylic acid (1-(2-acrylic)-2-cyano group-1H-pyrroles-4-yl) methyl esters.
Embodiment 54:1R, along 2,2-dimethyl-3-(2,2-two bromo vinyl) cyclopropane-carboxylic acid (1-(2-acrylic)-2-cyano group-1H-pyrroles-4-yl) methyl esters.
Embodiment 55:1R, along 2,2-dimethyl-3-(2,2-two bromo vinyl) cyclopropane-carboxylic acid (R, S)-cyano group-(1-(2-acrylic)-2-cyano group-1H-pyrroles-4-yl) methyl esters.
Embodiment 56:1R, along (E) 2,2-dimethyl-3-(2-fluoro-3-ethyoxyl-3-oxo-1-acrylic) cyclopropane-carboxylic acid (1-(2-acrylic)-1H-pyrroles-3-yl) methyl esters.
Embodiment 57:1R, along (E), 2,2-dimethyl-3-(2-fluoro-3-ethyoxyl-3-oxo-1-acrylic) cyclopropane-carboxylic acid 1-(1-(2-propinyl)-2-cyano group-1H-pyrroles-4-yl) propine-2-ester.
Embodiment 58:1R, along (E) 2,2-dimethyl-3-(2-fluoro-3-ethyoxyl-3-oxo-1-acrylic) cyclopropane-carboxylic acid (R.S)-cyano group-(1-(2-acrylic)-2-cyano group-1H-pyrroles-4-yl) methyl esters.
Embodiment 59:1R, along 2,2-dimethyl-3-(2, the rare base of 2-two bromo second) cyclopropane-carboxylic acid (1-(2-propinyl)-2-cyano group-1H-pyrroles-4-yl)-the 1-ethyl ester.
Figure 911111123_IMG95
Preparation 15:
(2-cyano group-1-(2-propenyl)-1H-pyrroles-4-methyl alcohol as embodiment 53 raw materials) can be prepared as follows:
Steps A: 2-cyano group-1-(2-acrylic)-1H-pyrroles-4-formaldehyde.
At 20g2-cyano group-4-formoxyl-1H-pyrroles and 250Cm 3Be suspended in suspension in the vaseline oil with the sodium hydride that bit by bit adds 8.01g50% in the mixture of oxolane, add 14Cm down at 20 ℃ then 3Allyl bromide, bromoallylene and 20Cm 3The mixture of oxolane stirred 2 hours at 60 ℃, and then added 14Cm 3Allyl chloride, stirred 2 hours at 60 ℃ again, reactant is poured into used dichloromethane extraction in the water then, this extract decompression distillation is concentrated into dried, residue separates in the enterprising circumstances in which people get things ready for a trip spectrum of silica gel, obtains 24.1g purpose product with 6: 4 hexanes and eluent ethyl acetate.
Step B: (2-cyano group-1-(2-propenyl)-1H-pyrroles-4-methyl alcohol).
With 14.1g4-formoxyl-2-cyano group-1-(2-acrylic)-1H-pyrroles, 160Cm 3Oxolane and 43Cm 3Water mixes, and adds the 481mg lithium borohydride, stirs 30 minutes down at 20 ℃.Add the 493mg lithium borohydride again, stirred again 20 minutes at 20 ℃, add ethyl acetate then, use ethyl acetate extraction after it is poured into saturated sodium-chloride water solution, decompression distillation is concentrated into dried, residue separates in the enterprising circumstances in which people get things ready for a trip spectrum of silica gel, with 55: 45 hexanes and ethyl acetate mixture elution, obtains 13.882g purpose product.
Nuclear magnetic resoance spectrum (tri-chlorination deuterium)
Peak at the 1.97ppm place represents-hydrogen of OH
Peak at the 4.5ppm place is represented-CH 2The hydrogen of O
Peak at the 4.5-4.7ppm place is represented-N=CH 2Hydrogen
Peak at 5.0～5.4ppm place is represented=CH 2Hydrogen
Represent from the peak of 5.7-6.2ppm-hydrogen of CH=
The hydrogen of representing aromatics at the peak at 6.8-6.9ppm place
Embodiment 54:
Figure 911111123_IMG96
Figure 911111123_IMG97
Preparation 16:
Be used as Alpha-hydroxy-(the 2-cyano group-1-(2-acrylic) of embodiment 55 raw materials)-1H-pyrroles-4-acetonitrile can be prepared as follows:
With 1.072g2-cyano group-1-(2-acrylic)-1H-pyrroles-4-formaldehyde, 15Cm 3Methyl alcohol, 4.5Cm 3Water and 2.5Cm 3Acetate mixes, and then, adds the 2g Cymag at 0 ℃, stirs 4 hours 30 minutes at 20 ℃, and then adds 3Cm 3Acetate and 3g Cymag stirred 2 hours at 20 ℃, after washing with water, used dichloromethane extraction again, and decompression distillation is concentrated into dried, obtains 1.25g purpose product.
Embodiment 56:1R, along (E) 2,2-dimethyl-3-(2-fluoro-3-ethoxy carbonyl-1-acrylic) cyclopropane-carboxylic acid 1-(2-acrylic-1H-pyrroles-3-yl) methyl esters.
With 700mg1R, along (E) 2,2-dimethyl-3-(2-fluoro-3-carbethoxyl group-1-acrylic) cyclopropane-carboxylic acid 1-(2-propinyl-1H-pyrroles-3-yl) methyl esters.0.14Cm 3Quinoline and 200mg are attached to palladium on the barium sulfate with 5% amount and send in the hydrogenation plant together and feed hydrogen and stir, when absorption of hydrogen to 45Cm 3In time, stop to react, and after reactant filtered, decompression distillation is concentrated into did this filtrate, and chromatographic isolation residue on silica gel with the triethylamine washing of 7: 3 hexanes and ethyl acetate and 2%, obtains the purpose product of 482mg.
(α) D=+15.5 ° (C=0.4% toluene)
Figure 911111123_IMG98
Preparation 17:
Be used as the 1(R of raw material among the embodiment 57, S) hydroxyl-(2-cyano group-1-(2-propinyl)-1H-pyrroles-4-yl)-the 2-propine can be prepared as follows:
At 20 ℃ with the 3g1-(2-propinyl)-2-cyano group-4-formoxyl-1H-pyrroles is dissolved in 20Cm 3In the oxolane, poured this solution into 70Cm that titration concentration is 0.82mmole/l with 10 minutes 3In the tetrahydrofuran solution of acetenyl bromination magnesium.Stir after 3 hours 30 minutes, reactant is poured in the saturated biphosphate sodium water solution, and use extracted with diethyl ether, the extract decompression distillation is concentrated into dried, residue is used chromatographic purification on silica gel, obtain 2.897g purpose product with 1: 1 hexane and ethyl acetate mixture wash-out, fusing point=66 ℃.
Nuclear magnetic resoance spectrum (tri-chlorination deuterium)
The hydrogen of representing hydroxyl at the peak at 2.3-2.4ppm place
Represent at the peak at 2.51-2.55-2.59ppm place on the propinyl-hydrogen of C ≡ CH
Peak at the 2.61-2.65ppm place is represented
Figure 911111123_IMG99
Hydrogen
Peak at the 4.74-4.82ppm place is represented-CH 2The hydrogen of methylene on the-C ≡ CH
Peak at the 5.40ppm place is represented
Figure 911111123_IMG100
Hydrogen
Represent each hydrogen on 3 and 5 of pyrrole at the peak at 6.90-6.93ppm place.
Figure 911111123_IMG101
Figure 911111123_IMG102
Raw materials used 2-cyano group-4 (1(R.S) ethoxy-1-(2-propinyl among the embodiment 59))-1H-pyrroles can be with the preparation of following method:
To contain the 4g1-(2-propinyl)-2-cyano group-4-formoxyl-1H-pyrroles's 45Cm 3Tetrahydrofuran solution slowly joins 50Cm under 10 ℃ 3Contain in the oxolane mixed liquor (titration concentration 1.7mmol/l) of methyl magnesium iodide.Stirring is after 4 hours down at 20 ℃, and reactant mixture is poured in the biphosphate saturated aqueous solution of sodium, and uses extracted with diethyl ether.With the extract decompression distillation: be concentrated into drying, residue separates at the enterprising circumstances in which people get things ready for a trip layer of silica, with hexane and ethyl acetate mixed liquor (1-1) wash-out, obtains the required product of 2.855g.Fusing point is lower than 50 ℃.
Nuclear magnetic resoance spectrum (CDCl 3)
1.4-1.5ppm between the peak represent hydrogen in the methyl
2.50-2.54-2.58ppm between the peak represent-hydrogen among the C ≡ C-H
4.68-4.80 and the peak between the 4.90-5.03ppm is represented
Figure 911111123_IMG103
4.76-4.80ppm between the peak represent CH 2Hydrogen on the methylene among the-C ≡ C-H
6.80-6.83ppm and 4.91 and 5.03ppm between the peak represent last 3 and 5 s' of pyrroles hydrogen
With the operating procedure of embodiment 43, or, obtain following product according to the method (I) of the synthetic route of pointing out below:
Embodiment 60:1R, along (E) 2,2-dimethyl-3-(2-fluoro-3-ethyoxyl-3-oxo-1-acrylic) cyclopropane-carboxylic acid (1-(2-propinyl)-2-cyano group-1H-pyrroles-4-yl) ethyl ester.
Embodiment 61:1R, along 2,2-dimethyl-3-(2,2-two bromo vinyl) cyclopropane-carboxylic acid 1R, the S/1-(2-propinyl)-2-cyano group-1H-pyrroles-4-base/propine-2-ester.
Embodiment 62:1R, along 2,2-dimethyl-3-(2,2-two bromo vinyl) cyclopropane-carboxylic acid (1-(2-propinyl)-4-cyano group-1H-pyrroles-3-yl) methyl esters.
Embodiment 63:1R, along (E) 2,2-dimethyl-3-(2-fluoro-3-ethyoxyl-3-oxo-1-acrylic) cyclopropane-carboxylic acid (1-(2-propinyl)-4-cyano group-1H-pyrroles-3-yl) methyl esters.
Embodiment 64:1R, along 2,2-dimethyl-3-(2,2-two bromo vinyl) cyclopropane-carboxylic acid (R, S)-cyano group-(1-(2-propinyl)-4-cyano group-1H-pyrroles-3-yl) methyl esters.
Embodiment 65:1R, along (E) 2,2-dimethyl-3-(2-fluoro-3-ethyoxyl-3-oxygenate-1-acrylic) cyclopropane-carboxylic acid (2-cyano group-(1-(3-chloro-2-(Z)-acrylic)-1H-pyrroles-4-yl) methyl esters.
Embodiment 66:1R, along (E) 2,2-dimethyl-3-(2-fluoro-3-ethyoxyl-3-oxo-1-acrylic) cyclopropane-carboxylic acid (2-cyano group-(1-(3-chloro-2-(E)-acrylic)-1H-pyrroles-4-yl) methyl esters.
Embodiment 67:1R, along (E) 2,2-dimethyl-3-(2-fluoro-3-ethyoxyl-3-oxo-1-acrylic) cyclopropane-carboxylic acid (R, S)-cyano group-(1-(2-propinyl)-2-cyano group-1H-pyrroles-3-yl) methyl esters.
Figure 911111123_IMG104
Figure 911111123_IMG105
Figure 911111123_IMG106
Figure 911111123_IMG107
Preparation 19:
Raw material 4-((R, S) alpha-cyano methanol-based)-1-(2-propinyl)-1H-pyrroles-3-nitrile used among the embodiment 64 can prepare with following method:
Steps A: 1,3-butadiene (1, two (the dimethylamino)-2-cyano group of 4--3-methyl formate.
With 23g alpha-cyano methyl propionate and 126Cm 3Two (dimethylamino) methane blended of tert-butoxy, placed 5 hours down at 170 ℃.Isobutanol at first steams.Reaction mixture temperature is reduced to 50 ℃, then vacuum (0.1 millimetres of mercury), 110 ℃ of following placements 1 hour.Mixture is after the silica chromatogram is purified, and mixed liquor (1-9) elution with hexane and ethyl acetate obtains the required product of 15.9g, and fusing point is 106 ℃.
Step B:3-cyano group-1-(2-propinyl)-1H-pyrroles-4-methyl formate.
With 14.5g1,3-butadiene 1, two (the dimethylamino)-2-cyano group of 4--3-methyl formate, 400Cm 3Ethanol and 4.2Cm 3Single propargylamine mix, refluxed 5 hours.With the reactant mixture cooling, pour in the saturated aqueous sodium chloride subsequently, use dichloromethane extraction.The decompression distillation extract is concentrated into drying.Residue separates in the enterprising circumstances in which people get things ready for a trip spectrum of silica, and mixed liquor (65-35) elution with hexane and ethyl acetate obtains the required product of 3.75g, and fusing point is 134 ℃.
Step C:4-methylol-1-(2-propinyl)-1H-pyrroles-3-nitrile.
With 3.90g3-cyano group-1-(2-propinyl)-1H-pyrroles-4-methyl formate, 35Cm 3Oxolane, 11Cm 3Water and 1.556g lithium borohydride mix, and 20 ℃ were stirred 3 hours 30 minutes down.Reactant mixture is poured in the saturated aqueous sodium chloride, stirred, use ethyl acetate extraction.The decompression distillation extract is concentrated into drying.Residue separates in the enterprising circumstances in which people get things ready for a trip spectrum of silica, and mixed liquor (4-6) elution with hexane and ethyl acetate obtains the required product of 1.33g, and fusing point is 95 ℃.
Step D:4-formoxyl-1-(2-propinyl)-1H-pyrroles-3-nitrile.
With 18Cm 3The dichloromethane solution of 1M dimethyl sulfoxide (DMSO) dropwise drips to 9.5Cm under-60 ℃ 3In the dichloromethane solution of 1M oxalyl chloride, stirred 5 minutes down at-60 ℃.Under-60 ℃, dropwise splash into 724g4-methylol-1-(2-propinyl)-1H-pyrroles-3-nitrile solution, under same temperature, stirred 5 hours.Subsequently, in 30 minutes, dropwise add 25Cm while stirring under-60 ℃ 3The dichloromethane solution of 1M triethylamine.The question response mixture temperature reaches environmental temperature, adds water, stirs.Clarification then.Wash organic facies with saturated aqueous sodium chloride, decompression distillation is concentrated into drying.Residue separates in the enterprising circumstances in which people get things ready for a trip spectrum of silica, and mixture (1-1) elution with hexane and ethyl acetate obtains the required product of 702mg, and fusing point is 114 ℃.
Step e: 4-((R, S) alpha-cyano methanol-based)-1-(2-propinyl)-1H-pyrroles-3-nitrile.
With 495mg4-formoxyl-1-(2-propinyl)-1H-pyrroles-3-nitrile, 15Cm 3Methyl alcohol, 2.1Cm 3Water, 1.2Cm 3Acetate and 900mg Cymag mix.When temperature reaches 20 ℃, stirred 15 minutes down at 20 ℃.Wash reactant mixture with water, use ethyl acetate extraction, and distillation under reduced pressure, concentrated extract obtains being used for the required crude product of embodiment 46 to dry.
Embodiment 65:1R, along (E) 2,2-dimethyl-3-(2-fluoro-3-ethyoxyl-3-oxo-1-acrylic) cyclopropane-carboxylic acid (2-cyano group-1-(3-chloro-2-(Z)-acrylic)-1H-pyrroles-4-yl) methyl esters.
With 1.55g (2-cyano group-1-(3-chloro-2-(Z+E)-acrylic)-1H-pyrroles-4-yl)-methyl alcohol, 1.8g1R, along (E) 2,2-dimethyl-3-(2-fluoro-3-ethyoxyl-3-oxo-1-acrylic) cyclopropane-carboxylic acid and 20Cm 3Carrene mixes, and then, under+5 ℃, adds 1.625 gram dicyclohexyl carbodiimides gradually, 10Cm 3The mixture of carrene and 29mg4-dimethylamino pyridine, and under 20 ℃, stirred 20 hours.After the filtration, decompression distillation filtrate is concentrated into drying.Separate in the enterprising circumstances in which people get things ready for a trip spectrum of silica,, obtain the required product of 0.83g with 7-3 and the hexane of 9-1 ratio and the mixed liquor elution successively of ethyl acetate.
(α) D=+32.5 ° (C=0.8% toluene)
Embodiment 66:1R, along (E) 2,2-dimethyl-3-(2-fluoro-3-ethyoxyl-3-oxo-1-acrylic) cyclopropane-carboxylic acid (2-cyano group-1-(3-chloro-2-(E)-acrylic)-1H-pyrroles-4-yl) methyl esters.
From the follow-up distillate of embodiment 65 chromatographic isolation, can obtain the required product of 0.32g.
(α) D=+28 ° (C=0.5% toluene)
Preparation 20: the raw material 4-methylol among the embodiment 65 and 66-2-cyano group-1-(3-chloro-2-acrylic)-the available following method preparation of 1H-pyrroles's (suitable, anti-):
Steps A: 4-formoxyl-2-cyano group-1-(3-chloro-2-acrylic)-1H-pyrroles's (suitable, anti-)
4.15g2-cyano group-4-formoxyl-1H-pyrroles is added to 20Cm 3In the dimethyl formamide, be cooled to+10 ℃ after, bit by bit add and contain 1.563g55% and be dispersed in sodium hydride in the oil, then stirred 30 minutes down at+15 ℃.Be cooled to+5 ℃ after, in 20 minutes, add 32Cm 31, the 3-dichloropropylene ,+15 ℃ were stirred 2 hours down.Reactant mixture is poured in the water, used extracted with diethyl ether.Drying concentrates the ether phase, and chromatographic isolation residue on silica with mixed liquor (1-1) elution of hexane and ethyl acetate, obtains 6.4g expection product.
Step B:4-methylol-2-cyano group-1-(3-chloro-2-acrylic)-1H-pyrroles's (suitable, anti-).
With the 4g product that obtains in the steps A, 100Cm 3Oxolane, 22Cm 3Distilled water and 4.4g potassium borohydride mix, and stir 45 minutes, add ether, stir 2 hours again.By the solution clarification, the extraction that adds diethyl ether again, the method for dry organic facies obtains required product.
Preparation 21:
Used raw material 2-hydroxyl among the embodiment 67-(R, S)-2-cyano group-1-(2-propinyl)-1H-pyrroles-3-acetonitrile can be with following method preparation:
Steps A: 3-formoxyl-2-cyano group-1-(2-propinyl)-1H-pyrroles
With 27Cm 3The dichloromethane solution (1M) that contains oxalyl chloride is cooled to-60 ℃, adds 13.5Cm then 3The dichloromethane solution (1M) that contains dimethyl sulfoxide (DMSO).Stir after 5 minutes, add again and contain 1.09g3-methylol-1-(2-propinyl)-20Cm of 1H-pyrroles-2-acetonitrile 3Carrene was placed 2 hours down for-60 ℃.Add 70Cm 3The dichloromethane solution (1M) that contains triethylamine ,-60 ℃ were stirred 10 minutes down, temperature are risen to 20 ℃ subsequently.Add 20Cm 3Water stirs, and clarification is concentrated into drying.Residue separates in the enterprising circumstances in which people get things ready for a trip spectrum of silicon dichloride, and mixture (6-4) elution with hexane and ethyl acetate obtains the required product of 456mg.
Nuclear magnetic resoance spectrum (CDCl 3)
2.59-2.63-2.65ppm the peak of locating represents-proton on the C ≡ CH
6.75-6.8 and the proton on the pyrroles is represented at the peak at 7.15-7.18ppm place
4.9-4.95ppm CH in the propinyl is represented at the peak of locating 2On proton
The proton on the formyl is represented at peak on the 10ppm
Step B:2-hydroxyl-(R, S)-2-cyano group-1-(2-propinyl)-1H-pyrroles-3-acetonitrile.
By step e operation in the preparation 19, with 546mg3-formoxyl-2-cyano group-1-(2-propinyl)-1H-pyrroles does raw material, obtains required product.
With the operating procedure of embodiment 1,, obtain following product according to the synthetic route of pointing out below:
Embodiment 68:1R, along (E) 2,2-dimethyl-3-(2-fluoro-3-ethyoxyl-3-oxo-1-acrylic) cyclopropane-carboxylic acid (R, S)-cyano group-(1-(2-propinyl)-3-cyano group-1H-pyrroles-4-yl) methyl esters.
Embodiment 69:1R, along (Z) 2,2-dimethyl-3-(3-methoxyl group-3-oxo-1-acrylic) cyclopropane-carboxylic acid (R, S)-cyano group-(1-(2-propinyl-2,2,2-three fluoro methyl isophthalic acid H-pyrroles-4-yl) methyl esters.
Embodiment 70:1R, along (E) 2,2-dimethyl-3-(2-fluoro-3-ethyoxyl-3-oxo-1-acrylic) cyclopropane-carboxylic acid (1-(2-propinyl)-2,2,2-three fluoro methyl isophthalic acid H-pyrroles-4-yl) methyl esters.
Embodiment 71:1R, along (Z) 2,2-dimethyl-3-(3-methoxyl group-3-oxo-1-propylene) cyclopropane-carboxylic acid (1-(2-propinyl)-3,3,3-Trifluoromethyl-1 H-pyrroles-4-yl) methyl esters.
Embodiment 72:1R, along (E) 2,2-dimethyl-3-(2-fluoro-3-ethyoxyl-3-oxo-1-acrylic) cyclopropane-carboxylic acid (1-(2-propinyl)-3,3,3-Trifluoromethyl-1 H-pyrroles-4-yl) methyl esters.
Embodiment 73:1R, along 2,2-dimethyl-3-(2,2-dibromo vinyl) cyclopropane-carboxylic acid (2-cyano group-1-(3-chloro-2(Z)-acrylic)-1H-pyrroles-4-yl) methyl esters.
Embodiment 74:1R, along 2,2-dimethyl-3-(2,2-two bromo vinyl) cyclopropane-carboxylic acid (2-cyano group-1-(3-chloro-2(E)-acrylic)-1H-pyrroles-4-yl) methyl esters.
Figure 911111123_IMG110
Preparation 22:
Raw material 2-three fluoro methyl isophthalic acids-(2-propynyl)-1H-pyrroles-4-methyl alcohol used among the embodiment 69 and 70 can prepare with following method:
Steps A: 4-(1-(2-propinyl)-2-three fluoro methyl isophthalic acid H-pyrroles) Ethyl formate.
With 9g3-azepine-5-hexin-1-acid-hydrochloride 120Cm 3Toluene and 9.15Cm 3Ethyl propionate mixes, and adds 18.6Cm under+5 ℃ gradually 3Trifluoroacetic anhydride.After reactant mixture returns 4 hours 45 minutes, be cooled to+30 ℃; Add 9.3Cm 3Trifluoroacetic anhydride, reaction mixture refluxed 5 hours also stirred 12 hours under 20 ℃, added 5.6Cm 3Acetic anhydride with reaction mixture refluxed 2 hours, after the cooling, is poured in the water, adds ether, and neutralizes with saturated solution of sodium bicarbonate.Use the extracted with diethyl ether mixed liquor, decompression distillation is concentrated into drying, chromatographic isolation residue on silica, and mixed liquor (8-2) elution with hexane and ethyl acetate obtains the required product of 3.964g.Fusing point is lower than 50 ℃.
Infrared spectrum (chloroform)
-at 1712Cm -1The place absorbs, expression ester C=0
-at 3140Cm -1, 1572Cm -1, 1519Cm -1The place absorbs, expression heterocycle=CH
-at 1187Cm -1, 1162Cm -1, 1116Cm -1The place absorbs, expression CF 3
-at 3307Cm -1The absorption at place, expression C ≡ CH, ≡ CH
-at 2125Cm -1The place absorbs, expression C ≡ C
Step B:2-three fluoro methyl isophthalic acids-(2-propynyl)-1H-pyrroles-4-methyl alcohol.
With 4.785g4-(1-(2-propinyl)-2-Trifluoromethyl-1 H-pyrroles) Ethyl formate is dissolved in 40Cm 3In the oxolane.Bit by bit add 750 milligrams of lithium aluminium hydride reductions under 0 ℃ ,+7 ℃ were stirred 30 minutes down, stirred 3 hours down at 20 ℃ again, added several ethyl acetate and 10Cm then 3The saturated aqueous solution of disodium tartrate.Filter reaction mixture, filtrate are concentrated into drying by decompression distillation, and residue is chromatographic isolation on silica, and mixed liquor (6-4) elution with hexane and ethyl acetate obtains the required product of 3.45g.
Infrared spectrum (chloroform)
-at 3610Cm -1The place absorbs, expression-OH
-at 3308Cm -1The place absorbs, expression-C ≡ CH
-at 1580Cm -1, 1510Cm -1The place absorbs, expression
Figure 911111123_IMG112
Figure 911111123_IMG113
Figure 911111123_IMG114
Figure 911111123_IMG115
Embodiment 75: the preparation of soluble concentrate
Homogeneous mixture is prepared by following material:
The product of embodiment 1 ... 0.25g
Piperonyl butoxide ... 1.00g
Tween 80 (TWeen80) ... 0.25g
Holder handkerchief Nore A(TopanolA) ... 0.1g
Water ... 98.4g
Embodiment 76: the preparation of emulsible concentrate
Following material is mixed fully:
The product of embodiment 2 ... 0.015g
Piperonyl butoxide ... 0.5g
Holder handkerchief Nore A(TopanolA) ... 0.1g
Tween 80 (Tween 80) ... 3.5g
Dimethylbenzene ... 95.885g
Embodiment 77: the preparation of emulsible concentrate
Homogeneous mixture is prepared by following material:
The product of embodiment 40 ... 1.5g
Tween 80 (Tween 80) ... 20.00g
Holder handkerchief Nore A(TopanolA) ... 0.1g
Dimethylbenzene ... 78.4g
Embodiment 78: stifling preparation of compositions
Following material is evenly mixed:
The product of embodiment 1 ... 0.25g
The Tabu powder ... 25.00g
The cedar leaf powder ... 40.00g
Pine powder ... 33.75g
Shell is green ... 0.5g
P-nitrophenol ... 0.5g
Embodiment 79: the compound foodstuff embodiment of animal
Comprise corn, dehydrated alfalfa, straw, the basic foodstuff of the foodstuff of Areca plant, the urea element of honey, vitaminized inorganic flavor enhancement as balance arranged.
This foodstuff contains minimum 11% thick protein material (2.8%, from the urea element), 2.5% fatty material, maximum 15% cellulosic materials, 6% mineral matter and 13% moisture.
The every 100Kg of foodstuff that uses is equivalent to 82 fodder unit, and every 100Kg contains vitamin A 910,000I.u, vitamin D 391,000Iu, vitamin E 150mg, vitamin C 150mg.
Every 100Kg total eclipse material contains the compound 0.3Kg of embodiment 1 in this foodstuff.
Embodiment 80: the compound foodstuff embodiment of animal
Application is as the basic foodstuff of the identical balance of using in embodiment 79.Every in the present embodiment 100Kg total eclipse material contains the compound of 0.04Kg embodiment 1.
Biological study
1) housefly is knocked down activity research
The test insect is 4 days a female housefly.This test is with acetone (5%) and IsoparL(petrolic solvent) mixture as solvent (solvent load per second 2ml), in Ji En and Ma Qi chamber (Ktans and March Chamber), undertaken by direct spraying.The each test with 50 insects.The per minute check was checked in the time of 15 minutes then once up to 10 minutes.Measure KT 50 with usual way.
Obtain following result:
The KT50(branch of embodiment) the KT50(branch of embodiment)
Compound concentration 0.1g/L compound concentration 0.1g/L
1 1.3 50 3.5
2 1.6 56 4.0
3 5.8 43 2.9
4 2.4 53 2.4
5 3.2 54 4.7
6 4.7 55 8.7
15 1.8 60 1.8
26 3.5 57 4.0
40 5.6 65 3.1
44 2.2 66 7.9
48 3.7 67 3.8
51 1.9 45 6.1
52 1.5 72 3.8
49 11.0 69 4.8
70 3.9
Conclusion: product of the present invention has good knockdown effect for housefly.
2) by cockroach De Fu joint contact carrying out activity research
The male cockroach of insect (Blatella germanica) is used in test.Carry out at the end of the Petri dish of this test by certain density acetone soln being deposited on diameter 20Cm.After the drying, 20 male cockroaches of each concentration kept 1 hour on culture dish, then cockroach is transferred on the medium of health, and at 24 hours, 48 hours, the 3rd day and the 5th day check cockroach lethality.
Result of the test is with the lethal concentration of 50 (lethal Concentration 50(LC50)) mg/m 2Expression.
Embodiment LC50
43 2.8
45 6.4
72 6.7
70 4.5
Conclusion: product of the present invention has biocidal activity for cockroach.
3) to the research of aphid (Cracivora) lethal effect
The adult of using 7 days, 10 aphids of each concentration are with contacting the method for ingesting.Handle with the Fisher sprayer on the beans leaf, the beans leaf is placed in the plastics Petri dish on the moistening paper disc.Use in test the acetone soln (every 1ml of leaf) that 2ml contains product, put insect after the leaf drying.Keep insect to contact 1 hour with leaf, then insect is placed on the leaf that does not have processing, check lethality after 24 hours.
The result of the test that obtains is summarised in the following table:
Embodiment LD50
The mg/ insect
49 6.5
43 7.5
Conclusion: product of the present invention has lethal effect to aphid.
4) acaricidal activity is to the lethal effect test of adult
Application has dicots pulses leguminous plants, and leaf is handled with the Fisher sprayer with the acetone soln that contains product.After the drying, put 25 female mites (Tetranychus urticae) on the every leaf, i.e. 50 mites of each test dose of each plant.Contact testing effect after 80 hours, LD50 represents with mg/hl.
Embodiment LD50
40 32
43 342
45 264
70 2126
Conclusion: the product of the present invention particularly product of embodiment 40 has significant acaricidal action to Tetranychus urticue.

Claims (18)

1, a kind of Pesticidal combination comprises that the formula I compound of 0.005%-99% is an active component, a kind of excipient and/or surfactant and add or do not add a kind of pyrethroid,
Figure 911111123_IMG2
(Ⅰ)
Wherein:
R 2Or R 3One of represent the base of following formula:
Figure 911111123_IMG3
A represents the base of following formula in the formula:
Z in the formula 1And Z 2Represent a methyl separately,
Or Z 1Represent H,
Z 2Represent the base of following formula:
Figure 911111123_IMG5
Z in the formula 3Represent H or fontanelle atom,
T 1And T 2Identical, represent H, fontanelle atom or CF 3,
Z 2Or represent the base of following formula:
Figure 911111123_IMG6
D represents H or fontanelle atom in the formula,
G represents O,
The J representative contains the straight or branched alkyl of 1-4 carbon atom,
A or represent the base of following formula:
Figure 911111123_IMG7
U in the formula on any position of benzene nucleus, represents fontanelle atom, contains the alkyl of 1-4 carbon atom, and m represents 0 or 1,
Z represents H, C ≡ N, C ≡ CH, CF 3Base or contain the alkyl of 1-3 carbon atom,
Do not represent
Figure 911111123_IMG8
R 2Or R 3, and R 4And R 5, identical or different each other, represent H, fontanelle atom, CN base, CF 3Base, contain 4 carbon nearly-CO 2Alkyl or NO 2Base,
R 1Represent a following formula base:
Figure 911111123_IMG9
X and Y can be identical or different in the formula, represent H, fontanelle atom,
R 1Or represent a following formula base:
Figure 911111123_IMG10
X ' and Y ' in the formula can be identical or different, represent the implication of above-mentioned X and Y, and Y ' represents phenyl, and dotted line is represented also can form a two key between carbon atom 1 and 2,
R 1Or represent a following formula base:
R ' can represent above-mentioned R in the formula 4And R 5Implication, but do not represent fontanelle atom, CN and NO 2
2, according to the composition of claim 1, R wherein 1Representative-CH 2-C ≡ CH base.
3, according to the composition of claim 1 or 2, R wherein 2And R 3In a base of representing following formula:
Z represents hydrogen atom in the formula.
4, according to the composition of claim 1 or 2, R wherein 2And R 3A base of representing following formula in the base:
Figure 911111123_IMG13
Z represents cyano group in the formula.
5, according to the composition of claim 1 or 2, substituent R wherein 3Represent the base of following formula:
Figure 911111123_IMG14
Z represents H, C ≡ N, C ≡ CH, CF in the formula 3Base or contain the alkyl of 1-3 carbon atom.
6, according to the composition of claim 1 or 2, substituent R wherein 2, R 4And R 5In one represent hydrogen atom.
7, according to the composition of claim 1 or 2, substituent R wherein 2, R 4And R 5In one represent nitro.
8, according to the composition of claim 1 or 2, substituent R wherein 2, R 4And R 5In one represent cyano group.
9, according to the composition of claim 1 or 2, substituent R wherein 2, R 4And R 5In one represent trifluoromethyl.
10, according to the composition of claim 1, wherein A represents the base of following formula:
Figure 911111123_IMG15
Hal represents fontanelle atom in the formula.
11, according to the composition of claim 1, wherein A represents the base of following formula:
Figure 911111123_IMG16
The J representative contains the alkyl of straight chain, side chain or the ring-type of 1-4 carbon atom in the formula, and the geometric configuration of two keys is cis (Z).
12, according to the composition of claim 1, wherein A represents the base of following formula:
Figure 911111123_IMG17
Hal represents fontanelle atom in the formula, and the J representative contains the alkyl of 1-4 carbon atom, and the geometric configuration of two keys is trans (E).
13, according to the composition of claim 12, wherein A represents the base of following formula:
Hal represents fluorine atom in the formula, and the J representative contains the alkyl of 1-4 carbon atom, and the geometric configuration of two keys is trans (E).
14, according to the Pesticidal combination of one of claim 1-13, the application in killing off plant parasite, indoor parasite and warm-blooded animal parasite.
15, according to the application of claim 14, wherein composition is as the parasitic nematode agent extremely of plant.
16, according to the application of claim 14, wherein composition is as miticide.
17, according to the application of claim 14, wherein composition is as insecticide.
18,, wherein contain a kind of pyrethroid that is selected from following compounds according to the composition of claim 1-13:
Allethrin alcohol ketone (allethrolones), 3,4,5,6-tetrahydrochysene phthalimido methyl alcohol, 5-benzyl-3-furfuralcohol, the ester that 3-phenoxy group benzylalcohol and α-Qing Ji-3-Ben Yangjibianchun and chrysanthemumic acid generate, 5-benzyl-3-furfuralcohol and 2,2-dimethyl-3-(2-oxo-3-tetrahydrochysene sulfo-cyclohexadienylene-methyl) ester of cyclopropane-1-formic acid generation, 3-phenoxy group benzylalcohol and α-Qing Ji-3-Ben Yangjibianchun and 2,2-dimethyl-3-(2, the 2-dichloroethylene) ester of cyclopropane-1-formic acid formation, α-Qing Ji-3-Ben Yangjibianchun and 2,2-dimethyl-3-(2, the 2-dibromo vinyl) ester of cyclopropane-1-formic acid formation, the ester that 3-phenoxy group benzylalcohol and 2-rubigan-2-isopropyl acetate generates, the allethrin alcohol ketone, 3,4,5,6-tetrahydrochysene phthalimido methyl alcohol, 5-benzyl-3-furfuralcohol 3-phenoxy group benzylalcohol and α-Qing Ji-3-Ben Yangjibianchun and 2,2-dimethyl-3-(1,2,2,2-four fontanel ethyls) ester that generates of cyclopropane-1-formic acid, wherein fontanel is represented fluorine, the chlorine or bromine atom, the connection of acid in certain above-mentioned pyrethroid and alcohol can exist with they all possible stereoisomer forms.
CN91111112A 1985-04-23 1991-11-20 Contain the Pesticidal combination and the application thereof of new azole derivatives Pending CN1062071A (en)

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FR8506134A FR2580637B2 (en) 1984-08-14 1985-04-23 NOVEL PYRROLE DERIVATIVES, THEIR PREPARATION PROCESS AND THEIR APPLICATION AS PESTICIDES
FR8506134 1985-04-23
CN85106411A CN1015626B (en) 1985-04-23 1985-08-26 Process for preparing new derivatives of pyrrole

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1041629C (en) * 1992-11-03 1999-01-13 美国氰胺公司 Pyrrole thiocarboxamide insecticidal and acaricidal agents

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IL98235A (en) * 1990-07-31 1999-07-14 American Cyanamid Co Process for the preparation of insecticidal acaridical and nematicidal 2-aryl-5-(trifluoromethyl) pyrrole compounds and intermediates thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1041629C (en) * 1992-11-03 1999-01-13 美国氰胺公司 Pyrrole thiocarboxamide insecticidal and acaricidal agents

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