DK164740B - ESTERS OF CYCLOPROPANCARBOXYLIC ACIDS CONDUCTED WITH PYRETHRIC ACID, AND THEIR PREPARATION AND PREPARATIONS CONTAINING THEREOF TO CONTROL PARASITES - Google Patents

Abstract

1. Claims (for the Contracting States : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE) In all possible isomeric forms, or in the form of a mixture of isomers, the compounds with the formula I see diagramm : EP0050534,P45,F2 in which the cyclopropane acid copula is of 1R cis structure and the geometry of the double bond is E and in which R represents either a linear, branched or cyclic alkyl radical, saturated or unsaturated, containing from 1 to 8 carbon atoms, possibly substituted by one or more functional groups, identical or different, or an aryl group containing from 6 to 14 carbon atoms, possibly substituted by one or more functional groups, identical or different, or a heterocyclic radical possibly substituted by one or more functional groups, identical or different, X represents a halogen atom and B represents either a benzyl radical possibly substituted by one or more radicals chosen from the group composed of alkyl radicals including from 1 to 4 carbon atoms, alkenyl radicals including from 2 to 6 carbon atoms, alkenyloxy radicals including from 2 to 6 carbon atoms, alkadienyl radicals including from 4 to 8 carbon atoms, the methylene dioxy radical and halogen atoms, or a see diagramm : EP0050534,P46,F1 group in which the substituent R1 represents a hydrogen atom or a methyl radical and the substituent R2 represents a monocyclic aryl or a -CH2 -C=-CH group and in particular a 5-benzyl-3-furyl methyl group, or a see diagramm : EP0050534,P46,F2 group in which a represents a hydrogen atom or a methyl radical and R3 represents an organic aliphatic radical including from 2 to 6 carbon atoms and one or more carbon-carbon unsaturations and in particular the -CH2 -CH=CH2 , -CH2 -CH=CH-CH3 , -CH2 -CH=CH-CH=CH2 , -CH2 -CH=CH-CH2 -CH3 radical, or a see diagramm : EP0050534,P46,F3 group, in which a represents a hydrogen atom or a methyl radical, R3 retains the same significance as before, each of R'1 and R'2 , identical or different, represents a hydrogen atom, a halogen atom, an alkyl radical including from 1 to 6 carbon atoms, an aryl radical including from 6 to 10 carbon atoms, an alkyloxycarbonyl group including from 2 to 5 carbon atoms, or a cyano group, or a see diagramm : EP0050534,P46,F4 group, in which B' represents an oxygen or sulphur atom, a see diagramm : EP0050534,P46,F5 or -CH2 - group or a sulphoxide group or a sulphone group and R4 represents a hydrogen atom, a -C=-CN radical, a methyl radical, a -CONH2 radical, a -CSNH2 radical or a -C=-CH radical, R5 represents a halogen atom or a methyl radical and n represents a numeral, 0, 1 or 2, and in particular the 3-phenoxybenzyl, alpha-cyano-3-phenoxybenzyl, alpha-ethynyl-3-phenoxybenzyl, 3-benzoylbenzyl, 1-(3-phenoxyphenyl) ethyl or alpha-thioamido-3-phenoxybenzyl group, or a see diagramm : EP0050534,P47,F1 group, or a see diagramm : EP0050534,P47,F2 group, in which the substituents R6 , R7 , R8 , R9 represent a hydrogen atom, a chlorine atom, or a methyl radical and in which S/l symbolises an aromatic ring or an analogous dihydro or tetrahydro ring, or a see diagramm : EP0050534,P47,F3 group or a see diagramm : EP0050534,P47,F4 group, in which R10 represents a hydrogen atom or a CN radical, R12 represents a -CH2 -radical or an oxygen atom, R11 represents a thiazolyl or a thiadiazolyl radical, whose bond with see diagramm : EP0050534,P47,F5 can be found at any one of the available positions, R12 being linked to R11 by the carbon atom contained between the sulphur atom and a nitrogen atom, or a see diagramm : EP0050534,P48,F1 group 1. a see diagramm : EP0050534,P48,F1 group or a see diagramm : EP0050534,P48,F2 group in which R13 represents a hydrogen atom or a CN radical, or a see diagramm : EP0050534,P48,F3 group in which R13 is defined as above, and the benzoyl radical is at position 3 or 4, or a see diagramm : EP0050534,P48,F4 group in which R14 represents a hydrogen atom, a methyl, ethynyl or cyano radical and each of R15 and R16 being different, represents a hydrogen, fluorine or bromine atom, or a see diagramm : EP0050534,P48,F5 group in which R14 is defined as above, each of the R17 'S represents independently an alkyl group containing from 1 to 4 carbon atoms, an alkoxy group containing from 1 to 4 carbon atoms, an alkylthio group containing from 1 to 4 carbon atoms, an alkyl sulphonyl group containing from 1 to 4 carbon atoms, a trifluoromethyl group, a 3,4-methylene dioxy group, or a chloro, fluoro or bromo group, p represents a numeral 0, 1 or 2 and B" represents an oxygen atom or a sulphur atom. 1. Claims (for the Contracting State AT) Process for preparing, in all possible isomeric forms, or in the form of a mixture of isomers, the compounds with the formula I : see diagramm : EP0050534,P52,F3 in which R represents either a linear, branched or cyclic alkyl radical, saturated or unsaturated, containing from 1 to 8 carbon atoms, possibly substituted by one or more functional groups, identical or different, or an aryl group containing from 6 to 14 carbon atoms, possibly substituted by one or more functional groups, identical or different, or a heterocyclic radical possibly substituted by one or more functional groups, identical or different, B represents either a linear, branched or cyclic alkyl radical, saturated or unsaturated, containing from 1 to 18 carbon atoms, or the residue of an alcohol used in the synthesis of esters of the pyrethrinoid series and X represents a halogen atom, the ethylene double bond having the geometry Z or E, characterized in that an acid with the formula II : see diagramm : EP0050534,P52,F4 in which X and R retain the same significance as previously, this acid being in the form of mixtures of E or Z isomers or in the form of an E or Z isomer, the substituted cyclopropane ring being able to be in all its possible sterio-isomeric forms, or in the form of a mixture of stereo-isomers or a functional derivative of this acid, is made to react with an alcohol with the formula III : where B retains the same significance as previously or with a functional derivative of this alcohol, so as to obtain a corresponding compound with the formula I, which if desired, is submitted to the action of a selective cleavage agent of the CO2 R group so as to obtain a compound with the formula IV : see diagramm : EP0050534,P53,F1 in which B retains the same significance as previously, then, this acid with the formula IV or a functional derivative of this acid, is submitted to the action of an alcohol with the formula R-OH in which R retains its previous significance, so as to obtain a corresponding compound with the formula I.

Description

in

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The invention relates to novel esters of cyclopropanecarboxylic acids which are related to pyrethric acid, and to a process for their preparation, as well as compositions containing them for controlling parasites.

The compounds of the invention are characterized by the general formula I of claim 1.

Prior art must state the following: a) J. Chem. Soc. Perkin I, 1974, pages 2470-2474 relates to esters of the formula

10 \ J H

βΓ "^ 0Λ

Me 15 where R 1 represents a butyl group.

To avoid collision with this prior art, the scope of the present invention is limited so as not to include B = alkyl.

b) Chemical Abstracts, Vol. 85, No. 17, October 25, 1976, page 150 relates to esters of (5-benzyl-3-furyl) methyl or allethrolone and 2'-halogen-2'-ethoxycarbonylvinyl.

Nothing in this disclosure relates to the stereochemistry of dis.se 2 '-halo-2 1 -ethoxycarbonylvinyl derivatives.

To avoid collision with this known technique is

25 application limited to E geometry. Annex I below

clearly shows that the compounds I, where the geometry of the double bond is E, the Z compounds are superior.

c) French Patent Specification 2185612, in its general formula, includes some compounds which are included in the general formula I of the present application. However, these are general indications, the patent not including any example similar to the general formula of the application.

In addition, the French patent publication strongly insists that the compounds in which the cyclopropane grouping is 35 trans are the most interesting.

For purposes of this prior art, the application is limited to the IR, cis compounds.

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The following Annex II clearly shows that the IR, trans compounds are not as active as insecticides and that the effect of the IR, cis compounds is therefore surprising.

The compounds of formula I have interesting properties which enable their use in the control of parasites. It can for example. revolve around the control of parasites on plants, on premises and on warm-blooded animals.

Thus, the present compounds can be used to control insects, nematodes and acarides, which are 10 parasites on plants and animals.

In particular, the compounds of formula I can be used to control insects in agriculture, e.g. aphids and larvae of lepidopterans and coleopts. They are used in doses between 10 g and 300 g of active substance per day. ha.

The compounds of formula I can also be used to control insects in rooms, especially flies, mosquitoes and cockroaches.

The compounds of Examples 1, 7 and 11 are particularly notable compounds, as the test results below show. They have an excellent lethal effect and a very good Mknock-downM effect.

Furthermore, the compounds of formula I are light stable and are not toxic to mammals.

The combination of these properties causes the compounds of formula I to be compounds which are very similar to the requirements of the modern agricultural chemical industry. They make it possible to protect the crops while preserving the environment.

The compounds of formula I can also be used to control acarides and nematodes which are parasites on plants.

The compounds of formula I can be further used to control acarides which are parasites on animals, 3h. for combating e.g. blood mites and especially of the species

Boopbilus, Hyalomnin, Amblyomnia and Ehipicephalus or to combat all kinds of enclosures and especially sarcoptic in psoroptic and chorioptic enclosures.

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3

The invention thus also includes compositions for the control of parasites on warm-blooded animals, on premises and on plants and peculiar in that they comprise at least one of the compounds of formula I.

5 Among the preferred especially insecticidal compounds, particular mention is made of the compositions containing the compounds of Examples 1, 7 and 11.

These preparations are prepared according to the methods customary in the agricultural chemical or veterinary industry or in the industry working with animal feed preparations.

In the preparations for use in agriculture as well as in premises, the active compound (s) may optionally have one or more other pesticides added. These compositions may be present as powders, granules, suspensions, emulsions, solutions, aerosol solutions, combustion tapes, baits or other preparations classically used for the utilization of this form of compounds.

In addition to the active ingredient, these preparations usually contain a carrier and / or a non-ionic surfactant, which furthermore ensures a uniform distribution of the constituents of the mixture. The carrier used may be liquid form such as water, alcohol, hydrocarbons or other organic solvents, a mineral oil or an animal or vegetable oil, a powder such as talc, clay, silicates, diatomaceous earth or a solid combustible substance.

The insecticidal compositions of the invention preferably contain 0.005-10 # of active ingredient by weight.

According to an advantageous working method, the compositions of the invention are used in rooms as smoke preparations.

The compositions may then, in the case of the non-active part, be a combustible insecticidal coil or, on the other hand, a non-combustible fibrous substrate. In this latter case, the smoke preparation with the incorporated active substance is placed in a heating apparatus such as an electrical insecticides.

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In the case where an insecticidal coil is used, the inert carrier, e.g. consist of pyre-thrum quas, powder of leaves of Machilus thumbergii, powder of pyre thrum ten lke, powder of cedar, sawdust such as pine-sawdust, starch and coconut shell powder.

The dose of active material may then be, for example, 0.03-1% by weight.

In the case where a non-combustible fibrous carrier is used, the dose of active material may e.g. be 0.03 10 -95% by weight.

The preparations for blasting in rooms can also be obtained by preparing an active ingredient sprayable oil, which is absorbed into a lamp shaft and incinerated.

The active ingredient concentration in the oil is preferably 0.03 to 95% by weight.

The insecticidal, acaricidal and nematodicidal preparations may optionally be added to one or more other pesticidal agents. The acaricidal and nematodicidal compositions may be present in particular as powders, granules, emulsions, suspensions and solutions.

For acaricide use, wettable powder is preferably used for spraying on the foliage and containing 1-80 $ or liquids for spraying on the foliage and containing 1-500 g of active substance per day. liter. Powder can also be used for 25 powdering of the foliage and containing 0.05-3 $ active substance.

For nematodic use, liquids are preferably used to treat the soil and containing 300-500 g of active substance per day. liter.

The acaricidal and nematodicidal compounds of the invention are preferably used in doses reaching 1-100 g of active substance per day. ha.

To enhance the biological effect of the compounds of the invention, classic synergistic agents used in such cases may be added, for example, "35 1- (2,5,8-trioxadodecyl) -2-propyl-4,5-methylenediorybenzene ( or piperonylbutoxide) or N- (2-ethylheptyl) bicyclo (2,2-l)

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5Haepten-2,3-dicarboximide or piperonyl-bis- (N-but-oxyethoxy) -ethylacetal (or tropital) When it comes to combating acarides which are parasites in animals, very often, the subject matter is incorporated. Compounds in foodstuffs in conjunction with a nutrient mixture suitable as animal feed. The nutritional composition may vary by animal species and may contain cereals, sugar and seeds, soybean, peanut and sunflower seed cake, animal flour, fish meal, synthetic amino acids, mineral salts, vitamins and 1Q antioxidants.

The compounds of the general formula I have excellent tolerance and can be used in warm-blooded animals to control blood mites and enclosures and also to combat lice, both preventive and curative. The compounds I can be used by evaporation, saponification, bathing or lubrication.

The compounds I can also be applied to the animals' backs by the pouring method. Fe can also be administered through the digestive tract or parenterally, 20 Feet should also be stated that the compounds of the present invention can be used as biocides and growth regulators.

The invention also relates to a process for the preparation of the compounds of formula I, and this process is characterized by that of claim 4.

The esterification of the acid II with the alcohol of formula III can be carried out in the presence of a tertiary base such as pyridine. This esterification can advantageously be carried out in the presence of a mixture of pyridine, dicyclohexyl, carbodiimide and 4-dimethylaminopyridine.

The esterification can also be carried out by reacting a chloride of the acid II with the alcohol of formula III or on a metal derivative of this alcohol such as the silver salt.

The following examples illustrate the method of the invention.

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Example 1 »(IR, cis) -2,2-Dimethyl-5- (E) - (2-fluoro-2- (ethoxycarbonyl) ethanyl) -cyclopropane-1-carboxylic acid ( S) -g-cyano-5-phenoxybenzyl ester. T a solution of 3.87 g (1R, cis) -2,2-dimethyl-3-.

5 - (Z + E) - (2 € Luor-2-ethoxycarbonylethenyl) -cyclopropane-1-carboxylic acid in 30 ml of methylene chloride 1.5 ml of pyridine and 3.7 g of dicyelohexylcarbodiimide are added, stirred for 10 minutes and added in one once a solution of 4.05 g of (S) -α-cyano-3-phenoxybenzyl alcohol in 10 ml of methylene chloride, stir 1 hour 30 minutes, add 25 mg of 4-dimethylaminopyridine, stir 1 hour 30 minutes, cool to 0 ° C, eliminates the insoluble material formed by filtration, evaporates the filtrate to dryness under reduced pressure, chronographs the residue on silica gel eluting with a mixture of cyclohexane and ethyl acetate (80:20), crystallizes the residue of ethyl acetate, isolates the precipitate formed by suction and chromatographs the mother liquors on silica gel eluting with a mixture of cyclohexane and ethyl acetate (9: 1) to give a total of 4.28 g (IR, cis) -2,2-dimethyl-3- (E) - (2-Fluoro-2- (ethoxycarbonyl) -ethenyl) -cyclopropane-1-carboxylic acid - (S) -α-cyano-3 -phenoxybenzyl ester and 2.8 g of 3- (Z) derivative.

Analysis: C ^ HHg ^ ENOg = 437.47 calculated: C # 68.64 5.53 N # 3.20 E $ 4.34 found: 68.8 5.5 3.1 4.2 IR, spectrum (chloroform ): - absorption at 1738 cm -1 and 1722 cm -1, attributed to carbonyl and conjugated ester, - absorption at 1611 cm -1 x attributed to the ethylenic double bond, -1 - Ί 30 - absorption at 1589 cm - 1489 cm attributed to the aromatic rings,

J

absorption at 1380 cm x, attributed to the twin methyl groups.

R.M.R. spectrum (deuteroehloroform): - peaks at 1.2-1.27 ppm attributed to the hydrogen atoms in the twin methyl groups, - peaks at 1.23 - 1.35 - 1.47 ppm, 4.15 - 4.26 ppm and 7

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4.38 - 4.50 ppm attributed to the hydrogen atoms of the ethyl group in ethoxycarbonyl, - peaks at 1.88 - 2.02 ppm, attributed to the hydrogen at the 1-position in cyclopropyl, 5 - peaks at 2.8 - 3.13 ppm attributed to the hydrogen at the 3-position in cyclopropyl, - peaks at 6.05 - 6.21 and 6.38 - 6.55 ppm attributed to the hydrogen in the ethylcene double bond, - peak at 6.36 ppm attributed the hydrogen carried by the same ear atom as the group CN, - peaks at 6.9 - 7.58 ppm, which are attributed to the hydrogen atoms in the aromatic rings.

(IR, cis) -2,2-dimethyl-3- (E, Z) - (2-fluoro-2-ethoxycarbonylethenyl) -cyclopropane-1-carboxylic acid is obtained in the following manner e: In a solution of 12, 1 g of diethylphosphorous fluoroacetic acid ethyl ester in 120 ml of dimethylcoxyethane is introduced at 5 ° C 2 g of sodium hydride of 60 # in oil, stirred for 30 minutes, introduces at 0 ° C 5.7 g of lactone of (1R, cis) -2,2 -Dimethyl-3- (dihydroxymethyl) cyclopropane-1-carboxylic acid, stirring for 2 hours 30 minutes at 20 ° C, pouring the reaction mixture into a mixture of water and ice containing monosodium phosphate, extracting with ethyl ether, washing the combined organic phases with water, drying them, evaporating them to dryness under reduced pressure, chromatographing the residue on silica gel eluting with a mixture of cyclohexane, ethyl acetate and acetic acid (50: 50: 1) to obtain 3.87 g of a mixture of (IR, cis) -2,2-dimethyl-3 - (1, Z) - (2-fluoro-2-ethoxycarbonyl-thenyl) -cyclopropane-1-carboxylic acid.

3h 35 8

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Example 2.

(1R, cis) -2,2-dimethyl-5- (E) - (2-chloro-2- (methoxycarbonyl) -ethhenyl) -cyclopropane-1-oreboxylic acid (S) -g-isane-3-3-henogy benzyl ester.

In a solution of 3 g (1R, cis) -2,2-dimethyl-3- (E) - - (2-chloro-2-methoxycarbonyletbenyl) cyclopropane-1-carboxylic acid chloride in 15 ml of benzene, 3 is introduced. g (5) -α-cyano-3-pbenoxybenzyl alcohol, introducing 1.3 ml of pyridine at 50 ° C, stirring for 15 minutes at 5 ° C and then for 16 hours at 20 ° C, pouring the reaction mixture into a mixture of water and hydrochloric acid, extract with ethyl ether, wash with water, dry, evaporate the organic solution to dryness under reduced pressure, chromatograph the residue on silica gel, successively eluting with a mixture of cyclohexane and ethyl acetate (8: 2) and then cyclohexane and ethyl acetate (9: 1) to give 2.1 g (1E, cis) -2,2-dimethyl-3- (E) - (2-ehloro-2- (methoxy-carbonylethylene) cyclopropane-1 carboxylic acid (S) -α-cyano-3-phenoxybenzyl ester, αD = 50.5 ° (c = 0.8% benzene).

Analysis: = 439.9 Calc'd: C # 65.53 H # 5.04 Cl # 8.05 R # 3.18 Found: 65.5 5.2 8.0 3.0 IR spectrum (chloroform): - absorption at 1738 cm ”^ and 1719 cm ^ ^ attributed to the carbonyl group in the ester, 25 - absorption at 1608 cm“ \ attributed to -C = C-, absorption at 1589 cm “² - 1489 cm som de attributed to the aromatic rings, - absorption at 1390 cm ”· 5 ·, attributed to the twin methyl groups.

30 RMR spectrum (deuterochloroform): - peaks at 1.24 - 1.25 ppm attributed to the hydrogen atoms in the twin methyl groups, - peaks at 1.93 - 2.07 ppm attributed to the hydrogen at the 1-position in cyclopropyl, 35 - peaks at 2.87 - 3.01 - 3.04 - 3.14 ppm, attributed to the hydrogen at the 3-position in cyclopropyl, - peak at 3.85 ppm, attributed to the methyl group in methoxy-carbonyl, 9

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- peak at 6.35 ppm attributed to the hydrogen carried by the same C-atcm as the group CN, - peaks at 6.91 - 7 * 5 ppm, attributed to the hydrogen atoms in the aromatic rings, 5 (1R, cis) - 2,2-Dimethyl-3- (E) - (2-chloro-2- (methoxycarbonyl) -ethenyl) -cyclopropane-1-carboxylic acid chloride can be prepared as follows:

Step A: (1R.cis) -2,2-Dimethyl-3- (E) - (2-chloro-2-methoxy-carbonyl) -ethenyl) -cyclopropane-1-carboxylic acid, 10 ml of tetrahydrofuran are introduced at 20 ml. 12.6 g of methoxycarbonyl chloromethylenetriphenylphosphorane, 4.85 g of lactone of (1R, cis) -2,2-dimethyl-3- (dibydroxymethyl) cyclopropane-1-carboxylic acid in solution in 40 ml of tetrahydrofuran and stirring 2 hours at 20 ° C, heat the reaction mixture to reflux and hold it there for 1 hour, evaporate to dryness under reduced pressure, add ethyl ether to the residue, eliminate the insoluble material (triphenylphosphine oxide) formed by filtration, evaporate the filtrate to dryness under reduced pressure, chromatograph the residue on silica gel eluting with a mixture of benzene and ethyl acetate (8: 2) containing 1 $> acetic acid to give 2.2 g (1R, cis) -2,2-dimethyl -3- (E) - (2-chloro-2-methboxycarbonylethenyl) -cyclopropane-1-carboxylic acid and 3 g (IR, cis) -2,2-dimethyl-3- (Z) - (2-chloro-2 -methoxyca (carbonyl ethynyl) cyclopropane-1-carboxylic acid.

(1R, cis) -2,2-dimethyl-3- (E) - (2-chloro-2-methoxycarbonyl-ethenyl) -cyclopropane-1-carboxylic acid has the following properties: I, R. Spectrum (chloroform): - absorption at 3500 cm "· *, so is attributed to the hydroxyl group 30 in carboxyl, - absorption at 1721 cm" 3 ·, 1713 cm-3 ·, 1700 cm "3 ·, attributed to carbonyl, - absorption at 1490 cm *" 3 · - 1410 cm 3, attributed to -C = C- absorption at 1393 cm 3 - 1380 cm 3, attributed to the hydrogen atoms in the twin methyl groups.

N.M.R. spectrum (deuterochloroform): - peaks at 1.3 - 1.32 ppm attributed to the twin methyl groups, 10

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- peaks at 1.87 - 2.02 ppm attributed to the hydrogen at the 1-position in cyclopropyl, - peaks at 2.82, 2.97 ppm - 2.98, 3.13 ppm attributed to the hydrogen at the 3-position in cyclopropyl, 5 - peak at 3.82 ppm attributed to the hydrogen atoms of the methyl group in methoxycarbonyl, - peaks at 6.72 - 6.78 ppm attributed to the hydrogen in the ethylenic double bond at the 3-position in cyclopropyl, 10 peaks at 11 ppm attributed to the hydrogen in carboxyl.

Step B: (1R.cis) -2- (2-dimethyl-3- (E) - (2-chloro-2- (methoxycarbonyl) -ethenyl) -eyclopropane-1-carboxylic acid oxychloride.

2.9 g (IR, cis) -2,2-dimethyl-3- (E) - (2-chloro-2- (methoxycarbonyl) -ethenyl) -cyclopropane-1-carboxylic acid, 20 ml of isoprene and 10 ml ml of thionyl chloride, stirring at 20 ° C for 3 hours, eliminates the isoprene and thionyl chloride by distillation under reduced pressure to obtain 6 g of crude (1R, cis) -2,2-d ime thy1-3- (E) (2-chloro) -2- (with th oxycarbonyl) -e th enyl) -cyclopropane-1-carboxylic acid chloride.

Example 3

(1R.cis) - 2,2-dimethyl-3- (E) - (2-bromo-2- (propoxycarbonyl) ethenyl) -cyclopropane-1-carboxylic acid (5) -q-cyano-3-phenoxy benzyl ester.

In a solution of 2.6 g (1R, cis) -2,2-dimethyl-3- (E) - - (2-bromo-2- (propyloxycarbonyl) -ethenyl) -cyclopropane-1-carboxylic acid in 40 g. 0.9 ml of pyridine, 2 g of dicyclohexylcarbodiimide, stir for 10 minutes, add 2 g of (S) -α-cyam-3-phenoxybenzyl alcohol, stir for 10 minutes, add 25 mg of 4-dimethylaminopyridine, stir in For 1 hour 30 minutes, eliminate the insoluble substance formed by filtration, evaporate the filtrate to dryness under reduced pressure, chromatograph the residue on silica gel eluting with a mixture of cyclohexane and 35 ethyl acetate (95.5) to obtain 0.743 g of the expected ester and 3.64 g of a mixture, which is dissolved in the heat in 4 volumes of isopropyl ether, is stirred at 20 ° C and isolates the formed precipitate by suction, it dries, combines it 11

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with the 0.743 g of substance obtained above to obtain 2.32 g (1R, cis) - 2,2-dimethyl-3- (E) - (2-bromo-2- (propoxycarbonyl) -ethenyl) -cyclopropane-1 -carboxylic acid (S) -α-cyano-3-phenoxybenzyl ester with m.p. 68 ° C.

Analysis: C26®23®r5 = 512.41 calculated: 60.95 th 5.11 th 2.73 Bt 15 15.6 found: 61 5.1 2.5 15.5 IR spectrum (chloroform): - absorption at 1737 cm -1, attributed to the carbonyl group 10 in the ester group, - absorption at 1705 cm -1, attributed to the carbonyl group in the conjugated ester, - absorption at 1605 - 1610 cm -1, attributed to -C = C - absorption at 1585-1485 cm 2, attributed to the aromatic rings.

NMR spectrum (deuterochloroform): - peaks at 0.88 - 1.0 - 1.12 ppm attributed to the hydrogen atoms of the methyl group in propoxyl, - peaks at 1.22 - 1.23 ppm attributed to the hydrogen atoms in the twin methyl groups, - peaks at 1.92 - 2.06 ppm attributed to the hydrogen at the 1-position in cyclopropyl, - peaks at 4.08 - 4.18 - 4.28 ppm attributed to the hydrogen atoms in the methylene at the 1-position in propyl, 25 - peaks at 6.38 ppm attributed to the hydrogen atom carried by the same carbon atom as CN, - peaks from 6.9 to 7.51 ppm attributed to the hydrogen in the ethylenic double bond, - peaks at 6.92 - 7.6 ppm attributed to the hydrogen atoms 30 in the aromatic rings.

(1R, cis) -2,2-dimethyl-3- (E) - (2-bromo-2- (propoxycarbonyl) -ethenyl) -cyclopropane-1-earboxylic acid can be prepared as follows:

To a solution of 3.1 g (IR, cis) -2,2-dimethyl-3-35 - (E) - (2-bromo-2- (propoxycarbonyl) -ethenyl) -cyclopropane-1-carboxylic acid tert -butyl ester obtained simultaneously with the 3- (Z) isomer of step A by the preparation of the corresponding 3 - (Z) acid, followed by Example 4 in 31 ml of toluene.

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0.51 g of p-toluenesulfonic acid monohydrate are charged, the vessel containing the reaction mixture is placed in an oil bath at 120 ° C for 15 minutes, rapidly brings the temperature of the reaction mixture to 20 ° C, extracted with ether, washed the organic extracts with water, dried evaporating them to dryness by distillation under reduced pressure to obtain 2.6 g (IR, cis) -2,2-dimethyl-3- (E) - (2-bromo-2- (propoxycarbonyl) ethanyl) -cyclopropane-l-carboxylic acid.

Example 4.

(IR, cis) -2,2-dimethyl-3- (E) -2-fluoro-2- (ethoxycarbonyl) -ethe-carbonyl) -cyclopropane-l-carboxylic acid.

(1R, cis) -2,2-dimethyl-3- (E, Z) - (2-fluoro-2-ethoxycarbonylethenyl) cyclopropane-1-carboxylic acid is prepared from 12.2 g of lactone of (1R, cis) -2,2-Dimethyl-3- (dihydroxymethyl) -cyclopropane carboxylic acid, working as in Example 1, replacing the chromatography of Example 1 with a chromatography on silica gel eluting with a mixture of cyclohexane and ethyl acetate (75 : 25) and then with the same mixture at a ratio of 50:50 to obtain 14.5 g (1R, cis) -2,2-dimethyl-3- (E) - (2-fluoro-2-ethoxycarbonylethenyl) -cyclopropane-1 - carboxylic acid, ap = -42.5 ° (c = 1 $, chloroform), Κ, Μ.Ε. spectrum (deuterochloroform): 25 - peak at 128 ppm attributed to the hydrogen atoms in the twin methyl groups, - peaks at 1.23 - 1.35 - 1.47 ppm and 4.13 - 4.25 - 4.37 - 4.48 ppm attributed to the hydrogen atoms of the ethyl group in ethoxycarbonyl, - 30 peaks at 1.82 - 1 , 97 ppm attributed to the hydrogen in the 1-position in cyclopropyl, - peaks at 2.75 - 2.9 - 3.05 ppm attributed to the hydrogen in 3-s the peak in cyclopropyl, - peaks at 6.12 - 6.28 - 6.47 - 6.63 ppm attributed to the ethylenic hydrogen (J approx. 21 Hz, corresponding to a cis derivative), - peak at 11, 28 ppm, which is attributed to the hydrogen in carboxyl.

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Working as in Example 1 from the corresponding alcohols, the following compounds are prepared (Examples 5, 6, 7 and 8): Example 5.

(1R, cis, AE) -2,2-dimethyl-3 - ((2-fluoro-2-ethoxycarbonyl) -ethenyl) -cyclopropanecarboxylic acid (R) -3-ethynyl-3-phenoxyphenylmethyl, yield $ 72 = + 40 ° + 1.5 ° (c = 1 $, CHCl3).

Example 6, # (IR, cis. ΔΕ) -2,2-dimethyl-3- (2-fluoro-2-ethoxycarbonylethenyl) cyclopropane carboxylic acid (R) - (3-phenoxyphenyl) ethyl ester, yield 81 $ , (¾ = 94.5 ° ± 2.5 ° (c = 0.5 $, OHCl 2).

Example 7, (IR, cis, ΔΕ) -2,2-D-dimethyl-3- ((2-fluoro-2-thoxycarbonyl) -e thienyl) -cyclopropane-1-carboxylic acid (S) -a-cyano-3-phenoxy-4-fluorobenzyl ester, = + 50 ° + 2.5 ° (c = 0.5 $, CHCl3).

Example 8.

(IR, cis, ΔΕ) -2,2-dimethyl-3- (((2-fluoro-2-thoxy-carbonyl) ethanyl) -cyclopropane-1-carboxylic acid-3-phenoxybenzyl ester.

I.R. Spectrum: C = 0 ester] 1725 about -1 C = 0 conjugated ester) C = C conjugated 1655 cm “^ aromatic groups 1588-1489 cm" ^ twin dimethyl 1390-1380 cm "* 30

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Example of Comparative Compound Preparation: trans Compound: (IR + trans) -2,2-dime thyl-3- ((ΔΕ-2-fluoro-3-oxo-3-ethoxyprope-nyl) -cyclopropane carboxylic acid (S) -a-cyan-5-phenoxybenzyl-5 ester »

Working as in Example 1 from (1R, trans) - 2,2-d ime thy 1-3 - (AE-2-fluoro-3-oxo-3-e thoxypropenyl) cyano-propane carboxylic acid and ( S) -α-cyano-3-phenoxybenzyl alcohol gives the expected compound, = -33.5 ° + 2.5 ° (c = 0.5 $, 10 CHCl

(IR, trance) -2,2-d ime t h y 1 -3 - (ΔΕ -2-fluoro-3-oxo-3-thoxy-propenyl) -cyclopropane carboxylic acid is prepared as follows:

At 2-10 ° C, a suspension containing 60 ml of 1,2-dimethoxyethane and 2.6 g of 15 60 $ sodium hydride suspension in oil is added over a 30 minute solution containing the 7.7 g of diethylphosphonofluoroacetic acid ethyl ester prepared as described in. Ann Chem. (1964) 674, 60 ml of 1,2-dimethoxyethane and 4 g of (1R, trans) -2,2-dimethyl-3-formylcyclopropane carboxylic acid.

Stirring is continued for 15 minutes at 5 ° C and then 3 hours at room temperature. A solution is obtained which is poured into an aqueous monosodium phosphate solution at 5 ° C and stirred for 10 minutes. It is extracted with ethyl acetate, washed with water, dried and evaporated to dryness at 25 ° C under reduced pressure. The crude is obtained 6.5 g of an oil which is chromatographed on silica gel eluting with a mixture of hexane, ethyl acetate and acetic acid (70: 30: 1). Thus, 4 g of the expected compound are obtained.

(IR.trans) -2,2-dimethyl-3- ((AE) -2-fluoro-3-oxo-3-methoxypropenyl) cyclopropane carboxylic acid (S) -g-cyano-3-phenoxybenzyl ester. Step A: (IR. Trans) -2,2-Dimethyl-3 - ((AE) -2-fluoro-3-oxo-5-hydroxy propenyl) cyclopropane carboxylic acid (S) -g-cyano --5-pbenoxybenzylester.

35 mg of p-toluenesulfonic acid monohydrate are added to a solution containing 1 g (IR, trans) -2,2-dimethyl-3- ((AE) -2-fluoro-3-oxo-3-e thoxy propylene 1) -cyclopropanecarboxylic acid - (S) -α-cyano-3-pbenoxybenzyl ester, 1 ml of water and 4 ml of dioxane.

15

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The reaction mixture is heated to reflux for 8 hours and evaporated to dryness at room temperature under reduced pressure. The residue is taken up in methylene chloride, washed with water and dried. Evaporate to dryness to give 1.1 g of oil, which is chromatographed on silica gel eluting with a mixture of hexane, ethyl acetate and acetic acid (60: 40: 1).

Thus, 280 mg of the expected compound is obtained.

Step B: (IR, trans) -2,2-Dimethyl-3 - ((ΔΕ) 2-fluoro-3-oxo-3-methoxypropenyl) -cyclopropane carboxylic acid (S) -g-cyano-5-phenoxy -10 benzyl ester.

At a temperature of 5-10 ° C, a small excess of diazomethane dissolved in methylene chloride is added to 2 ml of a solution of methylene chloride containing 860 mg of the compound prepared in step A. Stirring is continued for 15 minutes at 5 ° C and then 30 minutes at room temperature.

A few drops of acetic acid are added and evaporated to dryness. Thus, 950 mg of an oil is obtained which is chromatographed on silica gel eluting with a mixture of hexane and ethyl acetate (85ϊ15). 700 mg of the expected compound are obtained, = -31 ° + 2.5 ° (c = 0.25 $, CHCl

Reference Example II

(IR, cis) -2,2-dimethyl-3 - ((Z) -2-fluoro-3-oxo-5-tert-butoxy-propepyl) -oyclopropancarboxylsyre- (S) -g-cyano-5-phenoxybenzyl -25 z.

2.3 g of (1R, cis) -2,2-dimethyl-3- (2-fluoro-3-oxo-3-hydroxy- (Z) -propenyl) -cyclopropanecarboxylic acid (2) are stirred for 2 hours. S) -α-Cyan-3-phenoxybenzyl ester, 15 ml of ethyl acetate and 2.4 g of R- (1-methylethyl) -N '- (1-methylethyl) -carbamic acid 30-tert.-butyl ester. The filtrate is filtered, evaporated to dryness to give 2.6 g of product which is purified by chromatography on silica gel eluting with n-hexane and isopropyl ether (8: 2) under nitrogen pressure. 2.2 g of compound are obtained which is recrystallized from isopropyl ether. 1.4 g of the 35 expected compound are obtained with m.p. 103 ° C, = + 2.5 ° + 3 ° (c = 0.2 *, CHCl 3).

Li- (1-me thy le thyl) -N · - (1-zne thyle thyl) -carbamic acid acid, butyl ester is prepared as follows: 16

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98.7 g of N, H'-diisopropylcarbodiimide and 57.9 g of tert-butyl alcohol are stirred in the presence of 5 g of cuprous chloride for 4.5 days at room temperature. 117.7 g of the expected compound are obtained after distilling the reaction mixture under 9 x Hg (° g 74 ° C below 9 mm Hg),

Example 9

(IR, cis) -2,2-Dimethyl-3- (2-fluoro-3-oxo-3-methoxy- (E) -propenyl) oyclopropanecarboxylic acid (S) -g-oyan-3-phenoxybenzyl ester. Step At (IR, cis) -2,2-Dimethyl-3- (2-fluoro-3-oxo-3-hydroxy - (E) -propenyl) -cyclopropane carboxylic acid (S) -g-cyano-3 -Pbenoxybenzylester.

A solution containing 2.5 g of (1R, cis) -2,2-dimethyl-3- ((E) -2-fluoro-2-ethoxycarbonylethenyl) cyclopropane-1-carboxylic acid (24 g) is refluxed for 24 hours. S) -α-Cyan-3-phenoxybenzyl ester, 10 ml of dioxane, 2.5 ml of water and 1 g of p-toluenesulfonic acid monohydrate. It is allowed to re-enter room temperature, diluted with methylene chloride and washed with water. The organic phase is dried, filtered and the filtrate is evaporated under reduced pressure. The resulting residue is chromatographed eluting with a mixture of cyclohexane, ethyl acetate and acetic acid. (60: 40: 1). Thus, the expected compound (980 m 2) is obtained.

Step B: (1R, cis) -2,2-Dimethyl-3- (2-fluoro-3β-oxo-3-methoxy-25 (E) -propenyl) -cyolopropanecarboxylic acid (S) -g-cyano- 3-phenoxybenzyl ester.

Working as in Reference Example I, Step B from (IR, cis) -2,2-dimethyl-3- (2-fluoro-3-oxo-3-hydroxy- (E) -propyl) - cyclopropane carboxylic acid (S) -α-cyano-3-pbenoxybenzyl ester gives the expected compound, m.p. 70 ° C, g + = + 52 ° + 1.5 ° (c = 1 $, CHCl3).

Working as in the previous example from the corresponding alcohols, the following compounds are prepared: 35

Example 10.

(1R, cis) -2,2-Dimethyl-3- (2-fluoro-3-oxo-3-n-propyloxy- (E) -propenyl) -cyclopropane carboxylic acid (S) -α-cyano-3-phenoxy -______ ^ 0 / «__ <\ 17

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Example 11.

(IR, cis) -2,2-dimethyl-3- ((ΔΕ) -2-fluoro-3-oxo-3-tert-butoxy-propenyl) -cyclopropanecarboxylic acid (S) -α-cyano 3-phenoxybenzyl-benzyl ester.

5

Working as in reference example UU from (1R, cis) - 2,2-dimethyl-3- (2-fluoro-3-oxo-3-hydroxy- (E) -propenyl) -cyclopropanecarboxylic acid (S ) -α-Cyan-3-henoxybenzyl ester and N- (1-methylthyl J-IP-1-methylethyl) -orbaic acid · -teryl-butyl-ester, give the expected compound (yield 61 $) , ttp = + 26.5 ° (c = 0.25 #, CHCl 3).

Example .12.

(IR. Cis) -2,2-dimethyl-3 - ((AE) -2-fluoro-3-oxo-3- (11,3,3,3-hexafluoro) -isopropoxy-n-propenyl) -cyclopropane carboxylic acid - ( S) -q-cyan-3-phenoxybenzyl ester.

Working as in Reference Example I, Step B from (1R, cis) -2,2-dimethyl-3- (2-fluoro-3-oxo-3-hydroxy- (E) -propionyl) -cyclopropanecarboxylic acid (S) -α-eyan-3-phenoxybenzyl-ester and 1,1,1,1,3,3,3-hexafluoropropan-3-ol to give the expected compound, α α = + 21 ° + 2 ° ( c = 0.5 #, CHCl 3).

Example 1.3.

(IR, cis) -2,2-dimethyl-3- (2-fluoro-3-oxo-3-isopropyloxy- (E) -25-propenyl) -cyclopropanecarboxylic acid (S) -α-cyano-3 -phenoxy-benzyl ester, ap = 46 ° + 1 ° (c = 1 #, CHCl3).

Example 14.

(IR, cis) -2,2-Dimethyl-3- (2-fluoro-3-oxo-3-cyclopropyloxy- (E) -30-propenyl) -cyclopropanecarboxylic acid (S) -α-cyano-3-phenoxybenzyl ester , α-p = + 35 ° + 1 ° (c = 1.3 #, CHCl3), m.p. 50 ° C.

Example 1.5.

(IR, cis, ΔΕ) -2,2-dimethyl-3- (2-fluoro-3-oxo-3- (β-methoxyeth-3-oxy) -propenyl) -cyclopropanecarboxylic acid (S) -α-cyano -3-phenoxybenzyl ester, ap = 47 ° + 2.5 ° (c = 0.5 #, CHCl 3).

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18

Reference Example III

(IR, cis) -2,2-dimethyl-1-3 ((AZ) -2-chloro-2-methoxycarbonylethenyl) cyclopropanecarboxylic acid (S) -g-cyano-3-phenoxybenzyl ester Using, as in Example 1, starting from (1R, cis) - 2,2-di dimethyl-3- (Z) - (2-ehloro-2-methoxycarbonyl tfc enyl) -cyclopropane carboxylic acid and (S) -g-cyano-3-phenoxybenzyl ester gives the expected compound, g 2 = 62.5 ° + 1.5 ° (c = 1 $, benzene), 10

Example 16.

(IR, cis) -2,2-dimethyl-3 - ((AE) -2-chloro-2-methoxycarbonylethenyl) ocyclopropanoarboxylsyrene (S) -2-methyl-4- oxo-3- (2-propylene) -2-cyclopenten-1-ester.

The compound is prepared as a previous compound from (IR, cis) -2,2-dimethyl-3- (Z) - (2-chloro-2-methoxycarbonylethenyl) cyclopropane carboxylic acid chloride and (4S) -hydroxy-3-methyl -2- (2-propenyl) -2-cyclopent-1-one, g + = -15 ° + 4 ° (c = 0.25 #, benzene).

NMR spectrum, CDCl3, ppm: - 1.28 and 1.3H in the methyl groups at the 2-position - 3.8 Hi -CO2Cg3 - 2.02 Hi H3C ^ 25 - 6.8 - 7 ethylcenic H, which is supported of the carbon atom at the 1-position in 2-methoxycarbonylethanyl.

Example 17., (IR, cis) -2,2-Dimethyl 1-3- ((E) -3-oxo-2-chloro-3-ethoxypropenyl) -cyclopropane carboxylic acid (S) -g-cyano 3-phenoxybenzyl ester.

Working as in Example 1 from (1R, cis) - 2,2-dimethyl-3 - ((E) -3-cxo-2-chloro-3-ethoxypropenyl) cyclopropane arboxylic acid and (S) -α -cyan-3-phenoxybenzyl ester, gives the expected compound, gj, = + 19 ° + 2 ° (c = 1 $, chCl 3).

(1R, cis) -2,2-dimethyl-3- (3-oxo-2-chloro-3-thoxypropenyl) -cyclopropane carboxylic acid (isomers E and Z) prepared as follows: 19

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Step A; Ethoxycarbonylchlormethylentriphenylphosphoran.

A solution is prepared at ca. 2 ° C of 4 g of chlorine in 80 ml of chloroform. 20 g of ethoxycarbonylmethylenetriphenylphosphorane are added in 40 ml of chloroform. The reaction mixture temperature is allowed to rise to room temperature and evaporated to dryness under reduced pressure. An oil is obtained which is dissolved in 70 ml of methylene chloride and washed with a solution of 6.1 g of sodium carbonate in 40 ml of water and then with water. Dry and evaporate to dryness. 18.9 g of 10 of the expected compound are obtained, m.p. 116-118 ° C.

Step B: (IB ♦ ci s) -2,2-d ime thy 1- 5 - (5-oxo-2-chloro-3-e thoxyprope-nyl) -cyclopropane carboxylic acid (isomer E and Z),

6.9 g of lactone of (1B, cis) -2,2-dimethyl-3-dihydroxymethyleyelopropane-1-carboxylic acid in 100 ml of tetrahydrofurfuran are added to a solution containing 18.9 g of the compound of step A in 200 ml of tetrabydrofuran. The resulting solution is stirred for 6 hours 30 minutes at room temperature and the solvent is distilled off under reduced Jryk. An oil is obtained, which is taken up in 50 ml of ethyl ether, stirred at 0 ° C, filtered and washed with ether, and the filtrate is evaporated to dryness. 22.2 g of the expected compound are obtained which are chromatographed on silica gel eluting with a mixture of cyclohexane, ethyl acetate and acetic acid (75: 25: 1). A) partly 3.58 g of the expected compound in the form of E-isomer,

Cf. Spectrum, CDCl3, ppm: - 1.3 and 1.33 Hi methyl groups at the 2-position in cyclopropane, 30 - 1.89 - 2.02 Hi the carbon at the 1-position in cyclopropane, -2, 85 to 3.05 Hi carbon at the 3-position in cyclopropane, -6.78 - 6.95 Hi the carbon at the 1-position in propenyl, B) and 2.34 g of the corresponding Z compound, NME spectrum, CDCl , ppm; 35, - 1.33 and 1.36 H, the methyl groups at the 2-position, - 1.96 - 2.1 H, the carbon at the 1-position in cyclopropane, - 2.23 to 2.53 H in the carbon at the 3-position, cyclopropane.

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Example 18.

(IR) cis) -2,2-Dimethyl-3- ((E) -3-oxo-2-chloro-3-propoxypropenyl) cyclopropanecarboxylic acid (S) -g-cyano- (3-Phenoxybenzyl) - ester. Working as in Example 1 from (1R, cis) -5 -2,2-dimethyl-3 - ((E) -3-cxo-2-chloro-3-propoxypropenyl) -eyclopropane carboxylic acid and (S) -g-cyano-3-phenoxybenzyl alcohol gives the expected compound, g + = + 24.5 ° + 2 ° (c = 0.4 $, CECl +).

(IR, cis) -2,2-Dimethyl-3- ((E) -3-oxo-2-chloro-3-propoxy-propenyl) -cyclopropanearboxylic acid is prepared as follows:

Step A: Propoxycarbonylchloromethylentriphenylphosphorane,

Working as for the preparation of (1R, cis) - 2,2-dimethbyl-3 - ((E) -3-oxo-2-chloro-3-ethoxypropenyl) -cyclopropane carboxylic acid, Example 30, Step A, from propoxycarbonylmethylenetriphenylphosphorane, the expected compound is obtained.

Step B: (1R, cis) -2,2-Dimethyl-3 - ((E) -3-oxo-2-chloro-3-prop-oxypropenyl) -ocyclopropanecarboxylic acid,

Working as for the preparation of (1R, cis) -20 -2,2-dimethyl-3- ((E) -3-oxo-2-chloro-3-ethoxypropenyl) -eyclopropane carboxylic acid, Example 1 ", step B, from the compound prepared in step A, one obtains the expected compound and the corresponding ΔΖ isomer.

Example 19, (IR, cis) -2,2-Dimethyl-3- ((E) -3-oxo-3-tert.-butoxy-2-chloro-propenyl) -cyclopropanecarboxylic acid (S) -g -cyano-3-phenoxybenzyl-benzyl ester.

Working as in Example 1 from (1R, Eis) -30 -2,2-dimethyl-3- ((E) -3-oxo-3-tert.-butoxy-2-chloropropenyl) cyclopropane carboxylic acid and (S ) -g-cyano-3-phenoxybenzyl alcohol gives the expected compound, g + = + 30.5 ° + 2 ° (c = 0.7 $, chCl 5).

(1R, cis) -2,2-dimethyl- (3-oxo-3-tert-butoxy-2-chloro-propenyl) -cyclopropane carboxylic acid (isomers E and Z) are prepared as follows:

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21

Step A: tert-butoxycarbonyl chloromethylenetriphenylphosphorane.

Working as above (preparation of Example 30, step A), the expected compound is obtained from tert-butoxycarbonylmethylenetriphenylphosphorane, m.p. about 160 ° C,

Step 3: AE acid + AZ acid.

Working from the compound prepared in Step A as set forth in the Preparation of Example 30, Step B, one obtains (IR, cis) -2,2 · -dimethy1-3 - ((E) -3- oxo-3-tert-butoxy-2-chloropropenyl) -cyclopropanecarboxylic acid, m.p. 65 ° C and the corresponding Z-isomer, m.p. below 50 ° 0.

Example 20

(IR.cis) -2,2-Dimethyl-5- ((E + Z) -3-oxo-3-methoxy-2-bromogropanyl) cyclopropane carboxylic acid (S) -α-cyano-5-phenoxybenzyl ester .

Working as in Example 1 from (1R, cis) - 2,2-dimethyl-3- (2-bromo-3-oxo-3-methoxy- (E) -propenyl) -cyclopropane carboxylic acid and (S ) -α-cyano-3-phenoxybenzyl alcohol gives the expected compound, * = + 9.5 ° + 2.5 ° (c = 0.3 #, chCl 3).

(1R, cis) -2,2-Dimethyl-3- (2-bromo-3-oxo-3-methoxy- (E) -propenyl) -cyclopropanecarboxylic acid is prepared as follows: Step A: (IR. ois) -2.2 -dimethyl-3- (2-bromo-5-oxo-3-diethoxy- (E) -25-propenyl) -eyclopropanecarboxylic acid tert-butyl ester.

100 ml of 50 # sodium hydroxide solution is added to a mixture containing 120 ml of methylene anhydride, 6.7 g (1R, cis) -2,2-dimethyl-3- (1,2- (dibromo-R, S) -3- oxo-3-methoxy-propyl) -cyclopropane tert.-butyl ester and 120 mg of cetavlon 30 (trimethylcetylammonium bromide). The reaction mixture is stirred for 4 hours. The mixture is diluted by adding 100 ml of methylene chloride and decanting the organic phase which is extracted with 100 ml of methylene chloride. The organic phases are washed with 1 N hydrochloric acid to acidic pH and then 35 with water to pH 7. The organic phases are combined, dried and evaporated under reduced pressure at 40 ° C. 5.3 g of a material is obtained which is chromatographed eluting with a mixture of hexane and isopropyl ether (8: 2).

3.5 g of the expected compound are obtained.

22

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Step B; (IR, cis) -2,2-dimethyl-3- (2-bromo-5-oxo-5-methoxy - (E) -propenyl) -cyclopropane carboxylic acid.

A solution of 3.4 g of (1R, cis) -2,2-dimethyl-3- (2-bromo-3-oxo-3-methoxy- (E) -propenyl) -cyclopropanecarboxylic acid tert is refluxed butyl ester, 30 ml of toluene and 0.35 g of p-toluenesulfonic acid monohydrate. Reflux is maintained until the end of gas evolution. Cool to 0 ° C, filter, wash the precipitate obtained with cold toluene and evaporate the filtrate at 40 ° C under reduced pressure. 10 2.8 g of the expected compound are obtained.

Example 21, (IR, cis) -2,2-Dimethyl-5 - ((E) -2-bromo-3-oxo-3-tert, -butoxypropenyl) -cyclopropanecarboxylic acid (S) -q- cyan-5-phenoxybenzyl-ester.

Working as in Example 1 from (1R, cis) - 2,2-d ime thy 1-3 - ((E) -2-bromo-3-oxo-3-tert -butoxy propeny 1) -cyclopropane carboxylic acid and (S) -α-cyano-3-phenoxybenzyl alcohol give the expected compound, cc-q = + 16.5 ° + 2 ° (c = 0.7 $, 20 CHCl 3).

(IR, cis) -2,2-dimethyl-1-3 - ((E) -2-bromo-3-oxo-3-tert-butoxypropenyl) -cyclopropane carboxylic acid is prepared as follows: Step A: tert, - butoxycarbonylbrommethylentriphenylphosphoran.

Working as in the preparation of (1R, cis) - 2,2-dimethyl-3 - ((E) -3-oxo-2-chloro-3-ethoxypropenyl) -cyclopropane carboxylic acid (Example 30, Step A) from tert-butoxy carbonyl Ime thylentriphenylphosphorane derivative and bromine give the expected compound with m.p., 190 ° C.

Step 3: (IR, cis) -2,2-Cinethy 1-3- ((E) -2-bromo-3-oxo-3-tert-butoxy propenyl 1) -cyclopropaucarboxylic acid ♦

Working as in the preparation of (1R, cis) - 2,2-dimethyl-3 - ((E) -3-oxo-2-chloro-3-ethoxypropenyl) -cyclopropane carboxylic acid (Example 30, Step E) from the compound prepared in step A, one obtains the expected compound with m.p., 76 ° C, and the corresponding Z-isomer with m.p. 50 ° C.

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Example 22.

(IR, cis) -2,2-dimethyl-3- ((E) -3-oxo-2-bromo-3-thoxypropenyl) -cyclopropanecarboxylic acid (S) -cyan 3-pbenoxybenzylester,

Working as in Example 1 from (1R, cis) -5 -2,2-dimethyl-3- ((E) -3-oxo-2-bromo-3-ethboxypropenyl) cyclopropane carboxylic acid and (S) ~ α-cyano-3-pbenoxybenzyl alcohol gives the expected compound, aD = -70.5 ° + 2 ° (c = 0.7 #, ghci5).

(IR, cis) -2,2-dimethyl 1-3- ((E) -2-bromo-3-oxo-3-ethoxy-propenyl) -cyclopropane carboxylic acid is prepared as follows:

Step A: Etboxycarbonylbromomethylentriphenylphosphorane,

The compound is prepared according to the procedure given for (1R, cis) -2,2-dimethyl-3 - ((E) -3-oxo-2-15-chloro-3-ethoxypropenyl) -cyclopropane carboxylic acid in Example 30, step A from the ethboxycarbonylmethylenetriphenylphosphorus derivative and bromine. Thus, the expected connection with m.p. 150 ° C.

Step B: (IR, cis) -2,2-dimethyl-1-3- ((E) -2-bromo-3-oxo-3-ethoxy-propenyl) -cyclopropanoarboxylic acid,

The compound is prepared according to the process set forth for the preparation of the corresponding chlorinated acid from the substance prepared in step A.

Thus, one obtains the expected compound and the corresponding ΔΖ compound,

Example 23 ((IR, cis) -2,2-Dimethyl-3- ((E) -2-fluoro-3-oxo-3-ethylthoxypropenyl) cyclopropa-carboxylic acid (R, S) -α cyan-6-phenoxy-2-pyridylmethyl ester.

Working as in Example 1 from the corresponding acid and the corresponding alcohol gives the expected compound, aD = + 35 ° + 4 ° (c = 0.3 #, CHCl3), 24

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Example 24, (IR.cis) -2,2-dimethyl-5- ((E) -2-fluoro-5-oxo-3-ethoxypropenyl) cyclopropanecarboxylic acid 5- (2-propynyl) -2,5-dioxoimidazolidinylmethyl ester.

By working as in Example 1 from the corresponding acid and the corresponding alcohol, the expected compound is obtained, = + 12 ° + 2 ° (c = 0.5 $, CHCl3).

Example 25

(IR, cis) -2,2-Dimethyl-3- ((E) -2-fluoro-3-oxo-3-ethoxypropenyl) - c.volopropanecarboxylic acid (S) - 2-methyl-3 -allyl-4-oxo-2-cyclo-penten-1-ester.

Working as in Example 1 from the corresponding acid and the corresponding alcohol, the expected compound, cij, is obtained - + 41.5 ° + 2.5 ° (c = 0.5 $, CHCl .

Example a_

Preparation of a soluble concentrate.

Homogeneous: Compound of Example 1 is mixed 0.25 g of piperonylbutoxide 1.00 g

Tween 80 0.25 g

Topanol A 0.1 g water 98.4 g 25

Example P,

Preparation of an emulsifiable concentrate.

Thoroughly mixed: compound of Example 11 0.015 g piperonylbutoxide 0.5 g

Topanol A 0.1 g

Tween 80 3.5 g xylene 95.885 g Example c

Preparation of an emulsifiable concentrate.

Homogeneous mixing:

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25 compound of Example 21 1.5 g

Tween 80 20.00 g

Topanol A 0.1 g xylene 78.4 g 5

Example d

Preparation of a smoke preparation.

Homogeneous mixture: Compound of Example 1 0.25 g of taboo powder 25.00 g of 10 cedar powder 40.00 g of pine sawdust 33.75 g of brilliant green 0.5 g of p-nitrophenol 0.5 g of insecticide study of the compounds of the invention In this study using (IR, cis) -2,2-dimethyl-3- (E) - (2-chloro-2-methoxycarbonylethenyl) -cyclopropane-1-carboxylic acid (S) -alpha-cyano-3-phenoxybenzyl ester (Compound A, (1R, cis) -2f2-dimethyl-3- (E) - (2-bromo-2-propoxycarbonyl-ethylenyl) -cyclopropane-1-carboxylic acid (S) -alphacyan-3-phenoxybenzyl ester (compound B), and (IR, cis) -2,2-dimethyl-3 - ((E) -2-fluoro-2-ethoxycarbonylethenyl) -cyclopropanecarboxylic acid (S) -alpha-cyano-3-phenoxybenzyl ester (compound D).

25 A. Investigating the instantaneous knock-down effect on housefly`

The experimental insects are 4-day-old female flies. One works by direct atomization at a concentration of 0.25 g / ml. liters in Kearns and March * s chamber, using as a solvent a mixture of acetone ($ 5) and Isopar L (solvent of the mineral oil class) (amount of solvent used 2 ml per second). 50 insects are used per day. treatment. Control is performed every minute until 10 minutes and then after 15 minutes, and KT 50 is determined by the usual methods.

The test results obtained are shown in the following table:

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Compound KT 50 in minutes Compound A 5.6 Compound E 4.5 Compound D 2.1 5 33. Examination of the lethal effect of the compounds of the invention reach various insects.

a) Study of the lethal effect on housefly.

The experimental insects are 4-5 days old female flies.

10 Topical application of 1 μΐ acetone solution to the insect's dorsal thorax is performed using Arnold * s micro manipulator. 50 individuals are used per day. treatment. Mortality is checked 24 hours after treatment.

15 Le results obtained, expressed in DL 50 or the dose in nanograms per individual needed to kill $ 50 of the insects are as follows:

Compound DL 50 in ng no insect compound A 11.1 20 compound B 1.0 b) Study of the lethal effect on cockroach.

The tests are carried out by contact on film on glass by application by pipette of acetone solutions having different concentrations on the bottom of glass petri dishes, the edges of which are already talcumated to prevent the escape of the insects. Lethal concentration 50 (CL 50) is determined.

Le test results obtained are shown in the following table: Compound CL 50 in mg / m 2 Compound A 1.4 Compound E 0.40 35 27

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(c) Investigation of the lethal effect on larvae of Spodoptera littoralis.

The tests are performed by topically applying an acetone solution using Arnold's micromanaged octopus or on the dor-5 sale thorax of the larvae. 15 larvae are used per dose of the compound to be tested. The larvae used are larvae in the fourth larval stage, ie with an age of approx. 10 days when raised at 24 ° C and $ 65 relative humidity. After treatment, the individuals are placed on a 10 artificial nutritional environment (Poitout's environment).

Mortality is checked 48 hours after treatment.

The experimental results obtained are shown in the following table: Compound DL · 50 in ng per insect

Compound A 6.7 Compound B 3.2 Compound D 1.0 d) Investigation of the lethal effect on Epilacna 20 varivestris.

The tests are performed by topical application by analogy with the application to the larvae of Spodoptera. Larvae are used in the penultimate larval stage, and after treatment the larvae are nourished with bean plants. Mortality is checked 72 hours after treatment.

The results are shown in the following table:

Compound DL · 50 in ng per insect

Compound A 17.7 Compound 3 7.4 30 Compound D 0.85 e) Investigation of the lethal effect on Aphis cracivora.

You use adult individuals after 7 days and use 10 aphids per day. concentration used. A method of contact injection is used. Treatment 35 is performed with Fisher's gun of a bean leaf, which is placed in a plastic petri dish on a sheet of moistened paper. The treatment is carried out by means of 2 ml of acetone solution of the compound 28

DK 164740 B

see to be examined (1 ml on each side of the leaf). The insect infestation is performed after drying the leaf. The insects are kept in contact with the leaf for 1 hour. Insects are placed on untreated leaves and mortality is checked after 24 hours.

The test results obtained are shown in the following table:

Compound DL 50 in ng per insect compound B 6.4 10 f) Conclusion.

In the experiments described in sections a, b, c, d and e, compounds A and B exhibit an interesting insecticidal activity.

g) General conclusion.

The compounds of the invention have an interesting insecticidal activity in the experiments described above.

C. Acaricide study of the compounds of the invention.

Bean plants are used comprising two leaves infected with 25 females of Tetranychus urticae per leaf and 20 placed under the vented hood under a constant light panel.

The plants are treated with Fisher's gun: 4 ml of toxic solution per plant of a mixture of equal volume of water and acetone. Allow 12 hours to dry and then infect. Mortality checks are performed 80 hours later. The dose used in each experiment is 5 g of compound per day. hl.

Compounds A and B have good activity in this experiment.

30 29

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Annex I

Comparative study between certain compounds where the double bond has E geometry and their isomers with Z geometry.

The lethal effect on flies of the following compounds is compared: (IR, cis) -2,2-dimethyl-3- (E) - (2-fluoro-2- (ethoxycarbonyl) ethenyl) -eyeopropane-1- carboxylic acid (S) -alpha-cyano-3-ripenoxybenzyl ester (product of Example 1, designated product A °) and its isomer Z (designated product B *), (IR, cis) -2,2-dimethyl 3 (E) - (2-Fluoro-3-oxo-3-terbutoxy-propenyl) -cyclopropane carboxylic acid (S) -alpha-cyano-3-phenoxy-benzyl ester (product of Example 11, designated product C1 and its isomer Z (designated product D *), 15 - (IR, cis) -2,2-dimethyl-3- ((E) -3-oxo-2-chloro-3-ethoxypropenyl) -cyclopropanecarboxylic acid (S) -alpha -cyan-3-phenoxybenzyl ester (product of Example 17, designated product E °) and its isomer Z (designated product F °).

The trial protocol is as indicated above. The 20 results achieved, expressed in nanograms per day. insect, is as follows: DL 50 (Product A °) 0.4 (nanogram / insect) DL 50 (Product B °) 39 (nanogram / insect) DL 50 (Product C °) 4.2 (nanogram / insect) ^ DL 50 (Product D °)> 100 (Nanogram / Insect) DL 50 (Product E °) 1.7 (Nanogram / Insect) DL 50 (Product F °) 2 2.7 (Nanogram / Insect)

Conclusion 30 Product A °, C ° and E ° with geometry E are the corresponding isomers with Z geometry far superior.

35 30

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Annex II

Investigation of the biological effect of a compound of formula (I) of structure IR, trans.

The lethal effect on flies of (IR, 5 trans) -2,2-dimethyl-3 (deltaE-2-fluoro-3-oxo-3-: ethoxypropenyl) cyclopropanecarboxylic acid (S) -alpha-cyanoic acid is investigated. 3-phenoxybenzyl ester (product in the comparative example, designated product A ').

The lethal effect on flies of product A 'is investigated as indicated. The result is as follows: 10 DL50 ^ Pro ^ u ^ t A ')> 78 nanograms per. insect.

conclusion

Product A 'of structure IR, trans has a much weaker insecticidal activity than the derivatives of structure IR, cis.

15 Product A * of Annex II is the transisomer of product A of Annex I for which DL ^ q is 0.4 nanograms / insect.

20

Claims (4)

1. Cyclopropane carboxylic acid esters of formula I 5 * 'yCH, / 0 h 3 C> <3' / s' / 2 \ - C-OB RO-C IH 3 0 10 wherein R is a straight chain, branched or cyclic saturated alkyl group having 8 carbon atoms which may be substituted by one or more halogen atoms or low molecular alkoxy groups, 15. is the group CH I 3 ^^ ch 2 -ch = ch 2 Os 20 or the group 0 -CH.-N N-CH.-CSCH V 25 ^ 0 or the group p F r FF or the group R 14 35 c> ch - oK 32 DK 164740 B wherein R 14 is a hydrogen atom or a methyl, ethynyl or cyano group and R 1 is a hydrogen or fluorine atom or the group T o-f1) -L .γ ° Λ = / 10 and X is a halogen atom and in which compound In the ethylene double bond has the configuration E and the cyclopropane group has the structure IR, cis. Compound according to claim 1, characterized in that it is constituted by (S) -ct * cyano-3-phenoxybenzyl- (IR, cis) - 2-2-dimethyl-3- (E) - [2-fluoro-2- (ethoxycarbonyl) ethenyl] - cyclopropane-l-carboxylate. Composition for controlling plant parasites and house parasites, characterized in that they contain, as an active ingredient, at least one compound as claimed in claim 1. Process for the preparation of the compounds of formula I and defined in claim 1, characterized in that an acid of formula II, X H OH '> = <T H6 <7 /. c = o 11 RO-C 30 11 wherein X and R are as defined above, or a functional derivative of this acid is reacted with an alcohol of formula III B-OH III 33 where B is as defined above or with a functional derivative of this alcohol to give the corresponding compound of formula I, which if desired is reacted with an agent which selectively decomposes the group CC ^ R to give a compound of formula IV X \ / HCH, CH, o \ * /> <// 1 ° / X ^ \ sC-0B IV HO-C \ II XH 0 15 where B has the above meaning, after which the acid of formula IV or a functional derivative of this acid is reacted with an alcohol of formula R-OH, wherein R has the above meaning and the compound 1R, cis, E is separated from the mixture IR, cis (E + Z) by chromatography. 20