DK164047B - CYCLOPROPANCARBOXYLIC ACID DERIVATIVES, PROCEDURES FOR PREPARING THEREOF, AND PARASITE POLLUTANTS WITH CONTENTS - Google Patents

Abstract

1. Claims for the Contracting States : BE CH DE FR GB IT LI LU NL SE In all the possible isomeric forms or in the form of mixtures, the compounds with the formula (I') see diagramm : EP0048186,P72,F1 in which the cyclopropane copula is of IR cis structure and the double bond is of Z geometry and in which A' represents either an alkyl radical containing from 1 to 18 carbon atoms or a benzyl radical possibly substituted by one or more radicals chosen from the group composed of the alkyl radicals containing from 1 to 4 carbon atoms, the alkenyl radicals containing from 2 to 6 carbon atoms, the alkenyloxy radicals containing from 2 to 6 carbon atoms, the alkadienyl radicals containing from 4 to 8 carbon atoms, the methylene dioxy radical and halogen atoms, or a group see diagramm : EP0048186,P72,F2 in which the substituent R1 represents a hydrogen atom or a methyl radical and the substituent R2 a monocyclic aryl radical or a group -CH2 -C -= CH or a group see diagramm : EP0048186,P72,F3 in which a represents a hydrogen atom or a methyl radical and R3 represents the radical -CH2 -CH=CH2 , -CH2 -CH=CH-CH3 , -CH2 -CH=CH-CH=CH2 , CH2 -CH=CH-CH2 -CH3 , or a group see diagramm : EP0048186,P72,F4 in which a represents a hydrogen atom or a methyl radical, R3 retains the same significance as previously, R'1 and R'2 , being identical or different, represent a hydrogen atom, a halogen atom, an alkyl radical containing from 1 to 6 carbon atoms, an aryl radical containing from 6 to 10 carbon atoms, an alkyloxy-carbonyl group including from 2 to 5 carbon atoms, or a cyano group, or a group see diagramm : EP0048186,P72,F5 in which B represents an oxygen or sulphur atom or a group see diagramm : EP0048186,P73,F1 or -CH2 - and R4 represents a hydrogen atom, a -C -= N 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 number 0, 1 or 2, or a group see diagramm : EP0048186,P73,F2 or a group see diagramm : EP0048186,P73,F3 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 a similar dihydro or tetrahydro ring, or a group see diagramm : EP0048186,P73,F4 or a group see diagramm : EP0048186,P73,F5 in which R10 represents a hydrogen atom or a radical CN, R12 represents a radical -CH2 - or an oxygen atom, R11 represents a thiazolyl or a thiadiazolyl radical, of which the bond with -CH-/R10 can be found at any one of the available positions R12 being attached to R11 by the carbon atom included between the sulphur atom and a nitrogen atom, or a group see diagramm : EP0048186,P73,F6 or a group see diagramm : EP0048186,P73,F7 in which R13 represents a hydrogen atom or a radical CN, or a group see diagramm : EP0048186,P74,F1 in which R13 is defined as above, and the benzoyl radical is in position 3 or 4, or a group see diagramm : EP0048186,P74,F2 in which R14 represents a hydrogen atom, a methyl, ethynyl or cyano radical and R15 and R16 , are different and represent a hydrogen, fluorine or bromine atom, or a group see diagramm : EP0048186,P74,F3 in which R14 is defined as above, each of the R17 's represents independently an alkyl group containing from 1 to 4 carbon atons, an alkoxy group containing from 1 to 4 carbon atoms, an alkylthio group containing from 1 to 4 carbon atoms, an alkylsulphonyl group containing from 1 to 4 carbon atoms, a trifluoromethyl, 3,4-methylenedioxy, chloro, fluoro or bromo group, p represents a numeral 0, 1 or 2, and B' represents an oxygen atom or a sulphur atom and R represents an alkyl radical containing from 1 to 18 carbon atoms, substituted by one or more identical or different groups chosen from the group constituted by the halogen atoms, the OH or SH groups, the OR' or SR' groups in which R' represents an alkyl radical containing from 1 to 8 carbon atoms, the groups NO2 or see diagramm : EP0048186,P74,F4 in which R" and R'", being identical or different, represent a hydrogen atom or an alkyl radical containing from 1 to 8 carbon atoms, the groups C -= N, SO3 H or PO4 H2 or the groups COalk1 , SO2 alk2 , or SO3 alk3 in which alk1 , alk2 and alk3 represent alkyl radicals containing from 1 to 18 carbon atoms or R represents an alkyl radical containing from 1 to 18 carbon atoms substituted by an aryl radical, itself possibly substituted by one or more OH, Oalk or alk groups containing from 1 to 18 carbon atoms, by one or more CF3 , OCF3 SCF3 , or by a group (G) : see diagramm : EP0048186,P74,F5 or R represents an alkyl radical containing from 1 to 18 carbon atoms, substituted on two adjacent carbons by a group (G1 ) see diagramm : EP0048186,P74,F6 or substituted by a group see diagramm : EP0048186,P75,F1 or R represents an aryl group containing from 6 to 14 carbon atoms, possibly substituted by one or more OH, Oalk or alk groups containing from 1 to 8 carbon atoms or by a CF3 , OCF3 or SCF3 group, or R represents a pyridinyl, furanyl, thiophenyl, oxazolyl or thiazolyl radical. 1. Claims for the Contracting State : AT Process for preparing in all the possible isomeric forms or in the form of mixtures, the compounds with the formula (I') see diagramm : EP0048186,P82,F3 in which the cyclopropane copula is of IR cis structure and the double bond of Z geometry and in which A' represents either an alkyl radical containing from 1 to 18 carbon atoms or a benzyl radical possibly substituted by one or more radicals chosen from the group constructed by the alkyl radicals containing from 1 to 4 carbon atoms, the alkenyl radicals containing from 2 to 6 carbon atoms, the alkenyloxy radicals containing from 2 to 6 carbon atoms, the alkadienyl radicals containing from 4 to 8 carbon atoms, the methylene dioxy radical and halogen atoms, or a group see diagramm : EP0048186,P82,F4 in which the substituent R1 represents a hydrogen atom or a methyl radical and the substituent R2 a monocyclic aryl or a -CH2 - C -= CH group, or a group see diagramm : EP0048186,P82,F5 in which a represents a hydrogen atom or a methyl radical and R3 represents the radical -CH2 -CH=CH2 , -CH2 -CH=CH-CH3 , -CH2 -CH=CH-CH=CH2 , CH2 -CH=CH-CH2 -CH3 , or a group see diagramm : EP0048186,P82,F6 in which a represents a hydrogen atom or a methyl radical, R3 retains the same significance as previously, R'1 and R'2 , being identical or different, represent a hydrogen atom, a halogen atom, an alkyl radical containing from 1 to 6 carbon atoms, an aryl radical containing from 6 to 10 carbon atoms, an alkyl-oxycarbonyl group containing from 2 to 5 carbon atoms, or a cyano group, or a group see diagramm : EP0048186,P83,F1 in which B represents an oxygen or sulphur atom or a group see diagramm : EP0048186,P83,F2 or -CH2 - and R4 represents a hydrogen atom, a -C -= N 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, or a group see diagramm : EP0048186,P83,F3 or a group see diagramm : EP0048186,P83,F4 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 a similar dihydro or tetrahydro ring, or a group see diagramm : EP0048186,P83,F5 or a group see diagramm : EP0048186,P83,F6 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, of which the bond with -CH-/R10 can be found at any one of the available positions, R12 being attached to R11 by the carbon atom included between the sulphur atom and a nitrogen atom, or a group see diagramm : EP0048186,P84,F1 or a group see diagramm : EP0048186,P84,F2 in which R13 represents a hydrogen atom or a CN radical, or a group see diagramm : EP0048186,P84,F3 in which R13 is defined as above, and the benzoyl radical is in position 3 or 4, or a group see diagramm : EP0048186,P84,F4 in which R14 represents a hydrogen atom, a methyl, ethynyl or cyano radical and R15 and R16 , which are different, represent a hydrogen atom, a fluorine or a bromine atom, or a group see diagramm : EP0048186,P84,F5 in which R14 is defined as above, each of the R17 's represents independently an alkyl group containing from 1 to 4 carbon, an alkoxy group containing from 1 to 4 carbon atoms, an alkylthio group containing from 1 to 4 carbon atoms, an alkylsulphonyl group containing from 1 to 4 carbon atoms, a trifluoromethyl, 3,4-methylenedioxy, chloro, fluoro or bromo group, p represents a numeral 0, 1 or 2 and B' represents an oxygen atom or a sulphur atom and R represents an alkyl radical containing from 1 to 18 carbon atoms, substituted by one or more identical or different functional groups chosen from the group constituted by the halogen atoms, the OH or SH groups, the OR' or SR' groups in which R' represents an alkyl radical containing from 1 to 8 carbon atoms, the NO2 or see diagramm : EP0048186,P84,F6 groups in which R" and R'", which are identical or different, represent a hydrogen atom or an alkyl radical containing from 1 to 8 carbon atoms, the groups C -= N, SO3 H or PO4 H2 groups or the COalk1 , SO2 alk2 , or SO3 alk3 groups in which alk1 , alk2 and alk3 represent alkyl radicals containing from 1 to 18 carbon atoms, or R represents an alkyl radical containing from 1 to 18 carbon atoms substituted by an aryl radical, itself possibly substituted by one or more OH, Oalk or alk groups containing from 1 to 8 carbon atoms, by one or more CF3 , OCF3 SCF3 , or by a group (G) : see diagramm : EP0048186,P85,F1 or R represents an alkyl radical containing from 1 to 18 carbon atoms, substituted on two adjacent carbons by a group (G1 ) see diagramm : EP0048186,P85,F2 or su

Description

in

DK 164047B

The invention relates to novel cyclopropanecarboxylic acid derivatives as set forth in claim 1, their preparation and compositions therefor for the control of parasites on plants, animals and premises.

The invention relates to cyclopropane carboxylic acid derivatives,

which in the 3-position has an unsaturated side chain with Z-geometry and with the structure A

10 C --- -C · (A) R02C \ 15 Cyclopropanecarboxylic acid derivatives were known in advance with, at the 3-position, a chain having the structure R. ~ .....

/ 20 0 ====== 0 / \ ro2c but whose geometry is essentially E. For example. may be mentioned derivatives of pyrethric acid (R = CH 2, R 2 = H, R 2 = CH 3). Some derivatives where R 1 = R 2 = H are also described, namely in French Patent No. 2,185,612 and in the journal J. Chem.

Soc. Perkin I, pages 2470, 1974 and Pest. Sci. 1_, page 499, 1976. However, the side chain geometry of these links is 2

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see predominantly E. In fact, the synthetic methods used in the preparation of these derivatives lead almost exclusively to the E geometry (see Agr. Biol. Chem. 34, p. 1119 1970). For these compounds, whose geometry in the 5 side chain is essentially E, no remarkable property has been demonstrated.

It has now been found that certain compounds whose unsaturated side chain has the structure A but whose geometry is Z exhibit unexpected pesticidal properties, especially very good insecticidal properties, cf. the examples in the experimental section below.

The invention relates in particular to the compounds whose preparation is described below in the experimental part, and in particular to those compounds of Examples 1, 2, 23, 26, 29, 30 and 35.

The compounds of formula 1 'have interesting properties which enable their use in the control of parasites on plants, on warm-blooded animals and on parasites in premises. Thus, the compounds of the invention can be used to control insects, nematodes and acarides which are parasites on plants and animals.

Thus, the compounds of formula 1 'can be used in particular to control insects in agriculture, e.g. for the control of aphids and larvae by lepidopters and coleopters. They are used in doses of 10-300 g of active substance per day. ha.

The compounds of formula 1 'can also be used to control insects in rooms, in particular to control flies, mosquitoes and cockroaches.

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3

The compound of Example 1 is a very remarkable compound as shown by the results of the tests below. It has an excellent lethal effect and a very good knock-down effect.

The compounds of formula 1 'are also light stable and are not toxic to mammals.

- All of these properties make the compounds of formula 1 'compounds which correspond completely to the demands of the modern agricultural chemical industry, being able to protect the harvest while preserving the environment.

The compounds of formula 1 'can also be used to control acarides and nematodes which are parasites on plants.

The compounds of formula I * can also be used to control acarides which are parasites on animals, e.g. for the control of blood mites and in particular those of the species Boophilus, Hyalomnia, Amblyomnia and Bhipieephalus or for combating all kinds of enclosures and in particular sarcoptic, psoroptic and chorioptic enclosures.

Thus, the invention relates to particular compositions intended for the control of parasites on warm-blooded animals, in premises and on plants, characterized in that they contain at least one of the above-mentioned compounds.

The invention relates in particular to insecticidal compositions containing as active ingredient at least one of the compounds defined above.

Among the preferred insecticidal compositions are in particular those containing (1R, cis) -2,2-dimethyl-3 - ((Z) -3 - (2,2,2-trifluorophore) -3 -oxo-1-propenyl) -cyclo-propanecarboxylic acid ~ (S) -α-cyano-3-phenoxybenzyl ester, (IR, cis) -2,2-dimethyl-3 - ((Z) -3-oxo 3- (2- (1,1,1,3,3,3-hexafluoro) -propoxy) -1-propenyl) -cyclopropanecarboxylic acid (S) -α-cyano-3-phenoxybenzyl ester, (IR, cis ) -2,2-Dimethyl-3 - ((Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -3-propenyl) cyclopropane carboxylic acid (R) -α-e thynyl 3-phenoxybenzyl ester, (IR, cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -4

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-1-propenyl) -cyclopropanecarboxylic acid (RS) -cyan-6-phenoxy-2-pyridylmethyl ester, (IR, cis) -2,2-dime thyl -3 - ((Z) -3-oxo-3- ( 2-fluoroethoxy) -1-propenyl) -cyclopropane carboxylic acid (S) -α-cyano-3-phenoxybenzyl ester, (IR, cis) -2,2-dimethyl-3 - ((Z) -3- oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl) -cyclopropanecarboxylic acid (3-propargyl-2,5-dioxo-imidazolyl dinyl) methyl ester, (XR, Eis) - 2,2-dimethyl-3 - ((Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -10-1-propenyl) -cyclopropanecarboxylic acid (1S) -2-methyl-4 -GKo-3 - (2-propeny1) -2-cyclopenten-l-yl ester.

These preparations are prepared according to the usual methods of the agricultural or veterinary or feed industries.

15 X the preparations intended for use in agriculture or in the premises, one or more other pesticidal agents may be added to the active ingredient (s). These compositions may be in the form of powders, granules, suspensions, emulsions, solutions, aerosol solutions, combustible tapes, baits and other preparations normally used in the use of these kinds of compounds.

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

The insecticide compositions of the invention preferably contain from 0.005 $ to 10 $ by weight of active ingredient.

According to an advantageous working method for use in premises, the compositions of the invention are used in the form of combustion preparations.

The compositions according to the invention may then, for the benefit of the inactive part, be constituted by a combustible insecticidal coil or also by a non-combustible fibrous substrate.

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In this latter case, the smoke preparation obtained after incorporation of the active ingredient is placed in a heating apparatus such as an electric insecticide extinguisher.

In the case where an insecticidal spiral is used, the inert carrier may e.g. be it of pyrethrum brush or powder of leaves of Machilus thumbergii, powder of Pyrethrum stalk, powder of cedar needles, sawdust such as pine sawdust, starch and coconut shell powder.

The dose of active ingredient may then e.g. be 0.03-1 10% by weight.

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

The compositions of the invention for use in premises 15 may also be obtained by producing an active ingredient sprayable oil, which soaks up a lamp wall and then burns it.

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

The insecticidal compositions of the invention may optionally have one or more other pesticidal agents added to the acaricidal and nematodicidal preparations. In particular, the acaricidal and nematodicidal preparations may be in the form of powders, granules, suspensions, emulsions and solutions.

For acaricidal use, preferably wettable powder is used for spraying on the foliage containing 1-80 $ or liquids for spraying on the foliage containing 1-500 g / ml. liter of active ingredient. Powders can also be used to powder the foliage and contain 0.05-3 $ active ingredient.

For nematodic use, liquids are preferably used to treat the soil containing 300-500 g / liter of active ingredient.

The acaricidal and nematodicidal compounds of the invention are preferably used in doses between 1 and 100 grams of active ingredient per day. ha.

To increase the biological effect of enhancer 6

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to the binder of the invention may be added to the classic synergistic agents used in such cases as 1- (2,5,8-trioxadodecyl) -2-propyl-4,5-methylenedioxybenzene (or piperonylbutoxide) or N- (2- ethylheptyl) bicyclo (2.2-1) -5 -5-hepten-2,3-dicarboximide or piperonyl bis-2- (21-n-butoxyethoxy) ethyl acetal or tropital).

The compounds of formula 1 'have an excellent general tolerance and can be used on warm-blooded animals to control, in particular, the disorders caused by anemia and closet, as well as to combat lice, either preventive or curative.

The compounds 1 'of the invention can be administered topically, by evaporation, by saponification, by bathing or by lubrication.

The compounds 1 'according to the invention can also be administered by application to the spine of the animals according to the "poor on" method. They can also be used by the digestive tract or parenterally.

The invention also relates to a process for preparing the compounds of formula I ', and this method is characterized by subjecting an acid of formula II

R02C-CH = CHCO2H (11)

Wherein R has the same meaning as above, or a functional derivative of this acid treatment with an alcohol of formula III

A1 OH (III) where A 'has the same meaning as above to give 30

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7 shows the corresponding compound of formula I '.

The functional acid derivative used is preferably an acid chloride.

When reacting the acid of formula II with the alcohol - 5 of formula III, one preferably works in the presence of dicyclohexylcarbodiimide.

One method of preparation of the compound of formula II consists in subjecting a compound of formula 10 in an organic solvent.

C = C / \ (b1) 15 \ / in trans form or in the form of cis-laetone acting on a compound of formula B2 + (C5H5) 3 = P-CH-C0-OR (B2)

Wherein R has the same meaning as above to give the corresponding compound of formula II

R0OC-CH = CHV / \ CO-K (II) 25 2 \ / \ / 2 1 form a mixture of E and Z isomers which is separated into each of the isomers.

In a preferred embodiment, the solvent used is selected from ethyl ether, dimethyl sulfoxide, dimethylformamide, tetrahydrofuran, dimethoxyethane, alkanols, diethylene glycol monomethyl ether and diethylene glycol diethyl ether.

The compound of formula is prepared by the action of a compound of formula + - (C6H5) 3sp-CH2-CO2R, Hal 8

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where Hal represents a halide anion, on a strong base. As a strong base, for example. employ a hydride, an amide, an alkali metal alcoholate or an alkyl lithium.

The compound of formula II may also be prepared by

5 to react a compound of formula IV

Wherein Hal represents a halogen atom, and alc represents an alkyl group of 1-20 carbon atoms, in a first step with an alkaline agent capable of to detach the halogen atoms, and then in a second step - either with an agent capable of introducing a carboxyl group, to obtain a compound of the formula

20 len V

HOpC-C = C v / \ C02alc (V) 25

which is subjected to the action of an esterifying agent to obtain a compound of formula VI

30 / \ R02C-C Z c / \ CO2alc (VI) where E has the same meaning as above, - or with a derivative of the formula

Hal-CO2-S

wherein Hal represents a halogen atom and E has the same meaning as above to directly obtain the compound of form 9

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len VI

5 R02C-C s C

wherein the compound of formula VI is subject to the action of a gentle hydrogenation agent to obtain a compound of formula VII

10 \ /

\ = // XCO2alc (VID

3Π in which the double bond has Z geometry which is subjected to the action of an acid hydrolysis agent capable of selectively cleaving the ester & the group at the carbon atom of the 1-position 2q cyclopropane to obtain the corresponding compound of the formula In a preferred embodiment of the above process, the following applies: - Hal represents a bromine or chlorine atom.

- The substituent alc represents tert-butyl or benzyl.

- The alkaline agent capable of dispensing the vinylic halogens is butyllithium, - The agent capable of introducing the carboxyl group is CC 2 gas.

- The agent for gentle hydrogenation is hydrogen in the presence of a catalyst such as palladium in the presence of traces of quinoline. - The agent for acid hydrolysis, which is capable of selectively decomposing the ester group CC ^ alc, is p-toluenesulfonic acid.

The process also includes an obvious variant

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wherein the compound of formula V is first subjected to the action of a gentle hydrogenation agent and then in a second step to the effect of a reducing agent.

Thus, the variant of the method defined as above consists in first subjecting the compound to

Formula V has the effect of a gentle hydrogenation agent to give the compound of Formula VIII

10 / H 2 OC-CH »CHv ^^ // al c (VIII) 15

wherein the double bond has Z geometry which is subjected to the action of an esterifying agent to obtain the corresponding compound of formula VII

Where R has the same meaning as above, continuing the synthesis as described above.

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The invention also relates to a process for the preparation of compounds of formula I ', which is characterized by subjecting a compound of formula XI

Where the double bond has Z geometry, effect of an esterification agent to obtain the corresponding compound of formula I * # 15 I a preferred embodiment of the process above is the esterification with a functional alcohol derivative, namely with a derivative of NjIT'-diisopropylurea of the formula

20 V

ira «

-N = C -OR

The compound of formula XI is prepared by subjecting an acid of formula V 25 H3 ° \ / CH3 30 H02C-CSC2 \ ^ / CO2alc (V)

wherein alc represents an alkyl group of 1-8 carbon atoms, effect of 2,2,2-trichloroethanol to give a compound of formula XII

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12 H3C V yCH3 ^ csc \ ^^ x: o2aic (xnl 5 COoCH-CCl, d 2 2

subjecting the action of an acid hydrolysis agent to give the compound of formula XIII

H3C \ / CH3 10 / \ / \ yyCQ2H (XIII) CO2CH2CC13

15 under the influence of an alcohol of formula III

A'-OH (III)

where Α »has the same meaning as above, to give the compound of formula XIV

E3 \ / CK3 \ / CO2 ~ 'V (XIV) 25 / CO2CH2CC13

subjecting to the action of an agent for cleavage of the ester group carried by the acetylenic carbon atom to give a compound of formula XV

H3C / CH3 p = C \ / \ / CO2A '(XV) 35 / ^

C02H

13

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which is subject to the action of a means of gentle hybridization to obtain the compound of formula XI.

In a preferred embodiment of the process above, the following applies: 5 - The substituent alc of formula V represents tert-butyl or benzyl.

- The acid hydrolysis agent is p-toluenesulfonic acid.

The esterification of compound XIII occurs by reacting compound XIII with alcohol III in the presence of dicyclohexylcarbodiimide or diisopropylcarbodiimide.

- The cleavage of the ester XIV occurs, using a metal powder, e.g. zinc powder, in acidic environment.

The gentle hydrogenation agent is hydrogen in the near room of a catalyst such as palladium in the presence of traces of quinoline.

The process comprises an obvious variant consisting in exchanging the hydrogenation and esterification step, i.e., subjecting a compound of formula XV

20 r.3S / Ct-25 EQ2C-CH / \ ^ y £ 0zA1 (XV)

wherein A * is as defined above, the action of an esterifying agent to give the compound of formula X

03 = \> Η3 35 R02C- 'C ^ y \ ^ ° 2A' where E and A1 are defined as above, subject to the action of a scant hydrogenation agent to obtain the compound of formula I *.

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The preferred embodiment conditions for the above method are identical to those previously indicated for the analog operations.

In the event that one wishes to prepare a compound of formula I 'wherein E represents an alkyl group substituted by one or more hydroxy groups, one will first prepare, according to any of the above methods, a compound of formula I * wherein S represents a alkyl group substituted with one or more hydroxy groups which are protected by e.g. a dioxolanyl or tetrahydropyranyl group, then hydrolyzing this compound by an acid hydrolysis agent.

The acid hydrolysis agent used in the above process may e.g. be hydrochloric or p-toluenesulfonic acid.

The majority of the methods described above lead to compounds where the double bond has Z-geometry. Of course, these methods are the most suitable for the preparation of the compounds of formula If, where the double bond has Z geometry.

Excellent yields are obtained, as is clear from the experimental section below.

Compounds II, VI and VII as well as Compounds X are novel compounds.

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Example 1, (IR (cis) -2,2-dimethyl-3 - ((Z) -3- (2,2,2-trifluoroethoxy) -3-oxo-1-propenyl) -cyclopropane carboxylic acid (S) - g-cyan-3-phenoxybenzyl ester, 1.3 g (IR, cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3- (2.2) , 2-Trifluoroethoxy-1-propenyl) -cyclopropane carboxylic acid, 0.1 ml of pyridine and 15 ml of methylene chloride, to which 1.05 g of dicyclohexylcarbodiimide is added. hydroxy-3-phenoxybenzeneacetonitrile dissolved in 5 ml of methylene chloride. The mixture is stirred at room temperature for 5 hours, the insoluble material is filtered off and rinsed with methylene chloride. The filtrate is added 2 N hydrochloric acid. You decant, wash with water, dry and evaporate to dryness. The resulting oil is purified by chromatography on silica gel (eluent: cyclohexane and ethyl acetate (95: 5)). Thus, 1.33 g of the expected compound are obtained, ccp = + 42 ° + 2 ° (c = 0.7 $, benzene), H, M, R, spectrum, CDCl3, ppm; 1.26 and 1.28 H in the methyl groups at the 2-position, 1.97 - 2.11 H in the carbon at the 1-position in cyclopropane, 3.1 to 3.4 H in the carbon at the 3-position in cyclopropane, 6.5 to 6.9 Hi carbon at the 1-position in propenyl, 5.9 - 5.93 Hi carbon at the 2-position in propenyl, 6.3 Hi carbon carrying the CH group, 4.3 to 14, 7 Hi trifluoroethoxy group.

In Example 1, the acid used is prepared as follows:

Preparation I, (IR, cis) -2,2-dimethyl-3 - ((Z) -3- (2,2,2-trifluoroethoxy) -3-oxo-1-propenyl) -cyclopropane carboxylic acid.

Step A: (IR, cis) -2,2-Dimethyl-3- (3-hydroxy-3-oxo-1-propynyl) cyclopropane carboxylic acid 1,1-dimethylethyl ester.

26 g of (1R, cis) -2,2-dimethyl-3- (2,2-di-bromo-vinyl) -cyclopropane carboxylic acid-1,1-dimethylethyl ester are introduced into 175 ml of anhydrous tetrahydrofuran. 60 ml of a 20 $ solution of butyllithium in hexane are then added at -65 ° G.

Stir for 1 hour at -60 ° C and allow a stream of carbon dioxide to bubble for 1 hour 30 minutes, then 16

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the reaction mixture is poured into ice-cold water with 1 E sodium hydroxide solution «Wash with ether. The aqueous alkaline phase is acidified to a pH of 4 and extracted with ether. The organic phases are dried and evaporated to dryness under reduced pressure. There is thus obtained a compound which is recrystallized from petroleum ether (bp 60-80 ° C). Thus, 8.3 g of the expected compound is obtained with m.p. 144 ° C, HMR, spectrum, CDCl3, ppm: 10 1.22 and 1.37 protons in the methyl groups at the 2-position in cyclopropane 1.78 protons at the 1- and 3-position in cyclopropane 1.47 protons in tert. butyl

8.25 proton in the group -C0-0H

Step B: (IR.eis) -2,2-dimethyl-3- (3-oxo-3- (2,2,2-trifluoro-ethoxy.v) -1-propynyl) -cyclopropanecarboxylic acid 1.1-dimethylethyl ester.

4 g of the compound prepared in step A and 3.5 g of dicyclohexylcarbodiimide are introduced into a solution containing 20 ml of methylene chloride and 1 ml of pyridine. The reaction mixture is kept under stirring for 1 hour. 2.15 g of trifluoroethanol and 5 g of methylene chloride are then added. Stir under stirring at 20 ° C for 16 hours. Filter and rinse with methylene chloride. The filtrate is evaporated to dryness.

It is taken up in ether, washed with 1 N hydrochloric acid and then with water and dried. Evaporate and isolate 5 g of a compound which is chromatographed on silica gel (eluent: benzene and ethyl acetate (95: 5)). Thus, 3.5 g of the expected compound is obtained.

30 HMR Spectrum, CDCl3, ppm: 1.2 and 1.37 H in the methyl groups at the 2-position 1.77 H of the carbonator nuclei at the 1- and 3-position in cyclopropane 1.45 H in the methyl groups in 1,1-dimethylethyl 35 4.3 to 4.7 Hi trifluoroethoxy

Step C »(1R.cis) -2,2-dimethyl-5- (5-oxo-5- (2,2,2-trifluoro-, ethoxyM-propyl) -cyclopropane carboxylic acid.

A mixture containing 3.5 g 17 is refluxed

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of the compound prepared in the previous step, 30 ml of toluene and 100 mg of p-toluenesulfonic acid are kept under reflux until the end of gas evolution. You cool, wash with water, dry and evaporate to dryness. 2.6 g of the expected compound are then obtained, which is used immediately in the next step.

Step D ~: (IR.cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl) -cyolopropane carboxylic acid.

In a flask connected to a hydrogen apparatus 10, 500 mg of 10 $ palladium hydroxide is applied to barium sulfate and 5 ml of ethyl acetate. 2 g of the compound prepared in the previous step, 45 ml of ethyl acetate and 0.5 ml of quinoline are added. Hydrogenation until complete absorption is hydrogenated. Filter the obtained compound, wash the filtrate with 1N hydrochloric acid and then with water and evaporate to dryness. There is obtained 2 g of a compound which is chromatographed on silica gel (eluent: cyclohexane, ethyl acetate and acetic acid (70: 50: 1)). Thus 1.5 g of the expected compound, N.M.R. spectrum, CDCl3, ppm: 1.5 and 1.52 Hi the methyl groups at the 2-position 1.92 - 2.06 Hi the carbon at the 1-position in cyclopropane 5.07 to 5.38 Hi the carbon at the 3-position in the cyclopropane 6.6 to 6.9 Hi carbon at 1 position in propenyl 5.9 - 6.0 Hi carbon at 2 position in propenyl 4.5 to 4.7 Hi trifluoroethoxy

Example 2.

(IR.cis) -2,2-Dimethyl-3 - ((Z) -5-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl) -cyclopropane carboxylic acid (1S) -2 - methyl 4-oxo-30- (2-propenyl) -2-cyclopenten-1-yl ester.

1.9 g (1R, cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl) -cyclopropanecarboxylic acid are mixed. , 12 ml of methylene chloride and 100 mg of dimethylaminopyridine. Then, 1.4 g of dicyclohexylcarbodiimide and then in g (S) -5- (2-propenyl) -1-hydroxy-2-methyl-4-oxocyclopent-2-ene and 5 ml of methylene chloride are introduced. Stir under room temperature for 2 hours. The insoluble material formed 18

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removed by filtration. The filtrate is washed with 0.5 IT hydrochloric acid and then with water, dried and evaporated to dryness. Thus, 3 g of a compound is obtained which is chromatographed on silica gel (eluent: benzene and ethyl acetate (95: 5)).

Thus, 2.2 g of the expected compound is obtained, <* £ = + 38 ° + 2.5 ° (c = 0.5 $, benzene).

N.M.R, spectrum, CDCl3, ppm: 1.29. and 1.32 H in the methyl groups at the 2-position in cyclo-10 o propane 1.97 - 2.11 Hi 1 position in cyclopropane 3.05 to 3.37 Hi 3 position in cyclopropane 6.7 to 7 Hi carbon in 1 the position of propenyl H in the carbon at the 2-position of propenyl 15 6.1 µg 4.3 to 4.75 Hi of trifluoroethoxy 5.7 Hi of the cyclopentene at the α-position relative to: oo2 2 Hi of the methyl group carried by the cyclopentene 20 4, 8 to 5.25 Hi 3 position in propenyl carried by the cyclopentene

Example 3

(IR, cis) -2,2-Dimethyl-3- ((Z) -3-oxo-3- (phenylmethoxy) -1-propenyl) cyclopropane carboxylic acid (1S) -α-cyano-3-pyphenoxybenzyl ester.

Step A: (1R.cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3- (phenylmethoxy) -1-propenyl) cyclopropane carboxylic acid chloride.

A mixture containing 1.6 g of (1R, cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3- (phenylmethoxy) -1-propenyl) is stirred for 5 hours under a stream of nitrogen. ) -cyclopropane carboxylic acid, 10 ml of isoprene and 1 ml of thionyl chloride, evaporates and thus obtains 2 g of a compound which is used immediately in the next step.

Step S: (IR.cis) -2,2-Dimethyl 1-3 - ((Z) -3-oxo-3- (phenylmethoxy) -1-propenyl) -cyclopropane carboxylic acid (1S) -cyan-3-phenoxybenzyl ester.

1 g of the compound 19 prepared in step A is introduced

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part 1 a solution containing 700 mg of (S) -α-hydroxy-3-phenoxybenzeneacetonitrile, 20 ml of benzene and 0.6 ml of pyridine.

The reaction mixture is kept under stirring for 16 hours at room temperature, poured into a mixture of ice-cold water 5 and 1 in hydrochloric acid, the resulting suspension is stirred and extracted with benzene. The benzene extracts are washed with water, dried, filtered and evaporated to dryness. 1.5 g of a compound is obtained which is chromatographed on silica gel (eluent: cyclohexane and ethyl acetate (8: 2)).

Thus 861 mg of the expected compound is obtained with m.p., 83 ° C, <xjj = + 69 ° + 5 ° (c - 0.2 $, benzene).

K.M.R, spectrum, CDCl *, ppm: 1.25 H in the methyl groups at the 2-position of the cyclopropane 6.33 Hi carbon atom bearing the CN group 15

Preparation II.

(IR, cis) -2,2-Dimethyl-3- ((Z) -3-oxo-3- (phenylmethoxy) -1-prope-nyl) -cyclopropane carboxylic acid.

Step A: (1R, cis) -2,2-dimethyl-3- ((Z) -2-carboxyethenyl) -cyclopropanecarboxylsyric acid-1β-dimethylethyl ethyl ester.

2 g of (1R, cis) -2,2-dimethyl-3- (2-carboxyethynyl) -cyclopropane carboxylic acid -1,1-dimethylethyl ester 40 ml of ethyl acetate in the presence of 0.38 g of 10 $ palladium hydroxide on barium sulfate and 0.4 ml of quinoline. The filtrate is washed, the filtrate is washed with 0.5 S hydrochloric acid and then with water until neutrality, dried, evaporated to dryness under reduced pressure to give 2 g of the expected compound, m.p., 94 ° C. Step B: (IR, cis) -2,2-Dimethyl-3- ((Z) -3-oxo-3- (phenylmethoxy) -1-propenyl) cyclopropane carboxylic acid 1-dimethyl-ethyl ester.

2.4 g of the compound of step A is introduced into 20 ml of ethyl acetate. Then 2.34 g of O-benzy 1-17, N-diisopro py lis ourins are added (described by Eschimdt et al., Liebig Ann. Chem, 1965 685 161), stirred for 16 hours at room temperature, filter and evaporate the filtrate under reduced pressure. 4.3 g of a yellow oil are obtained which are chromatographed on silica gel (eluent: benzene and cyclohexane (7: 3)). Thus, 2 g of the expected formula is obtained

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"bind else.

li.MR spectrum, CDCl3, ppm: 1.22 and 1.28 H in the methyl groups at the 2-position in cyclopropane 5 1.77 - 1.91 Hi the carbon at the 1-position in cyclopropane 2.98 to 3.3 Hi the carbon in The 3-position in cyclopropane 6.5 'to 6.8 Hi the carbon at the 1-position in propenyl 5.8 - 6 Hi the carbon at the 2-position in propenyl 1.43 H in the methyl groups in dimethylethyl 5.1 Hi methoxy in phenylmethoxy

Step C: (IR.cis) -2,2-dimethyl-3- ((Z) -3-oxo-3- (phenylmethoxy) -1-propenyl) -cyclopropane carboxylic acid.

A mixture containing 2 g of the compound of the previous step, 30 ml of toluene and 100 mg of p-toluenesulfonic acid is heated to 90 ° C. Stir under stirring for approx. 2 hours. Evaporate to dryness to give 2 g of a compound which is ohromatographed on silica gel (eluent: cyclohexane, ethyl acetate and acetic acid (60: 40: 1)).

Thus, 1.4 g of the expected compound is obtained.

20 NMR, Spectrum, OHCl 3, ppm: 1.25 and 1.3 H in the methyl groups at the 2-position in cyclopropane 1.84 - 1.98 HI carbon at the 1-position in cyclopropane 3.14 to 3.43 HI carbon at the 3-position in cyclopropane 25 6.4 to 6.77 Hi carbon at the 1-position in propenyl 5.98 Hi the carbon at the 2-position in propenyl

Example 4

(IR.cis) -2,2-Dimethyl-3 - ((Z) -3-oxo-3- (phenylmethoxy) -1-propionyl) -cyclopropane carboxylic acid (1S) -2-methyl-4-oxo-3 - (2-propenyl) -2-cyclopenten-1-ester.

1 g (IR, cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3- (phenylmethoxy) -1-propenyl) cyclopropane carboxylic acid chloride is introduced into a mixture of 450 mg (S ) -3- (2-propenyl) -1-hydroxy-2-35-methyl-4-oxocyclopent-2-ene, 20 ml of benzene and 0.6 ml of pyridine. Stir under stirring for 16 hours and pour the reaction mixture into ice-cold water and 1 L hydrochloric acid. Extract with benzene, combine the benzene phases, wash them with water, 21

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dries and evaporates to dryness. Thus, 1.5 g of a compound which is chromatographed on silica gel (eluent: cyclohexane and ethyl acetate (8: 2)) is obtained, thus 500 mg of the expected compound is obtained, 5 ap = + 37 ° + 2 ° (c = 0.5 $, benzene).

NMR spectrum, CfCl 3, ppm: 1.27 and 1.31 H in the methyl groups at the 2-position in cyclopropane 1.87-2 Hi the carbon at the 1-position in cyclopropane 1 ° 3.12 to 3.45 Hi the carbon at the 3-position in cyclopropane 5.8 to 6.8 H at the 1- and 2-position in propenyl 5.2 Hi methoxy in phenylmethoxy 5.6 to 5.7 Hi cyclopentene at the α position relative to the eo2 15 2 Hi methyl group which is carried by the cyclopentene 4.8 to 5.2 Hi propenyl carried by the cyclopentene.

Example 5

(IR, ois) -2,2-dimethyl-3- ((Z) -5-oxo-3-phenoxy-1-propenyl) -20-cyclopropane carboxylic acid (S) -g-cyano-5-phenoxybenzyl ester.

Working as in Example 1 from 1.5 g (IR, cis) -2,2-dimethyl-3- ((Z) -3-oxo-3-phenoxy-1-propenyl) cyclopropane carboxylic acid and 1, 45 g (S) -g-hydroxy-3-phenoxy-benzeneacetonitrile gives 1.8 g of the expected compound, ctp = + 54 ° + 2.5 ° (c = 0.5 $, benzene) .

HMR spectrum, CfCl 2, ppm: 1.25 Hi 2 position in cyclopropane 1.97 - 2.12 H at 1 position in cyclopropane 3.25 to 3.6 Hi 3 position in cyclopropane 6.6 to 7 Hi 1 position in propenyl 6.1 - 6.3 Hi 2 position in propenyl 6.9 to 7.7 aromatic E atoms in 3-phenoxyphenyl

Preparation III.

(IR, cis) -2,2-Dimethyl-3- ((Z) -3-oxo-3-phenoxy-1-propenyl) -cyclopropanecarboxylic acid.

Step A: IR (cis) -2,2-Dimethylphayl-3- (3-oxo-3-phenoxy-1-propynyl) -cyclopropapcarboxylic acid-1,1-dimethylethyl ester. 25 g (IR, cis) -2,2-dimethyl-3- (2 *, 2'-di-22) are dissolved.

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bromovinyl) -cyclopropane carboxylic acid 1,1-dimethylethyl ester in 250 ml of tetrahydrofuran. 48 ml of 20 $ butyl lithium solution in cyclohexane is then introduced with stirring at -65 ° C.

Stirring is continued for 1 hour at -65 ° C and 5 9.6 ml of phenyl chloroformate are introduced. The mixture is kept under stirring at -65 ° C for 1 hour and allowed to re-enter room temperature with continued stirring. Pour into a saturated aqueous monosodium phosphate solution, extract with ether, wash with water, dry and give 24.6 g of an oil which is purified by chromatography on silica gel (eluent: cyclohexane and ethyl acetate (9: 1)). Thus, 14.4 g of the expected compound are isolated.

HMR spectrum, CDCl3, ppm: 1.23 and 1.42 H in the methyl groups at the 2-position in cyclopropane 1.82 H at the 1- and 3-positions in cyclopropane 1.5 Hi dimethylethyl 7 to 7.6 aromatic H atoms Step B: (1R, cis) -2,2-Dimethyl-3 - ((Z) -3-oxo-3-phenoxy-1-propenyl) -cyclopropanecarboxylic acid-1,3: -dimethylethyl ester.

In the presence of 800 mg of palladium hydroxide on barium sulfate, 0.8 ml of quinoline and 20 ml of ethyl acetate, hydrogenate 4 g of the compound prepared in Step A dissolved in 60 ml of 25 ethyl acetate and filter 200 ml of 2 ΪΓ hydrochloric acid. You decant, wash with water and dry. 4.1 g of an oil is obtained which is purified on silica gel (eluent: cyclohexane and ethyl acetate (95: 5)). 3.35 g of the expected compound are obtained.

30 UMR spectrum, CDCl3, ppm: 1.23 and 1.3 Hi 2 position in cyclopropane 1.83 - 1.97 Hi 1 position in cyclopropane 3 to 3.33 Hi 3 position in cyclopropane 1.44 H in methyl ethyl 35 6 , 7 to 7 Hi 1 position in propenyl 6.03 - 6.21 Hi 2 position in propenyl 7 to 7.5 aromatic H atoms 23

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Step C: (IR, cis) -2,2-Dimethyl-3 - ((Z) -3-oxo-3-phenoxy) -1-propenyl) cyclopropane carboxylic acid.

A mixture of 3.3 g of the compound prepared in the previous step, 35 ml of toluene and 100 mg of 5-p-toluenesulfonic acid monohydrate is refluxed. Reflux is stopped immediately upon cessation of gas evolution. Evaporate to dryness under reduced pressure to obtain 3.4 g of a compound which is chromatographed on silica gel (eluent: cyclohexane, ethyl acetate and acetic acid (70: 30: 1)) to give 2.4 g of it. expected compound with sap, 57 ° C, NMR, spectrum, CDCl3, ppm: 1.25 to 1.33 H in the methyl groups at the 2-position in cyclopropane 1.9 - 2.04 Hi 1 position in cyclopropane 15 3, 2 to 3.5 H at the 3-position in cyclopropane 6.6 to 6.9 Hi 1 position in propenyl 6.0 - 6.2 Hi 2 position in propenyl

Example 6, 20 (1H, III) -2,2-Dimethyl-5 - ((Z) -3-oxo-3-phenoxy-1-propenyl) cyclopropanecarboxylic acid (1S) -2-methyl-4-oxo-5 - (2-propenyl) - 2-cyclopenten-l-yl ester.

Working as in Example 2 from 1.5 g (IR, cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3-phenoxy-1-propenyl) -cyclopropane carboxylic acid and 1 g (S) -3- (2-propenyl) -1-hydroxy-2-methyl-4-oxocyclopent-2-ene gives 1.6 g of the expected compound, - + 66 ° +2, 5 ° (o = 0.5 $, benzene).

HMR spectrum, CDCl3, ppm: 1.26 and 1.33 H at the 2-position of cyclopropane 30 1.95 - 2.09 H at the 1-position of cyclopropane 5.7 Hi the cyclopentene at the α-position relative to the co2 4.8 to 5, 2 Hi 3 position in propenyl carried by cyclopenten 35 2 Hi methyl carried by cyclopenten 6.1 to 6.7 H in propenyl carried by cyclopropane 7 to 7.7 aromatic H atoms 24

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Example 7

(1R, cis) -2,2-dimethyl-3- ((Z) -3-oxo-3-methoxymethoxy-1-propenyl) -cyclopropaacarboxylic acid (RS) -Q> cyano-3-phenoxybenzyl ester, 5 · Step A; (1R, cis) -2,2-Dimethyl-3- (3-oxo-5-methoxymethoxy-1-propynyl) -cyclopropanecarboxylic acid (RS) -g-cyano--3-phenoxybenzyl ester.

A solution of 3 g (1R, cis) - 2,2-dimethyl-3- (3-hydroxy-3-oxo-1-propynyl) -cyclopropanecarboxylic acid (RS) -a is cooled to 10 ° C. -cyan-3-phenoxybenzyl ester in 30 ml of anhydrous dimethylformamide and adding portionwise 300 mg of 61 $ sodium hydride slurry and 2.5 ml of chloromethyl ether solution prepared as below. The mixture is stirred for 2 hours, poured into an aqueous monosodium phosphate solution and extracted with ethyl acetate, washed with water, dried and evaporated to dryness. The residue is chromatographed on silica gel and eluted with a mixture of cyclohexane and ethyl acetate (75:25) to give 2 g of the expected compound.

IT.MR, Spectrum, CEC1, ppm: 1.23 - 1.27 and 1.35 - 1.45 protons in the methyl groups at the 2-position in cyclopropane 1.95 protons in the 1- and 3-position in cyclo propane 5.28 protons in the methylene group in methoxymethoxyl 3.5 protons in the methyl group in methoxymethoxyl 6.42 and 6.47 protons carried by the same carbon atom

son GIT

6.92 to 7.58 aromatic protons

Preparation of the chloromethyl ether solution.

4.5 ml of methylal and 0.52 ml of methanol are mixed and then 3.53 ml of acetyl chloride are slowly added. The mixture is stirred for 36 hours at room temperature to obtain the expected solution.

25

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Step B: (IR) cis) -2 "2-Dimethylphyl-3- ((Z) -3-oxo-3-methoxymethoxy-1-propenyl) cyclopropane carboxylic acid (RS) -ct-cyano-3- phenoxybenzyl ester.

2.2 g of the compound obtained above was hydrogenated in 50 ml of ethyl acetate in the presence of 450 mg of 10 $ palladium hydroxide on barium sulfate in 30 ml of ethyl acetate and 0.5 ml of quinoline. The filtrate is filtered, washed with 1 U hydrochloric acid and with water, dried and evaporated to dryness. Chromatograph the residue on silica gel, elute with a mixture of cyclohexane and ethyl acetate (8: 2) to give 1.2 g of the expected compound, aD = + 41 ° + 3 ° (o * 0.3 # , CHCl3).

NMR Spectrum, CDCl3, ppm: 1.27 - 1.28 and 1.33 - 1.35 protons in the methyl groups at 2-position 15 in cyclopropane 1.93 - 2.1 protons at the 1-position in cyclopropane 3.17 to 3 , 5 protons at the 3-position in cyclopropane 6.47 to 6.82 ethylenic proton at the 1-position 5.85 - 6.0 and 5.88 - 6.1 ethylenic proton at the 2-position 5.27 and 5.3 protons in CH2 in methoxy 3.47 and 3.5 protons in methyl in methoxy,

6.4 which is carried by the same carbon atom as CN

6.92 to 7.67 aromatic protons The (1R, cis) -2,2-dimethyl-3- (3-hydroxy-3-oxo-1-propynyl) -cyclopropanecarboxylic acid (RS) -α-cyano -3-phenoxybenzyl ester used at the beginning of the example can be prepared by analogy with the (S) ester described later using the corresponding (RS) alcohol.

30

Example 8.

(1R.cis) -2,2-Dimethyl-3- ((Z) -3-oxo-3-cyano-methoxy-1-propenyl) -cyclopropane carboxylic acid (S) -q-cyano-3-phenoxybenzyl ester.

Step A: (IR.cis) -2,2-Dimethyl-5- (5-oxo-5-cyanomethoxy-1-propynyl) -cyclopropanecarboxylic acid (RS) -α-cyano-3-phenoxybenzyl ester.

One works as in Example 7 using 2 ml of chloroacetonitrile. After extraction with ether and elu- 26

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ring with a mixture of cyclohexane and ethyl acetate (9: 1) gives 2.69 g of the expected compound.

Step B: (IR.cis) -2,2-Dimethyl-3- ((Z) -3-oxo-3-cyanomethoxy-1-propenyl) -cyclopropane carboxylic acid (RS) -g-oyan-5-5-phenoxybenzyl ester.

Working as in Example 7 from 2.69 g of the above compound, 2.02 g of the expected compound is obtained after elution with a mixture of cyclohexane and ethyl acetate (9: 1).

1 ° Step C: (1R.cis) -2,2-Dimethyl ~ 5 ~ ((Z) -5 ~ oxo-3 ~ cyanomethoxy ~ -1-propenyl) oyclopropane carboxylic acid (S) -g-cyan-3-phenoxybenzyl ester .

Chromatograph on 1.4 g of the above compound, elute with methylene chloride to give 0.41 g of the expected compound, g> = + 55 ° ± 1 * 5 ° (c = 1 $, chCl 3).

Example 9

(1R.cis) -2,2-dimethyl-5- ((2) -3-oxo-3-ethoxyethoxy-1-propenyl) -. -Cyclopropane carboxylic acid (S) -g-oyan-3-phenoxybenzyl ester.

Step A: (IR) cis -2,2-Dimethyl-3- (3-oxo-3-ethoxyethoxy-1-propynyl) -cyclopropanoarboxylic acid (S) -g-cyano-3-phenoxy-benzyl ester.

2 g of (1R, cis) -2,2-dimethyl-3-25 - (3-hydroxy-3-oxo-1-propynyl) -cyclopropanecarboxylic acid (S) -g-cyano are cooled to 0-5 ° C. -3-phenoxybenzyl ester, 20 ml of methylene chloride and 0.7 ml of ethoxyethanol. 1.1 g of dicyclohexyl carbodiimide, 5 ml of methylene chloride and 15 mg of dimethylaminopyridine are added.

Stir for 1 hour at 5 ° C and 2 hours at ambient temperature. Filtrate, evaporate the filtrate to dryness and chromatograph the residue on silica gel eluting with a mixture of cyclohexane and ethyl acetate (75:25) to obtain 1.3 g of the expected compound.

N.M.R. spectrum, CEC1, ppm: 35 1.22 - 1.32 protons in the methyl groups in the 2-position in cyclopropane 1.93 protons in the 1- and 3-positions in cyclo propane

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27 4.17 to 4.58 protons at the 1-position of C00-CH2-CH2O

3.55 to 3.73 protons at the 2-position of COO-C 2 -CH 2 O

6.57 proton supported by the same carbon atom as CU

7 to 7.67 aromatic protons 1.08 - 1.2 - 1.3 and 1.52 (q) protons in ethyl

(B) (IR) cis) -2 "2-Dimethyl-3- ((Z) -5-oxo-3- (ethoxyethoxy) -1-propepyl) -cyolopropane carboxylic acid (S) -g-cyanoic acid 3-phenoxybenzyl ester,

Working as in Example 7, Step B, from 1.3 g of the above compound, 1.0 g of the expected compound, Kjj = + 37.5 ° + 2.5 ° (c = 0 , $ 5, ceci3).

Example 10, (1R 'cis) -2,2-Dimethyl-3 - ((Z) -5-oxo-3- (RS) - (1,1,1-trifluoromethylethoxy) -1-propenyl) -cyclopropane carboxylic acid (S ) q - cyano-3-phenoxybenzyl '

Work as in Step B of Example 7 using 2.6 g of (1R, cis) -2,2-dimethyl-3- (3-Όxo-3 - ((RS) -1,1,1) - (trifluoromethylethoxy) propynyl) cyclopropane carboxylic acid (S) -α-cyano-3-phenoxybenzyl ester. After eluting with a mixture of cyclohexane and ethyl acetate (9: 1), 2.1 g of the expected compound is obtained, + 44 ° + 2 ° (c = 0.4 $, benzene).

Preparation of (LR.cis) -2,2-dimethyl-5- (5-oxo-5 - ((RS) -1.1.1 - trifluoromethylethoxy) propynyl) -cyclopropanoarboxylic acid (S) -g-cyano-3-benbenoxybenzyl ester .

The step of Δ in Example 9 is used using 4.6 g of 1,1,1-trifluoromethylethylcanol and 3.8 g of (1R, cis) - 2,2-dimethyl-3- (3-oxo- 3-hydroxypropynyl) -cyclopropanecarboxylic acid (S) -α-cyano-3-phenoxybenzyl ester to give 2.6 g of the expected compound after elution with a mixture of cyclohexane and ethyl acetate (8: 2).

35 28

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Example 11.

(1R, cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3- (2,2-difluoroethoxy) propenyl) cyclopropane carboxylic acid (S) -α-cyano-3-phenoxy benzyl ester.

Step A; (1Ε, οϊ5) -2,2-άίιη6Ϊ] 3.ν1-5- (5-οχο-3- (2.2-άίΙ1ηοΓ6 ^ οχ.ν) -propynyl) -cyclopropane carboxylic acid tert, -butyl ester.

Working as in Step A of Example 9 from 5 g (IR, cis) -2,2-dimethyl-3- (3-hydroxy-3-oxo-1-propynyl) -10-cyclopropane carboxylic acid tert.- butyl ester, 5.25 g of the expected compound are obtained after elution with a mixture of n-hexane and isopropyl ether (7: 3).

IR spectrum, CHCl ·: - C ^C conjugated 2232 cm ”1 C = 0 ester 1725 cm” 1 asymmetric 1710 cm ”1 twin dimethyl (1393 cm >1380 cm” · 1 · tert.-butyl 1372 cm ”1 20

Step B; (IR.cis) -2- 2-Dimethyl-5- (3-oxo-3- (2,2-difluoroethoxy) -1-propynyl) -cyclopropane carboxylic acid.

At reflux, 5.2 g of the compound obtained above and 500 mg of p-toluenesulfonic acid are heated in 40 ml of toluene for 25 minutes. After cooling, 400 ml of 25 ether are added, washed with water, dried over the organic phase and evaporated to dryness to give 4.1 g of the expected compound.

Step C: (IR.cis) -2,2-Dimethyl-3- (5-oxo-3- (2,2-difluoroethoxy) -1-propyl) -cyclopropanecarboxylic acid (S) -g-cyano-5- Phenox.vbenzylester.

Working as in Step A of Example 9 from 4.1 g of the acid obtained above and 4.5 g of (S) -a-c3'an; r3 - phenoxybenzyl alcohol is obtained after elution with a mixture of petroleum ether (b.p. 40-70 ° C) and isopropyl ether (6: 4) 4.7 g of the expected compound.

29

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I, E. spectrum, CHCl3: OH 3580 cm cm 1 twin dimethyl (1392 cm ”1 1 fl380 cm" 1 -1 -1-C = C-conjugated 2235 cm 5 C = 0 ester 1755 cm ”1 1 conjugated ester 1725 cm” 1 aromatic (1588 cm (1488 cm)

Step D: (IR, cis) -2,2-Dimethyl-3- ((Z) -3-oxo-5- (2,2-cifluoro-ethoxy) -propenyl) -cyclopropane carboxylic acid (S) -g-cyano-3 -Pbenoxybenzyle5ter,

4.7 g of the above-obtained compound are hydrogenated in the same manner as in step B of Example 7. After eluting with a mixture of n-hexane and isopropyl ether (7: 3), 3.2 g of the expected compound are obtained. g + = + 44 ° + 2.5 ° (c = 0.5 °, OHCl 3).

Example 12.

(1R.cis) -2,2-dimethyl-3 - ((Z) -3- (2,2-dichloroethoxy) -1-propenyl) cyclopropane carboxylic acid (S) -g-cyano-5-pyphenoxybenzyl ester, Step As (1R, cis) -2,2-dimethyl-3 - ((Z) -5- (2,2-diohloroethoxy) -1-propenyl) -cyclopropane carboxylic acid tert, butyl ester.

As in Example 9, Step A, starting from 4.8 g of 25 (1R, cis) -2,2-dimethyl-3 - ((Z) -3-hydroxy-3-cxo-1-propenyl) - cyclopropane carboxylic acid tert, butyl ester and 2 ml of 2,2-dichloro-ethanol. After eluting with a mixture of cyclohexane and ethyl acetate (9 · Ί), 5.6 g of the expected compound are obtained. Step B: (IR, cis) -2,2-dimethyl-3- ((2) -3- (2,2-dichloroethoxyl) -30-1-propenyl) cyclopropanecarboxylic acid,

As in Step B of Example 11, one works from 5.6 g of the above compound and 4.5 g of the expected compound is obtained.

Step C: (IR, cis) -2,2-dimethyl-3- ((Z) -3- (2,2-dichloroethoxy) -35-1-propenyl) -cyclopropane carboxylic acid (S) -g-cyano-3 - -phenoxybenzyl ester.

As in Step A of Example 9, one works from 3 g

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30 of the compound obtained in step B and 2.25 g of (S) -α-cyano-3-phenoxybenzyl alcohol. After eluting with mixtures of cyclohexane and ethyl acetate (8: 3 and then 9: 1), 1.6 g of the expected compound is obtained, = + 54 ° + 2 ° (c = 1 $, benzene).

The following examples are carried out by analogy with Step A of Example 9 starting from: 1 °) (IR, cis) -2,2-dimethyl-3- ((Z) -3-oxo-3- (2,2-difluoro) 10 ethoxy) -1-propenyl) cyclopropane carboxylic acid and the corresponding alcohol;

Example 13

(IR. Cis) -2,2-Dimethyl-5 - ((Z) -5-oxo-3- (2,2-difluoroethoxy) -15-1-propenyl) -cyclopropanecarboxyl) acid (RS) -α cyano-6-phenoxy - 2-pyridylmethyl ester. aD = + 50.5 ° ± 2 ° (c = 0.8 $, CHCl3).

Example 14.

(1R.cis) -2,2-dimethyl-3- ((Z) -3-oxo-3- (2,2-difluoroethoxy) -1-propenyl) -cyclopropane carboxylic acid (R) -acyan-3-phenoxybenzene benzyl ester.

α-p = + 117.5 ° ± 3 ° (c = 0.6 $, CHCl3).

Example 15 «(1R.cis) -2,2-Dimethyl-3 - ((Z) -3-oxo-3- (2,2-difluoroethoxy) -1-propenyl) -cyclopropane carboxylic acid (3-propargyl-2,5 dioxo-imidazolidinyl) methyl ester.

= + 18 ° + 2 ° (c = 1 $, CHC15).

30

Example 16.

(1R.cis) -2,2-dimethyl-3- ((Z) -3-oxo-3- (2,2-difluoroethoxyKL- -propenyl) -cyclopropanecarboxylic acid (R) -α: -ethynyl-3-phenoxybenzyl ester .

AD = + 47 ° + 1.5 ° (c = 1 $, CHCl3).

(IR, cis) -2,2-dimethyl-3- ((2) -3-oxo-3- (2,2-difluoro-ethoxy) -1-propenyl) -cyclopropane carboxylic acid is prepared by analogy with that of preparation VI described from 2.2-di- 31

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fluoretbanol.

2 °) (1R, cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3- (2-fluoroethoxy) -1-propenyl) cyclopropane carboxylic acid and the corresponding al-cobole;

Example 17 «(1R.cis) -2,2-Dimethyl-3- ((Z) -3-oxo-3- (2-fluoroethoxy) -1-propenyl) cyclopropane carboxylic acid (3-propargyl-2,5 dioxoimidazole <3iQyl) "me'fcbyleS't; e: i: t« aD = + 18 ° + 2 ° (c = 1 YES, CHCl 3).

Example 18 &lt; 1 &gt; (IR, cis) -2,2-dimethyl-3 - ((Z) T-3-oxo-3- (2-fluoro-thoxy) -1-pro-Penyl] -cylolopropane carboxylic acid (RS) ) -g-cyano- (6-pfaenoxy-2-Py-ridyl) -aetbylester. aD = + 49.5 ° + 2.5 ° (c = 0.5 $, CHO1).

Example 19, 20 (1R, cis) -2,2-Diaethyl-3- ((2) -3-oxo-3- (2-fluoroethoxy) -1-propenyl) -cyclopropanoarboxylic acid (R) -α ae thyl-3-phenoxy benzyl ester.

= + 123 ° + 1.5 ° (c = 1%, CHCl3).

Example 20.

(LR.cis) -2.2-diaethyl-3 - ((Z) -3-oxo-3- (2-fluoroethoxy) l-propenyl) -cyclopropancarboxyl5yre-a-ethynyl-3-phenoxybenzyl ester. aD = + 47 ° + 1.5 ° (o = 1 $, CHCl 2).

(1R, cis) -2,2-Dimethyl-3 - ((Z) -3-oxo-3- (2-fluoroethoxy) -30-1-propenyl) oyclopropane carboxylic acid is prepared by analogy with Preparation VI from 2-fluoroethanol .

3 °) (1R, cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3- (2- (1,1,1,1,3,3,3- -hexafluoro) propoxy) -1-propenyl) -cyclopropane caxboxylic acid (Preparation VI) and the corresponding alcohol * 35

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32

Example 21.

(IR, cis) -2,2-Dimethyl-3 - ((Z) -5-oxo-3- (2- (1,1,1,3,3,3-hexa-fluoro) -propoxyKL-propenyl) -cyclopropanecarboxylic acid - ( R) -a - ethynyl) ~ 3- "Phenoxylbenzyl ester, aD = + 31.5 ° + 1.5 ° (c = 1 $, CHCl 3).

5 3

Example 22.

(1 R cis) -2,2-Dimethyl-3 - ((Z) - 5-oxo-3- (2- (11,3,3,3-hexa-fluoro) propoxy) -1-propenyl) -cyclopropane carboxylic acid - (R) -α - methyl-3-phenoxybenzyl ester.

10 = = + 97 ° + 2 ° (c = 1 $, CHCl3) #

Example 23

(R, cis) -2.2-dimethyl-3 - ((Z) -3-oxo-3- (2- (ll-1.3.3.3 Hexa-fluoro) propoxy) -1-propenyl) -cyolopropancarboxylsyre- (S ) -15-g-cyano-3-phenoxybenzyl ester.

aD = + 23.5 ° + 2 ° (c = 0.5 $, benzene).

Example 24.

(IR.cis) -2,2-dimethyl-3- ((Z) -3-oxo-3- (2- (1,1,3,3,5-faexa-O-fluoro) -propoxy) -1-propenyl) -cyolopropane carboxylic acid third 4.5 «6- -tetrabydrophthalimidomethyl ester.

ar> = "30 ° + 1 ° (c = 1 $, CHCl3).

Example 25

(IR.cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3- (2- (11,3,3,3-hexa-fluoro-3-propoxy) -1-propenyl) -cyclopropane carboxylic acid ( RS) -cyan - 6-phenoxy-2-pyridylmethyl ester aD = + 33.5 ° + 2.5 ° (c = 0.2 $, CHCl3).

4 °) (1R, cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3- (2,2,2-trifluoro-εthoxy) -1-propenyl) -cyclopropane carboxylic acid (preparation I) and the corresponding alcohol; 33

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Example 26

(IR, cis) -2,2-dimethyl-3- ((Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl) -cyclopropanecarboxylic acid (3-propargyl) -2,5-Clyoxoimidazolidinyl) methyl ester.

5 = -4 ° + 1 ° (c = 1 $, benzene).

Example 27

(IR. Cis) -2,2-Dimethyl-3- ((Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl) -cyclopropanecarboxylic acid (R) -α-phenethyl -3-Phenoxyl-10-benzyl ester.

aD = + lo8.5 ° + 2 ° (c = 1 $, CHCl3).

Example 28.

(IR.cis) -2,2-dimethyl-3- ((Z) -3-oxo-3- (2,2,2-trifluoroethyl) -15-1-propenyl) -ocyclopropanecarboxylic acid 5.4.5.6-tetrahydrophthalimidomethyl ester. ctjj = + 2.5 ° + 2 ° (c = 0.5 $, CHCl3)

Example 29.

(1R, cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3- (2,2-2-trifluoroethoxy) -1-propenyl) cyclopropane carboxylic acid (R) -t-ethyn. yl-3-phen-oxybenzylester.

aD = + 42 ° + 1.5 ° (c = 1 $, CHCl 3) Example 30.

(IR.cis) -2,2-Dimethyl-3- ((Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl) -cyclopropane carboxylic acid (RS) -acan-6 phenoxy - 2-pyridylmethyl ester.

(¾ = + 46.5 ° + 2 ° (c = 0.7 $, CHCl 3) 5 °) (IR, cis) -2,2-dimethyl-3 - ((Z) -3-hydroxy-3- oxo-1-propenyl) -cyclopropane carboxylic acid (S) -α-cyano-3-phenoxybenzyl ester (Preparation VII) and the corresponding alcohol * 35

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3 4

Example 31.

(IR, cis) -2,2-dimethyl-1-3- ((Z) -3-oxo-3- (2-trichloroethoxy) -propenyl) -cyclopropanecarboxylic acid (S) -g -cy and -3 -ph an oxy-benzyl ester, 5 oc = + 42.5 ° + 2 ° (c = 0.5 $, benzene Example 52, (1R.cis) -2,2-dimethyl-3 - (( Z) -3-oxo-3- (2-chloroethoxy) -1-propenyl) -ylopropanecarboxylic acid (S) -α-cyan-3-phenoxybenzyl ester, ctp = + 39 ° + 4 ° (c = 0 , $ 25, benzene)

Example 33, (IR, cis) -2-2-Dimethyl-3 - ((Z) -3-oxo-3- (2-methoxyethoxy) -1-propenyl) -cyclopropanecarboxylic acid (S) -g -cyan-3-phenoxy-benzyl ester, α D = + 37.5 ° + 2 ° (c = 1 $, CHCl ^).

Example 34, 20 (1R, cis) -2,2-Dimethyl-3- ((Z) -5-oxo-3- (RS) -CL-cyanethaphoxy) -1-propenyl) -cyclopropane carboxylic acid (S) -g- = + 64.5 ° ± 3 ° (c = 0.3 $, CHCl 3).

Example 35, (IR, cis) -2,2-Dimethyl-3- ((2) -3-oxo-3- (2-fluoroethoxy) -1-propenyl) -cyclopropane carboxylic acid (CS) -α cyan-3 ~ phenoxy benzyl ester, α- = + 48 ° (c = 0.25 $, benzene)

Example 36, (IR.cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3-phenethoxy-1-propenyl) cyclopropane carboxylic acid (S) -g-oyan-3-phenoxybenzyl ester. a-p = + 46 ° + 2.5 ° (c = 0.5 $, benzene).

35 35

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Example 37.

(IR) is -2,2-dimethyl-3- ((Z) -3-oxo-3- (2,2-dimethyldioxola-nyl-4- (R5) -methoxy) -1-propenyl) C, vclopropancarboyylsyre - (S) -g-cyano-3-phenoxybenzyl ester.

AD = + 46 ° + 2 ° (c = 0.75 $, benzene).

6 °) (IR, cis) -2,2-Dimethyl-3 - ((Z) -3-hydroxy-3-oxo-1-propenyl) -cyclopropanecarboxylic acid (RS) -oc-cyano-3-phenoxybenzyl ester and the corresponding alcohol: 10

Example 38

(IR.cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3- (2-dimethylaminoethoxy) -1-propenyl) -cyolopropanecarboxylic acid (RS) -g-cyano-3-phenoxybenzyl ester.

CcD = + 23 ° + 3 ° (c = 0.25 $, CHCl3) (1R, cis) -2,2-dimethyl-3 - ((Z) -3-hydroxy-3-oxo-1-propyl) nyl) -cyclopropanecarboxylic acid (RS) -α-cyano-3-phenoxybenzyl ester used at the beginning of the previous example is prepared by analogy to the (S) -α-cyano-3-phenoxybenzyl ester in preparations IV and VII.

7 °) (1R, Eis) -2,2-dimethyl-3 - ((Z) -3-hydroxy-3-oxo-1-propenyl) cyclopropanecarboxylic acid - (R) -oc-methyl 1-3-phen oxybenzy 1 ester (Preparation VIII) and the corresponding alcohol: 25

Example 39

ilR.cis) -2.2-dimethy1-3 - ((Z) -5-oxo-3- (2-methoxyethoxy) -l - propenyl) -cvclopropancarboxylsyre- (R) -g-methyl-3-phenoxy-benzyl ester.

3Q N, M.R. spectrum, CDCl3, ppm: 1.22 - 1.25 protons in the methyl groups at the 2-position of cyclopropane 1.45 - 1.55 protons in the methyl group in the ester at the 1-position in cyclopropane 5.7 to 6.0 protons in benzyl 3.42 protons in methoxyl 4.22 to 4.38 protons at the 1-position of the ester group at the 3-position in cyclopropane 36

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3.55 to 3.72 protons at the 2-position of the ester group at the 3-position of cyclopropane 5.85 - 6.05 and 6.32 to 6.8 ethylenic protons 5

Example 40 "(IR, cis) -2" 2-Dimethyl-3 - ((Z) -3-oxo -3- (1-methoxy) -1-trifluoromethylethOXy) -1- propenyl) -CyclOPropanca.rbOX.Vylic acid (S) -acyan-3-phenoxybenzyls te r.

1.02 g of (IR, cis) -2,2-dimethyl-3- ((Z) -3-ehloro-3-oxo-1-propenyl) -cyclo-propane carboxylic acid (S) α-cyano-3-phenoxybenzyl ester and S ml of methylene chloride. 1.2: 2 g of 1-methyl-1-trifluoromethyl-ethanol are added and stirring is continued for 48 hours at room temperature. Evaporate to dryness under reduced pressure, chromatograph the residue on silica gel, elute with a mixture of hexane and ethyl ether (8: 2) to give 250 mg of the expected compound, m.p. ca. 59 ° C, = + 57 ° + 2 ° (c = 0.4 °, benzene).

(1R, cis) -2,2-dimethyl-3- ((Z) -3-chloro-3-oxo-1-propanyl) -cyclopropane carboxylic acid (S) -α-cyano-3 -phenoxybenzyl ester used at the beginning of Example 40 is prepared by the action of thionyl chloride on (IR, cis) -2,2-dimethyl-3 - ((Z) -3-hydroxy-3-oxo-1-propenyl) -cyclopropane carboxylic acid - (S) - α-Cyan-3-pkenoxybenzyl ester (Preparation VI1) „25

Example 41 »(1R, 10) -2,2-Dimethyl-5 - ((Z) -5-oxo-3- (1-trifluoromethyl-1-methyl-propylloxy) -1-propenyl) -cyclopropane carboxylic acid (S) -g-cyano - 3-phenoxybenzyl ester.

900 mg (1R, cis) -2,2-dimethyl-3 - ((Z) -3- -chloro-3-oxo-1-propenyl) -cyclopropane carboxylic acid (S) -α-cyano-3 -phenoxybenzyl ester in 3 ml of methylene chloride, add 1 ml. 1-trifluoromethyl-1-methylpropanol and stir for 16 hours at room temperature under inert atmosphere and protected from humidity. After 3 days at room temperature, the reaction mixture is washed with a saturated aqueous sodium bicarbonate solution, dried and evaporated to dryness. The residue is chromatographed on silica gel, eluting with a mixture of hexane and

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37 ethyl ether (8: 2) to obtain 570 mg of the expected compound. Example 42

(1R (cis) -2,2-dimethyl-5- ((Z) -3-oxo-3- (2,3-dihydroxypropyl-5-oxy) -1-propenyl) -cyclopropane carboxylic acid (S) -α-cyano-3 -phen-oxybenzylester.

Reflux 4.65 g (1R, cis) -2,2 - dihydro-3 - ((Z) -3-cxo-3- (2,2-dimethyl-dioxolanyl-4- (RS) -) methoxy-1-propenyl) -cyclopropane carboxylic acid (S) -α-cyano-3-phenoxybenzyl ester (Example 37), 46 ml of dioxane, 9 ml of water and 0.45 g of p-toluenesulfonic acid for 45 minutes. the dioxane, by distillation at 40 ° C under reduced pressure, takes up the residue in 150 ml of methylene chloride and 25 ml of water, stirring, decanting, washing the organic phase with water, drying and evaporating to dryness under reduced pressure. elute with a mixture of cyclohexane and ethyl acetate (3: 7) to obtain 3.85 g of the expected compound, = + 53 ° + 2.5 ° (c = 0.5 $, CHCl 3).

20

Example 43

(IR, ois) -2- (2-dimethyl-3 - ((Z) -3-oxo-5- (2-tetrahydropyranyloxy-ethoxy) -1-propenyl) -cyclopropanecarboxylic acid (RS) -q-cyano-3- -phenoxybenzylester.

Step A: (IR.cis) -2,2-Dimethyl-3- ((Z) -3-oxo-3- (2-tetrahydro-pyranyloxyethoxy) -1-propynyl) -cyclopropane carboxylic acid (RS) gc.yan-3-Phenox.ybenzylester #

Analogously to Step A of Example 7, it is used from 2.3 g (1R, cis) -2,2-dimethyl-3 - ((Z) -3-hydroxy-3-oxo-1-propynyl) -30 cyclopropane carboxylic acid (RS) -α-cyano-3-phenoxybenzyl ester and 7.5 g of 1-bromo-2- (2-tetrahydropyranyl) oxyethane. 1.8 g of the expected compound are obtained after chromatography on silica gel with a mixture of cyclohexane and ethyl acetate (75:25).

Step B: (IR, cis) -2,2-Dimethyl-3 - ((Z) -3-oxo-3- (2-tetrahydro-pyranyloxyethoxy) -1-propenyl) cyclopropane carboxylic acid - (RS) -a-cyano-3-phenoxybenzyl ester.

In step 7, analogy is used in Example 7 from the product obtained in step A above. You get after cleansing

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38 by chromatography in a mixture of cyclohexane and ethyl acetate (80:20) 1.3 g of the expected compound, α-p = + 33 ° + 1 ° (c = 1 *, chci 5).

(IR, cis) -2,2-dimethyl-1-3 - ((Z) -3-hydroxy-3-oxo-1-propynyl) -cyclopropanecarboxylic acid (iS) -α-cyano -3-phenoxy benzyl ester used at the beginning of the previous example is prepared in analogy to (S) -α-cyano-3-phenoxybenzyl ester 1 Preparation IV.

Example 44 «(IR.cis) -2,2-dimethyl-3- ((Z) -3-oxo-3- (2-hydroxybenzo) -1-propenyl) -cyclopropanecarboxylic acid (RS) - g-cyano-3-phenoxybenzyl ester.

0.85 g of the compound prepared in Example 43 are mixed, 17 ml of ethanol, 5 ml of dioxane, 1 ml of water and 4 ml of 2N hydrochloric acid and then stirred at 20 ° C for 3 hours. One is then added 1 ml of triethylamine, evaporated to dryness, taken up in a mixture of water and ice, extracted with methylene chloride, washed the extract with water, dried and evaporated in the solvent. The residue is chromatographed on silica gel eluting with a mixture of cyclohexane and ethyl acetate (65 * 35) to give 0.65 g of the expected compound, α- = + 42.5 ° + 2.5 ° (c = 0.5 *, -CEClj).

The following compounds can also be obtained according to the process of the invention from the corresponding acids and alcohols: - (IR, cis) -2,2-dimethyl-3- ((Z) -3-oxo-3- (1,1) , 1,3,3,3-hexafluoropropoxy) propenyl) cyclopropane carboxylic acid 3-phenoxybenzyl ester, = + 26.5 ° + 2.5 ° (c = 0.5 *, CHCl , cis) -2,2-Dimethyl-3 - ((Z) -3-oxo-3- (1,1,3,3,3-hexafluoropropoxy) propenyl) cyclopropane carboxylic acid (S) - α - Cyan-3-phenoxy-4-fluorobenzyl ester, = + 27 ° + 2 ° (c = 0.8 *, benzene) 39

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Preparation IV (IR, cis) -2,2-dimethyl-5- (5 '-oxo-5-hydroxy-1-propynyl) -cyclo-propane carboxylic acid (S) -t-cyano-3-phenoxybenzyl ester.

Step A: (IR, cis) -2,2-dimethyl-3- (2-carboxyethynyl) oyclopropanecarboxylic acid tert, butyl ester.

Lian introduces 26 g of (1R, cis) -2,2-dimethyl-3- (2,2-dibromo vinyl) cyclopropane carboxylic acid tert-butyl ester in 175 ml of anhydrous tetrahydrofuran. Then, at -65 ° C, 60 ml of a 20 $ s solution of butyllithium in cyclohexane is added.

The mixture is stirred for 1 hour at -60 ° C and then a stream of carbon dioxide is bubbled for 1 hour 30 minutes, then the reaction mixture is poured into ice-cold water with 1 l sodium hydroxide. Wash with ether. The aqueous alkaline phase is acidified to a pH of 4 and extracted with ether. The organic phases are dried and evaporated to dryness under reduced pressure. There is thus obtained a compound which is crystallized from petroleum ether (b.p. 60-80 ° C). 8.3 g of the expected compound is obtained with m.p., 144 ° C.

K.M.R. Spectrum, CDCl3, ppm: 20 1.22 and 1.37 protons in the methyl groups at the 2-position in cyclopropane 1.78 protons at the 1- and 3-position in cyclopropane 1.47 protons in tert-butyl

8.25 protons in the -C-OH group

II

25 o

Step 5: (1R, cis) -2,2-dimethyl-3- (2,2,2-trichloroethoxycarbonylethynyl) -cyclopropane carboxylic acid tert, butyl ester.

6.2 g of dicyclohexylcarbodiimide are introduced into a solution containing 7.15 g of (1R, cis) -2,2-dimethyl-3- (2-carboxyethynyl) cyclopropane carboxylic acid tert-tutyl ester and 80 mg of dimethylaminopyridine. in 35 ml of methylene chloride. The reaction mixture is stirred for 10 minutes and 4.5 g of 2,2,2- trichloroethanol are added. Stir under stirring for 1 hour and eliminate the formed precipitate by filtration. The filtrate is washed with 1 L hydrochloric acid and then with water until neutrality, dried and evaporated to dryness. There are 40 available

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14 g of an oil which is chromatographed on silica gel eluting with a mixture of benzene and ethyl acetate (97s3) ·

Thus, 9 g of the expected compound are isolated with m.p. 70-71 ° C.

Step C: (IR) is -2,2-dimethyl-3- (2,2,2-trichloroethoxyoarbonylethynyl) oyolopropane carboxylic acid.

A mixture was refluxed for 1 hour containing 11.4 g of the compound of Step B, 120 ml of toluene and 300 mg of p-toluenesulfonic acid. The room temperature is re-allowed, the reaction mixture is washed with water, dried and evaporated to dryness. Thus, 9 »5 g of the expected compound is obtained, which is used immediately in the next step.

Step D: (1R, cis) -2,2-dimethyl-3- (2,2,2-trichloroethoxycarbonylethynyl) -cyclopropane carboxylic acid (S) -g-cyano-3-phenoxybenzyl ester.

6.2 g of dicyclohexylcarbodiimide are added to a solution containing 9 »5 g of the compound prepared in step C, 30 ml of methylene chloride and 3 ml of pyridine. The reaction mixture is stirred for 30 minutes and 6.8 g (§) - α-cyano-3-phenoxybenzyl alcohol are added. Stir for 1 hour 30 minutes. Filtration of the insoluble material formed is eliminated. The filtrate is washed with 1 IT hydrochloric acid and then with water until neutrality. It is dried, filtered and evaporated to dryness. 16.3 g of an oil is obtained which is chromatographed on silica gel eluting with a mixture of benzene and ethyl acetate (97s3). Thus, 12 g of the expected compound is isolated with m.p., 101 ° C. Step E: (IR. Cis) - 2,2-Dimethyl-3- (3-hydroxy-3-oxo-1-propynyl) -30-cyclopropanecarboxylic acid (3) -acyan-3-phenoxybenzyl - ester.

5 »9 g of zinc powder are introduced into a solution containing 6.5 g of the compound prepared in step D, 23.4 ml of acetic acid and 2.6 ml of water. The mixture is kept under stirring for 1 hour. The filtrate is filtered and decanted.

The organic phase is washed with water and the aqueous phase is extracted with methylene chloride. Methylene chloride-41 is combined

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the solutions, dry them, filter them and evaporate them to dryness. There are thus obtained 4.7 g of crude compound, which is immediately used, 5 Preparation V.

(IR, cis) -2,2-Dimethyl-3 - ((Z) - (3-Hydroxy-3-oxo-1-propenyl) -cyclopropane carboxylic acid tert-butyl ester.

2 g of (1R, cis) -2,2-dimethyl-3- (2-carboxyethynyl) -cyclopropane carboxylic acid tert, butyl ester prepared in step A of Preparation IV in 40 ml of ethyl acetate in the presence of 0 , 38 g of 10 # palladium hydroxide on barium sulfate and 0.4 ml of quinoline, Filter, wash the filtrate with 0.5 R hydrochloric acid and then with water until neutrality, dry, evaporate to dryness under reduced pressure to obtain 2 g of it. expected compound with mp, 94 ° C.

Preparation VI.

(IR, cis) -2,2-Dimethyl-5 - ((Z) -3-oxo-3- (2- (11,3,3-3-hexa-fluoro) propoxy) -1-propenyl) cyclopropane carboxylic acid Μη A: (1Rcia) -2,2-dimethyl, yl-3 - ((Z) -3-oxo-3- (2- (1,1,3,3,5,3-hexafluoro) propoxy) -1- propenyl) -cyclopropancarbox-yl acid tert.-butyl ester.

One works as in Step A of Example 9 using 3.6 g (IR, cis) -2,2-dimethyl-3- ((Z) -3-hydroxy-3-oxo-1-25-propenyl) -cyclopropane carboxylic acid tert-butyl ester (Preparation V) and 3 g of hexafluoroisopropanol. After eluting with a mixture of benzene and cyclohexane (4: 6), 4.9 g of the expected compound are obtained, m.p., 92 ° C.

Step 5: (IR, cis) -2,2-Dimethyl-3 - ((Z) -3-oxo-3- (2- (1,1,1, 3,3,3-hexafluoro) propoxy) (1-propenyl) -cyclopropane-oreboxylic acid.

As in Example 11, step B, 4.9 g of the compound prepared above are obtained and 4.2 g of the expected compound are obtained.

I, R, spectrum, CHClCl: OH monoacid), w) 3500 cm ~ x x + dimer ^ 42

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C conjugated ester (1755 cm ~ ^ shoulder "(-1 q> 1744 cm max acid 1695 cm-1 conjugated C = C 1627 cnT1 5 twin-dime thyl 1380 cm" '1' shoulder

Preparation VII.

(IR, cis) -2,2-Dimethyl-3- ((Z) -3-hydroxy-3-oxo-1-propenylr-cyclopropanecarboxylic acid (S) -α-cyano-3-phenoxybenzyl ester.

4.7 g (IR, cis) -2,2-dimethyl-3- (2-carboxyethynyl) -cyclopropanecarboxylic acid (S) -α-cyano-3-phenoxybenzyl ester (Preparation IV) in 45 ml of ethyl acetate are hydrogenated in the presence of 500 mg of 10 $ palladium hydroxide on barium sulfate and 6.5 ml of quinoline. Filter, wash the filtrate with 15 L of hydrochloric acid and then with water until neutral, dry and evaporate to dryness. 5.1 g of an oil is obtained which is chromatographed on silica gel eluting with a mixture of hexane, ethyl acetate and acetic acid (70: 30: 1). Thus, 3.8 g of the expected compound is obtained.

20

Preparation VIII.

(1R.cis) -2- [2-Dimethyl-3 - ((Z) -3-hydroxy-3-oxo-1-propenyl) oyclopropane carboxylic acid (R) -α-methyl-3-phenoxybenzyl ester. Step A: (IR, cis) -2,2-Dimethyl-3- (3-oxo-3- (2,2,2-trichloroethoxy) propynyl) -cyclopropanecarboxylic acid (R) -g-methyl-3-phenoxybenzyl ester .

Work as in step D of Preparation IY using 6 g (1R, cis) -2,2-dimethyl-3- (3-oxo-3- (2,2,2-trichloroethoxy) propynyl) -cyclopropane carboxylic acid and 4.1 g of Ι-ΒΟ - (R) - (3-phenoxyphenyl) ethanol. 4.38 g of the expected compound are obtained after chromatography in a mixture of cyclohexane and ethyl acetate (8: 2).

Step B: (IR, cis) -2,2-Dimethyl-3- (3-oxo-3-hydroxypropynyl) cyclopropanecarboxylic acid (R) -g-methyl-3-phenoxy-benzyl ester.

To 4.16 g of the above compound dissolved in 4 ml of methylene chloride is added 45 ml of acetic acid 43

DK 164047 B

with 10 $ water and 0.53 g of zinc powder and stirring for 30 minutes at room temperature, again adding 0.53 g of zinc powder until the end of the reaction (4 times). After 3 hours of contact, filter and extract with methylene chloride. The organic phase is washed with water, dried and evaporated to dryness by azeotropic immersion in toluene to obtain 3.05 g of the expected compound.

Step C: (IR.cis) -2,2-Dimethyl 1-3- ((Z) -3-hydroxy-3-oxo-1-propenyl) -cyclopropanecarboxylic acid (R) -α-methyl-5-yl-5 Phen-10 oxybenzyl ester.

As in Step B of Example 7, one works from the compound prepared in Step B above and obtains 2.9 g of the expected compound which is immediately used in the crude state.

15

Examples of preparations.

Example A: Preparation of a soluble concentrate.

A homogeneous mixture of: Compound of Example 1 is prepared 0.25 g of piperonylbutoxide 1 g

Tween 80 0.25 g topanol A 0.1 g water 98.4 g

Example B: Preparation of an emulsifiable concentrate.

Mix thoroughly: Compound of Example 1 0.015 g piperonylbutoxide 0.5 g topanol A 0.1 g

Tween 80 3.5 g 30 xylene 95.885 g

Example C: Preparation of an emulsifiable concentrate.

A homogeneous mixture of: Compound of Example 1 is prepared 1.5 g

Tween 80 20 g 35 topanol A 0.1 g xylene 78.4 g 44

DK 164047 B

Example D: Preparation of a smoke preparation

Homogeneous mixture: Compound of Example 1 0.25 g pyrethrum quas 25 g 5 cedar needle powder 40 g pine sawdust 33.75 g brilliant green 0.5 g n-nitrophenol 0.5 g 10 Investigation of the effect of the compounds in question on parasites 1) the lethal effect on housefly

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

Topical application of 1 µl of acetone solution 15 of the compound to the insect's dorsal thorax is employed by Arnold's micromanipulator. 50 individuals are used per day. dose and per treatment. Mortality is checked 24 hours after treatment.

The results obtained in DL50 or the dose in nanograms needed to kill 50% of the insects are as follows:

Compound of Example DL50, ng per individual 25 1 1,115 2 100 3 9,592 4 100 5 100 30 6 100 12 3,656 13 12,850 14 11,314 15 100 35 16 5,116 17 100

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45 18 10,051 19 44,828 20 9,647 21 2,267 5 22 10,977 23 0.962 24 37,372 25 0.736 26 72.026 10 27 7.570 28 100 29 0.825 30 1.792 15 Conclusion; In the samples used, the compounds of Examples 1, 23 and 29 have a remarkable activity.

2) Investigation of the effect on larvae of Spodoptera littoralis 20 The experiments are performed by topically applying an aceto-solution of the compound to be investigated, using Arnold's micromanipulator on the larval dorsal thorax. 15 larvae are used per day. dose of the compound to be tested. The larvae used are larvae in the fourth 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 in an artificial nutritional environment (Poitout's environment).

Mortality is checked 48 hours after treatment.

The results obtained are as follows:

Compound of Example DL50 n per individual 35 1 4,699 35 0.544 46

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conclusion:

In the samples used, the compounds of Examples 1 and 35 have good activity 3) Examination of the shock effect on housefly 5 The experimental insects are 4-5 days old female flies.

One works with direct atomization in Kearns and March's chamber; using as a solvent a mixture of equal volumes of acetone and isopar L (amount of solution used 2 x 0.2 ml). You use approx. 50 insects 10 per treatment dose. Control is performed every minute until 10 minutes and then at 15 minutes and KT50 is determined by the usual methods.

The results obtained are as follows: Compound Concentration according to Example KT50 in minutes g / liter 1 3,534 1 2 3,608 0.25 3 11,203 1 20 4 9,472 1 5 9,895 1 6 10,082 1 12 7,549 1 13 3,646 1 25 14 5,101 · 1 15 1,564 0.25 16 4,563 1 17 0.831 0.25 18 2,682 0.25 30 19 3,837 1 20 3,775 1 21 10,940 1 22 15/1000 1 23 11,159 1 35 24 2,723 1 25 5,832 1 26 1,550 0.25 47

DK 164047 B

27 13,178 1 28 1,961 0.25 29 4,247 1 30 3,498 1 5 35 2,894 1

Conclusion: In the sample used, the compounds of Examples 1, 2, 26, 30 and 35 have good activity.

4) Investigation of the activity of tarsal contact on cockroaches (compound of Example 1)

The insects studied are males of cockroaches (Blatella germanica). An acetone solution of particular concentration is applied to the bottom of a 15 cm diameter petri dish. After drying, 20 cockroach males are left there for each concentration for 1 hour, after which the insects are transferred to a healthy environment and their mortality is checked after 24 hours, 48 hours and 3 and 5 days.

The result expressed in lethal concentration 50 (CL50) gives 0.216 mg / m for the compound studied.

conclusion:

According to the test used, the compound has a very good activity.

5) Activity against Tetranychus urticae (compound of Example 1). Adulticide trial

Bean plants with 2 seedlings are used. These plants are treated with Fisher's gun with an acetone solution of the compound. After drying, 25 females of Tetranychus urticae are applied per leaf or 50 individuals per. dose investigated per leaf. The efficiency check is performed after a contact time of 1, 24, 48 and 72 hours.

At a dose of 2.8 mg / liter, the compound has a very good activity.

35

Claims (5)

48 DK 164047 B 1. O 30 or a group CN (/ V_ CH_ C- ° V 49 DK 164047 B or a group CN --- - ™ rv "0 5 and R is one having one or more halogen atoms, phenyl, C alkoxy, cyano, di (lower alkyl) amino, hydroxy, 2,2-dimethyl dioxolanyl or tetrahydropyranyloxy groups substituted C 1-6 alkyl group or a phenyl group. 1. Cyclopropane carboxylic acid derivatives in 1R, cis-isomer form of formula (I1) Λ R02C - CH = CHS / νοΟ, Α1 wherein the double bond has the geometric form Zf A 'is a group of CH group H OoOR4 where R 1 is a group -C = N, a methyl group or a group 20 -C = CH, or a group 25 or a group ^ O II n-ch 2 -c = ch -CH 2 -N J A process for the preparation of compounds of formula (I1) X (I '> R02C-CH = CHv // \ C02A' wherein the double bond has the geometric formula Z and A 'and R represent the same as in claim 1 , characterized in that the IR, cis, Z isomer of an acid of formula (II) YA i11 * R02C-CH = CHCO2H or a functional derivative thereof, is reacted with an alcohol of formula (III) A '- OH (III) where R and A' in formulas (II) and (III) denote the same -30 me as in claim 1. A process for preparing the compounds of formula (I ') as defined in claim 1, characterized in that a compound of IR, cis form and of formula (XI) is H-.C -CH-. Wherein the double bond has the geometric structure Z, and A1 denoted the same as in claim 1, is reacted with an esterifying agent to obtain the corresponding compound of formula (11). ). Process for the preparation of the compounds defined in claim 1, characterized in that a compound of formula (XV) H-C XH, 3 \ / 3 (XV) H02C-C = Cn2 / 2 \ C02A 'where A' is the same as in claim 1 is reacted with an esterifying agent to give the compound of formula (X) H3C \ Λ \ <(X) R ° 2C-C 2 v / \ / CO 2A 'wherein R and A' are the same as in claim 1, which compound is then reacted with a catalyzed hydrogenation agent to give the compound with the formula (I '). 5. Parasite control agents, characterized in that they contain, as a mainly active ingredient, at least one compound as defined in claim 1. 30