FI78066B - NYA 1RCIS, Z-ISOMERER AV CYCLOPROPANKARBOXYLSYRADERIVAT, FOERFARANDE FOER DERAS FRAMSTAELLNING, MELLANPRODUKTER ANVAENDBARA VID DERAS FRAMSTAELLNING SAMT INSEKTICIDA COMPOSITIONER INNEHA - 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

78066

The present invention relates to novel cyclopropanecarboxylic acid derivatives, to processes for their preparation, to insecticidal compositions containing them and to novel insecticidal compositions containing them.

The novel cyclopropanecarboxylic acid derivatives according to the invention are the 1R, cis-isomers of the pyrethroid compounds of the formula (I ') / X n ·) R02C - CH - ch-V ^ -VCO2A' in which the double bond is of geometric form z, A 'is group cp, ch2-ch = ch2 20 or group

B

»CV 0 -O" wherein R 4 is a group -C = N, a methyl group or a group -C = CH, or a group

O

30 rVs N-CH-- or group 3 5 ®

35 I

/ W-CH "-C = CH -CH - N I z

Y

78066 2 or group

CN

_

5 // \ _ O F

or a group 10 TN 2 O-f 15 -ch 15 and R is substituted by one or more halogen atoms, phenyl, C 1-8 alkoxy, cyano, di (lower alkyl) amino, hydroxy, 2,2-dimethyldioxolanyl- or a C 1-6 alkyl group or a phenyl group substituted by a tetrahydropyranyloxy group.

Preferred compounds of the invention are, in particular, the compounds whose preparation is shown in Examples 1, 2, 23, 26, 29, 30 and 35 below.

The 1Rcis, Z isomers of the compounds of formula (I ') as defined above have interesting properties which allow them to be used for the control of parasites, in which case plant parasites and dwellers can be considered. The products according to the invention can be used for controlling insects and parasites of plants.

The 1Rcis, Z isomers of the compounds of formula (I ') as defined above have been found to be vastly more potent in biological activity than the other isomers and mixtures of isomers of the compounds of formula (I1) described in e.g. FI patent application 811 566. Thus, for example, when studying the lethal effect of the compound of Example 23 (Compound 1) below and the corresponding 35 lRcis, E-, 1Rtrans, E- and 1Rtrans, Z-isomers (compounds B, C and D) below on houseflies the experiment 3,78066 described below (p. 50) gave the following results: Compound A DL50 = 0.91 ng / insect "B"> 100 "C"> 100 5 "D"> 100 "

Compound A was thus significantly more active than the other isomers. Further experimental results showing the excellent potency of the compounds of the invention are given in Proceedings of the 5th IUPAC Symposium 1983.

The compounds according to the invention can be used in particular for controlling insects in agriculture, for example for controlling leaf lice, butterfly larvae and beetles. They are applied in such a way that the dose of active substance is from 10 to 300 g per hectare.

15 These compounds can equally well be used to control insects in dwellings, in particular flies, mosquitoes and mosquitoes, as well as cockroaches.

The compound of Example 1 is a remarkably good product in all respects, as shown by the experiments below. It has an excellent killing ability and a very good stunning ability.

In addition, the compounds of the invention are photoresistant and non-toxic to mammals.

Thanks to this combination of properties, these compounds meet the requirements of the modern agrochemical industry perfectly: they can protect the crop while preserving the environment.

These compounds can also be used to control mites present in plant parasites.

The invention also relates to insecticidal compositions containing at least one compound as defined above as the main active ingredient.

Of the insect control combinations according to the invention, mention may be made of those which contain 4,78066 (1R cis) 2,2-dimethyl-3 - [(Z) 3- (2,2,2-trifluoroethoxy) -3-oxo- 1-Propenyl-7-cyclopropanecarboxylic acid (S) oC-cyano-3-phenoxy-benzyl ester, (1R cis) 2,2-dimethyl-3 Z ~ (Z) 3-oxo-3- (2- (1,1,1 (3,3,3) -Hex-5-fluoro) propoxy) -1-propenyl] cyclopropanecarboxylic acid (S) o6-cyano-3-phenoxybenzyl ester, (1R cis) 2,2-dimethyl-3ZT (Z) -3-oxo -3- (2,2,2-Trifluoroethoxy) -1-propenyl] cyclopropanecarboxylic acid (R) -α6-ethynyl-3-phenoxybenzyl ester, 10 (1R cis) 2,2-dimethyl-3-ZT (Z) - 3-Oxo-3- (2,2,2-trifluoro-ethoxy) -1-propenyl-7-cyclopropanecarboxylic acid (RS) -cyano-6-phenoxy-2-pyridylmethyl ester, (1R cis) 2,2-dimethyl-3Z1Z) -3-oxo -3- (2-Fluoro-ethoxy) -1-propenyl-cyclopropanecarboxylic acid (S) -cyano-3-15-phenoxy-benzyl ester, (1R cis) 2,2-dimethyl-3 - [(Z) -3-oxo-3- (2 , 2,2-trifluoro-ethoxy) -l-cyclopropyl-propenyyli7 Opanecarboxylic acid (3-propargyl-2,5-dioxo-imidazolidinyl) -methyl ester, (1R cis) 2,2-dimethyl-3 - [(Z) -3-oxo- (2,2,2-trifluoroethoxy-20-silyl)] ) -1-propenyl-cyclopropanecarboxylic acid (IS) 2-methyl-4-oxo-3- (2-propenyl) -2-cyclopenten-1-yl ester.

These compositions are prepared by conventional methods used in the agro-chemical industry.

25 In compositions intended for use in agriculture and housing, one or more other anticancer agents may be combined with the active substance or substances if desired. These compositions may be in the form of powders, granules, suspensions, emulsions, solutions, aerosol solutions, burnable tapes, feeds, or other conventional uses of compounds of this type.

In addition to the active ingredient, these compositions generally contain a carrier and / or nonionic surfactant which ensures a uniform distribution of the ingredients of the mixture. The carrier used may be a liquid such as water.

5 78066 alcohol, hydrocarbons or other organic solvents, mineral, animal or vegetable oil, powder such as talc, various clays, silicates, diatomaceous earth, or a combustible solid.

The insecticides according to the invention preferably contain 0.005 to 10% by weight of active ingredient.

A particularly preferred form in dwellings is to use the compositions according to the invention as smoky compositions.

The compositions according to the invention can thus very well be obtained from the inactive part of the combustible insecticide coil (or winding) or from the fibrous non-combustible substrate. In the latter case, the smoker obtained by adding the active substance is placed in a heating device, for example a so-called

15 electromosquito Destroyer.

In the case of using an insecticide, for example, crushed sawdust, Tabu powder (i.e., a leaf ground into Machilus Thumberg), ground sawdust, cedar leaf flour, wood flour (such as pine sawdust) from starch and starch powder and powder can be used as the inert medium. The dose of active substance can then be, for example, 0.03 to 1% by weight.

In the case where a non-combustible fibrous support is used, the dose of active substance may be, for example, 0.03 to 95% by weight.

The compositions according to the invention for use in living rooms can also be obtained by preparing a sprayable oil containing the main active ingredient, which impregnates the core of the lamp and which is then burned in this way.

The content of the main active ingredient in the oil is preferably 0.03 to 95% by weight.

78066

One or more other anticancer agents may be added to the insect control compositions of the invention, such as mite control compositions, if desired. Compositions for controlling mites 5 can be in particular in the form of powders, granules, suspensions, emulsions or solutions.

Wet leaf powders containing 1-80% of the main active ingredient or then leaf spray liquids containing 1-500 g / l of the main active ingredient are preferably used for controlling ticks.

Leaf dusting powders containing 0.05-3% of active ingredient can also be used.

In order to enhance the biological effects of the products according to the invention, synergistically active substances traditionally used in such contexts, such as 1- (2,5,8-trioxadodecyl) -2-propyl-4,5-methylenedioxybenzene (or piperonyl butoxide) or N- (2-ethyl-heptyl) -bicyclo [2.2.1] -5-heptene-2,3-dicarboximide, or piperonyl-bis-2- (2'-n-butoxy- ethoxy) -ethyl acetal (or tropital).

The products of the invention can also be used as biocides or growth regulators.

The invention also relates to compositions having insecticidal action against Tor-25, which contain as active ingredient at least one compound of the formula (I ') according to the invention and at least one pyrethrin ester selected from alletrolones, 3,4,5,6 ester formed with chrysanthemic acids of 5-benzoyl-3-yl-3-furyl-methyl-alcohol, 3-phenoxy-benzyl alcohol and ε-cyano-3-phenoxy-benzyl alcohol, 5-Benzyl-3-furylmethyl-alcohol Esters of furylmethyl alcohol with 2,2-dimethyl-3- (2-oxo-3-tetrahydrothiophenylidenemethyl) -cyclopropane-1-35 carboxylic acids, 3-phenoxybenzyl alcohol and p-cyano-3-phenoxybenzyl - Esters of 7,78066 with 2,2-dimethyl-3- (2,2-dichlorovinyl) -cyclopropane-1-carboxylic acids of alcohol, n-cyano-3-phenoxy-benzyl alcohol 2,2-dimethyl-3 - Esters with (2,2-dibromovinyl) -cyclopropane-1-carboxylic acids, 3-phenoxy-b esters of benzyl 2-parachlorophenyl-2-isopropylacetic acid, alletrolones, 3,4,5,6-tetrahydrophthalimidomethyl alcohol, 5-benzyl-3-furylmethyl alcohol, 3-phenoxybenzyl A group consisting of esters of alcohol and o, N-cyano-3-phenoxy-benzyl alcohol with 2,2-dimethyl-3- (1,2,2,2-tetrahalo) -cyclopropane-1-carboxylic acids, in which case "halo" means a fluorine, chlorine or bromine atom.

The latter compositions according to the invention have the property that, due to their wide-ranging effect, they can be used to control a wide variety of parasites and, on the other hand, in certain cases they produce a synergistic effect.

The invention also relates to a process for the preparation of compounds of formula (I1) as defined above, characterized in that the 1Rcis, Z-isomer of the acid of formula (II) is 25 x RQ2C-CH = CHn / CO 2 H (II) wherein R has the same meaning as above, or the acid chloride of this acid, is reacted with an alcohol of formula (III) A 'to OH (III) wherein A' has the same meaning as above to give the corresponding compound of formula (I). ').

When the acid of formula (II) is reacted with an alcohol of formula (III), this is preferably in the presence of dicyclohexylcarbodiimide.

A compound of formula (II) is prepared by reacting in a organic solvent a compound of formula (B ^) 78066 ιλ 5 ° "CV VCO 2 H <Bi) in trans or cis-lactone form with a compound of formula (B2) (((» ) 3 = P - CH - C - OR (B2) 10 0 wherein R has the same meaning as above to give the corresponding compound of formula (II) ro2c-ch = chn / \ ^ co2h (II) E- and Z as a mixture of isomers, from which the Z isomer is then separated.

In a preferred embodiment, the solvent used is selected from the group consisting of ethyl ether, dimethyl sulfoxide, di-methylformamide, tetrahydrofuran, dimethoxyethane, alkanols, diethylene glycol monomethyl ether and diethylene glycol diethyl ether.

A compound of formula (B2) is prepared by reacting a compound of formula 25 P - CH 2 - CO 2 R, Hal where Hal is a halide anion with a strong base. As the strong base, for example, hydride, amide or alkaline alcoholate or alkyllithium can be used.

Further, a compound of formula (II) may be prepared by reacting a compound of formula (IV)

35 Hal \ X

> = ^ / Vc02alc (IV)

Hai 9 78066 wherein Hal is a halogen atom and ale is an alkyl radical of 1 to 20 carbon atoms, reacting in a first step with an alkaline halogen-releasing agent and then in a second step 5 - either with a carboxyl group-binding agent to give a compound of formula ( V) H 2 CO-C 5 Cl 5 / CO 2 alc (V) 10 which in turn is reacted with an esterifying agent to give a compound of formula (VI) wherein R: has the same meaning as above - or with a derivative of the formula

Hal - CO2 - R

Wherein Hal is a halogen atom and R has the same meaning as above to directly give a compound of formula (VI) followed by reacting a compound of formula (VI) with a catalyzed hydrogenating agent to give a compound of formula (VII) 3 ° y

H \ / -A

XC = CX / CO 2 alc (VII) R 0 2c 35 wherein the double bond is of geometric form Z, and which compound is then reacted with an acidic hydrolyzing agent capable of selectively cleaving the ester group attached to the carbon atom at position 1 of cyclopropane, to give the corresponding compound of formula (II).

In a preferred embodiment of the process described above, - Hai is a bromine or chlorine atom, - ale is a tert-butyl or benzyl radical, - the alkaline substance capable of removing the halogens of the vinyl group is butyllithium, 10 - the substance capable of attaching the carboxyl group is carbon dioxide, - catalyzed hydrogen used in the presence of a palladium-like catalyst and a small amount of quinoline, a 15-acid hydrolyzing agent capable of selectively cleaving the ester group CCl 4c is paratoluenesulfonic acid. Alternatively, the compound of formula (V) is first reacted with a catalyzed hydrogenating agent and in a second step with an esterifying agent.

Compounds of formula (I *) as defined above may also be prepared by first reacting a compound of formula (V) with a catalyzed hydrogenating agent to give a compound of formula (VIII)

'25 X O

H2OC-CH = CHNy \ ^, COalc (VIII) wherein the double bond is of geometric form Z, which compound is then reacted with an esterifying agent to give the corresponding compound of formula (VII) ro2c-ch = chx / ^ \ ^ CO 2 alc (VII) 35 wherein R has the same meaning as above, after which the synthesis is continued as described above.

78066

The previously described method includes another alternative in which the order of certain steps is changed. In this case, a compound of formula (VI) H, C CH, 3 RQ2C-C = C ^ X \ ^ CO2alc (VI) in which R and ale are the same as above is reacted with an acidic hydrolysing agent capable of cleaving closely with an ester group in position 1 of cyclopropane to give a compound of formula (IX) H, CCH, N / RQ2C-C = Cxy / N, CO2H (IX) wherein R has the same meaning as above, and which compound is then - either, if desired as a functional derivative - reacted with an alcohol of formula (III) A '- OH (III) wherein A' has the same meaning as above to give a compound of formula ( X): 25 h3c ch3 R02C-C5Cx / \ ^ CO2A '(X) wherein R and A' have the same meanings as above, which compound in turn is reacted with a catalyzed hydrogenating agent to give the formula (I *) defined above. ), - or is first reacted with a catalyzed hydrogenating agent to give a compound of formula (II) H, C CH.

35 HHV 3 ro2-c = cv / \ ^ co2h (II) 12 78066 wherein R has the same meaning as above and the double bond is of geometric form Z, and which, if desired as a functional derivative, is then reacted with an alcohol (III), whereby a yh-5 diste of formula (I ') is obtained.

The preferred performance conditions for the method described above are the same as those described above for analogous procedures.

The invention also relates to a process for the preparation of compounds of formula (I ') as defined above, which comprises reacting a compound of formula (XI) H.-C CH-

V

H02C-HC = CH2 / CH2CO2A '(XI)

15 H H

wherein the double bond is of geometric form Z, to react with an esterifying agent to give the corresponding compound of formula (I ').

In a preferred embodiment of the process described above, the esterification is carried out with a functional derivative of an alcohol, namely an N, N'-diisopropylurea of the formula

NH

25> -N - == - C-OR

A compound of formula (XI) may be prepared by reacting an acid of formula (V) H-C / CH_

X

H02C-CsCN // CO2alc (V) wherein ale is an alkyl radical having 1 to 8 carbon atoms to react with 2,2,2-trichloroethanol to give a compound of formula (XII) 13 78066 H, C .CH0 / 3 XCsC \ Z __ ^ / CO2alc (XII) 5 CO2CH2CCl3 which in turn is reacted with an acidic hydrolysing agent to give a compound of formula (XIII) H2OXX / CH3? = Οχ / \ χθ, Η (XIII) CO2CH2CCl3. reacting with an alcohol of formula (III) A 'to OH (III) 20 wherein A' has the same meaning as above to give a compound of formula (XIV) H 3 C / CH 3 / C 5 Cl 2 / CO 2 -A '(XIV) 25 CO 2 CH 2 Cl 3 and which in turn is reacted with an acetylene carbon-associated ester group cleavage agent to give a compound of formula (XV) 30 H 3 Cl 2 / CH 3 s C = CKy / YCO 2 A' (XV)

CO 2 H

14,78066 and which in turn is reacted with a catalyzed hydrogenating agent to give a compound of formula (XI).

In a preferred embodiment of the process described above - ale in formula (V) is a tert-butyl or benzyl radical; - the acid hydrolysing agent is paratoluenesulfonic acid - the esterification of compound (XIII) is carried out by reacting compound (XIII) with an alcohol (III) in the presence of dicyclohexylcarbodiimide or diisopropylcarbodiimide; - cleavage of the ester (XIV) takes place using a metal powder, for example zinc flour, under acidic conditions; The 15-catalyzed hydrogenating agent is hydrogen used with a palladium-like catalyst and a small amount of quinoline.

The process described above includes an obvious alternative in which the hydrogenation step and the esterification step are reversed. The invention therefore also relates to a process as described above, characterized in that a compound of the formula (XV) H3C \ / CH3 is used. H2C-C = Cn ^ / \ ^ / CO2O '(XV) in which A': 11a has the same meaning as above, to react with an esterifying agent to give a compound of formula (X) H3C / CH3. RQ2C-CsCx / X ^ CC ^ A1 (X) 78066 wherein R and A 'are the same as above, and which compound is then reacted with a catalyzed hydrogenating agent to give a compound of formula (I').

The preferred performance-5 ratios of the method described above are the same as defined above for analogous procedures.

In the case where it is desired to prepare a compound of formula (I ') wherein R is an alkyl radical substituted by one or more hydroxyl radicals, a compound of formula (I') wherein R is one or more, for example dioxolanyl, is first prepared by any of the methods described above. or an alkyl radical substituted by a hydroxyl radical protected by a tetrahydro-pyranyl group, after which said compound 15 is hydrolyzed by means of an acid hydrolysing agent.

The hydrolyzing agent used in the process described above may be, for example, hydrochloric acid or paratoluenesulfonic acid.

The preferred performance conditions for the method described above are the same as defined above for analogous procedures.

Most of the methods described above result in compounds in which the double bond is of geometric form Z and are, of course, best suited for the preparation of the compounds (I ') of the invention. Otherwise, the Z-isomer must be separated from the mixture of isomers. In general, an isomer is used as starting material and intermediate which directly leads to the desired 1Rcis, Z isomer of the compound of formula (I ').

30 The methods have obtained excellent yields, as is clear from the examples below.

The 1Rcis, Z-isomers of the compounds of formulas (II) and (VII), which are intermediates in the preparation of the corresponding isomers of the compounds of formula (I '), are novel compounds and are also the subject of this invention.

16 78066

Example 1: (1R cis) 2,2-Dimethyl-3 - [(Z) 3- (2,2,2-trifluoroethoxy) -3-oxo-1-propenyl] -cyclopropanecarboxylic acid (S) cyano-3-phenoxybenzyl ester 1.3 g of (1R cis) 2,2-dimethyl-3 - [(Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl] -cyclopropyl were stirred. 3 3 of panic carboxylic acid, 0.1 cm of pyridine and 15 cm of methylene chloride and then 1.05 g of dicyclohexylcarbodiimide were added, followed by 1.35 g of 10 (S) o-cyano-3-phenoxybenzeneacetonitrile in solvents. Stirring was continued for 5 hours at room temperature, the insoluble matter was filtered off and the filter was rinsed with methylene chloride, and 2N hydrochloric acid was added to the filtrate.

The organic phase was decanted, washed with water, dried and evaporated to dryness. The obtained oily product was purified by chromatography on silica gel (eluent: cyclohexane-ethyl acetate 95-5). There was thus obtained 1.33 g of the desired product. = 42 ° + 2 ° (c = 0.7, benzene) NMR, CDCl 3: ppm 1.26 and 1.28 protons of methyls in position 2 1.97 to 2.11 proton of carbon in position 1 of cyclopropane 25 3, 1a 3,4 to the carbon proton at position 3 of the cyclopropane 6.5a 6.9 proton of the propenyl radical at position 1 5.9 to 5.93 proton of the propenyl radical at position 2 30 carbon proton of group 6.3 CN-bearing carbon proton 4.3 a 4.7 trifluoroethoxy radical protons 17 78066

The acid used in Example 1 was prepared as follows:

Preparation I: (1R cis) 2,2-Dimethyl-3 - [(Z) -3- (2,2,2-trifluoroethoxy) -3-oxo-1-propenyl] -cyclo-5-propanecarboxylic acid

Step A: (1R cis) 2,2-Dimethyl-3- (3-hydroxy-3-oxo-1-propynyl) -cyclopropanecarboxylic acid 1,1-dimethylethyl ester 26 g of (1R cis) 2,2-dimethyl-3- (2,2-di-10-bromo-vinyl) -cyclopropanecarboxylic acid 1,1-dimethylethyl ester in 175 cm of anhydrous tetrahydrofuran. A 20% solution of cyclohexane in 60 cin butyllithium was then added at -65 ° C. After stirring for 1 hour at -60 ° C, bubbles of a stream of carbon dioxide gas were added to the reaction mixture for 1.5 hours and then poured into ice water to which 1N sodium hydroxide had been added. Washed with ether. The alkaline aqueous phase was acidified to pH 4 and then extracted with ether. The organic phases were dried and evaporated to dryness under reduced pressure. The product thus obtained was recrystallized from petroleum ether (b.p. 60-80 ° C). 8.3 g of the desired product are thus obtained, melting at 144 ° C.

NMR, CDCl 3: ppm 25 1.22 and 1.37: protons of methyls in position 2 of cyclopropane 1.78 Protons in positions 1 and 3 of cyclopropane 1.47 protons of terbuthyl 30 8.25 -C-OH proton

II

0 18 78066

Step B: (1R cis) 2,2-Dimethyl-3- [3-oxo-3- (2,2,2-trifluoro-ethoxy) -1-propynyl] -7-cyclopropanecarboxylic acid 1,1-dimethylethyl ester Added 4 g of the product prepared in step A 3.5 g of dicyclohexylcarbodiimide in a solution containing 20 cm of methylene chloride and 1 cm of pyridine.

The reaction mixture was stirred continuously for one hour. 2.15 g of trifluoroethanol and 5 cm of methylene chloride were then added. Stirring was continued at 20 ° C for 16 hours. The mixture was filtered and the filter was rinsed with methylene chloride. The filtrate was evaporated to dryness. The residue was taken up in ethyl ether, washed with 1N hydrochloric acid and then with water and dried. The solution was concentrated to separate 5 g of product, which was purified by chromatography on silica gel (eluent: benzene-ethyl acetate 95-5). This gave 3.5 g of the desired product.

NMR, CDCl 3: ppm 1.2 and 1.37 Protons of methyls in position 2 1.77 Protons of carbons in positions 1 and 3 of cyclopropane 1.43 Protons of methyl of the 1,1-dimethylethyl radical 4.7 a 4.7 trifluoroethoxy radical proton 25 Step C: (1R cis) 2,2-Dimethyl-3- T3-oxo-3- (2,2,2-trifluoroethoxy-1-propynyl) -cyclopropanecarboxylic acid

A mixture of 3.3 g of the product prepared in the previous step 30 and 100 mg of paratoluenesulfonic acid was refluxed. Refluxing was continued until gas evolution ceased. The mixture was cooled, washed with water, dried and evaporated to dryness. There was thus obtained 2.6 g of the desired product, which was used as such in the next step.

78066

Step D: (1R cis) 2,2-Dimethyl-3-Z '(Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl-cyclopropanecarboxylic acid

500 mg of palladium hydroxide as a 10% mixture of barium-3 sulfate and 5 cm of ethyl acetate were placed in a round-bottomed flask connected to a source of hydrogen gas. 2 g of the product prepared in the previous step, 45 cm 3 of ethyl acetate and 0.5 cm 3 of quinoline were added. Hydrogenation until hydrogen absorption ceased. The resulting product was isolated by filtration. The filtrate was washed with 1N hydrochloric acid and then with water, dried and evaporated to dryness. 2 g of product were obtained, which was purified by chromatography on silica gel (eluent: cyclohexane-ethyl acetate-acetic acid, 70-30-1). This gave 1.3 g of the desired product.

NMR spectrum, CDCl 3: ppm 1.3 and 1.32 protons of methyls in position 2, 1.92 to 2.06 proton of carbon in position 1 of cyclopropane, 3.07 a 3.38 proton of carbon in position 3 of cyclopropane, δ, 6a 6.9 Proton of the carbon at position 1 of the propenyl radical 5.9-6.0 Proton of the 25 carbons at position 2 of the propenyl radical 4.3 a 4.7 Proton of the 4.7 trifluoroethoxy radical Example 2; (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl] -cyclopropanecarboxylic acid (IS) 2-methyl-4 -oxo-3- (2-propenyl) -2-cyclopenten-1-yl ester

1.9 g of (1R cis) 2,2-dimethyl-3-ZT (Z) 3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl-7-cyclopropanecarboxylic acid were mixed together, 12 cm-methyl-35-ene chloride and 100 mg of dimethylaminopyridine. Then 1.4 g of dicyclohexylcarbodiimide and a further 1.1 g of (S) 3- (2-propenyl) -1-hydroxy-2-methyl-4-oxo-cyclopent-2-ene and 5 cm-2 of methylene chloride were added. . Stirring was continued at room temperature for 2 hours.

5 The formed insoluble matter was removed by filtration. The filtrate was washed with 0.5 N hydrochloric acid, then with water, dried and evaporated to dryness.

There was thus obtained 3 g of product which was purified on silica gel (eluent benzene-ethyl acetate, 95-5).

This gave 2.2 g of the desired product.

= + 38 ° + 2.5 ° (c = 0.5%, benzene) NMR spectrum, CDCl 3, ppm 1.29 and 1.32 protons of methyls in position 2 of cyclopropane 1.97 to 2.11 protons of cyclopropane in position 1 3.05 a 3.37 proton in position 3 of the cyclopropane in position 3 6.7 a 7 proton of the carbon in position 1 of the propenyl radical, 5.9? 20 6 carbon proton at position 2 of the propenyl radical 4,3 a 4,75 proton of the trifluoroethoxy radical 5.7 proton of the cyclopentene in the «/ position of CO2, 2 protons of the cyclopentene-associated methyl, 25 4,8 and 5,25 cyclopentene-associated propenyl position sa 3 proton

Example 3: (1R cis) 2,2-Dimethyl-3-Z (Z) -3-oxo-3- (phenylmethoxy) -1-propenyl] -7-cyclopropanecarboxylic acid (IS) -Z-cyano-3- phenoxy-30 benzyl ester

Step A: (1R cis) 2,2-Dimethyl-3-Z '(Z) -3-oxo-3- (phenoxymethoxy) -1-propenyl-7-cyclopropanecarboxylic acid chloride

A mixture of 1.6 g of (1R cis) 2,2-dimethyl-3 '- (Z) -3-oxo-21,78066 3- (phenylmethoxy) -1-propenyl-4H-cyclopropanecarboxylate was stirred for 5 hours under a stream of nitrogen gas. 3 3 Silicic acid, 10 can isoprene and 1 can thionyl chloride were concentrated to give 2 g of product which was used as such in the next step.

Step B: (1R cis) 2,2-Dimethyl-3-Z- (Z) -3-oxo-3- (phenylmethoxy) -1-propenyl-7-cyclopropanecarboxylic acid (IS) ε-cyano-3 phenoxy-bent-benzyl ester

1 g of the product prepared in step A was added to a solution of 700 mg of (S) oC-hydroxy-3-phenoxy-3-3-benzeneacetonitrile, 20 cm of benzene and 0.6 cm of pyridine. The reaction mixture was stirred for 16 hours at room temperature, then poured into a mixture of ice water and 1N hydrochloric acid. The resulting suspension was stirred and then extracted with benzene. The benzene extracts were washed with water, dried, filtered and evaporated to dryness. 1.5 g of product were obtained, which was purified by chromatography on silica gel (eluent cyclohexane-ethyl acetate 8-2).

This gave 861 mg of the desired product, melting at 83 ° C.

<? D = +6 9 ° + 5 ° (c = 0.2%, benzene) NMR spectrum, CDCl 3: ppm 25 Protons of methyl at position 2 of cyclopropane Proton of the carbon atom bearing the CN 6.33 group.

Preparation II; (1R cis) 2,2-Dimethyl-3-Z ”(Z) -3-oxo-3- (phenylmethoxy) -1-propenyl] -7-cyclopropane-30-carboxylic acid

Step A; (1R cis) 2,2-Dimethyl-3-Z '(Z) 2-carboxyethenyl] -7-cyclopropanecarboxylic acid 1,1-dimethylethyl ester Hydrogenated 2 g of (1R cis) 2,2-dimethyl-3- [2-25 carboxyethynyl] 1,1-dimethylethyl ester of cyclopropanecarboxylic acid in 40 g of ethyl acetate in the presence of 0.38 g of palladium hydroxide as a 10% mixture of barium-3 sulphate and 0.4 cm of quinoline. The mixture was filtered, the filtrate was washed with 0.5N hydrochloric acid, then with water until the washings were neutral, dried, evaporated to dryness under reduced pressure to give 2 g of the desired product, melting at 94 ° C.

Step B: (1R cis) 2,2-Dimethyl-3-iT (Z) -3-oxo-3- (phenylmethoxy) -1-propenyl] -cyclopropanecarboxylic acid 1,1-dimethyl ester 10 Added 2.4 g of the product prepared in step A to 20 cm of ethyl acetate. 2.34 g of O-benzyl-N, N-diisopropylisourea (described by ESCHIMDT et al. Liebig Ann. Chem. 1965 685 161) were then added. After stirring for 16 hours at room temperature, the mixture was filtered and the filtrate was evaporated to dryness under reduced pressure. pressure. 4.3 g of a yellowish oil were obtained, which was purified by chromatography on silica gel (eluent benzene-cyclohexane, 7-3). There was thus obtained 2 g of the desired product. Nuclear Magnetic Resonance Spectrum: CDCl 3 ppm 1.22 and 1.28 Protons of methyls in position 2 of cyclopropane, 1.77 to 1.91 Proton of carbon in position 1 of cyclopropane, 2.98 a 3.3 Carbon in position 3 of cyclopropane proton, 6.5 a 6.8 proton of the carbon in position 1 of the propenyl radical, 5.8-6 proton of the carbon in position 2 of the propenyl radical, protons of the methyls of the 1.43 dimethylethyl radical, 5.1 protons of the methoxy of the phenylmethoxy radical.

23 78066

Step C: (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3- (phenylmethoxy) -1-propenyl] -cyclopropanecarboxylic acid

A mixture of 2 g of the product obtained in the previous step, 30 cm of toluene, 100 mg of paratoluenesulphonic acid was heated to 90 ° C. Stirring was continued for about 2 hours. The mixture was evaporated to dryness to give 2 g of product, which was purified by chromatography on silica gel (eluent: cyclohexane-10-ethyl acetate-acetic acid 60/40/1).

This gave 1.4 g of the desired product.

NMR spectrum, CDCl 3 ppm 1.25 and 1.3 protons of methyls in position 2 of cyclopropane, 1.84 to 1.98 proton of carbon in position 1 of cyclopropane, 3.14a 3.43 proton of carbon in position 3 of cyclopropane, 6.4 a 6.77 proton of carbon 20 in position 1 of the propenyl radical, 5.98 proton of the carbon in position 2 of the propenyl radical.

Example 4: (1R cis) 2,2-Dimethyl-3- (U) -3-oxo-3- (phenylmethoxy-1-yl) -7-cyclopropane-25-carboxylic acid (1S) -2- Methyl 4-oxo-3- (2-propenyl) -2-cyclopenten-1-yl ester

1 g of (1R cis) 2,2-dimethyl-3- [T (Z) -3-oxo-3- (phenylmethoxy) -1-propenyl] -cyclopropanecarboxylic acid chloride was added to a mixture of 450 mg of (S) - (2-propenyl) -1-hydroxy-2-methyl-4-oxo-cyclopent-3 3 2-ene, 20 cm of benzene and 0.6 cm of pyridine. Stirring was continued for 16 hours and the reaction mixture was then poured into a mixture of ice water and 1N hydrochloric acid. Extracted with benzene, combined the benzene phases, washed with water, dried and evaporated to dryness.

24 78066

1/5 g of product was obtained, which was purified by chromatography on silica gel (eluent: cyclohexane-ethyl acetate, 8-2).

This gave 500 mg of the desired product.

Δ D = -37 ° + 2.5 (c = 0.5%, benzene) NMR spectrum, CDCl 3, ppm 1.27 and 1.31 protons of methyls in position 2 of cyclopropane in position 1.87-2 of cyclopropane Proton of carbon 10 in position 3 3.12 a 3.45 Proton of carbon in position 3 of cyclopropane 5.8 a 6.8 Protons in positions 1 and 2 of the propenyl radical 5.2 Protons of methoxy of the phenylmethoxy radical 5.6 a 5.7 of the cyclopentene in the CO2 position protons 2 protons of cyclopentene-related methyl 4.8 a 5.2 protons of cyclopentene-related propenyl 20

Example 5: (1R cis) 2,2-Dimethyl-3- [T (Z) -3-oxo-3-phenoxy-1-propenyl] -cyclopropanecarboxylic acid (S) o (cyano-3-phenoxy) benzyl ester Proceeding as in Example 1 using 1.5 g of LR cis) 2,2-dimethyl-3-Z '(Z) -3-oxo-3-phenoxy-1-propenyl-cyclopropanecarboxylic acid as starting materials and 1.45 g ( S) -hydroxy-3-phenoxy-benzene-acetonitrile, 1.8 g of the desired product were obtained.

= + 54 ° + 2.5 ° (c = 0.5%, in benzene) 30 NMR spectrum, CDCl 3 ppm 1.25 Protons of methyls in position 2 of cyclopropane 1.97 - 2.12 Proton in position 1 of cyclopropane 35 3 , 25 a 3,6 Proton in cyclopropane 25 78066 6,6 a 7 Proton in position 1 of the propenyl radical 6,1 to 6,3 Proton in position 2 of the propenyl radical 5 6,9 a 7,7 Aromatic protons of the 3-phenoxybenzyl radical .

Preparation III: (1R cis) 2,2-dimethyl-3- (Z) -3-oxo-3-phenoxy-1-propenyl-7-cyclopropanecarboxylic acid Step A: (1R cis) 2,2-dimethyl-3 - E-3-oxo-3-phenoxy-1-propynyl / cyclopropanecarboxylic acid 1,1-dimethylethyl ester 25 g of (1R cis) 2,2 'dimethyl-3- (2,2,2-dibromovinyl) -cyclopropanecarboxylic acid 1.1 -dime- 3 15 ethyl ethyl ester to 250 cm of tetrahydrofuran.

A 20% cyclohexane solution of 48 tert-butyllithium was then added with stirring at -65 ° C. Stirring was continued for 1 hour at -65 ° C and 9.6 cm 3 of phenyl chloroformate were added. Stirring was continued at -65 ° C for 1 hour and then the mixture was allowed to warm to room temperature while stirring. The mixture was then poured into saturated aqueous monosodium phosphate solution, extracted with ether, washed with water, dried to give 24.6 g of an oil which was purified by chromatography on silica gel (eluent: cyclohexane-ethyl acetate, 9-1).

This gave 14.4 g of the desired product.

Nuclear Magnetic Resonance Spectrum, CDCl 3 ppm 3Q 1.23 and 1.42 Protons of methyls in position 2 of cyclopropane 1.82 Protons in positions 1 and 3 of cyclopropane 1.5 Protons of dimethylethyl radical f 35 7 and 7.6 Aromatic protons 26 78066

Step B; (1R cis) 2,2-Dimethyl-3-Z '(Z) -3-oxo-3-phenoxy-1-propenyl-7-cyclopropanecarboxylic acid 1,1-dimethylethyl ester Hydrogenated 4 g of the product obtained in step A dissolved in 60 cm To ethyl acetate in the presence of 800 mg of palladium hydroxide in a mixture of barium sulfate-3, 0.8 cm of quinoline and 20 cm of ethyl acetate, the mixture was filtered and 200 cm 2 of a 2N hydrochloric acid solution was added. The organic phase was decanted, washed with water and dried. 4.1 g of an oily product were obtained, which was purified on silica gel (eluent: cyclohexane-ethyl acetate, 95-5). 3.35 g of the desired product were obtained.

NMR spectrum, CDCl 3 ppm 1.23 and 1.3 Protons of methyls in position 2 of cyclopropane 1.83 to 1.97 Proton 3a in position 1 of cyclopropane 3.33 Proton in position 3 of cyclopropane 1.44 Protons of methylethyl radical 20 6 , 7 a 7 proton in position 1 of the propenyl radical 6.03 to 6.21 proton in position 2 of the propenyl radical 7 a 7.5 aromatic protons 25 Step C: (1R cis) 2,2-dimethyl-3-Z “(Z) - 3-Oxo-3-phenoxy-1-propenyl-7-cyclopropanecarboxylic acid A mixture of 3.3 g of the product obtained in the previous step, 35 cm of toluene and 100 mg of paratoluenesulphonic acid monohydrate was refluxed. The refrigeration of the soup was suspended when the cooking process had stopped. The reaction mixture was evaporated to dryness under reduced pressure to give 3.4 g of product, which was purified by chromatography on silica gel (eluent: cyclohexane-ethyl acetate-acetic acid-35 po, 70-30-1). 2.4 g of the desired product are obtained, melting at 57 ° C.

27 78066 NMR spectrum, CDCl 3 ppm 1.25 a 1.33 Protons of methyls in position 2 of cyclopropane 1.9 to 2.04 Proton 5 in position 1 of cyclopropane 3.2 a 3.5 Proton in position 3 of cyclopropane 6.6 a 6, 9 proton at position 1 of propenyl 6.0 to 6.2 proton at position 2 of propenyl.

Example 6; (1R cis) 2,2-Dimethyl-3 - [((Z) -3-oxo-3-phenoxy-1-propenyl] -cyclopropanecarboxylic acid (IS) 2-methyl-4-oxo-3- (2 - propenyl) -2-cyclopenten-1-yl ester Following the procedure as in Example 2, starting from 1.5 g of (1R cis) 2,2-dimethyl-3 - [(Z) -3-oxo-3-phenoxy-1 -propenyl-7-cyclopropanecarboxylic acid 15 and 1 g of (S) 3- (2-propenyl) -1-hydroxy-2-methyl-4-oxo-cyclopent-2-ene gave 1.6 g of the desired product. mp D = + 66 ° + 2.5 ° (c = 0.5%, benzene) NMR spectrum, CDCl 3 ppm 20 1.26 and 1.33 cyclopropane methyl protons 1.95 to 2.09 cyclopropane proton in position 1 5.7 proton of cyclopentene in position CO2: 4.8 a 5.2 proton of cyclopentene-related propenyl in position 3 protons of cyclopentene-related methyl protons 6.1 a 6.7 protons of cyclopropane-related propenyl 30 7 a 7.7 aromatic the protons.

780 6 6 28

Example 7; (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3-methoxy-methoxy-1-propenyl] -cyclopropanecarboxylic acid (RS) e-cyano-3-phenoxy-benzyl ester 5 Step A: (1R cis) 2,2-Dimethyl-3- (3-oxo-3-methoxymethoxy-1-propynyl) -cyclopropanecarboxylic acid (RS) [4-cyano-3-phenoxybenzyl ester] Cooled to + 10 ° C to a solution of 3 g of (1R cis) 2,2-dimethyl-3- (3-hydroxy-3-oxo-1-propynyl) cyclopropanecarboxylic acid (RS) -N-cyano-3-phenoxy benzyl ester in 30 cm 3 of anhydrous dimethylformamide, then 300 mg of sodium hydride as a 61% oil mixture were added in small portions, followed by 15 cm of chloromethyl ether solution prepared as described below over 15 minutes. After stirring for 2 hours, the mixture was poured into aqueous sodium monophosphate solution and extracted with ethyl acetate, the extracts were washed with water, dried and evaporated to dryness. The residue was purified by chromatography on silica gel eluting with a mixture of cyclohexane and ethyl acetate (75-25) to give 2 g of the desired product.

MMR CDCl 3 ppm 1.23 to 1.27λ and protons of methyls in position 2 of cyclopropane 1.35 to 1.45 / 1.95 Protons in positions 1 and 3 of cyclopropane 5.28 Methoxy-methoxyl methylene proton 3.5 Methoxy-methoxyl methyl proton 6.42 and 6.47 proton of the carbon atom bearing the CN group 30 6.92 a 7.58 aromatic protons

Preparation of chloromethyl ether solution

4.5 cm3 of methyl 3 and 0.52 cm of methanol were mixed together and then 3.53 cm of acetyl chloride was added. Stirred for 36 hours at room temperature to give the desired solution.

Step B; (1R cis) 2,2-Dimethyl-3-Z "(Z) -3-oxo-3-methoxy-methoxy-1-propenyl-7-cyclopropanecarboxylic acid (RS), p-cyano-3-phenoxy-benzyl ester 3

2.2 g of the product obtained above were hydrogenated in 50 cm of ethyl acetate in the presence of 450 mg of palladium hydroxide as a 10% mixture of barium sulphate, 30 ml of ethyl acetate and 0.5 cm of quinoline. The mixture was filtered, the filtrate was washed with 1N hydrochloric acid, then with water, dried and evaporated to dryness. The residue was purified by chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (8-2), to give 1.2 g of the desired product.

Δ = + 41 ° + 3 (c = 0.3 S CHCl 3) NMR CDCl 3 ppm 1.27 to 1.28 protons of cyclopropane in position 2 and 1.33 to 1.35 methyl protons in position 1.93 to 2.1 in cyclopropane Proton in position 3.17 a 3.5 proton in position 3 of cyclopropane 6.47 a 6.82 ethylene proton in position 1 5.85 - 6.0Ί and) ethylene proton in position 2 5.88 - 6.1 / 25 5.27 - Proton of 5.3 methoxy CH 2 3.47 and protons of 3.5 methoxy methyl 6.4 Proton of the carbon atom bearing the CN group 6.92 a 7.67 Aromatic protons

The (1R cis) 2,2-30 dimethyl-3- [3-hydroxy-3-oxo-1-propynyl] cyclopropanecarboxylic acid (RS) o <-cyano-3-phenoxybenzyl ester used as starting material in the example can be prepared below for the corresponding ( By a method analogous to that described for the S) ester using the corresponding (RS) alcohol.

30 7 8 0 6 6

Example 8: (1R cis) 2,2-Dimethyl-3- [T (Z) -3-oxo-3-cyanomethoxy-1-propenyl] -cyclopropanecarboxylic acid (RS) -N, cyano-3-f enoxy benzyl ester 5 Step A: (1R cis) 2,2-Dimethyl-3-ZT (Z) -3-oxo-3-cyanomethoxy-1-propynyl-7-cyclopropanecarboxylic acid (RS) ozyano-3- phenoxybenzyl ester The procedure was as in Example 7 using 2 cm 2 of chloroacetonitrile; extraction with ether and eluting with 10 ml of a mixture of cyclohexane and ethyl acetate (9-1) gave 2.69 g of the desired product.

Step B: (1R cis) 2,2-Dimethyl-3- [T (Z) -3-oxo-3-cyano-methoxy-1-propenyl] -cyclopropanecarboxylic acid (RS) * E-cyano-3-phenoxy Benzyl ester 15 Following the procedure of Example 7, starting from 2.69 g of the product obtained above, 2.02 g of the desired product were obtained after elution with a mixture of cyclohexane and ethyl acetate (9-1).

Step C: (1R cis) 2,2-Dimethyl-3- [7 "(Z) -3-oxo-3-cyano-20-methoxy-1-propenyl-7-cyclopropanecarboxylic acid (S) o-cyano-3-phenoxy Benzyl ester Chromatograph on silica gel with 1.4 g of the product obtained above, eluting with methylene chloride, to separate 0.41 g of the desired product.

25 ° C = -55 ° + 1.5 ° (C = 1% CHCl 3).

Example 9; (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3-ethoxy-ethoxy-1-propenyl] -cyclopropanecarboxylic acid (S) -6-cyano-3-phenoxy-benzyl ester 30 Step A: (1R cis) 2,2-Dimethyl-3- (3-oxo-ethoxy-ethoxy-1-propynyl) -cyclopropanecarboxylic acid (S) - * / cyano-3-phenoxy-benzyl ester Cooled to 0 to + 5 ° C 2 g of (1R cis) 2,2-dimethyl-3- [3-hydroxy-3-oxo-1-propynyl] -7-cycloprop-35-panicarboxylic acid (S) o-cyano-3-phenoxy-benzyl-3178066 3 3 esters, 20 cm methylene chloride and 0.7 cm ethoxyethanol. 1.1 g of dicyclohexylcarbodiimide, 3 3 cm of methylene chloride and 15 mg of dimethylaminopyridine were added. Stirred for 1 hour at + 5 ° C and 2 hours at room temperature. The mixture was filtered, the filtrate evaporated to dryness and the residue purified by chromatography on silica gel eluting with a mixture of cyclohexane and ethyl acetate (75-25) to give 1.3 g of the desired product.

10 NMR CDCl 3 ppm 1.22 to 1.32 Protons of methyls in position 2 of cyclopropane 1.93 Protons in positions 1 and 3 of cyclopropane

4.17 a 4.38 protons of the group COO-Cl 2 -Cl 2 -O

in position 1 3,5 5 a 3,7 3 protons of the group COO-Cl 2 -C 1-4 -O in position 2 6.57 proton of the carbon atom bearing the group CN 7 a 7.67 aromatic protons 20 1.08 to 1.3 ^ and J (q) ethyl protons 1.52

Step B: (1R cis) 2,2-Dimethyl-3- [T (Z) -3-oxo-3- (ethoxy-ethoxy) -1-propenyl] -7-cyclopropanecarboxylic acid (S) -N-cyano-3 -fenoksibentsyyliesteri

Following the same procedure as in Example 7, Step B, starting from 1.3 g of the product obtained above, 1.0 g of the desired product was obtained.

= + 37 ° + 2.5 (c = 0.5% CHCl 3).

Example 10; (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3- (RS) (1,1,1-trifluoromethyl-ethoxy) -1-propenyl] -cyclopropanecarboxylic acid (S) -> 4 "cyano 3-Phenoxy-benzyl ester The procedure was as in Example 7, Step B, using 2.6 g of (1R cis) 2,2-dimethyl-3- [3-oxo-3 - ((RS) 32 78066 1 / 1.1 (trifluoromethylethoxy) propynyl / cyclopropanecarboxylic acid (S) -N-cyano-3-phenoxy-benzyl ester. Elution with a mixture of cyclohexane and ethyl acetate (9-1) gave 2.1 g of the desired product.

Δ = + 44 ° + 2 (c = 0.4%, benzene) (1R cis) 2,2, d-methyl-3- [3-oxo-3 - ((RS) 1,1,1-trifluoro- Preparation of rimethylethoxy) -propynyl] -cyclopropanecarboxylic acid (S) -N-cyano-3-phenoxy-benzyl ester The procedure was as in Example 9, Step A, using 4.6 g of 1,1,1-trifluoromethylethanol and 3, 8 g of (1R cis) -2,2-dimethyl-3- [3-oxo-3-hydroxy-propynyl] -7-cyclopropanecarboxylic acid (S) -N-cyano-3-phenoxy-benzyl ester gave cyclohexane and with a mixture of ethyl acetate (8-2) eluting 2.6 g of the desired product.

Example 11; (1R cis) 2,2-Dimethyl-3- [3-oxo-3- (2,2-difluoroethoxy) -propenyl] -cyclopropanecarboxylic acid (S) -N-cyano-3-phenoxy-20-benzyl- ester

Step A: (1R cis) 2,2-Dimethyl-3- (3-oxo-3- (2,2-difluoro-ethoxy) -propynyl] -cyclopropanecarboxylic acid tert-butyl ester Following the procedure of Example 9, Step A, starting from 5 g '(1R cis) ) 2,2-Dimethyl-3- (3-hydroxy-3-oxo-1-propynyl) -cyclopropanecarboxylic acid tert-butyl ester and elution with a mixture of n-hexane and isopropyl ether (7-3) gave 5.25 g of the desired product.

30 IR CHCl 3 -C = C- conc. 2232 cm-2 = ester 1725 cm-2 asymmetric 1710 cm-2 double methyls (^ 1393 cm ^ 35 \ 1380 cm-1 terbutyl 1372 cm ^ 78066

Step B; (1R cis) 2,2-Dimethyl-3- [3-oxo-3- (2,2,2-difluoroethoxy) -1-propynyl] -7-cyclopropanecarboxylic acid

A mixture of 5.2 g of the product obtained above, 500 mg of 3 paratoluenesulphonic acid and 40 cm of toluene was refluxed for 25 minutes. After cooling, 400 cm of ether were added, washed with water, the organic phase was dried and evaporated to dryness to give 4.1 g of the desired product.

Step C: (1R cis) 2,2-Dimethyl-3- [T3-oxo-3- (2,2,2-difluoroethoxy) -1-propynyl] cyclopropanecarboxylic acid (S) oC-cyano-3 -phenoxy-benzyl ester Following the procedure of Example 9, Step A, starting from 4.1 g of the acid obtained above and 4.5 g of (S) 15 [(7-cyano-3-phenoxy-benzyl alcohol), petroleum ether (b.p. 40-70 ° C) was obtained and with a mixture of isopropyl ether (6-4) eluting 4.7 g of the desired product.

IR CHCl 3 OH 3580 cm -1 20 -C = C- conjugate 2235 cm -1 ester conjugate 1725 cm -1 aromatic 1588 cm -1 1488 cm -1 double methyl-.

25 lit 1392 cm ”1 1380 cm” 1

Step D; (1R cis) 2,2-Dimethyl-3-iT (Z) -3-oxo-3- (2,2-difluoroethoxy) -propenyl-7-cyclopropanecarboxylic acid (S) -acyano-3-phenoxy-benz-30-silyl ester

4.7 g of the product obtained above were hydrogenated in the same manner as in Example 7, Step B. Elution with a mixture of n-hexane and isopropyl ether (7-3) gave 3.2 g of the desired product.

35 ° <D = + 44 ° + 2.5 ° (c = 0.5% CHCl 3).

78066

Example 12; (1R cis) 2,2-Dimethyl-3- [T (Z) -3- (2,2-dichloroethoxy) -1-propenyl] -7-cyclopropanecarboxylic acid (S) -N-cyano-1-phenoxy Benzyl ester 5 Step A: (1R cis) 2,2-Dimethyl-3 - [(Z) -3- (2,2-dichloroethoxy) -1-propenyl] -cyclopropanecarboxylic acid tert-butyl ester The procedure of Example 1 was followed. 9 in step A, starting from 4.8 g of (1R cis) 2,2-dimethyl-3 - [(Z) -10 3-hydroxy-3-oxo-1-propenyl] -cyclopropanecarboxylic acid tert-butyl ester and 2 cm 2 , 2-dichloroethanol Elution with a mixture of cyclohexane and ethyl acetate (9-1) gave 5.6 g of the desired product.

Step B: (1R cis) 2,2-Dimethyl-3- [T (Z) -3- (2,2-dichloro-15-ethoxy) -1-propenyl] -cyclopropanecarboxylic acid

The procedure was as in Example 11, Step B, starting from 5.6 g of the product obtained above, thus obtaining 4.5 g of the desired product.

Step C: (1R cis) 2,2-Dimethyl-3- [f (Z) -3- (2,2-dichloro-ethoxy) -1-propenyl] -cyclopropanecarboxylic acid (S) -4-cyano-3- phenoxy benzyl ester The procedure was as in Example 9, Step A, starting from 3 g of the product 25 obtained in Step B and 2.25 g of (S) <? <<> cyano-3-phenoxybenzyl alcohol.

Elution first with an 8: 3 mixture of cyclohexane and ethyl acetate and then with a 9: 1 mixture gave 1.6 g of the desired product.

= + 54 ° + 2 ° (c = 1%, in benzene).

The following examples were prepared in a manner analogous to that described in Example 9, Step A, starting from: 1 °) (1R cis) 2,2-dimethyl-3-, E "(Z) -3-oxo-3- (2,2-difluoroethoxy) -1-propenyl-7-cyclopropanecarboxylic acid and the corresponding alcohol.

35 78066

Example 13; (1R cis) 2,2-Dimethyl-3 - ((Z) -3-oxo-3- (2,2-difluoroethoxy) -1-propenyl] -cyclo-propanecarboxylic acid (RS) * 4-cyano-6 -phenoxy-2-pyridyl methyl ester 5 ° C = + 50.5 ° + 2 ° (c = 0.8% CHCl 3)

Example 14: (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3- (2,2-difluoroethyl) -1-propenyl] -cyclopropanecarboxylic acid (R) -4-cyano-3 -phenoxy-benzyl ester 10 = + 117.5 ° + 3 ° (c = 0.6% CHCl 3)

Example 15: (1R cis) 2,2-Dimethyl-3-, T (Z) -3-oxo-3- (2,2-difluoroethoxy) -1-propenyl-7-cyclopropanecarboxylic acid E-3-propargyl-2,5 -dioxoimidazolidinyl / methyl ester 15 = + 18 ° + 2 ° (c = 1% CHCl 3)

Example 16: (1R cis) 2,2-Dimethyl-3-Z- (Z) -3-oxo-3- (2,2-difluoroethoxy) -1-propenyl] -cyclopropanecarboxylic acid (R) Ethynyl 3-phenoxy-benzyl ester 20 VD = + 47 ° + 1.5 ° (c = 1% CHCl 3) (1R cis) 2,2-dimethyl-3-ZT (Z) -3-oxo-3- (2 1,2-Difluoroethoxy) -1-propenyl-7-cyclopropanecarboxylic acid was prepared in analogy to the procedure described for Preparation VI using 2,2-difluoroethanol as starting material.

2 °) {1R cis) 2,2-dimethyl-3- (T (Z) -3-oxo-3- (2-fluoroethoxy) -1-propenyl) -cyclopropanecarboxylic acid and the corresponding alcohol. '

Example 17: (1R cis) 2,2-Dimethyl-3- [C (Z) -3-oxo-3-3q (2-fluoroethoxy) -1-propenyl] -7-cyclopropanecarboxylic acid (3-propargyl-2,5 -dioxoimidazolidinyl) methyl ester <D = -18 ° + 2 ° (c = 1% CHCl 3) 36 78066

Example 18: (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3- (2-fluoroethoxy) -1-propenyl] -cyclopropanecarboxylic acid (RS) cyano- (6-phenoxy-2-pyridyl) methyl ester δ = + 49.5 ° + 2.5 ° (c = 0.5% CHCl 3)

Example 19: (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3- (2-fluoroethoxy) -1-propenyl] -7-cyclopropanecarboxylic acid (R) o-methyl 3-Phenoxy-benzyl ester 10 eip = -123 ° + 1.5 ° (c = 1% CHCl 3)

Example 20: (1R cis) 2,2-Dimethyl-3 H - (Z) -3-oxo-3- (2-fluoroethoxy) -1-propenyl] -cyclopropanecarboxylic acid N-ethynyl-3-phenoxybenzyl ester 15 ° <0 = + 47 ° + 1.5 ° (c = 1% CHCl3) (1R cis) 2,2-dimethyl-3 - [(Z) -3-oxo-3- (2-fluoroethoxy) -1 -propenyl-7-cyclopropanecarboxylic acid was prepared analogously to the procedure described in Preparation VI using 2-fluoroethanol as starting material.

3 °) (1R cis) 2,2-dimethyl-3 - [, (Z) -3-oxo-3- (2- (1,1,1,3,3,3-hexafluoro) -propoxy) -1-propenyl-7-cyclopropanecarboxylic acid (Preparation VI) and the corresponding alcohol.

Example 21: (1R cis) 2,2-Dimethyl-3-Z- (Z) -3-oxo-3- (2- (1,1,1,3,3,3-hexafluoro) -propoxy) - 1-Propenyl-7-cyclopropanecarboxylic acid (R) -4-ethynyl-3-phenoxy-benzyl ester VD = 31.5 ° + 1.5 ° (c = 1% CHCl3) Example 22; (1R cis) 2,2-Dimethyl-3 - ((Z) -3-oxo-3- (2- (1,1,1,3,3,3-hexafluoro) propoxy) -1-propenyl] -7-cyclopropanecarboxylic acid (R) -N-methyl-3-phenoxy-benzyl ester <VD = + 97 ° + 2 ° (c = 1% CHCl 3).

78066

Example 23: (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3- (2- (1,1,1,3,3,3-hexafluoro) -4-propoxy) -1 -propenyl-7-cyclopropanecarboxylic acid (S) -cyano-3-phenoxybenzyl ester 5 ° D = + 23.5 ° + 2 ° (c = 0.5% benzene)

Example 24: (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3- (2- (1,1,1,3,3,3-hexafluoro) -propoxy) -1 -propenyl-7-cyclopropanecarboxylic acid 3,4,5,6-tetrahydro-phthalimidomethyl ester 10 DEG-D = -30 ° + 1 ° (c = 1% CHCl3)

Example 25: (1R cis) 2,2-Dimethyl-3- [7 (Z) -3-oxo-3- (2- (1,1,1,3,3,3-hexafluoro) -propoxy) -1 -propenyl-7-cyclopropanecarboxylic acid (RS) cyano-6-phenoxy-2-pyridyl-15-methyl ester ° D = + 33.5 ° + 2.5 ° (c = 0.2% CHCl3) 4 °) (1R cis) 2 , 2-Dimethyl-3H- (Z) -3-oxo- (2,2,2-trifluoroethoxy) -1-propenyl-4'-cyclopropanecarboxylic acid (Preparation I) and the corresponding alcohol.

Example 26: (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl] cyclopropanecarboxylic acid (3-propar methyl (2,5-dioxoimidazolidinyl) methyl ester 25 = -4 ° + 1 ° (c = 1% benzene)

Example 27; (1R cis) 2,2-Dimethyl-3- [N- (Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl] cyclopropanecarboxylic acid (R) -N-methyl-3- Phenoxybenzyl ester 30 = + 108.5 ° + 2 ° (c = 1% CHCl 3) 38,78066

Example 28; (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3- (2,2,2-trifluoro-ethoxy) -1-propenyl] -cyclopropanecarboxylic acid 3,4,5,6-tetrahydro-phthalimido methyl ester δ = -2.5 ° + 2 ° (c = 0.5% CHCl 3)

Example 29: (1R cis) 2,2-Dimethyl-3- [C (Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl] cyclopropanecarboxylic acid (R) o6-ethyl -nyl-3-phenoxy-benzyl ester 10 e <D = + 42 ° + 1.5 (c = 1% CHCl 3)

Example 30; (1R cis) 2,2-Dimethyl-3- [7 (Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl] -cyclopropanecarboxylic acid (RS) «C-cyano-6- phenoxy-2-pyridyl methyl ester 15 ° (D = + 46.5 ° + 2 ° (c = 0.7% CHCl 3) 5 °) (1R cis) 2,2-dimethyl-3 '- (z) - 3-Hydroxy-3-oxo-1-propenyl] -cyclopropanecarboxylic acid (S) -N-cyano-3-phenoxy-benzyl ester (Preparation VII) and the corresponding alcohol.

Example 31: (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3- (2,2,2-trichloroethoxy) -1-propenyl] -cyclopropanecarboxylic acid (S) o-cyano - 3-phenoxy-benzyl ester = + 42.5 ° + 2 ° (c = 0.5% benzene) Example 32; (1R cis) 2,2-Dimethyl-3-ZT (Z) -3-oxo-3- (2-chloro-ethoxy) -1-propenyl-7-cyclopropanecarboxylic acid (S) -N-cyano-3-phenoxy-benzyl ester = + 39 ° + 4 ° (c = 0.25% benzene) 39 78066

Example 33; (1R cis) 2,2-Dimethyl-3-Z '(Z) -3-oxo-3- (2-methoxyethoxy) -1-propenyl] -cyclopropanecarboxylic acid (S) -i-cyano-3-phenoxy- benzyl ester δ = + 37.5 ° + 2 ° (c = 1% CHCl 3)

Example 34; (1R cis) 2,2-dimethyl-3-Z '(Z) -3-oxo-3- (RS) -1-cyanoethoxy) -1-propenyl-7-cyclopropanecarboxylic acid (S) p (cyanoacid) 3-Phenoxy-benzyl ester 10 D = + 64 DEG + 3 DEG (c = 0.3% CHCl3)

Example 35: (1R cis) 2,2-Dimethyl-3- [T (Z) -3-oxo-3- (2-fluoroethoxy) -1-propenyl] cyclopropanecarboxylic acid (S) -4-cyano-3-phenoxy benzyl ester 15 = + =% benzene)

Example 36; (1R cis) 2,2-Dimethyl-3- (1Z) -3-oxo-3-phenethoxy-1-propenyl] -cyclopropanecarboxylic acid (S) -N-cyano-3-phenoxy-benzyl ester 20 VD = 46 ° + 2.5 ° (c = 0.50% benzene)

Example 37: (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3- (2,2-dimethyl-dioxolanyl-4- (RS) -methoxy) -1-propenyl] -Cyclopropanecarboxylic acid (S) * 4-cyano-3-phenoxy-benzyl ester 25 = + 46 ° + 2 ° (c = 0.75% benzene) 6 °) (1R cis) 2,2-dimethyl-3-ZT (Z) -3-Hydroxy-3-oxo-1-propenyl] -cyclopropanecarboxylic acid (RS) o-cyano-3-phenoxy-benzyl ester and the corresponding alcohol.

Example 38: (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3-30- (2-dimethylamino-ethoxy) -1-propenyl] -cyclopropanecarboxylic acid (RS) o-cyano- 3-Phenoxy-benzyl ester * D = + 23 ° + 3 ° (c = 0.25% CHCl 3) 40 78066

(1R cis) 2,2-Dimethyl-3 - [(Z) -3-hydroxy-3-oxo-1-propenyl] -cyclopropanecarboxylic acid (RS) n-cyano-3-phenoxybenzyl ester used as starting material in the previous example was prepared in an analogous manner to the (S) «C-cyano-3-phenoxybenzyl ester of Preparations 5 IV and VII.

7 °) (1R cis) 2,2-Dimethyl-3 - [(Z) -3-hydroxy-3-oxo-1-propenyl] -cyclopropanecarboxylic acid (R) * (.-Methyl-3-phenoxy-benzyl ester) (Preparation VIII) and the corresponding alcohol.

Example 39: (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3- (2-methoxyethoxy) -1-propenyl] -cyclopropanecarboxylic acid (R) o <-methyl-3- phenoxybenzyl ester 15 NMR CDCl 3 ppm 1.22 to 1.25 methyl protons of cyclopropane in position 2 1.45 to 1.55 methyl protons of cyclopropane in position 1 5.7 to 6.0 benzyl proton 3.42 methoxyl protons 4.22 a 4.38 Protons at position 1 of the ester in position 3 of the cyclopropane 3.55 2 3.72 Protons at position 2 of the ester in position 3 of cyclopropane 5.85-6.05 and ethylene protons 6.38 a 6.8

Example 40; (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3- (30-methoxy-1-trifluoromethyl-ethoxy) -1-propenyl] -cyclopropanecarboxylic acid (S) * 4, -cyano- 3-Phenoxy-benzyl ester 1.02 g of (1R cis) 2,2-dimethyl-3 - [(T) -3-chloro-3-oxo-1-propen-3-yl] -cyclopropanecarboxylic acid (S) were stirred together under an inert atmosphere. ) eC-cyano-3-3 41 78066 phenoxy benzyl ester and 9 cm methylene chloride. 1.12 g of 1-methyl-1-trifluoromethylethanol were added and stirring was continued for 48 hours at room temperature. The mixture was evaporated to dryness under reduced pressure, and the residue was purified by chromatography on silica gel eluting with a mixture of hexane and ethyl ether (8-2) to give 250 mg of the desired product, m.p. 59 ° C.

= + 57 ° + 2 ° (c = 0.4% benzene)

The (1R cis) 10,2-dimethyl-3 - [(Z) -3-chloro-3-oxo-1-propenyl] -cyclopropanecarboxylic acid (S) -cyano-3-phenoxybenzyl ester used as starting material in Example 40 was prepared reacting thionyl chloride with (1R cis) 2,2-dimethyl-3 - [(Z) -3-hydroxy-3-oxo-1-propenyl] -cyclopropanecarboxylic acid 15 (S) -N-cyano-3-phenoxy with benzyl ester (prepared te VIII).

Example 41; (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3- (1-trifluoromethylmethyl-propyloxy) -1-propenyl] -cyclopropane-20-carboxylic acid (S) cyano-3-phenoxybenzyl ester

900 mg of (1R cis) 2,2-dimethyl-3-ZT (Z) -3-chloro-3-oxo-1-propenyl-7-cyclopropanecarboxylic acid (S) -N-cyano-3-phenoxybenzyl ester were dissolved in 3 cm To 25 methylene chloride, 1 cm -1 of 1-trifluoromethyl-1-methylpropanol was added and stirred for 16 hours at room temperature under an inert atmosphere and protected from external moisture. The reaction mixture was allowed to stand for 3 days at room temperature and then washed with saturated aqueous sodium bicarbonate solution and then The residue was purified by chromatography on silica gel eluting with a mixture of hexane and ethyl ether (8-2) to give 570 mg of the desired product.

42 78066

Example 42; (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3- (2,3-dihydroxypropyloxy) -1-propenyl] -cyclopropanecarboxylic acid (S) -cyano-3- phenoxy-benzyl ester 5 A mixture containing 4.65 g of (1R cis) 2,2-dimethyl-3 - [(X) -3-oxo-3- (2,2-dimethyl-dioxolanyl-4-) was refluxed. RS) -methoxy) -1-propenyl-7-cyclopropanecarboxylic acid (S) -cyano-3-phenoxy-3,3-benzyl ester (Example 37), 46 cm of dioxane in 9 cm of water and 0.45 g of paratoluenesulphonic acid, for 45 minutes. Most of the dioxane was removed by distillation at 40 ° C under reduced pressure, and the residue 3 was taken up in 150 cm of methylene chloride and 25 cm of water. The mixture was stirred, the phases separated by decantation, the organic phase was washed with water, dried and evaporated to dryness under reduced pressure. The residue was purified by chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (3-7), to give 3.85 g of the desired product.

20 = + 53 ° + 2.5 ° (c = 0.5% CHCl 3)

Example 43: (1R cis) 2,2-Dimethyl-3-ZT (Z) -3-oxo-3- (2-tetrahydropyranyloxyethoxy) -1-propenyl-7-cyclopropanecarboxylic acid (S) -N-cyano-3-phenoxy benzyl ester 25 Step A; (1R cis) 2,2-Dimethyl-3-ZT (Z) -3-oxo-3- (2-tetrahydropyronyloxy) -1-propyl-17-cyclopropanecarboxylic acid ( RS) o-cyano-3-phenoxy-benzyl ester Prepared in an analogous manner to that described in Example 7, Step A, starting from 2.3 g of (1R cis) -2,2-dimethyl-3 '- (Z) -3-hydroxy 3-Oxo-1-propynyl-7-cyclopropanecarboxylic acid (RS)% E-cyano-3-phenoxy-benzyl ester and 7.5 g of 1-bromo-2- (2-tetrahydropyranyl) -oxyethane. 1.8 g of the desired product 35 were obtained by purification by chromatography on silica gel 43,78066, eluting with a mixture of cyclohexane and ethyl acetate (75-25).

Step B; (1R cis) 2/2-Dimethyl-3- [T (Z) -3-oxo-3- (2-tetrahydropyranyloxyethoxy) -1-propenyl] -cyclo-5-propanecarboxylic acid (RS) α-cyano-3- phenoxy si benzyl ester

The procedure was analogous to that described in Example 7, Step B, starting from the product obtained in Step A above. Chromatographic purification using a mixture of cyclohexane and ethyl acetate (80-20) as eluent gave 1.3 g of the desired product.

= + 33 ° + 1 ° (c = 1% CHCl 3).

The starting material used in the example is (1R cis) 2,2-di-15-methyl-S - ((Z) -3-hydroxy-3-oxo-1-propynyl) -7-cyclopropanecarboxylic acid (RS)? -Cyano-3-phenoxy- the benzyl ester was prepared in a manner analogous to that described for Preparation IV (S) o? -cyano-3-phenoxy-benzyl ester.

Example 44; (1R cis) 2,2-Dimethyl-3-Z1Z) -3-oxo-3- (2-hydroxyethoxy) -1-propenyl-7-cyclopropanecarboxylic acid (RS) o-cyano-3-phenoxy-benzyl ester

0.85 g of the product obtained in Example 43, 17 cm of ethanol, 5 cm of dioxane, 1 cm 3 of water and 4 cm 2N hydrochloric acid were mixed together and then stirring was continued for 3 hours. Then 1 cm of triethylamine was added, the mixture was evaporated to dryness, the residue was taken up in ice-water, extracted with methylene chloride, the extracts were washed with water, dried and the solvent was evaporated off. The residue was purified by chromatography on silica gel eluting with a mixture of cyclohexane and ethyl acetate (65-35) to give 0.65 g of the desired product.

30 D = + 42.5 ° + 2.5 ° (c = 0.5% CHCl 3).

44 78066

The following compounds can also be prepared by the process of the invention using the corresponding acids and alcohols as starting materials.

- (1R cis) 2,2-dimethyl-3 - [((Z) -3-oxo-3- (2- {1,1,1,3,3,3-hexafluoro) propoxy) propenyl] - 3-phenoxy-benzyl ester of cyclopropanecarboxylic acid.

= + 26.5 ° + 2.5 ° (c = 0.5% CHCl 3) - (1R cis) 2,2-dimethyl-3-Z "(Z) -3-oxo-3- (2- (1 (1,1,3,3,3-Hexafluoro) propoxy) -propenyl] -cyclopropanecarboxylic acid (S) o? -Cyano-3-phenoxy-4-fluorobenzyl ester (<= = 27 ° + 2 ° ( c = 0.8% benzene).

Preparation IV: (1R cis) 2,2-Dimethyl-3- (3-oxo-3-hydroxy-1-propynyl) -cyclopropanecarboxylic acid (S) -cyano-3-phenoxy-benzyl ester Step 15 A: (1R cis) 2,2-Dimethyl-3- (2-carboxy-ethynyl) -cyclopropanecarboxylic acid tert-butyl ester 26 g of (1R cis) 2,2-dimethyl-3- (2,2-dibromovinyl) - cyclopropanecarboxylic acid tert-butyl ester to 175 cm 3 of anhydrous tetrahydrofuran. Then, at -65 ° C, 60 cm 2 of a 20% solution of cyclohexane in butyllithium was added. After stirring for 1 hour at -60 ° C, bubbles of carbon dioxide gas were then added to the reaction mixture for 1.5 hours, then the mixture was poured into ice water to which 1N sodium hydroxide had been added. Washed with ether. The alkaline aqueous phase was acidified to pH 4 and extracted with ether. The organic phases were dried and evaporated to dryness under reduced pressure. The product thus obtained was recrystallized from petroleum ether (b.p. 60-80 °). 8.3 g of the desired product are thus obtained, melting at 144 ° C.

45 78066 NMR CDCl 3 ppm 1.22 and 1.37 Protons of methyls in position 2 of cyclopropane 1.78 Protons in positions 1 and 3 of cyclopropane 1.47 Protons of terbuthyl 8.25 Proton of group -C-OH

II

0

Step B; (1R cis) 2,2-Dimethyl-3- (2,2,2-trichloro-10-ethoxycarbonyl-ethynyl) -cyclopropanecarboxylic acid tert-butyl ester 6.2 g of dicyclohexylcarbodiimide were added to a solution of 7.15 g ( 1R cis) 2,2-Dimethyl-3- (2-carboxyethynyl) -cyclopropanecarboxylic acid terbuthyl ester, 80 mg of dimethylaminopyridine and 35 cm -1 of methylene chloride. The reaction mixture was stirred for 10 minutes and then 4.5 g of 2,2,2-trichloroethanol was added. Stirring was continued for 1 hour and the precipitate formed by filtration was removed. The batch of 20 was washed with 1N hydrochloric acid and then with water until the washings were neutral, dried and evaporated to dryness. 14 g of an oily product were obtained, which was purified by chromatography on silica gel eluting with a mixture of benzene and ethyl acetate (97-3). Thus 9 g of the desired product are isolated, melting at 70-71 ° C.

Step C; (1R cis) 2,2-Dimethyl-3- (2,2,2-trichloro-ethoxycarbonylethynyl) -cyclopropanecarboxylic acid Boil under reflux for 1 hour a mixture of 11.4 g of the product prepared in step B, 120 cm -1. toluene and 300 mg of paratoluenesulfonic acid. The mixture was allowed to cool to room temperature, then washed with water, dried and evaporated to dryness. There was thus obtained 9.5 g of the desired product, which was used as such in the next step.

46 78066

Step D: (1R cis) 2,2-Dimethyl-3- (2,2,2-trichloro-ethoxycarbonyl-ethynyl) -cyclopropanecarboxylic acid (S) -cyano-3-phenoxy-benzyl ester 6.2 g of dicyclohexylcarbodi were added. -imide 5 to a solution of 9.5 g of the compound 3 prepared in step C, 30 cm of methylene chloride and 3 cm of pyridine. The reaction mixture was stirred for half an hour and a solution of 6.8 g of (S) "C-cyano-3-phenoxy-bentsyylialko-alcohol. Stirring was continued for one and a half hours. The formed 10 insoluble matter was separated by filtration. The filtrate was washed with 1N hydrochloric acid and then with water until the wash water was neutral. The filtrate was dried, filtered and evaporated to dryness. 16.3 g of an oily product were obtained, which was purified by chromatography on silica gel eluting with a mixture of benzene and ethyl acetate (97-3). There was thus obtained 12 g of the desired product, melting at 101 ° C.

Step E; (1R cis) 2,2-Dimethyl-3- (3-hydroxy-3-oxo-1-propynyl) -cyclopropanecarboxylic acid 20 (S) o-cyano-3-phenoxy-benzyl ester

5.9 g of zinc flour were added to a solution of 6.5 g of the product prepared in step D, 23.4 cm 3 of acetic acid and 2.6 cm of water. The mixture was stirred for one hour. The mixture was filtered and the filtrate was decanted.

The organic phase was washed with water and the aqueous phase was extracted with methylene chloride. The methylene chloride solutions were combined, dried, filtered and evaporated to dryness. There was thus obtained 4.7 g of crude product, which was used as such.

30 Preparation V; (1R cis) 2,2-Dimethyl-3-Z '(Z) 3-hydroxy-3-oxo-1-propenyl-7-cyclopropanecarboxylic acid tert-butyl ester

Hydrogenation of 2 g of the (1R cis) 2,2-dimethyl-3-ZT2-carboxyethynyl7-35 cyclopropanecarboxylic acid tert-butyl ester prepared in Step IV of Preparation IV, 47 78066 ethyl acetate at 40 cm -1 in the presence of 0.38 g of palladium hydroxide as a 10% barium hydroxide mixture and 0.4 cm-1 quinoline. The mixture was filtered, the filtrate was washed with 0.5N hydrochloric acid and then with water until the washings were neutral, dried, evaporated to dryness under reduced pressure to give 2 g. the desired product, melting at 94 ° C.

Preparation VI; (1R cis) 2,2-dimethyl-3-Z "(Z) 3-oxo-3- (2- (1,1,1,3,3,3-hexafluoro) -propoxy) -1-10 propenyl] - -cyclopropanecarboxylic

Step N: (1R cis) 2,2-Dimethyl-3 - [(Z) 3-oxo-3- (2- (1,1,1,3,3,3,3-hexafluoro-propoxy) -1 -propenyl-7-cyclopropanecarboxylic acid tert-butyl ester The procedure was as in Example 9, Step A, using 3.6 g of (1R cis) 2,2-dimethyl-3-ZT (Z) -3-hydroxy-3-oxo-1-propenyl / -cyclopropanecarboxylic acid tert-butyl ester (Preparation V) and 3 g of hexafluoroisopropanol Elution with a 4: 6 mixture of benzene and cyclohexane gave 4.9 g of the desired product, mp = 92 ° C.

Step B: (1R cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3- (2- (1,1,1,3,3,3-hexafluoro) -propoxy) - 1-Propenyl-7-cyclopropanecarboxylic acid The procedure was the same as in Example 11, Step B, starting from 4.9 g of the product obtained above, and 4.2 g of the desired product were obtained.

IR CHCl 3 OH acid, mono 3500 cm -1 + dimer C = O ester, conj. 1755 cm? 30 1744 <»'acid 1695 cm C = 0 conjug. 1627 cm -1 double methyls 1380 cm ** ^ 48 78066

Preparation VII: (1R cis) 2,2-Dimethyl-3- [1 (Z) -3-hydroxy-3-oxo-1-propenyl] -cyclopropanecarboxylic acid (S) * E-cyano-3-phenoxybenzyl ester 5 4.7 g of (1R cis) 2,2-dimethyl-3- (2-carboxyethynyl) -cyclopropanecarboxylic acid (S) -N-cyano-3-phenoxybenzyl ester (Preparation IV) were hydrogenated in 45 cm of ethyl acetate in the presence of 500 mg of palladium - 3 hydroxides as 10% barium sulphate mixture and 6.5 cm 10 quinoline. The mixture was filtered, the filtrate was washed with 1N hydrochloric acid, then with water until the washings were neutral, dried and evaporated to dryness. 5.1 g of an oily product were obtained, which was purified by chromatography on silica gel eluting with a mixture of hexane, ethyl acetate and acetic acid (70-30-1). This gave 3.8 g of the desired product.

Preparation VIII; (1R cis) 2,2-Dimethyl-3-Z '(Z) 3-hydroxy-3-oxo-1-propenyl-7-cyclopropanecarboxylic acid (R) o-N-methyl-3-phenoxy-20-benzyl ester

Step A; (1R cis) 2,2-Dimethyl-3-ZT3-oxo-3- (2,2,2-trichloro-ethoxy) -propynyl-7-cyclopropanecarboxylic acid (R) β-methyl-3-phenoxy-benzyl ester The procedure was as described for the preparation. IV in Step D using 6 g of (1R cis) 2,2-dimethyl-3- [3-oxo-3- (2,2,2-trichloroethoxy) -propynyl] -cyclopropanecarboxylic acid and 4.1 g of 1- (R) (3-phenoxy-phenyl) -ethanol. Purification by chromatography gave a mixture of cyclohexane and ethyl acetate (8-2) eluting with 4.38 g of the desired product.

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Step B; (1R cis) 2,2-Dimethyl-3 - [(Z) 3-oxo-3-hydroxy-propynyl] -cyclopropanecarboxylic acid (R) oC-methyl-3-phenoxy-benzyl ester 3

4.16 g of the product obtained above were dissolved in 4 cm 3 of methylene chloride and 45 cm of a 10% aqueous solution of acetic acid and 0.53 g of zinc flour were added and stirred for 30 minutes at room temperature, 0.53 g of zinc flour was added again until the reaction was over (4 times). After 3 hours, the mixture was filtered and extracted with methylene chloride. The organic phase was washed with water, dried, evaporated to dryness by azeotropic distillation with toluene to give 3.05 g of the desired product.

Step C: (1R cis) 2,2-Dimethyl-3-ZT (Z) 3-hydroxy-3-oxo-15-propenyl] -cyclopropanecarboxylic acid (R) -4-methyl-3-phenoxybenzyl ester The procedure was as in Example 7. B starting from the product obtained in step B above and 2.9 g of the desired product were obtained as a crude product, which was used as such.

Examples of Compositions Example A: Preparation of a Soluble Concentrate A homogeneous mixture of the following ingredients was prepared: 0.25 g of the product of Example 1

Piperonylbutoxide 1 g

Tween 80 0.25 g

Topanol A 0.1 g

Water 98.4 g 50 78066

Example B: Preparation of an emulsifiable concentrate Thoroughly mixed together:

0.015 g of the product of Example 1

Piperonylbutoxide 0.5 g 5 Topanol A 0.1 g

Tween 80 3.5 g

Xylene 95.885 g

Example C: Preparation of an emulsifiable concentrate A homogeneous mixture of the following 10 ingredients was prepared:

1.5 g of the product of Example 1

Tween 80 20 g

Topanol A 0.1 g

Xylene 78.4 g Example D: Preparation of a smokable composition Homogeneously mixed together:

0.25 g of the product of Example 1

Taboo powder 25 g

Cedar leaf powder 40 g 20 Pine sawdust 33.75 g

Brilliant green 0.5 g p-nitrophenol 0.5 g

Study on the effect of the compounds according to the invention on parasites 25 l ^) __ Study ^ on the lethal effect on parasites

The insects tested were female houseflies 4-5 days old. The experiment was performed by externally placing 1 μl of the product's acetone solution in the middle body of the insects on the dorsal side using an Arnold 30 micromanipulator. The same dose and the same treatment were always given to 50 individuals. Mortality was observed 24 hours after treatment.

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The result obtained, expressed as the DL 2 value, i.e. the dose (in nanograms) required to kill 50% of the insects, was as follows:

Example compound ^ 50 5 (nanograms per individual __________) _ 1 1.115 23 0.962 29 0.825 10 Conclusion: In the test performed, the products of Examples 1, 23 and 29 were remarkably active.

2 °) Study on the effect on Sporodoptera littoralis larvae

The experiments were performed by placing an acetone solution of the product to be tested externally on the dorsal middle body of the larvae using an Arnold micromanipulator. The larvae used were in the fourth instar stage, i.e. about 10 days old, when kept at 24 ° C and 65% relative humidity.

20 After treatment, the individuals were placed in an artificial food environment (Poitout environment).

Mortality was examined 48 hours after treatment.

The experiments gave the following results: 25 Example DL50 compound___ (ng per individual) 1 4,699 35 0,544

Conclusion: In the test performed, the products of Examples 1 and 35 had good activity.

3 °) Study of the effect of shock on houseflies

The insects tested were 4-5 day old female houseflies. The experiment was performed by spraying directly in a Kerns and March chamber using a mixture of equal amounts of 78066 3 acetone and Isopar L (volume of solution used 2 x 0.2 cm) as solvent. Approximately 50 individuals were treated with each dose. The check was performed every minute for up to 10 minutes and then 15 minutes after the start of the treatment, and the KT 50 value was determined by conventional methods.

The following results were obtained:

Concentration of Example KT 50 product in minutes _ q / 1_ 10 1 3,534 1 2 3,608 0,25 26 1,550 0,25 30 3,498 1 35 2,894 1 15 Conclusion: In the test used, the products of Examples 1, 2, 28 30 and 35 had good activity.

4 °) Study of the effect on tarpaulin through tarsal contact (compound of Example 1)

The insects tested were male russa-20 moths (Blatella germanica). The experiment was performed by placing a certain concentration of acetone solution on the bottom of a 20 cm diameter petri dish. The solution was allowed to dry and then placed in a dish with 20 male brownheads and allowed to stand for one hour, after which they were transferred to normal environment and examined for mortality 24 hours, 48 hours and 5 days later.

The result, expressed as a 50% lethal concentration (CL 50), was 0.216 mg / m 2 for the product in question.

Conclusion: In the test used, the product showed very good activity.

5 °) Effect on Tetranychus urticae (Product of Example 1) Adultisidi study 35 Bean seedlings with 78066 two cotyledons each were used. The seedlings were treated with an acetone solution of the product in question using a Fisher spray. After the plants had dried, 25 female Tetranychus urticae mites, i.e. 50 individuals per test dose, were admitted to each leaf.

Efficacy was checked at 1, 24, 48, and 72 hours after the first contact.

At a dose of 2.8 g / l the product showed very good activity.

Claims (7)

1. Pyrethroid compounds in 1Rcis-isomeric form / which have the formula (I *) ro2c - CH = CUS 2 or a group H 0- ° -0R4 where R 2 is a group -CsN, a methyl group, or a group -CsCH, or a group 0 I n-ch 2 30. In 2 -CH 2 -nJ 0 or a group CN r \. <+ - C- ° 78066 or a group CN Γ, - \, - "yY" -G and R is one with one or more halogen atoms, phenyl, C amino, hydroxy, 2,2-dimethyl-dioxolanyl or tetrahydropyranyloxy groups substituted C 1-6 alkyl group or a phenyl group. A process for preparing pyrethroid compounds in 1Rcis isomeric form having the formula (I ') / K R02C-CH = CH, / \ CO R is the same as in claim 1, characterized in that the 1Rcis, Z-isomer of an acid of formula (II) - or a functional derivative thereof, is reacted with an alcohol of formula (III) A ' - OH (III) wherein R and A * in formulas (II) and (III) represent the same as in claim 1. A process for the preparation of the compounds of formula (I ') as defined in claim 1, characterized in that a compound of 1Rcis form and of formula (XI) H, C N / HO 2 C-HC = CH 2 ). 5 Process for the preparation of the compounds defined in claim 1, characterized in that a compound of formula (XV) H, C, CH, V Claim 1, is reacted with an esterification agent to obtain the compound of formula (X) H, C CH-vf RO 2 C-CsC \ y CO 2 H · (X) wherein R and A with a catalyzed hydrogenating agent to give the compound of formula (I '). 5. Insecticide compositions, characterized in that, as the main active ingredient, they contain at least one compound as defined in claim 1. Compounds useful as intermediates in the preparation of the compounds of formula (I ') as defined in claim 1, characterized in that they are 1Rcis, Z-isomers of compounds of formula (II) RQ2C-CHgCHX II) or their acid chlorides, in which formula R is the same as in claim 1. Compounds useful as intermediates in the preparation of compounds (I ') as defined in claim 1, characterized in that they are 1Rcis, Z-isomers of compounds of formula (VII)