NZ198515A

NZ198515A - Cyclopropane carboxylic acids,esters,and pesticidal and pharmaceutical compositions

Info

Publication number: NZ198515A
Application number: NZ198515A
Authority: NZ
Inventors: J Martel; J Tessier; A Teche
Original assignee: Roussel Uclaf
Priority date: 1980-10-01
Filing date: 1981-09-30
Publication date: 1985-03-20
Also published as: DK164740B; DE3169688D1; IL63979A0; HU195759B; PT73753B; ES505887A0; SU1473707A3; ATE12490T1; BR8106299A; MA19293A1; ZW24181A1; AU548041B2; DK432781A; FI78679C; DK164402B; FI78679B; EP0050534A1; FR2560189A2; DD211473A5; JPS57126447A

Abstract

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

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number 1 98515 4 ■*,' 9 1 Oqc i rr J;OJiJ • ■ a t ■ Prlcriiv •'[~'[9'*°'"V0.c}.,2i CooetsA*?^ wfschication R<3d. • .•■ • • • C07MCOlCb/;mfi/53/Op^ ,. c^'Am 3\/XtS £.0 MAR teas P.O. Jeurns!?, No 12U, Patents Form No. 5 NEW ZEALAND PATENTS ACT 1953 COMPLETE SPECIFICATION " ESTERS OF CYCLOPROPANE CARBOXYLIC ACIDS RELATED TO PYRETHRIC ACID, THEIR PREPARATION PROCESS AND THEIR APPLICATION FOR COMBATTING PARASITES" -I-/WE ROUSSEL-UCLAF, a French Body Corporate of 35 Boulevard des Invalides, 75007, Paris, France, hereby declare the invention, for which -i-/we pray that a patent may be granted to me/us , and the method by which it is to be performed, to be particularly described in and by the following statement:- - 1 - (followed by pa*e \ * ^ 198515 u- 1" [MMI I " """"* Esters of cyclopropane carboxylic acids related to pyrethric acid, their preparation process and their application for combatting parasites. Company named:.- ROUS SEL-UCLAF The invention is concerned with new esters of cyclopropane carboxylic acids, the process for preparing thsm and their application for combatting parasites. The subject of the invention is the compounds with 5 the formula I: |.n all t&ga»—poooiblo ioomorio forme/ in which R represents either a linear, branched or cyclic alkyl radical, saturated or unsaturated, containing from 1 to 8 carbon atoms, ftoasibly-' substituted by one or more functional 10 groups, identical or different, or an aryl group containing optxencoCUj from 6 to 14- carbon atoms, jHJSsibl/" substituted by one or more functional groups, identical or different, (I) 198515 2 or a heterocyclic radical optionally substituted by one or more functional groups, identical or different, B represents the residue of an alcohol utilized in the synthesis of the esters of the pyrethrinoid- (series, and X represents a halogen atom, the ethylene double bond having (E) geometry and the cyclopropane ring having (1R, cis) stereochemistry. The compounds with the formula (I) may exist in stereoisomeric forms where one or more centres of asymmetry are present in the part B and/or in the part R. When R represents a saturated linear or branched alkyl radical, it is preferably a methyl, ethyl, n-propyl, isopropyl, n—butyl, sec—butyl, isobutyl, n-pentyl, n—hexyl, tert-butyl, tert-pentyl or neopentyl radical. When R represents a cyclic alkyl radical, it is preferably 27SZP1984 - 3 - 198515 a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl radical, a linear or branched alkyl radical carrying a cyclic radical, or a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl radical substituted by one or more 5 alkyl radicals of which the bond with the -CCO- group is situated on any one of its apices, for example, a 1-methylcyclobutyl, 1-methylcyclopentyl, 1-methylcyclo-hexyl or 2,2, 3,3-tetramethylcyclopropyl radical. When R represents an unsaturated alkyl radical, it as, 10 may be an ethylene radical, sueV for example, a vinyl or a 1,1-dimethylallyl radical, or an acetylene as, radical, such/for example, an ethynyl or a propynyl radical. When R represents an alkyl radical substituted by 15 one or more functional groups, there is preferably understood by alkyl a radical containing from 1 to 8 carbon atoms, such, for example, as a methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl or tertbutyl radical. The functional groups may,for example, be selected, fra 20 halogen atoms, OH and SH groups, . OR' and SR' grovps in which R' represents an alkyl radical containing from 1 to 8 25 carbon atoms, /" r \ -NO2 groups,andfej- groups -N in which R" and R" 1 , R" 198515 - 4 - each identical or different,/ represent a hydrogen atom, or an alkyl radical containing from 1 to 8 carbon atoms, -C^N, -30jH, and -PO^I^ .groups and -COalk^, -S02alk2? arrl-SOjalkj groups, in which alk^, alk£ and 5 alk^ represent alkyl radicals containing from 1 to 18 carbon atoms. R can also represent an alkyl radical substituted by an aryl radical such as, for example, a benzyl or a phenethyl radical, itself optionally substituted by 10 one or more-0H,-0alk or alk groups containing from 1 to 8 carbon atoms, by one or more halogens or -CF^, -OCF^, -SCF^, or by a group (G): (G) R can also represent an alkyl radical substituted on two adjacent carbons by a group (G^) 0 H C ^ 0"^ " (Gx) 15 orsubstituted by a group -0- N.Z. PATENT C7-; 27 SEP L When R represents an alkyl radical substituted by one or more functional groups, preferred meanings for R are the radicals: 198515 s - -(CH^^-CHal^ in which n is an integer from X to 8 and Hal is a halogen atom, for example a -CH^CCl^, -CH^CF^, -CH2-CH2-CC1j or -CH2-CH2-CFj radical, -(CH2)n^, -CH Hal2 in which Hal is defined as above and n is a numeral from 0 to 8, for example a -CH2-CHC12, -CH2-CHF2 or -CHF2 radical, -(CH2)n-CH2 Hal in which n and Hal are defined as above, for example a -CHg-C^Cl or -C^-CH^ radical, -C-(CHal^)^ in which Hal is defined as above, for /0F5 example a -C-(CF^)^ or -C CF^ radical, CC1 3 or -C radical, or -(CH2)n-CN radical, in C—CN . -C CN which n is defined as previously CHal 3 C CN radical, in which Hal is defined as H XT5 .CC1 previously, for example a -C CN radical H i a p tr 1 c ' ■' I / u J l J - 6 - -(CHg^-OR' radical, in which n is defined as previously and R1 represents a hydrogen atom or a linear or branched alkyl radical, containing from 1 to 8 carbon atoms, for example a -CHg-OCH^, -C^-CH^O-CH^, 5 or -CHg-C^-OH radical, or a R' -(GH2)n radical, in which n and R1 are defined \r" as previously and the two R' radicals may not be identical, 10 ■ /CH? for example a -GH2~GH2-N^ , CH-x CH, / / 5 -CH0-GH 0-N or -CH0-CH0-Ir radical, or a 2 2 \ 2 2 \ 15 CH^ CH2-CH3 -(CH2)n-<jJH <j3H2 radical, in which n is defined as °x° H ^CH3 previously, for example a -GH^-CH GH2 radical., or a H^C CH^ 2° -(CH2)n -CH—-jJH2 radical, in which n is defined as OH OH previously, for example a -CHg-CH-CHg-OH radical, or a OH -(C^^-O- ^ N radical, in which n is defined as 198515 - ? - 10 15 20 previously, for example a or a -ch2-CH2-O-^/CN radical, or a -(CH2)n- ff \ radical, in which n is defined as previously, for example f~\ N> a benzyl or a phenethyl radical, or a -(CH~) 2'n 5 radical, in which n is defined- as previously, for example, When R represents an aryl radical optionally substituted, it is preferably a phenyl radical or a phenyl radical substituted by one or more OH, Oalk, or alk groups, containing from 1 to 8 carbon atoms, or by a halogen, or a -CF^, -OCFj or a -SCF^ group. When R represents a heterocyclic radical, it is preferably a pyridinyl, furanyl, thiophenyl, oxazolyl or thiazolyl radical. As halogen, is preferred. a fluorine, chlorine or bromine atom. N.Z. PATENT 2 7SEP1984 n -A c 'i; v ■. * Among the compounds according to the invention, there can be cited the compounds with the formula I in which X 198515 6 - represents a fluorine atom; there can also be cited the compounds with the formula I in which R represents a linear, branched or cyclic alkyl radical, containing from 1 to 8 carbon atoms, and in particular an ethyl 5 radical, a tert-butyl radical, or even a cyclopropyl or a cyclopropylmethyl radical. There can also be cited the compounds with the formula I in which R represents a linear or branched alkyl radical, containing from 1 to 8 carbon atoms, substituted by one or several halogen 10 atoms, for example those in which R represents a linear alkyl radical, containing from 1 to 8 carbon atoms, substituted by one or more fluorine atoms. There can also be cited the compounds with the formula I in which R represents a (CHg^OCCHg^-CH^ radical in which m 15 represents an integer from 1 to 8 and n represents O or i /an integer from G5 to 8, and in particular, the radical -CH^O-CH^. There can also be quite specially cited the compounds with the formula I for which B represents: 20 - either a benzyl radical optionally substituted by one or more radicals chosen from the group constituted by the alkyl radicals containing from 1 to 4 carbon atoms, the alkenyl 25 radicals containing from 2 to 6 carbon atoms, the alkenylox3 radicals containing from 2 to 6 carbon atoms, the alkadienyl radicals containing from A- to 8 carbon atoms, 2 7SEPS984 1 198515 - 9 - the methylene dioxy radical and halogen atoms, or a group CH2R2 in which the substituent R^ represents a hydrogen atom or a methyl radical and the substituent R2 represents a monocyclic aryl radical or a group -CH2~C = CH and in particular a 5-benzyl 3-furyl methyl group, - or a group a . 10 15 in which a represents a hydrogen atom or a methyl radical and R^ represents an aliphatic organic radical containing from 2 to 6 carbon atoms and one or more carbon-carbon unsaturations and in particular the radicals -CH2-CH=CH2, -CH2-CH = CH-CH^, -CH2-CH = CH-CH = CH2, or -CH2-CH = CH-CH2-GH5, - or a group a in which a represents a hydrogen atom or a methyl radical, R^ retains the same signifi^^^g^^reviously, R'^ and R'2, (* 16hov,98i 198 515 10 - 10 - identical or different, each represents 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 alkoxycarbonyl . group containing from 2 to 5 carbon atoms, or a cyano group, - or a group in which B' represents an oxygen or a sulphur atom or 0 II a -C- or -CH^- group, or a sulphoxide group or a sulphone group, and R^ represents a hydrogen atom, a C=N radical, a methyl radical, a -CONH2 radical, a CSNH2 radical or a -C=CH radical, R,. represents a halogen atom or a methyl radical, and n represents O, 1 or 2, and in particular, the 3-pbenoxy benzyl group, or the I5 a-cyano-3-phenoxy benzyl, a-ethynyl-3-pkenoxy benzyl, 3-benzoyl benzyl, l-(3-phenoxy-phenyl)ethyl, or the o-thioamido—3-pbenoxy benzyl group, vif & or a group ; 29H0V°i984 . /■ - 11 - 198515 CN - or a group -CEU- in which, the substituents Rg, R,-,, Rg and R^ each represent a hydrogen atom, a chlorine atom or a methyl radical and in which S/I symbolizes an aromatic pjold or analogous dihydro or tetrahydro cycle, - or a group -ch2 - / Ijf-CH2 - C = CH V or a group R, I 10 CH - R 11 " R12 -o 198515 - 12 - represents a hydrogen atom or a CN radical, in which R-j R^2 represents a -CH^- radical or an oxygen atom, represents a thiazolyl radical or a thiadiazolyl radical, of which the bond with -CH- can be found at any one of ^10 the available positions, R^ being attached to R^ by the carbon atom included between the sulphur atom and a nitrogen atom, - or a group - or a group 10 in which R^ represents a hydrogen atom, or a CN radical, - or a group & l9*> 1 198515 - 13 - in which R.^ is defined as above, and the benzoyl radical is in position 3 or 4, - or a group or- in which R^ represents a hydrogen atom^ a methyl, ethynyl CV»cf or cyano radical, and R, and R-,aj-whioijf are different/ <racJ\ rzprtt^esrts xe> a frepreacnt a hydrogen, fluorine or bromine atom, - or a group (ri?^p N -a; - ; V.-4 n - _ .7.. !• vrfcN? . •: 7SET1984 PF-' • *>' in which R-^ is defined as above, each of the R^r, represents independently an alkyl group containing from 1 to A- carbon atoms, an alkoxy group containing from 1 to 4 carbon atoms, an alkylthio group containing from 1 to 4 carbon atoms, an alkyl sulphonyl group containing 198515 - 14 - from 1 to 4 carbon atoms, a trifluoromethyl group, a 3,/J— methylene dioxy group, or a chlorine, fluorine or bromine atom, p represents /a numoraj 0, 1 or 2 and B" represents an oxygen or a sulphur atom. 5 When B represents a benzyl radical substituted by the (or each) altcyl fZLoUx.a£ one or more alkyl radicals, it is preferred to be a methyl or an ethyl radical. When B represents a benzyl radical substituted by one or more alkenyl radicals, they are preferred to be 10 vinyl, allyl, 2-methylallyl or isobutenyl radicals. When B represents a benzyl radical substituted by an alkadienyl radical, -if is preferred to be a benzyl radical substituted by an alkadienyl radical containing 4, 5 or 6 carbon atoms. 15 When B represents a benzyl radical substituted by one or more alkenyloxy radicals, they are preferred to be vinyloxy, allyloxy, 2-methylallyloxy or isobutenyloxy radicals. '//hen B represents a benzyl radical substituted by 20 one or more halogen atoms, they are preferred to be chlorine, bromine or fluorine atoms. When B represents the radical: •j preferably represents a a -CH2-CH=CH-CHj, 198515 - 15 - a -CH2-CH=CH-CH=CH2 or a -CH2-CH=CH-CH2-CHj radical. When R'^ and (or) R'2 represent a halogen atom, it is preferred to be a chlorine, bromine or a fluorine atom. When R'^ and (or) R'2 represent an alkyl radical, it is preferred to be a methyl, ethyl, n-propyl or n-butyl radical. When R'^ and (or) R'2 represent an aryl radical, it is preferred to be a phenyl radical. , When R'^ and (or) R'2 represent an ~arhrmy7 radical, it is preferred to be a methoxycarbonyl or an ethoxycarbonyl radical. When in the radical: R^y represents an alkyl, alkoxy, alkylthio or alkyl-sulphonyl radical, it is preferred to be a methyl, ethyl, methoxy, ethoxy, methylthio, ethylthio, methylsulphonyl or ethylsulphonyl radical. Among those compounds according to the invention for truzcLsiAsicf s which B has the ^ignifioane4 mentioned above, there can be cited the compounds corresponding to the formula 1^: - 16 - 1 Q P C. 1 C 1 / o 0 i O HXC CH, \ / 5 -H X H \ A in which A represents an oxygen atom, a methylene group, a carbonyl group, a sulphur atom, a sulphoxide group or a sulphone group, R^g represents a linear or branched alkyl radical containing from 1 to 8 carbon atoms, represents a fluorine, chlorine or bromine atom, the In the compounds with the formula can represent a linear or branched alkyl radical, in particular a methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl or octyl radical, these latter radicals being able to be linear or branched. double ethylene/bond having (E) the substituted cyclopropane ring having .stereochemistry. 198515 - 17 - In particular, the subject of the invention is the compounds with the formula 1^ for which A represents an oxygen atom. Among these preferred compounds, there can quite specially be cited ts) a-cyano-3-phenoxy benzyl tIR,eia) 2,2—dimethyl—3 (E) -2-f luoro—2- (ethoxy carbonyl) ethenyl/-eyelopropane-l-carboxylate. Among the preferred compounds according to the invention, there can also be cited the compounds with the formula I for which B represents a radical: (lH.cn) those for which B represents a radical: -CH 2 0 those for which B represents a radical: *29 HOV »9S4 193515 I 3 - 18 - /V / \ those for which B represents a radical: C=CH as well as those for which B represents a radical: There can also be cited as preferred compounds according to the invention the compounds for which B represents a radical /3-(propyn-2-yl) 2,5-dioxo imidazolidinyl/methyl and also a radical a-cyano 6-phenoxy 2-pyridyl methyl. Qui-ce particularly, the subject of the invention is the compounds of which the preparatiags=q=s==given further 198515 - 19 - on in the experimental part, and in particular, among i il these, the compounds of examples 1, H and^21. The compounds with the formula (I) offer useful properties which enable then to be utilized in 5 combatting parasites. It can, for example, be a question of combatting the parasites of vegetation, the parasites of premises and the parasites of warmblooded animals. In this way, the products of the invention can be used to combat insects, aca-ti ols 10 nematodes and ftoaridanparaoito6 of vegetation and animals. use. Thus a subject of the invention is the jbipplientioA of the compounds with the formula (I) for combatting parasites of vegetation, parasites of premises and 15 the parasites of warm-blooded animals. In particular the subject of the invention is the Application of the compounds with the formula 1^ for combatting parasites of vegetation, parasites of premises and parasites of warm-blooded animals. 20 The products with the formula (I) can jbfcW be utilized in particular to combat insects in the agricultural domain, to combat, for example, plant-lice, the larvae of lepidoptera and coleoptera. They are utilized at doses between 10 g and 300 g of 25 active material per hectare. 198515 - 20 - The products with the formula (I.) can also be utilized to combat insects in premises, in particular to combat flies, mosquitoes and cockroaches. 1 " The compounds of examples 1, yi and 2Z. are quite remarkable products as the results of the tests further on show. They offer an excellent lethal power and a very good knock-down power. The products of formula (I) are in addition n<m~tcocii photostable and are loot—to mammals. The combination of these properties makes the products with the formula (I) correspond perfectly to the demands of modern agrochemical industry; they enable harvests to be protected while preserving the environment. The products with the formula (I) can also be utilized to combat the parasitic acaridae and nematodes of vegetation. The compolands with the formula (I) can also be utilized to combat the parasitic acaridae of animals, to combat ticks,' for example, and especially ticks of the Boephilus species, of the Hyalomnia species, of the 'Amblyomnia species and of the Ehipicephalus species, or to combat all sorts of manges and particularly sarcoptic mange, psoroptic mange and chorioptic mange. Thus equally a -subject of the invention is the i\;.ri<' '•-= i 2 7SEFM984 i 1985 - 21 - compositions intended to combat parasites of warmblooded animals, parasites of premises and vegetation, characterized in that they contain at least one of the products with the formula (I) defined above and in particular the products with the formula I^. The subject of the invention is particularly the insecticidal compositions containing at least one of the products defined above as active principle. Among the particularly insecticidal compositions preferred by the invention, there can quite specially be cited the compositions containing the compound of 7 example 1, the compound of example H and the compound of example 2aL These compositions are prepared according to the usual procedures of the agrochemical industry or of the veterinary industry or of the animal nutrition products industry. In the compositions intended for agricultural usage and for usage in premises, the active material or materials can have added to them one or more other pesticidal agents. These compositions can be presented in the form of powders, granules, suspensions, emulsions, solutions, solutions for aerosols, combustible strips, baits, or other preparations normally employed for the utilisation of this class of compounds. 198515 - 22 - In addition to the active principle, these compositions generally contain a vehicle and/or a surface-pension /active agent, non-ionic, which in addition ensures a uniform dispersion of the constituent 5 substances of the mixture. The vehicle utilized can be a liquid, such as water, alcohol, hydrocarbons or other organic solvents, a mineral, animal or vegetable oil, a powder such as talc, clays, silicates, or kieselguhr, or a combustible solid. 10 The insecticidal compositions according to the bu invention preferably contain from 0.005 % to 10 % in ^ weight of active material. An advantageous operating method for use in premises is to utilize the compositions according to the invention 15 in the form of fumigating compositions. The compositions according to the invention can then advantageously be constituted, as regards the non-active part by a combustible insecticidal serpentine (or coil) or also by a fibrous incombustible 20 substrate. In the latter case, the fumigant obtained after incorporation of the active material is placed on a heating apparatus such as an electric mosquito destroyer. In the case where an insecticidal serpentine is 25 utilized, the inert support can, for example, be composed of pyrethrum residues, Tabu powder^ 198515 - 23 - (or Machilus Thunbergii leaf powder), powdered stem of pyrethrum, cedar leaf powder, powdered wood (such as pine sawdust), starch and coconut shell powder. 5 The dosage of active material can then, for example, be 0.03 to 1% by weight. In the case where a non-combustible fibrous support is used, the dose of active material can then, for example, be from 0.03 to 95% by weight. 10 The compositions according to the invention for use in premises can also be obtained by preparing an atomisable oil based on the active principle, this oil then being soaked up by the wick of a lamp and thus being submitted to burning. 15 The concentration of active principle incorporated in the oil is preferably from 0.03 to 95% by weight. The insecticidal compositions according to the invention, such as the acaricidal and nematocidal 20 compositions can have added to them one or more other pesticidal agents. The acaricidal and nematocidal compositions can be presented in particular in the form of powders, granules, suspensions, emulsions and solutions. 25 For acaricidal use, it is preferred to use 198515 - 24 - powders which can be wetted for spraying on foliage containing from 1 to 80% of active principle, or liquids for spraying on foliage containing from 1 to 500 g/1 of active principle. Powders can also be du s tui'ty 5 used for ftowdei*ing on foliage, which contain from 0.05 to 3% of active material. For nematocidal usage, it is preferred to use liquids for the treatment of soils containing from 300 to 500 g/1 of active principle. 10 The acaricidal and nematgcidal compounds according to the invention are preferably used at doses between 1 and 100 g of active material per hectare. In order to increase the biological activity of the products according to the invention, classical synergists 15 used in similar cases can be added to them, such as l-(2,5i8-trioxadodecyl) 2-propyl 4,5~methylenedioxy benzene (or piperonyl butoxide) or N-(2-ethyl heptyl) bicyclo/2,2-l/5-heptene-2,3-di carboximide, or piperonyl-bis-2-(2'-n-butoxy ethoxy) ethylacetal 20 (or tropital). When it is required to combat parasitic acaridae of animals, the products according to the invention are very frequently incorporated in alimentary compositions in association with a nutritive mixture 25 suitable for animal feeding. The nutritional .v.-: 27SEP19£4 198515 - 25 - mixture can vary according to the animal species, it can contain cereals, sugars and grains, soya, ground-nut or sun-flower cake, meals of animal origin, for example fish-meals, synthetic amino-acids, mineral salts, vitamins and anti-oxidants. Thus a subject of the invention is the alimentary compositions defined above. The compounds according to formula (I) offer an excellent general tolerance, and thus the subject of the invention is also the products with the formula (I), tri a Jorm S^cUcJgJbt fcr t*»e j^as medicamentB, in particular to combat the diseases caused by ticks and manges. The medicaments according to the invention can be used both in human and in veterinary medicine. The medicaments according to the invention are used in particular in human medicine to combat lice both preventively or curatively and to combat mange. They can also be used as anthelmintics. The medicaments according to the invention can jbis</ be administered externally, by vaporisation, by shampooing, by bathing or by painting on. The medicaments according to the invention for veterinary usage can also be administered by painting on the dorsal spine according to the so called "pour-on" method. They can also be administered by digestive or parenteral route. 198 515- 26 - Thus a subject of the invention is the pharmaceutical compositions containing as active principle at least one of the medicaments previously defined. It can also "be pointed out that the products according to the invention can be utilized as biocides or as growth regulators. cevnpos ittcri s A subject of the invention is also the ^onbinatiens endowed with insecticidal, acaricidal or nematocidal activity, characterized in that they contain as active material on the one hand at least one of the compounds with the general formula (I) and on the other hand favtei at least one pyrethrinoid ester selected from frhthaliaide-*methyl alcohol, 5~beazyl-3_furyl methyl alcohol, 3-phenoxy benzyl alcohol and a-cyano -- 3-phenoxy benzyl alcohol with chrysanthemic acid • esters of 5-benzyl-3~furyl methyl alcohol with 2,2-dimethyl—3- (2-oxo -3-tetrahydrothiophenylidene — methyl) cyclopropane-1-carboxylic acid • esters of 3-phenoxy benzyl alcohol and a-cyano-3-phenoxy benzyl alcohol with 2,2-dimethyl-3*~(2,2-dichlororinyl) — cyclopropane-l-carboxylic acid . j esters of a-cyano — 3-phenoxy benzyl alcohol with 2,2-dimethyl-3-(2,2--dibromovinyl) ^cyclopropane-l-carboxylic acid ♦ esters of 3*~phenoxy b.enzyl alcohol esters of allethrolone,: 3fi,-i5»&"tetrahydrc , // 198515 - 27 - *3th2-parachlorophenyl-2-isopropyl acetic acid*; and esters of allethrolone , of 3t4,5»6-tetrahydro-phtha.tun '<4O phthaliaidc/ methyl alcohol, of 5-^>enzyl""3rfuryl. methyl alcohol, of 3-phenoxy benzyl alcohol and of a-cyano - - 3-phenoxy benzyl alcohol with. 2t2-di*ethyl— - 3- (1«2,2,2-t e t rahaolethyl) cyclopropane-l-carboxylic acids ( Vhere "halo" represents a fluorine, chlorine or bromine atom ) it being understood that the compounds (I) can exist in all their possible stereo-isomeric pltart these ejust forms^and likewise for the acid and alcohol moieties of the above pyrethrinoid esters, adbcve: Comf>ositxcris The ^fliliiiidtiuni according~to -the. invention are of particular interest by making it possible, through the polyvalence of their action, to combat a more extended range of parasites, and by exhibiting, in certain cases, a synergistic effect. The invention also has as its subject a process for the preparation of the compounds with the formula I, characterized in that an acid with the formula (II) : 193515 - 28 - in which X and R retain the same signification as previously, this acid being found in the form of the (E) isomer, and the substituted cyclopropane ring having the (*R,cis) stereochemistry, or a reactive . derivative of this acid, is made to react with an alcohol with the formula (III) : B-OH (III) B retaining the same significance as previously or with 10 a reactive derivative of this alcohol, so as to obtain the corresponding compound with the formula (I) which, if desired, is submitted to the action of a selective cleavage agent of the CO^R group, so as to obtain the compound with the formula (IV) : V (IV) d - OB retain 15 in which B and X / the same significance as previously, then this acid with the formula (IV) or a reactive 198515 - 29 -* derivative of this acid is submitted to the action of an alcohol with.the formula fi-OH in which R retains its previous significance, so as to obtain the corresponding compound with the formula (I). 5 A particular subject of the invention is a process according to the preceding one, for preparing the compounds with the formula 1^, as previously defined, characterized in that an acid with the formula (HA) ' 10 in which X^ and R^g retain the same significance as previously, this acid being (gounq! in the form of £ mixture of E and Z isuuiers, ur in the form of (O the |E or- the -3 isomer, and the substituted cyclopropane Mid (lR, to ) Stzt~i£OCJiemi$ir<w ring being able to be in all its sterea^-isomeric forms 15 ot in the form uf a mli.lu.rc of afcereo-isomers, or a mcticnt functional derivative of this acid (11^), is made to -\<!T '1 2 7SEPI534 193515 - 30 - (s) react with an/alcohol with the formula (III.) C (S)-OH / ^ > JL (inA) in which A retains the same significance as previously, or with a reactive derivative of the alcohol with the formula (III^). 5 The esterification of the acid (II) or (H^) with the alcohol with the formula (III) or (III^) can be carried out in the presence of a tertiary base such as pyridine. This esterification can be carried 10 out advantageously in the presence of a mixture of pyridine, dicyclohexyl carbodiimide and ^-dimethyl amino pyridine. \ The esterification can also be realized by making a chloride of the acid (II) or (11^) react with the 15 alcohol with the formula (III) or (III^) or with a metallic derivative of this alcohol, such as a silver salt. 198515 - 31 - The Vittig reaction generally used for the Jjirfnvuj. <x. preparation of the acids with the formu3-&« (II) or (H^) provides acids of which the double bond is E + Z. The isomers at the level of the double bond 5 can be separated, when it is required, by physical methods, such as chromatography, either at the . >. l.(s inaction ujith thti alufad cj fajj.) ) acid level or at the ester levey. Examples of these two methods are given further on in the experimental part. 10 The (X^R group cleavage agent is preferably heat, used with an acid hydrolysis agent. As acid hydrolysis agent, p-toluene sulphonic acid can be used. The esterification of the compound with the formula (IV) 15 is effected by the standard esterification methods, particularly those described above. The subject of the invention is also a preparation process according to what has preceded, characterized in that the acids with the formulae (II) or (H^) ia which 20 R or R1q represents an alkyl radical containing from 1 to 5 carbon atoms, are prepared by making a cis aldehyde in the form of a lactone with the formula (V) : (V) 19851 5 - 32 - or a trans aldehyde with the formula (VI) (VI) HO react by the Wittig reaction, in the presence of a strong base, with a phosphorane with the formula (VII) of (p),=P - 21) VC - OR (VII) 19 in which formula represents an alkyl radical containing from 1 to 5 carbon atoms and X and X^ retain their previous significances, or with a phosphonate with the formula (VIII) j ' t _ ™ 0 0 ; 2 j ^0 lP - CH X - C - 0R19 - 33 - 198515 in which formula R^, X and X^ retain their previously-stated significances and represents an alkyl radical containing from 1 to 6 carbon atoms. Acids with the formula (II) having the desired stereochemistry can also be prepared according to the following reaction scheme : 0 \ j| BuLi C - 0 tert-Bu ^ Cl-C-OR H I In the formulae of this scheme, X represents a fluorine, fthromintf or bromine atom, R represents an alkyl radical containing from 1 to 8 carbon atoms and the compounds utilized have the desired steric configuration. The acids with the formula II for which X represents a bromine atom can also be prepared by submitting a \ compound with the formula (IX) KOxCf&^ CO^alk (IX) 1 c o c i r: i u J i u - 34 - in which the geometry of the double bond is E, R retaining its previous signification and alk representing an alkyl radical, to the action of a bromiding agent, such, for example, as pyridinium tri-5 bromide, then to the action of a debromhydration agent, so as to obtain the compound with the formula (X) : C02alk W 10 If the debromhydration agent is a basic agent acting in fairly mild conditions, the (Z) isomer is obtained but under more severe conditions, the desired (E) isomer is formed, The experimental part gives an example of such a preparation where is used sodium hydroxide/in order to get 15 the E isomer. The compounds with the formula X can then be submitted to the action of an agent to cleave the C02alk function, so as to obtain the corresponding acid with the formula II. Examples of preparations of acids with the 20 formula II are given in the experimental part. y ^ €■ 198515 - 35 - The acids with the formulae II and particular those with well defined stereochemistry as well as the acids with the formula IV obtained during the putting into operation of the 5 invention process, are new products and they themselves are a subject of the invention. The invention naturally has more particularly as its subject the products with the formulae II, 11^ and IV, as necessary intermediate products for the 10 preparation of the compounds with the formulae I and I . The following examples illustrate the invention without nevertheless limiting it. — —— ! 275EP1984 1985)5 - 36 - Example 1 : (lK,cis) 2,2-dimethyl 3-(E)/2-fluoro 2-(ethoxy carbonyl) ethenyl/ cyclopropane- -1-carboxylate of (S) a-cyano 3-Phenoxy benzyl. Into a solution of 3.87 g of (lR,cis) 2,2-dimethyl 3(Z + E) 2-fluoro 2-ethoxycarbonyl ethenyl) cyclopropane- x -1-carboxylic acid in 30 cur of methylene chloride, * 1.5 cur of pyridine, and 3.7 g' of dicyclohexyl carbodiimide are introduced, and after agitating for 10 minutes, a solution of 4.05 g of (S) a-cyano 3~phenoxy * benzyl alcohol m 10 cur of methylene chloride is added and agitated for one hour and 30 minutes; 25 mg of 4*-dimethyl amino pyridine is added, the whole is agitated for one hour and 30 minutes, cooled to 0°C, and the insoluble matter formed is eliminated by filtration. The filtrate is concentrated to dryness by distillation under reduced pressure, the residue is chromatographed on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (80/20), the residue obtained is crystallized from ethyl acetate, the precipitate formed being separated. ' The mother-liquors are chromatographed oh silica gel, eluting with a mixture of cyclohexane and ethyl acetate (9/1) and in all 4.28 g of (lR,cis) 2,2-dimethyl 3(E) /2-fluoro 2-(ethoxy carbonyl) ethenyl/ cyclopropane-l-carboxylate of (S) a-cyano 3'**phenoxy benzyl is recovered, and 2.8 g of the 3(2) derivative. 1 9851 - 37 - Analysis : FN02 (437-47) 7 C% H% N% F% 2 7S.CP 1984 | Calculated : 68.54 5-53 3-20 4.34 | Pound: :68.8 5«5 3.1 4.2 IR Spectrum chloroform) - absorption at 1738 cm~^ and 1722 cm~^ attributed to the carbonyl and to the conjugated ester. - absorption at 1611 cm~^ attributed to the ftoublc/ clcmJjLe. ethylene^bond - absorption at 1589cm-'*" - 1489 cm" ^ attributed to the aromatic nuclei. - absorption -at 1380 cm""^" attributed to the paired methyls NKR Spectrum (deuterochloroform) - peaks at 1.2 - 1.27 p.p.m. attributed to the hydrogens of the paired methyls. - peaks at 1.23 - 1.35 ~ 1.47 p.p.m., 4.15 - 4.26 p.p.m. and 4.38 - 4.50 p.p.m. attributed to the hydrogens of the ethyl radical of the ethoxy carbonyl group. - peaks at 1.88 - 2.02 p.p.m. attributed to the hydrogen in position 1 of the cyclopropyl. - peaks at 2.8 - 3«13 p.p.m. attributed to the hydrogen in position 3 of the cyclopropyl. - peaks at 6.05 ~ 6.21 and 6.38 - 6.55 p.p.m. attributed dcTuJb IC to the hydrogen of the ethylene/bond. - peak at 6.36 p.p.m..attributed to the hydrogen carried by the same carbon as the C s N group. - peaks at 6.9 - 7*58 p.p.m. attributed to the hydrogens of the aromatic nuclei. 198515 - 38 - The (lR,cis) 2,2-dimethyl 3*"(E,Z) /2-fluoro 2-ethoxy carbonyl ethenyl / cyclopropane-l-carboxylic acid is obtained in the following manner. Into a solution of 12.1 g of ethyl diethyl 5 phosphoro fluoro acetate in 120 cnr of dimethoxyethane, 2 g of a 60% suspension in oil of sodium hydride is introduced at + 5°C, and after agitation for 30 minutes, 5.7 g of the lactone of (lR,cis) 2,2-dimethyl 3-dihydroxymethyl) cyclopropane-l-carboxylic acid is 10 introduced at 0°G. After agitation for 2 hours 30 0 mctcix minutes at 20 C, the freactional mixture is poured into an ice and water mixture containing monosodium phosphate, which is then extracted with ethyl ether. The re-united organic phases are washed with water, dried, and concentrated 15 to dryness by distillation under reduced pressure, the residue is chromatographed on silica gel, eluting with a mixture of cyclohexane, ethyl acetate and acetic acid (30/50/1) and 3-87 g of a mixture of (lR,cis) 2,2-dimethyl 3(E,Z)/2-fluo ro 2-ethoxyc arbonylethenyl/cyclopropane-1-20 -carboxylic acid is obtained. F;x ample 2 : (lR,cis) 2,2-dimethyl 3~(Z^r?2-fluoro-—1— 2-(ethoxycarbonyl) ejfctfenyl/ -cyclopropane-1--carboxylate qf'fs) a-cyano 3-phenoxy benzyl. From the chrcjjaef^ography in Example 1, which enabled 25 the derivatrjze^with the structure 3(E) to be obtained 2.8 g of residue^containing the derivative with the structure 3(Z) r i-'ATr. >'1 1 1 27SEP1984 F^U£!VED 198515 10 3^ - l*C - - peak at 6.47 p.p.m. att^fbuted to the hydrogen carried by the sarf^carbon as the -CN group - peaks at 6.9 ■?''/.58 p.p.m. attributed to the hydrogens of the aperfnatic nuclei. a '< Example 3 • (lR,cis) 2,2-dimethyl 3(E) /2-chloro 2-(methoxycarbonyl) ethenyl/ cyclopropane--1-carboxylate of (S) a-cyano 3-phenoxy benzyl. Into a solution of 3 g of (lR,cis) 2,2-dimethyl 3(E) (2-chloro 2-methoxycarbonyl ethenyl) cyclopropane-1- * -carboxylic acid chloride m 1$ cur of benzene, 3 g of (S) a-cyano 3-phenoxy benzyl. alcohol is introduced and x o then 1.3 cm of pyridine is introduced at + 50 C. After agitation for 15 minutes at + 5°C and then for 16 hours _ r^txjcJxcyrx at + 20 C, the jeaot-ional mixture is poured into a ^ mixture of water and hydrochloric acid, and extracted with ethyl ether. By washing with water, drying, concentrating the organic solution to dryness by distillation tinder reduced pressure, and chromatographing the residue on silica gel, eluting successively with a 20 mixture of cyclohexane and ethyl acetate (8/2), and then with cyclohexane and ethyl acetate (9/1)» 2.1 g of (lR,cis) 2,2-dimethyl 3(E) /2-chloro 2-(methoxy carbonyl ethenyl/ cyclopropane-l-carboxylate of (S) a-cyano 3-phenoxy benzyl is obtained. -o 25 (<i)rj - 50.5 (C » 0.8-%, benzene). iV 2 7SEFI984 izzi - LfX) -X- 198515 Analysis : C^ &22 ^N°5 4-39.9 C% H% Cl% Calculated : 65-53 5-04 8.05 Found: : 65-5 5*2 8.0 IR Spectrum (chloroform) - absorption at 1738 cm ^ and 1719 cm ^ attributed to the carbonyl of the ester. - absorption at 1608 cbT^" attributed to -C = C- - absorption at 1589 cm""^" - 1489 cm ^ attributed to the aromatic nuclei - absorption at 1390 cm-1 attributed to the paired methyls. NMR. Spectrum (deuterochloroform) - peaks at 1.24 - 1.25 p.p.m. attributed to the hydrogens of the paired methyls - peaks at 1.93 - 2.07 p.p.m. attributed to the hydrogen in position 1 of the cyclopropyl - peaks at 2.87 - 3-01 - 3.04 - 3.18 p.p.m. attributed to the hydrogen in position 5 of the cyclopropyl - peak at 3«85 p.p.m. attributed to the methyl of the methoxy carbonyl - peak at 6.35 p.p.m. attributed to the hydrogen carried by the same carbon atom as the - Cs N group - peaks at 6.91 - 7.5 p.p.m. attributed to the hydrogens of the aromatic nuclei. The (lR,cis) 2y2-dimethyl 3(E) /2-chloro 2-(methoxy carbonyl) ethenyl/ cyclopropane-l-carboxylic acid chloride can be obtained in the following manner: N.Z. PATENT OFFICE * 27SEP1984 'Wts RECEIVE 3^5" 1 9851 Stage A : (lR,cis) 2,2-dimethyl 5(E) /2-chloro 2-methoxy carbonyl) ethenyl/ cyclonropane- -1-carboxylic acid. x Into 50 cur of tetrahydrofuran, 12.6 g of methoxy . carbonyl chloro methylene triphenyl phosphorane and 4.85 g of the lactone of (lR,cis) 2,2-dimethyl 3-(dihydroxymethyl) cyclopropane-l-carboxylic acid in solution in 40 cm of tetrahydrofuran are introduced at 20° C, and agitated for two hours at 20°C. The fzachcri poactional mixture is then taken to reflux, kept at reflux for one hour, concentrated to dryness by distillation under reduced pressure, and ethyl ether is added to the residue. The insoluble matter formed (triphenyl phosphine oxide) is eliminated by filtration, and the filtrate is concentrated to dryness by distillation under reduced pressure; the residue is chromatographed on silica gel, eluting with a mixture of benzene and ethyl acetate (8/2) containing 1% of acetic acid, and 2,2 g of (lR,cis) 2,2-dimethyl 3(E)-(2-chloro 2-methoxy carbonyl ethenyl) cyclopropane-l-carboxylic acid and 3 g of (lR,cis) 2,2-dimethyl 3(Z) (2-chloro 2-methoxy carbonyl ethenyl) cyclopropane-l-carboxylic acid are obtained. The (lR,cis) 2,2-dimethyl 3(E) (2-chloro 2-methoxy carbonyl ethenyl) cyclopropane-l-carboxylic acid 198515 & • >5 - 7 possesses the following characteristics : IR Spectrum (chloroform) - absorption at 3500 cm~^ attributed to the hydroxyl of the carboxyl 5 - absorption at 1721 cm 1713 cm 1700 cm"^" attributed to the carbonyl - absorption at 1490 cm~^ - 1410 cm""'*' attributed to the -C » C- - absorption at 1393 cm~^ - 1380 cm ^ attributed to 10 the hydrogens of the paired methyls. NHS Spectrum (deuterochloroform) - peaks at 1.3 - 1.32 p.p.m. attributed to the paired methyls - peaks at 1.87 ~ 2.02 p.p.m. attributed to the hydrogen 15 in position 1 of the cyclopropyl - peaks at 2.82, 2.97 p.p.m. - 2.98, 3.13 p.p.m. attributed to the hydrogen in position 3 of the cyclopropyl. - peak at 3-82 p.p.m. attributed to the hydrogens of 20 the methyl of the methoxy carbonyl - peaks at 6.72 - 6.78 p.p.m. attributed to the hydrogen of the (ttwafelrfe ethylene^bond of the lateral chain in position 3 of the cyclopropyl. - peak at 11 p.p.m. attributed to the hydrogen of the 25 carboxyl. The (lR,cis) 2,2-dimethyl 3(Z) (2-chloro 2-methoxy carbonyl ethenyl) cyclopropane-l-carboxylic ✓ u j 1 5 W; o q r N.Z. PATENT OFPCE 27SEP1984 •fizcEiv:") acid presents the following characteristics : IR Spectrum : (chloroform) - absorption at 3500 cm 1 attributed to the hydroxyl of the carboxyl (monomer + dimer) 5 - absorption at 1?25 cm"1 attributed to the -C- ester 0 - absorption at 1700 cm"1 attributed to the hydrogen of the carboxyl (monomer) - absorption at 1623 cm"1 attributed to the -C - C - - absorption at 1393 cm"1 - 1381 cm"1 attributed to the 10 hydrogens of the paired methyls. NMR Spectrum (deuterochloroform) - peaks at 1.32 - 1.35 p.p.m. attributed to the hydrogens of the paired methyls - peaks at 1.95 to 2.5 p.p.m. attributed to the hydrogens 15 in positions 1 and 3 of the cyclopropyl - peak at 3.83 p.p.m. attributed to the hydrogens of the methyl of the methoxyl. - peaks at 7«28 - 7«^5 p.p.m. attributed to the hydrogen of the double bond of the lateral chain in position 3 of the 20 cyclopropyl - peak at 10.75 p.p.m. attributed to the hydrogen of the carboxyl. Stage B ; (lR,cis) 2,2-dimethyl 3(E) /2-chloro 25 2-(methoxy carbonyl) ethenyl/ cyclopropane-1- -carboxylic acid chloride 2.9 g of (lR,cis 2,2-dimethyl 3(E) /2-chloro 198515 u.4-- 4-5 - 2-(methoxy carbonyl) ethenyl/ cyclopropane-l-carboxylic x x acid, 20 cur of isoprene and 10 cur of thionyl chloride are mixed together and agitated at 20°C for 3 hours. The isoprene and the thionyl chloride are 5 eliminated by distillation under reduced pressure, and 6 g of crude (lR,cis) 2,2-dimethyl 3(E)-/2-chloro 2-(methoxy carbonyl) ethenyl/ cyclopropane-l-carboxylic acid chloride is obtained. Example 4 : (lRvcis) 2,2-dimethyl 3(Z) /2-bromo 10 2-(propoxy carbonyl) ethenyl/ cyclop/opane-1- -carboxylate of (S) a-cyano 5-phezfoxy benzyl. To a solution of 2.9 g of (lR,cis) 2y2^-dimethyl 3(Z)-/2-bromo 2-(propyloxy carbonyl) ethinyl/ cyclopropane- 3 / -1-carboxylic acid in 40 cnr of methylene chloride, 0.9 x 15 cm-7 of pyridine and 2.1 g of dicyclohexyl carbodiimide are added, and the whole is agitated for 15 minutes. 2.5 g of (S) a-cyano 3-phenoxy benzyl in solution in 3 / 5 cnr of methylene chloride is introduced, and 25 mg of 4- dimethyl- amino pyridine JLs added. After agitating for 20 2 hours, the insoluble matter formed is eliminated by filtration, the filtrate is concentrated to dryness by distillation irnraer reduced pressure, and the residue is chromatographed on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (9/1), so obtaining 25 4.26 Df (lR,cis) 3(Z)-/2-bromo 2-(propoxy carbonyl) ! 2?sr.?t384 198515 ^ - #9 - - - J (lR,cis) 2,2-dimethyl 3(Z) /2-bromo 2-(pz'opyloxy carbonyl) ethenyl/ cyclopropane-l-captx>xylic acid in 35 cnr of toluene, 0.35 g mefaohydrated paratoluene sulphonic acid is introduced,yand the flask containing the reactional mixture is .placed in a bath of oil at 120°C for 10 minutes; Jrfie temperature of the reactional mixture J£s brought rapidly to 20°C, ether is added, the re-u^lted organic extracts are washed with water, dried/; concentrated to dryness by distillation 10 under reduced pressure, and 2.9 g of (lR,cis) 2,2-dimethyl 3(Z) -/2-bromo 2-(propyloxy carbonyl) eifnenyl/cyclopropane-l-carboxylic acid is obtained. Example (lR,cis) 2,2-dimethyl 3(E)-/2-bromo 2-(propoxy carbonyl) ethenyl/ cyclopropane-1-15 -carboxylate of (S) a-cyano 3-phenoxy benzyl). Into a solution of 2.6 g of (lR,cis) 2,2-dimethyl 3(E)-/2-bromo 2-(propyloxy carbonyl) ethenyl/cyclopropane--1-carboxylic acid in 40 cnr of methylene chloride, 7. 0.9 cnr of pyridine and 2 g of dicyclohexyl carbodiimide 20 are introduced, and the whole is agitated for 10 minutes; 2 g of (S) a-cyano 3-phenoxy benzyl alcohol is added, with agitation for 10 minutes,25mg of 4-dimethyl-amino--pyridine is added, with agitation for one hour and thirty minutes. The insoluble matter formed is eliminated by 25 filtration, the filtrate is concentrated to dryness 198515 M-k -X- "by distillation under reduced pressure, and by chromatographing the residue on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (95/5)i 0*74-3 g of the expected ester is obtained, 5 and 3.64 g of a mixture which is dissolved hot in 4 volumes of isopropyl ether. This latter is agitated at 20°C, the precipitate formed is separated, dried, and joined with the 0.743 g of the product previously obtained, and , 2.32 g of (IR, cis) 10 2,2-dimethyl 3(E) /2-bromo 2-(propoxy carbonyl) ethenyl/ cyclopropane-l-carboxylate of (S) a-cyano 3-phenoxy benzyl is recovered, M. Pt. 68°C. Analysis : Br NO^ (512.41) C% B% W/o Bi% N.Z. PATENT OFFICE 27SEP1984 15 Calculated : 60.95 5-U 2.73 15-6 , RECE1VED Found : 61 5-1 2.5 I5.5 IR Spectrum (chloroform) - absorption at 1737 cm 1 attributed to the carbonyl of the ester 20 - absorption at 1705 cm 1 attributed to the carbonyl of the conjugated ester - absorption at 1605 - 1610 cm"1 attributed to - C ■ C - - absorption at 1585 - 1485 cm"1 attributed to the aromatic nuclei. 25 NMR Spectrum (deuterochloroform) - peaks at 0.88 - 1.0 - 1.12 p.p.m. attributed to the hydrogens of the methyl of the propoxyl 198515 47 -2?si;ri984 ! L.T.'l - peaks at 1.22 - 1.23 p.p.m. attributed to the hydrogens of the paired methyls - peaks at 1.92 - 2.06 p.p.m. attributed to the hydrogen in position 1 of the cyclopropyl - peaks at 4.08 - 4.18 - 4.28 p.p.m. attributed to the hydrogens of the methylene in position 1 of the propyl - peaks at 6.38 p.p.m. attributed to the hydrogen carried by the same carbon as the -CsN - peaks from 6,9 to 7-51 p.p.m. attributed to the hydrogen of the ethylene double bond. - peaks at 6.92 - 7«6 p.p.m. attributed to the hydrogens of the aromatic nuclei. The (lE,cis) 2,2-dimethyl 3(E)-/2-(propoxy carbonyl) ethenyl/ cyclopropane-l-carboxylic acid can be obtained in the following manner : Stage A : (lR,cis) 2,2-dimethyl 5(2)- 2-bromo 2-(propyloxy carbonyl) ethenyl/ cyclopropane-1--carboxylate of tert-butyl Into a solution of 28.3 g of t-butyl ester of (lR,cis) 2,2-dimethyl 3~ ( 2,2-dibromovinyl) cyclopropane-l-carboxylic 3 5 acid in a mixture of 120 cnr of tetrahydrofuran and 120 cnr x of ethyl ether, 5° cnr of a solution of butyl lithium in hexane, titrating 1.6 N is introduced over about 25 minutes at -115°C. After agitating for 15 minute o 5 at -115 C, 10 cnr of n-propyl chlorofonnate is added tlv' ' progressively, and the whole is agitated for 20 minutes at -115°C, then for one hour at -65°C, after which the reactional mixture is poured on to an aqueous solution of monosodium phosphate, and extracted with ether. The re-united ethereal solutions are washed with water, dried, concentrated to dryness by distillation under reduced pressure, then chromatographed on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (95/5)* so obtaining 3-16 g of (lR,cis) 2,2-dimethyl 3(E)-/2-bromo 2-( propoxy carbonyl) ethenyl/ cyclopropane-l-carboxylate of tert-butyl and 3.52 g of (lR,cis) 2,2-dimethyl 3(Z)-/2-bromo 2-(propoxy carbonyl) ethenyl/cyclopropane-l-carboxylate of tert-butyl. Stage B: (IR,cis) 2,2-dimethyl 3(E)-/2-(propoxy carbonyl) ethenyl/cyclopropane-1-carboxylic acid To a solution of 3*1 g of the tert-butyl ester of (lR,cis) 2,2-dimethyl 3(E)-/2-bromo 2-(propoxy carbonyl) ethenyl/ cyclopropane-l-carboxylic acid obtained in Stage A in 31 cm"3 of toluene, 0.31 g of monohydrated paratoluene sulphonic acid is introduced; the flask containing the reaction mixture is placed in a bath of oil at 120°C for 15 minutes, then the - 48 - 198515 - 52 - temperature of the freactional mixture is brought rapidly to 20°C. By extracting with ether, washing the organic extracts with water, drying them, and concentrating them to dryness by distillation under reduced pressure, 2.6 g of (lR,cis) 2,2-dimethyl 3(E) /2-bromo 2-(propoxy carbonyl)ethenyl/ cyclopropane--1-carboxylic acid is obtained. Example $: (lR,cis) 2,2-dimethyl 5-(S) 2-fluoro-2 (ethoxy carbonyl) ethenyl/ cyclopropane-l--carboxylic acid. (lR,cis) 2,2-dimethyl 3-(E,Z) /2-fluoro 2-ethoxy carbonyl ethenyl/ cyclopropane-l-carboxylic acid is prepared, starting with 12.2 g of the lactone of (lR,cis) 2,2-dimethyl 3-(dihydroxy methyl) cyclopropane carboxylic acid by operating as in example 1, replacing the chromatography indicated in example 1 by chromatography on silica gel, eluting first with a mixture of cyclohexane and ethyl acetate (75/25)» then with the same mixture in 50/50 ratio, and 14-.5 g of (lR,cis) 2,2-dimethyl 3-(E) (2-fluoro 2-ethoxy carbonyl ethenyl) cyclopropane--1-carboxylic acid is obtained, /oc/^ *-42.5° (c = 1%, chloroform). NMR Spectrum (deuterochloroform) - peak at 1.28 p.p.m. attributed to the hydrogens of the paired methyls 1 98515 -if- - peaks at 1.23 - 1-35 - 1.47 p.p.m. and 4.13 - 4-.25 -4.37 "" 4.48 p.p.m. attributed to the hydrogens of the ethyl of the ethoxy carbonyl - peaks at 1.82 - 1.97 p.p.m. attributed to the hydrogen in position 1 of the cyclopropyl - peaks at 2.75 - 2.9 - 3.05 p.p.m. attributed to the hydrogen in position 1 of the cyclopropyl - peaks at 6.12 - 6.28 - 6.47 - 6.63 p.p.m. attributed to the ethylene hydrogen (J^21 H Hz corresponding to a cis derivative) - peak at 11.28 p.p.m. attributed to the hydrogen of the carboxyl. Example 7 : (lR^is) 2,2-dimethyl j/(Z) /2-fluoro 2-(ethoxy carbonyl) ethenyl/ cyclopropane--1-carboxylic acid/ By continuing the chromatography of example 6 4.64 g of (lR,cis) 2,2-dimethyl 3 (Z) /2-fluoro 2-(ethoxycarbonyl) ethenm/ cyclopropane-l-carboxylic acid is obtained. / By esterification by (S) a-cyano 3-phenoxy benzyl alcohol, the "E" arid "Z" acids lead to the esters of examples 1 and 24 Example 8 : QlR.,cis)2,2-dimethyl 3(Z) /2-fluoro-2-ethoxy / carbonyl) ethenyl/ cyclopropane-l-carboxylate of / (S) a cyano 3-phenoxy benzyl. to a solution of 4.9 g of (lR,cis) 2,2-dimethyl 19851 5 -5* - 3(Z) /2-fluoro-2 ethoxy carbonyl ethenyl/ cyclopropane-1- 3 3 -carboxylic acid in 39 cnr of methylene chloride, 1.9 cm of pyridine and 4.8 g of dicyclohejtyl carbodiimide are added. After agitation, a solution of 5-3 g of (S) . x a-cyano 3-phenoxy benzyl alcoh61 in 9.8 cnr of methylene chloride is added, with agitation for 2 hours, then 30 mg of 4-dimethyl amino ^pyridine is added, with agitation for 2 hours; /After cooling to 0°C, eliminating by filtration the insoluble matter formed, 10 concentrating to dryness by distillation under reduced pressure, suad chromatographing the residue on silica gel, eluting successively first by a mixture of cyclohexane anjz ethyl acetate (9/1), then with methylene chloride and/petroleum ether (B.Pt. 35-70°C) (6/4), 15 6.73 g of (?lR,cis) 2,2-dimethyl 3-(Z)-/2-fluoro-2/ethoxy carbonyl/ ethenyl/ cyclopropane-l-carboxylate of (S) a-dyano 3-pbenoxy benzyl is obtained, presenting the fsaxae physical characteristics as the compound obtained in/example 2« 20 By operating as at example 1 starting with the corresponding alcohols, the following products have keen pft-pG-fE-d. i (i&fcisriptii s"", t ~7 clsicI boon prepared t—(exomploo 9t 10*—11 and 12) « Example ^: (lR,cis &E) 2,2-dimethyl 3C(2-fluoro 2-ethoxy carbonyl ethenyl] cyclopropane 25 carboxylate of (R) 3~ethynyl 5-phenoxy^-phenyl- -methyl. Yield = 72%. aD . +40° + 1°5 (c - 1% CHCl^) n.2. pavk \ "1 2 7sep1984 198515 - 05 - Example Kf : (lR,cis AE) 2,2-dimethyl 3 C2 -fluoro 2-ethoxy carbonyl ethenyl] cyclopropane carboxylate of (R) 3-phenoxy phenyl) ethyl. Yield -81% / CHCi3 aD - + 94°5 + 2°5 (c » 0.5 % 0BGZ^) Example 3it : (lR,cis aE) 2,2-dimethyl 3 C(2 - fluoro 2 -ethoxy carbonyl) ethenyl] cyclopropane--1-carboxylate of (S)a-cyano 3-phenoxy 4-fluoro benzyl. aD - +50° + 2°5 (c =. 0.5 % CHCl^). g Example 3^ : (lR,cis AE) 2,2-dimethyl 3C(2-fluoro 2-ethoxy carbonyl) ethenyl] cyclopropane--l-carboxylate of 3-phenoxy benzyl. IR Spectrum : C=0 ester ) -1 C=0 conjugated ester ) ' 5 C«G conjugated 1655 cm"1 aromatics 1588-1489 cm"1 paired dimethyls 1390-1380"1 Example 13 : (IR trans) 2,2-dimethyl 3(X^E, 2-fluoro 3-oxo 3-ethoxy propenvylf'cyclopropane carboxylate of (S) ydi-cyano 3-phenoxy benzyl. By operating as in example 1, starting with (IR,trans) 2,2-dimethyl 3C AE 2-fluo^b 3~oxo 3-ethoxy propenyl] cyclopropane carboxy^rc acid and (S) a-cyano 3-phenoxybenzyl 198515 53 - jKL - Example 18 : (lR,cis) 2,2-dimethyl 3->,C(£Z) 2-fluoro 3-oxo 3 -(l,l,l,3,3,3->hexafluoro) isopropoxy n'-propen/l] cyclopropane carboxylate of (s)/a-cyano 5-phenoxy benzyl* At + 5° to +10° C, and oVer 10 minutes, a solution containing 0. 6 g off dicyclohexyl carbodiimide, / 3 21mg of 4-dimethylamino pyridine and 5 cm of methylene chloride is introduced in'co a solution containing 1.1 g of (lR,cis) 2,2-dimethyl 3r[2-fluoro 3~oxo 3-bydroxy (Z) propenyl] cyclopropane carboxylate of (S) a-cyano / 3 3 3-phenoxybenzyl, 5 of methylene chloride and 0.5 cm of l,l,l,3,3,3-he3fafluoropropen-2-ol. By filtering, taking the filtrate to dryness, and chromatographing the residue obtained on silica, eluting with a hexane-ethyl acetate (9~l/ mixture, and operating under nitrogen pressure, /50 mg of the product sought is obtained. + 18°5 + 1° Cc » 1 % benzene) Example ^ : (lR,cis) 2,2-dimethyl 5-[2-fluoro 5-oxo 5-methoxy (E) propenyl] cyclopropane carboxylate of (S) a-cyano 3-phenoxybenzyl. Stage A (lR,cis) 2,2 dimethyl 3-[2-fluoro 3-oxo 3-hydroxy (E) propenyl] cyclopropane carboxylate of (S) a-cyano 3-phenoxy benzyl. A solution containing 2.5 g of (lR,cis) 2,2 dimethyl 3-[(E) 2-fluoro 2-ethoxy carbonyl ethenyl] cyclopropane-1- -carboxylate of (3) a-cyano 3-pnenoxybenzyl, 10 cm^ of 198515 - 54 - 7. dioxan, 2.5 cm of water and 1 g of monohydrated paratoluene sulphonic acid are taken to reflux for 24 hours. The temperature is allowed to return to ambient, Cthe mixture] is then diluted with methylene 5 chloride and washed with water. The organic phase is dried and filtered, and the filtrate is concentrated under reduced pressure. The residue obtained is chromatographed, eluting with a mixture of cyclohexane, ethyl acetate and acetic acid (60-40-1). 980 mg of 10 the product sought is thus recovered. Stage B (lR,cis)-2,2~dimethyl 5~[2-fluoro 5-oxo 3-methoxy (E) propanyl] cyclopropane carboxylate of (g) a-cyano 5-phenoxy-benzyl. At a temperature between + 5°C and + 10°C, a 15 slight excess of diazomethane dissolved in methylene chloride is added to a solution of methylene chloride containing* >the product prepared at stage A. Agitation is maintained for 15 minutes at 5°C, then for 30 minutes at ambient temperature. A few 20 drops of acetic acid are added. After taking to dryness, an oil is obtained which is chromatographed on silica, eluting with a mixture of hexane and ethyl acetate (85-15) . In this way the product sought is obtained. 25 r< .2. f, I OFFiri 27SEP1984 198515 10 - 55 - M.Pt. 70°C. aD -+52° + 1°5 (c - 1 % CHCl5) By operating as in the previous example, starting with the corresponding alcohols, the following products have been prepared. Example 10 : (lR,cis) 2,2 dimethyl 5-C2-fluoro, 3-oxo 3-n-propyloxy (E) propenyl] cyclopropane carboxylate of (S) a-cyano 3-phenoxy benzyl aD - + 38.5° +2° c » 0.7 % CHClj Example ll : (lR,cis) 2,2-dimethyl 3-C(Ae) 2-fluoro 3-oxo 3-tert-butoxy propenyl] cyclopropane carboxylate of (S) a-cyano 5-phenoxy benzyl. (lR,cis) 2,2 dimethyl-3/2-fluoro 3-oxo 3-hydroxy (6) propenyl/ cyclopropane carboxylate of (S) a-cyano 3-phenoxy benzyl, ethyl acetate and N-(l-methyl ethyl) Nr-(1-methyl ethyl) carbamimidate of tert-butyl are maintained under agitation for two hours. After filtering and taking the filtrate to dryness, the product is obtained^ purified by chromatography on 198515 - 56 - silica, eluant: n-hexane and isopropyl ether (8-2) under nitrogen pressure and then recrystallized from isopropyl ether. (Yield 61%.) D = + 26°5 (c = 0.25% CHC13) The tert-butyl N-(l-methyl ethyl) N*-(l-methyl ethyl) carbamimidate was prepared as follows : 98.7 g of N,N* diisopropylcarbodiimide and 57-9 g of tert-butyl alcohol are agitated in the presence of 5 g of cuprous chloride for four and a half days at ambient temperature. 117.7 g of the expected product is obtained after distillation of the reaction mixture at 74-°C under a pressure of 9 mm of mercury. Example 12 : (lR,cis) 2,2-dimethyl 5C(£E) 2-fluoro 3-oxo 5(1,1,1,5i3«5) hexafluoro isopropoxy n-propenyl] cyclopropane carboxylate of (S) a-cyano 5-phenoxy "benzyl. By operating as in example 9, stage B, stating with (lR,cis) 2,2-dimethyl 3-C2-fluorO 3-oxo 3~kydroxy (E) propenyl] cyclopropane carboxylate of (S) a-cyano 3-phenoxy benzyl and 1,1,1,3,3,3-bexafluoropropan-2-ol, the product sought is obtained. aD « + 21° +2° (c » 0.5 % CHC15). > 1 ' 27SEF<*4 « r- -"-.T-.- i 198515 - 57 - Example 13 : (lR,cis) 2,2-dimethyl 5- [2-fluoro 5-oxo 5-isopropyloxy (E) propenyl] cyclopropane carboxylate of (S) a-cyano 3-phenoxy benzyl. aD . + 46° + 1° c - 1 % CHC1V Example 14 : (lR,cis) 2,2-dimethyl 3-[2-fluoro 3-oxo 5-cyclopropyloxy (E)-propenyl] cyclopropane carboxylate of (S) a-cyano 5-phenoxy benzyl. M. Pt. « 50°C -o * -.o aD . + 350 Z i° (c . 1.3 % CHC13) 10 Example 15 : (lR,cis,AE) 2,2-dimethyl 3C2-fluoro 3-oxo 3(B-methoxy ethoxy) propenyl] cyclopropane carboxylate of (s) a-cyano 5-phenoxy benzyl. aD - 47° + 2°5 (c - 0.5 % CHC13) / 198515 - &5 - Example 16 : (lR,cis) 2,2-dimethyl 5[(AE) 2-chloro 2-methoxy carbonyl ethenyl] cyclopropane carboxylate of (S) 2-methyl 4-oxo 5-(2-propenyl) 2-cyclopenten-l-yl By operating as in Example 1, , starting with (lR,cis) 2,2-dimethyl 3(Z)[2-chloro 2-methoxy carbonyl ethenyl] cyclopropane carboxylic acid chloride and with (4S)-hydroxy 3-methyl 2-(2-propenyl) 2-cyclopenten-l-one^ the product sought is obtained. aD ■-15° ±4-° (c = 0.25 % benzene) NMR Spectrum (CDCl^) . 1.28 and 1.3 p.p.m., attributed to the hydrogen of the methyls in position 2 3.8 p.p.m. attributed to the hydrogen of -002011^ 2.02 p.p.m. attributed to the hydrogen of 6.8 - 7 p.p.m. attributed to the ethylene hydrogen carried by the carbon in position 1 of the 2-methoxy carbonyl ethenyl radical. N.Z. PATENT OFFICE 27SEP1984 - 66 - 198515 Example 29 : (lR,cis) 2,2-dim9thyl 3-*[(Z) 2-chloro 2-methoxy carbtmyl ethenyl] cyclopropane carboxylate/of (IS) 2-methyl -4-oxo 3-(2-propenyl) -2-cyclopenten-l-yl. The product has/oeen prepared starting with (lR,cis) 2,2-dimethyl 3-C(Z) 2-chloro 2-methoxy carbonyl ethenyl] cyclopropane carboxylic acid chloride and with (4S) hydroxy 3/methyl 2-(2-propenyl) 2-cyclopenten-l-one and the product sought is obtained. 10 a^ / + 2?0 + 2°5 (c = 0.3 % CHC1?). Example : (lR,cis) 2,2-dimethyl 5C(E) 3~oxo 2-chloro ethoxy propenyl] cyclopropane carboxylate of (S) a-cyano 3-phenoxy benzyl. By operating as in example 1, starting with 15 (lR,cis) 2,2-dimethyl 3C(E) 3-oxo 2-chloro 3-ethoxy propenyl] cyclopropane carboxylic acid and (S) a-cyano 3-phenoxy benzyl alcohol, the product sought is obtained. aD - + 19° ±2° (c - 1 % CHCl^) The (lR,cis) 2,2-dimethyl 3Coxo 2-chloro 3~ethoxy 20 propenyl] cyclopropane carboxylic acid (E and Z isomers) has been prepared as follows : Stage A. ethoxy carbonyl chloro methylene triphenyl phosphorane. A solution is prepared at 2°C of about 4 g of chlorine 25 in 80 cm of chloroform. 20 g of ethoxy carbonyl \c C 198515 10 15 20 25 N.2. PATENT OFFiCE 27sep1984 methylene triphenyl phosphorane in 40 cnr of chloroform is added. Having allowed the temperature to return to ambient, the reactional mixture is taken to dryness under reduced pressure. An oil is obtained which is x dissolved in 70 cm of methylene chloride, washed with x a solution with 6.1 g of sodium carbonate in 40 cnr of water, then with water. After drying and taking to dryness, 18.9 g of the product sought is obtained. M. Pt. = 116° 118°C. Stag;e B (lB,cis) 2,2-dimethyl 3t3-oxo 2-chloro-3-ethoxy propenyl] cyclopropane carboxylic acid (E and Z isomers). 6.9 g of the lactone of (lR,cis) 2,2-dimethyl 3-dihydroxy methyl cyclopropane-l-carboxylic acid in • x 100 cm of tetrahydrofuran is added to a solution contain- x ing 18.9 g of the product prepared at stage A in 200 cm of tetrahydrofuran. The solution obtained is agitated for 6 hours 30 minutes at ambient temperature; the solvent is distilled off under reduced pressure. An oil is obtained x which is taken up in 50 cnr of ethyl ether, agitated at 0°C, filtered, the precipitate obtained is washed with ether, and the filtrate is taken to dryness. 22.2 g of the product sought is obtained, which is chromatographed on silica, eluting with a mixture of cyclohexane, ethyl acetate and acetic acid (75-25-1). In this way there is obtained : A) for the one part : 3.58 g of the product sought, in the form of the E isomer : receiv:: - £8 - 198515 NMR Spectrum 1.3 and 1.33 p.p.m. (CDC1,) 0 1.89 - 2.02 p.p.m. 2.85 to 3.05 p.p.m. 6»78 - 6.95 p.p.m. Hydrogen of the methyl in position 2 of the cyclopropane. Hydrogen of the carbon in position 1 of the cyclopropane. Hydrogen of the carbon in position 3 of the cyclopropane. Hydrogen of the carbon in position 1 of the propenyl radical. 10 B) for the other part : 2.34 g of the corresponding Z product : NHR Spectrum : (CDCl^) 1.33 arid 1.36 p.p.m. Hydrogen of the methyl in position 2 15 1.96 - 2.1 p.p.m. Hydrogen of the carbon in position 1 of the cyclopropane. 2.23 - 2.53 p.p»m. Hydrogen of the carbon in position of the cyclopropane. Example 31 (lR,cis) 2,2-dimethylAiZ) 2-chloro 5-oxo 20 3-ethoxy pro-penyl3 Cyclopropane carboxylate of (S) g-cyano (^phenoxy benzyl). •By operating as in example 1, starting with (lR,cis) 2,2-dimethyl 3t(Z) 3-oxo-^/chloro 3-ethoxy propenyl] cyclopropane carboxylicy^acid and with (3) g-cyano 25 3-phenoxy benzyl alcohol, the product sought is obtained, a. 3 + 21°5/£ 2°-5 (c = 0.3 % CHC1,). 198515 (?2<- - 69 - IS Example : (lR,cis) 2,2-dimethyl 3C(E) 3-oxo 2-chloro 3-propoxy propenyl] cyclopropane carboxylate of (S) a-cyano (3-phenoxy-benzyl). By operating as in example 1, starting with (lR,cis) 2,2-dimethyl 3C(E) 3-oxo-2-chloro 3-propoxy propenyl] cyclopropane carboxylic acid and (S) a-cyano 3-phenoxy benzyl alcohol, the product sought is obtained. aD - + 24°5 +2° (c = 0.4 % CHCl^ The (lR,cis) 2,2-dimethyl 3C(E) 3~oxo-2-chloro 3-propoxy propenyl] cyclopropane carboxylic acid has been prepared as follows : Stage A - propoxy carbonyl chloro methylene triphenyl phosphorane. By operating as for the preparation of (lR,cis) 2,2 dimethyl 3C(E) 3~oxo 2-chloro 3-ethoxy propenyl] J7 cyclopropane carboxylic acid, example stage A, starting with propoxy carbonyl methylene triphenyl phosphorane, the product sought is obtained. Stage B - (lR,cis) 2,2-dimethyl 3C(E) 3-oxo 2-chloro 3-propoxy propenyl] cyclopropane carboxylic acid. By operating as for the preparation of (lR,cis) 2,2 dimethyl 3C(E) 3~oxo 2-chloro 3-ethoxy propenyl] '7 cyclopropane carboxylic acid, example £© (stage B), starting with the product prepared at stage A, there is 1,3 - 7® - 198515 obtained on the one hand the product sought, and on the other hand, the corresponding AZ isomer. Example 33 : (lR,cis) 2,2-diaethyl 5C(Z) 3-oxo 2-chloro 5-T>n6r>oxy propenyl] cyclopropane 5 carboxylaty of (3) a-cyano/3-phenoxy benzyl- By operating as ill example 1, starting with (lR,cis) 2,2-dimethyl 3C(Z) 3-yoxo 2-chloro 3-propoxy propenyl] cyclopropane carboxylic acid and (S) a-cyano 3"*pbenoxy benzyl alcohol, Vne product sought is obtained. 10 an 3 + 2/ 5 ±2° (c - 0.7 % CHC1,) D TT Example £4 : (lR.,cis) 2,2-dimethyl 5C(E) 5-oxo 3-terbutoxy 2-chloro propenyl] cyclopropane carboxylate of (S) a-cyano 3-~Dhenoxy benzyl. By operating as in example 1, starting with (lR,cis) 15 2,2-dimethyl 3C(E) 3~oxo 3-terbutoxy 2-chloropropenyl] cyclopropane carboxylic acid, and with (S) a-cyano 3-phenoxy benzyl, alcohol, the product sought is obtained. aD » + 30°5 +2° (c « 0.7 % CHCl^) (lR,cis) 2,3-dimethyl 3-oxo 3-terbutoxy 2-chloro 20 propenyl) cyclopropane carboxylic acid (E and Z isomers) has been prepared as follows : Stage A terbutoxy carbonyl chloro methylene triphenyl phosphorane. By operating as previously (preparation given n 25 following example £0,. stage A), and starting with terbutoxy carbonyl methylene triphenyl phosphorane, the m.z. •"atp,\it r 2?.,. .> 198515 t<r - - product sought is obtained. M.Pt. 160°C. Stage B AE acid + AZ acid. By operating as it was indicated for the preparation • 7 given following example 2© stage B, starting with the product prepared in stage A, there is obtained, on the one hand, (lR,cis) 2,2-dimethyl 3C(E) 3-oxo 3"terbutoxy 2-chloro propenyl] cyclopropane carboxylic acid, M.Pt. = 65°C, and on the other hand, the corresponding (Z) isomer, M.Pt.>C500C. Example 35 i (lR,cis) 2,2-dimethyl 5/[(Z) 2-bromo 3-oxo 5-methoxy propenyl] cyclopropane carboxylate of (S) a-cyano 5-phepoxy benzyl. By operating as in example y, starting with (lR,cis) 2,2-dimethyl 3-C2-bromo 3-oxo 3-pethoxy (Z) propenyl] cyclopropane carboxylic acid ana with (S) a-cyano 3-phenoxy . benzyl alcohol, the product sc/ught is obtained. aD = + 29°5 + 2°5 /c = 0.5 % CHCl^) (lR,cis) 2,2 dimethyl/ 3-[2-bromo 3-oxo 3-methoxy (Z) propenyl] cyclopropams carboxylic acid has been prepared as follows : / Stage A Terbutyl (lfi/cis) 2,2 dimethyl 3~Cl»2-(dibromo RS) 3-oxo 3-methoxy propyl] cyclopropane carboxylate. 13•3 g of pyridinium tribromide is added to a solution containing 8.07 g of terbutyl (lR,cis) 2,2-dimethyl 3-C^-methoxy carbonyl (E) ethenyl] cyclopropane carboxylate prepared from corresponding acid 198515 - 7% - munohydrated paratoluene sulphonicyauid,—is taken to— reflux. The reflux is continued until the evolvement of gas ceases. After cooing to 0°C, filtering, washing the precipitate obtain^a with cold toluene and concentrating the filtrate at 40°C under reduced pTe'SSUre, 2.8 g the pruducl suu^kl is obtained. a.0 Example ¥? : (lR,cis) 2,2-dimethyl 3~C(E) 2-bromo 3-oxo 3-terbutoxy propenyl] cyclopropane carboxylate of (S) a-cyano 3-phenoxy benzyl. By operating as in example 1, starting with (lR,cis) 2,2-dimethyl 3C(E) 2-bromo 3-oxo 3-terbutoxy propenyl/ cyclopropane carboxylic acid and (S) a-cyano 3-phenoxy benzyl alcohol, the product sought is obtained. aD > + 16°5- 2° (c = 0.7 % CHCl^) The (lR,cis) 2,2 dimethyl 3C(E) 2-bromo 3-oxo 3-terbutoxy propenyl] cyclopropane carboxylic acid has been prepared as follows. Stage A terbutoxy carbonyl bromomethylene triphenyl phosphorane. By operating as for the preparation of (lR,cis) 2,2 dimethyl 3C(E) 3-oxo 2-chloro 3-ethoxy propenyl] n cyclopropane carboxylic acid (given in example stage A) starting with the derivative terbutoxy carbonyl methylene triphenyl phosphorane and with bromine, the product sought is obtained. M.Pt. 190°C. 198515 - 75 - Stage B (lR,cis) 2,2-dimethyl 3C(E) 2-bromo 3-oxo 3-terbutoxy propenyl] cyclopropane carboxylic acid. By operating as for the preparation of (lR,cis) 2,2-dimethyl 3C(E) 3-0x0 2-chloro 3-ethoxy propenyl] , 17 cyclopropane carboxylic acid (given in example ^0, stage B), starting with the product prepared at Stage A, there is obtained on the one hand the product sought, melting at 76°C, and on the other hand, the corresponding Z isomer, melting at 50°C. Example 38: (lR,cis) 2,2-dimethyl 2-bromo 3-oxo 3-terbutoxy propenyl] cyclopropane carboxylate of (S)/q-cyano 3-phenoxy benzyl. By operating as in example 1, starting with (lR,cis) 2,2-dimethyl 3C(Z) 2-bromo/3~oxo 3-terbutoxy propenyl] cyclopropane carboxylicyacid and with (S) a-cyano 3-phenoxy benzyl alcohol, the product sought is obtained. aD = + 16°5 +/2° (c = 0.5 % CHCl^) X/ Example £9": (lR,cis) 2,2 dimethyl 3C(E) 3~oxo 2-bromo 3-ethoxy propenyl] cyclopropane carboxylate of (£0 a-cyano 3-phenoxy benzyl. By operating as in example 1, starting with (lR,cis) 2,2-dimethyl 3C(E) 3~oxo 2-bromo 3-ethoxy propenyl] cyclopropane carboxylic acid and (S) a-cyano 3-phenoxy benzyl alcohol, the product sought is obtained. aD « - 70°5 + 2° (c - 0.7 % CHC13) The (lR,cis) 2,2-dimethyl 3C(S) 2-bromo 3-oxo 3-ethoxy - 76 - 198515 10 propenyl] cyclopropane carboxylic acid has been prepared as follows : Stage A ethoxy carbonyl brorao methylene triphenyl phosphorane. The product has been prepared according to the process indicated for (lR,cis) 2,2 dimethyl 3C(E) 3~oxo 2-chloro 3-ethoxy propenyl] cyclopropane carboxylic acid in example stage A, starting with the derivative ethoxy carbonyl methylene triphenyl phosphorane and with bromine. In this way, the product sought has been obtained, melting at 150°C. Stage B (lR,cis) 2,2 dimethyl 5C(E) 2-bromo 3-oxo 5-ethoxy propenyl] cyclopropane carboxylic acid. The product has been prepared according to the 15 process indicated for the preparation of the corresponding chlorated acid, starting with the product prepared at Stage A. In this way, on the one -hand, the product sought has been isolated, and on the other hand, the 20 corresponding AZ product. XL Example 40 : (lR,cis) 2,2 dimethyl 5~C(E) 2-fluoro 3-oxo 3-ethoxy propenyl] cyclopropane carboxylate of (RS) a-cyano 6-phenoxy 2-pyridyl methyl 25 By operating as in example 1, starting with the corresponding acid and alcohol, the product sought was - 77 - I 98515 obtained. aD - + 35° ±4° (c = 0.3 % CHC1,) xi Example M. : (lR,cis) 2,2 dimethyl 5-C(E) 2-fluoro 5-oxo 5-ethoxy propenyl] cyclopropane carboxylate of 5-(2-propynyl) 2,5 - dioxoimidazolidinyl methyl. By operating as in example 1, starting with the corresponding acid and alcohol, the product sought is obtained. aD - + 12° +2° (c - 0.5 % CHC1X) ztf. ' ' . Example 42 : (lR,cis) 2,2-dimethyl 5C(E) 2-fluoro 5-oxo 5-ethoxy propenyl] cyclopropane carboxylate of (S) 2-methyl 5-allyl 4-oxo 2-cyclopenten-l-yl. By operating as in example 1, starting with the corresponding acid and alcohol, the product sought is obtained. ocD « + 41°5 + 2°5 (c = 0.5 % CHC1,) asr Example 4*5 : preparation of a soluble concentrate. A homogeneous mixture is made of Product of example 1 0.25 g Butoxide of piperonyl .. 1.00 g Tween 80 0.25 g Topanol A 0.1 g Water .98. A- g I 2 7SEP 1904 - 78 - 19851 u Example -44 : preparation of an emulsifiable concentrate The following are mixed intimately : Product of example 0.015 g Piperonyl butoxide 0.5 g Topanol A 0.1 g Tween 80 „„ 3-5 g Xylene 95-885 g xi Example A5 : preparation of an emulsifiable concentrate A homogeneous mixture is made of : Product of example JZ1 1-5 g Tween 80 20.00 g Topanol A 0.1 g Xylene 78.4 g Example 46 : preparation of a fumigating composition There are mixed in a homogeneous manner : Product of example 1 0.25 g Tabu powder .25.00 g Cedar leaf powder 40.00 g Pine-wood powder 33«75 g Brilliant Green 0.5 g p-nitrophenol 0.5 g 198515 -io - 7% - x°\ Example Pf? : example of pharmaceutical composition Solutions corresponding to the following formula have "been prepared. "7 Compound of example A£ 5*00 g 5 Piperonyl butoxide 25.00 g Polysorbate 80 10.00 g Triton X 100 25.00 g Tocopherol acetate 1.00 g Ethyl alcohol q.s. for 100 cm3 10 In this way a solution is obtained which is diluted in 5 litres of water when it is required for use. 30 Example : example of pharmaceutical composition. A solution corresponding to the following formula has been prepared : 1 15 Compound of example 1i 0.5 g Piperonyl butoxide 2.5 g Polysorbate 80 ..10.00 g Triton X 100 ...25.00 g Tocopherol acetate 1.00 g 20 Ethyl alcohol q.s. for 100 cmj In this way a solution is obtained which is diluted with 5 litres of water when required for use. 1985 - jao - 3/ Example 4*9 : example of pharmaceutical compositions Capsulos have been prepared containing 1 g of the product of example 1. 32- Example 50 : example of compound food-stuff for animals. As basic balanced food-stuff, a food-stuff is used comprising maize, dehydrated lucerne, wheat-straw, palmetto with molasses, urea, and a mineral condiment with vitaminso This food-stuff contains at least 11 % of crude protein material (of which 2.8 % is supplied by the urea), 2.5 % of fatty substances, and at the most 15 % of cellulose materials, 6% of mineral materials and 13 % of humidity. The food-stuff used corresponds to 82 forage units per 100 kilos, and contains 910,000 I.U. of vitamin a, 91,000 I«U. of vitamin 150 ing of vitamin. E and 150 mg of vitamin C per 100 kilos. With this food—stuff, 0.3 kg of the compound of .2. example 3 is incorporated per 100 kg of total food-stuff. 33 Example : example of compound food-stuff for animals. The same basic balanced food-stuff is used as in example 50* 0.04 kg of the compound of example 1 is incorporated per 100 kg of total food-stuff. 198515 - pi - Insecticidal study of the compounds of the invention In this study there are used : (lR,cis) 2,2-dimethyl 3(E) /2-chloro 2-methoxy carbonyl ethenyl/ cyclopropane-l-carboxylate of (S) a-cyano 3-phenoxy benzyl (compound A) (lR,cis) 2,2-dimethyl 3(2) (2-bromo 2-propoxy carbonyl ethenyl) cyclopropane-l-carboxylate of (S) a-cyano 3-phenoxy benzyl (compound B)yasrcJ (lR,cis) 2,2-dimethyl 3(Z)X^bromo 2-propoxy carbonyl ethenyl) cyclopropan^l-carboxylate of (S) a-cyano 3-phenoxy benzy]—(compouadG) ,—and- (lR,cis) 2,2 dimethyl 3-/(E) 2-fluoro 2-ethoxy carbonyl ethenyl/ cyclopropane carboxylate of (3) a-cyano 3-phenoxy c benzyl (Compound JO. A - Stud:^ of the knock-down effect on domestic flies The test insects are female domestic flies, 4 days old. The test is carried out by direct spraying at a concentration of 0.25 g/1 into a Kearns and March chamber, using as solvent a mixture of acetone (5%) and Isopar L (petroleum solvent)(quantity of solvent utilized, 2 ml per second). 50 insects are used per treatment. Checks are made every minute up to 10 minutes, then at 15 minutes, and the KT 50 is determined by the usual methods. 198515 - &§ - The experimental results obtained are summarized in the following table : Compounds Kt^Q in minutes Compound (A) Compound (B) Compound (C) 3.6 4.5 -4^5 Compound (J3) 2.1 B - Study of the lethal effect of the compounds of the invention on different insects. a) Study of the lethal effect on domestic flies. The test insects are female domestic flies 4 to 5 days old. The test is carried out by topical application of 1 pi of acetone solution on the dorsal thorax of the insects by means of an Arnold micro-manipulator. 50 individuals are used per treatment. The mortality check is made twenty-four hours after treatment. The results obtained expressed in or the dosage (in nanograms per individual) necessary to kill 50% of ik -?<- 198515 insects, are the following : Compounds LD in ng/insect Compound (A) Compound (B) 11.1 1.0 5 b) Study of the lethal effect on cockroaches. The tests are carried out by contact with a film on glass, deposited with a pipette, of acetone solutions of different concentrations on the bottom of a glass Petri dish, the edges of which had previously been given 10 a layer of talc to prevent the escape of the insects. The, lethal concentration 50 (I-C 50) is determined. The experimental results obtained are summarized in the following table : 15 Compounds 2 LC 50 in mg/m Compound (A) Compound (B) 1.4 0.40 • PATEN fQFpgc 2 7 SEP 1984 198515 - s* - c) Study of the lethal effect on larvae of Spodoptera Littoralis. The tests are carried out by topical application of an acetone solution, by means of an Arnold micro-5 manipulator, on the dorsal thorax of the larvae. 15 larvae are used per dose of the product to be tested. The larvae utilized are of the fourth larval state, that is to say, aged about 10 days when they are bred at 24° C and 65 % relative humidity. After treatment, 10 the individuals are placed on an artificial nutritive medium (Poitout medium). The check on mortality is carried out 48 hours after treatment. The experimental results obtained are summarized 15 in the following table : v.-.""Nrr 0*,"K"C- 2 ? 2 5 P '934 Compounds LD 50 in ng/insect Compound (A) 6.7 Compound (B) 3.2 c Compound (15) 1.0 20 d) Study of the lethal effect on Epilachna varivestris. The tests are carried out by topical application 1 9851 -J*5- in a similar manner to that used for the larvae of Spodoptera. Larvae are used of the penultimate larval stage and after treatment the larvae are fed on bean plants. The mortality check is made 72 hours after treatment. The results are summarized in the following table : Compounds LD 50 in ng/insect Compound (A) Compound (B) c Compound (tf) 17.7 7.4-0.85 e) Study of the lethal effect on Aphis Cracivora. 7-day old adults are utilized and 10 aphis are used per concentration employed. A contact injection method is used. The treatment is carried out with a Fisher pistol on to a bean leaf which is placed in a plastic Petri dish on a disc of dampened paper. The treatment is made with 2 ml of acetone solution of the product to be tested (1 ml on each side of the leaf). The infestation with the insects is done after the leaf is dried. The insects are kept in contact with the leaf for one hour, then the insects are placed on non-treated leaves and mortality is checked at n,7. :v t-vr/'E 2.7s::' 34 198515 the end of 24 hours. The experimental results obtained are summarized in the following table : N.Z. Wl- , 'eg ^ Compound (B) 6.4 I J 1 2 7SEP1984 1 REChiVrg f) Conclusion : In the tests described in paragraphs a, b, c, d and e, compounds A and B both exhibit a useful insecticidal activity. g) General conclusion The compounds according to the invention are endowed with a useful insecticidal activity in the tests described previously. B Acaricidal study of the compounds according to 15 the invention Bean plants are used having two leaves infested with 25 females of Tetranychus Urticae per leaf, put under an open shade, under a bright ceiling, in constant illumination. The plants are treated with a Fisher 20 pistol; 4 ml of toxic solution per plant of a mixture of equal volumes of water and acetone. The Compound LD 50 in ng/insect Compound (B) 6.4 </div>

Claims

<div class="application article clearfix printTableText" id="claims"> 198515 -1* - 07 - infestation is carried out after allowing the solution to dry for 12 hours, and mortality checks are made 80 hours afterwards. The dosage used in each test is 5 6 product per hi. 5 The compounds A^ B/—aa4-^4 exhibit a good activity in this test. » 2 7SEP1984 | G 0 cr 1 £ / v j i j - 79 - WHAT WE CLAIM IS; CLAIMS Co mpousicfs

1. /In all frheir possible isomeric forma, ex- in the forirf 6f a mixture of isomers, tehc-eempoundd with the formula (I)

HO C

(I)

in which R represents either a linear, branched or cyclic

(i/ic imcus\ ^ ojcfocjjtijlcufccj i)

alky1^radical, saturated or unsaturated, containing from 5 1 to 8 carbon atoms, optionally substituted by one or more functional groups, identical or different, or an aryl group containing from 6 to 14 carbon atoms, optionally substituted by one or more functional groups, identical or different, or a heterocyclic radical, optionally 10 substituted by one or more functional groups, identical or different, B represents -^he residue of an alcohol utilized in the synthesis of esters of the pyrethrinoid series and X represents a halogen atom, the ethylene double bond having (E) geometry and the cyclopropane ring 15 having (lR,cis) stereochemistry.

/'■

]925)5

- 80 -

2. Compounds with the formula I as defined In claim l, in which X represents a fluorine atom.

3. Compounds with the formula I as defined in claim 1 or claim 2 in which R represents a linear, branched or cyclic alkyl radical containing from 1 to 8 carbon atoms.

4 .

Compounds with the formula I as defined in claim 3,

in which R represents an ethyl radical.

5 .

Compounds with the formula I as defined in claim 3,

in which R represents a tert-butyl radical.

6 .

Compounds with the formula I as defined in claim 3,

in which R represents a cyclopropyl or a cyclopropyl-

methyl radical.

7. Compounds with the formula I as defined in claim l or claim 2 in which R represents a linear or branched alkyl radical containing from 1 to 8 carbon atoms, substituted by one or more halogen atoms.

8 . Compounds with the formula I as defined in claim 7, in which R represents a linear alkyl radical containing from 1 to 8 carbon atoms, substituted by one or more fluorine atoms.

9. The compounds with the formula I as defined in claim

1 or claim 2 in which R represents a (CH„) O(CH^) -CH

c 2'm 2' n 3

radical (where m represents an integer of from 1 to 8.

and n represents 0 or an integer of from 1 to 8).

198515

- 81 -

10. The compounds with the formula I as defined in claim 9 in which. R represents the radical -CH^QCH^.

11. The compounds with, the formula I as defined in anyone of claims 1 to 10 in which B represents

5 - either a benzyl radical optionally si±>stituted by cue or more radicals chosen from the group constituted by alkyl radicals containing from i to 4 carbon atoms,

radicals containing from 2 to 6 carbon atoms,

10 radicals containing from 4 to 8 carbon atoms,

dioxy radical and halogen atoms,

- or a group

%

in which the substituent R^ represents a hydrogen atom 15 or a methyl radical and the substituent Rg represents a monocyclic $ryl radical or a -CH-C a CH

- or a group alkenyl alkenyloxy alkadienyl a methylene

■

- 92 -

198515

a in which a represents a hydrogen atom or a methyl radical and R^ represents an aliphatic organic radical containing from 2 to 6 carbon atoms and one or more carbon-carbon unsaturationa,/ and in partioulap—

jfcn2-on - cm-oii^, -on^ -on - ch ch - ch2,/

J CH2 CI1 - CH CH2 CH^ radical^

- or a group in which a represents a hydrogen atom or a methyl radical, E, retains the same significance as previously,

eacA rzf>/&ses)tS

R'^ and R'2» identical or different, repreoent a hydrogen atom, a halogen atom., an alkyl radical containing from 1 to 6 carbon atoms, an aryl radical containing from 6 to cx.1 ko3CijCasbc*nu (

10 carbon atoms, an Jilky 1 car bo uyl group containing from 2 to 5 carbon atoms, or a cyano group,

- or a group

1 c':r7ce

2 jsep t984

1 9851

<3 - -

J

in which B1 represents an oxygen or a sulphur atom,

a group -d- or or a sulphoxide group or a sulphone group, and R^ represents a hydrogen atom, a -C s N radical, a methyl radical, a -CONHg radical, a -CSNH2 radical or a -C - CH radical, R^ represents a halogen atom or a methyl radical and n represents fi. numeral 0, 1 or 2,

and In partlcular/S. 5-phenoxy benzyl, u-cyan^3-phenoxy benzyl, a-ethyfiyl 3-phenoxy benzyl, 3-benzoyl benzyl, 1-(3-phemylry phenyl) ethyl or rr-thioqafido 3-,phonoxy beaayl group ?—

- or a group

CN

- or a group

«, c o £ 1 [ / O J I ^

- 95 -

cxfxi isiclepe*

in which the substituents Eg, Er;, Bgj[ R<^ ^represent hydrogen atoms, chlorine atoms, or methyl radicals, and nrtet in which s/I symbolizes an aromatic ftyold or a similar dihydro or tetrahydro ringj - or a group

-ch2 - n ch2 - Csch

- or a group po

- CH - En - H12

•\c>

<\ (y~.

v-

1 98515

in which R^q represents a hydrogen atom or a CN radical, Rl2 represents a -CE^- radical or an oxygen atom, R^ represents a thiazolyl or a thiadiazolyl radical of which the bond with -^H- can be found in any one of the

*10

available positions, R^ being attached to R^ by the carbon atom included between the sulphur atom and a nitrogen atom,

- or a group

- or a group in which R^ represents a hydrogen atom or a CN radical, - or a group

27SEP1984

-

198515

in which R^ is defined as above, and the benzoyl radical is in position 3 or 4,

- or a group

Ri >1

/ VI;

err-

in which R, . represents a hydrogen atomJ a methyl, ethynyl an. cu>d ercuJt or cyano radical and R^ and R^gj^ different^

a hydrogen, a fluorine or a bromine atom,

- or a group r

:\! ?.. fi-'t

7 5 zf1984

i

(r17^P

in which R^ is defined as above, each of the R^'s represents independently an alkyl group containing from

10 1 to 4 carbon atoms, an alkoxy group containing from 1 to 4

carbon atoms, an alkylthio group containing from 1 to 4

carbon atoms, an alkyl sulphonyl group containing from

1 to 4 carbon atoms, a .trifluoromethyl group, /■©a/ a or A

3,4-methylene dioxy^ chloro, fluoro or bromo group, p 15 represents jin intege^ 0, 1 or 2, and BM represents an

198515

- 87 -

oxygen or a sulphur atom.

12. The compounds with the formula I as defined in claim 11 in which B represents - either a 5-benzyl-3-furylmethyl group, 5 - or a group a

in which a represents a hydrogen atom or a methyl radical and represents a -CH^-CH^CF^ , -C^-CH^CH-CH^, -CH2-CH=CH-CH=CH2 or -CH2-CH=CH-CH2-CH3 radical/ 10 - or a 3-phenoxybenzyl, <x-cyano-3-phenoxybenzyl,

c<-ethynyl-3-phenoxybenzyl, 3-benzoylbenzyl, 1-(3-phenoxy-phenyl) ethyl or <*-thioamido-3-phenoxybenzy 1 group.

1

&

1984

1 90515

5* - 9£> -

13. The compounds with the formula I as defined in any one of claims 1 to 12, corresponding to the formula 1^:

b1s°

10

15

0—q in vhich A represents an oxygen atom, a methylene group,

a carbonyl group, a sulphur atom, a sulphoxide group, or a sulphone group, E represents a linear or branched alkyl radical containing from 1 to 8 carbon atoms, X^

represents a fluorine, chlorine or bromine atom, the double ethylene/bond having (E) geometry, and the

{1R , cii)

substituted cyclopropane ring having jdRyqio} stereochemistry

14. The compounds with the formula (1^) as defined in claim 13 in which A represents an oxygen atom.

15. (S) a-cyano-3-phenoxy benzyl (lR,cis) 2,2-dimethyl--3(E)-/2-fluoro-2-(ethoxy carbonyl) ethenyl/cyclopropane-

-1-carboxylate.

16. ^The compounds with the formula I as defined in any one of the claims 1 to 12 in which B represents a radical^

si 1 98515

- off -

17. The compounds with the formula I as defined in any ux one of fchrti claims 1 to 12^ f03/ which B represents a radical,

18. The compounds with the formula I as defined in c/l any one of fchd claims 1 to 12^__fL©J? which B represents a radical,

19. The compounds with the formula I as defined in any ux one of Itefed claims 1 to- 12/—which B represents a radical,

- 9© -

198515

— CH

20. The compounds with the formula I as defined in

UX

any one of claims 1 to 12^ fm/ which B represents a radical.

2i^ The application of the compounds of formula I as-,

5 defined in any one of f&arej claims y to 12, 16 to 20, for combatting parasites of vegetati/n, parasites of premises and parasites of warm-blooded animals.

22. The application of the Compounds with the formula IA as defined in any one of Ahe claims 13 to 1^, for 10 combatting parasites of vegetation, parasites of premises i / r and parasites of wavrn blcrodod aniaejrs-. .

ai

.25. Compositions intended for combatting parasites of vegetation, parasites of premises and parasites of warmblooded animals, characterized in that they contain as as

15 active principle at least one compound^defined in any one of frhe} claims 1 to 12 and 16 to 20.

mr r

q\

- .99 -

1985?

22. Compositions intended, for combatting parasites of vegetation, parasites of premises and parasites of warm' blooded animals, characterized in that they contain as active principle at least one compound/defined in any one of . claims 13 to 15.

23. Insecticidal compositions, characterized in that they contain as active principle at least one compound as defined in any one of . claims 1 to 12 and 16 to 20,

24. Insecticidal compositions, characterized in that they contain as active principle at least one compound as defined in any one of claims 13 to 15.

25. Acaricidal compoa. tions, characterized in that they as contain as active principle at least one compound/defined in any one of claims 1 to 12 and 16 to 20.

26. Acaricidal compositions characterized in that they as contain as active principle at least one compound/defined in any one of claims 13 to 15.

27. Compositions intended for animal alimentation, characterized in that they contain as active principle at least one compound as defined in any one of claims 1 to 12 and 16 to 20, associated with an animal food-stuff.

28. Compositions intended for animal alimentation, characterized in that they contain as active principle at least one compound as defined in any one of claims 13 to 15, associated with an animal food-stuff.

as

27sep1984

198515

ioe -

Ccrmpos Un ori*,

29. pcmbinationg endowed with insecticidal, acaricidal or nematocidal activity, characterized in that they contain as active material, on the one hand, one at as defined in Claim 1

least of the compounds with the general formula (I)/{ and, on the other hand, at least one pyrethrinoid ester selected from esters of:

allethrolone,

3,4-,5,6-tetrahydrophthalimido ©ethyl alcohol, S-benzyl-3-furyl methyl alcohol,

3-phenoxy-benzyl alcohol, and a-cyano-3-phenoxy benzyl alcohol, , with chrysanthemic acids}

s-benzyl-3-furyl methyl alcohol with 2,2-dimethyl-3-(2-oxo -3-tetrahydrothiophenylidene methyl) cyclopropane-1--carboxylic acid ;

3-phenoxy benzyl alcohol and a-cyano-3-phenoxy benzyl alcohol with 2,2-dimethyl— -3-(2,2-dichlorovinyl) cyclopropane-l-carboxylic acid; a-cyano-3-phenoxy benzyl alcohol with 2,2-dimethyl-3-(2,2--dibromovinyl) cyclopropane-l-carboxylic acid «

3-phenoxy benzyl alcohol with 2-parachlorophenyl-2--isopropyl acetic acid; and

5»4,s,6-tetrahydrophthalimido methyl alcohol., 29NOV1984

w allethrolone,

q-benzyl—3-furyl methyl alcohol

3-phenoxy benzyl alcohol and a-cyano-3-phenoxy benzyl alcohol, with 2,2-dimethyl

10

15

^3

- lp-1 -

1 9B5 i

3-(l,2, 2,2-tetrahaloethyl)-cyclopropane-l-carboxylic acidst (where "halo" represents a fluorine, chlorine or bromine atom) it being understood that the compounds I

uAiertt these can exist in all their possible stereoisomeric forms/ and this applies also to the acid and alcohol moieties of the above pyrethrinoid esters.

30 «. The. conroounds with the formula I

as medicaments.

as defined in any one of . claims 1 to 20 suitable for use/ 31. Pharmaceutical compositions containing, as active principle, at least one of the medicaments defined in claim 30 .

32 . Preparation process for the compounds with the formula I as defined in any one of claims 1 to 12 and 16 to 20, characterized in that an acid with the formula (II):

CH-

(II)

in which X and R are as defined in Claim 1

this acid being in the form of the (E) isomer and the substituted cyclopropane ring having the (f^.fcis) stereochemistry,

- 102 L

198515

or a reactive derivative of this acid, is made to react with an alcohol with the formula (III):

B-OH (III)

in which B is as defined in Claim 1,

' , or a reactive . derivative of this alcohol, so as to obtain

5 the corresponding compound with the formula (I), which,

if desired, is submitted to the action of a selective cleavage agent for the group CO^, so as to obtain the compound with the formula (IV):

(IV)

in which B and X are as defined in Claim 1,

10 then this acid with the formula (IV) or a reactive derivative of this acid, is submitted to the action of an alahol with the formula R-OH in which R is as defined in Claim 1, , so as to obtain the corresponding compound with the formula (I).

15 33„ Preparation process for compounds with the formula 1^, as defined in any one of claims 13 to IS, characterized in that an acid with the formula (11^):

KZ.P&r v n u" c.i r ?>84

198515

- 95

*18°-°

o

-OH

<iia)

in which X. and R,Q are as defined in claim 13, this acid

1 io being in the form of the (E) isomer, the substituted cyclopropane ring having the (lR,cis) stereochemistry, or a reactive derivative of this acid (HA) / is made to react with an (S) alcohol with the formula (III ):

ciiia)

in which A is as defined in claim 13, or a reactive derivative of the alcohol with the formula (III ),. 10 34. Process according to claim 32 or 33, characterised in that the acids with the formula (II) or (11^) in which R or R^g represents an alkyl radical containing from 1 to

- 96 -

h r <"! r •' i / OJ I J

5 carbon atoms, are prepared by making a cis aldehyde in the form of a lactone with the formula (V):

(V)

or a trans aldehyde with the formula (VT):

G-OH

(VI)

react according to the Vittig reaction, in the presence of a strong base, with a phosphorane with the formula (VII);

X(or Zx)

({d, * P - c

(VII)

C - OR

&

19

in which formula R^ represents an alkyl radical 10 containing from 1 to 5 carbon atoms and X and X^ are as defined in claim 1 and claim 13 respectively, or with a

/ : 'J-1'

phosphonate with the formula (VIII) : /

' X?' "jS. / ■

A) >-* V

- 97 -

c 9. c i r

✓ O w' »

S20

0^ ^

P - CH X - C - 0R19 (VIII)

(or X,)

20 1

in which formula is as defined above, X and X^ are as defined in claim 1 and claim 13 respectively and R2q represents an alkyl radical containing from 1 to 6 carbon atoms.

35. The acids with the formulae II and II, as defined in claims 32 and 33, as well as the reactive derivatives of these acids.

36. The acids with the formula IV as defined in claim 32

den \scL~ti \J~es as well as the reactive florivatio^ of these acids.

37 . Compounds of formula (I) as defined in claim 1

substantially as herein described.

of

38. Compounds aa formula (I) as defined in claim 1 substantially as herein described in any one of Examples 1 to 24.

39. Parasiticidal compositions as claimed in claim 21 or claim 22 substantially as herein described.

40. Parasiticidal compositions as claimed in claim 21 or claim 22 substantially as herein described in any one of Examples 2 5 to 28.

41. A method of treating a site other than a human cA

infested with or susceptible to infestation by parasites ^ comprises applying to the said site an effective amount-'1-of-..,.

1 98 51-5

- 98 -

at least one compound of formula (I) as defined in claim 1.

42. A process for the preparation of compounds of formula (I) as defined in claim 1 which comprises submitting a compound of formula (IV) as defined in claim 32 to the

5 action of an alcohol of formula R-OH in which R is as defined in claim 1.

compowids

43. A process for the preparation of (ftompundfl of formula (I) as defined in claim 1 substantially as herein described.

44. A process for the preparation of compounds of.

10 formula (I) as defined in claim 1 substantially as herein described in any one of Examples 1 to 24.

45. Compounds of formula (I) as defined in claim 1 whenever prepared by a process as claimed in any one of claims 32 to 34, 42, 43 and 44.

15 46. A process for the preparation of compounds of formulae II and IV as defined in claim 32 substantially as herein described.

"TH A mathoa Of LlfcidLliiy d pdlieiiL yiiiresLeQ Willi Ui

susceptible to infestation by parasites which comprises 20 externally applying to the patient an effective amount of at least one compound o^/formula (I) as defined in claim 1.

ROUSSEL-UCLAF 29 NOV 1984

i by their attorneys ^x '> BALDWIN, SON & CAREY ' '

</div>