IE52212B1 - Esters of cyclopropane carboxylic acids related to pyrethric acid,their preparation process and their application for combatting parasites - Google Patents

Abstract

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

Description

The invention is concerned with new esters of cyclopropane carboxylic acids, the process for preparing them and their application for combatting parasites.

The subject of the invention is the compounds with 5 the formula I: in which the cyclopropane acid moiety is of iR 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, ___ X.. -F - 2 or a heterocyclic radical possibly substituted by one or more functional groups, identical or different, B represents the residue of an alcohol utilized in the synthesis of pyrethrinoid esters as defined hereinafter and X represents a halogen atom.

The compounds with the formula (I) may exist in different stereoisomeric forms when there are one or more centres of asymmetry in B and/or in R.

When R represents a saturated linear or branched alkyl 10 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 radical, it is preferably 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 alkyl radicals of which the bond with the -CCO- group is situated on any one of its apices, for example, a 1-methyloyclobutyl, 1-methyloyclopentyl, 1-methyloyclohexyl or 2,2,3,3-tetramethylcyclopropyl radical.

When R represents an unsaturated alkyl radical, it may be an alkylene radical, such for example, as a vinyl or a 1,1-dimethylallyl radical, or an alkynyl radical, such, for example, as an ethynyl or a propynyl radical.

When R represents an alkyl radical substituted by 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.

When R represents an alkyl radical substituted by one or more functional groups, there is preferably understood by functional group, a halogen atom, an OH or an SH group, an OR' or an SH' group in which R' represents an alkyl radical containing from 1 to 8 carbon atoms, an -NO2 group, or a group -N in which R and R' , - 4 identical or different, represent each a hydrogen atom, or an alkyl radical containing from 1 to 8 carbon atoms, a -CsN, an -30^H, or a -PO^Hj group, or a -COalk^, -SOgalkg, or -SO^alk^ group, in which' alk^, alk2 and alkrepresent 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 possibly substituted by one or more-0H,-0alk or alk groups containing from 1 to 8 carbon atoms, by one or more halogens or -CFj, -OCFj, -SCFj, or by a group (G): (G) R can also represent an alkyl radical substituted on two adjacent carbons by a group (G^) (G]_) When H represents an alkyl radical substituted by one or more functional groups, preferred values for R would be the radicals: 522 12 ίο -(CHg^-CHalj in which n is an integer from 1 to 8 and Hal is a halogen atom, for example a -CHg-CGlj, -CH2-CF3 -CHg-CHg-CClj or -CHg-CHg-CFj radical, -(GHg)^ -CH Haig in which Hal is defined as above and n is a numeral from 0 to 8, for example a -CHg-CHOlg, -CHg-CHFg or -CHFg radical, -(CHg^-CHg Hal in which n and Hal are defined as above, for example a -CHg-CHgCl or -CHg-CHgF radical, -C-(CHalj)j in which Hal is defined as above, for . xCT5 example a -0-(05^)^ or -C-—-CFj radical, .^CCl ’ /CF3 -C<_ch5X'cf3 cf5 -c-ch3 H CH5 - C^-CN CH, or cf5.

-C— CH, \ 3 CH5 -c-cf5XH CH, / 5 -C-CN ^H ZCF5 or CHj radical, ch2-ch3 radical, or -(CH2)n-CN radical, in which n is defined as previously, CHal, / * .- C<-CN radical, in which Hal is defined as ,CC1, X 5 previously, for example a -C— CN radical - 6 -(CH2)n-OH' 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 -CHj-OCH^, -CHg-CHg-O-CH^, -CH2-CH2-O-CH2-CH3 or -CHg-CHg-OH radical, or a -(CH2)n radical, in which n and R' are defined \h· as previously and the two R' radicals may not he identical, .GH, for example a -CHg-CHgCH, .CH, -CH2-GH2-N CH, or -CHg-CHg-N radical, or a ch2-ch3 -(CH2)n~2 radical, in which n is defined as z° H.C \η. previously, for example a -CH^-CH-CH2 radical, or a y H5Cz ‘CH, -(CHO)„ -CH—CHO radical, in which n is defined as n | [ 2 OH OH previously, for example a -CH2-CH-CH2-0H radical, or a OH -(CH2)n-0- radical, in which n is defined as previously, for example a -CH2-0-ch2-ch2-o-. or a radical, or a -(CH2)n- radical, in which n is defined as previously, for example a benzyl or a phenethyl radical, or a -(CH2)n5 radical, in which n is defined as previously, for example, a -CH. radical.

Q When R represents an aryl radical possibly substituted, it is preferably a phenyl radical or a phenyl radical substituted by one or more OH, Oalk, or alk groups, 10 containing from 1 to 8 carbon atoms, or by a halogen, or a -CKj, -OCRj or a -SCR^ group.

When R represents a heterocyclic radical, it is preferably a pyridinyl, furanyl, thiophenyl, oxazolyl or thiazolyl radical.

As halogen, it is preferred to be a fluorine, chlorine or bromine atom.

Among the compounds according to the invention, there can be cited the compounds with the formula I in which X - 8 represents a fluorine atom; there can also be cited the compounds with the formula I for which R represents a linear, branched or cyclic alkyl radical, containing from 1 to 8 carbon atoms, and in particular an ethyl radical, a tert-butyl radical, or even a cyclopropyl or a cyclopropylmethyl radical. There can also be cited the compounds with the formula I for which R represents a linear or branched alkyl radical, containing from 1 to 8 carbon atoms, substituted by one or several halogen atoms, for example those for 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 for which R represents a iGH2^m°^CH2^n"CH3 radical in which m represents an integer varying from 1 to 8 and n represents an integer varying from 0 to 8, and in particular, the radical -CHgO-CHy In the compounds of formula I β represents the residue of an alcohol utilized in the synthesis of pyrethrinoid esters selected from the following: a benzyl radical possibly substituted by one or more radicals chosen from the group constituted by the alkyl radicals containing from 1 to 4 carbon atoms, the alkenyl radicals containing from 2 to 6 carbon atoms, the alkenyloxy radicals containing from 2 to 6 carbon atoms, the alkadienyl radicals containing from 4 to 8 carbon atoms, - 9 the methylene dioxy radical and halogen atoms, or a group in which the substituent R^ represents a hydrogen atom or a methyl radical and the substituent Rg represents a monocyclic aryl radical or a group -CHg-C 3 CH and in particular a 5-benzyl 3-furyl methyl group, in which a represents a hydrogen atom or a methyl radical and Rj represents an aliphatic organic radical containing from 2 to 6 carbon atoms and one or more carbon-carbon unsaturations and in particular the radicals -CHg-CH^Hg, -CHg-CH = CH-CHj, -CHg-CH - CH-CH = CHg, in which a represents a hydrogen atom or a methyl radical, R^ retains the same significance as previously, R'^ and R'g, - 10 identical or different, each represent a hydrogen atom, a halogen atom, an alkyl radical containing from 1 to 6 carbon atoms, an aryl radical containing from 6 to 10 carbon atoms, an 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 II a -C- or -CHg- group, or a sulphoxide group or a sulphone group, and. R^ represents a hydrogen atom, a CSR radical, a methyl radical, a -CONHg radical, a CSNHg radical or a -CsCH radical, R^ represents a halogen atom or a methyl radical, and n represents a numeral 0, 1 or 2, and in particular, the 3-phenoxybenzyl group, or the α-cyano-J-phenoxybenzyl, «-ethynyl-3-phenoxybenzyl, 5-benzoylbenzyl, 1-(3-phenoxyphenyl) ethyl, or the α-thioamido -3-phenoxybenzyl group. or a group - or a group in which the substituents Rg, R?, Rg and. RQ each represents a hydrogen atom, a chlorine atom or a methyl radical and in which S/I symbolizes an aromatic ring or an analogous dihydro or tetrahydro ring. 2212 - 12 in which R^Q represents a hydrogen atom or a CN radical, R^2 represents a -CHg- 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 •ko 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 in which R^ represents a hydrogen atom or a CN radical, - or a group 4' 53218 - 13 in which R^ is defined as above, and the benzoyl radical is in position 3 or - or a group in which R^ represents a hydrogen atom, a methyl, ethynyl 5 or cyano radical, and R^ and R^, which are different,each representsa hydrogen, fluorine or bromine atom, - or a group in which R^ is defined as above, each of the R^? 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 - 14 from 1 to 4 carbon atoms, a trifluoromethyl group, a 5,4-methylene dioxy group, or a chlorine, fluorine or bromine atom, p represents a numeral 0, 1 or 2 and B represents an oxygen or a sulphur atom.

When B represents a benzyl radical substituted by 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 vinyl, allyl, 2-methylallyl or isobutenyl radicals.

When B represents a benzyl radical substituted by an alkadienyl radical, it is preferred to be a benzyl radical substituted by an alkadienyl radical containing 4, 5 or 6 carbon atoms.

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.

When B represents a benzyl radical substituted by one or more halogen atoms, they are preferred to be chlorine, bromine or fluorine atoms.

When B represents the radical: Rj preferably represents a a -CH2-CH=CH-CHj, - 15 a -CH2-CH-CH-CH«CH2 or a -CH^-CHCH-CHg-CH^ radical. When R'i and (or) R'2 represent a halogen atom, it is preferred to be a chlorine, bromine or a fluorine atom.

When R'j and (or) R'2 represent an alkyl radical, it is preferred to be a methyl, ethyl, n-propyl or n-butyl radical.

When R'2. (°r) Rl2 represent an aryl radical, it is preferred to be a phenyl radical.

When R'^ and (or) R'2 represent an alkoxycarbonyl radical, it is preferred to be a methoxyoarbonyl or an ethoxycarbonyl radical.

When in the radical: ^S17^P R^ represents an alkyl, alkoxy, alkylthio or alkyl15 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 which B has the significance mentioned above, there can be cited the compounds corresponding to the formula in which the cyclopropane acid moiety is of ]R cis structure and the geometry of the double bond is E and 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 and X^ represents a fluorine, chlorine or bromine atom.

In the compounds with the formula (1^), R^g 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. - 17 In particular, the subject of the invention is the compounds with the formula for which A represents an oxygen atom.

Among these preferred compounds, there can quite 5 specially be cited (s) ei- -cyano-3-phenoxybenzyl (lR,cis) 2,2-dimethyl-3|(E) -2-fluoro-2- (ethoxycarbonyl) ethenylj1cyclopropanc-I-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; those for which B represents a radical; those for which B represents a radical: 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-dioxoimidazolidinyl/methyl and also a radical a-cyano-6-phenoxy-2-pyridylmethyl.

Quite particularly, the subject of the invention is the compounds of which the preparation is given further - 19 on in the experimental part, and in particular, among these, the compounds of examples 1, 11 and 21.

The compounds with the formula (I) offer useful properties which enable them to be utilized in 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, nematodes and acaridan parasites of vegetation and animals.

Thus a subject of the invention is the application of the compounds with the formula (I) for combatting parasites of vegetation, parasites of premises and 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.

The products with the formula (I) can thus be utilized in particular to combat insects in the agricultural domain, to combat, for example, plantlice, the larvae of lepidoptera and coleoptera.

They are utilized at doses between 10 g and 300 g of active material per hectare. - 20 The products with the formula (I) can also be utilized to combat insects in premises, in particular to combat flies, mosquitoes and cockroaches.

The compounds of examples 1, 11 and 21 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 photostable and are not toxic 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 he utilized to combat the parasitic acaridae and nematodes of vegetation.

The compounds 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 Ehipioephalus species, or to combat all sorts of manges and particularly sarcoptic mange, psoroptio mange and chorioptic mange.

Thus equally a subject of the invention is the - 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 1^.

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 example 1, the compound of example 11 and the compound of example 21.

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. - 22 In addition to the active principle, these compositions generally contain a vehicle and/or a surface-tension active agent, non-ionic, which in addition ensures a uniform dispersion of the constituent substances of the mixture. The vehicle utilized can he 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.

The insecticidal compositions according to the 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 in the form of fumigating compositions.

The compositions according to the invention can then advantageously be constituted, as regards the non-active part hy a combustible insecticidal serpentine (or coil) or also hy a fibrous incombustible 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 utilized, the inert support can, for example, he composed of pyrethrum residues, Tabu powder - 23 (or Machilus Thunbergii leaf powder),powdered, stem of pyrethrum, cedar leaf powder, powdered wood (such as pine sawdust), starch and coconut shell powder.

The dosage of active material can then, for example, he 0.05 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 0.05 to 95% ty weight.

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.

The concentration of active principle incorporated in the oil· is preferably from 0.05 to 95% by weight.

The insecticidal compositions according to the invention, such as the acaricidal and nematccidal 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.

For acaricidal use, it is preferred to use powders which can he wetted for spraying on foliage containing from 1 to 80% of active principle, or liquids for sp-aying on foliage containing from 1 to 500 g/1 of active principle. Powders can also he used for powdering 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/l of active principle.

The acaricidal and nematocidal 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 used in similar cases can be added to them, such as 1-(2,5,8-t rioxadodecyl)-2-propyl-4,5-methylenedioxybenzene (or piperonyl butoxide) or N-(2-ethyl-heptyl) bicyclo/2,2-l/5-beptene-2,3-di2carboximide, or piperonyl-bis-2-(21-n-butoxy-ethoxy)-ethylacetal (or tropital).

When it is required to combat parasitic acaridae of animals, th'e products according to the invention are very frequently incorporated in alimentary compositions in association with a nutritive mixture suitable for animal feeding. The nutritional - 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), as medicaments, 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 also be administered externally, hy vaporisation, hy shampooing, by bathing or hy 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 he administered hy digestive or parenteral route. - 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.

A subject of the invention is also the combinations 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 one at least of the pyrethrinoid esters chosen from the group constituted by esters of allethrolones, 3,4,5,&-tetrahydrophthalimidejmethyl alcohol, 5~benzyl-3-furyl_methyl alcohol, 3-phenoxy£benzyl alcohol and a-cyano3-phenoxyZbenzyl alcohol, with ohrysanthemic acid , by esters of 5"benzyl'3-furyl~methyl alcohol with 2,2-dimethyl-3-(2-oxo-3-tetrahydrothiophenylidene methyl) cyclopropane-l-carboxylio acid , by esters of 3-phenoxy£benzyl alcohol and α-cyano-3-phenoxy_benzyl alcohol with 2,2-dimethyl~3-(2,2-dichlorovinyl) cyclopropane-1-carboxylic acid , by esters of α-oyano 3-phenoxyZbenzyl alcohol with 2,2-dimethyl-3-(2,2-dibromovinyl)-cyclopropane-1-carboxylic acid , by esters of 3-phenoxy~benzyl alcohol - 27 wih 2-parachlorophenyl-2-isopropyl-acetic acid ., by esters of allethrolone.·, of 3,4,5,e-tetrahydrophthalimidejmethyl alcohol, of 5benzyl-3~furyl2methyl alcohol, of 3-phenoxy2henzyl alcohol and of a-cyano 3-phenoxyChenzyl alcohol, with. 2,2-dimethyl3-(1,2,2,2-tetrahaolethyl)cyclopropane-l-carboxylic acids, in which halo represents a fluorine, chlorine or bromine atom, it being understood that the compounds (I) can exist in all their possible stereo-isomeric forms and likewise for the acid and alcohol moieties of the above pyrethrinoid esters.

The combinations according «-to. the. invention offer particular interest both 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) : H (II) II - 28 in which the cyclopropane acid moiety is of IR cis structure and the geometry of the double bond is E and in which X and R retain the same signification as previously or a functional 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 functional 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 COgH group, so as to obtain the compound with the formula (IV) s in which the cyclopropane acid moiety is of IR cis structure and the geometry of the double bond is E and in which B retains the same significance as previously, then this acid with the formula (IV) or a functional 53213 - 29 derivative of this acid is submitted to the action of an alcohol with the formula E-OH in which E retains its previous significance, so as to obtain the corresponding compound with the formula (I).

A particular subject of the invention is a process according to the preceding one, for preparing the compounds with the formula 1^, as previouslydefined, characterized in that an acid with the formula (Up s in which Lhe cyclopropane acid moiety is of 1. R cis structure and the geometry of the double bond is E and in which and R^g retain the same significance as previously, or a functional derivative of this acid , is made to 53212 - 50 react with an alcohol with the formula (Hip in which A retains the same significance as previously, or with a functional derivative of the alcohol with the formula (ΙΙΙΛ>, and the product obtained is separated so as to obtain a corresponding compound with the formula The esterification of the acid (II) or (Up with the alcohol with the formula (III) or (IIip can be carried out in the presence of a tertiary base such as pyridine. This esterification can - be carried out advantageously in the presence of a mixture of pyridine, dicyclohexyl carbodiimide and 4-dimethylaminopyridine.

The esterification can also be realized by making a chloride of the acid (II) or (Up react on the alcohol with the formula (III) or (Hip or on a metallic derivative of this alcohol, such as a silver salt.

The Wittig reaction generally used for the preparation of the acids with the formulae (II) or (lip 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 acid level or at the ester level. Examples of these two methods are given further on in the experimental part.

The C02R 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) 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 (Up in which R or Ε1θ 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) : HO .0.

(V) - 32 react by the Wittig reaction, in the presence of a strong base, with a phosphorane with the formula (VII) .X X(or Χχ) XC - OR.

(VII) '19 in which formula R^g 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) 0 ®20 °\T II XP - CH X - C - 0R19 / (oc Xl> (VIII) - 53 in which formulae X and. Χχ retain their previouslystated significances and represents an alkyl radical containing from 1 to 6 carbon atoms.

The acids with the formula (II) with definite 5 stereochemistry can also be prepared according to the following reaction scheme : In the formulae of this scheme, X represents a fluorine, chromine or bromine atom, B 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) ECO.

C02alk (IX) 53212 - 34 in which the geometry of the double bond is E, Ii retaining its previous signification and alk representing an alkyl radical, to the action of a braninating agent, such, for example, as pyridinium tri5 bromide, then to the action of a debromhydration agent, so as to obtain : - if the debromhydration agent is a basic agent acting in fairly mild conditions, the z isomer of the compound with the formula (Σ) : Br (Σ) is predominantly formed but by using more severe conditions the E isomer is predominantly formed. The experimental part gives an example of such a preparation where sodium hydroxide is used in order to get the E isomer. The compounds with the formula V can then be submitted to the action of an agent to cleave the CC^alk function, so as to obtain the corresponding acid with the formula II.

Examples of preparations of acids with the formula II are given in the experimental part. - 35 The acids with the formulae II and 11^ as well as the acids with the formula IV obtained during the putting into operation of the invention process, are new products and they themselves are a subject of the invention.

The following examples illustrate the invention without nevertheless limiting it. - 56 Example 1 ; (lR,cis) 2,2-dimethyl-?-£E)-2-fluorog-Cethoxy- carbonyl)-ethenyl·)-cyclopropane-1-carboxylate of (S) α-cyano-3-phenoxy-benzyl.

Into a solution of 3.87 g of (lR,cis) 2,2-dimethyl3(Z + E)~2-fluoro-2-ethoxycarhonyl-ethenyl)-oyclopropanex -1-carboxylic acid in 30 cnr of methylene chloride, 1.5 cm^ of pyridine, and 5*7 g of dicyclohexyl carbodiimide are introduced, and after agitating for 10 minutes, a solution of 4.05 g of (S) a-cyeno-3-phenoxybenzyl alcohol in 10 eiP 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 bn 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^(p) - 2-fluoro 2-(ethoxy-carbonyl)-ethenyl]-cyclopropane-l-carboxylate of (S) α-cyano-3~phenoxy-benzyl is recovered, and 2.8 g of the 3(2) derivative.

Analysis : C25 H2, FN02 (437.47) N% Calculated ; 68.64 5.55 5.20' 4.34 Found: : 68.8 5-5 5.1 4.2 XR Soectrum chloroform) - absorption at 1738 cnT^ and 1722 cnT^ attributed to the carbonyl and to the conjugated ester. - absorption at 1611 cm-^ attributed to the double ethylene bond - absorption at 1589cm-- 1489 cm~^ attributed to the aromatic nuclei. - absorption at 1380 cnT^ attributed to the paired methyls NMR 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.J8 - 6.55 p.p.m. attributed to the hydrogen of the double 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. 52213 - 38 The (lfi,cis) 2,2-dimethyl-3"'(E,Z) - 2-fluoro2- ethoxy-carbonyl-ethenylJ -cyclopropane-l-carboxylic acid is obtained in the following manner.

Into a solution of 12.1 g of ethyl diethyl z phosphoro-fluoro-acetate in 120 cm of dimethoxyethane, g of a 60% suspension in oil of sodium hydride is introduced at + 5°C, and after agitation for 30 minutes, .7 g of the lactone of (IK,cis) 2,2-dimethyl3- dihydroxymethyl)-cyclopropane-l-carboxylic acid is 10 introduced at 0°C. After agitation for 2 hours 30 minutes at 20°C, the reaction 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 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 (50/50/1) and 3.8? g of a mixture of (lK,cis) 2,2-dimethyl3j(E,Z)-2-fluoro-2-ethoxycarbonylethenyllcyclopropane-l20 carboxylic acid is obtained. - 39 Example 2 : (IB,cis) 2,2-dimethyl-5'Zfe) ~ 2-chloro2-(methoxycarbonyl) - ethenyl) - cyclo propane-1-carboxylate of (3) ct-cyano-5-phenoxy-benzyl. Into a solution of J g of (IB,cis) 2,2-dimethyl 5(E) (2-chloro 2-methoxycarbonyl ethenyl) cyclopropane-110 -carboxylic acid chloride in 15 cur of benzene, 5 g of (8) tx-cyano 5-pnenoxy benzyl. alcohol is introduced and X o then 1.3 cnr of pyridine is introduced at + 5° θ· After agitation for 15 minutes at + 5°c and then for 16 hours at + 20°C, the reaction 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 under 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 (IB,cis) 2,2-dimethyl- 3lfE)y 2-chloro-2-(methoxy-carbonylethenycyclopropane-l-carboxylate of (S) a-cyano3-phenoxy-benzyl is obtained. (α)ρ » 5Ο.50 (C 0.8 %, benzene).

Analysis :C24 H22 C11,05 439.9 Cl% C% H% Calculated : 65.55 5-04 8.05 3.1S Pound: 65-5 5-2 8.0 5-0 IH Spectrum (chloroform) - absorption at 1738 cm-1 and 1719 cm 1 ι to the carbonyl of the ester. - absorption at 1608 cm attributed to -C > C- absorption at 1589 cm-1 - 1489 cm3· attributed to the aromatic nuclei - absorption at 139θ 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 1.95 ~ 2.0? p.p.m. attributed to the hydrogen in position 1 of the cyclopropyl - peaks at 2.8? - 3.01 - 3.04· - 3.18 p.p.m. attributed to the hydrogen in position 3 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 - Ca N group - peaks at 6.91 - 7-5 p.p.m. attributed to the hydrogens of the aromatic nuclei.

The (lR,cis) 2,2-dimethyl-37(2) ~ 2-chlo to-^-(methoxycarbonyl)-ethenyl]-cyclopropane-l-carboxylie acid chloride can be obtained in the following manner: - .11 Stace A : (IK,cis) 2,2-dimethyl-3~fe) τ2-chloro2-faethoxy-carbonyl)-ethenylJ- cyclopropane1-carboxylic acid..

Into 50 cm^ of tetrahydrofuran, 12.6 g of methoxy 5 carbonyl chloro methylene triphenyl phosphorane and 4.85 S of the lactone of (IB,cis) 2,2-dimethyl3-(dihydroxymethyl)-cyclopropane-1-carboxylic acid in solution in 40 cm^ of tetrahydrofuran are introduced at 20° C, and agitated for two hours at 20°C. The reactional 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 (lfi,cis) 2,2-dimethyl-3^)~ 2-chloro20 2knethoxy-carbony^-ethenyi)-cyclopropane-l-carboxylic acid and 3 g of (lR,cis) 2,2-dimethyl-3’^Z)- 2-chloro-2-^methoxy carbonyl)-ethenylj-cyclopropane-1-carboxylic acid are obtained.

The (lfi,cis) 2,2-dimethyl-3'[fe) -.2-chloro_2-(methoxy carbonyl)-ethenylj-cyclopropane-1-carboxylic acid 53212 - 42 possesses the following characteristics : IR Spectrum (chloroform) - absorption at 3500 cm-1 attributed to the hydroxyl of the carboxyl - absorption at 1721 cm-'1', 1713 om \ 1700 cm attributed to the carbonyl - absorption at 14-90 cm-'*' - 1410 cm-^ attributed to the -C » C- absorption at 1393 cm-^ - 1380 cm attributed to the hydrogens of the paired methyls.

NMR 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 in position 1 of the cyclopropyl - peaks at 2.82, 2.97 p.p.m. - 2.98, *.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 the' methyl of the methoxy carbonyl - peaks at 6.72 - 6.78 p.p.m. attributed to the hydrogen of the double ethylene bond of the lateral chain in position 3 of the cyclopropyl. - peak at 11 p.p.m. attributed to the hydrogen of the carboxyl.

The (lR,cis) 2,2-dimethyl-3'ijZ) - 2-chloro2-(methoxy-carbony])-ethenyl^ -cyclopropane-l-earboxylic acid presents the following characteristics : IR Spectrum : (chloroform) - absorption at 3500 o®-3 attributed to the hydroxyl of the carboxyl (monomer + dimer) - absorption at 1725 cm1 attributed to the -C- ester - absorption at 1700 cm1 attributed to the hydrogen of the carboxyl (monomer) - absorption at 1623 cm1 attributed to the -C - C - absorption at 1393 cm-1 - 1381 cm1 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 - 7.45 p.p.m. attributed to the hydrogen of the double bond of the lateral chain in position 3 of the cyclopropyl - peak at 10.75 p.p·®· attributed to the hydrogen of the carboxyl.

Stage B ; (lR,cis) R.R-dimethyl-frife)—2-chloro25 2- (methoxy-carbonyl)- ethenylj- cyclonropane-l-carboxylic acid chloride 2.9 g of (IR,cis) 2,2-dimethyl-3^)3) - 2-chloro53313 - 44 2-(aethoxy-carbonyl)~ethenyll·cyclopropane-1-carboxylic acid, 20 cm^ of isoprene and 10 cm^ of thionyl chloride are mixed together and agitated at 20°C for 3 hours· The isoprene and the thionyl chloride are eliminated by distillation under reduced pressure, and 6 g of crude (IB,cis) 2,2-dimethyl-3flB)- 2-chloro2-(methoxy-carbonyl)-etheny3j-cyclopropane-l-carboxylic acid chloride ia obtained.

Example 3: (lB.cia) 2.2-dimethyi-3fe)-2-broao2-(propoxy-carbonyl)-ethenylj-cyclopropane-1-carboxylate of (S) «-cyano-3-phenoxy-benzyl . Into a solution of 2.6 g of (IB,cis) 2,2-diaethyl15 5$E)-,. 2-bromo-2-(propyloxy-carbonyl)-ethenyl3^yelopropane-1-earboxylic acid in 40 cm^ of methylene chloride, 0.9 cm^ of pyridine and 2 g of dicyclohexyl carbodiimide are introduced, and the whole is agitated for 10 minutes; 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 filtration, the filtrate is concentrated to dryness by - 45 10 by distillation under reduced pressure, and by chromatographing the residue on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (95/5), 0.743 g o£ the expected ester is obtained, 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 0.745 g of the product previously obtained, and , 2.32 g of (IS, cis) 2,2-dimethyl-3^) -'2-bromo-2-(propoxy-carbonyl) ethenyU- cyclopropane-l-carboxylate of (S) a-cyano-3-phenoxy benzyl is recovered, M. Pt. 68°C.

C26 *23 Br N05 (512.41) 0% N% Br% : 60.95 5.11 2.73 15.6 : 61 5.1 2.5 15.5 Calculated Found IB Spectrum (chloroform) - absorption at 1737 cm-1 attributed to the carbonyl of the ester - absorption at 1705 cm-^- attributed to the carbonyl of the conjugated ester ,-1 - absorption at 1605 - 1610 cm attributed to - 0 C - absorption at 1585 - 1485 cm"1 attributed to the aromatic nuclei.

NMB Spectrum (deuterochloroform) - peaks at 0.88 - 1.0 - 1.12 p.p.m. attributed to the hydrogens of the methyl of the propoxyl 52812 - 46 - 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 -Calf - peaks from 6.9 to 7.51 p.p.m. attributed to the hydrogen of the double ethylene bond. - peaks at 6.92 - 7.6 p.p.m. attributed to the hydrogens of the aromatic nuclei.

The (IS,ois) 2,2-dimethyl- 3^)-. 2-(propoxy-carbonyl)15 ethenyl]- cyclopropane-l-carboxylic acid can be obtained ia the following manner : Stage A : (lR.cis) 2.2-dimethyl-37^)- 2-bromo2-(nropyloxy-carbonyl)-ethenyl]-cyclopropane-1x, carhoxylate of tert-butyl Into a solution of 28.3 S of t-butyl ester of (IS,cis) 2,2-dimethyl-3-(2,2-dibromovinyl)-cyclopropane-l-carboxylic acid in a mixture of 120 cm^ of tetrahydrofuran and 120 cm^ of ethyl ether, 50 cm^ of a solution of butyl lithium in hexane, titrating 1.6 N is introduced over about minutes at -115°C. After agitating for 15 minutes at -115°C, 10 em^ of n-propyl chloroformate is added - 4Z progressively, end the whole is agitated for 20 minutes at -115°C, then for one hour at -65°C, after which the reaction 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 reduced pressure, then chromatographed on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (95/5)» bo obtaining 3.52 g of (IB,cis) io 2,2-dimethyl-5βδ)- 2-bromo-2-(propyloxy-carbonyl)ethenyl]-cyclopropane-l-carboxylate of tert-butyl, 3.16 g of (IB,cis) 2,2-dimethyl-3£(E)-(2-bromo2-(propyloxy- carbonyl)- ethenylj - cyclopropane-l-carboxylate < tert-butyl.

Stage B : (IB.cis) 2,2-dimethyl- 3fe)-, '2-bromo-g-(nropyloxycarbonyp-ethenyl]-cyclopropane-1-carboxylic acid.

To a solution of 3.1 g of the tert-butyl ester of (IB,cis) 2,2-dimethyl*3f(fe)—2-bromo-2-(propoxy-carbonyl)ethenyl]-cyclopropane- 1-carboxylic acid,, obtained in stagqA in 31 cm2 of toluene, 0.31 g of monohydrated paratoluene sulphonie acid is introduced; the flask containing the reaction mixture is placed in a bath of oil at 120°C for 15 minutes, then the 53212 - 48 temperature of the reaction 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 (IB,cis) 2,2-dimethyl3^5) -. 2-hromo-2-(propoxy-carhonyl)ethenyl]-cyclopropane1-carboxylic acid is obtained.

Example 4: (IB,cis) 2.2-dimethyl-3-Zfe)-2-fluoro-2(ethoxy-carhonyl)-ethenyll1-cyclopropane-1carboxylic acid. (lR,cis) 2,2-dimethyl 3j(E,Z) -2-fluoro-2-4thoxycarbonyl)-ethenyl]-cyclopropane-1-carboxylic acid is prepared, starting with 12.2 g of the lactone of (IB,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 5Ο/5Ο ratio, and 14.5 S ot (IB,cis) 2,2-dimethyl2-fluoro-2-£thoxy-carbony])-e.thenyl3-cyclopropane-1-oarboxylic acid is obtained. /a/D --42.5° (c 1%, chloroform).

NMB Spectrum (deuterochloroform) - peak at 1.28 p.p.m. attributed to the hydrogens of the paired methyls - 49 - 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 5 hydrogen in position 1 of the cyclopropyl - peaks at 2.75 ~ 2.9 ~ 3·Ο5 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 (21 H Hz corresponding to a cis derivative) - peak at 11.28 p.p.m. attributed to the hydrogen of the carboxyl.

By operating as in example 1 starting with the corresponding alcohols, the following products have been prepared : (examples 5, 6, 7 and 8).

Example 5: (IB.cis ΔΕ) 2,2-dimethyl-3t ,2-fluoro2-fethoxy-carbony3)-ethenyl3-cyclopropane carboxylate of (B) 3-ethynyl-3-phenoxy-phenylmethyl. Yield - 72%. 'op - +4015 + 1°5 (c - 1% CHClj) Example 6;; (IB.cis ΔΕ) 2.2-dimethyl-3~C2 -fluoro2-fethoxy-carbonyH-ethenyll-cyclopropanecarboxylate of (B) 3-phenoxy-phenyl,—ethyl.

Yield * 81% Op - ♦ 94°5 + 2°5 (c - 0.5 % CHCIj) - 50 10 Example 7 : (lB,cis aE) 2,2-dimethyl-3~C 2 - fluoro2 - «D - +50° ± 2°5 (c - 0.5 % CHOlj).

Example 8 : (lR.cia AE) 2,2-dimethyl-3[ '2-fluoro2-fethoxy-carbonyl)-ethenyl)-cyclopropane1-carboxylate of 3-phenoxy-benzyl.

IR Spectrum : C-0 ester C-0 conjugated ester C-C conjugated aromatics paired dimethyls 1725 cm .-1 1655 c® .-1 1588-1489 cm 1390-1380 ,-1 Example .9 : (lR,cis) 2.2-dimethyl-3-[2-fluoro~3-oxo3-methoxy-(E) -propenyl)-cyclopropanecarboxylate of (S) a-cyaao-5-phenoxybenzyl.

Stage A (lB,cis) 2.2 dimethyl-3-[2-fluoro-3-oxo 3-hydroxy-(E)-propenyl3-cyclopropane-carboxylate of (S) g-cyano-3-phenoxy-benzyl.

A solution containing 2.5 g of (lR,ois) 2,2 dimethyl3-C(E)-2-fluoro-2-(ethoxy-carbony^-ethenyl)-cyclopropane-1-carboxylate of (S) a-cyaao-3-phenoxybenzyl, 10 cm^ of 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, [the mixture) is then diluted with methylene - 51 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 the product sought is thus recovered.

Stage B (IB, cis)-2.2-dimethyl-3-[2-fluoro-5-oxo 5-methoxy-(E)-pro-penylJ-cyclopropane-carboxylate of (s) g-cyano-3-Phenoxybenzyl.

At a temperature between + 5°C and + 10°0, a 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°0, then for 30 minutes at ambient temperature.

A few drops of acetic acid are added. After taking to dryness, an oil is obtained which is chromatographed on silica, eluting with a mixture of hexape and ethyl acetate (85-15)· In this way the product sought is obtained.

M.Pt. 7O°C. -+52° ± 1°5 (c . 1 % CHC15) By operating as in the previous example, starting with the corresponding alcohols, the following products have been prepared. 5221 - 52 Example ίο : (lR.cis) 2,2 dimethyl·* 5-[S-fluorof 3-oxo-3-n-propyloxy(E)- propenyl]-cyclopropane carhoxylate of (S) α-cyano-3-Phenoxy-benzyl oD - + 38.5° + 2° c - 0.7 % CHClj Example 11 : (lR.cis) 2.2-dimethyl-3-[(AE)-2-fluoro-3-oxo5-tert-hutoxy-propenyll-cyclopropanecarboxylate of (S) α-cyano-3-phenoxy-benzyl.

(IS,cia) 2,2 dimethyl-3/2-f luoro-3-oxo3-hydroxy-( e)~propenyl]-cyclopropane-carboxylate of to (S) α-cyano-3-phenoxy-benzyl, ethyl acetate and N-(l-methyl ethyl) N'-(l-methyl ethyl) carbamimidate of tert-butyl are maintained under agitation for two hours. After filtering and taking the filtrate to dryness, a product is obtained which is purified by chromatography on silica, eluent : n-hexane and isopropyl ether (8-2) under nitrogen pressure· The product obtained x is recrystallized from isopropyl ether, ant aB . +2^5, + 3°, (c . 0.2306 CHClj) The tert-butyl N-(l-methyl ethyl) N'-(l-methyl ethyl) carbamimidate has been prepared as follows : 98.7 g of H,N' diisopropylcarbodiimide and 57·9 g of tert-butyl alcohol are agitated in the - 53 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 s (IB,cis) 2.2-dimethyl-5C(AE)-2-fluoro3-oxo-30.1,1.5.3.5. -hexafluoro-isopropoxy)n-propenyl3-cyclopropane-carboxylate of (S) g-cyano-5-Phenoxy-benzyl.

By operating as in example 9, stage B, starting with (IB,ois) 2,2-dimethyl-3~C2-fluoro-3-oxo-3-hydroxy-(E)propenyO-cyclopropane carboxylate of (S) a-cyano3-phenoxy-benzyl and l,l,l,3,3,3-hexafluoropropan-2-ol, the product sought is obtained. aD . + 21° + 2° (c- 0.5 % OHClj).

Example 13 : (IB,cis) 2,2-dimethyl-3- [2-fluoro-3-oxo3-isopropyloxy-(E)-propenyll-cyclopropane carboxylate of (S) a-cyano-3-phenoxy-benzyl. 'D . + 46° + 1° c - 1 % CHClj.

Example 14 : (IB,cis) 2,2-dimethyl-3-[2-fluoro-3-oxo~ 3-cyclopropyloxy-(E)-propenyll·· cyclopropane carboxylate of (S) a-cyano-3-phenoxybenzyl.

M. Pt. - 50°C 0 £ 1° (e - 1.3 % CHOi5) 5231 - 54 Example is : (IB.cis.ΔΕ) 2,2-dimethyl- 3£2-fluoro5-oxo- 3( B-methoxy-ethoxy - propenyl)] cyclopropane-carhoxylate of (S) g-cyano5-phenoxy-bengyl.

Ojj - 47° + 2°5 Example 16 : (IB.cis) 2.2-dimethyl-3C(AE)-2-chloro2- foethoxy-carbonyi)-ethenyl]- cyclopropane carboxylate of (S) 2-methyl~4-oxo3- (2-propenyl)-2-cyclopenten-l-yl By operating as in example 1, starting with (lR,cia) 2,2-dimethyl 3fe)(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. βρ »-15° +4° (c 0.25 % benzene) MMB Spectrum (CDCl^). 1.26 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 -C02CH^ 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. - 55 Example 17 : (IB.cis) 2.2-dimethyl-3C(E)-3-oxo-2-chloro3-ethbxy-propenylJ-cyclopropane-carboxylate of (S) «-cyano-5-Phenoxy-benzyl.

By operating as in example 1, starting with (IB,cis) 2,2-dimethyl 3C(E)-3-oxo-2-chloro-3-ethoxypropenyl]-cyclopropane-carhoxylic acid and (S) a-cyano3-phenoxy-benzyl alcohol, the product sought is obtained. а, . + 19° + 2° (c - 1 % CHC1,) ® ~ C-3- 3 The (IB,cis). 2,2-dimethyl-3^/oxo~2-chloro-J-ethoxy10 propenyl]-cyclopropane-carboxylic acid (E and Z isomers) has been prepared as follows : Stage A. ethoxy-carhonyl-chloro-methylene-triphenyl phosphorane.

A solution is prepared at 2°0 of about 4 g of chlorine 15 in 80 cm3 of chloroform. 20 g of ethoxy carbonyl methylene triphenyl phosphorane in 40 cm3 of chloroform is added. Having allowed the temperature to return to ambient, the reaction mixture is taken to dryness under reduced pressure. An oil is obtained which is dissolved in 70 cm3 of methylene chloride, washed with a solution with 6.1 g of sodium carbonate in 40 cm3 of water, then with water. After drying and taking to dryness, 18.9 g of the product sought is obtained.

M. Pt. . 116° o/ 118°C.

Stage B (IS,cis) 2,2-dimethyl-3i5-oxo-2-chloro-3-ethoxy— propenyl]-cyclopropane-carboxylic acid (E and Z isomers). б. 9 g of the lactone of (IB,cis) 2,2-dimethyl— - 56 3-dihydroxy-nethyl-cyclopropane-1-carboxylic acid in 100 cm^ of tetrahydrofuran is added to a solution containing 18.9 g of the product prepared at stage A in 200 ca^ of tetrahydrofuran. The solution obtained is agitated for 6 hours JO minutes at ambient temperature; the solvent is distilled off under reduced pressure. An oil is obtained which is taken up in 50 cm^ of ethyl ether, agitated at O°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 t NMB Spectrum s (CDClj) 1.3 and 1.33 p.p.m ' 1.89 - 2.02 p.p.m. 2.85 to 3.05 p.p.m. 6.78 - 6.95 p.p.m B) for the other part : 2.34 g of the corresponding Z product : Hydrogen of the methyl in position 2 of the cyclopropane. Hydrogen of the carhon in position 1 of the cyclopropane. Hydrogen of the carbon in position 3 of the cyclopropane. Hydrogen of the carhon in position 1 of the propenyl radical. - 57 NMB Spectrum : (CDCl^) . 1.33 and 1.36 p.p.n. Hydrogen of the methyl in position 2 1.96 - 2.1 p.p.m. Hydrogen of the carbon in 5 position 1 of the cyclopropane 2.23 - 2.53 p.p.m. Hydrogen of the carbon in position of the cyclopropane.

Example 18 : (IB.cis) 2,2-dimethyl-3((E)-3-oxo 2-chloro-3-propoxy-propenyl]-cyclopropane 10 carboxylate of (S) g-cyano-(3-phenoxybenzyl).

By operating as in example 1, starting with (IB,cis) 2,2-dimethyl-3((E)-3-oxo-2-chloro-3-propoxypropenylJ-cyclopropane-carboxylic acid and (S) a-cyano— 3-phenoxy-benzyl alcohol, the product sought is obtained.

D - + 24°5 + 2° (c - 0.4 % CHOI^) The (IB,cis) 2,2-dimethyl-3((E) -3-oxo-2-chloro— I 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 (IB,cis) 2,2 dimethyl-3((E)-3-oxo-2-chloro-3-ethoxy-propenyl3 cyclopropane carboxylic acid, example 17 stage A, starting with propoxy-carbonyl methylene triphenyl phosphorane, the product sought is obtained. - 58 Stage Β - (IS.cis) 2.2-dimeth.Tl-3£(E)-3-oxo-2-chloro 3-propoxy-propenyl]-cyclopropane-carboxylic acid.

By operating as for the preparation of (IE,cis) 2.2- dimethyl-3£(E)-3-oxo-2-chloro-3-ethoxy-propenyl]~ cyclopropane-carboxylic acid, example 17 (stage B), starting with the product prepared at stage A, there is obtained on the one hand the product sought, and on the other hand, the corresponding ΔΖ isomer.

Example 19 : (IE,cis) 2.2-dimethyi-3£(E)-3-oxo10 3-terbutoxy-2-chloro-propenyll·· cyclopropanecarboxylate of (S) cc-cyano-3-phenoxy-benzyl.

By operating as in example 1, starting with (IB,cis) 2.2- dimethyl-3f(E)-3-oxo-3-terbutoxy-2-chloropropenyl] cyclopropane-carboxylic acid, and with (S) α-cyano15 3-phenoxy-benzyl. alcohol, the product sought is obtained. aD - + 3O°5 + 2° (c - 0.7 % CHClj) (IB,cis) 2,3-dimethy^-3"OXo-3-terbutoxy-2-chloro~ 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 following example 17, stage A), and starting with terbutoxy carbonyl methylene triphenyl phosphorane, the 52813 - 59 product sought is obtained. M.Pt. 160°G.

Stage Β ΔΕ acid + ΔΖ acid.

By operating as it was indicated for the preparation given following example 30 stage B, starting with the product prepared in stage A, there is obtained, on the one hand, (IE,cis) 2,2-dimethyl-3C(E)-3-oxo-3-terbutoxy2- chloro-propenyl]-cyclopropane-carboxylic acid, M.Pt. » 65°C, and on the other hand, the corresponding (£) isomer, M.Pt.<50°c· Example 20 : (lR.cis) 2.2 dimethyl-3-C(E)-3-oxo— · 3-methoxy-2-bromopropenyl3-cyclopropane — carboxylate of (S) g-cyano-3-Phenoxy-benzyl.

By operating as in example 1, starting with (lR,cis) 2,2-dimethyl-3-C2-bromo-3-oxo-5-®ethoxy-(E) 15 propenylj-cyclopropane-oarboxylic acid and (S) α-cyano 3- phenoxy-benzyl alcohol, the product sought is obtained. aD . + 9°5 + 2°5 (c - 0.3 % OHCl^) (IR,cis) 2,2-diaethyl~3- [2-bromo-3-oxo-3-methoxy20 (E)-propenyl]-cyclopropane carboxylic acid has been - 60 prepared as follows: Stage A Terbutyl (lStcis)-2.2 dimethyl-3-C2-bromo5-oxo-3-methoxy-(S)-propenyl3-cyclopropane-carboxylate. 100 cm^ of a 5° % solution of sodium hydroxide 5 is added to a mixture containing 120 cm^ of methylene chloride, 6.7 g of terbutyl (IE,cis) 2,2 dimethyl3-Cl,2-(dibromo ES)-3"OXO-3-methoxy-propylJ-cyclopropane and 120 mg of Cetavloa (trimethyl cetyl ammonium bromide) and the reaction mixture is agitated for four hours.

After diluting by the addition of 100 cnr of methylene chloride, the organic phase is decanted and re-extracted with 100 cm** of methylene chloride. The organic phases are washed with N hydrochloric acid until an acid pH is shown, then with water until pH 7* ®he organic phases are reunited, dried and concentrated, under reduced pressure at 40°C. 5·3 g of a product is obtained which is chromatographed, eluting with a mixture of hexane and isopropyl ether (8-2) 3.5 g of the product sought is obtained.

Stage B (IE,cis) 2,2 dimethyl-3"C2-bromo-3-oxo-3-methoxy(E)-propenylJ-cyclopropane-carboxylic acid A solution of 3·4 g of terbutyl (IE,cis) 2,2-dimethyl-3-(2-bromo-3-oxo-3-methoxy~(E)-propenylJ ~ cyclopropane, 30 cm^ of toluene and 0.35 g of - 61 monohydrated paratoluene sulphonic acid, is taken to reflux. The reflux is continued until the evolvement of gas ceases. After cooling to 0°C, filtering, washing , the precipitate obtained with cold toluene and concentrating the filtrate at 4O°G under reduced pressure, 2.8 g of the product sought is obtained.

Example 21 : (IB.cis) 2,2-dimethyl-3-[(E)-2-bromo 3-oxo-3-terbutoxy-propenyl]-cyclopropane carboxylate of (S) g-oyano-3-phenoxy-benzyl. 10 By operating as in example 1, starting with (IB,cis) 2,2-dimethyl-(E)-2-hromo-3-oxo-3-terhutoxy-propenyV cyclopropane-carboxylic acid and (S) α-cyano-3-phenoxybenzyl alcohol, the product sought is obtained. aD . + 16°5- 2° (c - 0.7 % 0Η01?) The (IB,cis) 2,2 dimethyl-3C(S)~2-bromo-3-oxo3-terbutoxy-propenyl]-cyclopropane-carboxylic acid has been prepared as follows.

Stage A terbutoxy carbonyl bromomethylene triphenyl phosphorane.

'By operating as for the preparation of (IE,cis) 2,2 dimethyl- 3ΐ (E) -3-oxo -2-chloro -3-rethoxy-propenyl] cyclopropane-carboxylic acid (given in example 30, stage A) starting with the derivative terbutoxy carbonyl methylene triphenyl phosphorane and with bromine, the product sought is obtained. M.Pt. 190°C. 52213 Stage B (IB.cia) 2.2-dimethyl-3E(E)-2-bromo-3-oxo5-terbutoxy-propenylJ-cyclopropane-carboxylic acid.

By operating as for the preparation of (IB,cis) 2,2-dimethyl-3£(E)-3-oxo-2-chloro-3-ethoxy-propenyl]5 cyclopropane-carboxylic acid (given in examplel7 , 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 5O°C. io Example 22¾ (lR.cis) 2.2 dimethyl-5[(E)-3-oxo-2-bromo3-ethoxy-propenyl]-cyclopropane-carboxylate of (S) a-cyano-5-phenoxv benzyl.

By operating as in example 1, starting with (IB,cis) 2,2-dimethyl(E)-3-oxo-2-bromo-3-ethoxy-propenyl]15 cyclopropane-carboxylic acid and (S) α-cyano-3-phenoxy benzyl alcohol, the product sought is obtained. 'aD . - 7O°5 + 2° (c - 0.7 % CHC1?) The (IB,cis) 2,2-dimethyl-3ΐ(Ε) 2-bromo-3-oxo~3-ethoxy53212 propenyl3-cyclopropane-oarboxylio acid has been prepared as follows : Stage A ethoxy-carbonyl bromo-methylene triphenyl phosphorane.

The product has been prepared according to the process indicated for (IB,cis) 2,2 dimethyl- 3£(E)-J-oxo2-chloro-3-ethoxy-propenylJ-cyclopropane carboxylic acid in example 17 , stage A, starting with the derivative ethoxy-carbonyl methylene triphenyl phosphorane and 10 with bromine. In this way, the product sought has been obtained, melting at 15O°C.

Stage B (IB,cis) 2.2 dimethyl-5f(E)-2-bromo-5-oxo5-ethoxy-propenyl3-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 corresponding·ΔΖ product.

Example 23 : (IB,cis) 2,2 dimethyl-5-[(E)-2-fluoro' 5-oxo-3-ethoxy-propenyl3-oyclopropane earboxylate of (BS) a-cyano-6-phenoxy2-pyridyl-methyl By operating as in example 1, starting with the corresponding acid and alcohol, the product sought was - 64 10 obtained. aD . + 35° + *° (c « 0.3 % CHC13) Example 24 : (lB.cia) 2.2 dimethyl-3-C(E)-2-fluoro-5-oxo 3-ethoxy-propenyl)-cyclopropane-carboxylate of 3-(2-propynyl)-2.5 - dioxoimidazolldinylmethyl.

By operating as in example 1, starting with the corresponding acid and alcohol, the product sought is obtained. aD . + 12° + 2° (c - 0.5 % CHClj) Example 25 : (IB.cis) 2.2-dimethyl-5f(E) 2-fluoro-3-oxo5-ethoxy-propenyl3-cyclopropane-carboxylate of (S) 2-methyl-3~alIyl-4-oxo-2-cyclopcnten-1-yl.

By operating as in example 1, starting with the corresponding acid and alcohol, the product sought is obtained.

D . + 41°5 + 2°5 (c - 0.5 % CHClj) Example 26 ; preparation of a soluble concentrate.

A homogeneous mixture is made of Product of example 1...........................0.25 Butoxide of piperonyl.......................... 1.00 Tween 80....................... 0.25 Topanol A ............................0.1 Water .......................................98.4 E g g g ε 52312 - 65 Example 27 s preparation of an emulsifiable concentrate The following are mixed intimately ; Product of example 7 ..........................0.015 g Piperonyl hutoxide........... 0-5 g Topanol A ......................................0.1 g Tween 80 ................................ 3.5 g Xylene ........................................ 95.885 g Example 28 : preparation of an emulsifiable concentrate A homogeneous mixture is made of ; Product of example 11 .......................... 1·5 g Tween 80 ...................................... 20.00 g Topanol A............................-.........0.1 g Xylene ........................................78.4 g Example 29 : 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 .............................-.35.75 g Brilliant Green.............................. 0.5 g p-nitrophenol......................... 0.5 g 53212 Exanple 30 : example of pharmaceutical composition Solutions corresponding to the following formula have been prepared.

Compound of example 7...................... $.00 g 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 In this way a solution is obtained which is diluted in 5 litres of water when it is required for use.

Example 31 : example of pharmaceutical composition.

A solution corresponding to the following formula has been prepared : Compound of example 7......................0.5 g Piperonyl butoxide ......................... 2.5 g Polysorbate 80 ..............................10.00 g Triton X 100 ................................25.00 g Tocopherol acetate .......................... 1.00 g Ethyl alcohol q.s. for......................100 cm3 In this way a solution is obtained which is diluted with 5 litres of water when required for use. - 67 Example 32 : example of pharmaceutical compositions Capsules have been prepared containing 1 g of the product of example 1.

Example 33 s example of compound food-stuff for animals 5 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 vitamins.

This food-stuff contains at least 11 % of crude 10 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 15 per 100 kilos, and contains 910,000 I.U. of vitamin A, 91,000 I.U. of vitamin 150 mg of vitamin. E and 150 mg of vitamin C per 100 kilos.

With this food-stuff, 0.3 kg of the compound of example 2 is incorporated per 100 kg of total food-stuff.

Example 34 : example of compound food-stuff for animals The same basic balanced food-stuff is used ae in example 50. 0.04 kg of the compound of example 1 is incorporated per 100 kg of total food-stuff. - 68 Insecticidal study of the compounds of the invention In this study there are used : (IE,cis) 2,2-dimethyl-3$3)~ '2-chloro~2-(methoxy-carbonyl) ethenyll'cyclopropane-1-carboxylate of (S) a-cyano-3-phenoxy5 benzyl (compound A) (IS,cis) 2,2-dimethyl- 3’$2) 2-bromo 2-{propoxy-carbonyl)ethenylj-cyclopropsne- 1-carboxylate of (S) a-cyano3-phenoxy-benzyl (compound B) and (IE,cis) 2,2 dimethyl 3-Jj{E)-2-fluoro-2-^thoxy-carbony]) io ethenylJ-cyclopropane-carhoxylate of (S) a-cyano-3-phenoxyhenzyl (Compoundc).

A - Study 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/l into a Kearns and March chamber, using as solvent a mixture of acetone (5%) and Isopar I (petroleum solvent)(quantity of solvent utilised, 2 ml per second). 50 insects are used per treatment. Checks are made every minute up to minutes, then at 15 minutes, and the KT 5θ is determined by the usual methods. 53213 - 69 The experimental results obtained are summarized in the following table : Compounds Kt^Q in minutes Compound (A) 3.6 5 Compound (B) 4.5 Compound (D) 2.1 B - Studv 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 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 LD^q or the dosage (in nanograms per individual) necessary to kill 5θ% 5221 - ΊΟ insects, are the following : Compounds LD in ng/insect Compound (A) 11.1 Compound (B) 1.0 b) Study of the lethal effect on cockroaches.

The tests are carried out hy 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 a layer of talc to prevent the escape of the insects.

The lethal concentration 50 (IO 50) is determined.

The experimental results obtained are summarized in the following table : Compounds LC 50 in mg/m^ Compound (A) 1.4 Compound (B) 0.40 - 71 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 micro5 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, 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 ! Compounds LD 50 in ng/insect Compound (A) 6.7 Compound (B) 3.2 Compound ( c) 1.0 d) Study of the lethal effect on Epilachna varivestris.

The tests are carried out by topical application - 72 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 ?2 hours after treatment.

The results are summarized in the following table : Compounds LD 50 in ng/insect Compound (A) 17.7 Compound (B) 7.A Compound (c) 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 - 73 53213 the end of 24 hours.

The experimental results obtained are summarized in the following table s Compound LD 50 in ng/insect Compound (B) 6.4 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 studv of the compounds according to 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 pistol; 4 ml of toxic solution per plant of a mixture of equal volumes of water and acetone. The I .J - 74 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 g ot product per hl.

The compounds A and B exhibit a good activity in this test.

Claims (34)

1. In all their possible isomeric forms, or in the form of a mixture of isomers, the compounds with the formula (I) in which the cyclopropane; acid moiety is of IR cis structure and the geometry of the double bond is £ and 5 in which H 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 10 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 15 radicals chosen from the group constituted by alkyl radicals containing from 1 to 4 carbon atoms, alkenyl 5 2212 - 76 radicals containing from 2 to 6 carbon radicals containing from 2 to 6 carbon radicals containing from 4 to 8 carbon dioxy radical and halogen atoms, - or a group -CH. 0¾ atoms, atoms, atoms, alkenyloxy alkadienyl a methylene io in which the substituent represents a hydrogen atom or a methyl radical and the substituent Hg represents a monocyclic aryl radical or a -CH-C * CH and in particular a 5-benzyl 3-furyl methyl group, - or a group in which a represents a hydrogen atom or a methyl radical and represents an aliphatic organic radical containing from 2 to 6 carbon atoms and one or more carbon-carbon unsaturations, and in particular -CHg-CH-CHg, 15 CH 2 -CH - CH-CHj, -CH 2 -CH - CH-CH - CH 2 , -CH 2 -CH = CH-CH 2 -CH 3 radicals , - or a group - 77 52212 in which a represents a hydrogen atom or a methyl radical, Bj retains the same significance as previously, B'and B' 2 , 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 ΐ in which B* represents an oxygen or a sulphur atom, io a group -c— or -CHg- or a sulphoxide group or a sulphone group, and B^ represents a hydrogen atom, a radical a methyl radical, a -C0HH 2 radical, a -CSHH 2 radical or a -C = CH radical, represents a halogen atom or a - 78 methyl radical and n represents a numeral 0, 1 or 2, and In particular a 3-phenoxy benzyl, o<-cyano-3-phenoxybenzyl, α-ethynyl-3-phenoxy benzyl, 3-benzoylbenzyl, l-(3-phenoxy-phenyl) ethyl or 5 group, - or a group CN - or a group in which the substituents Βθ, Β?, Ηθ, Βθ each represents a hydrogen atom , chlorine atom, or methyl radical, and 10 in which S/I symbolizes an aromatic ring or an analogous dihydro or tetrahydro ring, - 79 - or a group in which Η^θ represents a hydrogen atom or a CN radical, 5 12 re P reseirts a -CHg- radical or an oxygen atom, R^ represents a thiazolyl or a thiadiazolyl radical of which the bond with -CH- can be found in any one of the available positions, R^g being attached to Rjj by the carbon atom between the sulphur atom and a nitrogen atom, - or a group - or a group in which ia defined as above, and the benzoyl radical 5 is in position 3 or 4-, - or a group in which fi 14 represents or cyano radical and B·^ a hydrogen atom, a methyl, ethynyl and B 1& , being different, each represents 53212 - 81 a hydrogen, fluorine or bromine atom, - or a group in which B^ is defined as above, each of the B^y's represents independently an alkyl group containing from 5 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, or a 3,4—methylene dioxy, chloro, fluoro or bromo group, p 1C represents 0, 1 or 2, and B represents an oxygen or a sulphur atom.

2. Compounds with the formula 1 as defined in claim 1 in which X represents a fluorine atom.

3. Compounds with the formula I as defined in claim l or 15 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 B represents an. ethyl radical. A 20 5. Compounds with the formula I as defined in claim 3 in which B represents a tert-butyl radical. - 82 6 . Compounds with the formula I as defined In claim 3 in which R represents a cyclopropyl or a cyclopropylmethyl radical. 7 . Compounds with the formula X as defined in claim 1 5 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, g . Compounds with the formula I as defined in claim 7 in · which S represents a linear alkyl radical containing 10 from 1 to 8 carbon atoms, substituted by one or more fluorine atoms. 9 . The compounds with the formula I as defined in claim l or claim 2 in which R represents a (CHg^OCCHg^-CHj radical in which m represents an 15 integer of from 1 to 8 and n represents 0 or an integer from 1 to 8 and in particular the radical -CHgO CHj. 10 . The compounds with the formula I as defined in any one of claims 1 to 9, corresponding to the formula X A : and the geometry of the double bond is E and in. which A represents an oxygen atom, a methylene group, a carbonyl group, a sulphur atom, a sulphoxide group, or

5. A sulphone group, represents a linear or branched alkyl radical containing from 1 to 8 carbon atoms and represents a fluorine, chlorine or bromine atom . li. The compounds with the formula (1^) as defined in claim io, in which A represents an oxygen atom.

6. 10 i2. (S') α-cyano-9-phenoxybenzyl (lR,cis) 2,2-dimethy 15βΕ)—r 2- fluoro-2-( ethoxy carbonyl) ethenylj-cyclopropane-1-carboxylate.

7. 13 . The compounds with the formula I as defined in any one of claims 1 to 9 in which B represents a radical^ HjC

8. 14 . The compounds with the formula I as defined in anyone of claims 1 to 9 in which B represents a

9. 15 . The compounds with the formula I as defined in 5 any one of claims 1 to 9 in which B represents a radical,

10. 16 . The compounds with the formula I as defined in any one of claims 1 to 9 in which B represents a radical,

11. 17 . The compounds with the formula I as defined in any one of claims 1 to 9 in which B represents a radical,

12. 18 · Use of the compounds of formula I as 5 defined in any one of claims 1 to 9 and 13 to 17 in combatting parasites of vegetation, parasites of premises and parasites of warm-blooded animals on an inaminate locus.

13. 19. Use of the compounds of formula I A as defined in any one of claims 10 to 12 in io combatting parasites of vegetation, parasites of premises ·« and parasites of warm-blooded animals on an inaminate locus.

14. 20. Compositions intended for combatting parasites of vegetation, parasites of premises and parasites of warmblooded animals, characterized in that they contain as 15 active principle at least one compound as defined in any one of claims 1 to 9 and 13 to 17. - 86

15. 21. Compositions intended for combatting parasites of vegetation, parasites of premises and parasites of warmblooded animals, characterized in that they contain as active principle at least one compound as defined in any one of claims 10 to 12.

16. 22. Insecticidal compositions, characterized in that they contain as active principle at least one compound as defined in any one of claims 1 to 9 and 13 to 17.

17. 23. Insecticidal compositions, characterized in that they contain as active principle at least one compound as defined in any one of claims 10 to 12.

18. 24· Acaricidal compod. tions, characterized in that they contain as active principle at least one compound as defined in any one of claims 1 to 9 and 13 to 17.

19. 25· Acaricidal compositions characterized in that they contain as active principle at least one compound as defined in any one of claims 10 to 12.

20. 26· Compositions intended for animal feeding, characterized in that they contain as active principle at least one of the compounds defined in any one of claims 1 to 9 and 13 to 17 in association with an animal foodstuff.

21. 27. Compositions intended for animal feeding, characterized in that they contain as active principle at least one of the compounds defined in any one of claims io to 12, in association with an animal foodstuff. - 87

22. 28. Combinations endowed with insecticidal, acaricidal or nematocidal activity, characterized in that they contain as active material, on the one hand, one at least of the compounds with the general formula (I) as claimed in claim 5 1, and, on the other hand, one at least of the pyrethrinoid esters chosen from the group constituted by: esters of allethrolone, 3,4,5,6-tetrahydrophthalimidomethyl alcohol, 5-benzyl-3-furyl_methyl alcohol, 3-phenoxybenzyl alcohol and 10 esters of 5-benzyl-3-furylmethyl alcohol with 2,2-dimethy13-(2-oxo-3-tetrahydrothiophenylidenemethyl)cyclopropanel-carboxylic acid; esters of 3-phenoxybenzyl alcohol and «-cyano-3-phenoxyben2yl alcohol with 2,2-dimethyl 3-(2,2dichlorovinyl)cyclopropane-l-carboxylic acid; esters of qC15 cyano-3-phenoxybenzyl alcohol with 2,2-dimethyl-3-(2,2dibromovinyl)-cyclopropane-l-carboxylic acid; esters of 3-phenoxybenzyl alcohol with 2-parachlorophenyl-2-isopropylacetic acid; and esters of allethrolone, 3,4,5,6-tetrahydrophthalimido-methyl alcohol, 5-benzyl-3-furyl_methyl alcohol, 20 3-phenoxybenzyl alcohol and <*-cyano-3-phenoxybenzyl alcohol with 2,2-dimethyl 3-(1,2,2,2-tetrahaloethyl)cyclopropanel-carboxylic acids in which halo represents a fluorine, chlorine or bromine atom.

23. 29 . As medicaments, the compounds with the formula I 25 as defined in any one of claims 1 to 17.

24. 30 . Pharmaceutical compositions containing, as active principle, at least one of the medicaments defined in claim 29. - 88

25. 31 . Preparation process for the compounds with the formula I as defined in any one of claims 1 to 9 and 13 to 17, characterized in that an acid with the formula (II): 5 in which the cyclopropane moiety is of IR cis structure and the geometry of the double bond is E and in which X and R retain the same significance as previously, or a functional derivative of this acid, is made to react with an alcohol with the formula (III): B-OH (III) 10 where B retains the same significance as previously, or a functional 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 for the group OOgH, so as to obtain the 15 compound with the formula (IT): ΞΟ-C •Ο-OB il (IV) in which the cyclopropane moiety is of IR cis structure and the geometry of the double bond is E and In which B retains the same significance as previously, then this acid with the formula (IV) or a functional 5 derivative of this acid, is submitted to the action of an alahol with the formula E-OH in which E retains its previous significance, so as to obtain the corresponding compound with the formula (I).

26. 32. Preparation process for compounds with the formula 10 1^, as defined in any one of the claims 10 to 12 , characterized in that an acid with the formula (11^): '-OH (¾) - 90 in which the cyclopropane moiety is of 1 R cis structure and the geometry of the double bond is E and in which and R^g retain the same significance as in claim 10, or a functional derivative of this acid (IX A >, is made to react 5 with an alcohol with the formula (III^) ! in which A retains the same significance as in claim .10, or a functional derivative of the alcohol with the formula (IIT ft ), and the product obtained is separated so as to obtain a corresponding compound with the formula l ft . 10 33 . Process according to claim 31 or 32 , characterized in that the acids with the formula (II) or (Up in which B or B^g 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) 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 -CH 2 -0H=GH 2 , 5 CH 2 -CH - CH-CHp -CH 2 -CH » CH-CH = CH 2 , in which a represents a hydrogen atom or a methyl radical, R^ retains the same significance as previously, 10 R'-^ and R' 2 , identical or different, represent a hydrogen atom, a halogen atom, an alkyl radical containing from 1 to 6 carbon atoms, an aryl radical containing from 6 to 10 carbon atoms, an alkyloxycarbonyl group containing from 2 to 5 carbon atoms, or a cyano group, 15 - or a group 5221 - 92 36 . Compounds of formula (I) as claimed in claim 1 substantially as herein described.

27. 37 . Compounds as formula (I) as claimed in claim 1 substantially as herein described in any one of Examples 5 1 to 25.

28. 38 . Parasiticidal compositions as claimed in claim 20 substantially as herein described.

29. 39 . Parasiticidal compositions as claimed in claim 20 substantially as herein described in any one of Examples 10 26 to 29.

30. 40 . a method of treating a site infested with or susceptible to infestation by parasities which comprises applying to the said site an effective amount of at least one compound of formula (I) as claimed in claim 1.

31. 41 . 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 31 to the action of an alcohol of formula R-OH in which R is as defined in claim 1.

32. 42 . A process for the preparation of compounds of formula (X) as claimed in claim 1 substantially as herein described.

33. 43 . A process for the preparation of compounds of formula (I) as claimed in claim 1 substantially as herein described in any one of Examples 1 to 25.

34. 44 . Compounds of formula (I) as claimed in claim 1 whenever prepared by a process as claimed in any one of claims 31 to 36,41 ,42 and 43. - 93 45 · A process for the preparation of compounds of formulae II and IV as defined in claim 31 substantially as herein described.