New derivatives of the carboxylic acid cyclopropane their preparation, their application to the fight against the parasites of the plants, of the animals and the buildings, the compositions containing them and new intermediaries obtained.

The present invention relates to novel derived from cyclopropanecarboxylic acid, their preparation, their application to the control of parasites in plants, animals or e - premises, the compositions the * Repudiation and intermediates obtained.

The invention relates to all forms of ISO * mother possible or as mixtures, the compounds of formula (I-*)

- either a radical aicoyle containing 1 to 18 carbon atoms,

- either a radical benzyla perse or optionally substituted more radicals selected from the group consisting perceived the radicals alkyls comprising 1 to 4 carbon atoms, thealcényies radicals comprising 2 to 6 carbon atoms ", radicals having from aicényioxy2 to 6 muted carbon, aicadiényles radicals having from K to 8 sluggish

carbon, the methylene radical dicxy and halogen atoms,

- either a group

wherein the substituent R ^ U.S. or hydrogen represents a methyl radical and the RG represents a substituent. aryl or a group - oouocyclic Ch-C." CH and noted U.S. group 5benryl - 3methyl substituted furyl -,

either an_has

wherein a represents hydrogen atom or U.S. a methyl radical and Rj represents an aliphatic organic radical having 2 to 6 carbon atoms and one or more carbon-carbon unsaturated bonds and especially the radical

- HC₂- CH-CH-*₂ , - Ch CH-ch CHj, HM -₂THE CK CH CH - HM *₂ ,

- hC₂- ch ch-cr₂- hC₃ ,

either a group

wherein a represents a hydrogen atom or a methyl radical, a rj retains as defined hereinbefore, and R '₂ , identical or different, represent a hydrogen atom, a halogen atom'd *, an alkyl radical '* rènfermant of 1 to 6 carbon atoms, an aryl radical with 6 to 10 carbon atoms, a group alcoyloxycarbonyle comprising 2 to 5 carbon atoms, a cyano group had,

- either a group

wherein b denotes oxygen or sulfur or S a group

G

The c - - or-Ch - and R ^ d-* represents hydrogen, a radical - c-hindered n, a methyl radical, a radical "CONKj" SU - CSJîHg residue or a radical - gm * CK20, represents

•halogen or a methyl radical and n is a number 10 equal to c, 1 or 2, and particularly the group 3-phenoxy cradle." tyle, α-cyano-benzyl 3 a-phénaxy, has-ethynyl 3 para benzyl, 3 benzoyl-benzyl, 1 - (3 phenoxyphenyl) ethyl or s-thioanido 5-phenoxy benzyl,

- either a group

wherein the substituents the rg, said RY, the rg, represent a hydrogen atom, a chlorine atom, a methyl radical or a V

and wherein s/1 symbolizes an aromatic ring or a dihydro or tetrahydro tetrahydro-like cycle,

- either a group

wherein represents a hydrogen atom or CN, hr₁₂ represents a radical ch-•^ - or an oxygen atom,

represents a radical or thiadiazolyl thiazolvle whose bond CWG may lie at any of

- CH2 -

disponiblesj locations2 e ^ ATs linked to by the lifeless carbon between the atom 3ouïreatcse and nitrogen,

- either a group

wherein represents a hydrogen atom or a - denoting

I¹³

CH_

mu9 in "which R ^, is defined coasse above," le theS ' ** zoyle BEAs residue is at position 3 or 4,

either an

wherein R_{the LL}} represents a hydrogen atom " methyl, ethynyl or cyano and R ^ and R, gm, different, represent a hydrogen atom, fluorine or bromine.

wherein R ^ is defined as above, each of the independently represents an alkyl group containing 114 carbon atoms, alkoxy having from I to 4 carbon atoms•, alcoyltteio containing 1 to 4 carbon atoms, a sulfonyl containing alcoyi. 1 to 4 carbon atoms, IFFT&e *■orométhyl, 3.4 and 8tethylene dioxymethylene, chlorine, or bromo flucæo, w "has a presentiment of an equal number of I 0, I or 2 and b 'represents a atcïa'd' oxygen or sulfur and R represents a radical AIs *" Coyle to containing 1 to 13 carbon atoms substituted by AU.^{: V.} one or more functional groups. identical or " different, or a group - aryie containing 6 to 14 atoms optionally substituted carbeetfe, by ., . or a more groups pit®tionnels same or different, or a radical hétérocycligîaj optionally substituted by one or more identical or different functional groups, compounds in which the double bond at the Z-geometry.. or e..

The compounds of formula (! ') can exist in many forms stéricisomères: they have indeed

two asymmetric carbons in 1 and in 3 cyclopropane; they have equalled a iscmsrie e/2 at the double bond; they may, moreover, have one or more centers of asymmetry in the a portion therefrom as in part R *

When a represents an alkyl radical, it is preferably methyl, ethyl, n-propyl, #1 isopropyl, n-butyl, isobutyl, or terbutyle.

When a represents a benzyl radical substituted with one or more alkyl radicals, it is preferably methyl or ethyl radicals.

When a represents a benzyl radical substituted with one or more alkenyl radicals, these are preferably vinyl radicals, allyl, 2- méthylailyle, isobutenyl or "

When a is a substituted benzyl radical

by one or more alkenyloxy, is preferably the radical a vinyloxy, allyloxygroups, 2- aéthylallyloxy or isebutényloxy.

When a represents a benzyl radical substituted with one or more halogen atoms, it is preferably chloro, bromo or fluoro.

When R is an alkyl radical substituted with one or more functional groups, is meant preferably by alkyl radical containing 1 to 8 carbon atoms such as, for example, methyl, ethyl, propyl methacrylamide # " isopropyl, n-butyl, isobutyl or tertbutyl.

When R is an alkyl radical substituted with one or more functional groups, is meant preferably by functional group, a halogen atom, OH or SH, a group OR or SR *' wherein R * represents alkyl containing 1 to 8 carbon atoms.

a g wherein R "and R" ', iden -

ticks or different, represent a hydrogen atom, or an alkyl radical containing 1 to 8 carbon atoms, a group C■D, ^ ^ OS p0 H-H or₂ or a group c0alc₁ , ^ ^ Âic OS, or SOjâlCj in which CIC a-j, alk2 ^ and alk represents alkyl radicals containing 1 to 18 carbon atoms.

49 MSEC H can also represent an alkyl radical substituted with an aryl radical such as the benzyl or phenethyl radical itself optionally substituted by one or more groups. The OH, have had wedge comprising 1 to 3 carbon atoms, by one or more groups JTC, 0c? Y, 3cf,, or by a group (grams):

R may also represent an alkyl radical substituted on two adjacent carbons by a group (grams ^ ii

When R is an alkyl radical substituted with one or more functional groups, it may be mentioned as preferred values of R radicals:

- (EYC ^ - this&subscribes wherein n is an integer from 1 The I 3 and diagonalizing a halogen atom, for example the radical - C. CClj ^ -, - EMC-to-JTC,

Ch-to-CHj-DC - ^ - ^ - or ch-Ch-to-JTC,

(CR39,) - * - ch-Silj wherein bai is defined as above and n₁ is the number of 0I8, for example the radical - CH2 - ^ CîSlg

THE C ^ - CFK -!₂ or - CHFj "

Hal-wherein n and Hal are as defined byd *⁹ - juice, by example the radical - Ch-to-CHjCl or - this ^ - CHgF,

- - C. (CHal,), wherein hal is as defined above, for example the radical - (JTC) ^ - C.

the n!'/³ HM, or - (^ îgCN ci * wherein a is as defined hereinbefore,

- C - ℮ν.., wherein hal is as defined hereinbefore, ^ ^ CHal₃

for example the radical

"(CHgJ-to-g" ', wherein n is defined as above and R * represents a hydrogen atom or a linear or branched alkyl radical, having from there s-carbon atoms, for example the radical - Ch-to-Osh ^, the CK - ^ - extended Chu-O CHj, Cîîg-to-ci - ^ - ^ c FS - CHj - or to CKG-to-Ch OH,

The n -, wherein n and R * are defined as experie - naked dessnent and the two radicals R ' may be different between for example the radical - CKG's-to-Ch-n-them. /VBE1HR HC,

- Ch-to-Ch n ^ - or Ch-to-Ch-R." ³ the n ^ \ α-H3 - HC₃ , HM,

previously, for example the radical - CH2₂ THE CK - 0, THE P '

- (¾ - pii-to-çhg₉ wherein n is as defined hereinbefore, oh

for example the radical - ^ - ch-ch Ch-to-Qt

THE OH

·0^ ^ · γ, wherein^{n is T-} as defined hereinbefore, -0, Ω■- Canada provide

for example the radical "RC ^ --C-R ^ X or" ^ - CK-ch-a-j-C.

- (CH2₂ )_has ~^ ^ -, wherein n is defined 'ccisae' précédeeser T-., for example the radical beazyle had phéaéthyle,

i-in-wherein n is defined comae - headed "

telling, for example the radical

When R represents an optionally substituted aryl radical, it is preferably phenyl or phenyl substituted by one or more OH groups * Cato or have, 1 of the I - containing 3 carbon atoms, or

grouping the CF ^, ^ ^ OCF - or FCB.

When R represents a heterocyclic radical, it is preferably pyridinyl, furanyl, thiophenyl, οχΗ2ο1ν1β or thiazoiyle.

The invention particularly to ob - ^ and the compounds of formula (I-'), as defined above, of formula (I-)/VBE1

wherein a represents

" either an alkyl radical containing 1 to 18 atoms because " tone service,

- either a benzyl radical optionally substituted, such as defined previously,

- either a group

(I-)

wherein the substituents R ^ and RG are defined as précédemraent,

therein THE R *

- either a group VBE1 /

wherein s denotes oxygen, a group

O

- the W - or R ^ is defined as preceded, represents a chlorine atom or a radical aéthyle and a represents a number equal to 0, 1 or 2, and particularly the group 3- phenoxy benzyl, α-cyano 3-phenoxy bensyle or a-étbyayl3phenoxy - benzyl,

* either a group

" either a group

wherein the substituents the rg, the R ^, ARQ, RG and O/9.ï are defied as above,

- either a group

and R is as defined previously cccme *

The invention has for its object the compounds of di formula 07} for which the double bond at the geometry THE Z *

A watershed preferred compounds of the invention, may be mentioned the compounds of OA fear which the coupling the cydcçropene carboxyiic acid structure is the OIS 1r 1r or trans and any advantage " Cull good e was particularly those for which the coupling the acid eyeâàçcqeœm -anto -xylic the OIS 1r * has the structure

The L * invention noted concerns the compounds d # formula (I-*) as defined previously, wherein confectioneries' represents U.S.. 3 a-phéncxy Bas ocyanc group2yl as e, R or R as well as those in which a represents a group. 2 a-métàyi-to-£~cxo - * 3 - ( 2- propenyl) 2 "eyclop" stea " 1-yl form 3, R or R.

L^F. invention more especially relates to the compounds of formula (I-*) for which R represents U.S. alkyl radical contain? "of 1 to 18 carbon atoms, substituted with one or more functional groups, and any special" telling those in which R is an alkyl radical substituted with one or more halogen atoms, e.g. fluorine atoms or US more * lug - example■alkyl radical substituted by ' one or more atoms D^F. halogen, include especially the radical " ^ ^ * CF of PK

L^{the R} invention particularly for the ob - ^ and LAS compounds whose preparation is given # more laws in the experimental part and in particular, a watershed thereof, the compounds of examples 1, 2, 23, 26, 25, 30 and 35 *

The compounds of formula (I-') have interesting properties ^ which enable their use in pest control, it may be for example from there for combating plant pests, parasites premises and parasites from warm-blooded animals. It is thus usable products de the invention for combating insects, nematodes and webs parasitic mites of plants and animals ".

The invention thus has the pcurobjet applying compounds of formula (1'). to the pests are * plants, parasites premises and parasites from warm-blooded animals "

The products of formula (! ') may thus be used especially for insect control in agriculture, to control, for example against aphids, the cabbage and beetles " US are used dosed between 10 g and 300 g of active material per hectare "

The products of formula (I-^{the R} ) can also be used to control insects in the premises, for fighting a flies, mosquitoes and cockroaches.

The compound of the example 1 is a product extremely remarkable as shown by the test results below El lethal is excellent and a very good level of knock-down syndrome *

The products of formula (I-) are more stable and are not toxic to mammals.

All of these properties to products of formula (I-') products that are ideally suited to the requirements of industry agrochiaic modern ii they provide privacy crops while preserving the environment *

jetproof products of formula (the X ') may also be used to control mites and nematodes paratroopers! a TES plants.

The compounds die. formula (I-*) can still be used to combat the parasitic mites of animal-"readouts for example against ticks and noted ticks of the species Boophilus, those of the species Hyalomnia, those of the species Amalyomnia and those of the species Rhipicephalus, or to combat all sorts of gall and nota derivatives" telling the scabies ** - the mange and scabies choriop tick.

The invention therefore also relates to the ccuposi -

- would like for the control of parasites in animals, hot, parasites. local and plants, characterized in had¹ they contain at care one of the products defined above,

The invention particularly pourobjet - the insecticidal compositions containing ' as active ingredient at least the UA products defined above.

Among the compositions-in particular preferred insecticide of the present invention, may be: include all 'specially the compositions, containing the (IR-cis-)' 2.2-dimethyl 3/(2) 3 (2, 2, 2 a-trifluoroethoxy) - 3 oxo-I? / the cyclopropane carhoxylateropenyl * (2) of. dC-cyano-3-phenoxy benzyls, the (IR-cis-) 2.2-to-dlméthyl/3 (2) 3 3 oxo - (2 - (1, 1, 1, 3, 3, 3 a-hexaxluoro) propoxv) cyclopropanecarboxylic carhoxylate/1 a-propenyl - (O) of the X-cyano-benzyl 3-phenoxy,

the (cis-1r) 2.2 a-substituted dimethyl 3/(2) 3 - 3 oxo (2, 2.2-a-trifluoro ethoxy) - cyclopropanecarboxylic/1 a-propenyl - carhoxylate of (the R)-éthyayl 3-phenoxy benzyl,

the (cis-1r) 2.2-dimethyl 3/(2) - 3 ax-© 3 (2.2_F. 2 a-triîluoro ethoxy) 1the cyclopropane - propenyl/carhoxylate (R) a cyano-concerns-phenoxy 2the pyridyl-methyl -,

the (cis-1r) 2.2-dimethyl 3/(25 3 oxo 3 - {2 fluoro ethoxy) 1 a-propenyl/(e) of the cyclopropane carhoxylate s cyarcyar.o 3-phenoxy benzyl,

the (cis-1r) 2.2-dimethyl 3/(2) 3 3 oxo - (2, 2, 2-a-trifluoro ethoxy) 1the cyclopropane - propénvl/carhoxylate of (3-? ropargyl 2.5 a-dioxoimidazolidinyl) methyl,

the (cis-1r) 2.2-dimethyl 3/ (2) 3 oxo 3 - (2, 2, 2-a-trifluoro ethoxy) 1 a-propenyl/carhoxylate cyclopropane derivatives of (1 e) 2 a-m2fchy!

4 oxo - 3 - (2 a-propényi) 2 a-cyelcpen.ten.-I therein the.

The compositions are prepared lounge, the methods ' -._:

customary industry âgro chemical or veterinary or industry products intended to animal nutrition.

In these compositions for agricultural and

in use premises, the active materials can be added optionally a where. more other pesticidal agents. They may be in. pre - ' will eventually occur in the form of powders, granules, suspension, éaulsions, solution, solutions for aerosols ., bands fuels, bait or other preparations esplcyés conventionally for by using this kind of compound ".

In addition to the active ingredient, the compositions contain,

in general, a vehicle and/of the a - tensic-active agents, nonionic, ensuring, the EH addition, uniform dispersion of the constituents of the mixture. The vehicle can be a liquid, such eUE is water, alcohol, hydrocarbons or other organic solvents, mineral oil, animal or vegetable, unterstanding a powder such as talc, clays, SAL silicate, the kisselguhr or solid fuel.

The insecticidal compositions preferably contain living room of 0,005 ¾ to ΐΟ ¾ weight of active material.

According to an advantageous procedure, for use

in the premises, the compositions of the invention are

•fumigarttes used as compositions.

The compositions of the invention may then

be avantag had lover made, for the inactive portion, an insect coil (or coil) fuel, or even of a noncombustible fibrous substrate. In the latter case, the fumigant obtained after incorporation of the active material is placed on a heating apparatus such as a électromoscuito DDH.

In the case of employing an insect coil, ; the inert support can be, for example, pyrethrum marc compound, Tabu powder (or powder. ThusbergiiMachilus sheets), pyrethrum stem powder, cedar leaf powder, wood powder (such as pine sawdust) starch and powder, cocue of coconut.

. The dose of active material can then be *, for example, Da and■-0,05.4 ii|ar. *

In the case of uses - - the m the incombustible fibrous support, - the dose of material may then be activated, for example, of 0.03 to 95 c/o by weight. '

The compositions of the invention for use - emitted from premises may also be obtained by preparing an oil-based sprayable active ingredient " soaking up this oil

- the wick of a lamp and then being: subjected to combustion " the concentration of the active ingredient incorporated into oil

. is, preferably, of 0.03 to 95C/o-weight.

The insecticidal compositions according to the invention, since the compositions acaricides and nematicides may be addi " tionaées optionally UE - more other pesticidal agents. The nénaticides acaricidal compositions and can be in the form of powdered -, granules, suspension, emulsion, solution..

For ' usage acaricidal, preferably used powders, aouillahles, for foliar spray, containing 1 to % QS or - liquid for foliar spray containing 1 to. 500 g/l of active ingredient. There can further be used dusting powders containing foliar

of 0.05 35s to active material.

For use nematicide, preferably liquids used for soil treatment containing 300 to 500 g/l of active ingredient.

Acaricidal compounds and nematicidal according 1' are used, preferably, at doses between 1 and 10The O g of active material per hectare.

- To enhance the activity ' biological products of the invention can be admixed with synergists employed conventional in such a case as the 1- {2,5,8- trioxadodecyl) 2- propylbiphenyl 4.5 to-methylenedioxy benzene (or piperonyl butoxide) or the? ii~(2- heptyl-ethyl) bicyclo-/2,2 - 1/5- heptene-a 2,3-the di carboxiaide, or piperonyl bis -2- (2' - n-butoxy ethoxy) éthylacêtal (or tropital).

In the case of combating parasitic mites of animals, incorporated very often the products of the invention in food compositions in combination with a nutrient mixture adapted to 1* animal feed, tee nutritiel mixture can vary depending on the animal species, that may incorporate cereals, sugars and grains, soya bean, peanut and sunflower, flours of animal origin, such as fish meal, synthesis aainés acids, mineral salts, vitamins and antioxidants "

The invention thus relates to the food compositions defined. above,

The compounds of formula (ii *) exhibit in Excel -

slow general tolerance, and therefore the invention-also pot? products of formula (! '), as medicaments, the fight, especially against disorders. created by tick and gall,

The medicaments of the invention are seventeen•used both in human had * in medicine ' veterinary.

The medicaments of the invention are noted signi -

sés fear in human lice - as preventive or curative and for ' combat scabies. Us. equalled can be used cbmaeranthéSâsfntiçnes -...

The medicines of 1' can be administered externally, by spraying, by shampoo, bath or whirler perse, .

The medicines for veterinary use can also be administered by painting. the dorsal column according to the method designated method^M for on earth ", US may also be administered by parenteral.

The intention is thus an object compositions - Pharma S.

containing as active ingredient at least one of the medicaments defined above previously,

Often called also indicate that the products of the invention can be used comae biocidal or horn growth regulators.

The L * invention also relates to the associations activity.in insecticidal, acaricidepunéaaticide, characterized tata.ee they contain terminal active material, on the one hand at least one of compounds of general formula (9.ï¹ ), and on the other hand, at least one of ester pyréthrinoîdes selected in the group consisting of esters of allétfarolones, alcohol 3, ^,5-6- tétrahydrophtalisido aethylic, 5 benzyl alcohol 3- substituted furyl aethylic, alcohol 3-phenoxy benzyl alcohols and DC-cyano-benzyl 3-phenoxy chrysanthesic acids, alcohol esters by the 53-furyl-- ylbenzyl aethylic acids 2, 2" substituted dimethyl 3 - (2 - οχο 3 a-tetrahydrothicphenylidene aéthyl) cyclopro-to-breaded I-carboxylic acids, esters of alcohol 3- phenoxy bensy " llque and of alcoolsc cyano 3- phenoxy beasylic acids 2,2" diaéthyl - 3 (2.2 above dichlorovinyl) cyclcpropane-1 - carboxylic acids, esters of alcoolsct cyano 3- phenoxy acid benzyl 2,2- diaéthyl3- ( 2,2- dibroaovinyl) cycleprc? speed bumps "1- carboxylic acids, esters of alcohol 3- phenoxy benzyl acids 2- parachiorophényl2- iscpropyl acetic acids, esters of alléthrolones, alcohol 3, HAS -,5,6- tetrahydrophtaliaidoaethylic, 5 benzyl alcohol 3-furyl-aethylic, alcohol 3-phenoxy benzyl alcohols of OC-cyano- 3- phenoxy benzylic acids 2,23 - diaéthyl - (L-,2,2,2- tetrahalo) - cyclopropaae1- carboxylic acids, in which "bloom" denotes fluorine, chlorine or brone, it being understood that the compounds can exist (! ') in all their fornes stereo isomers possible Copula model as well as the acids and alcohols esters pyrethrinoid above.

the associations according to 1 ' invention have noted the interest or it allows combat, by the versatility die their action,, a range of pests, wider, either die exhibit, in some cases, a synergistic effect.

The invention also relates to a process for preparing the compounds of formula (! '), characterized in that comprises reacting an acid of formula (IX-)

wherein R retains as defined hereinbefore, or a functional derivative of this acid, with an alcohol of formula (II)

wherein A * maintains AEG seated meaning 'that preceded * centeredly, to obtain the compound of formula (I-*) corresponding, the derivative - fohctiomeT' acid used -&CD. die pre of £&*.

conference an acid chloride.

5■when L * is reacted the acid of formula (III), on the alcohol of formula (121) is carried out preferably in the presence of. - cUcyclûhexylcarbodiimide.

The invention equalize for; the ob ^ and US method of pre -. ' paratioa as defied précédâsmenty carscterized._; - 10 in that the compound of formula (III) is prepared by subjecting within, an organic solvent, a compound of formula (d -)

as trass, or arranged as cis-lactose, to the action of a compound ' of formula

wherein R retains its previous meaning, for_;

obtain the compound the formula (Tl) corresponding

as a mixture of isomers S and Z, that the bone separates, 2The Q, if desired, in each of the isomer content aces.

In a preferred embodiment, the solvent used¹ is selected from in-ie~groupé '-constituted by * - éthyli ether

* - that. - .the; - diséthylsulfo ' ^ dd.e..te-to-diiièthylforsaëdde, tetra■hjrdrofurane>. the rüaéthoîqréthane, - the^; alkanols, t'a monomethyl ether diéthylènegiycol ATs * diethylene glycol diethyl ether

Le - compound of formula (3 ^) is prepared. by actios of a compound formula

Φ ©

(<$) 5 - P Ch-to-COgR, Hal-

Hal representing a halogen anion, on spent HAse found strong®. The OSA®strong base may be used for example a hydride, a friend " hard, or an alkali metal alkoxide, or a alcoyllithien.

The invention also relates to a method of pre " the pa-serving as defined previously, characterized in ES that the compound of formula (O) is prepared by reacting a U " compound of formula (VI)

wherein hal represents halogen atom and U.S. have represents alkyl containing 1 to 20 carbon atoms, - in - first with an alkaline agent capable of tearing the halogen atoms and then, in a second step,

- either with an agent capable of introducing the group carboxylieue to obtain the compound of formula (•/)

which is subjected to the action of a-Agent of esterification, for wherein R retains the same ^ - meaning ' that ptéeéêeméat

- either with a derivative of formula.

Hal c0₂ R -

wherein hal represents halogen atom and year R retains its previous meaning, to directly obtain the compound of formula (71)

then subjecting the compound of formula (IV) to the action of a hydrogenating agent provided, to obtain the compound of formula (seen)'

wherein the double bond at the geometry A Z, which is subjected to the action of an acid capable of hydrolyzing agent selectively cleave the ester function on the carbon in the cyclopropane 1, to obtain the compound of formula (ll) corresponding.

In a preferred embodiment of the above method,

- Hal is bromine or chlorine,

represents a radical - IEA terbutylebenzyls or,

the L - ' alkaline agent able ^ pluck jetproof vinyl halogens is butyllithium,

the L - ' agent capable of introducing the carboxylic group is carbon dioxide,

the L - ' provided hydrogenating agent is hydrogen in the presence of a catalyst such as palladium in the presence of traces of quinoline,

the L - ' acid capable of hydrolyzing agent selectively cleave the ester function Ο02℮1Suifonic ℮ is para.

The method also includes an alternative obvious

for the chemist in which the compound of formula (V-) is firstly subjected to the action of a hydrogenating agent provided # and in the second place to the action of a reducing agent.

The invention therefore also relates to a variant

the method such unterstanding defined above, characterized in that the first subjected the compound of formula (V-) to the action of a hydrogenating agent provided to obtain the compound of formula (VIII-)

(mi)

wherein the double bond. I measurement geometry A Z, which is subjected to the action of an esterification agent, to obtain the compound of formula (VIII) corresponding

(vil)

wherein R retains SSs previous meaning, then for * follows the synthesis as described above.

The above method has a second alternative pharmacokinetic -.

serrated, wherein the order of certain stages is modified.

The invention therefore also relates to a method as defined above, characterized in that the subjected

wherein R and have, are defined as above,

to the action of an acid capable of hydrolyzing agent cleave selectively the ester function in 1 cyclopropane, strip to obtain a compound of formula (E.C.)

wherein R is defined as préeédenment, that

- either is subjected, optionally in the form of a functional derivative, to the action of SU alcohol of formula (îu)

Has' a-OH(1 Π) wherein A ' retains the same meaning that preceded®*

(S)

wherein R and a 'are as defined previously, which is subjected to the action of a hydrogenating agent provided, to obtain the compound of formula (I-'),

- either is subjected, first to the action of a hydrogenating agent provided, to obtain the compound of formula (ll)

cms

wherein R is defined as above and the double bond at the Z-geometry, and then, where appropriate in the form of d * a functional derivative, to the action of an alcohol (II), to obtain the compound of formula (I-*).

Preferential conditions for carrying out the method above are identical the K there which CAT-been hereinbefore defined for the like operations.

- Invention is also a process for preparing compounds of formula I-<*), characterized in that a compound of formula (IX)

wherein the double bond at the geometry 2, to L^F. action of an esterifying agent, to obtain the compound of formula (I-*) corresponding,

-Cans a preferred embodiment of the above method ., 1' esterification is effected with a functional derivative of alcohol, i.e. a derivative? ii, the n * diisopropylurée of formula

The invention also relates to a method as defined above, characterized in that the product of formula (XII) is prepared by subjecting an acid of formula (V-)

wherein IEA represents alkyl containing 1 to 8 carbon atoms, to the action of the 2,2,2- trichloroethanol to obtain the compound of formula (XIII)

(XII) which is subjected to the action of an acid hydrolysis agent to obtain the compound of formula (xxi}

which is subjected to the action of an alcohol of formula (112)

Has' Ch cms} wherein A ' retains as defined hereinbefore, . to obtain the compound of formula (-XIV)

(XIV).

which is subjected to the action of a cleaving agent of the ester function carried by the acetylenic carbon, to obtain the compound of formula (Xv frames)

(XV)

which is subjected to the action of a hydrogenating agent provided to obtain the compound of formula (redundantable).

In a preferred embodiment of the method of the invention above,

- iEA in formula (V-) represents a radical terbutylebenaylef or

the hydrolyzing agent - acid is paratoluene sulfcni-to-aluminum surface?

- the esterification of the-compound (XIII is) is carried out by reacting the compound (XIII is) with the alcohol (II), in the presence of dieyclo®carbcdiimide or diisopropyl carbodiimide ethylhexyl unsightly;

- cleavage of the ester (-XIV) is by using a metal powder, such as zinc powder, in acid medium;

- provided the hydrogenating agent is hydrogen in the pre SEEN - " this of a catalyst such as palladium, in the presence of traces

•quinoline.

The above method comprises a variant evident in accordance which the stages hydrogenation and esterification are reversed.

The invention thus also relates to a method as defined above, characterized in that a

in

a

which has' is as defined hereinbefore, to the action of an esterification agent, to obtain the compound of - zu

wherein R and a 'are defined as above, which is subjected to the action of a hydrogenating agent provided, to obtain the compound of formula (!') #

Preferential conditions for carrying out the method above are identical to those which have been previously defined for the like operations.

In the case where it is desired to prepare a compound of formula (! ') wherein R is an alkyl radical substituted with one or more hydroxy radicals, first prepared, according to any of the methods above, a compound of formula (I-^F. ) wherein R is an alkyl radical substituted with one or more hydroxy protected, for example by a group or tetrahydropyranyl dioxolanyl,

*. mu9

and hydrolyzing said compound to 1' agent is acid hydrolysis.

The hydrolyzing agent acid used in the above method can be, for example, acid, hydrochloric acid or paratoluene suifonic.

Most of the methods just described above, lead to cosmoses in which the double bond at the geometry Z that are isturs! it." aeaé; côs methods that are most suitable for the preparation of compounds of formula (I- ' ) in which the double bond; has the Z-geometry.^; '. '

Excellent yields are obtained comae clearly shows the experimental part exposed below *

The compounds (III), (71) and (seen), and the aluminum compounds (IX.) and (s), obtained upon insertion of the implementation of the method of the invention are novel chemical products.

Thus the invention provides also for the ob ^ and these products, chemical products and novel, and more particularly, as intermediate products for the preparation of compounds of formula (I-*) dice as defined hereinbefore.

Example 1: (IR-cis-) 2,2- diméthyrV(V) 3 - (2, 2.2 and trlfluorcéthoxy.) 3 oxo.1- propenyl/(e) of the cyclopropane earboxylata<* -

a cyano - 3 a-phérphér.oxy beszyle.

Is mixed under agitation 1.3 g acid (cis-cyle) 2.2 a-substituted dimethyl (A Z) A V 3 oxo - 3 ( 2, 2.2 and rev iflucr © ethoxy) 1 a-properly1the cyclopropane carboxyiic /, 0.1 cms3 de - pyridine and ' 15 cms3 - methylene chloride and then added 1.05 g dicyciohexyicarbodiimide. Then added 1.35 g of (e)" * T-hydroxyl 3- phenoxy benzene acetonitrile derivative in solution in 5 " has? Da and methylene chloride. Was stirred at room temperature 5 hours 1 ., filter and flushes the insoluble to methylene chloride. Added hydrochloric acid filtrate 2:00. Decanted, - lare, confectioneries and water, dry and causes the I dry. The oil obtained is purified by chromatography on-silica (eluent.* cyclohexane acetate 95 - 5 ethyl) · hereby 1.53 s of the desired product.

^0 =+ T-2DEGREES *2^I (=C. 0.7 benzene)

1.2, 6 and

1.9? -

3.1 to

6.5 to

5.9 '

6.3

."■, 3 to

1, -23. H of methyl in 2,

2.11 H of the carbon 1 cyclopropane, 3" th - 1H-carbon in 3 cyclopropane, 6.9 H of the carbon 1 of the-radical-propenyl, 2 carbon■5.93 H of the propenyl radical, H-Da and carbon bearing the CH group, '•}, ? Hr of the radical trifluereéthoxy..

In ' 1 * such as I the acid used is prepared as follows:

Preparation I : Acid cis - end) 2,, 2 a-substituted dimethyl 3 cents/1) 5 - (2.2, 2 -trifluoroethoxy) 3 oxo or cyclopropane carboxylic/1 a-orcoenyl does.. E§§greatly accelerated§" à_i_ii-to-_S±ê2_£i£ldlmithylr2 3; 2 i3thydrox_{the I -} 3; çxo_i< the I_: grc2vr.2l)

Introduced 26 g of (cis-IR-) 2.2-to-diaéthyi - 3 (2.2 to-dibromovinyi) cyclopropanecarboxylic carbcxylate of 1, i dimëtfcyléthyl in 1? 5 cm3, of anhydrous tetrahydrofuran. Gold then adds the I

- 65the EM>* 50 C. a solution of butyl lithium-I- 2Bone in cyclohexane ;. 1 Hour was stirred the I - 50⁵ C. and then bubbled through a stream of carbon gas during - a. hour, and a half, lodging there and then reaction mixture in the L - ' ^ water ice. - - - added.

soda H - L-washed|'ether, lala.phase' aqueous, alkaline is acidified to pH 4 and extracted with ether. The organic phases dried -,, causes dry under reduced pressure * the obtained product that rscristallisedanâ petroleum ether (60 and 80° to EB). The result is 8.3 g of the desired product melts at 144 °c.

NMR CDC1,

draft

1.21 and 1.37

1.78

a

8, 25

Ee of £§<=GBP§_ _i U-shapes3_çis} _g_WITH2- dimgth£l I ^ - ^ an OXC/liter (2_{the I}2_{the I}2^ - iFFT letlet us uorgprotons methyls in 2 cyclopropane, proton abstraction ' in 1 and 3 cyclopropane,

the proton terhutyle, '

proton-. group - c EO

4 G of the product of CN introduced prepared in step a, 3.5 g of àicyclohexylcarbodiimide -, in a solution containing

20 cm} methylene chloride and 1 cms3 pyridine. Cr * hand holds under stirring the reaction mixture for one hour.

Then added 2.15 s of trifluoroethanol and 5 cm3 of methylene chloride. Is maintained under stirring at 20 * 0 during 16 hours. NC filter, and rinses to methylene chloride. Bringing the filtrate to dry. 1 Is taken up with ether sulfuric, hydrochloric acid washed and then the n T- water and dry.

Is concentrated and isolates 5 g of a product wherein the product is chromatographed on silica (eluent-benzene-ethyl acetate (§5 - 5). This provides 3.5 S desired product.

1.2■and the I, 37 hr methyls in 2,

1.77 H of carbons in I and 3 cyclopropane, 1.43 h of methyl radical 1, 4.3 to 4.7 I diaéthyléthyle W of the radical trifluoroethoxy.

Stage_<i>Ç_>> Y_{the I} __> The £Açide_lR_çis]_> _2_WITH2; dimethyl_3/3; the oxo33; 002_GJs2_WITH2; - sorting

. tiu2 £2i $!} 2 £2l £l2t2h252k~'ï2 £à22 £22§2î-s-§of £theS. 2 of £2li§§th "

Refluxes is a mixture containing 3.3 g of the product prepared in the previous step, 30 cms3 toluene and

100 mg suironic paratoiuene acid. Refluxing is maintained until the end of the off-gas. Or cools, washed I-water, dry and causes the I dry. This provides 2.6 g of the desired product used for BD - it is in the following step, ;

Stage s2i £sa222ts&25li " ir2222ê02i£-to-S22lS2£2$iS§- .2is 2s2üs2â · ^

Is placed in a flask connected to a. apparatus hydroisomerization " discomfort 500 ®g of palladium hydroxide-I THE IQ % on barium sulfate, and 5 cm3 ethyl acetate. 2 G of the product are added at previous stay in the prepared, 45 T-1® ethyl acetate and 0.5 cms3 of cuinoliane. NC hydrogen until the end of abs c? " btion. Is filtered and the filtrate is washed * to hydrochloric acid H and then to water." and amine obtained dry * 2 g of a product wherein the product is chromatographed on silica (eluent hexane, ethyl acetate, acetic acid - OSB-to-30 angiotensinll hereby 1.3 g of the desired product "

Spectrum BftSTCPC1 - ATCP

. . 1, and 3 - 1.32■H of méthyles.-to-en.. 2 *'

' 1.22 - - 2, β 0 - 1 carbon H of the cyclopropane,

3.07 - to3.38 . H of the carbon 3 cyclopropane,

6.6 to 6.2 H of the propenyl radical L-shaped carbon, carbon 2 5.2 - 6.0 H of the propenyl radical,

4.3 to 4.7 hr - trifluorcêthoxy radical.

Example 2': (cis-cyle) has, "5" 2 a-diaéthyI 7cl) - 5 a-c %o-a 5" {2.2,2-to-trifiuoroéthoxy) a j-orocenyl/cycloorosane carboxylate<133.

23 - 1 - 4 - οχο digtéthy - - ( 2- propenyi) L cyclonenten L-Y-the.

1.9 G of mixed acid (cis-IR-) 2.2-dimethyl THE V {%) 3 - oxocyclohexyl " 3 - (2, 2, 2 a-trifluoroethoxy) 1- propeny1the cyclopropane because /boxy League, 12 cm3 of methylene chloride and 100 © diméthylamina g of pyridine derivatives. 1.4 Grams is then inserted di "

■eyclohexylcarbodüaide, then 1.1 (e) 3 g -<2 a-propenyl) 1- hydroxyl 24 oxo - méthyicyelopent -2- ene and 5 cms3 methylene chloride. Is maintained under stirring at the temperature

. ambient during 2 hours.* removed by filtration the insoluble - formed. The filtrate is washed with hydrochloric acid 0.5 The n, and then water, the sèche,-and. causes it to dry. The result is 3 g of a product that gold, chromatography on silica (eluant ethyl benzene aeêtate (95-5)}"

This gives 2.2 g of the desired product "

- * JS IN⁰ VBE1 GBP. 2*5Degrees (_=C.0,5* benzene.}

NMR spectrum■.' CSCs1" aCP

2.29 and 1, 3:2 hr methyls in 2 cyclopropane,

1.97 2.11 H 1 cyclopropane,

-3.05 - to - 3, 37 " H in 3 a-.du, the cyclopropane,

Example 3: (15 cis-) 2.2 a-substituted dimethyl THE J/(Z-)- 3 - οχο 3 a-Cchénylaéthose?) I-a greedy.? 1/cyclopropane group ', (ls) cartcxylate Da are " C.? anogenital 3 a-Yoo-hoonoscy benzyl.

CD§de_A_ ^ * theS ftiorure. D._{- E} the I; açidt. (ihih.çis>.2_WITH the R/LIX 22di3ith2i ^. 2=2 * degrees=lli2fei5fôiS£SXï2 to; ss22t22k. to-s2el2ss2s* Of £S2Zl§3 $SH-O] ii **

Stirred 5 hours under nitrogen stream, ' a mixture containing 1.6 g acid (cis-le) 2,2substituted dimethyl - 3/ (2) 3an OXC - 3- (p-' born nylmitdoxy) cyclopropanecarboxylic acid/L propenyl, 10 cms3 d.' ls of core eô does 1 cms3 chloride. the thiony, concentrate and thus obtains 2 g .d'a product unterstanding. is used as it is in /. the following step.

A SF-to-ii.i, I-§2§^ - SilI-to-2i22di3|>MC - 5/00 - 5i to GBP_: gBP - 3r 2x2 lRi 2l2îl®fthox2) I-" KSSSIZk-to-£zçis5s2aiaê-to-SSSL population [SSs: ii£â ' a-âë-to-ilSl2fc££SS2rS; if: 43S22

bSSS&confectioneries * '.

•introduced 1 g of the product prepared in step the K in a solution - containing Never mg of PK)* hydroxyl - 3-phenoxy benzene aeëtonitrile, 20 cm3 benzene and c', 6 cm3.de pyridine derivatives. The reaction mixture is maintained under stirring for ls _ hours, the L the temperature¹ room, poured over a-mixture of water, ice and hydrochloric Large nor by-agitates the suspension cbfcsnue and extract to benzene. The previews benzanic - washed, th water, dry, filter and causes th dry "/ obtieht VBE1 is1,5; g of a, product which ohroœatography: - on. siliea :. C.. eluent cyclohexâ babies ethyl chloroacetate (8-2) ') ": -^V.

Obtained-and per se mg of the desired product melting s3 °C.

^=+< 69Benzene®+ - 5 * ce=0.25).

Spectrum RftîNCOCiy ACP

ii, 25. H of the methyls in. 2; the cyclopropane, .

8.33 E of the carbon bearing the group. HM.

' Preparation an IR - f - cis-CIRs acid) 2, 2 - 3 - 1 άχη℮ τ ^ - ^ /) - - - - 3 3 οχο

(phenyl) -1the cyclopropane - / L-Propriéte carboxyligue.

t£â¾.A..·-V ^ - βis2-to-β * confectioneries: gisSt5ïi-to-S£iîi. 2: OSS δ ^ " LfS δ SBXll $9.ï β tournaments.■

Hydrogen is 2 g of (cis-IR-) 2.2-to-dimétbyl 3/2 and CARB SCM<Mqr ethynyl-cyclopropane carboxylate/L, diaêthyléthyl~I-in.

40 cm3 acetate D.^{the R} ethyl in the presence of 0.38 g of hydroxide of. 105 palladium on barium sulfate and 0.4 cm3 of quinoiéîne. Is filtered, washing the filtrate T-hydrochloric acid 0.5 The n, followed by water until neutrality, dry, concentrated

dry under reduced pressure and obtains 2 g of the product rtcberchë melts at 94 °c.

Sc§§- β-L-I-a i4h .çis2. 2_WITH 2 a-DIA of a Fe||^ L._{the R} the L - / i22_: confectioneries_: 2S_S - 2llS5fSIl.l->■®tiisïï: / - SMBSMieZcl2fir2B§GS ss5&22SlâSS.âe L * of £Ss4 e 00 sec.&24f&Zll•

2.4 G of the product introduced prepared in step the K 20 cm3 in ethyl acetate. Then added 2.34 grams of o-to-bensyl the n, n diisopropyi isourea (described by spinner ©? and neck Liebig ANNs. Mal. 1965635 ΐ β ΐ.). Was stirred at room temperature TMs confectioneries hours, filter and concentrate the filtrate under reduced pressure.

The CN obtains 4.3 g of a yellow oil that chromatography on silica (eluent benzene cycichexahe (7 - 3/)* 3n obtained 2 g of the desired product.

CDCl NMR spectrum, aCP

§tadetade.ç _i_Açid§" iir_çi32_2a₂ :_D.imith ^ 2" 2:_/ ii 2:2: 2X2i2rUülS2l-to-5isti22îz2.ic 2r 2si02li-to-2z £i22r22§Sê-posed&2ï2li3H2 *

Is heated to 90 °c a mixture containing 2 g of the product prepared in the previous step, 30 cm3 toluene, 100 * d-SGs suifonic para. Is maintained under stirring for 2 hours. Bringing confectioneries dry and obtains 2 g of a product wherein the product is chromatographed on silica (eluant: cyclohexane derivatives * acetate of ethyl-acetic acid/60" 0/i>.

This gives 1.4 g of the desired product.

CDCl MR spectrum, the PSM

1 * 25 and 1.3 K of 2 methyl-cyclopropane,

1,S4 " 1.98 3 carbon in 1 cyclopropane,

3.14 £3.43 b of the cyclopropane carbon 3,

6.4 ii 6, 77 B of the propenyl radical carbon in 1",

5.98 H of the propenyl radical 2 carbon ".

Example 4: (cis-1r) 2.2-dimethyl 3 - / the CZ) 5 oxo-3 - (Phenylmethoxy) propenyl•^ / cyclopropane carboxylate of (1s)" - 2the oxo méthyi and 4 """ 5 ( 2- propenyl) 2and cyclopent -; er. L -? the.

Introduced 1 g of acid chloride (IR-goose} 2.2-dimethyl 3/ (2) - 3 - (phenylmethoxy) οχ α 3 1- propenyl/cyclopropanecarboxylic acid in a mixture of 450 mg of (e) 3" (2- propényi) 1- hydroxyl 24 a-cxocyciopentmêthyX - -2- in L-yl, benzene and $20 cm. 0.6 cm3 die pyridine derivatives. Is maintained under agitation for lo and hours and pouring the reaction mixture on an ice-water mixture and hydrochloric acid N.■extract to benzene, joins the phases benzene, washed £water, dry and causes the I dry. 1.5 G of an obtained product which silica chromatography (Sluant: cyclohexane-ethyl acetate (5 - 2)).

the cyclopropane propenyl/carboxylase (sec.)" a cyano 3-phenoxy benzyl.

By operating as to the example 1, 1.5 from th g acid (cis-1st) 2.2-dimethyl 3/(Z-) 3 oxo-3-phenoxy-lpropenyl/1.45 g of cyclopropane carboxylic and (e) hydroxyl * 5- phéhoxy benzene acetonitrile, is obtained 1, E g of the product - - search.

*=' 5 ^ ' tee. 2>5®(=C. 0, 52 in benzene)

Spectrum ' had c5s11. ppm.

Preparing ΠΧ: acid (1Η sLE) 2.2-to-dlaéthvl and 3/(A Z) 3 oxo 3 a-ohénoxy t-propenyl/carboxylioue cyclopropane group.

$§TEIs ^ ls.the R *~&Ais îmizlzùlz2mzlz2&îwnzizmuzûi 00 - 00Sïk-to-£ïsl22s2iane-to-2arboS_{Of Zl} aTs " -_toS_. 4|_{the I}I₄4Œ|§2l|Sli2ls * sec.

25 Grams is dissolved<* I (IR-SLE) 2.2-to-diaéthyl 3 - (2 ", 2" dibromcvinyl) cyclopropanecarboxylic carbcxylate of I, I-a dimethyl ethyl - 250 in the tetrahydrofuran. Is then introduced under stirring °g i - 65, 48 cm3 D.^F. a solution e 209.Ï of butyllithiu " in cyclohexane. Is' holds 1' stirring for one hour the I -65°C and introduced 9.6 cms3phënyie chloroformate. Is maintained to new stirring the L -65 °c, for one hour, and leaves return confectioneries ambient temperature while maintaining the agitation. NC is poured onto a saturated aqueous solution of phosphate acnoscdic, confectioneries ether extract * T the washing water, dry and obtains 24.6 g of an oil which is purified by chromatography on silica (eluant: cyclohexane-ethyl acetate (9 a-lii). Thus isolated 14.4 g of the product P # * sought.

TbMn spectrum

1 * 23 and

1.82

the I, 5

COCl to ^ ppm.

1.42 Hr methyls in 2 cyclopropane,

H 1 and 3 cyclopropane,

H of the diséthyl ethyl group,

7

2.7.6 Hr aromatic.

A Fe§§4s s " I ILR scale ^ if§L 2_{the I} 2₌diffl|th2l_: the I ^ ill.3 oxo-2 a-2h|p2xy_: ^ / SSSsénylçyclçoroo.rboxylate§ne.c§_V. àeàe.l_{the X} the L_: the L ^ ^ ll.it dimiç2,

In the presence of palladium hydroxide Ag of 800 on barium sulfate, 0.8 cms3 quinoline and 20 cms3 ethyl acetate, hydrogen is 4 g of the product prepared in step a in solution in 80 cm3 ethyl acetate, in filter and adds 200 cm3 of a hydrochloric acid solution 2k. Decanted, washed with water and dried. Obtained 4.1 g of an oil which is purified over silica (eluent: cyclchexarcyclchexar.e-acetate ethyl (5 - 5 $))" obtained 5>35 g of the desired product.

Stage_<-Ç_: _acide, (infrared, ICFTU 2 ,, 2-dimethyl -3 - / _ (1) 3 NiOxq3c3~fsg *? the L " loorocanecyc_{the U}çarboxy|4THE S - S-YEN

It carries a refluxing a mixture of 3" 3 g of the product prepared in the previous step, 35 cms3 toluene and 100 ag of sulfcnic paratcluêne acid monohydrate. The backflow is stopped immediately after the end of the off-gas. The mixture is brought to dry under reduced pressure and obtains 3.4 g of # ameliorant Céluant silica chromatography: cyciohexane-to-acêtate of ethyl-acetic acid {70-30-1). 2.4 G of the product obtained desired flux of I 57^I C..

prooenyl/cyclopropane carboxylate of custom) - 2 a-aéfehyl οχ℮ - 3 - 4(2- propenyl) 2- cyelopentan-to-l~yle.

By operating as to the example 2, from 1.5 g acid (IR-the OIS) 2.2-to-dimêthyl and 3/(Z-) - 3 oxo 3 a-phêtt © XY-T-propenyl-cyclopropanecarboxylic acid and/(e) 1 g of 3 - (2 a-ρτοpenyl) 1- hydroxyl 2- methyl 4 oxo and cyclopent -2- in L-yl, is obtained 1.6 g of the desired product.

* e 66^I + 2.5 (c=0.5 * benzene)

Spectrum HW ENCRYPTIONUNIT CDC1 " ppm.

" - - - *■mmpmmr R. i-I-im-# -

1.26 and 1.33 H 2 cyclopropane,

1.95 - 2.09 K 1 cyclopropane,

5.7 H of the cyclopentëne in CO ^,

4.8 5.2 h 3 of the T-propenyl carried by cyclo -

pentene,

2 H of the methyl carried by the cyclopentëne,

β, ΐ to, 6.7 H of the propenyl carried by cyclopropane * 7 7.7 SEC. Hr aromatic "

SxemoleT : (I.R. the cis) 2, 2 a-diaéthyI-a 3'/(Z-) - 3 oxo-3 a-métbox? aéthoxr-L-propenyl/ETL/cycloorooanecarboy of (the HS) 3 a-ohénoxy TDC-cyano-benzol.

T-|§de.A. :. ILR scale. ^ 2 cis2cis2.2._:diaith2l; the I_I has_: the oxo_: 2_: has|5 {22xj-its ^ 3i-I e 002aisïuaisïu.s22the I2SROs2The R sne.c|: cubicle2i-|tete.â§- lHSi.2tiSïâsa -2rBs ^ e2ii bengyle.

* Is cooled to10°C 3 g of a solution (lb IC *) 2,2- diméthy1- 3 - (3" hydroxyl 3- οχ α-L-propynyl) cyclopropane-th "rboxylate of (R)O-<- a cyano 3-phenoxy beasyie in 30 cm3 di" méthyIforaamide anhydrous, adds per fraction, 300 * hydrur mg of sodium 6ls in oil and then 15 timed, 2.5 cms3 of ether solution calorornethylic prepared as below * mixture is stirred 2 hours, poured onto an aqueous solution of monosodium phosphate T-extract and ethyl acetate, washed|water, dry and dry concentrate confectioneries. The residue is chromatography on Si - running, eluted with a mixture: cyclohexane-ethyl acetate (?5/ 25) and collects 2 g of desired product.

THMN CISC, ppm.

1.23 1.27 1.35 - 1.45 and proton ' methyls in 2 cyclopropane,

1.55 proton in I and 3 cyclopropane, 5.28 raéthoxy proton-methylene of the methoxyl, 3.5 methyl proton from methoxy néthoxyle, 6.42 and 6.4? proton is carried by the same carbon a CB, 6.92 1, 7.58 aromatic protons.

Preparation of the ether solution cfaloroaétfeyliaue.

Mixed 4.5 cm3 of méchylal and 0.52 cm3 of oéfclit " nol and then slowly added 3.53 cm3 chloride aeétyla, OA is stirred for 35 hours at room temperature to obtain the expected solution.

Ill diaéthylrl sîaâgsîaâg.l.r.ilr.sisl. ^ / lZl-to-Jroxo-to-lxffiéthe ^ ^ lîjsÿgIt ^ i: bss8■&sïsl2b obêssobêss.b§sb2 . 00 * 00 iâxS-to-is-is 15§^ - L-: sïsqb-to-ii: B6fB8IJEbensyie.

Is hydrogen 2.2 g product obtained as mentioned- top 50 cm3 in ethyl acetate in the presence of 450 RAGs of palladium hydroxide 10S on barium sulfate in 30 cms3 of hascétate ethyl and 0.5 cm3 of quinolëine. Is filtered, washing the filtrate THE L n-hydrochloric acid, water confectioneries, dry and dry T-arene. Chromatography on silica is the residue, creeps by a mixture: cyclohexan - acetate .'d ' ethyl (8-2} and collects 1.2 g of desired product.

THE D *"^{+ 4}I^I 13 (c=0.32 CKClj)

NMR CDC1~ppm.

the I, 27 * - 1.28 and 1.33 - 1 * 35 methyls protons 2 cyclopropane,

1.93 - 2.1 i-proton-cyclopropane,

3.17 to 3.5 proton at 3 cyclopropane,

6.47 I- 6.82 in proton from ethylenic 1,

5.35 - 6.0 and 5.88 - 6.1 2 * 5.27 and 5.3 ethylenic in proton-proton-this ^ of the séthoxy,

3.47 and 5.5 methyl protons of the aéthoxy.

6.4 carried by the same hard-bound than CN, 8 * 92 1, 7.67 aromatic protons.

The (IR-cis-) 2.2-to-diaétfcyi - 3^/ 3 hydroxy - 3 - δ Χο I prcpynyl/carhoxyiate of the cyclopropane (r3)" - a cyano 3- pfeénoxybensyle used at the beginning of the example can be prepared in a manner similar T-that of the ester (e) described;: farther, using the corresponding alcohol (R).

Example 8 : (IR-cis-) 2,2- diaéth7the L -3The c / - 2) 3 - methoxy - 3 - ℮χο ον℮ηό 1 a-orooényl/cyclopropane carboxylate of (e) (X-to-eyanc 5 a-afeénoxybenzyl.

GBP - 2s222b2l4 S22i2SE22iS§- 2i u2252i§GBP-s-β -§lSil5l222§s2-to-22Sèi522S benzol -

Operation is carried out as in example 7 using confectioneries 2 cm3 of chloro-acêtonitrile; after extraction th ether: and elution with a mixture cyclohexane ethyl acetate (9-1), is obtained 2.69 g of desired product.

Stade_B. t-{1Η ℮ ^1ε) ^2,2- ά1η℮ΡΟν1-3-/(Ζΐ -3- οχο ^3ό -1℮ηο néthoxyBBBBBBWBB αBB αBB ΒΒ β Β · 4bb ·Β αBB 4. ^ ÊÊ 94V ^ ^ * b * 4b Β dual Β αBB BBBB ^ ^ b. Β αBB ^ Β .4b αBB BBbBhBBBBBBBBB4B αBB 4 b*bb β ··ΒΒbb3b * bb.bb^b * bi=bi!: QBicyi /__< ç2çignrooane_çarbçx2late_àe^x3si^. - çyano_3:ph|nox2

By operating as to the example 7 starting at 2.69 g of the product obtained previously, is obtained 2.02 g of desired product after elution with a mixture ii cyclohexane ethyl acetate (9-1).

. IX.§3ê-to-S.i " takeover-to-i4§). 2ilrdisixt2ir2 *: GBP LIT: 2: 2ïs-to-22ç2§ü2-to-SiSï2ri * 'F.' lsl0ç.-to-5ïa32. 3₌ 2:00|ns5ï · benzol

Silica chromatography is 1.4 g of the above product, elutes at methylene chloride and obtains 0, 4i g of desired product.

% 55° * 1.5=+ (- C. U HCC1₃ )

Example 9: (13 cis-) 2.2-dimethyl 3 - (Z-)/- 5 oxo 3 a-éthoxyéthûrr 1 a-oropényl/cyclopropane carboxylate of (e)- 3 a-phtnogrçyano'd benzyl.

GBP -§SIs&- i. il5-to-si22-to-âaSrâ4séSôzlr2 ^3: 2ïsi2: s SbSK&b.2-&lr85sfimu sïsisbs2b "has ^"!" SlUift-to-4sj.3lj&Sïm8. ^. 3: artBWHf.

4SSS2lS•

Is cooled to - 5 °c erffective powerU +, 2 g of (cis-IR-) 2.2-to-diaéthyl 33 - /- hydroxyl 3-0the X0 the L-propynyl) cyclopropane carboxylate of (e) a cyano - * 3phenoxy - benzyl, 20 cms3 methylene chloride and 0.7 cm3 of ethoxy ethanol. 1.1 G of dicyclohexyicarbodiistide added, 5 cms3 methylene chloride and 15 mg of dimithylaminop-to-yridine. Agitated 1 hour 9.ï + 5 °c and 2 hours at room temperature. Is filtered, and the filtrate concentrated to dry the residue on silica chromatography, eluted by a mixture: cyclohexane-ethyl acetate (75 - 25) and 1.3 g of expected product is obtained.

NMR ÇDC1, ppm.

1.22 1.32 methyls protons 2 cyclopropane, 1.93 proton in 1 and 3 cyclopropane,

4.17 the L 4.33 proton in 1 COO-Ch-to-Ch O

3.55 Z 3.73 proton in 2 COO-CFUs Ch ^ - the O

6.57 proton is carried by the same carbon than CN 7 Z 7.67 aromatic protons

1.08 1.2 1.3 and - 1 , 52 (qs) ethyl proton, .

§2§4s b-I-a NS si52-a 2_t-< 2;diméth2l_- 2 2rliJS iizlriizlr 2r 222. "aQLiJ! the HP ^ JUl2£2Bê2ïU-to-s22l2s £22§sësë.s§S42Xïlâ 00 sec" 4ê.S2_. 00 *_ ex§of gG and 2 - - b4is222 èSSS ' 2sê *

By operating as in example 7 confectioneries, step b, from 1.3 g of the product obtained above is obtained 1.0 g of desired product.

tDC_D s + 37^I , + 5 2.5 (- c. 0.5%CHClj)

Example 10: (IR-cis-) 2.2-to-ûiméthyl-a 3 - / 3 - (Ζ) - οχο 3 (RSHl-I ltrlfluorométhyl ethoxy) cyclopropane carboxylate of L propënyl

(E) a cyano - benzyl 3 a-ohénoxy.

Operation is carried out as in step b of example 7 in utlli *

^{: 38}# nIRC

heterozygous 2.6 the g ' of (IR-cis-) 2,2- diaéthyl3- /33 - οχο - ((5 Η.) 1,1,1- trifluoro ethoxy oméfehyl) propynyl or cyclopropane carboxylase/(e) the X-cyano-benzyl 3-phenoxy. After elution from a mixture cyclohexane ethyl acetate (9-1) is obtained 2.1 g product atteisdu.

.">44° + 2 (e C. 0.45 benzene)

Preparation of ( An IR-cis) .2.23 - diméthvl/3 oxo - 3 ((rs3 ll.l.t-to-tnifluorométfcyiéthoxy) propynyl/cycloorooane carboxylate (if•• Of OC-cyano-benzyl 3-phenoxy.

Operation is carried out as in step a of example 9 using 4.6 g of 1,1,1- trifluordméthyl ethanol and 3 * 8 g of (I-IR-El * 2,2-<Üméthyl3- /3- οχο 3the cyclopropane carboxyl hydroxyl - propynyl/ETL * (e) of the c - a cyano<3-phenoxy benzyl to obtain, after elected * except by a mixture cyclobexane ethyl chloroacetate (3 - 2} 2.6 g of desired product.

Example 11: (IR-cis-) 2, 2 dimethyl-le -/(2)* 3 - oxocyclohexyl -3 (2.2 to-dlfluoroéthoxy) propenyl/cyclopropane carboxylate of (.6) X-α-cyano 3- yoo-hoonoxy benzyl.

=it 1A it : 00 2r2 Directors 5i5iSt4lrlr ^ 2; - 2ritxlzûit i-&? s at the £1 ΐ) 23 of Zl / Σ > Drooyn _02cl2crgoane_ç§RBGs ^ ^ of lace terbutyle.

By operating as in step a of example 9 from the I

of 5 g of (cis-IR-) 2.2-to-diaêthyl and 3 / - 3 hydroxy 3- cxo-1 - propyny1/ cyclopropane carboxylate of terbutyle and after êlution by a mixture of n-hexane isopropyl ether (- T-3) is obtained 5.25 g of desired product.

THE IR CHC1,

cono - CSCs - 2232 cms and 1

Grown-ester 1725 cms"¹

asymmetric 1710 heart I-

gEMs dimethyl ' .0.393 cms-1

|1380 cms-1

terbutyle1372 aC-1 Stade_3_i_açide_ {lr __{the R}çis}_> 2 __{the I} 2;diff4ih ^ lxl; ^ Oxg_3liaaildiriugrg - / -. Sè2ï22.î;li!2s2îi2l^ - si2^22s2s§3ê-to-sfî5sé2lî2àê *!

Heated at reflux 5.2 g of the product obtained above, 500 mg of paratoluene sulfonic acid in toluene during 25 minutes to 40 cm3. After cooling added 400 cm3 of Ither, confectioneries washing water, dry the organic phase and concentrate to dry to obtain 4.1 g of desired product.

ethoxy?_{the I} the L-propynyl/_{the n}cycloprop " mth, carboxylate groups.._i-> of.

the ISS iie binding&&sasEls *&L.

By operating lug in step a of example $I-from 4.1 g of the acid obtained above and 4.5 g of alcohol (3) "*" cjrano3- phenoxy bensylic obtained after ion through a elected *

•mixture petroleum ether (40 - 70 to EB^I C) - isopropyl ether (6 - 4) 4.7 g of desired product.

THE IR CKC1₃

0:00 3580 Cms and 1 mth GEMs-di $$ 2 Çv aC-1

1, 1380 cms-1

The CAC - conj - 2235 AC-1

' C.=0 the ester 1755 AC-1

the ester conj 1725 AC-1

aromatic fl.588 aC-1

|1488 AC-1 §fcsasfcsas.s-to-i, custom ii2-to-2a2 ^₌ the I/22:2 diafthzi-to-2i=2ï9 will happen._hasliâiniser. ^ ^ 2 a-2222is2l tSfe2 - aZ2s22E2S§is s ^ * 2SEiêlS 4s-to-iliSl: sesôs2the R2t iü22E LSG§ll®*

Is hydrogen 4.7 g of the product obtained above the likes so as that in the step b of example 7. After elution to per - a mixture n-hexane-isopropyl ether (7-3) is obtained 3 * 2 g of product. expected.

"_D. the m 44^I + 2.5 (c=0, 5ï CHClj)

Example 12: Abduction of cis) 2, 2 a-dlméthyl-a 3 - / - (Z-) 3 - (2.2 to-dichloroéthoxy) of L-propenyl/cyclopropane carboxylate of (3) of OC-cyano- 3-phenoxy benzyl.

^ ^ ^ ln stsdeizi ^ gzdjgêtizzlzïzlLllzizLZAza&&I-sist&9.ï

It is performed comae I-the example 9 step a from I to 4 * 8 g of (cis-IR-) 2.2-to-diaéthyl and 3/(Z-) - 3 hydroxy 5 oxo 1 a-propenyl/cyclopropane carboxylate of terbutyle and 2 cms3 of 2,2- dichloroéthanol. After elution from a mixture cyclohexane ethyl acetate<3-1) is obtained 5 * 8 g of desired product.

§SSâS-to-drunk-to-è£4deè£4de.ilr, cis-^ 2_has ^_: the Thyl|DIA of₌ 2_:/ i2i and 2 a-i2 ^ - ^ vaccinica i2r5-ethoxy)_has the I- propény1the cyclopropane /. cftrbqxyUou ' *.

Operation is carried out as in step b of 1 * exemple it starting from 5 * 6 g of the above product and obtains 4.5 g of desired product.

Sfcide_- has._{the II} the LL.^ ^§SIA._<K. 2 a-DIA of|th2X " ^ ^ Sll2S2 2;alskl: ll *'ÜtSSïl-to-ii lSS2S! e? I-S2 and 00 00 - ^. ^ e l2SS2iSSâ2 ^ Documents-to-iâ£-to-Iii5L " s2 ^ b. iz2lai52 of £2J 52 Is *!

Operation is carried out as in step a of example 9 to from

of 3 g of the product obtained in 3 and 2.25 s (e) alcohol0(a cyano 3-phenoxy bensylic. After elution from the blends cyclphexane-to-aeétate (8 - 3) then ethyl (9 - 1) is obtained

1.6 g of desired product *

C. ^_D e♦54°♦2Degrees (grams " 15 in benzene)

The following examples are similarly prepared! that described in step a of example 9 from confectioneries:

1^I ) of I " acid (IR-the OIS) 2_F. 2 a-diaéti ^ L 3 - (I-)/- 3 oxo 3 - (2, 2 - U-<* ^ PMQs ethoxy)/I propényi cyclopropanecarboxylic acid and the corresponding alcohol.

Example 15: Abduction of cis) 2 * 2-dimethyl 3 - (2)/3 oxo - 3 a-c2 * 2 a-difluoroéthoxy)/L cropényi cyclopropane carboxylate of (WHR-cyano- 6-2 A-the pyridyl methyl phenoxy.

X-<_D ** 2° + 50.5 degrees (c * 0.85 CHClj)

Example 1 has the R (IR-cis-) 2.2-to-diaéthyl-a 3 - / - (e)- 3 oxo - 3 (2.2 difluoro " ethoxy) 1- prcpé rr.yl/ (e.) cyclopropane carboxylate of a cyano - X. 3^bhénoxy benzyls.

_X0 ='. + 117 degrees, 5 I-3° (CHClr ^ c=0.65)

Example 15: cis-key) 2, 2 dimethyl 3 - / - (Z-)55 - - οχο<2.2-to-difluorfl *" ethoxy)/L propénypropény.l cyclopropane carboxylate of / - 3 a-proeargyl2, 5 - ^ lQyoimldazolidiny 1/ methyl.

*_DThe V + 18° + 2 degrees (c=15 Weifeng ^)

Example 16 the R (IR-cis-)* 2 - 2.-to-diséthyi-a 5/(Z-) - 5 a-cxo 5 - (2 * 2 a-difluorc -

•. ethoxy) 1- oropényl/(hr) cyclopropane carboxylate of X-< - ethynyl 3-phenoxy benzyls*

%² * 47°♦1.5 (c * 15 CHClj)

The acid (cis-IR-) 2.2-to-diméthFl-a 3 - / - (2) - 3 oxo j. (2 * 2 difluoro ethoxy) of L-propenyl/cyclopropanecarboxylic acid was

: ufte ^ d-prepared similarly District Supervisor in our pre -, by-ationIfï. i-from 2,2- difluoroéthanoî.

2nd⁾ acid (cis-IR-) 5 / - 2.2 to-diaéthyl (2) - 3 - 3 - οχο (2-fluorine © ethoxy), L propenyl/cyclopropanecarboxylic acid and the corresponding alcohol.

Example 17; (IR-cis-) 2.2-to-diaéthyl-a 5 - / the CZ) - 3 oxo - 3 (2 fluoro ethoxy) 1- propënyi/cyclopropane carboxylate of (3- oropargyl2v5- dioxoimida201the I ' diny 1 ) methyl*'

Example 18 : (Cis-le) 2.2-to-diaéthyl-a 3'~/ Cts-3 oxo - 5 (~2-fluoro-ethoxy). - t gropényl /-cyclopropane carboxylate of. (SO)-<*' * cygnsr... the I6" alkyloxy - ^ Novadaq^: 2.' a-pyrt4yl) methyl ·ν·. -

- "dd=^ 4 + 5" + 2t5 (C.^; \ Α=0, 5S GHC1₅ )

19 Sxenrole: (IR-cis-) 2, 2 a-dimétiayl-to-a-3/(2) - 3 - -3 ·οχο · (2 fluoro Ithoxy) - L propény1the cyclopropane carboxylata/ Cr) 3c "" £polyethylene resins 3 A-Pbénoxy Bas' gyle.

· ¾ ≈ + 123° T- i->5, (C.. =LS

Example 20: (IR-cis-) 2_T- 2 a-dimëthyl~3 "/ (Z-) -5" 3 - substituted oxo (2 a-fluoroethoxy) -1the cyclopropane - propenyl /, carboxylate-OC-éthypyl.

■ 3-phenoxy ténayla.

VBE1%^O * ** 7 * i -; I, 5®- the I - (- I -; " ilCE €L.₃ >; "■

' ·; Vâ "<I-ie; the ITS '* - t-fcisy-àîaêthyl and 3 / - {2) - 3 - 3 - οχο (· 2-fluoro-ethoxy) -1- propêny1cyclopropane carboxylic / I-prepared on in a similar way. T- cells involved the preparation described in TT from the 2- flouro ethano1.

3 Degrees) acid (1Hr udder) 2.2-to-ofi®650? L 3 / - (2) - 3 - 3 - οχο (2 - (1, 1, 1, 3, 3j3- hexariuoro) propoxyl) 1the cyclopropane carboxyl propényi - / - " 11 that (preparation. Vi) and the corresponding alcohol.

Example 21; (IR-' cis-) 2>2 a-dimethyl 3 - (3) - 5 / - 3 - οχο (2 - (1, 1, 1.

3 "3" 3 a-hexaCluoro>propoxyl) 1- propenyl /-cyclopropane carboxylate of (the R)*<. 3 a-ohénoxybensyle - ethynyl.

%.^O +. 31.5 Degrees♦1.5 degrees (c=15 this,)

Example 22: (IR-cis-) 2.2-to-diaéthyl-a 3 - / 3 - (Ζ) - 3 - οχο (2 - (T-I "I".

3^3 3 a-bexafluoro) propoxyl) L propény1/-cyclopropane carboxylate

•of (R.). <theS - mëthyl3phenoxy - benzyl.

*_D +=9.7 DEGREES F.^{the Z}CHCLj)

Example 23 the I (1Cis-hr) 2, 2 a-diméthyI-a 3 - / - (2) - 3 - οχο 3 (2 - (L-"l.l" 3.3.3-to-hexafluoropropylene) oxypropylene)/1 a-propenyl-cyclopropane carboxylate (e) 0^of the cyano - 5-phenoxy bensyle.

*_D += 23*5+ DEGREES 2(C=0.55 benzene) degrees

Example 2M : (IR-cis-) 2 , 2 dimethyl 3 - / - (Z-) 3 - (2 - (1.1,1.3 3 oxo,3',3- tiexariuoro) propoxyl). 1- propenyl /-cyclopropane carboxylate of 3', 4.5.6~tétrahydrophtaliaido methyl.

^0^O " I + 30 degrees (c=15 CHCljV

Example 25; Abduction of cis) 2, 2 a-diméthy1 and 3/(2) - - 3 oxo - 3 (2 - (1, 1, 1.

3, .3 " 3 a-hexafluoropropylene) propoxyl? 1- propenyl /-cyclopropane carboxylate of (R? cyano-e-to-phënoxy 2 a-pyridyi methyl.

*=^ d-I-5°♦33 2.5 degrees (c=0.25 CHClj)

M^O ) acid (IR-intraconnect) 2, 2 - ^ ^ η℮ ℮ 1 / - 1 - 3 - (Ζ) οχο 3 - (2" 2.2, trifluoroacetic ithoxy)/L cropênylcarboxyliçue-cyclopropane (pre®ordering the I) and the corresponding alcohol.

Example 26 : (IR-cis-) 2,2- άΐ℮ΐ℮№7ΐ -3-/(2)*3-0X0 3~(2,2"2-..

trifliioro ethoxy)/L orooényl cyclopropane carboxylate of.

(3~propargy 1, 2 " 5- dloxoimiaagoliàtnyI) methyl.

the j ^? - 4^I + i° (≈ 15 C. benzene)

Example 27: CBL intraconnect? 2, 2 a-diaéthyI-a 5/(2)~5 - substituted oxo * 5-<2"2"2~^:

ferifluoroëthory)/orooényl~I-cyclopropane carboxylate of

(The R) d-benzyl - 3 a-'Qhénoxymëthyl.

s + 10 fl®5 ±2Degrees (c=15 CHCIj)

Example 23: (15 cis-) 2, 2 a-diméthyl~5~/(2) -3-0Χ02- (2^2,2--trifluoro ethoxy)/L prooényl cyclopropane carboxylate of

3 4. 6rtê: trahydroohtaliiaidoaêtfeyleà - -■

<*_D *=.2, 5 DEGREES + 2 (c=0.55 *.

Example 2.9: CBL-cis) 2"21 - 3 - / - diaëthyZ-<)~?~5 - substituted oxo (2.2, 2-a-trifluoro ethoxy)/L oropényl ' cygloagogane ACTR0the X7eTL of '

(R.) - & éthyréthyr.yl 3 a-ohéncxybenzyls..

" 2^{e +} The I ^ 2° 1.5 (^ 0# I-SSs);^:

Example 30: (IR-cis-) 2i2-dimethyl *? the m *) 3 - 5 oxo "<~2, 2, 2 -trifluoro ethoxy) 1the cyclopropane - ρΡόρ℮ητΐΛ carboxylase (Rs)* a cyano 62 - ohénoxy " oyridyl methyl"

% **46.5 ° to + 2 * (* C. CHCl ^)

5®) of (cis-ls) 2,2-01ΐϋ℮·ύ1ΐ7ΐ -3The CZ - /) 3 a-hydrcxy-a 3 * oxy/1 a-propëayX cyclopropane carboxylate of (e) a cyano - * C. 3-phenoxy benzyl (preparation art VXI) and the corresponding alcohol^; Example 31 /. v-♦(infrared, cis-). 2.2 to-diaéthyl." ^ 3/(Z) - 3 oxo 3* (2"' trichij5ga-ethoxy)_ / I-a propenyl cyoloorooane carboxylate. KIHC " ctana1" Phenoxy benzyl._:

42=+ - + °5 2 (c - 0.55 benzene)

1Χ Ρ ^1℮32Iv ; (IR-cis-) 2,2- diaétfayl-a 5 */(2) - 3 oxo 3- (2chlorine - ethoxy), because b-alkyloxy or cyclopropane lypropényl/ETL (e) of the cyano - O-< phenoxy-bengyle.

*= 3|degrees + 4 (c=0,255 benzene)

Example ^: (IR-intraconnect) 2.2-to-dlméthyl-a 3 - / - (Z-) 3 - 3 oxo (2 a-BiéthQxyIthoxy) dl-propenyl/eycloprooane. carboxylate (E) LCa cyano - Phenoxy benzyl.

Example UT: PK-cis) - 5 -<ttag6h3rl 2.8 / -: I) - ii-to-03c0 WRSs) 1-cyano-éthcxy) dl-propenyl/cycloorooane (e) carboxylate

a cyano - 5 a-phérphér.oxy * benzyl.

*_D^O +6*, 5' i-3° (c has CHC1 0.35₃ )

Example 35: (IR-intraconnect) 2.2-to-dlnéthyl-a 3 - / - (2) - 3 oxo 3 (2 fluoro ethoxy)/L oropénylcycloorooane carboxylate (O) and " a cyano

•■3 A-phérphér.oxy benzyl.

* 3^{e +} 43° (=O. 0.25% benzene)

Example 3 β: CBL-cis) 2, 2 a-diaéthyl-a 3 - / - (2) - 3 οχο 3 a-ohérohér.gthoxy 1 a-propenyl/(e) cyclopropane-carboxylase of OC - 5 a-ohénoxy a cyano benzyl.

** 3 ^=5³ + 2^I 5 (c=0.55 benzene)

Example 5t: ' 13 cis-) 2.2-to-diaétfayl-a 3 - / - (2) - 3 oxo 3:2,2dioxolanyldiaéthy1 - ^ - (RCL-to-néthoxy)/L orooényl-cyclopropane carboxylate of (E) oC - cyarcyar.o 3 A-phérphér.oxy benzyl.

* 3 + Β=4³ (c=0,755 benzene) + 2

6Degrees) of the (IR-cis-) 2, 2 a-diaéthyl and 3/(2) - 3 hydroxy - 3 oxo 1 a-propenyl/cyclopropane carboxylate of (R) a cyano 3 a-phënoxy benzyl and the corresponding alcohol.

Example 53: (1? .the cis) 2.2-to-diaéthy1-a 3 - / 3 - (Ζ) - οχο 3 a-.' 2 a-diaéthy! amino ethoxy) dl-propenyl/'cyclopropane carboxylate of, ' r5)<I-. a cyano 3chénoxy - benzyl.

*_D - 23°>3 + (c=0, 25s CHClj)

The (L-R, the cis) 2, 2 1 - 3 - - dimé thy a/(Z-} - 3-hydro-XY-3 oxo 1- propénjrl/cyclopropane carboxylate of (1$) of OC-cyano- 3-? hénoxy benzyl used at the beginning of the previous example was prepared analogously to that of the ester (e)- TDC cyar.c 3-phenoxy benzyl preparations 17 and VII,

7 Degrees) of the (IR-cis-) 2.2-dimethyl 3 - (Z-)/3 hydroxy - 3 oxo-I-propenyl/cyclopropane carboxylate of (- Rîetmëthyl3phéncxy - benzyl (preparation tills) and the corresponding alcohol.

Example 59: (IR-SID) 2 "2-dimethyl 3 -/(2) - 3 - οχο 3 - (2-methoxy ethoxy) L oropényl/cyclopropane carboxylate of (the R)" - rnéthyl 3-phenoxy benzyl.

Exmol ' th 40: CIRs' cis-) 5 - 2.. 2 a-diftéthgi ^ / {00 V~5-to-MO-L and tl méthdær 1- trifluoromethyl ethoxy) cyclopropane-carboxylato/I orapénr'orapénr' i (e) of the cyano - ά bensyie 5' para.

Gold under an inert atmosphere. agitates 1.02 g of (cia5 lb 2J2- dimethy1-a 3 -/(Z-} -3- chch.ioro 3the oxo~I prdpény lii (e) of the cyclopropane earboxylate TDC-cyano-ii ^ plsénosyPansyle and 9 cm3 Chl © " methylene fluoride. 1.12 G of added I aétfcyl ii-to-trifluoromstüyl ethanol and maintains/agitation during 48 hours 8 ambient tespérature. 2. is concentrated dry under pressure, reduced, residue on the chromatography: silica, eluted by a mixture: hexaue ethyl ether. C..8the I ^ -^: ; and obtains 250 mg of expected product? - 59DEGREES0.

& o + ψ 57° 2° (≈ 0.4 C. hensene *).

the U -t-<

. The (LHRH, cis-) 2.2-to-diaéthyi-a 3 -/(zî-to-3-chloro-3 a-a CXC/1 a-prspinylearboxylate of the cyclopropane (O-s3 (a cyano - 5-phenoxy tees " ^ zyle used initially for example 40 was prepared by the action of chloride on the thicnyle (1The OIS e) 2,2- dsaaéthyî -3- / v.2} -3" hydroxy 3 oxo-L propényîcarhoxylate/(e) of the cyclopropane the Tc a cyano 3" Phsnoxybenzyls preparation VII below.

Sxegole 41: (IR-cis-) 2_T 2 a-diméthvi-a 3 - / - 5 (Ζ) οχο 3 a-c - 1 tri gaéthyl fluorine 1- aéthylorooyloxy) cyclopropane-housing I ggQoényl /? in the broad (e) of the c - 5-phenoxy<cyano-benzyl.

900 Mg of dissolved (1Cis-hr).2,2-5ΐΜ℮Ρ1ΐ7ΐ -3-/(2ΐ -5^ Ihloro-to-3-the oxo-L-propenyl/carhoxylate of the cyclopropane (E) C. (3 - eyûitsin phënoxy - benzyl 3 C.3® methylene chloride, added 1 cms3 die 1- trifluoroisêfchyl l-methyl propanol and stirred for L.6 i-hours at room temperature under an inert atmosphere and 1 in the absence of moisture. After 3 days to room temperature © has washing the reaction mixture with an aqueous solution to saturated soduim then 1 water, dried and concentrated dry confectioneries. The residue on silica chromatography is eluted by a mixture the hex&do-ethyl ether (8-2) and obtains 5? 0 mg of desired product.

Example 42: (IR-cis-) 2, 2 a-diséfchdiséfch.vi-a 3 - / - (2) - 3 - οχο 3 (2" 3 a-dihydroxrorooyloxy) 1- orooényl/cyclopropane carboxylate of (e3 " - cyane3 a-phënoxy benzyl.

Heated at reflux 4.65 g of (cis-IR-) 2,2- dimethyl-3-/ (2)-3-οχο 5- (2,24 - dimethyl dioxolanyl - (R) methoxy.) 1the pro - "/ pényl cyclopropane group (O)O-carboxylase (a cyano - 3 a-phéncxybtaiyle (example 37), 46 cm3 of dioxane, water and 9 cm3 paratoluene acid 0, 45g suifonic during 45 min. The majority of the dioxane is removed by distillation at 40 °c under reduced pressure, the residue by resumes 150 cms3 25 cm3 of methylene chloride and water. Agitated, decanted, washed the organic phase the L water, dried and concentrated to dry under reduced pressure. The residue on silica is shroaatography, eluted by a mixture cyclohe * xane-to-acétafce ethyl (3~7) and obtains 3.85 g of product âfcteadu

*_D =⁺ 53^I * 2.5 Degrees (c=0, 5 * CHCl ^)

Example 45; (IH-ci3) 2, 2 - 7 - ^ ά ℮Ρη ΐ / - 3 - 3 - (Ζ) οχο 3 * (2 a-tétrahydropyranyloxyéthoxy) 1- sropényl/cyclopropane carboxylate of (Rs) and - cyar.c 5 a-ohéno: Cy of benayle.

confectioneries. ^ ^ stids aa.î .iir.siâi àatsBïirîiimsiîSïS-to-SiiSrSteeteft ^ -; -; - 2ïïi3ï; 2riithox2l_l; oropynïi./ S2 and the £losr25ênssacèox2i.§2g ^ g (3The I 2 ^§; Ζ δ. 22 2 1 2 1 2 θ ΐ ΰ Σ Ζ - ≥ 2 · Σ ΐ 225

Operations are carried out analogously to that described at stage A of the example 7, starting with 2.3 g of (cis-IR-) 2.2-to-dimêthyl-a 3 - / - (Z-) 3-hydroxy 3 oxo-L prcpynyl/cyclopropane carboxylate of (R) and a cyano - 3-phenoxy benzyl and 7 * 5 S 1-bromo- 2- (2as TR - tee. ahydropyrany 1) alkyloxy ethane. Obtained 1.8 g desired product after silica chromatography in the MLdiaper clohe ethyl-Tate xane-to-CEA(75 - 25).

§uâsuâs.b.i.iise_O the I $24i_yew dE|lb|sii} Xl-to-2z iSl3has2. ^ j-;* lfcSîîcèilte 2yï: anyloxyéthoxanyloxyéthox 5r 2.irs222iszk-to-222l 22r 22s0î-to-2§Cfe2Xïlft! jsjs.ie.ig§ϋΐ Ζ 122 - 2 I 2 ζ ^ 2^32 - 22 Η β=1•Ζ

It is carried out similarly I as described in step b of example 7, at ' starting from the product obtained in step with reduced di above. Is obtained after purification by chrhœatogr " Retrieval of £IE in the mixture cyclohexane ethyl acetate (80-20),1.3 g of desired product.

^O + 33° 1I^I (c=l CHClj *)

- the (1The R ICFTU 2, 7 a-didédidé.thÿl 3 - / - (2) -3 " hydra 3 oxo 1 " propynyl/eycloprepeaë carboxylate (R) α-cyano 3-phenoxy Cusing2yl used at. start of previous exeaple was prepared in a manner saslsgue to that of ii ' esters (3) R-α-cyano - 3<? hénoxybenzyls Da and the preparation * VI.

Example: ( AN IR intraconnect). 2.2-to-diaéthy1-a 3 - / (A Z ) - 3 - οχο 3- (2- hr7drex? ethoxy) I orooényl/cyclopropane carboxylate of (AE)" M. the cyan - © 3 a-ohéaoxy benzyl * ■

0.85 G of mixed product obtained in example 43# 17 cm3 ethanol, 5 cm3 of dioxane, 1 cms3 4 cm3 of water and hydrochloric joint paper®has 2D and agitates confectioneries 20°C during 3 hours. 0has then adds 1 cms3 of triétbylamine, evaporated to dry, resumes' by a mixture of water and ice, extracted chloride ' methylene, iâ®ue 1' water extract, the dry and evaporates the solvent is chro®* eatography rédidu on silica by eluting the mixture eyclohe®xane ethyl chloroacetate (65 - 35) and 0.05 g of expected product is obtained.

<*_D V * 42.5 ° to + 2.5 degrees this^O 0.5Î CKC1-)

The following compounds may also be obtained, its " ion in the method of the invention, starting from corresponding acids and alcohols:

- the (1Hr IC3) 2.2-to-diaéthyi-a 3 - / - (Z-) 3 a-oxq 3~ii * i"1 * 3 * 5" 3 a-hexa-fluoro-propoxyl) propenyl/carbcxylafce.de the cyclopropane 3~pH value of £nosy benzyl.

% " + 28.5^I + 2.5^I (c=0.55 CHGlj)

* cis-CLR) 2.2-to-dimêttayl-a 3 - / 3 - (Ζ) οχο 3 - "U-shaped, I-, li3, 3.3 and he and" flouro-propoxyl) propenyl/(e) cyclopropane carboxylate of cyans 3" phenoxy 4 fluoro benzyl.

^O *^2Te the I² DEGREES⁽ⁱ * ^0.85 &" hzene)..

Preparation of IV: clrclr.cîs) 2.2 * 3 * c5 dimethyl~" substituted oxo 5 a-hh.vdroxy 1the pro -&rayl) cyclopropane carboxylate of (time to - 3 a-obéhoxyevano

benzyl..

Step A: JlR. çis)._J2^23diaft ¾ yj ^3WITH2a Ga - ^ ^ boffi_¾e|YNB π: gI/_tCIçyeio-to-Iis22âü§" êiià2; ^ i-L-§§00 sec.. îsSS GBP.222* lT.

26 G of introduced (IR-the OIS) 2.2-to-diffiéthyl - 3 (2.2 to-dibrofficvinyl) cyclopropane carboxylate of terbutyle in 175 cm3 of têtrahydrofurane anhydrous. Then added confectioneries -65®°C 60 C.3'β' FNR ^ solution of butyl lithium-T-205 in cyclohexane.

Oa-lus âgita1 hour - 0060^I C and bubbled : m. current carbon gas during 1 half hours, verseverse.le-mix, in cases " tee members corresponding in chilled water added soda H is washed

to 1' ether. The aqueous phase is acidified alkaline pH of the I " and extracted with ether. The organic phases are dried, deliverance I-dry under reduced pressure. The result is a product that the RT * crystallizes in the PK&petroleum ether 60-80°C). The result is 8.3 g of the desired product melting î44 °C.

NMR CDC1, a POM

1.22 and 1.37 methyls protons 2 cyclopropane 1.78 proton at L and 3 cyclopropane

1.47 terbutyle protons of the

8.25 proton-group - c-OH

iF

0 §4adâ. 3.: _ of £Ir, çisi_- 2_WITH 2_:diaéth2l. 3: * lâiâ confectioneries: 22 ** 2Nicotinic SS2iSS2222ê2S2i^00 éthynsllcaaloaroasne. carboxylate terbutyl derivativesth.

6.2 G of dicyclchexylcarbodiimid introduced " in a solution including 7.13 g of (IR-ICFTU 2.2-to-diséthyl 3 -<2 a-carboxyéthynyl) cyclopropane carboxylate of terbutyle and SO TAG dimethylaminopyridine in 35 cms3 methylene chloride.

The reaction mixture was stirred for 10 minutes and added 4.5 g of 2, 2, 2 a-trichloroethanol. Is maintained under stirring for one hour and eliminated by filtration the precipitate fonaé.

The filtrate is washed with hydrochloric acid and then the n the L water to neutrality, dried and causes it to dry. Is obtained 1" g of an oil which is chromatographed on silica by eluting the benzene acetate Ithyle<$7 - 3). Thus isolated 9 g of the desired product melting the I 70 - 7 i °C.

GBP GBP ss.ç§confectioneries. i âsiât. U.S._ of £I-§2 " O

çarbony1 _ 11 i-hyny2 the cyclopropane. çarboxy. lipue.

It refluxes for one hour a mixture containing Island Lake Group of the product prepared according to step b, 300 mg of toluene and 120 cm3 paratcluêne sulfonic acid. Allowed to return to room temperature, the reaction mixture is washed with water, dried, and 1' causes dry. This provides 9.5 g of the desired product is used as such for the next step.

Stage of £_D_ _ (lR_çie]_>-2_WITH2the th ^ - DlM|l_27the I2_{the I} ,2_{the I}23thoxytrichloro_|its 00 good2l_éthyny: ^ _SY2lgDrçnan§_earbgxyl§tejïe_- E 00 00 theS (_> ; cyscys.sio 2iSîïiSS2fiE Fe-t5s2lt *

6.2 G of dicyclohexyl carbodiimide is added in a

•containing solution; 9.5 g of the product prepared in step C., -

30 jME methylene chloride and pyridine - 3 cm3. ** VBE1 is acted te the reaction mixture for about half an hour and adds 6.8 (e) g of RT a cyano 3 a-ohénoxybensyliq ' UEs. Is maintained under stirring for one hour and a half. Removed by filtration * the insoluble formed. Washed, the filtrate to the m hydrochloric acid and then with water until neutrality. Dried, ieflitre and brings it I-dry. Obtained β 1, 3 s by a oil on silica by eluting itsgchromatography that by. the mixture bensëneacétate ethyl (97 - 3). Thus isolated 12 g of the product sought flux 1 law °C. -

lSf4i " s i.u5 -=ial.2i2-to-Si3liilli-to-2lUiS2droxv. 2 a-oxooxo.l-to-orosfS2l) Sïsi2ksbss£-to-SSSSS2-to-ls -&ât ' a-llISLSïSlS=" 3l®sb8s3r^sbsîls *.

5 * 9 Introduced g powder of polyolefin in a solution containing a-6 * 5 g of the prepared product ' in step d, 23.4 m3 acetic acid and 2.6 cm3 of water. The mixture is kept under stirring for one hour. Is filtered and settle upon the filtrate. The washing of the organic phase I-water and extract the aqueous phase to methylene chloride. NC joins the solutions chloromethyienic, dried, the filter and the causes I-dry. This gives 4.7 g of crude product used as is.

Preparation of V: (IR-cis-) 3 - 2.2 to-diméthvl/(2) (3 a-hvdroxy οχο - 3. 1- prooényl/cycloorooaneterbutyle carboxylase:

Hydrogen is 2 g of (1Cis-hr) 2.2-to-diméthyI ^ 3/2 a-carboy ethynyl-cyclopropane carboxyiate of STCs&terbutyle prepared at the Q WITH the preparation _IV. in 40, ethyl acetate cm3. an in situ thermal desorption of§~ 0.38 g of palladium hydroxide on the I ioî barium sulfate and 0.4 cm3 quinoline. NC filter, washing the filtrate 1. hydrochloric acid 0.5 D and confectioneries water up to neutrality, dried, concentrated to dry under reduced pressure and obtains 2 g of the desired product melting 94° C..

Preparation IV; acid (cis-IR-) 3 - 2.2 to-dlméthyl (2)/5 oxo 3- (-2(1,1,1,3)3.3 the hexafluoro) propoxyl) 2- propé nyny.l/ cyclopropaRQcarboxyligue.

terbutyle.

Operation is carried out as in step a of the example. 9, using 3, δ s (I.R. intraconnect) 2.2-to-diaéthdiaéth.yx - 1/(2} 3 hydroxy 3 oxo. L propényï/cyclopropane carboxylate of terbutyle {V-preparation) and 3 s by the hexafluoro-propanol. After elution by'M' mixture: benzene-Cy-clohexane {4 - 6) obtained 4.9 g of the pro * bro expected? 92 °C *.

aUflEâ -

The operation is carried out as I/II-stage existplè8, 3 from IDD, ;

' 4.9 g of the product obtained above and obtains. 4.2 g of desired product.

the Ta U-CSCS).

The OH mono

+ dimer

C. conj esters Ç1755 cm from L-shouldered

the O the K the I? 44 Fifth chamber I-max.

- acid '■16 - 95 cm.-1

CCEAconj1627 cms-1

eWG. dimethyl - 1330 cm; shouldered

Preparation VIII; (IR-cis-) 2.2-dimethyl 3/(2) 3 a-hvdrcxy 3 oxo 1- prooénylcycloorooane carboxylate (e)FS-cyano-3 a-ohénoxybenzyl.

4 Is hydrogen, T-g of (IH-SIA) 2.2-dimethyl 3 a-c2-carboxy-ethynyl) cyclopropane carboxylate of {e) of O (a cyano - 3-phenoxy benzyl (preparation of IV) 4f cm3 in ethyl acetate in the presence of 500 mg of palladium hydroxide 3 law on barium sulfate and 6.5 cm3 quinoline. Is filtered, washing the filtrate 2 n-hydrochloric acid, and then T-I-water until neutrality, dry and causes dry. Obtained 5.1 g of an oil which is chromatographed on silica by eluting the mixture of hexane, ethyl acetate, acetic acid (70 - 30 - 1). The result is 3.8 g of the desired product.

Preparation HIV: (IR-cis-) 2.2-dimethyl 3 -^/ ? O) 3 hydroxy 3 oxo-L prooényl/cyclopropane carboxylate of (the R) - methyl 3 a-ohénoxybenzyl.

$$§û$A-to-I.ii. *. 2izlmlzïizîïv ' ilil.lziïz? ** of £2AzLZ lz domain % of R * ii if&l2 *&92' Z2jer88m&£.s £sl9bs9biqs.s3&SXZiS 00 sec....* IS2 is&L7&iKlIlBhfü.2S2- bSs022the LS.

0a operates as in step s of the Taxus preparation "" cyle using 5 g acid (1The OIS I) 2,2- diaéthyI3- /3- οχο 3- (2Y2.2

- trichloroethoxy) propynyl/the cyclopropane carboyxic and L " g-d-I-L-®≈ (Ε) (- a j-phenoxy phényi) ethanol. Obtained after chroaatography in a cyclohexane - ethyl acetate (8 - 2>4.38 g of expected product therein.

L-§§di. ii.i-to-us.sis2-a 2_{the I} 2₌â4Eéth2l_- The j - / - ii₂xo.2-to-hydr2 ^ ^ I/n2022B2|cyclooropane carboxylate (I)- methyl<C..3^ - qhfnoxyengyle.

Has 4, ΐ β g of the product obtained above dissolved in

4 cm3 methylene chloride is added 45 cm3 105 acetic acid to water and 0.53 s of powder and stirred 30 min sinc T- room temperature, adds! new 0.53 g polyolefin powder up to the end of the reaction. (4 times). After 3 hours of contact is filtered and extracted by methylene chloride. The organic phase is washed with water, dried, concentrated to dry by drive azeotropic to toluene and obtains 3 * 05 g of desired product.

pfnyl / ^ ^ of carboxylate-cgclgprooane. 3géthyi,2; the benzylidene phéngxy ^.

Operation is carried out as in step 3 in the example F., starting from the product obtained in step b above and obtains 2.9 g of crude desired product, used as such.

Mixed homogeneously of:

The product of example!. 0.25 grams to oxide. I-piperonyl Tvveen grams 80 0.25 grams Topsnol has *... V. 0.1 g water................ 98.4 grams Example 5: preparation of d-'un emulsifiable concentrate.

Product of the example 1 0,015 g to 0.5 grams of piperonyl butoxide Topsaot %; *; *■. , the O, I-grams The Tween -;8a Py *.... 3.5 grams Xylèhe I-;*.............. 95,885 grams Example 0 ; Preparing an emulsifiable concentrate..

Mixed homogeneously 4th ii

Product of the example 1 1.5 grams of Tween 80............... 20 grams Topanol 0.1 grams xylene 78.4 grams-e example: preparation of a smoke composition.

A homogeneously mixed:

Product of the example 1 ........... 0.2Ç g powder of tabu 25 g powder of fetüllee cedar 40 g powder of pine 33" 75 grams brilliant green 0.5 grams of P-nitrophenol 0.5 grams Study of the activity of the compounds according to the invention on

parasites.

1^I ) ii study of the lethal effect on Mouths domestic•

Insects tests are strains of Fe - domesticBeautiful 4/5 days of age. It is performed by topical application of 1 of 1 μ a solution of the product acetoaic dorsal thorax, insects by the micro-manipulator of Arnold. Used 50 individuals per dose and processing. Is performed control mortality twenty-four hours after treatment *

The result expressed DL 50 or dose (in nanogrames) necessary to kill 50 ¾ insects, T-is as follows

Product 9.ï LD 50

1' example 9.ï (ng per individual)

1 ii 1,115

(( 3 ! 0,96has

29 the I 0,825

Concluding ii on the test used, the products of the exeaples 1, 23 and 29 have a remarkable activity.

2ΐ⁹ ) studying ^ LEDeffect on larvae. of, L-littoralisitto -

ralis.

The assays are performed by topical application

an acetone solution of the product to be tested using the then manipulator of Arnold on strip back chest * larvae used 15 larvae per dose of product to be tested. The larvae used are larvae of the fourth larval stage, it is to say aged about 1o days when grown to 24^I C and 65>3 relative humidity. After treatment, the individuals are placed on an artificial diet (medium Poitout)"

We monitor mortality of 48 hours

after processing.

The experimental outcome obtained is as follows:

Concluding : on the test used, the products of the exeoples1 and 35 have a ton activity *

3 DEGREES) the IStude activity impact on touched dooesticu•*

Insects tests are flies domestic female 4/5 days of age. It is performed by a direct spray in chamber * Keans and March using as solvent a mixture in equal volumes of acetone and L-isopar (amount de solution used Z The X 0.2 cm3). NC uses about 50 insects by treatment dose. Checks are carried out every minute until 10 min, and then 15 minutes and determination is the XT IS 50 by the usual methods.

The results obtained are as follows I-

Concluding ii on the test used, the products of examples 1_F.2, 26_grams 30 and 35 have a good activity.

4^has ): Stude of 1¹the ACoA is legislation in differentr. C.ontacttarsal sur_blattegermanic. (compound 1* g. 1)

The insects tested are males of cockroach germari V<EUI (Blatella9.ï. It is carried out by depositing an acetone solution determined concentration on the bottom of a petri plate #20 AC diameter. After drying is allowed dwell 2c male cockroaches by concentration during T-hour are transferred insects on medium healthy and checked their mortality to 24 hr, 48 hr, 3 and 5 days.

The result expressed lethal concentration (LC 50) 50 © donations, for the product in question, the Ag/®0,2162.

Concluding : as judged used the product exhibits very good activity.

5DEGREES)_T-ii Activity on the authorisation Tstranychus. (1 compound of example 1 *} An adulticide test

Plants are used bean cotyledonary comprising two sheets. These plants are treated at gun Fisher method with an acetone solution of the product. After drying 25 F. © stool acarid Tétranychus authorisation of are arranged by bankrupts is 50 individuals per dose experienced ' by seedling, efficacy controls are performed after 1, 24, 48 and 72 hours of contact.

To the dose of 2.8/L being the abrasive product has a-very good activity.