CH655302A5 - ESTERS OF AROMATIC OR HETEROAROMATIC ALCOHOLS, THEIR PROCESS AND MEANS FOR IMPLEMENTING THE METHOD, THEIR USE IN THE FIGHT AGAINST ECTOPARASITES AND THE COMPOSITIONS CONTAINING THEM. - Google Patents

Description

The present invention relates to new esters of aromatic or heteroaromatic alcohols, their process and the means of implementing the process, their use in the fight against parasites and the compositions containing them.

The subject of the invention is the compounds of formula I:

R, together form a cycloalkyl radical containing 3 to 6 carbon atoms or a radical:

in which the ketone is a with respect to the double bond and in which X represents an oxygen or sulfur atom or an NH radical,

or Z2 represents a radical:

in which R *, R5, R6 and R7, identical or different, each represent a halogen atom,

or Z2 represents a radical:

, x_

C1 \ / 2

vs -

X, 0

3 II

■ O-C-B

(I)

30

H

in which Ar represents an aromatic or heteroaromatic radical, which, optionally substituted, Xj, X2, X3, identical or different, represent a hydrogen atom or a halogen atom, at least one of the radicals Xls X2 and X3 representing a halogen atom, and

B represents:

a) or an alkyl radical containing from 1 to 18 carbon atoms,

b) or a radical:

in which:

- or else Z: and Z2 each represent a methyl radical,

- either Z1 represents a hydrogen atom, and either Z2 represents a radical:

NOT /

ro2c

/ \

E or Z geometry

in which Rs represents a hydrogen atom or a chlorine, fluorine or bromine atom, and R represents:

- or a linear, branched or cyclic, saturated or unsaturated, alkyl radical containing from 1 to 18 carbon atoms, optionally substituted by one or more identifiable functional groups

40 ques or different,

Either an aryl group containing 6 to 14 carbon atoms, optionally substituted by one or more identical or different functional groups,

- either a heterocyclic radical optionally substituted by 45 one or more identical or different functional groups,

c) or B represents a radical:

CH

50

/ H *

CH.

60

in which R3 represents a hydrogen or halogen atom, Ri and R2, which are identical or different, represent a halogen atom or an alkyl radical containing from 1 to 8 carbon atoms, or R] and

(y).

in which y, in any position on the benzene nucleus, represents a halogen atom, an alkyl radical containing from 1 to 8 carbon atoms, or an alkoxy radical containing from 1 to 8 carbon atoms, m representing the number 0, 1 or 2, in all their possible isomeric forms, as well as mixtures of isomers, with the exception of the compounds of formula I in which Xj, X2 and X3 simultaneously represent a fluorine atom and with the exception of 3- (2 -methyl-1-propenyl) -2,2-dimethylcyclopropane-1-carb-oxylate of 2-chloro-1- (3-phenoxyphenyl) ethyl.

When Ar represents a substituted aromatic or heteroaromatic radical, it is preferably an aromatic or heteroaromatic radical substituted by one or more hydroxy radicals, by one or more alkyl radicals containing from 1 to 4 atoms

5

655302

carbon, by one or more alkoxy radicals containing from 1 to 4 carbon atoms, by an aryloxy, arylcarbonyl, arylmethyl, arylthio, arylsulfenyl or arylsulfonyl group, by one or by several halogen atoms, by a trifluoromethyl radical, or by a combination of these various substituents, and which can also be substituted by another aromatic or heteroaromatic radical which can itself be substituted by one or more of the radicals indicated above.

The term “aromatic radical” preferably means the phenyl radical.

By substituted aromatic radical is preferably meant the radicals:

y preferably represents a halogen atom, for example a chlorine atom, in the para position on the benzene nucleus. m preferably represents the number 1.

A more specific subject of the invention is the compounds of formula I for which B represents a radical:

in which Z represents a hydrogen atom and Z2 a radical:

V

in which yj and y2, in any position on the benzene nucleus, represent a hydrogen atom, a halogen atom or a methyl radical, n and n 'representing the numbers 0, 1 or 2, A represents a atom oxygen, a methylene group, a carbonyl group, a sulfur atom, a sulfoxide group or a sulfone group.

As preferred substituted aromatic radical, there may be mentioned for example the radicals:

and

By heteroaromatic radical is preferably meant the radicals derived from pyridine, thiophene, furan or pyri-midine; among these heteroaromatic radicals, mention may be made of substituted heteroaromatic radicals, for example the radical:

, or the radical

-0

in which Rls R2 and R3 are defined as above, and in particular those for which R, and R2 represent identical halogen atoms and R3 a hydrogen atom.

Among the preferred compounds of the invention, mention may be made of the compounds of formula I for which Ar represents a radical:

in which there! and y2, in any position on the benzene nucleus, represent a hydrogen atom, a halogen atom or a methyl radical, n and n 'represent the number 1 or 2 and A represents an oxygen atom, a group methylene, a carbonyl group, a sulfur atom, a sulfoxide group or a sulfone group, in particular those for which A represents an oxygen atom and those for which yl and y2 each represent a hydrogen atom.

Among the preferred compounds of the invention, special mention may be made of the compounds for which X! and X2 represent a hydrogen atom and X3 represents a halogen atom and, among these, those for which X3 represents a chlorine atom. 45 The subject of the invention is also a process for preparing the compounds of formula I, characterized in that an acid of formula II is subjected:

BCO, H

(II)

When Xx, X2 and X3 represent a halogen atom, it is preferably a fluorine, chlorine or bromine atom.

When B represents an alkyl radical, it is preferably an alkyl radical, linear, branched or cyclic, containing from 1 to 18 carbon atoms, such as the methyl, ethyl, n-propyl, isopropyl, cyclopropyl, butyl radical , terbutyl, cyclobutyl, or n-pentyl.

When R1; R2 and R3 represent a halogen atom, it is preferably a fluorine, chlorine or bromine atom.

When Rt and R2 represent an alkyl radical, it is preferably a methyl radical.

When R 1 and R 2 together form a cycloalkyl radical, it is preferably the cyclopropyl radical.

R4, R5, R6 and R7 preferably represent fluorine, chlorine or bromine atoms.

R preferably represents a methyl, ethyl, n-propyl, isopropyl, terbutyl, phenyl, benzyl, thienyl, furyl radical.

50 in which B is defined as above, or a functional derivative of this acid, to the action of an alcohol of formula III:

NC -—> /

A -CH-OH r

(III)

or a functional derivative of this alcohol, Ar, Xj, X2 and X3 being 60 defined as above, to obtain the compound of formula I corresponding:

(I)

Ar-CH-O-C-B

655,302

6

The functional acid derivative used is preferably a halide-nure, for example a chloride.

In a preferred embodiment of the process of the invention, the acid and the alcohol are reacted in the presence of dicyclohexylcarbodi-imide or diisopropylcarbodiimide.

It goes without saying that the esterification reaction can be carried out according to the other conventional esterification methods.

A more particular subject of the invention is a preparation process, characterized in that an acid of formula BC02H or a functional derivative of this acid, in which B is defined as above, is subjected to the action of an alcohol of formula IIIA:

(iii'a)

y ;, y2, n, n ', Xl5 X, and X3 being defined as above.

The subject of the invention is very particularly, under the title mentioned above, the compounds of formula III "A:

-OH (IIIA)

in which yj, y2, n, n ', A, Xt, X, and X3 are defined as above, or a functional derivative of this alcohol, to obtain the corresponding compound of formula IA:

OR "a)

The compounds of formulas III, IIIA, III'A and III "A are of particular interest as starting materials for preparing the compounds of formula I.

The compounds of formula III can be prepared by reacting a compound of formula IV:

Ar — CHO (IV)

(IA) 30 Ar being defined as above, with a compound of formula:

Alcohols and functional derivatives of alcohols of formula III:

'\ /

X

c ~ 3

A -Ç-OH r

35 Xj, X2 and X3 being defined as above, to obtain the corresponding compound of formula III.

In a preferred embodiment, the operation is carried out at low temperature between -30 and -100 ° C, in the presence of an alkaline alcoholate such as potassium terbutylate or in the presence of any other strong base capable of forming an anion with the compound:

(III)

in which Ar, X ,, X2 and X3 are defined as above, it being understood that Xj, X2 and X3 cannot simultaneously represent a fluorine atom, are new products; the invention therefore relates to these products as means for the implementation of the process defined above.

The subject of the invention is very particularly, as means for the implementation of said process, alcohols of formula IIIA:

When it is desired to prepare compounds of formula III in which X], X2 and X3 represent chlorine or bromine atoms, it is possible to react a compound of formula V:

50

(V)

(VI)

(IIIa)

as well as the functional derivatives of these alcohols, y1, y2, n, n ', A, X ,, X2 and X3 being defined as above.

Among the last compounds of formula IIIA, special mention may be made of the compounds of formula III'A:

Ar — CQCH3

Ar being defined as above, with a halogen, to obtain the compound of formula VI corresponding:

O H (3-n ")

; II I

Ar — C —C (Hal) „

n "representing the number 1, 2 or 3, which is subjected to the action of a reducing agent, to obtain the compound of formula III corresponding:

(III)

As an reducing agent, an alkali metal hydroboride such as BH4Na can be used.

The compounds of formula VI obtained intermediately are new.

7

655,302

If one wants to obtain compounds of formula III in which there are two different halogen atoms, one of the two halogens is reacted successively, then the other on the compound of formula V.

Depending on the operating conditions used, compounds of formula III are obtained in which there are 1, 2 or 3 halogen atoms.

One can also submit one of the compounds of formula III, obtained to the action of a reducing agent, to replace the most labile halogen atom with a hydrogen atom.

As reducing agent, (Bu) 3SnH or any other tin di- or trialkylhydride can be used.

The compounds of formula I have interesting properties which allow their use in the fight against parasites; it can be, for example, the fight against plant parasites, warm-blooded animals and against local parasites. This is how the products of the invention can be used to fight against insects, nematodes and parasitic mites of plants and warm-blooded animals.

A subject of the invention is therefore the use of the compounds of formula I intended for the fight against ectoparasites of warm-blooded animals and against parasites of plants and premises.

The product of Example 2 gave quite remarkable results.

The subject of the inversion is also compositions intended for the control of parasites from warm-blooded animals, plants and premises, characterized in that they contain at least one product of formula I as active principle.

The products of formula I can therefore be used in particular for combating insects in the agricultural field, for example against flies but also against aphids, lepidopteran larvae and beetles. They are preferably used in doses of between 10 and 300 g of active ingredient per hectare.

The products of formula I can also be used to fight against insects in premises, in particular against flies, mosquitoes and cockroaches.

A subject of the invention is therefore in particular insecticide compositions containing as active principle at least one product of formula I.

The products of formula I can also be used to combat mites and parasitic nematodes of plants.

The compounds of formula I can also be used to fight against parasitic mites of animals, for example against ticks and in particular ticks of the species Boophilus, those of the species Hyalomnia, those of the species Amblyomnia and those of l 'Rhipicephalus species, or to fight against all kinds of scabies and, in particular, sarcoptic scab, psoroptic scab and cho-rioptic scab.

A subject of the invention is therefore also compositions intended for the fight against parasitic nematodes of plants and against parasitic mites of warm-blooded animals, premises and plants, characterized in that they contain at least one of the products defined above.

The subject of the invention is in particular acaricide compositions containing as active principle at least one of the products defined above.

When it comes to combating parasitic mites of animals, the products of the invention are very often incorporated into food compositions in combination with a nutritive mixture suitable for animal feed. The nutritive mixture can vary according to the animal species; it may contain cereals, sugars and grains, soybean, peanut and sunflower meal, meal of animal origin, for example fish meal, synthetic amino acids, mineral salts, vitamins and antioxidants.

The invention therefore therefore relates to the food compositions defined above.

The compositions of the invention are prepared according to the usual methods of the agrochemical industry, the veterinary industry or the industry of products intended for animal nutrition.

In the compositions intended for agricultural use and for use in premises, the active ingredient (s) may optionally be added with one or more other pesticidal agents. These compositions can be in the form of powders, granules, suspensions, emulsions, solutions, solutions for aerosols, combustible strips, baits or other preparations conventionally used for the use of this type of compound.

In addition to the active principle, these compositions generally contain a vehicle and / or a nonionic surfactant ensuring, in addition, a uniform dispersion of the constituent substances of the mixture. The vehicle can be a liquid, such as water, alcohol, hydrocarbons or other organic solvents, a mineral, animal or vegetable oil, a powder, such as talc, clays, silicates, kieselgur or a combustible solid, such as tabu powder or pyrethrum marc.

The insecticidal compositions according to the invention preferably contain from 0.005 to 10% by weight of active material.

The acaricide and nematicide compositions can more particularly be presented in the form of powders, granules, suspensions, emulsions, solutions.

For acaricide use, wettable powders for foliar spraying, containing from 1 to 80% by weight of active ingredient, or liquids for foliar spraying, containing from 1 to 500 g / l of active ingredient, are preferably used. It is also possible to use powders for leaf dusting, containing from 0.05 to 3% by weight of active material.

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

The acaricide and nematicide compounds according to the invention are preferably used in doses of between 1 and 100 g of active ingredient per hectare.

To enhance the biological activity of the products of the invention, they can be added to conventional synergists used in such cases, such as l- (2,5,8-trioxadodecyl) -2-propyl-4,5- methylenedioxyben-zene (or piperonyl butoxide) or N- (2-ethylheptyl) bicyclo- [2,2-l] -5-heptene-2,3-dicarboximide, or piperonylbis-2- (2'-n- butoxyethoxy) ethylacetal (or tropital).

The compounds of formula I have an excellent general tolerance and the invention therefore also relates to the products of formula I, as medicaments, in particular for combating conditions created by ticks and scabies.

The medicaments of the invention can be used both in human medicine and in veterinary medicine.

45 The medicaments of the invention are used in particular in human medicine to combat lice as a preventive or curative measure and to combat scabies.

The medicaments of the invention can be administered externally, by spraying, by bath or by brushing. The medicaments of the invention for veterinary use can also be administered by brushing the backbone according to the method known as the pour-on method. They can also be administered by the digestive route or parenterally.

The subject of the invention is therefore pharmaceutical compositions 55 containing as active principle at least one of the drugs defined above.

It may also be indicated that the products of the invention can be used as biocides or as growth regulators.

60 The subject of the invention is also the associations endowed with insecticidal, acaricidal, fungicidal or nematocidal activities, characterized in that they contain as active material, on the one hand, at least one of the compounds of general formula I and, d on the other hand, at least one of the pyrethroid esters chosen from the group consisting of 65 esters of allethrolones, 3,4,5,6-tetrahydrophthalimidomethyl alcohol, 5-benzyl-3-furylmethyl alcohol, d 3-phenoxy-benzyl alcohol and a-cyano-3-phenoxybenzylic alcohols of chrysanthemic acids, by esters of 5-benzyl-3-furylmethyl alcohol

655,302

8

2,2-dimethyl-3- (2-oxo-3-tetrahydrothiophenylidenem-thyl) cyclopropane-1-carboxylic acids, by esters of 3-phen-oxybenzyl alcohol and α-cyano-3-phenoxybenzyl alcohol 2,2-dimethyl-3- (2,2-dichlorovinyl) cyclopropane-1-carboxylic acids, by esters of α-cyano-3-phenoxybenzyl alcohols of 2,2-dimethyl-3- (2 , 2-dibromovinyl) cyclopropane-1-carboxylic acids, by 3-phenoxybenzyl alcohol esters of 2-parachloro-phenyl-2-isopropylacetic acids, by allethrolone esters, of 3,4,5,6 alcohol -tetrahydrophthalimidomethyl, 5-benzyl-3-furyl-methyl alcohol, 3-phenoxybenzyl alcohol and α-cyano-3-phenoxybenzylic alcohols of 2,2-dimethyl-3- acids (1,2,2, 2-tetrahaloethyl) cyclopropane-1-carboxyls in which halo represents a fluorine, chlorine or bromine atom, it being understood that the compounds I can exist in all their stereoisomeric forms,

as well as the acid and alcohol copulas of the pyrethroid esters above.

The following examples illustrate the invention without, however, limiting it.

Example 1: 1 R-cis-3- (2,2-Diflnoro vinyl) -2,2-dimethylcyclopropane-carboxylate of RS- [2-chloro-1- (3-phenoxyphenyl)] ethyl

A solution containing 1.6 g of lR-cis-3- (2,2-difluorovinyl) -2,2-dimethylcyclopropanecarboxylic acid in 20 cm 3 of methylene chloride is cooled to 0 ° C. 1.6 g of dicyclohexylcarbodiimide and 15 mg of N, N-dimethyla-minopyridine are then added all at once. The mixture is stirred for 20 min and 1.5 g of 1RS-2-chloro-1- (3-phenoxyphenyl) ethan-1-ol and 20 cm 3 of methylene chloride are added. The solution obtained is stirred for 5 h while allowing it to warm up slowly to room temperature. It is filtered, the filtrate is washed with water, dried and evaporated to dryness. 3.1 g of product are obtained which is chromatographed on silica eluting with a hexane / ethyl acetate mixture 95: 5. 1.8 g of sought product is obtained.

NMR spectrum: CDC13 ppm

-1.18 to 1.22 H of CH3

- 1.83

- 3.67-3.77

- 4.3-4.7

- 5.8-5.9-6

- 6.9 to 7.6

the Hs of cyclopropyl in 1 and 3 the Hs of CH2C1

the H of CH = CïT

the H of C02CH \

Aromatic h

Example 2: 1R-cis-3- (2,2-Difluorovinyl) -2,2-dimethylcyclopropane-carboxylate of RS- [2-fluoro-1- (3-phenoxyphenyl)] ethyl

By operating as in Example 1, starting with 1.8 g of lR-cis-3- (2,2-difluorovinyl) -2,2-dimethylcyclopropanecarboxylic acid and 1.5 g of lRS-2-fluoro -l- (3-phenoxyphenyl) ethan-1-ol, 2.2 g of the desired product are obtained.

NMR spectrum: CDC13 ppm

- 1.12 and 1.23

- 1.8 to 2.08

- 4.15-4.25

- 4.95-5

- 4.17 to 5

- 5.8-5.9-6

- 6-6.1-6.2

- 6.9 to 7.6

the H of the methyls in 2

the H in 1 and 3 of cyclopropyl the H of CH2F y the H of CH = C

/ \

H from C02 — CH \

Aromatic h

NMR spectrum: CDC13 ppm

- 1.1-1.22-1.25

- 1.75 to 1.92 s - 3.5-3.6

- 4.25 to 5

- 5.8-5.9-6 • o - 7 to 7.6

H 2H methyls of cyclopropyl H of CH, Br

H of CH = C. /

H of C02CH. \

Aromatic h

Example 4: 1R-trans-3- (2,2-Difluorovinyl) -2,2-dimethylcyclopropane-carboxylate of RS- [2-fluoro-1- (3-phenoxyphenyl)] ethyl

By operating as in Example 1, starting with 1.8 g of 1R- 'trans-3- (2,2-difluorovinyl) -2,2-dimethylcyclopropanecarboxylic acid and 1.5 g of lRS-2- fluoro-1- (3-phenoxyphenyl) ethan-1- ol, 1.6 g of the desired product are obtained.

NMR spectrum: CDC13 ppm

25

30

1.13-1.25

H

1.52-1.6

H

3.75-3.88

1

4.2-4.3

} H

4.12-4.2

}

4.9-5

iH

5.7 to 6.25

H

6.8 to 7.5

H

H of the 2-methyls of cyclopropane H has CO-,

H of CH

H of CH, F

/

CH \

Example 5: 1R-trans-3- (2,2-Difluorovinyl) -2,2-dimethylcyclopropane-carboxylate of RS- [2-bromo-1- (3-phenoxyphenyl)] ethyl Using the procedure of Example 1 , from 0.88 g of 1R-trans-3- (2,2-difluorovinyl) -2,2-dimethylcyclopropanecarboxylic acid and lRS-2-bromo-l- (3-phenoxyphenyl) ethan-l-ol , 1.38 g of the desired product are obtained.

i NMR spectrum: CDC13 ppm

- 1.15 - 1.2 - 1.27

- 1.5-1.6

- 1.88 to 2.2 s - 3.55-3.65

- 3.8-3.9

- 4.2-4.3

- 5.8-5.9-6

H of methyls in 2 H has CO,

the other H of CH2Br cyclopropyl H

H of CH

/

H of C02CH \

Example 6: 1 R-trans-3- (2,2-Difluorovinyl) -2,2-dimethylcyclopropane-carboxylate of RS- [2-chloro-1- (3-phenoxyphenyl)] ethyl

By operating as in Example 1, from 1.6 g of 1R-trans-3- (2,2-difluorovinyl) -2,2-dimethylcyclopropanecarboxylic acid and 55 of 1.5 g of lRS-2- chloro-1- (3-phenoxyphenyl) ethan-1- ol, 1.7 g of the desired product are obtained.

NMR spectrum: CDC13 ppm

) - 1.15-1.18-1.21

- 1.53-1.62

- 1.88 to 2.13

- 3.72-3.8

Example 3: 1 R-cis-3- (2,2-Difluoroi'inyl) -2,2-dimethylcyclopropane-carboxylate of RS- [2-bromo-l- (3-phenoxyphenyl)] ethyl

By operating as in Example 1, starting from 0.88 g of IR-ss acid - 3.42 to 4.36 cis-3- (2,2-difluorovinyl) -2,2-dimethylcyclopropanecarboxylic acid and 1 g of lRS-2-bromo-1- (3-phenoxyphenyl) ethan-1-ol, one obtains - 5.9-6-6.1

1.33 g of the desired product. - 6.9 to 7.6

H of CH3

H in 1 of cyclopropyl H in 3 of cyclopropyl H of CH2C1

H of CH = C

H of CO, -CH H of aromatics

9

655,302

Example 7: 1 R-trans-3- (2,2-Difluorovimi 1-2,2-dimethylcyclopro-panecarboxylate RS- [2,2-dichloro-2-fluoro-l- (3-phenoxyphenyl)] - ethyl

By operating as in Example 1, starting with 2.2 g of 1R-trans-3- (2,2-difluorovinyl) -2,2-dimethylcyclopropanecarboxylic acid and 3.8 g of lRS-2.2 -dichloro-2-fluoro-l- (3-phenoxyphenyl) ethan-l-ol, 4 g of sought product is obtained.

NMR spectrum: CDC13 ppm

- 1.15-1.18-1.21

- 1.92 to 2.13

- 1.55-1.64

- 3.8-3.9

- 4.2-4.3

- 6.18 - 6.33

- 6.38

- 6.9-7.6

H of methyls in 2> H of cyclopropane

• H of C02CH H aromatic

Example 8: (1R-cis) -3- (2,2-Difluorovinyl) -2,2-dimethylcyclopropane-carboxylate of RS- [2-fluoro-2-chloro-1- (3-phenoxyphenyl)] ethyl

By operating as in Example 1, starting with 0.86 g of (1R-cis) -3- (2,2-difluorovinyl) -2,2-dimethylcyclopropanecarboxylic acid and 1 g of 2-fluoro-2 -chloro-1- (3-phenoxyphenyl) ethan-1-ol, 1.4 g of the desired product are obtained.

NMR spectrum: CDC13 ppm

- 1.15 - 1.25 - 1.26

- 1.75 to 2

- 4.17 to 4.9

- 5.75-6.2

- 6.6-6.7

- 6.9 to 7.5

H 2H methyls of cyclopropane

H of

/ F

H of C02CH H of -CHC ^ "H aromatic

Example 9: 1 R-cis-3- (2,2-DibromovinylJ-2,2-dimethylcyclopropane-carboxylate of RS- [2,2-dichloro-2-fluoro-l- (3-phenoxyphenyl)] - ethyl

A solution containing 1.2 g of lRS-2,2-dichloro-2-fluoro-l- (3-phenoxyphenyl) ethan-l-ol, 40 cm3 of benzene and 1.8 g of 1 R-cis-3- (2,2-dibromovinyl) -2,2-dimethylcyclopropanecarboxylic acid chloride 0.7 cm3 of pyridine is added, the mixture is allowed to warm to ambient temperature and stirred for 17 h. an ice-cold solution of 0.1N hydrochloric acid, decanted, the benzene phase is washed with water, dried and evaporated to dryness under reduced pressure to give 2.9 g of product which is chromatographed on silica eluting with the hexane / ethyl acetate mixture 8: 2. This gives 1.9 g of the desired product.

NMR spectrum: CDC13 ppm

- 1.18-1.26-1.34

- 2-2.05

- 6-6.2

- 6.3

- 6.6-6.8

- 6.9 to 7.5

H 2-methyl methyls of cyclopropane /

H of CO-.CH * \

H ethylenic H aromatic 1R-cis-3- (2,2-dibromovinyl) -2,2-dimethylcyclopropanecarboxylic, 1.7 g of the desired product are obtained.

NMR spectrum: CDC13 ppm

- 1.15 and 1.27

- 1.83 to 2.08

- 4.13-4.22

- 4.9-5

- 5.7 to 6.25

- 6.6 to 6.9

- 6.8 to 7.5

H methyl in 2 H of cyclopropyl

H of CH2F

/

H of C02CH \

H of CH = C: Aromatic H

35

Example 11: 1 R-cis-3- [Dihydro-2-oxo-3- (2H-thienylidene) methyl] -2,2-dimethylcyclopropanecarboxylate RS- [2-chloro-1- (3-phenoxy-phenyl)] ethyl

Preparation of acid chloride

1 A mixture of 5 g of lR-cis-3- [dihydro-2-oxo-3- (2H-thienylidene) methyl] cyclopropane-1-carb-oxylic acid, 50 cm 3 of is brought to reflux for 4 h. petroleum ether and 10 cm3 of thio-nyl chloride. It is concentrated to dryness, taken up in benzene and concentrated to dryness again.

Esterification

Add 50 cm3 of benzene to the above acid chloride, cool to + 5 ° C. and add 6.5 g of lRS-2-chloro-l- (3-phenoxyphé-nyl) ethan-l-ol in 60 cm3 benzene. Stir and introduce in 30 min at + 5; C 7.3 cm3 of pyridine in 20 cm3 of benzene. Stirred for 16 h at 20 ° C., poured into water, decanted, washed the organic phase with 0.1N hydrochloric acid and then with water, dried and concentrated to dryness. The residue is chromatographed on silica eluting with a 75:25 cyclohexane / ethyl acetate mixture, and 9.3 g of the expected product are obtained.

not?? = 1.583. otD = + 25.5 ° + 1 = (c = 1% CHC13).

40

Example 12: 1 R-cis-3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropa-necarboxylate of RS- and S- [2-chloro-1- (3-phenoxyphenyl) Jethyl The procedure is analogous to that described in Example 11, starting from 5.05 g of 1 R-cis-3- (2,2-dibromoethenyl) -2,2-dimé-thylcyclopropanecarboxylic acid and 4.2 g of lRS- 2-chloro-1- (3-phenoxyphenyl) ethan-1- ol. After chromatography on

45 silica, eluting with a petroleum ether / isopropyl ether mixture 9: 1, 6.1 g of product which is recrystallized from petroleum ether. 1.9 g of the S. isomer is isolated. F = 76 "C.

"D = +67 ± 1.5 (c = 1% CHCl3). The mother liquors, evaporated to dryness, provide 3.6 g of isomer (RS).

50 aD = -26; ± 1.5 ° (c = 1% CHC13).

Example 13: (IR-cis, AZ) -2,2-Dimethyl-3- (2-methoxycarbonylethé-nyllcyclopropanecarboxylate de RS- [2-chloro-l- (3-phenoxyphenyl) Jethyl ss The procedure is analogous to that described in Example 1, starting from 1.8 g of acid (IR-cis, AZ) -2,2-dimethyl-3- (2-methoxycar-bonylethenyl) cyclopropanecarboxylic acid and 1.5 g of alcohol. 1.8 g of expected ester are obtained.

60

Analysis for C24H25C105 (428,912)

Calculated: Found:

C 67.2 C 67.0

H 5.9 Cl 8.3% H 5.9 Cl 8.8%

Example 10: 1 R- cis-3- (2,2-Dibromovinyl) -2,2-dimethylcyclopropane-carboxylate of RS- [2-fluoro-1- (3-phenoxyphenyl)] ethyl

By operating as in Example 9, starting with 1.2 g of lRS-2-fluo-ro-l- (3-phenoxyphenyl) ethan-l-ol and 2.5 g of acid chloride

Example 14: (IR-cis, AZ) -2,2-Dimethyl-3- (2-methoxycarbonylethé-6S nyljcyclopropanecarboxylate de RS- [2-fluoro-l- (3-phenoxyphenyl) Jethyl

The procedure is analogous to that described in Example 2, starting from 1.98 g of acid (IR-cis, AZ) -2,2-dimethyl-3- (2-methoxycar-

655,302

10

bonylethenyl) cyclopropanecarboxylic acid and 1.5 g of alcohol. 2.5 g of expected ester are obtained.

Analysis for C24H25FO5 (412,457)

Calculated: C 70.0 H 6.1 F 4.6%

Found: C 69.7 H 6.1 F 4.8%

Example 15: (1R-cis) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopro-panecarboxylate of R- and S- [2-bromo-1- (3-phenoxyphenyl)] ethyl

The procedure is analogous to that described in Example 3 using, at the start, 6.3 g of acid chloride (1R-cis) -3- (2,2-dibro-moethenyl) -2,2- dimethylcyclopropanecarboxylic acid and 5.86 g of alcohol and operating in the presence of pyridine in benzene. After crystallization from petroleum ether:

- 1.9 g of isomer S of the expected alcohol. F = 76 'C;

aD = +66.5 ± 1.5 '(c = 1% CHCl3);

—5.25 g of expected R isomer. aD = —18 ° ± T (c = 1.5% CHC13). nb1 = 1.593 (dry evaporation of the mother liquors).

Example 16: (1 R-cis) -3- [Dihydro-2-oxo-3- (2H) -thienylidénémé-thylJ-2,2-dimethylcyclopropanecarboxylate de (RS) - [2-bromo-l- <3-phenoxyphenyl ) Jethyl

The procedure is analogous to that described in Example 11 using, at the start, 5 g of acid and 7.6 g of lRS-2-bromo-1- (3-phenoxyphenyl) ethan-1-ol. Obtained 10.3 g of the expected product which is purified by chromatography on silica eluting with a benzene / ethyl acetate mixture 8: 2.

aD = +24.5 ± 1.5 (c = 0.8% CHCl3).

Example 17: 1 R-trans-3- / 2,2-Dimethylethylenyl) -2,2-dimethylcyclopro-panecarboxylate I RS) - [2-bromo-1- (3-phenoxyphenyl) Jethyl

The procedure is analogous to that described in Example 3 using, at the start, 5.6 g of 1 R-trans-3- (2,2-dimé-thyléthényl) -2,2-dimethylcyclopropanecarboxylic acid chloride and 8.8 g of alcohol, operating in benzene in the presence of pyridine. 6.15 g of expected product are obtained.

ng = 1.554.

Analysis for C24H27Br03 (443.38)

Calculated: C 65.0 H 6.13 Br 18.02%

Found: C 64.9 H 6.2 Br 17.8%

Example 18: (IR-cis, AZ) -2,2-Dimethyl-3- (2-methoxycarbonylethé-nyl) cyclopropanecarhoxylate de (RS) - [2-bromo-l- (3-phenoxyphenyl) Jethyl

The procedure is analogous to that described in Example 3 using, at the start, 0.99 g of acid (IR-cis, AZ) -2,2-dimethyl-3- (2-methoxycarbonylethenyl) cyclopropanecarboxylic acid and 1 g of alcohol. 1.33 g of expected ester are obtained.

Analysis for C24H25Br05 (473,368)

Calculated: C 61.15 H 5.3 Br 16.95%

Found: C 60.8 H 5.4 Br 17.0%

Example 19: lR-trans-2,2-Dimethyl-3- (2,2-difluoroethenyl) cyclopro-panecarboxylate de (RS) - [2-fluoro-2-chloro-l- (3-phenoxyphenyl) J-ethyl

The procedure is analogous to that described in Example 8 using, at the start, 0.86 g of lR-trans-2,2-dimethyl-3- (2,2-difluoroethenyl) cyclopropanecarboxylic acid and 1 g of 'alcohol. 1.5 g of expected ester are obtained.

Analysis for C22H2oCl F303 (424,846)

Calculated: C62.2 H 4.75 Cl 8.3 F 13.4%

Found: C 62.5 H 4.8 Cl 8.3 F 13.6%

Example 20: 1R-cis-2,2-Dimethyl-3-t 2,2-dibromoethenyl) cyclopropanecarhoxylate of (RSì- [2,2,2-trichloro-1- (3-phenoxyphenyl) Jethyl

The procedure is analogous to that described in Example 15 using, at the start, 10 g of acid which is converted into acid chloride and 3.8 g of 1 RS- [2,2,2- trichloro-1- (3-phenoxyphenyl)] ethan-1- ol. 5.97 g of expected ester are obtained.

Analysis for C22HlgBr2Cl303 (597,571)

Calculated: C 44.2 H 3.2 Br26.7 Cl 17.8%

Found: C44.4 H 3.3 Br26.3 Cl 17.4%

Example 21: 1R-trans-2,2-Dimethyl-3-cyclopentylidenemethylcyclo-propanecarboxylate from (RS) - [2,2,2-trichloro-1- (3-phenoxyphenyl) Jethyl

21.6 g of 1 R-trans-2,2-dimethyl-3-cyclo-pentylidenemethylcyclopropanecarboxylate are suspended in 75 cm3 of benzene and 60.5 cm3 of pyridine. 32.5 cm3 of oxalyl chloride are added slowly at +12: C maximum, maintained for 15 min at + 5 / +10 C, added 30 cm3 of benzene and maintained for 3 hours at 20 ° C. The mixture is filtered, concentrated dry filtrate, add 30 cm3 of benzene to the residue and concentrate again.

Esterification ^

The operation is carried out as indicated in Example 20 using, at the start, 3.96 g of alcohol. 2.57 g of expected ester are obtained after chromatography on silica using a 9: 1 mixture of cyclohexane / ethyl acetate and then petroleum ether / ethyl ether 95: 5.

Analysis for C20H27Cl3O3 (493,862)

Calculated: C 63.2 H 5.5 Cl 21.5%

Found: C 63.5 H 5.5 Cl 21.6%

Example 22: 1 R-trans-2,2-Dimethyl-3-cyclopentylidenemethylcyclo-propanecarboxylate of (RS / - [2,2,2-tribromo-l- (3-phenoxyphé-nyl) Jéthyl

The procedure is analogous to that described in Example 21 using, initially, 9.115 g of lRS-2,2,2-tribromo-1- (3-phenoxy-phenyl) ethan-1-ol. 3.76 g of expected ester are obtained.

Analysis for C2oH27Br303 (627.23)

Calculated: C49.8 H 4.3 Br38.2%

Found: C 50.2 H 4.6 Br38.4%

Example 23: 1 R-cis-2,2-Dimethy 1-3- / 2,2-dibromoethenyl) cyclopropanecarhoxylate of (RSÌ-J2,2,2-tribromo-l- (3-phenoxyphenyl) Jethyl

The procedure is analogous to that described in Example 15 using, at the start, 10 g of acid which is converted into acid chloride and 4.51 g of lRS-2,2,2-tribromo- 1- (3-phenoxyphenyl) ethan-1-ol. 4.71 g of expected ester are obtained.

NMR spectrum: CDC13 ppm

- 1.21-1.28-1.31 H of the methyls in 2

- 2.06 H of cyclopropane

- 6.4 and 6.43 H has - COO -

/ Br

- 6.72 to 6.88 H of - CH = C

Br

- 7 to 7.67 H aromatic

Example 24: (IR-cis, AZ) -2,2-Dimethyl-3- (2-methoxycarbonyleihê-nyl) cyclopropanecarhoxylate de (RS) - [2,2-dichloro-l- (3-phenoxyphenyl) Jethyl

The procedure is analogous to that described in Example 13 using, at the start, 1 g of acid and 0.89 g of 1 RS-2,2-dichloro-1- (3-phenoxyphenyl) ethan-1- ol. 1 g of expected ester is obtained.

5

10

15

20

25

30

35

40

45

50

55

60

65

11

655,302

NMR spectrum: CDC13 ppm

- 1.22-1.28-1.32

- 2-2.14

- 3.13 to 3.43

- 2.7-2.27

- 5.73 to 6.08

6.33 to 6.72 6.92 to 7.5

H of CH3 in 2 H in a of —COO - H of cyclopropane H of -COOCH3 H ethylen in a of -de -CHC12 H in p of -COOCH3 H aromatic

COO-CH, and H

Example 25: 1 R-cis-3- [Dihydro-2-oxo-3- (2H-thienylidenejmethylj-2,2-dimethylcyclopropanecarboxylate of (RSj- [2,2-dichloro-1-f3-phenoxyphenyl)

The procedure is analogous to that described in Example 11 using, at the start, 5 g of acid and 7.3 g of lRS-2,2-dichloro-1- (3-phenoxyphenyl) ethan-1-ol . 10 g of expected ester are obtained. aD = + 27.5 ° ± 1.5 ° (c = 1% CHC13).

Analysis for C25H24C1204S (491,422)

Calculated: C 61.09 H 4.92 Cl 14.42 S 6.52%

Found: C 61.2 H 5.0 Cl 14.4 S 6.4%

Example 26: 1 R-cis-2,2-Dimethyl-3- (2,2-dibromoêénényl) cyclopropanecarhoxylate de (RS) - [2,2-dichloro-l- (3-phenoxyphenyl) Jéthyl

The procedure is analogous to that described in Example 9, using 6.3 g of acid chloride and 6.52 g of lRS-2,2-dichloro-1- (3-phenoxyphenyl) ethan at the start. -l-ol. 9 g of expected product are obtained.

np'6 = 1.5915. aD = +11.5 "± V (c = 0.5% CHC13).

Analysis for C22H10Br2Cl2O3 (563.13)

Calculated: C 46.92 H 3.57 Br 28.38 Cl 12.59%

Found: C47.0 H 3.6 Br28.2 Cl 13.0%

Example 27: 1 R-trans-2,2-Dimethyl-3-f2-methyl-1-propenyl) cyclopropanecarhoxylate (RS) - [2,2-dichloro-1-f3-phenoxyphenyl)] - ethyl

The procedure is analogous to that described in Example 26 using, at the start, 4.04 g of 1 R-trans-2,2-dimé-thyl-3- (2-methyl-l-) acid chloride. propenyl) cyclopropanecarboxylic and 6.52 g of alcohol. 6.25 g of expected ester are obtained.

, 18.6

= 1.556. aD = + r ± r (c = 0.9% CHC13).

Analysis for C24H2 (iCl203 (433.36)

Calculated: C 66.51 H 6.04 Cl 16.36%

Found: C 66.2 H 6.1 Cl 16.5%

Preparation 1: 1 RS-2-Chloro-1- (3-phenoxyphenyl) ethan-1-ol

Stage A: 3-Phenoxy-a-chloroacetophenone

Is introduced at 21 ° C in 30 min, in a solution containing 10.5 g of 3-phenoxyacetophenone in 50 cm3 of acetic acid, a solution containing 3.6 g of chlorine in 50 cm3 of acetic acid. It is left for 30 min at room temperature, then brought to dryness under reduced pressure. It is taken up in ether, washed with a saturated solution of sodium hydrogen carbonate, the organic phases are dried and brought to dryness. 11.5 g of product are obtained which is chromatographed on silica eluting with a benzene / petroleum ether mixture (eb. 60 ~ 80 C). 8.1 g of the sought product are thus obtained.

Stage B: 1 RS-2-Chloro-1- (3-phenoxyphenyl) ethan-1-ol

3.7 g of sodium hydroboride in a solution containing 11.8 g of product prepared in stage A in 70 cm 3 of methanol are added at 10 ° C. over 30 min. Stirring is continued for 30 min at 10 ° C. and 4.5 cm3 of acetic acid are added. It is brought to dry, the dry extract is taken up in methylene chloride, washed with water, reextracted with methylene chloride, dried and brought to dryness under reduced pressure. 8.3 g of the sought product nj? = 1.5855.

5 Preparation 2: 1 RS-2-Bromo-1- (3-phenoxyphenyl) ethan-1-ol Stage A: 3-Phenoxybromoacetophenone

16 g of bromine are added dropwise in a solution containing 21.2 g of 3-phenoxyacetophenone, 120 cm 3 of dioxane and 60 cm 3 of ethyl ether. Maintained 40 min with stirring. The mixture is brought to dryness, taken up in 200 cm3 of ethyl acetate, washed with water, dried and brought to dryness under reduced pressure at 50 ° C. 29 g of a product are obtained which is chromatographed on silica eluting with the benzene / petroleum ether mixture (eb. 60 ~ 70 ° C) 9: 1. 21.5 g of sought product no.1.8 = 1.613 is obtained.

Stage B: lRS-2-Bromo-1- (3-phenoxyphenyl) ethan-1-ol

14.6 g of the product prepared in Stage A in 80 cm 3 of methanol are introduced with stirring at 20 ° C. over 30 min. 3.8 g of sodium borohydride are then added, the mixture is kept at 20 ° C. for 30 min, the pH is brought to 2 by addition of acetic acid and poured into 400 cm3 of water. Extracted with ethyl ether, the organic phase is dried,

brings to dryness at 50 ° C. under reduced pressure and obtains 11 g of sought product no = 1.605.

25

Preparation 3: lRS-2,2-Dichloro-2-fluoro-l- (3-phenoxyphenyl) ethan-l-ol

A. Condensation

30 cm3 of 2,2-dichloro-2-fluoromethane condensed at -40 ° C under nitrogen, 40 g of aldehyde-3-phenoxybenzyl and 250 cm3 of anhydrous ethyl ether are cooled to -60 ° C. 43 g of potassium terbutylate dissolved in 200 cm3 of tetrahydrofuran and 150 cm3 of terbutyl alcohol are then introduced. The mixture is stirred for 5 h at -40 ° C. and poured onto sodium phosphate, extracted with methylene chloride, washed with water, dried and evaporated to dryness. 59 g of the desired raw product are obtained.

B. Blocking with dihydropyran

40 g of the product prepared in stage A above, 300 cm 3 of benzene, 18 cm 3 of dihydropyran and 100 mg of paratoluenesulfonic acid are stirred at ambient temperature for 45 min. It is evaporated to dryness under reduced pressure. 50 g of a product are obtained which is chromatographed on silica eluting with a benzene-45 ne / ethyl acetate mixture 95: 5. 16.4 g of the expected blocked product are thus obtained.

C. Unblocking

16 g of product prepared in Stage B are introduced into 200 cm 3 of 50 methanol and 100 mg of paratoluenesulfonic acid. The mixture is stirred at ambient temperature and then heated to 40 ° C. for 2 h. Diluted with water, extracted with methylene chloride, the organic phase is washed with water, dried and evaporated to dryness under reduced pressure. Chromatography on silica with hexane / ethyl acetate 8: 2. Father 55 was thus collected 11.4 g of lRS-2,2-dichloro-2-fluoro-l- (3-phenoxyphé-nyl) éthan-l-ol.

NMR spectrum: CDC13 ppm - 2.95-3

5.5-13 6.9 to 7.6

H from OH mobile /

H of (p CH OH H aromatic

Preparation 4: 1 RS-2RS-2-Fluoro-2-chloro-l- (3-phenoxyphenyl) -ethan-l-ol

A mixture of 4.2 g of 1RS-2,2-dichloro-2-fluoro-1 - (3-phenoxyphenyl) ethan-1-ol as obtained in preparation 3, 10 is heated at reflux for 10 h. 2 g of tributyltin hydride and 50 cm3 of

655,302

12

benzene. Let cool. 100 cm 3 of ethyl ether are added and the mixture is stirred vigorously with an aqueous solution of potassium fluoride at 100 g / l. The aqueous phase is filtered, decanted and the organic phase is washed several times with water. It is dried and evaporated to dryness under reduced pressure. Chromatography on silica eluting with a hexane / ethyl acetate mixture 8: 2. 2.4 g of sought product is obtained.

NMR spectrum: CDC13 ppm

- 5.7-5.75 1 „,„ „/ ¥

- 6.5-6.6 \ \ l

- 4.7 to 5 H from ^ CHOH

- 2.65-2.7-2.8-2.9 H of OH

- 6.8 to 7.5 H aromatic

Preparation 5: lRS-2-Fluoro-l- (3-phenoxyphenyl) ethan-I-ol

Is heated under reflux for 54 h 10.5 g of 1 RS-2,2-dichloro-2-fluoro-l- (3-phenoxyphenyl) ethan-l-ol as obtained in preparation 3, 200 cm3 of xylene and 51 g of tributyltin hydride. The xylene is evaporated. It is taken up in ethyl ether and stirred with an aqueous solution of potassium fluoride at 100 g / l. It is filtered, the filtrate is washed with water, dried and evaporated to dryness under reduced pressure. The product obtained is chromatographed on silica eluting with a hexane / ethyl acetate mixture 8: 2. 7.4 g of sought product is obtained.

NMR spectrum: CDC13 ppm

- 2.5-2.55 H OH

- 3.9 to 4.2 H of CH OH

- 4.7 to 5.25 H of CH2F

- 6.8 to 7.5 H aromatic

Preparation 6: 1RS-2,2,2-Trichloro-1- (3-phenoxyphenyl) ethan-1-ol

4.95 g of aldehyde-m-phenoxybenzyl are dissolved in 40 cm3 of dimethoxyethane, 4 cm3 of chloroform are added, the mixture is cooled to -35; C and add in 15 min a solution of 3.36 g of potassium terbutylate in 15 cm3 of terbutanol and 15 cm3 of dimethoxyethane. Stirring is continued for 55 min, poured into ice water containing 35 mmol of hydrochloric acid. The mixture is stirred, extracted with ether, the ethereal phase is washed with water, dried and the solvent is evaporated. The residue is chromatographed on silica eluting with a cyclohexane / ethyl acetate mixture 8: 2 and 7.5 g of sought product is obtained.

Analysis for C ^ Hj, C1302 (317,602)

Calculated: C 52.9 H 3.5 Cl 33.5%

Found: C 52.9 H 3.6 Cl 33.5%

Preparation 7: lRS-2,2,2-Tribromo-l- (3-phenenphenphenyl) ethan-l-ol

The procedure is analogous to that described in Preparation 6, using 9.9 g of aldehyde-m-phenoxybenzyl and 8.7 cm 3 of bromoform. After purification by chromatography on silica, eluting with cyclohexane / ethyl acetate 85:15, 24.25 g of the expected product which is recrystallized from the petroleum ether / isopropyl ether mixture. 19.4 g of expected product are obtained. F = 70 C.

Analysis for CI4HnBr302 (450.96)

Calculated: C 37.3 H 2.4 Br53, l%

Found: C 37.2 H 2.7 Br 52.8%

Preparation 8: 1RS-2,2-Dichloro-1- (3-phenoxyphenyl) ethan-1-ol Stage A: 2,2-Dichloro-1- (3-phenoxyphenyllethan-1-one)

21.2 g of methylene chloride, 200 cm3 of tetrahy-drofuran and 100 cm3 of ethyl ether are mixed, introduced at -100 ° C 30 min with stirring 123 cm3 of a 15 g / 100 g solution of butyllithium in hexane. Stirred for 30 min, then add 24.2 g of ethyl 3-phenoxybenzoate in 100 cm3 of anhydrous ether. The mixture is left stirring for 3 h at -100: C, then introduced at - 60: C 150 cm3 of 2N hydrochloric acid. The temperature is allowed to rise to 0 ° C., decanted, extracted with ethyl ether, dried and the solvent evaporated. The residue is rectified (eb. 0.1 - 142-144 "C) and 18 g of expected product are obtained.

nj? = 1.610.

Stage B: 1 RS-2,2-Dichloro-1-t3-phenoxyphenyl) ethan-1-ol

18 g of 3-phenoxy- (û, Q3-dichloroacetophenone and 75 cm3 of ethanol are mixed, then 7 g of sodium borohydride are added at 20: C and the mixture is stirred for 1 h at 20 C. Then 1 cm3 is added of acetic acid, then pour into water, extract with ether, wash the organic phase with water, dry it, evaporate the solvent, take up in ether, treat with activated carbon, filter, evaporate the solvent and dry, 13 g of expected product are obtained.

ng = 1.5950.

Analysis for CI4H12C1202 (283.15)

Calculated: C 59.38 H 4.27 Cl 25.04%

Found: C 59.4 H 4.3 CI 24.9%

Example 28 Preparation of a Soluble Concentrate

A homogeneous mixture of:

- Product of Example 1 0.25 g

- Piperonyl butoxide 1 g

- Tween 80 0.25 g

- TopanolA 0.1g

- Water 98.4 g

EXAMPLE 29 Preparation of an Emulsifiable Concentrate The following are thoroughly mixed:

- Product of Example 1 0.015 g

- Piperonyl butoxide 0.5 g

- TopanolA 0.1g

- Xylene 99.385 g

Example 30 Preparation of an Emulsifiable Concentrate A homogeneous mixture of:

- Product of Example 1 1.5 g

- Tween 80 20 g

- TopanolA 0.1g

- Xylene 78.4 g

Example 31: Preparation of a smoke composition

We mix in a homogeneous way:

- Product of Example 1 0.25 g

- Tabu powder 25 g

- Cedar leaf powder 40 g

- Pine wood powder 33.75 g

- Brilliant green 0.5 g

- p-nitrophenol 0.5 g

Study of the activity of the compounds of the invention on parasites

Study of the activity of the compound of Example 2 by topical application on house flies (Musca domestica)

The insects tested are female house flies aged 4 to 5 d on which one operates by topical application of 1 (it of acetonic solution of the compound on the dorsal thorax of the insects using the micromanipulator of Arnold and at a rate of 50 individuals per dose tested.

Mortality checks are carried out 24 hours after treatment. The experimental results expressed in DL ,,, give the dose of 68.46 ng per individual necessary to kill 50% of the population.

5

10

15

20

25

30

35

40

45

50

55

60

65

13

655,302

Conclusion

The compound of Example 2 is endowed with an interesting insecticidal activity on houseflies.

Study of the lethal activity of the compound of Example 2 by tarsal contact on a German cockroach (Blattella germanica)

Male German cockroach insects stay for 1 hour on the glass bottom of a Petri dish previously treated with an acetone solution of the test compound. The mortality checks are carried out 1 h, 24 h and 3 d after the start of the experiment, the insects being transferred, after their contact with the poisonous, under normal breeding conditions. The experimental results expressed in CL10 give the concentration of 2.09 mg / m2 as necessary to kill, by tarsal contact, 50% of the population.

Conclusion

The compound of Example 2 is endowed with an interesting insecticidal activity on the German cockroach.

Study of the knock down activity of the compound of Example 2 by spraying on house flies

The insects used are females aged 4 d. The operation is carried out by direct spraying in an ICears and March chamber of a solution of the compound to be tested in a mixture of equal volumes of acetone and of petroleum solvent (Isopar L).

50 insects are used per dose and the abatement checks are carried out every minute up to 15 min, then the s KTS0 or time required to kill 50% of the insects is determined by traditional methods.

The abatement controls give for the compound of Example 2 a KT50 of 9.86 min.

10 Conclusion

The compound of Example 2 is endowed with good impact activity on houseflies.

Study of the miticide activity of the compound of Example 2 on the I5 mite Tetranychus urticae

Bean plants with 2 cotyledon leaves are treated at different doses. After the spray has dried, the leaves are infested with 50 female mites per dose. Mortality counts are made after 24 hours and the results obtained allow the LC50 to be calculated.

With the compound of Example 2, the LC50 is 1732.7 mg / hl.

Conclusion

The compound of Example 2 is endowed with good acari-25 activity on Tetranychus urticae.

R

Claims (16)

655,302 1. Compounds of formula (I): in which R4, R5, R „and R-, identical or different, each represent a halogen atom, or Z2 represents a radical: E or Z geometry VS-! H .O-C-B R02c in which Rs represents a hydrogen atom or a chlorine, fluorine or bromine atom, and in which Ar represents an aromatic or heteroaromatic radical - R represents: that, optionally substituted, X ,, X2, X3, identical or different, - either a linear, branched or cyclic alkyl radical, saturated or represent a hydrogen atom or a halogen atom, one of which is unsaturated, containing from 1 to 18 carbon atoms, optionally substituted by one or more identical or different functional groups, - or an aryl group containing 6 to 14 carbon atoms, optionally substituted by one or more groups - 20 identical or different functional elements, - either a heterocyclic radical optionally substituted by one or more identical or different functional groups, c) or B represents a radical: 25 minus radicals X [, X2, and X3 representing a halogen atom, and B represents: a) or an alkyl radical containing from 1 to 18 carbon atoms, b) or a radical: CH CH. 30 D ~ \ in which: - or else Z, and Z2 each represent a methyl radical, - either Zj represents a hydrogen atom, and either Z2 represents a radical: / 35 40 in which R3 represents a hydrogen or halogen atom, Ri and R2, identical or different, represent a halogen atom or an alkyl radical containing from 1 to 8 carbon atoms, or R, and R2 together form a radical cycloalkyl containing 3 to 6 carbon atoms or a radical: àr in which y. in any position on the benzene nucleus, represents a halogen atom, an alkyl radical containing from 1 to 8 carbon atoms, or an alkoxy radical containing from 1 to 8 carbon atoms, m representing the number 0, 1 or 2, in all their possible isomeric forms, as well as mixtures of isomers, with the exception of the compounds of formula (I) in which Xl5 X2 and X3 simultaneously represent a fluorine atom and with the exception of 3- (2-methyl-1 -propenyl) -2,2-dimethylcyclopropane-1 -carboxylate of 2-chloro-1 - (3-phenoxyphenyl) ethyl. 2. Compounds of formula (I) according to claim 1, for which B represents a radical: in which the ketone is a with respect to the double bond and in which X represents an oxygen or sulfur atom or an NH radical, or Z2 represents a radical: H 55 in which Zl represents a hydrogen atom and Z2 a radical: 60 in which Rj, R2 and R3 are defined as in claim 1. 2 3 655,302 3. Compounds of formula (I) according to claim 2, for which R] and R2 represent identical halogen atoms and R3 a hydrogen atom. 4 carboxylic, by 3-phenoxybenzyl alcohol esters of 2-parachlorophenyl-2-isopropylacetic acids, by allethrolene esters, 3,4,5,6-tetrahydrophthalimidomethyl alcohol, 5-benzyl alcohol -3-furylmethyl, 3-phenoxybenzyl alcohol and α-cyano-3-phenoxybenzylic alcohols of 2,2-dimethyl-3- (1,2,2,2-tetrahaloethyl) cyclopropane-1-carboxylic acids in which halo represents a fluorine, chlorine or bromine atom, it being understood that the compounds (I) can exist in all their stereoisomeric forms, as well as the acid and alcohol copulas of the above pyrethrioid esters. 4. Compounds of formula (I) according to one of claims 1 to 3, for which Ar represents a radical: in which yj and y2, in any position on the benzene ring, represent a hydrogen atom, a halogen atom or a methyl radical, n and n 'represent the number 1 or 2 and A represents an atom of oxygen, a methylene group, a carbonyl group, a sulfur atom, a sulfoxide group or a sulfone group. 5. Compounds of formula (I) according to one of claims 1 to 4, for which Xl5 and X2 represent a hydrogen atom and X3 represents a halogen atom. 6. A process for the preparation of the compounds of formula (I) as defined in one of claims 1 to 5, characterized in that one subjects ur xcide of formula (II): bco2h in which B is defined as in claim 1, or a functional derivative of this acid, to the action of an alcohol of formula (III): (II) / (III) Ar-CH-OH or a functional derivative of this alcohol, Ar, Xt, X2 and X3 being defined as in claim 1, to obtain the corresponding compound of formula (I): (I) 7. Method according to claim 6, characterized in that an acid of formula BC02H or a functional derivative of this acid, in which B is defined as in claim 1, is subjected to the action of an alcohol of formula (IIIA): (Ia) 8. As means for implementing the process according to claim 6, the alcohols of formula (III): (III) a-oh oh T as well as the functional derivatives of these alcohols, Ar, Xls X2 and X3 being defined as in claim 1, it being understood that X1; X2 and X3 cannot simultaneously represent a fluorine atom. 9. As a means according to claim 8, the alcohols of formula (IIIA): 30 (HI *) (hia) (y2> n in which yl5 y2, n, n 'and A are defined as in claim 4, Xj, X2 and X3 being defined as in claim 1, or a functional derivative of this alcohol, to obtain the compound of corresponding formula (IA): 35 as well as the functional derivatives of these alcohols, yi, y2, n, n 'and A being defined as in claim 4, Xj, X2, X3 being defined as in claim 8. 40 10. Use of the compounds of formula (I) according to one of claims 1 to 5, in the fight against ectoparasites of warm-blooded animals and against plant parasites and premises. 11. Compositions intended for the control of parasites of warm-blooded animals, plants and premises, characterized in 45 what they contain as active principle at least one product according to one of claims 1 to 5. 12. Insecticidal compositions according to claim 11, characterized in that they contain as active principle at least one 50 product according to one of claims 1 to 5. 13. acaricide compositions according to claim 11, characterized in that they contain as active principle at least one product according to one of claims 1 to 5. 14. Compositions endowed with insecticidal, acaracid, fungicidal or nematocidal activities according to claim 11, characterized in that. that they contain as active material, on the one hand, at least one of the compounds of general formula (I) according to claim 1 and, on the other hand, at least one of the pyrethroid esters chosen from the group consisting with esters of allethrolones, 3,4,5,6-tetra-60 hydrophthalimidomethyl alcohol, 5-benzyl-3-furylmethyl alcohol, 3-phenoxybenzyl alcohol and a-cyano-3- alcohols phenoxybenzylic chrysanthemic acids, by 5-benzyl-3-furylmethyl alcohol esters of 2,2-dimethyl-3- (2-oxo-3-tetrahydro-thiophenylidenemethyl) cyclopropane-1-carboxylic acids, by esters 65 of 3-phenoxybenzyl alcohol and a-cyano-3-phenoxybenzyl alcohols of 2,2-dimethyl-3- (2,2-dichlorovinyl) cyclopropane-1-carboxylic acids, by the esters of a-alcohols -cyano-3-phenoxybenzyli-ces of 2,2-dimethyl-3- (2,2-dibromovinyl) cyclopropane-l- acids 655,302 15. Pharmaceutical compositions according to claim 11, containing as active principle at least one of the products according to one of claims 1 to 5. 16. Compositions intended for animal feed, characterized in that they contain as active principle at least one product according to one of claims 1 to 5.