CH630890A5 - Esters of cyclopropanecarboxylic acids containing a halogenated substituent - Google Patents

Abstract

The compounds of the invention correspond to the formula: <IMAGE> in which X1 represents hydrogen, fluorine, chlorine or bromine, X2 represents fluorine, chlorine or bromine, X3 represents chlorine, bromine or iodine and R represents certain benzyl, furylmethyl, 2-cyclopentenyl, 3-phenoxybenzyl, phthalimidomethyl and tetrahydrophthalimidomethyl radicals as defined in Claim 1. These compounds have notable insecticidal, acaricidal and nematocidal properties; in addition, the compounds of formula I in which R represents an alpha -cyano-3-phenoxybenzyl radical are moreover distinguished by antifungal properties. They can thus be used, especially in agriculture, for controlling harmful insects, members of the Acarida and nematodes and, for the compounds of formula I, against pathogenic fungi of plants; they can also be used in veterinary medicine for controlling parasitic members of the Acarida. The compounds I can be prepared by subjecting to a chlorination, bromination or iodination either an ester corresponding to 2,2-dimethyl-(2'-X1-2'-X2-vinyl)cyclopropane-1-carboxylic acid or this acid itself or one of its functional derivatives and thereafter esterifying with an alcohol ROH.

Description

The subject of the invention is new esters of cyclopropane carboxylic acids comprising a polyhalogenated substituent, in all their stereoisomeric forms, of general formula I:

3 îm

HORN

in which Xi represents a hydrogen, fluorine, chlorine or bromine atom, X2, identical or different from Xj, represents a fluorine, chlorine or bromine atom, X3 represents a

45 atom of chlorine, bromine or iodine, and R represents:

- Or a benzyl radical optionally substituted by one or more radicals chosen from the group consisting of alkyl radicals containing from 1 to 4 carbon atoms, alkenyl radicals containing from 2 to 6 carbon atoms,

50 alkenyloxy radicals comprising from 2 to 6 carbon atoms, the alkadienyl radicals comprising from 4 to 8 carbon atoms, the methylene dioxyl radical, the benzyl radical, the halogen atoms,

- Or a group:

55

-CH

-CÎI2R2

60

in which the substituent R! represents a hydrogen atom or a methyl radical and the substituent R2 a monocyclic aryl or a group:

65 -CH2-C = CH

and in particular a 5-benzyl 3-furyl methyl group,

- Or a group:

630 890

4

in which R3 represents an aliphatic organic radical comprising from 2 to 6 carbon atoms and one or more carbon-carbon unsaturations, and in particular the vinyl radical,

propen-l-yle, buta-l, 3-dienyl or buten-l-yle,

- Or a group:

H

in which R4 represents a hydrogen atom, a group:

-C = N

or a group:

-C = CH

and R5 represents a chlorine atom or a methyl radical and n represents a number equal to 0.1 or 2, and in particular the group 3-phenoxy benzyl, a-cyano 3-phenoxy benzyl or a-ethynyl 3-phenoxy benzyl,

- Or a group:

in which the substituents R6, R7, Rg and R9 represent hydrogen, a chlorine atom or a methyl radical and in which the symbol S / I indicates an aromatic or analogous cycle, dihydro or tetrahydro.

By convention, in the alcoholic copula of the esters of formula I, when n is equal to 0, the nucleus to which the substituent R5 is fixed then represents a benzene nucleus.

The esters of formula I can exist in many isomeric forms. In fact, the cyclopropane carboxylic acids which form the acid copula of the esters of formula I generally have 3 asymmetric carbons, namely, the asymmetric carbons in position 1 and 3 of the cyclopropane ring and the asymmetric carbon in position 1 'of the polyhalogenated ethyl side chain attached in position 3.

In the case where the three substituents Xx, X2 and X3 are different from each other, an additional asymmetric carbon may exist at position 2 'of the polyhalogenated ethyl side chain.

Furthermore, the alcohol R-OH constituting the alcoholic copula of the esters of formula I may contain one or more asymmetric carbons and / or one or more double bonds giving rise to an E / Z isomerism.

The esters of formula I include, for a given definition of the substituents X2, X3 and R, all the compounds originating from the combination of an isomer (racemic or optically active) resulting from the existence of the different asymmetric carbons of the acid part of the molecule with an isomer (racemic or optically active) corresponding to the alcoholic copula.

5 In the case where the substituents Xt and X2 are identical, for a determined steric configuration of the asymmetric carbons in position 1 and 3 of the cyclopropane ring, as well as for a determined structure of the alcoholic part (which may itself comprise one or more asymmetric carbons and / or 10 one or more double bonds giving rise to isomerism E / Z), two diastereoisomeric forms of the esters (I) or of the corresponding acids (K), due to the existence of the asymmetric carbon in 1 ', can exist and be effectively characterized in particular by their NMR spectrum or their migration speed in thin layer chromatography. These isomers can, in general, be separated and isolated in the pure state, in particular by chromatography. These two diastereoisomers have been called here and in the following, isomers (A) and (B).

Among the esters I, mention will be made more particularly of those in which the cyclopropane carboxylic acids (K), forming the acid coupler of these esters, are of structure (1R, eis) or (1R, trans) and the names of which follow:

- 2,2-Dimethyl 3- (2 ', 2'-dibromo l', 2'-dichloro ethyl) cyclopropane-1-carboxylic acids;

25 - 2,2-Dimethyl 3- (1 ', 2', 2 ', 2'-tetrachloroethyl) cyclopropane-1-carboxylic acids;

- 2,2-Dimethyl 3- (2 ', 2'-difluoro l', 2'-dichloro ethyl) cyclopropane-1-carboxylic acids;

- 2,2-Dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromo 3o ethyl) cyclopropane-1-carboxylic acids;

- 2,2-Dimethyl 3- (2 ', 2'-difluoro l', 2'-dibromo ethyl) cyclopropane-1-carboxylic acids;

- 2,2-Dimethyl 3- (1 ', 2', 2'2'-tetrabromo ethyl) cyclopropane-1-carboxylic acids;

35 - 2,2-Dimethyl 3- (2 ', 2'-difluoro 2', l'-diodo ethyl) cyclopropane-1-carboxylic acids;

- 2,2-Dimethyl 3- (2 ', 2'-dichloro 2', l'-diodo ethyl) cyclopropane-1-carboxylic acids;

- 2,2-Dimethyl 3- (2 ', 2'-dibromo 2', 1 '-diodo ethyl) 40 cyclopropane-1-carboxylic acids;

- 2,2-Dimethyl 3- (1 ', 2', 2'-tribromo ethyl) cyclopropane-1-carboxylic acids;

- 2,2-Dimethyl 3- (l ', 2'-dichloro 2'-bromo ethyl) cyclopropane-1-carboxylic acids;

45 - 2,2-Dimethyl 3- (l ', 2', 2'-trichloro ethyl) cyclopropane 1-carboxylic acids;

- 2,2-Dimethyl 3- (1', 2'-dibromo 2'-chloro ethyl) cyclopropane-1-carboxylic acids;

- 2,2-Dimethyl 3- (l ', 2'-dichloro 2'-fluoro ethyl) cy-50 clopropane-l-carboxylic acids;

- 2,2-Dimethyl 3- (1 ', 2'-dibromo 2'-fluoro ethyl) cyclopropane-1-carboxylic acids; -

- 2,2-Dimethyl 3- (2'-fluoro 2 ', l'-diodo ethyl) cyclopropane-1-carboxylic acids;

55 - 2,2-Dimethyl 3- (2'-chloro 2 ', 1' -diodo ethyl) cy-clopropane-1-carboxylic acids;

- 2,2-Dimethyl 3- (2'-bromo 2 ', l'-diodo ethyl) cyclopropane-1-carboxylic acids;

- 2,2-Dimethyl 3- (1 ', 2', 2'-trichloro 2'-fluoro ethyl) 60 cyclopropane-1-carboxylic acids;

- 2,2-Dimethyl 3- (1', 2'-dibromo 2'-chloro 2'-fluoro ethyl) cyclopropane-l-carboxylic acids;

- 2,2-Dimethyl 3- (1 ', 2', 2'-trichloro 2'-bromo ethyl) cyclopropane-1-carboxylic acids;

65 - 2,2-Dimethyl 3- (1 ', 2', 2'-tribromo2'-chloro ethyl) cyclopropane-1-carboxylic acids;

- 2,2-Dimethyl 3- (2'-fluoro l ', 2', 2'-tribromo ethyl) cyclopropane-l-carboxylic acids;

5

630 890

- 2,2-Dimethyl 3- (2'-bromo 2'-fluoro 1 ', 2'-dichloro ethyl) cyclopropane-1-carboxylic acids;

- 2,2-Dimethyl 3- (2'-fluoro 2'-chloro 2 ', 1' -diodo ethyl) cyclopropane-1-carboxylic acids;

- 2,2-Dimethyl 3- (2'-fluoro 2'-bromo 2 ', 1' -diodo ethyl) cyclopropane-1-carboxylic acids;

- 2,2-Dimethyl 3- (2'-chloro 2'-bromo 2 ', 1' -diodo ethyl) cyclopropane-1-carboxylic acids.

Of course, the esters I can also come from cyclopropane carboxylic acids (K) of structure (IS, eis) or (1S, trans). Similarly, these esters I can be derived from either cyclopropane carboxylic acids (K) of structure dl-cis (equimolecular mixture of (1R, eis) and of (IS, eis) or dl-trans (equimolecular mixture of (IR, trans ) and (1S, trans), ie mixtures of acids of structure dl-cis and acids of structure dl-trans.

A more particular subject of the invention is compounds of general formula I, in which the acid copula is of structure (1R, eis) or (IR, trans), as well as compounds of general formula I, in which the acid copula is of dl-cis or dl-trans structure, and compounds of general formula I consisting of a mixture of esters whose acid copula is of dl-cis or dl-trans structure.

Among the alcohols constituting the alcoholic copula of the esters, there may be mentioned in particular benzyl alcohol, 2,5-dimethyl 4-allyl benzyl alcohol, 5-benzyl 3-furyl methanol, 5- (propyn-2'-yl ) 2-methyl 3-furyl methanol (or kikuthrol), 5- (propyn-2'-yI) 2-furyl methanol (or prothrol), 1-oxo 2-allyl 3-methyl cyclopent-2-ene 4- ol (or allethrolone), 1-oxo 2- (2 ', 4'-penta-dienyl) 3-methyl cyclopent-2-ene 4-oI, 1-oxo 2- (2'-butenyl) 3-methyl cyclopent-2-ene 4-ol, 3-phenoxy benzyl alcohol, a-cyano 3-phenoxy benzyl alcohol, a-ethynyl 3-phenoxy benzyl alcohol, 3,4,5,6- alcohol methyl tetrahydro phthalimido and more especially the optically active forms of those of these alcohols which have an asymmetric carbon.

Among the compounds of general formula I, there may be mentioned in particular those in which Xj represents a fluorine, chlorine or bromine atom, X2 is identical to Xj and represents a fluorine, chlorine or bromine atom, and X3 and R retain the abovementioned meanings, those in which Xt represents a hydrogen, fluorine, chlorine or bromine atom, X2 is different from Xj and represents a fluorine, chlorine or bromine atom, and X3 and R retain the abovementioned meanings , those in which X1; X2 and X3 retain the above-mentioned meanings and R represents a 5-benzyl 3-furyl methyl alcohol residue, a 1-oxo 2-allyl 3-methyl cyclopent-2-en 4-yl residue, an alcohol residue 3- benzyl phenoxy, a residue of α-cyano 3-phenoxy benzyl alcohol, these alcohols possibly being racemic or optically active, and those in which X! represents a fluorine, chlorine or bromine atom, X2 identical to X1 represents a fluorine, chlorine or bromine atom, X3 represents a chlorine, bromine or iodine atom and R represents an alcohol residue 5 -benzyl 3-furyl methyl, a 1-oxo 2-allyl 3-methyl cyclopent-2-en 4-yl residue, a residue of 3-phenoxy benzyl alcohol, a residue of a-cyano 3-phenoxy benzyl alcohol, these alcohols can be racemic or optically active.

The compounds of formula I, in the form of isomers (A), in the form of isomers (B), due to the existence of asymmetric carbon in position 1 ′ of formula I, or in the form of a mixture of these isomers, whose names follow:

- IR, eis 2,2-dimethyl 3- (1, 2 ', 2', 2'-tetrabromo ethyl) cyclopropane-1-carboxylate of (S) a-cyano 3-phenoxy benzyl;

- The 1R, cis 2,2-dimethyl 3- (2 ', 2'-dichloro 1', 2'-dibromo ethyl cyclopropane-1-carboxylate of (S) a-cyano 3-phenoxy benzyl, are of particular interest.

The compounds of general formula I, in the form of isomers (A), in the form of isomers (B), due to the existence of asymmetric carbon in position 1 ′ of formula I, or in the form of a mixture of these isomers , cited elsewhere in the examples are also preferred compounds of the invention.

The compounds can in particular be used in the form of a mixture of stereoisomers of structure eis and of trans structure in any proportions and more particularly in the form of mixtures of stereoisomers of structure eis and of trans structure in weight proportions 20 / 80.50 / 50 or 80/20.

The compounds of general formula I, which are subjects of the invention, can be prepared by reacting on an ester of general formula II:

15 IV

H 'H3C

X

(II)

GOLD

In which Xls X2 and R retain the abovementioned meanings, said ester II being in any of its isomeric forms, a chlorination, bromination or iodination agent capable of fixing Cl2, Br2 or I2 on the double bond of the side chain of cyclopropane-carboxylic acid. This method above is called method a.

As halogenating agent for esters II, chlorine, bromine or iodine is used in particular, and the halogenation for esters II is then carried out in an organic solvent which does not react with chlorine, bromine or l iodine, such as acetic acid, carbon tetrachloride, chloroform, methylene chloride.

Compounds of general formula I can also be prepared by reacting with an acid of general formula III:

35

X

N. I

(III)

40

in which Xj and X2 retain the abovementioned meanings, said acid III being in any of its isomeric forms a chlorination, bromination or iodination agent capable of fixing Cl2, Br2 or I2 on the side chain of the acid 45 III, then reacting the resulting acid, of general formula IV:

OH

(IV)

55 in which Xh X2 and X3 retain the abovementioned meanings or one of its functional derivatives, with an alcohol ROH or one of its functional derivatives, R retaining the abovementioned meaning.

This above method is called the ß method.

60 As an acid halogenating agent III, chlorine, bromine or iodine are used in particular, and the halogenation of acids III is then carried out in an organic solvent which does not react with chlorine, bromine or iodine, such as acetic acid, carbon tetrachloride, chloroform, methylene chloride.

The functional derivative of acid IV, used to effect esterification with alcohol ROH or with a functional derivative of this alcohol, is in particular chloride, anhydride, an anhy

630 890

6

mixed dride, a lower alkyl ester, a metal salt or an organic base salt of acid III, the functional derivative of the alcohol possibly being a chloride, a bromide or a sulfonate of this alcohol.

A variant of the process β for preparing the compounds of general formula I consists in reacting on a functional derivative of an acid of general formula III:

£ 1 \

C = C

C-OH (In)

X

formula in which Xi and X2 retain the abovementioned meanings, said functional derivative of acid III being in any of its isomeric forms, a chlorination, bromination or iodination agent capable of fixing Cl2, Br2 or I2 on the side chain of the functional derivative of acid III, then reacting the functional derivative resulting from acid IV:

(IV)

in which Xl5 X2 and X3 retain the abovementioned meanings with an alcohol ROH or one of its functional derivatives, R retaining the abovementioned meaning.

This above process is called the y process.

The agent used to carry out the halogenation of the functional derivative of acid III is preferably chlorine, bromine or iodine, and the halogenation is then carried out in a non-reacting organic solvent not with chlorine, bromine or iodine, such as acetic acid, carbon tetrachloride, chloroform, methylene chloride.

In order to obtain the compounds I from the IV acids or functional derivatives of the IV acids according to the methods ß and y, the IV acid or one of its functional derivatives is reacted with alcohol ROH or with a functional derivative of this alcohol.

For example, esterification can be carried out by the action of IV acid, chloride, anhydride or a mixed anhydride of this IV acid on alcohol ROH. The trans esterification method can also be used by reacting a lower alcohol ester of the acid IV with the alcohol ROH, in particular in the presence of a basic catalyst. It is also possible to react a salt of acid IV, for example, a salt of an alkali metal, of silver or of triethylamine with a functional derivative of alcohol ROH, such as a chloride, a bromide or a sulfonate.

It is also possible to use other conventional methods of esterification of the acid IV or one of its functional derivatives with alcohol ROH or one of its functional derivatives.

An advantageous embodiment of the β process consists in using the chloride of this acid as the functional derivative of IV acid.

An advantageous embodiment of the process consists in using as functional derivative of acid III and as functional derivative of acid IV, the chlorides of these acids.

The esterification of the acid chloride IV with alcohol ROH is then conveniently carried out in the presence of a tertiary base, such as pyridine or triethylamine.

In general, esters II, acids III and functional derivatives of acids III, used as starting materials for the processes mentioned above, are described in particular in French patents Nos. 2,185,612 and 2,240,914 or can be prepared by methods analogous to those described in these patents.

In the case where the radicals X [and X2 represent halogen atoms, Xj being different from X2, the esters II, the acids III and their functional derivatives are described in the thesis of DALE GORDON BROWN (DENTON, TEXAS) of December 1974, 5 entitled “Structure - activity studies of halo pyrethroids” or can be prepared by methods analogous to those described in this thesis.

Of course, the esters II, used at the start of the process a exist in many isomeric forms, these iso-io mother forms originating from the existence of asymmetric carbons in positions 1 and 3 of the cyclopropane cycle, as well as from the possible existence in the alcoholic part, either of one or more asymmetric carbons, or of one or more double bonds giving rise to an E / Z isomerism.

Likewise, acids III or their functional derivatives, used at the start of the β and y processes, also exist in various isomeric forms originating from asymmetric carbons in positions 1 and 3 of the cyclopropane ring.

The compounds of general formula I are endowed with remar-2C which have insecticidal properties, in particular, of an extremely intense lethal power and of a very good stability with respect to atmospheric agents (heat, light, humidity).

These compounds are particularly suitable for application to the fight against insects in the agricultural field. 25 For example, they make it possible to effectively fight against aphids, lepidopteran larvae, beetles.

They are then preferably used at doses of between 1 g and 100 g of active ingredient per hectare. By their rapidity of action, these compounds can also be used as insecticides in the domestic field.

The insecticidal activity of the compounds of the invention can be demonstrated in particular by tests on house flies, on SpodopteraLittoralis, as well as on larvae of Epilachna Varivestris, on Sitophilus Granarius and Tribolium Castaneum and 35 on Blatella Germanica.

These tests are described later in the experimental part.

The compounds of formula I can thus be used to prepare insecticide compositions containing as active principle at least one of the compounds of general formula I, such as 4 "as defined above, and more especially containing, as active principle, at least one of the compounds of general formula I, in the form of isomers (A), in the form of isomers (B), due to the existence of asymmetric carbon in position 1 'of formula I, or in the form of a mixture of these isomers, the 45 names are mentioned above.

The active ingredient (s) can 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, 50 bait fuel strips 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 non-ionic surfactant, ensuring, in addition, a uniform dispersion of the constituent substances of the mixture. The vehicle used can be a liquid, such as water, alcohol, hydrocarbons or other organic solvents, mineral, animal or vegetable oil, powder, such as talc, clays, silicates, Kieselguhr or a solid combustible, such as tabu powder (or pyrethrum marc).

60

To enhance the insecticidal activity of the compounds of the invention, they can be added to the conventional synergists used in such cases, such as l- (2,5,8-trioxa dodecyl 2-propyl 4,5-mé-thylènedioxy) benzene (or piperonyl butoxide), N- (2-65 ethyl heptyl) bicyclo [2,2, l] -5-heptene-2,3-dicarboximide, piperonyl-bis-2- (2'-n- butoxy ethoxy) ethyl acetal (or tropital).

These insecticidal compositions preferably contain between 0.005% and 10% by weight of active material. These composi-

7

630 890

tions may advantageously contain a synergizing agent and in particular piperonyl butoxide.

The compounds of formula I, as defined above also have interesting acaricide and nemati-cide properties.

Tests given below on Tetranychus Urticae and on Ditylenchus Mycellophagus demonstrate this.

The compounds of formula I can thus be used to prepare acaricide or nematicide compositions containing as active material at least one, in all their possible isomeric forms, of compounds of general formula I, as defined above, and more particularly at least one of the compounds whose names follow:

the isomers A and B of lR, cis 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrabromoethyl) cyclopropane-1-carboxylate of (S) a-cyano 3-phenoxy benzyl,

- the isomers A and B of lR, cis 2,2-dimethyl 3- (2 ', 2'-di-chloro l', 2'-dibromoethyl) cyclopropane-l-carboxylate of (S) a-cyano 3-phenoxy benzyl.

Like the above insecticide compositions, the acaricide and nematicide compositions can optionally be added with one or more other pesticidal agents. The acaricide and nematicide compositions can be in particular in the form of powder, granules, suspensions, emulsions, solutions.

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

For nematicide 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.

The anti-mite properties of the compounds of formula I, as defined above, moreover make it possible to use the said compounds in the fight against parasitic mites of animals and in particular in the fight against ixodidae and the parasitic sarcoptidae of animals. .

Tests given later in the experimental part show the activity of a compound of formula I on Rhipicephalus Sanguineus in dogs.

The compounds of formula I can be used in ani-io mal to fight against all kinds of scabies, such as sarcoptic mange, psoroptic mange and chorioptic mange. The compounds of formula I also make it possible to fight against all kinds of ticks such as, for example, the Boo-philus species, the Hyalomnia species, the Amblyoma species and the Rhi-15 picephalus species.

The compounds of formula I can therefore also be used to prepare pharmaceutical compositions intended for combating conditions caused by mites and containing, as active material, at least one of said compounds.

Said compositions can be used externally, but also parenterally or digestively.

Said compositions can also be advantageously added with a pyrethroid synergizing agent. Such an agent has been defined previously. These compositions can be prepared according to the usual methods.

Finally, it may be convenient for veterinary use to use compounds I in admixture with balanced compound feeds.

For example, compound feeds which contain 0.002 to 0.4% by weight of 1R, cis 2,2-dimethyl 3- (2 ', 2', 2 ', l -tetrabromoethyl) may be used a-cyano 3-phenoxy benzyl cyclopropane-1-carboxylate.

These compositions intended for animal feed consist of a compound, balanced feed for animals and they additionally contain at least one of the compounds of general formula I.

Furthermore, the compounds of formula IA:

corresponding to formula I,

in which X1 represents a hydrogen, fluorine, chlorine or bromine atom, X2, identical or different from Xi represents a fluorine, chlorine or bromine atom and X3 represents a chlorine, bromine or atom iodine, and in particular lR, cis 2,2-dimethyl 3- (2 ', 2', 2 ', (S) -tetrabromoethyl) cyclopro-pane-1 -carboxylate of (S) a-cyano 3-phenoxy benzyl and lR, cis 2,2-dimethyl 3- (2 ', 2'-dichloro 2', 1 '(RS) dibromo-ethyl) cyclopropane-l-carboxylate of (S) a-cyano 3-phenoxy benzyl have remarkable antifungal properties, making it possible to use them in the agricultural field to fight against pathogenic fungi of plants.

The antifungal activity of these compounds of formula IA can be illustrated in particular by tests on Fusarium Roseum, Botrytis Cinerea Phoma Specus, Penicillium Roqueforti, provided below.

The compounds of formula IA can also be used to prepare antifungal compositions containing as

50

active principle at least one of the compounds of formula IA, as defined above, and in particular antifungal compositions containing as active principle at least one of the compounds named above.

In these antifungal compositions, the active ingredient (s) may be optionally added with one or more other pesticidal agents. These compositions can be in the form of powders, granules, suspensions, emulsions, solutions, solutions for aerosols or other em-60 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 non-ionic surfactant, ensuring, moreover, a uniform dispersion of the substances constitutive of the mixture. The vehicle used can be a liquid, such as water, alcohol, hydrocarbons or other organic solvents, a mineral, animal or vegetable oil or a powder, such as talc, clays, silicates or Kieselguhr.

630 890

8

These antifungal compositions preferably contain, for powders for spraying from 25 to 95%, by weight of active material, for powders or liquids for spraying with salt from 10 to 30% by weight of active material.

The acids of formula IV below, in all their possible isomeric forms, are new:

in which Xj represents a hydrogen, fluorine, chlorine or bromine atom, X2, identical or different from X1; represents a fluorine, chlorine or bromine atom and X3 represents a chlorine, bromine or iodine atom, as well as their functional derivatives and in particular their chlorides.

These new products, obtained intermediately during the preparation of the compounds of formula I are described in Swiss patent no. 627,431, entitled “Process for the preparation of new cyclopropane carboxylic acids comprising a polyhalogenated group” (application no. 11567/77).

The following examples illustrate the invention.

Example 1

(1R, cis) 2,2-dimethyl3- (V, 2 ', 2', 2'tetrabromo ethyl) cyclo-propane-1-carboxylate of (S) a-cyano-3-phenoxy benzyl (Isomer A) and ( Isomer B)

In 100 cm3 of carbon tetrachloride, 7.57 g of (1R, cis) 2,2-dimethyl 3- (2 ', 2'-dibromo vinyl) cyclopropane-1-carboxylate of (S) a-cyano 3 are dissolved. -phenoxy benzyl, add 2.4 g of bromine dissolved in 15 cm3 of carbon tetrachloride stirred for 45 minutes at 20 ° C, concentrated to dryness under reduced pressure, separates the constituents from the residue (10 g) by gel gel chromatography silica; elution is obtained with a mixture of benzene and petroleum ether (Eb. 35-75 °) (1-1), first the isomer (A) (4.12 g), then the isomer ( B) (4 g) of (1R, cis) 2,2-dimethyl 3- (1, 2 ', 2', 2'-tetrabromo ethyl) cyclopropane-1-carboxylate of (S) a-cyano 3-phenoxy benzyl. The A isomer has the following characteristics: [a] D = - 53 ° (c = 0.5%, benzene)

Analysis: C22H19Br4N03 (665.037)

Calculated: C% 39.73 H% 2.88 Br% 48.06 N% 2.11 Found: 39.9 2.9 48.2 2.1

Spectrum I.R. (Chloroform)

Absorption at 1740 cm-1 (ester), absorptions at 1615.1558, 1573 and 1488 cm-1 attributed to the aromatic nuclei.

Spectrum R.M.N.

Peaks at 1.25-1.33 p.p.m. (hydrogens of the methyl radicals in position 2 of cyclopropane); peaks of 1.75 to 2.17 p.p.m. (hydrogens in positions 1 and 3 of cyclopropane); peaks at 5.19-5.55 p.p.m. (hydrogen in position 1 'of the side chain); peak at 6.38 p.p.m. (benzyl hydrogen); peaks of 6.91 to 7.59 p.p.m. corresponding to the hydrogens of the aromatic rings.

The (A) isomer is the most mobile in thin layer chromatography.

Circular dichroism (dioxane)

A e = - 3 at 224 nm;

Ae = -4.5-237 nm;

A e = - 0.05 at 290 nm.

The isomer (B) has the following characteristics: [a] D = + 111 ° (c = 0.6%, benzene)

Analysis: C22HmBr4N03 (665.037)

Calculated: C% 39.73 H% 2.88 Br% 48.06 N% 2.11 Found: 39.8 3.0 48.1 2.0

I.R. spectrum (chloroform)

Absorption at 1743 cm-1 (ester), absorption at 1615.1588, 5 1573 and 1488 cm-1 attributed to the aromatic nuclei.

Spectrum of R. M. N.

Peaks at 1.24-1.40 p.p.m. (hydrogens of the methyl radicals in position 2 of cyclopropane); peaks of 1.83 to 2.25 p.p.m. (hydrogens in positions 1 and 2 of cyclopropane); peaks at 3.98-5.20 10 p.p.m. (hydrogen in position 1 'of the side chain); peak at 6.39 p.p.m. (benzyl hydrogen); peaks from 6.92 to 7.52 p.p.m. corresponding to the hydrogens of the aromatic rings.

The (B) isomer is the least mobile in thin layer chromatography.

15 Circular dichroism (dioxane)

A e = +4.7 at 223 nm;

A e = +4.2 at 247 nm.

Example 2

20 (IR, eis) 2,2-dimethyl3- (2 ', 2'-dichloro V, 2'-dibromo ethyl) cyclopropane-l -carboxylate of (S) a-cyano-3-phenoxy benzyl (Isomer A) and (Isomer B)

In 200 cm3 of carbon tetrachloride, 2s 17.06 g of (1R, cis) 2,2-dimethyl 3- (2 ', 2'-dichloro vinyl) cyclopropane-1-carboxylate of (S) a-cyano are dissolved. 3-phenoxy benzyl, introduced 6.55 g of bromine in solution in 20 cm3 of carbon tetrachloride in about 10 minutes, stirred for 48 hours at 20 ° C, concentrated to dryness by distillation under reduced pressure and separated the constituents from the crude residue (23.8 g) by chromatography on silica gel eluting with a mixture of benzene and cyclohexane (7-3) and obtains 10.4 g of isomer (A) (most mobile in thin layer chromatography) and 10 g of (B) isomer (the least mobile in thin layer chromatography) of 3_ (1R, cis) 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromo ethyl) cyclopropane -l-carboxylate of (S) a-cyano 3-phenoxy benzyl. The isomer A has the following characteristics: [a] D = - 61 ° (c = 0.5%, benzene)

Analysis: C22H19Br2Cl2N03 (576,125)

4o Calculated: C% 45.85 H% 3.3 Br% 27.74 Cl% 12.3 N% 2.4 Found: 45.8 3.3 27.7 12.3 2.3

Spectrum I.R. (Chloroform)

Absorption at 1738 cm-1 (ester), absorption at 1485.1585 and 1610 cm-1 due to aromatic nuclei.

45 Spectrum of R. M. N.

Peaks at 1.29-1.37 p.p.m. (hydrogens of the twin methyls of cyclopropane); peak at about 2.05 p.p.m. (hydrogens in positions 1 and 3 of cyclopropane); peaks at 5.20-5.29-5.37-5.45 p.p.m. (hydrogen attached to the asymmetric carbon of the side chain 50); peak at 6.45 p.p.m. (benzyl hydrogen); peaks of 7.0 to 7.6 p.p.m. attributed to the hydrogens of the aromatic rings.

Circular dichroism (dioxane)

Ae = - 8 at 221 nm (inflection);

A e = + 0.14 at 289 nm (max.).

55 The (B) isomer has the following characteristics: [a] D = + 119 ° (c = 1% in benzene)

Analysis: C22H19Br2Cl2N03 (576,125)

Calculated: C% 45.86 H% 3.3 Br% 27.7 Cl% 12.3 N% 2.4 Found: 46.2 3.4 27.6 12.2 2.3

60

Spectrum I.R.

Absorption at 1740 cm-1 (ester); absorptions at 1610, 1585 and 1485 cm-1 (aromatic nuclei).

Spectrum of R. M. N.

65 Peaks at 1.25-1.38 p.p.m. (hydrogens of the geminated methyls of cyclopropane); peaks of 1.87 to 2.3 p.p.m. (hydrogens in positions 2 and 3 of cyclopropane); peaks at 4.97-5.01-5.11-5.16 p.p.m. (hydrogen attached to the asymmetric carbon of the chain

9

630 890

lateral); peak at 6.46 p.p.m. (benzyl hydrogen); peaks of 7 to 7.67 p.p.m. attributed to the hydrogens of the aromatic nuclei.

Circular dichroism (dioxane)

A e = +9 at 220—221 nm (max.)

A e = +0.23 at 289 nm (max.)

Example 3

(IR, eis) 2,2-dimethyl3 - (! ', 2', 2 ', 2'-tetrabromo ethyl) cyclopropane-l-carboxylate of (S) a-cyano 3-phenoxy benzyl Stage A: Acid (1R, cis) 2,2-dimethyl 3- (l ', 2', 2 ', 2'-tetrabromo ethyl) cyclopropane-l -carboxylic:

19.4 g of (1R, cis) 2,2-dimethyl 3- (2 ', 2'-dibromo vinyl) cy-clopropane-1-carboxylic acid are added to 150 cm 3 of carbon tetrachloride, 10 4 g of bromine in solution in 22 cm3 of carbon tetrachloride, stirred for one hour at 20 ° C, concentrated to dryness by distillation under reduced pressure and obtained 31.4 g of crude product (M = 145 ° C). This crude product is recrystallized from 110 cm3 of carbon tetrachloride and 22.12 g of acid (1R, cis) 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrabromo) are obtained. ethyl) cyclopropane-1-carboxylic acid. Mp 150 ° C.

This product is a mixture of two isomers (A) and (B) which are highlighted by the spectrum of R.M.N. Indeed, the spectrum of R.M.N. makes it possible to detect a compound (corresponding approximately to 2/3 of the mixture) having peaks at 1.31-1.43 ppm corresponding to the hydrogens of the geminated methyls, and peaks from 5.33 to 5.66 ppm corresponding to the hydrogen attached to the asymmetric monobrominated carbon and another compound (corresponding to approximately 1/3 of the mixture) having peaks at 1.28-1.48 ppm corresponding to the hydrogens of the twin methyls and peaks from 4.24 to 5.34 ppm corresponding to the hydrogen fixed on the asymmetric monobromo carbon.

In the mixture, we detect, moreover, peaks of 1.67 to 2.17 p.p.m. (hydrogens in positions 1 and 3 of cyclopropane) and a peak towards 11.25 p.p.m. (mobile hydrogen of the acid function).

The analysis of the mixture obtained (F = 150 ° C) is as follows: C8H10Br4O2 (457.804)

Calculated: C% 20.90 H% 2.20 Br% 69.82 Found: 20.9 2.2 70.2

Stage B: Acid chloride (IR.cis) 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrabromo ethyl) cyclopropane-1-carboxylic:

0.2 cm3 of dimethyl formamide, 8.5 cm3 of thio-nyl chloride are introduced into 179 cm 3 of petroleum ether (bp 35-75 °), the mixture is brought to reflux, 35.76 g of d 'acid (1R, cis) 2,2-dimethyl 3- (1, 2', 2 ', 2'-tetrabromo ethyl) cyclopropane-1-carboxylic acid in 150 cm3 of methylene chloride, stirred for 2 hours at reflux, cools, concentrates to dryness by distillation, adds toluene, concentrates again to dryness by distillation under reduced pressure and obtains 38 g of crude acid chloride (mp = 88 ° C.) used as it is for the following stage.

Stage C: (1R, cis) 2,2-dimethyl 3- (1, 2 ', 2', 2'-tetrabromo ethyl) cyclopropane-1-carboxylate of (S) a-cyano 3-phenoxy benzyl:

7.5 cm3 of pyridine are introduced into a solution of 18.4 g of (S) a-cyano 3-phenoxy benzyl alcohol in 100 cm3 of benzene, then at 38 ° C., under an inert atmosphere, the 38 g of the crude acid chloride obtained in stage B, stirred for 15 hours at 20 ° C, added water, stirred, separated the organic phase by decantation, extracted with benzene, washed the benzene phases with water, sodium bicarbonate, with water, with normal hydrochloric acid, then with water, dried, concentrated to dryness by distillation under reduced pressure, purifies the residue by chromatography on silica gel and obtains the (1R, cis) 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrabromo ethyl) cyclopropane-1-carboxylate of (S) a-cyano 3-phenoxy benzyl in the form of a mixture of isomer (A) and isomer (B).

Analogously to that of the preceding examples, the compounds described in the following examples were prepared.

Example 4

(IR, trans) 2,2-dimethyl 3- (l ', 2', 2'2'-tetrabromo ethyl) cy-clopropane-1-carboxylate de (RS) a-cyano 3-phenoxy benzyle

This compound is obtained by the action of bromine on (IR, trans) 2,2-dimethyl 3- (2 ', 2'-dibromo vinyl) cyclopropane-l-carboxylate de (RS) a-cyano 3-phenoxy benzyle, mixture of isomers (A) and (B).

Spectrum I.R. (Chloroform)

Absorption at 1740.1586 and 1486 cm-1.

Spectrum of R.M.N.

Peaks at 1.20 - 1.26 - 1.35 p.p.m. (2-methyl hydrogens of cyclopropane); peaks at 4.3-4.48 ^, 67 p.p.m. (hydrogen in 1 'of the ethyl chain in 3 of cyclopropane); peak at 6.48 p.p.m. (hydrogen attached to the same carbon as C = N); peaks from 6.97 to 7.17 p.p.m. (hydrogens of aromatic rings).

Example 5

(IR, trans) 2,2-dimethyl 3- (2 ', 2' -dichloro-1 ', 2' -dibromo ethyl) cyclopropane-l-carboxylate de (RS) a-cyano-3-phenoxy benzyle

This compound was obtained by bromination of (IR, trans) 2,2-dimethyl 3- (2 ', 2'-dichloro vinyl) cyclopropane-l-carboxylate of (RS) a-cyano 3-phenoxy benzyl, mixture of isomers (A) and (B).

Spectrum I.R. (Chloroform)

Absorption at 1743 cm-1.1588 cm-1.1487 cm-1.

Spectrum of R.M.N.

Peaks at 1.20-1.26-1.32—1.35 ppm (methyl hydrogens in position 2 of cyclopropane; peaks at 1.68-1.77 ppm (hydrogen in 1 of cyclopropane); peaks at 1, 95-2.42 ppm (hydrogen in 3-cyclopropane); peaks at 4.23-4.25-4.40-4.42- 4.57 ppm (hydrogen in the ethyl chain in 3-cyclopropane) ; peak at 6.48 ppm (hydrogen fixed on the same carbon as C = N); peaks from 7.0 to 1.67 ppm (hydrogen from aromatic rings).

Example 6

(IR, trans) 2,2-dimethyl3- (l ', 2', 2 ', 2'-tetrabromo ethyl) cyclopropane-l -carboxylate de (S) 1 -oxo-2-allyl 3-methyl cyclo-pent- 2-by-4-yle

Stage A: Acid (IR, trans) 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrabromo ethyl) cyclopropane-1-carboxylic:

This compound is obtained by bromination of (IR, trans) 2,2-dimethyl 3- (2 ', 2'-dibromo vinyl) cyclopropane-1-carboxylic acid, mixture of isomers (A) and (B).

Spectrum of R.M.N.

Peaks of 1.30 to 1.40 p.p.m. (hydrogens of the 2-methyls of cyclopropane); peaks at 1.65-1.74 and 1.97 at 2.37 p.p.m. (hydrogens in 1 and 3 of cyclopropane); peaks at 4.30-4.47 and 4.47-4.65 p.p.m. (hydrogen to ethyl); peak at 9.63 p.p.m. (carboxyl hydrogen).

Stage B: Acid chloride (IR, trans) 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrabromo ethyl) cyclopropane-1-carboxylic:

By the action of thionyl chloride on the acid (IR, trans) 2,2-dimethyl 3- (r, 2 ', 2', 2'-tetrabromo ethyl) cyclopropane-1-carboxylic obtained in stage A, the acid chloride used as is for the next stage.

Spectrum I.R. (Chloroform)

Absorption at 1778 cm-1.

Stage C: (IR, trans) 2,2-dimethyl3- (1 ', 2', 2 ', 2'-tetrabromo ethyl) cyclopropane-1-carboxylate of (S) 1 -oxo 2-allyl 3-methyl cyclopent- 2-by-4-yle:

By action (in the presence of pyridine) of (S) 1-oxo 2-allyl 3-methyl cyclopent-2-en 4-ol on the above acid chloride, the (IR, trans) 2,2-dimethyl is obtained 3- (l ', 2', 2 ', 2'-tétrabromo

5

10

15

20

25

30

35

40

45

50

55

60

65

630 890

10

ethyl) cyclopropane-1-carboxylate of (S) 1-oxo 2-allyl 3-methyl cycIopent-2-en 4-yl, mixture of isomers (A) and (B).

Spectrum I.R. (Chloroform)

Absorption at 1,725 cm-1,1710 cm-1,1655 cm-1,1638 cm "" 1,995 cm-1,918 cm-1.

Spectrum of R. M.N.

Peaks at 1.30-1.32-1.36 p.p.m. (2-methyl hydrogens of cyclopropane); peaks at 1.98 - 2.05 p.p.m. (3-methyl hydrogens of allethrolone); peaks at 4.82-5.25 p.p.m. (hydrogens of the terminal methylene of the allylic chain of allethrolone); peaks at 4.30-4.48 and 4.48 ^ 4.67 p.p.m. (hydrogens in 1 'of the ethyl side chain in 3 of the cyclopropane ring); peaks at 5.33-6.17 p.p.m. (hydrogen in position 2 'of the allylic chain of allethrolone.

Example 7

(1R, cis) 2,2-dimethyl 3- (1, 2 ', 2', 2'-tetrabromo ethyl) 5-benzyl 3-furyl methyl cyclo-propane-1-carboxylate Isomers (A) and (B )

By esterification, in the presence of pyridine, of the acid chloride obtained in Stage B of Example 3 with 5-benzyl 3-furyl methanol, one obtains:

a) The (A) isomer of (1R, cis) 2,2-dimethyl 3- (1, 2 ', 2', 2'-t-trabromo ethyl) cyclopropane-1-carboxylate of 5-benzyl 3- furyl methyl.

[a] D = —104 ° (c = 0.5%, benzene). The most mobile isomer in thin layer chromatography.

Spectrum of R.M.N.

Peaks at 1.23-1.37 p.p.m. (2-methyl hydrogens of cyclopropane); peaks at 1.65-2.03 p.p.m. (hydrogens in 1 and 3 of cyclopropane); peak at 3.92 p.p.m. (methylene benzyl hydrogens); peak at 4.92 p.p.m. (CO 2 -CH 2 methylene hydrogens); peaks at 5.27-5.67 p.p.m. (hydrogen in 1 'of the ethyl chain in 3 of cyclopropane); peak at 5.96 p.p.m. (hydrogen in 4 of furyl); peak at 7.25 p.p.m. (phenyl hydrogens); peak at 7.33 p.p.m. (hydrogen in 2 of furyl).

Circular dichroism (dioxane)

A e = - 6.5 to 2.17 nm.

b) The (B) isomer of (1R, cis) 2,2-dimethyl 3- (1,2 ', 2', 2'-t-trabromo ethyl) cyclopropane-1-carboxylate of 5-benzyl 3- furyl methyl.

[a] D = + 84 ° (c = 0.5%, benzene).

Spectrum of R.M.N.

Peaks at 1.20-1.42 p.p.m. (2-methyl hydrogens of cyclopropane); peaks of 1.67 to 2.17 p.p.m. (hydrogens in 1 and 3 of cyclopropane); peak at 3.92 p.p.m. (methylene benzyl hydrogens); peak at 4.95 p.p.m. (CO 2 -CH 2 methylene hydrogens); peaks from 4.95 to 5.18 p.p.m. (hydrogen in 1 'of the ethyl chain in 3 of cyclopropane); peak at 7.25 p.p.m. (hydrogens of the aromatic benzyl ring); peak at 7.33 p.p.m. (hydrogen in position 2 of furyl).

Circular dichroism (dioxane)

A e = + 4.30 at 247 nm.

Example 8

(IR.cis) 2,2-dimethyl3- (l ', 2', 2 ', 2'-tetrabromo ethyl) cyclopropane-l-carboxylate de (S) 1 -oxo 2-allyl 3-methyl cyclopent-2-en 4-yle (Isomers A and B)

By esterification of (S) 1-oxo 2-allyl 3-methyl cyclopent 2-en 4-ol, in the presence of pyridine, with acid chloride (1R, cis) 2,2-dimethyl 3- (l , 2 ', 2', 2'-tetrabromo ethyl) 1-carboxylic cyclopropane obtained in Stage B of Example 3, we obtain:

a) The (A) isomer of (1R, cis) 2,2-dimethyl 3- (1, 2 ', 2', 2'-t-trabromo ethyl) cyclopropane-1-carboxylate of (S) 1- oxo 2-al-lyl 3-methyl cyclopent-2-en 4-yl.

[a] D = - 56 ° (c = 0.6%, benzene).

Spectrum of R.M.N.

Peaks at 1.28-1.39 p.p.m. (2-methyl hydrogens of cyclopropane); peak at 1.96 p.p.m. (methyl hydrogens in 3 of allethrolone); peaks at 4.83-5.16 p.p.m. (hydrogens of the methylene terminal of the allylic chain); peaks of 5.33 to 6.16 5 p.p.m. (hydrogen in 1 'of the ethyl chain in position 3 of the cyclopropane and hydrogen in 2' of the allylic chain). Circular dichroism (dioxane)

Ae = +1.84 at 332 nm;

A e = +2.06 at 320 nm;

io A e = - 19 at 225 nm.

The (A) isomer is the most mobile in thin layer chromatography.

b) The (B) isomer of (IR, eis) 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrabromo ethyl) cyclopropane-1-carboxylate of (S) 1-oxo 15 2-allyl 3-methyl cyclopent-2-en 4-yl. Mp 110 ° C.

[a] D = + 81 ° (c = 0.6%, benzene).

Spectrum of R.M.N.

Peaks at 1.27-1.47 p.p.m. (2-methyl hydrogens of cyclopropane); peak at 2.07 p.p.m. (3-methyl methyl hydrogens of allethrolone); peaks from 4.83 to 5.33 p.p.m. (hydrogen in 1 'of the side chain in 3 of cyclopropane and hydrogen of methylene in 2' of the allylic chain); peaks at 5.5-6.16 p.p.m. (hydrogens in 2 ′ of the allylic chain); peak at 5.15 p.p.m. (hydrogens in 4 of allethrolone).

25 Circular dichroism (dioxane)

A 8 = +2.46 at 332 nm;

A 8 = +2.76 at 320 nm A e = +3.79 at 250 nm A 8 = —14.7 at 225 nm.

30

Example 9

(1R, cis) 2,2-dimethyl 3- (1 ', 2', 2'2'-tetrabromo ethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl (Isomers A and B) By esterification in the presence of pyridine, (1R, cis) 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrabromo ethyl) cyclopropane-1-carboxylic acid chloride with 3-phenoxy benzyl alcohol, obtains:

a) The (A) isomer of (1R, cis) 2,2-dimethyl 3- (1, 2 ', 2', 2'-t-trabromo ethyl) cyclopropane-1-carboxylate of 3-phenoxy ben-

40 zyle. Mp 90 ° C.

[a] D = - 106 ° (c = 0.5%, benzene).

Spectrum of R. M. N.

Peaks at 0.92-1.37 p.p.m. (2-methyl hydrogens of cyclopropane); peaks at 1.67-2.08 p.p.m. (hydrogens in positions 1 and 3 of cyclopropane); peak at 5.08 p.p.m. (CO 2 CH 2 methylene hydrogens); peaks at 5.38-5.56 p.p.m. (hydrogen in position 1 'of the ethyl fixed in 3 of the cyclopropane); peaks of 6.67 to 7.58 p.p.m. (hydrogens of the aromatic nucleus).

Circular dichroism (dioxane)

50 a e = - 10 to 218 nm.

The (A) isomer is the most mobile in thin layer chromatography.

b) The (B) isomer of (1R, cis) 2,2-dimethyl 3- (1, 2 ', 2', 2'-t-trabromo ethyl) cyclopropane-1-carboxylate of 3-phenoxy ben-

55 zyle.

[a] D = + 61.5 ° (c = 2.3%, benzene).

Spectrum of R. M.N.

Peaks at 1.22-1.42 p.p.m. (2-methyl hydrogens of cyclopropane); peaks of 1.67 to 2.08 p.p.m. (hydrogens in 1 and 3 n / a of cyclopropane); peaks from 4.93 to 5.33 p.p.m. (hydrogen in 1 'of ethyl in 3 of cyclopropane); peak at 5.15 p.p.m. (methylene hydrogens of CÓ2CH2); peaks of 6.75 to 7.58 p.p.m. (hydrogens of the aromatic nucleus).

Circular dichroism (dioxane)

65 A 8 = + 4.6 at 247 nm.

Example 10

(IR, trans) 2,2-dimethyl 3- (2 ', 2' -dichloro 1 ', 2'-dibromo

11

630 890

(S) 1-oxo-2-allyl 3-methyl cyclopent-2-en-4-yl ethyl) cyclopropane-1-carboxylate

Stage A: Acid (IR, trans) 2,2-dimethyl3- (2 ', 2'-dichloro 1', 2'-dibromo ethyl) cyclopropane-1-carboxylic:

By the action of bromine on the acid (IR, trans) 2,2-dimethyl 3- (2 ', 2'-dichloro vinyl) cyclopropane-1-carboxylic, the acid is obtained (IR, trans) 2,2- dimethyl 3- (2 ', 2'-dichloro l', 2'-di-bromo ethyl) cyclopropane-1-carboxylic, mixture of isomers (A) and (B).

Spectrum of R. M. N.

Peaks at 1.17-1.37 p.p.m. (2-methyl hydrogens of cyclopropane); peaks of 1.65-1.73 p.p.m. to 1.93-2.03 p.p.m. (hydrogens in 1 of cyclopropane); peaks at 4.23-4.45 and 4.45-4.62 p.p.m. (hydrogen in 1 'of ethyl in 3 of cyclopropane). Stage B: Acid chloride (IR, trans) 2,2-dimethyl3- (2 ', 2'-dichloro 1', 2'-dibromo ethyl) cyclopropane-1-carboxylic: By action of thionyl chloride on l acid prepared in the preceding stage A, the chloride of the acid (IR, trans) 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromoethyl) cyclopropane-1-carboxylic is obtained.

Spectrum I.R. (Chloroform)

Absorption at 1777 cm-1.

Stage C: (IR, trans) 2,2-dimethyl3- (2 ', 2'-dichloro 1', 2'-dibro-mo ethyl) cyclopropane-1-carboxylate of (S) 1-oxo 2-allyl3-mé -thyl cyclopent-2-en 4-yle:

By esterification in the presence of pyridine, of the acid chloride prepared previously in stage B, with (S) 1-oxo 2-allyl 3-methyl cyclopent-2-en 4-ol, the (IR, trans) 2 is obtained , 2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromo ethyl) cyclopropane-l-carboxylate de (S) 1-oxo 2-allyl 3-methyl cyclopent-2-en 4-yl sous form of mixture of isomers (A) and (B).

Spectrum of R. M. N.

Peaks of 1.30 to 1.34 p.p.m. (2-methyl hydrogens of cyclopropane); peaks of 1.63 to 3.0 p.p.m. (hydrogens in 1 and 3 of cyclopropane); peak at 2.05 p.p.m. (methyl hydrogens in 3 of allethrolone); peaks at 1.95-3.03 p.p.m. (methylene hydrogens at 1 'of the allylic chain); peaks at 4.25-4.43 ^, 61 p.p.m. (hydrogen in 1 'of ethyl in 3 of cyclopropane); peak of 4.25 p.p.m. (methylene hydrogens in the terminal position of the allylic chain); peaks 4.83 to 5.41 p.p.m. (hydrogen in position 2 'of the allylic chain); peak at 5.83 p.p.m. (hydrogens in 4 of allethrolone).

Example 11

(1R, cis) 2,2-dimethyl3- (2 ', 2'-dibromo 1', 2'-dichloro ethyl) cyclopropane-l-carboxylate de (RS) a-cyano 3-phenoxy benzyle

Stage A: (1R, cis) 2,2-dimethyl 3- (2 ', 2' -dibromo 1 ', 2'-dichloroethyl) cyclopropane-1-carboxylic acid:

11.8 g of chlorine are bubbled into 30 cm3 of carbon tetrachloride at -15 ° C., then slowly added at -10 ° C., 24 g of an acid solution (1R, cis) 2, 2-dimethyl 3- (2 ', 2'-dibromo vinyl) cyclopropane-1-carboxylic acid in 37 cm3 of methylene chloride, stirred for 1 hour and 30 minutes at 0 ° C and for 2 hours at 25 ° C, concentrated under reduced pressure, purifies by crystallization from carbon tetrachloride and obtains 7.4 g of acid (1R, cis) 2,2-dimethyl 3- (2 ', 2'-dibromo 1', 2'-dichloro ethyl) cyclopropane -l-carboxylic. M = 134 ° C (mixture of isomers (A) and (B)).

Spectrum of R. M.N.

Peaks at 1.32-1.44 and 1.28-1.48 p.p.m. (2-methyl hydrogens of cyclopropane); peaks at 5.08-5.45 and 4.67-5.0 p.p.m. (hydrogen at 1 'of the ethyl chain in position 3 of the cyclopropane); peak at 10.1 p.p.m. (carboxyl hydrogen).

Stage B: Acid chloride (IR.cis) 2,2-dimethyl 3- (2 ', 2'-di-bromo 1', 2 '-dichloro ethyl) cyclopropane-1-carboxylic:

By the action of thionyl chloride in the presence of pyridine on the acid obtained in the preceding stage A, the acid chloride is obtained (1R, cis) 2,2-dimethyl 3- (2 ', 2'-dibromo l' , 2'-dichloro ethyl) cyclopropane-1-carboxylic acid, used as it is for the following stage.

Stage C: (1R, cis) 2,2-dimethyl3- (2 ', 2'-dibromo 1', 2'-dichloro 5 ethyl) cyclopropane-1-carboxylate of (RS) a-cyano 3-phenoxy benzyl:

By esterification of the alcohol (RS) a-cyano 3-phenoxy benzyl in the presence of pyridine with the acid chloride obtained in the preceding stage B, the (1R, cis) 2,2-dimethyl io 3- (2 ', 2'-dibromo 1', 2'-dichloro ethyl) cyclopropane-1-carboxy-late from (RS) a-cyano 3-phenoxy benzyl, mixture of isomers (A) and (B).

Spectrum of R. M. N.

Peaks at 1.23-1.52 p.p.m. (2-methyl hydrogens of cyclopropane); peaks of 1.77 to 2.11 p.p.m. (hydrogens in 1 and 3 of cyclopropane); peaks at 4.72 ^, 88 and 5.02-5.21 p.p.m. (hydrogen at 1 'of the ethyl side chain in position 3 of cyclopropane); peaks of 6.40 to 6.43 p.p.m. (hydrogen carried by the same carbon as C = N); peaks from 6.94 to 7.66 p.p.m. 2o (hydrogens of aromatic rings.

Example 12

(1R, cis) 2,2-dimethyl3- (2 ', 2' -dibromo 1 ', 2'-dichloro ethyl) cyclopropane-l -carboxylate of (S) 1 -oxo 2-allyl 3-methyl cyclo-25 pent -2-in 4-yle

By esterification of the acid chloride obtained in stage B of Example 11, with (S) 1-oxo 2-allyl 3-methyl cyclopent-2-in 4-ol, the (1R, cis) 2 is obtained, (S) 1-oxo 2-allyl 3-methyl cyclopent-2-en 4-yl 2-dimethyl 3- (2 ', 2'-dibromo l', 2'-dichloro ethyl) cyclopropane-1-carboxylate, mixture of isomers (A) and (B).

Spectrum of R. M.N.

Peaks at 1.25-1.45 and 1.29-1.40 p.p.m. (2-methyl hydrogens of cyclopropane); peak at 1.96 p.p.m. (methyl hydrogens in 3 of allethrolone); peaks at 2.96-3.03 p.p.m. (methylene hydro-genes 1 'to the allylic chain); peaks at 4.83-5.16 p.p.m. (hydrogens of the methylene terminal of the allylic chain); peaks at 5.25-5.36 p.p.m. (hydrogen in 1 'of the ethyl chain in 3 of cyclopropane); peaks of 5.5 to 6.0 p.p.m. (hydrogens in 4 of allethrolone and hydrogen in 2 'of the allylic chain).

Example 13

(IR, trans) 2,2-dimethyl3- (2 ', 2'-dibromo 1', 2'-dichloro ethyl) cyclopropane-l-carboxylate de (RS) a-cyano 3-phenoxy 45 benzyl

By the action of chlorine on the acid (IR, trans) 2,2-dimethyl 3- (2 ', 2'-dibromo vinyl) cyclopropane-1-carboxylic, the acid is obtained (IR, trans) 2,2- dimethyl 3- (2 ', 2'-dibromo 1' ^ '- dichloro ethyl) cyclopropane-l-carboxylic which is transformed 5t into acid chloride by action of thionyl chloride, then esterified as before by alcohol (RS) a-cyano 3-phenoxy benzyl and obtains the (IR, trans) 2,2-dimethyl 3- (2 ', 2'-dibromo l', 2'-dichloro ethyl) cyclopropane- 1-carboxy-late from (RS) a-cyano 3-phenoxy benzyl, mixture of isomers 55 (A) and (B).

Spectrum of R. M. N.

Peaks at 1.22-1.27-1.37-1.4-1.45 p.p.m. (2-methyl hydrogens of cyclopropane); peaks of 1.67 to 2.5 p.p.m. (hydrogens in 1 and 3 of cyclopropane); peaks of 3.67 to 4.5 p.p.m. 60 (hydrogen in 1 'of the ethyl chain in 3 of cyclopropane); peak at 6.52 p.p.m. (hydrogen carried by the same carbon as C = N; peaks from 7.0 to 7.67 p.p.m. (hydrogen from aromatic rings).

65 Example 14

(IR, trans) 2,2-dimethyl3- (2 ', 2'-difluoro 1', 2'-dibromo ethyl) cyclopropane-l-carboxylate de (S) 1-oxo 2-allyl 3-methyl cyclopent-2- in 4-yle

630 890

12

Stage A: Acid (IR, trans) 2,2-dimethyl3- (2 ", 2'-difluoro 1 ', 2'-dibromo ethyl) cyclopropane-1-carboxylic:

Analogously to those described above by the action of bromine on (IR, trans) 2,2-dimethyl 3- (2 ', 2'-di-fluoro vinyl) cyclopropane-1-carboxylic acid, but operating at - 60 ° C, there is obtained (IR, trans) 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2'-dibromo ethyl) cyclopropane-1-carboxylic acid. M = 122 ° C (mixture of isomers (A) and (B)).

Spectrum of R. M.N.

Peaks of 1.33 to 1.36 p.p.m. (3-methyl hydrogens of cyclopropane); peaks of 1.60 to 2.23 p.p.m. (hydrogens in 1 and 3 of cyclopropane); peaks of 3.75 to 4.37 p.p.m. (hydrogen in 1 'of the ethyl chain in 3 of cyclopropane); peak at 10.96 p.p.m. (carboxyl hydrogen).

Stage B: Acid chloride (IR, trans) 2,2-dimethyl 3- (2 ', 2' -difluoro 1 ', 2'-dibromo ethyl) cyclopropane-1-carboxylic:

By the action of thionyl chloride on the acid obtained in the preceding stage A, the acid chloride (IR, trans) 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2'-) is obtained. dibromo ethyl) cyclopro-pane-1-carboxylic used as such for the next stage.

Stage C: (IR, trans) 2,2-dimethyl3- (2 ', 2' -difluoro 1 ', 2'-dibro-mo ethyl) cyclopropane-1-carboxylate of (S) 1-oxo 2-allyl 3- m-thyl cyclopent-2-en 4-yle:

By esterification of the acid chloride obtained in the preceding stage B, with (S) 1-oxo 2-allyl 3-methyl cyclopent-2-en 4-ol in the presence of pyridine, the (IR, trans) 2 is obtained, 2-dimethyl 3- (2 ', 2'-difluoro l', 2'-dibromo ethyl) cyclopropane-l-carboxylate de (S) 1-oxo 2-allyl 3-methyl cyclopent-2-en 4-yl, mixture of isomers (A) and (B).

Spectrum of R. M. N.

Peak at 1.32 p.p.m. (2-methyl hydrogens of cyclopropane); peaks of 3.26 to 1.68 and 1.73 to 2.19 p.p.m. (hydrogens in 1 ′ of cyclopropane); peak at 1.20 p.p.m. (methyl hydrogens in 3 of allethrolone); peaks of 2.93 to 3.05 p.p.m. (methylene hydrogens at 1 'of the allylic chain); peaks of 4.83 to 5.25 p.p.m. (hydrogens of methylene terminal of the allylic chain); peaks of 3.58 to 4.33 p.p.m. (hydrogen at 1 'of the ethyl chain in position 3 of the cyclopropane); peaks of 4.83 to 5.25 p.p.m. (hydrogen 2 'to the allylic chain); peak at 5.83 p.p.m. (hydrogens in 4 of allethrolone).

Example 15

(1R, cis) 2,2-dimethyl3- (2 ', 2'-dichloro 1', 2'-dibromo ethyl) cyclopropane-l-carboxylate de (RS) a-cyano 3-phenoxy benzyle

Stage A: Acid (1R, cis) 2,2-dimethyl3- (2 ', 2' -dichloro l ', 2'-di-bromo ethyl) cyclopropane-1 -carboxylic:

By the action of bromine on (lR, cis) 2,2-dimethyl 3- (2 ', 2'dichloro vinyl) cyclopropane-1-carboxylic acid, the (lR, cis) 2,2-dimethyl acid is obtained 3- (2 ', 2'-dichloro l', 2'-dibromo ethyl) cyclopropane-1-carboxylic, mixture of isomers (A) and (B).

Spectrum of R. M. N.

Peaks at 1.26-1.30 and 1.41-1.42 p.p.m. (3-methyl hydrogens of cyclopropane); peaks at 1.83-2.17 p.p.m. (hydrogens in 1 and 3 of cyclopropane); peaks of 4.83 to 5.58 p.p.m. (hydrogen in 1 'of ethyl in 3 of cyclopropane); peak at 8.17 p.p.m. (carboxyl hydrogen).

Stage B: Acid chloride (1R, cis) 2,2-dimethyl3- (2 ', 2'-di-chloro 1', 2'-dibromo ethyl) cyclopropane-1-carboxylic:

It is obtained by the action of thionyl chloride on the acid obtained in the preceding stage A.

Stage C: (IR.cis) 2,2-dimethyl3- (2 ', 2'-dichloro 1', 2'-dibromo ethyl) cyclopropane-1-carboxylate from (RS) a-cyano 3-phenoxy benzyl:

It is obtained by esterification in the presence of pyridine, the acid chloride obtained in the preceding stage B, with alcohol

(RS) a-cyano-3-phenoxy benzyl, mixture of isomers (A) and (B).

5 Example 16

1R, cis2,2-dimethyl3- (2 ', 2', 2 ', V-tetrabromoethyl) cyclo-propane-1 -carboxylate of RS a-cyano 3-phenoxy benzyl.

Stage A: Acid chloride 1R, cis 2,2-dimethyl3- (2 ', 2', 2 ', 1' -tetrabromoethyl) cyclopropane-1-carboxylic.

In a mixture of 40 cm3 of petroleum ether (bp 35-70 ° C) and 10 cm3 of thionyl chloride, 8.9 g of acid (1R, cis) 2,2-dimethyl are introduced. 3- (2 ', 2', 2 ', 1'-tetrabromoethyl) cyclopropane-l-carboxylic, brings to reflux, maintains reflux for 3 hours, eliminates petroleum ether and excess thionyl chloride by distillation and obtain the chloride of lR, cis 2,2-dimethyl 3- (2 ', 2', 2 ', l'-tetrabromoethyl) cyclopropane-1-carboxylic acid chloride.

Stage B: IR, is 2,2-dimethyl 3- (2 ', 2', 2 ', 1'-tetrabromoethyl) cy-clopropane-1-carboxylate of RS a-cyano 3-phenoxy benzyl. 20 g of a-cyano 3-phenoxy benzyl alcohol are introduced into a mixture of 5 cm 3 of benzene and 10 cm 3 of pyridine, crude acid chloride obtained in the stage at about 0 ° C. A, dissolved in 40 cm3 of benzene, stirred at 20 ° C, for 16 hours, acidified to pH 1 with a dilute aqueous solution of hydrochloric acid, extracted with benzene, washed the organic phase with water, dries over magnesium sulfate and concentrates the benzene solution to dryness; the residue is chromatographed on silica gel, eluting with benzene, to give 7.33 g of 1R, cis 2,2-dimethyl 3- (2 ', 2', 2 ', 1'-tetrabromoethyl) cyclopropane-1- R, S a-cyano 3-phenoxy benzyl carboxylate.

Analysis: Ç ^ HjgQsN Br4 (665.05)

Calculated: C% 39.73 H% 2.88 N% 2.10 Br% 48.06 Found: 39.7 3 2.2 47.4

35 Infra-Red Spectrum (chloroform)

Absorption at 1743 cm-1, characteristic of carbonyl; absorptions at 1613.1588.1477 cm-1, characteristics of aromatic nuclei.

40 Spectrum U. V. (ethanol)

Inflection at 230 nm (E | = 194);

Inflection at 270 nm (E | = 36);

45 Maximum at 278 nm (E j = 37);

Inflection at 285 nm (E j = 28).

Spectrum of R.M.N. (deuterochloroform)

50 peaks of 1.23-1.5 p.p.m., characteristics of the hydrogens of the twin methyls; peaks at 1.84 - 2.16 p.p.m., characteristics of the cyclopropyl hydrogens; peaks at 4.82-5.5 p.p.m., characteristics of the hydrogen in position 1 'of the substituted ethyl side chain, peaks at 6.37-6.42 p.p.m.; characteristics of the drogen hy-55 attached to the same carbon as the group -C = N, peaks of 6.83-7.58 p.p.m. characteristics of the hydrogens of the aromatic rings.

The 1R, cis 2,2-dimethyl 3- (2 ', 2', 2 ', 1' -tetrabromoethyl) cyclopropano-1-carboxylic acid used in stage A can be prepared in the following manner:

In 30 cm3 of carbon tetrachloride, 5 g of lR, cis 2,2-dimethyl 3- (2 ', 2'-dibromovinyl) cyclopropane-1-carboxylic acid are introduced, a solution of approximately 30 minutes is added. 0.9 cm3 of bromine in 10 cm3 of car-65 bone tetrachloride, stirred for one hour and 30 minutes, concentrated to dryness under reduced pressure and obtained 8.9 g of 1R acid, cis 2,2-dimé-thyl 3- (2 ', 2', 2 ', 1' -tetrabromoethyl) cyclopropane- 1-carboxyli-que crude.

13

630 890

Example 17

1 R, trans 2,2-dimethyl 3- (2 ', 2', 2 ', 1'-tetrabromoethyl) cyclo-propane-1-carboxylate of 3-phenoxy benzyl.

5 g of IR acid chloride, trans 2,2-dimethyl 3- (2 ', 2', 2 ', l'-tetrabromoethyl) cyclopropane-l-carboxylic acid, are dissolved in 20 cm 3 of benzene g of 3-phenoxy benzyl alcohol, cooled to 0 ° C, gradually introduced 4 cm3 of pyridine, stirred for 48 hours at 20 ° C, poured the reaction mixture into an aqueous solution of hydrochloric acid, extracted with benzene, washed with sodium bicarbonate, with water, dried over sodium sulfate and concentrated to dryness by distillation under reduced pressure. 6.2 g of residue are obtained which is chromatographed on silica gel eluting with a mixture of petroleum ether (bp 35-75 ° C) and ethyl ether (9/1) and thus collects 3 , 68 g of IR, trans 2,2-dimethyl 3- (2 ', 2', 2 ', 1' -tetrabromoethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl (mixture of isomers A and B).

Analysis: C2iH2oBr403 (640.03)

Calculated: C% 39.41 H% 3.15 Br% 49.94 Found: 39.9 3.2 50.2

I.R. spectrum (chloroform)

Absorption at 1728 cm-1, characteristic of carbonyl, absorptions at 1615-1590-1490 cm "1, characteristic of aromatic rings.

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.26-1.29-1.35 p.p.m., characteristic of the hydrogens of the twin methyls; peaks at 2.00-2.33 p.p.m., characteristics of the hydrogen in position 1 of the cyclopropyl; peaks at 1.70-1.79 ppm, characteristics of hydrogen in position 3 of cyclopropyl, peaks at 4.31-4.48-4.50-4.67 ppm, characteristics of hydrogen in position 1 ' substituted ethyl side chain; peaks at 5.17-5.20 p.p.m., characteristics of the methylene hydrogens of the benzyl radical, peaks at 6.92-7.58 p.p.m., characteristics of the hydrogens of the aromatic rings.

The IR acid chloride, trans 2,2-dimethyl 3- (2 ', 2', 2 ', l'-tetrabromoethyl) cyclopropane-l-carboxylic acid used from the present example can be obtained in the following way: Stage A: IR acid, trans 2,2-dimethyl3- (2 ', 2', 2 ', 1'-tetrabromoethyl) cyclopropane-1 -carboxylic.

Bromine is made to act on IR acid, trans 2,2-dimethyl 3- (2 ', 2'-dibromovinyl) cyclopropane-1-carboxylic acid in a similar fashion to that used in Example 16 and IR acid is obtained , trans 2,2-dimethyl 3- (2 ', 2', 2 ', 1' -tetrabromoethyl) cyclopropane-1-carboxylic (mixture of isomers A and B).

Spectrum of R.M.N. (deuterochloroform)

Peaks of 1.30 to 1.40 p.p.m. (hydrogens of the 2-methyls of cyclopropyl); peaks at 1.65-1.74 and 1.97-2.37 p.p.m., hydrogens at 1 and 3 of cyclopropyl; peaks at 4.30-4.47 and 4.47-4.65 p.p.m., (hydrogen in ethyl); peak at 9.63 p.p.m. (carboxyl hydrogen).

Stage B: IR acid chloride, trans 2,2-dimethyl3- (2 ', 2', 2 ', V-tetrabromoethyl) cyclopropane-1-carboxylic.

By the action of thionyl chloride on the acid obtained in Stage A, in a manner analogous to that of Example 16, the acid chloride IR, trans 2,2-dimethyl 3- (2 ', 2') is obtained. , 2 ', 1'-tetrabromoethyl) cyclopropane-l -carboxylic.

Example 18

1R, cis 2,2-dimethyl3- (2 ', 2', 2 ', 1'-tetrachloroethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl.

Stage A: 1R acid, cis 2,2-dimethyl3- (2'2 ', 2', f -tetrachloroethyl) cyclopropane-1 -carboxylic acid.

In 30 cm3 of carbon tetrachloride, the chlorine is bubbled until saturation (11.8 g of chlorine is dissolved), a solution of 16.7 g of lR acid, cis 2.2 is introduced in approximately 30 minutes. dimet ^ vl 3- (2 ', 2'-dichlorovinyl) cyclopropane-l-carboxylic

15

25

in 40 cm3 of methylene chloride, at a temperature below 0 ° C, stirred for 24 hours at 0 ° C, brought the temperature of the reaction mixture to +25 ° C, stirred for 3 hours at this temperature, removed the chlorine in bubbling excess of nitrogen, concentrated to dryness by distillation, under reduced pressure, purifies the residue by chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (8/2), crystallized from l 'petroleum ether (bp 35-75 ° C) and obtains 3.14 g of lR acid, cis 2,2-dimethyl3- (2', 2 ', 2', l'-tetrachloroethyl) cy-10 clopropane -l-carboxylic F = 144 ° C.

Analysis: C8H10Cl4O2 (279.98)

Calculated: C% 34.3 H% 3.6 Cl% 50.6 Found: 34.4 3.7 50.3.

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.26-1.42 p.p.m. and 1.30-1.42 p.p.m. characteristics of the hydrogens of twin methyls; peaks of 4.67-5.17 p.p.m. and 5.08 to 5.43 p.p.m. characteristics of the hydrogen in position 1 'of the substituted ethyl side chain; peaks of 1.67 to 2.0 p.p.m., characteristic of the cyclopropyl hydrogens; peak 20 to 10.2 p.p.m., characteristic of the carboxyl hydroxide.

Stage B: Chloride of IR.cis 2,2-dimethyl 3- (2 ', 2', 2 ', 1' -tetrachloroethyl) cyclopropane-1-carboxylic acid.

6.75 g of lR, cis 2,2-dimethyl 3- acid are introduced into a mixture of 60 cm3 of petroleum ether (bp 35-70 ° C) and 8.7 cm3 of thionyl chloride (2 ', 2', 2 ', l'-tetrachloroethyl) cyclopropane-l-carboxylic, brings the reaction mixture to reflux, maintains it there for 4 hours and 30 minutes, concentrates to dryness by distillation under reduced pressure, adds benzene, concentrated to dryness and obtains the chloride of the acid lR, cis 2,2-30 dimethyl 3- (2 ', 2', 2 ', crude tetrachloroethyl) cyclopropane-l-carboxylic acid used as it is for the next stage.

Stage C: 1R, cis-2,2-dimethyl3- (2 ', 2', 2 ', 1'-tetrachloroethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl.

The crude acid chloride is dissolved in 60 cm 3 of benzene, introduced at 75 ° C., 5.2 g of 3-phenoxy benzyl alcohol in solution in 50 cm 3 of benzene, then 2.6 cm 3 of pyridine, stirred for 16 hours at 20 ° C, pour the reaction mixture into a mixture of water and hydrochloric acid, extracted with ethyl ether, and after dry concentration of the ethereal solution, obtains 11 g of residue which is chromatographed on silica gel, eluting with a mixture of benzene and cyclohexane (1/1), crystallize from ether and obtain a first fraction of 4.6 g of 1R, cis 2,2-dimethyl 3- (2 ', 2 ', 2', 3-phenoxy benzyl 1'-tetrachloroethyl) cyclopropane-1-carboxylate F = 86 ° C.

20

[a] -p- = - 86.5 ° (c = 0.5%, benzene).

Analysis: C2iH2oCl403 (462.20)

Calculated: C% 54.56 H% 4.36 CI% 30.68 n / a Found: 54.9 4.5 30.3

Vitra-Violet spectrum (ethanol)

Inflection at 226 nm E | = 228,

Inflection at 266 nm E J = 36,

55 1

Maximum at 271 nm E * = 41,

Maximum at 277 nm E | = 40.

60 Spectrum of R. M. N. (deuterochloroform)

Peaks at 1.27-1.4 p.p.m., characteristics of the hydrogens of the twin methyls of the isomer A; peak at 5.13 p.p.m., characteristic of the hydrogens of the group -C-OCH2- of the isomer A;

II

65 O

peaks at 5.27-5.43 p.p.m, characteristics of hydrogen in position 1 'of the ethyl side chain of isomer A, peaks at

40

45

630 890

14

1.23-1.40 p.p.m, characteristics of the hydrogens of the twin methyls of the isomer B, peak at 5.18 p.p.m, characteristics of the hydrogens of the group -C-OCH2 of the isomer B, peaks at

II

O

4.83-5.17 ppm, characteristics of the hydrogen in position 1 'of the ethyl side chain of the isomer B, peaks at 1.61-2.03 ppm, characteristics of the hydrogens of cyclopropyl, peaks at 6, 92-7.58 ppm, characteristics of hydrogens in aromatic rings.

This spectrum of R.M.N. shows that the compound contains approximately 9/10 of the A isomer and 1/10 of the B isomer

Continuing the chromatography, after crystallization from ether, a second 3.3 g fraction of 1R, eis 2, is obtained,

2-dimethyl 3- (2 ', 2', 2 ', 3-phenoxy benzyl-tetrachloroethyl) cyclopropane-1-carboxylate. F = 62 ° C

20

[a] -Tdd- = - 9 ° (c = 1%, benzene).

Infrared spectrum (chloroform)

Absorption at 1725 cm'1 characteristic of carbonyl,

Absorption at 1615-1590-1490 cm'1 characteristic of hydrogens in aromatic rings.

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.23-1.41 p.p.m, characteristics of the hydrogens of the twin methyls of the isomer B; peaks at 4.83-5.17 p.p.m. characteristics of hydrogen in position 1 'of the ethyl side chain of the B isomer; peak at 5.2 p.p.m. characteristics of the hydrogens of the group: -C-O-CH2- of the isomer B.

he

O

Peaks at 1.28-1.4 p.p.m. characteristics of the hydrogens of the twin methyls of the isomer A; peaks at 5.27-5.43 p.p.m. characteristics of the hydrogen in position 1 'of the ethyl side chain of the isomer A; peak at 5.13 p.p.m. characteristic of the hydrogens of the group: -C-O-CH2 of the isomer A; peaks at

II

O

1.58-2.08 p.p.m. characteristics of the cyclopropyl hydrogens; parts at 6.9-7.16 p.p.m. characteristics of hydrogens in aromatic rings.

This spectrum of R.M.N. shows that the compound contains approximately 3/5 of the B isomer and 2/5 of the A isomer.

Example 19

1R, eis 2,2-dimethyl3- (2 ', 2', 2 ', 1'-tetrachloroethyl) cyclo-propane-1-carboxylate of R, S a-cyano 3-phenoxy benzyl.

Stage A: 1R acid chloride, cis 2,2-dimethyl3- (2 ', 2', 2 ', 1'-tetrachloroethyl) cyclopropane-1-carboxylic acid.

5.4 g of IR, corresponding cis acid is used and the procedure is analogous to that used in Stage B of Example 18. Stage B: IR, is 2,2-dimethyl 3- (2 ', 2 ', 2', 1'-tetrachloroethyl) cy-clopropane-1-carboxylate of (R, S) a-cyano 3-phenoxy benzyl.

The acid chloride obtained in stage A of the present example is dissolved in 50 cm 3 of benzene, introduced at + 5 ° C., a solution of 4.6 g of alcohol R, S a-cyano 3-phenoxy benzyl, in 30 cm3 of benzene, then 2.2 cm3 of pyridine, stirred for 48 hours at room temperature, pour the reaction mixture into a mixture of water and hydrochloric acid, extract with ether, concentrate the ethereal solution to dryness, chromatography the residue on silica gel, eluting with a mixture of benzene and cyclohexane (1/2) and obtained 4.7 g of 1R, cis 2,2-dimethyl

3- (2 ', 2', 2 ', l, -tetracliloroethyl) cyclopropane-1-R, S -carboxylate a-cyano 3-phenoxy benzyl

20

[a] -dd- = - 56.5 ° (c = 0.4%, benzene).

Analysis: C22HlyCl4N 03 (487.22)

Calculated: Found:

C% 54.23 H1 54.3

> 3.93 3.8

Cl% 29.11 29.0

N% 2.87 2.8

Spetre U. V. (Ethanol)

5 Inflection at 227 nm (E j = 225);

Inflection at 268 nm (E j = 35); 1Q Inflection at 272 nm (E j

38);

Maximum at 278 nm (E = 43);

Inflection at 284 nm (E

1

33);

15

Spectrum of R. M. N (deuterochloroform)

Peaks at 1.22 - 1.43 p.p.m., characteristics of the hydrogens of the twin methyls; peaks at 1.67-2.08 p.p.m., characteristics of the cyclopropyl hydrogens; peaks at 4.83-6.47 p.p.m., characteristics of the hydrogen in position 1 'of the substituted ethyl side chain; peaks at 6.38-6.46 p.p.m., characteristics of the hydrogen carried by the same carbon as the CN group; peaks at 6.92—7.58 p.p.m., characteristics of the hydrogens of aromatic rings.

■ - 25

Example 20

1R, cis 2,2-dimethyl 3- (2 ', 2', 2 ', 1'-tetrachloroethyl) cyclopropane-1-carboxylate of (RS) allethrolone.

Stage A: 1R acid chloride, cis 2,2-dimethyl3- (2 ', 2', 2 ', V-tetrachloroethyl) cyclopropane-1-carboxylic.

It is prepared as in Stage B of Example 12 starting from 7 g of 1R acid, corresponding cis.

Stage B: IR, eis 2,2-dimethyl 3- (2 ', 2r, 2', 1'-tetrachloroethyl) cyclopropane-1-carboxylate of (RS) allethrolone.

The acid chloride obtained in stage A of the present is dissolved

35 example in 20 cm3 of benzene, introduced at + 5 ° C, a solution of 4 g of allethrolone in 15 cm3 of benzene, then 2.55 cm3 of pyridine, stirred for 18 hours at 20 ° C, poured into a mixture of water and hydrochloric acid, extracted with ether, concentrated the ethereal solution to dryness, chromatography the

40 residue on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (9/1) and obtained 8 g of lR, cis 2,2-dimethyl 3- (2 ', 2', 2 ' , (RS) allethrolone-tetrachloroethyl) cyclopropane-1-carboxylate

45 M ~ q ~ = - 54.7 ° (£ = 0> 5%, chloroform)

Analysis: C17H2oC1403 (414.15)

Calculated: C% 49.30 H% 4.87 Cl% 34.24 Found: 49.5 4.9 34.1

U. V. spectrum (ethanol)

50 -I

Maximum at 227 nm (E * = 334).

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.31-1.42 p.p.m., characteristics of the hydrogens of

55 twin methyls, peaks at 1.67-2.17 p.p.m., characteristics of cyclopropyl hydrogens; peaks at 4.83-6.17 p.p.m., characteristics of hydrogen in position 1 of the substituted ethyl side chain.

60 Example 21

1 R, trans 2,2-dimethyl3- (2 ', 2', 2 ', 1'-tetrachloroethyl) cyclo-propane-1-carboxylate of (RS) a-cyano 3-phenoxy benzyl. Stage A: IR acid, trans 2,2-dimethyl3- (2 ', 2', 2 ', 1' -tetrachloroethyl) cyclopropane-1-carboxylic.

65 In 30 cm3 of carbon tetrachloride, 13.25 g of chlorine is dissolved at -10 ° C., approximately 18.8 g of IR, trans 2,2-dimethyl 3- (2 ', 2'-dichlorovinyl) cyclopro-pane-1-carboxylic in solution in 30 cm3 of chloride

15

630 890

methylene, the reaction vessel being surmounted by a condenser in which a liquid circulates at - 60 ° C to condense the unreacted chlorine, stirred for one hour and 30 minutes at - 10 ° C, then for one hour and 30 minutes at 0 ° C, eliminates chlorine or excess, at 20 ° C, by bubbling nitrogen, concentrated to dryness under reduced pressure, purifies the residue by chromatography on silica gel, eluting with a mixture of cyclohexane and acetate ethyl (7/3) and obtains 23 g of IR, trans 2,2-dimethyl 3- (2 ', 2', 2 ', l--tetrachloroethyl) cyclopropane-1-carboxylic acid used as it is for the next stage:

Stage B: IR acid chloride, trans 2,2-dimethyl3- (2 ', 2', 2 ', tetrachloroethyl) cyclopropane-1-carboxylic.

In a mixture of 30 cm3 of petroleum ether (bp 35-75 ° C) and 16 cm3 of thionyl chloride, 12.276 g of acid obtained in stage A are introduced, and brought to reflux, maintains reflux for 4 hours and 30 minutes, concentrated to dryness by distillation under reduced pressure, added benzene, concentrated again to dryness and obtains the chloride of the acid lR, trans-2,2-dimethyl 3- (2 ', 2', 2 ', 1'-tetrachloroethyl) cyclopropane-l-carboxylic acid, used as it is for the following stage:

Stage C: 1 R, trans 2,2-dimethyl3- (2 ', 2', 2'-tetrachloroethyl) cyclopropane-1-carboxylate from (RS) a-cyano 3-phenoxy benzyl.

25 cm3 of benzene are added to the acid chloride obtained previously in Stage B, a solution of 10.5 g of alcohol (RS) a-cyano 3-phenoxy benzyl in 20 cm3 of benzene, quickly introduced 4.5 cm3 of pyridine, stirred for 16 hours at 20 ° C, poured the reaction mixture into a mixture of water, ice and hydrochloric acid, extracted with ethyl ether, washed the ethereal phases with water, dries them, concentrates to dryness by distillation under reduced pressure, chromatographs the residue on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (90/10) and obtains 14.18 g of IR, trans 2,2-dimethyl 3- (2 ', 2', 2'1 '"tetrachloroethyl) cyclopropane-l-carboxylate from (RS) a-cyano 3-phenoxy benzyl 20

[a] = - 22.5 ° (c = 0.5%, benzene).

Analysis: C22HlyCI4N03 (487.21)

Calculated: C% 54.2 H% 3.9 N% 2.9 Cl% 29.1 Found: 54.0 4.0 2.7 29.0

I.R. spectrum (chloroform)

Absorption at 1742 cm-1, characteristic of carbonyl; absorptions at 1610,1584,1484 cm-1, characteristics of aromatic nuclei.

U. V. spectrum (ethanol)

Inflection at 230 nm (E j = 230);

Inflection at 267 nm (E j = 41);

Inflection at 271 nm (E j = 44);

Maximum at 277 nm (E j = 49);

Inflection at 283 nm (E j = 37);

Inflection at 305 nm (E j = 4).

Spectrum of R.M.N. (deuterochloroform)

Peaks of 1.22-1.42 p.p.m., characteristics of the hydrogens of the methyl group, peaks of 1.50 to 2.50 p.p.m., characteristics of the hydrogens of cyclopropyl; peaks of 3.66 ppm to 4.41 ppm, characteristics of the hydrogen in position 1 'of the side chain, peak at 6.5 ppm, characteristic of the hydrogen carried by the carbon in α of -C = N, peaks from 7.00 to 7.66 ppm, characteristics of the hydrogens in aromatic rings.

Example 22

IR, trans 2,2-dimethyl 3- (2 ', 2', 2 ', V-tetrachloroethyl) cyclo-propane-1-carboxylate of 3-phenoxy benzyl.

Stage A: acid chloride 1 R, trans 2,2-dimethyl 3- (2 ', 2', 2 ', V-tetrachloroethyl) cyclopropane-1-carboxylic.

It is prepared as in Example 21 starting from 10.4 g of acid, dissolving the acid chloride obtained in 30 cm3 of benzene and obtaining 37.2 cm3 of benzene acid chloride solution.

Stage B: IR, trans 2,2-dimethyl3- (2 ', 2', 2 ', 1'-tetrachloroethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl.

In 18.6 cm3 of the acid chloride solution obtained above, 4 g of 3-phenoxy benzyl alcohol dissolved in 15 cm3 of benzene are added at 0 ° C., 2 cm3 of pyridine are added, the mixture is stirred for 18 hours at 20 ° C., pour the reaction mixture into a mixture of water, ice and hydrochloric acid, extract with ethyl ether, wash the organic phase with water, dry over magnesium sulphate, filter and concentrate to dry by distillation under reduced pressure. The residue (8.6 g) is purified by chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (95/5) then cyclohexane and benzene (5/5).

Analysis: C21H2oCl43 (462.20)

Calculated: C% 54.6 H% 4.4 Cl% 30.7 Found: 55.2 4.5 29.4.

I.R. spectrum (chloroform)

Absorption at 1728 cm - characteristic of C = 0, absorption at 1615-1587 cm "1, characteristics of the hydrogens of aromatic nuclei

U. V. spectrum (ethanol)

Inflection at 227 nm (E j = 245);

Inflection at 266 nm (E * = 36);

v 1

Maximum at 272 nm (E j = 42);

Maximum at 277 nm (E j = 40).

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.19-1.33 ppm, characteristics of hydrogens in twin methyls, peaks 1.66-2.25 ppm, characteristics of cyclopropyl hydrogens, peaks 4.0-4.41 ppm characteristics of hydrogen in position a substituted ethyl side chain; peak at 5.18 p.p.m, characteristic of methylene of the benzyl radical; peaks at 6.83-7.67 p.p.m, characteristics of hydrogens in aromatic rings.

Example 23

1 R, trans 2,2-dimethyl3- (2 ', 2', 2 ', 1'-tetrachloroethyl) cyclo-propane-1-carboxylate of (S) allethrolone.

Stage A: IR acid chloride, trans 2,2-dimethyl 3- (2 ', 2', 2 ', /' - tetrachloroethyl) cyclopropane-1 -carboxylic acid.

It is prepared as in Stage B of Example 21 starting from 10.4 g of IR acid, corresponding trans.

Stage B: IR, trans 2,2-dimethyl3- (2 ', 2', 2 ', /' - tetrachloroethyl) cyclopropane-1-carboxylate of (S) allethrolone.

The acid chloride obtained in Stage A is dissolved in 30 cm3 of benzene and 37.2 cm3 of an acid chloride solution (solution A) are obtained.

3.2 g of (S) allethrolone dissolved in 15 cm3 of benzene, stirred, added 2 cm3 of pyridine, stirred for 16 hours, are introduced into 18.6 cm3 of solution (A), cooled to + 5 ° C. at 20 ° C, pour the reaction mixture into a mixture of water, ice and hydrochloric acid, extract with ether, concentrate to dryness by distillation under reduced pressure, purify the residue by chromatography on silica gel, eluting by a me-

5

10

15

20

25

30

35

40

45

50

55

60

65

630 890

16

lange of cyclohexane and ethyl acetate (80/10) and obtains 4.56 g of IR, trans 2,2-dimethyl 3- (2 ', 2', 2 ', l'-tetrachloroethyl) cyclopropane-l (S) allethrolone carboxylate F = 85 ° C.

Analysis: C17H20C143 (414.16)

Calculated C% 49.3 H% 4.8 CI% 34.2 Found: 49.0 4.8 35.5.

Infrared spectrum (Chloroform).

Absorption at 1710 cm-1 and 1730 cm- \ characteristics of C = 0; absorptions at 1655 and 1538 cm- \ characteristics of C = C; absorptions at 918.992 cm "1, characteristics of -C = CH2.

Spectrum U. V. (Ethanol)

Maximum at 227-228 nm (E j = 357);

Maximum at 278 nm (E

8);

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.32-137 p.p.m. characteristic of the hydrogens of the twin methyls, peak at 2.08 p.p.m. characteristic of the methyl hydrogens in position 2 of the allethrolone; peaks at 2.98-3.08 p.p.m. characteristics of the hydrogens of methlylene of the allylic chain of allethrolone, contiguous to the cycle; peaks at 4.12-4.23 and 4.28-4.39 p.p.m. characteristics of the hydrogen in position 1 'of the substituted ethyl side chain; peaks of 4.83-5.25 p.p.m. characteristics of the terminal methylene of the allylic chain of allethrolone; peaks of 5.5 to 6.17 p.p.m. characteristics of the hydrogen attached to the carbon in position 1 'of the allethrolone, and of the hydrogen of the carbon in position ß of the allylic chain of the allethrolone.

Example 24

1R, cis 2,2-dimethyl 3- (l ', 2' -dibrome 2 ', 2' -dichloroethyl) cy-clopropane-1-3-phenoxy benzylcarboxylate.

In a solution of 4.65 g of chloride of lR acid, cis 2,2-dimethyl 3- (1 ', 2'-dibrome 2', 2'-dichloroethyl) cyclopropane-1-carboxylic acid and 2 , 40 g of 3-phenoxy benzyl alcohol in 20 cm 3 of benzene, 4 cm 3 of pyridine are gradually introduced at 0 ° C., stirred for 17 hours, pour the reaction mixture into an aqueous solution of hydrochloric acid, extracted with benzene , wash the organic phase with saturated sodium bicarbonate solution, with water, dry over magnesium sulfate and concentrate to dryness by distillation under reduced pressure.

The residue is chromatographed on silica gel, eluting with a mixture of petroleum ether (bp 35-75 ° C) and ethyl ether (9/1) to obtain 2.37 g of 1R, cis 2.2 -dimethyl 3- (1 ', 2'-di-bromo 2', 2'-dichlororethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl (mixture of isomers A and B) F = 75 ° C.

Analysis: C2iH2oBr2Cl203 (551.11)

Calculated: C% 45.76 H% 3.65 Br% 29.0 Cl% 12.86 Found 45.8 3.6 28.5 12.9.

Spectrum of I.R. (chloroform)

Absorption at 1725 cm-1, characteristic of carbonyl; absorptions at 1615-1590-1492 cm "characteristic of aromatic nuclei.

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.25-1.37 and 1.22-1.39 p.p.m. characteristics of the hydrogens of the twin methyls, peaks at 1.75-2.17 p.p.m. characteristics of the hydrogens of cyclopropyl; peaks at 5.1-5.16 ppm characteristic of methylene hydrogens of the benzyl radical, peaks at 5.0-5.42 and 5.35-5.53 ppm characteristic of hydrogen in position 1 'of the side chain substituted ethyl; peaks at 6.83-7.59 p.p.m. characteristics of hydrogens in aromatic rings.

The R.M.N. shows that the compound consists of 2/3 of the A isomer and 1/3 of the B isomer

The chloride of lR, cis 2,2-dimethyl 3- (1 ', 2'-dibro-mo-2', 2'-dichloroethyl) cyclopropane-1-carboxylic acid by garlic-5 described in Example 15, can be prepared as described in Example 16, starting from lR, cis 2,2-dimethyl 3- (2 ', 2'-dichlorovinyl) cyclopropane-1-carboxylic acid.

Example 25

10 lR, cis 2,2-dimethyl 3- (1 ', 2' -dibromo 2 ', 2'-dichloroethyl) cyclopropane-1-carboxylate of (S) allethrolone.

Stage A: 1 R acid chloride, eis 2,2-dimethyl3- (1 ', 2'-dibro-mo 2'2' -dichloroethyl) cyclopropane-1 -carboxylic.

It is prepared in a similar manner to that used in Example 24 starting from 3.6 g of 1R acid, cis 2,2-dimethyl 3- (1 ', 2'-dibromo 2', 2'-dichlorethyl ) cyclopropane-1-carboxyli-que and obtains 4 g of acid chloride.

Stage B: 1R, cis 2,2-dimethyl3- (1 ', 2' -dibromo 2 ', 2'-dichloro-ethyl) cyclopropane-1-carboxylate of (S) allethrolone

In 40 cm3 of benzene, 4 g of acid chloride obtained in stage A and 1.75 g of (S) allethrolone are dissolved, a mixture of 2 cm3 of pyridine and 2 cm3 of benzene is introduced at 0 ° C. stirred for 24 hours at 20 ° C., pour the reaction mixture into a mixture of water, ice and hydrochloric acid, extract with benzene, wash the organic phase with a saturated aqueous solution of sodium bicarbonate, at 1 water, dried over sodium sulfate and concentrated to dryness by distillation under reduced pressure. The residue (5.1 g) is purified by chromatography on silica gel, eluting with a mixture of benzene and ethyl acetate (97/3) and 4.25 g of 1R, cis 2.2- are obtained. (S ') allethrolone dimethyl 3- (l', 2'-di-bromo 2 ', 2'-dichloroethyl) cyclopropane-l-carboxylate.

Analysis: CllE.20Br2Cl2O3 (503.07)

Calculated: C% 40.58 H% 4.0 Br% 31.76 Cl% 14.09 35 Found: 41.3 4.1 31.0 14.2

I.R. spectrum (chloroform)

Absorption at 1718 cm-1, characteristic of C = 0; Absorption at 1655.1638 cm- ', characteristics of C = C; Absorption 40 to 918—997 cm-1, characteristics of-CH = CH2

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.25-1.28 p.p.m. and 1.39-1.42 p.p.m., characteristics of the hydrogens of the twin methyls; peaks at 1.95-2.07 p.p.m., characteristics of the methyl hydrogens in 3 'of allethro-45 Ione; peaks at 4.83-6.17 p.p.m., characteristics of the hydrogens of the terminal methylene of the allylic side chain of allethrolone; peaks at 4.83-6.17 p.p.m., characteristics of the hydrogen in position 1 of the substituted ethyl side chain; peak at 5.75 p.p.m., characteristic of hydrogen in position 4 'of so allethrolone.

Example 26

1R, cis 2,2-dimethyl 3- (2 ', 2' -dichloro 1 ', 2'-dibromo ethyl) cyclopropane-1-carboxylate of 5-benzyl 3-furyl methyl.

55 Stage A: 1R acid chloride, cis 2,2-dimethyl 3- (2 ', 2'-dichloro 1', 2'-dibromoethyl) cyclopropane-1-carboxylic.

It is prepared in a similar manner to that used in Example 24, starting from 10 g of 1R acid, cis 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromoethyl) cyclopropane -l-carboxy-60 lique.

Stage B: 1 R, is 2,2-dimethyl3- (2 ', 2'-dichloro 1', 2'-dibromoethyl) cyclopropane-1-carboxylate of 5-benzyl 3-furyl methyl.

The acid chloride obtained in the preceding stage A is dissolved in benzene and 27 cm 3 of a-65 acid chloride solution (solution A) are obtained.

12 cm3 of acid chloride solution A are introduced into a solution of 2.9 g of 5-benzyl 3-furyl methyl alcohol in 15 cm3 of benzene, cooled to 0 ° C., 3 cm3 of pyridine are introduced,

17

630 890

stirred for 48 hours at 20 ° C, poured over a mixture of water, giace and hydrochloric acid, extracted with benzene then, after the usual treatments, concentrated to dryness by distillation. The residue is purified by chromatography on silica gel, eluting with a mixture of petroleum ether (Eb. 35-75 ° C) and ether (95/5), then petroleum ether (Eb. 35- 75 ° C) and ether (9/1) and obtains 2.2 g of 1R, cis 2,2-dimethyl 3- (2 ', 2'-dichloro 1', 2'-dibro-moethyl) cyclopropane- 5-Benzyl 3-furyl methyl l-carboxylate.

20

[a] = - 57.5 ° (c = 0.4%, benzene)

Analysis: C2oH20Br2Cl203 (539,104)

Calculated: C% 44.56 H% 3.74 Br% 29.04 Cl% 13.15 Found: 44.9 3.8 29.1 13.3

U. V. spectrum (ethanol)

Inflection at 252 nm (E j = 20)

Inflection at 258 nm (E j = 15)

Inflection at 264 nm (E j = 11)

Inflection at 268 nm (E | = 9).

I.R. spectrum (chloroform)

Absorption at 1720 cm-1, characteristic of carbonyl, absorptions at 1600.15222, 1493 cm "1, characteristics of-C = C- and of the aromatic nucleus.

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.23-1.35 and 1.20-1.38 p.p.m. characteristics of the methyl hydrogens in position 2 of the cyclopropyl; peaks at 1.67-2.17 p.p.m. characteristics of the cyclopropyl hydrogens; peak at 3.93 p.p.m. characteristic of the methylene hydrogens of the benzyl radical; peaks at 4.93-5.0 p.p.m. characteristics of the hydrogens carried by the carbon contiguous to the carboxyl; peaks 6.02-6.1 p.p.m. characteristics of hydrogen in position 3 of the furan nucleus; peaks at 4.83-5.16-5.33-5.58 p.p.m. characteristics of hydrogen in position 1 'of the ethyl side chain; peak at 7.3 p.p.m. characteristic of the hydrogens of the phenyl radical; peaks at 7.37 p.p.m. characteristic of hydrogen in position 5 of the furan nucleus.

Example 27

1R, cis 2,2-dimethyl 3- (2 ', 2' -dichloro 1 ', 2'-dibromo ethyl) cyclopropane-l-carboxylate of 3,4,5,6-tetrahydrophthalimido methyl.

Stage A: 1R acid chloride, cis 2,2-dimethyl3- (2 ', 2'-dichloro 1', 2'-dibromoethyl) cyclopropane-1-carboxylic

It is prepared in a similar manner to that used in Example 24, starting from 10 g of 1R acid, cis 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromoethyl) cyclopropane -l-carboxylic.

Stage B: 1 R, eis 2,2-dimethyl 3- (2 ', 2' -dichloro 1 ', 2' -dibromoethyl) cyclopropane-l-carboxylate of 3,4,5,6-tetrahydrophthalimido methyl

The acid chloride obtained in stage A is dissolved in benzene and 27 cm 3 of benzene solution (solution A) are obtained in a solution of 1.4 g of 3,4,5,6-tetrahydrophthalimi-do methyl alcohol in 15 cm3 of benzene, 7.5 cm3 of acid chloride solution A are introduced, then at 0 ° C, 2 cm3 of pyridine, stirred for 36 hours at 20 ° C, pour the reaction mixture onto a mixture of ice and hydrochloric acid, extracted with benzene, wash the organic phase with a saturated aqueous solution of sodium bicarbonate, then with water, dry over sodium sulfate and concentrate to dryness by distillation under reduced pressure. The residue is purified by chromatography on silica gel, eluting with a mixture of benzene and ethyl acetate (9/1).

1.89 g of lR, cis 2,2-dimethyl 3- (2 ', 2'-dichloro 1', 2'-dibromoethyl) cyclopropane-l-carboxylate of 3,4,5,6-tee-trahydrophthalimido are obtained. methyl.

20

s [a] = - 53.5 ° (c = 0.98%, benzene)

Analysis: C17H1gBr2Cl2N04 (532.07)

Calculated:

C% 38.37 H% 3.6 N% 2.63 Br% 30.03 Cl% 13.32 Found:

io 39.0 3.6 2.6 28.3 12.7

I.R. spectrum (chloroform)

Absorption at 1778 cm-1-1735-1723 cm-1 characteristic of carbonyl; absorption at 1665 cm-1 characteristic of -C = C-

15 Spectrum of R. M. N (deuterochloroform)

Peaks at 1.21-1.22-1.39 p.p.m. characteristics of the hydrogens of the twin methyls, peaks at 1.67-1.83 p.p.m. characteristics of the hydrogens of cyclopropyl and of the methylenes in a de-C = C; peak at 2.37 p.p.m. characteristic of methylenes in 20 'of -C = C-, peaks at 5.0-5.5 p.p.m. characteristic of hydrogen in 1' of the ethyl side chain; peaks at 5.5-5.75 p.p.m. characteristics of the methylene hydrogens at the carboxyl.

25 Exempel 28

dl-cis-trans 2,2-dimethyl 3- (2 ', 2' -dichloro 1 ', 2'-dibromo-ethyl) cyclopropane-l-carboxylate of R, S a-cyano 3-phenoxy benzyl.

A dl-cis-trans 2,2-dimethyl 3- (2 ', 2'-dichlorovi-30 nyl) cyclopropane-1-carboxylate of R, S a-cyano 3-phenoxy benzyl is used, the characteristics of which are as follows:

U. V. spectrum (ethanol)

Inflection at 230 nm (E \ = ^ 22)

35 1

Inflection at 267 nm (E j = 43)

Inflection at 272 nm (E | = 47)

40 Maximum at 278 nm (E j = 52)

Spectrum of R.M.N. (deuterochloroform)

Peaks of 1.20 to 1.30 p.p.m. characteristics of the hydrogens of the methyl groups; peaks at 5.60-5.75 ppm characteristic of hydrogen in position 1 'of the dichlorovinyl chain, corresponding to the trans isomer, peaks at 6.20-6.31 ppm characteristic of hydrogen in position 1 'of the dichlorovinyl chain, corresponding to the eis isomer, peaks at 6.41-6.46 ppm characteristic of the hydrogen carried by the carbon in a of the function 50 = N; peaks of 7.0 to 7.66 p.p.m. characteristics of the hydrogens of the aromatic rings.

6.7 g of dl-cis-trans 2,2-dimethyl 3- (2 ', 2'-dichlorovinyl) cyclopro-pane-l-carboxylate of R, S a-cyano are introduced into 30 cm 3 of carbon tetrachloride 3-phenoxy benzyl of which 55 the characteristics have been given above, introduced in about one hour a solution of 0.85 cm3 of bromine in 10 cm3 of carbon tetrachloride, stirred for 2 hours at 20 ° C, concentrated to dryness under reduced pressure and obtains 10 g of crude product which is chromatographed on silica gel eluting with a mixture of cyclohexane and ethyl acetate (9/1) and obtains 7.5 g of dl-cis-trans 2,2-dimethyl 3- (2 ', 2'-dichloro 1', 2'-dibro-moethyl) cyclopropane-1-carboxylate of (R, S) a-cyano 3-phenoxy benzyl.

Analysis: C22H1903N Cl2Br2 65 Calculated:

C% 45.86 H% 3.32 N% 2.43 Cl% 12.30 Br% 27.74 Found:

46.2 3.6 2.4 12.5 27.5

630 890

18

U. V. spectrum (ethanol)

Inflection at 267 nm (E | = 34)

Inflection at 272 nm (E j = 35)

Maximum at 277 nm (E j = 38)

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.20-1.44 p.p.m. characteristics of the hydrogens of the methyl groups, peaks of 1.54 to 2.40 p.p.m. characteristics of the hydrogens in positions 1 and 3 of the cyclopropane ring; peaks of 4.21 to 4.51 p.p.m. characteristics of the hydrogen in position 1 'of the dichlorovinyl chain and corresponding to the trans isomer; peaks from 4.97 to 5.40 p.p.m. characteristics of the hydrogen in position 1 'of the dichlorovinyl chain and corresponding to the isis isomer; peaks from 6.42 to 6.50 p.p.m. characteristics of the hydrogen carried by the carbon in a of the group -C = N; peaks of 7.0 to 7.55 p.p.m. characteristics of the hydrogens of the aromatic rings.

Example 29

IR, trans 2,2-dimethyl3- (2 ', 2'-dichloro 1', 2'-dibromoethyl) cyclopropane-1-carboxylate of 5-benzyl 3-furyl methyl.

7.6 g of IR acid chloride, trans 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromo-ethyl) cyclopropane-l- are introduced into 30 cm 3 of benzene carboxylic, 3.2 g of 5-benzyl 3-furyl methyl alcohol, drop by drop 5 cm3 of pyridine, stirred for 48 hours at 20 ° C, added water, separated by decantation of the organic phase, extracted aqueous phase with benzene, combines the organic phases, dries them, concentrates them to dryness by distillation under reduced pressure, chromatographs the residue on silica gel, eluting with a mixture of benzene and cyclohexane (7/3) and obtains 6.1 g of IR, trans 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromoethyl) cyclopropane-1-carboxy-late of 5-benzyl 3-furyl methyl.

20

[a] = —19 ° (c = 0.5%, benzene)

Analysis: C2oH2oBr2Cl203 (539.09)

Calculated: C% 44.56 H% 3.74 Br% 29.65 Cl% 13.15 Found: 44.2 3.7 29.4 13.5

Spectrum I.R.

Absorption at 1725 cm-1, characteristic of carbonyl; absorptions at 1555,1540,1498,1495 cm-1, characteristics of -C = C— and aromatic nuclei.

U. V. spectrum (ethanol)

Inflection at 216 nm (E | = 265)

Inflection at 251 nm (E j = 10.5)

Maximum at 257 nm (E j = 8.5)

Inflection at 261 nm (E | = 7)

Inflection at 263 nm (E j = 6)

Maximum at 268 nm (E j = 4.5)

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.22-1.25 - 1.28 p.p.m. characteristics of the hydrogens of the twin methyls; peaks at 1.6-2.32 p.p.m. characteristics of cyclopropyl hydrogens; peak at 3.93 p.p.m. characteristic of the methylene hydrogens of the benzyl radical; peaks at 4.25-4.37-4.54 ppm characteristic of hydrogen in position 1 'of the substituted ethyl side chain, peaks at 4.95-4.97 ppm and 6.0-6.05 ppm characteristic hydrogens of methylene contiguous to the carboxyl; peak at 7.33 p.p.m. characteristic of hydrogen in position 4 of the furyl nucleus; peak at 7.25 p.p.m. characteristic of phenyl hydrogens.

The acid chloride used from the present example, further described in Example 10, can be prepared in the manner described in Example 16, starting from IR acid, trans 2,2-dimethyl 3- (2 ', 2'-dichlorovinyl) cyclopropane-1-carboxylic.

Example 30

IR, trans 2,2-dimethyl3- (1 ', 2'-dibromo 2', 2'-dichloroethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl.

A solution of 19.35 g of IR acid chloride, trans 2, is introduced dropwise into a solution of 9 g of 3-phenoxy benzyl alcohol in a mixture of 50 cm 3 of benzene and 10 cm 3 of pyridine. , 2-dimethyl 3- (1 ', 2'-dibromo 2', 2'-dichloroethyl) cyclopropane-1-carboxylic, stirred for 18 hours at 20 ° C, pour the reaction mixture into water, extract with benzene, dried over magnesium sulfate, concentrated to dryness by distillation. The residue is purified by chromatography on silica gel, eluting with a mixture of petroleum ether (bp 35-75 ° C) and ethyl ether (95/5) to obtain 8.1 g of IR, trans 2 , 2-dimethyl 3- (1 ', 2'-dibromo 2', 2'-dichloroethyl) cyclopropa-ne-3-phenoxy benzyl carboxylate.

20

[a] —- = - 20.5 ° (c = 0.6%, benzene).

D ~~

Analysis: C21H20Br2Cl2O3 (551.11)

Calculated: C% 45.17 H% 3.66 Br% 29.0 Cl% 12.87 Found: 45.7 3.7 28.5 13.0

I.R. spectrum (chloroform)

Absorption at 1730 cm-1 characteristic of carbonyl; absorptions at 1618.1590 cm-1 characteristic of hydrogens in aromatic rings.

U. V. spectrum (ethanol)

Inflection 228 nm (E | = 216)

Inflection 267 cnm (E j = 34)

Maximum at 272 nm (E j = 37.5)

Maximum at 278 nm (E j = 36).

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.22-1.27-1.29 p.p.m. characteristics of the hydrogens of the twin methyls; peaks at 1.66-1.75 p.p.m. and 1.92-2.13 p.p.m. characteristics of the hydrogen in position 1 of the cyclopropyl; peak at 1.92-2.33 p.p.m. characteristic of hydrogen in position 3 of cyclopropyl; peaks at 4.22-4.38 and 4.38-4.57 p.p.m. characteristics of hydrogen in position 1 of the substituted ethyl side chain; peaks at 5.12-5.13 p.p.m. characteristics of the methylene hydrogens of the benzyl radical; peaks at 6.83-7.53 p.p.m. characteristics of hydrogens in aromatic rings.

Example 31

IR, trans 2,2-dimethyl3- (V, 2'-dibromo 2 ', 2'-dichloroethyl) cyclopropane-l-3,4,5,6-tetrahydrophthalimido methyl carboxylate.

In 20 cm3 of benzene, 2 g of IR acid chloride, trans 2,2-dimethyl 3- (1 ', 2'-dibromo 2', 2'-dichloroethyl) cyclopropane-1-carboxylic acid and 0.930 g are dissolved. of 3,4,5,6-tetrahydrophthalimido methanol, dropwise 2.5 cm3 of pyridine, stirred for 48 hours at 20 ° C, added water, decanted, extracted with benzene, concentrated to dryness, Chromatograph the residue on silica gel, eluting with a mixture of benzene and ethyl acetate (9/1) and obtain 2.17 g of IR, trans 2,2-dimethyl 3- (1 ', 2'- dibromo 2 ', 2'-dichloroethyl) cyclopropane-1-car-boxylate of 3,4,5,6-tetrahydrophthalimido methyl M = 117 ° C.

5

10

15

20

25

30

35

40

45

50

55

60

65

19

630 890

[a] -dd "6.5 ° (c = 0.9%, benzene)

Analysis: CI7H19Br2Cl2N04 (532,066)

Calculated:

C% 38.38 H% 3.60 Br% 30.04 Cl% 13.32 N% 2.63 Found:

C% 38.5 H% 3.5 Br% 29.9 Cl% 13.4 N% 2.5 I.R. spectrum (chloroform)

Absorption at 1783 cm-1 characteristic of C = 0; absorptions at 1728 cnr! and 1750 cm-1 characteristics of C = 0 and of the ester function, absorption at 1669 cm-1 characteristic of C = 0.

U. V. spectrum (ethanol)

Maximum at 223 nm (E j = 301);

Maximum at 229-230 nm (E J = 293);

Inflection at 236 nm (E j = 172);

Inflection at 272 nm (E j = 8).

Example 32

IR, trans 2,2-dimethyl 3- (2 ', 2' -dibromo / ', 2' -dichloroethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl.

Stage A: IR acid chloride, trans 2,2-dimethyl3- (2 ', 2' -di-bromo V, 2'-dichloroethyl) cyclopropane-1-carboxylic.

The procedure is analogous to that of Example 16, starting with 4.5 g of IR, trans 2,2-dimethyl 3- (2 ', 2'-dibromo 1 \ 2'-dichloroethyl) cyclopropane-1 acid. -carboxylic and obtains the chloride of IR acid, trans 2,2-dimethyl 3- (2 ', 2'-dibromo 1', 2'-dichloroethyl) cyclopropane-1-carboxylic.

Stage B: IR, trans 2,2-dimethyl3- (2 ', 2'-dibromo /', 2'-dichloroethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl.

The solution obtained by dissolving the acid chloride obtained in Stage A in 7 cm3 of benzene is added to a solution of 2.7 g of 3-phenoxy benzyl alcohol in 7 cm 3 of benzene, at 0 ° C. , 5 cm3 of pyridine, stirred for 16 hours at 20 ° C., poured the reaction mixture into a mixture of water, ice and hydrochloric acid, extracted with ethyl ether, washed the organic phase with water, dried over magnesium sulfate and concentrated to dryness by distillation under reduced pressure. The residue (6.37 g) is purified by chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (90/10) and 2.09 g of IR, trans 2 are obtained. , 2-dimethyl 3- (2 ', 2'-dibromo-l', 2'-dichloroethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl.

Analysis: C21H2uBr2CI203 (551.12)

Calculated: C% 45.7 H% 3.6 Br% 29 Cl% 12.8 Found: 46.0 3.8 29.4 12.6

I.R. spectrum (chloroform)

Absorption at 1730 cm-1, characteristic of C = O, absorptions at 1615-1590 cm-1, characteristic of aromatic nuclei.

U. V. spectrum (ethanol)

Inflection at 220 cnm (E | = 205);

Inflection at 266 nm (E j = 33);

Maximum at 271-272 nm (E j = 36);

Maximum at 278 nm (E j = 34)

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.25-1.28-1.33 p.p.m. characteristics of the hydrogens of the twin methyls; peaks at 1.7-2.42 p.p.m. characteristics of cyclopropyl hydrogens; peaks at 3.98-4.35 p.p.m. characteristics of the hydrogen in position 1 'of the substituted ethyl chain; peaks at 6.85-7.5 p.p.m. characteristics of the hydrogens of the aromatic rings; peak at 5.23 p.p.m. characteristic 5 of methylene hydrogens of the benzyl radical.

IR, trans 2,2-dimethyl 3- (2 ', 2'-dibromo 1', 2'-di-chloroethyl) cyclopropane-1-carboxylic acid can be prepared as follows:

24 g of IR, trans 2,2-dimethyl 3- (2 ', 2'-dibromovinyl) cyclopropane-l- acid are introduced into a mixture of 20 cm3 of carbon tetrachloride and 20 cm3 of methylene chloride carboxylic, bubbled at - 10 ° C, chlorine in the reaction solution ed adapting to the reaction vessel, a condenser in which methanol circulates at - 60 ° C, stirred for iS two hours and 30 minutes at - 10 ° C, for one hour and 30 minutes at +10 ° C, allows excess chlorine to evaporate, removes the solvents by distillation under reduced pressure, purifies the residue by chromatography on silica gel, eluting with a mixture of cyclohexane, acetate ethyl and acetic acid (75/25/1) 20 then cyclohexane of ethyl acetate and acetic acid (80 / 20/1) and obtains 16.3 g of IR acid, trans 2.2 -dimethyl 3- (2 ', 2'-dibromo 1', 2'-dichlorethyl) cyclopropane-1-carboxylic.

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.33-1.56 p.p.m. characteristics of the hydrogens of the twin methyls, peaks 1.7-12.25 p.p.m. characteristics of the hydrogens of cyclopropyl; peaks 4.11-4.37 p.p.m. characteristics of the hydrogen in position 1 'of the substituted ethyl side chain; peak at 10.8 p.p.m. characteristic of the hydrogen of the carboxyl.

30

Example 33

IR, trans 2,2-dimethyl 3- (2 ', 2'-dibromo V, 2'-dichloro-ethyl) cyclopropane-1-carboxylate of (S) allethrolone.

Stage A: acid chloride 1 R, trans 2,2-dimethyl 3- (2 ', 2'-di-bromo 1', 2'-dichloroethyl) cyclopropane-1-carboxylic.

The procedure is analogous to that of the preceding examples, starting from 4.5 g of IR acid, trans 2,2-dimethyl 3- (2 ', 2'-dibro-mo 1', 2'-dichloroethyl) cyclopropane- l-carboxylic acid and obtains IR acid chloride, trans 2,2-dimethyl 3- (2 ', 2'-dibromo 40 1', 2'-dichloroethyl) cyclopropane-l-carboxylic acid.

Stage B: 1 R, trans 2,2-dimethyl3- (2 ', 2'-dibromo 1', 2'-dichlo-roethyl) cyclopropane-1-carboxylate of (S) allethrolone.

In a solution of 2.05 g of S-allethrolone in 7 cm 3 of benzene, a solution of 45 acid chloride obtained in stage A, in 7 cm 3 of benzene, is introduced at 0 ° C., 1.5 cm 3 of pyridine, stirred for 16 hours at 20 ° C., poured the reaction mixture into a mixture of water, ice and hydrochloric acid, extracted with ether, washed the organic phase with water, dried over magnesium sulfate and concentrated to dryness by distillation. The residue 50 (5.15 g) is purified by chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (80/20), crystallized from isopropyl ether and obtained 1.86 g of IR, trans 2,2-dimethyl 3- (2 ', 2'-dibromo 1', 2'-dichloroethyl) cyclopropane-l-carboxylate of S-allethrolone F = 126 ° C. 55 Spectrum I.R. (chloroform)

Absorption at 1713—1730 cm "1 characteristic of C = 0, absorption at 1658-1642 cm-1 characteristic of -C = C—; absorption at 923-995 cm" 1 characteristic of -CH = CH2.

60 U.V. spectrum (ethanol)

Maximum at 229 nm (E j = 315)

Inflection at 300 nm (E j = 1)

65

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.32-1.35-1.38 p.p.m. characteristics of the hydrogens of the twin methyls; peaks at 4.23-4.4 p.p.m. 4.1-4.27

630 890

20

ppm characteristics of hydrogen in position 1 'of the substituted ethyl side chain, peaks at 2.08-2.15 ppm characteristics of methyl hydrogens in position 3 of allethrolone, peaks at 2.98-3.08 ppm characteristics of methylene in position 5 of allethrolone; peaks 4.83-5.25 p.p.m. characteristics of the hydrogens of the terminal methylene of allethrolone; peaks at 5.5-6.17 p.p.m. characteristics of the hydrogen in position β of the allyl radical of allethrolone; peak at 5.83 p.p.m. characteristic of hydrogen in position 4 'of allethrolone.

Example 34

IR.cis 2,2-dimethyl3- (2 ', 2'-dibromo /', 2'-dichloroethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl.

Stage A: 1R acid chloride, cis 2,2-dimethyl 3- (2 ', 2'-dibromo 1', 2 '-dichloroethyl) cyclopropane-1 -carboxylic acid.

In a mixture of 30 cm3, petroleum ether (bp 35-70 ° C) and 10 cm3 of thionyl chloride, 5 g of 1R acid, cis2,2-dimethyl 3- (2 ', 2'-dibromo l ', 2'-dichloro-ethyl) cyclopropane-l-carboxylic, brings the reaction mixture to reflux, maintains it there for 4 hours, concentrates to dryness by distillation under reduced pressure, adds benzene, concentrates to dry again by distillation under reduced pressure and obtains 5.4 g of lR acid chloride, cis 2,2-dimethyl 3- (2 ', 2'-dibro-mo 1', 2'-dichloroethyl) cyclopropane- l-carboxylic.

Stage B: 1R, cis 2,2-dimethyl3- (2 ', 2'-dibromo 1', 2 '-dichloro-ethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl.

To 3.2 g of 3-phenoxy benzyl alcohol, 5.4 g of acid chloride obtained in the preceding stage A, 38 cm 3 of benzene are added, then gradually towards +8 ° C., 4.35 g of pyridine, dissolved in 10 cm3 of benzene, stirred for 17 hours at 20 ° C, poured into a mixture of water and ice, extracted with benzene, dried over magnesium sulfate and concentrated to dryness the benzene solution, purifies the residue by chromatography on silica gel, eluting with a mixture of benzene and ethyl acetate (7/3), crystallized from petroleum ether (bp 35-70 ° C) and obtained 4.7 g of lR, cis 2,2-dimethyl 3- (2 ', 2'-dibromo l', 2'-di-chloroethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl. Mp 68 ° C.

20

[a] —- = - 34 ° C (c = 1%, chloroform);

Analysis: CjiH ^ C ^ BrjOj (551.20)

Calculated: C% 45.76 H% 3.66 Br% 29.00 Cl% 12.86 Found: 46.0 3.6 29.3 12.7

Infrared spectrum (chloroform)

Absorption at 1725 cm-1 characteristic of carbonyl; absorptions at 1615—1588 cm-1 and 1490 cm-1 characteristic of aromatic nuclei.

U. V. spectrum (ethanol)

Inflection at 227 nm (E j = 214)

Inflection at 226 nm (E | = 33)

Maximum at 272 nm (E j = 35)

Maximum at 278 nm (E j = 36)

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.22-1.39 p.p.m. and at 1.26-1.42 p.p.m. characteristics of the hydrogens of the methylated gemines; peaks at 1.66-2.08 p.p.m. characteristics of cyclopropyl hydrogens; peaks at 4.8-5.37 p.p.m. characteristics of the hydrogens of the -C-CH2 group, peaks at 6.83-7.58 p.p.m. characteristics of the hydrogens

O

aromatic nucleus genes.

The 1R, cis 2,2-dimethyl 3- (2 ', 2'-dibromo l', 2'-dichlo-roethyl) cyclopropane-1-carboxylic acid used in stage A of the present example is prepared in stage A of Example 11 above.

Example 35

1R, cis 2,2-dimethyl 3- (2 ', 2' -difluoro 1 ', 2'-dibromoethyl) cy-clopropane-1-carboxylate of (S) allethrolone.

Stage A: acid 1 R, eis 2,2-dimethyl3- (2 ', 2' -difluoro 1 ', 2'-dibro-moethyl) cyclopropane-1-carboxylic.

17 g of lR, cis 2,2-dimethyl 3- (2 ', 2'-difluorovinyl) cyclopropane-1-cyrboxylic acid, introduced at -65 ° C., are introduced into 120 cm3 of methylene chloride. about two hours, 15.2 g of bromo dissolved in 40 cm3 of carbon tetrachloride, stirred for two hours and 30 minutes at -65 ° C, allows the temperature to rise to 20 ° C, concentrated to dryness by distillation under reduced pressure , dissolves the residue, hot, in 50 cm3 of carbon tetrachloride, cools to 0 ° C, agitates at this temperature for 45 minutes, eliminates the insoluble matter by filtration, concentrates the filtrate to dryness by distillation under reduced pressure, residue in 40 cm3 of carbon tetrachloride, stirred for 30 minutes at -10 ° C., removes the insoluble matter by filtration, concentrated the filtrate to dryness by distillation under reduced pressure, purified the residue by chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (75/25), crystallizes from petroleum ether (Eb. 35-75 ° C) and obtains 1.465 g of lR, cis 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2'-dibromoethyl) cyclopropane-l-carboxylic acid F i 24 "C.

Spectrum of R. M. N. (deuterochloroform)

Peaks at 1.28—1.38 p.p.m. characteristics of the hydrogens of the twin methyls, peaks 1.67—2.0 p.p.m. characteristics of the hydrogens of cyclopropyl; peaks at 4.67-5.33 p.p.m. characteristics of the hydrogen of the substituted ethyl side chain; Stage B: 1R acid chloride, cis 2,2-dimethyl3- (2 ', 2' -difluoro 1 ', 2'-dibromoethyl) cyclopropane-1-carboxylic.

1.43 g of lR, cis 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2 ') are introduced into 15 cm3 of petroleum ether (bp 35-75 ° C). -dibro-moethyl) cyclopropane-l-carboxylic, add 2.5 cm3 of thionyl chloride, bring to reflux, maintain reflux for 4 hours and 30 minutes, remove excess thionyl chloride and the solvent by distillation under pressure reduced, added benzene to the residue, concentrated to dryness by distillation under reduced pressure, and obtains the chloride of lR acid, cis 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2'-dibromoethyl ) crude cyclopropane-1-carboxylic acid used as is for the next stage.

Stage C: 1R, eis 2,2-dimethyl3- (2 ', 2' -difluoro 1 ', 2'-dibromoethyl) cyclopropane-1-carboxylate of (S) allethrolone.

0.7 g of (S) allethrolone dissolved in 5 cm3 of benzene are added to a solution of the acid chloride IR, cis obtained in stage B, in 10 cm 3 of benzene, at + 2 ° C. 5 cm3 of pyridine, stirred for 16 hours at 20 ° C, pour the reaction mixture into a mixture of water, ice and hydrochloric acid, extracted with ethyl ether, wash the organic phase with water, dry over magnesium sulfate and concentrated to dryness. 2.02 g of crude ester are obtained, which is purified by chromatography, eluting with a mixture of cyclohexane and ethyl acetate (80/20). 1.224 g of lR, cis 2,2-dimethyl 3- (2 ', 2'-difluoro 1', 2'-dibromoethyl) cyclopropane-1-carboxylate of (S) allethrolone are obtained.

Analysis: C17H2oBr2F203 (470,162)

Calculated: C% 43.4 H% 4.3 Br% 34.0 F% 8.1 Found: 43.2 4.4 33.7 8.1

U. V. spectrum (ethanol)

Maximum at 227-228 nm (E j = 348)

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.25-1.36 p.p.m. characteristics of the hydrogens of the twin methyls, peaks at 2.0-2.06 p.p.m. characteristics of the

5

10

15

20

25

30

35

40

45

50

55

60

65

21

630 890

methyl hydrogens in position 2 of allethrolone; peaks of 4.83-5.25 p.p.m. characteristics of the hydrogens of the methylene terminal of the side chain of allethrolone; peaks of 5.5 to 6.17 ppm characteristic of hydrogen in the β position of the side chain of allethrolone and of the hydrogen carried by the carbon in position 1 of allethrolone, peaks of 4.83- 6.17 ppm characteristic of hydrogen in position 1 'of the substituted ethyl side chain; peaks of 1.67-2.16 p.p.m. characteristic of cyclopropyl hydrogens; peaks at 2.95-3.05 p.p.m. characteristics of the methylene hydrogens in position a of the side chain of allethrolone; peaks from 1.67 to 3.17 p.p.m. characteristics of methylene from the allethrolone cycle.

Example 36

1 R, eis 2,2-dimethyl3- (2 ', 2'-difluoro /', 2'-dibromo ethyl) cyclopropane-1-carboxylate of (R, S) a-cyano 3-phenoxy benzyl.

Stage A: 1R acid chloride, cis 2,2-dimethyl3- (2 ', 2' -difluo-ro V, 2'-dibromoethyl) cyclopropane-1-carboxylic.

2.5 g of petroleum ether (bp 35-75 ° C.) are introduced into 15 cm 3 of petroleum ether (cis. Obtained in Stage A of Example 35), 7 cm 3 of thionyl chloride are added, reflux, maintains reflux for 13 hours and 30 minutes, concentrates to dryness by distillation under reduced pressure, adds benzene, concentrates to dryness and obtains the chloride of lR acid, cis 2,2-dimethyl 3- (2 ', Crude 2'-difluoro, 2'-dibromoethyl) cyclopropane-l-carboxylic acid, used as it is for the following stage.

Stage B: 1 R, eis 2,2-dimethyl 3- (2 ', 2'-difluoro 1'. 2 '-dibromoethyl) cyclopropane-1-carboxylate of (R, S) a-cyano 3-phenoxy benzyl.

The acid chloride obtained in Stage A is dissolved in 15 cm3 of benzene, added at + 2 ° C, 1.995 g of alcohol (RS) a-cyano-3-phenoxy benzyl dissolved in 10 cm3 of benzene, introduced 1 cm3 of pyridine, stirred for 16 hours at 20 ° C, pour the reaction mixture into a mixture of water, ice, and hydrochloric acid, extract with ether, concentrate to dryness by distillation, purify the residue by chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (90/10) and obtaining 1.972 g of lR, cis 2,2-dimethyl 3- (2 ', 2'-difIuoro l', 2 '-dibromoethyl) cyclopropane-1-carboxylate of (R, S) a-cyano 3-phenoxy benzyl.

Analysis: (543.22)

Calculated:

C% 48.6 H% 3.5 Br% 29.4 F% 7.0 N% 2.6 Found:

48.9 3.5 29.6 7.1 2.5

I.R. spectrum (chloroform)

Absorption at 1735 cm-1, characteristic of C = 0; absorptions at 1588-1610 cm-1 and 1487 cm-1, characteristic of aromatic nuclei.

U. V. spectrum (ethanol)

Inflection at 230 nm (E j = 208)

Inflection at 268 nm (E j = 34)

Inflection at 273 nm (E j = 37)

Maximum at 278 nm (E J = 40)

Inflection at 285 nm (E j = 29).

Spectrum of R.M.N. (deuterochloroform)

Peaks of 1.03 to 1.45 p.p.m. characteristics of the hydrogens of the twin methyls; peaks of 1.75-2.0 p.p.m. characteristic of cyclopropyl hydrogens; peaks of 4.42-5.17 p.p.m. characteristics of hydrogen in position 1 'of the side chain

ethyl; peaks at 6.4-6.47 p.p.m. characteristics of hydrogen at C = N; peaks of 6.92-7.67 p.p.m. characteristics of hydrogens in aromatic rings.

5 Example 37

1 R, trans 2,2-dimethyl3- (2 ', 2'-difluoro 1', 2'-dibromoethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl.

Stage A: IR acid chloride, trans 2,2-dimethyl 3- (2 ', 2' -di-fluoro l ', 2' -dibromoethyl) cyclopropane-1 -carboxylic. io In 40 cm3 of petroleum ether (bp 35-75 ° C), 11 g of IR acid, trans 2,2-dimethyl 3- (2 ', 2'-difluoro 1' ^ '- dibromoethyl) are introduced. ) cyclopropane-1-carboxylic, add 10 cm3 of thionyl chloride, bring the reaction mixture to reflux, keep it there for 4 hours, remove the excess of thio-nyl chloride and of solvent by distillation under reduced pressure, add benzene, concentrate again to dryness and obtain the IR acid chloride, trans 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2'-dibromo-ethyl) cyclopropane-l-carboxylic used as is for the next stage.

Stage B: IR, trans 2,2-dimethyl 3- (2 ', 2'-difluoro 1', 2'-dibro-moethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl.

The acid chloride obtained in stage A is dissolved in 50 cm3 of benzene and 56 cm3 of solution (solution A) are obtained. 2.4 g of 3-phenoxy benzyl alcohol dissolved in 2.5 cm3 of benzene are added to 18.5 cm3 of solution A at + 2 ° C. Add 1 cm3 of pyridine and stir for 16 hours. 20 ° C, pour the reaction mixture into a mixture of water, ice and hydrochloric acid, extract with ether, wash the organic phase with water, dry over magnesium sulfate, concentrate to dryness, purify 30 the residue by chromatography on silica gel eluting with a mixture of cyclohexane and benzene (95/5) and obtains 3.204 g of IR, trans 2,2-dimethyl 3- (2 ', 2'-difluoro 1', 2 '-dibromoethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl.

Analysis: C2iH2oBr2F203 (518,206)

35 Calculated: C% 48.7 H% 3.9 Br% 30.9 F% 7.3 Found: 48.9 3.9 31.0 7.1

= 225);

= 33)

= 37)

= 36)

Spectrum of R.M.N. (deuterochloroform)

Peak at 1.27 p.p.m. characteristic of the hydrogens of methyl-50 gemini, peaks at 1.58-2.17 p.p.m. characteristics of the hydrogens of cyclopropyl; peaks at 3.67-4.33 p.p.m. characteristics of the hydrogen in position 1 of the substituted ethyl side chain; peak at 5.13 p.p.m. characteristic of methylene at carboxyl; peaks of 7.58-7.75 p.p.m. characteristics of the hy-55 drogenes of the aromatic nuclei.

The IR, trans 2,2-dimethyl 3- (2 ', 2'-difluoro 1', 2'-di-bromoethyl) cyclopropane-1-carboxylic acid used in stage A of the present example can be prepared in the following manner :

26.4 g 60 of IR, trans 2,2-dimethyl 3- (2 ', 2'-difluorovinyl) cyclopropane-1-carboxylic acid, introduced into the resulting solution, are dissolved in 150 cm 3 of methylene chloride. at - 60 ° C, in about one hour and 30 minutes, a solution of 24 g of bromine in 50 cm3 of carbon tetrachloride; stirred for 3 hours at -60 ° C., brought the temperature of the reaction medium to 20 ° C., concentrated to dryness by distillation under reduced pressure, crystallized from petroleum ether and obtained 14.09 g of IR acid, trans 2,2-dimethyl 3- (2 ', 2'-difIuoro l', 2'-dibromo-ethyl) cyclopropane-1-carboxylic M = 116 ° C.

U. V. spectrum (ethanol) Inflection at 225 nm (E \

40 1

Inflection at 265 nm (E *

1

i

Maximum at 271 nm (E „

v 1

45 Maximum at 277 nm (E}

v 1

630 890

Analysis: C8H10Br2F2O2 (335.98)

Calculated: C% 28.6 H% 3.0 Br% 47.6 F% 11.3 Found: 28.8 3.1 47.7 11.5

Spectrum of R.M.N. (deuterochloroform)

Peak at 1.33 p.p.m. characteristic of the hydrogens of twin methyls; peaks at 1.5—2.33 p.p.m. characteristics of the cyclopropyl hydrogens; peaks of 3.67 to 4.41 p.p.m. characteristics of the hydrogen in position 1 'of the substituted ethyl side chain; peak at 10.9 p.p.m. characteristic of the hydrogen of the carboxyl.

Example 38

IR, trans 2,2-dimethyl3- (2 ', 2'-difluoro /', 2'-dibromoethyl) cyclopropane-1-carboxylate from (RS) a-cyano 3-phenoxy benzyl.

The acid chloride IR, trans 2,2-dimethyl 3- (2 ', 2'-difluoro 1', 2'-dibromoethyl) cyclopropane-1-carboxyli-is prepared only from 11 g of acid, as in Example 37, and dissolving the resulting acid chloride in 50 cm3 of benzene, 56 cm3 of acid chloride solution (solution A) are thus obtained.

5.4 g of solution A are introduced, at 0 ° C., 5.4 g of α-cyano-3-phenoxy benzyl alcohol dissolved in 5 cm3 of benzene, 2 cm3 of pyridine are added, the mixture is stirred for 16 hours at 20 ° C, pour the reaction mixture into a mixture of water, ice and hydrochloric acid, extracted with ethyl ether and after the usual treatments concentrated to dryness by distillation under reduced pressure. The residue is purified by chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (90/10). 5.46 g of IR is obtained, trans 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2'-dibromoethyl) cyclopropane-l-carboxy-late from (RS) a-cyano 3-phenoxy benzyl.

Analysis: C22H19Br2F2N 03 (543.22)

Calculated:

C% 48.6 H% 3.5 Br% 29.4 N% 2.6 F% 7 Found:

49.1 3.5 28.8 2.5 6.7

I.R. spectrum (chloroform)

Absorption at 1745 cm-1 characteristic of carbonyl; absorptions at 1615—1590 cm-1 characteristic of hydrogens in aromatic rings.

U. V. spectrum (ethanol)

Inflection at 230 nm (E | = 192)

Inflection at 269 nm (E J = 34)

Inflection at 273 nm (E j = 36)

Maximum at 278 nm (E j = 39)

Inflection at 305 nm (E j = 1).

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.2—1.33 p.p.m. characteristics of the hydrogens of the twin methyls, peaks at 1.9-2.25 p.p.m. characteristics of the hydrogens of cyclopropyl; peaks at 3.66 ^, 33 p.p.m. characteristics of the hydrogen in position 1 'of the substituted ethyl side chain; peak at 6.45 p.p.m. characteristics of hydrogen carried by the same carbon as the radical C = N, peaks at 6.91-7.58 p.p.m. characteristics of hydrogens in aromatic rings.

Example 39

1R, cis 2,2-dimethyl 3- (2 '(RS) -fluoro 2'-chloro V, 2'-dibro-moethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl (isomer A and isomer B).

22

Stage A: 1R acid, cis 2,2-dimethyl3- (2 '(RS) -fluoro 2'-chlo-rol', 2 '-dibromoethyl) cyclopropane-1-carboxylic.

In 100 cm3 of carbon tetrachloride, 8.9 g of lR, cis 2,2-dimethyl 3- (2'-chloro 2'-fluorovinyl) 5-cyclo-propane-1-carboxylic acid (mixture of isomers) are dissolved. E 4- Z), add at -10 ° C, in about 30 minutes, 2.4 cm3 of bromine dissolved in 20 cm3 of carbon tetrachloride, stirred for 4 hours at +10 ° C, concentrated to dryness by distillation under reduced pressure, chromatograph the residue on silica gel, eluting with ethyl acetate, to obtain 13.7 g of 1R acid, cis 2,2-dimethyl 3- (2 '(RS) -fluoro 2'- chloro l ', 2'-dibromoethyl) cyclopropane-l-carboxylic.

I.R. spectrum (chloroform)

Absorption at 1710 cm-1, characteristic of C = O, absorption at 3510 cm-characteristic of OH,

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.30-1.32—1.42 p.p.m. characteristics of the hydrogens of the twin methyls; peaks at 1.75-2.08 p.p.m. characteristics of cyclopropyl hydrogens; peaks at 4.67-5.50 p.p.m. characteristic of hydrogen in position 1 'of the substituted ethyl side chain; peak at 10.75 p.p.m. characteristic of the hydrogen of the carboxyl.

Stage B: 1 R, is 2,2-dimethyl3- (2 '(RS) -fluoro2'-chloro V, 2' -dibromoethyl) cyclopropane-1-carboxylate of 3-phenoxy ben-25yl.

3.5 g of lR, cis 2,2-dimethyl 3- (2 '(RS) -fluoro 2'-chloro l', 2'-dibromoethyl) cyclopropane-1-carboxylic acid obtained in stage A are mixed , 3.5 g of 3-phenoxy benzyl alcohol, 3.5 g of neopentyl dimethyl formamide acetate, 35 cm 3 of benzene, brings the reaction mixture to 50 ° C., maintains it for 17 hours at this temperature, cools , concentrated to dryness by distillation under reduced pressure, chromatographs the residue on silica gel eluting with a mixture of benzene and cyclohexane (1/1) and obtains, on the one hand, 1.050 g of isomer A 35 of lR, cis 2,2-dimethyl 3- (2 '(RS) -fluoro 2'-chloro l', 2'-dibro-moethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl. M = 50 ° C.

Analysis: C2H20Br2Cl F 03 (534.65)

Calculated:

40 C% 47.17 H% 3.77 Cl% 6.63 F% 3.55 Br% 29.89 Found:

47.4 3.8 7.2 3.7 29.4

I.R. spectrum (chloroform)

45 Absorption at 1735 cm-1 characteristic of C = 0, absorption at 1675-1590-1490 cm- \ characteristic of aromatic rings.

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.23-1.39 p.p.m. characteristics of the hydrogens of the 50 twin methyls; peaks at 1.73-2.01 p.p.m. characteristics of cyclopropyl hydrogens; peak at 5.08 p.p.m. characteristic of the methylene hydrogens of the benzyl radical; peaks of 5.08-5.50 p.p.m. characteristics of the hydrogen in position 1 of the substituted ethyl side chain; peaks at 6.83-7.58 p.p.m. ca-55 characteristics of hydrogens in aromatic rings. On the other hand, 0.62 g of isomer B is collected.

Analysis:

Calculated:

C% 47.17 H% 3.77 Cl% 6.03 F% 3.55 Br% 29.89

60 Tr0Vé:

47.5 3.8 6.2 3.6 29.6

I.R. spectrum (chloroform)

Identical to that of the A isomer.

Spectrum of R.M.N. (deuterochloroform)

65 Peaks at 1.22—1.34 p.p.m. characteristics of the hydrogens of the twin methyls; peaks at 1.75-2.0 p.p.m. characteristics of cyclopropyl hydrogens; peak at 5.12 p.p.m. characteristic of the methylene hydrogen of the benzyl radical; peaks from 4.83 to

23

630 890

5.33 p.p.m. characteristics of hydrogen in position 1 'of the substituted ethyl side chain; peaks of 5.83 to 7.5 p.p.m. characteristics of the hydrogens of the aromatic rings.

The 1R, cis 2,2-dimethyl 3- (2'-chloro 2'-fluorovinyl) cy-clopropane-1-carboxylic acid used in stage A can be prepared in a similar manner to that used by D. BROWN in his 1974 thesis, entitled Structure Activity studies of halopyre-throïds, published in 1976, by "Xerox University Microfilms Ann. Arbor. Michigan USA on pages 27 to 29, to prepare the corresponding dl-trans acid, but using t-butyl 2,2-dimethyl 3S-formyl cyclopropane-1R-carboxylate instead of 2,2-dimethyl 3RS-formyl cyclopropane-1 RS-t-butyl carboxylate.

Example 40

(1 R, cis) -2,2-dimethyl-3- (1, 2 ', 2', 2'-tetrabromoethyl) cyclo-propane-1-carboxylate of 3,4,5,6-tetrahydrophthalimidomethyl Stage A: (1R, cis) 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrabromo ethyl) cyclopropane-1-carboxylic acid:

19.4 g of acid (IR.cis) 2,2-dimethyl 3- (2 ', 2'-dibromo vinyl) cy-clopropane-1-carboxylic acid are added to 150 cm 3 of carbon tetrachloride, 10. 4 g of bromine in solution in 22 cm3 of carbon tetrachloride, stirred for one hour at 20 ° C, concentrated to dryness by distillation under reduced pressure and obtained 31.4 g of crude product (M = 145 ° C). This crude product is recrystallized from 110 cm3 of carbon tetrachloride and 22.12 g of acid are obtained (1R, cis 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrabromo ethyl ) cyclopropane-1-carboxylic, mp 150 ° C.

This product is a mixture of two isomers (A) and (B) which are highlighted by the spectrum of R.M.N. Indeed, the spectrum of R.M.N. allows a compound to be detected (corresponding approximately to 2/3 of the mixture having peaks at 1.31-1.43 ppm corresponding to the hydrogens of the twin methyls and peaks from 5.33 to 5.66 ppm corresponding to the fixed hydrogen on the asymmetric monobrominated carbon and another compound (corresponding to approximately 1/3 of the mixture) having peaks at 1.28-1.48 ppm corresponding to the hydrogens of the twin methyls and peaks from 4.24 to 5.34 ppm corresponding with hydrogen fixed on asymmetric monobromed carbon.

In the mixture, we detect, moreover, peaks of 1.67 to 2.17 p.p.m. (hydrogens in positions 1 and 3 of cyclopropane) and a peak towards 11.25 p.p.m. (mobile hydrogen of the acid function).

The analysis of the mixture obtained (F = 150 ° C) is as follows: C8H10Br4O2 (457.804)

Calculated: C% 20.99 H% 2.20 Br% 69.82 Found: 20.9 2.2 70.2

Stage B: Acid chloride (1R, cis) 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrabromo ethyl) cyclopropane-1-carboxylic:

0.2 cm3 of dimethyl formamide are introduced into 179 cm 3 of petroleum ether (bp 35-75 ° C), 8.5 cm3 of thionyl chloride brings the mixture to reflux, 35.76 g of acid are introduced (1R, cis) 2,2-dimethyl 3- (1, 2 ', 2', 2'-tetrabromo ethyl) 1-carboxylic cyclopropane in 150 cm3 of methylene chloride, stirred for 2 hours at reflux, cooled, concentrated to dryness by distillation, add toluene, concentrate again to dryness by distillation under reduced pressure and obtain 38 g of crude acid chloride (mp = 88 ° C) used as it is for the following stage. Stage C: (1R, cis) 2,2-dimethyl-3- (1, 2 ', 2', 2'-tetrabromoethyl) 3,4,5,6-tetrahydrophthalimidomethyl-cyclopropane-1-carboxylate)

7.7 g of acid chloride prepared in the preceding stage are mixed with 2.9 g of neopynaminol in 50 cm 3 of anhydrous benzene, cooled to 0 ° C., introduced with stirring 3 g of pyridine, leaves to return to ambient temperature while maintaining stirring for 18 hours, pour the reaction mixture into a dilute hydrochloric acid solution, extract with benzene, wash with an aqueous solution of sodium bicarbonate, rinse with water until neutral, isolate the organic phase, dried over magnesium sulphate, filtered and concentrated under reduced pressure, obtains 10 g of crude product which is purified by chromatography on 5 silica (eluent: benzene-ethyl acetate 95-5), collects 3, 3 g of (1R, cis) 2,2-dimethyl 3- (r, 2 ', 2', 2'-tetrabromoethyl) cyclopro-pane-1-3,4,5,6-tetrahydrophthalimidomethylcarboxylate, in the form of mixture of isomers A and B and 0.5 g in the form of isomer (B)

Characteristics of the product obtained in the form of a mixture of isomers A and B:

20

[a] -rj- = - 21.5 ° ± 1 ° (c = 1%, benzene)

Analysis: C17H19Br4N04 PM = 620.982 15 Calculated: C% 32.88 H% 3.08 N% 2.25 Br% 51.47

Find:

33.8

3.2

Spectrum U. V. (ethanol) 1

Infi. = 218 nmE

20

1

= 243 = 275 = 269 = 170

2.1

e = 17,100 e = 16,700 e = 10,500

50.2

Max. = 223 nm E

Max. = 229 nm E

25 Infi. = 238 nm E

1

Infi. = 295 nm E] = 8 1

Spectrum R.M.N. (deuterochloroform)

30 Peaks at 4.98-5.17 ppm characteristic of hydrogen in position 1 'of the ethyl side chain of the isomer B, peaks at 1.2-1.45 ppm characteristic of the hydrogens of the methylated gemines of the isomer B, peaks at 5.17-5.38 ppm characteristic of hydrogen at position 1 'of the ethyl side chain of isomer A. Peaks at 1.2-1.38 ppm characteristic of hydrogens of the methyl methylated of the (A) isomer, peaks at 1.58-2.08 ppm characteristic of cyclopropyl hydrogens and cyclohexyl methyls.

Mass at 2.33 p.p.m. characteristics of the hydrogens of 40 methylenes of cyclohexyl.

Peaks at 5.33-5.70 p.p.m. characteristics of the hydrogens of the COOCH2N group

Characteristics of the product obtained as an isomer

(B)

"20

[a] - = + 72.5 ° ± 2.5 ° (c = 0.5%, benzene)

Analysis: C17H19Br4N04 PM = 620.982 Calculated: C% 32.88 H% 3.08 N% 2.25 Br% 51.47

50

Find:

33.5

3.3

2.2

50.1

Spectrum U. V.

55 Infi. 218 nmE 1

248

Max. 223 nm E = 278 Max. 228-229 nm E} = 272

Infi. 238 nm = E 1 = 172

Infi, around 295 nm E J = 7

65 Spectrum of R.M.N. (deuterochloroform)

Peaks at 4.98-5.16 p.p.m. characteristics of hydrogen in position 1 'of the ethyl side chain; peaks at 1.21—1.45 p.p.m. characteristics of the hydrogens of twin methyls;

630 890

24

peaks at 1.5-2 p.p.m. characteristic of the hydrogens of cyclopropyl and of the methylenes at β in cyclohexyl; Mass at 2.38 p.p.m. characteristic of the hydrogens of methylenes of cyclohexyl; peaks at 5.38-5.57 and 5.57-5.75 p.p.m. characteristics of the hydrogens of the COOCH2N group.

Example 41

(IR, trans) 2,2-dimethyl 3- (V, 2 ', 2', 2'-tetrabromoethyl) 3,4,5,6-tetrahydrophthalimido methyl cy-clopropane-1-carboxylate

Stage A: (1 R, trans) 2,2-dimethyl 3- (V, 2 ', 2', 2 ', ■ -tetrabromo ethyl) cyclopropane-1-carboxylic acid:

This compound is obtained by bromination of (IR, trans) 2,2-dimethyl 3- (2 ', 2'-dibromo vinyl) cyclopropane-1-carboxylic acid, mixture of isomers (A) and (B).

Spectrum of R.M.N.

Peaks of 1.30 to 1.40 p.p.m. (hydrogens of the 2-methyls of cyclopropane); peaks at 1.65-1.74 and 1.97 at 2.37 p.p.m. (hydrogens in 1 and 3 of cyclopropane); peaks at 4.30 ^, 47 and 4.47-4.65 p.p.m. (hydrogen in ethyl); peak at 9.63 p.p.m. (carboxyl hydrogen).

Stage B: Acid chloride (IR, trans) 2,2-dimethyl 3- (V, 2 ', 2'2'-tetrabromo ethyl) cyclopropane-1-carboxylic:

By the action of thionyl chloride on the acid (lR.tans) 2,2-dimethyl 3- (l ', 2', 2 ', 2', - tetrabromo ethyl) cyclopropane-l-carboxylic obtained in stage A, we obtains the acid chloride used as it is for the next stage.

I.R. spectrum (chloroform)

Absorption at 1778 cm "*.

Stage C: (IR, trans) 2,2-dimethyl3- (1, 2 ', 2', 2 ', - 3,4,5,6-tetrahydrophthalimi-do- tetrabromo-ethyl) cyclopropane-l-carboxylate methyl.

7.7 g of acid chloride prepared in the preceding stage are treated according to a procedure identical to that used in Stage C of Example 1.

9.2 g of crude product are obtained which are purified by chromatography on silica (eluent: benzene-ethyl acetate 9-1). After crystallization, the product is taken up in petroleum ether (40 ° C-70 ° C), drained, dried and recovered 5.4 g of (IR, trans) 2,2-dimethyl 3- (l ', 2', 2 ', 2'-tetrabromoethyl) cyclopropane-1-carboxylate of 3,4,5,6-tetrahydrophthalimido methyl. Mixture of isomers A and B. F = 124 ° C.

20

[a] -dd- = -l ° ± l ° (c = 1% benzene)

Analysis: C17H19Br4N04 PM = 620.982 Calculated: C% 32.88 H% 3.08 Br% 51.47 N% 2.25 Found: 33.1 3.2 51.1 2.1

Spectrum (ethanol)

Max. 224 nm E J = 274 e = 17,000

Max. 228 nm E j = 269 e = 16,700

Infi. 235 nmE j = 167 e = 10,400

Infi. 280 nmE j = 9

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.25-1.30-1.31 p.p.m. characteristics of the hydrogens of the twin methyls; peaks of 1.58 to 2.16 p.p.m. characteristic of the hydrogens of cyclopropyl and of the methylenes in β in cyclohexyl; peaks of 2.16 to 2.25 p.p.m. characteristics of the hydrogens of the methylenes a in cyclohexyl; peaks at 4.24-4.41 and 4.43-4.61 p.p.m. characteristics of hydrogen in position 1 'of the ethyl side chain; peaks at 5.51 and 5.55 p.p.m. characteristics of the COOCH2N group.

Example 42

(IR, trans) 2,2-dimethyl-3- (2 ', 2'-dichloro 1'2'-dibromo-ethyl) cyclopropane-1-carboxylate of (S) a-cyano 3-phenoxy benzyl.

5 Stage A: Acid (IR, trans) 2,2-dimethyl3- (2 ', 2'-dichloro l', 2'-dibromo ethyl) cyclopropane-1-carboxylic:

By the action of bromine on the acid (IR, trans) 2,2-dimethyl 3- (2 ', 2'-dichloro vinyl) cyclopropane-1-carboxylic, the acid is obtained (IR, trans) 2,2- dimethyl-3- (2 ', 2'-dichloro l', 2'-di-îo bromo ethyl) cyclopropane-1-carboxylic, mixture of isomers (A) and (B).

Spectrum of R.M.N.

Peaks at 1.17-1.37 p.p.m. (2-methyl hydrogens of cyclopropane); peaks of 1.65-1.73 p.p.m. to 1.93-2.03 p.p.m. 15 (hydrogens in 1 of cyclopropane); peaks at 4.23-4.45 and 4.45-4.62 p.p.m. (hydrogen in 1 'of 1' ethyl in 3 of cyclopropane).

Stage B: Acid chloride (IR, trans) 2,2-dimethyl 3- (2 ', 2' -dichloro 1 ', 2' -dibromo ethyl) cyclopropane-1-carboxylic: 20 By action of thionyl chloride on the acid prepared in previous stage A, the acid chloride is obtained (IR, trans) 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromo ethyl) cyclopropane-l -carboxylic.

I.R. spectrum (chloroform)

25 Absorption at 1777 cm "1

Stage C: (IR, trans) 2,2-dimethyl 3- (2 ', 2' -dichloro Y, 2 '-di-brorno ethyl) cyclopropane-1-carboxylate of (S) a-cyano 3-phenoxy benzyl.

4.45 g of the acid chloride prepared in the preceding stage are mixed with 2.6 g of (S) α-cyano 3-phenoxy benzyl alcohol in 100 cm 3 of anhydrous benzene.

Cool to + 15 ° C., add a solution of 5 cm3 of pyridine in 20 cm3 of anhydrous benzene. Stirring is continued for 3 hours at room temperature and the reaction medium is poured onto 100 cm 3 of 2N hydrochloric acid, the organic phase is isolated, washed with water and concentrated to dryness under reduced pressure.

After chromatography on silica (eluent: benzene), 4.9 g of (IR, trans) 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-40 dibromoethyl) cyclopropane-1-carboxylate are obtained. of (S) a-cyano 3-phenoxy benzyl, in the form of a mixture of isomers A and B.

20

Tal —- = 0 ° benzene l J D

45 Analysis: C22HltJCl203N PM = 576.12 Calculated:

C% 45.86 H% 3.32 Br% 27.74 Cl% 12.31 N% 2.43 Found:

46.0 3.4 27.5 12.2 2.2

50 Circular dichroism:

Max. at 287 nm A e = +0.12 Max. at 282 nm A e = +0.11 Max. at 265 nm A e = +0.042 55 Spectrum of R. M. N.

Peaks at 1.20-1.26-1.31 p.p.m. characteristics of the hydrogens of the twin methyls; peaks at 4.20 ^, 35 and 4.36-4.52 p.p.m. characteristics of hydrogen in position 1 'of the ethyl chain; peaks from 1.68 to 1.78 - from 1.97 to 2.07 and from 1.97 60 to 2.42 p.p.m. characteristics of the cyclopropyl hydrogens; peak at 6.42 p.p.m. characteristic of hydrogen from the COOCHCN group; peaks from 6.92 to 7.58 p.p.m. characteristics of the hydrogens in aromatic rings.

Stage D: Separation of the isomers A and Bdu (IR, trans) 2,2-dimé-65 thyl3- (2 ', 2'-dichloro 1', 2'-dibromoethyl) cyclopropane-1-carboxylate from (S) a-cyano 3-phenoxy benzyl.

Chromatography on silica 4.69 g of the mixture of isomers A and B of (IR, trans) 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibro-

25

630 890

moethyl) cyclopropane-1-carboxylate of (S) a-cyano 3-phen-oxy benzyl obtained in stage C, eluting with a hexane-pentane-ether-acetonitrile-isopropanol mixture (30-12-0.4—1, 2-0.03) and obtains:

-1.385 g of isomer A [a] = +35.5 ± 2.5 °

D

20 D

= -17.5 ± 2 ° (c = 0.8%,

(c = 0.5% benzene) and

- 0.980 g of isomer B [a]

benzene)

The benzyl alcohol (S) a-cyano 3-phenoxy used in Stage C of Example 3 is described in the patent application filed by the titular Company on January 31, 1978 under the number: 78.02.621 and entitled "Alcohol optically active substituted benzyl and its preparation process ". An example of the preparation of this alcohol is given below:

Stage A: Mixture of (1R, 5S) 6,6-dimethyl 4 (R) [(S) -cyano (3'-phenoxy phenyl) methoxy 3-oxa bicyclo (3-1-0) hexan-2-one and of (1R, 5S (6,6-dimethyl4 (R) [(R) -cyano (3'-phenoxyphenyl) methoxy] 3-oxa bicyclo (3-1-0) hexan-2-one.

22.5 g of alcohol (R, S) a-cyano 3-phenoxy benzyl, 9.46 g of lactone of acid (1R, 3S) cis 2,2-dimethyl 3- (dihydroxymethyl) cyclopropane are mixed. l-carboxylic, 0.150 g of paratoluene sulfonic acid monohydrate, brings to 80 ° C.

under a vacuum of 10 ~ 2 mm of mercury, maintains the reaction mixture for 2 hours under these conditions, the water formed being removed by distillation. Cool to 20 ° C. and obtains 30.7 g of crude mixture of (1R, 5S) 6,6-dimethyl 4 (R) [(S) -cya-no (3'-phenoxy phenyl) methoxy] 3-oxa bicyclo (3-1- 0) hexan-

2-one and (1R, 5S) 6,6-dimethyl 4 (R) [(R) -cyano (3'-phenoxy phenyl) methoxy] 3-oxa-bicyclo (3-1-0) hexan-2- one (mainly containing unreacted starting materials as impurities) (mixture A).

Stage B: (1R, 5S) 6,6-dimethyl4 (R) [(S) -cyano (3'-phenoxy phenyl) methoxy] 3-oxa bicyclo (3-1-0) hexan-2-one.

The mixture A obtained in Stage A is chromatographed on silica gel, eluting with a mixture of benzene and ethyl acetate (95/5) and 10.9 g of (1R, 5S) 6,6-dimethyl are obtained. 4 (R) [(S) -cyano (3'-phenoxy phenyl) methoxy] 3-oxa bicyclo (3-1-0) hexan-2-one 20

F = 126 ° C, [a] - = - 71 ° (ç = 1%, benzene)

Stage C: Alcohol (S) a-cyano 3-phenoxy benzyl.

10 g of (1R, 5S) 6,6-dimethyl 4 (R) ((S) cyano (3'-phenoxy phenyl) methoxy) 3 are introduced into a mixture of 100 cm 3 of dioxane and 50 cm 3 of water -oxabicyclo (3-1-0) hexan-2-on, obtained in stage B above, then 1 g of paratoluene sulfonic acid monohydrate, brings the reaction mixture to reflux, keeps it there for 23 hours, concentrated by distillation under reduced pressure, until half the initial volume is obtained, add ethyl ether, stir, separate the organic phase by decantation, wash it with water, dry it and concentrate it to dryness by distillation under reduced pressure , Chromatograph the residue (9.5 g) on silica gel, eluting with a mixture of benzene and ethyl acetate (9/1) and obtain 6.1 g of alcohol (S) a-cyano 20

Benzyl 3-phenoxy (a) —— = - 16.5 ° ± 1.5 ° (c = 0.8%, benzene.).

Spectrum of R.M.N. (deuterochloroform)

Peak at 3.25 p.p.m. characteristic of hydrogen of the alcohol function. Peak at 5.42 p.p.m. characteristic of hydrogen carried by the same carbon as the nitrile group.

Example 43

(1R, cis) 2,2-dimethyl 3- (2 ', 2'-dibromo 1', 2'-dichloroethyl) cyclopropane-1-carboxylate of (S) a-cyano 3-phenoxy benzyl Stage A: Acid (1R , cis) 2,2-dimethyl3- (2 ', 2'-dibromo 1', 2'-dichloroethyl) cyclopropane-1 -carboxylic:

11.8 g of chlorine are bubbled into 30 cm3 of carbon tetrachloride at 15 ° C., then added slowly to

- 10 ° C, 24 g of a solution of (1R, cis) 2,2-dimethyl 3- (2 ', 2'-dibromo vinyl) cyclopropane-1-carboxylic acid in 37 cm3 of methylene chloride, stirred for one hour and 30 minutes at 0 ° C, and for 2 hours at 25 ° C, concentrated under reduced pressure, purified by crystallization from carbon tetrachloride and obtained 7.4 g of acid (1R, cis) 2, 2-dimethyl 3- (2 ', 2'-dibromo l', 2'-dichIoro ethyl) cyclopropane-1-carboxy-lique. Mp 134 ° C. (mixture of isomers (A) and (B)).

Spectrum of R. M. N.

10 Peaks at 1.32-1.44 and 1.28-1.48 p.p.m. (2-methyl hydrogens of cyclopropane); peaks at 5.08-5.45 and 4.67-5.0 p.p.m. (hydrogen at 1 'of the ethyl chain in position 3 of the cyclopropane); peak at 10.1 p.p.m. (carboxyl hydrogen). Stage B: Acid chloride (1R, cis) 2,2-dimethyl3- (2 ', 2'-di-15 bromo 1', 2'-dichloro ethyl) cyclopropane-1-carboxylic:

By the action of thionyl chloride in the presence of pyridine on the acid obtained in the preceding stage A, the chloride of the acid (1R, cis) 2,2-dimethyl 3- (2 ', 2'-dibromo 1') is obtained. , 2'-dichloroethyl) cyclopropane-1-carboxylic acid, used as it is for the next stage.

Stage C: (1R, cis) 2,2-dimethyl3- (2 ', 2'-dibromo 1', 2'-dichloroethyl) cyclopropane-1-carboxylate of (S) a-cyano 3-phenoxy benzyl.

3.8 g of acid chloride prepared in the pre-yield stage are mixed with 2.5 g of (S) a-cyano 3-phenoxy benzyl alcohol in 100 cm 3 of anhydrous benzene. Cool to +15 ° C and add a solution of 4 cm3 of pyridine in 20 cm3 of anhydrous benzene. Stirring is continued for 4 hours at room temperature and the reaction medium is poured onto 100 cm 3 of 2N hydrochloric acid. The organic phase is isolated, washed with water, dried and concentrated to dryness under reduced pressure. After chromatography on silica / eluent: petroleum ether (40 ° -70 ° C) isopropyl ether (100-20), (1R, cis) 2,2-dimethyl 3- (2 ', 2'- di-bromo l ', 2'-dichloro ethyl) cyclopropane-l-carboxylate de (S) 35 a-cyano 3-phenoxy benzyle, in the form of 1.8 g of isomer A rf = 0.30 and 1, 4 g of isomer B rf = 0.25.

Physical controls of the A 20 isomer

[a] -g- = 0-21 ° ± 1% (c = 1 °, benzene).

40 Circular dichroism.

Max. at 300 nm A e = - 0.003 Max. at 288 nm A e = +0.29 Max. at 264nm Aë = + 0.11 Max. at 232 nm A e = - 1.8

45

Spectrum R.M.N. (deuterochloroform)

Peaks at 1.28-1.37 p.p.m. characteristics of the hydrogens of the twin methyls; peaks at 5.05-5.10 -5.18-5.23 p.p.m. characteristics of the hydrogen in position 1 'of the ethyl-50 lique side chain; peaks at 1.83-2.10 p.p.m. hydrogen characteristics of cyclopropyl.

Peaks at 6.38, p.p.m. characteristics of hydrogen from the COOCHCN group; peaks from 6.92 to 7.55 p.p.m. characteristics 55 of the hydrogens of the aromatic rings.

Physical controls of the B isomer.

20

[a] -dd- = + 80 ° ± 2.5 ° (c = 1%, benzene)

Circular dichroism 60 Max. at 288 nm A s = +0.22 Inf. at 263 nm At e = +0.62 Max. at 220 nm Ae = +3.7

Spectrum R.M.N. (deuterochloroform)

Peaks at 1.23-1.38 p.p.m. characteristics of the hydrogens of the 65 twin methyls; peaks of 4.6 to 4.95 p.p.m. characteristics of the hydrogen in position 1 'of the ethyl side chain; peaks of 1.75 to 2.16 p.p.m. characteristics of the cyclopropyl hydrogens; peak at 6.38 p.p.m. characteristic of hydrogen from

630 890

COOCHCN group; magpies from 6.88 to 7.57 p.p.m. characteristics of hydrogens in aromatic rings.

Example 44

(IR, eis) 2,2-dimethyl3- (1, 2 ', 2', 2'-tetrachloroethyl) cyclo-propane-1-carboxylate of (S) a-cyano 3-phenoxy benzyl.

Stage A: AcidflR, cis) 2,2-dimethyl 3- (Y, 2 ', 2', 2'-tetrachloroethyl) cyclopropane-1-carboxylic.

In 30 cm3 of carbon tetrachloride, the chlorine is bubbled until saturation (11.8 g of chlorine is dissolved), a solution of 16.7 g of acid (1R, cis) 2 is introduced in approximately 30 minutes 2, 2-dimethyl 3- (2 ', 2'-dichloro vinyl) cyclopropane-1-carboxyli-that in 40 cm3 of methylene chloride, at a temperature below 0 ° C, stirred for 24 hours at 0 ° C, brings the temperature of the reaction mixture at +25 ° C., stirred for 3 hours at this temperature, removes excess chlorine by nitrogen bubbling, concentrated to dryness by distillation, under reduced pressure, purifies the residue by chromatography on silica gel eluting with a mixture of cyclohexane and ethyl acetate (8/2), crystallizes from petroleum ether (bp 35-75 ° C) and obtains 3.14 g of acid (1R, cis) 2,2-dimethyl 3- (l '^' ^ '^' - tetrachloroethyl) cyclopropane-l-carboxylic. Mp 144 ° C.

Analysis: CsH10C14O2 (279.98)

Calculated: C% 34.3 H% 3.6 Cl% 50.6 Found: 34.4 3.7 50.3

Spectrum of R.M.N. (deuterochloroform)

Peaks at 1.26-1.42 p.p.m. and 1.30-1.42 p.p.m. characteristics of the hydrogens of twin methyls; peaks of 4.67-5.17 p.p.m. and 5.08 to 5.43 p.p.m. characteristics of the hydrogen in position 1 'of the substituted ethyl side chain; peaks of 1.67 to 2.0 p.p.m. characteristic of the cyclopropyl hydrogens; peak at 10.2 p.p.m. characteristic of 1 carboxyl hydroxide.

Stage B: Acid chloride (1R, cis) 2,2-dimethyl 3- (1 ', 2', 2 ', 2' -tetrachloroethyl) cyclopropane-1-carboxylic acid.

6.75 g of (1R, cis) 2,2-dimethyl acid are introduced into a mixture of 60 cm3 of petroleum ether (bp 35-70 ° C) and 8.7 cm3 of thionyl chloride 3- (l ', 2', 2 ', 2'-tetrachloroethyl) cyclopropane-l-carboxylic, brings the reaction mixture to reflux, maintains it there for 4 hours and 30 minutes, concentrates to dryness by distillation under reduced pressure, add benzene, concentrated to dryness and obtain the acid chloride (lR, cis) 2,2-dimethyl! 3- (1 ', 2', 2 ', 2'-tetrachloroethyl) cyclopropane-1-carboxylic acid used as it is for the following stage.

Stage C: (1R, cis) 2,2-dimethyl3- (1, 2 ', 2', 2'-tetrachlroethyl) cyclopropane-1-carboxylate of (S) a-cyano 3-phenoxybenzyl.

3.19 g of the acid chloride prepared in the preceding stage are mixed with 2.6 g of (S) a-cyano 3-phenoxybenzyl alcohol in 30 cm 3 of anhydrous benzene. Cooled in an ice bath and slowly add 3 cm3 of pyridine. The mixture is stirred for 24 hours at room temperature and then the reaction mixture is poured onto dilute, cold hydrochloric acid. It is extracted with benzene, the organic phases are isolated, washed with a sodium bicarbonate solution, rinsed with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification is carried out by chromatography on silica (eluent: benzene-cyclohexane 7-3) and the 1R, cis) 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrachloro-ethyl) cyclopropane-1 is obtained. -carboxylate of (S) a-cyano 3-phenoxy-benzyl in the form of 2.258 g of the isomer (A) and 1.48 g of the mixture of isomers A and B.

Physical analysis of the isomer (A)

20

[a] = + 35.5 ° ± 2 ° (c = 0.6%, benzene)

Analysis: C22Hi9Cl4N03 = 487.213 Calculated: C% 54.23 H% 3.93 N% 2.87 Cl% 29.1 Found: 54.4 3.8 2.8 28.5

26

Spectrum R.M.N. (deuterochloroform)

Peaks at 1.28-1.37 p.p.m. characteristics of the hydrogens of the twin methyls; peaks of 1.75 to 2.08 p.p.m. characteristic of the cyclopropyl hydrogens; peaks from 5.07 to 5.25 p.p.m.

5 characteristics of hydrogen in position 1 'of the ethyl side chain; peak at 6.35 p.p.m. characteristic of the hydrogens of the group COOCHCN; peaks from 6.92 to 7.58 p.p.m. characteristics of the hydrogens in aromatic rings.

10 Physical analysis of the AetB 20 isomer mixture

[at]

D

= —33.5 ° ± 2.5 ° (c = 0.4% benzene)

20

25

30

35

Analysis: C22H19CI4N03 = 487.213 Calculated: C% 54.23 H% 3.93 N% 2.87 Cl% 29.1 Found: 54.5 3.9 2.8 28.8

Spectrum R.M.N. (deuterochloroform)

Peaks at 1.2-1.35 p.p.m. characteristics of the hydrogens of the twin methyls of the R isomer; peaks at 1.27-1.35 p.p.m. characteristics of the hydrogens of the twin methyls of the S isomer; peaks at 1.75-2.08 p.p.m. characteristics of the cyclopropyl hydrogens; peaks of 4.77 to 4.94 p.p.m. characteristics of the hydrogen in position 1 'of the ethyl side chain; peaks of 5.08 to 5.26 p.p.m. characteristics of the hydrogen in position 1 'of the ethyl side chain; peaks at 6.35 and 6.37 p.p.m. characteristics of the hydrogen of the group COOCHCN; peaks of 7.93 to 7.58 p.p.m. characteristics of the hydrogens of the aromatic rings.

Example 45

(IR, trans) 2,2-dimethyl3- (2 ', 2'-dichloro 1', 2 '-dibromoethyl) cyclopropane-1-carboxylate from (R) a-cyano 3-phenoxy benzyl.

By operating as in stage C of Example 3, starting from 2 g of acid chloride (IR, trans) 2,2-dimethyl 3- (2 ', 2'-di-chloro l', 2 ' -dibromoethyl) cyclopropane-1-carboxylic acid, obtained in stage B of Example 3, and 1.1 g of alcohol (R) a-cyano 3-phenoxy benzyl, 1.4 g of (IR, trans) 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromoethyl) cyclopropane-l-carboxylate of (R) a-cyano 3-phenoxy benzyl, as a mixture of isomers A and B.

20

[a] -r— = - 28 ° ± 2 ° (c = 0.7%, benzene)

U

Analysis: C22H19Br2Cl2N03 PM = 576.122 Calculated:

C% 45.87 H% 3.32 N% 2.43 Cl% 12.31 Br% 27.74 Found:

46.3 3.3 2.4 12.4 27.4

Spectrum R.M.N. (deuterochloroform)

50 Peaks at 1.31—1.35 p.p.m. characteristics of the hydrogens of the twin methyls; peaks of 1.66 to 2.42 p.p.m. characteristics of the cyclopropyl hydrogens.

Peaks at 4.23-4.42 p.p.m. characteristics of hydrogen in and at 4.42-4.58 p.p.m. position 1 'of the ethyl-55 lique side chain.

Peak at 6.47 p.p.m. characteristic of hydrogen from the COOCHCN group; peaks from 6.92 to 7.58 p.p.m. characteristics of the hydrogens in aromatic rings.

60 Circular dichroism (Dioxane)

Maximum at 219 nm e = - 5.4 Maximum at 280 nm e = - 0.28 Inflection at 285 nm e = - 0.27

The mixture of isomer A and B 65 prepared above is chromatographed on silica eluting with a hexane-pentane-ether mixture (7-2.8-0.17) and the A and B isomers are obtained separately. Isomer A

Spectrum R.M.N. (deuterochloform)

45

27

630 890

Peaks at 1.32-1.37 p.p.m. characteristics of the hydrogens of the twin methyls.

Peaks at 1.66-1.76 p.p.m. characteristics of hydrogens due to 2.08-2.17 p.p.m. cyclopropane and 2.26-2.35 p.p.m.

Peaks at 4.2-4.37 p.p.m. characteristics of the hydrogen in position 1 'of the ethyl side chain; peak at 6.42 p.p.m. characteristic of hydrogen from the COOCHCN group;

peaks from 6.92 to 7.58 p.p.m. characteristics of the hydrogens in aromatic rings.

Isomer B

Spectrum R.M.N. (deuterochloroform)

Peaks at 4.37-4.53 p.p.m. characteristics of the hydrogen in position 1 'of the ethyl side chain;

The alcohol (R) a-cyano 3-phenoxy benzyl used starting from Example 6 was prepared as follows:

Stage A: (1R, 5S (6,6-dimethyl4 (R) [(R) cyano (3'-phenoxyphé-nyl) méthoxy] 3-oxa bicyclo (3-1-0) hexan-2-one.

The chromatography started in Stage B of the preparation described in Example 3 is continued and 7.32 g of expected product is obtained.

r ï 20

[a] - = - 120 ° ± 2.5 ° (c = 0.9%, benzene)

Stage B: Alcohol (R) a-cyano 3-phenoxy benzyl.

The procedure is analogous to that described in stage C of the preparation described in example 3, starting from 12.8 g of product described in the preceding stage, and obtaining after the same purification by chromatography 5 g of expected product .

20

[a] -dd- = + ll ° ± 2 ° (c = 0.5%, benzene)

Study of the insecticidal properties of the (A) and (B) isomers of (IR, eis) 2,2-dimethyl3- (l ', 2', 2 ', 2'-tetrabromo ethyl) cyclopropane-l-carboxylate of (S) a-cyno 3-phenoxy benzyl (compounds Y, and Y2), insecticidal properties of the isomers (A), and (B) of (lR, cis) 2,2-dimethyl 3- (2 ', 2' -dichloro V , 2 '-dibromoethyl) cyclopropane-1-carboxylate of (S) a-cyano 3-phenoxy benzyl (compounds Y3 and Y4) as well as of the following compounds:

dl-cis-trans 2,2-dimethyl 3- (2 ', 2'dichloro 1' ^ '- dibromoethyl) cyclopropane-1-carboxylate of RS a-cyano 3-phen-oxy benzyl (compound Y5); IR, trans 2,2-dimethyl 10 3- (1,2 ', 2', 2 ', 2'-tetrabromoethyl) cyclopropane-1-carboxylate from (RS) a-cyano 3-phenoxy benzyl (compound Y6); 1R, cis 2,2-dimethyl 3- (2 ', 2'-dibromo l', 2'-dichloroethyl) cyclopropane-1-carboxylate from (RS) a-cyano 3-phenoxy benzyl (compound Y7); IR, trans 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromo-15 ethyl) cyclopropane-1-carboxylate de (RS) a-cyano 3-phenoxy benzyle (compound Y8) ; 1R, cis 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-t-trabromoethyl) cyclopropane-1-carboxylate of 5-benzyl 3-furyl methyl (compound Y9).

Study of the lethal effect of compound Y7 on house flies

20

ques.

1) Study of the activity of the compounds Y ,, Y2, Y3 and Y4.

The test insects are 4-day-old female house flies. One operates by topical application of 1 μl of acetonic solution on the dorsal thorax of the insects using the micro-manipulator from Arnold. 50 individuals are used per treatment. The mortality check is carried out twenty-four hours after treatment.

The tests are carried out without a synergist or with the addition of piperonyl butoxide (10 parts of synergist for 1 part 30 of test compound).

The experimental results, summarized in the following table, are expressed in LD 50 or dose (in nanograms) necessary to kill 50% of the insects:

LD 50 in nanograms Compound Y! Compound Y2 Compound Y3 Compound Y4 (Isomer A) (Isomer B) (Isomer A) (Isomer B)

without synergist with synergist

1.13 0.24

1.0

0.55

1.25 0.83

0.60 0.46

Conclusion: Compounds Y1; Y2, Y3 and Y4 of the invention have extremely high lethal activity on houseflies. This activity is enhanced by the addition of piperonyl butoxide

2) Study of the activity of compound Y7 The conditions of this study are the same as above. The results were as follows:

Compound Y7 not synergized

Synergized Y7 compound

Doses in mg active ingredient /

liter

5

3.75 2.50 1.25 5

2.5 1.0 0.5

Percentage of 24-hour mortality

83.3 76.7 63.3 26.6 100 93.3

46.6

16.7

DL5ü in ng / insect.

2.03

0.99

Conclusion: compound Y7 is endowed with a strong insecticidal activity with regard to houseflies.

B) Study of the lethal effect on larvae of Spodoptera littoralis: 1) The tests are carried out by topical application of an acetonic solution using the micro manipulator of Arnold on the dorsal thorax of the larvae. 10 to 15 larvae are used per dose of

45 product to be tested. The larvae used are larvae of the fourth larval stage, that is to say about 10 days old when raised at 24 ° C and 65% relative humidity. After treatment, the individuals are placed on an artificial nutritive medium (Poitoit medium).

50 Mortality checks are carried out 48 hours after treatment.

The experimental results are summarized in the following table:

55 DL 50 in nanograms

Compound Y! Compound Y2 (Isomer A) (Isomer B)

0.6

0.32

Conclusion: The compounds Y (and Y2 of the invention are endowed with an extremely high lethal activity on larvae of Spodoptera littoralis.

2) Study of the insecticide activity on caterpillars of Spodoptera Littoralis of an approximately equimolecular mixture of compound Y] and of compound Y2, of a substantially equimolecular mixture of compound Y3 and of compound Y4, of compound Y7 and of compound

Yg.

630 890

28

The tests are carried out by topical application. 1 ni of an acetone solution of the product to be tested is placed on the dorsal thorax of each individual. 15 caterpillars of Spodoptera Littoralis in the 4th larval stage are used, for each dose used. After treatment, the individuals are placed on an artificial nutritive medium (Poitoit medium). The efficacy control is carried out (percentage of mortality taking into account an untreated control) 24 hours then 48 hours after treatment and the lethal dose 50 (LD50) in nanograms per caterpillar is determined.

The experimental results are summarized in the following table:

Compound mg of ma-% efficiency LD50 to

48 hours

active per liter per ng / ng / track track 24 H 48 H

The K.T. 50 or knock-time 50 indicates the time required to kill 50% of the insects with a fixed dose of product to be tested. This time is inversely proportional to the speed of action of the product.

5 Conclusion: The compounds Y 1: Y2, Y3 and Y4 of the invention have an interesting impact activity on flies.

D) Study of the insecticidal activity of the compounds Y3 (isomer A) and Y4 (isomer B) Y5, Y6, Y7, Ys, on larvae of Epilachna Varivestris.

The tests are carried out by topical application in a manner analogous to that used for the larvae of Spodoptera. Larvae of the penultimate larval stage are used and after treatment the larvae are fed by bean plants. The mortality control is carried out 72 hours after treatment.

The experimental results are summarized in the following table:

Doses

%of

LD50 in

Mixed

Compound

in mg / 1

mortality

ng / insect noticeably

0.5

80.0

66.7

20

equimolecular

40.0

1.25

100

decomposed Y!

0.375

53.3

Compound Y3

1

90

(isomer

0.38

(isomer A)

0.37

A) and of

0.25

33.3

33.3

0.625

60

compound Y2

25

0.312

50

(isomer B)

0.125

0

0

Compound Y4

1

0.625

90.0 80.0

Mixed

(isomer B)

0.20

noticeably

0.5

100

100

30

0.312

70.0

equimolecular

0.156

40.0

of compound Y3

0.375

76.7

73.3

(isomer

0.31

5

100

A) and of

0.25

40

40.0

Compound Y5

2.5

80

compound Y4

35

0.53

(isomer B)

0.125

2.5 1.25

49.3

20.0

100 66.6

1.25 0.625

70 50

Compound Y7

0.51

4o Compound

Doses

%of

LD50 in

0.625

53.3

in mg / 1

mortality

ng / insect

0.312

40.0

1

93.2

Compound Y5

2.5

90

0.75

66.6

1.25

80

Compound Ya

0.50 0.25

46.6 13.3

0.51

45

0.625 0.312

60 40

0.44

Control: zero mortality.

Conclusion: The compounds tested have a very high insecticidal activity with respect to Spodoptera Littoralis.

C) Study of the shock activity on houseflies: Compound Y7

The test insects are 4-day-old female house flies. The operation is carried out by direct spraying in a Kearns and March chamber, using a mixture of 55 Compound Y8 equal volumes of acetone and keronese as solvent (quantity of solution used 2 X 0.2 cm3). About 50 insects are used per treatment. The controls are carried out every minute up to 10 minutes, then at 15 minutes and the KT 50 is determined by the usual methods.

The experimental results obtained are summarized in the following table:

60

5

100

2.5

90

1.25

50

0.625

40

5

100

2.5

80

1.25

60

0.625

40

0.312

20

0.93

0.88

KT 50 in minutes (for a concentration of 1 g / 1 Compound Y! Compound Y2 Compound Y3 Compound Y4 (Isomer A) (Isomer B) (Isomer A) (Isomer B)

3.5

6.5

4.5

4.2

E) Study of the insecticidal activity on Sitophilus Granarius and Tribolium Castaneum, of a mixture in substantially equimolecular proportion of compound Y! (isomer A) and of com-65 posed Y2 (isomer B), and of a mixture in approximately equimolecular proportion of compound Y3 (isomer A) and of compound Y4 (isomer B).

The test is carried out by direct spraying on infested wheat.

29

630 890

5 ml of acetone solution of the product to be tested is sprayed and after 7 days taking into account an untreated control and 0.1 cm3 of water on 100 g of wheat contained in a 1 liter flask averaging over 100 individuals and we determine them with a rotary evaporator (in motion). Lethal concentrations 50 (LC 50) are carried out.

artificial festation by 50 individuals (Sitophilus or Tribolium). The experimental results obtained are summarized in the

For each dose, the percentage of mortality is determined in the following table:

Compound

Doses in p.p.m.

% efficiency at

CL 50

CL 50

7 days

in in

Sito

Tribo p.p.m.

p.p.m.

philus lium pour pour

Grana

Casta-

Sito

Tribo rius néum.

philus lium.

Mixing in proportion substantially

equimolecular 1,67.0 100.0

compound Y [(isomer A) and 0.5 28.7 92.0 0.75 0.32

compound Yz (isomer B) 0.25 4.0 24.3

Mixing in proportion substantially

1 62.5 100 equimolecular

compound Y3 (isomer A) and 0.5 18.4 99.0 0.85 0.22

compound Y4 (isomer B) 0.25 2.0 62.6

Natural mortality control: Sitophilus 1.0%, Tribolium 4.0%.

Conclusion: The mixtures tested are endowed with a strong insecticidal activity on Tribolium Castaneum.

Their activity on Sitophilus Granarius is a little lower.

F) Study of the insecticidal activity on Blatella Germanica (adult males) of a mixture in approximately equimolecular proportion of compound Y! (isomer A) and of compound Y2 (isomer only to 10 mg / 1 of product to be tested, then leaves the acetone to evaporate; the film formed corresponds to 1.3 mg of active material per m2. The insects are placed on the We count the 30 insects killed after 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 40 minutes, 50 minutes, 60 minutes. We remove the insects from the Petri dish and transfer them to clean jars. Mortality checks are carried out after 24 hours, 48 hours and 72 hours (the

B) and a roughly equimolecular mixture of 35 percent slaughtered and dead insects is determined

compound Y3 (isomer A) and compound Y4 (isomer B).

The test carried out is a test by film on glass. 154 cm2.2 cm3 of acetonitrile solution are placed in petri dishes.

Compounds

% of slaughter (K.D.)

mined taking into account an untreated witness.

The experimental results are summarized in the following table:

% mortality

active ingredient

in mg / 1

5

10

15

20

25

30

40

50

60

24h

48 H

72 H

mn mn mn mn mn mn mn mn mn mn

Substantially mixed

10

20.0

40.0

70.0

75.0

80.0

85.0

90.0

100

100

95.0

90.0

95.0

equimolecular of

compound Y! (isomer A)

1

15.0

10.0

10.0

20.0

30.0

35.0

60.0

70.0

85.0

40.0

70.0

70.0

and of

compound Y2 (isomer B)

0.1

0

0

0

10.0

10.0

O ©

15.0

20.0

30.0

0

0

0

Substantially mixed

10

30.0

45.0

70.0

85.0

95.0

95.0

100

100

100

100

100

100

equimolecular of

compound Y3 (isomer A)

1

5.0

10.0

35.0

55.0

60.0

70.0

70.0

95.0

100

50.0

65.0

65.0

and of

compound Y4 (isomer B)

0.1

0

0

5.0

5.0

10.0

20.0

30.0

30.0

35.0

10.0

10.0

10.0

Witness

0

0

0

0

0

0

0

0

0

0

0

0

Conclusion: The mixtures in roughly equimolecular proportions of compound Yt and of compound Y2, as well as the mixtures in roughly equimolecular proportions of compound Y3 and compound Y4, are endowed with a remarkable insecticidal activity, with respect to Blatella Germanica.

Example 41

Study of the acaricidal activity of compound Y2, of a mixture of compound Y, (isomer A) and of compound Y2 (isomer B) and of a mixture of compound Y3 (isomer A) and of compound Y4 (isomer B)

A) Activity on Tétranychus Urticae.

s Ovicide and larvicide test.

Bean leaves are infested with 10 females of Tetranychus Urticae per leaf and coated with glue around their periphery; the females are allowed to lay eggs for twenty-four

630 890

30

hours, remove them and divide the leaves infested with eggs in two groups.

a) a first group is treated with the test compound; the operation is carried out by spraying 0.5 cm 3 of aqueous solution onto each sheet using concentrations of 50 and 25 g of test compound per hectare.

b) a second group of leaves is not treated and serves as a control group.

The count of live eggs and live larvae takes place nine days after the start of treatment. The results expressed as a percentage of mortality of eggs and larvae are summarized in the following table (taking into account the untreated control).

The experimental results are summarized in the following table:

Compounds

Grams number% mortality

of active egg material laid.

per ha. eggs larvae

Substantially mixed

equimolecular 50 103 25.2 33.8

compound Yj (isomer A)

and compound

Y2 (isomer B) 25 161 22.4 22.4

Substantially equimolecular mixture of 50

compound Y3 (isomer A)

and of compound Y4 (isomer B) 25

85 45.9 23.9

i love

61 19.7 21.5 0 181 7.7 2.4

Dose 2.5 g / hl of compound Y2 338 Control 492

7 days 16 days 26 days

453,967

356,696

Conclusion: Compound Y2 has a clear miticide activity on adults and larvae of Panonychus Ulmi.

Study of the nematicidal activity on Ditylenchus Myceliophagus of a mixture of compound Y \ (isomer A) and compound Y2 (isomer B) and of a mixture of compound Ys (isomer A) and compound Y4 (isomer B).

In a pill box containing 10 ml of aqueous acaricide solution to be tested, 0.5 ml of water containing approximately 2000 nematodes is deposited. The mortality checks are carried out with a binocular microscope twenty-four hours after the treatment and on three repetitions each corresponding to a sample of 1 ml of the solution to be tested.

The experimental results obtained are summarized in the following table (results expressed as percentages of mortality) taking into account an untreated control.

io Material Compound% of active mortality in mg / 1

Mixture in substantially 15 equimolecular proportion of 10 99%

compound Y! (isomer A)

and of compound Y2 (isomer B). 1 23.5%

Mixing in proportion substantially

2oequimolecular of 10 99.3% compound Y3 (isomer A)

and of compound Y4 (isomer B). 1 41.5%

Conclusion: the mixtures of compounds Yt and Y2 and of compounds Y3 and Y4 treated have ovicidal and vis-larvicidal activity. with regard to Tetranychus Urticae.

B) Activity on Panonychus Ulmi.

The test was carried out with the compound Y2 on the “SIRAH” grape vine. It includes 4 repetitions for each dose, according to the block method. An untreated control is introduced into each block.

Each elementary plot is made up of 10 vines.

A single treatment is carried out, on the basis of 1000 liters of spray mixture per hectare, using a Van de Weij sprayer at constant pressure.

The control is carried out 7 days, 16 days, then 26 days, after treatment. There are the mobile forms (larvae and adults) present on 15 leaves, by harvesting them by brushing and the results are expressed relative to the untreated control.

The experimental results obtained are summarized in the following table:

Number of mobile forms on 15 sheets:

Witness 0 3.2

25 Conclusion: The mixtures tested are endowed with an interesting nematicidal activity with respect to Ditylenchus Myceliophagus.

Study of the ixodicidal activity of an equimolecular mixture of compound Yt and compound Y2.

To carry out these tests, a solution was used, the preparation of which is given below in Example 52.

This 0.5 percent solution of active ingredient is diluted at the time of use in 50 times its volume of water, which leads to a concentration of 1 / 10,000.

35 A) In vitro test

Ticks of the genus "Rhipicephalus Sanguineus" were collected from dogs. They were brought into contact for 30 minutes with the preparation containing 1 / 10,000 of active principle. It was found that after 30 minutes, the ixodes are 40 animated by uncoordinated movements and that 4 hours later, they are dead (while control ixodes are unharmed).

B) Dog test

Two dogs infested with Iododes of the genus Rhipicephalus Sanguineus were used; ticks are attached mainly to the head; on the 45 ears, on the neck and on the chest.

The body of each animal is soaked with a solution containing 1 / 10,000 of active principle (2.5 liters per dog).

The room where the animals are kept is sprayed with the remainder of the solution used to treat them.

n / a We note, after 24 hours that the ticks are still fixed and still show movements.

After 72 hours, the ticks are still fixed but are dead.

The local and general tolerance is excellent, the animals 55 being observed for 8 days after the treatment.

Example 44

Study of the antifungal activity of lR, cis 2,2-dimethyl 3- (l ', 2', 2 ', 2' - (RS) tetrabromoethyl) cyclopropane-l-carboxy-60 late of (S) a-cyano 3-phenoxy benzyl (compounds Y2 + Y2 or A) and IR, eis 2,2-dimethyl3- (2 ', 2'-dichloro 1', 2 '- (RS) dibromoethyl) cyclopropane-1-carboxylate of (S ) a-cyano 3-phenoxy benzyl (compounds Y3 + Y4 or B).

The fungistatic efficacy of the compound to be tested is studied by introducing 65 cm3 of the solution of the compound and 0.5 cm3 of a suspension of spores of the fungus to be controlled adjusted to approximately 100,000 spores per cm3 in 4 cm3 of nutrient medium. from STARON.

31

630 890

The reading is carried out, after 7 days of incubation, by visual control of the development of the fungus or of its lack of development (0% or 100% efficiency).

The nutrient medium of STARON with the following composition:

- glucose = 20 g

- peptone - 6 g

- yeast extract = 1 g

- corn steep = 4 g

- sodium chloride = 0.5 g

- monopotassium phosphate = 1 g

- magnesium sulfate = 0.5 g

- ferrous sulfate = 10 mg

- water sufficient for 1 liter.

A) Test on Fusarium Roseum.

Using the operating protocol given above, we find that the fungistatic thresholds of compounds A and B are between 25 and 50 p.p.m.

B) Test on Botrytis Cinerea

The fungistatic thresholds of compounds A and B are between 25 and 50 p.p.m.

C) Test on Phoma Species

The fungistatic threshold of compound A is between 25 and 50 p.p.m. and that of compound B is between 10 and 25 p.p.m.

D) Test on Roqueforti Penicillium

The fungistatic threshold of compound B is between 150 and 200 p.p.m.

E) Conclusion: Compounds A and B are endowed with an interesting antifungal activity with respect to the fungi tested.

Study of the insecticidal activity of (IR, trans) 2,2-dimethyl 3- (2 ', 2'-dichloro 1', 2'-dibromoethyl) cyclopropane-l-carboxylate of (S) a-cyano 3-phenoxy benzyl (compound A), of the A isomer of (1R, cis) 2,2-dimethyl3- (2 ', 2'-dibromo 1', 2'-dichloroethyl) cyclopropane-1-carboxylate of (S) a- cyano 3-phenoxy benzyl (compound B) and the isomer B of the same compound (compound C).

1) Study of the lethal activity of compounds A, B and C, on houseflies.

The test insects are 4-day-old female house flies. One operates by topical application of 1 [A, acetonic solution on the dorsal thorax of insects using the ARNOLD micromanipulator. 50 individuals are used per treatment. The mortality check is carried out twenty-four hours after treatment.

The tests are carried out without a synergist or with the addition of piperonyl butoxide (10 parts of synergist for 1 part of compound to be tested).

The experimental results, summarized in the following table, are expressed in LD 50 or dose (in nanograms) necessary to kill 50% of the insects:

treatment. The controls are carried out every minute up to 10 minutes, then at 15 minutes and the KT 50 is determined by the usual methods.

The experimental results obtained are summarized in the following table:

KT5ü in minutes Compound A 6.00

Compound B 6.12

io Compound C 6.02

Conclusion: Compounds A, B and C have an interesting knock down power against house flies.

3) Study of the insecticidal activity, on house flies of compound A used in the form of a smoke coil. 15 Neutral supports of smoke coils are impregnated with active material in solution in acetone. 20 female 4 to 5 day old female house flies are dropped into a closed glass cylinder of 13.50 dm3 and a smoke coil burning at one end is introduced for 2 minutes. The knock-down control is carried out every minute and the test is stopped 5 minutes after all the insects have been killed. Three series of tests are performed for each dose.

Doses by weight KT50 KT5û KT5û KTso average 25 of active material for coil weight

30 Compound A

0.4% 7.5 8.8 6.6 7.75

0.2% 11.8 10.2 9.2 10.22

Conclusion: Used in fumigant composition, compound A shows good insecticidal activity.

35 4) Study of the insecticidal activity of compounds A, B and C, on caterpillars of Spodoptera Littoralis.

The tests are carried out by topical application. 1 μl of an acetone solution of the product to be tested is deposited on the dorsal thorax of each individual. 15 caterpillars of Spodoptera 40 Littoralis in the 4th larval stage are used, for each dose used. After treatment, the individuals are placed on an artificial nutritive medium (Poitoit medium). The efficacy control is carried out (percentage of mortality taking into account an untreated control) 24 hours then 48 hours after treatment and the lethal dose 50 (LD50) in nanograms per caterpillar is determined.

The experimental results are summarized in the following table:

Compound A non-synergized Compound A synergized Compound B non-synergized Compound B synergized Compound C non-synergized Compound C synergized

LD 50 in ng / insect

5.75

0.91

1.67

0.88

2.95

0.82

50 Compound A Compound B Compound C

LD50 in ng / tracks

0.22

0.57

0.65

Conclusion: Compounds A, B and C are endowed with a strong insecticidal activity towards house flies.

2) Study of the knock-down activity of compounds A, B and C on house flies.

The test insects are 4-day-old female house flies. The operation is carried out by direct spraying in a KEARNS and MARCH chamber, using as solvent a mixture of equal volumes of acetone and kerosene (amount of solution used 2 X 0.2 cm3). We use about 50 insects per

Conclusion: Compounds A, B and C are endowed with a strong insecticidal power with regard to the caterpillars of Spodoptera Littoralis.

5) Study of the insecticidal activity on larvae of Epilochna vari-vestris

The tests are carried out by topical application in a manner analogous to that used for the spodoptera larvae. Larvae of the penultimate larval stage are used and after treatment the larvae are fed by bean plants. The mortality control is carried out 72 hours after treatment. The experimental results are summarized in the following table: 65 LD50 ng / per individual

Compound A 0.18

Compound B 4.26

Compound C 6.95

630 890

32

Conclusion: Compounds A, B and C are endowed with a strong insecticidal activity on the larvae of Epilachna variverstris. Compound A, in this area, has a particularly marked activity.

6) Study of the insecticidal activity of compound A on Aedes Aegypti larvae.

370 ml jars are used, into which 200 ml of water are introduced. The water in each jar is treated with 1 ml. of acetone solution containing the product to be tested. Each jar is infested with 10 Aedes Aegypti larvae (at the last larval stage). The larvae are brought from the roost in 49 ml of water. The effectiveness checks are carried out 24 hours to 48 hours after the infestation. For the duration of the test, the jars are stored in an oven at 25 ° C.

Conclusion: Compound A is endowed with a strong insecticidal activity with respect to Dysdercus fasciatus.

9) Study of the insecticidal activity of compound A on Sitophilus Granarius and Tribolium Castaneum.

5 The test is carried out by direct spraying on infested wheat. 5 ml of acetone solution of the product to be tested and 0.1 cm3 of water are sprayed onto 100 g of wheat contained in a 1 liter flask of a rotary evaporator (in motion). An artificial infestation is carried out by 50 individuals (Sitophilus or Tribolium). io For each dose, the percentage of mortality is determined after 7 days by taking the compote from an untreated control and averaging over 100 individuals and the lethal concentrations in p.p.m. are determined.

The results obtained are summarized in the following table:

15 Doses

Sitophilus granarius

Tribolium

Castaneum

in p.p.m.

CL5U in p.p.m.

% mor

LC50 in

% mor

CLgo in

Compound A 3.24 X 10 ~ 5

tality

p.p.m.

tality

p.p.m.

1.5

90.0

100

Conclusion: Compound A has a strong activity

20 1.0

66.70

96.9

insecticide on Aedes Aegypti larvae.

0.75

35.3

0.80

89.5

0.19

7) Study of the insecticidal activity of compound A on Blattella

0.5

18.2

85.3

germanica.

0.25

2.0

62.0

This test is performed by topical application. Male adults of Blattella germanica, chosen according to the length criterion, receive two micro-liters of acetone solution of the product to be tested between the second and third pair of legs. After treatment, the "test insects" are stored in the dark at 20 ° C and are fed. Doses of 10-7.5-5-3.75 - 2.5 ng / insect are used. The checks are carried out twenty-four hours, forty-eight hours and six days after treatment. The experimental results, expressed in LD50 in nanograms per insect, are summarized in the following table:

Compound A

LD50 in ng per insect 1.06

Conclusion: Compound A has a strong insecticidal activity against Blattella germanica.

8) Study of the insecticidal activity of compound A, with respect to Dysdercus fasciatus.

A microliter of acetone solution of product to be tested is placed on the ventral thorax of each individual. Doses of 3.75-2.5-1.25-1-0.625 nanograms per insect are used. Efficacy checks are carried out 24 hours, 48 hours and 5 days after treatment.

The results obtained are mentioned in the following table:

Conclusion: Compound A is endowed with a good insecticidal activity with respect to Sitophilus granarius and tribolium castaneum.

Study of the acaricidal activity of compound A on Tetranychus Urticae

Bean leaves infested with 10 females of Tetranychus Urticae per leaf and coated with glue at their periphery are used; the females are allowed to lay eggs for twenty-four hours, remove them and divide the leaves thus infested with eggs into two groups.

A) a first group is treated with the test compound; the operation is carried out by spraying 0.5 cm3 of aqueous solution onto each sheet using concentrations of 50 and 25 g of test compound per hectare.

b) a second group of leaves is not treated and serves as a control group.

The count of live adults, live eggs and live larvae takes place nine days after the start of treatment. The results expressed as a percentage of mortality of adults, eggs and larvae are summarized in Table 45 below (taking into account the untreated control).

50

Compound A

% mortality% eggs of adults not hatched 52.3 54.3

% larval mortality 47.6

Compound A

DL5U in nanograms per insect 1.06

Conclusion: Compound A is endowed with an interesting miticide power with regard to Tetranychus Urticae.

VS

Claims (12)

630 890 2. Compounds according to claim 1, characterized in that the acid copula of these esters is of structure 1R eis or IR trans. 2 CLAIMS 1. In all their stereoisomeric forms, the compounds of general formula: in which R3 represents an aliphatic organic radical comprising from 2 to 6 carbon atoms and one or more carbon-carbon unsaturations, - Or a group: in which R4 represents a hydrogen atom, a group -C = N or a group -C = CH and R5 represents a chlorine atom or a methyl radical and n represents a number equal to 0.1 or 2, - Or a group: 2T — c: -i0- in which Xj represents a hydrogen, fluorine, chlorine or bromine atom, X2, identical or different from X1; represents a fluorine, chlorine or bromine atom, X3 represents a chlorine, bromine or iodine atom and R represents: - Or a benzyl radical optionally substituted by one or more radicals chosen from the group consisting of alkyl radicals containing from 1 to 4 carbon atoms, alkenyl radicals containing from 2 to 6 carbon atoms, alkenyloxy radicals comprising from 2 to 6 carbon atoms, alkadienyl radicals containing from 4 to 8 carbon atoms, the methylene dioxyl radical, the benzyl radical, the halogen atoms, - Or a group: ch2R2 in which the substituent Rt represents a hydrogen atom or a methyl radical and the substituent R2 a monocyclic aryl or a group -CH2-C = CH, - Or a group: 3 630 890 - IR trans 2,2-dimethyl 3- (l ', 2', 2 ', 2'-tetrabromoethyl) cyclopropane-l-carboxylate de (S) 1-oxo 2-allyl 3-methyl cy-clopent-2- en-4-yle. - IR eis 2,2-dimethyl 3- (l ', 2', 2 ', 2'-tetrabromoethyl) cyclopropane-1-carboxylate of 5-benzyl 3-furyl methyl. - IR eis 2,2-dimethyl 3- (l ', 2', 2 ', 2'-tetrabromoethyl) cyclopropane-l-carboxylate de (S) 1-oxo 2-allyl 3-methyl cy-clopent-2- en-4-yle. - IR eis 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrabromoethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl. - IR trans 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibro-moethyl) cyclopropane-l-carboxylate de (S) 1-oxo 2-allyl 3-methyl cyclopent-2 -en-4-yle. - IR eis 2,2-dimethyl 3- (2 ', 2'-dibromo l', 2'-dichloro-ethyl) cyclopropane-l-carboxylate de (RS) a-cyano 3-phenoxy benzyle. - The IR eis 2,2-dimethyl 3- (2 ', 2'-dibromo l', 2'-dichloro-ethyl) cyclopropane-l-carboxylate de (S) 1-oxo 2-allyl 3-methyl cyclopent-2 -en 4-yle. - IR trans 2,2-dimethyl 3- (2 ', 2'-dibromo 1', 2'-dichlo-roethyl) cyclopropane-l-carboxylate de (RS) a-cyano 3-phen-oxy benzyle. - IR trans 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2'-dibro-moethyl) cyclopropane-l-carboxylate de (S) 1-oxo 2-allyl 3-methyl cyclopent-2 -en-4-yle. - IR eis 2,2-dimethyl 3- (2 ', 2'-dichloro 1', 2'-dibromo-ethyl) cyclopropane-1-carboxylate from (RS) a-cyano 3-phenoxy benzyl. 3. Compounds according to claim 1, characterized in that the acid copula of these esters is of dl eis or di trans structure. 20 4. Compounds according to claim 1, characterized in that they consist of a mixture of esters whose acid copula is of dl eis or di trans structure. 5. Compounds according to claim 1, characterized in that Xx represents a fluorine, chlorine or bromine atom, X2 is 25 identical to Xi and represents a fluorine, chlorine or bromine atom and X3 and R retain the meanings of claim 1. 6. Compounds according to claim 1, characterized in that X1 represents a hydrogen, fluorine, chlorine or 30 bromine, X2 is different from Xt and represents a fluorine, chlorine or bromine atom and X3 and R retain the meanings of claim 1. 7. Compounds according to claim 1, characterized in that Xx, X2, X3 retain the meanings of claim 1 and 35 R represents a residue of 5-benzyl 3-furyl methyl alcohol, a 1-oxo 2-allyl 3-methyl cyclopent-2-en-4-yl residue, a residue of 3-phenoxy benzyl alcohol, a residue of a-cyano 3-phen-oxy benzyl alcohol, these alcohols can be racemic or optically active. 40 8. Compounds according to Claim 1, characterized in that Xj represents a fluorine, chlorine or bromine atom, X2 identical to Xj represents a fluorine, chlorine or bromine atom, X3 represents a chlorine, bromine atom or of iodine and R represents a residue of 5-benzyl 3-furyl methyl alcohol, a 45 remains 1-oxo 2-allyl 3-methyl cyclopent-2-en-4-yl, a residue of 3-phenoxy benzyl alcohol, a residue of a-cyano 3-phenoxy benzyl alcohol, these alcohols may be racemic or optically active. 9. Compounds according to claim 1 in the form of isomers 50 (A), in the form of isomers (B) due to the existence of the asymmetric carbon in position 1 ′ of formula I, or in the form of a mixture of these isomers, the names of which follow: - IR eis 2,2-dimethyl 3- (l ', 2', 2 ', 2'-tetrabromoethyl) -cyclopropane-l-carboxylate de (S) a-cyano 3-phenoxy ben- 55 zyle. - The 1R eis 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromo-ethyl) cyclopropane-l-carboxylate de (S) a-cyano 3-phenoxy benzyle. 10. Compounds according to claim 1 in the form of iso- 60 mothers (A), in the form of isomers (B) due to the existence of asymmetric carbon in position 1 'of formula I or in the form of a mixture of these isomers, the names of which follow: - IR trans 2,2-dimethyl 3- (l ', 2', 2 ', 2'-tetrabromoethyl) cyclopropane-l-carboxylate de (RS) a-cyano 3-phenoxy ben- 65 zyle. - IR trans 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibro-moethyl) cyclopropane-l-carboxylate de (RS) a-cyano 3-phenoxy benzyle. 10 in which the substituents R6, R7, R8, R9 represent hydrogen, a chlorine atom, or a methyl radical and in which the symbol S / I indicates an aromatic ring or a ring Dihydro or tetrahydro analog. 11. Compounds according to claim 1 in the form of isomers (A), or in the form of isomers (B) due to the existence of asymmetric carbon in position 1 'of formula I, or in the form of a mixture of these isomers whose names follow: - IR, eis 2,2-dimethyl 3- (2 ', 2', 2 ', 1'-tetrabromoethyl) cycfopropane-1 -carboxylate of RS a-cyano 3-phenoxy benzyl. - IR, trans 2,2-dimethyl 3- (2 ', 2', 2 ', r-tetrabromo-ethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl. IR, is 2,2-dimethyl 3- (2 ', 2', 2 ', 3-phenyl benzyl-tetrachloroethyl) cy-clopropane-1-carboxylate. - IR, is 2,2-dimethyl 3- (2 ', 2', 2 ', 1'-tetrachloroethyl) cyciopropane-1-carboxylate of (RS) a-cyano 3-phenoxy benzyl. - IR, eis 2,2-dimethyl 3- (2 ', 2', 2 ', l'-tetrachloroethyl) cyclopropane-l-carboxylate of 3-phenoxy benzyl. - IR, eis 2,2-dimethyl 3- (2 ', 2', 2 ', l'-tetrachloroethyl) cyclopropane-l-carboxylate of RS allethrolone. - IR, trans 2,2-dimethyl 3- (2 ', 2', 2 ', l'-tetrachloroethyl) cyclopropane-l-carboxylate de RS a-cyano 3-phenoxy benzyle. - IR, trans 2,2-dimethyl 3- (2 ', 2', 2 ', r-tetrachloroethyl) cyclopropane-l-carboxylate of 3-phenoxy benzyl. - IR, trans 2,2-dimethyl 3- (2 ', 2', 2 ', l'-tetrachloroéthyl) cyclopropane-l-carboxylate de (S) alléthrolone. - The IR, is 2,2-dimethyl 3- (2 ', 2'-dichloro 1', 2'-dibromo-ethyl) cyclopropane-1-carboxylate of (S) allethrolone. - IR, eis 2,2-dimethyl 3- (1 ', 2'-dibromo 2', 2'-dichloro-ethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl. - 1R, eis 2,2-dimethyl 3- (l ', 2'-dibromo 2', 2'-dichloro-ethyl) cyclopropane-l-carboxylate of 5-benzyl 3-furyl methyl. - The IR, eis 2,2-dimethyl 3- (l ', 2'-dibromo 2', 2'-dichloro-ethyl) cyclopropane-l-carboxylate of 3,4,5,6-tetrahydro phthalimide methyl. - The dl eis trans 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-di-bromoethyl) cyclopropane-l-carboxylate of RS a-cyano 3-phenoxy benzyl. - IR, trans 2,2-dimethyl 3- (1 ', 2'-dibromo 2', 2'-dichlo-roethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl. - IR, trans 2,2-dimethyl 3- (l ', 2'-dibromo 2', 2'-dichloro-ethyl) cyclopropane-l-carboxylate of 3,4,5,6-tetrahydro phthalimide methyl, - IR, trans 2,2-dimethyl 3- (l ', 2'-dibromo 2', 2'-dichlo-5 roéthyl) cyclopropane-l-carboxylate de 5-benzyl 3-furyl methyl, - IR, trans 2,2-dimethyl 3- (2 ', 2'-dibromo l', 2'-dichlo-roethyl) cyclopropane-l-carboxylate of (S) allethrolone, - IR, trans 2,2-dimethyl 3- (2 ', 2'-dibromo l', 2'-dichlo- isoethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl, - 1R, eis 2,2-dimethyl 3- (2 ', 2'-dibromo l', 2'-dichIoro-ethyl) cyclopropane-l-carboxylate of 3-phenoxy benzyl, - 1R, eis 2,2-dimethyl 3- (2 ', 2'-difluoro 1', 2'-dibromo-ethyl) cyclopropane-l-carboxylate of (S) allethrolone, 15 - 1R, eis 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2'-dibromo-ethyl) cyclopropane-l-carboxylate de RS a-cyano 3-phenoxy benzyl, - IR, trans 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2'-dibro-moethyl) cyclopropane-1-carboxylate of 3-phenoxy benzyl, 20 - IR, trans 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2'dibro-moethyl) cyclopropane-l-carboxylate of RS a-cyano 3-phenoxy benzyl, - IR, eis 2,2-dimethyl 3- (2'-fluoro 2'-chloro 2 ', l'-di-bromoethyl) cyclopropane-1-carboxylate of 3-phenoxy 25 benzyl. 12. Compounds according to claim 1, in the form of a mixture of stereoisomers of eis structure and of trans structure.