HU194799B - Process for production of derivatives of cyclopropan carbonic acid and insecticides and acarycides containing these compounds as active substance - Google Patents

Abstract

According to the process of the present invention, (IR, cis) -2,2-dimethyl-3 - [(Z) -3-phenoxy / III) is of the formula (I). substituted alkoxy-3-oxo-1-propenyl] cyclopropanecarboxylic acid derivatives. Compounds of formula (I) are prepared by: a) reacting an acid of formula (II) or a functional derivative thereof with an alcohol of formula (III) - or (b) a compound of formula XI with an alcohol R-OH or (c) a compound of formula (I ') in which R is one or two C 1-5 alkyl groups substituted by one or two protected hydroxy groups to produce R as a substituent of one or two C 1-5 alkyl groups substituted by one or more hydroxy groups; or (d) reacting the compound of formula (VI) with an acid hydrolyser which selectively cleaves an ester group attached to the carbon atom of the cyclopropane ring 1, and the compound of formula (IX), the compound of formula (X) thus obtained is treated with a weak hydrogenating agent, or is first treated with a weak hydrogenating agent and the resulting compound of formula (II) is optionally reacted with an alcohol of formula (III) in the form of a functional derivative thereof. Some of the compounds of formula (Γ) prepared by the above process are active ingredients of the compositions of the invention. (XI) -1-

Description

The present invention relates to a process for the preparation of (R, cis) - (Z) -forms of the compounds of formula (I) and to insecticidal and acaricidal compositions containing such compounds as active ingredients. In the general formula (F)

- A 'is a group of formula (2) - in which

R ₂ is methyl and

R ₃ is C 2 -C 5 alkenyl;

A group of the formula wherein R 1 is cyano, methyl or ethynyl or hydrogen;

A group of Formula (6) wherein the S / I designates a benzene ring or a dihydro or tetrahydro derivative;

A group of formula (7); benzyl;

A group of formula (12) wherein R _u is cyano,

R ₁₅ is halogen, group 13,

R ₆ is hydrogen or cyano;

R is phenyl or C 1 -C 5 alkyl substituted with cyano, phenyl, C 1 -C 4 alkoxy or di- (C 1 -C 4 alkyl) amino, singly or twice with hydroxy, or once with halogen.

The substituent R may also be phenyl-substituted alkyl, such as benzyl or phenethyl, and the alkyl may be substituted by one or two -CF ₃ groups.

When R is an alkyl group having one or more functional groups, R preferably represents the following groups:

- _(CH2) "- Chalon ₃ group wherein n is from 1 to 4 integer, Hal represents a halogen atom, such groups as _-CH2 -CC1 _3, -CH ₂ -CF _3, -CH ₂ -CH ₂ -CC ₁₃ and -CH ₂ -CH ₂ CF ₃ ;

- (CH ₂ ) -, -CHHal ₂ wherein Hal is as defined above and n is an integer from 0 to 4, such as -CH ₂ -CHCl ₂ , -CH ₂ -CHF ₂ and -CHF ₂ ;

- (CH ₂ ) - - CH ₂ Hal wherein Hal and n are as defined above, such as -CH ₂ -CH ₂ Cl and -CH ₂ -CH ₂ F;

and a group of formula (17), (18) or (19); and a group of formula (20) or (21); and a group of formula (22), (23) or (24) wherein n is as defined above;

-Ί wherein n is as defined below and R 'is hydrogen or C 1-4 straight or branched alkyl such as -CH ₂ -OCH ₃ , -CH ₂ -CH ₂ -O-CH ₃ , -CH ₂ -CH ₂ -O-CH ₂ -CH _3, and -CH ₂ -CH ₂ -OH;

A group of formula (28) wherein n and R 'are as defined above and the two R' groups may be the same or different, such as those of formulas (30) and (31);

A group of formula (34) wherein n is as defined above, such as a group of formula (35);

A group of formula (36) wherein n 'is 0 to 5, such as groups (37) and (38);

Benzyl group (39).

Preferably, the process of the present invention provides compounds of formula (I) which are within the scope of Formula (F). In the general formula (I)

A is benzyl, a group of the formula (2) in which R ₂ and R ₃ are as defined above, a group of the formula (4) in which R ₄ is as defined above, A is preferably 3-phenoxybenzyl, a- cyano-3-phenoxybenzyl or 2-ethynyl-3-phenoxybenzyl, or a group of formula (6) wherein S / I is as defined above, or a group of formula (7) or a compound of formula (13) wherein R ₆ is cyano,

R has the same meaning as previously defined.

The process of the present invention provides compounds of formula (Γ) in which the double bond is of Z geometry and has the cyclopropylmethanoic acid side chain configuration (IR, cis).

Preferably, the process of the present invention provides compounds of formula (I) and (I) wherein A is a-cyano-3-phenoxybenzyl, in the form of S, R or RS, and those wherein A 'is 2 methyl-4-oxo-3- (2-propenyl) -2-cyclopenten-1-yl, also SR '. [? ς o ...... ...

The process of the present invention preferably provides compounds of formula (Γ) wherein R is substituted C 1 -C 5 alkyl, which may carry one or more functional groups as substituents. Particularly preferred compounds are those wherein R is alkyl substituted with one to six halogens, such as one to six fluorine atoms. An example of a halogen substituted alkyl group is -CH ₂ CF ₃ .

Of the compounds of formula (F), those set forth in Examples 1, 2, 23, 26, 29, 30 and 35 are specifically highlighted.

The compounds of formula (Γ) have properties which make them suitable for use in the control of insects and mites. Thus, these compounds can be used to control the above parasites of warm-blooded animals, plants and buildings. The compounds of the present invention can thus be used to control insects and mites, which are parasites of plants and animals.

Therefore, a further object of the present invention is to provide insecticidal and acaricidal compositions comprising the compounds of formula (F).

Thus, the compounds of formula (Γ) are particularly useful in agriculture for controlling insects such as aphids and lepidoptera and coleoptera larvae. The dose of active ingredient is between 10 g and 300 g per hectare.

The compounds of formula (Γ) may also be used to control insects in buildings, such as flies, mosquitoes, and cockroaches.

The following experimental results show that the compound was prepared according to the procedure of Example 1

-2194 799 has excellent lethal and knock-down effects (insect repellent).

In addition, the compounds of formula (Γ) are non-photosensitive and non-toxic to mammals.

All these properties make the compounds of formula (Γ) perfectly compatible with the requirements of the modern agrochemical industry; these compounds are able to protect the product while protecting the environment.

The compounds of formula (Γ) may also be used to control plant parasites such as mites.

The compounds of formula (Γ) can also be used to control parasitic mites in animals. Examples of such parasites are ticks, especially Hyalomnia sp., Amblyomnia sp. and Rhipicephalus sp. ticks, and all kinds of scabies, especially mites.

Thus, the compounds of formula (Τ ') can be used in the preparation of compositions for controlling the above parasites of warm-blooded animals, plants and buildings, which contain the compounds of formula (Γ) as an active ingredient.

The compounds of formula (I) are particularly useful as active ingredients in insecticidal compositions.

Among the formulations of the present invention, those containing the following compounds as active ingredient are particularly noteworthy:

(S, 2-zz-cyano-3-phenoxybenzyl) - (1R, cis) -2,2-dimethyl-3 - [(Z) -3- (2,2,2-trifluoroethoxy) -3 oxo-l-propenyl] cyclopropanecarboxylate,

6 (S) -α-cyano-3-phenoxybenzyl] - (1H, cis) -2,2-dimethyl-3 (Z) -3-oxo-3- (2- (1,1,1,1,3) , 3,3-hexafluoro) -propoxy) -1-propenylcyclopropanecarboxylate, 1 (R) -ethyl-ethynyl-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-34 (Z) -3-oxo -3- (2,2,2-trifluoromethoxy) -1-propenyl · cyclopropanecarboxylate,

1S) -cyano-6-phenoxy-2-pyridine 1-methyl · 1 · methyl; 1R, Cis) -2,2-Dimethyl-3-yl (Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl] cyclopropanecarboxylate, 1 (S) cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2-fluoroethoxy) -1-propenyl) cyclopropanecarboxylate, [(3-Propargyl-2,5-dioxoimidazolidinyl) methyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2,2,2- trifluoroethoxy) -1-propenyl] cyclopropanecarboxylate and [(1S) -2-methyl-4-oxo-3- (2-propenyl) -2-cyclopenten-1-yl] - (1R, cis) -2 , 2-Dimethyl-3 - [(Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl] cyclopropanecarboxylate.

These formulations are prepared according to the usual processes in the agrochemical industry, the veterinary industry, or the animal feed industry.

Formulations for use in agriculture or in buildings may contain, in addition to the active substance (s), one or more pesticidal agents. These compositions may be in the form of powders, granules, suspensions, emulsions, solutions, aerosol solutions, flammable ribbons, baits, or other customary formulations.

In addition to the active ingredient, said formulations contain carriers and / or non-ionic surfactant which helps to form a more uniform dispersion of the constituents of the mixture. The carrier may be a liquid, such as water, alcohol, hydrocarbons or other organic solvents;

or mineral, animal or vegetable oils; or a powder such as talc, clay, silicates or diatomaceous earth; or a combustible solid.

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

In one embodiment, the compositions of the present invention, when used in buildings, are used in the form of smoke compositions.

In this case, the carrier for the compositions is preferably comprised of a flammable insecticide roll or a non-flammable fibrous substrate. In the latter case, the smoking compositions obtained after incorporation of the active ingredient are placed on a heating device (e.g., an electric mosquito control device).

When an insecticide roll is used, the inert carrier may be, for example, Pyrethrum rubble, Taboo powder (or Machilus Thumbergili leaf powder), Pyrethrum powdered stem, Cedar needle powder, Wood powder (e.g. Pine sawdust), Starch or Coconut nut powder. The amount of active ingredient may be, for example, 0.03 to 1% by weight.

When a non-combustible fibrous material is used as carrier, the active ingredient may be present in an amount of from 0.03% to 95% by weight.

If the carrier is an oil, the amount of active ingredient is preferably from 0.03% to 95% by weight.

The insecticidal and acaricidal compositions of the invention may be mixed with one or more other known pesticides. The acaricidal compositions are preferably in the form of powders, granules, suspensions, emulsions and solutions.

Preferably for use as a kid, wettable powders are provided which are in powder form

They contain from 1 to 80% by weight of the active ingredient, while from 1 to 500 g / l of the active ingredient as foliar spray liquids. Foliage spray powders containing from 0.05 to 3% by weight of the active ingredient may also be used.

The acaricidal active compounds of the present invention are preferably applied at a dose of 1 to 100 g / ha.

In order to increase the efficacy of the compositions of the invention, the compositions may also include other standard adjuvants.

Examples of such compounds are: 1- (2,5,8-trioxadodecyl) -2-propyl-4,5-methylenedioxybenzene (or piperonyl butoxide), N- (2-ethylheptyl) - bicyclo [2,2,1] 5-heptene-2,3-dicarboximide and piperonylbis-2- (2'-n-butoxyethoxy) ethyl acetal (or tropital).

When the compositions are used to control animal parasitic mites, the compositions may be incorporated into the nutritional mixture used to feed the animals. The nutrient mixture will vary depending on the animal species and may include cereals, sugars, soybean, hazelnut and sunflower cakes, animal flours (such as fishmeal), synthetic amino acids, mineral salts, vitamins and antioxidants.

Thus, the compounds of formula (Γ) may be used in the preparation of formulations for animal feed.

The harmless dose of the compounds of formula (I ') is very high and is therefore useful in the treatment of ticks and scabies in warm-blooded animals.

194,799 gels, as well as preventive or curative treatment of the lice.

The compounds of formula (I ') may also be administered externally, for example, by evaporation, shampooing, bathing or anointing.

The compounds of formula (Γ) can be administered by applying the so-called "pour on" method to the spinal column of the animals.

The compositions of the present invention are of particular interest in that they are capable of controlling a broader range of insects and mites by virtue of their multiple effects.

Compounds of formula (Γ) are prepared according to the invention by reacting an acid of formula (II) - in which R is as previously defined - or a functional derivative thereof with an alcohol of formula (III). In the formula (III), A 'has the same meaning as previously given - they are reacted.

The functional derivative of the acid of formula II is preferably acid chloride.

The reaction of the acid (II) with the alcohol (III) is preferably carried out in the presence of dicyclohexylcarbodiimide.

The compound (II) of formula is prepared by reacting a compound, trans- or cis-lactone form, (B) an organic solvent a (B ₂₎ a compound of formula - in the formula (B ₂₎ or dialkylamino as previously defined reacting and then separating the mixture of E and Z isomers of the resulting compound of formula (II), if desired, into isomers.

According to the invention, this reaction is preferably carried out in ethyl ether, dimethylsulfoxide, dimethylformamide, tetrahydrofuran, dimethoxyethane, alkanols, diethylene glycol monomethyl ether or diethylene elicol diethyl ether.

Compounds of formula (B ₂ ) may be prepared by treating a compound of the formula (phenyl) ₃ = P $ -CH ₂ -CO ₂ R -Hal® wherein Hal is a halogen ion with a strong base. For example, strong bases include hydrides, amides, alkali metal alcoholates or alkyl lithium derivatives. . · ,, i

The compounds of formula (II) may also be prepared by first reacting a compound of formula (IV), wherein Hal is halogen and alkyl is C 1 -C 6 alkyl, with an alkaline halogen removal agent. and then, in a second step, (a) reacting with a carboxyl-capable compound and then reacting the resulting compound (V) with an esterifying agent, or (b) a Hal-CO ₂ -R compound wherein Hal is halogen, while R is as defined above, the compound of formula (VI) obtained in the process of (a) and (b), wherein R and alk are as defined above, is hydrogenated with a weak hydrogenating agent and then Compound of Formula VII - Compound VII in the formula R and alk are as defined above, while the double bond is Z-treated with an acid hydrolyzant capable of selectively cleaving an ester group at the C-position of the cyclopropane ring.

In preferred embodiments of the above process, compounds of the formula are used

- Fish represents a bromine or chlorine atom;

alk represents a tert-butyl group;

butyl lithium is used as the alkaline agent capable of removing the halogen atoms of the vinyl group;

- carbon dioxide is used as the carboxyl-introducing agent;

hydrogen is used as a weak hydrogenation agent in the presence of a catalyst such as palladium and traces of quinoline; and

- p-toluenesulfonic acid is used as the acid hydrolyzant capable of selectively cleaving the CO ₂ alk ester group.

The process of the present invention also involves a modification obvious to chemists that the compound of formula (V) is first exposed to a weak hydrogenating agent and then reacted with a reducing agent as a second step.

Thus, a further object of the present invention is to provide a modified version of the above process wherein the compound of formula (V) is first treated with a weak hydrogenating agent and then the compound of formula (VIII) thus obtained is reacted with the compound of formula (VIII). alk is as defined above and is reacted with an esterifying agent of the double bond Z geometry, and the compound of formula VII thus obtained is used in the synthesis described above for R and alk in formula VII.

The above procedure involves two obvious variants in which the order of certain steps is changed.

Therefore, a further object of the present invention is to provide a process for the preparation of compounds of formula (,) which comprises reacting a compound of formula (VI) wherein R and alk have the meanings given in formula (VI) with a cyclopropane ring. is reacted with an acid hydrolyzing agent to selectively remove the ester group attached to its carbon atoms of formula (IX) - where R is as defined above (a) when available as a functional derivative, with an alcohol of formula (III) reacting - wherein A'in formula (III) is as previously described - treating the compound of formula (X) - wherein R and A 'in formula (X) are as defined above - with a weak hydrogenation carbon; or (b) first treated with a weak hydrogenating agent to give the product The compound of formula (II), wherein R is as defined above, and the double bond is of Z-geometry, when available as a functional derivative, is reacted with an alcohol of formula (III).

Preferred reaction parameters for carrying out the above process are the same as those described above for similar operations.

The invention further relates to a process for the preparation of a compound of the formula: wherein a compound of the formula XI has the same meaning as defined above in the formula XI and the double bond has the Z geometry, with an esterifying agent.

194,799

In a preferred embodiment of the above esterification process, the esterification is carried out with a functional derivative of an alcohol, namely a Ν, Ν'-diisopropylurea derivative of the formula (XVII).

Compounds of formula (IX) are prepared by reacting an acid of formula (V), wherein alk is C 1-8 alkyl in formula (V), with 2,2,2-trichloroethanol; is treated with an acid hydrolyzing agent, and the resulting compound of formula XIII is reacted with an alcohol of formula III, wherein A 'has the same meaning as previously described - reacting the compound of formula (XIV) thus obtained, wherein A 'in formula (XIV) has the above meaning, with an agent capable of cleaving the carbon ester of an acetylene carbon atom, and then reacting the compound of formula (XV) wherein A 'is as defined above, with a weak hydrogenating agent.

In preferred embodiments of the above process

- a compound of formula (V) wherein alk is tert-butyl;

p-toluenesulfonic acid is used as acid hydrolyzing agent;

- esterifying the compound of formula (XIII) by reacting the compound of formula (XIII) with the alcohol of formula (III) in the presence of dicyclohexylcarbodiimide;

- the cleavage reaction of the ester of formula (XIV) is carried out in an acidic medium using a metal powder such as zinc powder; and

the weak hydrogenation agent used is hydrogen in the presence of a catalyst such as palladium and traces of quinoline.

The above process also includes the obvious variant that the hydrogenation and esterification steps are interchangeable.

Therefore, a further object of the present invention is a process for the preparation of compounds of formula F wherein a compound of formula XV wherein A 'has the same meaning as previously described is reacted with an esterifying agent and then the compound of formula X is prepared by reacting In the general formula X, R and A 'have the same meaning as previously described - by reaction with a weak hydrogenating agent.

The conditions for performing this latter procedure are the same as those previously described for similar operations.

In cases where one of the compounds of formula (tartalmazó) containing one or two hydroxy groups substituted by R is desired, the compounds of formula (eljárások) which contain one or two protected hydroxy groups in place of R are first obtained first. the protecting group may be, for example, dioxolanyl or tetrahydropyranyl, and then these compounds are hydrolyzed with an acid hydrolyzing agent.

The acid hydrolyzing agent used in the above process is, for example, hydrochloric acid or p-toluenesulfonic acid.

Most of the methods described above lead to compounds in which the double bond is of Z-geometry. Of course, these methods are the most suitable for the preparation of compounds of formula (Γ) in which the double bond is of Z-geometry.

The compounds of the present invention obtained excellent results, which will be described later in the experimental section.

The compounds of the formulas (II), (VI) and (VII) obtained by the process of the invention are novel compounds.

The invention is illustrated by the following non-limiting examples.

Example 1 f (S) -N'-Cyano-3-phenoxybenzyl (1R, cis) -2,2-dimethyl-3 - [(Z) -3- (2,2,2-trifluoroethoxy) ) Preparation of -3-oxo-1-propenyl] -cyclopropanecarboxylate.

1.3 g of (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl] cyclopropanecarboxylic acid, 1 cm ^{3 of} pyridine and 15 cm ^{3 of} methylene chloride were added followed by 1.05 g of dicyclohexylcarbodiimide. Next, a solution of 1.35 g of (S) -ff-hydroxy- (3-phenoxy-phenyl-acetonitrile) to a solution of 5 cm ³ of methylene chloride. After stirring for 5 hours at room temperature, the insoluble material was filtered off and washed with methylene chloride. To the filtrate was added 2N hydrochloric acid solution, then decanted, washed with water, dried and evaporated. The resulting oil was chromatographed on silica gel using a 95: 5 mixture of cyclohexane and ethyl acetate. This way

1.35 g of the expected product are obtained.

_{α D} = + 42 ° ± 2 ° (c = 0.7, benzene)

Nuclear Magnetic Resonance Spectrum (CDC1 _3, ppm):

1.26 and 1.28: hydrogen atoms at the 2-position;

1.97 and 2.11: hydrogen at the C-position of the cyclopropane ring;

3.1-3.4: hydrogen attached to the C-position 3 of the cyclopropane ring;

6.5-6.9: hydrogen attached to C 1 of the propenyl group;

5.9 and 5.93: hydrogen attached to C2 of the propenyl group;

6.3: hydrogen attached to the carbon atom bearing the cyano group; and

4.3-4.7: hydrogen atom of the trifluoroethoxy group.

The acid used in Example 1 was prepared as follows:

Production Example I

Preparation of 1R, cis) -2,2-dimethyl-3 - [(Z) -3- (2,2,2-trifluoroethoxy) -3-oxc-1-propenyl] cyclopropanecarboxylic acid Step A: (1.1) , -Dimethylethyl) - (1R, cis) -2,2-dimethyl-3- (3-hydroxy-3-oxo-1-propynyl) cyclopropanecarboxylate.

26 g of (1,1-dimethylethyl) - (1R, cis) -2,2-dimethyl-3- (2,2-dibromo-vinyl) -cyclopropanecarboxylate were introduced into 175 cm ^{3 of} anhydrous tetrahydrofuran and then -65 ° C. C was added a 20% cyclohexane solution of butyl lithium in 20 cm ^3, distinguishing. The reaction mixture was stirred at -60 ° C for 1 hour, then a stream of carbon dioxide was bubbled through the mixture for 1.5 hours and then poured into ice water, to which 1N sodium hydroxide was added. The whole mixture was washed with ether. The alkaline aqueous phase was acidified to pH 4 and extracted with ether. It's organic

The 194,799 phases were dried and evaporated under reduced pressure. The product was recrystallized from petroleum ether (b.p. 60-80 ° C) to give 8.3 g of the desired product. Mp 144 ° C. Nuclear Magnetic Resonance Spectrum (CDCl ₃ , ppm):

1.22 and 1.37 protons of the 2-position methyl groups of the cyclopropane ring;

1.78: Protons 1 and 3 of the cyclopropane ring;

1.47: protons of the tert-butyl group; and

8.25: proton of the -CO-OH group.

Step B: (1,1-Dimethylethyl) - (1R, cis) -2,2-dimethyl-3- [3-oxo-3- (2,2,2-trifluoroethoxy) -1-propynyl] cyclopropanecarboxylate production.

g of the product of this step and 3.5 g of dicyclohexylcarbodiimide were introduced into a solution containing 20 cm ^{3 of} methylene chloride and 1 cm ^{3 of} pyridine. After stirring for 1 hour, 2.15 g of 2,2,2-trifluoroethanol and 5 cm ^{3 of} methylene chloride were added. The entire reaction mixture was stirred for 16 hours at 20 ° C, then filtered and washed with methylene chloride. The filtrate was evaporated to dryness and taken up with thioether, washed first with 1N hydrochloric acid, second with water and dried. The solution was evaporated to give 5 g of product which was chromatographed on silica gel using a 95: 5 mixture of benzene and ethyl acetate as eluent. 3.5 g of the expected product are obtained. Nuclear Magnetic Resonance Spectrum (CDC1 _3, ppm):

1.2 and 1.37: hydrogen atoms of the 2-position methyl groups;

1.77 hydrogen atoms attached to the 1 and 3 carbon atoms of the cyclopropane ring;

1.43: hydrogen atoms of methyl groups of 1,1-dimethylethyl; and ^;

4.3-4.7: hydrogen atom of the trifluoroethoxy group.

Step C: Preparation of (1R, cis) -2,2-dimethyl-3- [3-oxo (2,2,2-trifluoroethoxy-1-propynyl] cyclopropanecarboxylic acid

A mixture of the product from the previous step (3.3 g), toluene (30 cm ³⁾ and p-toluenesulfonic acid (100 mg) was refluxed until gas evolution ceased. The mixture was cooled, washed with water, dried and evaporated to dryness. The product (2.6 g) thus obtained was used as such in the next step.

Step D: Preparation of (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo (2,2,2-trifluoroethoxy) -1-propenyl] cyclopropanecarboxylic acid.

A round bottom flask connected to a hydrogenation apparatus was charged with 500 mg of 10% palladium hydroxide on barium sulfate and 5 cm ^{3 of} ethyl acetate, followed by the addition of 2 g of the product from the previous step, 45 cm ^{3 of} ethyl acetate and 0.5 cm ³ quinolines. Hydrogenation was continued until absorption was complete. The product was filtered off, and the filtrate was washed with 1N hydrochloric acid, water, and evaporated to dryness. The product (2 g) was chromatographed on silica gel using cyclohexane / ethyl acetate / acetic acid (70: 30: 1) as eluent. This way

1.3 g of the expected product are obtained.

Nuclear Magnetic Resonance Spectrum (CDC1 _3, ppm):

1,3 and 1,32: hydrogen atoms of the 2-position methyl groups;

1.92 and 2.06: hydrogen at the C-position of the cyclopropane ring;

3.07-3.38: hydrogen at the 3-position of the cyclopropane ring;

6.6 to 6.9: hydrogen bonded to C 3 of the propenyl group;

5.9 and 6.0: hydrogen at the 2-position of the propenyl group; and

4.3 to 4.7: hydrogen atom of the trifluoroethoxy group.

Example 2 [(1S) -2-Methyl-4-oxo-3- (2-propenyl) -2-cyclopenten-3-yl] - (R, cis) -2,2-dimethyl-3 - [(Z) -3 Preparation of -oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl] cyclopropanecarboxylate 1.9 g of (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl] cyclopropanecarboxylic acid, 12 cm ^{3 of} methylene chloride and 100 mg of dimethylaminopyridine. Then 1.4 g of dicyclohexylcarbodiimide, 1.1 g of (S) -3- (2-propenyl) -1-hydroxy-2-methyl-4-oxocyclopent-2-ene and 5 cm ^{3 of} methylene chloride were added. The reaction mixture was stirred for 2 hours at room temperature. The insoluble material was removed by filtration. The filtrate was washed with 0.5 N hydrochloric acid then water, dried and evaporated to dryness. The product (3 g) was chromatographed on silica gel using a 95: 5 mixture of benzene and ethyl acetate as eluent. 2.6 g of the expected product are thus obtained. _{α D} = + 38 ° ± 2.5 ° (c = 0.5%, benzene)

Nuclear Magnetic Resonance Spectrum (CDC1 _3, ppm):

1.29 and 1.32: hydrogen atoms at the 2-position of the cyclopropane ring;

1.97 and 2.11: H-position of the cyclopropane ring;

3.05-3.37: position 3 hydrogen of the cyclopropane ring;

6.7-7: hydrogen at the 1-position of the propenyl group;

5.9 and 6.1: hydrogen bonded to carbon 2 of the propenyl group;

4.3 to 4.75: hydrogen atom of the trifluoroethoxy group;

5.7: hydrogen atom of cyclopentene at alpha position relative to CO ₂ ;

2: hydrogen of the methyl group attached to the cyclopentene group; and

4.8 - 5.25: hydrogen at the 3-position of the propenyl group attached to the cyclopentene group.

Example 3 t (1S) -acyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-34 (Z) -3-oxo-3- (phenylmethoxy) -1-propenyl] preparation of cyclopropanecarboxylic acid chloride.

Step A: Preparation of (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (phenylmethoxy) -1-propenyl] cyclopropanecarboxylic acid chloride.

1.6 g of (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (phenylmethoxy) -1-propenyl] cyclopropanecarboxylic acid, 10 cm ^{3 of} isoprene and 1 cm ³ Thionyl chloride was stirred for 5 hours under a stream of nitrogen and then concentrated. This gave 2 g of product which was used as such in the next step.

Step B: [(1S) -U-Cyano-3-Phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (phenylmethoxy) -1 preparation of propenyl] cyclopropanecarboxylate.

The product of step A) was introduced into a solution containing 700 mg of (S) -? - hydroxy- (3-phenoxyphenyl) acetonitrile, 20 cm ^{3 of} benzene and 0.6 cm ^{3 of} pyridine. The reaction mixture was stirred at room temperature for 16 hours and then poured into a mixture of ice water and 1 N hydrochloric acid. The resulting suspension was stirred and

-611

Extracted with 194,799 benzene. The benzene extracts were washed with water, dried, filtered and evaporated to dryness. The product (1.5 g) was chromatographed on silica gel using cyclohexane / ethyl acetate 8: 2 as eluent. 861 mg of the desired product are obtained. M.p. 83 ° C.

_n = +69 "+ 5 ° (c = 0.2% in benzene)

Nuclear Magnetic Resonance Spectrum (CDCl3, ppm):

1.25: hydrogen atoms at the 2-position of the cyclopropane ring; and

6.33: hydrogen bonded to a carbon atom bearing the cyano group.

II. Preparation Example 1R (cis) -2,2-Dimethyl-3 - [(Z) -3-oxo-3- (phenylmethoxy) 1-propenyl] cyclopropanecarboxylic acid.

Step A: Preparation of (1,1-dimethylethyl) - (1R, cis) -2,2-dimethyl-3 - [(Z) 2-carboxyethenyl] cyclopropanecarboxylate.

g of (1,1-dimethylethyl) - (1R, cis) -2,2-dimethyl-3- [2-carboxyethynylcyclopropanecarboxylate in 40 cm <^{3> of} ethyl acetate, 0.38 g of 10% barium sulfate hydrogenated in the presence of palladium hydroxide and 0.4 cm ^{3 of} quinoline. The mixture was filtered, and the filtrate was washed with 0.5 N hydrochloric acid solution, then with water until neutral, dried and evaporated to dryness under reduced pressure.

This gave 2 g of the desired product. Melting point: 94 ° C.

Step B: (1,1-Dimethylethyl) - (1R, cis) -2,2-dimethyl-3 - [(Z) 3-oxo-3- (phenylmethoxy) -1-propenyl] cyclopropanecarboxylate production.

2.4 g of the product of Step A were introduced into 20 cm ^{3 of} ethyl acetate. Then, 2.34 g of O-benzyl-N, N-diisopropylurea (this compound is described by Eschidt et al., Liebig Ann. Chem., 685, 161 (1965)) are added. The whole was stirred for 16 hours at room temperature, filtered and the filtrate was concentrated under reduced pressure. The product obtained as a yellow oil was chromatographed on silica gel using a 7: 3 mixture of benzene and cyclohexane as eluent.

This gave 2 g of the desired product. Nuclear Magnetic Resonance Spectrum (CDC1 _3, ppm):

1.22 and 1.28: hydrogen atoms at the 2-position of the cyclopropane ring;

1.77 and 1.91: hydrogen at the C-position of the cyclopropane ring; 2.98-3.3: hydrogen attached to the C-position of the cyclopropane ring;

6.5-6.8: hydrogen at the 1-position of the propenyl group;

5.8 and 6: hydrogen at the 2-position of the propenyl group; 1.43: hydrogen atoms of the dimethyl ethyl group; and

5.1: hydrogen atoms of the methoxy groups of the phenylmethoxy group;

Step C: Preparation of (R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (phenylmethoxy) -1-propenylcyclopropanecarboxylic acid.

A product according to 2 g of the preceding step, a mixture containing 30 cm mg of p-toluenesulfonic acid and 100 ³ toluene was heated to 90 ° C. The reaction mixture was stirred at this temperature for 2 hours and then concentrated. This gave 2 g of product, which was chromatographed on silica gel using cyclohexane: ethyl acetate: acetic acid (60: 40: 1) as eluent. 1.4 g of the expected product are obtained.

Nuclear Magnetic Resonance Spectrum (CDC1 _3, ppm):

1.25 and 1.3: hydrogen atoms at the 2-position of the cyclopropane ring;

1.84 and 1.98: hydrogen at the C-position of the cyclopropane ring; 3.14-3.43: hydrogen attached to the C-position 3 of the cyclopropane ring;

6.4-6.77: hydrogen at the 1-position of the propenyl group; 5.98: hydrogen at the 2-position of the propenyl group.

Example 4 [(1S) -2-Methyl-4-oxo-3- (2-propenyl) -2-cyclopenten-1-yl] - (1R, cis) -2,2-dimethyl-3 - [(Z) Preparation of -3-oxo-phenylmethoxy-1-propenyl] -cyclopropanecarboxylate.

450 mg of (S) -3- (2-propenyl) -l-hydroxy-2-methyl-4-oxo-cyclopent-2-ene, 20 cm ³ of benzene and 0.6 cm ³ of pyridine was introduced a mixture of 1 g of (IR, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (phenylmethoxy) -l-propenyl} -cyclopropanecarboxylic acid. The reaction mixture was stirred for 16 hours and then poured into a mixture of ice water and 1 N hydrochloric acid. The whole was extracted with benzene, the benzene phases were combined, washed with water, dried and evaporated to dryness. The product (1.5 g) was chromatographed on silica gel using cyclohexane / ethyl acetate 8: 2 as eluent. 500 mg of the desired product are obtained. _{α D} = + 37 ° ± 2.5 ° (c = 0.5%, benzene)

Nuclear Magnetic Resonance Spectrum (CDC1 _3, ppm):

1.27 and 1.31: hydrogen atoms at the 2-position of the cyclopropane ring;

1.87 and 2: hydrogen at the C-position of the cyclopropane ring;

5.12-3.45: hydrogen at the 3-position of the cyclopropane ring;

5.8 to 6.8: hydrogen at position 1 and 2 of the propenyl group;

5.2: hydrogen of the methoxy group of the phenylmethoxy group;

5.6 to 5.7: hydrogen atom of cyclopentene at alpha position relative to CO ₂ ;

2: hydrogen atom of the methyl group on the cyclopentene group; and

4.8 - 5.2: hydrogen of the propenyl group on the cyclopentene group.

Example 5 t (S) -? - cyano-3-phenoxybenzyl} - (1R, cis) -2,2-dimethyl-3t (Z) -3-oxo-3-phenoxy-1-propenyl] cyclopropanecarboxylate production.

The procedure of Example 1 was followed, but starting from 1.5 g (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3-phenoxy-1-propenyl] cyclopropanecarboxylic acid and 1.45 g (S) α-Hydroxy- (3-phenoxyphenyl) acetonitrile was used to obtain 1.8 g of the desired product.

a _D = + 54 ° ± 2.5 ”(c = 0.5%, benzene)

Nuclear Magnetic Resonance Spectrum (CDC1 _3, ppm):

1.25: C-position 2 of the cyclopropane ring;

1.97 and 2.12: the 1-position hydrogen atom of the cyclopropane ring;

3.25-3.6: the 3-position hydrogen of the cyclopropane ring;

6.6-7: H-position of the propenyl group;

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194,799

6.1 and 6.3: the 2-position hydrogen of the propenyl group; and

6.9-7.7: aromatic hydrogen atoms of the 3 phenoxymethyl groups.

III. Preparation Example 1R (cis) -2,2-Dimethyl-3 - [(Z) -3-oxo-3-phenoxy-1-propenyl] cyclopropanecarboxylic acid.

Step A: Preparation of (1,1-dimethylethyl) - (1R, cis) -2,2-dimethyl-3- [3-oxo-3-phenoxy-1-propynyl] -cyclopropanecarboxylate.

25g of (1,1-dimethylethyl) - (1R, cis) -2,2-dimethyl-3- [3-oxo-3- (2,2'-dibromovinyl)] - cyclopropanecarboxylate was dissolved in 250 cm ^{3 of} tetrahydrofuran and At -65 ° C, 48 cm <^3> of a 20% solution of butyl lithium in cyclohexane were added with stirring. Stirring was continued for an hour at -65 ° C and then added

9.6 cm ^{3 of} phenyl chloroformate. The whole reaction mixture was stirred for 1 hour at -65 ° C and then allowed to warm to room temperature while stirring was maintained. The mixture was poured into an aqueous solution of monosodium phosphate, extracted with ether, washed with water and dried. The resulting oil (24.6 g) was purified by chromatography on silica gel using a 9: 1 mixture of cyclohexane and ethyl acetate as eluent. 14.4 g of the expected product are obtained. Nuclear Magnetic Resonance Spectrum (CDC1 _3, ppm):

1.23 and 1.42: hydrogen atoms at the 2-position of the cyclopropane ring;

1.82: hydrogen atoms 1 and 3 of the cyclopropane ring;

1.5; the hydrogen atoms of the dimethylethyl group; and

7-7,6: aromatic hydrogen atoms.

Step B: Preparation of (1,1-dimethylethyl) - (1R, cis) -2,2-dimethyl-3t (Z) -3-oxo-3-phenoxy-1-propenyl] -cyclopropanecarboxylate.

In the presence of 800 mg of palladium hydroxide on barium sulfate, 0.8 cm ^{3 of} quinoline and 20 cm ^{3 of} ethyl acetate, a solution of 4 g of the product of Step A in 60 cm ^{3 of} ethyl acetate was added and 200 cm ^{3 of} 2N hydrogen were added. chloride solution. The whole mixture was then decanted, washed with water and dried. The resulting oil (4.1 g) was purified by chromatography on silica gel (95: 5 cyclohexane: ethyl acetate). This gave 3.35 g of the desired product.

Nuclear Magnetic Resonance Spectrum (CDC1 _3, ppm):

1.23 and 1.3: the 2-position hydrogen of the cyclopropane ring;

1.83 and 1.97: cyclopropane ring in position 1

atoms may; 3 to 3.33: the 3-position hydrogen atom of the cyclopropane ring; 1.44: the hydrogen atom of the methylethyl group; 6.7 to 7: a 1-position hydrogen atom of the propenyl group;

6.03 and 6.21: the 2-position hydrogen of the propenyl group; and

7-7.5: aromatic hydrogen atoms.

Step C: Preparation of (R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3-phenoxy-propenyl] cyclopropanecarboxylic acid.

A mixture of 3.3 g of the product from the previous step, 35 cm ^{3 of} toluene and 100 mg of p-toluenesulfonic acid monohydrate was heated to reflux until gas evolution ceased. The mixture was evaporated to dryness under reduced pressure and the resulting product (3.4 g) was chromatographed on silica gel using cyclohexane / ethyl acetate / acetic acid (70: 30: 1) as eluent. 2.4 g of the desired product are thus obtained. Melting point: 57 ° C.

Nuclear Magnetic Resonance Spectrum (CDC1 _3, ppm):

1.25-1.33: hydrogen atoms at the 2-position of the cyclopropane ring;

1.9 and 2.04: hydrogen at position 1 of the cyclopropane ring;

3.2-3.5: hydrogen at the 3-position of the cyclopropane ring;

6.6-6.9: hydrogen at the 1-position of the propenyl group; and

6.0 and 6.2: the 2-position hydrogen of the propenyl group.

Example 6 t (1S) -2-Methyl-4-oxo-3- (2-propenyl) -2-cyclopentenyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) - Preparation of 3-oxo-3-phenoxy-1-propenyl] cyclopropanecarboxylate.

The procedure of Example 2 was followed, but starting from 1.5 g of (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3-phenoxy-1-propenyl] -cyclopropanecarboxylic acid and 1 g of (S) ) -3- (2-propenyl) -1-hydroxy-2-methyl-4-oxocyclopent-2-ene was used. 1.6 g of the expected product are thus obtained. _α = + 66 ° ± 2.5 ° (c = (0.5%, benzene)

Nuclear Magnetic Resonance Spectrum (CDC1 _3, ppm):

1.26 and 1.33: position 2 hydrogen of the cyclopropane ring;

1.95 and 2.09: hydrogen at position 1 of the cyclopropane ring;

5.7: hydrogen atom of cyclopentene in alpha position relative to CO ₂ ;

4.8-5.2: hydrogen at the 3-position of the propenyl on the cyclopentene;

2: hydrogen atom of the methyl group on the cyclopentene group;

6.1-6.7: hydrogen of the propenyl group on the cyclopropane ring; and

7-7,7: aromatic hydrogen atoms.

Example 7 [(RS) -? - Cyano-3-Phenoxybenzyl) - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (methoxymethoxy) -1- preparation of propenyl] cyclopropanecarboxylate.

Step A: [(RS) -Ircyano-3-phenoxybenzyl] - (1R, cis) 2,2-dimethyl-3- (3-oxo-3- / methoxymethoxy / -1-propynyl) - Preparation of cyclopropanecarboxylate.

g [(RS) - <2-cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3- (3-hydroxy-3-oxo-1-propynyl] cyclopropanecarboxylate 30 cm ³ anhydrous The solution of dimethylformamide was cooled to +10 ° C, 300 mg of a 61% solution of sodium hydride in oil was added portionwise, followed by the addition of 2.5 cm ³ of chloromethyl ether solution prepared as described below. The whole mixture was stirred for 2 hours and then poured into an aqueous solution of monosodium phosphate, extracted with ethyl acetate, washed with water, dried and evaporated to dryness, and the residue was chromatographed on silica gel (75:25) using cyclohexane / ethyl acetate as eluant. g of the product obtained from NMR-spectrum (CDC1 ₃ ppm).:

1.23-1.27 and 1.35-1.45: protons of the 2-position methyl groups of the cyclopropane ring;

1.95: Protons 1 and 3 of the cyclopropane ring;

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5.28: proton of the methoxy-methoxy group;

3.5: proton of the methoxymethoxy group;

6.42 and 6.47: proton bound to a carbon atom bearing a cyano group; and

6.92- 7.58: aromatic protons.

The chloromethyl ether solution was prepared as follows:

4.5 cm ^{3 of} formaldehyde and 0.52 cm ^{3 of} methanol were mixed and 3.53 cm ^{3 of} acetyl chloride was added slowly. The mixture was stirred at room temperature for 36 hours to give the desired solution.

Step B: [(RS) -N'-Cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3-methoxy-1-propenyl] - Preparation of cyclopropanecarboxylate.

A solution of 2.2 g of the product of the preceding step in 50 cm ^{3 of} ethyl acetate was hydrogenated in the presence of 450 mg of 10% palladium hydroxide on barium, 30 cm ^{3 of} ethyl acetate and 0.5 cm ^{3 of} quinoline. The mixture was filtered, and the filtrate was washed with 1 N hydrochloric acid, water, dried and evaporated to dryness. The residue was chromatographed on silica gel using cyclohexane / ethyl acetate 8: 2 as eluent. 1.2 g of the expected product are thus obtained.

_{α D} = + 41 ° ± 3 ° (c = 0.3%, chloroform)

Nuclear Magnetic Resonance Spectrum (CDC1 _3, ppm)

1.27-1.28 and 1.3 3-1.35: protons of the 2-position methyl group of the cyclopropane ring;

1.93 and 2.1: the 1-position proton of the cyclopropane ring;

3.17-3.5: 3-position proton of the cyclopropane ring;

6.47-6.82: ethylene proton at position 1;

5.85-6.0 and 5.88-6.1: the ethylene proton at position 2;

5.27 and 5.3: hydrogen of the methoxy group;

3.47 and 3.5: protons of the methoxy group;

6.4: proton bound to the carbon atom bearing the cyano group; and

6.92-7.67: aromatic protons.

The process used in example [(R, S) ^{-u-cyano-3-phenoxybenzyl]} as the starting material - (lR, cis) -2,2-dimethyl-3] 3-hydroxy-3-oxo-l-propynyl] cyclopropanecarboxylate same can be prepared as the (S) ester described below using only the appropriate (RS) alcohol.

Example 8 ((S) -N'-cyano-3-phenoxybenzyl) - (1R, cis) -2,2-dimethyl-3t (Z) -3-oxo-3- (cyanomethoxy) -1 -propenyl] cyclopropanecarboxylate.

Step A: [(RS) -d'-cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3- [3-oxo-3- (cyanomethoxy) -1-propynyl] - Preparation of cyclopropanecarboxylate.

using cm ^{3 of} chloroacetonitrile, the procedure of Example 7 was followed; Extraction with ether and elution with 9: 1 cyclohexane / ethyl acetate gave 2.69 g of the desired product.

Step B: [(RS) -N'-Cyano-3-phenoxybenzyl] -F ', cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (cyanomethoxy) -1-propenyl] cyclopropanecarboxylate production.

Starting from 2.69 g of the product obtained in the preceding step, following the procedure of Example 7 and eluting with 9: 1 cyclohexane: ethyl acetate, 2.02 g of the expected product are obtained.

Step C: [(S) - (2-cyano-3-phenoxybenzyl) - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (cyanomethoxy) -1-Propenyl] cyclopropanecarboxylate.

The product from the previous step was chromatographed on silica gel with methylene chloride as eluent to give 0.41 g of the desired product.

_α = + 55 ° ± 1.5 ° (c = 1%, chloroform)

Example 9 t (S) -? - cyano-3-phenoxybenzylC1R, cis) -2,2-dimethyl-3t (Z) -3-oxo (3-2-ethoxyethoxy) -1-propenyl] - Preparation of cyclopropanecarboxylate.

Step A: [(S) -N'-Cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - [- 3-oxo (3-2-ethoxyethoxy) - Preparation of 1-propynyl] -cyclopropanecarboxylate.

g [(S) -α-cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3- [3-hydroxy-3-oxo-1-propynyl] cyclopropanecarboxylate, 20 cm ³ A mixture of methylene chloride and 0.7 cm ^{3 of} 2-ethoxyethanol was cooled to 0-5 ° C and 1.1 g of dicyclohexylcarbodiimide, 5 cm ^{3 of} methylene chloride and 15 mg of dimethylaminopyridine were added. The whole was stirred at 5 ° C for 1 hour and then at room temperature for 2 hours. The mixture was filtered, and the filtrate was evaporated to dryness, and the residue was chromatographed on silica gel using a 75:25 mixture of cyclohexane and ethyl acetate. This gave 1.3 g of the desired product.

Nuclear Magnetic Resonance Spectrum (CDC1 _3, ppm):

1.22 and 1.32: protons of the 2-position methyl groups of the cyclopropane ring;

1.93: Protons 1 and 3 of the cyclopropane ring;

4.17-4.38: 1-position protons of COO-CH ₂ -CH ₂ -O-;

3.55-3.73: 2-position protons of COO-CH ₂ -CH ₂ -O-;

6.57: proton bound to the carbon atom bearing the cyano group;

7-7.67: aromatic protons; and

1.08, 1.2, 1.3, and 1.52: protons of the ethyl group (q).

Step B: [(S) - [2-cyano-3-phenoxybenzyl] -R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2-ethoxyethoxy) -1 Preparation of -propenyl] -cyclopropanecarboxylate.

The procedure of Example 7, Step B was followed except that 1.3 g of the product of Step A was used as starting material. 1.0 g of the expected product is thus obtained. [α] _D = + 37.5 ° + 2.5 ° (c = 0.5%, chloroform)

Example 10 1 (S) -N'-Cyano-3-phenoxybenzyl] (- 1R, cis) -2,2-dimethyl-3 (Z) -3-oxo-3- (RS) - (1, Preparation of 1,1-trifluoromethyl-ethoxy) -1-propynyl] -cyclopropanecarboxylate.

Procedure of Example 7, Step B, was followed, but using 2.6 g of [(S) ^{-u-cyano-3-phenoxy-benzyl]} - (1R, cis) -2,2-dimethyl-3- [3-oxo- 3- (RS) - (1,1,1-Trifluoromethyl-ethoxy) -1-propynyl] -cyclopropanecarboxylate was used. Elution with 9: 1 cyclohexane: ethyl acetate gave 2.1 g of the desired product.

m.p. - 44 ° ± 2 ° (c = 0.4%, benzene) 1 (S) -yl-cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 [-3 Preparation of -oxo-3- (RS) -1,1,1-trifluoromethylethoxy) -1-propynyl] cyclopropanecarboxylate.

Example 9 The procedure described in Step A was followed, but using 4.6 g of 1,1,1-trifluoro-ethanol and 3.8 g of methyl [(S) ^{-u-cyano-3-phenoxy-benzyl]} - (1R, cis) -2,2-Dimethyl-313-oxo-3-hydroxy-1-propinylcyclopropanecarboxylate was used. Elution with cyclohexane / ethyl acetate (8: 2) gave the desired product (2.6 g).

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Example 11 t (S) -N'-Cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3- (2,2-difluoro) -ethoxy) -1-propenyl] cyclopropanecarboxylate.

Step A: Preparation of tert-butyl (1H, cis) -2-dimethyl-3- [3-oxo-3- (2,2-difluoroethoxy) -1-propynyl] cyclopropanecarboxylate.

Example 9 The procedure of Step 9 was followed except that 5 g of tert-butyl (1R, cis) -2,2-dimethyl-3-hydroxy-3-oxo-1-propynyl} cyclopropanecarboxylate were used as starting material. Elution with 7: 3 n-hexane: isopropyl ether gave 5.25 g of the desired product.

IR spectrum: (chloroform):

C = C- conjugated: 2232 cm 3 = 0 esters: 1725 cm ' asymmetric: 1710 cm ' geminal dimethyl: 1393 cm and tert-butyl: 1372 cm

and 1380 cm '

Step B: Preparation of (1R (, cis) -2,2-dimethyl-3- [3-oxo-3- (2,2-difluoroethoxy) -1-propynyl] cyclopropanecarboxylic acid).

5.2 g of the above product and 500 mg of p-toluenesulfonic acid in cm ^{3 of} toluene were refluxed for 25 minutes. After cooling, ether (400 cm ³⁾ was added to the reaction mixture, the whole was washed with water, then the organic phase was dried and evaporated to dryness. 4.1 g of the expected product are thus obtained.

Step C: [(S) -R-Cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - [- 3-oxo-3- (2,2-difluoroethoxy) l-Propynyl] cyclopropanecarboxylate.

The procedure of Example 9, Step A was followed, but starting from 4.1 g of the acid obtained in the previous step and 4.5 g of (S) -yl cyano-3-phenoxybenzyl alcohol. Elution with petroleum ether (boiling point 40-70 'C) and isopropyl ether (6: 4) afforded 4.7 g of the desired product.

IR spectrum (chloroform): OH:

-C = C- conjugated:

C = O ester:

conjugate ester: aromatics: geminal dimethyl:

3580 cm f 2235 cm 1755 cm ';

1725 cm ^-1 ;

1588 and 1488 cm ^-1 ; 1392 by 1380 cm '·

Step D: [(S) -N'-Cyano-3-phenoxybenzyl] - (1R, cis) 2,2-dimethyl-3 - [(Z) -3-oxo-3- (2,2-difluoro) -ethoxy) -1-propenyl] -cyclopropanecarboxylate.

4.7 g of the above product were hydrogenated according to the procedure of Example 7, Step B. Elution with hexane / isopropyl ether (7: 3) gave 3.2 g of the desired product.

W) = + 44 '± 2.5' (c = 0.5%, chloroform)

Example 12

(N, R) - hourly cyanophenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) 3- (2,2-dichloroethoxy) -1-propenyl] cyclopropanecarboxylate.

Step A: Preparation of tert-butyl (1R, cis) -2,2-dimethyl-3 - [(Z) -3-2,2-dichloroethoxy) -1-propenyl] cyclopropanecarboxylate.

The procedure of Example 9, Step A, was followed, but starting from 4.8 g of tert-butyl (1R, cis) -2,2-dimethyl-3 - [(Z) -3-hydroxy-3-oxo-1- propenyl-cyclopropanecarboxylate and 2 cm ^{3 of} 2,2-dichloroethanol were used. Elution with 9: 1 cyclohexane / ethyl acetate gave 5.6 g of the desired product.

Step B: Preparation of (1R, cis) -2,2-dimethyl-3 - [(Z) -3- (2,2-dichloroethoxy) -1-propenyl] cyclopropanecarboxylic acid.

All. Example 5b The procedure of Step B was followed, but 5.6 g of the product was used as starting material. 4.5 g of the expected product are thus obtained.

Step C: [(S) -α-Cyanophenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3- (2,2-dichloroethoxy) -1 Preparation of -propenyl] -cyclopropanecarboxylate.

The procedure of Example 9, Step A was followed, but starting from 3 g of the product of Step B and 2.25 g of (S) -α-cyano-3-phenoxybenzyl alcohol. Elution with cyclohexane / ethyl acetate 8: 3 then 9: 1 gave 1.6 g of the desired product.

Wd = +54 ”± 2” (c = 1%, benzene)

The final products of the following Examples were prepared according to the procedure of Example 9, Step A, starting from the compounds (I) to (7) below.

1) (1R, cis) -2,2-Dimethyl-3 - [(Z) -3-oxo (2,2-difluoroethoxy) -1-propenyl} cyclopropanecarboxylic acid and the corresponding alcohol.

Example 13 t (RS) -1'-Cyano-6-phenoxy-2-pyridylmethyl} - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- ( Preparation of 2,2-difluoroethoxy) -1-propenyl] cyclopropane carboxylate.

Wd = + 50.5 ± 2 (c = 0.8%, chloroform)

Example 14

1R) -α-cyanophenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) 3-oxo-3- (2,2-difluoroethoxy) -1-propenyl] - Preparation of cyclopropanecarboxylate.

[Α] D = 117.5 ± 3 '(c = 0.6%, chloroform)

Example 15 13-Propargyl-2,5-dioxoimidazolidinylmethyl] - (1R, cis) 2,2-dimethyl-3 - [(Z) -3-oxo-3- (2,2-difluoroethoxy) Preparation of -1-propenyl-cyclopropanecarboxylate.

Wd = +18 ”± 2” (c = 1%, chloroform)

Example 16 [(R) -N'-Ethynyl-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3'L) -3-oxo-3- (2,2-difluoroethoxy) Preparation of -1-propenyl] cyclopropanecarboxylate.

[alpha = + 47 '± 1.5' (c = 1%, chloroform)] (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2,2) -difluoroethoxy) -1-propenylcyclopropanecarboxylic acid according to the procedure described in VI. Prepared in the same manner as in Preparation Example 3, except that 2,2-difluoroethanol was used as starting material.

2) (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2-fluoroethoxy) -1-propenyl] cyclopropanecarboxylic acid and the corresponding alcohol.

Example 17

3-Propargyl-2,5-dioxoimidazolidinylmethyl] - (1R, cis) 2,2-dimethyl-3 - [(Z) -3-oxo-3- (2-fluoroethoxy) -1-propenyl] - Preparation of cyclopropanecarboxylate.

time = + 18 ”± 2 ° (c = 1%, chloroform)

Example 18 '(RS) -''-Cyano (6-phenoxy-2-pyridyl) methyl] - (1R cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2) -Fluoroethoxy) -1-propenyl · cyclopropanecarboxylate.

Wd = + 49.5 * ± 2.5 '(c = 0.5%, chloroform)

Example 19 [(R) -A-Methyl-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3- (2-fluoroethoxy) Preparation of -1-propenyl] cyclopropanecarboxylate.

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Wt, - + 123 + 1.5 '(c = 1%, chloroform)

Example 20 1S-Ethynyl-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2-fluoroethoxy) -1- preparation of propenyl] cyclopropanecarboxylate.

Ud = + 47 '± 1.5 (c = 1%, chloroform)

(1R, cis) -2,2-Dimethyl-3 - [(Z) -3-oxo-3- (2-fluoroethoxy) -1-propenyl] -cyclopropanecarboxylic acid is described in Example VI. Prepared according to the procedure for Preparation Example 2, except starting material was 2-fluoroethanol.

3. (1R, cis) -2,2-Dimethyl-3 - [(Z) -3-oxo-3- (2-, 1,1,1,3,3,3-hexafluoro-propoxy) -1-propenyl ] -cyclopropanecarboxylic acid (Preparation Example VI) and the corresponding alcohol.

Example 21 [(R) -6-Ethynyl-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 [(Z) -3-oxo-3- (2- (1, Preparation of 1,1,3,3,3-hexafluoro) -propoxy) -1-propenyl] -cyclopropanecarboxylate.

[α] = + 31.5 ± 5 ”(c = 1%, chloroform)

Example 22 (R) -α-Methyl-3-phenoxybenzyl] - (1R, cis) -2-dimethyl-3 - [(Z) 3-oxo-3- (2- (1,1,1,1) Preparation of 3,3,3-hexafluoropropoxy) -1-propenyl] cyclopropanecarboxylate.

+ 97 + 2 '± 2 ° (c = 1%, chloroform;

Example 23 i (S) -α-cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3kZ) -3-oxo-3- (2- (1,1,1 l) , 3,3,3-hexafluoro) -propoxy) -1-propenyl-cyclopropanecarboxylate.

W = + 23.5 ° ± 2 "± 8" (c = 0.5%, benzyl)

Example 24 (3,4,5,6-Tetrahydro-phthalimidomethyl) - (1R, cis) -2,2-dimethyl-3-f (Z) -3-oxo-3- (2- (1, 1,1,3,3,3-Hexafluoro-propoxy) -1-propenyl-cyclopropanecarboxylate.

Ια] ρ = -30χ1 '(c = 1%, chloroform)

Example 25 [(RS) -A-Cyano-6-phenoxy-2-pyridylmethyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2) - (1,1,1,3,3,3,3-Hexafluoro) propoxy) -1-propenyl] cyclopropanecarboxylate.

H = e33.5 + 2.5 (c = 0.2%, chloroform)

4) (R, cis) 2,2-Dimethyl-3 - [(Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl] cyclopropanecarboxylic acid (Preparation I) and appropriate alcohol.

Example 26 [3-Propargyl-2,5-dioxoimidazolidinylmethyl] - (1R, cis) 2,2-dimethyl-3 - [(Z) -3-oxo-3- (2,2,2- preparation of trifluoroethoxy) -propenyl] cyclopropanecarboxylate.

[ _{α D} ] = -4 '± 1 (c = 1%, benzene)

Example 27 [(R) -U-Methyl-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3KZ) -3-oxo-3- (2,2,2-trifluoroethoxy) ) -1-propenyl] cyclopropanecarboxylate.

taL = +108.5 ″ ± 2 (c = 1%, chloroform)

Example 28

O, 4,5,6-Tetrahydro-phthalimidomethyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2,2,2-trifluoro-) preparation of ethoxy) -1-propenyl] cyclopropanecarboxylate.

[α] _d = + 2.5 + 2 (c = 0.5%, chloroform)

Example 29 [(R) -α-Ethynyl-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3i (Z) -3-oxo-3- (2,2,2-trifluoro) -ethoxy) -1-propenyl] -cyclopropanecarboxylate.

ta] _D +42 ”+1.5 (c = 1%, chloroform)

Example 30 [(RS) -α'-Cyano-6-phenoxy-2-pyridylmethyl] -R, cis) -2,2-di20-methyl-3 - [(Z) -3-oxo-3- (2,2) , 2-Trifluoroethoxy) -1-propenyl] cyclopropanecarboxylate.

+46.5 +2 ° (c = 0.7%, chloroform)

5) [(S) -o-cyano-3-phenoxybenzyl] - (1R, cos) -2,2-dimethyl-3 - [(Z) -3-hydroxy-3-oxo-1-propenyl] -cyclopropanecarboxylate ( Preparation Example VII) and the corresponding alcohol.

Example 31 1- (S) -Z-Cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 [(Z) -3-oxo-3- (2,2,2- trichloroethoxy) -1-propenyl] cyclopropanecarboxylate.

Wd = 42.5 ° ± 2 (c = 0.5%, benzene)

Example 32 [(S) -α-cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3t (Z) -3-oxo-3- (2-chloroethoxy) Preparation of -1-propenyl] cyclopropanecarboxylate.

= + 39 '+ 4 "(c = 0.25% benzene)

Example 33

I (S) α-cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3t (Z) -3-oxo-3- (2-methoxyethoxy) -1-propenyl] - Preparation of cyclopropanecarboxylate.

[α] D = + 37.5 ± 2 ° (c = 1%, chloroform)

Example 34 [(S) -u-Cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3I (Z) -3-oxo-3- (RS) -1-cyano preparation of ethoxy) -1-propenyl] cyclopropanecarboxylate.

Md - + 64.5 '+ 3' (c = 0.3%, chloroform)

Example 35 (S) -U-Cyano-3-phenoxybenzyl] - (1 R, cis) -2,2-dimethyl-3 (Z) -3-oxo-3- (2-fluoroethoxy) Preparation of -1-propenyl] cyclopropanecarboxylate.

[α] ρ = +48 (c = 0.25%, benzene)

Example 36 t (S) -α-cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3t (Z) -3-oxo-3-phenethoxyethoxy] -1-propenyl] cyclopropanecarboxylate production.

[α] D = + 46 + 2.5 ° (c = 0.5%, benzene).

Example 37 [(S) -U-Cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 [(Z) -3-oxo-3- (2,2-dimethyl) Preparation of dioxolanyl-4- (RS) -methoxy) -1-propenyl] cyclopropanecarboxylate.

Wd = + 46 + 2 '(c = 0.75%, benzene)

6) [(RS) -α-cyano-3-phenoxy: benzyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-hydroxy-3-oxo-1-propenyl] -cyclopropanecarboxylate and the corresponding alcohol.

Example 38 [(RS) -Cyano-3-phenoxybenzyl} - (1R, cis) -2,2-dimethyl-3I (Z) -3-oxo-3- (2- (dimethylamino) ethoxy). ) -1-propenyl] cyclopropanecarboxylate.

[ _α ] _D = + 23 ± 3 (c = 0.25%, chloroform)

The starting material of the previous example was (RS) δ-cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-hydroxy-3-oxo-1-propenyl]. Cyclopropanecarboxylate was prepared in the same manner as (S) -cyano-3-phenoxybenzyl ester in Example IV. and VII. preparation example.

7) [(R) -α-Methyl-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-hydroxy-3-oxo-1-propenyl] - cyclopropanecarboxylate (Preparation VIII) and the corresponding alcohol.

Example 39 [(R) -A-Methyl-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3- (2-methoxyethoxy) Preparation of -1-propenyl] cyclopropanecarboxylate.

Nuclear Magnetic Resonance Spectrum (CDC1 _3, ppm):

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1.22 and 1.25: protons of the 2-position methyl groups of the cyclopropane ring;

1.45 and 1.55: protons of the methyl in the 1-position ester of the cyclopropane ring;

5.7-6.0: protons of the benzyl group;

3.42: protons of the methoxy group;

4.22-4.38: position 1 protons of the 3-position ester of the cyclopropane ring;

3.55-3.72: position 2 protons of the 3-ester group of the cyclopropane ring; and

5.85, 6.05 and 6.32-6.8: ethylene protons.

Example 40 t (S) -n-cyano-3-phenoxybenzyl) Cl, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (1-methoxy-1-trifluoro) preparation of methyl (ethoxy) -1-propenyl] cyclopropanecarboxylate.

1.02 g of [(S) -6'-cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-chloro-3-oxo-1- propenyl] -cycloporpanecarboxylate and 9 cm ^{3 of} methylene chloride were stirred under inert atmosphere and 1.12 g of 1-methyl-1- (trifluoromethyl) ethanol were added and stirring continued for 48 hours at room temperature. The reaction mixture was evaporated to dryness under reduced pressure and the residue was chromatographed on silica gel using hexane / ethyl ether 8: 2 as eluent. This gave 250 g of the desired product. Melting point: 59 C. [α] D = + 57 ° ± 2 ”(c = 0.4%, benzene)

4o. [(S) -Acyano-3-phenoxybenzyl-P (1R, cis) -2,2-dimethyl-3 - [(Z) -3-chloro-3-oxo-1-propenyl [cyclopropanecarboxylate] was used that [(S) -yl'-cyano-3-phenoxybenzyl · (1R, cis) -2,2-dimethyl-3 - [(Z) -3-hydroxy-3-oxo-1-propenyl] - cyclopropanecarboxylate (Preparation VII) was reacted with thionyl chloride.

Example 41 i (S) -? - Cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (1-trifluoride) preparation of methyl (-1-methylpropyloxy) -1-propenyl] cyclopropanecarboxylate.

900 mg of [(S) -''-cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-34 (Z) -3-chloro-3-oxo-1-propenyl] cyclopropanecarboxylate was dissolved in 3 cm ³ of methylene chloride, and added with 1 cm ³ 1 - (trifluoromethyl) - 1-methyl-propanol, and the mixture was stirred under an inert moisture blocking at room temperature for 16 hours. After standing for 3 days at room temperature, the mixture was washed with saturated aqueous sodium bicarbonate solution and water and then evaporated to dryness. The residue was chromatographed on silica gel using hexane / ethyl ether 8: 2 as eluent. This gave 570 mg of the desired product.

EXAMPLE 42 [(S) ^{-u-cyano-3-phenoxybenzyl} -benzyl (lR, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3 - (2,3-dihydroxy -propyloxy) -1-propenyl] cyclopropanecarboxylate.

4.65 g of [(S) -n-cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-34 (Z) -3-oxo-3- (2,2-dimethyl-) A mixture of dioxolanyl-4- (RS) methoxy) -1-propenyl] cyclopropanecarboxylate (Figure 37), 46 cm ^{3 of} dioxane, 9 cm ^{3 of} water and 0.45 g of p-toluenesulfonic acid was refluxed for 45 minutes. Most of the dioxane was removed by distillation under reduced pressure at 40 ° C and the residue was taken up in a mixture of 150 cm ^{3 of} methylene chloride and 25 cm ^{3 of} water. After stirring and decanting, the organic phase was washed with water, dried and evaporated to dryness under reduced pressure. The residue was chromatographed on silica gel using a 3: 7 mixture of cyclohexane and ethyl acetate. This gave 3.85 g of the desired product.

nl ·) = + 53 ± 2.5 ′ (c = 0.5% chloroform)

Example 43

I (RS) -? -Cyano-3-phenoxybenzyl] - (1R, cis) 2,2-dimethyl-3 - [(Z) -3-oxo-3- (2-tetrahydropyranyloxyethoxy)] Preparation of -propenyl-cyclopropanecarboxylate.

Step A: [(RS) -α-Cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2-tetrahydropyranyloxyethoxy) - Preparation of l-propenyl] cyclopropanecarboxylate.

Example 7 The procedure of Step 7 was followed, but starting from 2.3 g of [(RS) -γ-cyano-3-phenoxybenzyl] (1R, cis) -2,2-dimethyl-3-yl (Z) - 3-Hydroxy-3-oxo-1-propyl] -cyclopropanecarboxylate and 7.5 g of 1-bromo-2- (2-tetrahydropyranyloxy) -ethane were used. Elution with cyclohexane / ethyl acetate (75:25) gave 1.8 g of the desired product.

Step B: [(RS) -α-Cyano-3-phenoxybenzyl] - (1,1 cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2-tetrahydropyranyloxy) -ethoxy) -1-propenyl] -cyclopropanecarboxylate.

The procedure of Example 7, Step B was followed, but the product of Step A was used as starting material. Purification by chromatography, eluting with 80:20 cyclohexane / ethyl acetate, gave 1.3 g of the desired product.

= +33 ”± Γ (c = 1%, chloroform)

[(RS) -O-Cyano-3-phenoxybenzyl] (1R, cis) -2-dimethyl-3 [(Z) -3-hydroxy-3-oxo-1-propynyl] cyclopropanecarboxylate used as starting material in the preceding step was prepared in a similar manner. as in IV. (S) -Z-cyano-3-phenoxybenzyl ester according to the Preparation Example.

Example 44 [(RS) -α-Cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2-hydroxyethoxy) ) - Preparation of -1-propenyl N-cyclopropanecarboxylate.

0.85 g of the product of Example 43, 17 cm ^{3 of} ethanol, 5 cm ^{3 of} dioxane, 1 cm ^{3 of} water and 4 cm ^{3 of} 2N hydrochloric acid solution were mixed and the mixture was stirred for 3 hours at 20 ° C. Then 1 cm ^{3 of} triethylamine was added and the reaction mixture was evaporated to dryness. The residue was taken up in water / ice and extracted with methylene chloride. The extract was washed with water, drying needles and the solvent was evaporated. The residue was chromatographed on silica gel using 65:35 cyclohexane / ethyl acetate as eluent. 0.65 g of the expected product is obtained.

; a] n = + 42.5 ± 2.5 ”(c = 0.5%, chloroform)

The present invention also provides the following two compounds (using the appropriate acid and alcohol as starting materials): (3-phenoxybenzyl) - (1R, cis) -2,2-dimethyl-3 - [(Z) -3 -oxo- (1,1,1,3,3,3,3-hexafluoropropoxy) -1-propenyl] clopropanecarboxylate.

Y] d = + 26.5 '± 2.5' (c = 0.5%, chloroform); and [(S) -Zicyano-3-phenoxy-4-fluorobenzyl} - (1R, cis) -2,2-dimethyl-3 - ((Z) -3-oxo- (1,1,1,3,3,3), 3-hexafluoropropoxy) -1-propenyl] cyclopropanecarboxylate.

W _D = + 27 '± 12' (c = 0.8% benzene).

ARC. Preparation Example S Preparation of (S) -α-cyano-3-phenoxybenzyl] - (1R cis) -2,2-dimethyl-3 - [(3-oxo-3-hydroxy-1-propynyl] cyclopropanecarboxylate.

Step A: Preparation of tert-butyl (1R, cis) -2,2-dimethyl-3- [2-carboxyethynylcyclopropanecarboxylate.

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175 cm ³ of dry tetrahydrofuran was treated with tert-Butyl (lR, cis) -2,2-dimethyl-3- (2,2-dichlorovinyl) cyclopropanecarboxylate. It was then added to 60 cm ^3, 20% in cyclohexane butyllithium -65 C. After stirring for 1 hour at -60 ° C, carbon dioxide was bubbled through the reaction mixture, which was then poured into water, to which 1N sodium hydroxide solution was added. The mixture was then washed with ether. The alkaline aqueous solution was acidified to pH 4 and extracted with ether. The organic phases were evaporated to dryness under reduced pressure and the product recrystallized from petroleum ether (b.p. 60-80 ° C). 8.3 g of the expected product are obtained. Melting point: 144 'C.

Nuclear Magnetic Resonance Spectrum (CDCl 3, ppm):

1.22 and 1.37: protons of the 2-position methyl groups of the cyclopropane ring;

1.78: Protons 1 and 3 of the cyclopropane ring;

1.47: protons of the tert-butyl group; and

8.25: proton of the -CO-OH group.

Step B: Preparation of tert-butyl (1R, cis) -2,2-dimethyl-3- (2,2,2-trichloroethoxycarbonyl-ethynyl) -cyclopropanecarboxylate.

To a solution of 7.15 g of tert-butyl (1 R, cis) -2,2-dimethyl-3- (2-carboxyethynyl) cyclopropanecarboxylate and 80 mg of dimethylaminopyridine in 35 cm ^{3 of} methylene chloride was added 6.2 g of dicyclohexyl- DCC. The reaction mixture was stirred for 10 minutes and then 4.5 g was added

2,2,2-trichloroethanol. Stirring was continued for one hour, and the precipitate formed was removed by filtration. The filtrate was washed with 1 N hydrochloric acid, then with water until neutral, dried and evaporated to dryness. 14 g of an oil are obtained which is chromatographed on silica gel using a 97: 3 mixture of benzene and ethyl acetate as eluent. 9 g of the desired product are obtained. Melting point: 70-71 ° C.

Step C: Preparation of (1R, cis) -2,2-dimethyl-3- (2,2,2-trichloroethoxycarbonylethynyl) cyclopropanecarboxylic acid.

A mixture of 11.4 g of the product of Step B, 120 cm ^{3 of} toluene and 300 mg of p-toluenesulfonic acid was refluxed for 1 hour. The reaction mixture was then allowed to cool to room temperature, washed with water, dried and evaporated to dryness. This gave 9.5 g of the desired product which was used as such in the next step.

Step D: [(S) -U-Cyano-3-Phenoxy-benzyl] - (1R, cis) -2,2-dimethyl-3- (2,2,2-trichloro-ethoxycarbonyl-ethynyl) -cyclopropanecarboxylate production.

To a solution of 9.5 g of the product from Step C in 30 cm ^{3 of} methylene chloride and 3 cm ^{3 of} pyridine was added

6.2 g of dicyclohexylcarbodiimide. After stirring for half an hour, (S) -cyano-3-phenoxybenzyl alcohol (6.8 g) was added. The reaction mixture was stirred for 1.5 hours and the insoluble material was removed by filtration. The filtrate was washed with 1 N hydrochloric acid, then with water until neutral, dried, filtered and evaporated to dryness. The resulting oil (15.3 g) was chromatographed on silica gel using a 97: 3 mixture of benzene and ethyl acetate as eluent. 12 g of the expected product are thus obtained. Melting point: 101 'C.

Step B: Preparation of [(S) -2-cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3- (3-hydroxy-3-oxo-1-propynyl) cyclopropanecarboxylate.

6.5 g of product from Step D with 23.4 cm ^{3 of} acetic acid and

To a solution of 2.6 cm ^{3 of} water was added 5.9 g of zinc powder. The reaction mixture was stirred for 1 hour and then filtered. The filtrate was decanted, the organic layer was washed with water, and the aqueous layer was extracted with methylene chloride. The methylene chloride solutions were combined, dried, filtered and evaporated to dryness. This way

4.7 g of crude product are obtained, which product is used as such.

Production Example V

Preparation of tert-butyl (1R, cis) -2,2-dimethyl-3 - [(Z) -3-hydroxy-3-oxo-1-propenyl] cyclopropanecarboxylate.

The IV. Preparation Example 2 2 g of tert-butyl (1R, cis) -dimethyl-3- [2-carboxyethynyl] -cyclopropanecarboxylate prepared in Step A was hydrogenated into 0.38 g of 10% barium sulfate in 40 cm ^{3 of} ethyl acetate. in the presence of palladium hydroxide and 0.4 cm ^{3 of} quinoline. The mixture was filtered, and the filtrate was washed with 0.5 N hydrochloric acid solution, then with water until neutral, dried and evaporated to dryness under reduced pressure. This gave 2 g of the desired product. Melting point: 94 'C.

VI. preparation example

1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2- [1,1,1,3,3,3-hexafluoro-propoxy) -1-propenyl] - Preparation of cyclopropanecarboxylic acid.

Step A: tert-Butyl (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3 (2- / 1,1,1,3,3,3-hexafluoropropoxy) ) -1-Propenyl] cyclopropanecarboxylate.

The procedure of Example 9, Step A, was followed, but using 3.6 g of tert-butyl (1R, cis) -2,2-dimethyl-3 - [(Z) -3-hydroxy-3-oxo-1-propenyl] starting material. cyclopropanecarboxylate (Preparation Example V) and 3 g of hexafluoroisopropanol were used. Elution with benzene / cyclohexane (4: 6) gave 4.9 g of the desired product. Melting point: 92 'C.

Step B: (R, cis) -2,2-Dimethyl-3 - [(Z) -3-oxo-3- (2-

1,1,1,3,3,3-Hexafluoro-propoxy) -1-propenyl] cyclopropanecarboxylic acid.

All. The procedure of Step B of Example 1B was followed except that 4.9 g of the product of the previous step was used as starting material. 4.2 g of the expected product are thus obtained.

IR spectrum: (chloroform):

OH monosav3500 ^cm-1;

+ prize

C = O conjugated ester: 1755 cm <^-1> (shoulder) and 1744 cm <^1>(maxi);

Sav: 1695 cm ^-1 ;

Conjugated C = C: 1627 cm and gem-dimethyl: 1380 ^cm-1 (shoulder).

VII. Preparation Example [(S) -t-cyano-3-phenoxybenzyl] - ((1R, cis) -2,2-dimethyl-3 - [(Z) -3-hydroxy-3-oxo-1-propenyl) Preparation of cyclopropanecarboxylate.

In the presence of 500 mg of 10% palladium hydroxide on barium sulfate and 6.5 cm ^{3 of} quinoline, 4.7 g of ((S) -α-cyano-3-phenoxybenzyl) - (1 R, cis) -2.2 dimethyl-3- (2-karboxietinil) cyclopropanecarboxylate. (Preparation Example IV) was hydrogenated in 45 cm ^{3 of} ethyl acetate. The reaction mixture was filtered, and the filtrate was washed with 1N hydrochloric acid, then with water until neutral, dried and evaporated to dryness. The resulting oil (5.1 g) was chromatographed on silica gel with hexane / ethyl acetate / acetic acid 70: 30: 1 as eluent. This gave 3.8 g of the desired product.

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VIII. Preparation Example [(R) -ylmethyl-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-hydroxy-3-oxo-1-propenyl] - Preparation of cyclopropanecarboxylate.

Step A: [(R) -6-Methyl-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3- [3-oxo-3- (2,2,2-trichloroethoxy) ) -proponyl] cyclopropanecarboxylate.

The IV. Prepared according to Preparation Example D, Step D, but starting from 6 g of (1R, cis) -2,2-dimethyl-3- [3- (2,2,2-trichloroethoxy) propynyl] cyclopropanecarboxylic acid and 4.1 g. g 1- (R) - (3-phenoxyphenyl) ethanol was used. Chromatography on cyclohexane / ethyl acetate (8: 2) afforded 4.38 g of the desired product.

Step B: Preparation of [(R) -n-methyl-3-phenoxybenzyl-N (1R, cis) -2,2-dimethyl-3- [3-oxo-3-hydroxy-1-propynyl] cyclopropanecarboxylate.

The product from the previous step (4.16 g) was dissolved in methylene chloride (4 cm ³ ) and acetic acid (45 cm @ ⁵ , 10% water and 0.53 g zinc powder) was added. The reaction mixture was stirred for 30 minutes at room temperature and then 0.53 g of zinc powder (4 times) was added repeatedly until the reaction was complete. After 3 hours, the mixture was filtered and extracted with methylene chloride. The organic phase was washed with water, dried and evaporated to dryness by azeotropic distillation with toluene. This gave 3.05 g of the desired product.

Step C: [(R) -ylmethyl-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-hydroxy-3-oxo-1-propenyl] - Preparation of cyclopropanecarboxylate.

The procedure of Example 7, Step B was followed, but the product of the previous Step B was used as starting material. This gave 2.9 g of the desired crude product which was used as such.

Example 45 [(S) -Cyano (3-phenoxyphenyl) methyl} - (1R, cis) -2,2-dimethyl-3- [3-oxo-3- (RS) - (1,1) , 1-Trichloropropyl-2-oxy) (Z 1 -propenyl-cyclopropanecarboxylate).

3.52 g [(S) -cyano- (3-phenoxyphenyl) methyl] - (1R, cis) 2,2-dimethyl-3- [3-oxo-3-chloro- (Z) -1-propenyl] To a solution of (1R, cis) 2,2-dimethyl-3-oxo-3-chloro- (Z) -1-propenyl] cyclopropanecarboxylate in 15 ml of dichloromethane was added 5.6 g of trichloroisopropanol, followed by After stirring at C, the reaction mixture was poured into an ice cold solution of sodium dihydrogen phosphate, extracted with dichloromethane, the organic phase was washed with water, evaporated to dryness in vacuo and the residue chromatographed on silica gel. Elution with 85:15 cyclohexane / ethyl acetate gave the title compound (2.85 g, m.p. 78 ° C, [α] D = + 50 '(c = 1, chloroform).

starting material [(S) -cyano-3-phenoxyphenyl) methyl] -R 1, cis) -2,2-dimethyl-3- {3-oxo-3-chloro (Z) -1-propenyl] - Preparation of cyclopropanecarboxylate.

0.5 g of [(S) -cyano (3-phenoxyphenyl) methyl] - (1R, cis) -2,2-dimethyl-3-oxo (Z) -1-propenyl] cyclopropanecarboxylate and

To a mixture of dichloromethane (7.5 ml) was added a solution of 1-chloro-N, N, 2-trimethylpropenylamine (0.25 ml) in dichloromethane (7.5 ml) and tert-butanol (1.5 ml), and the mixture was stirred for 48 hours. The organic solution was washed with water, evaporated to dryness in vacuo and the residue chromatographed on silica gel. Elution with hexane / ether (8: 2) gave the title compound (0.43 g, m.p. 86 'C).

Example 46 [Cyano (3-phenoxyphenyl) methyl] - (1R, cis) -3- [3- (2-tetrahydropyranyloxy) -3-oxo (Z) -1-propene (1- Preparation of 2,2-dimethylcyclopropanecarboxylate.

1.5 g [cyano (3-phenoxyphenyl) methyl] - (1R, cis) -3-oxo-3-hydroxy (Z) -1-propenyl] -2,2-dimethylcyclopropanecarboxylate (1 molecule of exacetic acid) to 10 ml of dichloromethane solution, 4.5 ml of dehydropyran are added and 1 N hydrochloric acid in methanol is added dropwise with stirring at 15 ° C, followed by stirring at room temperature for 30 minutes, followed by the addition of calcium carbonate, evaporate and chromatograph the residue on silica gel. Elution with 8: 2 hexane: ether afforded the title compound (1.07 g).

= +47 '(c = 0.5, benzene).

Example 47 [Cyano (3-phenoxyphenyl) methyl] - (1R, cis) -3- [3- (2-tetrahydrofuranyloxy) -3-oxo-3- (Z) -propenyl] - Preparation of 2,2-dimethylcyclopropanecarboxylate.

The procedure described in Example 46 was followed except that 4,5-dihydrofuran was used. The title compound was obtained, [α] _D = +42.5 '(c = 1, benzene).

Example 48 [(S) -Cyano (3-phenoxyphenyl) methyl] - (1R, cis) -2,2-dimethyl-3-β-oxo-3 (R or S) - (1,1) , 1-trifluoropropyl-2-oxy) - (Z) -1-propenyl] -cyclopropanecarboxylate ("A isomer") and [(S) -cyano (3-phenoxyphenyl) methyl] - (1R, cis) -2,2-dimethyl-3- [3-oxo-3- (S or R) - (1,1,1-trifluoropropyl-2-oxy) - (Z) -1-propenyl} cyclopropanecarboxylate (" Isomer B ").

3.36 g of [(S) -cyano (3-phenoxyphenyl) methyl] - (1R, cis) 2,2-dimethyl-343-oxo-3-hydroxy (Z) -1-propenylcyclopropanecarboxylate and 6.95 g of trifluoropropanol were cooled to 0 ° C, 140 mg of dimethylaminopyridine was added, followed by 1.76 g of dicyclohexylcarbodiimide and stirred at 20 ° C for 2 hours 30 minutes. The mixture was then concentrated by distillation in vacuo and chromatographed on silica gel. Elution of the two with cyclohexane / ethyl acetate (9: 1) yields the A and B isomers.

Isomer A has a melting point of 74 ^l C, [n] _D = + 34 '(c = 0.6, chloroform).

Isomer B had a melting point of 40 'C, [?] D = + 44 (c = 0.5, chloroform).

Example 49 [(S) -Cyano-1- (3-phenoxyphenyl) methyl] - (1R, cis) -3- [3-oxo-3-bromomethoxy (Z) - and (E) -1 -propenyl] -2,2-dimethylcyclopropanecarboxylate

a) Preparation of acid bromide

5.4 g of [(S) -cyano (3-phenoxyphenyl) methyl] - (1R, cis) -3R (Z) -3-oxo-3-hydroxy-1-propenyl} -2,2- To a mixture of dimethylcyclopropanecarboxylate and 18 ml of toluene was added 0.1 ml of pyridine and 1.8 ml of phosphorus (III) tribromide at -10 ° C, the mixture was stirred for 16 hours at + 5 ° C, The organic phase is decanted to dryness in vacuo. 4.62 g of the acid bromide are thus obtained.

b) Condensation

A mixture of 3.7 g of the acid bromide obtained in step a), 330 mg of formaldehyde and 100 mg of zinc bromide was heated to + 50 ° C for 1 hour, then cooled to give the crude product on silica gel. gel. Elution with cyclohexane and

-1 427

194,799 ethyl acetate (8: 2) gave 300 mg (Z) ester and 1 g (E) ester.

Isomer Z:

1 H-NMR (CDCl ₃ , δ ppm): 1.27-1.31 (H, geminal methyl groups): 1.99-2.13 (H, 1-position of cyclopropyl group); 3.2-3.5 (H at the 3-position of the cyclopropyl group); 5.8-5.9 and 5.51-6.01 (H, BrCH ₂ O-); 5.9-6.1 (2'H, ethylene); 6.4 (H on carbon bearing CN); 6.6-6.95 (H in the Γ position, ethylene); 6.95-7.6 (H; aromatic core).

Isomer E:

Flfl = -18.5 (c = 1.2, chloroform)

1 H-NMR (CDCl 3, δ ppm): 1.26-1.3 (H; geminal methyl groups); 1.92-2.17 (H; 1 and 3 in the cyclopropyl group); 5.9 (H; BrCH ₂ O-); 5.9-6.2 (H; 2'-ethylene); 6.5 (H; carbon atom of CN); 7.0-7.7 (H; aromatic core).

Example 50 1- (S) -Cyano (3-phenoxy-4-fluorophenyl) methyl] - (1R, cis) 2,2-dimethyl-3- [3-oxo-3- (RS) -1,1 , 1-Trifluoropropyl-2-oxy) - (Z) -1-propenyl] -cyclopropanecarboxylate.

2.05 g of I (S) -cyano- (3-phenoxy-4-fluorophenyl) methyl] -1R, cis) -2,2-dimethyl-3- [3-oxo-3-hydroxy-2- of propyloxy (Z) -1-propenyl] cyclopropanecarboxylate in 10 ml of dichloromethane at 0 ° C, 2.14 g of 1,1-trifluoro-2-propanol and 50 mg of 4- (dimethylamino) pyridine, followed by

Dicyclohexylcarbodiimide (1.3 g) was added, the mixture was stirred for 30 minutes at 20 ° C, filtered, the filtrate was evaporated to dryness in vacuo and the residue was stirred with 6 ml of a 9: 1 mixture of cyclohexane and ethyl acetate. the filtrate is concentrated to dryness in vacuo and the residue is chromatographed on silica gel. Elution with 9: 1 cyclohexane / ethyl acetate gave 1.8 g of the title compound. Mp .: 88 'C.

k] n = + 45 = c = 0.5, chloroform).

I (S) -Cyano (3-phenoxy-4-fluorophenyl) methyl] - (1R, cis) 2,2-dimethyl-3- [3-oxo-3-hydroxy (Z) -propenyl] cyclopropanecarboxylate production.

the step:

(S) -Cyano- (3-phenoxy-4-fluorophenyl) methyl] - (1R, cis) 2,2-dimethyl-3- [3-oxo-3-tert-butoxy-1 (Z) -propenyl · Preparation of cyclopropanecarboxylate.

310 g of (S) -cyano- (3-phenoxy-4-fluorophenyl) methanol and 310 g of (1R, cis) -2,2-dimethyl-3- [3-oxo-3-tert-butoxyl ) -propenyl} -cyclopropanecarboxylic acid is stirred until it is dissolved in 1.55 L of dichloromethane, cooled to -5 DEG C. and 263.5 g of dicyclohexylcarbodiimide and

A solution of 3.1 g of 4- (dimethylamino) pyridine in 530 ml of dichloromethane. The mixture was stirred at -5 ° C for 1 hour and then at room temperature for 3 hours, filtered and the filtrate was washed with 1N hydrochloric acid, water, dried and evaporated to dryness in vacuo. The residue was stirred in isopropanol (1.185 L), water (80 mL) and triethylamine (72 mL) for 36 hours, filtered and washed with isopropanol. 518 g of the expected product are obtained. 114 DEG C.

Step b:

Preparation of t (S) -cyano (3-phenoxy-4-fluorophenyl) methyl] - (1R cis) 2,2-dimethyl-3- [3-oxo-3-hydroxy-1 (Z) -propenyl] cyclopropanecarboxylate .

350 g of the product of step a) and 35 g of toluenesulfonic acid are dissolved in 3.5 L of toluene and refluxed for 45 minutes, cooled, washed with water, dried and concentrated in vacuo. 328 g of crude product are obtained.

Example 57 [(S) -Cyano (3-phenoxyphenyl) methyl] - (1R, cis) -2,2-dimethyl-3 '[3-oxo-3- (2,2,2-trifluoro) ) - 1 (RS) -ethoxy-1 (Z) -propenyl] -cyclopropanecarboxylate.

In a similar manner to that described in Example 50, but starting from ((S) -cyano- (3-phenoxyphenyl) methylR 1 R, cis) -2,2-dimethyl-3-β-oxo-3H-hydroxy (Z). -1-propenyl cyclopentanecarboxylate and

2,2,2-Trifluoro-1-ethoxyethanol is used.

L = +37,5 '(c = 1, chloroform).

Example 52

I (S) -cyano- (3-phenoxyphenyl) methyl] - (1R, cis) -2,2-dimethyl-3- [3-oxo-3- (chloromethoxy) - (Z) -1 Preparation of -propenyl-cyclopropanecarboxylate.

(S) -Cyano- (3-phenoxyphenyl) methyl] - (1R, cis) -2,2-dimethyl-3-l (R) -3-oxo-3-hydroxy-1-propenyl] cyclopropanecarboxylate ( A mixture of dichloromethane (18.5 g), dichloromethane (50 ml) and thionyl chloride (50 ml) was stirred at 20-25 ° C for 2 hours, then evaporated to dryness, and after adding 1.38 g paraformaldehyde and 0.15 g zinc chloride Keep at 70 ° C for 2.5 hours. After work up, the product obtained is chromatographed on silica gel, eluting with 8: 2 hexane: ethyl acetate. This affords the title compound. 1 H-NMR (CDCl 3 δ ppm): 1.27-3 (H; geminal methyl groups); 5.9-6.1 and 6.6-7 (H; ethylene); 5.8 (H; CO, CH ₂ Cl).

Example 53 (S) -Cyano (3-phenoxyphenyl) methyl] - (1R, cis) -2,2-dimethyl-3- [3-oxo-3- (fluoromethoxy) - (Z ) -1-propenyl] cyclopropanecarboxylate.

A solution of the product of Example 52 (g) in diethyl ether (60 ml) was cooled to 0 ° C, treated with silver tetrachloroborate and stirred at 0 ° C for 30 minutes and then at 20 ° C for 90 minutes. The reaction mixture was poured into a solution of bicarbonate, washed with water and separated, and the resulting product was chromatographed on silica gel. Elution with benzene gave 1.95 g of the title compound.

1 H-NMR (CDCl 3, ≤ 5 ppm): 1.27-1.3 (H; geminal methyl groups); 6.6-6.8 (H; ethylene at position 1');

5.9-6.1 (H; ethylene at 2 '); 5.3-6.3 (H; CO ₂ CH ₂ F).

Example 54

Preparation of benzyl (1R, cis) -2,2-dimethyl-3- [3-oxo (2-fluoroethoxy) - (Z) -1-propenyl] -cyclopropanecarboxylate. The procedure of Example 45 is followed; Starting with benzyl (1R, cis) -2,2-dimethyl-3- [3-oxo-3-hydro- (Z) -1-propenyl] -cyclopropanecarboxylate and 2-fluoroethanol.

L4, +53 '(c = 0.5, chloroform).

Preparation of benzyl (1R, cis) -2,2-dimethyl-3- [3-oxo-3-hydroxy- (Z) -1-propenyl} cyclopropanecarboxylate as starting material.

the step:

Preparation of benzyl (1R, cis) -2,2-dimethyl-3- [3-oxo-3- (tert-butoxy) (Z) -1-propenyl] cyclopropanecarboxylate.

To a mixture of 2.6 g of sodium hydride and 100 ml of tetrahydrofuran at 10 ° C is added 25 g of (1R, cis) -2,2-dimethyl-3- [3-oxo-3- (tert-butoxy) - (Z) -1- pr.openill-ciklopro15

-1 529

A mixture of 194,799 pannicarboxylic acid (prepared according to European Patent Application Publication No. 0041021) and 250 ml of tetrahydrofuran was added with stirring, followed by stirring at 30 ° C for 30 minutes, followed by addition of 35 ml of benzyl bromide and 100 ml of tetrahydrofuran. and stirred for 48 hours at 50 ° C. The reaction mixture was cooled, poured into aqueous sodium dihydrogen phosphate solution and extracted with diisopropyl ether. The organic layer was washed with water, dried and evaporated to dryness in vacuo. The residue was chromatographed on silica gel. Elution with hexane / diisopropyl ether (9: 1) gave the title product of step a) (30 g).

Step b:

Preparation of benzyl (1R, cos) -2,2-dimethyl-3- [3-oxo-3- (tert-butoxy) - (Z) -1-propenyl] -cyclopropanecarboxylate.

A mixture of 30 g of the product obtained in step a), 30 ml of toluene and 250 g of p-toluenesulfonic acid is refluxed for 1 hour and then, after cooling, chromatographed on silica gel. The eluent was 1: 1 hexane / ethyl acetate (1% acetic acid). The product was recrystallized from diisopropyl ether to give 3.05 g of the title compound of Step b). Mp .: 69 'C.

L (R, S) -1- (6-phenoxy-2-pyridyl) ethyl] - (1R, cis) -2,2-dimethyl-3- [3-oxo-3-hydroxy (Z) -1 Preparation of -propenyl] -cyclopropanecarboxylate.

the step:

(R, S) -1- (6-Phenoxy-2-pyridyl) -ethyl] - (1R, cis) -2-2-dimethyl-3-oxo-3- (tert-butoxy) - (Z) - Preparation of 1-propenyl] cyclopropanecarboxylate.

g of (R, cis) -2,2-dimethyl-3-β-oxo-3- (tert-butoxy) (Z) -1-propenyl] cyclopropanecarboxylic acid, 650 mL of dichloromethane and 70 g of (R, S) ) -1- (6-phenoxy-2-pyridyl) -ethanol cooled to + 5 ° C over the same time at 55 ° C, 55.7 g of dicyclohexylcarbodiimide and 2.6 g of dimethylaminopyridine in 450 ml of dichloromethane. methane solution. After stirring at 20 ° C for 4 hours, the precipitate was filtered off and the filtrate was evaporated to dryness. The residue is taken up in 240 ml of diethyl ether, filtered again and the filtrate is evaporated to dryness and the residue is chromatographed on silica gel. Elution with n-hexane: ethyl acetate (100: 4) gave the title product of step a) in a yield of 101 g.

= +64 '(c = 1, toluene).

Step b:

t (R, S) -1 -6-phenoxy-2-pyridyl) ethyl (1R, cis) -2,2-dimethyl-3- [3-oxo-3-hydroxy (Z) -1-propenyl] Preparation of cyclopropanecarboxylate.

A solution of 5.649 g of the product obtained in step a), 9.5 g of p-toluenesulfonic acid and 70 ml of toluene is refluxed until gas evolution ceases, then cooled to 0 'C, filtered and the filtrate is evaporated to dryness. Yield: 4.741 g (b).

Example 55

Preparation of benzyl (1R, cis) -2,2-dimethyl-3- [3-oxo-3- (2,2-difluoroethoxy) - (Z) -1-propenyl] cyclopropanecarboxylate.

Following the procedure described in Example 50, benzyl (1R, cis) -2,2-dimethyl-3- [3-oxo-316-hydroxy- (Z) -1-propenyl-cyclopropanecarboxylate and difluoro-ethanol were used as starting materials.

t (i) = +52 (c = 0.2, chloroform).

Example 56

Preparation of benzyl (1R, cis) -2,2-dimethyl-3- [3-oxo-3- (2,2,2-trifluoroethoxy) (Z) -propenyl] -cyclopropanecarboxylate.

Following the procedure described in Example 50 but starting from benzyl (1R, cis) -2,2-dimethyl-3- [3-oxo-3-hydroxy (Z) -1-propenyl] cyclopropanecarboxylate and trifluoroethanol applying the title compound.

[?] d = +45 (c = 0.6, chloroform).

Example 57 [(R, S) - (6-Phenoxy-2-pyridyl) -methyl} - (1R, cis) -2,2-dimethyl-3- [3-oxo- (1,1,1, Preparation of 3,3,3-hexafluoroisopropoxy) -3- (Z) 1-propenyl] cyclopropanecarboxylate.

Following the procedure described in Example 50, but starting from (R, cis) -2,2-dimethyl-3- [3-oxo-3-hydroxy (Z) -1-propenyl] -cyclopropanecarboxylate - [(R, S) - (6-Phenoxy-2-pyridyl) -methyl] -ester is obtained to give the title compound.

need = + 55 ° (c = 0.2, chloroform).

Example 58 1- (R, S) -Cyano (3-phenoxy-4-fluorophenyl) methyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo] Preparation of 3-tertiary-butoxy) -propenyl] -cyclopropanecarboxylate.

The step:

1 R, S) -cyano- (3-phenoxy-4-fluorophenyl) methyl] - (1 R, cis) -2,2-methyl-3 - [(Z) -3-oxo-3 - [(Z) Preparation of -3-oxo-tert-butoxy-2-propenyl] -cyclopropanecarboxylate. 30 g of (R, cis)) 2,2-dimethyl-3 - [(Z) -3-oxo-3- (tert-butoxy) -1-propenyl] cyclopropanecarboxylic acid in 100 ml of dichloromethane at -5 ° C 30 g of (R, S) -cyano- (4-fluoro-3-phenoxyphenyl) methanol, 300 ml of 4- (dimethylamino) pyridine and 50 ml of dichloromethane are added at one time and then at 0 ° C. To this solution is added a solution of 25.5 g of dicyclohexylcarbodiimide and 50 ml of dichloromethane, followed by stirring at the same temperature for 30 minutes and then at 20 ° C for 3 hours. The insoluble precipitate is filtered off and the filtrate is evaporated to dryness. the residue is chromatographed on silica gel. Elution with 8: 2 n-hexane: ethyl acetate gave 53.9 g of the title product.

Step B t (S) -Cyano (3-phenoxy-4-fluorophenyl) methyl] - (1R, cis) 2,2-dimethyl-3 - [(Z) -3-oxo-3- ( Preparation of tert-butoxy) -1-propenyl] cyclopropanecarboxylate.

(a) Isolation of product by crystallization:

In 215 ml of diisopropyl ether, 53.9 g of the (R, S) alcohol prepared in the previous step is dissolved, quenched with an ester crystal from some of the (S) alcohol, stirred for 16 hours at 20 ° C and the precipitate formed is filtered off. 21.4 g of (S)-alcohol ester are thus obtained. 114 ° C.

(b) Isolation of the product by racemization and reduction of solubility:

The mother liquors were evaporated to dryness in vacuo, to the residue was added isopropanol (74 ml), water (5 ml), triethylamine (4.5 ml) and some ester crystals from (S) -alcohol. The mixture was stirred at ambient temperature for 20 hours. the mother liquor is evaporated to dryness, and isopropanol, water and triethylamine are repeatedly added to the residue.

-1 631

Step 194,799 is repeated to give 25 g of the crude (S) alcohol ester which is recrystallized from n-hexane to give 20.7 g of the (S) alcohol ester. 114 ° C.

A total of 21.4 g + 20.7 g (42.1 g) of the desired product is obtained, m.p.

Step C:

(S) -cyano (3-phenoxy-4-fluorophenyl) methyl] - (1R, cis) 2,2-dimethyl-3 - [(Z) -3-oxo-3-hydroxy-1-propenyl] - Preparation of cyclopropanecarboxylate.

16.4 g of [(S) ^-U, cyano- (3-phenoxy-4-fluorophenyl) methyl] (1R, cis) -2,2-dimethyl-3 - [(Z) -3- [ To a solution of (Z) -3-oxo-3- (tert-butoxy) -1-propenyl} -cyclopropanecarboxylate and 160 ml of toluene was added 1.6 g of p-toluenesulfonic acid monohydrate, the mixture was refluxed and heated to reflux. until the evolution of gaseous isobutylene is complete (this takes about 30 minutes). At this time, the mixture was cooled to 0 ° C, the insoluble material was filtered off, the filtrate was evaporated to dryness in vacuo and the residue was chromatographed on silica gel. Elution with n-hexane: ethyl acetate: acetic acid (70: 30: 1) gave the title product of Step C (13.3 g). M.p .: 99 ° C, [alpha] + 52.5 '± 2.5 (c = 0.5, chloroform).

Step D:

Preparation of [(S) -cyano (3-phenoxy-4-fluorophenyl) methyl] - (1R, cis) 2,2-dimethyl-3 - [(Z) -3-oxo-3-chloro-1-propenyl] cyclopropanecarboxylate .

4.5 g of ((S) -cyano-3-phenoxy-4-fluorophenyl) methyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- of hydroxy-1-propenyl] -cyclopropanecarboxylate and 20 ml of dichloromethane are added 10 ml of thionyl chloride at 20 ° C, stirred for 45 minutes and then evaporated to dryness in vacuo. Yield: 4.7 g (Step D).

Step E:

1 (S) -Cyano (3-phenoxy-4-fluorophenyl) methyl] - (1R, cis) 2,2-dimethyl-3 - [(Z) -3-oxo-3- (2,2,2) Preparation of -trifluoroethoxy) -propenyl] cyclopropanecarboxylate.

2.14 g of [(S) -cyano- (3-phenoxy-4-fluorophenyl) methyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxychloro] To a mixture of 1-propenyl] -cyclopropanecarboxylate and 8 ml of dichloromethane was added 2 ml of 2,2,2-trifluoroethanol at 20 ° C, the mixture was stirred for 90 minutes, then poured into aqueous sodium dihydrogen phosphate solution, the organic phase separated by decantation, washed with water, dried, evaporated to dryness in vacuo and chromatographed on silica gel. Elution with 9: 1 cyclohexane / ethyl acetate gave 2.33 g of the title product. M.p. 56 ° C, U _D = + 42 '± 1 (c = 1, chloroform).

The starting material [(S) -cyano- (4-fluoro-3-phenoxyphenyl) pmethanol] can be prepared as follows:

The step:

(1R, 2R, 5S) -6,6-Dimethyl-3-oxa-2 - [(R) -α-cyano (3-phenoxy-4-fluorophenyl) methoxy] bicyclo [3.1.0] -hexane (Compound A) and (1R, 2R, 5S) -6,6-dimethyl-3-oxa-2 - [(S) -cyano (3-phenoxy-4-fluorophenyl) - methoxy] -bicyclo [3.1.θΡ] hexane (Compound "B").

g of 4-fluoro-3-phenoxy (R, S) -cyanobenzyl alcohol,

100 ml of dichloromethane, 9.4 g of (1R, 2S, 5S) -6,6-dimethyl-3-oxa-bicyclo [3.1.0] hexan-2-ol and 0.1 g of p-toluenesulfonic acid are refluxed After boiling for 90 minutes, the reaction mixture is poured into dilute aqueous sodium bicarbonate solution, the organic phase is separated off and concentrated to dryness in vacuo. Yield: 25.06 g of (1R, 2R, 5S) 6,6-dimethyl-3-oxa-2 - [(R, S) -cyano (3-phenoxy-4-fluorophenyl) methoxy] - bicyclo [3.1. newhexane t.

The product thus obtained is chromatographed on silica gel. Elution with 8: 2 hexane: ether afforded (1R, 2R, 5S) -6,6-dimethyl-3-oxa-2 - [(R) -cyano- (3-phenoxy-4-fluoro) (8.85 g). -phenyl) -methoxy] -bicyclo [3.1.0] hexane, m.p.

This compound has the following characteristics:

Circular dichroism (in dioxane): max. At 279 nm, Αε = -0.27.

1 H-NMR (CDCl ₃ , ≤ 5 ppm): 1.07 (H; geminal methyl groups); 1.33-1.78 (H, cyclopropyl); 3.7-4.1 (H; -CH ₂ O); 5.2-5.5 (H; O-CH-); 6.9-7.6 (H; aromatic core).

Chromatography gave (R, 2R, 5S) -6,6-dimethyl-3-oxa-2 - [(S) -cyano- (3-phenoxy-4-fluorophenyl) methoxy] (9.05 g). - bicyclo [3.1.0] hexane,

M.p. 65 'C, [α] D = + 50' (C = 0.4, benzene).

The latter product has the following characteristics: Circular dichroism (in dioxane):

Inflexion at 275 nm, Αε = + 0.13; max. At 281 nm, Αε = + 0.15.

1 H-NMR (CDCl 3, δ ppm): 1.0 (H; geminal methyl groups); 1.55-1.57 (H; cyclopropyl); 3.8 to 3.9 and

4.1-4.3 (H, -CH ₂ 0-); 4.9-5.3 (H; O-CH <); 6.9-7.6 (H; aromatic core).

Step B:

4-fluoro-3-phenoxy- (S) ^-O, cyano-benzyl alcohol Preparation. 9 g of (1R, 2R, 5S) -6,6-dimethyl-3-oxa-2 - [(S) -cyano- (3-phenoxy-4-fluorophenyl) methoxybicyclo] 3.1.0] hexane A mixture of methanol (100 mL) and p-toluenesulfonic acid (90 mg) was stirred at 20 ° C for 90 minutes. Elution with hexane / ethyl acetate (7: 3, 1% acetic acid) gave 4.9 g of the title product of Step B, [α] D = -30 ° (c = 0.5, pyridine).

Example 59 [(3- (2-Propin-1-yl) -2,5-dioxoimidazolidinyl) methyl] (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo Preparation of 3- (hexafluoroisopropoxy) -1-propenyl] cyclopropanecarboxylate.

The step:

[3- (2-propin-1-yl) -2,5-dioxoimidazolidinyl) methyl] (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3-hydroxy] Preparation of -1-propenylcyclopropanecarboxylate.

3.7 g [1- (3- (2-propin-1-yl) -2,5-dioxoimidazolidinyl) methyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) - To a solution of 3-oxo-3- (tert-butoxy) -1-propenyl] cyclopropanecarboxylate (described in European Patent Application 0 041021) and 35 ml of toluene was added 300 mg of p-toluenesulfonic acid monohydrate, followed by the reaction mixture with isobutylene. until the evolution of gas is complete (about 25 minutes), it is refluxed, then cooled, the insoluble matter is removed by filtration, the filtrate is evaporated to the dry state in a vacuum and the residue is chromatographed on silica gel. Elution with 60:40: 1 n-hexane: ethyl acetate: acetic acid gave the title product of Step A (3.1 g, 1 _D = + 16 '(c = 0.25, chloroform).

-1 733

194,799

Step B:

O- (2-propin-1-yl) -2,5-dioxoimidazolidinyl] methyl- (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (hexafluoro) -isopropoxy) -1-propenyl] cyclopropanecarboxylate.

1.39 g of [3- (2-propin-1-yl) -2,5-dioxoimidazolidinyl] methyl (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- of hydroxy-1-propenyl] cyclopropanecarboxylate and 10 ml of dichloromethane at 5 ° C in a solution of 1.2 ml of hexafluoroisopropanol, followed by a solution of 1.0 g of dicyclohexylcarbodiimide and 30 mg of 4-dimethylamino-pyridine in 5 ml of dichloromethane After stirring for 10 minutes at 5 ° C and then at 20 ° C for 3 hours, the insoluble precipitate is filtered off, the filtrate is evaporated to the dry state in a vacuum and the residue is chromatographed on silica gel. Elution with n-hexane: ethyl acetate (7: 3) gave the title product of Step B (1.6 g), m.p.

Md = + 16 + 2 '(c = 0.5, benzene).

Example 60 13- (2-Propyn-1-yl) -2,5-dioxoimidazolidinylmethyl] (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- Preparation of (hexafluoroisopropoxy) -1-propenyl] cyclopropanecarboxylate.

The step:

13- (2-propin-1-yl) -2,5-dioxoimidazolidinyl] methyl (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3-hydroxy-1 Preparation of -propenityl-cyclopropanecarboxylate.

700 mg [3- (2-propin-1-yl) -2,5-dioxoimidazolidinylmethyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3 -methoxy-1-propenylcyclopropanecarboxylate (described in European Patent Publication No. 0041021), 400 ml of p-toluenesulfonic acid monohydrate are added four times every 2 hours to a mixture of 3.5 ml of dioxane and 1 ml of water, and the reaction mixture is refluxed for 7 hours. After stirring for 16 hours at 20 ° C, the solvent was distilled off in vacuo, dichloromethane was added to the residue, the organic phase was washed with water, dried and evaporated to dryness in vacuo. The residue was chromatographed on silica gel. Eluting with 200mg of [3- (2-propin-1-yl) -2,5-dioxoimidazolidinylmethyl] -1R, cis) using n-hexane: ethyl acetate: acetic acid (60: 40: 1). dimethyl 3 - [(Z) -3-oxo-3-hydroxy-1-propenyl] -cyclopropanecarboxylate is obtained which is identical to the product obtained in Example 2 (A).

The following procedure was carried out as in Example 59, Step B, but using hexane: diisopropyl ether (8: 2) as eluent. Rf = 0.15. Thus, [3- (2-propin-1-yl) -2-5-dioxoimidazolidinylmethyl) - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (hexafluoro-) isopropoxy-1-propenyl] cyclopropanecarboxylate is obtained.

Examples of preparations

The example

Preparation of soluble concentrate

We have compiled an example of komB listed below

Preparation of Emulsifiable Concentrate The following ingredients were thoroughly mixed:

homogeneous mixtures containing ponens:

Example 1 0.25 g Piperonyl butoxide 1g Tween 80 * 0.25 g Topanol A ** 0.1 g Water 98.4 g

** 1: 20 molar copolymer of sorbitol anhydride and sorbitol oleate, ethylene oxide.

** 2,4-dimethyl-6-tert-butyl-phenol.

The product of Example 1 was 0.015 g

Piperonyl butoxide 0.5 g

Topanol A 0.1 g

Tween 80 3.5 g

Xylene 95.885 g

Example C

Preparation of Emulsifiable Concentrate A homogeneous mixture containing the following components was prepared:

The product of Example 1 was 1.5 g

Tween 80 20 g

Topanol A 0.1 g

Xylene 78.4 g

Example D

Preparation of incense composition

A homogeneous mixture was prepared from the following components:

The product of Example 1 was 0.25 g

Taboo-por 25 g

Cedar needle powder 40 g

Pine wood powder 33.75 g

Brilliant green 0.5 g p-Nitrophenol 0.5 g

This is an example

Preparation of soluble concentrate

A homogeneous mixture is prepared from the following components:

The product of Example 9 (Isomer A) was 0.25 g

Piperonyl butoxide 1 g

Tween 80 0.25 g

Topanol A 0.1 g

Water 98.4 g

Example F

Preparation of an emulsifiable concentrate

An internal mixture was prepared from the following components: The product of Example 9 ("B" isomer) was 0.015 g.

Piperonyl butoxide 0.5 g

Topanol A 0.1 g

Xylene 95.885 g

Tween 80 3.5 g

Example G

Preparation of Emulsifiable Concentrate A homogeneous mixture is prepared from the following components:

All. Example 1 1.5 g

Tween 80 20 g

Topanol A 0.1 g

Xylene 78.4 g

Example H

Preparation of a smoke flavoring composition

A homogeneous mixture is prepared from the following components:

The product of Example 8 was 0.25 g

Tabupor 25 g

Cedar needle powder 40 g

Pine Powder 33.75 g

Brilliant green 0.5 g p-Nitrophenol 0.5 g

Example 1

Preparation of soluble concentrate

The following components are mixed together:

Example 1 10 g

-1 835

194,799

Piperonyl butoxide 1 g

Tween 80 2.5 g

Topanol A 0.5 g

Water 86 g

Examination of the activity of the compounds of the present invention against parasites

I. Investigation of lethal effects on domestic flies

Female insects, 4-5 days old, were used as test insects. 1 microliters of acetone solution of test compounds was applied to the dorsal thorax of insects using an Amold micromanipulator. 50-50 insects were used per dose and treatment. Mortality is monitored 24 hours after treatment.

The results obtained were expressed as LD 50 values, i.e. the dose, expressed in nanograms, required to kill 50% of the insects. These results are summarized in the table below.

Example product LD 50 [ng / specimen] First 1,115 Third 9.592 12th 3.656 * 13th 12.850 * 14th 11.314 * 16th 5.116 * 18th 10.051 * 19th 11.828 * 20th 9.647 * 21st 2.267 22nd 10.977 23rd 0.962 24th 37.372 25th 0.736 26th 72.026 27th 7.570 29th 0.824 30th 1,792

Conclusion: The products of Examples 1, 23 and 29 have remarkable effects.

* The active ingredients were used in the form of their formulation according to Formulation Example B.

2. Investigation of lethal effect on Spodoptera littoralis larvae

In the assays, an acetone solution of the test compounds was applied to the larval thorax using an Amold manipulator. Individual doses of the test compounds were tested on 15-15 larvae. The larvae in the fourth larvae pool were used in the study, i.e., they were approximately 10 days old (culture conditions: 24 C and 65% relative humidity). After treatment, the subjects were placed on medium (Poitout's medium).

Mortality was assessed 48 hours after treatment. The results are summarized in the table below.

Example LD 50 product [ng / specimen]

1. 4,699

35. 0.544

3. Investigation of Knock-down Effects on Domestic Flocks 4-5 day old female domestic flocks were used for the experiment. Direct spraying in a Keams and Marc chamber was used. A mixture of equal volumes of acetone and isopar L (2x0.2 cm ³ ) was used as solvent. Approximately 50 individuals were tested per dose. The effect was determined every minute for the first 10 minutes after treatment and thereafter by methods.

The results are summarized in the following table:

Example product KT 50 RPM] Concentration Ig / L] First 3.534 1 Second 3.608 0.25 Third 11.203 1 4th 9.472 1 5th 9.895 1 6th 10.082 1 12th 7.549 1 13th 3.646 1 14th 5.101 1 15th 1,564 0.25 16th 4.563 1 17th 0.831 0.25 18th 2.682 0.25 19th 3.837 1 20th 3.775 1 21st 10.940 1 ' 23rd 11.159 1 24th 2.723 1 25th 5.832 1 26th 1,550 0.25 27th 13.178 1 28th 1,961 0.25 29th 4.247 1 30th 3.498 1

4. Effect of Insect Exposure of Example 1 on German Cockroaches Male / German cockroaches (Blatella germanica) were used as experimental insects. A fixed concentration of acetone solution of the compound was poured into the bottom of a 20 cm diameter petri dish. After drying, 20-20 male cockroaches were placed in the cups for 1-1 hour, according to each concentration, then the insect was transferred to a healthy environment. Mortality was assessed at 24 hours, 48 hours, 3 days and 5 days.

The 50% lethal concentration (LD 50) of the test compound was found to be 0.250 mg / m ² . Conclusion: The test compound shows very good efficacy.

f. Product Effects Test for Examples 1 and 23 Two-cotyledon bean seedlings were used on Tetranychus urticae (adult insects). The seedlings were treated with an acetone solution of the compound of Example 1 using a Fiscber gun. After drying, 25-25 female Tetranychus urticae mites were placed on each leaf, i.e. 50-50 individuals per plant and dose tested. The effect was tested after 1, 24, 48 and 72 hours of contact time.

IC _S0 = 2.834 mg / hl.

The compound prepared according to Example 23 is IR, cis Z (product A), IR, cis E (product B), IR, trans Z (product C) and IR, trans E) ("D"). 'Product).

-1 937

The lethal dose was measured as described above. The following results were obtained.

LD _S0 [ng / insect] Product A Product 0.91 Product B> 100 Product C> 100 Product D> 100

The results confirm that the biological activity of the IR, cis-Z product is significantly higher than that of the other products.

Claims (10)

Claims A process for the preparation of (1R, cis) -2,2-dimethyl-3 - [(Z) -3-phenoxy] yl of formula (Γ). for the preparation of substituted alkoxy-3-oxo-1-propenyl] cyclopropanecarboxylic acid ester derivatives of the formula (Γ). - A 'is a group of formula (2) - in which R ₂ is methyl and R ₃ is C 2 -C 5 alkenyl; wherein R ₄ is cyano, methyl, or ethynyl; or hydrogen; wherein S 1 is a benzene ring or a dihydro or tetrahydro derivative; A group of the formula (7), a benzyl group of the formula (12) wherein R ₄ is a cyano group, R ₅ is halogen, group 13; R _{16 is} hydrogen or cyano; - R is phenyl or C 1-5 alkyl singly or twice substituted by cyano, phenyl, C 1 -C 4 alkoxy or di- (C 1 -C 4 alkyl) amino, singly or twice or mono- or di-substituted by halogen, characterized in that a) (R, cis) -2,2-Dimethyl - ((Z) -3-oxo-3-phenoxy / yl) -substituted alkoxy-1-propenyl] -cyclopropanecarboxylic acid of formula (II) - wherein R or a functional derivative of this acid, preferably a halide thereof, is reacted with an alcohol of formula (III) - wherein A 'is as defined above - or b) A (R, cis) -2,2-dimethyl-3t (Z) -3-oxo-3-hydroxy-1-propenyl] -cyclopropanecarboxylic acid ester derivative of formula XI: wherein A 'is within the scope of the present invention esterified with an alcohol of the formula R-OH wherein R is as defined above except for the phenyl group, or c) for the preparation of compounds of formula (Γ) having from 1 to 2 carbon atoms substituted with one or two hydroxy groups as R, A 'as defined herein, wherein r is substituted with one or two protected hydroxy groups C 1 -C 5 alkyl, treated with an acid hydrolyzing agent, or d) (1R, cis) -2,2-dimethyl-3- [320-oxo-3-phenoxy] - (VI). a substituted alkoxy-1-propynyl] -cyclopropanecarboxylic acid alkyl ester of formula (VI) wherein R is as defined above and alk is a C 1-6 alkyl group; with an acidic hydrolyzing agent to give (1R, cis) -2,2-dimethyl-3-β-oxo-3-phenoxy / III of formula IX. substituted alkoxy-1-propynyl] -cyclopropanecarboxylic acid - in the formula (IX) - R is as defined above - in the formula (III) - in the formula (A) is the object of the invention - 2,2-Dimethyl-3- [3-oxo-3-phenoxy / (X) - (R, cis). substituted alkoxy-1-propynyl] -cyclopropanecarboxylic acid ester - wherein R and A'in formula (X) are as defined above - are treated with a weak hydrogenating agent, or - first treated with a weak hydrogenation sieve to give the (R, cis) -2,2-dimethyl-34 (Z) -3-oxo-3-phenoxy / III compound (II) thus obtained. substituted alkoxy / propenylcyclopropanecarboxylic acid, wherein R is as defined above in formula (II), optionally in its functional derivative, preferably in the form of its halide, by reaction with an alcohol of formula (III) wherein A 'is as defined above. 2. A process according to claim 1 for the preparation of a compound of formula (I) which is a narrower group of compounds of formula (-). A is a benzyl group, or a group of formula (2) wherein R ₂ and R ₃ are as defined in claim 1 or a group of formula (4) wherein R ₄ is as defined in claim 1, preferably 3-phenoxy benzyl, u-ethynyl-3-phenoxybenzyl, or a group of formula (6) wherein S / I is as defined in claim 1, or a group of formula (7) or a group of formula (13), wherein R ₁₆ is cyano, and R is as defined in claim 1, wherein the starting material is a compound of formula (III) or (XI), wherein A is as defined above. 3. A process according to any one of claims 1 to 4, wherein the starting material is a compound of formula (III) or (XI) wherein A'is a (R) -form cyano-3-phenoxy benzyl or 2-methyl-4-oxo-3- (2-propenyl) -2-cycloprenten-1-yl in the (R) form. 4. Processes a), b) or d) according to any one of claims 1 to 3, characterized in that the starting material is a compound of the formula (II) or (VI) or R-OH wherein R is one or more of the compounds according to claim 1. C 1-5 alkyl substituted by a functional group. The process of claim 4, wherein -2 039 194,799, wherein the starting material is a compound of formula (II) or (VI) or · R-OH wherein R is a C 1 -C 5 alkyl group substituted with one to six halogens. 6. A process according to claim 5 wherein the starting material is a compound of formula (II) or (VI) or R-OH wherein R is C 1-5 alkyl substituted with one to six fluorine atoms. 7. A process according to claim 6 wherein the starting material is a compound of formula (II) or (VI) or R-OH wherein R is -CH2-CF3. 8. The process of claim 1, a) 15c) -6-cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - ((Z) -3- (2,2,2-trifluoro) -ethoxy) -3-oxo-1-propenyl] cyclopropanecarboxylate, t (S) -u-cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 [(Z) -3-oxo] 3- (2- / 1,1,1,3,3,3-Hexafluoro- / propoxy) -20 l-propenyl] -cyclopropanecarboxylate, [(R) -α-ethynyl-3-phenoxybenzyl] - (1R , cis) -2,2-dimethyl-3 - ((Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl) -cyclopropanecarboxylate, 1 (RS) - cyano -6-phenoxy-2-pyridylmethyl] - (1R cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1 -propeniljciklopropánkarboxilát, I (S) -? - cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - ((Z) -3-oxo (2-fluoroethoxy) -1-propenyl) cyclopropanecarboxylate, 30b-Propargyl-2,5-dioxoimidazolidinyl) methylR1R, cis) 2,2-dimethyl-3 - ((Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl) -cyclopropanecarboxylate or (1S) -methyl-4-oxo-3- (2-propenyl) -2-cyclopenten-1-yl] (1R, cis) -2,2-dimethyl-3 - [(Z) -3- oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl] cyclopropanecarboxylate, characterized in that (R, cis) -2,2-dimethyl-3 - [(Z) - 3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl] cyclopropanecarboxylic acid and (S) -a-hydroxy- (3-phenoxyphenyl) acetonitrile; 40 (1R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2- (1,1,1,3,3,3-hexafluoro-propoxy) -1- propenyl] cyclopropanecarboxylic acid and (S) -α-cyano-3-phenoxybenzyl alcohol; (R, cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl] cyclopropanecarboxylic acid and (R) - 45 ethynyl-3-phenoxybenzyl alcohol; t (S) -? - cyano-3-phenoxybenzyl] - (1R, cis) -2,2-dimethyl-3 - [(Z) -3-hydroxy-3-oxo-1-propenyl] cyclopropanecarboxylate and ( RS) -a-cyano-6-phenoxy-2-pyridyl-methanol; (1R-cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2-fluoroethoxy) -1-propenyl] -cyclopropanecarboxylic acid and (S) -α-cyano-3-phenoxybenzyl alcohol; (1 R cis) -2,2-Dimethyl-3 - [(Z) -3-oxo-3- (2,2,2-trifluoroethoxy) -1-propenyl] cyclopropanecarboxylic acid and 3-propargyl-2,5 methanol-dioxo-imidazolidinyl; and (1R cis) -2,2-dimethyl-3 - [(Z) -3-oxo-3- (2,2,2-trifluoroethoxy) 1-propenyl] cyclopropanecarboxylic acid and (1S) -2-methyl -hydroxy-4-oxo-3- (2-propenyl) cyclopent-2-ene. 9. Insecticidal and acaricidal compositions, characterized in that the active ingredient is (R, cis) -2,2-dimethyl-3 - [(Z) -3-phenoxy] or (I) as an active ingredient. substituted alkoxy-3-oxo-1-propenyl] cyclopropanecarboxylic acid ester derivative - A 'is a group of formula (2) wherein R ₂ is methyl, R ₃ is C 2 -C 5 alkenyl; A group of Formula ₄ wherein R ₄ is cyano, methyl or ethynyl; A group of Formula (6) wherein S / I represents a tetrahydro derivative of a benzene ring; A group of formula (7) or a group of formula (13) wherein R ₁₆ is cyano; R represents a phenyl group, a benzyl group or a C 1-5 haloalkyl group containing from 1 to 6 halogens, containing from 0.0005 to 10% by weight of a carrier, preferably an aromatic solvent and optionally a surfactant, preferably sorbitan anhydride and sorbitol oleate , a 1:20 molar copolymer of ethylene oxide and / or optionally an adjuvant, preferably piperonyl butoxide. The insecticidal composition according to claim 9, characterized in that it contains as an active ingredient any of the compounds of the process according to claim 8 in an amount of 0.0005 to 10% by weight with a carrier, preferably an aromatic solvent and optionally a surfactant, preferably sorbitan anhydride. sorbitol oleate, mixed with a 1:20 molar copolymer of ethylene oxide and / or optionally an adjuvant, preferably piperonyl butoxide. * A group of formula (13) wherein R ₁₆ is cyano.