FI78679B - NYA CYKLOPROPANKARBOXYLSYRADERIVAT, DERAS FRAMSTAELLNINGSFOERFARANDE OCH PREPARAT INNEHAOLLANDE DESSA DERIVAT FOER BEKAEMPNING AV PARASITER. - Google Patents

Abstract

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

Description

1 73679

The invention relates to novel cyclopropanecarboxylic acid esters, to a process for their preparation and to preparations containing them for controlling parasites.

The invention relates to compounds of formula I

10

X H

H3CX ^ CH3 / I

RO-C s' ^ C-OB

1 '3 0 6 15 wherein R is a straight-chain, branched or cyclic saturated alkyl group having 1 to 8 carbon atoms, which may be substituted by one or more halogen atoms or a lower alkoxy group, 20 B is a group CH- | J ^^ ch2-ch = ch2 or a group

O

30 -Λ

-CH-N N-CH 2 -C = CH

V

o or group

F F

s "-.- H- -

F F

ί 2 * 7 ^ ^ ^ λ) Ιο 0/9 or group R1 „| 14 <ry '" ~ or group CN -.

And X is a halogen atom, and in Compound I, the ethylene double bond has the E-configuration and in which the cyclopropanoic acid backbone has a 1R cis structure.

When B is an alkyl group, it is a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tertiary butyl group.

When R is a saturated, linear or branched alkyl group, it is methyl, ethyl, n-propyl, isopropyl, n-butyl, secondary butyl, isobutyl, n-pentyl, n-hexyl, tertiary butyl, tertiary pentyl or neopentyl.

When R is a cyclic group, it is a cyclopropyl, ·: cyclobutyl or cyclohexyl group, a linear or branched alkyl group having a cyclic group or a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group substituted by one or more alkyl groups; having a bond to the COO group located at one of its ring tips, e.g., 1-methyl-cyclobutyl, 1-methyl-cyclopentyl, 1-methyl-cyclohexyl, or 2,2,3,3-tetramethyl-cyclopropyl.

Among the best compounds of formula I, mention may be made in particular of (S) O1-cyano-3-phenoxy-benzyl- (1R, cis) -2,2-dimethyl-3 (E) fluoro-2- (ethoxycarbonyl) ethenyl ) cyclopropane-l-carboxylate.

3 78679

Among the best compounds of the invention, mention may also be made of compounds of the formula I in which B is a group

Mention may also be made, as the preferred compounds of the invention, of compounds in which B is a group β- (propyn-2-yl) -2,5-dioxoimidazolidinyl-4-methyl or a Q, -cyano-6-phenoxy-2-methylpyridyl group.

The invention relates in particular to the compounds whose preparation is described below in the experimental part of the description, and in particular to the compounds of Examples 1, 11 and 21 among them,

The compounds of formula I have interesting properties which allow them to be used for controlling parasites. This is the case, for example, with plant parasites and housing cancers.

Thus, the compounds of the invention can be used to control insect and plant nematodes and mites.

The invention relates to the application of the compounds of the formula I for controlling plant cancers and house cancers.

The compounds of the formula I can be used in particular for controlling insects in the field of agriculture, for example for controlling leaf lice, butterflies and beetle larvae. They are applied in doses of 10 to 300 g of active ingredient per hectare.

The compounds of the formula I can also be used for controlling insects, in particular flies, mosquitoes and cockroaches, which are found in dwellings.

The compounds of Examples 1, 11 and 21 are preferred products, as shown in the experimental results below. They have excellent killing power and very good stunning power.

4,73679

The compounds of formula I are the most light resistant and are not toxic to mammals. The combination of these properties makes the compounds of formula I products perfectly suited to the requirements of the modern agrochemical industry 5; they can protect the crop while keeping the environment unchanged.

The compounds of the formula I can also be used for controlling plant mites and nematodes.

The invention therefore also relates to preparations for the control of plant and dwelling carcinogens which contain at least one compound of the formula I as defined above.

In particular, the invention comprises insecticidal preparations in which the active ingredient is at least one of the compounds defined above. Among the best insecticide preparations according to the invention, mention may be made in particular of preparations containing a compound of Example 1, a compound of Example 11 or a compound of Example 21.

The preparations are made by the usual methods used by the agrochemical industry.

Active substances in preparations intended for agricultural or residential use may also be added to other pesticides. These preparations may be in the form of powders, granules, suspensions, emulsions, solutions, solutions for aerosols, burnable tapes, attractants, or other classical preparations made for the use of such compounds.

In addition to the active ingredient, these preparations generally contain a carrier and / or a nonionic surfactant which provides a uniform suspension in the composition of the ingredients. The carrier used may be a liquid such as water, alcohol, hydrocarbons or other organic solvents, mineral, vegetable or animal oil, a powder such as talc, clay, silicates, kieselguhr or a solid fuel.

5 73679 t

The insecticidal preparations according to the invention preferably contain 0.005 to 10% by weight of active ingredient.

The preferred use in dwellings for the preparations according to the invention is smoke-forming preparations. Thus, the preparations according to the invention may preferably be in the form of a combustible insecticide coil or a combustible fibrous substance for the non-active substance. In the latter case, the smoky substance, after the addition of the active substance, is placed on top of a heated device, such as an electric mosquito repellent.

When an insecticide coil is used, the inert carrier may be, for example, sawdust, Tabu flour (flour made from the leaves of Machilus Thumbergii), flour made from sawdust stems, flour made from cedar leaves, flour made from wood (e.g. pine sawdust), starch flour or starch made flour. The content of the active substance can be, for example, 0.03 to 1% by weight.

When a combustible fiber carrier is used, the content of the active substance 20 may be, for example, 0.03 to 95% by weight.

The preparations according to the invention for use in dwellings can also be made by preparing an oil based on the active ingredient; this oil is absorbed into the heart of the lamp and then burned in it. The content of active substance mixed with the oil is preferably 0.03 to 95% by weight.

The insecticidal compositions of the invention, such as mite and nematode pesticides, may also be added to one or more other pesticides. Pesticides for mites 30 and shuttle mats may be in particular in the form of powders, granules, suspensions, emulsions or solutions.

Foam powders are most preferably used to control mites for spraying leaves, which powders contain 1 to 80% of active ingredient, or a spray liquid containing 1 to 500 g / l of active ingredient. Powders containing 0.05 to 3% of active ingredient can also be used for powder spraying of leaves.

6 73679

In the control of nematodes, liquids containing 300 to 500 g / l of active substance are preferably used for soil treatment.

The compounds according to the invention for the treatment of ticks and nematodes Tor-5 are preferably used in concentrations of 1 to 100 g of active ingredient per hectare.

To enhance the biological activity of the products of the invention, they may be added to classical synergists used in similar cases, such as 1- (2,5,8-trioxydodecyl) -2-propyl-4,5-methylenedioxybenzene (or piperonyl butoxide) or N - (2-etyylihept-

OF

yl) bicyclo [2.2.1] -5-heptene-2,3-carboximide or piperonyl-bis-2- (2''n-butoxyethoxy) ethylacetal (tropital).

The products of the invention can be used as biocides and growth regulators.

The invention also comprises combinations which are insecticides or mite or nematode pesticides and in which at least one compound of the formula I and on the other hand at least one of the pyrethrinoid esters belonging to the group: esters of alletrons, 3,4,5 , 6-Tetrahydrophthalimidomethyl esters, 5-benzyl-3-furylmethyl esters, 3-phenoxybenzyl esters and esters of chrysanthemic acids and $-cyano-3-phenoxybenzylalcohol, 5-benzyl-3-furylmethanol and 2,2-di- Esters of methyl 3- (2-oxo-3-tetrahydrophenylidenemethyl) -cyclopropane-1-carboxylic acids, 3-phenoxybenzyl alcohol and N, N-cyano-3-phenoxybenzyl alcohol and 2,2-dimethyl-3- (2.2 esters of cyclopropane-1-carboxylic acids, esters of CV-cyano-3-phenoxybenzyl alcohol and 2,2-dimethyl-3- (2,2-dibromovinyl) cyclopropane-1-carboxylic acids, 3-phenoxybenzyl alcohol and 2 -Esters of parachlorophenyl-2-isopropylacetic acid, esters of alletrolone , 3,4,5,6-Tetrahydrophthalimidomethyl-35-alcohol esters, 5-benzyl-3-furylmethyl-alcohol esters, 3-phenoxybenzyl alcohol and N-cyano-3-phenoxybenzyl alcohol and 2,2-dimethyl-3- ( Esters of 1,2,2,2-tetrahalo-ethyl) -cyclopropane-1-carboxylic acids in which 7 73679 "halo" means fluorine, chlorine or bromine towers and in which the compounds of the formula I can exist in all possible stereoisomeric forms as well as acids and alcohols. in the above pyretrinoid ester-5 combinations.

The combinations according to the invention make it possible, in particular because of the versatility of their action, either to control numerous cancers or, more broadly, in certain cases to act synergistically.

The invention also relates to a process of formula I.

for the preparation of these compounds, which process is characterized in that the acid of formula II

X H H C ° H

15 / - ^ C = O II

RO-C ----: x <f 11

O H

wherein X and R are as defined above and which is a mixture of E and Z isomers or an E or Z isomer, and wherein

the substituted cyclopropane ring in the 1R cis stereoisomeric form, or a functional derivative of this acid, is reacted with an alcohol of formula III

25 B-OH III

wherein B is as defined above or with a functional derivative of this alcohol to give a compound of formula I which, if desired, is reacted with a selective cleavage agent of the CC 4 R group to give a compound of formula IV

X H

\ _ / CH3C «3 O

3 5 / V ^ / \ ^ C = OB

H ° -9 IV

Il o β 78679 wherein B is as defined above, after which the acid of formula IV or a functional derivative thereof is reacted with an alcohol of formula R-OH wherein R is as defined above and that the compound 1R cis E is separated from the mixture 1R by cis (E + Z) chromatography.

Esterification of acid II with an alcohol of formula III can be performed in the presence of a tertiary base such as pyridine. This esterification can be readily performed in a mixture of pyridine, dicyclohexylcarbodiimide and 4-dimethylaminopyridine.

The esterification can also be carried out by reacting the chloride of acid II with an alcohol of formula III or a metal derivative of this alcohol, such as a silver salt.

The Wittig reaction, which is commonly used to prepare acids of formula II, yields acids with a double bond E + Z.

Isomers with respect to the double bond can be separated using physical methods such as chromatography, either at the level of acids or at the level of esters. Examples of these two methods are given in the experimental section below.

The cleavage of the CCl 4 moiety is preferably heat together with the hydrolysis acid. As the hydrolysis acid, p-toluenesulfonic acid can be used.

The esterification of a compound of formula IV is carried out according to classical esterification methods, in particular according to the methods described below.

The invention also relates to a manufacturing method which is

described above, and wherein the acid of formula II wherein R is an alkyl group of 1 to 5 carbon atoms is prepared by reacting a cis-aldehyde of formula 35 in the form of a lactone according to the Wittig reaction in the presence of a strong base.

hvv

9 '9 73679 or an aldehyde of formula VI to react H \ / °

1 Y I

5 0 = C'XV /// \\> ^ C ~ CH VI

With a phosphorane of formula VII,

X

(φ) ΞΡ = θ ("VII

C-0R19 15 0

wherein R 9 is an alkyl group having 1 to 5 carbon atoms and X is as defined above, or with a phosphonate of formula VIII

20 0

Ron ° * 0 20 \ Γ J | P = CH-X-C OR.q

/ Ay VIII

R20 ° 1 wherein R19 and X are as defined above and R2Q r is an alkyl group having 1 to 6 carbon atoms.

10 78679

Stereochemically defined acids of formula II can be prepared according to the following reaction scheme: 5 ° C-OH-O-tert.-Bu C1-C-OR

X \ \ / I

15 N- χ \ C-OH

/ "Y-Y

| \ r h h 20

In the reaction scheme, X is a fluorine, chromium or bromine atom and R is an alkyl group having 1 to 8 carbon atoms; and the compounds used have a well-defined etheric configuration.

Acids of formula II wherein X is a bromine atom may also be prepared by administering a compound of formula IX

RC02> W vX

30 n ^ ^ X ^ \ ^^, CO2alk IX

wherein the double bond geometry is E, R is as defined above and ale is an alkyl group, react with a brominating agent, for example pyridine bromide, and then with a substance which causes debromic hydration to give, 11 73679 - if the debromic hydrating agent is basic and acting under sufficiently mild conditions, a compound of formula X 5 oh3co2 10 or - if the debrom hydrating agent is basic and acting under sufficiently severe conditions, isomer E.

The experimental section provides an example of a preparation method using triethylamine to give the Z-isomers and Na 2 CO 3 to give the isomers.

The compounds of formula V are then reacted with a CO 2 alc cleavage agent to give an acid of formula II.

Examples of the preparation of acids of formula II are given in the experimental section.

The acids of the formulas II, in particular those whose stereochemistry is well defined, such as the acids of the formula IV obtained by the process according to the invention, are new products and as such are one of the objects of the invention.

The invention naturally deals in particular with the compounds of the formula II as essential intermediates for the preparation of the compounds of the formula I.

The following examples illustrate the invention, in which Examples 1, 3, 5, 9 to 14, 18 to 25, 28, 30, 32, 34, 37 and 39 to 43 illustrate the preparation of compounds of formula I.

i2 78679

Example 1 (S) (* - Cyano-3-phenoxybenzyl- (1R, cis) 2,2-dimethyl-3- (E) / 2-fluoro-2- (ethoxycarbonyl) ethenyl) cyclopropane-1- carboxylate 5 To a solution of 3.87 g of (1R, cis) 2,2-dimethyl-3 (Z + E) (2-fluoro-2-ethoxycarbonylethenyl) cyclopropane-1-carboxylic acid in 30 cm3 of methylene chloride - 3 rides, 1.5 cm of pyridine and 3.7 g of dicyclohexylcarbodiimide are added, the mixture is stirred for 10 minutes and a solution of 4.05 g of (S) -cyano-3-phenoxy-3-benzyl alcohol is added in 10 portions. Stir for 1.5 hours, add 25 mg of 4-dimethylaminopyridine, stir again for 1.5 hours, cool to 0 [deg.] C., remove the insoluble material formed by filtration, concentrate the filtrate to dryness by distillation under reduced pressure, chromatograph the residue. on silica gel using a mixture of cyclohexane and ethyl acetate (80/20) as eluent and crystallizing the residue from ethyl acetate. Separate the precipitate formed by drying in air. a, the mother liquors are chromatographed on silica gel using a mixture of cyclohexane and ethyl acetate (9/1) as eluent to give a total of 4.28 g of (S) Ct-cyano-3-phenoxybenzyl- (1R, cis) 2,2-dimethyl- 3 (E) 2-fluoro-2- (ethoxycarbonyl-25) ethenyl 4-cyclopropane-1-carboxylate and 2.8 g of the 3 (Z) derivative.

Analysis: C25H24FNO2 (437.47) C% H% N% F%

Calculated: 68.64 5.53 3.20 4.34 30 Found: 68.8 5.5 3.1 4.2 13 73679 IR spectrum (in chloroform) - absorption at 1738 cm-1 and 1722 cm-1, due to carbonyl and conjugated ester, - absorption at 1589 cm -1 to 1489 cm -1 due to 5 aromatic rings, - absorption at 1380 cm -1 due to methyl pair. NMR spectrum (in deuterochloroform) - peaks 1.2-1.27 ppm due to methyl pair hydrogen 10 - peaks 1, 23-1, 35-1, 47 ppm, 4.15-4.26 ppm and 4.38- 4.50 pp due to the hydrogens of the ethyl group of the ethoxycarbonyl group, - peaks 1.88-2.02 ppm due to the hydrogenation of cyclopropyl in position 1, 15 - peaks 2.8 to 3.13 ppm due to the hydrogenation of cyclopropyl in position 3, - peaks 6.05-6.21 and 6.38-6.55 ppm due to the hydrogenation of the ethylene double bond, - a peak of 6.36 ppm due to hydrogen on the same carbon as the group C = N, - peaks 6, 9-7.58 ppm due to aromatic ring hydrogens.

(1R, cis) 2,2-Dimethyl-3- (E, Z) -2-fluoro-2-ethoxycarbonylethenyl) cyclopropane-1-carboxylic acid is prepared as follows:

To a solution of 12.1 g of diethyl ethylphosphorofluoroacetate ethyl ester in 120 cm of dimethoxyethane is added at + 5 ° C, 2 g of 60% sodium hydride in oil, stirred for 30 minutes and at 0 ° C is added 5.7 g of g of 30 (1R, cis) 2,2-dimethyl- (3-dihydroxymethyl) cyclopropane-1-carboxylic acid lactone. After stirring for 2 hours 14,73079 for 30 minutes at 20 ° C, the reaction mixture is poured into a water-ice mixture of monosodium phosphate and ethyl ether extract. Wash the combined organic phases with water, dry, concentrate to dryness by distillation under reduced pressure, chromatograph the residue on silica gel using a mixture of cyclohexane, ethyl acetate and acetic acid (50/50/1) as eluent to give 3.87 g (1R, cis) of 2.2 -dimethyl-3 (E, Z) -2-fluoro-2-ethoxycarbonylethenyl} cyclopropane-1-10 carboxylic acid.

Example 2 (S) Q'-Cyano-3-phenoxybenzyl- (1R, cis) 2,2-dimethyl-3- (Z) / 2-fluoro-2-ethoxycarbonyl) ethenyl-4-cyclopropane-1- carboxylate 15 The chromatography of Example 1, which makes it possible to obtain a derivative of the 3 (E) structure, gives 2.8 g of a residue containing a derivative of the 3 (Z) structure. This residue is taken up in ethyl acetate and the insoluble matter formed is removed by filtration. The filtrate is concentrated to dryness by distillation under reduced pressure to give a residue which is chromatographed on silica gel using a mixture of cyclohexane and ethyl acetate (9/1) as eluent to give 1.0 g of (S) Ct-cyano-3-phenoxybenzyl- (1R, cis) -25 2 , 2-dimethyl-3- (Z) -2-fluoro-2- (ethoxycarbonyl) ethenylcyclopropane-1-carboxylate.

IR spectrum (in chloroform) - absorption at 1730 cm -1 due to carbonyl and conjugated ester, 30 - absorption at 1620 cm -1 due to ethylene double bond, - absorption at 1589 to 1489 cm -1 due to aromatic rings.

- absorption at 1380 cm due to the methyl pair.

is 78,679 NMR spectrum (in deuterochloroform) - peaks at 1.2-1, 32-1, 43 ppm and 4, 12-4, 23-4, 35-4, 47 ppm due to the ethyl group of the ethoxycarbonyl group, 5 - peaks 1.23-1.27 ppm due to hydrogen of the methyl pair, - peaks 6.2-6.36 ppm and 6.73-6.9 ppm due to hydrogen of the ethylene double bond, - peak 6.47 ppm due to hydrogen , which is on the same carbon as the -CN moiety, peaks 6.9-7.58 due to the hydrogen of the aromatic rings.

Example 3 (S) β-Cyano-3-phenoxybenzyl (1R, cis) 2,2-di-15-methyl-3 (E) -2-chloro-2- (methoxycarbonyl) ethenyl] cyclopropane-1-carboxylate J * '- —i -

To a solution of 3 g of (1R, cis) 2,2-dimethyl-3 (E) (2-chloro-2-methoxycarbonylethenyl) cyclopropane-1-carboxylic acid chloride in 15 cm3 of benzene is added 3 g of (S ) N-cyano-3-phenoxybenzyl alcohol at 50 ° C, 1.3 cm 3 of pyridine are added, stirred for 15 minutes at 5 ° C, then for 16 hours at 20 ° C, the reaction mixture is poured into a mixture of water and hydrochloric acid. , extracted into ethyl ether, washed with water, dried, concentrated to dryness by distillation under reduced pressure; Chromatograph the residue on silica gel using successively a mixture of cyclohexane and ethyl acetate (8/2) and then a mixture of cyclohexane and ethyl acetate (9/1). 2.1 g of (S) α-cyano-3-phenoxybenzyl (1R, cis) -2,2-dimethyl-3 (E) -2-chloro-2-methoxycarbonylethenyl} cyclopropane-1-carboxylate are obtained , (0t) D = 50.5 ° (C = 0.8%, benzene).

Analysis: C24H22ClNO5 439.9 C% H% Cl% N% 35 Calculated: 65.53 5, 04 8, 05 3, 18

Found: 65, 5 5, 2 8, 0 3, 0.

16 73679 IR spectrum (in chloroform) - absorption at 1738 cm-1 and 1719 cm-1 due to the carbonyl of the ester, - absorption at 1608 cm-1 due to the -C = C- bond 5 - absorption 1589 cm-1489 cm-1 in ^ due to aromatic rings, absorption in 1390 em due to methyl pair. IMR spectrum (in deuterochloroform) - peaks 1.24 to 1.25 ppm due to hydrogen of methyl pair 10, - peaks 1, 93 to 2.07 ppm due to hydrogenation of cyclopropyl at position 1, - peaks 2, 87 to 3.01 -3.04-3, 18 ppm due to cyclopropyl hydrogens at position 3, 15 - peak 3, 85 ppm due to methoxycarbonylmethyl, - peak 6.35 ppm due to hydrogen on the same carbon atom as the group -CSN peaks 6.91-7.5 ppm due to the hydrogen of the aromatic ring.

(1R, cis) -2,2-Dimethyl-3 (E) / 2-chloro-2- (methoxycarbonyl) ethenyl] cyclopropane-1-carboxylic acid chloride can be prepared as follows:

Step A; (1R, cis) 2,2-dimethyl-3 (E) / 2-chloro-2- (methoxy-25-carbonyl) ethenyl] cyclopropane-1-carboxylic acid.

Add 50 cm 2 of tetrahydrofuran at 20 ° C to 12.6 g of methoxycarbonylchloromethylenetriphenylphosphorane, 4.85 g of (1R, cis) 2,2-dimethyl-3-dihydroxymethyl) cyclopropane-1-carboxylic acid lactone 40 In a 30 cm solution of tetrahydrofuran and stirred for 2 hours at 20 ° C. Transfer the reaction mixture to a reflux condenser, keep for one hour and concentrate to dryness by distillation under reduced pressure. Ethyl ether is added to the residue. The insoluble matter formed (triphenyl-phosphine oxide) is removed by filtration, the filtrate i7 78679 is concentrated to dryness by distillation under reduced pressure and chromatographed on silica gel using a mixture of benzene and ethyl acetate (8/2) with 1% acetic acid as eluent. 2.2 g of (1R, cis) -5,2-dimethyl-3 (E) - (2-chloro-2-methoxycarbonylethyl) cyclopropane-1-carboxylic acid and 3 g of (1R, cis) -2 , 2-dimethyl-3 (Z) (2-chloro-2-methoxycarbonylethynyl) cyclopropane-1-carboxylic acid.

(1R, cis) 2,2-Dimethyl-3 (E) (2-chloro-2-methoxy-10-carbonylethynylcyclopropane-1-carboxylic acid has the following properties: IR spectrum (in chloroform) - absorption at 3500 cm -1 due to from the hydroxyl of the carboxyl, absorption at 1721 cm -1 / 1713 cm -1 and at 700 cm -1 due to carbonyl, absorption at 1490 cm -1 to 1410 cm -1 due to -C = C-, absorption at 1393 cm -1 to 1380 cm 2 due to hydrogen from 20 pairs of methyl.

NMR spectrum (in deuterochloroform) - peak 1.3-1.32 ppm due to methyl pair, - 1.87-2, 02 ppm due to hydrogenation of cyclopropyl at position 1, 25 - peaks 2, 82, 2, 97 ppm - 2.98, 3.13 ppm due to cyclopropyl hydrogen at position 3, - peak 3.82 ppm due to hydrogen of the methoxycarbonyl methyl group, - peaks 6.72 to 6.78 ppm due to cyclopropyl at position 3, side chain hydrogen of the ethylene double bond, - a peak of 11 ppm due to the hydrogenation of the carboxyl.

(1R, cis) 2,2-Dimethyl-3 (Z) (2-chloro-2-methoxycarbonylethenyl) cyclopropane-1-carboxylic acid 35 has the following properties: 18 73679 IR spectrum: (in chloroform) - absorption 3500 cm -1 in hydrogen due to the hydrogenation of the carboxyl (mono + dimer), - absorption in 1725 cm -1 due to the -C ester.

B

50 - absorption at 1700 cm -1 due to the carboxyl of hydrogen (monomer), - absorption at 1623 cm -1 due to -C = C-, - absorption at 1392 cm -1 to 1381 cm -1 due to 10 methyl pairs of hydrogens.

NMR spectrum (in deuterochloroform) - peak 1, 32-1, 35 ppm due to methyl pair hydrogens, - peaks 1.95 and 2.5 ppm due to cyclopropyl hydrogen at positions 1 and 3, - peak 3.83 ppm, due to the hydrogens of the methyl group of the methoxyl, - peak 1, 32-1, 35 ppm due to the hydrogen of the methyl pair, 20 - peaks 1.95 2.5 ppm due to the hydrogen of the cyclopropyl in positions 1 and 3, - peak 3.83 ppm due to the hydrogenation of the methyl group of the methoxyl, - peaks 7, 28 to 7.45 ppm due to the hydrogenation of the side chain double bond to the cyclopropyl in position 3, - peak 10.75 ppm due to the hydrogenation of the carboxyl. Step B; (1R, cis) 2β-Dimethyl-3 (E) [2-chloro-2-methoxycarbonyl) -ethenyl] -cyclopropane-1-carboxylic acid chloride.

2.9 g of (1R, cis) 2,2-dimethyl-3 (E) / 2-chloro-2- (methoxycarbonyl) ethenyl / cyclopropane-1-carboxy-3β-silicic acid, 20 cm of isoprene and 10 cm of thionyl chloride are mixed. -ridia. After stirring at 20 ° C for 3 hours, the isoprene and thionyl chloride are removed by distillation under reduced pressure to give 78 g of (1R, cis) 2,2-dimethyl-3 (E) -12-chloro-2- (methoxycarbonyl) ethenyl] cyclopropane. -1-carboxylic acid chloride.

Example 4 5 (S) Qt-Cyano-3-phenoxybenzyl- (1R, cis) 2,2-dimethyl-3 (Z) - [2-bromo-2- (propoxycarbonyl) ethenyl] cyclopropane-1- carboxylate To a solution of 2.9 g of (1R, cis) 2,2-dimethyl-3 (Z) - [2-bromo-2- (propoxycarbonyl) ethenyl] cyclo-3-propane-1-carboxylic acid 40 cm in methylene chloride, 0.9 cm of pyridine and 2.1 g of dicyclohexylcarbodiimide are added. Stir for 15 minutes, add 2.5 g of (N, N-cyano-S-phenoxybenzyl in 5 cm of methylene chloride, add 25 mg of 4-dimethylamino-15 pyridine, stir for 2 hours. Remove the formed insoluble material by filtration, concentrate dry by distillation under reduced pressure and chromatograph the residue on silica gel using a mixture of cyclohexane and ethyl acetate (9/1) as eluent, * to give 4.26 g of (S) C 1-4 cyano-3-phenoxybenzyl- (1R, cis) -2 , 2-dimethyl-3 (Z) -Q-bromo-2- (propoxycarbonyl) ethenyl-cyclopropane-1-carboxylate, mp = 64 ° C.

Analysis: C 26 H 26 BrN 2 O 5 512.41 C% H% N% Br% 25 Calculated: 60, 95 5, 11 2, 73 15, 6

Found: 61.1 5.3 2.7 15.5 IR spectrum (in chloroform) - absorption at 1743-1718 cm-1 due to carbonyl of the ester and conjugated ester, 30 - absorption at 1615 cm-1 due to - C = C- -1 - absorption at 1588-1488 cm due to aromatic rings, - absorption 1390-1380 cm -1 due to methyl pair NMR spectrum (in deuterochloroform) 35 - peaks 0.88 - 1.0- 1.12 ppm due to the hydrogen of the propyl methyl group, 20 78679 - peaks 1.27 to 1.32 ppm due to the hydrogen of the methyl pair, - peaks 4.08 to 4.2 to 4.32 ppm due to the propyl position 1, 5 - peak 6.4 ppm due to hydrogen in the same carbon as the group -C = N, - peaks 7, 57 to 7, 67 ppm due to hydrogenation of the ethylene double bond, - peaks 6, 9 to 7.58 ppm due to the hydrogen of the aromatic rings.

(1R, cis) -2,2-Dimethyl-3 (Z) - [2-bromo-2- (propoxycarbonyl) -ethenyl] -cyclopropane-1-carboxylic acid is prepared as follows:

Step A: t-Butyl (1R.cis) 2,2-dimethyl-3 (Z) -N-bromo-15 2- (propoxycarbonyl) ethenyl] cyclopropane-1-carboxylate.

To a solution of 28.3 g of (1R, cis) 2,2-dimethyl-3- (2,2-dibromovinyl) cyclopropane-1-carboxylic acid tertiary butyl ester in a mixture of 3 3 20 is 120 cm of tetrahydrofuran and 120 cm of ethyl ether, about 50 3 cm of a 1.6 N solution of butyllithium in hexane are added over a period of 25 minutes at -115 ° C. Stir for 15 minutes at -115 ° C, add gradient-3

10 cm of n-propyl chloroformate are stirred for 20 minutes at -115 ° C, then for one hour at -65 ° C. The reaction mixture is poured into aqueous monosodium phosphate solution, extracted into ether, the combined ethereal solutions are washed with water, dried and concentrated to dryness by distillation under reduced pressure. Chromatograph on silica gel using a mixture of cyclohexane and ethyl acetate (95/5) as eluent to give 3.52 g of t-butyl- (1R, cis) 2,2-dimethyl-3 (Z) - / 2-bromo-2- (propoxycarbonyl). ) ethenyl 4-cyclopropane-1-carboxylate and 3.16 g of t-butyl- (1R, cis) 2,2-35 dimethyl-3 (E) - (2-bromo-2- (propoxycarbonyl) ethenyl) -cyclopropane-1 carboxylate instead.

21,73679 t-Butyl (1R, cis) 2,2-dimethyl-3 (Z) -2H-bromo-2- (propoxycarbonyl) ethenyl] cyclopropane-1-carboxylate has the following properties: IR spectrum (in chloroform ) 5 - absorption at 1715 cm -1 due to the bond C = O, - absorption at 1614 cm -1 due to the bond C = C NMR spectrum (in deuterochloroform) - peak 0.9 to 0.97 to 1.05 ppm, which due to the hydrogen of the terminal methyl of the propyl, 10 - peaks 1.3 to 1.33 ppm due to the hydrogen of the methyl pair, - peak 1.52 due to the hydrogen of the 5-butyl group, - peaks 1, 88 to 1.97 - and 2, 05 - 2, 15 to 2.24 ppm due to the hydrogen of cyclopropyl in positions 1 and 3, - peaks 4, 1 to 4.18 to 4.26 ppm due to the hydrogen of methylene in position 1 of propyl 15, - peaks 7, 6 - 7.75 ppm due to hydrogenation of the ethylene double bond.

Step B: (1R, cis) 2,2-Dimethyl-3 (Z) -2H-bromo-2- (propoxycarbonyl) ethenyl] cyclopropane-1-carboxylic acid.

To a solution of 3.45 g of (1R, cis) 2,2-dimethyl-3 (Z) / 2-bromo-2- (propoxycarbonyl) ethenyl] cyclopropane-1-carboxylic acid tertiary butyl ester 35 toluene, 0.35 g of paratoluenesulfonic acid monohydrate is added. Place the flask containing the reaction mixture in an oil bath at 120 ° C for 10 minutes. The reaction mixture is suddenly cooled to 20 ° C, ether is added, the combined organic phases are washed with water, dried, concentrated to dryness by distillation under reduced pressure to give 2.9 g of (1R, cis) 2,2-di-30-methyl-3 (Z) - ^ 2-bromo-2- (propoxycarbonyl) ethenyl ^ -cyclopropane-l-carboxylic acid.

22 73679

Example 5 (S) <% -cyano-3-phenoxybenzyl (1R, cis) 2,2-dimethyl-3 (E) -N-2-bromo-2- (propoxycarbonyl) ethenyl / cyclopropane-1-carboxylate To a solution of 2.6 g of (1R, cis) 2,2-dimethyl-3 (E) - (2-bromo-2- (propoxycarbonyl) ethenyl) cyclopropane-1-carboxylic acid in 40 g of methylene chloride. 3 chloride, add 0.9 cm of pyridine and 2 g of cyclohexylcarbodiimide, stir for 10 minutes, add 10 (S) (X-cyano-3-phenoxybenzyl alcohol), stir for 10 minutes, add 25 mg of 4-dimethylaminopyridine and stir for one hour and thirty minutes The insoluble matter formed is removed by filtration, the filtrate is concentrated to dryness by distillation under reduced pressure, the residue is chromatographed on silica gel using a mixture of cyclohexane and ethyl acetate (95/5) as eluent to give 0.743 g of the desired ester and 3.64 g. Stir at 20 ° C, separate the precipitate from dryness and evaporate to a volume of hot isopropyl ether. dried and combined with 0.743 g of the product obtained above to give 2.32 g of (S) Qt-cyano-3-phenoxybenzyl- (1R, cis) 2,2-dimethyl-3 (E) 2 -bromo-2- (propoxycarbonyl) ethenyl cyclopropane-1-carboxylate.

Analysis: C ^ g H23 Br NB5 (512.41) C% H% N% Br%

Calculated: 60, 95 5, 11 2, 73 15, 6

Found: 61 5.1 2.5 15.5 IR spectrum (in chloroform) 30 - absorption at 1737 cm-1 due to ester carbonyl, - absorption at 1705 cm-1 due to conjugated ester carbonyl - absorption 1605 - 1610 cm-3 due to the bond -C = C-23 73679 - absorption at 1585-1485 cm-3 due to aromatic rings.

NMR spectrum (in deuterochloroform) - peaks 0.88 to 1.0 to 1.12 ppm due to the hydrogen of the methyl group of the propoxyl, - peaks 1.22 to 1.23 ppm due to the hydrogen of the methyl pair, - peaks 1, 92 to 2.06 ppm due to hydrogen at position 1 of cyclopropyl, 10 peaks from 4.08 to 4.18 to 4.28 ppm due to hydrogen at position 1 of methylene, peak 6.38 ppm due to due to hydrogen on the same carbon as - C = N, - peak 6.9 to 7.51 ppm due to hydrogenation of the ethylene double bond, - peak 6.92 to 7.6 ppm due to hydrogen of the aromatic ring (1R , cis) 2,2-Dimethyl-3 (E) -2H-bromo-2- (propoxycarbonyl) ethenylcyclopropane-1-carboxylic acid 20 can be prepared in the following manner:

To a solution of 3.1 g of (1R, cis) 2,2-dimethyl-3- (E) - [(2-bromo-2-propoxycarbonyl) ethenyl} cyclopropane-1-carboxylic acid tert-butyl ester which obtained simultaneously in the preparation of 3 (Z) -acid corresponding to the 3 (Z) -isomer in step A and according to Example 4 3 in 31 cm of toluene, 0.31 g of para-toluenesulfonic acid monohydrate are added. Place the flask containing the reaction mixture in a 120 ° C bath for 15 minutes and rapidly lower the temperature of the reaction mixture to 20 ° C. Extract with ether, wash the organic extracts with water, dry, concentrate to dryness by distillation under reduced pressure to give 2.6 g of (1R, cis) 2,2-dimethyl-3 (E) E-2-bromo-2- (propoxycarbonyl) ethenyl] cyclopropane -1-carboxylic acid.

λ 24 73679

Example 6 (1R, cis) 2,2-Dimethyl-3- (E) -N-fluoro-2- (ethoxycarbonyl) ethenyl / cyclopropane-1-carboxylic acid 5 (1R, cis) 2,2-Dimethyl -3- (E, Z) / 2-Fluoro-2-ethoxycarbonyl-ethenyl-4-cyclopropane-1-carboxylic acid is prepared starting from 12.2 g of (1R, cis) -2,2-dimethyl-3- (dihydroxymethyl) cyclopropanecarboxylic acid lactone and proceeding as in Example 10 1, replacing the chromatography shown in Example 1 with silica gel chromatography using a mixture of cyclohexane and ethyl acetate (75/25) and then the same mixture in ratios (50/50) as eluent to give 14.5 g (1R, cis) 2,2-Dimethyl-3- (E) - (2-fluoro-2-15 ethoxycarbonylethenyl) cyclopropane-1-carboxylic acid 42-42.5 ° (c = 1%, chloroform).

NMR spectrum (in deuterochloroform) - peak 1.28 due to methyl pair hydrogen, - peaks 1.23-1.35-1.47 ppm, and 4, 13-4, 25-4.37-4, 48 ppm, 20 due to the hydrogens of the ethyl group of the ethoxycarbonyl, - peaks 1.82-1.97 ppm due to the hydrogen in position 1 of the cyclopropyl, - peaks 2, 75-2, 9-3, 05 ppm due to the hydrogen in the position 3 of the cyclopropyl 25 - peaks 6.12-6.28-6.47-6.63 ppm due to hydrogen of ethylene (J - 21 H Hz corresponding to the cis derivative) - peak 11.28 ppm due to hydrogenation of the carboxyl .

Example 7 (1R, cis) 2,2-Dimethyl-3- (Z) / 2-fluoro-2- (ethoxycarbonyl) ethenyl] cyclopropane-1-carboxylic acid

According to the chromatography of Example 6, 4.64 g of (1R, cis) 2,2-dimethyl-3 (Z) -2-fluoro-2- (ethoxy-35-carbonyl) ethenyl] cyclopropane-1-carboxylic acid are obtained.

25 78679

Esterification of the acids (E) and (Z) (S) with Cfc-cyano-3-phenoxybenzyl alcohol gives the esters of Examples 1 and 2.

Example 8 5 (S) C 1 -Cyano-3-phenoxybenzyl (1R, cis) 2,2-dimethyl-3 (Z) / 2-fluoro-2-ethoxycarbonyl) ethenyl / cyclopropane-1-carboxylate To solution with 4.9 g of (1R, cis) 2,2-dimethyl-3 (Z) -2-fluoro-2-ethoxycarbonylethenyl-cycloprop-10-end-1-carboxylic acid, in 39 cm @ 4 of methylene chloride , 1.93 cm of pyridine, 4.8 g of dicyclohexyl-1-carbodiimide are added. Stir, add a solution of 5.3 g of (S) Cf-cyano-3-phenoxybenzyl alcohol 9.8 in 3 cm of methylene chloride, stir for 2 hours, add 30 mg of 4-dimethylaminopyridine, stir for 2 hours; cooled to 0 ° C. Remove the insoluble matter formed by filtration, concentrate to dryness by distillation under reduced pressure, chromatograph the residue on silica gel, eluting first with a mixture of cyclohexane and ethyl acetate (9/1), then with a mixture of methylene chloride and petroleum ether (b.p. 35/4 ° C). and 6.73 g of (S) Q> -cyano-3-phenoxybenzyl- (1R, cis) 2,2-dimethyl-3 (Z) -f-fluoro-2- (ethoxycarbonyl) ethenyl / cyclopropane-1 carboxylate having the same physical properties as the compound obtained in Example 2.

Following the same procedures as in Example 1, the following products have been prepared: (Examples 9, 10, 11 and 12).

Example 9 R, N, N-ethynyl-3-phenoxyphenylmethyl [(R, cisAE) -2,2-dimethyl-3 '* (2-fluoro-2-ethoxycarbonyl) ethenyl] cyclopropenecarboxylate. Yield = 72%. αO = +400 + 1.5 ° (c = 1% chCl3).

26 73679

Example 10 (R) (3-Phenoxyphenyl) ethyl (1R, cis, Δ. E) 2/2-dimethyl-3- (2-fluoro-2-ethoxycarbonyllethenyl / cyclopropanecarboxylate, yield 81% · 50 D = + 94.5 ° + 2.5 ° (c = 0.5% CHCl 3).

Example 11 (S) Cfr-Cyano-3-phenoxy-4-fluorobenzyl (1R, cis. Δε) 2,2-dimethyl-3 [T2-fluoro-2-ethoxycarbonyl) ethenyl] cyclopropane-1-carboxylate .

Δ D = + 50 ° + 2.5 ° (c = 0.5% CHCl 3).

Example 12 3-Phenoxybenzyl (1R / Cis Δε) 2,2-dimethyl-3- (2-fluoro-2-ethoxycarbonyl) ethenyl / cyclopropane-1-carboxylate.

IR spectra: C = 0 esters 1? 25 cm -1

C = 0 conjugated ester J

C = C conjugated 1655 cm -1 aromatics 1588-1489 cm 1 20 dimethyl pair 1390-1380 cm 1

Example 13 (S) Cf-cyano-3-phenoxybenzyl (1R, trans) 2,2-dimethyl-3H, 2-fluoro-3-oxy-3-ethoxypropenyl-cyclopropanecarboxylate.

By proceeding as in Example 1 using (1R + trans) 2,2-dimethyl-3H-E-2-fluoro-3-oxy-3-ethoxypropenyl-cyclopropanecarboxylic acid and (S) QE-cyano-3-phenoxybenzyl alcohol as starting materials, desired product: 30 00 = -33.5 °? 2.5 ° (c = 0.5% CHCl 3).

(1R, trans) 2,2-Dimethyl-3H-E-2-fluoro-3-oxy-3-ethoxypropenyl / cyclopropanecarboxylic acid was prepared as follows:

At a temperature of 2-10 ° C over a period of 30 minutes 3 35, a solution containing 60 cm of dimethoxymethane and 2.6 g of a 60% suspension of sodium hydride in oil is added 27,73679 containing 7.7 g of diethylphosphonofluorocarbon. acetate ethyl ester prepared from Ann.

3

Chem. (1964) p.674, 60 cm of 1,2-dimethoxyethane and 4 g of (1R, trans) 2,2-dimethyl-5-formylcyclopropanecarboxylic acid.

Stirring is continued for 15 minutes at 5 ° C and then for 3 hours at room temperature. A solution is obtained which is poured into 5 ° C aqueous monosodium phosphate solution and stirred for 10 minutes. Extract with ethyl acetate-10a, wash with water, dry and concentrate at 40 ° C under reduced pressure. 6.5 g of an oil are obtained, which is chromatographed on silica gel using a mixture of hexane and ethyl acetate-acetic acid (70: 30: 1) as eluent. This gives 4 g of the desired product.

15

Example 14 (S) α-Cyano-3-phenoxybenzyl (trans) -2,2-dimethyl-3 / C (AE) 2-fluoro-3-oxy-3-methoxypropenyl-cyclopropanecarboxylate.

Step Ai (S) Q6-cyano-3-phenoxybenzyl (1R, trans) -2,2-dimethyl-3- (trans) -2-fluoro-3-oxy-3-hydroxypropenyl] -cyclopropanecarboxylate. Add 50 mg of paratoluenesulfonic acid monohydrate to a solution of 1 g of (S) Q2-cyano-3-phenoxybenzyl- (1R, trans) -2,2-25-dimethyl-3- (N2) -2-fluoro-3-oxy -3-ethoxypropenyl 4-cyclopropanecarboxylate, 1 cm 3 of water and 4 cm 3 of dioxane. The reaction mixture is transferred to a reflux condenser for less than 8 hours and dried at room temperature under reduced pressure. The residue is extracted with methylene chloride, washed with water and dried. Dry to give 1.1 g of an oil which is chromatographed on silica gel using hexane-ethyl acetate-acetic acid (60: 40: 1) as eluent. This gives 280 mg of the desired product.

28 7 3 6 7 9

Step B: (S) Q: -Cyano-3-phenoxybenzyl (1R, trans) 2,2-dimethyl-3- [α] 2-fluoro-5-oxy-5-methoxypropenyl] -4-cyclopropanecarboxylate.

A slight excess of diazomethane dissolved in methylene chloride at +5 to 10 ° C is added to 2 cm of a methylene chloride solution containing 860 mg of the product prepared in step A. Stir for 15 minutes at 5 ° C, then for 30 minutes at room temperature. Add a few drops of acetic acid. Dried. This gives 950 mg of an oil which is chromatographed on silica gel using hexane-ethyl acetate (85:15) as eluent. 700 mg of the desired product are obtained.

° * O = 31 ° + 2.5 ° (c = 0.25% CHCl 3)

Example 15 (SO 2 -cyano-3-phenoxybenzyl (1R, trans) 2,2-methyl-3H-2) -2-fluoro-3-oxy-3-ethoxypropenyl-4-cyclopropanecarboxylate.

By operating as in Example 1 starting from (1R, trans) 3,3-dimethyl-3 (T 2 Z) -2-fluoro-3-20 oxy-3-ethoxypropenyl / cyclopropanecarboxylic acid and (S) -C bryano-3-phenoxybenzyl alcohol, desired product.

Δ = +150 + 2 ° (c = 0.5% CHCl 3) (1R, trans) 2,2-dimethyl-3R, 2'-fluoro-3-oxy-25-ethoxypropenyl] cyclopropanecarboxylic acid was prepared as follows:

A solution of 4 g of (1R, trans) 2,2-dimethyl-3-formyl-cyclopropanecarboxylic acid and 7 g of the sodium salt of diethyloxafluoro-30 acetate is placed under a condenser for one hour. Allow to cool to room temperature. Pour into saturated 0-5 ° C monosodium phosphate solution. Extract with ether, wash with water and dry. 8.2 g of product are obtained, which product is chromatographed on silica gel using a hexane-35-ethyl acetate-acetic acid mixture (70: 30: 1) as eluent.

4.3 g of the desired product are thus isolated.

29 73679

Example 16 (sX & cyano-3-phenoxybenzyl (1R, cis) 2,2-dimethyl-3H) 2-fluoro-3-oxy-3-hydroxypropenyl / cyclopropanecarboxylate Step A: (SK% - cyano-3-phenoxybenzyl (1R, cis) 2,2-dimethyl-3H) -2-fluoro-3-oxy-3-hydroxypropenyl] -N-cyclopropanecarboxylate.

By proceeding as in Example 13, Step A, starting from the product (S) -β-cyano-3-phenoxy-10-benzyl- (1R, cis) 2,2-dimethyl-3 - ((2Z) -2-fluoro-2-ethoxycarbonyl) ethenyl- cyclopropanecarboxylate gives the desired product.

Step B: By proceeding as in Example 14, Step B, starting from the product prepared in Step A, the desired product is obtained.

O & D = -2.5 ° i 2 ° (c = 0.4% CHCl 3)

Example 17 (S) tert-Cyano-3-phenoxybenzyl (1R, cis) 2,2-dimethyl-3 (Z) -2-fluoro-5-oxy-S-t-butoxypropenyl] -20 cyclopropanecarboxylate,

After stirring for 2 hours, 2.3 g of (S) 4-cyano-3-phenoxybenzyl (1R, cis) 2,2-dimethyl-3,2-fluoro-3-oxy-3-hydroxy (Z) propenyl / cyclopropanecarboxylate 15 cm 3 of ethyl acetate and 2.4 g of t-butyl N- (1-methylethyl) N '- (1-methylethyl) urea imidate. Filter, dry the filtrate to give 2.6 g of product, which is purified by chromatography on silica gel using hexane-isopropyl ether (8 · 2) as eluent under nitrogen pressure. 2.2 g of product are obtained, which is recrystallized from isopropyl ether. 1.4 g of the desired product are obtained, melting at 103 ° C.

= 2.5 ° Ϊ 3 ° c = 0.2% CHCl 3 t-butyl N- (1-methylethyl) -N 1 - (1-methylethyl) urea imidate was prepared as follows: 30 ° 3679

98.7 g of N, N1-diisopropylcarbodiimide and 57.9 g of t-butyl alcohol and 5 g of copper chloride are stirred for 4.5 days at room temperature. 117.7 g of the expected product are obtained after distillation of the reaction mixture with 95 mm of mercury (74 mm Hg at 74 [deg.] C.).

Example 18 (S) Qs »-Cyano-3-phenoxybenzyl- (1R, cis) 2,2-dimethyl-3 - [(Δ E, N-fluoro-5-oxy-Sd, N, N-hexane) fluorine) isopropoxy-n1-propenyl / cyclopropanecarboxylate.

A solution of 0.6 g of dicyclohexylcarbodiimide, 21 mg of 3 4-dimethylaminopyridine and 5 cm of methylene chloride is added over 10 minutes at 5-10 ° C to a solution of 1.1 g of (S) Ct-cyano-3- phenoxybenzyl 15 (1R, cis) 2,2-dimethyl-3- [2-fluoro-3-oxy-3-hydroxy (Z) propenyl] cyclopropanecarboxylate, 5 cm-1 methylene chloride and 0.5 cm-1, 1, 1, 1,3,3,3-heksafluoripro-propane-2-ol. Filter, dry the filtrate, chromatograph the resulting residue on silica gel using hexane-ethyl acetate (9-1) as eluent and operating under a nitrogen atmosphere. This gives 750 mg of the desired product.

= + 18.5 ° + 1 ° (c = 1% benzene).

Example 19 (S) C 1-4 Cyano-phenoxybenzyl (1R, cis) 2,2-dimethyl-3- [2-fluoro-3-oxy-3-methoxy (E) propenyl] -cyclopropanecarboxylate.

Step A; (S) Cyano-3-phenoxybenzyl (1R, cis) -2, α-dimethyl-3H-2-fluoro-3-oxy-3-hydroxy (E) propenyl 30-cyclopropanecarboxylate!

A solution of 2.5 g of (S) Ct-cyano-3-phenoxybenzyl- (1R, cis) -2,2-dimethyl-3- (JE) -2-fluoro-2-ethoxycarbonyl ether) is placed under a condenser for 24 hours. nyl cyclopropane-1-carboxylate (10 cm -1) dioxane-35 n, 2.5 cm 2 water and 1 g paratoluenesulfonic acid monohydrate. Allow to warm to room temperature, dilute to 31,73679 with methylene chloride and wash with water. The organic phase is dried, filtered and the filtrate is concentrated under reduced pressure. The residue obtained is chromatographed using a mixture of cyclohexane-5-ethyl acetate-acetic acid (60: 40: 1) as eluent. This gives 980 mg of the desired product.

Step B: (S) N-Cyano-3-phenoxybenzyl (1R, cis) 2/2 dimethyl-3- [2-fluoro-3-oxy-3-methoxy (E) propenyl] cyclopropanecarboxylate .

By proceeding as in Example 14, Step B, starting from (S) C 6 -cyano-3-phenoxybenzyl- (1R, -cis) 2,2-dimethyl-3H-2-fluoro-3-oxy- (E) propenyl 4-cyclopropanecarboxylate gives the desired product m.p. = 70 ° C.

15 = + 1.5 ° (c = 1% CHCl 3).

By proceeding as in the previous example and using the corresponding alcohols as starting materials, the following products have been prepared.

Example 20 (S) Cf-cyano-3-phenoxybenzyl- (1R, cis) -2,2-dimethyl-3- [2-fluoro-3-oxy-3-n-propoxy (E) propenyl] - cyclopropanecarboxylate.

Δ = + 38.5 ° + 2 ° (c = 0.1% CHCl 3)

Example 21 (S) Qi-Cyano-3-phenoxybenzyl- (1R, cis) -2,2-dimethyl-3- (AE) -2-fluoro-3-oxy-3-t-butoxypropenyl / cyclopropanecarboxylate.

By proceeding as in Example 17 starting from (S) Cfc-cyano-3-phenoxybenzyl- (1R, cis) -3,2,2-dimethyl-3/2-fluoro-3-oxy-3-hydroxy (E) propenyl cyclopropanecarboxylate and t-butyl N- (1-methylethyl) -N1- (1-methylethyl) urea imidate, the desired product is obtained (yield 61%).

α D = + 26.5 ° (c = 0.25% CHCl 3) 32,73679

Example 22 (S) Cb-Cyano-3-phenoxybenzyl- (1R, cis) -2,2-dimethyl-3- (Δε) -2-fluoro-3-oxy-3 (1,1,1,3 , 3, 3) -hexafluoro-isopropoxy-n-propenyl / cyclopropanecarboxylate.

By proceeding as in Example 14, Step B, starting from (S) <2i-cyano-3-phenoxybenzyl- (1R, cis) -2,2-dimethyl-3- (2-fluoro-3oxy-3-hydroxy (E) propenyl cyclopropanecarboxylate and 1,1,1,3,3,3-hexafluoropropan-2-ol give the desired product.

Δ = + 21 ° + 2 ° (c = 0.5% CHCl 3).

Example 23 (S) O-Cyano-3-phenoxybenzyl (1R, cis) 2,2-di-15-methyl-3- (2-fluoro-3-oxy-3-isopropoxy (E) propenyl) -cyclopropanecarboxylate .

OiD = + 46 + 1 ° c = 1% CHCl 3 Example 24 (S) <% - cyano-3-phenoxybenzyl- (1R, cis) 2,2-di-20-methyl-3,2-fluoro-3-oxy- 3-cyclopropoxy (E) -propenyl) 1 cyclopropanecarboxylate M.p. = 50 ° C = + 35 ° + 1 ° (c = 1.3% CHCl 3)

Example 25 (S) O-Cyano-3-phenoxybenzyl- (1R, cis, Δ%) 2,2-di-25-methyl-3/2-fluoro-3-oxy-3 (β-methoxyethoxy) propenyl li / ^ cyclopropanecarboxylate. "= 47 ° + 2.5 ° (c = 0.5% CHCl 3)

Example 26 (S) <% - Cyano-3-phenoxybenzyl- (1R, trans) 2,2-di-30-methyl-3 - [(Δ Z) -2-fluoro-3-oxy-3-methoxypropenyl] ) 1- - »v ......— - - cyclopropanecarboxylate.

Step A: (S) N, N-Cyano-metaphenoxybenzyl (1R, trans) -2,2-dimethyl-3- (Δζ) -2-fluoro-3-oxy-3-hydroxypropenyl] cyclopropanecarboxylate.

33 78679

By operating as in Example 14, Step A, starting from the corresponding (AZ) ester, the desired product is obtained.

Step B; (S) N-cyano-3-phenoxybenzyl (1R, trans) 2,2-5 dimethyl-3 (Z) Z--2-fluoro-3-oxy-3-methoxypropenyl cyclopropanecarboxylate.

By operating as in Example 14, Step B, using the product obtained in Step A as a starting material, the desired product is obtained.

10 ° D = + 15 »5 ° + 2/5 ° (c = 0.3% CHCl 3)

Example 27 (S) Q-Cyano-3-phenoxybenzyl (1R, cis) 2,2-dimethyl-3H-Z2-chloro-2-methoxycarbonylethenyl-7-cyclopropanecarboxylate.

By working as in Example 1 using (1R, cis) 2,2-dimethyl-3 (Z) 2-chloro-2-methoxycarbonylethenyl-4-cyclopropanecarboxylic acid and (S) -cyano-3-phenoxybenzyl alcohol as starting materials, desired product.

20 ° C = 62.5 ° + 1.5 ° (c = 1% benzene).

Example 28 (S) 2-Methyl-4-oxy-3- (2-propenyl) -2-cyclopenten-1-yl- (1R, cis) 2,2-dimethyl-3 / (Ae) 2-chloro- 2-Methoxycarbonylethenyl-cyclopropanecarboxylate.

The product was prepared as above using (1R, cis) 2,2-dimethyl-3 (Z) -2-chloro-2-methoxycarbonylethenyl} cyclopropanecarboxylic acid chloride and (4S) -hydroxy-3-methyl-2- (2) -30 propenyl) -2-cyclopenten-1-one.

Δ D = -15 ° = 4 ° (c = 0.25% benzene).

NMR CDCl 3 ppm 1.28 and 1.3 H of the methyls in position 2 from 3.8 H -CO 2 CH 3 35 2.02 H of H 3 -C -> Nj == 0 at the carbon atom in position 1 of the ethenyl group.

34 73679

Example 29 (1S) 2-Methyl-4-oxy-3- (2-propenyl) -2-cyclopenten-1-yl- (1R, cis) 2,2-dimethyl-3E (Z) 2-chloro -2-methoxycarbonyllethenyl cyclopropanecarboxylate.

The product was prepared using (1R, cis) 2,2-dimethyl-3β, [Z] 2-chloro-2-methoxycarbonylethenyl] cyclopropanecarboxylic acid and (4S) -hydroxy-3-methyl-2- (2-propenyl) as starting materials. ) -2-cyclopenten-1-one, the desired product is obtained.

10% = + 27 ° + 2 ° c (c = 0.3% CHCl 3)

Example 30 (S) CK-Cyano-3-phenoxybenzyl (1R, cls) 2/2-dimethyl-3 ', (Ε) 3-oxy-2-chloroethoxypropenyl / cyclopropanecarboxylate.

Acting as in Example 1 using (1R, cis) 2,2-dimethyl-3 / (E) 3-oxo-2-chloro-3-ethoxy-cipropenyl-cyclopropanecarboxylic acid and (S) O-cyano-acid as starting materials 3-phenoxybenzyl alcohol, the desired product is obtained.

20% = + 19 ° + 2 ° (c = 1% CHCl 3) (1R, cis) 2,2-dimethyl-3- [T-oxy-2-chloro-3-ethoxypropenyl] cyclopropanecarboxylic acid (Isomers E and Z ) was prepared as follows:

Step A; -ethoxycarbonyl-chloromethylene-phenylphenyl-25-phosphorane.

A solution of about 4 g of 3 chlorines in 80 cm of chloroform is prepared at 2 ° C. 20 g of ethoxy-3-carbonyl-methylene-triphenylphosphorane in 40 cm of chloroform are added. The reaction mixture is allowed to warm to room temperature and dried under reduced pressure. An oil is obtained which is dissolved in 70 cm of methylene chloride, washed with a solution of 6.1 g of sodium carbonate in 40 cm of water, then with water. Dried. 18.9 g of the expected product are obtained. Sp. 116-118 ° C.

35 73679

Step B; - (1R, cis) 2,2-dimethyl-3,3-oxyl-2-chloro-3-ethoxypropenyl] cyclopropanecarboxylic acid (isomers E and Z).

6.9 g of (1R, cis) 2,2-dimethyl-3-dihydroxy-5-dimethyl) cyclopropane-1-carboxylic acid lactone in 100 cm 3 of tetrahydrofuran are added to a solution of 18.9 g of the product prepared in step A 200 cm of tetrahydrofuran. The resulting solution is stirred for 6 1/2 hours at room temperature, the solution is distilled off under reduced pressure. An oil is obtained which is dissolved in 50 cm of ethyl ether, stirred at 0 [deg.] C., filtered, the precipitate obtained is washed with ether and the filtrate is dried. 22.2 g of the expected product are obtained, which product is chromatographed on silica gel using a cyclohexane-ethyl acetate-acetic acid mixture (75: 25: 1) as eluent. Thus: A) On the other hand, 3.58 g of the desired product as the E-isomer; NMR CDCl 3 ppm

1.3 and 1.33 of the 20 methyls in position 2 of cyclopropane

1.89 to 2.02 of carbon H in position 1 of cyclopropane

1.85 to 3.05 of carbon H in position 3 of cyclopropane

25 6.78-6.95 of the propenyl group in position 1

carbon H

B) On the other hand, 2.34 g of the corresponding Z-product NMR CDCl 3 ppm 1.33 and 1.36 of methyl H 3 in position 2 1.96 to 2.1 in cyclopropane in position 1

carbon H

2, 23 to 2.53 of the carbon H in position 1 of the cyclopropane.

36 73679

Example 31 (S) Di-cyano-3-phenoxybenzyl (1R, cis) 2,2-dimethyl-3- (Z) 2-chloro-3-oxy-3-ethoxypropenyl] cyclopropanecarboxylate.

By proceeding as in Example 1 using (1R / Cis) 2,2-dimethyl-3 (Z) -3-oxy-2-chloro-3-ethoxypropenyl] cyclopropanecarboxylic acid and (S) -N-cyano-3-phenoxybenzyl alcohol as starting materials, desired product.

10% = "21 '5 ° Ϊ 2.5 ° (c = 0.3% CHCl 3)

Example 32 (S) Cy-cyano-3-phenoxybenzyl (1R, cis) 2,2-dimethyl-3- [E] 3-oxy-2-chloro-3-propoxypropenyl} -cyclopropanecarboxylate.

By proceeding as in Example 1 using (1R, cis) 2/2-dimethyl-3 (E) 3-oxy-2-chloro-3-propoxypropenyl-cyclopropanecarboxylic acid and (SXX-cyano-3-phenoxybenzyl alcohol) as starting materials, the desired product is obtained. .

20 DEG = 24.5 ° + 2 ° (c = 0.4% CHCl3 (1R, cis) 2,2-dimethyl-3 / (E) 3-oxy-2-chloro-3-propoxypropenyl / cyclopropanecarboxylic acid was prepared as follows:

Step A; propoxycarbonylchloromethylene-1-triphenyl-25-l-phosphorane.

By proceeding as in the preparation of (1R, cis) 2,2-dimethyl-3E (E) -3-oxy-2-chloro-3-ethoxypropenyl-cyclopropanecarboxylic acid in Example 30, Step A, starting from propoxycarbonyl-methylene-triphenylphosphorane the desired product is obtained.

False B: (1R, cis) 2,2-Dimethyl-3 '(E) 3-oxy-2-chloro-3-propoxypropenyl] cyclopropanecarboxylic acid

By proceeding as in the preparation of (1R, cis) 2,2-dimethyl-3 - [(E) -3-chloro-3-ethoxypropenyl] -cyclopropanecarboxylic acid in Example 30 (Step B) using the product prepared in Step A as starting material, 37 78679 is obtained in part as the desired product, in part as the corresponding ΔΖ isomer.

Example 33 (S) -cyano-3-phenoxybenzyl (1R, cis) 2,2-di-g-methyl-3 ', (Z) 3-oxy-2-chloro-3-propoxypropenyl] cyclopropanecarboxylate.

By proceeding as in Example 1 using (1R, cis) 2,2-dimethyl-3E (Z) 3-oxy-2-chloro-3-propoxypropenyl] cyclopropanecarboxylic acid 10 and (S) Q6-cyano-3-phenoxybenzyl alcohol as starting materials, the desired product.

= + 22.5 ° + 2 ° (c = 0.7% CHCl 3) Example 34 (S) Qk-Cyano-3-phenoxybenzyl- (1R, cis) 2,2-di-15-methyl-3 'E) 3- oxy-3- (t-butoxy) -2-chloropropenyl) cyclopropanecarboxylate.

By proceeding as in Example 1, starting from (1R, cis) 2,2-dimethyl-3β, [E) 3-oxy-3- (t-butoxy) -2-chloropropenyl] cyclopropanecarboxylic acid and (S) 06-cyano-3 -phenoxybenzyl alcohol, the desired product is obtained.

% = + 30.5 ° + 2 ° (c = 0.7% CHCl 3) (1R, cis) 2,2-dimethyl-3-oxy-3- (t-butoxy) -2-chloropropenyl) cyclopropanecarboxylic acid (iso- 25 mers E and Z) were prepared as follows:

Step A: - t-butoxycarbonyl-chloromethylene-triphenyl-phosphorane ♦

By proceeding as above (method described in Example 30, Step A), the desired product 30 was obtained using t-butoxycarbonylmethylene-triphenylphosphorane as starting material.

Sp. - 160 ° C

Step B? ΛΕ-acid + Δ.Ζ-acid Using the product prepared in Step A as a starting material as shown in the procedure described in Example 30 38 73679, Step B, on the other hand, (1R, cis) 2,2-dimethyl-3β (E) 3 was obtained. oxy-3 (tert-butoxy) -2-chloro-ripropenyyli ^ cyclopropane carboxylic acid.

Sp. = 65 ° C

5 and the corresponding (Z) -isomer, on the other hand, m.p. <50 ° C.

Example 35 (S) O-cyano-3-phenoxybenzyl (1R, cis) 2,2-dimethyl-3 ', 2-bromo-3-oxy-3-methoxypropenyl] cyclopropanecarboxylate.

Acting as in Example 1 using (1R, cis) -2,2-dimethyl-3- (2-bromo-3-oxy-3-methoxy (Z) propenyl / cyclopropanecarboxylic acid and Cfc-cyano-3-phenoxybenzyl alcohol as starting materials, the desired product is obtained.

15 = + 29.5 ° + 2.5 ° (c = 0.5% CHCl 3) (1R, cis) 2 N 2 -dimethyl-3- [2-bromo-3-oxy-3-methoxy (Z) propenyl / cyclopropanecarboxylic acid was prepared as follows:

False A: - t-butyl (1R, cis) 2,2-dimethyl-3- [1,2] - 20 (dibromo RS) -3-oxy-3-methoxypropyl] cyclopropanecarboxylate.

1.3 g of pyridine tribromide are added to a solution of 8.07 g of t-butyl (1R, cis) 2,2-dimethyl-3/2-methoxycarbonyl (ethenyl) cyclopropanecarboxylate prepared from the corresponding acid by a method which is described in European Patent Application No. 0018 894, and 50 cm dimethyl sulfoxide The reaction mixture is stirred for 3 hours 30 minutes and poured into ice-cold water, extracted with methylene chloride, combined with the organic phases, dried and concentrated to dryness under reduced pressure to give 14.3 g. g of an oil which is chromatographed on silica gel using hexane-ethyl acetate (9: 1) as eluent to give 4.3 g of the desired product.

39 73679

Step B: - t-Butyl (1R, cis) 2,2-dimethyl-3- [2-bromo-3-oxy-3-methoxy (1-propenyl] cyclopropanecarboxylate.

3

Add 4 cm of triethylamine to the solution / if there is 40 cm of benzene and 4.2 g of t-butyl- (1R, cis) -2,2-dimethyl-3H-1,2 (dibromo RS) 3-oxy- 3-methoxypropyl-propyl / cyclopropanecarboxylate. Stir the reaction mixture for 6 1/2 hours at 22-24 ° C. Dilute with ether, wash with monosodium phosphate solution -10a and then with water. Dried. Concentrate under reduced pressure at 40 ° C. This gives 3.3 g of the desired product.

Step C: (1R, cis) 2,2-Dimethyl-3- [2-bromo-3-oxy-3-methoxy (Z) propenyl] cyclopropanecarboxylic acid.

15 Place under a vertical condenser a mixture of

O

is 3.3 g of the product prepared in step B, 30 cm 3 of toluene and 0.33 g of paratoluenesulphonic acid monohydrate. Keep under a vertical condenser until gas evolution has ceased. Cool to 20 ° C, dilute to ethyl ether, wash with water. Dry and concentrate under reduced pressure at 40 ° C. This gives 2.9 g of the desired product.

Example 36 (S) β-Cyano-3-phenoxybenzyl (1R, cis) 2,2-di-methyl-3- (E + Z) -3-oxy-3-methoxy-2-bromophenyl] cyclopropanecarboxylate.

By proceeding as in Example 1 using (1R, cis) 2,2-dimethyl-3- [2-bromo-3-oxy-3-methoxy (E) propenyl] cyclopropanecarboxylic acid 30 and (S) QE-cyano-3-phenoxybenzyl alcohol as starting materials , the desired product is obtained.

0 * D = + 9.5 ° + 2.5 ° (c = 0.3% CHCl 3) (1R, cis) 2,2-dimethyl-3- [2-bromo-3-oxo-3-methoxy (E) Propenyl-7-cyclopropanecarboxylic acid 35 was prepared as follows: 4073679

Step A - t-Butyl (1R, cis) -2t-dimethyl-3- [2-bromo-3-oxy-3-methoxy (E) propenyl] cyclopropanecarboxylate.

3

Add 100 cm of a solution of 50% sodium 5 carbonate in a mixture of 120 cm of methylene chloride, 6.7 g of t-butyl- (1R, cis) 2,2-dimethyl-3- [1,2- (dibromo RS) 3-oxy-3-methoxypropyl / cyclopropane and 120 mg Cätavlon (cetyltrimethylammonium bromide). Stir the reaction mixture for 4 hours. The dilution is diluted with 100 cm of methylene chloride and the organic phase is decanted and re-extracted with 100 cm3 of methylene chloride. Wash the organic phases with 1N hydrochloric acid to acidic pH and pH 7 with water. The organic phases are combined, dried and concentrated under reduced pressure at 40 ° C. 5.3 g of product are obtained, which product is chromatographed using a mixture of hexane-isopropyl ether (8-2) as eluent. 3.5 g of the expected product are obtained.

Step B - (1R, cis) 2,2-Dimethyl-3- (2-bromo-3-oxy-3-20 methoxy (E) propenyl] cyclopropanecarboxylic acid was prepared as follows:

A solution of 3.4 g of t-butyl- (1R, cis) 2,2-dimethyl-3- [2-bromo-3-oxy-3-methoxy (E) propenyl] cyclopropane, 30 cm3 of toluene and 0.35 g of paratoluenesulfonic acid monohydrate. Keep under a condenser until gas evolution ceases. Cool to 0 ° C, filter, wash the resulting precipitate with cold toluene and concentrate the filtrate at 40 ° C under reduced pressure. 2.8 g of the desired product are obtained.

Example 37 (S) QT-cyano-3-phenoxybenzyl- (1R, cis) 2,2-dimethyl-3 - [(E) 2-bromo-3-oxy-3- (t-butoxy) propenyl]? -syklopropaanikarboksylaatti.

By proceeding as in Example 1 using (1R, cis) 2,2-dimethyl-3E (E) 2-bromo-3-oxy-3- (t-butoxy) -propenyl] -cyclopropanecarboxylic acid as starting materials 41,73679 and (S) C & cyano-3-phenoxybenzyl alcohol, the desired product is obtained.

= -16.5 ° + 2 ° (c * 0.7% CHCl 3) (1R / Cis) -2H-dimethyl-1H / 2) -bromo-3-oxy-3-5 (t-butoxy) propenyl cyclopropanecarboxylic acid was prepared as follows:

Step A - t-Butoxycarbonyl-bromoethylene-triphenylphosphorane.

x-

By proceeding as in the preparation of (1R, cis) 2,2-dimethyl-3β (E) -10,3-oxy-2-chloro-3-ethoxypropenyl] cyclopropanecarboxylic acid (described in Example 30; step A), starting from t-butoxy -carbonyl-methylene-triphenyl phosphorane derivative, the desired product is obtained, melting at 190 ° C.

15 Step B; (R, cis) 2,2-dimethyl-3 / (E) 2-bromo-3-oxo-3- (t-butoxy) propenyylj ^ -cyclopropane carboxylic acid.

By proceeding as in the preparation of (1R, cis) 2,2-dimethyl-3β (E) -3-oxy-2-chloro-3-ethoxypropenyl] cyclopropanecarboxylic acid (described in Example 30} Step B), starting from the product prepared in Step A, to give part of the desired product, melting at 76 ° C and part of the corresponding Z-isomer, melting at 50 ° C.

Example 38 (S) GE-Cyano-3-phenoxybenzyl (1R, cls) 2,2-dimethyl-3 / (Z) 2-bromo-3-oxy-3- (t-butoxy) propenyl] cyclopropanecarboxylate .

Acting as in Example 1 using (1R, cis) 2,2-dimethyl-3 / (Z) 2-bromo-3-oxy-3-30 (t-butoxy) propenyl / cyclopropanecarboxylic acid and (S) O-t-cyano-3 as starting materials -phenoxybenzyl alcohol, the desired product is obtained.

° ° O = + 16.5 ° + 2 ° (c = 0.5% CHCl 3).

42 73679

Example 39 (S) QE-Cyano-3-phenoxybenzyl (1R, cis) 2 [2-dimethyl-3 / (E) 3-oxy-2-bromo-3-ethoxypropenyl] cyclopropanecarboxylate.

By proceeding as in Example 1 using (1R, cis) 2,2-dimethyl-3- (E) -3-oxy-2-bromo-3-ethoxypropenyl-4-cyclopropanecarboxylic acid and (S) -C 1-4 cyano-3-phenoxybenzyl alcohol as starting materials , the desired product is obtained.

10 -D = -70.5 ° + 2 ° c = 0.7% (CHCl-j) (1R, cls) 2,2-dimethyl-3 / TE) 2-bromo-3-oxy-3-ethoxypropenyl Cyclopropanecarboxylic acid was prepared as follows:

Step A - Ethoxycarbonyl-bromomethylene-triphenyl-15-phosphorane.

The product was prepared by the method described for (1R, cis) 2,2-dimethyl-3 - [(E) 3-oxy-2-chloro-3-ethoxypropenyl] cyclopropanecarboxylic acid in Example 30, Step A, starting from ethoxycarbonylmethylene. -triphenylphosphorane derivative female and bromine.

Step B: (1R, cis) 2,2-Dimethyl-3 - [(E) 2-bromo-3-oxy-3-ethoxy-propenyl] -cyclopropanecarboxylic acid. The product was prepared according to the procedure described for the preparation of the corresponding chlorinated acid, starting from the product prepared in Step A.

Thus, part of the desired product, part of the corresponding Ajz product, was isolated.

Example 40 (RS) CE-Cyano-6-phenoxy-2-pyridylmethyl (1R, cis) -2,2-dimethyl-3 H - (E) 2-fluoro-3-oxy-3-ethoxypropenyl-7-cyclopropanecarboxylate ♦

By proceeding as in Example 1 using the corresponding acid and alcohol as starting materials, the desired product is obtained. ° ° D = -15 ° ± 4 ° (c = 0.3% CHCl 3).

43 73679

Example 41 3- (2-Propynyl) 2,5-dioxoimidazolidinylmethyl (1R, cls) 2,2-dimethyl-3H- (E) 2-fluoro-3-oxy-3-ethoxypropenyl-cyclopropanecarboxylate.

By proceeding as in Example 1 using the corresponding acid and alcohol as starting materials, the desired product is obtained.

OO = 12 ° + 2 ° (c = 0.5% CHCl 3

Example 42 10 (S) 2-Methyl-3-allyl-4-oxy-2-cyclopenten-1-yl- (1R, cls) 2,2-dimethyl-3 (E) 2-fluoro-3-oxy-3 -etoksipropenyyli ^ cyclopropanecarboxylate.

By proceeding as in Example 1 using the corresponding acid and alcohol as starting materials, the desired product is obtained.

Q * d = + 41.5 ° + 2.5 ° (c = 0.5% CHCl 3)

Example 43

Pentafluorophenylmethyl (1R, cis, E) -2,2-dimethyl-3- [2-fluoro-5-oxo-S-methoxy-1-propenyl] cyclopropanecarboxylate.

By proceeding as in Example 1 using the corresponding acid and alcohol as starting materials, the desired compound was obtained. = 15 ° (c = 1% CHCl 3).

Example 44

Preparation of soluble concentrate.

Product of Example 1 0.25 g piperonyl butoxide 1.00 g

Tween 80 0.25 g

Topanol A 0.1 g 30 water 98.4 g

Example 45

Preparation of emulsifiable concentrate.

Mix very well:

Product of Example 11 0.015 g Piperonyl butoxide 0.5 g

Topanol A 0.1 g

Tween 80 3.5 g xylene 95.885 g 44 73679

Example 46

Preparation of emulsifiable concentrate:

Prepare a homogeneous mixture:

Product of Example 21 1.5 g 5 Tween 80 20.00 g

Topanol A 0.1 g xylene 78.4 g

Example 47

Making a smoky preparation: 10 Mix homogeneously:

The product of Example 1 0.25 g

Taboo powder 25.00 g cedar leaf flour 40.00 g pine sawdust 33.75 g 15 green dye 0.5 g p-nitrophenol 0.5 g A. Study of the stunning effect on Musca Domestica 20 Experimental insects were 4-day-old female houseflies . Spraying was performed directly at a concentration of 0.25 g / l in a Kearns and March chamber using a mixture of acetone (5%) and Isopar L (petroleum solvent) as the solvent (the amount of solvent used was 2 ml / sec.). an insect. Monitoring was performed every minute for up to 10 minutes, then after 15 minutes, and the KT 50 (Knock down time) was determined by standard methods.

The experimental results obtained are summarized in the following 30 tables:

Compound 50 A 3.6 B 4.5 C 4.5 35 D_2.5 45 73679 B. Study on the lethal effect of the compounds according to the invention on various insects a) Study on the lethal effect on Musca Po-mestica 5 Experimental insects were 4-5 days old female half houseflies. The treatment was performed by applying 1 ul of acetone solution to the back of the insect's thorax using an Arnold * micromanipulator. 50 individuals were used for treatment. Mortality was calculated 24 to 10 hours after treatment.

The results obtained, expressed as LD50 or dose (in nanograms per individual, which dose is needed to kill 50% of the insects) were as follows:

Compound LD50 n? F / insect 15 3 A 11.0 B 1.0 b) Study of the lethal effect on Blatella 20 Germanica beetle

The experiments were performed by adhering to a glass film by pipetting acetone solutions of different concentrations onto the bottom of glass Petri dishes, the edges of which had previously been talcated to prevent insect escape. A 50% lethal concentration (LD50) was determined.

The results obtained are summarized in the following table.

Compound LP50 ng / m A 1.4 B 0.40 30 - c) Study on the lethal effect on Spodoptera Littoralis larvae

The experiments were performed by applying an acetone solution to the larvae of the larvae-35 with an Arnold micromanipulator. 15 larvae were used per dose of test product. The larvae used were in the fourth larval stage, i.e. about 10 days 46 78679 years old, when grown at 24 ° C and 65% relative humidity. After treatment, the larvae were transferred to an artificial medium (Poitout's medium).

Mortality was calculated 48 hours after treatment. The results obtained are summarized in the following table.

Compound LD50 ng / insect A 6.7 B 3.2 D 1.0 10 - d) Study of lethal effect on Epilachna Varivestris

The experiments were performed using a similar smearing technique to that used for Spodoptera larvae. Larvae in the second to last larval stage were used; and after treatment, the larvae were fed bean plants. Mortality was calculated 72 hours after treatment.

The results are summarized in the following table.

20 Compound LD50 ng / hydraulic A 17.7 B 7.4 D 0.85 1 2 3 4 5 6 7 8 9 10 11 2 e) Study of lethal effect on Aphis Cra-3 civora insect 4

7-day-old adult insects were used in the experiment, and 10 insects were used for each concentration. The touch-injection method was used. The treatment was performed with a Fisher * pistol on a bean 8 leaf placed on a moist round paper placed on the bottom 9 of a plastic Petri dish. The treatment was performed with 2 ml of an acetone solution of the test compound (Imi 11 on each side of the leaf). The insects were allowed to be in contact with the leaf for one hour, then placed on untreated leaves and mortality calculated after 24 hours.

47 78679

The results obtained are summarized in the following table.

Compound LD50 ng / insect B 6.4 5 f) Conclusion

In the experiments described in a), b), c), d) and e), compounds A and B also have an interesting insecticidal effect.

10 g) General conclusion

The compounds of the invention have an interesting insecticidal activity in the experiments described above.

B. Mite-killing effect of the compounds of the invention Bean plants with 2 leaves per 25 female Tetranychus Urticae insects per leaf were used; and the plant was placed under an air-conditioned hood with a constant light on the roof. Plants were treated with a Fsiher gun; 4 ml of toxic solution per plant mixed with equal volumes of 20 volumes of water and acetone. It was allowed to dry for 12 hours, after which the insects were allowed to continue destroying the leaves.

Mortality was calculated after 80 hours.

The concentration used in each experiment was 5 g of yh-25 distal per 100 liters.

Compounds A, B and C have good potency in this experiment.

48 73679

Biological comparative tests

The lethal effect of the compounds of formula (I) having the double bond E configuration on flies was compared to the corresponding effect of the Z-isomers of the compounds.

The compounds tested were: (S) Oi-cyano-3-phenoxybenzyl (1R, cis) -2,2-dimethyl-3- (E) -Cl-fluoro-2- (ethoxycarbonyl) ethenyl] cyclopropanecarboxylate (Compound from Example 1, hereinafter denoted A: 11a) and its Z-isomer (compound from Example 2, hereinafter denoted by B); (S) N-cyano-3-phenoxybenzyl (1R, cis) -2,2-dimethyl-3-E- [2-fluoro-3-oxy-3-tert-butoxy propenyl] cyclopropanecarboxylate (compound from Example 21, hereinafter denoted by C) and its Z-isomer, hereinafter denoted by 15 D; (S) Q 1-Cyano-3-phenoxybenzyl (1R, cis) -2,2-dimethyl-3- [trans-3-oxo-2-chloroethoxypropenyl] -cyclopropanecarboxylate (compound of Example 30, hereinafter denoted by E ) and its Z-isomer (compound from Example 31, denoted by F in the following).

The experiments were performed using the technique shown on page 45.

The result was: DL__ (Compound A) 0.4 ng / insect

DU

DL50 (Compound B) 39 - "- 25 DL50 <Compound 4.2 -" - DL50 (Compound D)> 100 DL50 (Compound E) 1.7 - "- DL50 (Compound F) 22.7 -" -

It can be seen from the results that the insecticidal activity of compounds A, C and E having the (E) configuration is considerably higher than the corresponding activity of the Z isomers of the compounds.

49 73679

The biological activity of pentafluorophenylmethyl (1R cis, E) -2,2-dimethyl-3- [2-fluoro-3-oxo-3-methoxy-1-propenyl] cyclopropanecarboxylate was compared with that of its isomers (1R trans, E), (1R cis, Z) and (1R trans, Z) 5 to the corresponding activity. The following results were obtained: KT min. Dose a) Stunning effect on musca domestica 50 10 1R cisAe 1.09 250 mg / 1 1R trans Δ E 2.25 1 g / 1 1R cisAz 1.5 1 g / 1 1R trans ^ Z 2.09 1 g / 1.

The results show that at a dose of 250 mg / l, the (1R cis, E) isomer is lower (i.e., the activity is higher) than the other isomers. The (1R cis, E) isomer is 4 times as active as the corresponding isomers.

20 b) Lethal effect on Spodoptera Littoralis larvae DL50

Compound 1R cisZ \ E 27 ng / insect "1R transZ ^ E> 100 ng / insect H 1R cis / \ z> 100 ng / insect 25" 1R cisA E> 100 ng / insect The (1R cis, E) isomer has 3 -4 times as high activity as the other isomers.

30 c) Lethal effect on Blatella Germanica beetles CL50 mg / m2

Compound 1R cisZ ^ E 0.26 "1R transZ \ E 10 35" 1R cisZ ^ Z 10 "1R trans Δζ 10 (1R cis, E) isomer has about 40 times as much activity as other compounds.

so 73679

Biological research

A compound of formula (I) having a 1R trans structure.

The compound tested was (S) -cyano-3-phenoxybenzyl 5 (1R, trans) -2,2-dimethyl-3 - [(N-2-fluoro-3-oxy-3-ethoxypropenyl) 7-cyclopropanecarboxylate (Compound from Example 13, hereinafter denoted A ': 11a).

The lethal effect in flies was studied by the technique shown on page 45.

The result was: DL50 (Compound A ')> 78 ng / insect

It is noted that the insecticidal activity of Compound A 'having the 1R transstructure is much lower than that of Compound A having the 1R cis structure, which has a DL50 of 0.4 ng / insect.

Using the experimental method described in the present application, the effect of the compounds of Examples 28 and 29 or on the Musca Domestica fly was investigated.

20 The result was:

Compound from Example KT 50 min 28 8.1 29 1.1.

The E-isomer is 8 times as active as the Z-isomer.

Claims (15)

5i 78679 1. Compounds of formula I 5 X .H H3CX ^ CH3 // ° I RO-C C-OB "3 OJ 10 wherein R is a straight-chain, branched or cyclic saturated alkyl group having 1 to 8 carbon atoms, which may be substituted by one or more halogen atoms or a lower alkoxy group , B is a group 15 CH- | Λ ^^ CH2-CH = CH2 20. or a group 0 -CH0-N N-CH0-CSCH.25 v O or a group FF 30 FFF or a group O "5" - A-oT WR! 5 52 7 3 6 7 9 wherein R14 is a hydrogen atom or a methyl, ethynyl or cyano radical and R15 is a hydrogen or fluorine atom, or a group J "» vO tj and X is a halogen atom, and in which the ethylene double bond of Compound I has the E configuration and wherein the cyclopropanoic acid backbone has a 1R cis structure. Compound according to Claim 1, characterized in that it is (S) Ct-cyano-3-phenoxy-benzyl- (1R, cis) -2,2-dimethyl-3- (E) - / 2-fluoro- 2- (ethoxycarbonyl) ethenyl N-cyclopropane-1-carboxylate. Use of compounds according to claim 1 for controlling parasites of plants and dwellings. Preparations for controlling parasites of plants and dwellings, characterized in that they contain at least one compound as defined in claim 1 as active ingredient. Insecticidal preparations, characterized in that they contain at least one compound as defined in claim 1 as active ingredient. Mite control preparations, characterized in that they contain at least one compound as defined in claim 1 as active ingredient. Process for the preparation of compounds of formula I as defined in claim 1, characterized in that the acid of formula II 35. c 0 H RO-C 1 -C = O 11 0 H 53 78679 wherein X and R are as defined above, or a functional derivative of this acid, is reacted with an alcohol of formula III B-OH III wherein B is as defined above, or with a functional derivative of this alcohol to give the corresponding compound of formula I, which, if desired, is reacted with a selective cleavage agent of the CC 4 R group to give a compound of formula IV XH <* 3) ^ * 3, 0 H01 IV 0 wherein B is as defined above, after which the acid of formula IV or a functional derivative of this acid is reacted with an alcohol of formula R-OH where R is as defined above. above, and that the compound 1R cis E is separated from the mixture 1R cis (E + Z). . chromatography. Process according to Claim 7, characterized in that the acid of the formula II in which R is an alkyl group having 1 to 5 carbon atoms is prepared by reacting, in the presence of a concentrated base, a cis-aldehyde in the lactone form of the formula V avV 1 or a trans-aldehyde of the formula VI 54 7 8 6 7 9 H \ / O 1 X 1 VI 0 = C. .C-OH "" "H 5 is reacted with a phosphorane of the formula VII x /« P) * P = C VII -5 c-or1q 1 | 19 'o 10 having an alkyl group having 1 to 5 carbon atoms and X represents the same as above, or with a phosphonate, or with a phosphonate of formula O * 20 ° P-CH-X-C-OR, Q / 19 VIII R20 ° 1 wherein R 1g and X have the same meaning as above and R 2Q is an alkyl group having 1 to 6 carbon atoms. 55 73679