DK164402B - (1R, CIS) -2,2-DIMETHYL-3- (2-HALOGEN-2- (SUBSTITUTED HYDROXY) - (E) -CARBONYLETHENYL) -CYCLOPROPAN-1-CARBOXYLIC ACID FOR USE BY PREPARING THE EQUIVALENT EQUIPMENTS WHEREOF - 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

DK 164402B

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The invention relates to novel (1R, cis) -2,2-dimethyl-3- (2-halogen-2 - (substituted hydroxy) - (E) -carbonyl-ethenyl) -cyclopropane-1-carboxylic acids of formula II as as set forth in claim 1 - for use as intermediates for the preparation of the corresponding esters of formula I below with pesticidal action - and a process for their preparation.

Said pesticidal esters have the general formula I 10 X Yes H3C

^ · \ X / / \ £ - OB (I)

RO — C S

Wherein R and X have the same meaning as in claim 1 and B is the group CH, I ^^ ch2-ch = ch2

Os or the group 0 25

-CH - N N-CH - CHCH

V

o or the group

30 F F

-CH2- ^ V p

Έ F

35 or the group

DK 164402 B

- 2 - _ δ> “-

fy / T

5 W * 15 wherein K 14 is a hydrogen atom or a methyl, ethynyl or cyano group, and R 1 is a hydrogen or fluorine atom, or the group

J-Ø'O

15 in which compounds In the ethylene double bond have the configuration E and the cyclopropane group has the structure IR, cis.

The compounds of formula I have interesting properties which enable their use in the control of parasites. It can for example. revolve around the control of parasites on plants, on premises and on warm-blooded animals.

Thus, the compounds of the present invention can be used to control insects, nematodes and acarides, which are parasites on plants and animals.

In particular, the compounds of formula I can be used to control insects in agriculture, e.g. aphids and larvae of lepidopters and coleopts. They are used in doses between 10 g and 300 g of active substance per day. ha.

The compounds of formula I can also be used .30 for controlling insects in rooms, especially flies, mosquitoes and cockroaches.

The compounds of Examples 1, 7 and 11 are particularly remarkable compounds, as the test results below show. They have an excellent lethal effect 35 and a very good knock-down effect.

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Furthermore, the compounds of formula I are light stable and are not toxic to mammals.

The combination of these properties causes the The bonding compounds of formula I are compounds which very well correspond to the requirements of the modern agricultural chemical industry. They make it possible to protect the crops while preserving the environment.

The compounds of formula I can also be used to control acarides and nematodes, which are parasites on 10 plants.

The compounds of formula I can further be used to control acarides, which are parasites on animals, to control e.g. blood mites and in particular of the species Boophilus, Hyalomnina, Amblyomia and Rhipicephalus or for the control of all kinds of enclosures and in particular sarcoptic, psoroptic and chorioptic enclosures.

Among the preferred especially insecticidal compositions, particular mention is made of the compositions containing the compounds of Examples 1, 7 and 11.

20 These preparations are prepared according to the methods customary in the agricultural or veterinary or in the industry which works with animal feed preparations.

In the preparations for use in agriculture as well as in premises 25, the active compound (s) may optionally have one or more other pesticides added. These compositions may be present as powders, granules, suspensions, emulsions, solutions, aerosol solutions, combustion tapes, baits or other preparations classically used for the use of this type of compound.

In addition to the active ingredient, these compositions usually contain a carrier and / or a non-ionic surfactant which furthermore ensures a uniform distribution of the constituents of the mixture. The carrier used may be liquid such as water, alcohol, hydrocarbons or other organic solvents, a mineral oil or an animal or vegetable oil, a

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- 4 - powders such as talc, clay, silicates, diatomaceous earth or a solid combustible substance.

The insecticidal compositions preferably contain 0.005 - 10% by weight of active ingredient.

According to an advantageous working method, the compositions of the invention are used in premises as smoke preparations.

The compositions may then, in the case of the non-active part, be a combustible insecticidal coil or, on the other hand, a non-combustible fibrous substrate. In this last case, the smoke composition with the active ingredient incorporated is placed in a heating apparatus such as an electrical insecticidal apparatus.

In the case where an insecticidal coil is used, the inert carrier, e.g. consist of pyrethrum ash, 15 powder of leaves of Machilus thumbergii, powder of pyre-thrum stalk, powder of cedar needles, sawdust such as pine sawdust, starch and coconut shell powder.

The dose of active material may then e.g. be 0.03 - 1% by weight.

In the case where a non-combustible fibrous carrier is used, the dose of active material may e.g. be 0.03 - 95% by weight.

The compositions for use in rooms can also be obtained by preparing an active ingredient atomizable oil, which is absorbed into a lamp wall and incinerated.

The concentration of active ingredient in the oil is preferably 0.03 - 95% by weight.

The insecticidal, acaricidal and nematodicidal preparations 30 may optionally be added to one or more other pesticidal agents. In particular, the acaricidal and nematodicidal preparations may be present as powders, granules, emulsions, suspensions and solutions.

For acaricide use, preferably wettable 35 powders are used for spraying on the foliage and containing 1 - 80% or liquids for spraying on the foliage and containing 1-500 g of active substance per day. liter. You can also use

DK 164402 B

- 5 - powder for powdering the foliage and containing 0.05 - 3% active substance.

For nematodic use, liquids are preferably used to treat the soil and containing 300 - 500 g of active substance 5 liters per liter.

The acaricidal and nematodicidal compounds of the invention are preferably used in doses of 1 to 100 g of active ingredient per day. ha.

To enhance the biological effect of the compounds of the invention, classic synergistic agents used in such cases may be added, e.g. 1- (2,5,8-Trioxadodecyl) -2-propyl-4,5-methylenedioxybenzene (or piperonylbutoxide) or N- (2-ethylheptyl) bicyclo- (2.2-1) -5-hepten-2 , 3-dicarboximide or piperonyl bis-2-15 (2'-n-butoxyethoxy) -ethylacetal (or tropital).

In the case of combating acarides, which are parasites on animals, the compounds of the present invention are very often incorporated into a nutritional mixture suitable as animal feed. The nutrients may vary by animal species and may contain cereals, sugar and seeds, soy, peanut and sunflower seed cake, animal flour, fish meal, synthetic amino acids, mineral salts, vitamins and antioxidants.

The compounds of the general formula I have excellent tolerance and can be used in warm-blooded animals for the control of mites and enclosures and also for the control of lice, both preventive and curative.

The compounds I can be used by external evaporation, saponification, bathing or lubrication.

The compounds I may also be "smeared on the backs of animals by the pouring method. They may also be administered through the digestive tract or parenterally.

It should also be noted that the compounds of the present invention can be used as biocides and growth regulators.

The use of the acids II is carried out by reacting the compounds of formula I

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an acid of formula II or a functional derivative of this acid with an alcohol of formula III

B-OH (III) 5

wherein B has the same meaning as above, or a functional derivative of this alcohol to give the corresponding compound of formula I, which if desired is subjected to the effect of a means for selective cleavage 10 of the group CC₂R to give the compound of formula IV

15 / \ P (IV)

/ \ / \ / C »OB

HO-C '' L-

, 1. XH

Wherein X and B have the same meaning as above, subjecting this acid of formula IV or a functional derivative of this acid to an alcohol of formula R7OH, where R has the same meaning as above, and by physical means the isomeric E and Z with respect to the double bond by chromatography.

The esterification of the acid II with the alcohol of formula III may be carried out in the presence of a tertiary base such as pyridine. This esterification can advantageously be carried out in the presence of a mixture of pyridine, dicyclohexyl, carbodiimide 30 and 4-dimethylaminopyridine.

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

Wittig's reaction, which is usually used to prepare acids of formula II, yields acids whose double bond is E + Z.

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The isomers with respect to the double bond can be separated, if appropriate, by physical methods such as chromatography or with respect to the acids and also with respect to the esters. Examples of these two methods are given below in the experimental part.

The cleavage agent for the group CO 2 R is preferably heat which is used in conjunction with an acid hydrolysis agent.

As an acidic hydrolysis, p-toluenesulfonic acid may be used.

The esterification of the compound of formula IV is carried out according to classical esterification methods, especially those described above.

The invention also relates to a process for the preparation of the acids of formula II, and this process is characterized by the characteristic part of claim 2.

The acids of formula II with particular stereochemistry can also be prepared according to the following reaction scheme: 20

V =% V_Jvi - 0 _! _> K / \ J-0H

In the formulas in this scheme, X represents fluorine, chlorine 3 or bromine, R represents an alkyl group of 1-8 carbon atoms, and the compounds used have a well-defined control. risk configuration.

6

The acids of formula II, wherein X represents a bromine atom,

may also be prepared by subjecting a compound of formula IX

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Where the geometry of the double bond is E and R has the same meaning as above, and alc represents an alkyl group, the effect of a brominating agent such as e.g. pyridinium bromide and then the action of a dehydrobrominating agent to give:

- If the dehydrobrominant is a basic agent which works under relatively mild conditions, compounds of formula X

- if the dehydrobrominating agent is a basic agent acting under more intense conditions, the E isomer.

25

The compounds of formula V are then subjected to a means for cleavage of the group CClc to obtain the corresponding acid of formula II.

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

The acids of formula II and especially those of well-established stereochemistry as well as the acids of formula IV obtained during the practice of the process of the invention are novel compounds.

The following examples illustrate the method according to the invention.

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Example 1 (Application Example) (1Rf cis) -2,2-dimethyl 3- (E) - (2-fluoro-2- (ethoxyearbonyl) ethanyl) oyclopropane-1-oreboxylic acid (S) - g-oyan-3 - phenoxybenzyl ester.

X a solution of 3.87 g (1R, cis) -2,2-dimethyl-3- '- (Z + E) - (2'-Luoro-2-ethoxycarbonylethenyl) -cyclopropane-1-carboxylic acid in 30 ml of methylene chloride are introduced with 1.5 ml of pyridine and 3.7 g of dicyclohexylcarbodiimide, stirred for 10 minutes and at a time a solution of 4.05 g of (S) -α-eyan-5-phenoxybenzyl alcohol is added in 10 ml of methylene chloride. stir for 1 hour 30 minutes, add 25 mg of 4-dimethylaminopyridine, stir for 10 hours 30 minutes, cool to 0 ° C, eliminate the insoluble material formed Ted filtration, evaporate the filtrate to dryness under reduced pressure, chromatograph the residue on silica gel eluting with a mixture of cyclohexane and ethyl acetate (80i20), crystallizing the resulting residue of ethyl acetate, isolating the formed precipitate by suction and chromatographing the mother liquors on silica gel eluting with a mixture of cyclohexane and ethyl acetate (9: 1) a total of 4.28 g (1R, cis) -2,2-dimethyl-3-CB) - (2-fluoro-2- (ethoxycarbonyl) ) -ethenyl) cyclopropane-1-carboxylic acid 20 - (S) -α-cyano-3-phenoxybenzyl ester and 2.8 g of 3- (Z) -deriyate.

Analysis: C25E24: KiO2 s * 37.47 calculated: <# 68.64 E £ 5.53 3.20-4.34 found: 68.8 5.5 3.1 4.2 I · R # spectrum (chloroform ): 25 —1 –1 - absorption at 1738 cm and 1722 cm attributed to carbonyl and conjugated ester, - absorption at 1611 οπΓ1 attributed to the ethylenic double bond, - absorption at 1589 cm * “~ - 1489 cm” attributed to the aromatic rings, - absorption at 1380 cm 2, attributed to the twin methyl groups · EMR spectrum (deuterochloroform): - peaks at 1.2-1.27 ppm attributed to the hydrogen atoms in the twin thyl groups, - peaks at 1.23 - 1.35 - 1.47 ppm, 4.15 - 4.26 ppm and

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- 10 - 4.38 - -4.50 ppm attributed to hydrogen atoms in the ethyl group in ethorycarbonyl, - peaks at 1.88 - 2.02 ppm attributed to the hydrogen at the 1-position in cyclopropyl, 5 - peaks at 2.8 - 3.13 ppm attributed to the hydrogen at the 3-position in cyclopropyl, - peaks at 6.05 - 6.21 and 6.38 - 6.55 ppm, ascribed to the hydrogen in the ethylenic double bond, - peak at 6.36 ppm attributed to the hydrogen carried by the same ear carbon as the CIT group - peaks at 6.9 - 7.58 ppm attributed to the hydrogen atoms in the aromatic rings' (IR, cis) -2,2-dime Thyl-3- (E, Z) - (2-Fluoro-2-ethoxycarbonylethenyl) cyclopropane-1-carboxylic acid is obtained as follows (Preparation Example): In a solution of 12.1 g of diethylphosphorofluoroacetic acid ethyl ester in 120 ml of dime tb oxy ethane introduces at 5 ° C 2 g of sodium hydride of $ 60 in oil, stirs for 30 minutes, introduces at 0 ° C 5.7 g of lactone of (1R, cis) -2,2-dimethyl-3 - (dihydroxymethyl) -cyclopropane-1-carboxylic acid, stirring for 2 hours 30 minutes at 20 ° C, pour the reaction mixture into a mixture of water and ice containing monosodium phosphate, extract with ethyl ether, wash the combined organic phases with water, dry them, evaporate them to dryness under reduced pressure, chromatograph the residue on silica gel eluting with a mixture of cyclohexane, ethyl acetate and acetic acid (50: 50: 1) to obtain 3.87 g of a mixture of (IR, cis) -2,2-dimethyl 1-3- (2, Z) - (2-fluoro-2-ethoxycarbo-3 (ylmethenyl) -cyclopropane-1-carboxylic acid

Example 2. {Application Example) (1R »cis) -2,2-Dimethyl-5- (E) - (2-chloro-2- (methoxyearbonyl) e thenyl) -cyclopropane-1-carboxylic acid (S) -g -cyan-3- $ henogy-benzyl ester, in a solution of 3 g (1R, cis) -2,2-dimethyl-3- (E) -

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- II - - (2-Chloro-2-1-ethoxycarbonylethenyl) -cyclopropane-1-carboxylic acid chloride in 15 ml of benzene is introduced 3 g of (S) -α-azan-3-phenoxybenzyl alcohol and introduced at 50 ° 0 1, 3 ml of pyridine, stirring for 15 minutes at 5 ° C and then for 16 hours at 20 ° 0, 5 reaction mixture does not pour into a mixture of water and hydrochloric acid, extract with ethyl ether, wash with water, dry, evaporate the organic solution to dryness. by distillation under reduced pressure, chromatograph the residue on silica gel, successively eluting with a mixture of cyclohexane and 10 ethyl acetate (8: 2) and then cyclohexane and ethyl acetate (9 * 1) to give 2.1 g (lfi, cis) -2, 2-dimethylbyl-3- (E) - (2-chloro-2- (methoxy-carbonylethenyl) -cyclopropane-1-carboxylic acid (S) -ocyan-3-phenoxybenzyl ester, = 50.5 ° (c = 0.8 #, benzene).

Analysis: σ24Η22σ · ^ ° 5 s 439 »9 15 calculated: C # 65.53 H # 5.04 Cl # 8.05 K # 3.18 found: 65.5 5.2 8.0 3.0 IU spectrum (chloroform): - absorption at 1738 cm "1 and 1719 cm" 1, which is attributed to the carbonyl group in the ester, - absorption at 1608 cm "1, which is attributed to -C = C-, - absorption at 1589 01 ^ -1489 cm "1 attributed to the aromatic rings - absorption at 1390 cm" 1 attributed to the twin methyl groups.

IT, Μ, E. spectrum (d euterochloroform): - peaks at 1.24 - 1 »25 ppm attributed to hydrogen atom island in the twin methyl groups, - peaks at 1.93 - 2.07 ppm attributed to the hydrogen at the 1 position of cyclopropyl, 30 - peaks at 2.87 - 3.01 - 3.04 - 3.14 ppm attributed to the hydrogen in the 3-position of cyclopropyl, - peak · at 3.85 ppm attributed to the methyl group in methoxycarbonyl, - peak at 6.35 ppm, which is attributed to the hydrogen carried by the same C-at about the group EAST, - peaks at 6.91 - 7.5 ppm attributed to the hydrogen atoms in the aromatic rings.

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- 12 - ((IR, cis) -2,2-dimethyl-3- (E) - (2-chloro-2- (methoxy-carbonyl) -ethenyl) -cyclopropane-1-carboxylic acid chloride can be prepared as follows: grin A? (IR, cis) -2,2-Dimethyl-3- (E) - (2-chloro-2-methoxy-carfconyl) -ethenyl) -cycloprooan-1-carboxylic acid. (Inheritancexl.) 5 In 50 ml of tetrahydrofurajj, at 20 ° C, 12.6 g of th oxy c arb onylch lo rme th y len tr iph eny lpb us ph o ran, 4.85 g of lactone of (lR, cis) is introduced. -2,2-Dimethyl-3- (dihydroxymethyl) -cyclopropane-1-carboxylic acid in solution in 40 ml of tetrahydro-uranium and stirred for 2 hours at 20 ° C, the reaction mixture is heated to reflux and quenched. there, for 1 hour, evaporating to dryness by distillation under reduced pressure, adding ethyl ether to the residue, eliminating the insoluble material formed (triphenylphosphine oxide) by filtration, evaporating the filtrate to dryness under reduced pressure, chromatographing the residue on silica gel eluting with di mixture of benzene and ethyl acetate (8: 2) containing 1 # acetic acid to give 2.2 g (1R, cis) -2,2-dimethyl-3- (E) - (2-ehloro-2-methoxycarbonylethenyl) cyclopropane -1-carboxylic acid and 3 g (IR, cis) -2,2-dimethyl-3- (Z) - (2-chloro-2-methoxycarbonylethenyl) -cyclopropane-1-carboxylic acid.

(1R, cis) -2,2-dimethyl-3- (E) - (2-chloro-2-methoxycarbonyl-ethenyl) -cyclopropane-1-carboxylic acid has the following properties: I, R. Spectrum (chloroform): - absorption at 3500 cm * "1 attributed to the hydroxyl group 25 in carboxyl, - absorption at 1721 cm -1, 1713 cm -1, 1700 cm * '3" attributed to carbonyl, - absorption at 1490 cm -1 "1410 cm , which is attributed to -C = G-, - absorption at 1393 cm * "1 - 1380 cm" 1, which is attributed to the hydrogen atoms in the twin methyl groups.

R # M'R spectrum (deuterochloroform): - peaks at 1.3 - 1.32 ppm attributed to the twin methyl groups, - peaks at 1.87 - 2.02 ppm attributed to the hydrogen at the 1-position in cyclopropyl,

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- 13 - - peaks at 2.82, 2.97 ppm - 2.98, 3.13 ppm, s attributed to the hydrogen at the 3-position in cyclopropyl, - peak at 3.82 ppm attributed to the hydrogen atoms in the methyl group in methorycarbonyl, 5 - peaks at 6.72 - 6.78 ppm attributed to the hydrogen in the ethylenic double bond in the side chain at the 3-position in cyclopropyl, - peaks at 11 ppm attributed to the hydrogen in carboxyl.

1Rf cis) -2,2-Dimethyl-3- (Z) - (2-chloro-2-methoxycarbonylethylbenzyl) -eyclopropane-1-carboxylic acid has the following properties: I, IL spectrum (chloroform):

_ * T

- absorption at 3500 cm attributed to the hydroxy islet of carboxyl (monomer + dimer), 15 - absorption at 1725 cm "**", attributed to ester CO, - absorption at 100 cm "1 attributed to the hydrogen in carboxyl ( monomer), - absorption at 1623 cm "1, which is attributed to -0-0-, - absorption at 1393 cm" 1- 1381 cm "1, which is attributed to the hydrogen atoms in the twin methyl groups.

20 JF.MR spectrum (deuterochloroform): - peaks at 1.32 - 1.35 ppm attributed to the hydrogen atoms in the twin methyl groups, - peaks at 1.95 to 2.5 ppm attributed to the hydrogen atoms at the 1 and 3 positions of cyclopropyl, - peak at 3.83 ppm, which is attributed to the hydrogen atoms in the methyl group in methoxyl, - peaks at 7.28 - 7.45 ppm, attributed to the hydrogen in the double bond in the side chain at the 3-position in cyclopropyl, - peak at 10 , 75 ppm, which is attributed to the hydrogen in carboxyl. Step B: (IR.cis) -2,2-dimethyl-3- (E) - (2-chloro-2- (methoxymoronyl) -e thenyl) oyclopropane-1-oreboxylic acid chloride.

2.9 g (1R, cis) -2,2-dimethyl-3- (E) - (2-ehloro-2- (methoxycarbonyl) -ethenyl) -cyclopropane-1-carboxylic acid, 20 ml of isoprene and 10 ml ml of thionyl chloride, stirring at 20 ° for 3 hours, eliminates isoprene and thionyl chloride by distillation.

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- 14 - lation under reduced pressure to give 6 g of crude (IR, cis) -2,2 - dimethyl-3- (E) (2-chloro-2- (methoxycarbonyl) -ethenyl) cyclopropane-1-carboxylic acid chloride .

Example 3 (Application Example) (IR # cis) -2,2-Dimethyl-3- (E) - (2-bromo-2- (propoxycarbonyl) -ethenyl) -cyclopropane-1-carboxylic acid (S) - alpha-cyano-3-phenoxybenzyl ester In a solution of 2'6 g (1R, cis) -2,2-dimethyl-3-10 - (E) - (2-bromo-2- (propyloxycarbonyl) ethenyl) cyclopropane - -1-carboxylic acid in 40 ml of methylene chloride is introduced 0.9 roll of pyridine, 2 g of dicyclohexylcarbodiimide stir 10 minutes, add 2 g of (S) -alpha-cyam-3-phenoxybenzyl alcohol, stir for 10 minutes, add 25 mg of 4-dimethylaminopyridine , stirring for 1 hour 30 minutes, eliminating the insoluble matter formed by filtration, evaporating the filtrate to dryness by distillation under reduced pressure, chromatographing the residue on silica gel eluting with a mixture of cyclohexane and ethyl acetate (95: 5) to obtain 0.743 g of the expected ester and 3.64 g of a mixture which dissolves in the heat in 4 volumes of isopropyl ether, stirring at 20 ° C and isolating the formed precipitate by suction drying it combines it with the 0.743 g substance obtained above and yields 2.32 g (1R, cis) - 2,2-dimethyl-3- (E) - (2-bromo-2- (propoxycarbonyl) -ethenyl) - Cyclopropane-1-carboxylic acid (S) -alpha-cyano-3-phenoxybenzyl ester with m.p. 68 ° C.

Analysis: δ 26.23 ° C δ 512.41 Calcd: C $ 60.95 H # 5 # 11 2.73 Brj £ 15.6 Found: 61 5.1 2.5 15.5 IR spectrum (chloroform) : - Absorption at 1737 cm -1, attributed to the carbonyl group of the ester group, - Absorption at 1705 cnf \ attributed to the carbonyl group of the conjugated ester, 35 - 1 - Absorption at 1605 to 1610 cm attributed to -C = C- - absorption at 1585-1485 cm cm \ attributed to the aromatic rings.

-15-

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N, M. R. spectrum (deuterochloroform): - peaks at 0.88 - 1.0 - 1.12 ppm attributed to the hydrogen atoms of the methyl group in propoxyl, - peaks at 1.22 - 1.23 ppm attributed to the hydrogen atoms in - the peaks at 1.92 - 2.06 ppm attributed to the hydrogen at the 1-position in cyclopropyl, - peaks at 4.08 - 4.18 - 4.28 ppm attributed to the hydrogen atoms of the methylene in 1- the position in propyl, 10 - peaks at 6.38 ppm attributed to the hyarogen atom cured by the same carbon atom as CiT, - peaks from 6.9 to 7.51 ppm attributed to the hydrogen in the ethylenic double bond, - peaks at 6 , 92 - 7.6 ppm, ascribed to the hydrogen atoms of the aromatic rings # (IR, cis) -2,2-d ime thy 1-3 - (E) - (2-bromo-2 - (propoxy c arbo (Nyl) -ethenyl) -cyclopropane-1-carboxylic acid can be prepared as follows (Preparation Example):

To a solution of 3.1 g (1R, Eis) -2,2-dimethyl-3- O - (E) - (2-bromo-2- (propoxycarbonyl) -e thenyl) -cyclopropane-1-carboxylic acid -tert * -butyl ester obtained simultaneously with the 3- (Z) isomer in step A by the preparation of the corresponding 3 - (Z) acid in Example 4 in 3.1 ml of toluene. 0.31 g of p-toluenesulfonic acid monohydrate is charged, the container containing the reaction mixture is placed in an oil bath at 120 ° C for 15 minutes, rapidly brings the temperature of the reaction mixture to 20 ° 0, extracted with ether, washed the organic extracts with water, dried evaporating them to dryness by distillation under reduced pressure to give 2.6 g of 30 (IR, cis) -2,2-dime thy 1-3- (E) - (2-bromo-2- (propozycarbonyl) -e the -nyl) -cyclopropane-1-carboxylic acid.

Example 4 (Application Example) (IR. Cis) -2- (2-Dimethyl-3- (E) -2-fluoro-2- (ethory carbonyl) -e thenyl) -cyclopropane-1-carboxylic acid #

(IR, cis) -2,2-dimethyl-3- (E, Z) - (2-fluoro-2-ethoxycarbonylethenyl) -eyclopropane-1-earboxylic acid is prepared from 12.2 g of lactone of (1R, cis) ) -2,2-Dimethyl-3- (3-hydroxymethyl) -cyclopropane-arboxylic acid, working as in Example 1

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- 16 - Substituting the ehromatography of Example 1 with a chromatography on silica gel eluting with a mixture of cyclohexane and ethyl acetate (75:25) and then with the same mixture at a 50:50 ratio to obtain 14.5 g (1R) , cis) -2,2-Dimethyl-3- (E) - (2-fluoro-2-e-thoxycarbonylethenyl) -cyclopropane-1-carboxylic acid, (¾ - -42.5 ° (c = 1) (chloroform).

NMR, spectrum (deuterochloroform): - peak at 128 ppm, attributed to the hydrogenate urns in the bilingual thiol groups, - peaks at 1.23 - 1.35 - 1.47 ppm and 4.13 - 4.25 - 4.37 -4.48 ppm attributed to hydrogen atoms in. the ethyl group in ethoxycarbonyl, - peaks at 1.82 - 1.97 ppm, which is attributed to the hydrogen at the 1-position in cyclopropyl, - peaks at 2.75 - 2.9 - 3.05 ppm, which is attributed to the hydrogen in 3 the position in cyclopropyl, - peaks at 6.12 - 6.28 - 6.47 - 6.63 ppm attributed to the ethylenic hydrogen (J about 21 Hz, corresponding to a 20 cis derivative), - peak at 11 , 28 ppm, which is attributed to the hydrogen in carboxyl.

Working as in Example 1 from the corresponding alcohols, the following compounds are prepared (Examples 5, 6, 7 and 8 (Examples of Use));

Example 5. (Application Example) (1 R, Eis, ΔΕ) -2,2-dimethyl thy 1-3 - ((2-fluoro-2-th oxy carboxy 1) -e the-nyl) -cyclopropane carboxylic acid (R ) -3-Ethynyl-3-phenoxyphenyl methyl ester, m.p .: 72 $, α- = + 40 ° + 1.5 ° (c = 1 $, CHCl 3).

30

Example 6¾ (Application Example) (IR, cis. ΔΕ) -2,2-D ime thy 1-3 - (2-fluoro-2-thioxy carboxylic th e new 1) -cyelopropanecarboxylic acid- (R) - (3-phenoxyphenyl) thiols, yield 81 $, α $ $ 94.5 ° + 2.5 ° (c = 0.5 $, OHCl₂).

35.

_ 17 _

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Example 7. (Application Example) (IB, cis, ΔΕ) -2,2-Dimethyl-3- ((2-fluoro-2-ethoxycarbonyl) -ethyl) -eyclopropane-1-carboxylic acid (S) -α -cyan-3-phenoxy-4-fluorobenzyl ester, aD = + 50 ° + 2.5 ° (c = 0.5 $, CHCl3).

5

Example 8 .. (Application Example) (IR, cis, ΔΕ) -2,2-dimethyl thy 1-3 - ((2-fluoro-2-thioxycarbony) ethylene-cyclopropane -l-earboxylic acid 3-phenoxybenzyl ester, I .R. spectrum: 10 0 = 0 ester J 1725 cm -1 C = 0 conjugated ester) C = C conjugated 1655 cm * 1 aromatic groups 1588-1489 cm * 1 twin dimethyl 1390-1380 cm * 1 15

Example of preparation of comparison compound: Trans compound.

(IR, trans) -2,2-Dimethyl-3- ((AE-2- fluoro-3-oxo-5-ethoxypropylene) -cyclopropanecarboxylic acid (S) -g-cyano-3-Ph enoxybenzyl) ester '

Working as Example 1 from (IR, trans) - -2,2-dimethyl thy 1-3- (ΔΕ-2-fluoro-3-oxo-3-ethoxypropenyl) -cyclopropane carboxylic acid and ( S) -α-cyano-3-phenoxybenzyl alcohol gives the expected compound, - -33.5 ° ± 2.5 ° (c = 0.5 #, chci5.

(IR, trans) -2,2-D ime thy 1-3 - (ΔΕ-2-fluoro-3-oxo-3-thioxy-propenyl) -cyclopropanecarboxylic acid is prepared as follows. over 30 minutes a suspension containing 60 ml of 1,2-dimethoxyethane and 2.6 g of 60 µl sodium hydride suspension in oil a solution containing 7.7 g of diethylphosphonofluoroacetic acid ethyl ester prepared as described in Ann, Chem * (1964) 674, 60 ml of 1,2-dimethoxyoxyethane and 4 g (IR, trans) -2,2-dimethyl 1-3-formylcyclopropane carboxylic acid *

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- 18 ~

Stirring is continued for 25 minutes at 5 ° G and then 5 hours at room temperature. A solution is obtained which is poured into an aqueous mixture to allow us to dissolve at 5 ° C and stir for 10 minutes. Extract with ethyl acetate, wash with water, dry and evaporate to dryness at 40 DEG C. under reduced pressure # 6.5 g of an oil which is chromatographed on silica gel eluting with a mixture of hexane, ethyl acetate and acetic acid (70:30 -: 1). Thus, 4 g of the expected compound are obtained.

10

Reference Example I

(IR. Trans) -2,2-dimethyl-5 - ((AE) -2-fluoro-3-oxo-3-methoxyprope-phenyl) -cyclopropanecarboxylic acid (S) -g-cyano-3-phenoxy-benzyl ester. Grin As (IR.trans) -2,2-dimethyl-3 - ((AE) -2-fluoro-3-oxo-3-hydroxypropenyl) -cyclopropanecarboxylic acid (S) -g-azane-5-phenoxybenzyl ester.

50 mg of p-toluenesulfonic acid monohydrate are added to a solution containing 1 g (IR, trans) -2,2-dimethyl 1-3 - ((ΔΕ) -2-fluoro-3-oxo-3-e thoxypropenyl) - cyclopropane carboxylic acid (S) - α-cyano-3-phenoxybenzyl ester, 1 ml of water and 4 ml of dioxane.

The reaction mixture is heated to reflux for 8 hours and evaporated to dryness at room temperature under reduced pressure. The residue is taken up in methylene chloride, washed with water and dried. Evaporate to dryness to give 1.1 g of oil which is chromatographed on silica gel eluting with a mixture of hexane, ethyl acetate and acetic acid (60: 40: 1).

Thus, 280 mg of the expected compound is obtained.

Step B: (IR. Tran s) -2,2-fluoromethyl-1-3 - ((ΔΕ) -2-fluoro-3-oxo-3-meth th -oxypropenyl) -cyclopropanoarboxylic acid (S) -tt -cyano-5-phenoxy-benzyl ester.

At a temperature of 5-10 ° 0, a small excess of diazomethane dissolved in methylene chloride is added to 2 ml of a solution of methylene chloride containing 860 mg of the compound prepared in step A. Stirring is continued for 15 minutes at 5 ° C and then 30 minutes at room temperature. Add a few drops of acetic acid and evaporate to dryness. Thus, 950 mg of an oil is obtained which is chromatographed on silica gel eluting with a mixture of hexane and ethyl acetate (85il5). Looks available 700 mg of the expected compound - 19 -

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Reference Example II

(IR. Cis) -2,2-dimethyl by 1-3- ((AZ) -2-fluoro-3- (3-tert-butoxy-propenyl) -cyclopropane carboxylic acid (S) - g-oyan-3-phenoxybenzyl-benzyl ester.

2.3 g of (IR, cis) -2,2-dimethyl-3- (2-fluoro-3-oxo-3-hydroxy- (Z) -propenyl) cyclopropanecarboxyl is stirred for 2 hours. Y is - (S) -α-cyan-3-ph an oxybenzyl ester, 15 ml of ethyl acetate and 2.4 g of N- (1-methylethyl) -H1 - (1-methylethyl) -carbamic acid acid-butyl ester, Filtrate, evaporate the filtrate to dryness and give 2.6 g of product which is purified by chromatography on silica gel eluting with n-hexane and isopropyl ether (8: 2) under nitrogen pressure. There are obtained 2.2 g of compound which is recrystallized from isopropyl ether. 1.4 g of the expected compound are obtained with m.p. 103 ° C, + = 2.5 ° + 3 ° (c = $ 0.2, CHCl3).

N- (1-methylthyl) -3- (1-methylethyl) -carbamic acid tert.-butyl ester is prepared as follows:

98.7 g of H 2 -diisopropylcarbodiimide and 57.9 g of tert-butyl alcohol are stirred in the presence of 5 g of cuprous chloride 20 for 4.5 days at room temperature. Rer is obtained 117.7 g of the expected compound after distilling the reaction mixture below 9 mm Hg (and 74 ° C below 9 mm Hg).

Example 9. (Application Example) (IR, cis) -2,2-Dimethyl-3- (2-fluoro-5-oxo-3-methoxy- (E) -propyl) -cyclopropane carboxylic acid (S) 5-phenoxybenzyl ester. Step_JL: (IR, cis) -2- 2-Dimethyl 1-3- (2-fluoro-3-oxo-5-hydroxy- - (E) -propenyl) oyclopropanoarboxylic acid (S) 30 -5-Phenoxybenzyl ester.

A solution containing 2.5 g of (1R, cis) -2,2-dimethyl-3 - ((E) -2-fluoro-2-ethoxycarbonylethenyl) cyclopropane-1-carboxylic acid (S) was refluxed for 24 hours. ) -α-Cyan-3-phenoxy-benzyl ester, 10 ml of dioxane, 2.5 ml of water and 1 g of p-toluenesulfonic acid monohydrate. It is allowed to re-enter room temperature, diluted with methylene chloride and washed with water. The organic phase is dried, filtered and the filtrate is evaporated under reduced pressure. Chromatograph the obtained one

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- 20 - residue elutes with a mixture of cyclohexane, ethyl acetate and acetic acid · (60: 40; l) · Thus the expected compound (980 m 2 · laughing B: (IR «cis) -2« 2- diroethyl-3- (2-fluoro-3-oxo-3-methoxy-5 (E) -propenyl) -cyolopropanecarboxylic acid (S) -g-cyano-3-phenoxybenzyl ester

Working as in Reference Example I, Step B from (1R, cis) -2,2-dimethyl-3- (2-fluoro-3-oxo-3-hydroxy- (E) -propyl) -cyclopropane carboxylic acid (S) -α-Cyan-3-phenoxybenzyl-ester, gives the expected compound, mp 70 ° C, + 52 ° + 1.5 ° (c * 1 #, CHOlj).

Working as in the previous example from the corresponding alcohols, the following compounds are prepared: 15

Example 10. (Application Example) (IR, cis) -2,2-Dimethyl-3- (2-fluoro-3-oxo-3-n-propyl) (E) -propenyl) cyclopropane carboxylic acid - (S) -α-Cyan-3-phenoxybenzyl ester, = + 38.5 ° + 2 ° (c »0.7 $>, GHC1-) · 20 y

Example 11. (Application Example) (IR, cis) -2,2-Dimethyl-3- ((ΔΕ) -2-fluoro-3-oxo-3-tert-butoxy-propenyl) -cydopropane carboxylic acid (S) - α-cyano-3-phenoxybenzyl ester.

25

Working as in Reference Example II from (1R, cis) - 2,2-dimethyl-3- (2-fluoro-3-oxo-3-hydroxy- (E) -propenyl) -cyclic acid clopropanecarboxylic acid (S) -α-cyano-3-phenoxybenzyl ester and R- (1-methylethyl) ~] i * - (1-methylethyl) -arboxylic acid tert -butyl ester give the expected compound (yield 61 $)

At = + 26.5 ° (c = 0.25 $, CHCl3).

Example 12: (Application Example) (IR IR «) -2-2-dimethyl-3- ((AB) -2-fluoro-3-oxo-3- (1 «1 «1 «3,3-hexafluoro) - is.opropoxy-n-propenyl) -oyclopropane carboxylic acid - (S) -α-cyano-3-phenoxybenzyl ester,

Working as in Reference Example I, Step B based on - 21 -

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(IR, cis) -2,2-dimethyl-3- (2-fluoro-3-oxo-3-hydroxy- (E) -propenyl) -cyclopropanecarboxylic acid (S) -α-cyaric acid 5-pienoxy-benzyl ester and 1,1,1,1,3 * 3,3-hexafluoropropan-3 * -ol, to give the expected compound, = + 21 ° + 2 ° (c = 0.5 $, CHCl3) , 5

Example 13. (Application Example) (IR, cis) -2,2-Dimethyl-3- (2-fluoro-3-oxo-3-isopropyloxy- (E) -propenyl) -ecyclopropane carboxylic acid (S) -α-cyano -3-phenoxybenzyl ester, Or, - 46 ° + 1 ° (c * 1 #, CHCl *).

10 n J

Example 14. (Application Example) (IR, cis) -2,2-Dimethyl-3- (2-fluoro-3-oxo-3-cyclopropyloxy- (E) -propenyl) -cyclopropanecarboxylic acid - ('S) -α-cyano -3 · phenoxybenzyl ester, cu. = + 35 ° + 1 ° (c = 1.3 $, CHCl *), m.p. 50 ° C.

15 Ώ p

Example 15, (Application Example) (IR, cis, ΔΕ) -2,2-dimethyl-3- (2-fluoro-3-oxo-3- (β-methoxyethoxy) propenyl) cyclopropane carboxylic acid (S ) -a-eyan-3-phenoxy-benzyl ester, ou - 47 ° + 2.5 ° (c = 0.5 $ CHCl *).

20

Reference Example III

(IR, cis) -2,2-dime thy 1-3- ((AZ) -2-chloro-2-methoxycaronylethanyl) -cyclopropanecarboxylic acid - (S) -α-cyano-3-pb enoxybenzyl ester, 3Q Working as in Example 1 from (1R, cis) - 2,2-dime thy 1-3- (Z) - (2-chloro-2-methoxycarbonyl thenyl) -cyclo-propane carboxylic acid and (S) -α -cyan-3-phenoxybenzyl ester gives the expected compound, s 62.5 ° + 1.5 ° (c «1 $, benzene).

35

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- 22 -

Example 16. (Application Example) (IR, cis) -2,2-D-dimethyl-3 - ((AE) -2-chloro-2-methoxycarbonylethylethane-1) -oyelopropanecarboxylic acid - (S) -2- Methyl 4-oxo-3- (2-prope-nyl) -2-cyclopenten-1-yl ester The compound is prepared as the previous compound from (1R, cis) -2,2-dimethyl-3- (Z ) - (2-Chloro-2-methoxycarbonylethenyl) -cyclopropane carboxylic acid chloride and (4S) -hydroxy-3-methyl-2- (2-propenyl) -2-cyclopent-1-one, aD = -15 ° +4 ° (c = 0.25 $, benzene).

10 H.M.R. spectrum, CDCl3, ppm: - 1.28 and 1.3 Hi methyl groups at the 2-position - 3.8 Hi -002C | 3 -2.02 H in Η30χ β O- X5 · · - 6.8 - 7 ethylenic H, which is carried by the carbon atom in the 1-position of 2-methoxycarbonylethanyl.

. Example 17. (Referring to Example) (IR, cis) -2,2-dimethyl-1-3 - ((E) -3-oxo-2-chloro-oxypropenyl) -oyclopropanoarboxylic acid - (S) - g-cyano-3-phenoxybenzyl ester.

Working as in Example 1 from (1R, cis) - 2,2-d ime thi1-3 - ((E) -3-oxo-2-chloro-3-thoxypropenyl 1) -cyclo-propane carboxylic acid and (S) -α-cyano-3-phenoxybenzyl ester, gives 6 $ η when the expected compound, ajj * +19 +2 (c »1 $, chci3).

(IR, cis) -2,2-d ime thy 1-3- (3-o-2-chloro-3-thoxypropenyl) -cyclopropanoarboxylic acid (isomers E and Z) prepared 3Q as follows (Preparation Example):

Step A: Ethoxycarbonylcloromethylentriphenylubosphorane.

A solution is prepared at ca. 2 ° C of 4 g of chlorine in 80 ml of chloroform. 20 g of ethoxycarbonylmethylenetriphenylphosphorane are added in 40 ml of chloroform. The reaction mixture temperature is allowed to rise to room temperature and evaporated to dryness under reduced pressure. An oil is obtained which is dissolved in 70 ml of methylene chloride and washed with a solution of 6.1 g of sodium carbonate in 40 ml of water and then with water. Dry and evaporate to dryness. 18.9 g of the expected compound are obtained, m.p. 116-118 ° 0th

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- 23 -

Step B: (IR · cis) -2,2-dimethyl-3- (5-oxo-2-chloro-5-ethoxypropenyl) oyclopropanoarboxylic acid (isomers E and Z),

6.9 g of lactone of (IR, cis) -2,2-dimethyl-3-dihydroxymethylcyclopropane-1-carboxylic acid in 100 ml of tetrahydrofurfuran are added to a solution containing 18.9 g of the compound of step A in 200 ml of tetrahydrofuran · The resulting solution is stirred for 6 hours at room temperature and the solvent is distilled off under reduced pressure. An oil is obtained, which is taken up in 50 ml of ethyl ether, then stirred at 0 ° C, filtered and washed. precipitate obtained with ether and evaporates the filtrate to dryness. Rer is obtained 22.2 g of the expected compound which is chromatographed on silica gel eluting with a mixture of cyclohexane, ethyl acetate and acetic acid (75 * 25 * 1). is thus obtained »15 A) and 3.58 g of the expected compound in the form of E-isomer, M # M # R. spectrum, CRClCl, ppm: - 1.3 and 1.33 H of the methyl groups at the 2-position of cyclo-ProPPa · - 1.89 - 2.02 H of the carbon at the 1-position of eyclopropane, - 2.85 to the 3.05 Hi carbon at the 3-position in eyclopropane, -6.78 - 6.95 Hi the carbon at the 1-position in propenyl, B) and 2.34 g of the corresponding Z compound, HMR spectrum, CRCl, ppm:

25 P

- 1.33 and 1.36 H in the methyl groups at the 2-position, - 1.96 - 2.1 Hi the carbon at the 1-position in eyclopropane, - 2.23 to 2.53 Hi the carbon at the 3-position in the eyclopropane · Example 18. (Application Example) (1R, cis) -2,2-Aimethyl-3- (CE) -5-oxo-2-chloro-5-propoxypropenyl) cyclopropanoarboxylic acid (S) -α-cyano- (3- phenoxybenzyl) ester. Working as in Example 1 from (1R, cis) - 2,2-dimethyl-3- ((1) -3-oxo-2-chloro-3-propoxypropenyl) -cyclo-propane carboxylic acid and (S) -α-cyano-3-phenoxybenzyl alcohol gives the expected compound, ctjj = + 24.5 ° + 2 ° (c * 0.4 $, CHCl 2).

_ 24 -

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(1R, cis) -2,2-Aimethyl-3- ((E) -3-oxo-2-chloro-3-propoxy-propenyl) -cyclopropane carboxylic acid is prepared as follows: (Preparation Example): 5

Step A: Propoxyoarbonylohlormethylentriphenylphosphorane.

is employed as for the preparation of (1R, cis) - 2,2-dimethyl-3 - ((E) -3-oxo-2-chloro-3-ethylthoxypropenyl) -cyclopropanecarboxylic acid, Example 17 Step A, ua from propoxy arbonylmethylenetriphenylphosphorane, to give the expected compound, laughter B: (1R, O8) -2,2-dimethyl-3 - ((E) -3-oxo-2-chloro-3-propane). oxypropenyl) -cyclopropane carboxylic acid,

Working as for the preparation of (1R, cis) -15 -2,2-dimethyl-3 - ((E) -3-oxo-2-chloro-3-ethoxypropenyl) -cyclopropane carboxylic acid, Example 17, Step B , from the compound prepared in step A, one obtains the expected compound and the corresponding ΔΖ isomer.

20

Example 19. (Application Example) (IR, cis) -2,2-Dimethyl-3- ((E) -3-oxo-5-tert.-butoxy-2-obloro-propenyl) -cyclopropane carboxylic acid (S) -g -cyano-3-phenoxybenzyl-zyleater.

Working as in Example 1 from (1R, cis) - -2,2-dime thyl-3- ((E) -3-oxo-3-tert-butoxy-2-chloropropenyl 1) - cyclopropane carboxylic acid and (S ') - α-cyano-3-peneoxybenzyl alcohol give the expected compound, ap = + 30.5 ° + 2 ° (c «0.7 $, CHCl 3), 30 (IR, cis) -2 , 2-dimethyl-0-oxo-3-tert. -butoxy-2-chloro-propenyl) -cyclopropane carboxylic acid (isomers E and Z) are prepared as follows (Preparation Example): Layer A: tert, -butoxyoarbonylchloromethylenetripbenylphosphorane. Working as above (preparation of continuation of Example 30, Step A), the expected compound is obtained from tert-butoxycarbonylmethylenetriphenylphosphorane, m.p. ca. 160 ° C,

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25η B: ΔΕ acid + AZ acid,

Working from the compound of Step A as set forth in the preparation of Example 250, Step B, one obtains (1R, cis) -2,2-dimethyl-3-5 ~ ((E) -3- oxo-3-tert-butoxy-2-chloropropenyl) -cyclopropanecarboxylic acid, m.p. 65 ° C and partly the corresponding Z-i s omer, m.p. below 50 ° C, 10

Preparation.

(1R, cis) -2,2-dimethyl-3- (2-bromo-3-oxo-3-methoxy- (Z) -propenyl) -eyclopropanecarboxylic acid is prepared as follows: Grin A: (1R.ois) -2'-2-Dimethyl-5- (1,2- (dibromo-R 6S) -3-oxo-5--methoxypropyl) oyclopropanecarboryl acid tert -butyl ester.

13.3 g of pyridine bromide are added to a solution containing 8.07 g (1R, cis) -2,2-dimethyl-3- (2-methoxy-carbonyl- (E) -e thenyl) -eyclopropane carboxylic acid -tea · butyl ester, prepared from the corresponding acid disclosed in European Patent Application No. 0018 894, and 25 ml of dimethyl sulfide oxide * The reaction mixture is stirred for 3 hours 30 minutes and poured into ice-cold water '

Extract with methylene chloride. The organic phases are combined, dried and evaporated to dryness under reduced pressure. 14.3 g of oil are obtained which are chromatographed on 30 silica gel eluting with a mixture of hexane and ethyl acetate (9 · * 1) · 4.3 g of the expected compound are obtained «35 - 26 -

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Step B: (IR, ois) -2,2-dimethyl-3- (2-bromo-3-oxo-3-methoxy- (Z) -. Propenyl) oyclopropanoarboxylic acid tert, butyl ester. 4 ml of triethylamine are added to a solution containing 40 ml of benzene and 4.2 g of (1R, Eis) -2,2-dimethyl-3- (1,2, 2-5 - (dibromo-R, S) -3-oxo- 3-methoxypropyl) -cyclopropancarboxyl acid tert-butyl ester. The reaction mixture is stirred for 6 hours 30 minutes at 22-24 ° C, diluted with ether and washed with a solution of monosodium phosphate and then with water. Dry and evaporated under reduced pressure 10 µl at 40 DEG C. Thus 3.3 g of the expected compound are obtained, grin 0: (IR, cis) -2,2-dimethyl-3- (2-bromo-3 -oxo-3-methoxy- (Z) - propenyl) -cyolopropancarboxylsyre.

A mixture of 3.3 g of the compound prepared in step B, 30 ml of toluene and 0.33 g of p-toluene-sulfonic acid monohydrate is refluxed. Reflux is maintained until gas development is completed. It is cooled to 20 ° C, diluted with ethyl ether and washed with water. Dry and evaporated under reduced pressure at 40 ° C. Thus, 2.9 g of the expected compound are obtained.

Eksempel20 '. (Example) (IR, cis) -2,2-dimethyl 1-5 - ((E + Z) -3-oxo-5-methoxy-2-bromopropyl-nyl) -cyclopropanoarboxylic acid (S) -g-cyano-5-phenoxybenzyl ester. Working as in Example 1 from (1R, Eis) -25 -2,2-dimethyl-1-3 - (2-bromo-3-oxo-3-methoxy- (E) -propenyl) -cyclo -propane carboxylic acid and (S) -α-cyano-3-phenoxybenzyl alcohol give the expected compound, * = + 9.5 ° + 2.5 ° (cs 0.3 $, CHCl 3).

(IR, e s) -2,2-dimethyl-1-3 - (2-bromo-3-oxo-3-methoxy- (E) -propenyl) -cyclopropane carboxylic acid is prepared as follows:

Preparation Example: Layer A: (IR, cis) -2,2-Dimethyl-3- (2-bromo-5-oxo-5-methoxy- (E) -35-propenyl) -cyclopropane carboxylic acid tert -butyl ter.

100 ml of 50 $ sodium hydroxide solution are added. -

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to a mixture containing 120 ml of methylene chloride, 6.7 g (1B, e s) -2,2-d ime thy 1-3 - (1,2- (d ibromo-R, S) -3-oxo-3 - with th oxy-propyl) -cyclopropan tert.-butyl ester and 120 mg of cetavlon (trimethylcetylammonium bromide). The reaction mixture is stirred for 4 hours. The mixture is diluted by adding 100 ml of methylene chloride and decanting the organic phase which is re-extracted with 100 ml of methylene chloride. The organic phases are washed with 1 H hydrochloric acid to acidic pH and then with water to pH 7. The organic phases are combined, 10 dried and evaporated under reduced pressure at 40 ° 0 # 5 »3 g of a material which is chromatographed eluting with a mixture of hexane and isopropyl ether (8: 2).

3 »5 g of the expected compound are obtained. * Grin B: (1Rtcis) -2- 2-dimethyl 1-3- (2-bromo-3-oro-5-methoxy-15 - (E) -propenyl) -cyclopropanecarboxylic acid.

A solution of 3 * 4 g (1R, cis) -2,2-dimethyl-3- (2-bromo-3-one-3-methoxy- (E) -propenyl-1) pancarboxylic acid tert-butyl ester, 30 ml of toluene and 0.35 g of p-toluenesulfonic acid monohydrate. Reflux is maintained until the end of gas evolution. Cool to 0 ° 0, filter, wash the precipitate obtained with cold toluene and evaporate the filtrate at 40 ° C under reduced pressure. 2.8 g of the expected compound are obtained.

Example 21y (Application Example) (1R.ois) -2,2-dimethyl-5- ((E) -2-bromo-5-oxo-3-tert.-butoxypropenyl) -cyclopropanoarboxylic acid (S) -tt-cyanoic acid 3-nhenoxybenzyl ester.

Working as in Example 1 from (1R, cis) -30 -2,2-dimethyl-1-3- ((E) -2-bromo-3-oxo-3-tert-butoxypropenyl) - cyclopropane carboxylic acid and (S) -α-cyano-3-phenoxybenzyl alcohol give the expected compound, ctp = + 16.5 ° + 2 ° (c »0.7 #» chci5).

(IR, cis) -2,2-dimethyl-1-3 - ((E) -2-bromo-3-oxo-3-tert-35-butoxypropenyl) -cyclopropane carboxylic acid is prepared as follows.

yeast (manufacturing example):

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- 28 -

Step A; tert, -butoxyoarbonyl bromomethylentriphenylphosphorane.

Working as in the preparation of (IR, cis) - 2,2-dimethylphayl-3- ((E) -3 -ozo-2-chloro-3-eth oxypropenyl) -cyclo-propane carboxylic acid (Example 30, Step A) from the tert-butoxycarbonylmethylenetriphenylphosphorane derivative and bromine give the expected compound at m.p., 190 ° C.

Step B: (IR) cis -2-2-Diraethyl-3- ((E) -2-bromo-3-oxo-5-tert, - (butoxypropenyl) -oyolopropanoarboxylic acid.

Working as in the preparation of (1R, cis) -10 -2,2-dimethyl-3- ((E) -3-oxo-2-chloro-3-ethboxypropenyl) -eyclo-propane carboxylic acid (Example 30, Step B ) from the compound prepared in step A, one obtains the expected compound with m.p. 76 ° C and the corresponding Z-isomer with m.p. Example 22 (Application Example) (1R.cis) -2,2-dimethyl-3- ((E) -3-oxo-2-bromo-3-ethoxypropenyl) cyclopropane carboxylic acid (S) -g -cyan-3-phenoxybenzyles ter.

Working as in Example 1 from (1R, cis) - 2,2-dimethyl 1-3- ((E) -3-oxo-2-bromo-3-ethboxypropenyl) cyclopropane carboxylic acid and ( S) -α-cyano-3-phenoxybenzyl alcohol gives the expected compound, α D = -70.5 ° + 2 ° (c »0.7 $, chCl 5).

(IR, cis) -2,2-Dimethyl 1-3- ((E) -2-bromo-3-oxo-3-thoxy-propenyl) -cyclopropanecarboxylic acid is prepared as follows (Preparation Example):

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- 29 -

Step A: Ethory carbonyl bromine thi len tri phenyl ph os ph oran.

The compound is prepared according to the procedure set for (1R, cis) -2,2-dimethyl-3 - ((E) -3-o: x: o-2-chloro-3-ethoxypropenyl) cyclopropane carboxylic acid in Example 30, Step A from e th oxy c arbonylme thy lent riph eny lph os -phorane derivative and bromine. Thus, the expected connection with m.p. 150 ° C.

Step B: (IR.cis) -2,2-dimethyl-1-3 - ((E) -2-bromo-3-oxo-3-ethoxy-propenyl) -cyclopropanecarboxylic acid.

The compound is prepared according to the process set forth for the preparation of the corresponding chlorinated acid from the substance prepared in step A.

Thus, you get the expected connection and the corresponding AZ connection.

15

Example 23. (Application Example) (1R.cis) -2,2-Dimethyl-3- ((E) -2-fluoro-5-oro-3-ethoxypropenyl) cyclopropanoarborylic acid -pyrid.vl-metbvlester.

o n

Working as in Example 1 from the corresponding acid and alcohol, the expected compound is obtained, o = = 35 ° + 4 ° (c = 0.3 $, CHCl 2).

Example 24. (Application Example) (1R, 10) -2- 2-Dimethyl-3 - ((E) -2-fluoro-3-oro-3-ethorypropenyl) oyclopropane carboxylic acid 3- (2-propypyl) - 2.5-dioroimidazoli-dinylmethylester.

Working as in Example 1 from the corresponding acid and alcohol, the expected compound is obtained, 0¾ = + 12 ° + 2 ° (c = 0.5 $, CHClCl).

Example 25. (Application Example) (IR. Cis) -2,2-Dimethyl-3- (((E) -2-fluoro-3-axo-3-ethboxypropenyl) -cyclopropanecarboxylic acid (S) -2-methyl-3 -allyl-4-oro-2-cyclopentene-1-ester.

Working as in Example 1 based on the - 313 -

DK 164402B

of acid and the corresponding alcohol gives the expected compound, - + 41.5 ° + 2.5 ° (c = 0.5 $, CHCl

Example a 5 Preparation of a soluble concentrate «

Homogeneous: Compound of Example 1 is mixed 0.25 g of piperonyl butoxide 1.00 g

Tween 80 0.25 g Topanol A 0.1 g water 98.4 g

Example b;

Preparation of an emulsifiable concentrate, 15

Thoroughly mixed: compound of Example 11 0.015 g piperonylbutoxide 0.5 g

Topanol A 0.1 g

Tween 80 3.5 g 20 rylene 95.885 g

Example c, ·

Preparation of an emulsifiable concentrate.

Homogeneous: Compound of Example 21 is mixed 1.5 g

Tween 80 20.00 g

Topanol A 0.1 g rylene 78.4 g 30, -

Example a

Preparation of a smoke preparation.

Homogeneous mixture: Compound of Example 1 0.25 g taboo powder 25.00 g 35 cedar powder 40.00 g pine sawdust 33.75 g brilliant green 0.5 g p-nitrophenol 0.5 g

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- .31-

Insecticidal examination of the compounds of the invention. In this study, (1R, cis) -2,2-dimethyl-3- (E) - (2-chloro-2-methoxycarbonylethenyl) -cyclopropane-1-carboxylic acid (S) -α-cyano- 3-phenoxybenzyl ester (compound 5A), (1R, cis) -2,2-dimethyl-3- (E) - (2-bromo-2-propoxycarbonyl-ethenyl) -cyclopropane-1-carboxylic acid (S) - α-cyano-3-phenoxy-benzyl ester (Compound B) and 10 (IR, cis) -2,2-dimethyl-3- ((E) -2-fluoro-2-e thoxy carbonyl thenyl) - cyclopropane carboxylic acid (S) -α-cyano-3-phenoxybenzyl ester (compound D), A, Investigation of the instantaneous knock-down effect on 15 housefly.

The test insects are 4-day-old female flies "Work at direct atomization at a concentration of 0.25 g per liter in Kearns and March's chamber, using as a solvent a mixture of acetone (5fi) and Isopar 20 L (solvent of the mineral oil class) (amount of solvent used 2 ml per second) 50 insects per treatment are used. Control is performed every minute until 10 minutes and then after 15 minutes, and KT 50 is determined by the usual methods.

The test results obtained are shown in the following table:

Compound KT 50 in minutes Compound A 3 »6 3q Compound B 4.5 'Compound D 2.1 B. Examination of the lethal effect of the compounds of the invention on various insects, 35 a) Examination of the lethal effect on housefly.

The test insects are 4-5 days old female flies.

Topical application of 1 μΐ acetone solution to the insect's dorsal thorax is performed using Arnold's micro-manipulator. 50 individuals are used per treatment. Mortality is checked 24 hours after treatment # - 32 -

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The results obtained, expressed in DI 50 or den (3ose in nanograms per individual, needed to kill 50 # of the insects) are as follows:

Compound DL 50 in ng per insect 5 compound A 11.1 compound B 1.0 b) Study of the lethal effect on cockroach.

The tests are carried out by contact on film on glass by application by pipette of acetone solutions with 10 different concentrations on the bottom of glass petri dishes, whose edges are already talcumated to prevent the escape of the insects. The lethal concentration 50 (01 50) is determined.

The experimental results obtained are shown in the following table: p

Compound CL 50 in mg / m Compound A 1.4 Compound B 0.40

20 N

(c) Investigation of the lethal effect on larvae of Spodoptera littoralis.

The tests are carried out by topically applying an acetone solution using Arnold's micromanipulator on the larval thoracic thorax. 15 larvae are used per day. dose of the compound to be tested. The larvae used are larvae in the fourth larval stage, ie with an age of approx. 10 days when breeding at 24 ° C and 65 # relative humidity. After treatment, individuals are placed in an artificial nutritional environment (Poitout's environment).

Mortality is checked 48 hours after treatment.

The test results obtained are shown in the following table: Compound DL. 50 µg per ng. insect

Compound A 6.7 Compound B 3.2 Compound D 1.0 d) Investigation of the lethal effect on Epilacna varivestris.

The tests are performed by topical application in analogy with

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- 33 - application to the larvae of Spodoptera * Larvae are used in the penultimate larval stage and after treatment the larvae are nourished with bean plants. Mortality is checked 72 hours after treatment. The results are shown in the following table:

Compound DL 50 in ng per insect

Compound A 17.7 Compound B 7.4 Compound D 0.85 10 e) Investigation of the lethal effect on Anhi's craoivora.

Adults are used after 7 days and 10 aphids per day are used. concentration used. A method of contact injection is used. Fisher1's gun is treated with a bean leaf, which is placed in i5 a plastic petri dish on a sheet of moistened paper. The treatment is carried out by means of 2 ml of acetone solution of the compound to be examined (1 ml on each side of the leaf). The insect infestation is performed-after drying the leaf. The insects are kept in contact with the leaf for 1 hour. The 20 insects are placed on untreated leaves and the mortality is checked after 24 hours.

The test results obtained are shown in the following table:

Compound DL 50 in ng per, insect 25 compound 3Γ 6.4 f) Conclusion.

In the experiments described in sections a, b, c, d and e, compounds A and B exhibit an interesting insecticidal activity.

(g) general conclusion.

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

C. Acaricide study of the compounds of the invention.

Bean plants are used comprising two leaves infected with 25 females of Tetranychus urticae per leaf and placed under the vented hood under a constant-light light panel. The plants are treated with Fisher's gun: 4 ml of poisonous solution per day. plant of a mixture of equal volumes of water and acetic acid

DK 164402 B

- 34 - tone. Allow 12 hours to dry and then infect. The mortality is checked 80 hours later. The dose used in each experiment is 5 g compound per day. hl.

Compounds A and b have good activity in the tea experiment, 10 15 20

Claims (3)

X represents a halogen and R represents a straight-chain, branched or cyclic saturated alkyl group of 1-8 carbon atoms, optionally substituted by one or several halogen atoms or low molecular alkoxy groups. Analogous process for the preparation of compounds II according to claim 1, wherein X and R have the same meaning as above, characterized in that, according to Wit-tig's reaction in the presence of a strong base, a cis-aldehyde in the form of lactone is reacted with formula V 25 ΛΚ H0 \ / XW 30 or a trans-aldehyde of formula VI! X J 35 / DK 164402 B - 36 - with a phosphorane of formula VII (C, H,), = P = C-X (VII) o 3 | C-OR, o 5 || Represents a alkyl group of 1 to 5 carbon atoms and X has the same meaning as above, or of a phosphonate of formula VIII 020 to II R20 ° -P ~ CH X "C" R19 (VIII) R ~ «“ 0 in which formula R ^ g and X have the same meaning as above and R₂ bet represents an alkyl group of 1-6 carbon atoms.