DD202422A5 - PROCESS FOR PREPARING PYRETHRINSACE-RELATED CYCLO-POLAR ACID ACID ACIDS - 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

-Jf-

2 Q ⁴ X 7 1 B 2 Berlin, 28.9.1982 ό O f * V AP C 07 C

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Process for the preparation of pyrethric acid-related cyclopropane carboxylic acid esters

Field of application of the invention

The invention relates to methods of preparation of pyrethric acid-related cyclopropanecarboxylic acid esters in all possible isomeric forms or isomeric mixtures. The novel compounds can generally be used in animal pest control, both alone and in mixtures with other compounds.

Characteristic of the known technical solutions

There are already a number of cyclopropane carboxylic acid derivatives known · It has been shown, however, that their effectiveness is not sufficient in each case.

Object of the invention

It is therefore an object of the invention, the state d r technique to enrich by new compounds.

Explanation of the essence of the invention

The object of the invention is to provide novel pyrethric acid-related cyclopropanecarboxylic esters and processes for their preparation.

According to the invention, compounds of the formula I are prepared in all possible isomeric forms or in the form of isomer mixtures

, 1982 * 038 912

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Therein R is either an unbranched, branched or ring-shaped saturated or unsaturated alkyl radical having 1 to 8 carbon atoms, which may be substituted by one or more identical or different functional groups, or an aryl group having up to 14 carbon atoms, possibly by one or more identical or different functional groups may be substituted, or a heterocyclic radical, which may be substituted by one or more identical or different functional groups. B is either an unbranched, branched or cyclic saturated or unsaturated alkyl radical having from 1 to 18 carbon atoms or the radical of an alcohol used in the synthesis of the pyrethrinoidene esters "and X is a halogen atom. The ethylene double bond has the geometric form Z or E.

The compounds of formula (I) may exist in many stereoisomeric forms. They have two asymmetric C atoms at the 1st and 3rd positions of the cyclopropane "

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also have E / Z isomerism of the double bond and may also have one or more Asymmetry Centers in Part B and Part R.

When B is an alkyl radical, it is preferably the methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl radical.

When B is the residue of aer for synthesizing the pesticide ester Pyrethrinoidreihe alcohol used, it is preferably one of the radicals that are further specified in a list below.

When R is a saturated unbranched or branched alkyl radical, it is preferably a methyl, ethyl, n-propyl, isopropyl, η-butyl, sec-butyl, isobutyl, n-pentyl, n-hexyl, tert-butyl, tert-pentyl or neopentyl.

When R is a cyclic radical, it is primarily a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl radical, an unbranched or branched alkyl radical bearing a cyclic radical, or the cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl radical substituted by one or more alkyl radicals attached to the group -COO- at any of its peaks, for example, 1-methylcyclobutyl, 1-methylcyclopentyl, 1-methylcyclohexyl or 2,2,3 , 3-Tetramethylzyklopropylradikal.

When R is an unsaturated alkyl radical, it is preferably an ethylene radical such as, for example

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3 3716 2 - * - «say /«

a vinyl radical or a 1,1-dimethylallyl radical or ura an acetylene radical such as the ethynyl or propynyl radical.

When R is an alkyl radical substituted by one or more functional groups, alkyl is preferably understood as meaning a radical of 1 to 8 carbon atoms, such as methyl, ethyl, propyl, isopropyl, η-butyl, isobutyl or tert .-butyl radical ·

When R 1 is an alkyl radical substituted by one or more functional groups, functional group is preferably taken to mean a halogen atom, a group -OH or -SH, a group OR * or SR * in which R 'is an alkyl radical of 1 to 8 carbon atoms is, a group

NO ₂ , -N

R ¹

in which R * 'and R *' *, which are the same or different, represent a hydrogen atom, or an alkyl radical having 1 to 8 carbon atoms, a group -0ΞΝ, SO ₃ H or PO.Hp or a group -COaIc ₁ , SCUaIc ₂ or SO 4 aIc ₃ in which alc ', alc ₂ and alc _{3 are} alkyl radicals having 1 to 18 carbon atoms.

R may also be an alkyl radical substituted by an aryl radical, such as the benzyl radical or the phenethyl radical, which may itself be substituted by one or more groups -OH, -OaIc or -alc of 1 to 8 carbon atoms.

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R can also be an alkyl radical which can be substituted by two adjacent C atoms by a group (G *)

0 H

/ C

0 H

or by a group

W _e nn R is an alkyl radical which is substituted by one or more functional groups, are the preferred radicals:

- (CHp) -C shark, in which η is an integer from 1 to 8 and Hal is a halogen atom, for example the radical -CH ₂ -CCl ₃ ,

-CH ₂ -CF ₃ , -CH ₂ -CH ₂ CCl ₃ or -CH ₂ -CH ₂ -CF ₃ ,

- (CH ₁₃ ) -CH Hai- = »wherein Hai is as defined above έ. n < c.

and n is a number from 0 to 8, for example the radical -CH ₂ -CHCl ₂ , -CH ₂ -CHF ₂ or -

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- (CH ₂ ) -CHp Hal, wherein η and Hal are as defined above, for example the radical -CH ₂ -CH ₂ Cl or -CH ₂ -CH ₂ F, -C- (CHaI,), wherein Hal as defined above, for example, the radical

-C- (CF ₃ J ₃ or -C-CF ₃

CCl ₃ ,

CF_. CF, CF,

3> * 3 ^ y 3

C is --CH, -C-CH, or -C-CH, N 3. 3 N ³

CF ^ CH, 3 3

^CF 3 ^CF 3

C - CH, or -C CF,

H H

CH-CH,

-C - CN, -C-CN or - (O-U) -CN, wherein η is as above

CH ₃ H

is defined above

chai

/ ³

~ C - CN, where shark is defined as before,

for example the radical -C CN,

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3 3 7 16 2 - ⁷ - ⁵⁹ ™ n *

- (ChU) -OR ', wherein η is as previously defined and R' is a Zn

Is hydrogen or an unbranched or branched alkyl radical of 1 to 8 carbon atoms, for example the radical -CH ₂ -OCH, -CH ₂ -CH ₂ -O-CH ₃ , -CH ₂ -CH ₂ -O-CH ₂ -CH ₃ or -CH ₂ -CH ₂ -OH,

R ¹ - (CH ₂ ) -N v wherein η and R "are as previously defined

R ¹

and the two radicals R * can be different from each other,

for example the- radical or -CH ₂ -CH ₂ -N • ^CH 3 in which H CH CH ₃ -CH ₂ -CH ₂ -N ^ ^CH 3 -CH ₂ -CH ₂ -N _n ^ CH ₂ -CH ₃ , η ₍ O I. ² O η as before is defined, for ^CH 3

For example, the radical -CH ₉ -CH CH, - i

II ^:

0 0

H ₃ C - ^CH 3

37 16 2.

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(CH ₂ ) _n -CH-OH

CH_, where η is as previously defined, t £

OH

for example the radical -

OH

- (CH ₂ ) -Ο- S * '. in which η is defined as before,

for example the radical -CH ₂ -O-j '''^ s or

-OP ⁰ N, -

»In which η as before

is defined, for example, the benzyl or the Phenetnylradikal,

2 η

in which η is as previously defined,

Example the radical

28,9.1982

s λ η ι C O ^{ΑΡ c} ° ^{7 c / 233 716/2}

3 y / y ö L · 9 - 59 837/12

When R is an aryl radical which may be substituted, it is preferably the phenyl radical or the phenyl radical represented by one or more groups -OH, OaIc or alc of 1 to 8 carbon atoms, by a halogen or by a -CF ₃ -, -OGF-- or -SCF_ group is substituted.

When R is a heterocyclic radical, it is preferably the pyridinyl, furanyl, thiophenyl, oxazolyl or thiazolyl radical.

By halogen is meant preferably a fluorine, chlorine or Bromatora.

More particularly, the invention relates to a process for the preparation of the compounds of formula (I) wherein the cyclopropanoic acid configuration has the structure IRycis or IRytrans.

The compounds prepared by this invention may include the compounds of formula (I) _f in which the double bond has the geometric form E and those in which X is a fluorine atom. For this purpose, the compounds of formula (I) are also to include, where R is a linear, branched or cyclic alkyl group having 1 to 8 carbon atoms and in particular an ethyl radical, a tert-butyl radical or a Zyklopropyl- or Zyklopropylmethylrest. Also to be mentioned are the compounds of the formula (I) in which R is an unbranched or branched alkyl radical having 1 to 8 carbon atoms which is substituted by one or more halogen atoms, for example those in which R is an unbranched alkyl radical

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with 1 to 8 carbon atoms substituted by one or more fluorine atoms. Also included are the compounds of formula (I) in which R is (CH ₀₎ O (CH_) -CH radical is represented in the m is an integer between 1 and 8, and η is an integer between O and 8 , and in particular the radical -CH

It is also possible to name the compounds of the formula (II) in which B is particularly specific

either an alkyl radical having 1 to 18 carbon atoms,

or a benzyl radical optionally substituted by one or more radicals selected from the group consisting of the alkyl radicals having from 1 to 4 carbon atoms, the alkenyl radicals having from 2 to 6 carbon atoms, the alkenyloxy radicals having from 2 to 6 carbon atoms, the alkadienyl radicals

radicals with 4 to 8 carbon atoms, the methylenedioxy radical and the halogen atoms are formed,

- or a group

in which the substituent R * is a hydrogen atom or a methyl radical and the substituent R _{2 is} a monocyclic aryl radical or a group -CH ₂ -CsCH and in particular a 5-benzyl-3-furylmethyl group, or a group

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in which a is a hydrogen atom or a methyl radical and R represents an aliphatic organic radical having 2 to 6 carbon atoms with one or more unsaturated CC bonds, in particular the radical -CH ₂ -CH =CH ₂ , -CH ₂ -CH = CH-CH ₃ , -CH ₂ -CH = CH-CH = CH ₂ , -CH ₂ -CH = CH-CH ₂ -CH- or a group

^a Λ

R '

ΛΑ

in the a is a hydrogen atom or a methyl radical, R_ defined the same as indicated previously, RV ₁ and R '', which may be identical or different, represent a hydrogen atom, a halogen atom, an alkyl radical having 1 to 6 carbon atoms, an aryl group having 6 to 10 carbon atoms, an alkyloxycarbonyl group having 2 to 5 carbon atoms or a cyano group, - or a group

in the B ^{1 is} an oxygen atom or a sulfur atom or 0

a group is -C- or -CH ₂ - or a sulfoxide group or a sulfo group and R is a hydrogen atom

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Radical -C = N, a methyl radical, a radical -CQNH ₂ , a radical -CSNH ₂ or a radical -C = CH, R _{5 is} a halogen atom or a methyl radical and η is an integer equal to 0, 1 or 2, and in particular the 3-phenoxybenzyl, the C-cyano-3-phenoxybenzyi, the rf-ethynyl-3-phenoxybenzyl, the 3-benzoylbenzyl, the 1- (3-phenoxyphenyl) ethyl or the "i Thioaraido-3-phenoxybenzyl group, or a group

- or a group

in which the substituents R, - R-, R and R "are a

6 7 ₈ 9

stoffatoro, represent a chlorine atom or a methyl radical and in the S / I denotes an aromatic ring or an analogous Dihydro- tetrahydro ring, or a group

233716 2 ---

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- N

- or a group

CH "- CH CH

^R 10

" ^CH

" ^R

in which R ^ _{0 is} a hydrogen atom or a radical -CN, R _{12 is} a radical -CH ₂ - or an oxygen atom, R ₁ ,. is a thiazolyl '* or thiadiazolyl radical', its attachment to -CH- at any disposal

^R 10

can stand, where R ^ ₂ with R ₃ . is joined by the carbon atom which is between the sulfur atom and a nitrogen atom, or a group ₀

- or a group

2 3 3 7 16 2-

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in which represents t or a group

a hydrogen atom or a radical -CN

in FL ₃ as defined above and the benzoyl radical is at the 3rd or 4th position, or a group

in which R _{14 is} a hydrogen atom, a methyl, ethynyl or cyano radical and R ₁₅ and R _1S t are different, a hydrogen, fluorine or bromine atom,

or a group

in the R.. as defined above, each of R 1 - independently of one another is an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms.

3 3 7 16 2 - "- ⁵⁹

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atoms, an alkylthio group having 1 to 4 carbon atoms, an alkylsulfonyl group having 1 to 4 carbon atoms, trifluoromethyl, 3,4-methylenedioxy, chloro, fluoro or bromo group, and ρ is an integer equal to 0, 1 or 2 and B "represent an oxygen or sulfur atom.

When B is a benzyl radical substituted by one or more alkyl radicals, it is preferably the methyl or ethyl radical.

When B is a benzyl radical * substituted by one or more alkenyl radicals, it is preferably the vinyl radical; allyl; 2-methylallyl or isobutenyl radical.

If B is a benzyl radical | which is substituted by an alkadienyl radical, is preferably a benzyl radical substituted by an alkadienyl radical having 4, 5 or 5 carbon atoms.

When B is a benzyl radical substituted by one or more alkenyloxy radicals, they are preferably the vinyloxy, allyloxy, 2-ethylallyloxy or isobutenyloxy radicals.

When B represents a benzyl radical substituted by one or more halogen atoms; they are preferably chlorine, bromine or fluorine atoms.

If B is the radical

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R _{3 is} preferably the radical -CH ₂ -CH = CH ₂ , -CH ₀ -CH = CH-CH-, -CH ₀ -CH = CH-CH = CH ₀ or -CH ₀ -CH = CH- CH ₀ -CH ,.

When R '* and (or) R' _{2 represent} ^a halogen atom, they are primarily chlorine, bromine or fluoratoni.

When R ** and (or) R ' _{o represent} an alkyl radical, it is predominantly the methyl, ethyl, n-propyl or n-butyl radical.

When R 'and (or) R' are an aryl radical, it is preferably the phenyl radical,

When R '. and (or) R 'represents an alkyloxy carbonyl radical, it is preferably the methoxy carbonyl or ethoxy carbonyl radical.

If in the radical

R ^ _{7 is} an alkyl, alkoxy- _s alkylthio or alkylsulfonyl radical, it is preferably ura the methyl,

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Ethyl, methoxy, ethoxy, methylthio, ethylthio, methylsulfonyl or ethylsulfonyl radical.

To the compounds obtained according to this invention, in which B has the meaning given above, one can count the compounds which correspond to the formula I *:

^H 3 ^C. ? ^H 3

in the A an oxygen atom! is a methylene group, a carbonyl group, a sulfur atom, a sulfoxide group or a sulfo group, R ₈ © in straight or branched alkyl is radical having 1 to 8 carbon atoms, X _{1 is} a fluorine, chlorine or bromine atom, wherein the ethylene Double bond in the geometric form (E) or (Z) is present and the substituted cyclopropane ring can occur in all its stereoisomeric forms or in the form of a mixture of these stereoisomers

In the compounds of formula (I _A ), R _{8 can represent} an unbranched or branched alkyl radical, in particular a methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl or octyl radical, the latter radicals being unbranched or can be branched. In the

23 37 16 2 - «-

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Compounds of formula (Ia), the Zyklopropanring in the configuration (IRycis), (IS.cis), (IR, trans), (IS, trans), but preferably (lR, cis) or (lR _t trans) present.

Compounds of the formula (3a) which can be prepared according to this invention can be counted in particular those in which A is an oxygen atom, and more particularly the (IR, cis) 2,2-dichloro-3 (E. ) / '2-fluoro-2- (ethoxycarbonyl) ethenyl} cyclopropanecarboxylic acid (S) ct-cyano 3-phenoxybenzyl ester S: - _,

Compounds of formula (X) * to be prepared according to this invention may also include those compounds of formula I in which B is a radical

is, those in which B is a radical

-CH

is, those in which B is a radical

233716 2

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59 837/12

is, those in which B is a radical

-CH

is, as well as those, xx which B is a radical

represents.

Furthermore, as according to this invention hefgestellten preferred compounds is given to those in which B is a £ 3- (propyn-2 ~ yl) 2, S-dioxo-i! Bidazolidiny 1} methyl radical or a * c -2yan-6-phenoxy Is -2-pyridylroethyl radical.

The compounds of the formula I prepared according to this invention are in particular the compounds of the

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37 16 2 - ^2o - 59 _837/12

to count games 1, 11 and 21.

The compounds of formula (I) have interesting properties that permit their pest control application. It may be, for example, the control of plant pests, parasites occurring in rooms and parasites of warm-blooded animals.

Thus, the products according to the invention can be used to control insects; Threadworms and mite parasites of plants and animals are used »

The invention accordingly relates to the use of the compounds of the formula (I) for controlling the plant, space pests and parasites of warm-blooded animals *

The invention particularly relates to the application of the compounds of formula (I. _A) for the control of plant and RauBischädlinge and pests of warm-blooded animals.

The products of formula (I) can be used in particular for insect control in agriculture, for example for the control of aphids, butterfly larvae and beetles. They are used at dose levels between 10 g and 300 g of active ingredient per hectare.

The products of formula (I) can also be used to control insects indoors, especially for controlling flies, mosquitoes and cockroaches.

The compounds of Examples 1, 11 and 21 are very noteworthy products, such as the following experimental

233716 2.

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show results. They have an excellent lethal effect and a very good "knock down" effect,

The products aer formula (I) are also fade resistant and non-toxic "for mammals

By virtue of their total properties, the products of formula (I) are such that they fully meet the requirements of modern agrochemistry. They enable the protection of crops as well as of the environment.

The products of formula (I) can also be used to combat the mite and nematode parasites of plants. "

The compounds of formula (I) can be used for the control of mites parasite of animals continue for example to control oer ticks and in particular aer ticks oer genus Boephilus, the genus Byalotnnia, the genus Amblyorania and the genus Phipicephalus and to combat all kinds of mange, "especially the sarcoptic mange," Psoroptes mange, and Chori ^ pte-Räudie.

The compounds of formula (I) can also be used for the preparation of compounds which serve to combat the parasites of warm-blooded animals, plant and space insects, which contain as a principle of action at least one of the compounds of formula (I).

The compounds of the formula (I) can be used in particular for the preparation of insecticidal compounds.

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3 3 7 16 ^2-22 - ^{59 837/12}

The preferred compositions obtained according to this invention may more particularly include those containing the compound of Example 1, the compound of Example 11 and the compound of Example 21.

These compositions are made according to the procedures customary in the agrochemical or veterinary industry or in the feed-producing industry.

In these compositions, which are intended for use in agriculture and in rooms, it is possible for the active substance or other active substances to be added other pesticides. These compositions can be made in Forra from powders, granules, suspensions, emulsions, aerosol solutions, fuel strips, baits, or other conventional forms for the application of this type of compound.

In addition to the mode of action, these compounds generally contain a vehicle and / or surfactant which is non-ionic and ensures uniform dispersion of the mixture components. The carrier used may be a liquid such as water, alcohol, hydrocarbons or other organic solutions , a mineral oil, an animal or vegetable oil or a powder such as, for example, talc, jTone, silicates, kieselguhr or a solid fuel.

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

According to an advantageous working method, the compounds according to the invention are used for application in rooms in the form of nebulizing agents,

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The compounds of the invention may thus consist of the non-effective part of a combustible insecticide paper coil (or COiI) or of a non-combustible fibrous carrier substance. In the latter case, the nebulizer obtained after storage of the active substance is stored on a heater or an electric mosquito killer. »

When an insecticide composition is used, so may the inert carrier, for example, pyrethrum Mark, from Tabu powder (or powder of leaves of Machilus Thumbergii) ^ from powder of Pyrethrumstengel powder aer Sdernblätter, wood powder (such. B "powder from pine chips ), Starch or powder of coconut shells. The dose of the active ingredient may then be, for example, 0/03 to 1% by weight.

When using a non-combustible fibrous carrier, for example, the dose of active ingredient may be from 0.03 to 95% by weight.

The erfindungsgeiBäßen compounds that are intended for use in rooms, can also be obtained by the production of atomizable oil on the basis of a principle of action, wherein after soaking the Lampenendochtes with the oil this is burned.

The concentration of the active substance incorporated in the oil is preferably 0.03 to 95% by weight.

The insecticides according to the invention may, like the compounds for controlling mites and nematodes

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AP C 07 C / 233 716/2 37 1 6 2- ²⁴ - 59837/12

receive an addition of one or more pesticides. The agents for combating mites and Fadenwunnern can be prepared in particular in the form of powders, granules, suspensions, emulsions or solutions.

For use against mites, it is preferred to use powders which can be moistened to dust the leaves containing from 1 to 80 % of active ingredient or foliar fluid containing from 1 to 500 g / l of active ingredient. It is also possible to use powder for dusting the leaves containing 0.05 to 3 % of active ingredient.

For use against Fadenwörroer preferably liquids are used to treat the soil containing 300 to 500 g / l of active ingredient.

The compounds according to the invention for combating mites and roundworms are preferably used in dosage strengths between 1 and 100 g of active ingredient per hectare.

In order to increase the biological activity of the products according to the invention, they can be added to conventional synergists used in such cases, such as! - (2,5,8-trioxadodecyl) -2-propyl-4,5-methylenedioxybenzene (or piperonyl butoxide) or N- (2-ethylheptyl} -bicyclo / 2 »2-l] 5-heptene-2,3-dikarboximide or piperonyl-bis-2- (2 * -n-butoxyethoxy) -ethylacetal (or tropital).

When mite parasites are to be fought in animals, the products of the invention very often become feed mixtures in conjunction with one for animal nutrition

23 37 16 2.

09/28/1982

AP C 07 C / 233 716/2 25-59 837/12

The food mixture may vary according to the species. It can cereals, sugar and grains "soybean, peanut and Sonnenbluraentrester, animal flours, z. Fish meals, synthetic amino acids, mineral salts, vitamins and antioxidants »

The compounds of formula (I) can thus be used for the preparation of compositions intended for animal nutrition.

The compounds aer formula (2) have an excellent general tolerance, and the invention therefore also relates to products of formula (I) as medicaments in particular for the control of * caused by ticks and dross affections.

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

The medicaments according to the invention are used in human medicine especially as preventatives or remedies against lice and for controlling the scabies. They can also be used as anthelmintics.

The medicaments according to the invention can be applied externally by spraying, washing the head ^ bathing or brushing in «

The erfindungsgeraäßen drugs for veterinary medicine can also by brushing the spine after the

28.9 · 1982 AP C 07 C / 233 716/2 37 16 2 - »- 59837/13

They can also be administered by way of the alimentary canal or parenterally.

The compounds of the formula (I) can therefore be used for the preparation of pharmaceutical compounds which contain as a principle of action at least one of the compounds mentioned.

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

The compounds of the formula (I) can furthermore be used for the preparation of compounds which have the action of an insecticide, a miticidal composition or a nematode control agent and are characterized in that they have on the one hand at least one of the compounds of the general formula (I) as active ingredient and, on the other hand, at least one of the pyrethrinoid esters from the group of the allethrolone esters, 3,4,5,6-tetrahydrophthalimidomethyl alcohol, 5-benzyl-3-furylmethyl alcohol, 3-phenoxybenzyl alcohols and oi-cyano-3 phenoxybenzyl alcohols of chrysanthemum acids, the esters of 5-benzyl-3-furylmethyl alcohols of 2,2-dimethyl-3- (2-oxo-3-tetrahydahydrothiophenylidenemethyl) cyclopropanecarboxylic acids, the esters of 3-phenoxybenzyl alcohol and of oi, -cyano-3 -pbenoxylalkoholen of 2,2-dimethyl-3- (2,2-dichlorovinyl) zyklopropen-l-carboxylic acids, the esters of «* -Zyano-3-phenoxybenzylalkoholen 2,2 ~ dimethyl-3- (2-dibromovinyl _J 2 ) zyklopropan- l-carboxylic acids, the ester of 3-phenoxybenzyl alcohol of 2-p-chlorophenyl-2-isopropylacetic acids,

28.9 · 1982

AP C 07 C / 233 716/2

3 3 7 1 6 2 - ²⁷ - ^{59 837 / i2}

the ester of allethrolones, 3,4,5,6-tetrahydrophthalimidomethylalcohol, 5-benzyl-3-furylmethylalcohol, 3-phenoxybenzylalcohol and oi-cyano-3-phenoxybenzylalcohol of 2,2-dimethyl-3- (1 , 2,2,2-tetrahaloethyl) cyclopropane-1-carboxylic acids in which "halo" represents a fluorine, chlorine or bromine atom, wherein the compounds (I) may of course be present in all their possible stereoisomeric forms as well as the acids and Alcohol Structures of the Above Pyrethrinoid Esters

The combinations according to the invention serve, in particular, to combat a larger number of parasites, either by the polyvalence of their action, or in some cases to show a synergy effect.

The process according to the invention for the preparation of the compounds of the formula (I) is characterized in that an acid of the formula (II)

retain the meaning previously defined in which X and R, the shape of this acid is in mixtures of isomers E and Z or the acid is in the form of isomer E or Z and the substituted Zyklopropanring all its stereoisomeric forms or as a mixture of Stereoisoroeren or a functional derivative thereof

28.9.1982.

AP C 07 C / 233 716/2

3 3 7 16 2 - ^2β - ⁵⁹ β37 / ΐ2

Acid can be reacted with an alcohol of formula (III):

ί

B-OH (IH) *

wherein B retains the same meaning as defined above, or a functional derivative of said alcohol, to obtain the corresponding compound of formula (I) which, if desired, is exposed to the action of a selective cleavage agent of the group CO ₂ R, ura to obtain the compound of formula (IV):

CH ₃ CH ₃

in which B has the same meaning reserves as previously defined, and then the acid of formula (IV) or a functional derivative of this acid exposes aer action of an alcohol of the formula R-OH, in which R is as defined previously retains the corresponding compound of the formula (I).

In particular, the invention has as its object a process as defined above, with which the compounds of the formula (I _A ) * as defined above can be prepared, which is characterized in that an acid of the formula (II.):

1:37 1 6 2 - 29 - 28 AP 59 f ^H 3 O .9.1982 C 07 C / 233 716/2 837/12 X ₁ . \.  MM " H ₃ C / ¹ X ^R is ° - • c O \ / \ H in the ^X l and R ₈ 7 H meaning the same have as before

this acid is in the form of a mixture of isomers E and Z or in the form of the isomer E or Z, and the substituted cyclopropane ring may have any of its possible stereoisomeric forms or the form of a mixture of stereoisoroerenes or a functional derivative of this acid ( H *.) ¹⁰ ^ t an alcohol of the formula

CN

in which A retains the same meaning as previously defined, or reacts with a functional derivative of the alcohol of formula (III _A ) and possibly by physical means separates isomers E and Z at the double bond.

The esterification of the acid (II) or (II.) With the alcohol of the formula (III) or (III _A ) can be carried out in the presence of a tertiary base pyridine. This esterification can be carried out favorably in the presence of a mixture of pyridine, dicyclohexylcarbodiimide and 4-disiethylaminopyridine.

09/28/1982

AP C 07 C / 233 716/2

37 16 2 - *> - 59 _837/12

The esterification can * be performed a silver salt such as * B by reacting a chloride of acid (II) or (H _A) with the alcohol of formula (III) or (III _A) or a metal derivative of this alcohol.

The generally used for preparation of the acids of formula (II) or (H _A) applied Wittig reaction leads to acids whose double bond is E + Z.

Optionally, the isomers on the double bond may be separated by physical methods such as chromatography, either with the acids or with the esters. Examples of these two methods are given below in the experimental section.

The cleavage agent of group CCUR is preferably heat used with an acidic hydrolyzing agent. The acidic hydrolysis agent used may be p-toluenesulfonic acid »

The esterification of the compound of formula (IV) is carried out according to the classical methods of esterification, in particular according to those described above.

The invention also relates to a preparation process as defined above, characterized in that the acids of the formula (II) or (II.) In which R or R _{18 is} an alkyl radical having 1 to 5 carbon atoms are prepared by a cis-aldehyde in the form of a lactone of the formula (V) according to the Wittig reaction in the presence of a strong base:

233716 2-3, -

09/28/1982

AP C 07 C / 233 716/2 59 837/12

(V)

or a trans-aldenyde of the formula (VI):

(VI)

with a phosphorane of the formula (VII)

X'Coder X-)

C - OR M

wherein R _{19 is} an alkyl radical having 1 to 5 carbon atoms and X and X - retain their previously defined meaning, or rait a phosphonate of the formula (VIII) OO

^R ₂ o ° t I!

p - CH X - C - OR

^R 20 °

χ (or

19

(VIII)

09/28/1982

AP C 07 C / 233 716/2 3 3 7 1 6 2 " ³² " ^{59 837 / i2}

wherein R ^ q * X and X ₁ retain their above-mentioned meaning and R _{20 is} an alkyl radical having 1 to 6 carbon atoms, react.

The acids of formula (II) of a given stereochemical form can also be represented by the following reaction scheme: <

HH «iPOR H H

In the formulas of this scheme, X is a fluorine, chlorine, or bromine atom, R is an alkyl radical of 1 to 8 carbon atoms, and the compounds used have a very particular steric configuration.

The acids of the formula (H) in which X represents a bromoanoma can also be prepared by reacting a compound of the formula (IX)

RCO ₂

(IX),

in which the geometric shape of the double bond is E, R retains its previously mentioned meaning, and alc represents an alkyl radical, the effect of a neutralizing agent

09/28/1982

AP C 07 C / 233 716/2

3 3 7 16 ^2-33 - ^{59 837/12}

like ζ. B, pyridinium bromide, and then exposed to the action of a debromination hydration agent * to obtain;

if the degermination hydration agent is a basic agent which acts under fairly mild conditions, the compound of the formula (X)

CH ₃ CO ₂

C0 _£ alc (X),

if the debromeration hydration agent is a basic agent acting under heavier conditions, the isomer E.

The experimental part gives an example of such a representation in which triethylamine is used to obtain the isomer Z and sulfur is used to obtain the isomer E.

The compounds of the formula V are then subjected to a cleavage agent aer Function CO ^ alc to obtain the corresponding acid of formula II »

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

The acids of the formulas II and H _A. # Especially those of a specific stereochemistry, and the acids of formula IV, which are obtained in carrying out the method of the invention, are new products.

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

233716 2

Example 1 : (1R | c is) 2,2-Dimethyl-3 (E) / 2-fluoro-2- (ethoxycarbonyl) -ethyiylcyclopropane-1-carboxylic acid (S) c <-cyano-3-phenoxy-obilyl ester .

To a solution of 3.87 g (1R, cis) of 2,2-dimethyl-3 (E) / * 2-fluoro-2- (ethoxycarbonyl) ethenyl-7-cyclopropane-1-carboxylic acid in 30 ml of methylene chloride are added 1, Pyridine and 3.7 g of dicyclohexylcarbodiimide, stirred for 10 minutes and added in one go a solution of 4.05 g of (S) e ^ -cyano-3-phenoxybenzyl alcohol in 10 cm of methylene chloride, stirred for 1 hour and 30 minutes, cooled to 0 ⁰ G from, removed by filtration the insoluble material formed, the filtrate by distillation under reduced pressure verv a chromatograph! öen ert residue with silica gel vjobei one (by a mixture of cyclohexane and Bthylazetat 80/20 evaporated to dryness, ), crystallized the residue obtained in ethyl acetate, then isolated by air drying, the precipitate formed, then chromatographed the mother solutions with silica gel, Ttobei eluted through a cyclohexane and Ethylazetatmischung (9/1) vsird, and you get a total of 4.28 g (1R, cis) 2,2-dimethyl-3 (E) / 2-fluoro> -2- (et h.sub.z: yar bebonyl) ethenyl7cyclopropane-1-carboxylic acid ^ S) c.sup.-cyano-3-phenoxybenzyl ester and. 2.8 g of derivative 3 (Z).

Analysis; C ₂₅ E ₂₄ FNOg (437.47) C% E% Έ%

calculated; 68.64 5.53 3.20 4.34; 68.8 5.5 3.1 4.2

IR spectrum '(infrared spectrum) (chloroform)

Absorption at 1738 cm "and 1722 cm" attributed to the carbonyl group and the associated ester; Absorption is written at;

Absorption at 166 cm, which is attributed to the ethylene-double bond

Absorption at 1589 cm.sup.-1489 cm ascribed to the aromatic nuclei;

- Absorption at 1380 cm ^-1 , which is attributed to the coupled methyl grape.

233716 2

RMN spectrum (nuclear magnetic resonance spectrum) (deuterochloroform)

- spikes at 1.2 - 1.27 ppm attributed to the hydrogen atoms of the coupled methyl groups;

Piks at 1.23-1.35-1.47 ppm, 4.15-4.26 ppm and 4.38 4.50 ppm assigned to the hydrogen atoms of the ethyl radical of the bethoxycarbonyl group;

- spikes at 1.88 - 2.02 ppm attributed to the hydrogen atom at the 1o site of the cyclopropyl;

- Spiks at 2.8 - 3.13 ppm, which are attributed to the hydrogen atom at the 3-position of the cyclopropyl;

Piks at 6.05-6.21 and 6.38-6.55 ppm assigned to the hydrogen atom of the ethylene double bond;

Spike at 6.36 ppm attributed to the hydrogen atom carried by the same carbon atom vsie the group C = U; ,

- Piks at 6.9 - 7.58 ppm, which are attributed to the hydrogen atoms of the aromatic nuclei.

The (1R, cis) 2 _} 2-dimethyl-3 (E, Z) -fluoro-1-ethoxy-carbonyl-tetrahydroxycyclopropane-1-carboxylic acid is prepared as follows

In a solution of 12.1 g Diethylphosphorofluorethylazetat in 120 cnr dirnethoxyethane is added at +5 C 2 g of a 60% • Sodium hydride suspension in oil, stirred for 30 minutes, at 0 ⁰ C 5.7 g of lactone (1 .R, cis) 2,2-dimethyl-3-dihyroxymethyl) cyclopropane-1-carboxylic acid, stirred again for 2 hours and 30 minutes up to 20 ⁰ C, pour the reaction mixture into a water and ice mixture, the Schv? 1 phosphate, extracted with ethyl ether, washed with water, the combined organic phases, dried, evaporated to dryness by distillation under reduced pressure, the residue chromatographed with silica gel, with a mixture of cyclohexane, ethyl acetate and acetic acid ( 50/50/1) and recovering 3.87 g of a (1R, cis) 2,2'-dimethyl-3 (E, Z) _< / 2 fluoro-2-ethoxy-3-carbonyl-tethenyl-yl-7-cycloalkane-1-carboxylic acid mixture.

23 37 16 2

Example 2: (1R, cis) 2,2-Pimethyl-3 (Z) / 2-fluoro-2- (ethoxy-carbonyl ) -ethyl / cyclopropane-1-carboxylic acid (S) p (. -Cyano-3) phenoxybenzyl

At the end of the chromatography in Example 1, in which the derivative of structure 3 (E) could be recovered, 2.8 g of residue containing the derivative of structure 3 (Z) were obtained. This residue is thickened in ethyl acetate, the insoluble portion formed is removed by filtering; then the filtrate is evaporated to dryness by distillation under reduced pressure. A residue is obtained, which is chromatographed on silica gel, eluting with a mixture of cyclones xane and ethyl acetate (9/1), to obtain 1.0 g of (1R, cis) 2,2-dimethyl-3 (Z). [2-t Luor-2 (ehoxy carbonyl) ethenyl] cyclopropan-1-carboxylic acid (S) e ^ -cyano-3-phenoxybenzyl ester.

IR spectrum (chloroform)

Absorption at 1730 cm ~ attributed to the carbonyl group and the associated ester; Absorption b <is ordered; Absorption b is attributed;

-1

Absorption at 1620 cm, added to the ethylene double bond

- Absorption at 1589 - 1489 cm, the aromatic nuclei

Absorption at 1380 cin ~ attributed to the coupled methyl groups.

RMN spectrum (deuterochloroform)

- spikes at 1.2 - 1.32 - 1.43 ppm and 4.12 - 4.23 - 4.35 - 4.47 ppm attributed to the hydrogen atoms of the ethyl radical of the ethoxy carbonyl group;

- Piks at 1.23-1.27 ppm attributed to the hydrogen atoms of the coupled methyl groups;

- spikes at 6.2 - 6.36 ppm and 6.73 - 6.9 ppm, which are assigned to the hydrogen atom of the ethylene double bond;

- Pik at 6.47 ppm, attributed to the hydrogen atom attached to the same carbon atom as the group

-CK; ;

- Piks at 6.9 - 7.58 ppm, which are attributed to the hydrogen atoms of the aromatic nuclei _o

233716 2

Example 3: (IR, ice) 2 »2-Dimethyl-3 (E) Z2-chloro-2- (methoxycarbonylphenyl) cyclopropane-1-carboxylic acid (S) c-cyano-3-phenoxy: benzyl ester

In a solution of 3 g of chloride of (1R, cis) 2,2-dimethyl-3 (E) (2-chloro-2-methoxyeth-2-methoxy) cyclopropane-1-carboxylic acid in 15 cnr benzene is added 3 g ( S) ₀ C -fyano ^ -phenosylbenzyl alcohol, and 1.3 cm of pyridine from 50 C, stirred for 15 minutes at +5 C and then for 16 hours at + 20 ⁰ C, pouring the Reaktionsgeniis cn into a water / Ciilorvsasserstoffsäuremischung , extracted with ethyl ether, washed with water, dried, the organic solution is evaporated to dryness by distillation under reduced pressure, the residue is chromatographed on silica gel, successively through a. Mixture cyclohexane / ethyl acetate (8/2) and then eluted through a mixture cyclohexane / ethyl acetate (9/1), and there are obtained 2.1 g (1R, ice) of 2,2-dimethyl-3 (E) ^ 2-chloro -2- (methoxy-carbocyclethenyl / cyclopropane-1-carboxylic acid- (S) o- (cyano-3-phenoxybenzyl) ester, (^) _, = 50 °, 5 (C = 0.8 %, benzene).

Analysis : C ₅₄ E ₂₂ ClIiO ₅ 439.9

C % where -C US Έ%

calculated: 65.53 5.04 8.05 3.18

obtained: 65.5 5.2 8.0 3.0

IR spectrum (chloroform)

-1 -1

- Absorption at 1738 cm and 1719 cm, that of the carbonyl group

attributed to the Istars vsird;

- Absorption at I6O8 cm * "attributed to the group -C = C-

becomes; ,

- 1 -1

- absorption at 1589 cm - 1489 cm containing the aromatic

Attributed to nuclei;

_ -ι

Absorption at 1390 cm attributed to the coupled methyl groups.

RM:! - Spectrum (deuterochloroform)

- Piks at 1.24 - 1.25 ppm, which are assigned to the hydrogen atoms of the coupled methyl groups;

Piks at 1.93-2.07 ppm attributed to the hydrogen atom at 1, site of the cyclopropyl;

233716 2 -

Piks at 2.87-3.01-3.04-3.18 ppm attributed to the hydrogen atom at the 3- position of the cyclopropyl;

Pik at 3.85 ppm attributed to the methoxy carbonyl methyl;

- spike at 6.35 ppm, ascribed to the hydrogen atom carried by the same carbon atom vs the group -C = U;

- Piks at 6.91 - 7.5 ppm, which are assigned to the Ifesserstoffomen the aromatic nuclei.

The chloride of (1E, cis) 2,2-dimethyl-3 (S) / 2-chloro-2- (methoxy- ^ carbonyl) ethenyl7-cyclopropane-1-carboxylic acid can be obtained in the following manner:

Stadj-um Ai. L1R »£ i§) ^ '^ - ^ l jDiniejfch 3 (βΣ ISSZ ° ϊβ-2 ^{τ ζ} 2-methorykarbon2Il ethenyl7 cyclopropane-1-carboxylic acid.

In 50 cnr tetrahydrofuran is at 20 ⁰ C 12.6 g Methoxykarbonylmethylentriphenylphosphoran and 4.85 g of the lactone dissolved in 40 cnr tetrahydrofuran (1R, cis) 2,2-Bimetliyl-3- (diliydroxymethyl) cyclopropane-1-carboxylic acid, stirred two hours 20 C, the reaction mixture brings to reflux and leaving it for one hour at this stage, then evaporated to dryness by distillation under reduced pressure, the residue is ethyl ether to removed by filtering the r resulting insoluble component (oxide of Triphenylphosphine), the filtrate is evaporated to dryness by distillation under reduced pressure, the residue is chromatographed on silica gel, eluting with a mixture of Benz en / Bthy laze tat (8/2) containing 1 % acetic acid, and receives 2,2, g (1R, cis) 2,2-dimethyl-3 (S) (2-chloro-2-methoxycarbonylethenyl) cyclopropane-1-carboxylic acid and 3 g (1R, ice) 2,2-dimethyl-3 (Z) ^ -chloro-methoxy-carbonyl-ethenyl) cyclopropane-1-carbon acid.

The (1R, cis) 2 _> 2-dimethyl-3 (E) (2-chloro-2-methoxycarbonylethenyl) cyclopropane-1-carboxylic acid has the following properties;

IR spectrum (chloroform)

Absorption at 3500 cm ", which is attributed to the hydroxyl group of the carboxyl;

23 37 16 2

Vsird attributed to absorption at 1490; absorption at 1721 cm, 1713 cm "" ^1, 1700 cm ^"1, which is attributed to the carbonyl group -;

- 1 -1 - absorption at 1490 cm - 1410 cm, that of the group -C = C -

- Absorption at 1393 cm " ¹ - 1380 cm *" ¹ , which is attributed to the hydrogen atoms of the coupled methyl groups.

_RMN spectrum (deuterochloroform)

- spikes at 1.3 - 1.32 ppm attributed to the coupled methyl groups;

Spikes at 1.87-2.02 ppm assigned to the hydrogen atom at the 1st position of the cyclopropyl;

- Spiks at 2.82, 2.97 ppm - 2.98, • 3, T3 ppm, assigned to the hydrogen atom at the 3-position of the cyclopropyl;

- Spik at 3.82 ppm, which is assigned to the hydrogen atoms of the methyl of methoxy carbonyl;

- Piks at 6.72 - 6.78 ppm, which are assigned to the hydrogen atom of the ethylene double bond of the side chain at the 3 'position of the cyclopropyl;

- Spik at 11 ppm attributed to the hydrogen atom of the carboxyl.

The (1R, cis) 2,2-dimethyl-3 (Z) (2-chloro-2-metho-2-ylcarbonylethenyl) -cyclopropane-1-carboxylic acid has the following properties

IR spectrum (chloroform)

Absorption at 3500 cm assigned to the hydroxyl group of the carboxyl (monomer + dimer);

Absorption at 1725 cm -1 assigned to the -C. ester;

Absorption at 1700 cm ", which is assigned to the hydrogen atom of the! Carboxyl group (monomer);

- 1

Absorption at 1623 cm, attributed to the group -C = C-.

-1 -1

Absorption at 1393 cm - 1381 cm, which is the hydrogen

atoms of the coupled methyl groups.

BIaN spectrum (deuterochloroform)

- spades at. 1.32-1.35 ppm assigned to the hydrogen atoms of the coupled methyl groups;

233716 2

- spikes at 1.95 to 2.5 ppm attributed to the hydrogen atoms at the 1st and 3rd positions of the cyclopropyl;

Spike at 3.83 ppm, attributed to the hydrogen atoms of the methyl group of the methoxy group;

- Piks at 7.28 - 7.45 ppm, which add to the hydrogen atom of the double bond of the side chain at the 3 - position of the cyclopropyl. be ordered;

- Pik at 10.75 ppm assigned to the hydrogen atom of the! Carboxyl group.

Stadlum Bi_Chlorid_der_ (lR _J .c_is22 _a 2-Dimethyl-_3 (E) __ / X_ 2-OhI _- Or-2

2.9 g of (1R, cis) 2,2-dimethyl-3 (E) /J-chloro-2- (methoxycarbonyl) -ethhenyl7.7-cyclopropane-1-carboxylic acid, 20 cm of isoprene and 10 cm of thionyl chloride are mixed, Stirred to 20 ⁰ C for 3 hours, eliminates the isoprene and the thionyl chloride by distillation under reduced pressure to give 6 g of crude chloride of (1R, cis) 2,2-dimethyl 3 (E) ₍ / 2-chloro-2- (methoxycarbonyl ) ethenyl _i / ζ ykl ο per pan-1 -! carboxylic acid O

Example 4? (1R, cis) 2,2-Dimethyl-3 (Z) Z ^ 2-bromo-2- (propoxycarbonyl) ethenyl7 cyclopropane-1-carboxylic acid (S) o -cyano-3-phenoxybenzyl ester

In a solution of 2.9 g of (1R, cis) 2,2-dimethyl-3 (Z) ^ 2-bromo-2- (propyloxy-carbonyl) ethenyl7-cyclopropane-1-carboxylic acid in 40

3 3

cm of methylene chloride are added 0.9 cm of pyridine, 2.1 g of dicyclohexylcarbodiimide, stirred for 15 minutes, 2.5 g of (S) ei-Zj-'ano-3-phenoxybenzyl alcohol dissolved in 5 cm of methylene chloride are added, 25 mg of 4- Dimethylaminopyridine, stirred for 2 hours, removed by filtering the insoluble portion formed, the filtrate is evaporated by distillation under reduced pressure to dryness. Chromatograph the residue on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (9/1), to give 4.26 g of (1R, cis) 2,2-dimethyl-3 (Z) / 2-bromo-2 - (propoxykarbonyl) ethenyl3 cyclopropane-1-fcarbonsäure- (S) 4- -zyano-3-phenoxybenzyl ester, P = 64 ⁰ + Cc) Note d... Ü. : In: Original text is missing ⁿ 2,2-dimethyl- ^f '.

233716 2

Analysis: Cp / - H, BrIOp; f. 51 2, , 73 C% E ⁰ , W , 7,. br calculated: 60.95 5, 2 15 , 6 receive: 61.1 5. 2 15 , 5 IR spectrum , 11 3 (Chloroform)

-1 -

- Absorption at 1743 - 1718 cm, the! Carbonyl of the ester

and the assigned ester!

- Absorption at 1615 cm "attributed to the group -C = C-

becomes; From s or; is assigned;

- Absorption at 1588 - 1488 cm ", the aromatic nuclei

-1

Absorption at 1390-1380 cm associated with the coupled methyl groups.

RMK spectrum (deuterochloroform)

- Spiks at 0.88 - 1.0 - 1.12 ppm, attributed to the hydrogen atoms of the methyl of the propyl;

- Piks'bei 1.27 - 1.32 ppm, which are assigned to the hydrogen atoms of the coupled methyl groups;

- Piks at 4.08 - 4.2 - 4.32 ppm, which are attributed to the hydrogen atoms at the 1st site of Propyls vsiräK;

Pik at 6.4 ppm, attributable to the hydrogen atom carried by the same carbon atom as the group -CsK;

- Piks at 7.57 - 7.67 ppm assigned to the hydrogen atom of the ethylene double bond

- Piks at 6.9 - 7.58 ppm, attributed to the oleic acid atoms of aromatic nuclei.

The (1R, cis) 2,2-dimethyl-3 (Z) / 2-bromo-2- (propoxycarbonyl) ethenyl / cyclopropane-1-carboxylic acid is prepared as follows:

Stage Ai _- (JR ₁ ice) 2_, 2-Dimethyl-3 (Z) / 2-bromo-2- (propyloxy-gycarbonyi) -th- _n- butyl-2-cyano-2-pyridylcarboxylic acid. z ^ B ^ JZ ^ - J§.s_t e_r

In a solution of 28.3 g of tert-butyl ester of (1R, cis) 2,2-dimethyl-3 (2, 2-dibromovin3 ⁷ l) cyclopropane-1-lCarbonsäure in a mixture of 120 cm * 'tetrahydrofuran and 120 cm of ethyl ether is added at -115 ⁰ C in 25 minutes, about 50 cm * ⁵ a Lithiumbutyl-

233716 2 -

in hexane, titrated 1.6 Ή, stirred for 15 minutes at -115 ⁰ C, gradually added to 10 cm of n-propyl chloroformate, stirred for 20 minutes at -115 ⁰ C and. after one hour at -65 ⁰ C, cas pour reaction mixture into an aqueous Schiefel-1-phosphate solution, extracted with ether, washed the combined ethereal solutions with 'water, dried, they evaporated by distillation under reduced pressure "to dryness Chromatographed with silica gel, which is obtained with a mixture of cyclohexane and ethyl acetate (95i5) v ^U and. 3 »52 g (1R, cis) 2,2-dimethyl-3 (Z) / 2-bromo-2 (propylo 2: ycarbonyl) etheny! L7 cyclopentane-1-carboxylic acid tert-butyl ester and 3 »16 g (1R, cis) 2,2-dimethyl-3 (E) _i / 2-bromo-2- (propyloxycarbonyl) ethenyl7-cyclopropane-1-fcarbonsäure tert-butyl ·

The (1R, cis) -2,2-dimethyl-3 (Z) / J2-bromo-2- (propyloxycarbonyl) ethenyl7-cyclopropane-1-carboxylic acid tert-butyl ester has the following properties: J

IR spectrum (chloroform)

Absorption at 1715 cm "attributed to group C = 0;

- absorbance at 1614 cm ", attributed to the group C = C vsird ..

RMN spectrum (deuterochloroform)

Piks at 0.9-0.97-1.05 ppm attributed to the hydrogen atoms of the final methyl of propyl;

- Piks at 1.3 - 1.33 Ppm, which are assigned to the hydrogen atoms of the coupled methyl groups;

Spike at 1.52 ppm, attributed to the hydrogen atoms of the tert-butyl radical;

- Piks at 1.88-1.97 and 2.05 - 2.15 - 2.24 ppm, which are assigned to the hydrogen atoms at the 1st and 3rd place of the cyclopropyl;

- Piks at 4.1 - 4.18 - 4.26 ppm, which are attributed to the hydrogen atoms of the methylene at the first position of the propyl;

- Piks at 7.6 - 7.75 ppm, which are assigned to the hydrogen atom of the ethylene double bond.

2 3 3 7 16 2

StadjLum Bi_ (jK _x cj.s22_ _t 2-Dj.m_ethj ^ l-3 (Z) _Z | -br_oni-2_ _z ( _i 2rop_ £ l_oxjvkarbo-

A solution of 3.45 g tert-butyl ester of (1R, cis) 2,2-dimethyl-3 (Z) / 2-bromo-2- (propyloxy carbonyl) ethenyl7 cyclopropane-1-anxiety acid in 35% toluene is added 0.35 g of p-toluenesulfonic acid monohydrate, brings the flask with the reaction mixture in an oil bath of 120 ⁰ C _5-1 for 10 minutes, brings the temperature of the reaction mixture-again to 20 ⁰ C, ether is added, washes with water, the combined organic extracts, it is dried, evaporated to dryness by distillation under reduced pressure and receives 2.9 g (1R, cis) 2, '2-D ^J imethyl-3 (Z) / 2-bromo 2- (propyloxycarbonyl) ethene3'1 / cyclopropane-1-carboxylic acid.

Example 5i (1R, cis) 2,2-Dimethyl-3 (E) / 2-bromo-2- (propoxycarbonyl) ethenyl-7-cyclopropane-1-carboxylic acid- (S) g -cyano-3-phenoxybenzoiester

In a solution of 2.6 g (1R, cis) of 2,2-dimethyl-3 (E) / 2-bromo-2- (propyloxykarbonyDethenyl / γyklopropan-1-carboxylic acid in 40 cm ^ methylene chloride are added 0.9 cm Pyriüin , 2 g of dicyclohexylcarbodiimide, stirred for 10 minutes, 2 g of (S) c <-2yano-3-phenoxybenzylalkohol added, stirred for 10 minutes, 25 mg of 4-DimethylamJBOpyridin added, stirred for one hour and thirty minutes, eliminated by precipitation of the resulting insoluble Portion, the filtrate is evaporated to dryness by distillation under reduced pressure, the residue is chromatographed with silica gel, eluting with a mixture of cyclohexane and JSthylasetat (95/5), receives 0.743 g of the expected ester and 3.64 g of a mixture which is dissolved in 4 volumes of isopropyl ether to heat, the mixture is stirred at 20 ⁰ C, isolated by spin 6s precipitate formed, dried, gives it added to 0.743 g of the product previously obtained, and obtains 2.32 g of (1R, cis) 2 , 2-dimethyl-3 (E) -2-bromo-2- (propoxycarbonyl) ethenyl-cy klopropan-1-carbonic acid (S) tk -zyano-3-phenoxybenzyl, F = 68 ⁰ C.

233716 2

Analysis: C ₂₆ ii ₂₃ br fej O VJl (5 -r - \ _ _ 12 calculated; 60,95 5,11 2, 73 - * ta VJi »i , 6 receive? 61 5.1 2, 5 15 , 5 IR spectrum (Chloroform)

-1

Absorption at 1737 cm attributed to the carbonyl of the ester;

-1

- Absorbed at 1705 cm, the carbonyl of the assigned

Attributed to Esters;

absorptio

wrote

Absorption at 1605-1610 cm ~, which is added to the group -C = C-

- 1

- absorption at 1585 - 1485 cm, the aromatic nuclei

is assigned »

RMH spectrums (deuterochloroform)

- Spiks at 0.88 - 1.0 - 1.12 ppm, attributed to the hydrogen atoms of the methyl of the propoxyl;

- Piks at 1.22 - 1.23 ppm, which are assigned to the hydrogen atoms of the coupled methyl groups;

- spikes at 1.92 - 2.06 ppm, which are assigned to the hydrogen atom at the first position of the cyclopropyl;

- Piks at 4.08 - 4.18 - 4.28 ppm, which are assigned to the hydrogen atoms at the first position of the propyl;

- spike at 6.38 ppm, assigned to the hydrogen atom carried by the same carbon atom vs the group - C ^ N;

- Spiks at 6.9 to 7.51 ppm, which is assigned to the hydrogen atom of the ethylene double bond vsird;

- Spikes at 6.92 - 7.6 ppm, which are associated with the first off atoms of the aromatic nuclei.

Pie (1R, cis) 2,2-Dimethyl-3 (B) / 2-bromo-2- (propoxycarbonyl) ethenyl / cyclopropane-1-carboxylic acid can be recovered as follows;

To a solution of 3.1 g of tert-butyl ether of (1R, cis) 2,2-dimethyl-3 (E) -2-bromo-2- (propoxycarbonyl) ethenyl7 cyclopropane-1-carboxylic acid, which at the same time it has obtained the isomer 3 (Z) at stage A in the production of the corresponding.

233716 2

4-if-

Acid 3 (Z) according to Example 4 in 31 cm toluene are added 0.31 g of p-toluenesulfonic acid monohydrate, bringing the flask with the reaction mixture in an oil bath of 120 ⁰ C - 15 minutes long, brings the temperature of the reaction mixture quickly on 20 ⁰ C, the extracted ether, the organic extracts washed with "water, dried, they evaporated by distillation under reduced pressure up" to dryness and obtains 2.6 g (1P4cis) 2,2-Dirnethyl-3 (B) / 2-bromo-2- (propox5'carbonyl) ethenyi7 syklopropane-1-carboxylic acids

Example 6: (1R, cis) 2,2-dimethyl-3 (B) Z 2, -fluoro-2- (ethoxycarbonyl) ethenyl-7-cyclopropane-1-carboxylic acid .

The (1R, cie) 2,2-dimethyl-3 (S, Z) ^ 2-fluoro-2-ethoxy-carbonyl-ethenyl-7-cyclopropane-1-carboxylic acid is prepared from 12.2 g of lactone (iR, cis) 2,2-dimethyl -3- (dihydroxymethyl) cyclopropanecarboxylic acid by proceeding as in Example 1 and replacing the chromatography indicated therein by chromatography with silica gel with a mixture of cyclohexane / ethyl acetate in the ratio 75 J 25 and then with the same mixture in. 50 ratio i 50 eluted. 14.5 g of (1R, cis) 2-dimethyl-3 (E) (2-fluoro-2-ethoxycarbonylethenyl) cyclopropane-1-carboxylic acid / csC are then obtained. ρ / = -42.5 ° (c = 1 %, chloroform).

RIM spectrum (deuterochloroform)

Pik at 1.28 ppm attributed to the hydrogen atoms of the coupled methyl groups;

Piks at 1.23-1.35-1.47 ppm and 4.13-4.25-4.37-4.48 ppm assigned to the hydrogen atoms of ethyl of ethoxy carbonyl;

- spikes at 1.82 - 1.97 ppm attributed to the hydrogen atom in the 1-position of the cyclopropyl;

Spikes at 2.75-2.9-3.05 ppm assigned to the hydrogen atom at the 3-position of the cyclopropyl;

- Piks at 6,12 - 6,28 - 6,47 - 6,63 ppm, which are assigned to the hydrogen atom of ethylene (J ⁴ ^ 21 Hz corresponding to a cis-derivative);

- spike at 11.28 ppm attributed to the hydrogen atom of the carboxyl *

233716 2

Example 7: (IR, cis) 2, 2-dimethyl-3- (Z) 'Fe-t Luor-2- (ethoxycarbonyl) ethenyl-cyclopropane-1-carboxylic acid

Continuing the chromatography of Example 6, 4.64 g of (1R, cis) 2,2-dimethyl-3 (Z) _/ / J-fluoro-2- (ethoxycarbonyl) ethenyl / cyclopropane-i-carboxylic acid are obtained.

By esterification with (S) ei.-ynano-3-phenos: ybenzylalkohol lead the acids "E" and "Z" to the esters of Examples 1 and 2.

Example 8: (1E, cis) 2,2-Dimethyl-3 (Z) / 2-fluoro-2-ethoxy-carbonyl) ethenyl-7-cyclopropan-1-carboxylic acid- (S) c -cyano-3-phenoxybenzyl ester . ·

In a solution of 4.9 g (1R, cis) of 2,2-dimethyl-3 (Z) / 2-fluoro-2-ethoxy-carbonyl-ethenyl-72-cyclopropane-1-carboxylic acid in 39 cm of methylene chloride is added 1.9 cm of pyridine, '4 , 8 g Dizyklohesylkarbodiimid, stirs, using a solution of 5 * 3 g of (S) d - £ yano-3-phenoxybenzyl alcohol in 9 _S 8 cm ^ of methylene chloride, stirred for 2 hours at, cooled to 0 ⁰ C, eliminates the The insoluble fraction formed by filtering, evaporated by distillation under reduced pressure to dryness, the residue is chromatographed with egg-gel and eluted sequentially with a cyclohexane / Ethylazetatgeinisch (9/1) and then with a mixture of methylene chloride / petroleum ether (boiling point! ⁰ C) to give 6.73 g of (1R, ice) 2,2-dimethyl-3 (Z) ^ 2-fluoro-2- (ethoxycarbonyl) ethenyl-7-cyclopropane-1-carboxylic acid (S) o (-zyano-3 phenoxybenzyl ester having the same physical properties as the compound obtained in Example 2.,

By proceeding as in Example 1 and starting from the corresponding alcohols, the following products have been obtained: Examples 9, 10, 11 and 12

Example S: (IR, ice h E) 2, 2-Dimethyl-3 / '(2-fluoro-2-ethoxycarbonyl) ethenyl-7-cyclopropanecarboxylic acid (R) (3-ethenyl-3-phenoxyphenyl) -niethyl ester. R * = 72 %.

^ ₁ J = + 40 ° + 1 °, 5 c = 1 % CHCl ₃

233716 2

Example 10: ( ML, da ΔE ) 2, 2-dimethyl-3 Z 2 -fluoro-2-ethoxy-carbonyl-ethenyl / cyclicpropanecarboxylic acid iR (3-phenoxyphenyl) ethyl ester. Yield 81 % <.

* _D = + 94 ° 5 + 2 °, 5 c = 0.5 % CHCl ₃

Example 11; (1R, cis ΔE) 2, -2-dimethyl-3Z "(2-fluoro-2-ethoxycarbonyl) ethenyl / cyclopropane-i-carboxylic acid (S) et-cyano-3-phenoz: y-4 -fluorbenzylester,

<* _π = + 50 ° + 2 °, 5 (ο = .0.5 % CHCl.).

Example 12; (IR, cis 4 E) 2,2-Dimethyiyl-3Z2-fluoro-2-ethoxycarbonyl) ethenyl-1-acarboxylic acid-3-pienylbenzylester »

IR spectrum

C = O ester) ^ ₃₅ ^ -1 -

C = O assigned ester) C = C assigned 16? 5 cm ~

Aromatics. 1588-1489 cm " ¹

Dimethyl pairs 1390-1380 cm " ¹

Example 13 ?

(1R, trans) 2,2-I) im6th; y-l-3 / X & E) 2-fluoro-3-oxo-3-ethoxypropenyl7 cyclopropane carboxylic acid (S) tk -zyano-3 ~ phgnoxybenz3 ^r lester

By proceeding in the example 1-procedure and by the (1R trans) 2,2-dimethyl-3Z (AE) 2-fluoro-3-02: 0-6 tlioxypropenyH ^ cyclopropanecarboxylic acid and from (S) ^ k -Byano- 3-ρheήox3-ben23 ^! lalkohol goes out, you get the desired product *

oC-j. = -33 °, 5 + 2.5 ° (c = 0.5 % CHCl ₃ ).

Prepared Lie (1 R trans) 2,2-dimethyl-3 £ ^ ά 2-fluoro-3-oxo-3-'6thozypropenyl / zyklopropankarbonsäure vmrde -As follows; It is within 30 minutes at 2 ° ^ 10 ⁰ C in a suspension containing 60 cnr 1,2-dimethoxyethane and 2.6 g of a 60% Katriumiiydridsuspension in oil _; a solution containing 7.7 g of ethylphosphonofluoroethylacetate prepared by the method described in Ann. Chem. (1964) 674, 60 cnr

233716 2 -

1,2-dimethoxyethane and 4 g (1R, trans) contains 2,2-dimethyl-3-forniylcyclopropejacarboxylic acid.

The mixture is stirred for 15 minutes at 5 ⁰ C and then for 3 hours at room temperature. A solution is obtained which is poured onto an aqueous Schiefel-1-phosphate solution at 5 ^° C. and stirred for 10 minutes. It is then extracted with Bthylazetat, rinsed with water, dried and evaporated at 40 C under reduced pressure to dryness. 6.5 g of an oil are obtained, which is chromatographed on silica gel, eluting with a mixture of hexane / ethyl acetate / bis (70/30/1). In this way, 4 g of the desired product are obtained.

Example 14

(IH trans) 2,2-Pimethyl; yl-3Z ^ ΔE) 2-fluoro-3-oxo-3-methoxy-propenyl-7-cyclopropanecarboxylic acid (S) -cyano-3-phenoxybenzyl ester stage A; (1 R trans) 2,2-Dimethy 1- 2> C (ΔΕ) of 2-fluoro-3-oxo-3-hydroxypropenylj zyklopropankarbonsäure- (S) ^ 3-phenoxybenzyl * -zyano-

Llan 'is 50 mg of p-toluenesulfonic acid monohydrate in a solution of 1 g of (1R trans) 2,2-dimethyl-3if ( ΔΈ) 2-fluoro-3-oxo-3-ethoxypropenyl7zyklopropankarbonsäure- (S) dk-zvano-3 -phenoxybenzyl-

3 3

ester, 1 cn * of water and 4 cm of dioxane. The reaction mixture is brought to reflux for 8 hours and evaporated to room temperature under reduced pressure to dryness. The residue is again taken up with methylene chloride, rinsed with water and dried. Evaporate to dryness to give 1.1 g of oil, which is chromatographed on silica gel, but eluted with a mixture of hexane / ethyl acetate / acetic acid (60/40/1). Obtained in this way 280 mg of the desired product.

Stage 3? (IR trans) 2,2-dimethyl-3 / ΔE 2-fluoro-3-oxo-3-methoxy-propenyl-cyclopropane-carboxylic acid iso) -4-cyano-3-phenoxybenzyl ester. At a temperature between + 5 ⁰ C and + 10 ⁰ C is in 2 CKi of a methylene chloride solution containing 860 mg of the product prepared in stage A, a slight excess of

23 37 16 2-

4-3 -

Diazoca ethane, which is dissolved in methylene chloride, is 'stirred continuously at 5 ⁰ C for 15 minutes and then at room temperature for 30 minutes.' A few drops of acetic acid are added. It is evaporated to dryness. This gives 950 mg of an oil, which is eluted with an egg-white chromatograph and eluted with a mixture of hexane and ethyl acetate (85/15). 700 mg of the desired product are obtained.

c * _D = -31 ° + 2 °, 5 c = 0.25%, CHCl ₃

Example 15?

(1R, trans) 2,2-dimethyl-3 </ f (AZ) 2-fluoro-3-oxo-3-ethoxy-propenyl-7-cyclopropanecarboxylic acid (S) ef »-cyano-3-phe- noxybenzyl ester.

By carrying out the procedure of Example 1 and of (1R, trans) 2,2-dimethyl-3Z (^ · 2) 2-fluoro-3-o: o-3-ethoxypropenyl-7-cyclopropanecarboxylic acid and of (S) t £ -uysno ^ - Phenoxybenzylalkohol starting, gives the desired product.

_L = + 15 ⁰ * + 2 ° c = 0.5 % CHCl ₃

The (1R, trans) 2,2-dimethyl-3 / '(AZ) 2-fluoro-3-oxo-3-ethoxypropenyl / cyclopropanecarboxylic acid was prepared as follows: i

A solution containing 4 g (1R trans) of 2,2-bimethyl-3-foraiyl-cyclopropanecarboxylic acid and 7 g of diethyloxalofluoroacetate sodium salt is refluxed for one hour. The solution vsieder aur room temperature is brought and poured onto a saturated Schvsefel-1 -Phosphatlösung of 0 ⁰ C, + 5 ⁰ C. The mixture is extracted with ether, rinsed with water and dried. 8.2 g of a product are then obtained, which is chromatographed with silica gel and eluted with a mixture of hexane, ethyl acetate and acetic acid (70/30/1). 4.3 g of the desired product are separated in this way. ,

Example 16

(1R, ice) 2,2-Dimethyl-3Z '(AZ), 2-fluoro-3-oxo-3-methoxy-propenyl-7-cyclopropanecarboxylic acid (S) <- cyano-3-pheJeoxybenzyl ester

Stage A; (IR, ice) 2,2-dimethyl-3 <T (^ Z) 2-fluoro-3-oxo-3-hydroxypropenyl-1-cyclopropanecarboxylic acid iso) - ^ -cyano-3-phenoxybenzyl-

233716 2

.- fro -

ester.

By proceeding as in Example 14, Stage A, the product (1R, 6) 2,2-lirahethyl-3 / (Z) 2-fluoro-2-ethoxycarbonyl-ethenyl-7-cyclopropanecarboxylic acid (S) A .-CYANO-3-phenoxybenzylester starting, you get the desired products

Stage B: By proceeding as in Example 14, Stage B, proceeding from the product produced in Stage A, the desired product is obtained.

«* _D = -2 °, 5 + 2 ° c = 0.4 % CHCl.,

Example 17

(1R, cis) 2,2-Dimethyl-3 / (ΔΖ) 2-fluoro-3-oxo-3-tert-butoxypropenyl-7-cyclopropane carboxylic acid ~ (S) ^ -cyano-3-phenoxybenzyl ester 2.3 g of (1R, cis) 2,2-pi-methyl-3Z2-fluoro-3-03Co-3-hydro 2: y- (Z) -propenyl-7z3 ^r- klopropanecarboxylic acid (S) -6-cyano-3-phenoxy Example: 15 cm ³ ethyl acetate and 2.4 g U- ( ¹ -methylethyl) -U ¹ - (i-methylethyl) -carbamic acid-butyl ester (tert.) with stirring. The mixture is filtered and the filtrate is evaporated to dryness. Then, 2.6 g of the product, which is purified by chromatography on silica gel, and zvsar by elution with n-hexane / isopropyl ether (8/2) under nitrogen pressure. This gives 2.2 g of the product, which is recrystallized in isopropyl ether. This gives 1.4 g of the desired product, which melts at 103.degree.

^ _L = + 2.5 ° + 3 ° c = 0.2 % CHCl ₃

Pas 17- (1-methylethyl) -1 '- (1-ethylethyl) -carbamic acid butyl ester (tert.) Was prepared as follows:

98.7 g of ^, IT'-diisopropylcarbodiimide and 57.9 g of tert-butyl alcohol are stirred in the presence of 5 g of copper-containing chloride for 4 1/2 days at room temperature. 117.7 g of the expected product are obtained after the reaction mixture is distilled below 9 mm Hg pressure (and 74 ^° C. under 9 mm Hg).

233716 2

Example 18

(1R, cis) 2,2-Dimethyl-3 £ (£ Z) 2-fluoro-3-oxo-3- (1,1,1,3,3,3-hexafluoro) isopropoxy-n'-propenyl-7-cyclopropanecarboxylic acid ( S) o (cyano-3-phenoxybenzyl ester.

One at + 21 mg of 4-Dimethylaminopy- are 5 C ⁰ / + 10 ⁰ C within 10 minutes, a solution in which 0.6 g Dizyklohexylkärbodiimid,

3 rdine and 5% methylene chloride are added to a solution containing 1.1 g of (1R, cis) 2,2-pi-methyl-3/2-fluoro-3-oxo-3-hydroxy (Z) -propenyl-cyclopropanecarboxylic acid (S. ) ^ ₁ -cyano-3-phenoxybenzyl ester,

3 3

.5 cnr methylene chloride and 0.5 cnr 1,1,1,3,3,3-hexafluoropropan-2-ol. The mixture is filtered, the filtrate is evaporated to dryness, the residue obtained is chromatographed with silica gel and eluted with a mixture of hexane / ethyl acetate (9/1) and under nitrogen pressure. This gives 750 mg of the desired product »,

G ^ p = + 18 ° 5 + 1 ° c = 1 % benzene

Example 19

(1R, cis) 2,2-Dimethyl-3Z2-fluoro-3-oxo-3-methoxy- (E) -propenyl7-cyclopropanecarboxylic acid (S) ^ -cyano-3-phenoxybenzyl ester.

Stage A: (1R, cis) 2,2-dimethyl-3/2-fluoro-3-oxo-hydroxy- (e) -propenyl-7-cyclopropanecarboxylic acid (S) - d -cyano-3-phenyl-oxybenzyl ester *

i-ian brings for 24 hours a solution containing 2.5 g of (1R, cis) 2,2-ethyl-3 / (E) 2-fluoro-2-ethoxy-carbonyl-ethenyl-7-cyclopropane-1-carboxylic acid (S) d. -cyano-3-phenoxybenzylester, 10 cnr dioxane and 2.5 cnr water and 1 g p-toluenesulfonic acid monohydrate, to reflux. »It is brought back to room temperature, diluted with methylene chloride and rinsed with water. The organic phase is dried, filtered and the filtrate is evaporated under reduced pressure. The resulting residue is chromatographed by elution with a mixture of hexa-hexane / ethyl acetate / acetic acid (60/40/1) to give the desired product (980 mg).

16-2 -. * -

Stage B-: (1R, c is) 2,2-Dimethyl-3,3'-2-fluoro-3-oxo-3-methoxy- (E) -propene-1-ylcopropene carboxylic acid - (S) <o ( - -cyano-3-phenoxybenzylester ..

By proceeding in Example 14 (Stage B) and (1R, cis) 2,2-dimethyl-3- ^ 2-fluoro-3-os: o-3-hydroxy- (E) -propenyl-7-cyclopropanecarboxylic acid (S) 4s -cyclo-3-phenoxybenzylester starting, gives the desired product, P = 70 ⁰ C,

«* P = + 52 °. + 1.5 ° c = 1 % CHCl ₃

By comparing workers in the previous example and the corresponding alcohols, the following products were produced *

Example 20

(1R, ice) 2,2-Dimethyl-3-fluoro-3-oxo-3-n-propyloxy- (E) -propenyl7-cyclopropanecarboxylic acid (S) ol-cyano-3-phe- noxybenzyl ester.

⁰ Sd ^{= + 38} »5 ° + 2 ° c = 0.7 % CHCl ₃

Example 21

(1R, ice) 2,2-Pimethyl-3Z2-fluoro-3-oxo-3-tert-butoxypropenyl / cyclopropane carboxylic acid (S) cfe-cyano-3-phenoxybenzyl ester.

By proceeding as in Example 17, starting from "(1R, cis) 2,2-dimethyl-3/2-fluoro-3-oxo-3-hydroxy- (E) -propenyl-7-cyclopropanecarboxylic acid (S) dv-cyano- 3-phenoxybenzyl ester and tert-butyl { ^T (1-methylethyl) K ^f - {i-methylethyl) carbamate (tert.), The desired product is obtained (yield .61 %).

^ ₁ , = + 26 ° 5 (c = 0.25 % CHCl ₃ )

Example 22

(1R, cis) 2,2-dimethyl-3 / (AE) 2-fluoro-3-oxo-3 (1,1,1,3,3,3) hexafluoropropoxy-n-propenyl-7-cyclopropane carboxylic acid - (S) c <Zyano-3-phenoxybenz5 ⁷ lester.

by carrying out the reaction in Example 14, Stage B, and of (1R, cis) 2,2-DL-ethyl-3-Z 2 -fluoro-3-oxo-3-hydroxy- (E) -propenyl-7-cyclopropanecarboxylic acid (S) g -cyano-3-phenoxy-3-benzyl ester and 1,1,1,. 3s3,3-Hexafluoropropan-2-ol, the desired

233716 2

Product"

= + 21 ° + 2 ° c = 0.5 %

Example 23

(1R, cis) 2,2-Dimethyl-3-Z 2 -fluoro-3-os: o-3-isopropyloxy- (E) -propenyl-7-cyclopropanecarboxylic acid (S) * -cyano ^ -phenoxybenzyl ester.

dk _D = + 46 ° + 1 ° c = 1 $ CHCl ₃

Example 24

(1R, ci £) 2,2-Dimethyl-3/2-fluoro-3-oxo-3-cyclopropyloxy- (B) -propenyl-7-cyclopropane-carboxylate (S) cfe -cyano-3-plienoylbenzyl ether

P = 50. ⁰ C

* -, = + 35 ° + 1 ° c = 1.3 5S CHCl,)

example 25 '

(1R, cie, AE) 2,2-dimethyl-3- _i / 2-fluoro-3-oxo-3 (/ 3-methoxyethoxy) propenyl / cyclopropanecarboxylic acid CS) ^ -cyano-3-pienoxybenzyl ester.

= 47 ° + 2 °, 5 c = 0.5

Example 26

(1R, trans) 2,2-dimethyl-3 - / (L · Z) 2-fluoro-3-oxo-.3-methO3: ypropenyl / zyklopropankarbonsäure- (S) C ^ -zyano-3-pbejiO2ybenzylester _e

Stacimn Ai

(1R trans) 2,2-Dimethyl-3 / "(UZ) 2-fluoro-3-ozo * -3-hydroxypropyl} -7-cyclopropanecarboxylic acid (S) flv -cyanopaphenoxybenzyl ester.

By never proceeding in Example 14, Stage A, and zvsar starting from the corresponding ester (ΔΖ), one obtains. the desired product «,

Stage B; (1R, trans) 2, 2-Dimethyl-3Z '(4Z) 2-fluoro-3-oxo-3-methoxy-propenyl-2-cyclopropane-carboxylic acid CS) ^ -cyano-3-phenoxy-acyl ester. .-

233716 2 -

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

<£ _D = + 15 °, 5 + 2 ° 5 G = 0.3% GHC1 ₃

Example 27

(1R, cis) 2,2-dimethyl-3 ^ T Δ Z) 2-chloro-2-methoxykarbonyIetheny l / zyklopropankarbonsäure- (S) o ^ -zyano-3-phenoxybenzyl ester.

By proceeding as in Example 1, starting from (1R, cis) 2,2-dimethyl-3 (Z) / 2-chloro-2-methoxycarbonylethenyl-7-cyclopropane carboxylic acid and from (S) O-1-yano-3-p-pseudoeoxybenzyl alcohol you get the desired product.

^ P = 62 ° 5 + 1 ° 5 c = 1 % benzene

Example 28

(1R, cis) 2,2-Dimethyl-3Z (AE) * 2-chloro-2-metho3: ycarbonylethenyl 7-cyclopropanecarboxylic acid (S) 2-methyl-4-O2: o-3- (2-propenyl) 2- "cyclopentene-1-yl ester ·

The product was recovered as the previous product, from (1E, cie) chloride of 2,2-dimethyl-3 (Z) / 2-chloro-2-niethoxy carbonylethenyl-2-yl-propane carboxylic acid and from (4S) -hydroxy-3-methyl- 2- (2-propenyl) -2-cyclopentene-1-one.

«Λ = - 15 ° + 4 ° c = 0.25 % benzene

RME CDCl ₃ ppm

1,28 and 1,3 H of the methyl groups at 2 »position 3,8 H of the group 2,02 H of H-C

6.8-7 H of the ethylene borne by the carbon atom at the first position of the 2-methoxycarbonylethenyl radical

example ZS

(1R, cis) 2,2-dimethyl-3Z (Z) 2-chloro-2-methoxycarbonylethenyl 7-cyclopropane carboxylic acid (1S) 2-methyl-4-ozo-3- (2-propenyl) -2-cyclooyl

233716 2

pentene ~ 1-yl ester.

The product is obtained from the chloride of the (1R, cis) 2,2-dimethyl-3 - / (Z) 2-chloro-2-methoxycarbonylethenyl / cyclopropane carboxylic acid and (4S) hydroxy-3-niethyl-2- (2S). propenyl) -2-cyclopentene-1-one * Then the desired product is obtained «

ot _D = + 27 ° + 2 ° 5 c = G, 3 ^ CHCl ₃

Example 30

(1R, cis) 2,2-Dimethyl-3Z (E) 3 "-oxo-2-chloroethoxypropenyl-72-cyclopropanecarboxylic acid (S)" - "- cyano-3-pk'e: aoxybenzyl ester _e

By proceeding as in Example 1, starting from (1R, ice) 2,2-dimethyl-3 / (E) 3-oxo-2-chloro-3-ethoxypropenyl7 cyclopropanecarboxylic acid and (S ^^ -iyano-3- phenoxybenzyl alcohol, the desired product is obtained

«< _{3 = +1} 9 ° + 2 ° (c = 1 SS CHCl ₃ )

The (1R, cis) 2,2-diniethyl-3/3-oxo-2-chloro-3-ethoxy-propenyl-7-cyclopropane-carboxylic acid (isomers E and Z) was obtained as follows:

Stadium "Ai Ethoxykarbonylchlormethylentriphenylphosphorano Prepare a solution of about 2 ⁰ C aue 4 g of chlorine in 80 a chloroform forth Add 20 g Ethoxykarbonylmethylentriphenylphosporan in 40 cm of chloroform added Man let the temperature of the reaction mixture to rise to .Zimmertemperatur and evaporated it under reduced pressure. An oil is obtained which is dissolved in 70% of methylene chloride, washed with a solution of 6.1 g of sodium carbonate in 40 cm of water and then with water, dried and evaporated to dryness 18.9 g of the desired product.

F = ii6 ^G ~ ns ⁰ C

Stage Bi (1R, cis) 2,2-dimethyl-3/3-oxo-2-chloro-3-ethoxypropenyl / cyclopropane carboxylic acid (isomers E and Z).

In a solution containing 18.9 g of the product prepared in stage A in 200 cm- ³ tetrahydrofuran, are added 6.9 g of lactone

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-, 56 -

the (1R, cis) 2,2-dimethyl-3 (dihydroxymethyl) zyklopropankarbonsäure in 100 cirr tetrahydrofurans The resulting solution vsird 6 ^1/2 hours at room temperature, stirred and the solvent is distilled under reduced pressure. An oil is obtained, which is added to 50 cm of ethyl ether, stirred to 0 C, filtered, • washed with ether, the resulting precipitate and the filtrate evaporated to dryness «obtained 22.2 g of the desired product, which with Kiesel chromatograph It is extracted, eluting with a mixture of cyclohexane / ethyl acetate / acetic acid (75-25-1). »In this way one obtains:

a) on the one hand 3.58 g of the desired product in the form of iso

ppm

H of the methyl groups at 2 "place of the cyclopropane

H at the carbon atom 1 of the cyclopropane

H at the carbon atom 3 of the cyclopropane

H at the carbon atom 1 of the propenyiradical

b) and on the other hand 2.34 g of the corresponding product Z.

RMl CDCl-ppm

1.33 and 1.36 H of the methyl groups at 2 «. location

1.96-2.1 × H of the carbon atom 1 of the cyclohexane

propane

2.2.3 to 2.53 H of the carbon atom .3 of the cyclopropane

Example 31

(1R, c is) 2,2-dimethyl-3 / (Z) 2-chloro-3-oxo-3-ethoxypropenyl / cyclopropanecarboxylic acid (S) -cyano- (3-pheioxybenzyl) ester

By proceeding as in Example 1, starting from (1R, ice) 2,2-dimethyl-3Z (Z) 3-oxo-2-chloro-3-ethoxypropenyl-7-cyclopropanecarboxylic acid and (S) o4-byano-3-phenoxybenzyl alcohol, , you win the desired product «

<* + 21 ° 5 + 2 ° 5 · (c β 0,3 Si CHCl,)

E's; RM and CDCl ₃ 1.3 - 2 1.33 1.89 to , 02 2.85 - 6 3.05 6.78 95

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Example 32

(1R, cis) 2,2-Mmethyl ~ 3Z (£) 3 ~ oxo-2-chloro-3-propoxy-propenyl7 cyclopropanecarboxylic acid (S) δ-cyano (3-phenoxybenzyl) ester »

By proceeding as in Example 1, starting from (1R, cis) 2,2 ~ diiaethyl-3Z ( ^B ) 3-oxo-2-chloro-3-propoxypropenyl-7cyclo-. propane carboxylic acid and (S) - (-! "yano-3-phenylhexybenzyl alcohol, the desired product is obtained.

_D = + 24 ° 5 + 2 ° c = 0.4 % CHCl ₃

The (1R, cis) 2,2-dimethyl-3ZlE) 3-oxo-2-chloro-3-propoxypropenyl / cyclopropanecarboxylic acid was prepared as follows ί

Stage Ai Propoxycarbonylchloromethylenetriphenylphosphorane »

By proceeding as in the preparation of the (1R, cis) 2,2-dimethyl-3 - / * (E) 3-oxo-2-chloro-3-ethoxypropeny] _s 7zyklopropanecarboxylic acid, Example 30, Stage A, starting from Prop # - cxycarbonylmethylenetriphenylphosphorane, the desired product is obtained *

Stage Bi (1R, cis) 2,2-dimethyl-3 / "(1) 3-oxo-2-chloro-3-propoxypropenyl ^ cyclopropanecarboxylic acid.

By proceeding with the preparation of the (1R, cis) 2 _J 2-dimethyl-3 - / (E) 3-Gro-2-clilor-3-et3ioxypropenyl-7-propanolanecarboxylic acid, Example 30, stage B, starting from the product obtained in stage A, one obtains on the one hand a desired product and on the other hand the corresponding isomer Δ 2 »

Example 33

(1R, cis) 2 _i 2-Diniethyl-3 _i / r (Z) 3-oxo ~ 2 ~ chloro-3-propoxypropenyl7 zyklopropankarbonsäure- (S) c ^ -zyano-3-phenoxybenzyl ester.

By doing as described in Example 1 and (1R, cis) 2 "2-dimethyl-3 _J / (Z) -3-oxo-2 ~ chloro ~ ^3-p2> cpoxypropenyl / zyklopropankarbon ~ acid and (SM -iyano- 3-phenoxybenzyl alcohol, the desired product is obtained »

° 5 + 2 °

= 22

5 + 2 ° C * 0.7 % CHCl ₃

2 3 3 7 16 2

Example 34

(1R, cis) 2,2-Dimetyl-3 / (E) 3-oro-3-tert-butoxy-2-ciiloropropenyl / cyclopropanecarboxylic acid (S) c-cyano-3-phenoxybenzyl ester _e

By proceeding as in Example 1 and from (1R, cis) 2,2-dimethyl-3 / XE) 3-oxo-3-tert-butoxy-2-chloropropenyl-7-cyclopropanecarboxylic acid and from (S) -z ^ ano-3 starting from phenoxybenzyl alcohol, the desired product is obtained.

<* _D = + 3O ° 5 + '2 ° (c = 0.7 %

The (1R, cis) 2,2-dimethyl-3 (oxo-3-tert-butoxy-2-chloropropenyl) cyclopropane carboxylic acids (isomers E and .Z) -J were prepared as follows:

Stad-ium Ai Tert "-butoxycarbonylchloromethylenetriphenylphosphorane.

By working previously (indicated preparation according to Example 30, stage A), the desired product was obtained from tert-butoxycarbonylmethylenetriphenylphosphorane

P '* 160 ⁰ C

Stadiom 3: acid Δ E + acid Δ Ζ

By starting from the product prepared in stage A, as indicated for the preparation according to example 30, stage B, on the one hand (1R, cis) 2,2-dimethyl-3 - / (E) 3-oxo was obtained. 3-tert-butoxy-2-chloropropenyl-7-cyclopropanecarboxylic acid (P = 65 "C) and, on the other hand, the corresponding isomer (Z) (P <50 ^° C.) ₆

Example 35

(1R, cis) 2,2-dimethyl-3 / (Z) 2-bromo-3-oxo-3-methoxy-propenyl-7-cyclopropane-carboxylic acid (S) -ti . - cyano-3-phenoxybenzylester _e

By proceeding as in Example 1, starting from (1R, cis) 2,2-dimethyl-3/2-bromo-3-oxo-3-methoxy- (Z) propenyl-7-cyclopropanecarboxylic acid and (S) vV- Yano-3-phe noxybenzyl alcohol, he ^ one keeps the desired product

^ ₁ J = 29 °, 5 + 2 °, 5 (c = 0.5 % CHCl ₃ )

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The (1R, Gis) 2,2-dimethyl-3/2-bromo-3-oxo-3-methoxyj (Z) -propenyl / cyclopropanecarboxylic acid was prepared as follows : Stage A: (1R, cis) 2,2-dimethyl-3. / i »2- (dibromo-RS) 3- ^ co-3-metheoxypropyl-cyclopropane carboxylic acid tert. butyl ester ·

13.3 g of pyridinium tribromide are introduced into a solution containing 8.07 g (1R, cis) of 2,2-dimethyl-3-n-2-methoxycarbonyl- (E) -ethenyl / cyclopropanecarboxylic acid butyl ester (tert corresponding acid, which is published in the published European

3 see application Kr. 0018 894, and 50 cm diam.

- contains m.ethylsulf oxide «. The reaction mixture is kept under stirring for 3 hours and 30 minutes, after which it is poured into ice water. Extraction is carried out with methylene chloride. The organic phases are collected »dried and evaporated under reduced pressure to dryness. This gives 14.3 g of oil, which is chromatographed with silica and eluted with a hexane / Ethylazetatmischung (9/1). 4 g of the desired product are obtained. *

Stage B? (1R, cis) 2,2-Dimethyl-3/2-bromo-3-oxo-3-methoxy ~ (Z) -propenyl-7-cyclopropanecarboxylic acid butyl ester (terto).

4 cnr of triethylamine are added to a solution containing 40 cm of benzene, 4.2 g of (1Rpis) 2,2-dimethyl-3 / i, 2 (dibromo RS) 3-oxo-3-methoxypropyl-cyclopropanecarboxylic acid butyl ester, Crt.). It is stirred for 6 hours and 30 minutes the reaction mixture at 22 - ^ 24 Cc E _n is diluted with ether, washed with a Schvsefei-1-phosphate solution and then rinsed with water, is dried and concentrated under reduced pressure at 40 C ₀ is obtained in this manner , 3.3 g of the desired product,

Stage Cf (1R, cis) 2,2-Dimethyl-3-i2-bromo-3-oxo-3-methoxy- (Z) -propenyl-7-cyclopropanecarboxylic acid

A mixture of 3.3 g of the product prepared in stage B, 30 cc toluene and 0.33 g p-toluenesulfonic acid monohydrate is brought to reflux. The reflux is maintained until gas formation ceases. It vsird to 20 ⁰ C cooled and diluted Bthylether and ater-rinsed with Y /. It is dried and concentrated under reduced pressure at 40 C. Obtained

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2.9 g of the desired product in this way,

Example 36

(IR, cis) 2,2-Oimethyl-3-ZE + Z) 3-oxo-3-methoxy-2-bromopropenyl-2-cyclopropane-carboxylic acid (S) efc-cyano-3-pienoxybenzyl ester.

By proceeding as in Example 1 and from (1R, ice) 2,2-dimethyl-3- / 2-bromo-3-oxo-3-methoxy- (E) -propylene / cyclopropanecarboxylic acid and from (S) c £ -iyano 3-piienoxybenzyl alcohol, the desired product is obtained.

* < _D = + 9 ° 5 + 2 °, 5 (c = 0.3 % CHCl ₃ )

The (1 R, ois) of ^{2,2-dimethyl-3-Z2-'bi%} omo-3-oxo-3-methoxy- (E) is prepared as follows propenyljzyklopropankarbonsäure stage i Ai (1R, cis) 2,2-dimethyl 3 ~ / 2-bromo-3-oxo-3- ⁱ Eiethoxy- (e) propenyl7zyklopropankarbonsäurebutylester (tert,) * There are a 100 cm ^ 50 'ifchwefellösung in a mixture optionally containing 120 cm- ⁵ methylene chloride, 6.7% (IR, ice) 2,2-Dimethyl-3- / 1,2- (dibromo RS) 3 -oxo-3-methoxypropylcyclopropanebutyl ester (tert.) And 120 mg of zetavlon (trimethylzetylammonium bromide). The reaction mixture is stirred for 4 hours, Man diluted by adding 100 cc of methylene chloride and decanting the organic phase, which is extracted again through 100 cm of methylene chloride ( The organic phases are washed with n-hydrochloric acid to an acidic pH and then with Yifasser to a pH of 7 washed. the organic phases are concentrated and dried under reduced pressure at 40 ⁰ C evaporated to give 5.3 g of a product which Chro Matograph! ert and by a mixture of hexane / isopropyl ether (8/2) is eluted. 3.5 g of the desired product are obtained.

Stage Bi (1R, cis) 2,2-Dimethyl-3/2-bromo-3-oxo-3-methoxy- (E) -propenyl-cyclopropane carboxylic acid was prepared as follows!

A solution of 3.4 g of (1R, cia) 2,2-dimethyl-3-Z2-bromo-3-o3co-3-methoxy- (E) -propene3 / 1 _; 7-cyclopropanebutyl ester (tert.), 30 cm

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-H-

Toluene and 0.35 g of p-toluenesulfonic acid monohydrate are refluxed until gas formation ceases. It is cooled to 0 ⁰ C and filtered, washing the resulting precipitate with kaltem'Toluen evaporated and the PII occurred under reduced pressure at 40 C. This gives 2.8 g of the desired product. "

Example 37

(1R, cis) 2,2-Dimethyl-3 - ((E) 2-bromo-3-oxo-3-tert-butoxy-propenyl-7-cyclopropanecarboxylic acid (S) i -cyano-3-phenoxybenzyl ester

By using in Example 1 - starting from (1R, cis) 2,2-dimethyl-3 / 1E) 2-bromo-3-oxo-3-tert-butoxypropenyl-cyclopropanecarboxylic acid and from (S) <* -xyano-3 Phenoxybenzylalkohol - proceeds, you get the desired products

% = + 16 ° 5 + 2 ° (c = 0.7 % CHCl ₃ )

The (IR, ice) 2,2-dimethyl-3H (E) 2-bromo-3-oxo-3-tert- _e -butoxypropenyl-2-cyclopropanecarboxylic acid was obtained as follows;

Stage Ai Tert "-Butoxykarbonjj-lbromethylenetriphenylphosphorane",

By working as in the preparation of (1R, cis) 2,2-dimethyl-3H-T (E) 3-oxo-2-chloro-3-ethoxy-propenyl-7-cyclopropanecarboxylic acid (indicated in Example 30, Stage A) and extracting from the derivative Butozykarbonylmethylentriphenylphosphoran and starting from bromine, gives the desired product whose melting point is 190 ⁰ C »

Stage B; (IR, ice) 2,2-dimethyl-3-E) 2-bromo-3-oxo-3-tert-butoxy: ypropenyl-7-cyclopropane carboxylic acid.

By proceeding as in the preparation of (1R, cis) 2,2-dimethyl 3/2 E) 3-0X0-2- c hloro ^ -ethoxypropenirl / zyklopropankarbonsäure ((specified in the Example 30, Stage B) and from the Starting at stage A, the desired product with the melting point JG ⁰ C and, secondly, the corresponding isomer Z with P = 50 ° C. »

23 37 16 2

Example 38

(1R, cls) 2,2 ~ Dimethyl-3 / "(Z) 2-bromo-3-ozo-3-tert-bαtoxypropenyl-7-cyclopropanecarboxylic acid (S) (3-cyano-3-phejiozybenzyl ester

By operating as in Example 1 and of (1R, cis) 2,2-dimethyl-3ZT (Z) 2-bromo-3-oz: o-3-tert-butoxypropenyl-7-cyclopropanecarboxylic acid and of (S) ₀ → 2-yano-3-phenoxybenzyl alcohol, the desired product is obtained.

* _D = + 16 ° 5 + 2 ° c = 0.5 % CHCl ₃

Example 39

(1R, cis) 2,2-dimethyl-3HT CE) 3-O3co-2-bromo-3-e-thoxypropenyl / cyclopropanecarboxylic acid (S) -cyano-3-phenoxybenzyl ester _e

By proceeding as in Example 1, starting from (IR, ice) 2 »2-dimethyl-3 / (E) 3-oxo-2-bromo-3-ethoxy-propenyl-7-cyclopropanecarboxylic acid and from (S) eV-yano- 3-phenoxybenzy! Alcohol, the desired product is obtained.

, c * _D = - 7O ° 5 + 2 ° c = 0.7 % (CHCl ₃ )

The (1R, cis) 2,2-bis-ethyl-3Z (E) 2-bromo-3-oxo-3-ethoxy-propenyl-7-cyclopropane-carboxylic acid is prepared as follows;

Γ Stage Ai Ethoxycarbonylbromomethylenetriphenylphosphorane «,

The product is recovered according to the procedure given for the (IR, cis) 2,2-dimethyl-3Z (E) 3-oxo-2-chloro-3-ethoxy-propenyl-7-cyclopropane carboxylic acid in Example 30, Stage A, and sv? Ar from the derivative Ethoxykarbonylmethylentriphenylphosphoran and Brom._Man obtained in this way the desired product whose melting point is 150 ⁰ C.

Stage B; (IR, ice) 2,2-Dimethyl-3 / "(E) 2-bromo-3-oxo-3-ethoxy-propenyl-1-carboxylic acid The product was prepared from Stage A according to the procedure given for obtaining the corresponding chlorous acid product obtained.

In this way, on the one hand, the desired product and, on the other hand, the corresponding product AZ has been separated off,

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Example 40

(1R, cis) 2,2-DImethyl-3 / * (B) 2-fluoro-3-oxo-3-ethoxypropenyl / cyclopropanecarboxylic acid (RS) "<-cyano-G-phenoxy-pyridylmethyl ester"

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

^ ₁ , = + 35 ° + 4 ° Cc = 0.3 % CHCl ₃ J

Example 41

(1R, cis) 2,2-Dimethyl-3 / (I) 2-fluoro-3-oxo-3-ethoxy-propenyl-7-syklopropanecarboxylic acid 3 "" (2-propenyl) 2,5-dioxoimidazolidinylmethyl ester *

By proceeding in Example 1 vsie and starting from the corresponding acid * and the corresponding alcohol, you get the desired products,

* _D = + 12 ° + 2 ° c = 0.5 % CHCl ₃

Example 42

(1R, cis) 2,2-Dimethyl-3Z * (E) 2-Fluo2> -3-oxo-3-ethoxy-propenyl-7-cyclopropanecarboxylic acid (S) 2-methyl-3-2-llyl-4-oxo-2-cyclopentene -1-yl ester. "

By proceeding as in Example 1 and thereby of the corresponding. , Acid and starting from the corresponding alcohol, you get the desired product

S ^ _D = + 41 ° 5 + 2 °, 5 c = 0.5 % CHCl ₃

Example 43? Preparation of a soluble concentrate.

M.an produces a homogeneous mixture of: product from Example 1 0.25 g

Piperonyl butoxide 1.00 g "

Tvseen 80 0.25 g

Topartol A "0.1 g

Water 98.4 g

2 3 3 7 16 2 -

Example 44i ' Preparation of an Emulsifiable Concentrate

One mixes very gat:

Product of Example 1 0.015 g

Piperonyl butoxide 0.5 g

Topanol Λ 0.1 g

Tween 80 3.5 g

Jylene. , 95.885 g

Example 45? Preparation of an emulsifiable concentrate

It is e'in homogeneous mixture made of ί

Product of Example 21 1.5 g

Tv »een 80 20.00 g

Topanol A 0.1 g

lylene 78.4 g

Example 46: Preparation of a fogging agent

They are homogeneously mixedί

Product of Example 1 0.25 g

Tabun powder 25,0Og

Cedar leaf palette 40,00 g

Pinewood powder 33.75 g

Brilliant green 0.5 g

p-Uitrophenol 0.5 g

Example 47? Preparation of a pharmaceutical compound

Solutions were prepared which correspond to the following formula ί

Compound of Example 11 5.00 g

Piperonyl butoxide · 25.0Og

Polysorbate 80 10.00 g

Triton Σ 100 25.00 g

Tocopherol acetate - .1-00 g

Ethyl alcohol q.s.p. 100 ml

This gives a solution which, when used in 5 l of water, is dilute »

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Example 48 ί Example of a pharmaceutical composition

A solution was prepared which has the following formula-ί

Compound of Example 11 0.5 g of piperonyl butoxide 2.5 g

Polysorbate 80 10.00 g

Triton X 100 25.00 g

Tocopherol acetate .1.0 g

Ethyialcohol q »s.p. 100 cm

In this way, a solution is obtained, which is to be diluted in 5 liters of water when used. "

Example 49s Example of pharmaceutical compositions

Capsules are prepared containing 1 g of the product of Example i

Example 50? Example of a plant for animals

As a balanced forage is used a feed containing corn, dried alfalfa, cereal straw, palm molasses pomace, urea and vitamin-containing mineral spice.

This feed contains at least 11 % raw protein (2.8 % of which is covered by urea), 2.5 % fat and at most 15 % cellulose, 6 % minerals and 13 % water.

The feed used corresponds to 82 feed units for 100 kg and contains per 100 kg of 910 000 ü.I. " ¹ "'Vitamin A, 91 000 UoIa ⁺ ' Vitamin D, 150 mg Vitamin E and 150 mg Vitamin C.

This feed is supplemented with 0.3 kg of the compound from Example 3, totaling 100 kg of the feed. «

Example 51ί Example of a feed connection for animals

The same balanced forage is used as in Example 50 ". To this feed, 0.04 kg of the compound from Example 1 is added to a total of 100 kg of the feed

+) Note: "I. = 'Unites internationales (internat * units)

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^ - study of insecticide * bg-e-ften effect of erfindmigagemäßen ^compounds':

In this investigation are used; (1R, cis) 2,2-dimethyl-3 (E) ^ -chloro ^ -ffiethoxycarbonylethenyl-cyclopropane-i-carboxylic acid- (S) <- cyano-3-phenoxybenzyl ester (Compound A), (1R, ice) 2,2 - dimethyl-3 (E) -bromo-3-propoxy-carbonyl-ethenyl) cyclopropane-1-carboxylic acid (S) c <* - »cyano-3-phenoxybenzyl ester (compound B), (1R, cis) 2,2-dimethyl- 3 (Z) (2-bromo ~ 2-propecs: ycarbonylethenyl) cyclopropane-1-carboxylic acid (S) oC-cyano-3-phenoxybenzyl ester (Compound C) and (IR, ice) 2,2-dimethyl-

2-flucro-2-ethos: γ-carbonyl-ethenyl-7-cyclopropanecarboxylic acid-cyano-3-phenoxybenzyl ester (Compound D) _β

A. Investigation of the paralyzing effect on house-lines

The 'test insects are 4-day-old female house flies.' Bs is a direct atomization in a concentration of 0j25 g / l in a Kearns-ZMarch-Kaminer, using as solvent a mixture of acetone (5 %) lind Isopar L (Erdb'l) Solvent) (amount of solvent applied 2 ml in one second). 50 insects are taken per treatment. The controls are performed every minute to ten times and then 15 minutes after the treatment and KT 50 is determined by conventional methods. "

The experimental results obtained are summarized in the following table

verDinounge in jit _c 50 3 in mm. connection (A) 4 »6 connection (B) 4 , 5 connection (C). · 2 > 5 connection (D) ,1

B » investigation of the deadly effect of the compounds of the invention on various insects

a) Investigation of the deadly effect on house flies

The test insects are female 4-5 day old houseflies _e They are used locally by 1 / ul azetonischer solution

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on the dorsal thorax of the insects, and zvvar by means of Arnold's micromanipulator »50 animals are used per treatment, the control of mortality is 24 hours after the treatment«

The results obtained, expressed in DL 50 or required dose (in "Eanoe" per animal to kill 50 % of insects) are as follows;

Connections DL in ng / Inaekt

Compound (A) 11.1 Compound (B) 1.0

k) Examination of the deadly effect on cockroaches

The tests are carried out by contact with glass film by applying acetone solutions of various concentrations - by means of a pipette - to the bottom of a glass Petri dish, the edges of which were previously lubricated to prevent the removal of the insects. ", The deadly concentration 50 ( CL 50) is determined »

The experimental results obtained are summarized in the following table

Compounds OL 50 in mg / m Compound (A) 1.4 Compound (B) 0.40

c) Investigation of the deadly effect on larvae of Spodoptera littoralis

The experiments are carried out by local application of an acetone solution by means of the Arnold micromanipulator on the dorsal thorax of the larvae. 15 larvae are used per dose of the product to be tested. "The larvae used are larvae of the 4th instar, that is, they are about 10 days old when kept at 24 ⁰ C and a relative humidity of 65 % Treatment, the larvae are placed in an artificial putter medium (poitout environment) ♦

Mortality is controlled 48 hours after treatment,

23 37 16 2 -. «* ·

The experimental results obtained are summarized in the following table

Compounds Dl x 50 in ng / insect

Compound (A) 6,7 Compound (B) 3 _> 2 Compound (D) 1,0

d) Investigation of the deadly effect on Bpilachna varivestris

The experiments are carried out by topical application in the same way as for the Spodoptera larvae. Man-used r larvae of the penultimate .Larvenstudiums and after the treatment, the larvae are fed by bean plants "The control mortality is carried out 72 hours after the treatment,

The results are shown in the following table:

Compounds DL 50 in ng / insect

Compound (A) 17.7 Compound (B) 7.4 Compound (D) 0.85

e) Examination of the deadly effect on Aphis Cracivora

One uses mature 7-day-old Aphis C = 10 pieces per applied concentration. A contact-injection method is used * The treatment is carried out with the Fischer gun on a broad bean leaf, which is placed in a plastic Petri dish on a moistened paper disc. The treatment is carried out with 2 ml of acetone solution of the product to be tested (1 ml per leaf side). The Insekteninfizierang takes place after drying the sheet. The insects are kept in contact with the leaf for 1 hour, the insects are then placed on untreated leaves and the mortality is checked after 24 hours.

The obtained experimental results are shown in the following table;

connection VL 50 in ng / insect

Compound (B) 6.4.

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f) Conclusion:

In the experiments described in sections a, b, c, d and e, the compounds A and 3 also show a significant insecticidal action »

g) General conclusion?

In the previously described experiments, the compounds according to the invention have a significant effect on activity .beta

C) Investigation of the mite-destroying effect of the compounds according to the invention

One uses bean plants, which have 2 by 25 in each case tetranychus urtioae- infected sheets, over which a ventilated filter is put on and on which constant light is acted on. The plants are treated with the Fischer pistol, 4 ml of poison solution per plant equal volume of water and acetone mixture. It is allowed to dry for 12 hours and then the infection takes place. The mortality controls are performed 80 hours later. The dose used in each test is 5 g of product per hl _o

Compounds A, B and C show good activity in this assay

Claims (2)

invention claim 1) Process for the preparation of the compounds of
Formula I: in all possible isomeric forms or in the form of
Isomergemi see in which R is either a linear, branched or ring al ky Ir adik al, saturated or unsaturated, with 1 to / 8 carbon atoms and possibly substituted by one or more identical or different functional groups substituted or possibly by one or several same or different functional
Groups substituted aryl group having 6 to 14 carbon atoms, or possibly one or more
identical or different functional groups represent substituted heterocyclic radical, B either
a linear, branched or ring alkyl radical, saturated or unsaturated, of 1 to 18 carbon atoms or
Represents a radical of an alcohol used in the synthesis of the pyrethrin series and X represents a halogen atom, the ethylene double bond having Zr or Ε geometry, characterized in that an acid of the formula (II) ': retained in the X and R above meaning, this 23 3 7 1b ί Acid in the form of E- and Z-Isomergemisehen or * is present in the form of E or Z isomers, the substituted cyclopropane ring in all its stereoisomeric forms or may occur in the form of stereoisomeric mixtures or / a functional derivative of this acid, the reaction of an alcohol of formula (III): B-OH (III) is retained in the above-mentioned meaning, or is exposed to a functional derivative of this alcohol, to obtain the corresponding compound of formula (I) which is optionally exposed to the action of a cleaving agent to be selected from the COpR group to form the compound of formula (IV):. in which B has the meaning given above, according to which this acid of formula (IV) or a functional derivative of this acid is subjected to the action of an alcohol of the formula 'R-OH in which R has the above meaning, the respective compound of formula. (I) to receive. 2) Process according to item 1, characterized in that an acid of the formula II with 1R-cis or 1R-trans structure is used at the beginning. 3) Method according to item 1 or 2, characterized in that an acid of the formula II is used at the beginning, in which the double bond has Ε geometry. 4) Method according to one of the items 1 to 3, characterized I 6 Ö / I Ό * ~ - ^ - is characterized in that at the beginning an acid of the formula II is used in which X represents a fluorine atom. 5) Method according to one of the items 1 to 4, characterized in that'is used an acid of the formula II, or also an alcohol of the formula R-OH, in which E is a linear, branched or ring alkyl radical. with 1 to 8 carbon atoms: 6) Method according to item 5, characterized in that R is an ethyl or tert-butyl radical. C 7) Process according to one of the items 1 to 4, characterized in that at the beginning of an acid of the ^ FörmeT II or an alcohol of the formula R-OH is used, in which R represents a cyclopropyl or a Cyclopropylinethylradikal. 8) Process according to one of the items 1 to 4, characterized in that an acid of the formula II or an alcohol of the formula R-OH is used at the beginning, in which R is a linear or branched alkyl radical having 1 to _r . 8 carbon atoms substituted by one or more halogen atoms. 9) Method according to one of the items 1 to 4, characterized in that an acid of the formula II or an alcohol of the formula R-OH is used in the beginning, in which R is a substituted by one or more fluorine atoms linear Älkylradikel having 1 to 8 carbon atoms represents. 10) Method according to one of the items 1 to 5, characterized in that at the beginning an acid of the formula II or an alcohol of the formula R-OH is used, in which , R represents a (CE ^ O (CH ₂ J _n -QH ^ radical in which m 23 37 16 2 - «- an integer between 1 and 8 and η represents an integer between 0 and 8, and especially the radical: -CH ₂ OCH ₅ . 11) Process according to one of the items 1 to 10, characterized in that initially an alcohol of the formula B-OH is used, in which 3 represents: either an alkyl radical having 1 to .18 carbon atoms, or a benzyl radical, possibly represented by one or more radicals of the group of alkyl radicals having from 1 to 4 carbon atoms, alkenyl radicals having from 2 to 6 carbon atoms, alkenoxy radicals having from 2 to 6 carbon atoms, alkenyl radicals having from 4 to 8 carbon atoms, Methylenedioxyradikals and the halogen atoms substituted, - or a group in which the substituent K, a hydrogen atom or methyl radical and the substituent R _{2 represent} a monocyclic aryl or a -CHO-C =CH-GrUpOe and in particular a e-5-benzyl-3-furyl-methyl group,
- or a group in the a is a hydrogen atom or a LietVrylradikal and κ, an aliphatic organic radical having 2 to 6 carbon · and one or more carbon-carbon unsaturations and in particular the -CHO-CH = CH ₀ -, -CH ₀ -CH = CH-CH ^ -, -CH ₂ -CH = CH-CH = CH ₂ -J -CH _{2 represents} -CH = CH-CH ₂ -CH ₅ -Rsdikal, - or a group wherein a represents a hydrogen atom or a methyl radical, R represents the above-mentioned meaning, R 'and R'p "equal to" or different from each other, a hydrogen atom, a halogen atom, an alkyl radical having 1 to 6 carbon atoms, an aryl radical having 6 to 10 carbon atoms, a Alkyloxycarbonylradikal having 2 to 5 carbon atoms or a yanogruppe ^u represent, - or a group (R ₅ ) _n in the B! represents an oxygen or sulfur atom, a - * - or -CHp group or a sulfoxide group or a sulfone group, and E, a hydrogen atom, a C = N radical, a methyl radical, a -CONHg-Rsclikal, a CSNHg-Rsdikal or represents a C = CH radical, R represents a halogen atom or an IJeth / l radical, and η is a number equal to O, T or 2, and in particular the J-phenoxy-benzjrl, el -uj'ano-J- phenoxybenzyl, ^ -synyl - ^ - phenoxybenzyl, J-benzoylbenzyl, \ - (3-phenoxy-phenyl) -ethyl or c (, -thioamido-3-phenoxybenzyl! - or a group - or a group ^Γι 8 N-CH ₂ - in which the substituents Rg, R ^, Rg, Rg represent a hydrogen atom, a chlorine atom or a methyl radical and in which S / I symbolizes an aromatic ring or an analogous dihydro- or tetrahydro ring, - or a group
P -CH ₂ - N. N ⁷ - CH ₂ - C = CH - or a group. J ^ J ** Cn - R <<- Ri r ~
in which R 1 represents a hydrogen atom or an O-N radical, R ₁ 2 represents sin -CHP radical or an oxygen atom, R ₁ represents a thiazolyl or thiadiazolyl radical whose binding to -CH- is present at an available position tion can be located, wherein R- ₂ to R. is bonded by the carbon atom between the sulfur atom and a nitrogen atom. - or a group or a group F R -ui in which IL ,, represents a hydrogen atom or a UN radical, - or a group in which R "is as defined above and the benzoyl radical is in position 3 or 4, - or a group R ₁ ., in the R., a 'is hydrogen atom, a methyl, ethynyl or Uyanoradikal represents and E, R ₁ c and g> different vonein another, a hydrogen, fluorine or bromine atom, - or a group in which P ^ χ is as defined above, each of the R. η independently of one another is an AlkvlgruDDe with -1 to 4 κοΜ enst.nff ato an alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to 4 carbon atoms, an alkylsulfonyl group having 1 to 4 carbon atoms, a trifluoromethyl, 3,4-Liethy 1 en-dioxy, chlorine, fluorine or bromine group , ρ is a number equal to 0, 1 or 2 and 3 "represents an oxygen or a sulfur atom. 12) Method according to item 11, characterized in that S is selected from the group of: radicals mentioned below: -CH-  13) Process according to item 1 for the preparation of the compounds according to formula (I): wherein A represents an oxygen atom, a liethyl group, a carbonyl group, a sulfur atom, a sulfoxide group or a sulfonic group, E _{g represents} a linear or branched alkyl radical having 1 to 5 carbon atoms, X. represents a fluoro, chloro or bromo atom having the ethylene double bond (E) or (Z) geometry and the substituted cyclopropyl ring may occur in all its stereoisomeric forms or in the form of mixtures of these stereoisomers, characterized in that an acid of formula (H _a): H, C V / J in the X. and R, g retain the abovementioned meaning and wherein the acid is in the form of a mixture of the E and Z isomers or in the form of the E or Z isomer, and wherein the substituted cyclopropane ring in all its ste · Isomeric forms or in the form of a mixture of stereoisomers, or a fractional derivative of this acid (II.) With an / alcohol of the formula (III.): xi. Λ. H (S) (III in the A maintains above, or reacts with a functional derivative of the alcohol of formula (III.) And possibly separated by physical means the E and Z isomers in the region of the double bond. 14) Method according to item 15, characterized in that A represents an oxygen atom, 2.3 37 16 2 15) Process according to item 13 or 14, characterized in that (1 R, iso) -2,2-dimethyl-3- (E) / - 2-fluoro-2- (ethoxycarbonyl) -ethenyl / -cyclapropane-1 carboxylate of (S) -ex-cyano-3-phenoxy-37-benzyl.