CS241457B2 - Method of cyclopropancarboxyl acids and their derivatives production - Google Patents

Description

The present invention relates to a process for the preparation of cyclopropanecarboxylic acids and derivatives thereof useful as intermediates in the manufacture of pyrethrin-type synthetic insecticides.

V ěs. U.S. Patent 241,452 discloses, inter alia, the production and use of the insecticidal esters of formula (II) and further that when each of the substituents R @ ^{1 * * V} and R @ ³ is hydrogen and R @ ² is alkyl, the alkyl group contains at least 2 carbon atoms, and provided that when R ^{2 is} an alkyl group, R ^{3 is} not halogen, and

R is a group of formula (I) ³ {/? ^Z JC = CCH-CH-COOR ^x c ^x c ^ ₃ ; lil) where

R ¹ represents hydrogen or methyl,

R ² represents hydrogen or halogen or alkyl having 1 to 6 carbon atoms,

R ³ is halogen or hydrogen or C 2 -C 4 alkoxycarbonyl, or C 3 -C 4 in the case where R ² is methyl 3 by the fact that only one of the substituents R ² and R ³ is hydrogen only when R 3 ¹ denotes methylthio

Í2

OF

(Z 1 -CH 3 C 5 CH 2 CH 3) means an aromatic ring or its dihydro- or tetrahydroanalo-g, each of X ¹ , X ² , X ³ and X ⁴ , which are the same or different, represents hydrogen, chloro or methyl,

Z ³ is -CH 2 - or -O- or -CO- or -S-,

D represents hydrogen, -CN or -C == CH, each of Z ¹ and Z ^2, which are identical or different, each represent chlorine or a methyl group and n is 0, 1 or 2, provided that R is not a group allethronylovou when R ⁴ is hydrogen, each of the substituents R ² and R ³ is chlorine and the compound is racemic.

The insecticidal esters of formula (II) may be prepared as described in the above-mentioned U.S. Pat. from the corresponding cyclopropanecarboxylic acid or its salts, halides or alkyl halides.

The present invention provides a process for the preparation of compounds of formula IIA

----- -i-v / A) .........

f VI B) wherein ..; _; ./. . ..

Z is -O-, -S-, -CH 2 - or -CO-.

Y represents hydrogen or an alkyl, alkenyl or alkynyl group of up to 6 carbon atoms or a phenyl or furyl group optionally substituted on the nucleus with 1 to 4 alkyl, alkenyl or alkoxy groups of up to 6 carbon atoms or halogen atoms, each of R ⁷ and ^R8, which are identical NetB different, is hydrogen or alkyl having 1 to 4 carbon atoms,

R ⁹ is hydrogen or methyl, each of R ¹⁹ and R ¹¹ , which may be the same or different, represents hydrogen or alkyl of 1 to 6 carbon atoms,

R ¹² represents a furyl group, a phenyl group optionally substituted by 1 to 4 alkyl or alkoxy groups having 1 to 4 carbon atoms or halogen atoms, or an alkenyl group having 2 to 4 carbon atoms having an unsaturated carbon-carbon bond at least in position and relative to the -CH 2 group To which R ^{42 is} bound, R (R ² ) c = c-ch-ch-cqe;

7 ^c \ ch ₃ ch ₃

(11A) where

R ⁴ represents hydrogen or methyl,

R ² represents hydrogen or halogen or alkyl having 1 to 6 carbon atoms,

R ³ is hydrogen or halogen or a (C 1 -C 6) alkoxycarbonyl group, provided that at least one of R ² and R ³ is halogen, and

E is halogen or OE ⁴ , wherein E ¹ is hydrogen or a cation of salt or C 1 -C 6 alkyl, provided that when R ¹ is hydrogen and the compound is racemic, both R ² and R ^{3 are not} chlorine and provided that when it is halogen, R ^{2 is not} an alkyl group.

As will be described in more detail below, the new alkyl esters of the invention may be prepared in this form by Wittig synthesis and there is no need to convert these alkyl esters to the free carboxylic acids to obtain the insecticidal esters from the US. However, if desired, these may be used

The 2414S7 alkyl esters can be converted to the free carboxylic acids by, for example, hydrolyzing the ester to form salts and then converting the salt into an acid.

Esters of formula (IIA) wherein R ² is an alkyl group and R ⁵ is an alkoxycarbonyl group are useful intermediates for the preparation of insecticidal esters which can be converted by acid catalysis, for example using toluene-4-sulfonic acid in benzene, into the corresponding free carboxylic acid without attacking an alkoxycarbonyl group as R ³ . As will be described in more detail below, the novel alkyl esters of the invention are prepared in this form by Wittig synthesis and there is no need to convert these alkyl esters into the free carboxylic acid to obtain the above insecticidal esters. This is best achieved by the selective use of tert-butyl ester (R = tert-butyl). However, if desired, the tert-butyl ester or other alkyl ester can be converted into the free carboxylic acid by partial saponification, but it is difficult to prevent the saponification of the alkoxycarbonyl group R ³ simultaneously.

With respect to the meanings given for the substituents R ² and R ³ , it is preferred that, when the substituents are alkyl or alkoxy, these radicals contain up to 6 carbon atoms, preferably up to 3 carbon atoms, and in particular represent a methyl group, an ethyl group, propyl, methoxy, ethoxy and propoxy. Means where R ² and / or R ³ halogen is preferably fluorine, chlorine or bromine. Means where each of R ² and R ³ halogen are preferably, but not necessarily the same halogen.

Compounds of the invention can, after the structure into different subclasses, particularly according to the nature of the substituents R ² and R ^3rd

One particularly preferred subclass consists of compounds wherein each of R ¹ and R ³ is hydrogen and R ² is chlorine or bromine.

The intermediates that lead to the most effective insecticidal esters of the invention are those wherein R ¹ is hydrogen and each of R ² and R ³ is halogen, for example difluoro, dlchloro or dibromvinyl derivatives.

Other preferred halogenated subclass are those compounds in which R ¹ denotes hydrogen, R ² is halogen and R ³ represents an alkoxycarbonyl group. The acid residues in these compounds are pyrethyric acid analogues wherein the methyl substituent on the β-carbon atom of the 3-position of the substituent is replaced by halogen, and homologues of these acids wherein the methoxycarbonyl group is replaced by an alkoxycarbonyl group of at least 3 carbon atoms. Halogen is preferably chlorine or bromine, and the alkoxycarbonyl group is preferably a methoxycarboxycarbonyl group.

Preferred compounds produced by the process of the invention include those derived from 2,2-dimethyl-3-substituted cyclopropanecarboxylic acids wherein the substituent at the 3-position is one of the groups of the formula

Cl—,

Br — CH = CH—,

CHsOOC — C = CH—,

Cl

C2H5OOC — C-CH—,

Cl

Cl \

OCH—

OF

Cl or

Br \

C — GH—

OF

Br

When the esters produced by the process of the invention are alkyl esters, it is preferred that the alkyl group contains up to 6 carbon atoms; It has been found that methyl, ethyl and tert-butyl esters are among those which can be readily prepared by the process of the invention.

The compounds produced by the process of the invention are geometric and optical isomers and can therefore be prepared in optically active forms, which can then be mixed, or as racemic mixtures, which can later be resolved into optically active forms. In addition, optically active forms or racemic mixtures can be resolved into individual geometric isomers. In addition to geometric isomerism by virtue of the mutual configuration of the substituents on the cyclopropane ring and of the relationship between the substituents and the ring is also possible geometric isomerism in the side chain at the 3-position, when R ^1, R ^{2, R} are such that the unsaturated side chain is unsymmetrically substituted.

The compounds obtained by the process according to the invention which have hydrogen atoms at the 1 and 3 positions of the cyclopropane ring in the trans configuration with each other are stereo analogues of (+) - transchrysanthemic acid and therefore represent a preferred group of compounds according to the invention; however, the invention also includes compounds wherein both of said hydrogen atoms are in the cis configuration. Therefore, preferred compounds are compounds having (+) -trans, (-t -) - cis, (± j-trans, (±) - cis and (± j-cis-trans-configuration).

Insecticidal esters described in MS. No. 241,452, can be prepared by esterification by reacting an alcohol or a derivative of formula R-Q with a cyclopropanecarboxylic acid or a derivative of formula IX

R @ ¹ = CC-CH-CH-COQ?

X CH ₃ \ ₃ H (IX) wherein Q and COQ @ ¹ are functional groups or atoms which react to form an ester linkage and R, R ^1, R ² and R ³ are as defined above.

It is usually convenient in practice either to react the acid or acid halide with an alcohol (COQ ¹ = COOH or CO-halide and Q = OH) or to react the halogen compound (Q = halogen) with a carboxylic acid salt (COQ ¹ = ^_ COO M ⁺ wherein

M is, for example, silver cation or triethylammonium cation).

For the reasons described below, the compound of formula (IX) is generally obtained initially in the form of a lower alkyl ester (COQ ¹ = COO-alkyl) wherein the alkyl group contains 1 to 6 carbon atoms; for this reason, a particularly suitable process for the preparation of the insecticide esters according to U.S. Pat. ^No. 241,452 except where R ³ is an alkoxycarbonyl group when the alkyl ester of formula (IX) is transesterified using an ROH alcohol, for example in the presence of a basic catalyst. When the alkyl ester contains a base-sensitive group, i.e., when R ³ is an alkoxycarbonyl group, a base-catalyzed transesterification is not suitable and can be avoided by preparing a tert-butyl ester which can be converted to the free acid by acid-catalyzed decomposition and free carboxylic acid. the group may be esterified directly or via a salt or a halide.

The esters of the invention can be prepared by reacting a hypophosphite or ylide of formula X with a 2,2-dimethylcyclopropanecarboxylic acid ester substituted in the 3-position with an acetyl or aldehyde group of formula XI:

(XJ

In formulas X and XI, R @ ¹ , R @ ² and R @ ^{3 have} the meanings given above, E @ ² is a non-Wittig reaction group, usually C1 -C6 alkyl and Z ^{@ 4} which can in principle be any organic radical will generally represent a phenyl moiety, since the stability of the trisubstituted phosphorus pentoxide formed as a by-product in the reaction is particularly high, promoting a complete reaction between the hypophosphite of formula X and the aldehyde or ketone of formula XI.

Esters of the invention wherein R ¹ is hydrogen may be prepared by reaction with an aldehyde of formula XI, while esters of the invention wherein R ¹ is methyl may be prepared by reaction of a 3-acetyl compound of formula XI. The phosphorane X and the aldehyde or ketone XI are preferably reacted in practically equimolar amounts, preferably in a solvent, in

2.

XCH — CH-COOE \ /

X \ i

CH ₃ CH ₃ (XI) in which phosphorane was prepared. As further detailed below, the solvent may be an aromatic hydrocarbon such as benzene, or a polar solvent such as dimethylsulfoxide, or a chlorinated hydrocarbon such as dichloromethane. The reaction is preferably carried out under an inert atmosphere, for example under a nitrogen atmosphere. The reaction of the phosphorane with said aldehyde or ketone usually proceeds fairly quickly and the ester produced can be isolated from the reaction mixture after a reaction time of less than 1 hour, although reaction times of up to 24 hours have been used. The ester produced can be isolated from the reaction product by solvent extraction, for example, diethyl ether or white spirit.

Phosphorane of formula X, where R ² and / or R ³ is halogen, can be prepared from the corresponding phosphonium salt, which can again be obtained by reacting an appropriately substituted methyl halide with trlorganophosphine according to the reaction scheme

I ft.

K \ ft

2. * ^ 3 by dehydrohalogenesis using fP '\ ₇ *

The advantage of the synthesis according to the invention lies in the fact that the original starting material is a substituted methyl halide of the formula R ^{with (} R2) CH-hal and the availability of a number of such substituted halo halides allows the production of a wide range _of ? -2-dimethylcyclopropanecarboxylic acids groups and which have hitherto been difficult to prepare or could not be prepared at all. In the above hypophosphite synthesis, it is useful to start with a substituted methyl bromide which is reacted with triphenylphosphine to give the corresponding triphenylphosphonium bromide, whereupon the phosphonium salt is converted to a phosphorous or ylide, which may be described by the above formula. Conversion of the phosphonium salt into phosphorous can be accomplished by treating the foophilate salt with an alkali metal amide or an alkali metal methylsilyl methmethide (GGHžSOOCHí).

For example, natrlumamide can be prepared by reacting sodium in liquid ammonia and carrying out the reaction in the presence of an excess of ammonia as a liquid medium. At the end of the reaction, the ammonia liquid is allowed to evaporate and the phosphorane is taken up with an organic solvent, for example benzene, and the subsequent reaction with an aldehyde or ketone of formula XI is carried out in this organic solvent. Alternatively, dimethylsulfoxide can be reacted with sodium hydride to form sodium trimethylsulfinyl methide and the phosphonium salt formation can be carried out using this reagent, and after phosphorus formation, the subsequent reaction with an aldehyde or ketone of formula X1 can be carried out in the same reaction medium.

When R is ^an alkenylcarbonyl group, the conversion of the phosphonium salt into phosphorous can be accomplished by treating the phosphonium salt with an alkali metal amide in liquid ammonia or in an aqueous solution of an alkali metal hydroxide, such as 5% sodium hydroxide. The liberated phosphorous may be isolated from the solution by filtration and then reacted with an aldehyde of formula XI in a suitable solvent, for example dichloromethane CH 2 Cl 2.

If each of the substituents R ² and R ^{3 is} halogen, a carbon halide may be used instead of the substituted methyl halide, the reaction being carried out according to the scheme

R '

O ² ·

The R 4 and dehydrohalogenation of the quaternary phosphonium halide proceeds spontaneously.

Halogenated phosphates are also possible

R ^Ž CH _Ž -PZ |

R ² CK, fa + + PZ * · may be prepared by the halogenation of non-halogenated phosphorate, which is again obtained according to the above-described procedures according to this reaction scheme!

By dehydrobalogenation using a base

R ³ Chtr) CA ^

Also by dehydrohydrogenation using a base

Rx ^ Z * r ^3>

241437 il where hal means halogen ,,

R ³ is halogen

R ² is as defined above.

It has been found desirable that the carboxyl group in the aldehyde or ketone reactant of formula XI be esterified as a lower alkyl ester (i.e. as a C1 -C6 alkyl ester in the > alkyl moiety) in order to react with an amine of formula X That is, the alkyl esters of the invention are obtained directly and since it is possible to convert these alkyl esters into the insecticidal esters of the invention, except those containing a base-sensitive group, for example R ³ = alkoxycarbonyl It is not necessary to convert the alkyl esters of the invention into the corresponding acid to obtain insecticidal esters, but the indirect conversion of the alkyl esters into the insecticidal esters is possible and, if this is done, the alkoxycarbonyl group in the ester of formula II can be converted. b by hydrolysis to the appropriate group of the free carboxylic acid, for example via an alkali metal salt or other salt, and the carboxylic acid may be directly esterified as described above, or alternatively may first be converted to an acid halide, e.g. chloride, and the halide The acid can be converted to the ester by reaction with the appropriate alcohol of formula ROH as described above.

Where E is a tert-butyl group, the alkyl ester can be converted to the free acid by heating with a small amount of toluene-4-sulfonic acid. This reaction can be carried out in benzene and the resulting carboxylic acid can be converted to the acid chloride in the benzene solution without isolation.

The carbonyl compounds of formula XI can also be prepared by ozonolysis of the corresponding chrysanthemic acid ester when the double bond in the isobutenyl side chain is saturated with oxygen. Thus, provided that the OE does not contain a group degradable under ozonolysis conditions, the desired carbonyl compound of formula XI can be obtained directly by ozonolysis of the chrysanthemate.

The invention is illustrated by the following examples.

He did

A mixture of 2.1 g (0.006 mol) of chloromethylene triphenylphosphonium chloride and 0.51 g (0.006 mol) of anhydrous piperidine in 15 ml of anhydrous diethyl ether was treated with a 8% solution of n-butyllithium in hexane (4.8 ml, [0.388 g, i.e. 0.006 mol]). The mixture was stirred at room temperature for 1.5 hours and then t-butyl-trans-caronaldehyde (1.27 g, 0.0064 mol) in 5 ml of anhydrous benzene was added. After stirring for 3 days, the solution was filtered and the residue was washed with anhydrous diethyl ether. The filtrate is washed with 10% sulfuric acid and water, followed by evaporation of the solvent dried over sodium sulphate followed by distillation to give a colorless liquid having a boiling point of 100 DEG C./70 mbar (70%). According to the Nuclear Magnetic Resonance Spectrum, the liquid is an ester of formula (IIA) wherein R ³ is chlorine, R ² is hydrogen, R ¹ is also hydrogen, and E ¹ is tert-butyl, whose refractive index n _D = 1.4670. Stereochemistry at the double bond α, β with respect to the ring is 20:80 (Z: E).

A mixture of 410 mg of the above tert-butyl ester, 47.5 mg of toluene-4-sulfonic acid and 15 ml of anhydrous benzene was refluxed for 2 hours and then cooled to give a solution of the corresponding carboxylic acid. 163 mg of pyridine and 213 mg of thionyl chloride were added and the mixture was allowed to stand for 2 hours to give the acid chloride.

Example 1 a d 2

A mixture of 1.0 g of tert-butyl (+) - transcaronaldehyde, obtained by ozonolysis of tert-butyl ester of (+ 1-trans-chrysanthemic acid), and 2.65 g of triphenylphosphine, dissolved in 10 ml of anhydrous carbon tetrachloride, is heated under stirring under nitrogen. The reaction mixture is evaporated under reduced pressure and the residue is extracted with about 30 ml of diethyl ether, the organic extract is washed with water, dried over sodium sulphate and evaporated, and the residue is extracted with petroleum ether (b.p. 40-60 ° C). The solution was evaporated and the residue was distilled to give 0.77 g of crude product, b.p. 100 ° C / 1 mm Hg, which was purified by crystallization to give tert-butyl ester [IR, trans] -2.2. dimethyl-3- (2,2-dichlorvinyljcyklopropankarboxylové m.p. 52-53 ^Q C (compound P 21 ' i.

Example 1 a d 3

With vigorous stirring, 1.32 g of triphenylphosphine is added to a solution of 0.84 g of tetrabromomethane in 15 ml of anhydrous dichloromethane, then 0.5 g of tert-butyl- (+) -trans-caronaldehyde is added and the solution is stirred overnight at room temperature. After work-up as described in Example 2, the crude product is distilled to give two fractions: 1. Boiling point 83-90 degrees C / 93.3 Pa and refractive index n _D = 1.4749 0.15 g and 2. a product having a boiling point of 90 to 107 ° C / 93.3 Pa and a refractive index n _D = 1.4910 in an amount of 0.24 g. According to gas chromatography, the second fraction contains approximately 95% of the desired tert-butyl ester [1R]. , trans] -2,2-dimethyl-3- (2,224,1457)

-dihr omvinyl) cyclopropanecarboxylic (compound P21B‘Jexample 1 a d 4

280 mg of the tert-butyl ester described in Example 2 was refluxed with 55 mg of toluene-4-sulfonic acid in 10 ml of anhydrous benzene for 1.5 hours, then the mixture was cooled to give a solution of the corresponding acid. 108.5 mg of pyridine and 126 mg of thionyl chloride were added and the mixture was allowed to stand at room temperature for 2 hours to give the acid chloride.

The above procedure was repeated with ester P 21 B ', described in Example 3, to give [R, transj-acid and the acid chloride (R ² = R ³ = Br and ^R1 = hydrogen).

Example 1 a d 5

13 g of triphenylphosphine are dissolved in 60 ml of anhydrous benzene and 8.3 g of methyl bromoacetate are added dropwise. The solution was heated for 2 days at 70 ^F C, then cooled and filtered sc. The residue is washed with benzene and dried to give approximately 16 g of (methoxycarbonylmethyl) triphenylphosphonium bromide, 10 g of this phosphonium salt are dissolved in 250 ml of water and 5% aqueous sodium hydroxide solution is added dropwise with stirring until the solution becomes alkaline to litmus. The precipitate was filtered off, washed with water and dried, and crystallized from ethyl acetate / petroleum ether to give (methoxycarbonylmethylene) triphenylphosphine.

Compound E ¹ R ² P 24 B ‘ tert-butyl COOC2H5 P 24 C ‘ tert-butyl COO-n-CsH? P 24 D tert-butyl COOC2H5

Example 1 a d 7

A mixture of 320 mg of compound P 24 A ‘from Example 5 and 50 mg of toluene-4-sulfonic acid in 10 ml of anhydrous benzene was refluxed for approximately 2 hours and then cooled. According to the nuclear magnetic resonance spectrum, 2,2-dimethyl-3- (2-chloro-2-methoxycarbonylvinyl) cyclopropanecarboxylic acid is present in the solution. To the solution of this acid was added 111 mg (114 μΐ) of pyridine and 132 mg (80 μΐ) of thionyl chloride and the mixture was left forane as a colorless solid for about 80% yield.

3.34 g (methoxycarbonylmethyl) triphenylphosphorane in 70 mL of methylene chloride was cooled to -70 ^Q C, then under stirring 1.01 g trlethylaminu and 0.77 g of chlorine in 11 ml of carbon tetrachloride. Stirring was continued for 30 minutes at this temperature and then for 1 hour during which the reaction mixture spontaneously warmed to room temperature. The resulting mixture was washed three times with 50 ml of water each time, dried over sodium sulfate and evaporated to give 2.8 g of chlorinated phosphorane [(C 6 H 5) s P 4 C (Cl) COOCH 3].

A mixture of 0.7 g of tert-butyl (+) -trans-caronaldehyde, formed by ozonolysis of (+) -trans-cbrysanthemic acid tert-butyl ester, and 1.3 g of chlorinated phosphorus in 10 ml of perfect benzene was heated under reflux for 1 hour. . After the benzene has been distilled off, the product obtained is distilled under reduced pressure to obtain 0.65 g of 2,2-dimethyl-3- (2-chloro-2-ethoxycarbonyl-tinyl) cyclopropanecarboxylic acid tert-butyl ester, b.p. 110 ° C / 53 3 Pa and the refractive index n _D ²⁰ = 1.4749.

This compound is designated as compound P24A *.

Example 6

The procedure described in Example 5 was repeated except that ethyl bromoacetate or propyl bromoacetate was used instead of methyl bromoacetate, and bromine hypophosphite was used instead of chloride. Compounds of formula HA are obtained as follows.

R ³ Boiling point n _D ²⁰ Cl 110-112 ° C / 53.3 Pa 1,4883 Cl 160-180 ° C / 0.107 kPa 1.4688 Br 120 - 124 ° C / 5.3 Pa 1.4830 state at room temperature. According to nuclear-

For example, 2,2-dimethyl-3- (2-chloro-2-methoxycarbonylvinyl) cyclopropanecarboxylic acid chloride is present in the magnetic resonance spectrum.

Example 8

The procedure described in Example 8 was repeated using the compounds P 24 B ‘, P 24 C‘ and P 24 D ‘from Example 6. The corresponding acids and acid chlorides were obtained.

Claims (16)

SUBJECT A process for the preparation of cyclopropanecarboxylic acids and derivatives thereof having the general formula IIA 7C = C - CH - CH - COE R * CH 2 CH ₃ (II A) wherein R ¹ represents hydrogen or methyl, R ² represents hydrogen or halogen or alkyl having 1 to 6 carbon atoms, R ³ is hydrogen or halogen or an alkoxycarbonyl group having 1 to 6 carbon atoms, alkoxy group provided that at least one of R ² and R ³ is halogen and E represents halogen or OE ¹ , where E ¹ represents hydrogen, a salt cation or a (C 1 -C 6) alkyl group, wherein when R ¹ is hydrogen and the compound is racemic, both R ² and R ^{3 are not} chlorine and, when R ³ is halogen, R ^{2 is} not an alkyl group, characterized in that the hypophosphite of the general formula X \ _z <thx> where R ² and R ³ are as defined above and Z ⁴ represents an organic radical which forms a stable oxide triorganofosforečný reacted with a carbonyl compound of formula XII O = C-CH-CH-COOE ^Z CH ₃ \ h (XI) where R ¹ has the abovementioned meaning and E ² represents an alkyl group having 1 to 6 carbon atoms, whereupon optionally the resulting alkyl ester of formula IIA is converted YNALEZU to the corresponding free carboxylic acid or acid halide or acid salt. 2. A method according to claim 1, characterized in that as starting material a compound of formula XI, wherein R ¹ is as defined in claim 1 and E ² is methyl, ethyl or tert-butyl, and the resultant alkyl ester is optionally converted into an appropriate free carboxylic acid, sodium salt thereof, or acid chloride. 3. A process according to claim 1 or 2, wherein the corresponding compounds of formulas X and XI are used as starting materials to produce cyclopropanecarboxylic acid or a derivative of formula IIA having (+) - or - (±) -. trans configuration in which the individual general symbols have the meaning as in point 1 or 2. 4. Process according to claims 1-3, characterized in that as starting material a compound of formula X, wherein R ² is halogen, R ³ represents an alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, and Z ⁴ is as defined in 1. 5. The process of item 1, for producing compounds of formula IIA wherein: R ¹ represents hydrogen or methyl, R ² and R ^3, which may be identical or different, represent a halogen atom and E is as in point 1, provided that when R ¹ is hydrogen and the compound is racemic, then both R ² and R ^{3 do} not simultaneously represent a chlorine atom, characterized in that the compound of formula X is reacted with a compound of formula XI wherein R ¹ , R ² and R ³ are as defined herein and E ² and Z ⁴ are as defined in item 1, whereupon the resulting alkyl ester is optionally converted to the corresponding free carboxylic acid or acid halide or to an acid salt. 6. Method according to claim 5, characterized in that as starting material a compound of formula XI, wherein R ¹ is as defined in claim 5, and E ² is methyl, ethyl or tert-butyl, and the resultant alkyl ester is optionally converted into an appropriate free carboxylic acid, sodium salt or acid chloride thereof. 7. A process according to any one of Claims 5 and 6, wherein the corresponding compounds of formulas X and XI are used as starting materials to produce a cyclopropanecarboxylic acid or a derivative of formula IIA having (+ j-trans or (±) j-trans configuration in which each general symbol has the meaning as in point 5 or 6. 8. Process according to claims 5-7, characterized in that as starting material a slou241457 substituting Compound of formulas X and XI wherein each R ² and R ³ is fluorine, or each of them is bromine, R ¹ is hydrogen and E ² and Z ⁴ have the meaning given in point 5. 9. A process according to claim 5 or 6, wherein the corresponding compounds of formulas X and XI are used as starting materials to form optically active compounds of formula IIA wherein R @ ¹ is hydrogen, R @ ² and R @ ³ are atoms. chlorine and E have the meaning as in point 5. 10. The method of claim 8 or 9, wherein the resulting alkyl ester is converted to the corresponding free carboxylic acid. 11. The process of item 1, for producing compounds of formula IIA wherein: R ¹ represents a hydrogen atom, R ² represents halogen, R ³ represents an alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety a E is as defined in 1, wherein the compound of formula X is reacted with a compound of formula XI wherein R ¹ , R ² and R ³ are as defined herein and E ² and Z ⁴ are as defined above. as in 1, whereupon the resulting alkyl ester is optionally converted to the corresponding free carboxylic acid. 12. The method of claim 11, characterized in that as starting material a compound of formula XI, wherein R ¹ is as defined in paragraph 11 and E ² is methyl, ethyl or tert-butyl, and the resultant alkyl ester is optionally converted into the corresponding free carboxylic acid, 13. A process according to claim 11 or 12, wherein the corresponding compounds of formulas X and XI are used as starting materials to form a cyclopropanecarboxylic acid or a derivative of the formula II having (+) -trans or (±) -trans- a configuration in which each general symbol has the meaning as in point 11. 14. The process of item 1, for producing compounds of formula IIA wherein: R ¹ represents hydrogen or methyl, R ² represents halogen, R ³ represents a hydrogen atom and E is as defined in claim 1, characterized in that the compound of formula X is reacted with a compound of formula XI ¹ wherein R ^1, R ² and R ³ have the roll defined, and E ² and Z ⁴ are meaning as in point 1. 15. The method according to item 14, characterized in that as starting material a compound of formula XI wherein E ² is methyl, ethyl or tert-butyl and R ¹ is as defined in point 14. 16. A process according to claim 14 or 15, wherein the corresponding compounds of formulas (X) and (XI) are used as starting materials to form a cyclopropanecarboxylic acid or a derivative of formula (IIA) having a (+) -trans or (±) - a trans-configuration in which the individual general symbols have the meaning as in point