CH630601A5 - Cyclopropanecarboxylic acids containing a polyhalogenated group - Google Patents

Description

The subject of the invention is new cyclopropanecarboxylic acids comprising a polyhalogenated group in all their stereoisomeric forms, of general formula:

H

H-C

VS

• C-OH

X

in which X represents a hydrogen, fluorine, chlorine or bromine atom, X2, identical to or different from Xj, represents a fluorine, chlorine or bromine atom, and X3 represents a chlorine atom, bromine or iodine, as well as the chlorides of these acids.

These cyclopropanecarboxylic acids have asymmetric carbons in positions 1 and 3 and can therefore exist in several stereoisomeric forms.

For a determined steric configuration of asymmetric carbons in position 1 and 3 of the cyclopropanic cycle, two diastereoisomeric forms of these acids, due to the existence of the asymmetric carbon in 1 ', of the substituted ethyl side chain can, in addition, exist and be effectively characterized in particular by their NMR spectrum or their migration speed in thin layer chromatography. These isomers can, in general, be separated and isolated in the pure state, in particular by chromatography. These two diastereoisomers have been called here and in the following isomers A and B.

In the case where the three substituents Xi, X2 and X3 are different from each other, an additional asymmetric carbon may exist at position 2 'of the polyhalogenated ethyl side chain.

Among the compounds of general formula I, mention will be made in particular of those which are characterized in that Xj represents a fluorine, chlorine or bromine atom, X2 is identical to Xt and represents a fluorine, chlorine or bromine atom, and X3 retains the abovementioned meanings, and those which are characterized in that Xj represents a hydrogen, fluorine, chlorine or bromine atom, X2 is different from Xj and represents a fluorine, chlorine or bromine atom, and X3 retains the above meanings.

Among the acids of formula I which are subjects of the invention, mention may be made of cyclopropanecarboxylic acids (K) of structure (1R, eis) or (IR, trans), the names of which follow:

- 2,2-dimethyl 3- (2 ', 2'-dibromo l', 2'-dichloro-ethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrachloro-ethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2'-dichloro-ethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromo-ethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2'-dibromo-ethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl (r, 2 ', 2', 2'-tetrabromo-ethyl) cyclopropane-1 -carboxylic acids;

- 2,2-dimethyl 3- (2 ', 2'-difluoro 2', l'-diodo-ethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl 3- (2 ', 2'-dichloro 2', l'-diodo-ethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl 3- (2 ', 2'-dibromo 2', l'-diodo-ethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl 3- (r, 2 ', 2'-tribromoethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl 3- (l ', 2'-dichloro 2'-bromo-ethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl (r, 2 ', 2'-trichloroethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl 3- (1 ', 2'-dibromo 2'-chloro-ethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl (l ', 2'-dichloro 2'-fluoroethyl) cyclo-propane-1-carboxylic acids;

- 2,2-dimethyl (l ', 2'-dibromo 2'-fluoro-ethyl) cyclopropane-1 -carboxylic acids;

- 2,2-dimethyl 3- (2'-fluoro 2 ', l'-diiodo-ethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl 3- (2'-chloro 2 ', l'-diiodo-ethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl 3- (2'-bromo 2 ', l'-diiodo-ethyl) cyclopropane-1 -carboxylic acids;

- 2,2-dimethyl 3- (r, 2 ', 2'-trichloro 2'-fluoro-ethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl 3- (1 ', 2'-dibromo 2'-chloro 2'-fluoro-ethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl 3- (l ', 2', 2'-trichloro 2'-bromo-ethyl) cyclopropane-1-carboxylic acids;

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- 2,2-dimethyl 3- (r, 2 ', 2'-tribromo 2'-chloro-ethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl 3- (2'-fluoro l ', 2', 2'-tribromo-ethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl 3- (2'-bromo 2'-fluoro I ', 2'-dichloro-ethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl 3- (2'-fluoro 2'-chloro 2 ', l'-diiodo-ethyl) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl 3- (2'-fluoro 2'-bromo 2 ', l'-diiodo-ét hy l) cyclopropane-1-carboxylic acids;

- 2,2-dimethyl 3- (2'-chloro 2'-bromo 2 ', l'-diiodo-ethyl) cyclopropane-1-carboxylic acids.

Among these acids, there may be mentioned more particularly in any of their isomeric forms and in particular in the form of isomer A, isomer B or a mixture of these isomers, the acids whose names follow:

- IR acid, eis 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrabromo-ethyl) cyclopropane-1 -carboxylic,

- IR, trans 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrabromo-ethyl) cyclopropane-1-carboxylic acid,

- 1 R, trans 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromo-ethyl) cyclopropane-1 -carboxylic acid,

- IR acid, eis 2,2-dimethyl 3- (2 ', 2'-dibromo l', 2'-dichloro-ethyl) cyclopropane-1 -carboxylic,

- IR, trans 2,2-dimethyl 3- (2 ', 2'-dibromo l', 2'-dichloro-ethyl) cyclopropane-1 -carboxylic acid,

- IR acid, trans 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2'-dibromo-ethyl) cyclopropane-1 -carboxylic,

- 1 R, eis 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromo-ethyl) cyclopropane-1-carboxylic acid,

- IR acid, eis 2,2-dimethyl 3- (2 ', 2', 2 ', l'-tetrachloroethyl) cyclopropane-1 -carboxylic,

- IR acid, trans 2,2-dimethyl 3- (2 ', 2', 2 ', l'-tetrachloro-ethyl) cyclopropane-1 -carboxylic.

The nine products that have just been named are called K products.

We can also cite:

- 1 R acid, eis 2,2-dimethyl 3- (2 ', 2'-difluoro 2', 1 '-dibromo-ethyl) cyclopropane-1-carboxylic acid,

- acid 1 R, eis 3- (2 '(RS) fluoro 2'-chloro 1', 2'-dibromo-éthy l) cyclopropane-1 -carboxylic.

The acids of formula I and their chlorides can be prepared by reacting with an acid of general formula:

(II)

:-OH

in which X and X retain the abovementioned meanings, said acid II being in any of its isomeric forms or on one of its functional derivatives, a chlorination, bromination or iodination agent capable of fixing Cl2 , Br2 or I2 on the side chain of acid II and, if necessary, if an acid was used at the start, by transforming the acid obtained into a functional derivative.

As an acid halogenating agent II, chlorine, bromine or iodine are used in particular, and the halogenation of acids II is then carried out in an organic solvent which does not react with chlorine, bromine or l 'iodine, such as acetic acid, carbon tetrachloride, chloroform, methylene chloride.

The functional derivative of acid II can in particular be anhydride, a mixed anhydride, a lower alkyl ester, a metal salt, an organic base salt or preferably chloride.

The possible transformation into a functional derivative, as defined above, in the case where an acid of formula II was used at the start of the process, is carried out according to the usual methods.

The above cyclopropanecarboxylic acids (I) are endowed with antifungal properties which make them suitable for use in the fight against fungi. They can in particular be used for the fight against the fungi parasites of the cultures, for example, the various parasites fungi of the vine, tomatoes and cucumbers.

Tests on Botrytis, Fusarium, Phoma, Penicillium, described later in the experimental part, demonstrate the antifungal activity of these acids.

The new cyclopropanecarboxylic acids (I) can therefore be used to prepare antifungal compositions containing, as active principle, at least one of said acids.

In these compositions, the active ingredient (s) can optionally be added with one or more other pesticidal agents. These compositions can be in the form of powders, granules, suspensions, emulsions, solutions or other preparations conventionally used for the use of this type of compound.

In addition to the active principle, these compositions generally contain a vehicle and / or a nonionic surfactant ensuring, in addition, a uniform dispersion of the constituent substances of the mixture. The vehicle used can be a liquid such as water, alcohol, hydrocarbons or other organic solvents, a mineral, animal or vegetable oil, a powder such as talc, clays, silicates, kieselguhr.

The antifungal compositions preferably contain: for powders for spraying, from 25 to 95% by weight of active material; for powders for foliar dusting, from 2.5 to 95% by weight of active material; for powders or liquids for ground spraying, from 10 to 30% by weight of active material.

The above cyclopropanecarboxylic acids (I) are also endowed with bactericidal properties which make them suitable for use as industrial biocides.

Tests given below in the experimental part, and carried out under conditions analogous to those encountered in the fight against bacteria in an industrial environment, illustrate the high biocidal activity of these acids.

These tests were carried out for adhesives and for industrial charges of the Slurry type of kaolin, infested with a complex mixture of bacteria usually developing in industrial substrates.

The aforementioned cyclopropanecarboxylic acids (I) can therefore be used in general as industrial biocides, in particular for the protection of adhesives, industrial charges, and when using cutting oils. They can also be used to prevent and eliminate the formation of microbial sludge in stationery circuits or for the treatment of skins,

tanning liquors and leathers.

The new cyclopropanecarboxylic acids (I) can therefore be used to prepare biocidal compositions containing, as active principle, at least one of said acids.

In these compositions, the active ingredient (s) may be added with one or more other pesticidal agents. These compositions may be in forms analogous to the antifungal compositions described above, that is to say in the form of powders, suspensions, emulsions or solutions and may contain, in addition to the active ingredient (s), a solid or liquid vehicle and a surfactant.

The biocidal compositions preferably contain from 20 to 95% by weight of active material.

Furthermore, the cyclopropanecarboxylic acids of formula (I), as defined above, as well as their functional derivatives which are subjects of the invention, are intermediate compounds useful in the synthesis of new esters of said acids, new esters which have remarkable insecticide, acaricide, nematicide and antifungal properties. The preparation of these esters is described in Belgian patent No. 858894 entitled "Process for the preparation of new esters of cyclopropanecarboxylic acids comprising a polyhalogenated substituent".

The preparation of acids of formula (I) as well as some of

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their chlorides and the application of said acids and chlorides to the preparation of some insecticidal esters are described later in the experimental part.

The following examples as well as the study of the antifungal activity and the biocidal activity of the compounds (I) illustrate the invention.

Example 1:

IR acid, eis 2,2-dimethyl3- (1 ', 2', 2 ', 2'-tetrabromoethyl) cyclo-propane-1-carboxylic:

19.4 g of lR, cis 2,2-dimethyl 3- (2 ', 2'-dibromovinyl) cyclopropane-1-carboxylic acid are added to 150 cm3 of carbon tetrachloride, 10.4 g of bromine are added. solution in 22 cm3 of carbon tetrachloride, stirred for 1 h at 20 ° C, concentrated to dryness by distillation under reduced pressure and obtains 31.4 g of crude product (F = 145 C). This crude product is recrystallized from 110 cm3 of carbon tetrachloride and 22.12 g of IR acid, eis 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrabromoethyl) cyclopropane are obtained. -l-carboxyli-que.F = 150 C.

This product is a mixture of two isomers A and B which are highlighted by the NMR spectrum. Indeed, the NMR spectrum makes it possible to detect a compound (corresponding approximately to 2/3 of the mixture) having peaks at 1.31-1.43 ppm corresponding to the hydrogens of the twin methyls, and peaks from 5.33 to 5 , 66 ppm corresponding to the hydrogen attached to the asymmetric mono-brominated carbon and another compound (corresponding to approximately 1j3 of the mixture) having peaks at 1.28-1.48 ppm corresponding to the hydrogens of the twin methyls and peaks of 4.24 to 5.34 ppm corresponding to the hydrogen fixed on the asymmetric monobrominated carbon.

In the mixture, moreover, peaks of 1.67 to 2.17 ppm are detected (hydrogens in positions 1 and 3 of cyclopropane) and a peak towards 11.25 ppm (mobile hydrogen of the acid function).

The analysis of the mixture obtained (F = 150 ° C) is as follows:

Analysis for C8H10Br4O2 (457,804):

Calculated: C 20.99 H 2.20 Br 69.82%

Found: C 20.90 H 2.20 Br 70.20%

Example 2:

IR acid chloride, is 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrabromo-ethyl) cyclopropane- 1-carboxylic

0.2 cm3 of dimethylformamide, 8.5 cm3 of thionyl chloride are introduced into 179 cm 3 of petroleum ether (eb. 35-75 ° C.), the mixture is brought to reflux, 35.76 g of acid are introduced. 1R, eis 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrabromoethyl) cyclopropane-l -carboxylic acid in 150 cm3 of methylene chloride, stirred for 2 h at reflux, cooled, concentrated to dryness by distillation, add toluene, concentrate again to dryness by distillation under reduced pressure and obtain 38 g of crude acid chloride (mp = 88 ° C.).

Example 3:

JR acid, trans 2,2-dimethyl 3-f ', 2', 2 ', 2'-tetrabromo-ethyl) cyclopropane-l-earboxylic

This compound is obtained by bromination of IR acid, trans 2,2-dimethyl 3- (2 ', 2'-dibromovinyl) cyclopropane-1-carboxylic acid, mixture of isomers A and B as described in Example 1.

NMR spectrum

Peaks of 1.30 to 1.40 ppm (hydrogens of the 2-methyls of cyclopropane); peaks at 1.65-1.74 and 1.97-2.37 ppm (hydrogens in 1 and 3 of cyclopropane); peaks at 4.30-4.47 and 4.47-4.65 ppm (hydrogen to ethyl); peak at 9.63 ppm (carboxyl hydrogen).

Example 4:

IR acid chloride, trans 2,2-dimethyl 3- (1 ', 2', 2 ', 2'-tetrabromo-ethyl) cyclopropane-l-carboxylic

By action of thionyl chloride on IR acid, trans 2,2-

flimethyl 3- (r, 2 ', 2', 2'-tetrabromoethyl) cyclopropane-1-carboxylic obtained in Example 3, the acid chloride is obtained.

IR spectrum (chloroform)

Absorption at 1778 cm- '.

Examples:

IR acid, trans 2,2-dimethyl3- (2 ', 2'-dich'loro 1', 2'-dibromo-ethyl) cyclopropane-1 -carboxylic

By the action of bromine on IR acid, trans 2,2-dimethyl 3- (2 ', 2'-dichlorovinyl) cyclopropane-1-carboxylic acid, 1R acid, trans 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromo-ethyl) cyclopropane-1-carboxylic, mixture of isomers A and B. NMR spectrum

Peaks at 1.17-1.37 ppm (2-methyl hydrogens of cyclopropane); peaks of 1.65-1.73 ppm to 1.93-2.03 ppm (hydrogens in 1 cyclopropane); peaks at 4.23-4.45 and 4.45-4.62 ppm (hydrogen in 1 'of ethyl in 3 of cyclopropane).

Example 6:

IR acid chloride, trans 2,2-dimethyl 3- (2 ', 2'-dichiaro 1', 2'-dibromoethyl) cyclopropane-1 -carboxylic

By the action of thionyl chloride on the acid prepared in Example 5 above, the chloride of IR acid is obtained, trans 2,2-dimethyl 3- (2 ', 2'-dichloro r, 2'-dibromoethyl ) cyclopropane-1-carboxylic.

IR spectrum (chloroform)

Absorption at 1777 cm-1.

Example 7:

IR acid, eis 2,2-dimethyl 3- (2 ', 2'-dibromo 1', 2'-dichloro-ethyl) cyclopropane-l-carboxylic

11.8 g of chlorine are bubbled into 30 cm3 of carbon tetrachloride at -15 ° C, then 24 g of an IR acid solution, eis 2.2, are added slowly at -10 ° C. -dimethyl 3- (2 ', 2'-dibromovinyl) cyclopropane-1-carboxylic acid in 37 cm3 of methylene chloride, stirred for 1 hour at 0 ° C and for 2 hours at 25 ° C, concentrated under reduced pressure, purified by crystallization from carbon tetrachloride and obtains 7.4 g of IR acid, eis 2,2-dimethyl 3- (2 ', 2'-dibromo 1', 2'-dichloroethyl) cyclopropane-1-carboxylic. M = 134 ° C (mixture of isomers A and B).

NMR spectrum

Peaks at 1.32-1.44 and 1.28-1.48 ppm (hydrogens of methyl en2 of cyclopropane); peaks at 5.08-5.45 and 4.67-5.0 ppm (hydrogen at the end of the ethyl chain in position 3 of the cyclopropane); peak at 10.1 ppm (carboxyl hydrogen).

Example 8:

Acid chloride 1R, eis 2,2-dimethyl 3- (2 ', 2'-dibromo l', 2'-dichloroethyl) cyclopropane-l-carboxylic

By the action of thionyl chloride in the presence of Pyridine on the acid obtained in Example 7 above, the chloride of IR acid is obtained, eis 2,2-dimethyl 3- (2 ', 2'-dibromo l' , 2'-dichloro-ethyl) cyclopropane-1-carboxylic.

Example 9:

IR acid, trans 2,2-dimethyl 3- (2 ', 2'-dibromo l', 2'-dichloro-ethyl) cyclopropane-l-carboxylic

In a mixture of 20 cm3 of carbon tetrachloride and 20 cm3 of methylene chloride, 24 g of 1 R, trans 2,2-dimethyl 3- (2 ', 2'-dibromovinyl) cyclopropane-1 - acid are introduced. carboxylic, cools to -10 ° C, saturates the chlorine solution, overcomes the reaction vessel with an ascending cooler supplied with a fluid at -60 ° C (methanol / Dry ice) so as to avoid losses of chlorine, agitates for 2 '' At h at -10 ° C then during A h at + 10 ° C, leaves to evaporate the excess chlorine, removes the solvents by distillation under reduced pressure, purifies the residue (35.5 g) by chromatography

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on silica gel, eluting with a mixture of cyclohexane, ethyl acetate and acetic acid (75/25/1) then with a mixture of the same solvents in the proportion 80/20/1 and obtains 16.3 g of 1R acid,

trans 2,2-dimethyl 3- (2 ', 2'-dibromo l', 2'-dichloro-ethyl) cyclopropane-1 -carboxylic.

NMR spectrum (deuterochloroform)

Peaks at 1.33-1.56 ppm, characteristic of the hydrogens of the methylated gemines in position 2 of the cyclopropyl; peaks at 1.70-2.25 ppm, characteristics of the hydrogens in positions 1 and 3 of cyclopropane; peaks at 4.10-4.38 ppm, characteristic of hydrogen in position 1 'of the substituted ethyl side chain; peak at 10.9 ppm, characteristic of the carboxyl hydrogen.

Example 10:

IR acid, trans 2,2-dimethyl 3- (2 ', 2'-difluoro 1', 2'-dibromo-ethyl) cyclopropane-l-carboxylic

Analogously to those described above by the action of bromine on the acid 1 R, trans 2,2-dimethyl 3- (2 ', 2'-difluoro-vinyl) cyclopropane-1-carboxylic, but operating at -60 ° C, IR, trans 2,2-dimethyl 3- (2 ', 2'-difluoro r, 2'-dibromo-ethyl) cyclopropane-1-carboxylic acid are obtained. M = 122 ° C (mixture of isomers A and B).

NMR spectrum

Peaks of 1.33 to 1.36 ppm (methyl hydrogen in 3-cyclopropane); peaks of 1.60 to 2.23 ppm (hydrogens in 1 and 3 of cyclopropane); peaks of 3.75 to 4.37 ppm (hydrogen at the end of the ethyl chain at 3 of the cyclopropane); peak at 10.96 ppm (carboxyl hydrogen).

Example 11:

IR acid chloride, trans 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2'-dibromoethyl) cyclopropane-1 -carboxylic

By the action of thionyl chloride on the acid obtained in preceding example 10, the chloride of IR acid, trans 2,2-dimethyl 3- (2 ', 2'-difluoror, 2'-dibromoethyl) is obtained. cyclopropane-1 -carboxylic.

Example 12:

IR acid, eis 2,2-dimethyl 3- (2 ', 2'-dichloro 1', 2'-dibromo-ethyl) cyclopropane-l-carboxylic

By the action of bromine on IR acid, eis 2,2-dimethyl 3- (2'-2'-dichlorovinyl) cyclopropane-1-carboxylic, we obtain 1R acid, eis 2,2-dimethyl 3 - (- 2 ', 2'-dichloro 1 \ 2'-dibromo-ethyl) cyclopropane-1-carboxylic (mixture of isomers A and B). NMR spectrum

Peaks at 1.26-1.30 and 1.41-1.42 ppm (3-methyl hydrogens of cyclopropane); peaks at 1.83-2.17 ppm (hydrogens in 1 and 3 of cyclopropane); peaks of 4.83 to 5.58 ppm (hydrogen in V of ethyl in 3 of cyclopropane); peak at 8.17 ppm (carboxyl hydrogen).

Example 13:

IR acid chloride, eis 2,2-dimethyl3- (2 ', 2'-dichiaro l', 2'-dibromoethyl) cyclopropane-l-carboxylic

It is obtained by the action of thionyl chloride on the acid obtained in Example 12 above.

Example 14:

IR acid, eis 2,2-dimethyl 3- (2 ', 2', 2 ', 1'-tetrachloro-ethyl) cyclopropane-l-carboxylic

In 30 cm3 of carbon tetrachloride, the chlorine is bubbled until saturation (11.8 g of chlorine is dissolved), a solution of 16.7 g of IR acid, eis 2.2- is introduced in approximately 30 min. dimethyl 3- (2 ', 2'-dichlorovinyl) cyclopropane-1-carboxylic acid in 40 cm3 of methylene chloride, at less than 0 ° C, stirred for 24 h at 0 ° C, brings the temperature of the reaction mixture to +25 ° C, stirred for 3 h at this temperature, removes excess chlorine by bubbling nitrogen, concentrated to dryness by distillation under reduced pressure, purifies the residue by silica gel chromatography, eluting with a mixture of cyclohexane and ethyl acetate (8/2), crystallizes from petroleum ether (eb. 35-75 ° C) and obtains 3.14 g of IR acid, eis 2,2-dimethyl 3- (2 ', 2 ', 2', r-tetrachloroethyl) cyclo-propane-1-carboxylic. Mp = 144 ° C.

Analysis for C8H10Cl4O2 (279.98);

Calculated: C34.3 H 3.6 Cl 50.6%

Found: C34.4 H 3.7 Cl 50.3%

NMR spectrum (deuterochloroform)

Peaks at 1.26-1.42 ppm and 1.30-1.42 ppm, characteristic of the hydrogens of the twin methyls; peaks of 4.67 to 5.17 ppm and 5.08 to 5.43 ppm, characteristic, of the hydrogen in the 1-position of the substituted ethyl side chain; peak at 10.2 ppm, characteristic of hydrogen from carboxyl; peak from 1.67 to 2.0 ppm, characteristic of cyclopropyl hydrogens.

Example 15:

Acid chloride (1R, eisj 2,2-dimethyl 3- (2 ', 2', 2 ', l'-tetrachloro-ethyl) cyclopropane-l-carboxylic

In a mixture of 60 cm3 of petroleum ether (bp 35-70 ° C) and 8.7 cm3 of thionyl chloride, 6.75 g of 1R acid, eis 2,2-dimethyl 3- is introduced. (2 ', 2', 2 ', 1' -tetrachloroethyl) cyclopropane-1 -carboxy-lique, brings the reaction mixture to reflux, keeps it there for 4 'A h, concentrated to dryness by distillation under reduced pressure, adds benzene, concentrated to dryness and obtains the chloride of the IR acid, eis 2,2-dimethyl 3- (2 ', 2', 2 ', 1' -tetrachloroethyl) cyclopropane-1-carboxylic crude.

Example 16:

IR acid, trans 2,2-dimethyl 3- (2 ', 2', 2 ', l'-tëtrachloro-ethyl) cyclopropane-l-carboxylic

In 30 cm3 of carbon tetrachloride, 13.25 g of chlorine is dissolved at -10 ° C, and approximately 15.8 g of 1 R, trans 2,2-dimethyl 3- (2 ') acid is added in 15 min. , 2'-dichlorovinyl) cyclopropane-1 -carboxylic solution in 30 cm3 of methylene chloride, the reaction vessel being surmounted by a condenser in which circulates a liquid at -60 ° C to condense the unreacted chlorine, stirred for 1 h at -10 ° C, then for a h at 0 ° C, removes excess chlorine at 20 ° C by bubbling nitrogen, concentrated to dryness under reduced pressure, purifies the residue by Chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (7/3), to obtain 23 g of IR, trans 2,2-dimethyl 3- (2 ', 2', 2 ') acid , r-tetrachloroethyl) cyclopropane-1-carboxylic.

NMR spectrum (deuterochloroform)

Peaks at 1.25-1.53 ppm, characteristic of the methyl hydrogens in position 2 of the cyclopropyl; peaks at 1.68-2.21 ppm, characteristics of the hydrogens in positions 1 and 3 of cyclopropyl; peaks at 4.12-4.21 ppm, characteristic of the hydrogen in position 1 of the substituted ethyl side chain; peak at 11.3 ppm, characteristic of the hydrogen of the carboxyl.

Example 17:

IR acid chloride, trans 2,2-dimethyl 3- (2 ', 2', 2 ', l'-tetrachloro-ethyl) cyclopropane-l-carboxylic

In a mixture of 30 cm3 of petroleum ether (bp 35-75 ° C) and 16 cm3 of thionyl chloride, 12.276 g of acid obtained in Example 16 is introduced and brought to reflux, maintains reflux for 4 lA h, concentrated to dryness by distillation under reduced pressure, adds benzene, concentrates again to dryness and obtains the chloride of the acid IR, trans 2,2-dimethyl 3- (2 ', 2', 2 ' , r-tetrachloroethyl) cyclopropane-1-carboxylic acid.

Example 18:

1R acid, eis 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2'-dibromoethyl) cyclopropane-l-carboxylic

17 g of acid are introduced into 120 cm3 of methylene chloride

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IR, eis 2,2-dimethyl 3- (2 ', 2'-difluorovinyl) cyclopropane-1-carboxylic, introduced at -65 ° C, in about 2 h, 15.2 g of bromine in solution in 40 cm3 of tetrachloride of carbon, stirred for 2 h at -65 ° C, allows the temperature to rise to 20 ° C, concentrated to dryness by distillation under reduced pressure, dissolves the residue, hot, in 50 cm3 of carbon tetrachloride, cools to 0 ° C, stir at this temperature for 45 min, remove the insoluble matter by filtration, concentrate the filtrate to dryness by distillation under reduced pressure, dissolve the residue in 40 cm3 of carbon tetrachloride, stir for 20 min at -10 ° C, eliminates the insoluble matter by filtration, concentrates the filtrate to dryness by distillation under reduced pressure, purifies the residue of cyclohexane and ethyl acetate (75/25), crystallizes from petroleum ether (eb. 35-75 ° C) and obtains 1.465 g of IR acid, eis 2,2-dimethyl 3- (2 ', 2'-difluoro 1', 2'-dibromoethyl) cyclopropane-1 -carboxylic. M = 124 ° C.

NMR spectrum (deuterochloroform)

Peaks at 1.28-1.38 ppm, characteristic of the hydrogens of the twin methyls; peaks 1.67-2.0 ppm, characteristics of cyclopropyl hydrogens; peaks at 4.67-5.33 ppm, characteristics of hydrogen in the substituted ethyl side chain.

Example 19:

IR acid chloride, is 2,2-dimethyl3- (2 ', 2'-difluoro 1', 2'-dibromoethyl) cyclopropane- 1-carboxylic

1.43 g of IR acid, isis 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2 ') -dibromo-ethyl) cyclopropane-1-carboxylic acid, add 2.5 cm3 of thionyl chloride, bring to reflux, maintain reflux for 4 h, eliminate the excess of thionyl chloride and the solvent by distillation under reduced pressure, add benzene to the residue, concentrate to dryness by distillation under reduced pressure, and obtain the acid chloride 1R, eis 2,2-dimethyl 3- (2 ', 2'-difluoro, l', 2'-dibromoethylâcyclopropane- 1-crude carboxylic.

Example 20:

Acid 1R, eis 2,2-dimethyl3- (2 '(RS) fluoro 2'-chloro 1', 2'-dibromo-ethyl) cyclopropane-l-carboxylic

In 100 cm3 of carbon tetrachloride, 8.9 g of 1 R, eis 2,2-dimethyl 3- (2'-chloro 2'-fluorovinyl) cyclo-propane-1-carboxylic acid (mixture of isomers) are dissolved. E + Z), add 2.4 cm 3 of bromine in solution in 20 cm 3 of carbon tetrachloride at -10 ° C, stirred for 4 h at + 10 ° C, concentrated to dryness by distillation under pressure reduced, chromatograph the residue on silica gel, eluting with ethyl acetate to obtain 13.7 g of 1R acid, eis 2,2-dimethyl 3- (2 '(RS) fluoro 2'-chloro l' , 2'-dibromoethyl) cyclopropane-1 -carboxylic.

IR spectrum (chloroform)

Absorption at 1710 cm characteristic of C = 0, absorption at 3510 cm ■ 'characteristic of OH,

NMR spectrum (deuterochloroform)

Peaks at 1.30-1.32-1.42 ppm, characteristics of the hydrogens of the twin methyls; peaks at 1.75-2.08 ppm, characteristic of cyclopropyl hydrogens; peaks at 4.67-5.50 ppm, characteristics of the hydrogen in position 1 of the substituted ethyl side chain; peak at 10.75 ppm, characteristic of the hydrogen of the carboxyl.

Study of antifungal activity

- IR acid, eis 2,2-dimethyl 3- (2 ', 2'-dibromo r, 2'-dichloro-ethyl) cyclopropane-1-carboxylic (compound A)

- IR, trans 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2'-dibromoethyl) cyclopropane-l-carboxylic acid (compound B)

- IR acid, eis 2,2-dimethyl 3- (2 ', 2 / -dichloro r, 2'-dibromo-ethyl) cyclopropane-1-carboxylic (compound C)

- IR acid, trans 2,2-dimethyl 3- (2 ', 2', 2 ', r-tetrabromo-ethyljcyclopropane- 1-carboxylic (compound D)

- IR acid, eis 2,2-dimethyl 3- (2 ', 2', 2 ', l'-tetrachloro-ethyl) cyclopropane-l-carboxylic (compound E)

- 1R, is 2,2-dimethyl 3- (2 ', 2', 2 ', r-tetrabromo-ethyl) cyclopropane-1-carboxylic acid (compound F)

- IR, trans 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromoethyl) cyclopropane-l-carboxylic acid (compound G).

The fungistatic effectiveness of the compound to be tested is studied by introducing 0.5 cm3 of the solution of the compound and 0.5 cm3 of a suspension of spores of the fungus to be controlled, adjusted to approximately 100,000 spores / cm3 in 4 cm3 of nutrient medium. Staron.

The reading is carried out, after 7 d of incubation, by visual control of the development of the fungus or of its lack of development (0% or 100% efficiency).

Staron's nutrient medium has the following composition:

- glucose 20 g

- peptone 6 g

- yeast extract 1 g

- cornsteep 4 g

- sodium chloride 0.5 g

- monopotassium phosphate 1 g

- magnesium sulfate 0.5 g

- ferrous sulfate 10 mg

- water sufficient for 11.

Using the above-mentioned protocol, the following fungistic thresholds have been found:

1. Tests on Botrytis Cinerea

Compound A: between 150 and 200 ppm Compound E: between 75 and 100 ppm

2. Tests on Fusarium roseum

Compound A: between 100 and 150 ppm compound C: between 100 and 150 ppm compound D: between 75 and 100 ppm compound E: between 50 and 75 ppm compound G: between 100 and 150 ppm

3. Tests on Phoma species compound A: between 50 and 75 ppm compound B: between 100 and 150 ppm compound C: between 150 and 200 ppm compound D: between 100 and 150 ppm compound E: between 50 and 75 ppm compound G: between 100 and 150 ppm

4. Tests on Penicillium roqueforti compound A: between 50 and 75 ppm compound B: between 100 and 150 ppm compound C: between 150 and 200 ppm compound D: between 100 and 150 ppm compound E: between 50 and 75 ppm compound G: between 100 and 150 ppm

5. Conclusion:

Compounds A, B, C, D, E and G are endowed with an interesting antifungal activity.

Study of the biocidal activity of compounds A, B, C, D, E, F and G Tests on adhesive:

A solution of 3 g of carboxymethyl starch in 91 g of water is used. The test compound is incorporated into 1 cm 3 of acetone solution, 5 cm 3 of an inoculum consisting of a mixture of spores of Aerobacter aerogenes, Pseudomonas aeruginosa, Escherichia coli, Serratia marcescens, Bacillus subtilis and Staphylococcus are added. aureus. This mixture is brought to the oven at 37 ° C for 48 h, then at 20 ° C for 6 d.

The bacterial population is checked 48 h and 8 d after treatment and contamination by the dilution method in the serum and incorporation in the agar broth.

Using this operating protocol, the following results were obtained:

5

10

15

20

25

30

35

40

45

50

55

60

65

Population (colonies / ml)

% mortality (compared to control)

after treatment and infestation

after treatment and infestation

48 h after

8 after

48 h after

8 after

0.05%

0.025%

Untreated

0.05%

0.025%

Untreated

0.05%

0.025%

0.05%

0.025%

Compound A

0

12 x 10 "

57x10®

0

15x10 "

17 x 107

100

78.947

100

91.176

Compound B

0

0

57 x 10®

0

0

17 x 107

100

100

100

100

Compound C

0

12x10 *

57 x 10 "

0

16 x 105

17 x 107

100

99,789

100

99,050

Compound D

0

0

73 x 106

0

630

17x10 "

100

100

100

99.996

Compound E

0

30 x 105

57x10 "

0

12x10 "

17 x 107

100

94,737

100

92,941

Compound F

300

87 x 105

85x10 "

270

21 x 10 "

73 x 10 "

99.999

89,764

99.999

71.233

Compound G

0

47 x 104

44x10 "

0

51x10 "

54x10 "

100

98,932

100

95,555

Conclusion:

Compounds A, B, C, D, E, F and G are endowed with an interesting biocidal activity.

Claims (6)

630,601 1 „ X c C \ -V2 '1> N <rC-0H (I) in which X! represents a hydrogen, fluorine, chlorine or bromine atom, X2, identical to or different from Xl5 represents a fluorine, chlorine or bromine atom, and X3 represents a chlorine, bromine or iodine atom , as well as the chlorides of these acids. 1. Cyclopropanecarboxylic acids, in all their stereoisomeric forms, of formula: 2. As compounds according to claim 1, the compounds of formula I, as defined in claim 1, in the form of isomer A, isomer B or a mixture of these isomers, the names of which follow: - IR, trans 2,2-dimethyl 3- (r, 2 ', 2', 2'-tetrabromo-ethyl) cyclopropane-1-carboxylic acid, - IR, trans 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromo-ethylicyclopropane-l-carboxylic acid, - IR acid, eis 2,2-dimethyl 3- (2 ', 2'-dibromo l', 2'-dichloro-ethyl jcyclopropane-1 -carboxylic, - IR, trans 2,2-dimethyl 3- (2 ', 2'-dibromo l', 2'-dichloro-ethyl) cyclopropane-1-carboxylic acid, and - 1R acid, trans 2,2-dimethyl 3- (2 ', 2'-difluoro l', 2'-dibromo-ethyljcyclopropane-1 -carboxylic. 2 3. In the form of isomer A, isomer B or a mixture of these isomers, the following compounds according to claim 1: - IR acid, eis 2,2-dimethyl 3- (r, 2 ', 2', 2'-tetrabromo-ethy 1 Jcyclopropane-1 -carboxylic. 4. In the form of isomer A, isomer B, or a mixture of these isomers according to claim 1: - 1 R acid, eis 2,2-dimethyl 3- (2 ', 2'-dichloro l', 2'-dibromo-ethyl) cyclopropane-1 -carboxylic. 5. According to claim 1, the compounds of formula I, as defined in claim 1, in the form of isomer A, isomer B or a mixture of these isomers, the names of which follow: - IR acid, eis 2,2-dimethyl 3- (2 ', 2', 2 ', r-tetrachloroethyl) cyclo-propane-1-carboxylic acid, and - acid 1 R, trans 2,2-dimethyl 3- (2 ', 2', 2 ', l'-tetrachloro-ethyl jcyclopropane-1 -carboxylic. 6. According to claim 1, the compounds of formula I, as defined in claim 1, in the form of isomer A, isomer B or a mixture of these isomers, the names of which follow: - IR acid, eis 2,2-dimethyl 3- (2 ', 2'-difluoro 2', l'-dibromo-ethyl) cyclopropane-1-carboxylic acid, and - 1R acid, eis 3- (2 '(RS) fluoro 2'-chloro l', 2'-dibromo-ethyl) cyclopropane-1 -carboxylic.