CH651557A5 - ESTERS OF CARBOXYLIC CYCLOPROPANE ACIDS COMPRISING A POLYHALOGEN SUBSTITUENT, THEIR PREPARATION PROCESS AND THEIR USE IN THE CONTROL OF PESTS. - Google Patents

Description

The present invention relates to new esters of cyclopropane carboxylic acids comprising a polyhalogenated substituent, their preparation process and their use in the fight against parasites.

The subject of the invention is, all of their possible isomeric forms or in the form of a mixture of isomers, the compounds of formula (I):

45

50

° 2 Cîi2 "

in which X! represents a hydrogen, fluorine, chlorine or bromine atom, X2 identical or different from Xb represents a fluorine, chlorine or bromine atom, X3 represents a chlorine, bromine or iodine atom, the one of the radicals A 55 or B is a carbonyl group and the other a methylene, ethylidene or propylidene group and R] is a lower alkyl, a lower alkenyl or a lower alkynyl containing at most three carbon atoms.

The compounds of formula (I) can exist in many name-60 isomeric forms. Indeed, the cyclopropane carboxylic acids forming the acid copula of the esters of formula (I) have at least 3 asymmetric carbons, namely the asymmetric carbons in position 1 and 3 of cyclopropane and the carbon in position 1 of the polyhalo ethyl side chain. - "gene fixed in position 3.

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

In the case where the substituents Xt and X2 are identical, for a determined steric configuration of the asymmetric carbons in position 1 and 3 of the cyclopropane ring, two diastereoisomeric forms of the products of formula (I), due to the existence of the asymmetric carbon in 1 ', may exist and be 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.

When R 1 is a lower alkyl radical, it is preferably a methyl, ethyl or propyl radical.

When R] represents an alkenyl radical, it preferably acts on the radical -CH2CH = CH2.

When R! represents an alkynyl radical, it is preferably the radical -CH-C s CH.

The subject of the invention is very particularly the compounds corresponding to formula (IA)

The subject of the invention is in particular the compounds of formula (I) for which the cyclopropanic acid copula has a trans IR or 1R eis structure, as well as the compounds of formula (I) for which Xb X2 and X3 represent the same atom. halogen, for example a bromine atom.

The compounds of formula (I) have interesting properties which allow their use in the fight against parasites. It can be for example the fight against plant parasites, ectoparasites of warm-blooded animals and parasites of premises. This is how the products of the invention can be used to fight against insects, nematodes and parasitic mites of plants, animals and premises.

The products of formula (I) can be used in particular to fight against insects in the agricultural field, to fight for example against aphids, lepidopteran larvae and beetles. They are used in doses of between 10 g and 300 g of active ingredient per hectare.

The experimental part set out below clearly highlights the remarkable knock-down power of the products of the invention, as well as its lethal effect after poten-tialisation by the synergists.

The products of the invention and more particularly the B isomer obtained in Example 4 also have the advantage of having good photostability, which allows them to be used in the agricultural field, for example.

The products of formula (I) can also be used to fight against insects in premises, to fight in particular against flies, mosquitoes and cockroaches.

The products of formula (I) can also be used to fight against mites and parasitic nematodes of plants.

The compounds of formula (I) can also be used to fight against parasitic mites of animals, to fight for example against ticks and in particular ticks of the species Boophilus, those of the species Hyalommia, those of the species Amblyomma and those of the species Rhipicephalus, or to fight against all kinds of scabies and in particular sarcoptic scabies, psoroptic scabies and chorioptic scabies.

A subject of the invention is therefore also the application of the products of formula (I) for combating parasites of plants, warm-blooded animals and premises.

A subject of the invention is also the compositions intended for combating plant and animal parasites

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with warm blood and premises, characterized in that they contain, as active principle, at least one of the products defined above.

These compositions are prepared according to the usual methods of the agrochemical industry, the veterinary industry or the industry for products intended for animal nutrition.

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, solutions for aerosols, combustible strips, baits or other preparations conventionally used for the use of this kind of compounds.

In addition to the active principle, these compositions generally contain a vehicle and / or a non-ionic surfactant, ensuring, moreover, 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 or a solid fuel.

The invention particularly relates to insecticide compositions containing as active ingredient at least one of the products defined above.

The insecticidal compositions according to the invention preferably contain from 0.005% to 10% by weight of active material.

According to an advantageous procedure, for domestic use, the compositions according to the invention are used in the form of fumigant compositions.

The compositions according to the invention can then advantageously consist, for the non-active part, of a combustible insecticide coil (or coil), or also of an incombustible fibrous substrate. In the latter case, the fumigant obtained after incorporation of the active material is placed in a heating device such as an electromosquito destroyer.

In the case where an insecticidal coil is used, the inert support can be, for example, composed of pyrethrum marc, Tabu powder (or Machilus Thumbergii leaf powder), pyrethrum stem powder, cedar leaf powder , wood powder (such as sawdust) starch and coconut shell powder.

The dose of active ingredient can then be, for example, from 0.03 to 1% by weight.

In the case where an incombustible fibrous support is used, the dose of active material can then be, for example, from 0.03 to 95% by weight.

The compositions according to the invention for domestic use can also be obtained by preparing a pulverisable oil based on active principle; this oil soaking the wick of a lamp and then being subjected to combustion.

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

The subject of the invention is also the acaricide and nematicide compositions containing as active principle at least one of the products of formula (I) defined above.

Like the insecticide compositions according to the invention, the acaricide and nematicide compositions can optionally be added with one or more other pesticidal agents. The acaricide and nematicide compositions may be in particular in the form of powders, granules, suspensions, emulsions, solutions.

For acaricide use, wettable powders for foliar spraying, containing from 1 to 80% by weight of active ingredient, or liquids for foliar spraying containing from 1 to 500 g / l of active ingredient are preferably used. We can

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also use powders for foliar dusting, containing from 0.05 to 3% by weight of active ingredient.

For nematicide use, liquids are preferably used for soil treatment containing 300 to 500 g / L of active ingredient.

The acaricide and nematicide compounds according to the invention are preferably used, at doses of between 1 and 100 g of active material per hectare.

The compounds of formula (I) have an excellent general tolerance, and the invention therefore also relates to the products of formula (I), as medicaments, in particular for combating conditions created by ticks and scabies.

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

The drugs of the invention are used in particular in human medicine to fight against lice as a preventive or curative measure and to fight against scabies. They can also be used as anthelmintics.

The medicaments of the invention can be administered externally, by spraying, by bathing or brushing.

The medicaments of the invention for veterinary use can also be administered by brushing the backbone according to the method known as the “pour-on” method. They can also be administered by the digestive or parenteral route.

A subject of the invention is therefore pharmaceutical compositions containing as active principle at least one of the medicaments defined above, and in particular compositions intended for the fight against parasitic mites of animals, containing as active product at least one of the products defined above, to fight for example against all kinds of ticks and scabies.

When it comes to combating parasitic mites of animals, the products of the invention can be incorporated into food compositions in combination with a nutritive mixture suitable for animal feed. The nutritive mixture may vary according to the animal species, it may contain cereals, sugars and grains, soybean, peanut and sunflower meal, meal of animal origin, for example fish meal, synthetic amino acids, mineral salts, vitamins and antioxidants.

The invention therefore therefore relates to the food compositions defined above.

It can also be mentioned that the products of the invention have a very good repellant effect. Finally, it can be indicated that the products of the invention can be used as biocides or growth regulators.

To enhance the biological activity of the products of the invention, they can be added to conventional synergists used in such cases, such as l- (2,5,8-trioxadodecyl) 2-propyl-4,5-methylene dioxy benzene (or piperonyl butoxide) or N- (2-ethyl) heptyl) bicyclo [2,2-l] -5-heptene-2,3-dicarbox-imide or piperonyl-bis 2- (2'-n -butoxy ethoxy) ethylacetal (or tropital) or S, S, S, -tributyl phosphorotrithioate.

Depending on the use to be made of it, it may be advantageous to combine the products of formula (I) with other well known products having, for example, an insecticidal activity such as organochlorines, organophosphates, carba- mates and pyrethroids, acaricidal activity such as chlorinated carbinols, compounds belonging to the group of benzene derivatives, quinoxalines, formamidines, stannic derivatives, benzimidazoles, benzhydroxamic acid derivatives and pyrethroid derivatives, nematocides such as carbamates, products which decompose into carbamates and organophosphates, a herbicidal or ixodicidal activity such as organophosphates, carbamates and pyre-trinoids or a growth-regulating activity.

A subject of the invention is therefore also the associations of at least one of the products of formula (I) with at least one of the products chosen from the group consisting of esters of allethrolones, of alcohol 3,4,5,6 -methyl tetrahydrophthalimido, 5-benzyl 3-furyl methyl alcohol, 3-phenoxy benzyl alcohol and a-cyano 3-phenoxy benzylic alcohols of chrysanthemic acids, 5-benzyl 3-furyl methyl esters of 2,2-dimethyl 3- (2-oxo 3-tetrahydrothiophenylidene methyl) cyclopropane-1-carb-oxylic acids, esters of 3-phenoxy benzyl alcohol and a-cyano 3-phenoxy benzylic alcohols of 2,2 acids -dimethyl 3- (2,2-dichlorovinyl) cyclopropane-1-carboxylic, esters of α-cyano 3-phenoxy benzylic alcohols of 2,2-dimethyl 3- (2,2-dibromovinyl) cyclopropane-l- carboxylic, 3-phenoxy benzyl alcohol esters of 2-para-chlorophenyl-2-isopropyl acetic acids, esters of allethrolones, 3,4,5,6-tetrahydrophthalimidomethyl alcohol, 5- benzyl 3-furyl methyl, 3-phenoxy benzyl alcohol and a-cyano 3-phenoxy benzyl alcohols of 2,2-di-methyl 3- (r, 2 ', 2', 2'-tetrahaloethyl) cyclopropane 1-carboxylics in which “halo” represents a fluorine, chlorine or bromine atom, it being understood that the compounds (I) can exist in all their stereoisomeric forms, as do the acid and alcohol copulas of the pyrethroid esters or analogs above.

The associations according to the invention present in particular the advantage either of making it possible to combat, by the versatility of their action, a wider range of parasites, or of manifesting, in certain cases, a synergistic effect, or finally of combining for example, a pesticidal activity has a herbicidal activity, or a growth-regulating activity, or any other activity.

The subject of the invention is also a process for the preparation of the compounds of formula (I), characterized in that an acid of formula (II) is reacted:

H

VS

X.

in which Xj, X2 and X3 retain their previous meaning, or a functional derivative of this acid, with an alcohol of formula (III)

VS

H ° -CH2- <Cy R1 min in which A, B and R] retain their previous meaning, or a functional derivative of this alcohol, to obtain the corresponding compound of formula (I).

By functional acid derivative is preferably meant an acid chloride or an anhydride.

The esterification reaction is preferably carried out by reacting the acid of formula (II) with the alcohol of formula (III) in the presence of dicyclohexylcarbodiimide or diisopropylcarbodiimide.

The compounds of formula (II) used as starting materials are known products which can be prepared according to the process described in French patent 2,364,884.

The compounds of formula (III) also used as

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starting materials are also known products, which can be prepared according to the process described in French patent application 2,415,105.

Example 1

(IR, trans) 2,2-dimethyl-3- [1 '(RS) 2', 2'2'-tetrabromoethyl] cyclopropane carboxylate of [3- (propyn-2-yl) 2,5-dioxo imidazolidinyl] methyl .

A mixture containing 4 g of acid (IR, trans) 2,2-dimethyl 3- [1 '(RS) 2', 2 ', 2'-tetrabromoethyl] is maintained under stirring and under a stream of nitrogen for 30 minutes. cyclopropane carboxylic, 50 cm3 of methylene chloride, 15 mg of dimethylamino pyridine and 1.8 g of dicyclohexylcar-bodiimide. 1.5 g of [3- (propyn-2yl) 2,5-di-oxo-imidazolidinl] methanol are then added. The reaction mixture is kept under stirring for 16 hours; filtered and concentrated the filtrate to dryness; 6.17 g of the sought product is obtained in the "crude" form which is purified by chromatography on silica eluting with a cyclohexane-ethyl acetate mixture 73-27. 3.5 g of the sought product are thus obtained.

- 4.1

H of n

NOT

bN

- 4.2-4.3

H of

10

ti-

l

C - C s CH

■ N /

15 - 2.37-2.39-2.41 H acetylene.

(B) 1.6 g of the R diastereoisomer

[a] D = + 71.5 ° ± 1.5 ° (c = 1.5% in CHC13)

NMR CDCI3 p.p.m.

- 1.27-1.31-1.33-1.35

- 1.62 to 2.33

- 4.3-4.4 and 4.4-4.6

- 5.6 and 5.63

- 4.03 and 4.06

- 4.2 to 4.3

- 2.34-2.38-2.43

H of the methyls in 2 H of the carbons in 1 and 3 H of the radical 1,2,2, 2 tetrabromo ethyl H of the carbon of the chain in CO 2

H of the carbon in 3 of the imidazolidinyl radical

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NMR CDCI3 p.p.m.

1.23 and 1.47 H of methyls in 2

H of the tetrabromoethyl radical

H of the side chain carbon has

C °> K »

H ^

- 5.0 to 5.1

- 5.4-5.6

5.6-5.6

- 4.03-4.05

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H of ti

4.2-4.3

H

H

I

H

35

H of the triple bond -C = ÇH

N 'NC = CH - 2.36-2.38-2.40 H-C = CH

Example 2

(IR eis) 2,2-dimethyl 3 [1 '(S) 2', 2 ', 2'-tetrabromoethyl] cyclopropane carboxylate of [3- (propyn-2-yl) 2,5-dioxo imidazoli-dinylmethyl and ( 1R eis) 2,2-dimethyl 3 [V (R) 2 ', 2', 2'-tetrabromoethyl] cyclopropane carboxylate of [3- (propyn 2-yl) 2,5-dioxo imidazolidinyl] methyl:

2 g of dicyclohexylcarbodiimide are introduced with stirring and under a stream of nitrogen into a solution containing 5.2 g of acid (lCis) 2,2-dimethyl 3 [1 '(RS) 2', 2 ', 2'-tetrabromoethyl ] carboxylic cyclopropane, 20 cm3 of methylene chloride and 150 mg of dimethylaminopyridine. The reaction mixture is kept under stirring for 15 to 20 minutes at room temperature and 1.8 g of 3- (propyn-2-yl) -2,5-dioxo imidazolidinyl methanol are introduced. The reaction mixture is kept under stirring for 2 hours 30 minutes, filters the urea formed, rinses it with methylene chloride. The filtrate is washed with a 1N hydrochloric acid solution, then with water, dried and concentrated to dryness under reduced pressure. 8.2 g of an oil are obtained which is chromatographed on silica eluting with a benzene-ethyl acetate mixture 85-15.

On the one hand, we isolate:

(A) 2.2 g of the diastereoisomer S

[a] D = 101 ° 5 ± 3 ° (C = 0.75% CHC13)

NMR CDCI3 p.p.m.

- 1.36 and 1.42 H of the 2-methyls of cyclopropane

- 5.3 to 5.4 H of the tetrabromoethyl radical

- 5.4-5.5 H of the carbon in the a chain of C02 5.6-5.7

Example 3

40 (IR trans) 2,2-dimethyl 3 [2'-bromo-2 ', 2'-dichloro I'-bromo ethyl] cyclopropane carboxylate of 1 [3- (propyn-2-yl) 2,5-dioxo imidazolidinyl ] methyl:

The product was prepared according to the process indicated above, starting from the corresponding acid and alcohol.

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[a] D = + 12 ° ± T (c = 0.5% CHCI3)

Example 4

(IR eis) 2-dimethyl3- (2'-bromo-2 ', 2'-dichloro 1'-bromo ethyl) 50 cyclopropane carboxylate 1 [3- (propyn-2-yl) 2,5-dioxo imidazolidinyl [methyl (isomer A) and (IR eis) 2,2-dimethyl 3- [2'-bromo 2 ', 2'-dichloro l'-bromoethyl] cyclopropane carboxylate from 1- [3- (propyn-2-yl) 2, 5-dioxo imidazolidinyl] methyl (isomer B):

The products were prepared according to the method indicated above in Example 2, starting from the corresponding acid and alcohol. Isomer A and B isomer were separated by chromatography.

60 [a] D = -122 ° ± 2 ° (c = 1% CHCI3) (isomer A)

[a] D = + 85 ± 2.5 ° (c = 1% CHCl3) (isomer B).

Example 5

65 A: Study of the shock activity on house flies.

Experience # 1:

The insects tested are female house flies

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4 to 5 days old and raised under constant laboratory conditions (25 ° C-70% relative humidity). The operation is carried out by direct spraying in a Kearnset March chamber using as solvent a mixture of acetone (5%) and petroleum solvent Isopar L (95%) (amount of solution used 2 x 0.2 cm3). About 50 insects are used per treatment. The controls are carried out every minute up to 10 minutes, then at 15 minutes and the KT 50 is determined by the usual methods.

The experimental results obtained are summarized in the following table:

KT 50 (in minutes) for a concentration of 0.25 g / 1

Product of Example 1 2.8

Product of Example 2 (S isomer) 1

Product of Example 2 (R isomer) 1.1

Conclusion:

The products of the application exhibit remarkable shock activity on this test.

Experiment 2:

The same technique is used, the same concentrations, but the controls are carried out every fifteen seconds up to 10 minutes and the KT 50 is determined by the usual methods.

The experimental results obtained are summarized in the following table:

KT 50 (in minutes) for a concentration of 0.25 g / 1

Product of Example 1 1.82

Product of Example 2 (S isomer) 1.34

Product of Example 2 (R isomer) 1.32

Conclusion:

Confirming and clarifying the conclusions of experiment 1, the products of the application exhibit remarkable shock activity on this test.

B: Potentialisation studies of demand products:

The insects used are female house flies aged 4 to 5 days and reared under constant laboratory conditions (25 ° C and 70% RH). We are looking for the LD 50 and we operate by topical application to Arnold's microapplicator, of a microliter of toxic acetone solution of each of the products on insects previously anesthetized with carbon dioxide.

The synergistic compounds used are on the one hand piperonyl butoxide (PB), on the other hand DEF or SSS tri-butyl phosphorotrithioate. They are used in solution with the products on demand.

Mortality checks are performed 24 hours after topical application.

The experimental results obtained are summarized in the following table:

DL <n in nanograms per insect

Product of Example 1: 191

Product of Example 1 + PB] 0 (used 10 times. ^

the dose of the product)

Product of Example 1 + DEF

10 (used 10 times.

the dose of the product)

Product of Example 1 + PB 10 + DEF 10: 13

DL5o in nanograms per insect:

R-isomer of Example 2: 327

R isomer of Example 2 + PB 10: 77

R isomer of Example 2 + DEF 10: 38

R isomer of Example 2 + PB 10 + DEF 10: 13.7

Conclusion:

Demand products can be highly potenialized by synergists and therefore exhibit remarkable lethal activity.

Example 6

Preparation of a soluble concentrate or aqueous spray

A homogeneous mixture of

Product of Example 1 0.25 g

Piperonyl butoxide 1 g

Tween80 0.25 g

TopanolA 0.1 g

Water 98.4 g

Example 7 Preparation of an emulsifiable concentrate:

We intimately mix:

Product of Example 1 0.015 g

Piperonyl butoxide 0.5 g

Twenn 80 3.5 g

TopanolA 0.1 g

Xylene 95.885 g

Example 8 Preparation of an emulsifiable concentrate:

A homogeneous mixture of:

Product of Example 1 1.5 g

Tween 80 20 g

TopanolA 0.1g

Xylene 78.4 g

Example 9 Preparation of a smoke composition:

Product of Example 1 0.25 g

Tabu powder 25 g

Cedar leaf powder 40 g

Pine wood powder 33.75 g

Bright green 0.5 g p-nitrophenol 0.5 g

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Claims (15)

651557 CLAIMS 1. In all their possible isomeric forms or in the form of a mixture of isomers, the compounds of formula I: li / Cxw_r O — CH — N, K1 2 2 \ / VA — B (I) in which X] represents a hydrogen, fluorine, chlorine or bromine atom, X2 identical or different from Xi, represents a fluorine, chlorine or bromine atom, X3 represents a chlorine, bromine or d atom 'iodine, one of the radicals A or B is a carbonyl group and the other is a methylene, ethylidene or propylidene group and Rj is a lower alcohol, lower alkenyl or lower alkynyl containing at most three carbon atoms . 2. Compounds according to claim I corresponding to formula (IA): has a fluorine, chlorine or bromine atom, it being understood that the acid and alcohol copulas of the pyrethroid esters or the like above can exist in all their stereoisomeric forms. 12. Compositions intended for animal feed containing as active principle at least one of the products defined in one of claims 1 to 5, combined with a nutritive mixture intended for animal feed. 13. Process for the preparation of compounds of formula I as defined in one of claims 1 to 5, characterized in that an acid of formula is reacted: .y. corCHr " . .CH -C = CH 2 (IA) 15 20 25 in which Xb X2 and X3 are defined as in claim 1. 3. Compound according to claim 1 or 2 for which the cyclopropanic acid copula is of IR trans or IR eis structure. 4. Compounds according to one of claims 1 to 3 for which X], X2 and X3 represent the same halogen atom. 5. Compounds according to claim 4 for which X], X2 and X3 each represent a bromine atom. 6. Method for combating plant parasites, ec-toparasites of warm-blooded animals and local parasites using the compounds of formula I as defined in one of claims 1 to 5. 7. Compositions intended for the fight against parasites of plants, warm-blooded animals and premises containing as active principle at least one of the products defined in one of claims 1 to 5. 8. Insecticidal compositions according to claim 7. 9. The acaricide and nematicide compositions according to claim 7. 10. Compositions according to claim 7, further comprising a synergistic agent. 11. Compositions according to claim 10, characterized in that they also close at least one compound chosen from the group consisting of esters of allethrolones, 3,4,5,6-tetrahydrophthalimido methyl alcohol, alcohol 5-benzyl 3-furyl methyl, 3-phenoxy benzyl alcohol and a-cyano 3-phenoxy benzyl alcohols of chrysanthemic acids, 5-benzyl 3-furyl methyl alcohol esters of 2,2- acids dimethyl 3- (2-oxo 3-tetrahydrotMophenylidene methyl) cyclopropane-1-carboxylic esters of 3-phenoxy benzyl alcohol and a-cyano 3-phenoxy benzylic alcohol esters of 2,2-dimethyl 3- (2, 2-dichlorovinyl) cyclopropane-1-carboxylic, esters of a-cyano 3-phenoxy benzylic alcohols of 2,2-dimethyl 3- (2,2-dibromovinyl) cyclo-propane-1-carboxylic acids, 3-phenoxy benzyl alcohol esters of 2-parachlorophenyl-2-isopropyl acetic acids, esters of allethrolones, 3,4,5,6-tetrahydrophthalimi-do-methyl alcohol, 5-benzyl 3- alcohol furyl met hylic, 3-phenoxy benzyl alcohol and a-cyano 3-phenoxy benzyl alcohols of 2,2-dimethyl 3- (r, 2 ', 2', 2'-tetrahalo-ethyl) cyclopropane-1-carboxylic acids in which “halo” re- 40 / (II) in which Xb X2 and X3 are defined as in claim 1, or a functional derivative of this acid, with an alcohol of formula: HO-CH2-N A B T (III) 30 in which A, B and Rj are defined as in claim 1, or a functional derivative of this alcohol. 35