FR2502462A1 - NOVEL CYCLOPROPANE ACID ESTERS COMPRISING A POLYHALOGEN SUBSTITUTE, PROCESS FOR THE PREPARATION THEREOF AND THEIR USE IN THE FIGHT AGAINST PESTS - Google Patents

Abstract

THE SUBJECT OF THE INVENTION, IN ALL THEIR POSSIBLE ISOMERIC FORMS, IS THE COMPOUNDS OF FORMULA: (CF DRAWING IN BOPI) IN WHICH X REPRESENTS AN ATOM OF HYDROGEN, FLUOR, CHLORINE OR BROMINE, X IDENTICAL OR DIFFERENT FROM X REPRESENTS AN ATOM OF FLUOR, OF CHLORINE OR OF BROMINE, X REPRESENTS AN ATOM OF CHLORINE, OF BROMINE OR OF IODINE, ONE OF RADICALS A OR B IS A CARBONYL GROUP AND THE OTHER IS A METHYLENE, ETHYLIDENE OR PROPYLIDENE GROUP AND R IS A LOWER ALCOYL, LOWER ALKENYL, OR LOWER ALCYNYL CONTAINING NOT MORE THAN THREE CARBON ATOMS, AND MIXTURES OF THESE ISOMERS. THE SUBJECT OF THE INVENTION ALSO IS A PROCESS FOR THE PREPARATION OF THE COMPOUNDS OF FORMULA I. THE COMPOUNDS OF FORMULA I ARE APPLIED TO THE CONTROL AGAINST PARASITES.

Description

The present invention relates to novel cyclopropane esters

  carboxylic acid having a polyhalogen substituent, process for their preparation and their application

the fight against parasites.

  The subject of the invention is, in all their possible isomeric forms, the compounds of formula (I) ## STR1 ## in which X 1 represents a hydrogen, fluorine, chlorine or hydrogen atom. bromine, X2 identical or different from X1 represents a fluorine, chlorine or bromine atom, X3 represents a chlorine, bromine or iodine atom, one of the radicals A or B is a carbonyl group and the other a methylene, ethylidene or propylidene group and R1 is lower alkyl, lower alkenyl or lower alkynyl containing not more than

  three carbon atoms, as well as mixtures of these isomers.

  The compounds of formula (I) can exist in many isomeric forms. Indeed, the cyclopropane carboxylic acids forming the acidic copula of the esters of formula (I) generally have 3 asymmetric carbons, namely the asymmetric carbons at position 1 and 3 of the cyclopropane and the carbon at the 1 'position of the ethyl side chain.

  polyhalogenated fixed in position 3.

  In the case where the three substituents X1, X2 and X3 are different from one another, an asymmetric carbon

  may exist in position 2 'of the chain la-

polyhalogenated teral.

  In the case where the substituents X1 and X2 are identical,

  For a given steric configuration of the asymmetric carbons in positions 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 'can exist and be characterized in particular by their spectrum of NMR or

  their migration rate in thin layer chromatography.

  These isomers can in general be separated and isolated at - 1 -

  the pure state in particular by chromatography.

  When R1 is a lower alkyl radical, it is

  preferably the methyl, ethyl or propyl radical.

  When R 1 represents an alkenyl radical, it is preferably the -CH 2 CH-CH 2 radical. When R1 represents an alkynyl radical it is

  preferably the radical-CH2-C X CH.

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

H CH _

3 0 3

X2C Co2CH2N <C CH

3 -) 3- CH2 (IA)

  The subject of the invention is in particular the compounds of formula (I) for which the cyclopropane acid copula is of structure 1R trans or 1R cis, as well as the compounds of formula (I) for which X1, X2 and X3 represent the same

  halogen atom, for example a bromine atom.

  The compounds of formula (I) have interesting properties which allow their use in the fight against parasites. This may include, for example, the control of plant pests and warm-blooded animals. Thus, the products of the invention can be used for

  to control insects, nematodes and mites

  rasites of plants and animals.

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

per hectare.

  The experimental part below sets out clearly

  highlighting the remarkable eknock-down power of the products of the invention, as well as its lethal effect after

  potentiation by synergists.

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  The products of the invention furthermore have the advantage

  to have a good photostability which allows their use

  in the agricultural field for example.

  The products of formula (I) can also be used to control insects in the field of

  in particular against flies,

ticks and cockroaches.

  The products of formula (I) can also be used

  to control mites and parasitic nematodes

Plant.

  The compounds of formula (1) can still be used

  to fight against parasitic mites of animals, to fight for example against ticks and especially ticks of the species Boophilus, those of the species Hyalommia,

  those of the species Amblyomma and those of the species Rhipicepha-

  read, or to fight against all kinds of scabies and especially

  sarcoptic mange, psoroptic mange, and chorioptic mange.

  The invention therefore also relates to the applica-

  products of formula (I) to the fight against

  sites of warm-blooded animals and plants.

  The subject of the invention is in particular insecticidal compositions containing as active ingredient at least one

products defined above.

  These compositions are prepared according to the processes

  of the agrochemical industry, the veterinary industry,

  or industry of products for animal nutrition. In these compositions, the active substance (s) may optionally be added with one or more

  other pesticide agents. These compositions can be

  in the form of powders, granules, suspensions, emulsions

  solutions, solutions, aerosol solutions, fuel belts

  baits, baits or other preparations conventionally used

  for the use of this kind of compounds.

  In addition to the active ingredient, these compositions contain, in general, 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, hydro-

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4 2502462

  carbides or other organic solvents, mineral, animal or vegetable oil, powder such as talc, clays, silicates, kieselguhr or a combustible solid, such as

  than tabu powder (or pyrethrum marc).

  The insecticidal compositions according to the invention preferably contain from 0.005% to 10% by weight of active ingredient. The subject of the invention is also the acaricide and nematicide compositions containing as active principle the

  at least one of the products of formula (I) defined above.

  As the insecticidal compositions according to the invention

  acaricidal and nematicidal compositions can be added

  possibly one or more other pesti-

  cides. The acaricide and nematicide compositions may be in particular in the form of powders, granules, suspensions,

emulsions, solutions.

  For acaricidal use, wettable powders for foliar spraying containing from 1 to 80 percent of active ingredient or foliar spray liquids containing from 1 to 500 g / l of active ingredient are preferably used. Powder for dusting can also be used

  foliar, containing from 0.05 to 3 percent active ingredient.

  For the nematicide use, it is preferable to use soil treatment liquids containing from 300 to 500 g / L of active principle

  Acaricidal and nematicidal compounds according to the invention

  are preferably used, at

  between 1 and 100 g of active ingredient per hectare.

  The subject of the invention is also the compositions intended for the fight against parasitic mites of animals, for example to fight against all kinds of ticks and

scabies.

  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 to fight against diseases created by ticks

and scabies.

  The drugs of the invention can be used

  in both human medicine and veterinary medicine.

  The medicaments of the invention are especially useful

  in human medicine to fight head lice

  preventive or curative and to fight against scabies.

  The medicaments of the invention may be

  very externally, by spraying, bathing or

  geonnage. Medicines of the invention for veterinary use

  may also be administered by painting the

  dorsal pin according to the so-called "for-on" method. They can also be administered digestive or parenteral.

  The subject of the invention is therefore pharmaceutical compositions

  which contain as active ingredient at least one

  previously defined drugs.

  When it comes to combating dust mites,

  sites of animals, the products of the invention may be incorporated

  in food compositions in association with

  a nutritious mixture suitable for animal feed. To me-

  The nutrient mixture may vary according to the animal species, it may contain cereals, sugars and grains, soy, peanut and sunflower cakes, flours of animal origin, for example fishmeal, synthetic amines, mineral salts, vitamins and antioxidants. The subject of the invention is thus the compositions

defined above.

  It can also be mentioned that the products of the in-

  vention with a very good repelling effect. We can indicate

  Finally, the products of the invention can be used

  as biocides or growth regulators.

  To exalt the biological activity of the products of

  the invention, they can be added to classical synergists

  used in such a case, such as 1- (2,5,8-trioxa)

  dodecyl) 2-propyl-4,5-methylene dioxy benzene (or butoxide)

  piperonyl) or N- (2-ethylheptyl) bicyclo / 2 ', 2-1 / -5-

  heptene-2,3-dicarboxamide or lepiperonyl-bis2- (2'-n-butoxy)

  ethoxy) ethylacetal (or tropital) or S, S, S-tri-

butyl phosphorotrithioate.

  Depending on the use that one wants to make, it can be interesting to associate the products of formula (I) with

  other well-known products with insect activity

  such as organochlorines, organophosphorus compounds - carbamates and pyrethrinols, acaricides such as chlorinated carbinols, compounds belonging to the group of benzene derivatives, quinoxalines, formamidines, stanic derivatives, benzimidazoles, derivatives thereof. benzhydroxamic acid and pyrethrinol derivatives, nematocides such as carbamates, products decomposing into carbamates

  and organophosphors, herbicides or ixodicides such as

  phosphates, carbamates and pyrethroids or

growth, for example.

  For example, at least one of the products of formula (I) may be associated with at least one of the products selected from the group consisting of allethrolone esters,

  alcohol 3,4,5,6-tetrahydrophthalimido methyl, alcohol 5-

  benzyl 3-methyl furyl, 3-phenoxy benzyl alcohol and

  of 3-phenoxy benzyl α-cyano alcohols of chrysanthemic

  5-Benzyl-3-furyl methyl alcohols of 2,2-dimethyl-3- (2-oxo-3-tetrahydrothiophenylidene

  methyl, cyclopropane-1-carboxylic acid, alcohol esters 3-

  benzyl phenoxy and 3-phenoxy benzyl alkyes

  2,2-dimethyl-3- (2,2-dichlorovinyl) cyclopropane-

  1-carboxylic acid, 3-phenoxybenzyl alcohol-cyano esters

  of 2,2-dimethyl-3- (2,2-dibromovinyl) cyclopropane-1- acids

  carboxylic acid esters, esters of 3-phenoxy benzyl alcohols and 2-parachlorophenyl-2-isopropyl acetic acid esters,

  3,4,5,6-tetrahydrophthalimidomethyl alcohol allethrolones

  that of 5-benzyl 3-methyl furyl alcohol, alcohol 3-

  benzyl phenoxy and 3-phenoxy benzyl alkyes

  2,2-dimethyl-3- (1 ', 2t, 2', 2'-tetrahalo) cyclopropane-

  1-carboxylic compounds in which "halo" represents a fluorine, chlorine or bromine atom, it being understood that the compounds (I) may exist in all their stereoisomeric forms

  as well as the acidic copulas and alcohols of the pyrethrum esters

noldes.

  The associations according to the invention in particular

  the interest of being able to fight, by means of

  their action a wider range of parasites, ie to show, in some cases, a synergistic effect

  to combine, for example, a pesticidal activity with an

  herbicide activity, or 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: ## STR1 ##

X3 / X3

  in which X1, X2 and X3 retain their previous meaning, or a functional derivative of this acid, with an alcohol of formula (III) where

HO-CH2- (II-R1 (II)

A_B

  in which A, B and R1 retain their pre-existing

  cedente, or a functional derivative of this alcohol, to obtain

  the compound of formula (I) corresponding.

  By functional derivative of acid 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

of diisopropylcarbodiimide.

  The compounds of formula (II) used as starting products are known products which can be prepared according to the method described in the French patent application.

2,364,884.

  The compounds of formula (III) also used as starting products are also known products which can be prepared according to the process described in the application

French patent 2,415,105.

  Example 1: (1R.trans) 2,2-dimethyl-3 '(RS) 2] 2, 21-tetrabromide

  / 3-propyn-2-yl / 2,5-methyl-cyclopropane carboxylate

dioxo imidazolidinyl / methyl.

  A mixture containing 4 g of (1R, trans) 2,2-dimethyl-3 '(RS) 2', 2 ', 2-tetrabromethyl / cyclopropane acid is stirred under a stream of nitrogen for 30 minutes.

  carboxylic acid, 50 cm3 of methylene chloride, 15 mg of di-

  8-methylamino pyridine and 1.8 g of dicyclohexylcarbodiimide. 1.5 g of β-propyn 2,5-dioxo-imidazolidinyl methanol are then added. The reaction mixture is stirred for 16 hours; the mixture is filtered and the filtrate is concentrated to dryness; 6.17 g of the desired product is obtained in "crude" form which is purified by chromatography on silica eluting with a cyclohexane-ethyl acetate mixture 73-27. We obtain

3.5 g of the desired product.

NMR CDCl3 p.p.m.

  - 1,27 - 1,31 - 1,33 - 1,35 H methyl in 2 - 1,62 to 2,33 H of carbons in 1 and 3

  - 4.3 - 4.4 and 4.4 - 4.6 H of the radical 1, 2, 2, 2 tetra-

  bromo ethyl - 5.6 and 5.63 H of carbon in the chain CO2 - 4.03 and 4.06 H of carbon in 3 of the radical imidazolidinyl - 4.2 to 4.3 H of - 2.34 2 , 38 - 2.43 H of the triple bond-C a

  EXAMPLE 2 (1R cis) 2,2-dimethyl 3/1 '(S) 2', 2 ', 2'-tetrabromo-

  ethenyl / cyclopropane carboxylate of / 3- (propyn-2-yl) 2,5-

  dioxo imidazolidinyl / methyl and (1R cis) 2,2-dimethyl 3/1 '

  (R) 2 ', 2', 2'-tetrabromoethyl / cyclopropane carboxylate

  (propyn 2-yl) 2,5-dioxo imidazolidinyl / methyl: 2 g of dicyclohexylcarbodiimide are introduced under agitation and under a stream of nitrogen in a solution containing 5.2 g.

  of acid (1R cis) 2,2-dimethyl-3 '(RS) 2', 2 ', 2'-tetrabromo-

  ethyl cyclopropane carboxylic acid, 20 cm3 of methyl chloride

  and 150 mg of dimethylaminopyridine. We keep the mixture

  stirring reaction for 15 to 20 minutes at room temperature

  room temperature and introduced 1.8 g of 3-propyn-2-yl-2,5-

  dioxo imidazolidinyl methanol. The reaction mixture is maintained

  With stirring for 2 hours 30 minutes, filter the urea formed, rinsed with methylene chloride. The filtrate is washed with a normal solution of hydrochloric acid,

  then with water, dry and dry concentrate under

  reduced. 8.2 g of an oil are obtained which is chromatographed

  on silica, eluting with the benzene-acetate mixture

85-15 ethyl.

  On the one hand, the following is isolated: (A) 2.2 g of the diastereoisomer S / o / D = -101 5 + 3 (C = 0.75% CHCl 3)

NMR CDCl3 p.p.m.

  - 1.36 and 1.42 H methyl in 2 of the cyclopropane - 5.3 to 5.4 H of the tetrabromoethyl radical - 15.4 - 5.5 H of the carbon of the chain in CO2

5.6 - 5.7 N

N - 4.1 H of! H - 4.2 - 4.3 H of H2

C - C - CH

NOT"

  - 2.37 - 2.39 - 2.41 H acetylenic.

  (B) 1.6 g of the diastereoisomer R // = + 71.50 + 1.5 (c = 1.5% in CHCl 3)

// D 37, +1

NMR CDCl3 p.p.m.

  - 1.23 and 1.47 H methyl in 2-5.5 to 5.1 H of the tetrabromoethyl radical -5.4 - 5.6 H of the side chain carbon in CO2

5.6 - 5.7N N

- 4.03- 4.05 H

H

- 4.2- 4.3 H H H

\ C 1-l

N \ C - CH

- 2.36 - 2.38 - 2.40 H -C = CH

  Example 3: (1R trans) 2,2-dimethyl-3/2-bromo-2,2-dichloro-1

  1/3-propargyl-2,5-bromo ethyl / cyclopropane carboxylate

dioxo imidazolidinyl / methyl:

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  The product was prepared according to the methods indicated above. ## STR2 ## Example 4: (1R cis) 2,2-dimethyl-3- (2-bromo-2,2-dichloro-1-bromoethyl) cyclopropane carboxylate, 1: 3 -propargyl 2,5-dioxoimidazolidinylmethyl: The product was prepared according to the methods given above: / e / D = -112 2 (c = 1% CHCl 3) Example 5: (1R cis) 2,2-dimethyl 3 / 2Lbromo 2>, 2-dichloro, 1 '

  bromo ethyl) cyclopropane carboxylate 1/3-propargyl 2,5-

  dioxo imidazolidinyl / methyl: / "/ D: +85 + 2.5 (c = 1% CHCl3) Example6: A: Example of shock activity on house flies Experiment 1: Test insects are female houseflies aged 4 to 5 days and elevated under constant laboratory conditions (25 C - 70% RH).

  direct to Kearns and March's room using as sol-

  a mixture of acetone (5%) and petroleum solvent Iso-

  by L (95%) (amount of solution used 2 x 0.2 cm3). About 50 insects are used per treatment. Checks are done every minute for up to 10 minutes, then at 15

  minutes and the KT 50 is determined by the usual methods

  the. 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 ............... 1 2nd product of example 2 .......... 1,1

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  Conclusion: Demand-side products show an activity

  remarkable shock on this test.

  Experiment No. 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 the product of Example 2 .......... 1.34 2nd product of Example 2 ......... 1.32

  Conclusion: Confirming and clarifying the conclusions of the ex-

  period 1 the products of the application show an activity

  remarkable remarkable shock on this test.

  B: Depotification Studies of Demand Products:

  Insects used are female houseflies

  4 to 5 days old and raised in constant laboratory conditions (25 C and 70% RH). The LD 50 is sought and the topical application is made to the Arnold microapplicator of a microlitre of toxic acetone solution of each of the

  insect products previously anesthetized with car-

  bonique. The synergistic compounds used are, on the one hand, piperonyl butoxide, (PB) and on the other hand the DEF or SSs tributyl phosphorotrithioate, they are used in solution with the

demand products.

  Mortality checks are carried out 24 hours later

topical application.

  The experimental results obtained are summarized in the following table: L 50 in nanograms per produced insect of Example 1: 191 product of Example 1 + PB10 (used at 10 times 87 the dose of the product)

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  Product of Example 1 + DEF 10 (used 10 times: the dose of the product) Product of Example 1 + PB 10 + DEF 10: 13 LD50 in nanograms per insect: 2nd product of Example 2 =: 327 2nd product of example 2 + PB 10: 77 2nd product of example 2 + DEF 10: 38 2nd product of example 2 + PB 10 + DEF 10: 13,7

  Conclusion: The products of demand can be strong-

  potentiated by the synergists and then present a

remarkable lethal activity.

  Example 7 Preparation of a Soluble Concentrate or Aqueous Spray A homogeneous mixture of Product of Example 1 is carried out .......................... 0.25 g

  Piperonyl butoxide ..........................

* Tween 80 .........................................

  Topanol A .......................................

  Water ...... Example 8: Preparation of an emulsifiable concentrate: We mix thoroughly:

  Product of Example 1 ...........................

  Piperonyl butoxide ..................

  Tween 80 ............................

Topanol A ..................

  xylene ............................-

  Example 9 Preparation of an emulsifiable concentrate: A homogeneous mixture of:

  Product of Example 1 ... .........................

  Tween 80 ................................

  Topanol A ........................................

  Xylene ...........................................

  Example 10 Preparation of a Smoke Composition

  Product of Example 1 ..........................

  Tabu powder ...................................

  Cedar leaf powder .........................

  Pine wood powder ......................

  Bright green ........................

  p-nitrophenol. ............. .........

  1 g 0.25 g 0.1 g 98.4 g 0.015 g 0.5 g 3.5 g 0.1 g, 885 g 1.5 0.1 78.4 0, 25 33.75 0.5 0 , 5 gggggggggg

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Claims (11)

R E V E N D I C A T IONS   1) In all their possible isomeric forms, the compounds of formula I: H C H O X 3 3 He C 02 CH2-N   wherein X 1 represents a hydrogen or fluorine atom,   chlorine or bromine, X2 identical or different from X1   fluorine, chlorine or bromine atom, X3 represents a bromine or iodine chlorine atom, one of the radicals A or B is a carbonyl group and the other is a methylene, ethylidene or propylidene group and R1 is lower alkyl, lower alkenyl or lower alkynyl containing not more than three carbon atoms, as well as mixtures of these isomers.   2) The compounds as defined in claim 1 corresponding to formula (IA): H3C CH3 X H CH-C CH 1 CO1 CH2-N N CIA) 1 2 2 \ CH X X 2 3 3 O   3) The compounds defined in claim 1 or 2 for which the cyclopropanic acid copula is of structure 1R trans or 1R cis. - 14 -   4) Compounds as defined in any of the   Claims 1 to 3 for which X1, X2 and X3 represent the same halogen atom.   ) The compounds defined in claim 4 wherein X1, X2 and X3 each represent a bromine atom.   6. Application to the control of plant pests   levels and animals of the compounds of formula I as defined   in any one of claims 1 to 5.   7) Compositions for combating parasites   sites of plants and animals containing as active ingredient at least one of the products defined in any one of Claims 1 to 5.   (8) The insecticidal compositions containing as their main   at least one of the products defined in any one than claims 1 to 5.   9) As a medicament, the compositions containing as active ingredient at least one of the products defined in one   any of claims 1 to 5.   ) Pharmaceutical compositions containing as   at least one of the medicinal products defined in the 9.   11) Compositions intended for animal feed containing as active ingredient at least one of the products   defined in any one of claims 1 to 5, associated   to a feed intended for animal feed.   12) Association for pest control   animals and plants, characterized in that it   on the one hand closes a compound of formula I as defined in claim 1 and on the other hand a compound selected from the group consisting of esters of allethrolone, alcohol, 3,4,6-tetrahydrophthalimido methyl, 5-benzyl 3-furyl methyl alcohol, 3-phenoxy benzyl alcohol and 3-phenoxy benzyl alcohols, chrysanthemic acids, 5-benzyl 3-furyl methyl alcohol esters of dimethyl 3- (2-oxo-3-tetrahydrothiophenylidene methyl, cyclopropane-1-carboxylic acid, 3-phenoxy benzyl alcohol esters and 3-phenano-benzyl alcohol   2,2-dimethyl-3- (2,2-dichlorovinyl) cyclopropane-1-acid   carboxylic acid esters, alcohols -cyano 3-phenoxy benzyl- - 15 -   of 2,2-dimethyl-3- (2,2-dibromovinyl) cyclopropane   1-carboxylic acid esters, 3-phenoxy benzyl alcohol and 2-para-chlorophenyl-2-isopropyl acetic acid esters,   of allethrolones, alcohol 3,4,5,6-tetrahydrophthalimido   methyl, 5-benzyl alcohol 3-methyl furyl, 3-phenoxy benzyl alcohol and 3-phenano-benzyl alcohol-cyano   2,2-dimethyl-3- (1 ', 2', 2 ', 2'-tetrahalo) -cycloacetate   propane-1-carboxylic compounds in which "halo" represents a   atom of fluorine, chlorine or bromine.   13) Process for the preparation of compounds of formula I   as defined in any one of claims 1 to 5   characterized in that an acid of formula II is reacted: H3C CH3 x1 2 / I x2 / 3 X3   in which X1, X2 and X3 are defined as in claiming   1, or a functional derivative of this acid, with an alcohol of formula III: HO-CH2-N N-R III   Wherein A, B and R 1 are as defined in claim 1, or a functional derivative thereof, to obtain the   corresponding compound of formula I.