IE47990B1 - Cyclopropane carboxylic acid esters containing a polyhalogenated substituent - Google Patents

Abstract

A compound selected from (S)- alpha -cyano3-phenoxybenzyl (1R,trans)-2,2-dimethyl-3-(2',2'- dichloro-1',2'-dibromoethyl)- cyclopropane-1 -carboxylate; (S)- alpha -cyano-3-phenoxybenzyl (1R,cis)-2,2-dimethyl-3-(2',2'-dibromo- 1',2'-dichloroethyl)-cyclopropane-1- carboxylate; 3,4,5,6-tetrahydrophthalimidomethyl (1R,trans)-2,2-dimethyl-3-(1',2',2',2'- tetrabromoethyl)-cyclopropane-1- carboxylate; 3,4,5,6-tetrahydrophthalimidomethyl (1R,cis)-2,2-dimethyl-3-(1',2',2',2'- tetrabromoethyl)-cyclopropane-1- carboxylate; (S)- alpha -cyano-3-phenoxybenzyl (1R,cis)-2,2-dimethyl-3-(1',2',2',2'- tetrachloroethyl)-cyclo-propane-1- carboxylate; and (R)- alpha -cyano-3-phenoxybenzyl (1R,trans)-2,2-dimethyl-3-(2',2'- dichloro-1',2'-dibromoethyl)-cyclo- propane-1-carboxylate which compounds possess interesting insecticidal activity.

Description

This invention relates new cyclopropane carboxylic acid esters containing a polyhalogenated substituent, to process for their preparation and to compositions containing them, In Patent Specification No. 45595 we have described in all their possible isomeric forms, compounds of general formula I, wherein X^ represents a hydrogen, fluorine, chlorine or 10 bromine atom; X2 represents a fluorine, chlorine or bromine atom; X^ represents a chlorine, bromine or iodine atom; and R represents a benzyl radical (optionallysubstituted by one or more radicals selected from alkyl - 2 radicals containing from 1 to 4 carbon atoms, alkenyl and alkenyloxy radicals containing from 2 to 6 carbon atoms, alkadienyl radicals containing from 4 to 8 carbon atoms, methylenedioxy radicals, benzyl radicals and halogen atoms), a group of formula h2r2 (in which represents a hydrogen atom or a methyl radical and R2 represents a monocyclic aryl radical or a group of formula -Ci^-CsCH), a group of formula '3 (in which Rg represents an unsaturated organic aliphatic radical containing from 2 to 6 carbon atoms), a group of formula H t C. t R,. (in which represents a hydrogen atom or a cyano or ethynyl radical, R^ represents a chlorine atom or a methyl radical and n is 0, 1 or 2) or a group of formula (in which Rg, R? Rg and Rg, which may be the same or - 3 different, each.represents a hydrogen or chlorine atom or a methyl radical and the symbol S/I indicates that the 6-membered ring is aromatic or a dihydro or tetrahydro analogue thereof), as well as processes for their preparation and composition containing them, particularly insecticidal compositions.

The present invention relates, inter alia, to certain compounds falling Within general formula I above but not specifically disclosed in the abovementioned application.

Thus, according to one feature of the present invention there are provided the following compounds: (S)-a-cyano-3-phenoxybenzyl (IR,trans)-2,2dimethyl-3-(2',2'-dichloro-lj2’-dibromoethyl)cyclopropane-1-carboxylate, (S)-a-cyano-3-phenoxybenzyl (lR,cis)-2,2dimethyl-3-(2',2'-dibromo-1',2'-dichloroethyl)cyclopropane-1-carboxylate, 3.4.5.6- tetrahydrophthalimidomethyl (IR,trans)2.2- dimethyl-3-(l',2',2’,2'-tetrabromoethyl)cyclopropane-1-carboxylate, 3.4.5.6- 1 e trahydrophthalimidomethy1 (IR,cis)2.2- dimethyl-3-(l’,2’,2',2’-tetrabromoethyl)cyclopropane-l-carboxylate, (S)-a-cyano-3-phenoxybenzyl (lR,cis)-2,2dimethyl“3-(l',2',2',2’-tetrachloroethyl)cyclopropane1-carboxylate and (R)-a-cyano-3-phenoxybenzyl (IR,trans)-2,2dimethyl- 3-( 2' ,2'-dichloro-l',2'-dibromoethyl)cyclopropane-l-carboxylate. -4These compounds, denoted hereinafter as the *’Y” group of compounds, may exist in a number of isomeric forms. Thus, it will be appreciated that the cyclopropane carboxylic acids forming the acid moiety of the Y group of compounds possess, in general, asymmetric carbon atoms, namely the asymmetric carbon atoms at positions 1 and 3 of the cyclopropane ring and tlie asymmetric carbon atom at position 1' of the polyhalogenated ethyl side chain fixed at position 3. The alcohol ROH constituting the alcoholic moiety of the X group of compounds may also contain an asymmetric carbon atom giving rise to the possibility of further isomerism.

The substituents of the Y group of compounds corresponding to X^ and formula I are the same and thus for a fixed steric configuration of the asymmetric carbon atoms at position 1 and 3 of the cyclopropane ring and for an unequivocal stereochemical structure of the alcoholic part there can exist two diastereoisomeric forms of the esters, due to the existence of the asymmetric carbon atom at position 1*. Such isomers can, in general, be separated and isolated in the pure state; they are called herein isomers (A) and (B).

In particular there may be mentioned the 'V group of compounds in the form of a mixture of cis and trans stereoisomers and especially mixtures where the cis and trans stereoisomers are present in a proportion by weight of about 20/80, 50/50 or 80/20. - 5 67990 The Y group of compounds may, for example be prepared by the processes disclosed in the abovementioned application for the preparation of the compounds of general formula I. Thus, the present invention includes as a further feature, a process for the preparation of the Y group of compounds, which compounds may be defined by the general formula i'; (wherein Xp X^ and R possess meanings corresponding to the substituents of the Y group of compounds) selected from the following; A. Reaction of an ester of formula II, (wherein Xp Xg and R possess meanings corresponding to the substituents of the 'Ύ” group of compounds) with a chlorination or bromination agent capable of adding or Br^ across the double bond of the side chain of the ester of formula II. - 6 As chlorination or bromination agent for the esters of formula II is preferably used molecular chlorine or bromine. The reaction is preferably carried out in the presence of an organic solvent which does not react with chlorine or bromine such as acetic acid, carbon tetrachloride, chloroform or methylene chloride.

B. Reaction of an acid of formula IV; (IV) (wherein Xj, X2 and possess the meanings corresponding to the substituents of the “Y group of compounds) or a functional derivative thereof, with an alcohol of formula ROH or one of its functional derivatives (R possessing the meanings of the corresponding Y group compound).

Functional derivatives of the acid of formula III which may be used to carry out the esterification with the alcohol of formula ROH or a functional derivative thereof include, for example, the chloride, the anhydride, a mixed anhydride, a lower e.g. alkyl ester, a metallic salt and a salt with an organic base. Functional derivatives of the alcohol of formula ROH which can be used include, for example, the chloride, bromide and sulphonate of this alcohol. 4·7θθθ - 7 The acid of formula IV may be obtained, if desired, by reaction of an acid of formula III, H3C\ /CH3 0 / \ yC-OH (III) H (wherein X^ and X2 possess the meanings of the 5 corresponding Y group compound) with a chlorination or bromination agent capable of adding Cl2 or Br2 across the double bond in the side chain of the acid of formula III. As chlorination or bromination agent molecular chlorine or bromine are preferably used. The reaction with the chlorination or bromination agent is preferably effected in the presence of an organic solvent which does not react with chlorine or bromine such as acetic acid, carbon tetrachloride, chloroform or methylene chloride.

(S)-a-cyano-3-phenoxybenzyl alcohol may be obtained, for example, by the process described in our Irish Patent Application No. (Case 1833) corresponding to French Patent Application No.78-02621 and, by an analogous process thereto, may, for example, be obtained, (R)-a-cyano-3-phenoxybenzyl alcohol. lhe Y group of compounds possess strong insecticidal activity as may be illustrated by tests on flies, on larvae of Spodoptera Littoralis, on larvae of Epilachna Varivestris, on larvae of Aedes Aegypti, on Blatella Germanica, on Dysdercus Fasciatus and on Sitophilus Granarius and Tribolium - 8 Castaneum.

Endowed with great photochemical stability, the Y group of compounds are very suitable for use in the control of insects in the agricultural sphere.

For example they enable aphides, larvae of lepidoptera and coleoptera to be controlled effectively.

They are used preferably at dosages of from 1 g to 100 g of active material per hectare. Due to their speed of action these compounds can also be used as insecticides in the domestic sphere.

According to still further feature of the present invention there are provided insecticidal compositions comprising, as active ingredient, at least one of the Y group of compounds in association with a carrier of excipient. Such compositions may, if desired, contain one or more other pesticidal agents. These compositions may be presented in the form of, for example, powders, granules, suspensions, emulsions, solutions, solutions for aerosols, combustible strips, baits or other preparations normally employed for such compositions.

In addition to the active ingredient these compositions contain a carrier or excipient which may also include a non-ionic surface-active agent ensuring uniform dispersion of the constituents of the mixture. The carrier or excipient used can, for example, be a liquid such as water, an alcohol, a hydrocarbon or some other organic solvent, a mineral, animal or vegetable oil, or a powder such as talc, a clay, a silicates, Kieselguhr or a combustible solid such as tabu powder (or pyre thrum marc); 7990 - 9 To increase the insecticidal activity of the compositions a synergising agent may be included, for example one of those known in the art, such as l-(2,5,8-trioxadodecyl-2-propyl-4,5-methylenedioxy)benzene [piperonyl butoxide], N-(2-ethyl-heptyl)bicyclo[2,2,l]-5-heptene-2,3-dicarboximide or piperonylbis-2-(2'-n-butoxy-ethoxy)-ethyl acetal [tropital].

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

Particular insecticidal composition which may be mentioned are those containing (S)-a-cyano-3phenoxybenzyl (lR,trans)-2,2-dimethyl-3-(2',2'dichloro-1’,2’-dibromoethyl)-cyclopropane-l-carboxylate in the form of isomer A, isomer B or a mixture of these isomers A and B.

The Y group of compounds also possess acaricidal activity as may be illustrated by tests on Tetranychus Urticae as well as nematocidal activity.

According to the present invention there are also provided acaricidal compositions and nematocidal compositions comprising, as active ingredient, at least one of the Y group of compounds in association with a carrier or excipient.

For acaricidal use, wettable powders for foliar spraying are preferably employed containing from 1 to 80% by weight of active ingredient or alternatively liquids for foliar spraying containing from 1 to 500 g/1 of active ingredient. Powders for foliar dusting may also be used, containing for example, 47900 - 10 0.05 to 3% of active ingredient. For nematocidal use preferably liquids for soil treatment are employed, such liquids generally containing from 300 to 500 g/1. of active ingredient and which may optionally be diluted before use.

TheY group of compounds are preferable used at doses of from 1 to 100 g of active material per hectare for acaricidal use and from 10 to 200 g of active material per hectare for nematocidal use.

The anti-acarid properties of the ¥ group of compounds permit these compounds to be used in the form of pharmaceutical compositions e.g. for veterinary use in the control of parasitic acarids in animals and especially in the control of parasitic ixodides and sarcoptides in animals. The compounds can be used in animals to control in particular all kinds of scabies such as e.g. sarcoptic scabies, psoroptic scabies and chorioptic scabies. These compounds also permit the control of all kinds of ticks such as, for example, the 2o Boophilus species, the Hyalomnia species, the Amblyoma species and the Rhipicephalus species.

The invention, therefore, also relates to pharmaceutical compositions comprising, as active ingredient, at least one of the '7 group of compounds in association with a carrier or excipient.

Such pharmaceutical compositions may be administered externally, but may also be administered by a parenteral, oral or rectal route. If desired, a synergising agent may be added to the compositions, e.g. a synergising - 11 agent for the pyrethrinoides, for example one of the synergising agents exemplified above. These compositions may be prepared according to the usual methods.

Finally, it can be convenient for veterinary use 5 to administer the active compounds in the form of a balanced foodstuff for animals. · Thus, according to a still further feature of the invention there are provided animal foodstuff compositions comprising at least one of the Y group of compounds in combination with a nutrient material.

Such foodstuff compositions for animals may, for example, contain from 0.002 to 0.4% by weight of a Y group compound such as e.g. (S)-a-cyano-3-phenoxybenzyl (lR,trans)-2,2-dimethyl-3-(2',2'-dichloro-1',2']^5 dibromoethyl)-cyclopropane-l-carboxylate.

Also according to the invention is a method of preventing or inhibiting the growth and/or proliferation of insects, acarids and/or nematodes which comprises administering to a site other than a human or animal body infested with or susceptible to infestation with insects acarids and/or nematodes an effective amount of a γ group compound.

The following non-limiting examples serve to illustrate the present invention. - 1 2 Example 1: 3 ,Α,3,6-tetrah-ydronhtha] imidomethyl (IR,cis)-2,2-dimethyl-3-(l' ,2' ,2' ^'-tetrabrowoethyl) cyclopropane-l-carboxylate.

Stage A; (!R,cis) 2,-2-dimethyl 3-(11.2',2'^'-tetrabromo ethyl) cyclopropane-l-carboxylio acid.

Into 150 cm^ ofcarbon tetrachloride one introduces 19.4 g of (lR,cis) 2,2-dimethyl 3—(2*,2‘-dibromo vinyl) cyclopropane-1-carboxylic acid, adds 10.4 g of bromine in solution in 22 cZ of carbon tetrachloride, agitates for one hour at 2C°C, concentrates to dryness by distillation under reduced pressure and obtains 31.4 g of crude product (E.Pt. = 145°C). This crude product ir reerystallised from 110 cm of carbon tetrachloride and one obtains 22.12 g of (lR,cis 2,2-dimethyl 3-(l*,2',2',2'-tetrabromo ethyl) cyclopropane-l-carboxylic acid, M.Et. - 150°C.

This product is a mixture of two isomers (A) and (S) which are made evident by the NMR spectrum. In fact, the NMR spectrum enables a compound to be revealed (corresponding approximately to 2/3 of the mixture) having peaks at 1.311.43 ρ.ρ.ω. corresponding to the hydrogens cf the geminal methyls and peaks from 5.55 to 5·66 p.p.m. corresponding to the hydrogen fixed on the monobrominated asymmetric carbon atom and another compound (corresponding to about 1/5 cf the mixture) having peaks at 1.28-1.Λ8 p.p.m. correspondingto the hydrogens of the geminal methyls and peaks from 4.24 to 5.54 p.p.m. corresponding to the hydrogen fixed on the mcnobrominated asymmetric carbon atom. - 13 In the mixture there are revealed, moreover, peaks from 1.67 to 2.17 p.p.m. (hydrogens at positions 1 and 3 of the cyclopropane) and a peak at about 11.25 p.p.m. (mobile hydrogen of the acid function).

The analysis of the mixture obtained (M.Pt. = 150°C) is as follows: CgH10Br402 (457.50ή-) Calculated: 0?) 20.99 2.20 Br# 69.82 Found : 20.9 2.2 70.2 Stage B: (IR,cis) 2,2-diinethyl 5-(11.21,21,2',-tetrabromo ethyl) cyclopropane-1-carboxylic acid chloride.

Into 179 em^ of petroleum ether (B.Pt. 35~7C>OC) one z introduces 0.2 cur of dimethyl formamide and 8.5 cm of thionyl chloride, takes the mixture to reflux, introduces 35.76 g of (lR,cis) 2,2-dimethyl 3-(l’,2’;2‘,2',-tetx'abromo ethyl) cyclopropane-l-carboxylic acid ir. I5O cm^ of methylene chloride, agitates for 2 hours at reflux, cools, concentrates to dryness by distillation, adds toluene, concentrates again to dryness by distillation under reduced pressure and obtains 38 S of crude acid chloride (M.Pfc. = 88°C) used as it is for the following stage.

Stage C; 5,^-,5,6-tetral)ydr-ophthalimidomethyl (lR,cis) 2,2-dimethyl-3-(1',21,21,21-tetrabromoethyl) cyclopropane-l-carboxylate.

One mixes 7·7 S of acid chloride prepared in the previous stage containing 2.9 g of neopynaminol, in 50 cm^ of • - . · . -o- ... . ·, . auutYuruue uwwwie, cuuxs gu v u, xuuruuut;t;t> imer aftj-b&b.njj.'i 3 g of pyridine, allows to return to ambient temperature _ 14 maintaining the agitation for 18 hours, pours the reaction mixture into a dilute solution of hydrochloric acid, extracts with benzene, washes with an aqueous solution of sodium bicarbonate, rinses with -water until neutral, isolates the organic phase, dries on magnesium sulphate, filters and crude concentrates under reduced pressure, obtains 10 g of/product which one purifies by chromatography on silica (eluant: benzene/ethyl acetate 95:5) and recovers 3.3 g of 3,Λ,5,6~ -tetrahydrophthalimidomethyl (12,cis) 2,2-dimethyl 3-(l',2', 2',2'-tetrabromoethyl) cyclopropane-l-carboxylate, in the form of a mixture of isomers A and B and 0.5 g in the form of isomer (B).

Characteristics of the product obtained in the form of a mixture of isomers A and B: ta]2° = -21 .5° ί 1° (c = 1%, benzene) Analysis :G17H19Br4K°4 H.W. = 620.982 Calculated: C% 32.88 H% 3.08 2.25 Br% 51.4? Found : 33.8 5.2 2.1 50.2 U.V. Spectrum, (ethanol) Infl. = 218 nm E^ = 243 Max. = 223 nm 4 = 275 ε = 17 ICO Max. = 229 nm = 269 e * 16 700 Infl. = 258 nm 4 = 170 ε - 10 500 Infl. 2i 295 nm e| = 8 KUK Spectrum (deuterochloroform) Peaks at 4.98-5.17 p.p.m., characteristic of the hydrogen at position 1' of the ethyl side chain of isomer· B. - 15 Peaks at 1.2-1.45 p.p.m., characteristic of the hydrogens of the geminal methyls of isomer B.

Peaks at 5.17-5.38 p.p.m., characteristic of the hydrogen at position 1' of the ethyl side chain of isomer A.

Peaks at 1.2-1.33p.p.m., characteristic of the hydrogens of the geminal methyls of isomer (A).

Peaks at 1=58-2.08 p.p.m., characteristic of the hydrogens of the cyclopropyl and of the methylenes of the cyclohexyl. Range of peaks at 2.33 p.p.m., characteristic of the hydrogens of the methylenss of the cyclohexyl.

Peaks at 5-33-5-70 p.p.m., characteristic of the hydrogens of the group GOOCHgN.

Characteristics of the product obtainsdin the form of isomer (Ώ) [ Analysis : H.W. = 620.982 Calculated: C% 32.88 3-08 K% 2.25 Br% 51.47 Pound : 33-5 3-3 2.2 50.1 U.V. Suectrum.

Infl. 218 nm E£ = 248 Max. 223 nm hj = 2?8 Max. 228-229 nm = 272 Infl. 238 nm eJ = 172 Infl. at about 295 nm ^=7 NMR Spectrum. (Deuterochloroform) Peaks at 4,98-5-16 p.p.m., characteristic of the hydrogen at position 1' of the ethyl side chain.

Peaks at 1.21-1.45 p.p.m., charactei-istic of the hydrogens of the geminal methyls. - 16 Peaks at 1.5-2 p.p.ia., characteristic of the hydrogens of the cyclopropyl and of the methylenes at β in the cyclohexyl .

Range of peaks at 2.38 p.p.m., characteristic of the hydrogens of the methylenes of the cyclohexyl.

Peaks at 5.58-5-57 and 5-57-5-75 p.p.m., characteristic of the hydrogens of the group COOCHpN.

Example 2.· 3,4,5,S--setrahydiOnbthalimido methyl (IE,trans) 2.2- dlraethyl 3-(11,21 ,2' ,2' ,-tetrabromogthy?.) cyc'lopropane-1-carhoy.ylate.

Stare A: (IR,trans) 2,2-dimethyl 3-(11,21,21,21-tetrnbrorao ethyl) cycloproprne-1-carboxylic acid.

This compound is obtained by bromination of (IR, trens) 2.2- dimethyl 3-(2',2'-dibromo vinyl) cyclopropane-l-carboxylic acid, a mixtui'e of isomers (A) and (E).

I'STE Spectrum Peaks frora 1.30 to 1.40 p.p.m. (hydrogens of the methyls at 2 of the cyclopropane).

Peaks at 1.65-1.74 and 1.97 to 2.37 p.p.m. (hydrogens at 1 and 3 of the cyclopropane^ Feaks at 4.50-4.47 and at 4.47-4-65 p.p.m. (hydrogen at 1' of the ethyl).

Peak at 9.63 p.p.m. (hydrogen of the carboxyl).

Stage E; (lR,trans) 2,2-dimethyl 5-(11.2',2',2'-tetrabromo ethyl) cyclopropane-l-carboxylic acid chloride.

By the action of thionyl chloride on (IR, .trans) 2,2-dimethyl 5~(1',2',2',2'-tetrabromo ethyl) cyclo|>rupane-l47990 “ 17 “ -carboxylic acid obtained in stage A one obtains the acid chloride used as it is for the following stage.

IR Spectrum (chloroform) Absorption at 1778 era \ 5 Stage C: 5,4,5,6-tetrahydrophthalimido-methyl (IR,trans) 2,2-dimethyl 3-(1', 2', 2 ',2' -tetrabromoethyl·') cycl onropane-l-carboxylate.

One treats 7·7 S of acid chloride prepared in the previous stage according to a modus operand! identical to that used in stage C of Example 1.

One obtains 9-2 g of crude product which one purifies by chromatography on silica (eluant: benzenc/ethyl acetate 9*l) After crystallisation one takes up the product in petroleum ether (aO°C-7O°C) vacuum-filters it, dries it and recovers ·Λ S °f 3>4,5,6-tetrahydrophthalimido methyl (IR,trans) 2,2-dimethyl 3-(l’,2',2',2'-tetrabromoetliyl) cyclopropane-1-carboxylate.

Mixture of isomers A and B. M.Pt. = 124°C.

CalJO = _l0 -1° (c = 1%, benzene) Analysis : °17Η19ΒγΛ 1 •l.V. = 620.982 Calculated: CX 32.88 H% 3.08 Bi% 51.47 2.25 Found : 33.1 3-2 51.1 2.1 UV Spectrum. (ethanol) Max. 224 nm Bj = 274 ε = 17 000 Max. 228 nm E^ = 269 ε = 16 700 Infl. 235 nm eJ = 167 ε = 10 400 Infl. 280 nm eJ = 9 - is NHR Spectrum (Deuterochloroform) Peaks at 1.25-1.30-1.31 p.p.m. characteristic of the hydrogens of the geminal methyls.

Peaks from 1.58 to 2.16 p.p.m. characteristic of the hydrogens of the cyclopropyl and of the methylenes at β in the cyclohexyl .

Peaks from 2.16 to 2.5 p.p.m. characteristic of the hydrogens of the methylenes at a. in the cyclohexyl.

Peaks at 4.24-4.41 and at 4.43-4.61 p.p.m. characteristic of the hydrogen at position 11 of the ethyl sjde chain.

Peaks at 5*51 and 5.55 p.p.m. characteristic of the group COOCHgH.

Example 3* (S) *x-cyano 3-phenoxy benzyl (lR,trnqa) 2.2-dimethyl-3-(21^'-dichloro 1'.2t-dlbromoethvl) cyclooropang-l-carboxylaks.

Stage A; (IR,trans) 2,2-dimethyl 3-(2'.R'-dlcliloro 11,21 — -dibromoethyl) cyclopropane-l-carboxylic. acid.

By the action of bromine on (IR,trans) 2,2-dimethyl 3~ -(21,2'-dichloro vinyl) cyclopropane-1-carboxylic acid, one obtains (IR,trans) 2,2-dimethyl 3-(21,2:-dichloro 1',2'-dibromoethyl) cyclopropane-l-carboxylic acid, a mixture of isomers (A) and (B).

NMR Spectrum.

Peaks at 1.17-1.37 p.p.m. (hydrogens of the methyls at 2 of the cyclopropane).

Peaks from 1.65-1.73 p.p.m. to 1.93-2,05 p.p.m. (hydrogens at 1 of the cyclopropane. 47390 “ 19 Peaks at a.23-4.4-5 and at 4.45-4.62 p.p.m. (hydrogen at 1' of the ethyl at 3 of the cyclopropane).

Stage B: (IR,trans) 2,2-dimethyl 3-(21,2‘-dichloro l',2'dibromo ethyl) cyclopropane-l-carboxylic acid chloride.

By the action of thionyl chloride on the acid prepared in stage A above one obtains (IR,trans) 2,2-dimethyl 3-(2',2‘dichloro 1',2'-dibromoethyl) cyclopropane-l-carboxylic acid chloride.

I.R, Spectrum (chloroform) Absorption at 1777 cm Stage C: (3)n-cyajio j-phenoxy benzyl (IR,trans) 2,2-dimethyl 5-(21,2’-dichloro 11,2'-dibroao ethyl) cyclopropane-1-. -carboxylate.

One mixes a,45 g of the acid chloride prepared in the previous stage containing 2.6 g of (S) α-cynno 3-phenoxy x benzyl alcohol, in 100 cm· of anhydrous benzene. o 3 One cools to +15 C and adds a solution of 5 cm of x pyridine in 20 car of anhydrous benzene. One maintains the agitation for 5 hours at ambient temperature and pours the reaction mixture on to 100 cm^ of 2N hydrochloric acid, one isolates tne organic phase, washes the latter with water and concentrates to dryness under reduced pressure.

After chromatography on silica (eluant: benzene) one obtains 4.9 g of (S)a-cyano 3-phenoxy benzyl (IR,trans) 2,2-dimethyl 3-(2',2'-dichloro 1',2'-dibromoethyl) cyclopropane-1 -carboxylate in the form of a mixture of isomers A and B. ' ’ (ούρθ = o° (benzene) 4788 Analysis; CgpH^ClgOjS Ii.W. =576.12 Calculated: C% 45.86 B% 3.32 Br% 27.74 Cl% 12.31 2.43 Found : 46.0 3.4 27·5 12.2 2.2 Circular dichroisa: Max.at 287 no Max.at 282 nm Max. at 265 nm Δ ε = + 0.12 Δ ε ~ + 0.11 Λ ε = + 0.042 I1MR Spectrum.

Peaks at 1.20-1.26-1.31 p.p.m. characteristic of the hydrogens of the geminal methyls.

Peaks at /(-.20-4.35 and at 4.36-4.52 p.p.m. characteristic of the hydrogen at position 1* of the ethyl chain.

Peaks from 1.68 to 1.78 - from 1.97 to 2.07 and from 1.97 to 2.42 p.p.m. characteristic of the hydrogens of the cyclopropyl. Peak at 6.42 p.p.m. characteristic of the hydrogen of the group COOCHCN.

Peaks from 6.92 to 7.58 p.p.m. characteristic of the hydrogens of the aromahc nuclei.

Stage D: Separation of the isomers A and B of fs) tx-cyano 3-phenoxy henzyl (lR,trans) 2,°-dimgthyl 3-(21,2’-d.i.chloro 11,2'-dibrop.oet’^yl) cycloproppqe-'l-carboyyiate.

One chromatographs on silica 4.69 g of the mixture of isomers A and B of (S)a-cyano 3~phenoxy benzyl (IR,trans) 2,2-dimethyl 3-(2',2'-dichloro 1',2'-dibromoethyl) cyclopropane-1-carboxylate obtained in Stage C, eluting with a hexane/ pentane/ether/acetonitrile/isopropanol mixture ( 50:12:0.4:1.2: 0.03) and obtains: 7 9 9 0 - 1.585 g of isomer A [α]= +35·5 - 2.5° (ο = 0.5% benzene) and - 0.980 g of isomer B = -17.5 -2° (c = 0.8% benzene) The (G) α-cyano 3-phenoxy benzylalcohol used in stage 0 of Example 3 is described in the Patent Application filed by the Applicant Company on 31st January 1978 under the number 78.02.621 and entitled Optically-active substituted benzyl alcohol and precess for preparing it. An example of preparing this alcohol is given hereinafter: Stage A: Mixture of (IB,50) 6.6-dimethyl '-'-(R) 65)-cyano (5'-phenoxy phenyl) methoxy) 5-oxa blcyclo (3-1-0) hexan-2-one and of (IB,5c) 6,6-diiaethyl -'(£) C(H)-cyano (^'-phenoxy phenyl) methoxy) 5-oxa bicyclo (3~1~Q) hexan-2-one.

One mixes 22. S g of (R,S) a-cyano 5-phenoxy benzyl alcohol, 9.46 g of (13,3S)cis 2,2-dimethyl 3-(dihydroxymethyl) cyclopropane-l-carboxylic acid lactone and 0.150 g of monohydrated paratoluene sulphonic acid, takes to SO°C under a _2 vacuum of 10 mm of mercury and maintains the reaction mixture for 2 hours under these conditions, the water formed being removed by distillation. One cools to 20cC and obtains 30.7 g of crude mixture of (1H,5S) 6,6-dimethyl 4(H) C(3)-cyano (3'-phenoxy phenyl)methoxyJ 3-oxa bicyclo (3-1-0) hexan-2-one and of (1H,5S) 6,6-din:ethyl 4-(R) C(R)-cyano (3'-phenoxy phenyl) methoxy] 3-oxa-bicycIo (3-1-0) hexan-2-one (containing as impurities mainly the starting products which have not reacted) (mixture A).

Stage B: (1H,5S) 6,6-dimethyl a(R) C(ij)-cyano (5!-phenoxy “ 22 ” phenyl) methoxy] 3-oxn bicyclo (5-1-0) hox,- One chromatographs the mixture A obtained in stage A on silica gel, eluting with a mixture of benzene and ethyl acetate (95i5) a»d obtains 10.9 g of (1R,53) 6,6-dimethyl if. (R) [(S)-cyano (3’-phenoxy phenyl) methoxy! 3~°xa bicyclo (3-1-0) hexan-2-one.

H.Pfc. = 126°G, ta]2° = -71° (£ = 1%, benzene) Stage 0; (3) tx-cyano 3-phenoxy benzyl alcohol. 3 Into a mixture of 100 cm of dioxan and 50 cm- of wgter one introduces 10 g of (1R,53) 6,6-dimethyl 4(R) ((3) cyano (3'-phenoxy phenyl) methoxy) 3-oxabicyclo (3-1-0) hexan-2-one obtained in stage B above, then 1 g of monohydrated paratoluene sulphonic acid, takes the reaction mixture to reflux, maintains it there for 23 hours, concentrates by distillation under reduced pressure until half the initial volume is obtained, adds ethyl ether, agitates, separates the organic phase by decanting, washes it with water, dries it, concentrates to dryness by distillation under reduced pressure, chromatographs the residue (9.5 g) on silica gel, eluting with a mixture of benzene and ethyl acetate (9:l) and obtains 6.1 g of (S) α-cyano 3-pbenoxy benzyl alcohol (a)p° = -16.5° - 1.5° (c, = 0.8%, benzene).

NMR Spectrum, (deuterochloroform) Peak at 3.25 p.p.m. characteristic of the hydrogen of the alcohol function.

Peak at 5.42 p.p.m. characteristic of the hydrogen borne by me same cernon annul as r/ne nitrile group. - 23 Example a: (8) g-cyano 3-phenoxy benzyl (lR,cia) 2,2-dimethyl 3-(21,21-dibromo 1',2'-dichloroethyl) cyclopropane-1-ciirborylate.

Stage A: (15,pin) 2,2-dimethyl 5-(21,2'-dibromo 1',2'-dicbloro ethyl) cyclonromne-l-carboxylic acid.

Into 30 cm·3 of carbon tetrachloride one introduces, by bubbling in at -15°C, 11.8 g of chlorine then adds slowly, at -1O°C 24 g of a solution of (lR,cis) 2,2-dimethyl 3-(21, X 21-dibromoviny]) cyclopropane-l-earboxylic acid in 37 cm of methylene chloride, agitates for one hour 30 minutes at 0°C and for 2 hours at 25°C, concentrates under reduced pressure, purifies by crystallisation from carbon tetrachloride and obtains 7-4 g of (IE,cis) 2,2-dimethyl 3-(21,2'-dibromo 11,21-dichloro ethyl) cyclopropane-l-carboxylic acid.

M.Pt. - 13a°C (mixture of isomers (A) and (B)).

HMR Spectrum.

Peaks at 1.32-1.44 and at 1.28-1.48 p.p.m. (hydrogens of the methyls at 2 of the cyclopropane.

Peaks at 5.08-5.45 and at 4.67-5.0 p.p.m. (hydrogen at 1' of the ethyl chain at position 3 of the cyclopropane).

Peqk at 10.1 p.p.m, (hydrogen of the carboxyl).

Stage B; (lR,cis) 2,2-dimethyl j-(21,21-dibromo 1',2'-dichloro ethyl) cyclopropane-l-carboxylic acid chloride.

By the action of thionyl chloride in the presence of pyridine on the acid obtained in stage A above one obtains (lR,cis) 2,2-dimethyl 3-(21,2'-dibromo 1',2'-dichloro ethyl) cyclopropane-l-carboxylic acid chloride, used as it is fox’ the following stage. - 24 Stage C; (S) α-cyano 3-phenoxy benzyl (IK,cis) 2,2-dimethyl 3-(21^'-dibromo 1',2'-dichloroethyl) cyclopropane-1-carboxylate.

One mixes 3.8 g of acid chloride prepared in the previous 5 stage, containing 2.5 g of (S) α-cyano 3-phenoxy benzyl X Q alcohol, in 100 cm of anhydrous benzene. One cools to +15 G and adds a solution of 4 cm^ of pyridine in 20 cm·2 of anhydrous benzene. One maintains the agitation for 4 hours at ambient z temperature and pours the reaction mixture on to 100 cm of 2N hydrochloric acid. One isolates the organic phase, washes it with water, dries it and concentrates‘to dryness under reduced pressure. After chromatography ο* silica (eluant: petroleum ether (40°-70°C)/isopropyl ether (100-20)) one obtains (S) α-cyano 3-phenoxy benzyl (lH,cis) 2,2-dimethyl 3-(2',2'-dibromo 1',.2'-dichloro ethyl) cycloprppanc-1-carboxylate in the form of 1.8 g of isomer A, Rf = 0.30 and 1.4 g of isomer B Rf = 0.25· Physical tests of isomer A [a3p° = -21° - 1° (c » 1%, benzene).

Of) Circular dichroism.

Max. at 300 nm Max.at 288 nm Max. at 264 nm Max. at 232 nm Δε»- 0.003 Δ ε = + 0.29 Δ ε = + 0.11 Δε»- 1.8 NMR Spectrum (deuterochloroform) Peaks at 1.28-1.37 p.p.m. characteristic of the hydrogens of the geminal methyls. 479θθ “ Peaks at 5.O5-5.IO - 5.18-5.23 p.p.m. characteristic of the hydrogen at position 1' of the ethyl side chain.

Peaks at 1.83-2.10 p.p.m. characteristic of the hydrogens of the cyclopropyl.

Peaks at 6.38 p.p.m. characteristic of the hydrogen of the group COOCHCN.

Peaks from 6.92 to 7.55 p.p.m. characteristic of the hydrogens of the aromatic nuclei.

Physical tests of isomer B. [aD^0 = +80° - 2.5° (c = 1%, benzene) Circular dichroism Max. at 288 nm Δε = + 0.22 Inf. at 263 nm Δ e = + 0.62 Max. at 220 nm Δ ε « + 5.7 ΝΙΊΗ Spectrum (deuterochloroform) Peaks at 1.23-1.38 p.p.m. characteristic of the hydrogens of the geminal methyls.

Peaks from 4.6 to 4-95 p.p.m. characteristic of the hydrogen at position 1’ of the ethyl side chain.

Peaks from 1.75 to 2.16 p.p.m. characteristic of the hydrogens of the cyclopropyl.

Peak at 6.38 p.p.m. characteristic of tne hydrogen of the group COOCHCN.

Peaks from 6.88 to 7*57 p.p.m. characteristic of the hydrogens of the aromatic nuclei.

Example 5: (S) α-cyano 3-phenoxy benzyl (lR,cis) 2,2-dimethyl 3-(11.2'.2',2'-tetranhloroethyl) cyclouropane-l-carboxylate.

Stage A; (lR,cis) 2,2-dimethyl 3-(11,2',2',2'-tetrachloroethyl) 4-7990 ~ 2o cyclopropane-l-carboxylic acid.

Into 30 cm^ of carbon tetrachloride one bubbles chlorine until saturation (one dissolves 11.8 g of chlorine) introduces over about 30 minutes a solution of 16.” g of (IR.cis) 2,2-dimethyl 3~(2',2'-dichloro vinyl) cyclopropane-l-carboxylic acid in 40 cm^ of methylene chloride at a temperature below O°C, agitates for 24 hours at 0°0, brings the temperature of the reaction mixture to +25°0, agitates for 3 hours at this temperature, removes the excess chlorine by bubbling in nitrogen, concentrates to dryness by distillation under reduced pressure, purifies the residue by chromatography on silica gel eluting with a mixture of cyclohexane and ethyl acetate (8:2), crystallises from petroleum ether (B.Pt. 35“ ?5°C) and obtains 3.14 g of (IR.cis) 2,2-dimethyl 3-(11>2', 2',2'-tetrachloroethyl) cyclopropane-l-carboxylic acid.

M.Pt. = 144°C.

Analysis : (279.93) Calculated: C& ^.'5 H% 3.6 Cl% 50.6 Pound : 34.4 3·7 5θ.3 NMR Spectrum, (deuterochloroform) Peaks at 1.26-1.42 p.p.m. and 1.3O-l.n2 p.p.m. characteristic of the hydrogens of the geminal methyls.

Peaks from 4.67-5.17 p.p.m. and from 5.08 to 5.43 p.p.m. characteristic of the hydrogen at position 1' of the substituted ethyl side chain.

Peaks from 1.67 to 2.0 p.p.m. characteristic of the hydrogens ui lhe cjcluprup.yi.

Peak at 10. 2 p.p.m. characteristic of the hydroxide of the “27“ carboxyl.

Stage B: (lR,cxs) 2,2-dimethyl 5-(11,2',2',2'-tetrachloroethyl) cyclopropane-l-carboxylic acid chloride.

Into a mixture of 60 cm^ of petroleum ether (B.Pt* 3570°C) 5 and 8.7 cm^ of thionyl chloride one introduces 6.75 6 of (IR, cis ) 2,2-dimethy 1 3-(1^2^2^21 -tetrachloroethyl) cyclopropane-l-carboxylic acid, takes the reaction mixture to reflux, maintains it there for 4 hours 30 minutes, concentrates to dryness by distillation under reduced pressure, adds benzene, concentrates to dryness and obtains crude (lR,cis) 2,2-dimethyl 3-(11,2',2',2'-tetrachloroethyl) cyclopropane-l-carboxylic acid chloride used as it is for the following stage.

Stage C: (S) α-eynno 3~phenoxybeuzyl (iKp.is) 2,2-dimethyl 15 3—Ci-1-2'-2'^'-tetrachloroethyl) cyclopropane-l-carboxylate.

One mixes 3*19 g of the acid chloride prepared in the previous stage containing 2.6 g of (S) α-cyano 5-phenoxy z benzyl alcohol in 30 cur of anhydrous benzene. One cools in x an ice-bath and adds slowly 3 cm' of pyridine. One agitates 20 for 24 hours at ambient temperature then pours the reaction medium on to cold dilute hydrochloric acid. One extracts with benzene, isolates the organic phases, washes them with a solution of sodium bicarbonate, rinses with water, dries on sodium sulphate, filters and concentrates under reduced pressure. One purifies by chromatography on silica (eluant: benzene/cyclohexane 7:3) and obtains (8) α-cyano 3-phenoxybenzyl (IB,cis) 2,2-dimethyl 3-(l',2',2',2'-tetrachloroethyl) cyclopropane-l-carboxylate in the form of 2.258 g of isomer (A) and 1.48 g of the mixture of isomers A and B. “ 28' Physical analysis of isomer (A) [a]p° =. + 35.5° - 2° (c = 0.6%, benzene) Analysis : CgpH-^Cl^HOj = 487.213 Calculated: C% 54.23 - H% 3.93 N% 2.87 Cl% 29-1 Found : 54.4 3·θ 2.8 28.5 NHR Spectrum (deuterocblorofoim) Peaks at 1.28-1.37 p.p.m. characteristic of the hydrogens of the geminal methyls.

Peaks from 1.75 to 2.08 p.p.m. characteristic of the hydrogens of the cyclopropyl.

Peaks from 5.07 to 5.25 p.p.m. characteristic of the hydrogen at position 1' of the ethyl side chain.

Peak at 6.35 p.p.m. characteristic of the hydrogens of the group COOCHCN. teaks from 6.92 to 7.58 p.p.m. characteristic of the hydrogens of the aromatic nuclei.

Physical analysis of the mixture of isomers A and B [«1^0 = -53.5° ί 2.5° (c = 0.4% benzene) Analysis : C^H^Cl^HOj = 487.213.

Calculated: C% 54.23 H% 3.93 M% 2.87 Cl% 29.1 Found : 54.5 3.9 2.8 28.8 NHR Spectrum (deuterochloroform) Peaks at 1.2-1.35 p.p.m. characteristic of the hydrogens of the geminal methyls of the isomer R.

Peaks at 1.27-1.35 p.p.m. characteristic of the hydrogens of the geminal methyls of the isomer 8.

Peaks at 1.75-2.08 p.p.m. characteristic of the hydrogens of the cyclopropyl. 7 9 9 0 Peaks from 4.7? to 4.94 p.p.m. characteristic of the hydrogen at position 1’ of the ethyl side chain.

Peaks from 5.08 to 5.26 p.p.m. characteristic of the hydrogen at position 1' of the ethyl side chain.

Peaks at 6.35 and 6.37 p.p.m. characteristic cf the hydrogen of the group COOCHCN.

Peaks from 7.93 to 7.58 p.p.m. characteristic of the hydrogens of the aromatic nuclei.

Example 6: (R) α-cyano 3-phenoxy henzyl (IR,trans) 2,2-diroethyl 3~(2*,2'-dichloro 1',2'-dibromoethyl) cyclopropane-1-carboxylat e.

Operating as in stage C of Example 3. starting with 2 g of (IR,trans) 2,2-dimethyl 3-(2',2'-dichloro 11,21-dibromo ethyl) cyclopropane-l-carboxylic acid chloride obtained in ’stage B of Example 3 and 1.1 g of (R) a,-eye no 3-phenoxy benzyl alcohol, one obtains 1.4 g of (R) α-cyano 3-phenoxy benzyl (IR,trans) 2,2-dimethyl 3“(2‘,2'-dicKoro 1',2'-dibromoethyl) cyclopropane-l-carboxylate in the form of a mixture of isomers A and B. [a]p° - -28° - 2° Analysis (c = 0.7% benzene) M.W. = 578.122 52H19Br2Cl2NO5 Calculated: 0% 45-87 3-32 R% 2.43 Cl% 12.31 Br% 27.74 Pound 46.3 3-3 2.4 12.4 27-4 NMR Spectrum (deuterochloroform) Peaks at I.31 - 1.35 p.p.m. characteristic of the hydrogens of the geminal methyls.

Peaks from 1.66 to 2.42 p.p.m. characteristic of 'the hydi’ogens of the cyclopropyl. -2)Peaks at 4.23-4.42 p.p.m. Characteristic of the hydrogen at and at 4.42-4.58 p.p.m. )position 1’ of the ethyl side chain. Peak at 6.47 p.p.m. characteristic of the hydrogen of the group COOCHCN.

Peaks from 6.92 to 7-58 p.p.m. characteristic of the hydrogens of the aromatic nuclei.

Circular dichroism (dioxan) Maximum at 219 nm Maximum at 280 nm Inflection at 285 nm e = -5.4 ε = -0.28 e = -0.2? One chromatographs on silica the mixture of isomers A and 2 prepared above eluting with a hexane/pentane/ether mixture (7-2.8-0.17) and obtains the isomers A and B separately. Isomer A NMR Spectrum (deuterochloroform) Peaks at 1.32-1.37 p.p.m. characteristic of the hydrogens of the geminal methyls.

Peaks at 1.66-1.76 p.p.m. ) characteristic of the hydrogens at 2.08-2.17 p.p.m. ) of the cyclopropane. and at 2.26-2.35 p.p.m. ) Peaks at 4.2-4.37 p.p.m. characteristic of the hydrogen at position 1' of the ethyl side chain.

Peak at 6.42 p.p.m. characteristic of the hydrogen of the group COOCHCN.

Peaks from 6.92 to 7·5θ p.p.m. characteristic of the hydrogens of the aromatic nuclei. isomer h NMR Spectrum (deuterochloroform) 7 9 9 0 - 31 Peaks at 4.37-4.53 p.p.m. characteristic of the hydrogen at position 1' of the ethyl side chain.

The (R) α-cyano 3-phenoxy benzyl alcohol used at the start of Example 6 was prepared as follows: Stage A: (1R.5S) 5.β-dimethyl a(B) [(R) cyano (31-phenoxyphenyl )aethoxy 3 y-oxa bicyclo (3-1-0) hexan-2-one.

One continues the chromatography begun in stage B of the preparation described in Example 3 and obtains 7·?2 g of expected product. = -120° ί 2.5° (c = 0.9%, benzene) Stage B: (R) a-cyano 3-phcnoxy benzyl alcohol.

One works in a manner similar to that which is described in stage C of the preparation described in Example 3, starting with 12.8 g of product described in the previous stage and obtains, after the same purification by chromatography, 5 g of expected product. [al= +11° - 2° (c = 0.5%, benzene) Example 7Study of the insecticidal activity of (S) a-cyano 3-phenoxy benzyl (IR,trans) 2,2-dimethyl 3-(21 ^'-dicliloro 11,2'-dibromoethyl) cyclopropane-l-carboxylate (compound A), of the isomer A of (S) α-cyano 3-phenoxy benzyl (lR,cls) 2,2-dimethyl 3-(21^'-dibromo I1,2'-dichloroethyl) cyclopropane-l-carboxylate (compound B) and of the isomer B of the same compound (compound C). 1) Study of the lethal activity of compounds A, B and G on the house fly.

The test insects are female house flies, four days old. 47890 - 32 Work is carried out by topical application of 1μ of acetonic solution to the dorsal thorax of the insects using the ASKOLD, micromanipulator. One uses 50 individuals per treatment. One carries out the mortality check twenty-four hours after treatment.

The tests are carried out without a synergist or with the addition of piperonyl butoxide (10 parts of synergist to 1 part of compound to be tested).

The experimental results, summarised in the following 10 table, are expressed in LD 50 or dose (in nanograms) necessary to kill 50% of the insects: — LD 50 in ng/insect COMPOUND A, not synergised 5.75 COMPOUND A, synergised 0.91 COMPOUND B, not synergised 1.67 COMPOUND B, synergised 0.88 COMPOUND C, not synergised 2.95 COMPOUND C, synergised 0.82 Conclusion: Compounds A, B and C are endowed with strong insecticidal activity with regard to house flies. 2) Study of the knock-down activity of compounds A, B en The test insects are female house flies, 4 days old. 479 9 0 ~ S3 * Work is carried out by direct spraying in a KEARNS and MARCH chamber, using as solvent a mixture in equal volumes of acetone and kerosene (amount of solution used 2 x 0.2 cm· ). One uses about 50 insects per treatment. One carries out checks every minute up to 10 minutes, then at 15 minutes and one determines the KT 50 by the usual methods.

The experimental results obtained are summarised in the following table: ΚΤ,-θ in minutes. COMPOUND A 6.00 COMPOUND B 6.12 COMPOUND C 6.02 Conclusion: Compounds A, B and G possess an interasting knock-down capacity with regard to house flies.

) Study of the insecticidal activity on house flies of compound A used in the form of a smoke-producing coil.

Neutral supports of smoke-producing coils are impregnated with active material in solution in acetone. One releases into a closed cylinder, made of glass, of 13.5Q dm^ capacity, 20 female house flies, 4 to 5 days old, and introduces, over 2 minutes, a smoke-producing coil burning at one end. One carries out the knock-down check every minute and stops the test 5 minutes after all the insects have Deen knocked down. One carries out three series of tests for each dose.

DOSES by weight of active material per weight of coilKT50KT5O KT50 KT5Q average COMPOUND A 0.4# 7.5 8.8 6.6 7.75 0.2% 11.8 10.2 9.2 10.22 Conclusions Used as a fumigant composition compound A shows good insecticidal activity. 4) Study of the insecticidal activity of compounds A, B and C on caterpillars of Spodoptera Littoralis.

The tests are carried out hy topical application. One deposits 1 μ 1 uf an acetonic solution of the product to be tested on the dorsal thorax of each individual. One uses 15 caterpillars oi Spodoptera Littoralis at the 4th larval stage for each dose employed. After treatment the individuals are placed on an artificial nutrient medium (Poitoit medium). One carries out an efficacy check (percentage mortality taking into account an untreated control) 24 hours then 48 hours after treatment and one determines the lethal dose 50 (LDq0) in nanograms per caterpillar.

The experimental results are summarised in the following table: LD^q in ng/caterpillar COMPOUND A 0.22 COMPOUND B 0.57 COMPOUND C 0.65 - 35Conclusion: Compounds A, B and C are endowed with strong insecticidal capacity with regard to caterpillars of Spodoptera Littoralis.

) Study of the insecticidal activity on larvae of Epilochna varivestris.

The tests are carried out by topical application in a manner similar to that used for the larvae of Spodoptera. One uses larvae from the penultimate la^-val stage and after treatment the larvae are fed with bean plants. One carries out the mortality check 72 hours after treatment. The experimental results are summarised in the following table: LDj-q ia ng/per individual COMPOUND A 0.18 COMPOUND B 4.26 COMPOUND C 6.95 Conclusion: Compounds A, B and C are endowed with strong insecticidal activity against the larvae of Epilaehna varivestris Compound A, in this sphere, possesses particularly marked activity. 6) Study of the insecticidal activity of Compound A on larvae of Andes Aeirypti.

One uses 370 ml wido-mouiiied jars into which one intro200 C— ΟϋΘ ΫΖΌΡίΓΞ χ.γ»4·λτ» SaT* with 1 ml of acetonic solution containing the product to be 47890 - 36 tested. One infests each jar with 10 larvae of Aedee Aegypti (in the final larval stage). The larvae are transferred into a9 ml of water. Efficiency checks are carried out 24 hours to 48 hours·after the infestation. For the duration of the test the jars are kept in an incubator at 25°0.

The results obtained are summarised in the following table: LD^q in p.p.m. COMPOUND A 3.24 x IO5 Conclusion: Compound A is endowed with strong insecticidal activity against larvae of Aedes Aegypti. 7) Study of the insecticidal activity of Compound A bn Blattella germanica.

This test is carried out by topical application. Male adults of Blattella germanica, selected according to the criterion of length, receive two micro-litres of acetonic solution of the product to be tested between the second and the third pairs of legs. After the treatment the test insects are kept in dim light at 20°C and are fed. One uses doses of 10 - 7·5 - 5 - 3.75 - 2.5 ng/insect. Checks are carried out twenty-four hours, forty-eight hours and six days after treatment. The experimental results, expressed in LD^q in nanograms per insect are summarised in the following table: LD^0 in ng per insect COMPOUND A 1.06 7 9 9 0 - 37 Conclusion: Compound A is endowed with strong insecticidal activity with regard to Blattella germanica. 3) Study of the insecticidal activity of Compound A with regard to Dysdercus fasciatus.

One deposits one microlitre of acetonic solution of product to he tested on the ventral thorax of each individual One uses doses of 3.75 - 2.5 - 1.25 - 1 - 0.625 nanograms per insect. Efficiency checks are carried out 24 hours, u.Q hours and 5 days after the treatment.

The results obtained are mentioned in the following tablf LD^0 in nanograms per insect COMPOUND A . 1.06 Conclusion: Compound A is endowed with strong insecticidal activity with regard to Dysdercus fasciatus. 9) Study of the insecticidal activity of Compound A on Sitonhilus Granarius and Tribolium Castaneum.

The test is carried out by direct spraying on to infested. wheat. One sprays 5 ml of acetonic solution of product to x be tested and 0.1 cm of water on to 100 g of wheat contained 20 in a 1 litre flask of a rotary evaporator (in motion). One carries out artificial infestation with 50 individuals (Sitophilus or Tribolium). For each dose one determines the percentage mortality at the end of 7 days taking into account an unti'eated control and talcing an average of 100 individuals OC ---! - — - «3 “4· - -j — - - +-V. — 1 — XU —1 4_ 4 „ 4^ _ C.7J CXi-itA tine uc U CX 111X11 C. O UXXU mu tit, e* u/xxu* Az XX ly X LX ly I, UJ4U ι,·» ρ· μ* XLX. . - 3S DOSES in p.p.m. SITOPHILUS GRARARXUS PRISOLIUM lASTAIl E3!M /mortality LD^q inp.p.n /mortality LD50 in p.p.m. 1.5 90.0 0.80 100 0.19 1.0 66.70 96.9 0.75 35.3 89.5 0.5 18.2 85.3 0.25 2.0 ' 62.0 Conclusion; Compound A is endowed with good insecticidal activity with regard to Sitophiius granarius and triboliu® castaneum.

Example 8; Study of the acaricidal activity of Compound A on Tetranychus IJrticae.

One uses bean leaves infested with 10 females of Tetranychus Urticae per leaf and smeared with bird lime on their peripheries; one allows the females to lay for twentyfour hours, removes them and divides the leaves thus infested with eggs into two groups. a) A first group is treated with the compound to be z tested; work is carried out by spraying 0.5 cur of aqueous solution on to each leaf using concentrations of 50 and 25 g of compound to be tested per hectare. b) A second group of leaves is not treated and serves as control group.

Counting of the live adults, the live eggs and the live larvae takes place nine days after the beginning of 7 9 9 0 - 39 the treatment. The results, expressed in percentage mortality of the adults, the eggs and the larvae, are summarised in the following table (taking into account the untreated control). % mortality of the adults % unbatched eggs % mortality of the larvae COMPOUND A 52.3 54.3 47.6 Conclusion: Compound A is endowed with interesting insecticidal capacity with regard to Tetranychus Urticae.

ExampΊ e 9: insecticidal composition : an emulsifiable concer.tra' is prepared by mixing intimately : - (S) α-cyano J-phenoxy benzyl IR,trans 2,2-dimethyl 3-(21,2'-dichloro 1',2'-dibromoethyl) cyclopropane-l-car'boxylate .......................................... 0.015 g - Piperonyl butoxide .............................. O.5 g - Topanol A.......................................0.1 g - Xylene .......... .99.385 S Example 10: insccticidal composition : an emulsifiable concentre in : following π.-innor, One makes a homogeneous mixture of: - (S) α-cyano 3-phenoxy benzyl IR,trans 2,2-dimethyl 3-(2',2',-dichloro 1',2'-dibromoethyl) cyclopropane-lcarboxylate ....................................... 1.5 g - Tween 80 ........................................ 20 g - Topanol A....................................... o.l g - Xylene .......................................... 75.4 g “ 40 Example 11 i Acaricldal composition.

An emulsifiable concentrate war. proparod containing by weight 20 per cent of (s) y-cyano 3-phenoxy benzyl IK, trans 2,2-dimethyl 3-(2',2’-dichloro 1',2•-dibromoethyl cyclopropano-1-cr.rboxylate, 6.5 per cent by weight of Atlox 4851 (ethylene oxide triglyceride combined with a sulphonate, acid index 1.5), 3.3 per cent of Atlox 4855 (ethylene oxide triglyceride combined with a sulphonate, acid index : 3 and 70.2 per cent of xylene.

Example 12 ; Nematocidal Composition.

An emulsifiable concentrate for treatment of the ground was prepared containing by weight 45 per cont of (s) n(-cyano 3-phenoxy benzyl 1R,ti-ans 2,2-dimethyl 3-. (2’.2’-dichloro 1',2’-dibromoethyl)cyclopropano-1carboxylate, 6,4 per cent of Atlox 4851 (ethylene oxide triglyceride combined with a sulphonate, acid index 1.5), 3.2 per cent of Atlox 4855 and 45.4 per cont of xylene. Example 13 s Ixodicldal Composition. Λ solution was prepared having tho following composition s (s) #-cyano 3-phonoxy benzyl 1R,trans 2,2-dimothyl 3-(2’,2’dichloro 1',2,-dibroraoothyl)cyclopropane-1-carboxylato...0,5 Polysorbate 80,........................................ 10 g Triton X 100........................................... 25 g Tocopherol acetate.·................................... 1 g Ethanol, q.s...........................................100 ml This solution is employed for external use after dilution in 50 times its volume of water.

Example 14 ; Ixodlclal composition.

An injectable solution was prepared containing (s) v-cyano 3-phenoxy benzyl IR,trans 2,2-dimethyl 3-(2',2‘“dichloro 11,21-dibromocthyl) cyclopropane—1-carboxylate.......... 2 g - Piporonyl butoxido . ·.. . ..........······>.............. 6.65 C - Tocopherol acetate.................................. 0.33 { - Oily excipient, *q.s, ................................100 cm3.

* This oily excipient is made up from 29 g of benzyl benzoate» and sufficient arachis oil to yield a total volume of 100 cm3.

Example 15 ; Foodstuff Composition for animals.

As the basic balanced foodstuffs one uses a foodstuff including maize, dehydrated lucerne, wheat straw, molassessweetened cabbage-palm cake, urea, a vitaminized mineral supplement.

This foodstuff contains at least 11% of crude proteinaceous raateriul (of which 2.8% is derived from the urea); 2.5 per cent of fatty matter and at most 15 per cent of cellulosic material, 6 per cent of mineral matter and 13 per cent of moisture.

The foodstuff employed corresponds to 82 forage units per 100 kilos and contains for each 100 kilos : 910,000 I. U, of vitamin A, 910,000 I.U. of vitamin 156 mg of vitamin li and 150 mg of vitamin C.

In this foodstuff one incorporates 0.04 leg· of (s) /-cyano 3-phonoxy benzyl 1R,trans 2,2-dimethyl 3-(21,2'-dichloro II, 2'-dibromoethyl)cyclopropane-1-carboxylate.

Claims (27)

1. , A compound selected from (S)-a-cyano-3-phenoxybenzyl (lR,trans)-2,2dimethyl-3~(2',2’-dichloro-l’,2’-dibromoethyl)cyclopropane-l-carboxylate; (S)-α-cyano-3-phenoxybenzyl (IR,cis)-2,2dimethyl-3-(2',2'-dibromo-l*,2'-dichloroethyl)cyclopropane-l-carboxylate; 3.4.5.6- tetrahydrophthalimidomethy1 (IR,trans)2.2- dimethyl-3-(l’,2',2*,2’-tetrabromoethyl)cyclopropane-l-carboxylate; 3.4.5.6- tetrahydrophthalimidomethyl (IR, cis)2.2- dimethyl-3-(l',2',2',2'-tetrabromoethyl)-cyclopropanel-carboxylate; (S)-a-cyano-3-phenoxybenzyl (lR,cis)-2,2-dimethyl3-(1’,2’,2',2'-tetrachloroethyl)-cyclopropane-lcarboxylate; and (R)-α-cyano-3-phenoxybenzyl (IR,trans)-2,2dimethyl-3-(2',2'-dichloro-l',2'-dibromoethyl)-cyclopropane-l-carboxylate.

2. (S)-a-Cyano-3-phenoxybenzyl (lR,trans)-2,2dimethyl-3-(2',2'-dichloro-1',2'-dibromoethyl)cyclopropane-l-carboxylate.

3. A compound as claimed in any preceding claim in the form of a 1’-position diastereoisomer.

4. A compound as claimed in any preceding claim in the form of a cis or trans stereoisomer.

5. A compound as claimed in any one of claims 1 to 3 in the form of a mixture of cis and trans stereoisomers.

6. A compound as claimed in claim 5 wherein the cis and trans stereoisomers are present in a proportion byweight of about 20/80, 50/50 or 80/20.

7. A process for the preparation of compounds as claimed in claim 1, the said compounds having the / (I') (wherein X^ , corresponding to claimed in claim X3 and R possess the meanings the substituents of the compounds 1), which comprises reacting an (wherein X^, X^, and R possess the meanings corresponding to the substituents of the compounds claimed in claim 1) 15 with a chlorination or bromination agent capable of adding Cl^ or across the double bond in the side chain of the ester of formula II. 4799

8. A process for the preparation of compounds of general formula 1' as defined in claim 7 which comprises reacting an acid of formula IV, 5 (wherein Xp Xj and X^ possess the meanings corresponding to the substituents of the compounds claimed in claim 1) or a functional derivative thereof with an alcohol of formula ROH (wherein R possesses tte meanings of the corresponding compounds claimed in claim l) or a 10 functional derivative thereof.

9. A process as claimed in claim 8 wherein a chloride, anhydride, mixed anhydride, lower alkyl ester, metallic salt or salt with an organic base of the acid of formula IV is reacted with the alcohol of formula ROH 15 or reactive derivative thereof.

10. A process as claimed in claim 8 or claim 9 wherein the acid of formula IV or functional derivative thereof is reacted with a chloride, bromide or sulphonate of the alcohol of formula ROH. 20

11. A process as claimed in any one of claims 8 to 10 wherein the acid of formula IV is obtained by reaction of an acid of formula III, (III) (wherein X^ and X 2 possess the meanings of the corresponding compound as claimed in claim 1) with a chlorination or bromination agent capable of adding Cl 2 or Br 2 across the double bond in the side chain of the acid of formula III.

12. A process as claimed in claim 7 or claim 11 wherein the chlorination or bromination agent is molecular chlorine or bromine.

13. A process as claimed in any one of claims 7, 11 or 12 wherein the reaction with the chlorination or bromination agent is carried out in the presence of acetic acid, carbon tetrachloride, chloroform or methylene chloride as solvent.

14. A process for the preparation of compounds as claimed in claim 1 substantially as herein described.

15. A process for the preparation of compounds as claimed in claim 1 substantially as herein described in any one of Example 1 to 6.

16. Compounds as claimed in claim 1 whenever prepared by a process as claimed in any one of claims 7 to 15.

17. Insecticidal compositions comprising, as active ingredient, at least one compound as claimed in claim 1, in association with a carrier or excipient. 4799

18. Insecticidal compositions as claimed in claim 17 further including a synergising agent.

19. Insecticidal compositions as claimed in claim 18 wherein the synergising agent is piperonyl butoxide. 5 20. Insecticidal compositions as claimed in any one of claims 17 to 19 containing from 0.005% to 10% by weight of active ingredient. 21. Acaricidal compositions comprising, as active ingredient, at least one compound as claimed in claim 1, ]Q in association with a carrier or excipient. 22. Acaricidal compositions as claimed in claim 21 containing from 1% to 80% by weight of active ingredient. 23. Acaricidal compositions as claimed in claim 21 15 containing from 0.05% to 3% by weight of active ingredient. 24. Nematocidal compositions comprising,as active ingredient, at least one compound as claimed in claim 1, in association with a carrier or excipient.

20. 25. Pharmaceutical compositions comprising, as active ingredient, at least one compound as claimed in claim 1, in association with a carrier or excipient. 26. Pharmaceutical compositions as claimed in claim 25 further including a synergising agent.

21. 25 27. Animal foodstuff compositions comprising at least one compound as claimed in claim 1 in combination with nutrient material.

22. 28. Animal foodstuff compositions as claimed in claim 27 containing from 0.002% to 0.4% by weight of a compound as 30 claimed in claim 1.

23. 29. Compositions as claimed in any one of claims 17 to 28 containing a compound as claimed in any one of claims 3 to 6.

24. 30. Compositions as claimed in any one of claims 17 to 29 containing a compound as claimed in claim 2.

25. 31. Compositions containing a compound as claimed in claim 1 substantially as herein described.

26. 32. Compositions containing a compound as claimed in claim 1 substantially as herein described in any one of Examples 9 to 15.

27. 33. A method of preventing or inhibiting the growth and/or proliferation of insects, acarids and/or nematodes which comprises administering to a site other than a human or animal body infested with or susceptible to infestation with insects, acarids, and/or nematodes an effective amount of a compound as claimed in claim 1.