CH638774A5 - Method for the control of insects and mites, with the exception of the therapeutic treatment of the animal body - Google Patents

Description

The invention relates to a method for controlling insects and mites with the exception of the therapeutic treatment of the animal body, which is characterized in that the insects and mites, 20 their habitat, their breeding grounds or their feed with an insecticidal or acaricidal activity Amount of an m-phenoxy-benzyl ester of a 2- (haloalkoxy, alkylthio, alkylsulfinyl or alkylsulfonylphenyl) alkanoic acid of the formula:

CH-C-O-CH

(I)

wherein the substituent of the formula RCF2X- is in the m- or 30-position to the carbon atom to which the alkanoic acid ester group is attached, X sulfur, oxygen, the sulfinyl or sulfonyl group ,. R is hydrogen, fluorine, chlorine, the difluoromethyl or trifluoromethyl radical, R2 is the ethyl, n-propyl, isopropyl, tert-butyl or isopropenyl group 35 and R3 is hydrogen or the cyano group. You can e.g. use the optical isomers of the compounds of formula I.

The invention further relates to an insecticidal agent comprising a compound of formula I, e.g. an optical isomer thereof, an emulsifier, a surfactant and a solvent.

The invention also relates to a process for the preparation of the compounds of the formula I, which is characterized in that a compound of the formula:

45

(ii)

(ii)

wherein A represents a halogen atom and the substituent of the formula RCF2X- is in the m- or p-position to the carbon atom to which the alkanoic acid halide group is bound, in the presence of a tertiary organic amine as acid acceptor and an inert organic solvent in one Temperature from 10 to 30 ° C with an m-phenoxybenzyl alcohol of the formula:

60

wherein A represents a halogen atom and the substituent of the formula RCF2X- is in the m- or p-position to the carbon atom to which the alkanoic acid halide group is attached, in the presence of a tertiary organic amine as acid acceptor and an inert organic solvent at a temperature of 10 up to 30 ° C with an m-phenoxybenzyl alcohol of the formula:

ch-oh

(iii)

implements.

The invention further relates to a process for the preparation of compounds of the formula I in which X is

3rd

638774

is the sulfinyl or sulfonyl group, which is characterized in that a compound of the formula I in which X is sulfur is prepared by the above processes and this is oxidized.

The compounds of the formula I in which R 2 is tert-butyl can also be prepared by using an acid of the formula:

Rcp.x-j ^ ll— ÇH COOH

2> 5 ^ R

(XXVIII)

where R2 is tert-butyl, correspondingly esterified.

The compounds of the formula I in which R 2 is isopropenyl can also be prepared by using a compound of the formula:

RCF2X

with a compound of the formula:

BrC

COOH

(XIX)

R.

(XXX)

reacted and from the compound of the formula obtained:

RCP.x ^ ir-f H-c ° - ° - °

A (XXXI)

Loh

HjC ^ CH3

cleaves water with phosphorus pentoxide, the substituent of the formula RCF2X in the m or p position to the group of the formula:

-CH-

stands.

C-OH Hj / XCH3

South African patent application No. 73/4462 by Sumitomo Chemical Company, Limited, is to be regarded as the state of the art that is the applicant's closest known. This patent application describes tens of thousands of phenyl-5-acetic acid esters, including a-isopropyl-4-methoxyphenylacetic acid-3'-phenoxybenzyl ester,

a-isopropyl-3-methoxyphenylacetic acid 3'-phenoxybenzyl ester,

'<> a-Isopropyl-4-chlorophenylacetic acid 3'-phenoxybenzyl ester, a-isopropyl-4-methylphenylacetic acid-3'-phenoxybenzyl ester, a-isopropyl-3-chlorophenylacetic acid-3'-phenoxybenzyl ester, and a-isopropyl-4-fluorophenylacetic acid -3'-phenoxybenzyl ester. 15 It is also stated that many of these compounds are potent pesticides and can be used to control a variety of insects and mites. In this patent application, however, neither the 2- (haloalkoxy, alkylthio, alkylsulfinyl and alkyl 2osulfonylphenyl) alkanoic acid m-phenoxybenzyl esters of the formula I are described, nor is a synthesis process suitable for the preparation of these compounds.

It has now surprisingly been found that the compounds of the formula I are not only effective insecticidal agents, but also have a strong action against ticks. The compounds of formula I are also systemic insecticidal and iododicidal agents for animals. They have a high safety margin and can be used effectively to protect pets, laboratory animals and agricultural animals against attack by insects and ticks. Compared to known pyrethroids, such as permethrin, phenotrin, allethrin or the like, the compounds of the formula I furthermore have a superior residual iodicidal and insecticidal action and are particularly effective for combating the tobacco caterpillar (Heliothis virescens) and mosquitoes.

The first process according to the invention is shown in the reaction scheme below, where A preferably denotes chlorine. The reaction is carried out in the presence of an inert organic solvent, such as diethyl ether, benzene or toluene, at a temperature of 10 to 30 ° C and in the presence of an acid acceptor. Tertiary organic amines such as trimethylamine, triethylamine and pyridine are used as acid acceptors.

Reaction scheme I

r \

R-CF2X '

-CH-COA +

(II)

(III)

638774

Those compounds are particularly preferred in which X is oxygen or sulfur, R is hydrogen or fluorine, R3 is hydrogen or the cyano group and R2 is the ethyl, n-propyl or isopropyl radical.

It should also be noted that various optical isomers of these compounds can be obtained in the preparation of the compounds of the formula I described.

For example, esters of the formula I in which Rs denotes a hydrogen atom have a chiral center in the region of the group R2, so that d and i isomer pairs are formed. Furthermore, an a-cyano group R3 forms a further chiral center, so that an additional pair of d and ^ isomers is possible.

For example, it has been found that when 1 mole of a-isopropyl-4-trifluoromethoxyphenylacetic acid is mixed with about 0.5 to 1.0 moles of (-) - a-phenylethylamine in a suitable solvent such as ethanol or aqueous ethanol, the salt of ( +) - acid fails. On acidification, the salt releases the acid, which generally contains more than 85% of the (- ^ - isomer. A higher yield of the (+) - isomer is obtained by recrystallizing the (-) - a-phenylethylamine salt or by Repetition of the procedure with fresh (-) - a-phenylethylamine The m-phenoxybenzyl or a-cyano-m-phenoxybenzyl esters of pure (+) - a-isopropyl - 4-trifluoromethoxyphenylacetic acid have about twice the insecticidal activity compared to the In the case of the a-cyano-m-phenoxybenzyl ester, a further increase in activity can be achieved by using the corresponding optically active a-cyano-m-phenoxybenzyl alcohol in the ester preparation.

The compounds of the formula II, in which Rj denotes the ethyl, n-propyl or isopropyl radical, can be prepared using suitable toluenes of the formula IV as starting materials. The manufacturing process involves five stages, the first of which involves halogenating toluene IV with bromine, chlorine, N-bromosuccinimide (NBS), or the like. This reaction is preferably carried out in the presence of an inert organic solvent such as carbon tetrachloride and a radical initiator such as light, benzoyl peroxide or azo-bis-isobutyronitrile to give the benzyl halide of formula V. The benzyl halide of formula V is then converted to the corresponding phenylacetonitrile of formula VI by reacting with sodium or potassium cyanide in the presence of dimethyl sulfoxide (DMSO), ethanol or the like at elevated temperature. This substituted phenylacetonitrile VI is readily alkylated by treatment with an alkyl halide in the presence of a base and an inert organic solvent, it having been shown that crown ethers are advantageous catalysts for this reaction. The compound of formula VII formed in the above reaction is hydrolyzed using an Al-2s potassium metal hydroxide in the presence of an alkylene glycol and water, thereby providing the compound of formula VIII. Treatment of acid VIII with thionyl chloride, thionyl bromide or the like preferably in the presence of an aromatic solvent such as benzene or toluene, then provides the compound of formula II. These reactions are shown in Reaction Scheme II below.

Reaction scheme II

rcf2x rcf2x

(v)

CH-j + Br2 or N3S-

rcf2x

(iv)

^ ^ -CH2Br + NaCN

(v)

- f \

rcf2x

(vi)

ch2cn

^) - CH2CN + R2A

rcf2x

(vi)

(f 7-chcn +

- / r rcf2x 2

(vii)

-> y — chcn

(vii)

KOH

H20

hoch2ch2oh rcf2x rcf2x

^ ^ -chcooh (viii)

chcooh + soci 2 benzene |> y-chcocl

R2 r2

(VIII)

5

638774

To prepare the compounds of the formula II in which X is oxygen or sulfur, A is chlorine and the substituent of the formula RCF2X- is in the p-position to the carbon atom to which the alkanoic acid halide group is bonded, the corresponding compound of Formula IX chloromethylate using a mixture of paraformaldehyde or trioxane and zinc chloride and dry hydrogen chloride to give the benzyl chloride of formula X which can then be used to further synthesize the compounds of formula II in place of the bromides of formula V. This reaction can be represented as follows:

The compounds of the formula II in which X is oxygen, A is chlorine and R is fluorine can also be prepared via a reaction sequence which begins with the alkylation of m- or p-methoxyphenylaceto-nitrile of the formula XI, for which an alkyl halide can be used in the presence of a crown ether and a base. The compound of formula XII obtained can then be converted into the compound of formula XIII by treatment with boron tribromide, preferably in the presence of a solvent such as methylene chloride. The reaction of the phenol of the formula XIII thus formed with thiophosgene and a base in counter

(x)

If a solvent such as chloroform was obtained, the compound of the formula XIV would then be obtained. This compound can be converted with molybdenum hexafluoride into the compound of the formula XV, which would then be reacted with ethylene-25 glycol in the presence of alkali metal hydroxide and water to give the corresponding compound of the formula XVI is hydrolyzed. Treatment of the compound of formula XVI with thionyl chloride in the presence of an aromatic solvent such as benzene or toluene gives the corresponding 3o acid chloride of formula II, wherein X is oxygen and R is fluorine. These reactions are illustrated by Reaction Scheme III below.

rcf2y-

ê V + (CH2 °) n + HCl ZnCl2 p RCF

(ix)

Y = 0 or S

Reaction scheme III

ch30

"Vv_ch pn + r Sr crown ether v f ~ ch2CN R2Br 50% NaQH

(XI)

ch30

£> r

(XII)

/ \

CH30

CH-CN + BBr.

ch2ci2

CHCN

(XII)

v / i

HQ / \ = S r2

(XIII)

CH-CN + CSCl

CHC13 2 NaOH

ff y-CH-CN

(XIII)

s / Vçh-cn +

cl-ë "° (xiv) R2

"/ A" / P

Cl-CO 2

(XIV)

MoF.

CH-CN

638774

6

Reaction scheme 'III (continued)

CF ^ O

ch-cn + high ^ ch-oh? ~ l h2o

// VcH-

(XV)

cf30

/ i

S \ = J R

cooh

(XVI)

cf30

ch-cooh + soci.

(XVI)

cf30

.üt coc1

In the above reaction scheme, R2 stands for the ethyl, n-propyl or isopropyl radical.

While Reaction Scheme II is generally applicable to the preparation of numerous compounds of Formula II, it has been found that the alkaline hydrolysis of nitriles in which RCF2X- is HCFaO- or HCF2S- means that the HCF2- residue can be lost. However, it has also been found that this residue can be reintroduced by reacting the phenol or thiophenol thus formed in a mixture of aqueous alkali and dioxane with chlorodifluoromethane.

The introduction of the HCF20 group is best illustrated by Reaction Scheme IV, according to which the compound of formula XII is reacted with hydrobromic acid to the compound of formula XVII. Treatment with chlorodifluoromethane in aqueous alkali and dioxane gives the compounds of formula XVIII. These acids are then, as shown in Reaction Scheme III, converted into the desired compounds of formula II, wherein X is oxygen and R is hydrogen.

ch30 '

O-

(XII)

ch-cn R_

Reaction scheme IV

48% HBr ch-co2h

0-t

C02h

+ hccif.

(XVII)

Dioxane

wet-hearted

NaÖH

(XVII)

hcf20

d-

ch-co-h i '

R-

(XVIII)

The procedure of Reaction Scheme II is also suitable for the preparation of most compounds in which X represents the sulfinyl or sulfonyl group; however, it is often recommended; to produce the acids of formula VIII, in which X is sulfur, whereupon the sulfur atom with suitable oxidizing agents, such as m-chloroperbenzoic acid, sodium periodate or hydrogen peroxide,

is oxidized to form the desired sulfinyl or sulfonyl compounds.

The following reaction sequence can be used to prepare compounds of the formula I in which R2 is the tert-butyl radical, starting from the compound of the formula XIX:

1) reaction with tert-butyl magnesium chloride,

7

638774

2) converting the compound of formula XX obtained into the compound of formula XXI using thionyl chloride,

3) Preparation of the Grignard compound from the compound of formula XXI with magnesium in tetrahydrofuran and 5

4) Carboxylation with carbon dioxide.

This reaction sequence is shown in the example of a-tert-butyl - 3- (or 4) -trifluoromethoxyphenylacetic acid in reaction scheme V. The acids can then be esterified to the compounds of the formula I in which R 2 is tert-butyl.

cf30

^ CHO + t-

(XIX)

Reaction scheme V t-BuMgCl -

cf3o ff y — ch-oh x = j c (ch3) 3

(XX)

ff —ch-oh +

cf3o

/ I

S \ - / c soci.

(XX)

c (ch3) 3

cf30

c (ch.). (XXI) J 13

i- "% ■ THF

cf30

/ i

A = / c c (ch3) 3

(XXI)

2nd

3rd

c02 H +

cf30

ff y-ch-cooh c (ch3) 3

CXXII)

In the case of compounds of the formula I in which R2 is the isopropenyl radical, the introduction of the a-isopropenyl radical can be carried out by the following reactions, starting from the compound of the formula XXIII:

1) reaction with two equivalents of isopropyl magnesium chloride and acetone to give the compound of the formula XXIV,

2) esterification of the compound of formula XXIV to the compound of formula XXVI,

3) Elimination of water from the compound of formula XXVI with phosphorus pentoxide.

The synthesis is shown using the example of the a-isopropenyl-4 (or 3) -trifluoromethoxyphenylacetic acid-m-phenoxybenzyl ester in reaction scheme VI:

45

cf3o

D-

(XXIII)

ch2cooh j-

Reaction scheme VI

1. j-PrMgCl ch3coch3

CF-3O

/ "VçH-COOH + BrCH,

C-OH / \

ch3 ch3

(XXIV)

cf3o-

(XXIV)

ch-cooh

A0H

ch3 ch3

+ Et3N

(XXV)

638774

8th

Reaction Scheme VI (continued)

cf30

/ t \

ch-co-o-ch

CF3O

/ C \ H

ch, ch.

ch-co-o-ch

A0H

ch3 ch3

(XXVI)

P205

cfo0

(/ - ch-co-o-

• ^ A

ch3 ch2

In the preparation of the a-cyano-m-phenoxybenzyl esters of the formula I by the processes of reaction scheme I, it is not necessary to prepare the a-cyano-m-phenoxybenzyl alcohol beforehand. A mixture of m-phenoxybenzyaldehyde, an alkali cyanide such as sodium cyanide and the corresponding compound of the formula II can equally well, or even better, be converted in one step to the end product a-cyanoester.

The compounds of the formula I are extremely effective contact poisons and gastric poisons for ticks and a large number of insects, in particular double-winged insects, butterflies, beetles and common-wingers. They are characterized by the pyrethroids in that they exert a very long residual insecticidal action in plant tissue, are effective in the soil and are surprisingly effective for controlling ticks and for protecting animals against attack by insects and ticks when using these compounds administered to the animals by oral or parenteral route or by topical route in the form of insecticidal or acaricidal formulations. They do not need to be mixed with a stabilizer to give insecticidal and acaricidal agents with a stabilized effect. However, they can be used in combination with other biological chemicals, for example synergists for pyrethroids, such as piperonyl butoxide, sesamex or the n-octyl sulfoxide of isosafrol. They can also be used in combination with conventional insecticides, such as phosphates, carbamates, formamidines, chlorinated hydrocarbons or halogenbenzoyl ureas. To control insects, including soil insects which attack growing plants and / or harvested crops, including stored crops, the insecticidal compounds according to the invention can be applied to the foliage of the plants, the living environment of the insects and / or the food supply of the insects. In general, the active ingredient is applied in the form of a diluted spray liquid, although it can also be used in the form of an aerosol, a dusting powder, a granulate or a wettable powder.

Particularly suitable spray liquids are oil spray liquids and emulsifiable concentrates, which can be further diluted for use. Although they are made in the form of liquid concentrates for ease of handling and ease of transportation, these formulations are typically dispersed in water at the site of application and then applied to the foliage of the plants, the soil or the surface of the area to be treated as a diluted spray liquid -35 brings.

A typical emulsifiable concentrate that can be used to protect a variety of crops, such as cereals, cabbage, pumpkin, corn, cotton, tobacco, soybeans, ornamental plants, shrubs, and the like, can contain 40 to 20 percent by weight of the active ingredient; 4% by weight of an emulsifier, as is usually used for the preparation of pyrethroid formulations; 4% by weight of a surfactant; 25% by weight of an organic solvent such as cyclohexanone; and about 47% by weight of a petroleum 45 solvent with an aromatic content of at least about 83% by volume.

The systemic active ingredients advantageously have a good safety range and protect a large number of animals, in particular cattle and pets, such as cattle, sheep, horses, dogs, cats and the like, against one

Infestation by fleas, mosquitoes, flies, ticks and the like. chen.

Particularly preferred insecticidal and acaricidal active compounds of the formula I are: 55a-isopropyl-4-trifluoromethoxyphenyl-acetic acid-m-phenoxy-benzyl ester,

a-isopropyl-4-trifluoromethoxyphenyl-acetic acid-a'-cyan-m-

-phenoxybenzyl ester, a-isopropyl-3-trifIuormethoxybenzyl-acetic acid - «'- cyan-m-60 -phenoxybenzyl ester, a-isopropyl-4-chlorodifluoromethoxyphenyl-acetic acid-a'-cyan-

-m-phenoxybenzyl ester, a-isopropyl-4- (l, l, 2,2-tetrafluoroethoxy) -phenylacetic acid-m - phenoxybenzyl ester, «5a-isopropyl-4-pentafluoroäthoxyphenyl-acetic acid-a'-cyan-m - phenoxybenzyl ester , a-Ethyl-3-trifluoromethoxyphenyl-acetic acid-m-phenoxy-benzyl ester,

9

638774

a-n-propyl-4-chlorodifluoro'methoxyphenyl-acetic acid-a'-cyano-

-m-phenoxybenzlyester, a-tert-butyl-4-trifluoromethoxyphenyl-acetic acid-a'-cyan-m-

-phenoxybenzyl ester, a-isopropyl-4-difluoromethoxyphenyl-acetic acid-a'-cyan-m-

-phenoxybenzyl ester, a-isopropyl-4-trifluoromethylthiophenyl-acetic acid-a'-cyano-

-m-phenoxybenzyl ester, a-ethyl-4-trifluoromethylsulfinylphenyl-acetic acid-m-phenoxy-benzyl ester,

a-isopropyl-3-difluoromethylsulfonylphenyl-acetic acid-a'-

-cyan-m-phenoxybenzyl ester, a-ethyl-4-trifluoromethoxyphenyl-acetic acid-a'-cyan-m-phen-oxybenzyl ester,

a-Isopropenyl-4-trifIuormethoxyphenyl-acetic acid-a'-cyan-m - phenoxybenzyl ester.

example 1

A) Preparation of p- (l, l, 2,2-tetrafluoroethoxy) toluene

In a mixture of 10.8 g (0.100 mol) of p-cresol, 1.67 g (1.43 g real, 0.0255 mol) of potassium hydroxide biscuits and 70 ml of dried dimethylformamide, which had been stirred at 68 °, were stirred using a magnetic stirrer C is maintained, tetrafluoroethylene and nitrogen are passed in for 1 hour. After dilution with 250 ml of water, the reaction mixture is extracted with 100 ml of ether. The ether solution is washed with 200 ml of 5% sodium hydroxide solution and twice with 400 ml of water. The ether solution is then dried, filtered and evaporated on a rotary evaporator, giving 18.14 g (87%) of p- (l, l, 2,2-tetrafluoroethoxy) toluene.

Analysis: C9H9F40

calculated: C 51.93 H 3.87 F 36.51 found: C 52.06 H 3.76 F 41.52

B) Preparation of p- (1,1,2,2-tetrafluoroethoxy) benzyl bromide

A mechanically stirred mixture of 118.45 g (0.569 mol) of p- (l, l, 2,2-tetrafluoroethoxy) toluene and 123.00 g (0.691 mol, 121 mol%) of N-bromosuccinimide, 1 is heated. 00 g (4.13 mol, 0.73 mol%) of benzoyl peroxide and 350 ml of carbon tetrachloride for 2.25 hours at the boil on the back-flow. After cooling, the reaction mixture is diluted with 350 ml of carbon tetrachloride, filtered to remove the solids, dried over sodium sulfate, filtered and evaporated using a rotary evaporator to give 160.99 g (99%) of a clear, red oil. This product is used as it is in the next stage of the process. The infrared spectrum and the NMR spectrum show that the product is p- (l, l, 2,2-tetrafluoroethoxy) benzyl bromide.

C) Preparation of p- (1,1,2,2-tetrafluoroethoxy) phenylaceto-nitrile

Over the course of 40 minutes, a hot solution of 75.1 g (1.15 mol) of potassium cyanide in 140 ml of water is added to a mechanically stirred solution of 160.99 g (0.561 mol) of p- (l, l, 2.2 -Tetraf! Uoräthoxy) benzyl bromide and 500 ml of anhydrous alcohol (2B alcohol), which is kept at 75 ° C. The resulting mixture is then heated to reflux for 1.75 hours. After standing overnight, the reaction mixture is poured into 500 ml of cold water and 400 ml of ether. The combined ether solutions are washed twice with 500 ml of water, dried over sodium sulfate, filtered and then evaporated on a rotary evaporator to give 114.95% of an oil. Vacuum distillation of this oil gives the only distillate fraction 37.10 g (28%) of the nitrile, which boils at 85 to 100 ° C / 0.29 mm Hg.

D) Preparation of a-isopropyl-p- (1,1,2,2-tetrafluoroethoxy) -5-phenylacetonitrile

A mixture of 39.85 g (0.171 mol) of p- (l, l, -2,2-tetrafluoroethoxy) phenylacetonitrile, 3.71 g (9.96 mmol, 5.8 mol%) of dicyclohexyl-18 is stirred crown-6, 22.0 ml (28.8 g, 0.234 mol) of 2-bromopropane, 55 ml of benzene and 55 ml of 50% sodium hydroxide solution for 45 minutes, during which an exothermic reaction takes place, the temperature of 25 to 43 ° C. The reaction mixture is then heated to 45 ° C for 16.5 hours. After dilution with 200 ml of water, the reaction mixture is extracted with 200 ml of ether. 15 Wash the ether solution in 400 ml of 12% hydrochloric acid, 200 ml of 5% hydrochloric acid and 300 ml of water. Then the ether solution is dried with sodium sulfate, filtered, evaporated and 'is obtained 47.13 g of an oil. This oil is distilled in vacuo to give 34.83 g 20 (74%) of an oil boiling at 83 to 85 ° C / 0.055 to 0.090 mm Hg.

Analysis: C13H13F4NO

calcd: C 56.73 H 4.76 N 5.09 F 27.61 found: C 56.12 H 4.85 N 4.99 F 34.07

25th

E) Preparation of 3-methyl-2- [p- (l, l, 2,2-tetrafluoroethoxy) phenyl] butyric acid

A stirred mixture of 48.0 g (24.0 g real) (0.60 mol) 50% sodium hydroxide solution, 21.78 g 30 (0.0791 mol) a-isopropyl-p- (l, l, 2,2-tetrafluoroethoxy) -phe-nylacetonitrile and 240 ml ethylene glycol over 12 hours at 135 ° C. After dilution with 600 ml of water, the reaction mixture is washed twice with 100 ml of ether. The aqueous layer is acidified to 35 with concentrated hydrochloric acid and then extracted twice with 300 ml of ether. The ether solution is washed twice with 500 ml of water, dried over sodium sulfate, filtered, evaporated and 20.74 g (89%) of a brown solid are obtained which are at 92 to 97 ° C. (hexane)

melts.

Analysis: C13H14F403

calculated: C 53.06 H 4.80 F 25.83 found: C 53.04 H 4.79 F 25.93

F) Preparation of 3-methyl-2- [p- (1,1,2,2-tetrafluoroethoxy) -45 -phenylj-butyryl chloride

A stirred mixture of 20.00 g (0.0680 mol) of 3-methyl-2- [p- (1,1,2,2-tetrafluoroethoxy) phenyl] butyric acid, 20.00 ml (33.2 g, 0.280 mol) of thionyl chloride (Baker) and 75 ml of dried benzene at reflux for 4 hours. Then the reaction mixture is evaporated, the residue formed is diluted with 50 ml of benzene, evaporated again and 22.46 g (106%) of a clear, dark brown liquid are obtained. This product is used as it is in the next stage of the process. The infrared spectrum of the liquid shows that it is the title compound.

G) Preparation of a-isopropyl-4- (1,1,2,2-tetrafluoroethoxy) phenylacetic acid-m-phenoxybenzyl ester

60 A solution is added to a stirred mixture of 6.81 g (0.0340 mol) of m-phenoxybenzyl alcohol, 3.0 ml (2.95 g, 0.0372 mol) of dried pyridine and 20 ml of methylene chloride over the course of 20 minutes of 10.6 g (0.034 mol) of 3-methyl-2- [p- (1,1,2,2-tetrafluoroethoxy) phenyl] butyryl- "5 chloride in 20 ml of methylene chloride. The reaction mixture is stirred for 66 hours at room temperature and then diluted with 200 ml of ether. The ether solution is washed with 200 ml of 20% hydrochloric acid solution and 200 ml

638774

10th

Water, dry over sodium sulfate, filtered, evaporated and receives 16.24 g (100%) of the product. This product is purified using a column filled with dry silica gel (116 cm X 5 cm; eluent hexane / methylene chloride mixture [1/1]) by taking a sample between 85 cm and 63 cm (the solvent front being 113 cm) and receives 12.60 g (78%) of a clear, slightly yellow-colored oil.

Analysis: C, 6H „4F404

calculated: 'C 65.54 H 5.08 F 15.95 found: C 64.99 H 4.96 F 19.10

Example 2

Preparation of a-isopropyl-4- (l, l, 2,2-tetrafluoroethoxy) - phenylacetic acid-a'-cyan-m-phenoxybenzyl ester

To a stirred mixture of 8.81 g (7.49 g real, 0.0333 mol) of a-cyano-m-phenoxybenzyl alcohol, 3.0 ml (2.95 g, 0.0372 mol) of dried pyridine and 20 ml of methylene chloride a solution of 10.6 g (0.034 mol) of 3-methyl-2- [p- (l, l, 2,2-tetrafluoroethoxy) phenyl] butyryl chloride in 20 ml of methylene chloride is added over the course of 20 minutes. The reaction mixture is stirred for 66 hours at room temperature, then diluted with 200 ml of ether, washed with 200 ml of 20% hydrochloric acid and 200 ml of water and dried over sodium sulfate. filtered and evaporated to give a dark red oil. To remove the m-phenoxybenzaldehyde present as an impurity, the oil is reacted with 0.5 g of sodium borohydride at the ice bath temperature and the oil obtained is purified using a column charged with dry silica gel (121 cm × 5 cm. Eluent = hexane / methylene chloride mixture [1/1]), collecting a sample between 77 cm and 57 cm (with the solvent front at 113 cm), and obtained 11.17 g (66%) of a clear, orange oil.

Analysis: C, 7H ,, F, NO,

calculated: "C 64.67 H 4.62 N 2.79 F 15.16 found: C 65.26 H 4.81 N 2.82 F 17.94

Example 3

A) Preparation of a-isopropyl-4-methoxyphenylacetonitrile To a solution of 147 g (1 mol) of p-methoxyphenyl

acetonitrile, 18.63 g (5 mol%) of dicyclohexyl-18-crown-6 and 320 g (2.6 mol) of 2-bromopropane in 300 ml of benzene are added to 300 ml of a 50% sodium hydroxide solution. The reaction mixture is heated to 45 ° C. and left at this temperature for 4 days. The organic phase is then separated off, washed well with water (three times 200 ml), dilute hydrochloric acid (once 200 ml), water (twice 200 ml) and evaporated to an oil. Vacuum distillation provides 175.6 g (81% real) of the product, which boils at 96 to 100 ° C / 0.15 mm Hg. The NMR spectrum (CDC1S) shows that the distilled material contains 12.5 mol% of the nitrile used as the starting material.

B) Preparation of a-isopropyl-4-hydroxyphenylacetonitrile A solution of 51.0 g (0.2 mol) of boron tribromide in 20 ml of methylene chloride is added to a solution of 37.8 g (0.2 mol) of a-isopropyl 4-methoxyphenylacetonitrile in 35 ml methylene chloride, kept at -40 ° C. The red solution is then allowed to warm to room temperature and is stirred for 3 days. The reaction solution is added to ice, extracted with ether (three times 100 ml), washed with water (twice 100 ml) and evaporated to an oil. Vacuum distillation gives 28.9 g (81%) of a-isopropyl-4-hydroxyphenylacetonitrile which boils at 142 to 143 ° C / 0.25 mmHg.

C) Preparation of the thiocarbonic acid 0- [p- (l-cyano-2-methyl-propyl) phenyl] ester chloride

16.43 g (0.143 mol) of thiophosgene in 50 ml of chloroform are added over 30 minutes to a solution of 5 25.0 g (0.143 mol) of a-isopropyl-4-hydroxyphenylacetonitrile in a 5% sodium hydroxide solution (5, 72 g, 0.143 mol), occasionally using an ice bath to keep the temperature below 30 ° C. The mixture is stirred for 15 minutes, the chloroform layer is separated off, washed io with water and evaporated to a yellow oil (38.2 g). The product is used as it is in the Step D process.

D) Preparation of a.-isoprapyl-4-trifluoromethoxyphenyl-15 acetonitrile

Treat the 38.2 g of stage C thiocarbonate at -25 ° C with 15.8 g of molybdenum hexafluoride. Then the temperature of the thick reaction mass is allowed to rise to room temperature and then slowly heated to 160 ° C. using an oil bath. The mixture is cooled to room temperature, poured into water, extracted with ether (four times 50 ml), washed with water (once 50 ml) and evaporated to an oil. Vacuum distillation gives a-isopropyl-4-trifluoromethoxyphenylacetonitrile, which boils at 78 25 to 80 ° C / 0.15 mm Hg.

E) Another process for the preparation of a-isopropyl-4 - trifluoromethoxyphenylacetonitrile

I. Preparation of 4-trifluoromethoxybenzyl chloride

30 A mixture of 355 mg trioxane, 340 mg zinc chloride and 600 mg trifluoromethoxybenzene is heated to 73 ° C. while passing hydrogen chloride gas through it. Then the reaction mixture is cooled to room temperature and diluted with ether. The organic phase is washed with saturated sodium carbonate solution and water.

After removal of the solvents, 1.42 g of product are obtained in the form of a colorless liquid.

II. Preparation of 4-trifluoromethoxyphenylacetonitrile According to the procedure of Example IC, the above chlorine

40 compound converted into the Nitrii in 93% yield.

III. Preparation of œ-isopropyl-4-trifluoromethoxyphenyl acetonitrile

The 4-trifluoromethoxyphenylacetonitrile is alkylated according to the procedure of Example 1D, yielding 90% yield.

F) Preparation of a-isopropyl-4-trifluoromethoxyphenyl acetic acid

A mixture of 2.0 g of a-isopropyl-4-tri-50 fluoromethoxyphenylacetonitrile, 3.0 g of potassium hydroxide, 35 ml of ethylene glycol and 3 ml of water is heated at 140 ° C. for 8 hours. Then the solution is poured into water and extracted with ether (twice 10 ml). The aqueous layer is acidified with dilute hydrochloric acid and extracted with ether (three times 5511 ml), washed with water (once 25 ml), dried over sodium sulfate and evaporated to an oil (1.23 g). IR spectrum (of pure material) 1700 cm-1.

«O G) Preparation of a-isopropyl-4-trifluoromethoxyphenyl acetyl chloride

A solution of 1.2 g of a-isopropyl-4-tri-fluoromethoxyphenylacetic acid and 0.6 ml of thionyl chloride in 5 ml of benzene is heated at reflux for 4 hours. Evaporation of the solvent and excess thionyl chloride gives the acid chloride which is used as it is in the esterification described in Step H and Example 4.

11

638774

H) Preparation of x-isopropyl-4-trifluoromethoxyphenyl-acetic acid-a'-cyan-m-phenoxybenzyl ester A solution of 4.58 mmol of a-isopropyl-4-tri-fluoromethoxyphenylacetyl chloride in 5 ml of ether is added to a solution of 4. 58 mmol of a-cyan-m-phenoxybenzyl alcohol and 0.5 ml of pyridine in 20 ml of ether. The mixture is stirred overnight and filtered. Then the filtrate and the washing liquid are evaporated and the remaining oil is purified on plates coated with silica gel (5 × 2 mm), using a methylene chloride / hexane mixture (1/1) as eluent. The band with an Rr value of 0.55 is extracted with ether, evaporated and. receives the desired ester (0.85 g).

IR spectrum (of pure material) 1755 cm-1; NMR spectrum (CDC13) S 6.8-7.6 (m, 13H, ArH), 6.31 and 6.28 (S, 1H, -CH-Ar), 3.27 [d, J = 7Hz, 1H, CH-CH-

I,

CN

(CH3) 2], 2.0-2.6 [m, 1H, CH (CH3) 2], 0.6-1.2 (four duets, J = 7Hz, (H, isopropyl-CH3);

19F spectrum: chemical shift compared to CFC13 8 = 58.8.

Example 4

Preparation of o-isopropyl-4-trifluoromethoxyphenylacetic acid-m-phenoxybenzyl ester

5 To a solution of 1.98 g of m-phenoxybenzyl alcohol and 1 ml of pyridine in 6 ml of methylene chloride, 7 ml of a methylene chloride solution of a-isopropyl-4-trifluoromethoxy-phenylacetyl chloride (prepared from 2.46 g of the acid by the method of Example 3G ) added. The reaction mixture is stirred overnight, washed with water, dilute hydrochloric acid, dilute potassium hydroxide solution and water and concentrated to an orange oil. Purification by silica gel chromatography gives 2.76 g of the desired ester.

15 IR spectrum (of the pure material): 1738 cm-1; Nuclear Magnetic Resonance Spectrum (CDC13): 5 6.73-7.45 (m, 13H), 5.03 (S 2H), 3.20 (d, J = 10.5 Hz, 1H), 2.26 (m , 1H), 0.66 and 0.94 (two d, J = 6.6 Hz, 6H).

20 Example 5

Preparation of a-ethyl and a-n-propyl-4-trifluoromethoxy-phenylacetic acid and their esters

If the process of Example 3A is repeated, but 25 with ethyl bromide or 1-bromopropane instead of 2-bromo-propane and then the process steps of Examples 3B to 3D and 3F are carried out, the two acids a-ethyl-4-trifluoromethoxyphenylacetic acid are obtained and an-propyl-4-trifluoromethoxyphenylacetic acid. These 30 acids are then converted to the following esters using the procedures of Examples 3G, 3H and 14:

jt "V. -

cf30-v y-ch-c-ci

RI

Ra

NMR assignments

CSH5

H 60.83 (t, J = 7.5Hz, 3H, CH3), 1.90 (m, 2H, -CH, -),

3.49 (t, J = 7.5Hz, -CH-CH2CH3), 5.04 (s, 2H, -OCH2-),

7.10 (m, 13H, ArH)

c2h5

CN 50.84 (2 triplets, J = 7.6Hz, 3H, CH3),

1.94 (m, 2H, -CH2-),

3.55 (t, J = 7.4Hz, 1H,

-CHCHLjCHj), 6.33 (s, 1H, -CHCN-), 7.18 (m, 13H, ArH)

n-CJHL

H

50.6-2.4 (m, 7H, -CH2CH2CH3),

3.63 (t, J = 7.2Hz, 1H, -CH-C3HV), 7.12 (m, 13H, ArH)

n-C, H7

CN

50.65-2.4 (m, 7H, -CH2CH2CH3),

3.71 (t, J = 7.3Hz, 1H, -CH-C3H7), 7.20 (m, 13H, ArH)

638774

12

Example 6

A) Preparation of a-bromo-4-trifluoromethylthiotoluene To a solution of 29 g (0.15 mol) of 4-trifluoromethyl

thiotoluene in 90 ml carbon tetrachloride, which is heated to weak reflux under a 275 watt sunlight lamp, slowly add 20.5 g (0.13 mol) bromine in 20 ml carbon tetrachloride. After the addition has ended, the solution is heated under reflux for a further 1 hour. The majority of the solvent is then removed at normal pressure, the residue is distilled in vacuo. The 15.5 g heavy fraction, which boils at 0.6 to 0.8 mm at 64 to 77 ° C, consists of 92% of the monobromine compound according to gas / liquid chromatography.

B) Preparation of 4-trifluoromethylthiophenylacetonitrile 3.9 g (0.08 mol) of sodium cyanide are added to 40 ml of dimethyl sulfoxide at 65 ° C. under nitrogen. The heat of reaction is removed and then 14.3 g (real 0.053 mol) of a-bromo-4-trifluoromethylthiotoluene are added dropwise at such a rate that the reaction temperature does not rise above 75.degree. The red-colored reaction mixture is then heated to 90 to 95 ° C. for about 45 minutes, cooled to room temperature and mixed with 50 to 100 ml of ice water. The aqueous suspension is extracted several times with ether, the extracts are combined, washed with water and dried over sodium sulfate. Concentration in vacuo gives 9.7 g of a dark red oil, which is 95% pure according to gas / liquid chromatography.

C) Preparation of a, -isopropyl-4-trifluoromethylthiophenyl-acetonitrile

13.5 ml of 50% sodium hydroxide solution become a suspension of 9.7 g (0.045 mol) of 4-trifluoromethylthiophenylacetonitrile, 9.5 g (0.056 mol) of 2-iodopropane and 0.61 g (0.0023 Mol) 18-crown-6 in 13.5 ml of benzene was added dropwise, the reaction mixture reaching 43 ° C. After stirring for 2 hours at room temperature, a sample no longer shows any residual starting nitrile in gas / liquid chromatography. The reaction mixture is worked up by adding ice water and extracting with ether. The ether extract is washed with 10% hydrochloric acid and water and dried over sodium sulfate. Concentration in vacuo gives 10.2 g (86.8%) of a red-brown oil.

Comparable results are obtained if the 2-iodopropane is replaced by ethyl bromide or n-propyl iodide for the preparation of a-ethyl-4-trifluoromethylthiophenylaceto-nitrile and a-n-propyl-4-trifluoromethylthiophenylacetonitrile.

D) Preparation of a-isopropyl-4-trifluoromethylthiophenyl acetic acid

6.9 g (real, 0.0265 mol) of a-isopropyl-4-trifluoromethyl-thiophenylacetonitrile and 25 g (0.312 mol) of 50% sodium hydroxide solution are combined in 53 ml of ethylene glycol and heated under gentle reflux for 18 hours. The reaction mixture is poured into ice water and extracted with ether. The aqueous phase is acidified with concentrated hydrochloric acid, back extracted with ether, the extract is washed with water and dried over sodium sulfate. Concentration in vacuo gives 2.05 g of an oily product.

Comparable results are obtained by using a-ethyl-4-trifluoromethylthiophenylacetonitrile or a-n - propyl-4-trifluoromethylthiophenylacetonitrile as the starting material in the production of a-ethyl-4-trifluoromethyl

thiophenylacetic acid and a-n-propyl-4-trifluoromethylthiophenylacetic acid.

E) Preparation of a.-isopropyl-4-trijluoromethylthiophenyl-5-acetic acid-oc'-cyan-m-phenoxybenzyl ester

If a-isopropyl-4-trifluoromethylthio-phenylacetic acid is used as the starting material in the process of Examples 3G and 3H, the product is obtained as an oil. Analysis: C26H22F3N03S io calc .: C 64.32 H 4.57 F 11.74 N 2.89 S 6.60 found: C 64.27 H 4.62 F 11.66 N 2.68 S 6.43

Comparable results are obtained if, using a-ethyl-4-trifluoromethylthiophenylacetic acid-15-acid or an-propyl-4-trifluoromethylthiophenylacetic acid, the a-cyano-m-phenoxybenzyl esters of a-ethyl-4-trifluoromethylthiophenylacetic acid and the other Propyl-4-trifluoromethylthiophenylacetic acid.

20 Example 7

Preparation of a-isopropyl-4-trifluoromethylthiophenyl-acetic acid-m-phenoxybenzyl ester

If the a-isopropyl-4-trifluoromethylthiophenylacetic acid is used in the process of Examples 3G and 4 25, the title compound is obtained as an oil.

Example 8

30th

A) Preparation of a-isopropyl-4-mercaptophenylacetic acid A solution of 15.7 g (0.065 mol) of a-isopropyl-4-di-

fluoromethylthiophenylacetonitrile in 42 g 50% sodium hydroxide solution and 80 ml ethylene glycol is heated under reflux for 18 hours. Then the reaction mixture is poured into ice water and extracted with ether. The alkaline phase is acidified at 15 to 20 ° C with concentrated hydrochloric acid and extracted with ether. The ether extract is washed with water and saturated sodium chloride solution and concentrated to an oil (11.4 g, 83%). NMR and IR spectra indicate that the -CHF2 residue was removed in the reaction and the product consists of a thiol.

B) Preparation of a-isopropyl-4-difluoromethylthiophenyl-45 acetic acid

18.4 g (0.46 mol) of sodium hydroxide in 50 ml of water and 11 g (0.05 mol) of a-isopropyl-4-mercaptophenylacetic acid in 40 ml of dioxane are combined and heated to 50.degree. Chlorodifluoromethane (Freon-22) is slowly introduced below the surface of the liquid, causing the temperature to rise to 75 ° C immediately. The initiation continues until the exothermic reaction slowly subsides (about Yi hour). The reaction mixture is cooled to room temperature and 100 ml of ice water are added. 55 The aqueous phase is extracted three times with 200 ml ether each and then acidified at 15 to 20 ° C with concentrated hydrochloric acid. The resulting oil is removed by ether extraction, the ether solution is washed with water and saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo to give 10.2 g of a dark brown gum. This product is used for esterification without further purification.

C) Preparation of a-isopropyl-4-difluoromethylthiophenyl-65 acetic acid-a'-cyan-m-phenoxybenzyl ester

If the isopropyl-4-difluoromethylthiophenylacetic acid is used in the process of Examples 3G and 3H, the title compound is obtained as an oil.

13

638774

Analysis:; C26H23F2N03S

calc .: C 66.79 H 4.96 F 8.13 N 3.00 S 6.86 found: C 66.58 H 5.13 F 8.02 N 2.87 S 6.95

Example 9

A) Preparation of a-isopropyl-4-hydroxyphenylacetic acid A mixture of 40.0 g of a-isopropyl-4-methoxyphenyl-

Acetonitrile and 200 ml of 48% hydrobromic acid are heated on an oil bath for 14 hours at 126 to 128 ° C. under reflux. The reaction mixture is diluted with ice and water and extracted several times with ether. The extracts are washed with water and concentrated to a solid residue. This is boiled in 200 ml of chloroform, the mixture is cooled, filtered and dried. The yield is 23.8 g of solid, mp 172 to 174 ° C. IR spectrum (Nujol) 3250-2900 (broad, OH), 1690 cm-1 (C = 0).

Analogous results are obtained if a-ethyl-4-methoxyphenylacetonitrile or a-n-propyl-4-methoxyphenyl-acetonitrile is used for the preparation of a-ethyl-4-hydroxyphenyl-acetic acid and a-n-propyl-4-hydroxyphenylacetic acid.

B) Preparation of a-isopropyl-4-diflioriormethoxyphenyl-acetic acid

In a mixture of 10.00 g (0.0515 mol) of a-isopropyl-4-hydroxyphenylacetic acid, 65 ml of dioxane, 19.08 g (18.56 g real, 0.464 mol) of sodium hydroxide and 30 ml of water at 80 ° C., stirred with a magnetic stirrer 46 g (0.532 mol) of chlorodifluoromethane are introduced over the course of 4 hours. The reaction mixture is poured into 250 ml of ice water and the resulting mixture is washed with ether, acidified to pH 3 with concentrated hydrochloric acid and extracted with 200 ml of ether. The ether solution is washed with 100 ml of water, dried over sodium sulfate, filtered and concentrated to give a white paste. A mixture of hexane and methylene chloride is added and the resulting mixture is filtered to remove a solid consisting of starting material. When concentrated, the filtrate gives 5.41 g of a clear brown oil. The product is believed to be at least 85% pure (NMR spectrum).

Nuclear Magnetic Resonance Spectrum (CDCl3-d5 pyridine), 5 7.43 (d, J = 8.2 Hz, 2H), 7.08 (d, J = 8.2 Hz, 2H), 6.57 (t, J = 7 4.3 Hz, 1H), 3.63 (s, imp.), 3.25 (d, J = 10 Hz, 1H), 2.37 (m, 1H), 1.19 (d, J = 6.5 Hz, 3H), 0.78 (d, J = 6.5 Hz, 3H), 13.82 (s, 1H).

Similar results are obtained when using a-ethyl-4-hydroxyphenylacetic acid or a-n-propyl-4-hydroxyphenylacetic acid to produce a-ethyl-4-difIuormethoxyphe-nylacetic acid and a-n-propyl-4-difluoromethoxyphenylacetic acid.

C) Preparation of a-isopropyl-4-difluoromethoxyphenylacetic acid-m-phenoxybenzyl ester

If the a-isopropyl-4-difluoromethoxyphenylacetic acid is used in the process of Examples 3G and 4, the title compound is obtained as a pale yellow oil.

Analysis: C25H24F204

calculated: C 70.41 H 5.67 F 8.91 found: C 73.36 H 5.96 F 10.56

Analogous results are obtained if the m-phenoxybenzyl esters are prepared from a-ethyl-4-difluoromethoxyphenylacetic acid or a-n-propyl-4-difluoromethoxyphenylacetic acid.

Example 10

Preparation of u-isopropyl-4-difluoromethoxyphenylacetic acid-a .'-cyan-m-phenoxybenzyl ester

5 If a-isopropyl-4-difluoromethoxyphenylacetic acid is used in the process of Examples 3G and 3H, the title compound is obtained in the form of an oil.

NMR spectrum (CDC13) 5 0.88 (4 doublets, J = 6 Hz, 6H,

io CH3), 2.30 [m, 1H, -CH-CH (CH3) 2], 3.24 [d, J = 10.1

Hz, 1H, -CH-CH (CH3) 2], 6.33 (2 singlets, 1H, -CHCN),

6.45 (t, J = 74 Hz, 1H, CHF20-), 7.16 (m, 13H, ArH). Analysis: C26H23F2N04 15 calculated: C 69.17 H 5.13 F 8.42 N 3.10

found: C 69.41 H 5.20 F 10.25 N 3.70

Analogous results are obtained in the reaction of a-ethyl-4-difluoromethoxyphenylacetic acid or a-n-propyl-20 -4-difluoromethoxyphenylacetic acid to the a-cyano-m-phen-oxybenzyl esters.

Example 11

2j Preparation of a-isopropyl-4-trifluoromethylsulfinylphenyl-acetic acid-m-phenoxybenzyl ester

A mixture of 10.0 g of a-isopropyl-4-trifluoromethyl-thiophenylacetic acid-m-phenoxybenzyl ester (see Example 24) and 4.1 g of 85% strength m-chloroperbenzoic acid is heated in 100 ml of 30 methylene chloride for several hours. The mixture is filtered and the concentrated residue is purified on a dry silica gel column, eluting with a 2: 1 mixture of methylene chloride and hexane. The product is obtained as a pale yellow oil.

35 Analogous results can be achieved if the m-phenoxybenzyl esters of a-ethyl-4-trifluoromethylthiophenylacetic acid or an-propyl-4-trifluoromethylthiophenylacetic acid are used in this way to produce a-ethyl-4-trifluoromethylsulfinylphenyl acetic acid or Propyl-4-trifluoromethylsulfinylphenyl-40 acetic acid-m-phenoxybenzyl ester oxidized.

Example 12

Preparation of a-ethyl-3-difluoromethylsulfonylphenyl-acetic acid-a'-cyan-m-phenoxybenzyl ester

45

A mixture of 10.0 g of a'-ethyl-3-difluoromethylthiophene-nylacetic acid a'-cyano-m-phenoxybenzyl ester and 9.0 g of 85% m-chloroperbenzoic acid is refluxed overnight in 100 ml of ethylene dichloride. The mixture is filtered and concentrated and chromatographed on a dry silica gel column while eluting with a 2: 1 mixture of methylene chloride and hexane. The product is obtained as a yellow oil.

Analogous results are obtained if the a-cyan-55-m-phenoxybenzyl esters of a-isopropyl-4-trifluoromethylthio-phenylacetic acid or an-propyl-4-trifluoromethylthiophenyl-acetic acid are added in this way to the a-isopropyl-4-trifluoromethyl thylsulfonylphenylacetic acid or an-propyl-4-trifluoromethylsulfonylphenylacetic acid-ß'-cyan-m-phenoxybenzyl esters 60 oxidized.

Example 13

A) Preparation of 4-trifluoromethoxy - $, ß-dimethylatropa-65 acid

A solution of 22 g (0.1 mol) of p-trifluoromethoxy-phenylacetic acid (prepared by alkaline hydrolysis of the nitrile according to Example 12) in 50 ml of ether is added to an ice bath

638774

14

temperature a solution of commercially available isopropyl magnesium chloride (0.02 mol) in ether was added. The reaction mixture is stirred at room temperature for 2 hours, then 5.8 g (0.1 mol) of dry acetone are added and the mixture is heated under reflux for 5 hours. Then the reaction mixture is cooled, carefully acidified with aqueous sulfuric acid and extracted with ether. The combined organic phases are extracted with 10% sodium carbonate solution. The alkaline phase is acidified with hydrochloric acid and extracted with ether, the ether extract is dried over sodium sulfate and concentrated to give 4-trifluoromethoxy-β, β-dimethylatropic acid.

B) Preparation of 4-trifluoromethoxy-a-isopropefiylphenyl-acetic acid-m-phenoxybenzyl ester To a solution of 13.9 g (0.05 mol) of 4-trifluoromethoxy-ß, ß-dimethylatropic acid and 6.1 g (0, 06 mol) of triethylamine in 100 ml of acetone, 13.2 g (0.05 mol) of m-phenoxy-benzyl bromide are added at ice bath temperature, then the mixture is boiled under reflux for 4 hours. The mixture is poured into cold, dilute hydrochloric acid and extracted with ether. The ether phase is washed with 10% hydrochloric acid and water, dried over sodium sulfate and concentrated to give the hydroxyester, which is dehydrated with phosphorus pentoxide in benzene at 80 ° C. for 18 hours. After filtration and removal of the solvent, the crude ester is obtained. Dry column chromatography on silica gel using a 50:50 mixture of methylene chloride and hexane as the solvent gives the product as a pale yellow gum.

Example 14

A) Preparation of 4-trifluoromethoxy-a-tert-butylbenzyl alcohol

A solution of 56 g (0.4 mol) of 4-trifluoromethoxybenzaldehyde in 50 ml of tetrahydrofuran in a nitrogen atmosphere is added to a solution of commercially available tert-butylmagnesium chloride in tetrahydrofuran (1.0 mol) at 38 to 40 ° C. The solution is stirred overnight at room temperature and then carefully acidified with dilute sulfuric acid at 15 to 20 ° C. Then ether is added and the organic phase is washed with water, dried over sodium sulfate and concentrated to a gummy solid. The crude product is purified by silica gel chromatography to give the alcohol which is used in the step B process.

B) Preparation of p- (l-chloro-2,2-dimethylpropyl) -a, a, a-tri-fluoroanisole

To freshly distilled thionyl chloride (14.87 g, 0.125 mol), which is cooled in a salt / ice bath, 12.4 g (0.05 mol) of the neopentyl alcohol according to stage A are added in portions over the course of 30 minutes. The ice bath is removed and the slurry is left overnight. When the excess thionylchloride evaporates, a solid returns.

C) Preparation of a-tert-butyl-4-trifluoromethoxyphenyl acetic acid

The neopentyl chloride prepared according to stage B is converted into the corresponding Grignard reagent and then carbonated with carbon dioxide according to the Weinstein and Morse method (Journal of the American Chemical Society 74, 1133 [1952]), the desired acid being obtained as a white solid .

D) Preparation of oc-tert-butyl-4-trifluoromethoxyphenyl-acetic acid-a-cyan-m-phenoxybertzylester If the a-tert-butyl-4-trifluoromethoxyphenylacetic acid is used in the process of Examples 3G and 3H, 5 is obtained Title compound as an oil.

Example 15 Insecticidal Activity

10 The insecticidal activity of the compounds of the formula I is demonstrated by means of the following tests, in which the tobacco caterpillar, Heliothis virescens (Fabricus); the potato leafhopper (Western Potato Leafhopper) Empo-asca abrupta (DeLong); and the bean aphid Aphis fais bae (Scopoli) can be used as insect species. The procedures used are as follows:

Tobacco caterpillar (Heliothis virescens [Fabricus]) in the first stage of development:

A cotton plant with two real leaves folded out of 20 is immersed for 3 seconds with stirring in the solution to be tested (35% water / 65% acetone), which contains 300, 100 and 10 ppm of the compound to be tested. Then each leaf is placed in a cup with a wick and a gauze cloth filled with 50 to 100 newly hatched larvae is added before the cup is closed with a lid. After 3 days at a temperature of 27 ° C (80 ° F) and a relative humidity of 50%, the cups are examined and the kill of the newly hatched larvae is assessed. The 30 numerical values obtained are listed as a percentage of the kill in Table I.

Bean aphid (Aphis fabae [Scopoli])

Five pots of fiber, each containing a 5 cm (2 inch) nasturtium planted with 100 to 150 aphids two 35 days earlier, are placed on a turntable rotating at 4 rpm is operated and sprayed the plants with a solution containing 35% water and 65% acetone, which contains 100, 10, 1.0 and 0.1 ppm of the compound to be investigated, using the solution during two rotations a spray device (De-Vilbis Atomizer) which is operated with air at a pressure of 1.41 kg / cm2 (20 psi). The spray nozzle is placed about 15 cm from the plant and the spray is directed so that the aphids and plants are completely covered. The sprayed plants are then placed in white enamel bowls. Mortality is determined after one day at 21 ° C (70 ° F) and a relative humidity of 50%. The numerical values obtained are listed as a percentage of mortality in Table I below.

Potato leaf toppers (Empoasca abrupta [DeLong])

Dip a bean plant (Sieva lima) with the first leaf folded out to 7.5 to 10 cm (3 to 4 inches) in 55 a solution of 35% water and 65% acetone, the 100, 10 and 1 ppm of the compound to be examined contains. Then place the immersed plant in a hood to dry and cut a 2.5 cm piece of the top of a leaf and place it in a 10 cm (4 inch) diameter petri dish with a damp filter paper on the bottom contains. Then you transfer three to ten nymphs of the second stage of development into the petri dish, which is then covered. Mortality is then counted after storing Petri dish 65 for two days at 27 ° C (80 ° F) and a relative humidity of 50%. The numerical values obtained are listed in Table I below. Permethrin is used as the reference standard in these studies.

Percentage of mortality

Tobacco caterpillar aphid aphid

1.Development »r

stage

connection

300 ppm

100 ppm

10 ppm

"lö'ö"

ppm lo ppm

1

ppm

"TOTT

ppm

-IÏÏ1 ppm

■ "1"

ppm

0.1 ppm

-N

cf3o- ^ nVch-co-o-ch—

\ = / ch (ch3) 2

100

100

100

100

100

70

100

100

90

50

CHF ^ o / ^ - ÇH-CO-O-CH, -,

\ = j ch (ch3) 2

ox)

90

90

0

50

0

-

100

100

0

-

^ tjxj

100

100

0

100

0

-

100

100

50

-

f, cs - (/ xVch-co-o-ch-i ^ - 'pro-if ^ wc „, ch3,2 1 ^ / 1 ^

«K

100

100

61 to 70

100

100

-

100

100

80

-

jr ~ '\ ™

f chs-t Vch-co-o-ch - \ = / ch (ch3) 2

rO

100

71 to

85

0

tals 40

70

0

-

100

100

50

-

- = not examined

Percentage of mortality

Tobacco caterpillar larva 1st stage of development

Aphid aphid

connection

"v ch-co-o-

CH (CH3) 2

J ~ \ 'N

■ if n) -ch-co-o-ch ch (ch3) 2

F0CHO x

* • \ / i

VZZL / r

F »CO

-v v-ch-co-o-

\ _ / 1 \ zz-J c ch (ch3) 2

ch-co-o-ch ch2ch3

) - // ^ S-CH-CO-O-

CH2CH2CH3

/ y f3co- ^ y-ch-co-o-c \ = j ch2ch2ch3

300 PPS ..

100

100

100

100

100

100

100 pounds egg

100

100

100

100

86

to

99

100

10 PPro

Too J2E5L

0

to 40

86 to 99

100

100

0

to

40

61

to

70

100

100

0

to 40

71 to

85

100

100

~ TÖ "ppm '

100

70

50

T

EHL

tw EE5L

100

100

100

100

100

"To EESL

100

100

100

100

r

EEÜL

0.1

0

100

100

100

90

90

a oo

3rd

>

CO H

G

?

1

0Q

- = not examined

17th

638774

Example 16 Insecticidal Activity

The insecticidal activity of the compounds of the formula I is also determined using the following test methods, in which the activity against mosquito larvae, Mexican ladybugs and cotton worms is investigated.

Malaria mosquito (Anopheles quadrimaculatus Say)

Pipette 1 ml of a solution of 35% water and 65% acetone, which contains 300 ppm of the compound to be investigated, into a 400 ml beaker containing 250 ml of deionized water, stir with the pipette and reach a concentration of 1.2 ppm. Then aliquots of this solution are removed and further diluted to 0.4, 0.04, 0.004 ppm. In order to prevent the eggs from floating on the side wall of the beaker and drying out there, a wax paper ring with a width of 0.6 cm that fits into the beaker is floated on the surface of the solution to be examined. A sieve spoon is used to hold and transfer approximately 100 eggs (0 to 24 hours old) into the beaker. Hatching is observed after 2 days at 27 ° C (80 ° F) and 50% relative humidity. The percentage mortality is shown in Table II below.

Mexican ladybird (Epilachna varivestis Mulsant)

Bean plants (Sieva lima) (two per pot) with 7.5 to 10 cm long first leaves are immersed in the solution containing 300, 100, 10 or 1 ppm of the compound to be investigated and allowed to dry in the hood. Then you take a leaf from the plant and place it in a 10 cm petri dish, which contains a moist filter paper and 10 larvae in the last stage of development (13 days before hatching) on the bottom. The day after the treatment, another leaf is removed from the plant and fed to the larvae after the remains of the first leaf have been removed. Two days later, a third leaf is fed to the larvae, which is generally the last leaf required. The fourth leaf is given on the third day after the start of treatment when the larvae have not stopped feeding. The petri dishes are then set aside and stored until the adult animals have hatched, which is the case about 9 days after the start of treatment. After the animals have emerged completely, each petri dish is checked for killed larvae, pupa or adult animals, deformed pupa or adult animals; Intermediate stages between the larval stage and the pupa stage and i5 the pupa stage and the adult stage; or for any other effect on normal moulting, normal development and appearance of dolls or adult animals.

The numerical values obtained are listed in the following Ta-2obelle II.

Cotton worm (Southern Armyworn, Spodoptera eridiana

[Cramer])

Bean plants (Sieva lima) with two folded 7.5 to 10 cm long first leaves are immersed in the treatment solutions with stirring for 3 seconds and then left to dry in a hood. After the leaves are dry, they are cut off, and each cut sheet is placed in a 10 cm petri dish containing a piece of damp filter paper and 10 third-stage cotton caterpillar larvae about 10 cm long. The petri dishes are covered and stored for 2 days at a temperature of 27 ° C (80 ° F) and a relative humidity of 50%. Mortality is counted after 2 days. The results obtained are summarized in Table II below.

Connection h2

ppm

Percentage of mortality

Mexican mosquito larvae cotton caterpillar ladybug

10 I 300

0.4

ppm

0.04 ppm

D, 00iJ ppm

1000 ppm

100 ppm

100

ppm Eppm1ppm

10 ppm

1

ppm a

oo cf30-ff y-ch-co-o-ch ch (ch3) 2

100

100

100

90

100

100

100 Ï100

100

100

100

chf2cf20- ^ \ ^ ch-c0-0-ch2

ch (ch3) 2

100

100

90

0

100

100

o a loo tö

et

Ci • t s

3 OQ

s- ^? >

dead

g W ^

& r 00 S- w s: a

3rd

s s

OQ

CHF-CF

, 0 "v 7-ch-c0-0-

2 2 \ / •

\ zrz / c ch <ch3> 2

100

100

80

100

100

0 Ï 100

/ r

AT

J36

F ^ CS-V

V-CH-CO-O-CH-i

r ° -rr ^

100

100

to

-

100

100

0

100

100

100

-

3 \ _

- / '.

1

1

99

\ _

- * CH (CH3) 2

f / ^? N ^

86

86

|

100

90

Fig-f'y-CH-CO-O-CH-ry rT

! loo up to

-

100

90

0 100

mm

\ = / CH (CH3) 2 | l ^ j

U

99

99

1

F2CHO- ^> y-CH-C0-0-CH2 ~ l ^ '^^ Y ^ - rj ^^ s

100

100

100

100

100

0

100

90

50

..

\ = / CH (CH3) 2 [I ^ J (I ^ J

- = not examined

Percentage of mortality

Mosquito larvae

Cotton 1 caterpillar

Mexican ladybug

connection

1.2

ppm

0.4 ppm

0.0T | 0.004 ppm | ppm

1000 ppm

100 ppm

10 | PPm!

300

ppm

100 ppm io ppm

1

ppm

/ T ~ V ^

F2CHO- ^ ^ CH-CO-O-CH-J ^^^ O-Y ^^ Ì

\ = / M (CH3) 2 (I ^ J

100

100

100

100

100

»

100;

100

100

50

F3C0 ^ f> V 2

n f ch2ch3

■ ch-co-o-ch.

100

100

100

100

100

70

90

>

w w r r w

►n o n>

FT e a

09

f3co

> "V

-ff 7-ch-c0-0-

\ _ / 1 Vm / r ch2ch3

f3co-r / y-ch-c0-0-ch2

\ = / œ2ch2ch3

100

100

100

100

100

100

80

90

50

100

100

100

100

100

100

90

vo f3co

-ff y-ch-co-o - \ = / ch2ch2ch3

100

100

100

100

100

70

100

100

100

cn h-co-o-ch-ch (ch3) 2

100

100

100

100

100

100

100

100

80

- = not examined

On

00 -4

638774

20th

Example 17 Insecticidal Activity

Spotted mite (Tetranychus urticae [Koch])

Bean plants (Sieva lima), the first leaves of which are 7.5 to 10 cm long, are planted with about 100 fully grown, phosphate-resistant mites per leaf, 4 hours before the examination is carried out, in order to allow eggs to be laid off before the treatment . The infected plants are then immersed for 3 seconds with stirring in the solution containing 1000, 300, 100 or 10 ppm of the active ingredient, whereupon the plants are placed in the fume cupboard to dry. After 2 days at 27 ° C (80 ° F), the mortality of the adult mites on a leaf is estimated under a stereoscopic microscope at 10X magnification. The other leaf is left on the plant for a further 5 days and then examined at 10-fold intensification in order to estimate the killing of the eggs of the newly hatched nymphs, as a result of which the ovicidal action or the remaining action can be determined. The results are summarized in Table III below.

Tobacco caterpillar (Heliothis virescens [Fabricus]) in the third stage of development

Three cotton plants with cotyledons just unfolded are dipped into the solution containing 1000 or 100 ppm of the active ingredient and then transferred to a hood for drying. After drying, each cotyledon is halved and 10 leaf sections are placed in a 28 g plastic cup containing a 5 1/2 inch dentist's tampon saturated with water, and a third stage of tobacco caterpillar is placed in the cup. The cup is closed and kept for 3 days at 27 ° C (80 ° C) and a relative humidity of 50%, after which the mortality is counted. The results obtained are summarized in Table III below.

Cabbage looper (Trichoplusia ni [Hübner]) in the third stage of development

A real leaf of a cotton plant is immersed in the solution to be examined, which contains 1000, 100 or 10 ppm of the compound to be examined, is stirred for 3 seconds, the plant is removed and the extractor 20 is left to dry. After drying, the sheet is transferred to a 9.0 cm petri dish, which contains a moist filter paper on the bottom. Then add three third-stage larvae and cover the dish with the cover. Mortality is counted after 3 days at 25 27 ° C (80 ° F) and a relative humidity of 50 ± 10%. The numerical values obtained are summarized in Table III below.

Percentage of mortality

Phosphate resistant 'tobacco caterpillar in cabbage caterpillar in' mites 3rd bit development 3rd development

stadium stage

connection

1000

ppm

300 ppm

100 ppm

10 ppm

1000 ppm

100 I 1000 ppm | ppm

100 ppm

10 ppm y-CH-CO-O-CH-j ^^ y

• CH (CH3) 2 1 ^ 1

r ° "0

100

100

80

0

100

loo | 100

100

100

CHF2CF20-T / y-CH-C0-0-CH2 - \ = / CH (CH3) 2

■ not

-

100

50

0

50

i | 100

0

-

CHF-CF-O-y '^ CH-00-0-CH-i <: ^: rN ^ 0 -

-

90

60

0

80

0

100

•

30th

0

W i „(CH3) || ^ | [IJ

-

100

100

100

100

100

100

100

-

jt \ ^

F2CKS-V y-CH-CO-O-CH-rj

\ = / ÌH (CH3) 2 (I ^ J (I ^ J

100

100

0

90

20th

100

1

1

loo;

F2CHO- ^> y-CH-C0-0-CH2—

\ = / CH (CH3) 2 [I ^ J [I ^ J

-

100

0

0

100

70

1

100

100

-

- = not examined

Percentage of mortality

Phosphate-resistant tobacco caterpillar in the cabbage caterpillar at mid 3rd developmental stage

Connection pLÖOÖ

1 ppm

300 ppm

100 ppm

10 ppm

1000 ppm

100 ppm

1000 ppm

100 ppm

10 ppm jt \ ^

F-CHO-V ^ V-CH-C0-0-CH-j | X was, (ch3.2

r ° 0

-

100

100

0

100

100 J 100

100

-

F3C0- ^ ^^ CH-CO-O-CHj ^ j ^^ O-j ^^

\ = / CH2CH3 (I ^ J (j ^ J

-

100

0

-

100

100

100

100

-

• N

F.CO-Q'y-CH-CO-O-CH-rf w ch2ch3. \ j

* 0

-

100

100

0 1 100

100 j 100

100

-

0 \ 00 -4

S

>

w w r r w

H-I IO

J-I?

Sf £

F, CO- ^ ^ -CH-CO-O-CH

if ^ l

-

80

0

60

30th

100

40

\ = / CHjCHjCHj H

M

I.

Y JZO- \

3rd

-. CN y-CH-C0-0-CH- | j ^

-

100

100

-

90

90

100

100

-

• = J CH2CH2CH3 (1st

CF3V- ^ ÇN

O ^ CH-CO-O-CH - ^^ i-O-K ^ N

-

100

100

0

100

90

100

90

0

\ == / CH (CH3) 2

- = not examined

23

638774

Example 18 Insecticidal effects via the soil

Corn Rootworm (Southern Corn Rootworm - Diabrotica un-decimpunctata howardi [Barber])

10 mg of the compound to be examined are diluted with 10 ml of acetone to form a stock solution A. Then 2 ml of this solution are diluted with acetone to 10 ml and solution B is obtained. Then a 28 g wide-mouth bottle is charged with about 0. 7 g of talc (Pyrax ABB) and add 1.25 ml of the solution to be examined to the talc, resulting in the following concentrations:

1.25 ml of solution A corresponds to an application dose of 56 kg / ha

1.25 ml of solution B corresponds to an application dose of 11.2 kg / ha.

The selected test solution is then mixed with the talc to evenly wet it before the material is dried for 10 to 15 minutes using an air jet dryer. Then 25 ml of moist, sterilized potting soil and about 0.6 g of millet seeds (as feed for the larvae) are placed in the bottles containing the compound to be examined. The bottles are closed and the contents are mixed using a vibration mixer. Then you put 10 corn rootworm larvae in each bottle at the age of 6 to 8 days. The bottles are loosely covered and placed in a room where they are kept under constant lighting at 27 ° C (80 ° F) and a relative humidity of 50%. Mortality is counted after 6 days.

In this study, a-isopropyl-4-trifluoro

methoxyphenylacetic acid a'-cyan-m-phenoxybenzyl ester 100% killing of the corn rootworms at an application dose of 56 kg / ha and 70% killing at a dose of 11.2 kg / ha.

5

Example 19

Remaining insecticidal action after the treatment of the leaves of cotton plants. Young cotton plants with at least two folded out real leaves, which are drawn in 10 cm plastic pots, are immersed in a solution of the compound to be investigated containing 65% acetone and 35% water, whereby the mixture is stirred for 3 seconds and a sheet 15 is immersed in each case. The concentration of the compound to be examined in the solutions is 30, 100, 300 or 900 ppm. of the active ingredient.

After the leaves have dried, two leaves are cut off from two plants and placed in Petri dishes 2o (90 mm X 10 mm) on moist filter paper (9 cm What-man No. 1). Five tobacco caterpillar larvae in the third stage of development are then placed on each leaf and the Petri dish is covered. The Petri dishes are then kept under constant lighting at a temperature 25 of 27 ° C (80 ° F) and a relative humidity of 50%. The larvae killed are counted after 72 hours.

The remaining plants are exposed to intense light in the greenhouse, which is switched on for 14 hours a day. Leaf samples are then populated with tobacco caterpillar larvae in the third stage of development after an exposure time in the greenhouse of 3, 7, 10 or 14 days. The percentage killing of these larvae is determined again.

638774

24th

TABLE IV

Residual insecticidal activity of the compounds examined on cotton plants using tobacco caterpillar larvae in the third stage of development

*

3rd

a u

•H

5

(0

0}

PC

ï

for fO

ro ro O

m r-l O O O

o m o o vo o \ o o co o o o o o omo © \ o o> © o o o o o o o o o

* 0000

m O

f> - r-t o o m m m o o

N 00 O H

m \ o •> »

-a- o o o omioo

VO ffi Ot m m

»-X

N o o o r-l m o o o • - »r- o o

• H r-l o o o o o o o o

CT. O O O H H H

o o o o o o o o

OiOOO H H H

W "H Ë

s Si o o o o

O O O O H n Ci

W //

r '

^ //

tN

m

Ci m o r »

M O O O

o «n o o m co o o m o o o o o m o m o

N O ON O '

en «n o r» •> CM O O O

m o «n o • ï» o * o m o o o o o m o o o o o o

HHH

rH

O O O O

m m o o vo co o o m

o o o o m in o o \ o oo o o o o o o m o o o h »

C • H) -i

■ C U tu

E

V h m o cTo o o m o m o o o o O

o o o o m o o o

H M O »

O 00

m r-l

«N

© OH

m en m c s

Oh

CQ bO

H B

S)

3 -S

O ïï

s ft

° .s

O <D

M h u a

I I

II II

rH CM

25th

638774

Example 20 Ixodicidal Activity (Action Against Ticks)

With the help of the following investigations, the effective control of mite larvae is investigated, larvae of Boophilus microplus, a host tick, which during their three developmental stages, i.e. the larval stage, the nymph stage and the adult stage can be present on a single host. In this test, a mixture of 10% acetone and 10 90% water is used, which contains 0.025.0.1, 0.5, 2.5 and 12.5 ppm of the compound to be tested. 20 larvae are introduced into a pipette which is closed at one end with a gauze material, and the solution containing the compound to be examined is drawn through the pipette with the aid of a vacuum hose, thereby simulating a spraying system. The ticks are then kept at room temperature for 48 hours, after which the mortality is determined. The results obtained are summarized in Table V below. 20th

TABLE V

Percentage kill of tick larvae (Boophilus microplus)

Compound ppm

12.15

V

0.5

0.1

0.025

CF-O-y '^ CH-CO-O-CH-f ^^ O-v ^ N W CH (C „3.2 XJ

100

100

100

100

100

The procedure described above is repeated with the difference that the active ingredient is used in a concentration of 0.1, 0.025, 0.005 or 0.001 ppm. The results obtained are given in Table VI below. 40

TABLE VI

Percent mortality from tick larvae (Boophilus microplus)

cf3o-

connection

-ch-co-o-ch ch (ch3) 2

ppm

0.1

0.025

0 * 005

0.001

100

100

80

80

The procedure described above is repeated, with the difference that the active ingredient indicated is used in a concentration of 0.1, 0.01, 0.001, 0.0001 or

0.00001 ppm. The results obtained are given in the following table Via.

638774

26

TABLE Via

Percent mortality from tick larvae (Boophilus microplus)

ppm: 0.1 0.01 0.001 0.0001 0.00001 100 100 100 50 0

The procedure is repeated, but with a concentration of the test compound of 100 ppm: 20

TABLE VIb

Percent mortality from tick larvae (Boophilus microplus)

Connection:

Example 21

The effectiveness of the compounds for formula I in combating adult substances is determined

Ticks (Boophilus microplus) using the following test method, in which the compound to be tested is dissolved in accordance with the procedure of Example 45.

27th

638774

with the difference that solutions are obtained which contain 125, 52.6, 31.2, 15.6 and 7.3 ppm of the compound to be investigated.

Then, adult, full, female ticks are immersed in the solutions to be examined for 3 seconds, 5 transferred to individual containers and kept for 48 hours at 27 ° C (80 ° F) and a relative humidity of 50%. After the storage period has elapsed, the ticks are examined and the egg deposits are counted. Rich female ticks that have not separated eggs are rated as dead. The results obtained are summarized in Table VII below.

TABLE VII

Ixodicidal activity against adult ticks (Boophilus microplus)

Connection percentage mortality of adult ticks at a concentration of (pian)

cf30

n 'ch (ch3) 2

125

62 j 5

31.2

15.6

7.3

ppm ppm ppm ppm ppm

1 100

100

99 j4

98; 8

87; 2

Example 22

The effectiveness of the compounds of 35 formula I in combating larvae of the golden fly (Cochliomyia hominivorax), a very dangerous livestock pest, is investigated, five larvae of Cochliomyia hominivorax in the first stage of development with a mixture of ground beef (8.0 g), Blood (7.0 ml), 40 water (2.1 ml) and 0.9 ml of a formulation containing 1, 5 and 25 ppm of the compound to be tested,

feeds.

For the evaluation, two repetitions are carried out on 20 larvae per dose. The larvae are supplied with the nutrient medium ad libitum for 24 hours.

At the end of this period, the number of larvae killed for each treatment and each repeat treatment is determined and the percentage mortality is calculated. The numerical values obtained are compiled in Table VIII below.

TABLE VIII

Evaluation of the compounds according to the invention with regard to controlling larvae of the golden fly (Cochliomyia hominivorax)

connection

Percent mortality at a concentration of:

1 ppm 5 PPm 25 ppm cf3O-

// w cn

-ch-co-o-ch-

ch (ch3) 2

2.4

69.2

100

638774

28

Example 23

Determination of the LCS0 value of the compounds of the formula I in relation to tobacco caterpillars on cotton plants

Young cotton plants with at least two real leaves folded out, which are drawn in 10 cm plastic pots, are immersed in a solution of the compound to be investigated in a mixture of 65% acetone and 35% water, each immersing one leaf and the liquid stirs. The active substance concentration of the solutions used is 1.1, 2.8, 7.5, 20, 60 and 150 ppm.

After the leaves have dried, two leaves are cut off from two plants and placed in Petri dishes (90 mm X 10 mm) on moist filter paper (9 cm, Whatman No. 1). Then each leaf is covered with five tobacco caterpillar larvae in the third stage of development and the petri dish is covered. The trays are then stored with 5-hour lighting, a temperature of 27 ° C (80 ° F) and a relative humidity of 50%. The larvae are counted after 72 hours. Each treatment is repeated four times. The numerical values obtained are compiled in the following Table IX, from which it can be seen that the compound according to the invention is two to five times more effective in combating tobacco caterpillar larvae than the conventional compounds tested in the same way.

TABLE IX

Determination of LCS0 values when using the compound to control tobacco caterpillars in the third stage of development

Example 24

Determination of the LCS0 value of the compounds used against adult 4J mosquitoes (Anopheles quadrimaculatus Say)

The compounds to be evaluated are dissolved in the desired concentration (in ppm) in acetone. Then 0.15 ml of the insecticide solutions, which are to be applied via an aerosol application, are pipetted into the upper part of an atomizer and passed through the atomizer nozzle. The atomized droplets are directed onto the caged mosquitoes 55 (containing 25 adult females per cage) using an air jet (at 6.436 km / h (4 miles / hour)), with the treatment during The mosquitoes are then anesthetized with carbon dioxide (3-4 seconds) and transferred to storage cages, and the treated mosquitoes are then placed in 60 of these storage cages at 29.4 ± 0.55 ° C (85 ± 1 ° F). and a relative humidity of 46 ± 2%. Mortality is counted after 24 hours.

The numerical values obtained are listed in the following Table X, from which it can be seen that the compound according to the invention is approximately four times as effective as the compound of the prior art in combating adult mosquitoes (Anopheles quadrimaculatus).

29

638774

table x

Determination of the LCS0 values of the investigated compounds in the control of washed-out female mosquitoes (Anopheles quadrimaculatus)

Connection cf3o-

\ / f

\ = / c

CH (CH3) 2

Concentration ppm

Percentage of mortality approximate LC50

(ppm)

0.5

10th

1.0

10th

2.0

5

3.0 5.0 15.0

5

52

95

5.0

(1) 10

(2) 6

10.0 20.0 40.0 80.0

14

26

66

60

62

73

92

90

**

Cl-

t \

r \ v-ch-co-o-

\ r = Z / C

ch: (ch3) 2

(1) 21

(2) 18; 8

* = Numerical values determined in two different examinations. ** = described in South African patent application No. 63/4462 (1) = test (1) (2) = test (2)

Example 25

Residual insecticidal activity determined by applying the compound to be examined in a small volume

The compounds to be investigated are dispersed in such a quantity in a mixture of 65% acetone and 35% water that there is an application dose of 0.08 kg of the compound per active substance in 19.311 (5.1 gallon) water. Cotton plants are then introduced into a spraying space and sprayed from above with the aid of a stationary spraying device as they pass under the spraying device.

After the leaves have dried, two 40 leaves each are cut from two plants and placed in petri dishes (90 mm × 10 mm) on moist filter paper (9 cm What-man No. 1). Then put five tobacco caterpillar larvae in the third stage of development on each leaf and cover the petri dish. The petri dishes are then stored at 45 constant lights and at a temperature of 27 ° C (80 ° F) and a relative humidity of 50%. The larvae killed are counted 72 hours later.

The remaining plants are then transferred to the greenhouse and irradiated with intense light. Then leaf samples are examined again after 3, 7, 10 or 14 days with tobacco caterpillar larvae in the third stage of development. The numerical values obtained are summarized in Table XI below. 55

638774

30th

TABLE XI

Remaining insecticidal activity against tobacco caterpillars, determined by applying the active substances to be examined in small volumes to cotton plants cf3o

Connection jt ~ \. 'N

■ V y-CH-CO-O-CH

\ = / ch (ch3) 2

Order |

dose l '- = - r, f kg / ha

Days of remaining effect

0.08 II 95

2 * i

0.03

100

90

2 **

0.03

10th

90

2 **

14

80

0.03

Cl-V V-CH-CO-O

CN

CH (CH3) 2 l ^ JJ l ^ lj

control

0.08 95

0.1

90

3; 0

80

2.5

80

0.78

50

1.6

92; 5

88.5

87.5

30th

41; 3rd

67 j 5

1 = mean percentage mortality 20 TBW / point (mortality count after 72 hours)

2 = mean of the damage caused by feeding / four repetitions

Example 26 Ixodicidal Activity

The test method described in Example 20 is used to determine the ixodicidal activity of the 30 compounds according to the invention in active compound concentrations of 12.5, 2.5, 0.5, 0.1, 0.02 and 0.004 ppm. The results obtained are shown in Table XII below.

TABLE XII

Percent mortality from tick larvae (Boophilus microplus)

Example 27

The effectiveness of the compounds according to the invention in combating adult multi-host ticks (Rhipicephalus sanguineus [RS]) and der-macentor variabilis [DV]) in dogs is determined, for which purpose the following test method is used, in which the test compound is prepared in this way as described in Example 20. The active ingredient is used in such an amount that solutions are obtained which contain 100, 10 or 1 ppm of the compound to be investigated.

Then, mature, full, female ticks are immersed in the solutions to be examined for 3 seconds, then placed in individual containers and kept for 48 hours at 27 ° C (80 ° F) and a relative

«Moisture up to 50%. Towards the end of the storage period, the ticks are examined and the egg laying is counted. Fat female ticks that have not laid eggs are rated as killed. The results obtained are summarized in Table XIII below.

60

31 638774

TABLE XIII

Ixodicidal activity against adult ticks, namely Rhipicephalus sanguineus (R.S.) and Dermacentor variabilis (D.V.)

connection

Concentration Percentage (ppm) Mortality r.s. d.v.

100 100 100

100 90 60

Example 28

Investigation of the action of the compounds of formula I ^

in vitro against adult fleas of the species Ctenoce-phalis felis

In this test, 10 adult fleas of the species Ctenocephalis felis are sprayed with an acetone / water solution which contains 100, 50, 10 25 and 1 ppm of the compound to be investigated for 30 seconds.

After this treatment, the fleas are kept for 48 hours at room temperature and a relative humidity of 80%, after which the fleas are examined after 24 hours and after 48 hours and counted for 30 mortality. The numerical values obtained are summarized in the following table XIV.

TABLE XIV

F2CHCF2

cn ch-cooch-

ch (ch3) 2

Hours Percent Mortality At Concentration Of (ppm)

Treatment 100 5Ö10 1

u

24 48

100 100

70 90

0 20

0 0

F2CHCF2

h-cooch ch (ch3) 2 u a

24 48

80 90

50 50

0 0

0 0

The procedure is repeated, but with test compound concentrations of 80, 40, 20, 10, 5 and 2.5 ppm, respectively. The values given are mean values of two repetitions at each concentration, unless stated otherwise.

638774

Action against fleas:

32

TABLE XlVa

connection

F2CHO-

-CH-CO-O CH (CH3) 2i

Hours after d. treatment

Percent mortality at a concentration of (ppm)

80 40 20 10 5 2.5

24th

100 '

70

45 50

40 20

+) = only one test

Example 29

The procedure of Example 27 is repeated, 25 but male and female adult multi-host ticks (Rhipicephalus sanguineus [R.S.] and Dermacentor variabilis [D.V.]) are used. The amounts of active ingredient are used in such a way that solutions with 1, 0.1, 0.01 or 0.001% of the test compound are obtained. Mortality 30 is counted 24 and 48 hours after treatment.

The results are summarized in Table XV.

TABLE XV

Ixodicidal activity against adult ticks, namely Rhipicephalus sanguineus (R.S.) and Dermacentor variabilis (D.V.) (mean values from two repetitions, unless stated otherwise)

connection

F2CKO

«J ~ \ c

\ / I

c

CH-CO-O-CH '

CH (CH3) 2

Concentration (?,)

Percent mortality R. «sanouinsus D. variabilis

24 S - a. 43 hours or 2-hour

100 100 * 100 100

100 * 100

100 * -100 * • 100 65

48 hours

100

65

*) = only one test

B.Example 30

The effectiveness of the compounds of the formula I in combating the flies Musca autumnalis is demonstrated in the following experiments, in which one day old fly larvae are fed on cow manure which contains 0.13, 0.25 or 0.50 ppm of the test compound.

Two replications with 10 larvae per dose or per comparison experiment are used in the evaluation.

For each amount of active ingredient, an acetone solution with the corresponding amount of the test compound is added to 1 kg of fresh cow manure and mixed in an electric mixer for 1 minute. For the comparison test, the cow dung is only mixed with acetone. The manure samples are spread over four paper cups. At each concentration (and in the comparative experiments) two beakers are infected with the one-day fly larvae. The cups are kept at about 27 ° C (80 ° F) and a relative humidity of 7 days

50% held. Then the dolls are counted and weighed and placed in plastic ampoules in which they hatch and die. The dead flies are counted and the ss percentage is calculated. The values obtained are shown in the following table XVI.

33

TABLE XVI

638774

Evaluation of the compounds according to the invention in vitro as a possible feed additive for combating the flies Musca autumnalis in cow manure

(Means of two repetitions)

Connection f2cho o

\ / C

ch-co-o-ch-

ch (ch3) 2

Manure concentration (ppm)

Comparison :

0.13 0.25 0.50

0.0

86.8

78.9 97.3

0, 0

90.6 84.4 9.19

V

Claims (12)

638774 2. The method according spoke 1, characterized in that one uses an optical isomer of a compound of formula I. 2nd PATENT CLAIMS 1. A method of combating insects and mites with the exception of the therapeutic treatment of the animal body, characterized in that the insects and mites, their habitat, their breeding grounds or their feed with an insecticidal or acaricidally effective amount of an m-phenoxybenzyl ester 2- (haloalkoxy, alkylthio, alkylsulfinyl or alkylsulfonylphenyl) alkanoic acid of the formula: R-CF2X CH-C-O-CH where the substituent of the formula RCF2X is in the m or p position to the carbon atom to which the alkanoic acid ester group is attached, X sulfur, oxygen, the sulfinyl or sulfonyl group, R hydrogen, fluorine, chlorine, the difluoromethyl or trifluoromethyl radical, R2 which means ethyl, n-propyl, isopropyl, tert-butyl or isopropenyl group and R3 is hydrogen or the cyano group. 3. The method according to claim 1, characterized in that one uses an m-phenoxybenzyl ester of a compound of formula I, wherein X is oxygen. 4. The method according to claim 1, characterized in that one uses a-isopropyl-4-trifluoromethoxyphenylacetic acid a - cyan-m-phenoxybenzyl ester. 5. The method according to claim 1, characterized in that one uses a-isopropyl-4-trifluoromethoxyphenylacetic acid-m - phenoxybenzyl ester. 6. The method according to claim 1, characterized in that a-isopropyl-4-difluoromethoxyphenylacetic acid-a - cyan-m-phenoxybenzyl ester is used. 7. The method according to claim 1, characterized in that one uses a-ethyl-4-trifluoromethoxyphenylacetic acid-a-cyan - m-phenoxybenzyl ester. 8. Insecticidal agent, characterized in that it contains a compound of the formula I given in claim 1, an emulsifier, a surface-active agent and a solvent. 9. Composition according to claim 8, characterized in that it contains an optical isomer of a compound of formula I. 10. Composition according to claim 8, characterized in that X is oxygen. 11. A process for the preparation of a compound of the formula I given in claim 1, characterized in that a compound of the formula: rcf2x (III) (I) implements. 12. A process for the preparation of compounds of the formula I given in claim 1, in which X represents the sulfinyl or sulfonyl group, characterized in that 10 a compound of the formula I is prepared by the process according to claim 11, in which X represents sulfur, and this oxidizes.