HU180418B - Insecticide and acaricide compositions and process for producing esters of phenyl-alkanne-carboxylic acids as active agents - Google Patents

Abstract

Phenoxybenzyl esters of formula (I) and their optical isomers are new. In (I), R = F, Cl, CF2H or CF3 and RCF2O is at the meta- or para-posn. R2= ethyl, n- or isopropyl, tert. butyl or isopropenyl. R3 is H or CN. Also new are thephenylalkanoic acids of formula (II). In (II), R1 is R or H. X is S, O, SO or SO2. R12 is R2 other than isopropenyl. (I) are useful for control of insects and mites in plant protection and veterinary medicine. They have a systemic effect and, unlike the pyrethrins, good residual activity. They are esp. used to control Heliothis virescens and mosquitoes. (II; X = O) are intermediates; no use is given for other (II).

Description

The present invention relates to insecticidal and acaricidal compositions, and to processes for the preparation of the phenylalkanoic acid esters of the formula I and their optical isomers, which are the active ingredients of the compositions. In formula I, 5-X is sulfur, oxygen, -S (O) - or -S (O ₂ ) -;

- R is hydrogen, fluorine or chlorine or difluoromethyl or trifluoromethyl; R ₂ is ethyl, η-propyl, isopropyl, tert-butyl or isopropenyl;

- R ₃ is hydrogen or cyano.

A 73/4462. There are published South African patent application No. 650 701 and Belgian Patent specification using ⁸ formulas several phenyl> acetic acid ester is disclosed, including the 3'-phenoxy | benzyl alpha-isopropyl-4-methoxyphenyl acetic acid, 3 > -phenoxybenzyl alpha-isopropyl-3-methoxyphenyl acetic acid, 3'-phenoxybenzyl alpha-isopropyl-4 esters of 3'-phenoxybenzyl-alpha-isopropyl-3-chlorophenyl-acetic acid and 3'-phenoxybenzyl-alpha-isopropyl-4-fluorophenylacetic acid. As used herein, several compounds are claimed to be potent pesticides and can be used to control a wide variety of insects and mites. 25

However, the foregoing anteriority does not disclose the m-phenoxybenzyl esters of 2-haloalkyl (oxy, thio, sulfinyl, or sulfonyl) -phenylalkanoic acids, nor does it contain a synthesis useful for the preparation of these compounds.

It has been found that the compounds of the formula I are not only potent insecticides, but also have very strong ticks and can be used systemically. The compounds can be effectively used to protect domestic animals and laboratory animals from attack by insects and ticks.

The compounds of the present invention exhibit a residual iododicidal and insecticidal activity greater than that of known pyrethroid compounds such as permethrin, phenothrin or allethrin and are excellent for controlling tobacco pests and mosquitoes.

The compounds of formula (I) are prepared by reacting a phenylacetyl halide of formula (II), X, R and R ₂ as defined above, A being halogen, preferably chlorine, with m-phenoxy of formula (III). with a benzyl alcohol derivative R ₃ is as defined above. The reaction is usually carried out in the presence of a solvent such as diethyl ether, benzene or toluene and an acid acceptor, preferably at a temperature of from 10 to 30 ° C. Preferably the acid acceptor is tertiary amines such as triethylarine, trimethylamine or pyridine. The reaction is illustrated in Scheme A.

Preferred compounds are those compounds of formula (I) wherein the substituent XF30 of RCF _{2 is} para and X

R, R ₂ and R ₃ are as defined above or the substituent RCF ₂ X is in the meta position and X, R, R ₂ and R ₃ are as defined above.

Within these vegyiiletcsoportokon especially interesting are those compounds having formula (I) wherein X is oxygen or sulfur, R is hydrogen or fluoro, _R2 is ethyl, n-propyl or isopropyl and R ₃ is hydrogen or cyano.

The compounds of formula I may have different optical isomers. Thus, the compounds of formula R ₃ is hydrogen place of (I) _the R substituent contains a chiral carbon atom, and, consequently, d- and 1-isomeric pairs are formed during synthesis. In the case where R ₃ is an alpha-cyano group, the compound also contains an additional chiral carbon atom and a further pair of d- and 1-isomer is formed.

For example, it has been found that, when alpha-isopropyl-4-trifluoromethoxyphenylacetic acid is mixed with 0.5-1.0 molar equivalents of (-j-alpha-phenylethylamine) in the presence of a suitable solvent such as ethanol or aqueous ethanol. , the salt of (+) - acid precipitates. When acidified, the salt is liberated, which generally consists of the (+) isomer in greater than 85%. A better resolution can be achieved by formation of (-) - alpha-phenylethylamine. the salt is recrystallized or the resolution is repeated using fresh (-) - alpha-phenylethylamine The fully resolved (+) - alpha-isopropyl-4-trifluoromethoxyphenylacetic acid is m-phenoxybenzyl or alpha- cyano-m-phenoxybenzyl esters are about twice as potent insecticides as racinic acid esters, and a further increase in activity can be achieved for the alpha-cyano-m-phenoxybenzyl ester if the corresponding optically active alpha-cyano-m-phenoxybenzyl -alcohol.

The starting material for the phenylacetyl halide of formula (II) wherein R ₂ is ethyl, n-propyl or isopropyl is X and R are as defined above, from a suitably substituted toluene derivative of formula (IV): X is as defined above. The synthesis consists of five steps and is illustrated in Scheme B.

First, the toluene derivative (IV) is halogenated with bromine, chlorine, N-bromosuccinimide or other halogenating agent. The halogenation is conveniently carried out in the presence of an inert organic solvent, such as carbon tetrachloride, using light, benzoyl peroxide or azo-bis-isobutyric acid nitrile to initiate the reaction. The resulting benzyl halide of formula (V), R and X being as defined above, is reacted with sodium or potassium cyanide in the presence of dimethyl sulfoxide, ethanol or other solvent at elevated temperatures. The resulting phenylacetonitrile of formula (VI), wherein R and X are as defined above, can be readily alkylated with an alkyl halide in the presence of a base and an inert organic solvent. Polyoxyacycloalkenes (crown ethers) have proved to be useful catalysts for this reaction. The resulting alpha-alkylphenylacetonitrile of formula VII, R, R _a and X being as defined above, is hydrolyzed with alkali metal hydr 2 oxide in the presence of alkylene glycol and water. The resulting acid of formula VIII - R, R ₂ and X are as defined above - is treated with a halogenating agent such as thionyl chloride or thionyl bromide, preferably in the presence of an aromatic solvent such as benzene or toluene. In this way, when thionyl chloride is used, the starting compound of formula IIa is obtained - R, R ₃ and X are as defined above.

In the case of the preparation of compound ¹ according to the invention in which the group RCF ₂ X has a para-position in the molecule, it is also possible, as illustrated in Scheme C, to chloromethylate a benzene derivative wherein R represents the above, Y is oxygen or sulfur, and the resulting benzyl chloride of formula (X) - R and Y are as defined above - is used instead of the compound of formula (V) to prepare the starting material of formula (II). Chloromethylation of the compound of formula (IX) is carried out with a mixture of paraformaldehyde or trioxane, zinc chloride and dry hydrogen chloride gas.

The alpha-alkyl-3- (or 4) trifluoro-methoxy-phenylacetic acid required ⁰ m-phenoxybenzyl and .alpha.-cyano-m-phenoxybenzyl benzilésztereinek preparation of alpha-alkyl-3 (or 4)-trifluoro The methoxyphenylacetic acid halide can also be synthesized by starting from m- or p-methoxy-phenylacetonitrile. Thus, the methoxyphenylacetonitrile of formula (XI) is reacted with an alkyl halide in the presence of a polyoxa-cycloalkene and a base. Of course, it is obvious that m-methoxyphenylacetonitrile gives alpha-alkyl-3-methoxyphenylacetonitrile, whereas p-methoxyphenylacetonitrile gives alpha-alkyl-4-methoxyphenylacetonitrile. It is understood that the position of the methoxy group attached to the phenyl group of the phenylacetonitrile determines the position of the trifluoromethoxy group of the final product.

The alkylation of the alpha-alkyl-3 (or 4) -methoxyphenylacetonitrile of formula (XII) - R ₂ is ethyl, n-propyl or isopropyl - is carried out with boron tribromide, preferably a solvent such as ethylene. in the presence of chloride. The resulting phenol of formula XIII - R ₂ is as defined above - is reacted with thiophosgene and a base in the presence of a solvent such as chloroform to give the chlorothio formate ester of formula XIV - R ₂ above. The ester of formula (XIV) is converted to alpha-alkyl-3 (or 4) -trifluoromethoxyphenylacetonitrile of formula (XV) with molybdenum hexafluoride. - R ₂ is as defined above with ethylene glycol and alkali metal hydroxide in the presence of water and g is hydrolyzed to the general formula (XVI) alfaalkil-3 (or 4) trifluoro-methoxy-phenyl-acetic acid.

(XVI) is converted to the acid of formula with thionyl chloride of the corresponding (XVII) with an acid chloride of formula θ - R ₂ is as defined above. The reaction is carried out in an aromatic solvent such as benzene or toluene.

The acid chloride of the general formula (XVII) corresponding to the starting compound (II) is prepared with m5-phenoxybenzyl alcohol or alpha-cyano-m-phenoxy.

with benzyl alcohol to form the compound of formula (I).

The above reactions are illustrated in Scheme D. In the formulas, R ₂ is ethyl, n-propyl or isopropyl, R ₃ is hydrogen or cyano.

While the methods depicted in Scheme B are generally applicable to the preparation of the compounds of the present invention, it has been found that in the case of nitrile compounds in which RCF ₂ X is HCF ₂₀ or HCF _is S, the alkali hydrolysis group is HCF _2. may break off. However, in our studies, it has been discovered that the cleaved group can be reintroduced into the molecule by reacting the appropriate phenol or thiophenol with chlorodifluoromethane in a mixture of aqueous alkaline solution and dioxane.

The synthesis of compounds containing the HCF ₂ O group is illustrated in Scheme E. In the scheme, an alpha-alkyl-3 (or 4) -methoxyphenylacetonitrile of formula (XII) - R ₂ is as defined above - with the aid of a hydrobromic acid solution of the corresponding alpha-alkyl-3 ( or 4) -hydroxyphenylacetic acid - R ₂ is as defined above. The latter compound is treated with aqueous alkali klórdifluormetánnal and dioxane, and thus the formula (XIX) of alpha-alkyl-3 (or 4), difluoro-methoxy-phenylacetic acid obtained in the above _R2. Compounds of formula (XIX) may be converted to esters of formula (I) according to Scheme D.

It will be noted that although the process shown in Scheme B is suitable for the preparation of compounds of formula I wherein X is -S (O) - or -S (O) ₂ - it is often more convenient to employ X an acid of formula VIII or an ester of formula I containing a sulfur atom and then oxidizing the sulfur atom to a -S (O) - or -S (O) ₂ - group with a suitable oxidizing agent such as m-chloroperbenzoic acid, sodium periodate or hydrogen peroxide.

Compounds of formula I wherein R ₂ is tert-butyl, wherein R and R ₃ are as defined above, are prepared by reacting an m- or p-substituted benzaldehyde with tert-butyl magnesium chloride. The resulting neopentyl alcohol derivative is chlorinated with thionyl chloride. The resulting chloride compound is made into a Grignard reagent using magnesium in tetrahydrofuran and then carbonized to form the carboxyl group.

The above reaction scheme is illustrated in Scheme F, by way of example of alpha-tert-butyl-3 (or 4) -trifluoromethoxyphenylacetic acid. The resulting acid of formula (XXIII) can be converted to the corresponding ester of formula (I) as described in Scheme A.

For the preparation of compounds of formula I wherein R ₂ is isopropenyl, R and R ₃ are as defined above, by reacting the corresponding meth or para-substituted phenylacetic acid with two molar equivalents of isopropyl magnesium chloride. reacting in the presence of acetone, converting the hydroxy acid formed to an ester, and then dehydrating the hydroxy ester with phosphorus pentoxide. The procedure is illustrated in Scheme G by the example of alpha-isopropenyl-3 (or 4) -trifluoromethoxyphenylacetic acid (m-phenoxybenzyl) ester (1b).

When proceeding as shown in Scheme B or D, it is not necessary to isolate the alpha-cyano-m-phenoxybenzyl alcohol precursor. In many cases, it is expedient to employ nt-phenoxybenzaldehyde, an alkali metal cyanide such as sodium cyanide and the corresponding alpha-substituted-2-haloalkyl (oxy, thio, sulfinyl or sulfonylphenylacetyl). reacting the halide mixture in one step to form the final alpha cyanoester.

The novel compounds of formula (I) of the present invention are highly effective in controlling ticks and various insects, particularly insects, such as dinoflagellates, scaly wings, hardwings and solids, both on contact and in the stomach.

The compounds of the present invention have very high residual insecticidal activity on plant tissue, are effective in soil, and are surprisingly effective against ticks. In addition, the animals are protected against attack by insects and ticks when the compounds are administered orally or parenterally, or in the form of a topical insecticide or acaricide.

The compounds of formula I do not need to be combined with a stabilizing agent to form a stabilized insecticidal and acaricidal formulation, although they may be combined with other biologically active compounds such as pyrethroid activators such as piperonyl butoxide, sesamex or isosafrol. n-octyl sulfoxide.

The compounds of formula I may also be combined with known insecticides such as phosphates, carbamates, formamidines, chlorinated hydrocarbons or halobenzoyl ureas.

For controlling insects attacking growing plants and / or harvested crops such as stored grain, insecticidal compounds of the invention may be applied to the foliage of the plant, the site of insects and / or the food of the insects. Generally, the active compound will be in the form of a dilute liquid spray, but may also be used in the form of an aerosol, powder, granulate or wettable powder formulation.

Of the liquid sprays, oily sprays or emulsifiable concentrates are preferred and the latter can be further diluted for use. These formulations are usually dispersed in water in the form of liquid concentrates for ease of handling and transport, and are then applied as a thin spray to the foliage of the plant, the soil or the surface to be treated.

A typical emulsifiable concentrate that can be used in a variety of crops such as cereals, corn, kale, pumpkin, cotton, tobacco, soybeans, ornamental plants, shrubs, and the like. may contain about 20% by weight of active ingredient, 4% by weight of emulsifier, 4% by weight of surfactant, 25% by weight of organic solvent such as cyclohexanone and about 47% by weight of petroleum based solvent. The emulsifier may be a substance known per se, for example, for use in pyrethroid formulations. The petroleum-based solvent contains at least 83% by volume of aromatic compound.

When the compounds of the invention are used as systemic veterinary insecticides and acaricides, they can be administered orally or parenterally to the host animal. For oral administration, the compounds may be used as any oral pharmaceutical preparation, such as in the form of a pill, capsule, tablet or solution. The pharmaceutical compositions may be prepared by any of the carriers conventionally used in the preparation of pharmaceuticals, in a manner known per se.

Alternatively, in the treatment of animals, the active ingredient is added to the animal feed in an amount of 0.0001-0.1% by weight, preferably 0.001-0.05% by weight.

If desired, the systemic insecticidal and acaricidal agent may be administered subcutaneously, intramuscularly or intraperitoneally, and the active ingredient is then distributed through the animal's circulatory system. In practice, the active ingredient may be dissolved or dispersed in a pharmaceutically acceptable carrier such as water, propylene glycol, vegetable oil for administration.

The compounds of the present invention are effective in protecting a wide variety of animals, especially cattle and domestic animals such as cattle, sheep, horses, dogs, cats and the like. fleas, mosquitoes, flies, ticks, etc. from attack.

Particularly preferred insecticides and acaricides among the compounds of the invention are: alpha-isopropyl-4- (trifluoromethoxy) phenylacetic acid (m-phenoxy) benzyl ester;

alpha-isopropyl-4- (trifluoromethoxy) -phenyl-acetic acid (alpha-cyano-m-phenoxy) -benzyl ester;

alpha-isopropyl-3- (trifluoromethoxy) -phenyl-acetic acid (alpha-cyano-m-phenoxy) -benzyl ester;

alpha-isopropyl-4- (chloro-difluoromethoxy) -phenyl-acetic acid (alpha-cyano-m-phenoxy) -benzyl ester;

alpha-isopropyl-4- (1,1,2,2-tetrafluoroethoxy) phenylacetic acid (- m -phenoxy) benzyl ester;

alpha-isopropyl-4-pentafluoroethoxy-phenylacetic acid (alpha-cyano-m-phenoxy) -benzyl ester;

alpha-ethyl-3-trifluoromethoxyphenylacetic acid (m-phenoxy) benzyl ester;

alpha-n-propyl-4- (chloro-difluoromethoxy) -phenyl-acetic acid (alpha-cyano-m-phenoxy) -benzyl ester;

alpha-tert-butyl-4- (trifluoromethoxy) phenylboronic acid (alpha-cyano-m-phenoxy) benzyl ester;

alpha-isopropyl 4- (difluoromethoxy) phenylacetic acid (alpha-cyano-m-phenoxy) -benzyl ester;

alpha-isopropyl-4- (trifluoromethylthio) -phenylacetic acid (alpha-cyano-m-phenoxy) -benzyl ester;

alpha-ethyl-4- (trifluoromethylsulfinyl) -phenyl-acetic acid (m-phenoxy) -benzyl ester;

alpha-isopropyl-3- (difluoromethylsulfonyl) -phenyl-acetic acid (alpha-cyano-m-phenoxy) -benzyl ester;

alpha-ethyl-4- (trifluoromethoxy) -phenyl-acetic acid (alpha-cyano-m-phenoxy) -benzyl ester and alpha-isopropenyl-4- (trifluoromethoxy) -phenylacetic acid (alpha-) cyano-m-phenoxy) benzyl ester.

The invention is illustrated in detail by the following examples.

Example 1 Preparation of p- (1,1,2,2-Tetrafluoro-extoxi) -toluene

A mixture of 10.8 g (0.100 mol) of p-cresol, 1.67 g (actual content 1.43 g, 0.0255 mol) of potassium hydroxide (in the form of pastilles) and 70 ml of dried dimethylformamide is kept at 68 ° C. , and with stirring with a magnetic stirrer, tetrafluoroethylene and nitrogen were bubbled into the mixture for 1 hour. Dilute with water (250 mL) and extract with ether (100 mL). The ethereal solution was washed with 200 mL of 5% sodium hydroxide solution and then with 2 x 400 mL of water. The ethereal solution was dried, filtered and evaporated on a film evaporator. 18.14 g (87%) of p- (1,1,2,2-tetrafluoroethoxy) -toluene are obtained.

Analysis calculated for C ₉ H ₄ F O _S Calc'd: C, 51.93% by weight, 3.87% by weight II, F 36.51 SRA ly 5 Found% C 52.06 H 3.76 weight weight %, Γ 41.52% by weight.

Example 2 Preparation of p- (1,2,2-Tetrafluoroethoxy) benzyl bromide

118.45 g (0.569 mol) of p- (1,1,2,2-tetrafluoroethoxy) -toluene, 123.00 g (0.691 mol, 121 mol%) of N-bromosuccinimide, 1.00 g (0.00413 mole) of benzoyl peroxide and 350 ml of carbon tetrachloride was stirred and refluxed for 2.25 hours. After cooling, the reaction mixture was diluted with 350 ml of carbon tetrachloride, filtered, dried over sodium sulfate, filtered and concentrated on a rotary evaporator. 160.99 g (99%) of a clear red oil are obtained. This product is used for further reactions. Infrared and MMR showed p- (1,1,2,2-tetrafluoroethoxy) benzyl bromide.

Example 3 Preparation of p- (1,1,2,2-Tetrafluoroethoxy) phenylacetonitrile

To a solution of 160.99 g (0.561 mole) of p- (1,1,2,2-tetrafluoroethoxy) benzyl bromide in 500 ml of anhydrous alcohol is added 75.1 g (1) with stirring at 75 ° C for 40 minutes. (15 moles) of hot potassium cyanide in 140 mL of water. The resulting mixture was refluxed for 1.75 hours. The reaction mixture was allowed to stand overnight and then poured into a mixture of water (500 mL) and ether (400 mL). The combined ethereal solutions were washed with water (2 x 500 mL), dried over sodium sulfate, filtered and concentrated on a rotary evaporator. The residual 114.95 g of oil was fractionated in vacuo. 37.10 g (28%) of p- (1,1,2,2-tetrafluoroethoxy) phenylacetonitrile are obtained, m.p. 85-100 ° C / 0.29 mm Hg.

Example 4 Preparation of alpha-isopropyl-p- (1,1,2,2-tetrafluoroethoxy) phenylacetonitrile

39.85 g (0.171 mol) of p- (1,1,2,2-tetrafluoroethoxy) p

1L nylacetonitrile, 3.71 g (0.00996 mol, 5.8 mol%) of 2,3,11,12-dicyclohexyl-1,4,7,10,13,16-hf.xaoxacyclooctadecane, 22.0 A mixture of 2-bromopropane (28.8 g, 0.234 mol), benzene (55 ml) and 50% sodium hydroxide (55 ml) was stirred for 45 minutes. During this time, the reaction mixture heats from 25 ° C to 43 ° C. The reaction mixture was then heated at 45 ° C for 16.5 hours.

The mixture was diluted with water (200 mL) and extracted with ether (200 mL). The ethereal solution was washed with 400 ml of 12% hydrochloric acid, 200 ml of 5% hydrochloric acid and 300 ml of water, dried over sodium sulphate, filtered and evaporated. The residual oil (47.13 g) was fractionated in vacuo. 34.83 g (74%) of alpha-isopropyl -? - (1,1,2,2-tetrafluoroethoxy) phenylacetonitrile are obtained, m.p. 83-85 ° C / 0.055-0.090 mmHg.

Analysis calculated for C ₁₃ H ₁₃ F ₄ NO: 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%.

Example 5

Preparation of 3-Methyl-2- [p- (1,1,2,2-tetrafluoroethoxy) phenyl] butyric acid

48.0 g (0.60 mole) of 50% sodium hydroxide, 21.78 g (0.0791 mole) of alpha-isopropyl-p- (1,1,2,2-tetrafluoroethoxy) phenylacetonitrile and A mixture of ethylene glycol (240 ml) was heated at 135 ° C for 12 hours with stirring. The reaction mixture was diluted with 6O0 mL water and washed with 2 x 100 mL ether. The aqueous phase was acidified with concentrated hydrochloric acid and extracted twice with 300 ml of ether. The ethereal solution was washed twice with water (500 mL), dried over sodium sulfate, filtered ₍ and evaporated) to give 20.74 g (89%) of a brown solid, mp 92-97 ° C (hexane).

Analysis calculated for C ₁₃ H ₄ F ₄ O ₃ : C, 53.06%; H, 4.80%; F, 25.83%;

Found: C, 53.04%; H, 4.79%; F, 25.93%.

Example 6

Preparation of 3-Methyl-2- [p- (1,1,2,2-tetrafluoroethoxy) phenyl] butyryl chloride

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, A mixture of thionyl chloride (28 moles) and dried benzene (75 mL) was heated under reflux for 4 hours. The reaction mixture was concentrated and the residue was diluted with benzene (50 mL) and concentrated again. 22.46 g (106%) of a clear dark brown liquid are obtained. The product thus obtained is used for further reaction steps. The resulting liquid corresponds to the title compound in terms of its infrared spectrum.

'7th Example 4 Preparation of alpha-isopropyl-4- (1,1,2,2-tetrafluoroethoxy) phenylacetic acid (m-phenoxy) benzyl ester

To a mixture of 6.81 g (0.034 mol) of m-phenoxybenzyl alcohol, 3.0 ml (2.95 g, 0.0372 mol) of dried pyridine and 20 ml of methylene chloride is added 10.6 g (0.034 g) of alcohol in 20 minutes with stirring. mole) of 3-methyl-2- [p- (1,1,2,2-tetrafluoroethoxy) phenyl] butyryl chloride in 20 ml of methylene chloride. The reaction mixture was stirred for 66 hours at room temperature and then diluted with 200 ml of ether. The ethereal solution was washed with 200 ml of 20% hydrochloric acid and 200 ml of water, dried over sodium sulfate, filtered and evaporated. 16.24 g (100%) of product are obtained, which is purified by passing through a silica gel column 116 cm high and 5 cm in diameter. The eluent is a 1: 1 by volume mixture of hexane and methylene chloride. The fraction between 85 cm and 63 cm (solvent front height 113 cm) was collected. 12.60 g (78%) of a clear, slightly yellow oil are obtained.

Analysis calculated for C ₂₆ H ₃₄ F ₄ O ₄ : C, 65.54%; H, 5.08%; F, 15.98%;

Found: C, 64.99%; H, 4.96%; F, 19.10%.

Example 8 Preparation of alpha-isopropyl-4- (1,1,2,2-tetrafluoroethoxy) phenylacetic acid (alpha-cyano-m-phenoxy) benzyl ester

8.81 g (7.49 g of 100%, 0.0333 mol) of alpha-cyano-m-phenoxybenzyl alcohol, 3.0 ml (2.95 g, 0.0372 mol) of dried pyridine and 20 ml of methylene chloride (10.6 g, 0.034 mol) was added with stirring over 20 minutes with 3-methyl-2- [p- (1,1,2,2-tetrafluoroethoxy) phenyl] butyryl chloride in 20 ml of methylene chloride. solution. After stirring for 66 hours at room temperature, the reaction mixture was washed with 200 ml of 20% hydrochloric acid and 200 ml of water, dried over sodium sulfate, filtered and evaporated. Dark red oil remains. To remove the m-phenoxybenzaldehyde impurity, the oil was treated with 0.5 g of sodium borohydride at ice bath temperature and the resulting oil was purified on a silica gel column 121 cm high and 5 cm in diameter. The eluent was eluted with a 1: 1 by volume mixture of hexane and methylene chloride. The fraction between 77 cm and 57 cm (solvent front height 113 cm) was collected. 11.17 g (66%) of a clear orange oil are obtained. Analysis calculated for C ₂₇ H ₂₃ F ₄ NO ₄ : 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 9 Preparation of alpha-isopropyl-4-methoxyphenylacetonitrile

147 g (1.0 mol) of p-methoxyphenylacetonitrile, 18.63 g of 2,3,11,12-dicyclohexyl-1,4,7,10,13,16-hexaoxacyclooctoctadecane, 320 g (2.6 mole) of 2-bromopropane and 300 ml of benzene are added 300 ml of 50% sodium hydroxide solution. The reaction mixture was heated at 45 ° C for 4 days. The organic layer was separated, washed well with 3 x 200 mL water, 200 mL dilute hydrochloric acid and 2 x 200 mL water, and the organic solution was concentrated. The residue was fractionated in vacuo to give the title compound (175.6 g, 81%), b.p. 96-100 ° C (0.15 mmHg). The MMR spectrum of deuterochloroform indicated that the distilled material contained 12.5 mol% of the starting nitrile.

Example 10 Preparation of alpha-isopropyl-4-hydroxyphenylacetonitrile 51.0 g (0.2 mole) of boron tribromide in mL of methylene chloride was added 37.8 g (0.2 mole) of alpha5.

-511 isopropyl 4-methoxyphenylacetonitrile in 35 ml of methylene chloride and kept at -40 ° C. Allow the red reaction mixture to warm to room temperature and stir at this temperature for 3 days. The mixture was then poured onto ice, extracted with ether (3 x 100 mL), the combined ethereal solutions were washed with water (2 x 100 mL), and the ether solution was evaporated. The residual oil was fractionated in vacuo. 28.9 g (81%) of alpha-isopropyl-4-hydroxyphenylacetonitrile are obtained, m.p. 142-143 ° C / 0.25 mm Hg.

Example 11

Preparation of Chlorothioic acid O- [p- (1-cyano-2-methylpropyl) phenyl] ester Thiophosgene (16.43 g, 0.143 mole) in chloroform (25 mL) was added over 30 minutes (0.143 mole). -isopropyl-4-hydroxyphenylacetonitrile, previously dissolved in a 5% solution of 5.72 g (0.143 mol) of solid sodium hydroxide. The mixture is occasionally cooled with an ice bath to prevent the temperature from rising above 30 ° C. The reaction mixture is stirred for 15 minutes, the chloroform phase is separated off, washed with water and evaporated. The residual yellow oil (38.2 g) was used without further purification as in Example 12 for the next reaction step.

Example 12 Preparation of alpha-isopropyl-4-trifluoromethoxyphenylacetonitrile

38.2 g of the chloro-thio-formic acid O- [p- (1-cyano-2-methylpropyl) -phenyl] ester prepared in Example 11 are treated with 15.8 g of molybdenum hexafluoride at -25 ° C. Allow the dense reaction mixture to warm to room temperature and then slowly heat to 160 ° C using an oil bath. The mixture was cooled to room temperature, poured into water and extracted with ether (4 x 50 mL). The combined ethereal solutions were washed with water (50 mL) and evaporated. The residual oil was fractionated in vacuo. This gives alpha-isopropyl-4-trifluoromethoxyphenylacetonitrile, m.p. 78-80 ° C / 0.15 mmHg.

Example 13 Preparation of alpha-isopropyl-4-trifluoromethoxyphenylacetonitrile (Alternative route)

A. Preparation of 4-Trifluoromethoxybenzyl chloride

A mixture of trioxane (0.355 g), zinc chloride (0.34 g) and trifluoromethoxybenzene (0.6 g) was heated at 73 ° C and hydrogen chloride gas was bubbled through the reaction mixture. The mixture was cooled to room temperature, diluted with ether, and the organic layer was washed with saturated aqueous sodium carbonate solution and water, and the solvent was evaporated. 1.42 g

4-Trifluoromethoxybenzyl chloride is obtained in the form of a colorless liquid.

B. Preparation of 4-Trifluoromethoxyphenylacetonitrile

The 4-trifluoromethoxybenzyl chloride obtained in (A) is converted to the corresponding nitrile according to Example 3. Yield 93%.

C. Preparation of alpha-isopropyl-4-trifluoromethoxyphenylacetonitrile

4. Trifluoromethoxyphenylacetonitrile was alkylated as described in Example 4. Yield 90%.

Example 14 Preparation of alpha-isopropyl-4-trifluoromethoxyphenylacetic acid

A mixture of 2.0 g of alpha-isopropyl-4-trifluoromethoxyphenylacetonitrile, 3.0 g of potassium hydroxide, 35 ml of ethylene glycol and 3 ml of water was heated at 140 ° C for 8 hours. The mixture was poured into water and extracted with ether (2 x 10 mL). The aqueous phase was acidified with dilute hydrochloric acid and extracted with ether (3 x 10 mL). The combined ethereal solutions were washed with water (25 mL), dried over sodium sulfate and evaporated. 1.23 g of the title compound are obtained in the form of an oily substance. The maximum in the infrared spectrum is 1700 cm ^-1 .

Example 15 Preparation of alpha-isopropyl-4-trifluoromethoxyphenylacetyl chloride

A mixture of 1.2 g of alpha-isopropyl-4-trifluoromethoxyphenylacetic acid, 0.6 ml of thionyl chloride and 5 ml of benzene is refluxed for 4 hours. The solvent and excess thionyl chloride were evaporated and the remaining acid chloride used without further purification for esterification as described in Examples 16 and 17.

Example 16 Preparation of alpha-isopropyl-4-trifluoromethoxyphenylacetic acid (alpha-cyano-m-phenoxy) -benzyl ester

To a solution of 0.00458 mol of alpha-cyano-m-phenoxybenzyl alcohol and 0.5 ml of pyridine in 20 ml of ether are added 0.00458 mol of alpha-isopropyl-4-trifluoromethoxyphenylacetyl chloride in 5 ml of ether. solution. The reaction mixture was stirred overnight and then filtered. The filtrate and washings were combined, evaporated and the residual oil was purified on 5 mm x 2 mm silica gel coated plates. Elution was carried out with a 1: 1 mixture of methylene chloride and hexane. The Rf 0.55 band was extracted with ether and the ether solution was evaporated. 0.85 g of alpha-isopropyl-4-trifluoromethoxyphenylacetic acid (alpha-cyano-m-phenoxy) -benzyl ester is obtained.

Infrared spectrum: up to 1755 cm ^-1 wavelength. MMR Spectrum: (deuterochloroform) δ values: 6.8-7.6 (multiphtt, 13H, protons of aromatic ring); 6.31 and 6.28 [singlet, 1H, -CH (CN) -Ar]; 3.27 [doublet, J = 7 Hz, 1Η, -CH-CH (CH ₃ ) ₂ ]; 2.0-2.6 [m, 1H, CH _{(CH3) 2],} 0.6 to 1.2 (four doublets, J = 7 Hz, 6H, isopropyl-methyl protons).

Example 17 Alpha-Isopropyl-4-trifluoromethoxyphenylacetic acid (m-)

preparation of (phenoxy) benzyl ester

To a mixture of 1.89 g of m-phenoxybenzyl alcohol, 1 ml of pyridine and 6 ml of methylene chloride is added a solution of 2.46 g of alpha-isopropyl-4-trifluoromethoxyphenylacetyl chloride in 7 ml of ethylene chloride. (Alpha-isopropyl-4-trifluoromethoxyphenylacetyl chloride is prepared from the corresponding carboxylic acid as described in Example 15.) The reaction mixture is stirred overnight, washed with water, dilute hydrochloric acid, dilute potassium hydroxide solution and again with water. , finally evaporate. The remaining orange oil is blue

Chromatography on Ali-613 gel. 2.76 g of the title compound are obtained.

Infrared spectrum: up to 1738 cm ^-1 wavelength. MMR Spectrum: (deuterochloroform)

Δ values: 6.73 - 7.45 (multiplet, 13H); 5.03 (singlet, 2H); 3.20 (doublet, J = 10.5 Hz, 1H); 2.26 (multiplet, 1H); 0.66 and 0.94 (two doublets, J = 6.6 Hz, 6H).

Example 18 Preparation of alpha-Ethyl-4-trifluoromethoxyphenylacetic acid and alpha-n-propyl-4-trifluoromethoxyphenylacetic acid esters

The procedure described in Example 9 was followed except that ethyl bromide and 1-bromopropane were used instead of 2-bromopropane, and the reaction steps of Examples 10, 11, 12 and 14 were followed to prepare the alpha-ethyl. -4-trifluoromethoxyphenylacetic acid and alpha-n-propyl-4-trifluoromethoxyphenylacetic acid. The acids obtained are described in Figures 15-17. are converted into esters according to Examples. In this way, the following compounds were prepared:

alpha-ethyl-4-trifluoromethoxy-phenylacetic acid (m-phenoxy) benzyl ester

NMR spectrum (deuterochloroform) δ values: 0.83 (triplet, J = 7.5 Hz, 3H, -CH _3); 1.90 (m, 2H, _-CH2 -); 3.49 (triplet, J = 7.5 Hz, CH-CH CH _3?); 5.04 (singlet, 2H, -0CH ₂ -); 7.10 (multiplet, 13H, protons of aromatic rings).

alpha-Ethyl-4-trifluoromethoxy-phenyl-acetic acid (alpha-cyano-m-phenoxy) -benzyl ester

MMR Spectrum: (deuterochloroform) δ values: 0.84 (two triplets, J = 7.6 Hz, 3H, --CH ₃ ); 1.94 (m, 2H, _-CH2 -); 3.55 (triplet, J = 7.4 Hz, 1H, = CHCH ₂ CH ₃ ); 6.33 (singlet, 1H, -CHCN); 7.18 (multiplet, 13H, protons of aromatic rings).

alpha-n-Propyl-4-trifluoromethoxyphenylacetic acid (m-phenoxy) benzyl ester

NMR spectrum (deuterochloroform) δ values: 0.6- 2.4 (m, 7H, -CH ₂ CH ₂ CH _3); 3.63 (triplet, J = 7.2 Hz, 1H, = C7Z-C ₃ H _7); 7.21 (multiplet, 13H, protons for aromatic rings).

alpha-n-Propyl-4-trifluoromethoxyphenylacetic acid (alpha-cyano-m-phenoxy) -benzyl ester

NMR spectrum (deuterochloroform) δ values: 0.65 to 2.4 (m, 7H, -CH ₂ CH ₂ CH _2); 3.71 (triplet, J = 7.3 Hz, 1H, = CH-C ₃ H _7); 7.20 (multiplet, 13H, protons of aromatic rings).

Example 19 Preparation of alpha-Bromo-4-trifluoromethyl-thiol-toluene To a solution of 4-trifluoromethyl-thiol-toluene (g, 0.15 mol) in 90 ml of carbon tetrachloride was slowly added 20 ml of carbon tetrachloride. Bromine (5 g, 0.13 mol) was added while the reaction mixture was slowly refluxed and exposed to 275 W of sunlight. After the addition was complete, the reaction mixture was refluxed for an additional hour and most of the solvent was evaporated under atmospheric pressure. The residue was fractionated in vacuo. 15.5 g (b.p. 64-77 ° C / 0.6-0.8 mmHg) of the main distillate are obtained, which contains 92% of the monobromo compound by gas-liquid chromatography.

Example 20

Preparation of 4-Trifluoromethylthiophenylacetonitrile To a solution of dimethylsulfoxide 65 ml at 65 ° C under nitrogen was added 5 mg of sodium cyanide under nitrogen. The heating was stopped and alpha-bromo-4-trifluoromethylthiotoluene (14.3 g, 0.053 mol) was added dropwise at such a rate that the exotherm did not heat the reaction mixture to above 75 ^° C. The red reaction mixture was heated at 90-95 ° C for about 45 minutes, then cooled to room temperature and treated with 50-100 mL of ice water. The aqueous suspension was shaken several times with ether, the ethereal solutions were combined, washed with water and dried over sodium sulfate. Concentration in vacuo gave 9.7 g of a dark red oil of 95% purity by gas-liquid chromatography.

Example 21 ^υ alpha-Isopropyl-4-trifluoromethyl-phenyl-thio-yloxyacetonitrile

9.7 g (0.045 mol) of 4-trifluoromethylthiophenylacetonitrile, 9.5 g (0.056 mol) of 2-iodopropane, 0.61 g (0.0023 mol) of 2.3, 11 -dicyclohexyl-1,4,7,10,13,16-hexaoxycyclooctadecane and 13.5 ml of benzene (suspension) are added dropwise over 30 minutes with 13.5 ml of 50% sodium hydroxide solution. During the addition, the reaction mixture is heated to 43 ° C. The reaction mixture was stirred at ambient temperature for 2.5 hours and then subjected to gas-liquid chromatography on an aliquot. When the starting nitrile compound is no longer detectable, the reaction mixture is worked up. Ice water was added, triturated with ether, the ether extract was washed with 10% hydrochloric acid and water, dried over sodium sulfate and evaporated in vacuo. 10.2 g (86.8%) of a red-brown oil remain.

If ethyl bromide or 40 m-propyl iodide is used instead of 2-iodopropane, but otherwise, alpha-ethyl-4-trifluoromethylthiophenylacetonitrile or alpha-n-propyl-4 trifluoromethylthio-phenylacetonitrile is obtained.

Example 22 Preparation of alpha-isopropyl-4-trifluoromethylthiophenylacetic acid

A mixture of 6.9 g (0.0265 mole) of alpha-isopropyl-4-trifluoromethyl-5θ-thiophenylacetonitrile, 25 g (0.312 mole) of 50% sodium hydroxide and 53 ml of ethylene glycol was heated under gentle reflux for 18 hours. while. The mixture was then poured into ice water and extracted with ether. The aqueous phase is acidified with concentrated hydrochloric acid, extracted again with ether, the ethereal solution is washed with water, dried over sodium sulfate and concentrated in vacuo. 2.05 g of an oily product are obtained.

If alpha-ethyl-4-trifluoromethyl-thiophenylacetonitrile or alpha-n-propyl-4-trifluoromethyl-thiophenylacetonitrile is used instead of alpha-isopropyl-4-trifluoromethylthiophenylacetitronitrile alpha-ethyl-4-trifluoromethylthiophenylacetic acid and alpha-n-pro65 pyl-4-trifluoromethylthiophenylacetic acid are used.

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Example 23 Alpha-Isopropyl-4-trifluoromethyl-thiophenylacetic acid

- Preparation of (alpha-cyano-m-phenoxy) -benzyl ester from alpha-isopropyl-4-trifluoromethylthiophenylacetic acid and proceeding as described in Examples 15 and 16. The title compound is obtained in the form of an oil.

Analysis calculated for C ₂₆ H ₂₂ F ₃ NO ₃ S: 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%

The procedure described above, except that alpha-ethyl-4-trifluoromethyl-thiophenylacetic acid and alpha-n- instead of alpha-isopropyl-4-trifluoromethylthiophenylacetic acid, was used. propyl 4-trifluoromethylthiophenylacetic acid was used. In this way, alpha-ethyl-4-trifluoromethyl-thiophenyl-acetic acid (alpha-cyano-m-phenoxy) -benzyl ester and alpha-n-propyl-4-trifluoromethyl-thiophenylacetic acid are added. (alpha-cyano-m-phenoxy) -benzyl ester is obtained.

Example 24 Alpha-Isopropyl-4-trifluoromethyl-thiophenylacetic acid

Preparation of (m-phenoxy) -benzyl ester from alpha-isopropyl-4-trifluoromethylthiophenylacetic acid according to Examples 15 and 17. The title compound is obtained in the form of an oil.

Example 25 Preparation of alpha-isopropyl-4-mercapto-phenyl-acetic acid 15.7 g (0.065 mol) of alpha-isopropyl-4-difluoromethylthiophenylacetonitrile with 42 g of 50% sodium hydroxide and 80 of ethylene glycol was refluxed for 18 hours. The reaction mixture was poured into ice water and extracted with ether. The alkaline phase is acidified at 15-20 ° C with concentrated hydrochloric acid and extracted with ether. The ether extract was washed with water, brine, and concentrated. 11.4 g (83%) of an oil are obtained. Nuclear magnetic resonance and infrared spectroscopy showed that the -CHF ₂ group was no longer present in the compound, which is thiol.

Example 26 Preparation of alpha-isopropyl-4-difluoromethylthiophenylacetic acid in 18.4 g (0.46 ml) of sodium hydroxide in water and 11 g (0.05 mol) of alpha-isopropyl-4-mercapto- a solution of phenylacetic acid in dioxane (40 mL) was added and the reaction mixture was heated to 50 ° C. Chlorodifluoromethane (Freon-22) is slowly bubbled under the liquid surface and the mixture warms to 75 ° C as a result of the exothermic reaction. Chlorodifluoromethane was introduced until the exothermic reaction slowly ceased (about 30 minutes). The mixture was cooled to room temperature and treated with 100 ml of ice water. The aqueous phase was extracted with ether (3 x 200 mL) and then acidified with concentrated hydrochloric acid at 15-20 ° C. The resulting oil was extracted with ether, the ethereal solution was washed with water and brine, dried over sodium sulfate and concentrated in vacuo. 10.2 g of a dark brown sticky substance are obtained which is used without further purification for esterification.

Example 27 Alpha-Isopropyl-4-difluoromethyl-thiophenyl-acetic acid (alpha-cyano-m-phenoxy) -benzyl ester starting from alpha-Isopropyl-4-difluoromethyl-thiophenyl-acetic acid and Examples 16 and 16. The title compound is obtained in the form of an oil.

Calcd for C ₂₆ H ₂₃ F ₂ NO ₃ S Calculated: C 66.79% weight% H, 4.96 weight%, F 8.13 weight% by weight N 3.00, S 6.86% by weight ;

Found: C, 66.58%; H, 5.13%; F, 8.02%; N, 2.87%; S, 6.95%.

Example 28 Preparation of alpha-isopropyl-4-hydroxyphenylacetic acid 40.0 g of alpha-isopropyl-4-methoxyphenylacetonitrile and

A mixture of 200 ml of 48% strength aqueous hydrobromic acid were heated in an oil bath for 14 hours under 126 to 128 ^c C to reflux. The reaction mixture was diluted with ice and water, extracted several times with ether, and the combined ethereal solutions were washed with water and evaporated. The solid residue was boiled with chloroform (200 mL), cooled, filtered and dried. 23.8 g of alpha-isopropyl-4-hydroxyphenylacetic acid are obtained, m.p. 172-174 ° C.

Infrared spectrum: (nujol) maxima at 3250-2900 (broad, hydroxyl) and at 1690 cm ^-1 (carbonyl).

When starting alpha-isopropyl-4-methoxyphenylacetonitrile instead of alpha-ethyl-4-methoxyphenylacetonitrile. and alpha-n-propyl-4-methoxyphenylacetonitrile was used to give alpha-ethyl-4-hydroxyphenylacetic acid and alpha-n-propyl-4-hydroxyphenylacetic acid.

Example 29 Preparation of alpha-isopropyl-4-difluoromethoxyphenylacetic acid

A mixture of 10.00 g (0.0515 mol) of alpha-isopropyl-4-hydroxyphenylacetic acid, 65 ml of dioxane, 19.08 g (0.464 mol, actual content 18.56 g) of sodium hydroxide and 30 ml of water is magnetic and stirred at 80 ° C for 46 hours (0.532 mol) in chlorodifluoromethane over 4 hours. The reaction mixture was poured into ice water (250 ml), washed with ether, acidified to pH 3 with concentrated hydrochloric acid and extracted with ether (200 ml). The ethereal solution was washed with water (100 mL), dried over sodium sulfate, filtered and evaporated. To the remaining white ointment was added a mixture of hexane and methylene chloride, and the resulting mixture was filtered. The filter retains unchanged starting material. The filtrate was evaporated to give 5.41 g of a clear brown oil of at least 85% purity by nuclear magnetic resonance spectroscopy.

MMR spectra (deuterochloroform - deuteropyridine) δ values:

7.43 (doublet, J = 8.2 Hz, 2H); 7.08 (doublet, J = 8.2 Hz, 2H); 6.57 (triplet, J = 74.3 Hz, 1H); 3.63 (singlet, pollution); 3.25 (doublet, J = 10 Hz, 1H); 2.37 (multiplet, 1H); 1.19 (doublet,

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J = 6.5 Hz, 3H); 0.78 (doublet, J = 6.5 Hz, 3H); 13.82 (singlet, 1H). g

When using alpha-ethyl-4-hydroxyphenylacetic acid or alpha-propyl-4-hydroxyphenylacetic acid instead of alpha-isopropyl-4-hydroxyphenylacetic acid, alpha-ethyl-4-difluoromethoxyphenyl- we get acetic acid.

Example 30 Alpha-Isopropyl-4-difluoromethoxyphenylacetic acid (m-

Preparation of (phenoxy) benzyl ester from alpha-isopropyl-4-difluoromethoxyphenylacetic acid according to the procedure of Examples 15 and 17. The title compound is obtained as a pale yellow oil.

Analysis calculated for C ₂₅ H ₂₄ F ₂ O ₄ : C, 70.41%; H, 5.67%; F, 8.91%;

Found: C, 73.36%; H, 5.96%; F, 10.56%.

If alpha-ethyl-4-difluoromethoxyphenylacetic acid or alpha-n-propyl-4-difluoromethoxyphenylacetic acid are used instead of alpha-isopropyl-4-difluoromethoxyphenylacetic acid, alpha-ethyl-4-difluoromethoxyphenylacetic acid (m-phenoxy) -benzyl ester is obtained.

Example 31 Preparation of alpha-isopropyl-4-difluoromethoxyphenylacetic acid (alpha-cyano-m-phenoxy) -benzyl ester starting from alpha-isopropyl-4-difluoromethoxyphenylacetic acid. and Example 16. The product is obtained in the form of an oil. NMR spectrum (deuterochloroform) δ values: 0.88 (four doublets, J = 6 Hz, 6H, CH _3); 2.30 [multiplet, 1H, -CH-CH (CH ₃ ) ₂ ]; 3.24 [doublet, J = 10.1 Hz, 1H, = (31-05 ((¾) ^ 6.33 (two singlets, 1H, C77 CN)); 6.45 (triplet, J = 74 Hz, 1H , CHF ₂ O-), 7.16 (multiplet, 13H, protons of aromatic rings).

Calcd for C ₂₆ H ₂₃ F ₂ NO ₄ Calculated:% C, 69.17% by weight H 5.13 weight F 8.42% by weight N 3.10% by weight;

Found: C, 69.41%; H, 5.20%; F, 10.25%; N, 3.70%.

When alpha-ethyl-4-difluoromethoxyphenylacetic acid and alpha-n-propyl-4-difluoromethoxyphenylacetic acid are used instead of alpha-isopropyl-4-difluoromethoxyphenylacetic acid, ethyl 4-difluoromethoxyphenylacetic acid (alpha-cyano-m-phenoxy) benzyl ester and alpha (n-propyl) -4-difluoromethoxyphenylacetic acid (alpha-cyano) m-phenoxy) benzyl ester is obtained.

Example 32 Alpha-Isopropyl-4-trifluoromethylsulfinyl-phenyl-acetic acid (m-phenoxy) -benzyl ester

10.0 g of alpha-isopropyl-4-trifluoromethylthiophenylacetic acid (m-phenoxy) benzyl ester (prepared according to Example 24), 4.1 g of 85% m A solution of hydrochloric acid in 100 ml of methylene chloride was heated for several hours. The mixture was filtered, the filtrate was concentrated and the residue was purified on a silica gel column eluting with a 2: 1 mixture of methylene chloride and hexane. The product is isolated in a pale yellow oil.

If alpha-ethyl-4-trifluoromethylthiophenylacetic acid (m-phenoxy) is substituted for alpha-isopropyl-4-trifluoromethyl-thiophenyl-acetic acid instead of the acid (m-phenoxy) -benzyl ester, benzyl ester or alpha-n-propyl-4-trifluoromethylthiophenylacetic acid (m-phenoxy) benzyl ester, alpha-ethyl-4-trifluoromethylsulfinylphenylacetic acid ( m-phenoxy) benzyl ester. and alpha-n-propyl-4-trifluoroethylsulfinylphenylacetic acid (m-phenoxy) benzyl ester.

Example 33 Alpha-Ethyl-3-difluoromethylsulfonyl-phenylacetic acid

- Preparation of (alpha-cyano-m-phenoxy) -benzyl ester

10.0 g of alpha-ethyl-3-difluoromethyl-thiophenylacetic acid (alpha-cyano-m-phenoxy) -benzyl ester, 9.0 g of 85% m-chloroperbenzoic acid and 100 ml dichloroethane was refluxed overnight. The mixture was filtered, concentrated and the residue was chromatographed on a silica gel column using methylene chloride / hexane (2: 1) as eluent. The product was obtained as a yellow oil.

When replacing alpha-ethyl-3-difluoromethylthiophenylacetic acid (alpha-cyano-m-phenoxy) benzyl ester with alpha-isopropyl-4-trifluoromethylthiophenylacetic acid (alpha-cyano-m phenoxy) benzyl ester or alpha-n-propyl-4-tritluoromethylthiophenylacetic acid (alpha-cyano-m-phenoxy) benzyl ester, alpha-isopropyl-4-trifluoromethyl sulfonylphenyl acetic acid (alpha-cyano-m-phenoxy) benzyl ester and alpha-n-propyl-4-trifluoromethylsulfonylphenylacetic acid (alpha-cyano-m-phenoxy) benzyl ester.

Example 34

Preparation of 4-Trifluoromethoxy-beta, beta-dimethyl-atropic acid for 22 g (0.1 mol) in p-trifluoromethoxyphenylacetic acid in ether (obtained by alkaline hydrolysis of the corresponding nitrile prepared in Example 12) at room temperature was added a solution of commercial ether isopropyl magnesium chloride (0.2 mol). After stirring for 2 hours at room temperature, dry acetone (5.8 g, 0.1 mol) was added and the reaction mixture was refluxed for 5 hours. The mixture is then cooled, carefully acidified with aqueous sulfuric acid and extracted with ether. The combined organic phases were extracted with 10% aqueous sodium carbonate. The alkaline phase is acidified with hydrochloric acid and extracted with ether. The ether extract was dried over sodium sulfate and evaporated. This gives 4-trifluoromethoxy-beta, beta-dimethyl-atropic acid.

Example 35 Alpha-Isopropenyl-4-trifluoromethoxyphenylacetic acid

- Preparation of (m-phenoxy) -benzyl ester

To a solution of 13.9 g (0.05 mole) of 4-trifluoromethoxy-beta, beta-dimethyl atropic acid and 6.1 g (0.06 mole) of triethylamine in 100 ml of acetone was added 13.2 g under cooling in an ice bath. M-phenoxybenzyl bromide (0.05 mol) was added and the reaction mixture was refluxed for 4 hours. The mixture was poured into cold dilute hydrochloric acid and extracted with ether. The ether layer was washed with 10 ° s / ₀ aqueous hydrochloric acid and water, dried over sodium sulfate and be9

Simmer -919. The residue was dehydrated in benzene medium with phosphorus pentoxide at 80 ° C for 18 hours. After filtration and evaporation of the solvent, the crude product is obtained, which is purified by column chromatography on silica gel. Elution was carried out with a 1: 1 by volume mixture of methylene chloride and hexane. The title compound is obtained as a pale yellow sticky substance.

Example 36

Preparation of 4-Trifluoromethoxy-alpha-tert-butylbenzyl alcohol

To a commercial solution of tert-butylmagnesium chloride (1.0 mol) in THF at 38-40 ° C was added a solution of 4-trifluoromethoxybenzaldehyde (56 g, 0.4 mol) in tetrahydrofuran (50 ml) under nitrogen. The reaction mixture was stirred overnight at room temperature and then carefully acidified with dilute aqueous sulfuric acid at 15-20 ° C. After addition of ether, the phases are separated, the organic phase is washed with water, dried over sodium sulfate and evaporated. The remaining sticky material was purified by chromatography on silica gel. The product obtained was used as in Example 37.

Example 37 Preparation of p- (1-Chloro-2,2-dimethylpropyl) -alpha, alpha, alpha-trifluoroanisole

To freshly distilled thionyl chloride (14.87 g, 0.125 mol) was added in portions over a period of 30 minutes with 12.4 g (0.05 mol) of 4-trifluoromethoxy-alpha-tert-butylbenzyl alcohol ( Example 36). Cooling was stopped and the suspension was allowed to stand overnight. The product obtained by evaporation of excess thionyl chloride is used without further purification for further synthesis.

Example 38 Preparation of alpha-tert-butyl-4-trifluoromethoxy-phenylacetic acid

The Grignard reagent was prepared from p- (1-chloro-2,2-dimethylpropyl) alpha, alpha, alpha-trifluoroanisole prepared according to Example 37 and reacted with carbon dioxide according to the method of Weinstein and Morse [J. Chem. Soc., 74, 1133 (1952)]. This gives the title compound as a white product.

Example 39 Alpha-tert-Butyl-4-trifluoromethoxy-phenylacetic acid

- Preparation of (alpha-cyano-m-phenoxy) -benzyl ester from alpha-tert-butyl-4-trifluoromethoxyphenylacetic acid according to the procedure described in Examples 15 and 16. The product is obtained in the form of an oil.

Example 40

Assay of the compounds of the invention for insecticidal activity

The insecticidal activity of the compounds of the invention is demonstrated in the following tests using the insect varieties Heliothis virescens (Fabricius), Empoasca abrupta (DeLong) and Aphis fabae (Scopoli). The following methods were used:

Heliothis virescens (Fabricius)

First larval condition

Cotton swabs containing two adult true leaves were immersed in the test solution for 3 seconds while moving. The solution contained 300, 100 or 10 ppm of the test compound in 35% water by weight and 65% acetone by weight. The leaves were placed in a dish containing a piece of gauze. 50-100 pieces of newly hatched larvae infected with larvae were placed in the cups and covered. After 3 days at 27 ° C and 50% RH, the contents were examined and the number of dead larvae recorded. The percentage of deaths is given in Table I.

Aphis fabae (Scopoli) cm, 5 cm diameter fiber pots containing 100-150 aphis fabae specimens infected 2 days earlier were placed on a rotating table at 4 rpm and the plants were sprayed with DeVilbiss and pressurized with 2 atm. was sprayed with a solution of the test compounds in 35% water and 65% acetone. Each solution contained compounds at concentrations of 100, 10, 1.0 and 0.1 ppm, respectively. During spraying, the nozzle was kept approximately 15 cm from the plants and the spray was directed to completely cover the insects and plants. The sprayed plants were placed on their sides in white enamel trays and kept for one day at 21 ° C and 50% RH. The number of dead insects was then determined. The percentage of deaths is shown in Table I.

Empoasca abrupta (DeLong)

Sieva limababs with primary leaves grown to 7.5-10 cm in length were immersed in a solution containing 100 ppm, 10 ppm and 1 ppm of the test compounds. The solvent consists of 35 wt% water and 65 wt% acetone. The immersed plant was then dried in a suction cup, cut off a 2.5 cm piece from the tip of one leaf and placed in a 10 cm diameter petri dish with wetted filter paper at the bottom. 3 to 10 second larvae were placed in the cup, covered and kept for 2 days at 27 ° C and 50% RH. The mortality rate was then determined. The data obtained are shown in Table I.

In the above tests, permethrin was used as a comparator.

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18041S

Table I

Evaluation of the insecticidal effect

Death%

Compound

Heliothis vircscens larvae, larval condition 1

Abrupta of Einpoasca

Aphia fabae

300 100 10 100 10 1 100 10 10 ppm ppm ppm ppm ppm ppm ppm pPM ppm pPM

alpha-isopropyl-4- (trifluoromethoxy) phenyl-acetic acid

acid (alpha-cyano-m-phenoxy) -bcnzil-éezter 100 100 100 100 100 70 100 100 90 50 alpha-isopropyl-4- (1,1,2,2-tetrafluoroethoxy (phenyl-acetic acid (m-phenoxy) -benzyl ester) 90 90 0 50 0 100 100 0 alpha-isopropyl-4- [1,1,2,2- (tetrafluoroethoxy)] phenylacetic acid (alpha-cyano-m-phenoxy) benzyl ester 100 100 0 100 0 100 100 50 alpha-isopropyl-4- (trifluoromethylthio) phenylacetic acid (alpha-cyano-m-phenoxy) -benzyl ester 100 100 kills 70 100 100 _ 100 100 80 - alpha-isopropyl (trifluoromethyl-thio) -phenyl acetic acid (alpha-cyano-m-phenoxy) benzyl ester 100 71-85 0-40 70 0 _ 100 100 50 - alpha-isopropyl-4- (difluoromethoxy) phenyl acetic acid (m-phenoxy) -benzyl ester 100 100 0-40 100 0 _ 100 100 0 _ alphal-isopropyl-4- (difluoromethoxy) phenyl-acetic acid (alpha-cyano-m-phenoxy) benzyl ester 100 100 86-99 100 100 _ 100 100 100 - alpha-isopropyl-4- (trifluoromethoxy) phenyl acetic acid (m-phenoxy) benzyl ester 100 100 0-40 100 0 _ 100 100 100 - alpha-ethyl-4- (trifluoromethoxy) phenyl eoetsav- - (alpha-cyano-m-phenoxy) benzyl ester 100 100 61-70 100 70 _ 100 100 100 _ alpha-propyl-4- (trifluoromethoxy) phenyl-acetic acid acid (m-phenoxy) benzyl ester 100 86-99 0-40 100 0 _ _ 0 _ _ alpha-propyl-4- (trifluoromethoxy) phenylboronic acid (alpha-cyano-m-phenoxy) benzyl ester 100 100 71-85 100 50 - 100 90 90 -

Example 41

Test for insecticidal activity

The insecticidal activity of the compounds of the invention is characterized by the following further assays.

Anophelex quadrimaculatus (Say) larvae, Epilachna varivestis (Mulsant) and Spodoptera eridania (Cramer) insects were used to evaluate the effects of the compounds.

Anopheles quadrimaculatus (Say) (Malaria mosquito)

1 ml of solution containing 300 ppm of the test compound (solvent weight 35 ° / ₀ by weight water and 65% acetone) was pipetted into a 400 ml beaker containing 250 ml of deionized water. The concentration of the diluted solution is thus 1.2 ppm. Aliquots of the resulting solution were further diluted to 0.4 ppm, 0.04 ppm and 0.004 ppm. Fits inside the beaker; A 0.6 cm wide wax paper ring was floated on the surface of the test solution to prevent the eggs from rising and drying on the side of the beaker along the curved meniscus. Using a sieve spoon, we kneaded about 100 eggs (0-24 hours) and placed them in a beaker. After two days at 27 ° C and 50% relative humidity, the hatches were observed. The percentage of fall is given in Table II. Table.

Epilachna varavestis (Mulasant)

Sieva lima beans, 7.5 to 10 cm long, were immersed in the test solution (two plants per dish). The tested solutions contain the compounds of the invention at concentrations of 300,100, 10 and 1 ppm, respectively. After immersion, the plants were dried in a suction cup. One leaf was removed from the plants and placed in a 10 cm diameter petri dish containing wet filter paper at the bottom and 10 last larvae at 50 (13 days after hatching). The day after treatment, the other leaf was also removed from the plants and used as food for the larvae after the remnants of the first leaf were removed. On the second 55 days after treatment, the third leaf was also used as a food for the larvae. More letters were usually not needed. The fourth leaf was used on the fourth day after treatment if the larvae had not finished feeding. The study was set aside 60 and awaited the development of adult individuals. This usually started on the 9th day after treatment. After the development was complete, we checked the number of dead larvae, puppet or adult insect, deformed 65 puppet or adult insect, larval puppet or puppet in each Petri dish11.

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II. spreadsheet

Evaluation of the insecticidal effect

Compound 1.2 ppm Anophele.i quadrimaculatus mosquito larvae Death% Epilachna varive3ti3 0.004 ppm Spodoptera 1000 ppm Eridania 100 ppm 10 ppm 0.4 ppm 0.04 ppm 300 ppm 100 ppm 10 ppm 1 ppm alpha-isopropyl-4- (trifluoromethoxy) -phenyl-acetic acid (alpha-cyano-m-phenoxy) -benzyl ester 100 100 100 90 100 100 100 100 100 100 100 alpha-isopropyl-4- [1,1,2,2- (tetrafluoroethoxy)] - phenylacetic acid (m-phenoxy) -benzyl ester 100 100 90 0 100 100 0 100 alpha-isopropyl-4- [1,1,2,2- (tetrafluoroethoxy)] - (phenylacetic acid (m-phenoxy) -benzyl ester 100 100 80 0 100 100 0 100 alpha-isopropyl-4- (trifluoromethyl-thio) -phenyl-acetic (alpha-cyano-m-phenoxy) -benzyl ester 100 100 86-99 100 100 0 100 100 100 alpha-isopropyl-N- (4'-methylthio) phenyl-acetic acid (alpha-cyano-m-phenoxy) benzyl ester 100 86-99 86-99 100 90 0 100 100 90 Alpha-isopropyl-4- (difluoromethoxy) -phenyl-acetic acid (m-phenoxy) -benzyl ester 100 100 100 100 100 0 100 90 50 alpha-isopropyl-4- (difluoromethoxy) phenyl-acetic acid (alpha-cyano-m-phenoxy) benzyl ester 100 100 100 100 100 100 100 100 50 alfa-4- (trifluoromethoxy) phenyl acetic acid (m-phenoxy) benzyl ester 100 100 100 _ 100 100 70 90 0 ~ 0 _ alfa-4- (trifluoromethoxy) phenylboronic acid - (alpha-cyano-m-phenoxy) benzyl ester 100 100 100 100 100 100 80 90 50 _ alpha-propyl-4- (trifluoromethoxy) phenyl acetic acid (m-phenoxy) benzyl ester 100 100 100 100 100 0 100 90 0 _ alpha-propyl-4- (trifluoromethoxy) phenylboronic acid (alpha-cyano-m-phenoxy) benzyl ester 100 100 100 100 100 70 100 100 100 alpha-isopropyl-3- (trifluoromethoxy) -phenylacetic acid (alpha-cyano-m-phenoxy) -benzyl ester 100 100 100 0 100 100 0 100 100 100 80

was an advanced insect intermediate. The data obtained are shown in Table II. Table.

Spodoptera eridenia (Cramer)

Two Sieva limabab plants with 7.5-10 cm long primary leaves were immersed in the test solutions for 3 seconds while the solutions were moved and dried in a vacuum oven. The dry leaves were cut off and placed in a 10 cm diameter petri dish containing a wet filter paper and 10 third larvae of approximately 1 cm in length in Spodoptera eridania larvae. The Petri dishes were covered and kept for 2 days at 27 ° C and 50% relative humidity. The number of dead larvae was then determined. The results obtained are shown in Table II. Table.

Example 42

Test for insecticidal activity

Tetranychus urticae (Koch)

Three Sieva limabab plants containing 7.5 to 10 cm long primary leaves were inoculated with approximately 100 adult phosphate-resistant insects per leaf 4 hours prior to assay to allow egg laying prior to assay. The infected plants were immersed in 1000, 300, 100, and 10 ppm test solutions for 3 seconds while moving the solutions, dried in a suction cup, stored at 27 ° C for 2 days, and 10 times the number of adult insects killed per leaf. using a microscope. The other leaf was left on the plant for another 5 days, at which time the eggs and the newly emerged pupae were examined for 10x magnification. In this way, an ovicidal and residual effect was obtained. The results obtained are shown in Table III. is shown in Table.

Heliothis virescens (Fabricus)

-1 225

Third larval condition

Three cotton buds of newly developed cotyledons were immersed in solutions of 1000 and 100 ppm respectively and dried in a suction cup. The dried cotyledons were cut in half and each of 10 sections was placed in a 28 gram plastic cup containing a 1.25 cm water-saturated dental gauze. One third larvae of Heliothis virescens were then placed in the dishes, covered and kept for 3 days at 27 ° C and 50% relative humidity. Finally, the death rate was determined. The results are shown in Table III. Table.

Trichoplusia ni (Hübner)

Third larval condition

Replace the true leaf of cotton with the test solution at concentrations of 1000 ppm, 100 ppm and 10 ppm, respectively. We immersed for 5 seconds while moving the solution and placed the leaf in a suction cup. The dried leaf was placed in a 9.0 cm diameter Petri dish containing a moistened filter paper at the bottom. 10 third larvae of 10 Trichoplusia ni were added and covered.

and maintained at 27 ° C for 50 days and 50 ± 1θ% relative humidity, and then the mortality rate was determined. The data obtained are shown in Annex III. Table.

III. spreadsheet

Evaluation of the insecticidal effect

Compound

Death% Fo3zfát-reziszten3 Heliothi3 virescens Trichoplusia ni Tetranychus urticae 3. larval status 3. larval status 1000 300 100 10 1000 100 1000 100 10 ppm ppm ppm ppm ppm ppm ppm ppm ppm

alpha-isopropyl-4- (trifluoromethoxy) phenylboronic acid

[alpha-cyano-m-phenoxy] -benzyl ester 100 100 80 0 100 100 100 100 100 alpha-isopropyl-4- [1,1,2,2- (tetrafluoromethoxy)] -phenyl-acetic acid (m-phenoxy) -benzyl ester 100 50 0 50 1100 0 - alpha-isopropyl-4- [1,1,2,2- (tetrafluoromethoxy)] - -phenylacetic acid (alpha-cyano-m-phenoxy) benzyl ester - 90 60 0 80 0 100 30 0 alpha-isopropyl-4- (trifluoromethylthio) phenylacetic acid (alpha-cyano-m-phenoxy) benzyl ester - 100 100 100 100 100 100 100 - alpha-isopropyl-4- (difluoromethyl) phenyl-eeetsav- - (alpha-cyano-m-phenoxy) -benzyl ester - 100 100 0 90 20,100 100 - alpha-isopropyl-4- (difluoromethoxy naetoxi) phenylboronic acid - (m-phenoxy) -benzyl ester - 100 0 0 100 70,100 100 - alpha-isopropyl-4- (difluoro-methoxy) phenyl-acetic acid - (alpha-cyano-m-phenoxy) -benzyl ester - 100 100 0 100 100 100 100 - alpha-ethyl-4- (trifluoromethoxy) phenylboronic acid (m- (phenoxy) benzyl ester - 100 0 _ 100 100 100 100 - alpha-ethyl-4- (trifluoromethoxy) -phenyl-acetic acid (alpha-cyano-m-phenoxy) -benzyl ester 100 100 0 100 100 100 100 - alpha-propyl-4- (trifluoromethoxy) -phenyl-acetic acid (m-phenoxy) -benzyl ester - 80 0 _ 60 30,100 40 - alpha-propyl-4- (trifluoromethoxy) phenylboronic acid - (alpha-cyano-m-phenoxy) -benzyl ester - 100 100 90 90,100 100 - alpha-isopropyl-3- (trifluoromethyl) phenylboronic acid - (alpha-cyano-m-phenoxy) - benzyl ester - 100 100 0 100 90,100 90 - Example 43 Investigation of insecticidal activity in soil Diabrotica undecimpunctata howardi (Barber) Dilute 10 mg of the test compound to 10 ml with acetone. The solution thus obtained is stock solution A. 2 ml of stock solution A was diluted again with acetone to 10 ml to give solution B. About 0.7 g of Pyrax ABB talc was weighed into a 28 gram wide mouth jar and 1.25 ml of solutions A and B were added to the talc. In this way, the following concentrations were obtained: S 1.25 ml of solution A corresponds to a concentration of 56 kg / ha, 55 1.25 ml of solution B corresponds to a concentration of 11.2 kg / ha. Cioni. The test solution was mixed with talc to evenly moisten it and then dried with a hair dryer for 10-15 minutes. Subsequently, 25 to 60 ml of wet sterilized soil and about 0.6 g of millet seed (nutrient for larvae) were added to the jars, sealed, and the contents were shaken. Each jar was then placed with 10 6-8 day old Diabrotica unde65 cimpunctata Howard larvae. The jars are loose

was sealed and stored at 27 ° C in a 50% relative humidity space under constant illumination. After 6 days, the number of dead individuals was determined.

In the study, alpha-isopropyl-4-trifluoromethoxyphenyl-acetic acid (alpha-cyano-m-phenoxy) -benzyl ester was found to be 100% of insects and 11.2 kg / ha at 56kg / ha. concentration killed 70% of the insects.

Example 44

Young cotton shrubs grown in cm diameter plastic pots containing at least two mature true leaves were immersed in the test solution for 3 seconds by treating the leaves of cotton shrubs with residual insecticidal activity. Usually, one leaf was placed in the solution at a time and moved. The solvent was 65% acetone and 35% water. The solutions tested contain 30 ppm, 100 ppm, 300 ppm and 900 ppm of the compounds of the invention.

After the leaves had dried, they were cut off and placed in a 90 mm x 10 10 mm petri dish on Whatman No. 1, 9 cm in diameter. five third larvae of Heliothis virescens were placed on each leaf and the Petri dishes were sealed. The inoculated petri dishes are then kept at 27 ^° C, 50% relative humidity, using a continuous light. After 72 hours, the larvae were counted.

The remainder of the cotton shrubs were subjected to 15 strong illuminations in the greenhouse for 14 hours a day. After 3, 7, 10 and 14 days, studies were performed on third larvae of Heliothis virescens. The results are shown in Table IV. Table.

ARC. spreadsheet

Residual insecticidal activity of the compounds on cotton using third larvae Heliothis virescons

Residual activity

Compound Concentration 1 · 0 2 ** 1 · 3 2 * * 1 7 2 * I * 10 · 2 * * 1 14 2 ** alpha-isopropyl-4- (trifluoromethoxy) - 30 90 0 90 0 60 0 60 0.03 60 1.3 phenylacetic acid (alpha-cyano-m-phenoxy) - 100 100 0 100 0 100 0 95 0 95 0.03 benzyl ester 300 100 0 100 0 100 0 100 0 100 0 900 100 0 100 0 100 0 100 0 100 0 permethrin 30 65 0.3 30 11.3 15 12.5 40 4.3 5 57.5 100 85 0 85 0.03 70 0.53 65 0.6 25 1.0 300 100 0 100 0 100 0 95 0 80 0 900 100 0 100 0 100 0 90 0 100 0 alpha-isopropyl-4-chloro-phenylacetic acid 30 65 0.03 65 0.1 75 0.05 45 2.3 75 0.03 - (alpha-cyano-m-phenoxy) benzyl ester 100 100 0 85 0 100 0 90 0.03 100 0 (known compound) 300 95 0 100 0 100 0 95 0 95 0 900 100 0 100 0 100 0 100 0 100 0 control - 0 100 0 96.3 5 90 0 73.8 13 80

1 * = Average death rate%

2 ** = Average Plant Damage%

Example 45

Investigation of ixodicidal activity

The efficacy of the compounds of the invention in killing larvae of mites was demonstrated by the following assays. The larvae of Boophilus mieroplus, which is a single host animal ticks and remains on a single host animal at three stages of its life, that is, larvae, pupae and adult insects, were used for the studies.

In the tests, solutions containing the compound of the invention at concentrations of 0.025 ppm, 0.1 ppm, 0.5 ppm, 2.5 ppm or 12.5 ppm were used, using a mixture of 10% acetone and 90% water as the solvent. Twenty larvae were aspirated into a pipette, one end sealed with gauze, and a solution containing the test compound was aspirated through a pipette with a vacuum hose, mimicking a spray system. The ticks were kept at room temperature for 48 hours and then the extent of their death was determined. The results are shown in Table V.

Table V.

Mortality of Boophilus mieroplus larvae,%

Compound ppm 12.5 2.5 0.5 0.1 0,025 alpha-isopropyl-4- - (Trifluoromethoxy) phenyl acetic acid (alpha-cyano-m-phenoxy) benzyl ester 100 100 100 100 100

The above assays were then repeated, except that the present invention was tested

The concentration of -1429 was 0.1 ppm, 0.025 ppm, 0.005 ppm and 0.001 ppm, respectively. The results are shown in Table VI. is shown in Table.

VI. spreadsheet

Mortality of Boophilus microplus larvae,%

Compound 0.1 0.025 0.005 0.001 Alpha-isopropyl-4-trifluoromethoxyphenylacetic acid (alpha-cyano-m-phenoxy) -benzyl ester 100 100 80 80

The above tests were repeated, except that the concentrations of the compound of the invention tested were 0.1 ppm, 0.01 ppm, 0.001 ppm, 0.0001 ppm and 0.00001 ppm, respectively. The results are reported in Vla. is shown in Table.

Vl / a. spreadsheet

Mortality of Boophilus microplus larvae,%

Compound alpha-isopropyl-4-difluoro-ethoxy-phenyl-acetic acid (alpha'-cyano-m-phenoxy) -benzyl ester

0.1 0.01 0,001 0.0001 0.00001 ppm ppm ppm PPni pPM 0.1 0.01 0,001 0.0001 0.00001 ppm ppm ppm ppm ppm 100 100 100 50 0

The above tests were repeated except that the concentration of the compound of the invention tested was 100 ppm. The results obtained are shown in Table VIb. Table.

V / b. spreadsheet

Mortality of Boophilus microplus larvae,%

Adult fertilized female ticks were then immersed in the test solution for 3 seconds, then kept in separate pots for 48 hours at 27 ° C and 50% relative humidity. We then examined the ticks and counted the eggs laid. Fertilized female ticks that did not lay eggs were considered dead. The data obtained are shown in Table VII. Table.

VII. spreadsheet

Ixodicidal activity against an edible boophilus microplus

Adult tick death,% of compound given. concentrations

Compound

125 02,5 31,2 15,6 7,3 ppm ppm ppm ppm ulfa-isopropyl-4 (trifluoromethoxy)

-phenylacetic acid (alpha-cyano-m-phenoxy) -benzyl ester 100 100 99.4 98.8 87.2

Example 47

The efficacy of the compounds of the invention was tested using Cochliomyia hominivorax. First larval Cochliomyia hominivorax larvae were fed on a mixture of 8.0 g of minced beef, 7.0 ml of blood, 2.1 ml of water and 0.9 ml of a composition containing the compounds of the invention in concentrations of 1 ppm, 5 ppm or 25 ppm.

In two replicates, 20 to 20 larvae were used at each concentration. The larvae were allowed to feed indefinitely for 24 hours. The number of dead larvae was then determined and the percent mortality was calculated. The data obtained are shown in Table VIII. Table.

Compound 100 ppm alpha-isopropyl-4-difluoromethylthio-phenylacetic acid (alpha-cyano-m-phenoxy) -benzyl ester 100 alpha-isopropyl-4-difluoromethoxy-phenylacetic acid - (m-phenoxy) benzyl ester 100 alpha-ethyl-4- (trifluoromethoxy) phenyl acetic acid (m-phenoxy) benzyl ester 100 alpha-ethyl-4- (trifluoromethoxy) phenyl acetic acid (alpha-cyano-m-phenoxy) -benzyl ester100 alpha-propyl-4- (trifluoromethoxy) phenylacetic acid (alpha-cyano-m-phenoxy) benzyl ester100

VIII. spreadsheet

Effect on larvae of Cochliomyia hominivorax

Compound Mortality,% at given compound concentrations 1 ppm 5 pPM 25 pPM alpha-isopropyl-4- (trifluoromethoxy) - phenylacetic acid (alpha-cyano-m-phenoxy) - benzyl ester 2.4 69.2 100

Example 46

In these tests, the compounds of the invention were tested for efficacy against adult Boophilus micoplus ticks. The test compound was tested in substantially the same solutions as in Example 45 except that the concentrations were 125 ppm, 52.6 ppm, 31.2 ppm, 15.6 ppm and 7.3 ppm, respectively.

Example 48

Determination of LC _S0 of the compounds Young cotton shrubs, usually one leaf at a time, were immersed in a solution of the test compound for three seconds using Heliotliis virescens in cotton swabs, containing at least two adult leaves. Solvents were 65% acetone and 35% water

-1531 mixture was used. The concentration of each compound was 1.1 ppm, 2.8 ppm, 7.5 ppm, 20 ppm, 60 ppm and 150 ppm, respectively.

After drying the leaves, two leaves of each of the two plants were cut and placed in 90 mm X10 mm Petri dishes on wet filter paper (9 cm Whatman No. 1). Five leaf third larvae of Heliothis virescens were placed on each leaf and the Petri dishes were sealed. The infected dishes were then stored at 27 ° C and 50% relative humidity under continuous illumination. After 72 hours, larvae were counted. Each treatment was repeated four times. The data obtained are shown in Table IX. Table. From the table it can be seen that the compound of the invention tested is 2-5 times as effective against the known compounds used for comparison as Heliothis virescens larvae.

IX. spreadsheet

Determination of LC ₅ q values of compounds in larvae 3 of Heliothis virescens

Compound Dose, ppm Number of insects tested Number of dead insects LCso alpha-isopropyl-4- 1.10 20 3 2.94 - (trifluoromethoxy) - 2.80 20 9 phenylacetic acid 7.50 20 18 - (alpha-cyano-m- 20.00 20 19 phenoxy) benzyl 60.00 20 20 ester 7.50 20 2 14.6 permethrin 20.00 20 16 60.00 20 19 150.00 20 20 alpha-isopropyl-4- 2.80 20 3 6.4 - (chlorophenyl) acetic acid 7.50 20 13 acid (alpha-cyano-m- 20.00 20 17 phenoxy) benzyl 60.00 20 20 ester (known 150.00 20 20 compound)

Example 49

Determination of LC _S0 values of compounds using adult Anopheles quadrimaculatus (Say) mosquitoes

Test compounds were prepared in various concentrations of acetone to form aerosols. 0.15 ml of the solution was pipetted onto the top of the nozzle. The sprayed droplets were fed to the mosquitoes at a flow rate of 6.4 km / h (25 adult females per dish) and treated for 4-5 seconds. The mosquitoes were then treated with carbon dioxide for 3 to 4 seconds and transferred to containers at 29.4 + 0.5 ° C and 46 + 2% RH. After 24 hours, dead individuals were counted.

The data obtained are shown in Table X. It can be seen that the compound of the invention is about four times more potent than the known comparator compound in adult individuals of Anopheles quadrimaculatus.

Table X.

Determination of LCjg of the compounds in adult female individuals of Anopheles quadrimaculatus

Compound Concentration, ppm Death, 0 / * / o Skidding LC50 value, ppm alpha-isopropyl-4- 0.5 10 5 - (trifluoromethoxy) - 1.0 10 phenylacetic acid 2.0 5 - (alpha-cyano-m- 3.0 5 phenoxy) benzyl 5.0 52 -ester 15.0 95 alpha-isopropyl-4- 5.0 (1) 10 (2) 6 '(1) 21 chloro-phenylacetic acid 10.0 14 26 i (2) 18.8 (Alpha-cyano-m- 20.0 66 60 phenoxy) benzyl 40.0 62 78 ester (73/4462). 80.0 92 90 s. South African published announcement known compound)

* Data from two different trials (1) Test # 1 (2) Test # 2

Example 50

Residual insecticidal activity when the compounds of the invention are used in small volumes

The test compounds were dispersed in a mixture of 65 wt% acetone and 35 wt% water to be sprayed at a concentration of 0.08 kg / ha when diluted with 19.3 liters of water. The cotton shrubs were then placed in a spray booth and the plants passing under the spray head were sprayed.

After the leaves had dried, two leaves were cut from each of two plants and placed in 90 mm x 10 mm petri dishes on wet filter paper. (9 cm Whatman No.

1). Five Heliothis virescens larvae with third instar larvae were placed on each leaf and the Petri dishes were sealed. The infected dishes were maintained at 27 ° C and 50% relative humidity under continuous illumination. After 72 hours, larvae were counted.

The rest of the plants were well lit in the greenhouse. After 3, 7, 10 and 14 days, leaf samples were exposed to third larval Heliothis virescens larvae.

The data obtained during the investigations are presented in Annex XI. Table.

Example 51

Ixodicidal activity of the compounds

The compounds of the invention were assayed for ixodicidal activity at a concentration of 12.5 ppm, 2.5 ppm, 0.5 ppm, 0.1 ppm, 0.02 ppm and 0.004 ppm, respectively, as in Example 45. The results obtained are shown in Table XII. Table.

-1 633

XI. spreadsheet

Residual insecticidal activity against Heliothis vireseens (sprayed on cotton at low volume)

VegyOIet Application rate kg / ha 1 · Residual activity on the specified day 0 · 2 * * 1 3 2 ** 7 1 '2 " 10 14 1 » 2 ·· 1 » 2 "· alpha-isopropyl-4- (trifluoromethoxy) phenyl -ecetBav- (alpha-cyano-m-phenoxy) - benzyl ester 0.08 95 0.03 100 0 90 0.03 90 0 80 0.03 alpha-isopropyl-4-chloro-phenyl-acetate - (alpha-cyano-m-phenoxy) benzyl ester 0.08 95 0.1 90 3.0 80 2.5 80 0.78 50 1.6 control - 0 92.5 0 88.5 0 87.5 30 41.3 0 67.5

* = Mean Mortality,% (72-hour mortality rate) * = Average Plant Damage,% (4 replicates)

XII. spreadsheet

Percentage mortality of Boophilus microplus larvae

post- Mortality at the indicated concentrations of the compounds Compound treatment Days 12.5 2.5 0.5 0.1 0.02 0.004

alpha-isopropyl-4- (l, l, 2,2-tetrafluoro- methoxy) phenyl

acetic acid (alpha-cyano-m-phenoxy) benzyl ester 2 100 100 100 100 0 0 3 100 100 100 100 45 25 alpha-isopropyl-4- (1,1,2,2-tetrafluoroethoxy) phenyl 2 100 100 100 0 0 0 acetic acid (m-phenoxy) benzyl ester 3 100 100 100 20 15 15

Example 52

The efficacy of the compounds of the present invention was tested using adult Rhipieephalus sanguineus and Dermacentor varicosities, which are parasitic ticks on several host animals in dogs. Test solutions were prepared as in Example 45. 100 ppm, 10 pp, and 1 ppm were used.

The mature and fertilized female ticks were immersed in the test solution for 3 seconds and then placed in separate dishes for 48 hours in a room having a temperature of 27 ° C and a relative humidity of 50%. The ticks were then examined and the eggs laid were counted. Fertilized female ticks that did not lay eggs were considered dead. The data obtained are shown in Table XIII. Table.

XIII. spreadsheet

Ixodicidal activity against adult individuals of Rhipieephalus sanquineus (R.S.) and Dermacentor variabilis (D.V.)

Compound Concentration in ppm Advanced tick death, K.S. 0 / /She D.V. alpha-isopropyl-4- (trifluoro- 100 100 100 methoxy) phenyl-acetic acid 10 100 90 - (alpha-cyano-m-phenoxy) - 1 100 60 benzyl ester

Example 53

Testing of compounds of the invention using adult Ctenocephalides felis in vitro

The studies and 10 adult Ctenocephalides felis fleas were sprayed with a solution of the test compound to 100 ppm, 50 ppm, 10 ppm and 1 ppm, acetone and water ^υ vei 30 seconds. After treatment, the fleas were kept for 48 hours at room temperature and 80% relative humidity. Dead fleas were counted after 24 hours and 48 hours. the results obtained are shown in Table XIV. Table of contents.

XIV. spreadsheet

Syphonepicidal activity of test compounds

50 Batting Mortality,% the given Compound time concentration in ppm hour 100 50 10 1 alpha-isopropyl-4- (l, l, 2,2- 55 -tetrafluoroethoxy) -phenylacetic acid (alpha-cyano-m-phenoxy) -benzyl- 24 100 70 0 0 -ester 48 100 90 20 0 alpha-isopropyl-4- (l, l, 2,2- 60 -tetrafluor-ethoxy) -phenyl-acetic acid (m- 24 80 50 0 0 phenoxy) -benzyl ester 48 90 50 0 0

The above tests were repeated, except that the test compound was 80 ppm,

They were used at concentrations of -1735 ppm, 20 ppm, 10 ppm, 5 ppm and 2.5 ppm, respectively. Two replicate assays were performed and the mean of the results is reported as XIVa. Table.

XLV / a. spreadsheet

Syphonaptericidal activity of test compound

Compound alpha-4-isopropyl-4-methyl-fluoro-methoxyphenyl-acetic acid (m-phenoxy) -benzyl ether

Two to two cups of each concentration and control were infected with overnight Musca autumnalis larvae and kept for 7 days at 27 ° C and 50% relative humidity. We then examined the contents of the cups, counted the puppets present, weighed them and placed them in plastic vials. The dead flies were counted and the data obtained were expressed as a percentage in XVI. Table.

After treatment time, hour

Mortality,% at the given concentration, ppm

20 10

2.5 0

100 * 70 45 30 40 20 0 * - Single examination

XVI. spreadsheet

Inhibition of Musca autumnalis in fertilizer (In the in vitro assay, the compound was used as 15 food additives.

Average of data from two replicates)

Example 54

The test described in Example 52 was repeated except that adult males and females of Rhipicephalus sanguineus and Dermacentor were used. The concentrations of the test compounds in the solutions were 1.0%, 0.1%, 0.01% and 0.001%, respectively. Mortality was assessed after 24 and 48 hours of post-treatment. The data obtained are shown in Table XV. Table.

XV. táblázst

Compound Concentration in manure, ppm Musca autumnalis tapping Inhibition of pupae % inhibition of hatching,% control 0.0 0.0 alpha-isopropyl-4- 0.13 86.8 90.6 - (difluoromethoxy) phenyl 0.25 78.9 84.4 acetic acid (alpha-cyano-m- 0.50 97.3 91.9

3θ-phenoxy-benzyl ester

Ixodicidal activity against adult individuals of Rhipicephalus sanguineus (R.S.) and Dermacentor variable (D.V.) (Mean data from two replicate studies, unless otherwise stated)

Adult tick death,% con-

Compound concentration % K. s. D.V. 24 hours 48 hours 24 hours 48 hours alpha-isopropyl-4-dif 1.0 100 * 100 * luoromethoxyphenyl 0.1 100 * - 100 * - acid / alfa-cyano 0.01 100 100 * 100 100 m-phenoxy / - benzyl- -ester 0,001 100 100 65 65

* single examination

Example 55

The efficacy of the compounds of the present invention against Musca autumnal flies was tested by the following tests in which day-old orphans were fed with cow fertilizer containing 0.13 ppm, 0.25 ppm and 0.50 ppm of the test compound, respectively. 55

Two replicates were performed at each concentration with 10-10 larvae and untreated controls were used for comparison.

An appropriate amount of the test compound in acetone solution was added to 1 kg of fresh cow manure and stirred with an electric mixer for 1 minute. Only acetone was added to the fertilizer used for control, without the compound of the invention.

The fertilizer samples were divided into 4 paper cups. 65

Moisturizing powder

The following components are mixed to form a wettable powder formulation: Compound of Formula I Sodium Lignosulfonate Synthetic Ca-Silicate

-5g

0.1-0.9 g

1.0-4 g of diatomaceous silicate 3-7 g

Any of the compounds of the invention is suitable for the preparation of a wettable powder composition thereof.

By mixing the following components, a wettable powder composition can be obtained:

Example 7 Compound 7g Sodium lignosulfonate0.5g Synthetic Ca-Silicate2g Diatomaceosilicate6.5g

Emulsifiable concentrate

An emulsifiable concentrate may be prepared

from the components below. Example 8 20g cyclohexanone 25g white active ingredient ⁴ g emulsifier 4g petroleum based solvent 47g

PATENT CLAIMS:

Claims (4)

Insecticidal and acaricidal compositions, characterized in that the active ingredient is a phenylalkanoic acid ester of the formula (1), optionally optically active. -1 837 180118 contains from 0.1% to 90% by weight - of the formula X in the formula (I) the RCF ₂ X is in the meta or para position, and - X represents an oxygen atom, a sulfur atom, -S (O) - or -S ( O ₂ ) -; - R is hydrogen, fluorine, chlorine or difluoromethyl or trifluoromethyl; - R ₂ is ethyl, η-propyl, isopropyl, tert- -butyl or isopropenyl; - R ₃ is hydrogen or cyano emulsifier, preferably sodium lignosulfonate and carrier, preferably diatomaceous earth. 2. The composition of claim 1 wherein the active ingredient is a compound of formula (I) wherein X is oxygen. 3. A process for the preparation of an active ingredient of formula (I) in an insecticidal composition according to claim 1, wherein the substituent RCF ₂ X in formula (I) is in the meta or para position, and - X is oxygen, sulfur, - S (O) -. or - S (O ₂ ) -; 5 - R is hydrogen, fluoro, chloro or difluoromethyl or trifluoromethyl; - R ₂ is ethyl, η-propyl, isopropyl, tert-butyl or isopropenyl; 10 - R ₃ is hydrogen or cyano characterized in that a compound of formula II - X, R and R ₂ are as defined above, A is halogen - is reacted with m-phenoxybenzyl alcohol derivative of formula (III) R ₃ is as defined above in the presence of an acid scavenger and an inert organic solvent, and if desired the resulting product is resolved in a manner known per se and the optical isomers are isolated. 4. The process of claim 3 wherein the acid acceptor is tertiary amine.