DD142961A5 - PROCESS FOR THE PREPARATION OF PHENYL ALKANSANIC M-PHENOXYBENYL ESTERS - Google Patents

Description

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File number: 26,387 DIV

(Excretion from patent application AP C 07 C / 203 805)

Applicant: American Cyanamid Company,

Wayne, New Jersey, V.St.A.

Representative: Patent Attorney Office Berlin

Frankfurter Allee 286 113 Berlin

Title of the invention: Process for the preparation of phenylalkanoic acid m

ph enoxybenzyl esters

Field of application of the invention;

The invention relates to a process for the preparation of phenylalkanoic acid m-phenoxybenzylestern of the general formula I.

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wherein the substituent of the formula RCF ₃ X- is in the m- or p-position to the carbon atom to which the alkanoic acid ester group is bonded, and

X is a sulfur atom, an oxygen atom, a sulfinyl group or a sulfonyl group,

R is a hydrogen atom, a fluorine atom, a chlorine atom, a difluoromethyl group or a trifluoromethyl group,

R _{2 is} an ethyl group, an n-propyl group, an isopropyl group, a tert-butyl group or an isopropenyl group, and

R-. a hydrogen a torn or a cyano group mean.

The novel phenylalkanoic acid m-phenoxybenzyl esters of formula I obtainable by the process according to the invention are particularly suitable for controlling insects and mites.

Characteristic of the known solutions:

The prior art known to the applicant is South African Patent Application No. 73/4462 of Sumitomo Chemical Company Limited.

^': Rt m in / μ *; · Si ν η;

12571

This patent application describes tens of thousands of phenylacetic acid esters, including oc-isopropyl-4-methoxyphenyl-acetic acid 3'-phenoxybenzyl ester, oC-isopropyl-3-methoxyphenyl-acetic acid 3'-phenoxybenzyl ester, c (isopropyl-4-chlorophenyl) acetic acid ~ 3'-phenoxybenzyl ester, (xi-isopropyl-4-methylphenyI-acetic acid 3'-phenoxybenzyl ester, o ^ -isopropyl-S-chlorophenyl-acetic acid S'-phenoxybenzyl ester, and oi-isopropyl-4-fluorophenyl-acetic acid 3 It is further stated that many of these compounds are effective pesticidal agents and can be used to control a variety of insects and mites, but neither the instant invention nor the 2- (haloalkoxyphenyl) alkanoic acid m-phenoxybenzyl esters of this invention are a suitable for the preparation of these compounds synthesis method described.

Pyrethroids such as permethrin, phenothrin or allethrin have also been used to control insects and mites.

However, all known agents against insects and mites have more or less pronounced disadvantages, such as too low efficacy, too narrow spectrum of activity, no sufficient residual ixodizide or insecticidal effect or too low a safety margin.

Object of the invention;

Due to the above-mentioned disadvantages of the known methods and agents for controlling insects and mites, the invention has now set itself the task

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In this regard, remedy by a process for the preparation of new compounds that are distinguished by their particularly good action against insects and mites.

Explanation of the essence of the invention:

The above object is achieved in the method of the type mentioned according to the invention now characterized in that a compound of the general formula

(/ \\ - CH-COA

RCF X

in which A represents a halogen atom and R and R "have the meanings indicated, with an m-phenyloxybenzyl alcohol of the general formula

in which R_ has the meaning given, in the presence of a tertiary organic amine as the acid acceptor and an inert organic solvent at a temperature of 10 to 30 ⁰ C reacted.

It has now surprisingly been found that the compounds obtainable according to the invention are not only effective insecticidal agents, but also a strong

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Exercise against ticks. These compounds also represent systemic insecticidal and ixodicidal agents. They exhibit a high safety margin and can be effectively used to protect pets, laboratory animals and farm animals from attack by insects and ticks. Compared with known pyrethroids such as permethrin, phenothrin, allethrin or the like, the compounds of the present invention further show superior residual ixodicidal and insecticidal activity and are particularly effective for controlling the tobacco caterpillar (Heliothis virescens) and mosquitoes.

As the oC-substituted 2-haloalkyl (oxy, thio, sulfinyl or sulfonyl) phenylacetyl halides of the above-defined general formula II, the corresponding chlorides are preferably used. The reaction is, as indicated, generally carried out in the presence of a solvent such as diethyl ether, benzene or toluene, and at temperatures between about 10 ⁰ C and 30 ⁰ C and in the presence of an acid acceptor. As acid acceptors one can use tertiary organic amines, trimethylamine, triethylamine and pyridine. This reaction can be illustrated by the following reaction scheme:

V W

/ \\ _ CH-C0A +

(II)

RCF X-

(III)

CH-CO-O-CH-

R ₂ R ₃

(D

acid acceptor

0-,

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The substituents contained therein have the meanings already given above, wherein the substituent A is preferably chlorine.

Preferred compounds of the above general formula I are

1. those in which the substituent of formula RCF "is X-in-position to the carbon atom to which the alkanoic acid ester group is attached, and R, R" and R are as defined above; and

2. those compounds in which the substituent of the formula RCFpX- is in the m-position to the carbon atom to which the alkanoic acid ester group is bonded, and R, R _? and R_ have the meanings given above.

It has also been found that of the compounds of these groups those are even more preferred in which X is an oxygen or a sulfur atom, R is a hydrogen atom or a fluorine atom, R ,. a hydrogen atom or a cyano group and R ~ an ethyl group, an n-propyl group or an isopropyl group.

It should also be noted that in the above-described preparation of the compound of general formula I according to the invention, various optical isomers of these compounds result.

For example, in the preparation of the esters of the general formula I, when R _{3 represents} a hydrogen atom, in the region of the group R _{3 is} a chiral center, so that d and 1-isomer pairs are formed. Furthermore, in the case of a cyano group as c ^ substituent in the region of the substituent R ₃ another

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formed chiral center, so that another d- and 1-Isornerenpaar is possible.

For example, it has been found that when mixed with about 0.5 to 1.0 molar equivalents of (-) - (/ - phenethylamine in a suitable solvent such as ethanol or aqueous ethanol), the salt of C 1-6 -propyl-4-trifluoromethoxyphenylacetic acid Upon acidification, this salt gives the acid, which is generally greater than 85% in the form of the (+) isomer, and an even better cleavage can be obtained by recrystallization of the (-) - 06-phenethylamine salt or by repeating the cleavage procedure with fresh (-) - ^ -phenylethylamine The m-phenoxybenzyl esters or 06-cyanom-phenoxybenzyl esters of fully resolved (+) - iP ^ -isopropyl-4-trifluoromethoxyphenylacetic acid are approximately twice as potent in insecticidal activity as the corresponding ones In the case of Oc-cyano-m-phenoxybenzyl ester, a further increase in activity is achieved by forming the corresponding optically active ester formation reaction n-cyano-phenoxybenzyl alcohol.

The c 1-5 substituted 2-haloalkyl (oxy, thio, sulfinyl or sulfonyl) -phenylacetyl halides of the general formula II in which R 1 is an ethyl group, an n-propyl group or an isopropyl group can be obtained by using the corresponding Tcluols of the general formula IV produce as starting material. The preparation process comprises five steps, the first of which comprises the halogenation of the toluene of general formula IV with bromine, chlorine, N-bromosuccinimide (NBS) or the like. This reaction is preferably carried out in the presence of a

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inert organic solvent such as carbon tetrachloride, and a radical-forming initiator such as light, benzoyl peroxide or azo-bis (isobutyronitrile) to form the benzyl halide of the general formula V is formed. The benzyl halide of general formula V is then converted to the corresponding phenylacetonitrile of general formula VI by reaction with sodium cyanide or potassium cyanide in the presence of dimethyl sulfoxide (DMSO), ethanol or the like at elevated temperature. This substituted phenylacetonitrile of general formula VI is readily alkylated by treatment with an alkyl halide in the presence of a base and an inert organic solvent, it being found that crown ethers are useful catalysts for this reaction. The cxi-position alkyl-substituted phenylacetonitrile formed in the above reaction is represented by the following general formula VII in Reaction Scheme I below and affords the corresponding C 1-6 alkyl-substituted phenylacetic acid of general formula VIII by hydrolysis using an alkali metal hydroxide in the presence of an alkylene glycol and water Reaction of the acid of general formula VIII with thionyl chloride, thionyl bromide or the like, which is preferably carried out in the presence of an aromatic solvent, such as benzene or toluene, affords the o (-alkyl-substituted phenylacetyl halide of general formula II, which is then m -formed. Phenoxybenzylalkohol the general formula III or c ^ cyano-m-phenoxybenzylalkohol to the desired m-phenoxybenzyl ester or the c ^ -cyano-m-phenoxybenzylester of the corresponding 2-haloalkyl (oxy, thio, sulfinyl or sulfonyl) - phenylalkanoic acid of general formula 1. This react ions are shown in Reaction Scheme I below.

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Reaction scheme I

Preparation of the 2-haloalkyl (oxy, thio, sulfinyl or sulfonyl) -phenylalkanoic acid m-phenoxybenzyl esters

(IV)

or (NBS) RCF X.

CH Br

(V)

(/ \\ - CH.Br +

NaCN DMSO

CH CN

(V)

(VI)

RCF X

CH CN + RX benzene NaOH / H 0

crown ether

RCF X

.CHCN

^R 2

(VI)

(VII)

RCF X

IHCN + KOH HIGH CH OH '

RCF X

HCOOH

(VIII)

(VII)

CHCOOH + SOCl, benzene ^

HCOCl

(VIII)

(ID

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Reaction Scheme I (continued)

(ID

CHCOCl +

CH-CO-O-CH-,

+ Pyridine -

(III)

benzene

As an alternative to the benzyl bromide of the general formula V indicated in the reaction scheme, if only p-substituted products are to be prepared, the corresponding haloalkyl (oxy or thio) benzene of the general formula IX can be prepared using a mixture of paraformaldehyde or Chloroformate trioxane and zinc chloride and dry hydrogen chloride to form the corresponding benzyl chloride of the general formula X, which can then be used in place of the benzyl bromide of the general formula V in the further synthesis of the compounds of general formula I according to the invention. This modification of the procedure can be described as follows:

ZnCl,

+ (CELO) + HCl 2 η

Y = O or S

(IX)

² \ / ^CH2C1

(X)

The preparation of the m-Phenoxybenzylester and oC-cyano-mphenoxybenzylester of o ^ -alkyl-3- (or 4) -trifluoromethoxyphenylacetic acid can also be achieved via a reaction sequence which begins with the alkylation of m- or p-methoxyphenylacetonitrile, what to one Alkyl halide used in the presence of a crown ether and a base. It will of course be appreciated that when m-methoxyphenylacetonitrile is used in this reaction, the i -alkyl-3-methoxyphenylacetonitrile is obtained while the o-j- alkyl-4-methoxyphenylacetonitrile is obtained using the p-isomer , It will be further understood from the discussion below that the position of the methoxy group on this phenylacetonitrile starting material determines the position of the trifluoromethoxy substituent of the final product.

The above-mentioned ^ -alkyl-3 (or 4) -methoxyphenylacetonitrile is then converted to ocf-alkyl-3 (or 4) -hydroxyphenylacetonitrile by treatment with boron tribromide, preferably in the presence of a solvent such as methylene chloride. Reaction of the phenol thus formed with thiophosgene and a base in the presence of a solvent such as chloroform / then gives the chlorothioester of 0 ~ / m- or p- (1-cyano-2-methylpropyl) -phenyiV-formic acid. This ester can be readily converted with molybdenum hexafluoride into the corresponding o.sup.3- alkyl-3 (or 4) -trifluoromethoxyphenylacetonitrile, which is then converted to the corresponding oC-alkyl-3 (or 4) by reaction with ethylene glycol in the presence of an alkali metal hydroxide and water. trifluoromethoxyphenylacetic acid is hydrolyzed.

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Treatment of the o-i-alkyl-3 (or 4) trifluoromethoxyphenylacetic acid with thionyl chloride in the presence of an aromatic solvent such as benzene or toluene affords the corresponding acid chloride which reacts with m-phenoxybenzyl alcohol or C 1-4 cyano-m-phenoxybenzyl alcohol to give the desired c ^ -Alkyl-3 (or 4) -trifluoromethoxyphenylacetic acid m-phenoxybenzyl ester or o -cyano-mphenoxybenzyl ester. These reactions are illustrated by the following Reaction Scheme II.

Reaction scheme II

CH CN + R Br

Crown ether 50% NaOH

- CH-CN + BBr.

CH-CN + CSCI,

Il

Cl-CO

CHCl.

NaOH

, -CH-CN R_

Cl-C-O ^

H-CN

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Reaction Scheme II (continued)

f /

KOH

CF.

CH-CN + HIGH CHOH

CF ₃ O CH-COOH

CF ₃ O

- CH-COOH + SOCl ₀ >

τ? CF ₀

I-COCI

CF ₃ O

CH-COCl + OH-CH-

I

R ₀ R.

2 -

pyridine

CF ₃ O

- CH-CO-O-CHY / ^ -

^ K / J

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In the above Reaction Scheme II, R _{2 is} an ethyl group, an n-propyl group or an isopropyl group and R- is a hydrogen atom or a cyano group.

Although Reaction Scheme I is generally applicable to the preparation of a variety of the compounds of this invention, it has been found that alkaline hydrolysis of the nitriles of those compounds wherein the substituent RCF ₃ X- is a difluoromethyloxy group (HCF ₂ O-) or a difluoromethylthio group ( HCF ₂ S-), which can split off Dif1uormethy1gruppe (HCFp-). However, it has been found that this group can be reintroduced by reacting the corresponding phenol or thiophenol with chlorodifluoromethane in a mixture of aqueous alkali and dioxane.

The actual synthesis employed of any compounds having a difluoromethoxy group of the formula HCF "O- can be best understood by reference to Reaction Scheme III, below, in which the corresponding o-alkyl-3- (or 4) -methoxyphenylacetonitrile (as described in U.S. Pat Reaction Scheme II) is converted to the corresponding o <i-alkyl-3- (4) -hydroxyphenylacetic acid using hydrobromic acid. Treatment with chlorodifluoromethane in aqueous alkali and dioxane gives the corresponding cv-alkyl-3- (4) -difluoromethoxyphenylacetic acids. These acids are then converted to the desired m-phenoxybenzyl esters or C 1 to cyano-m-phenoxybenzyl esters in the manner indicated in Scheme II.

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Reaction Scheme III

CH ₃ O

48% HBr

CH-CN

> - jCH-CO H ^R 2

HO

CH-CO H + HCClF, dioxane

aqueous NaOH

HCF O

CH-CO H

3 a au L-. tr? iu, ^ v !.

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It should also be noted that although the synthetic method illustrated by Reaction Scheme I is suitable for the preparation of most compounds of general formula I, in the X is a sulfinyl group

0. 0

Il

(-S-) or a sulfonyl group (-S-),

Il

It is often more convenient to first produce the acids of general formula VIII or the esters of general formula I in which X represents a sulfur atom, and then to oxidize the sulfur atom to the desired sulfinyl or sulfonyl analogues, to obtain suitable oxidizing agents such as m-chloroperbenzoic acid, sodium periodate or hydrogen peroxide.

For the preparation of the compounds of the general formula I in which R _{2 represents} a tert-butyl group, the following reaction sequence is used which starts from the corresponding m- or p-substituted aldehyde:

1. A reaction with tert-butyl magnesium chloride is effected;

2. convert neopentyl alcohol to the corresponding chloride using thionyl chloride;

3. from the chloride, using magnesium in tetrahydrofuran, form the corresponding Grignard reagent; and

4. Carboxylated with carbon dioxide.

BU, AOLi3 / 3 * Bii 8 Vc

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The reaction sequence is further enhanced by the synthesis of oo-tert. Butyl-3- (or 4) -trifluoromethoxyphenylacetic acid according to the following Reaction Scheme IV illustrates. The acids, as illustrated in Reaction Scheme I, can then be converted to the corresponding esters.

^r -f | ν ¹ ! · '-io o - :. Q> \ v · -. ' ,: ·

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Reaction scheme IV

.CHO + t-BuMgCl

CF O

H-OH

CF 0

ι-CH-OH + SOCl,

ι '

C (CH ₃ )

CF 0

CH-Cl

C (CH ₃ )

CF ₃ O

-CH-Cl

2. CO, CF O

 - CH-COOH

C (CH ₃ )

011A ubi 3 / DB ^(iy;;

- "212571

To prepare the compounds of general formula I, in which R ~ represents an isopropenyl group, the introduction of the oi ~ I can sopropenylgruppe be reached at which the corresponding m- or p-substituted phenyl acetic acid is used with the following reaction sequence:

1. It is first reacted with two equivalents of isopropylmagnesium chloride and acetone;

2. the hydroxy acid is transferred to the ester; and

3. Dehydrate the hydroxyester with phosphorus pentoxide.

The synthesis is illustrated by the following Reaction Scheme V for the preparation of cA "-isopropenyl-4- (or 3) -trifluoromethoxyphenylacetic acid m-phenoxybenzyl ester.

O.1SiT .j ρ -; λ. ·: -. J V. HU: L \ i / Π -? <···:.

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Reaction scheme V

CF. ο

.CH ₂ COOH

^CF 3 °

I-COOH

C-OH CH ₃ CH ₃

CF ₃ O

ί-COOH + BrCH

Λ ^0Η

CH ₃ CH ₃

+ Et N

CF ₃ O

CH-CO-O-CH

Λ ^0Η

CH CH

O-

CF O

CH-CO-O-CH

CH ₃ CH ₃

^P 2 ° 5

CF O

CH-CO-O-CH

CH

on ftiSi

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p .. = »-: '.-": <- · -. W i'; iiiinr.f the c ^ -cyano-m-phenoxybenzylesterprodukte using άο_ cv · .. ch the above Reaction Schemes I and II illustrated procedures It is not necessary to prepare cv-cyano-m-phenoxybenzylalRc ^ o-iT - ^^ It is exactly or even more preferred / a mixture of m-phenoxybenzaldehyde, an alkali cyanide such as sodium cyanide, and the corresponding < To implement x-substituted 2-haloalkyl (oxy, thio, sulfinyl or sulfonyl) phenylacetyl halide in one step to form the intended end product c ^ cyanoester.

The compounds according to the invention are extremely effective contact poisons and stomach poisons for ticks and a multiplicity of insects, in particular two-leaved insects, butterflies, beetles and equinoxes. They are superior to pyrethroids in that they have a very long residual insecticidal activity in plant tissues, are effective in the soil, and are surprisingly effective in controlling ticks and protecting animals against infestation by insects and ticks, when these compounds are present administered orally or parenterally or topically in the form of insecticidal or acaricidal formulations to the animals. They need not be mixed with a stabilizer to give stabilized insecticidal and acaricidal agents. However, they may be used in combination with other biological chemicals, for example synergists for pyrethroids such as piperonyl butoxide, sesamex or the ri-octylsulfoxide of isosafrole. They may also be used in combination with conventional insecticides such as phosphates, carbamates, formamidines, chlorinated hydrocarbons or halobenzoyl resins. To combat insects, including

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Soil insects that infest growing plants and / or crops, including stored crops, the insecticidal compounds of the present invention may be applied to the foliage of the plants, the insect life area, and / or the insect food stock. In general, the active substance is applied in the form of a dilute 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 fluids are oil spray fluids and emulsifiable concentrates, which can be further diluted for use. Although prepared for ease of handling and facilitated transport in the form of liquid concentrates, these formulations are usually dispersed in water at the point of use and then applied as a dilute spray to the foliage of the plants, the soil or the surface of the area to be treated.

A typical emulsifiable concentrate that can be used to protect a variety of crops such as cereals, cabbage, squash, corn, cotton, tobacco, soybeans, ornamentals, shrubs, and the like may contain about 20% by weight of the active ingredient; 4% by weight of an emulsifier as commonly used to prepare 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 solvent having an aromatic content of at least about 8 3% by volume.

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When used as a systemic insecticidal and acaricidal agent for the treatment of animals, the compounds of the invention can be administered either orally or parenterally to the animals to be treated. For administration by oral route, the. Drugs in any form suitable for this route of administration, for example in the form of a bolus, in the form of capsules, tablets or an orally administered drug. The active ingredient may also be incorporated in the animal feed, for example a nutritionally balanced feed containing from 0.0001% to 0.1%, preferably from 0.001% to 0.05%, by weight of the active ingredient based on the weight of the feed ,

If desired, the agent acting systemically against insects and mites may be introduced into the carcass by subcutaneous, intramuscular or intraperitoneal injection so as to spread throughout the animal body via the circulatory system of the animal. In practice, the systemically active agent may be dissolved or dispersed in a pharmaceutically acceptable carrier such as water, propylene glycol, a vegetable oil, glycerol formal or the like.

Advantageously, the systemic agents have a good safety range and protect a variety of animals, especially cattle and pets, such as cattle, sheep, horses, dogs, cats and the like, against infestation by fleas. Mosquitoes, flies, ticks and the like.

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Particularly preferred insecticidal and acaricidal active compounds according to the invention are:

P ^ -isopropyl-trifluoromethoxyphenyl-acetic acid in-phenoxy benzyl ester,

O ^ -isopropyl-4-trifluoromethoxyphenylacetic acid e-cC-cyano-m- phenoxybenzylester,

"Pt-isopropyl-S-trifluoromethoxybenzyl-acetic acid - ^ - cyanom-phenoxybenzyl,

cL- 1-sopropyl-4-chlorodifluoromethoxyphenylacetic acid & cC- cyano-m-phenoxybenzyl ester ,

oc-isopropyl-4- (1,1,2,2-tetrafluoräthoxy) phenylacetic acid-m-phenoxybenzyl ester,

^ Isopropyl-4-acetic acid pentafluoräthoxyphenyl-oC-cyanorn-phenoxybenzyl,

-3-trifluoromethoxyphenyl-acetic acid, m-phenoxybenzyl,

oC-n-propyl 1-4-chloro-fluorine-thoxyphenyl-acetic acid e-H-cyanom-phenoxybenzylester,

<? C-tert. Butyl-4-trifluoromethoxyphenyl-acetic acid-iTv-cyanom-phenoxybenzylester,

cC ~ I sopropyl-4-difluoromethoxyphenyl-s-acetic acid-o (f-cyano-mphenoxybenzyl ester,

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o -isopropyl-4-tr if luorme thy lthiophenyl-sacetic acid - ^ - cyanom-phenoxybenzylester,

c ^ -Äthy1-4-trifluormethy1sulfinylphenyl-acetic acid ^ cyanom-phenoxybenzyl,

o -Isopropyl-3-dif luorme thy 1 sul fony lphenyl-acetic acid e ~ J </ - cyanom phenoxybenzyl ester,

C 1-6 -ethyl-4-trifluoromethoxyphenyl-acetic acid <3 (f-cyano-m-phenoxybenzyl ester and

oL- ~ L sopropeny 1-4 -tr if luormethoxyphenylacetic acid e - ^ - cyanom phenoxybenzylester.

The following examples serve to further illustrate the invention.

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example 1

Preparation of p- (1,1,2,2-tetrafluoroethoxy) -toluene

In a stirred with the aid of a magnetic stirrer mixture of 10.8 g (0.100 mol) of p-cresol, 1.67 g (1.43 g real, 0.0255 mol) Kaliumhydroxidplätzchen and 70 ml of dried dimethylformamide kept at 68 ⁰ C. is introduced, one for 1 hour tetrafluoroethylene and nitrogen. 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 to give 18.14 g (87%) of p- (1,1,2,2-tetrafluoroethoxy) -toluene.

Analysis: C ₉ H ₉ F ₄ O:

Calculated: C 51.93% H 3.87% F 36.51% Found: 52.06 3.76 41.52

Example 2

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

A mechanically stirred mixture of 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, is heated. 00 g (4.13 mol, 0.73 mol%) of benzoyl peroxide and 350 ml of carbon tetrachloride for 2.25 hours to boiling at reflux. After cooling, the reaction mixture is diluted with 350 ml of carbon tetrachloride, filtered to remove the solid.

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dried over sodium sulfate, filtered and evaporated using a rotary evaporator to give 160.99 g (99%) of a clear, red oil. This product will be used as it is in the next stage of the process. The infrared spectrum and the NMR spectrum show that the product is p- (1,1,2,2-tetrafluoroethoxy) benzyl bromide.

Example 3

Preparation of p- (1,1,2,2-tetrafluoroethoxy) -phenylacetonitrile

In 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- (1,1,2,2 -Tetrafluoräthoxy) benzyl bromide and 500 ml of anhydrous alcohol (2B alcohol), which is maintained at 75 ⁰ C. The resulting mixture is then refluxed 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 g of an oil. The vacuum distillation of this oil gives as the only distillate fraction 37.10 g (28%) of the nitrile, which boils at 85 to 100 ° C / O, 29 mm Hg.

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Example 4

Preparation of ^ -isopropyl-p- (1,1,2,2-tetrafluoroethoxy) -phenylacetonitrile

A mixture of 39.85 g (0.171 mol) of p- (1,1,2, 2- Tetrafluoräthoxy) -phenylacetonitrile, 3.71 g (9.96 mmol, 5.8 MoI-I) dicyclohexyl / 18_ / 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 and 43 ⁰ C increases. 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. The ether solution is washed 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 47.13 g of an oil. This oil is distilled in vacuo to give 34.8 g (74%) of an oil boiling at 83-85 ° C / O, O55 to 0.090 mm Hg.

Analysis: C ₁₃ H ₁₃ F ₄ NO:

Calculated: C 56.73% H 4.76% N 5.09% F 27.61% Found: 56.12 4.85 4.99 34.07

Example 5

Preparation of 3-methyl-2- / p- (1,1,2,2-tetrafluoroethoxy) -phenyl / -butyric acid

A stirred mixture of 48.0 g (24.0 g real, 0.60 mole) 50% sodium hydroxide solution, 21.78 g (0.0791 mole) OL-isopropyl-p- (1.1, 2, 2-tetrafluoroethoxy) -phenylaceto-

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nitrile and 240 ml of ethylene glycol for 12 hours at 135 ⁰ C. After dilution with 600 ml of water, the reaction mixture is washed twice with 100 ml of ether. The aqueous layer is acidified with concentrated hydrochloric acid and then extracted twice with 300 ml of ether. Wash the ether solution washed twice with 500 ml water, dried over sodium sulfate, filtered, and evaporated to yield 20.74 g (89%) of a brown solid melting at 92-97 ⁰ C (hexane).

Analysis: C ₁₃ H ₁₄ F ₄ O ₃ :

Calculated: C 53.06% H 4.80% F 25.83% Found: 53.04 4.79 25.93

Example 6

Preparation of 3-methyl-2- / p- (1,1,2,2-tetrafluoroethoxy) -phenyl-butyryl chloride

A stirred mixture of 20.00 g (0.0680 mol) of 3-methyl-2- / p- (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 for 4 hours to reflux. Then the reaction mixture is evaporated, the residue formed is diluted with 50 ml of benzene, evaporated again and receives 22.46 g (106%) of a clear, dark brown liquid. This product will be used as it is in the next stage of the process. The infrared spectrum of the liquid indicates that it is the title compound.

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Example 7

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

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 is added over 20 minutes a solution of 10.6 g (0.034 mol) of 3-methyl-2- / p- (1,1, 2, 2-tetrafluoräthoxy) -pheny_l / -butyrylchlorid 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. Wash the ether solution with 200 ml of 20% hydrochloric acid solution and 200 ml of water, dry over sodium sulfate, filter, evaporate to obtain 16.24 g (100%) of the product. This product is purified using a dry silica column (116 cm χ 5 cm, eluent hexane / methylene chloride mixture (1/1)) by taking a sample between 85 cm and 63 cm (with the solvent front at 113 ° C) cm) and receives 12.60 g (78%) of a clear, pale yellow-colored oil.

Analysis: C ₂₆ H ₂₄ F ₄ O ₄ :

Calculated: C 65.54% H 5.08% F 15.95% Found: 64.99 4.96 19.10

Be ispiel 8

Preparation of <p <i-Isopropyl-4- (1,1,2,2-tetra-fluoroethoxy) phenylacetic acid cL- cyano-m-phenoxybenzene ester

To a stirred mixture of 8.81 g (7.49 g real, 0.0333 mole) of c'-cyano-m-phenoxybenzyl alcohol ,. 3.0 ml (2.95 g, 0.0372

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Mol) of dried pyridine and 20 ml of methylene chloride are added over 20 minutes a solution of 10.6 g (0.034 mol) of 3-methyl-2- / p- (1,1,2,2-tetrafluoräthoxy) -phenyl / - butyryl chloride in 20 ml of methylene chloride. 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 solution and 200 ml of water, dried over sodium sulfate, filtered and evaporated to give a dark red oil. To remove the present as impurity m-phenoxybenzaldehyde, the oil is reacted with 0.5 g of sodium borohydride at the ice bath temperature and purified the resulting oil using a dry silica gel column (121 cm χ 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) to give 11.17 g (66%) of a clear, orange oil.

Analysis: C ₂₇ H ₂ ^ F ₄ NO ₄ :

Calculated: C 64.67% H 4.62 I N 2.79 I F 15.16% Found: 65.26 4.81 2.82 17.94

Example 9

Preparation of C 1-4 isopropyl-4-methoxyphenylacetonitrile

To a solution of 147 g (1 mol) of p-methoxyphenylacetonitrile, 18.63 g (5 mol%) of dicyclohexyl-18 / crown-6 and 320 g (2.6 mol) of 2-bromopropane in 300 ml of benzene 300 ml of a 50% sodium hydroxide solution. The reaction mixture is heated to 45 ⁰ C and left for 4 days at this temperature. Then the organic phase is separated, washed well with water (three times 200 ml),

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dilute hydrochloric acid (once 200 ml), water (200 ml twice) and evaporated to an oil. The 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 (CDCl-) shows that the distilled material contains 12.5 mol% of the starting nitrile.

Example 10

Preparation of cv-isopropyl-4-hydroxyphenylacetonitrile

A solution of 51.0 g (0.2 mol) boron tribromide in 20 ml methylene chloride is added to a solution of 37.8 g (0.2 mol) ixi-isopropyl-4-methoxyphenylacetonitrile in 35 ml methylene chloride, which is 40 ⁰ C stops. The red solution is then allowed to warm to room temperature and 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. By vacuum distillation to obtain 28.9 g (81%) <X-isopropyl-4-hydroxyphenylacetonitrile, which boils at 142 to 143 ° C / O, 25 mm Hg.

Example 11

Preparation of the chlorothioic acid O-Zp (1-cyano-2-methylpropyl) phenyl / ester

16.43 g (0.143 mol) of thiophosgene in 50 ml of chloroform are added over 30 minutes to a solution of 25.0 g (0.143 mol) of c 1-5 -isopropyl-4-hydroxyphenylacetonitrile in a 5% sodium hydroxide solution (5, 72 g, 0.143 mol), wherein

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occasionally use an ice bath to keep the temperature below 30 ⁰ C. The mixture is stirred for 15 minutes, the chloroform layer is separated off, washed with water and evaporated to a yellow oil (38.2 g). The product is used as is in the procedure of Example 12.

Example 12

Preparation of i ^ -isopropyl-4-trifluoromethoxyphenylacetonitrile

Treating the 38.2 g of the thiocarbonate of Example 11 at -25 ⁰ C with 15.8 g of molybdenum hexafluoride. Then allowed to rise the temperature of the thick reaction mass to room temperature and then slowly heated using an oil bath at 160 ⁰ C., 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. The vacuum distillation gives c 1 -isopropyl-4-trifluoromethoxyphenylacetonitrile which boils at 78 to 80 ^° C / 0.15 mm Hg.

Example 13

Alternative method for the preparation of <X-isopropyl-4-trifluoromethoxyphenylacetonitrile

A. Preparation of 4-trifluoromethoxybenzyl chloride

A mixture of 355 mg of trioxane, 340 mg of zinc chloride and 600 mg of trifluoromethoxybenzoi is heated to 73 ^° C. and hydrogen chloride gas is passed through the reaction mixture. Then the reaction mixture is cooled to room temperature.

- 3 «- 2 1 2 5 7 1

temperature and diluted with water. The organic phase is washed with a saturated sodium carbonate solution and then with water. Removal of the solvents gives the product (1.42 g) as a colorless liquid.

B. Preparation of 4-trifluoromethoxyphenylacetonitrile

Following the procedure of Example 3, the chloro-compound obtained in step A above is converted to the corresponding nitrile in 93% yield.

C. Preparation of cx 1 -isopropyl-4-trifluoromethoxyphenylacetonitrile

Alkylation of the 4-trifluoromethoxyphenylacetonitrile by the procedure of Example 4 gives the desired compound in 90% yield.

Example 14

Preparation of <- (- Isopropyl-4-trifluoromethoxyphenylacetic acid

A mixture of 2.0 g of c <-isopropyl-4-trifluormethoxyphenylacetonitril, 3.0 g of potassium hydroxide, 35 ml of ethylene glycol and 3 ml of water for 8 hours at 140 ⁰ C. Then the solution is poured into water and extracted with ether ( twice 10 ml). The aqueous layer is acidified. Dilute hydrochloric acid and extracted with ether (3 times 10 ml), washed with water (once 25 ml), dried over sodium sulfate and evaporated to an oil (1.23 g). IR spectrum (of the pure material) 1700 cm

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Example 15

Preparation of O-isopropyl-4-trifluoromethoxyphenylacetyl chloride

A solution of 1.2 g of oo-isopropyl-4-trifluoromethoxyphenylacetic acid and 0.6 ml of thionyl chloride in 5 ml of benzene is refluxed 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 Examples 16 and 17.

Example 16

Preparation of α, ω-Isopropyl-4-trifluoromethoxyphenylacetic acid, C 1 -C -cyano-m-phenoxybenzyl ester

A solution of 4.58 mmol of C 1-4 -isopropyl-4-trifluoro-methoxyphenylacetyl chloride in 5 ml of ether is added to a solution of 4.59 mmol of C 1-8 cyano-m-phenoxybenzyl alcohol and 0.5 ml of pyridine in 20 ml of ether. The mixture is stirred overnight and filtered. The filtrate and wash are then evaporated and the residual oil is purified on silica gel coated plates (5x2 mm) using a methylene chloride / hexane mixture (1/1) as eluent. Extract the band with an R _f value of 0.55 with ether, evaporate and obtain the desired ester (0.85 g).

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_1

IR spectrum (of the pure material) 1755 cm NMR spectrum (CDCl ₃ ) </ * 6.8-7.6 (m, 13H, ArH), 6.31 and 6.28 (S, 1H, -CH-) Ar), 3.27 (d, J = 7Hz, 1H,

CN

-CH (CH ₃ ) ₂ ), 2.0-2.6 (m, 1H, CH (CH ₃ ) ₂ ), 0.6-1.2

(four doublets, J = 7Hz, 6H, isopropyl CHO;

F spectrum: chemical shift versus CFCl.

cT = 58.8.

Example 17

Preparation of cKrIsopropyl-4-trifluoroniethoxyphenylacetic acid m-phenoxybenzyl ester

To a solution of 1.89 g of m-phenoxybenzyl alcohol and 1 ml of pyridine in 6 ml of methylene chloride, a solution of c <l-isopropyl-4-trifluoromethoxyphenylacetylchlorids formed according to Example 15 from 2.46 g of the corresponding acid in 7 ml of methylene chloride , After stirring the reaction mixture overnight, it is washed with water, with dilute hydrochloric acid solution, with dilute potassium hydroxide solution and water, and evaporated to an orange oil. Chromatographic purification over silica gel gives 2.76 g of the desired ester.

IR spectrum (of the pure material): 1738 cm NMR spectrum (CDCl ₃ ): <Γδ, 73 to 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).

, ₃₇ - 212 5 71

Example 18

Preparation of o-ethyl and 6-n-propyl-4-trifluoromethoxyphenylacetic Acids and Their Esters

Following the procedure of Example 9, but using ethyl bromide and 1-bromopropane in place of the 2-bromopropane used there and using the process steps described in Examples 10, 11, 12 and 14, the c <r -ethyl-4- trifluoromethoxyphenylacetic acid or the o6-n-propyl-4-trifluoromethoxyphenylacetic acid. These acids are then converted to the following esters using the appropriate procedures of Examples 15, 16 and 17:

- ³⁸ - 212 5

CF ₃ O

-CH-C-O-CH

NMR bands

H <fo, 83 (t, J = 7.5 Hz, 3H, CH ₃ )

1.90 (m, 2H, -CH ₂ -)

3.49 (t, J = 7.5 Hz, -CH-CH ₂ CH ₃ )

5.04 (s, 2H, -OCH ₂ -)

7,10 (ra, 13H, ArH

CN d ~ O, 84 (two triplets, J = 7.6Hz, 3H, CH ₃ )

1.94 (m, 2H, -CH ₂ -)

3.55 (t, J = 7.4Hz, IH -CHCH ₂ CH ₃ )

6.33 (s, 1H, -CHCN-)

7.18 (m, 13H, ArH)

, 6-2,4 (m, 7H, -

3.63 (t, J = 7.2 Hz, 1H CH-C ₃ H ₇₎ 7.12 (m, 13H, ArH)

nC ₃ H_CN

(To, 65-2.4 (m, 7H, -CH ₂ CH ₂ CH ₃ )

3.71 (t, J = 7.3 Hz, 1H, -CH-C ₃ H ₇₎ 7.20 (m, 13H, ArH)

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Example 19 Preparation of ^ -bromo-4-trifluoromethylthiotoluene

A solution of 20.5 g (0.13 mol) of bromine in 20 ml of carbon tetrachloride is slowly added to a solution of 29 g (0.15 mol) of 4-trifluoromethylthiotoluene in 90 ml of carbon tetrachloride which is added to a moderate 275 W sunlight lamp Boiling is heated to reflux. After the addition is complete, reflux the solution for a further hour to reflux. Then remove the bulk of the solvent at atmospheric pressure and then distilled the residue in vacuo. The 15.5 g of the fraction with a boiling range of 64 to 77 ° C / 0.6 to 0.8 mm Hg contains 92% of the monobromo compound by gas chromatographic analysis.

Example 20

Preparation of 4-trifluoromethylthiophenylacetonitrile

Are added 3.9 g (0.08 mol) of sodium cyanide at 65 ⁰ C under nitrogen to 40 ml of dimethyl sulfoxide. Then, the heating is interrupted and added dropwise 14.3 g (real) (0.053 mol) of c ^ -Brom-4-trifluoromethylthiotoluol at such a rate that the temperature of the reaction mixture never rises above 75 ⁰ C as a result of the exothermic reaction. The red-colored reaction mixture is heated for about 45 minutes to 90-95 ⁰ C, then cooled to room temperature and treated with 50 to 100 ml of ice water. The aqueous suspension is extracted with several portions of ether, which are combined, washed with water and dried over sodium sulphate.

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net. Evaporation in vacuo gives 9.7 g of a dark red oil with a purity of 95% determined by gas chromatography.

Example 21

Preparation of c 1-5 -isopropyl-4-trifluoromethylthiophenylacetonitrile

In the course of 30 minutes, 13.5 ml of a 50% sodium hydroxide solution are added dropwise to a suspension of 9.7 g (O, O4 5 mol) of 4-trifluoromethylthiophenylacetonitrile, 9.5 g (0.056 mol) of 2-iodopropane and 0 , 61 g (0.0023 mol) of the crown ether / 18_ / crown-6 in 13.5 ml of benzene, the reaction mixture as a result of the exothermic reaction assumes a temperature of 43 ⁰ C. After stirring for 2.5 hours at room temperature, an aliquot portion analyzed by gas chromatography shows that there is no longer any nitrile used as the starting material. Then, the reaction mixture is worked up by adding ice water and extracting with ether, which is acid solution with a 10% hydrogen chloride solution and water and dried over sodium sulfate. Evaporation in vacuo gives 10.2 g (86.8%) of a red-brown oil.

Comparable results are obtained when ethyl bromide or n-propyl iodide is used instead of 2-iodopropane to give ^ -ethyl-4-trifluoromethylthiophenylacetonitrile or c6-m-propyl-4-trifluoromethylthiophenylacetonitrile.

"Π ^ ¹ I '" -! 0 7 Q -i · V ⁿ , '·''' * '-.'

ü U, hbl Ui J '" O \; O (U

, 212 5 71

Example 22

Preparation of ^ -isopropyl-4-trifluoromethylthiophenylacetic acid

6.9 g (real) (0.0265 mol) of isopropyl-4-trifluoromethylthiophenyl-acetonitrile and 25 g (0.312 mol) of 50% sodium hydroxide solution are mixed with 53 ml of ethylene glycol and heated to moderate reflux for 18 hours. Then pour the reaction mixture into ice-water and extract with ether. The aqueous phase is acidified with concentrated hydrochloric acid and extracted again with ether, which is washed with water and dried over sodium sulfate. Evaporation in vacuo gives 2.05 g of an oily product.

Similar results are obtained when for the synthesis of o''-ethyl-4-trifluoromethylthiophenyl-acetic acid or c / n-propyl-4-trifluoromethylthiophenyl-acetic acid as starting material, c'-ethyl-4-trifluoromethylthiophenyl-acetonitrile or cC-n-propyl-4-trifluoromethylthiophenyl-acetonitrile.

Example 23

Preparation of <x-Isopropyl-4-trifluoromethylthiophenyl-acetic acid c ^ -cyano-m-phenoxybenzyl ester

Using c <j-isopropyl-4-trifluoromethylthiophenylacetic acid and following the procedures of Examples 15 and 16, the title compound is obtained in the form of an oil.

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Analysis: C ₂₆ H ₂₂ F ₃ NO ₃ S:

Calculated: C 64.32% H 4.57% F 11.74% N 2.89% S 6.60 Found: 64.27 4.62 11.66 2.68 6.4 3

Comparable results are obtained when c ^ -ethyl-4-trifluoromethylthiophenylacetic acid or c <in-propyl-4-trifluoromethylthiophenyl-acetic acid as starting materials in the synthesis of o6-ethyl-4-trifluoromethylthiophenylacetic acid-i? 6-cyano-m- phenoxybenzylesters or the c (-n-propyi-4-trifluoromethylthiophenyl-acetic acid cocacytophenoxybenzylesters used.

Example 24

Preparation of cis-isopropyl-4-trifluoromethylthiophenylacetic acid m-phenoxybenzene ester

Using c <r -isopropyl-4-trifluoromethylthiophenylacetic acid and the procedures of Example 15, the title compound is obtained in the form of an oil.

Example 25

Preparation of c6-isopropyl-4-mercaptophenylacetic acid

A solution of 15.7 g (0.065 mol) of <- {isopropyl-4-difluoromethylthiophenyl-acetonitrile in 42 g of a 50% sodium hydroxide solution and 80 ml of ethylene glycol is heated to reflux for 18 hours. Then pour the reaction mixture into ice water and extracted with ether, is acidified, the alkaline layer at 15 to 20 ⁰ C using concentrated hydrochloric acid and extracted with ether, the ether extract is washed with water

-i η

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and a saturated sodium chloride solution and evaporated to give 11.4 g (83%) of an oil. The NMR and IR spectra show that the difluoromethyl group was split off during the reaction and that the thiol was obtained as a product.

Example 26

Preparation of QL-isopropyl-4-difluoromethylthiophenylacetic acid

Agar 18.4 g (0.46 mol) of sodium hydroxide in 50 ml of water and 11 g (0.05 mol) of co-isopropyl-4-mercaptophenylacetic acid in 40 ml of dioxane and the mixture is heated to a temperature of 50 ⁰ C. Then passes Slowly chlorodifluoromethane under the surface of the liquid, which immediately sets an exothermic reaction, which raises the temperature to 75 ⁰ C. The addition is continued until the exothermic reaction begins to slowly subside (after about 1/2 hour). Then the reaction mixture is cooled to room temperature and treated with 100 ml of ice water. The aqueous layer is extracted with three times 200 ml of ether and then acidified with concentrated hydrochloric acid at 15 to 20 ⁰ C. The formed oil is extracted with ether. The ether solution is washed with water and saturated sodium chloride solution before drying over sodium sulfate, drying and evaporation in vacuo to give 10.2 g of a dark brown resin. This resin is used without further purification in the subsequent esterification step.

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Example 27

Preparation of c-isopropyl-4-difluoromethylthiophenylacetic acid-o-cyano-m-phenoxybenzyl ester

Using cxi-isopropyl-4-difluoromethylthiophenylacetic acid and the procedures of Example 15, the title compound is obtained as an oil.

Analysis: C ₂₆ H ₃₃ F ₂ NO ₃ S:

Calculated: C 66.79% H 4.96% F 8.13% N 3.00% S 6.86 \ found: 66.58 5.13 8.02 2.87 6.95

Example 28

Preparation of ^ -isopropyl-4-hydroxyphenylacetic acid

A mixture of 40.0 go (isopropyl-4-methoxyphenylacetonitrile and 200 ml of 48% hydrobromic acid for 14 hours on an oil bath at a temperature of 126-128 ⁰ C to reflux. Then, dilute the reaction mixture with Ice and water, extracted repeatedly with ether, washed with water and evaporated to a solid residue, the solid is boiled with 200 ml of chloroform, cooled, filtered and dried to give 23.8 g of the title compound, mp 172. 174 ⁰ C.

IR Spectrum (Nujol): 3250-2900 (broad, OH), 1690 (C = O) cm " ¹

Comparable results are obtained when for the synthesis of c <~ ethyl-4-hydroxyphenyl-acetic acid or e {-n-propyl-4-hydroxyphenyl ~ acetic acid as starting materials

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caj-ethyl-4-methoxyphenyl-acetonitrile or o (-n-propyl-4-methoxyphenyl-acetonitrile used.

Example 29

Preparation of ot'-isopropyl-4-difluoromethoxyphenyl-acetic acid

In a stirred at 80 ⁰ C with a magnetic stirrer mixture of 10.00 g (0.0515 mol) of C ^ -isopropyl-4-hydroxyphenylacetic acid, 65 ml of dicxane, 19.08 g (18.56 g real, 0.464 mol) of sodium hydroxide and 30 ml of water is passed over 4 hours 46 g (0.532 mol) of chlorodifluoromethane. 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 then extracted with 200 ml of ether. Then the ether solution is washed once with 100 ml of water, dried over sodium sulfate, filtered and evaporated to a white paste. A mixture of hexane and methylene chloride is then added and the resulting mixture is filtered to remove the starting material in the form of a solid. The filtrate is then evaporated to give 5.41 g of a clear brown oil. From the NMR spectrum it can be estimated that the product has a purity of at least 85%.

Nuclear Magnetic Resonance Spectrum: (CDCl ₃ -O ₅ pyridine), <f 7.43 (d, J = 8.2 Hz, 2H), <f 7, O 8 (d, J = 8.2Hz, 2H), / 6.57 (t, J = 74.3Hz, 1H), <f3.63 (s. imp.), or ^r 3.25 (d, J = 10Hz, 1H), / 2.37 (m, 1H), cTi , 19 (d, J = 6.5Hz, 3H), (TO, 78 (d, J = 6, 5Hz, 3H), j "i 3.82 (s, 1H).

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Comparable results are obtained when using as starting materials cC-ethyl-4-hydroxyphenylacetic acid or c6-n-propyl-4-hydroxyphenylacetic acid, to give cd-ethyl-4-difluoromethoxyphenylacetic acid or oc-n-propyl-4-difluoromethoxyphenyl acetic acid receives.

Example 30

Preparation of 6-isopropyl-4-difluoromethoxyphenyl-acetic acid m-phenoxybenzyl ester

Using cv-isopropyl-4-difluoromethoxyphenylacetic acid and the procedures of Examples 15 and 17, the title compound is obtained as a light yellow oil.

Analysis: ^C ₂ ^H ₂ 4 ^F 2 ° 4 ^:

Calculated: C 70.41% H 5.67% F 8.91% Found: 73.36 5.96 10.56

Comparable results are obtained when for the synthesis of iX-ethyl-4-difluoromethoxyphenyl-m-phenoxybenzyl or cc-n-propyl-4-difluoromethoxyphenyl-acetic acid m-phenoxybenzylester as starting materials oC-ethyl-4-difluoromethoxyphenyl-acetic acid or o (, - n-propyl-4-difluoromethoxyphenyl-acetic acid is used.

Example 31

Preparation of C <r -isopropyl-4-difluoromethoxyphenylacetic Acid C 1 -C -cyano-m-phenoxybenzyl Ester

Using K-isopropyl-4-difluoromethoxyphenylacetic acid and the procedures of Examples 15 and 16, the title compound is obtained in the form of an oil.

1T / T

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NMR spectra: (CDCl ₃ ) cfo, 88 (four doublets, J = 6Hz, 6H, CH ₃ ), 2.30 / m, 1H, -CH-CH (CH ₃ ) ₂ _ /, 3.24 / d , J = 10.1Hz,

1H, -CH-CH (CH ₃ ) ₂ _ /, 6.33 (two singlets, 1H, -CHCN), 6.45 (t, J = 74Hz, 1H, CHF ₂ O-), 7.16 (m , 13H, ArH).

Analysis: ^C 96 ^H 23 ^F 2 ^NO 4 ^:

Calculated: C 69.17% H 5.13% F 8.42 I N 3.10% Found: 69.41 5.20 10.25 3.70

Comparable results are obtained when starting materials for the preparation of i ^ -ethyl-4-difluoromethoxyphenylessigsäureo ^ r-cyano-m-phenoxybenzylester or <? Vn-propyl-4-difluoromethoxyphenylessgisäurec ^ cyano-m-phenoxybenzyiester cxi-ethyl 4-difluoromethoxyphenylacetic acid or c * n-propyl-4-difluoromethoxyphenylacetic acid used.

Example 32

Preparation of c (isopropyl-4-trifluoromethylsufinylphenylacetic acid m-phenoxybenzyl ester

A mixture of 10.0 g of prepared according to Example 24 ^ -Iscpropyl-4-trifluoromethylthiophenyl-acetic acid m-phenoxybenzylesters and 4.1 g of m-chloroperbenzoic acid (85%) for several hours in 100 ml of methylene chloride. The mixture is then filtered and the concentrated residue is purified in a column packed with dry silica gel using a methylene chloride / hexane (2/1) mixture as eluent. The product is obtained in the form of a pale yellow oil.

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Comparable results are obtained when for the preparation of c ^ -ethyl-4-trifluoromethylsulfinylphenyl-acetic acid m-phenoxybenzylester or c ^ -n-propyl-4-trifluoromethylsulfinylphenyl-acetic acid m-phenoxybenzylester as starting materials o </ - Äthyl 4-trifluoromethylthiophenylacetic acid m-phenoxybenzyiester or <xn-propyl-4-trifluoromethylthiophenyl-acetic acid m-phenoxybenzylester used.

Example 33

Preparation of c <- Äthyl-3-difluoromethylsulfonylphenyl-acetic acid ^-cyano-m-phenoxybenzylester

A mixture of 10.0 g of O.sub.3-ethyl-3-difluoromethylthiophenyl-acetic acid cyano-m-phenoxybenzyl ester and 9.0 g of m-chlorobenzoic acid (85%) is refluxed overnight in 100 ml of ethylenedichloride. After filtration and concentration, the mixture is purified by dry column chromatography over silica gel using a methylene chloride / hexane mixture (2/1). The title compound is obtained in the form of a yellow oil.

Comparable results are obtained when for the synthesis of ^ -isopropyl-4-trifluoromethylsulfonylphenyl-acetic acid-oi'-cyano-m-phenoxybenzylester or c ^ -n-propyl-4-trifluoromethyIsulfony! Phenyl-acetic acid ° ^ -cyano-m Phenoxybenzylester as starting materials o <^ - isopropyl-4-trifluoromethylthiophenylacetic acid- oC-cyano-m-phenoxybenzylester or c <-n-propyl-4-trifluoromethylthiophenyl-acetic acid-cK-cyano-m-phenoxybenzylester used.

ο Γ ,, iiC -in ί ύ -χ Q i

212 5 71

Example 34

Preparation of 4-trifluoromethoxy-ß, ß-dimethylatropa-acid

To a solution of 22 g (0.1 mol) of p-trifluoromethoxyphenylacetic acid (which has been prepared by alkaline hydrolysis of the nitrile prepared according to Example 12) in 50 ml of ether is added at ice bath temperature, a commercial solution of 0.2 mol Isopropylmagnesxumchlorid in ether. The reaction mixture is stirred for 2 hours at room temperature, then 5.8 g (0.1 mol) of dry acetone to the reaction mixture and heated to boiling for 5 hours at reflux. The reaction mixture is then cooled, acidified cautiously with aqueous sulfuric acid and then extracted with ether. The combined organic layers are extracted with a 10% sodium carbonate solution. The alkaline layer is acidified with hydrochloric acid and extracted with ether. The ether extract is dried over sodium sulfate and evaporated to give the title compound.

Example 35

Preparation of 4-trifluoromethoxy- <X-isopropenylphenylacetic acid m-phenoxybenzyl ester

To a solution of 13.9 g (0.05 mol) of 4-trifluoromethoxy-ß, ß ~ dimethylatropasäure and 6.1 g (0.06 mol) of triethylamine in 100 ml of acetone is added at the ice bath temperature 13.2 g (0 , 05 mol) m-Phenoxybenzylbromid and then heated for 4 hours to boiling at reflux. Then pour the mixture into cold dilute hydrochloric acid and extract with ether. The ether layer is washed with a 10% hydrochloric acid solution and with water, dried with sodium sulfate and evaporated,

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to obtain the hydroxy ester, which is dehydrated for 18 hours at 80 ⁰ C in benzene with phosphorus pentoxide. By filtering off and removal of the solvent to obtain the crude ester. Purification of the material by dry column chromatography using silica gel and a methylene chloride / hexane mixture (50/50) as solvent affords the product as a light yellow resin.

Example 36

Preparation of 4-trifluoromethoxy- o-C-tert -butylbenzyl alcohol

To a solution of 1.0 mol of commercially available tert-butylmagnesium chloride in tetrahydrofuran is added at 38 to 40 ⁰ C and under a nitrogen atmosphere, a solution of 56 g (0.4 mol) of 4-trifluoromethoxybenzaldehyde in 50 ml of tetrahydrofuran. The reaction solution is stirred overnight at room temperature and then acidified carefully with dilute sulfuric acid at 15 to 20 ⁰ C. Ether is added, the organic phase is washed with water, dried over sodium sulfate and evaporated to a gummy solid. The crude material is purified by chromatography on silica gel to give the alcohol used in Example 37.

Example 37

Preparation of p- (1-chloro-2,2-dimethylpropyl) fluoroanisole

To 14.87 g (0.125 mol) of freshly distilled thionyl chloride, which is cooled with a salt-ice bath, is added portionwise

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Example, in the course of 30 minutes, 12.4 g (0.05 mol) of the prepared according to Example 36 Neopentylalkohols. Then remove the ice bath and leave the slurry overnight. Evaporation of the excess thionyl chloride gives a solid.

Example 38

Preparation of C-tert-butyl-4-trifluoromethoxyphenylacetic acid

The prepared according to Example 37 prepared neopentyl chloride in the corresponding Grignard reagent and obtained by subsequent carbonation with carbon dioxide by the method of Weinstein and Morse (Journal of the American Chemical Society 74 (1952) 1133) the desired acid in the form of a white solid.

Example 39

Preparation of c.sup.pt-butyl-4-trifluoromethoxyphenylacetic acid c.sup.-cyano-n-phenoxybenzyl ester

Using the c.i.-tert-butyl-4-trifluoromethoxyphenylacetic acid and the procedures of Examples 15 and 15, the title compound is obtained in the form of an oil.

Example 40 Insecticidal activity

The insecticidal activity of the compounds according to the invention is demonstrated by means of the following investigations,

on sii !. -m 7 Q * Q Π> ¹ V

21 2571

in which the tobacco caterpillar, Heliothis virescens (Fabricius); the potato leafhopper Empoasca abrupta (DeLong); and the bean aphid Aphis fabae (Scopoli) can be used as insect species. The procedures used are as follows:

Tobacco caterpillar , Heliothis virescens (Fabricius) in the first stage of development

Dive a cotton plant with two real unfolded leaves for 3 seconds with stirring in the test solution (35% water / 65% acetone) containing 300, 100 and 10 ppm of the compound to be tested. Then put each leaf in a beaker with a wick and add a 50 to 100 freshly hatched larvae gauze cloth before closing the cup with a lid. After 3 days at a temperature of 27 ⁰ C (80 ⁰ F) and a relative humidity of 50% to be examined of the cup and rated the kill of newly hatched larvae. The numerical values obtained are listed as percent kill in Table I.

Bean aphid, Aphis fabae (Scopoli)

Five fiber pots, each containing a 5 cm (2 inch) nasturtium plant, which has been pre-occupied with 100 to 150 aphids two days previously, are placed on a turntable operated at a speed of 4 minutes and spray the plants with a solution containing 35% water and 65% acetone containing 100, 10, 1.0 or 0.1 ppm of the compound to be tested, the solution being stirred for two revolutions using a spray device (DeVilbis Atomizer) apply that with

: = N. i \ ui: 19 7 3 - 8

212571

Air is operated at a pressure of 1.41 kg / cm ² (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 spattered plants are then deposited in white enamel shells. The mortality is determined after one day at 21 ⁰ C (70 ⁰ F) and a relative humidity of 50%. The numerical values obtained are listed as a percentage of the mortality in the following Table I.

Potato leafhopper, (Empoasca abrupta (DeLong)

Dive a bean plant (Sieva Lima) with a first leaf folded down to between 3 and 4 inches into a solution of 35% water and 65% acetone containing 100, 10 and 1 ppm, respectively, of the compound to be tested , The dipped plant is then placed in a fume hood to dry and cut off a 2.5 cm piece of the tip of a leaf and placed in a 10 cm (4 inch) diameter Petri dish containing wet filter paper on the bottom , Then transfer three to ten nymphs of the second stage of development into the Petri dish, which is then covered. The mortality is then counted after storage of the Petri dishes for two days at 27 ⁰ C (80 ⁰ F) and a relative humidity of 50%. The numerical values obtained are listed in Table I below. In these studies, permethrin is used as a reference standard.

Table I Evaluation of insecticidal activity

Percentage of mortality

Leafhopper aphid connection

Tobacco bead larva 1. Developmental

stage

ppm

300 100 10 100 10 11 100 100 1 0.1

ppm

ppm

CN-CH-CO-O-CH-

Z = J CH

100 100 100 100 100 7O 100 100 90

-CH-CO-O-CH "-Γ' ^ i -0

CH (CH ₃ )

90 90 0 50 O

100 100

CN

-CH-CO-O-CH-CH (CH ₃ ) ₂

-0

100 100 0 100 O

100 100

- = not examined

Table I (continued)

connection

Percentage of mortality

Tobacco bead larva 1. Sneading stadiu m

leafhopper

ppm

aphid

300 100 10 ICO 10 1 100 10 1 0.1

CN

100 100 61-70 100 lOO

1OO 1OO 80

co-o-CH-r ^ xh-o-./^x

100 71-85 0-40 70 0

100 100 5O

-CH-CO-O-CH-r \ "1-0

CH

100 100 0-40 100 0

100 lOOO

- = not examined

Table I (port setting)

connection

Percentage of mortality

Leafhopper aphid

Tobacco caterpillar larva

1. Development

stage

Ppm ,

300 100 10 lOO 10 1 100 10 1 0.1

ppm

CN-CH-CO-O-CH

CH (CH

3'2

-0

100 100 86-99 100 100

100 100 100

-CH-co-o-CH-r; \ vo

CH (CH

3'2

100 100 0-40 100 0

100 100 100

F ₃ CO-

CN

-CH-CO-O-CH-i CH ₂ CH ₃

-0

100 lOO 61-70 100 7O

100 100 100

- = not examined

Table I (continued)

connection

Percentage of mortality

leafhopper

aphid

Tobacco bead larva 1. Developmental

stage

Ppm _

300 lOO 10 lÖO ΙΟ 1 100 IO 1 0.1

PPm

VHZ / CH.,

-CH-CO-O-CH -

100 86-99 0-40 100 0

CN

-CH-CO-O-CH-

CH ₂ CH ₂ CH ₃

-0

100 100 71-85 100 50

100 90 9O

- = not examined

212571

Example 41 .

Insecticidal action

The insecticidal activity of the compounds according to the invention is further determined by means of the following test methods in which the activity against mosquito larvae, Mexican ladybirds and cotton caterpillars is investigated.

Malaria mosquito, Anopheles quadrimaculatis (Say)

Pipette 1 ml of a solution of 35% water and 65% acetone containing 300 ppm of the compound to be tested into a 400 ml beaker containing 250 ml of deionized water, stir with the pipette and reach a concentration of 1.2 ppm. Aliquots of this solution are then removed and diluted further to 0.4, 0.04 and 0.004 ppm, respectively. In order to prevent the eggs from floating up and drying out on the side wall of the beaker, a wax paper ring, 0.6 cm wide, is placed on the surface of the solution to be examined, and is then fitted into the beaker. Use a sifting spoon to pick up and transfer approximately 100 eggs (aged 0 to 24 hours) into the beaker. After 2 days at 27 ^° C. (80 ^° F.) and a relative humidity of 50%, hatching is observed. The percentage mortality is listed in the following Table II.

Mexican ladybugs , Epilachna varivestis (Mulsant)

One dips bean plants (Sieva lima) (two per pot) with 7.5 to 10 cm long first leaves in the 300, 100, 10 or 1 ppm of the compound to be examined containing solution and allowed to dry in a fume hood.

212571

Then take one leaf from the plant and place it in a 10 cm petri dish containing a wet filter paper and 10 last developmental larvae (13 days before hatching) on the bottom. On the day after the treatment, remove another leaf from the plant and feed it to the larvae after removing the remains of the first leaf. 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, if the larvae have not stopped eating. Then the Petri dishes are set aside and kept until the adult animals have hatched, which is about 9 days after the start of treatment. After complete leaching of the animals, each Petri dish is tested for killed larvae, pupae or adult animals, deformed pupae or adult animals; Intermediates between the larval stage and the pupal stage and the pupal stage and the adult stage; or for any other effects in normal moulting, normal development and the normal appearance of pupae or adult animals.

The numerical values obtained are listed in the following Table II.

Baumwoi! Caterpillar , (Southern Armyworm), Spodoptera eridania (Cramer)

One dips bean plants (Sieva lima) with two unfolded 7.5 to 10 cm long first leaves for 3 seconds with stirring in the treatment solutions and then allowed to dry in a fume hood. After the leaves are dry, they are cut out, and each cut leaf is placed in a 10 cm Petri dish,

which contains a piece of wet filter paper and 10 caterpillars larvae in the third developmental state with a length of about 1 cm. The Petri dishes are covered and stored for 2 days at a temperature of 27 ⁰ C (80 ⁰ F) and a relative humidity of 50%. Mortality is counted after 2 days. The results obtained are summarized in the following Table II.

Table II

connection Evaluation of insecticidal activity

Percentage of mortality

Mexican

ladybug

ppm

1.2 0.4 0.04 0.004 1000 lOO 10 300 lOO 10 1

Mosquito larvae ppm

Bumblebee PPm

100 100 100 90 100 100 100 100 100 100 100

-CH-CO-O-CH - </ '^ i-O-r' / Π 100 100 90 0 100 100 0 100

CH (CH ₃ )

100 100 80

O 100 100 O 100

- = not examined

Part II (continued)

connection

Percentage of mortality

mosquito larvae

ppm

Cotton caterpillar PPm

Mexican ladybugs

1.2 0.4 0.04 0.004 1000 100 1Ö 300 100 10

CN-CH-CO-OCH-

CH (CH ₃ )

-0

100 100 86-99 100 100 ο loo 100 100

F CHS

/ N) -CH-CO-OC

CN CH

CH (CH ₃ )

-0

100 86-99 86-99 100 9O 0 100 100 90

' W-CH-CO-O-

CH-CO-O-CH -

= J CH (CH ₃ )

\ >> 100 ICO

100 100 0 iOO 90 50

- = not examined

Table II (continued)

connection

Percentage of mortality

mosquito larvae

cotton caterpillar

Mexican ladybugs

ppm

1.2 0.4 0.04 0, Q04 10000 100 10 300 100 10

F CHO

CN-CH-CO-O-CH-

100 100 100

100 100 100 100 100

F ₃ CO- ^ ^ V) -CH-CO-O-CH ₂ -Γ ^ L \ - / CH ₂ CH ₃

100 '100 100

100 lOO 70 90 OO

' \\ - CH-CO-O-

Vz = 1 / CH ₂ CH

CN

CH-T ^ VO

100 100 100

100 lOO 100 80 90

- = not examined

T a b rush II (cont'd)

connection

Percentage of mortality

Mexican

Mosquito larva Cotton caterpillar Ladybug

ppm ppm ppm

1.2 0.4 0.04 0.004 lOOO lOO 10 30O lOO 10

100 100 100

lOO lOO 0 lOO 90

F ₃ C (H

CN

-CH-CO-O-CH- \ ZZZ / CH ₂ CH ₂ CH ₃

100 100 100

100 lOO 70 100 lOO

CN

CH-CO-O-CH-CH (CH ₃ ) ₂

100 100 100

0 100 100 ο 100 100 100

- = not examined

212571

Example 42

Insecticidal Effects Spiderwort mite , Tetranychus urticae (cook)

Bean plants (Sieva lima), the first leaves of which are 7.5 to 10 cm long, are populated with about 100 mature, phosphate-resistant mites per leaf, 4 hours prior to the study to allow eggs to be discarded prior to treatment , The infected plants are then immersed for 3 seconds with stirring in the 1000, 300, 100 or 10 ppm of the drug-containing solution, whereupon the plants are placed in the hood 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 10 × magnification. The other leaf is left on the plant for a further 5 days and then examined at 10-fold amplification to estimate the kill of the eggs of the newly hatched nymphs, whereby the ovicidal effect or the residual effect can be determined. The results are summarized in the following Table III.

Tobacco caterpillar , Heliothis virescens (Fabricius) in the third stage of development

Dive three cotton plants with just unfolded cotyledons in the 1000 or 100 ppm of the drug-containing solution and then transferred to dry in a hood. After drying, each cotyledon is halved and 10 biopsy sections are placed in a 28 g plastic drug cup,

- 66 - 212 5 71

containing a 1.25 cm thick dental tampo, which is saturated with water, after which a tobacco caterpillar in the third stage of development is introduced into the cup. Close the cup and store it for 3 days at 27 ⁰ C (80 ⁰ F) and a relative humidity of 50%, followed by counting the mortality. The results obtained are summarized in the following Table III.

Cabbage bead (cabbage looper) Trichoplusia ni (Hübner) in the third stage of development

A true leaf of a cotton plant is dipped into the solution to be tested containing 1000, 100 or 10 ppm of the compound to be tested, stirred for 3 seconds, removed from the plant and left to dry in a fume hood. After drying, the sheet is transferred to a 9.0 cm Petri dish containing moist filter paper on the bottom. Then, add three larvae in the third stage of development and cover the bowl with the lid. The mortality is counted after 3 days at 27 ⁰ C (80 ⁰ F) and a relative humidity of 50 - 10%. The numerical values obtained are summarized in the following Table III.

20. IM 19 7 9 - 8 DB ^; VH

Table III connection Insecticidal action

Percentage of mortality

phosphate resistant

mites

ppm

Tobacco caterpillar in the 3rd stage of development ppm

Kohlraupe in the 3rd development stage PPm

300 100 10 1000 100 1000

CF ₃ O-

CN

-CH-CO-O-CH-CH (CHJ,

-0

100 80

100

IOO 100

-CH-C0-O-CH ₂ - _f ^ ^> ^ -O- | ^ ^> ^ 50 0

50

1

, 0 - (/ \> - CH-C0-0-C

CN CH

CH

60 0

80

0 100

- = not examined

Tab eile III (cont'd)

connection

Percentage of mortality

tobacco budworm

Phosphate-resistant in the 3rd development - Caterpillar in the 3rd

Mites stage of development stage

ppm ppm ppm

3ÖÖ ~ 1ÖÖ IO 1000 iÖÖ lOOO 1ÖÖ

CN

-CH-CO-O-CH-i

CH (CH)

-0

100 100 100

100

100 100 100

F ^ CHS

CN -CH-CO-O-CH-;

CH

-0 ·

100 100

20 100 100

F CHO

, _ // W-CH-CO-

CH-CO-O-CH-;

CH

100

100

70 100 100

- = not examined

T abe lie III (continued)

connection

Percentage of mortality

Phosphate resistant mites

Tobacco caterpillar in the 3rd development

stage of development ppm

Caterpillar in the 3rd stage of development

PPJB

300 100 IO lOOO 100 lOOO 100

10

F CHO

CN

-CH-CO-O-CH CH (CH ₃ ) ₂

-0

100 0

100 100 ICO 100

F C0- «

/ \\ -CH-CO-O-CH,

CH ₂ CH ₃

-0

100

100 100 100 100

F.XO-C / \\ CH-

100

100

100 100 100

- = not examined

Table III (continued)

connection

Percentage of mortality

phosphate resistant

mites

ppm

Tobacco caterpillar in the 3rd stage of development ppm

Caterpillar in the 3rd stage of development PPm

10000 300 100 10 10000 100 10000

F ₃ CO-

-CH-CO-O-CH

CH ₂ CH ₂ CH ₃

-0

80

6O

3O 100 40

CN-CH-CO-O-CH-

100

90

90 100 100

CN

-CH-CO-O-CH-i CH (CH ₃ J ₂

100 0

100

90 100 9O

- = not examined

212571

Example 43 ·

Insecticidal action over the soil

Western corn rootworm , Diabrotica undecimpunctata howardi (Barber)

Dilute 10 mg of the compound to be tested with 10 ml of acetone to form a stock solution A. Dilute 2 ml of this solution with acetone to 10 ml and obtain the solution B. Then, a 28 g wide-mouth bottle with about 0.7 g Talc (Pyrax ABB) and add 1.25 ml of the test solution to the talc, giving 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 drying the material for 10 to 15 minutes with the aid of 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 introduced into the flasks containing the compound to be tested. The bottles are closed and the contents are mixed using a vibratory mixer. Then each of 10 corn rootworm larvae with an age of 6 to 8 days in each bottle. The bottles will be

21257t

loosely covered and placed in a room where they are kept as they are under constant illumination at 27 ^° C. (80 ^° F.) and a relative humidity of 50%. Mortality is counted after 6 days.

In this study, <ε-isopropyl-4-trifluoromethoxyphenylacetic acid c ^ -cyano-m-phenoxybenzyl ester causes 100% killing of corn rootworms at an application dose of 56 kg / ha and a 70% kill at a dose of 11 / 2 kg / ha.

Example 44

Residual insecticidal activity after treatment of the leaves of cotton plants

Dive young cotton plants with at least two unfolded real leaves, which are pulled in 10 cm plastic pots, in a 65% acetone and 35% water-containing solution of the compound to be examined, while stirring 'for 3 seconds and immersed one leaf. The concentration of the compound to be tested in the solutions is 30, 100, 300 or 900 ppm of the active ingredient.

After drying the leaves, two leaves of each of two plants are cut out and placed in Petri dishes (90 mm × 10 mm) on damp filter paper (9 cm Whatman No. 1). On each leaf are then placed five tobacco caterpillars in the third stage of development, whereupon the Petri dish is covered. The Petri dishes are then stored under constant lighting at a temperature of 27 ⁰ C (80 ⁰ F) and a relative humidity of 50%. The count of the killed larvae takes place after 72 hours.

212571

The remaining plants are exposed in the greenhouse to intense light, which is turned on every day for 14 hours. Then leaf samples are taken after a exposure time in the greenhouse of 3, 7, 10 or 14 days with tobacco caterpillars in the third stage of development. Again, the percentage kill of these larvae is determined.

30, Aiii

table

IV

Residual insecticidal activity of the compounds tested on cotton plants using tobacco caterpillars in the third stage of development

Days residual effect connection

CN-CH-CO-O-CH-

CH (CH ₃ )

dose 1* 0 2 ** 1 3 2 7 1 2 10 1 2 14 1 2 3 ppm 9O 0 90 0 60 O 60 0.03 60 1, 03 3O 100 0 100 0 loo O 95 O 95 ο, 100 100 0 100 0 100 O 100 O 100 O 300 100 0 100 0 100 O 100 O 100 O 900

Cl C = CH

CH-CH

-CO-O-CH -

permethrin

30 65 0.3 30 .11 3 15 12 5 40 4, 3 5 57 , 5 100 85 O 85 O , 03 70 O, 53 65 O, 6 25 1 , 0 300 100 O 100 O loo O 95 O 80 O 900 100 O 100 O loo O 90 O 100 O

Cl - // X) -CH-CO-O-CH-I

CN

CH (CH ₃ ) ₂ South African patent application 73/4462

30 65 O, 03 65 O, 1 75 O , 05 45 2, 3 75 O , 03 1OO 100 O 85 O 100 O 90 O, 03 100 O 300 95 O 100 O 100 O 95 O 95 O 900 100 O 100 O 1OO O 100 O 100 O

control

100

O 96.3

90

73.8

13 8O

1 * = mean mortality percentage 20 TBW / point 2 ** = mean percentage of feeding damage

. ". 212571

Example 45

Ixodizide effect (action against ticks)

The following investigations are being conducted to investigate the effective control of mite larvae, with larvae of Boophilus microplus of a single-hosted tick, which during its three stages of development, i. H. the larval stage, the nymph stage and the eroded stage on a single host. This test uses a mixture of 10% acetone and 90% water containing 0.025, 0.1, 0.5, 2.5 and 12.5 ppm, respectively, of the compound to be tested. Twenty larvae are placed in a pipette closed at one end with a gauze tube, after which the solution containing the compound to be tested is drawn through the pipette by means of a vacuum tube, simulating a spray system. The ticks are then stored for 48 hours at room temperature, after which the mortality is determined. The results obtained are summarized in the following Table V.

Table V

Percent killing of tick larvae (Boophilus microplus) connection

12 ppm 2 "5 ppm 0.5 ppm 0.1 ppm 0.025 ppm

CFOI

^ Λ.

CN

CH-CO-O-CH CH (CH)

-O

100 100

100

100

100

- "- 212571

The above procedure is repeated with the difference that one uses the active ingredient in a concentration of 0.1, 0.025, 0.005 and 0.001 ppm. The results obtained are shown in the following Table VI.

ii ["-J C \ " 7 Π

T a b e 1 1 e VI Percent mortality of tick larvae (Boophilus microplus)

connection

0.1 ppm 0.025 ppm 0.005 ppm 0.001 ppm

100

80

80

-79- 212571

The above procedure is repeated except that the tested compound is used in a concentration of 0.1, 0.01, 0.001, 0.0001 or 0.00001 ppm. The results obtained are shown in the following Table VIa.

Table Via Percent mortality of tick larvae (Boophilus microplus)

connection

0.1 ppm 0.01 ppm 0.001 ppm 0.0001 ppm 0.00001 ppm

CN

-CH-CO-O-CH-,

CH (CH ₃ )

-0

100

100

100

50

- 212571

The above procedure is repeated with the difference that the investigated compound is used in a concentration of 100 ppm. The results obtained are summarized in the following Table VIb.

Table VIb

Percent mortality of tick larvae (Boophilus microplus)

Connectivity ung CN

CH-CO-O-CH! CH (CH ₃ ) ₂

-0

ppm 100

V) -CH-CO-O-C

-CH-CO-O-CH CH (CH ₃ ) ₂

· 1-0

100

FCO-i

-CH-CO-O-CH

CH ₂ CH ₃

-0

100

ro

F ₃ CO;

CN

-CH-CO-O-CH-CH ₂ CH ₃

100

F., CO- (

100

212571

Example 46

The efficacy of the compounds according to the invention in the control of adult ticks (Boophilus microplus) is determined by the following test method in which the compound to be tested is solubilized according to the procedure of Example 45, with the difference that the active ingredient is in such Quantities used to obtain solutions containing 125, 52.6, 31.2, 15.6 and 7.3 ppm of the compound to be tested.

Then, full-grown, rich, female ticks are immersed in the solutions to be examined for 3 seconds, transferred to individual containers and stored for 48 hours at 27 ⁰ C (80 ⁰ F) and a relative humidity of 50%. At the end of the storage period, the ticks are examined and the egg deposits are counted. Whole male ticks that have not deposited eggs are considered dead. The results obtained are summarized in Table VII below.

Table VII Ixodicidal activity against adult ticks (Boophilus microplus) connection

Percent mortality of adult ticks at a concentration of (ppm)

62.5 100

31.2

99.4

15.6

98.8

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Example 47

The effectiveness of the compounds according to the invention in the control of larvae of the gold fly (Cocchliomyia hominivorax), a very dangerous cattle pest, is investigated, using five larvae of Cochliomya hominovorax in the first development state with a mixture of ground beef (8.0 g), blood (7 , 0 ml), water (2.1 ml) and 0.9 ml of a formulation containing 1, 5 and 25 ppm, respectively, of the compound to be tested.

For the evaluation one carries out two repetitions on 20 larvae per dose. The larvae are supplied ad libitum with the nutrient medium for 24 hours. At the end of this period, the number of larvae killed is determined for each treatment and each repeat treatment, and the percentage mortality is calculated. The numerical values obtained are summarized in the following Table VIII.

on

μη -iQ 7 ^ UK

Table VIII

Evaluation of the compounds according to the invention with respect to the control of larvae of the gold fly (Cochliomyia hominivorax)

connection

Percentage mortality at a concentration of (ppm) 1 5 25

2.4

69.2

100

212571

Example 48

Determination of the LC _5Q value of the _compounds according to the invention with respect to tobacco caterpillars on cotton plants

Dive young cotton plants with at least two unfolded true leaves, which are pulled in 10 cm plastic pots, in a solution of the compound to be examined in a mixture of 65% acetone and 35% water, immersing one leaf at a time and stirring the liquid. The active substance concentration of the solutions used is 1.1, 2.8, 7.5, 20, 60 or 150 ppm.

After the leaves have dried, cut two leaves from each of two leaves and place them in Petri dishes (90 mm χ 10 mm) on damp filter paper (9 cm, Whatman No. 1). Then each leaf is occupied with five tobacco caterpillars in the third stage of development and covers the Petri dish. The dishes are then stored under constant lighting, a temperature of 27 ⁰ C (80 ⁰ F) and a relative humidity of 50%. The counting of the larvae takes place after 72 hours. Each treatment is repeated four times. The numerical values obtained are summarized 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 controlling tobacco caterpillars than the conventional compounds investigated in the same way.

table

IX

Determination of LC ₁ . Values when using the compounds to combat tobacco caterpillars

in the third stage of development '_ ^

connection

CN

? jy- (f \\ - CH-co-o-CH-r '/

CH (CH ₃ )

(Ppm) number of number of T Γ * 10 investigated kill ^LC 50 dose 80 " insects insects 2.94 1, 50 20 3 2, 00 2O 9 7, 00 20 18 20 2O 19 60 2O 20

Cl ₂ C = CH

CH,

-CO-O-CH

7.50

20.00 60.00

150.00

20 2 2O 16 2O 19 20 20

CN

-CH-CO-O-CH-CH (CH ₃ ) ₂

2.80

7.50

20.00 60.00

150.00

20 3 20 13 20 17 20 20 20 2O

* = Permethrin ** = described in South African Patent Application No. 73/4462

212571

Example 4 9

Determination of the LC _5o value of the compounds used against adult 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 to be applied via aerosol application are pipetted into the top of a nozzle and passed through the atomizer nozzle. The atomized droplets are passed through an air jet (4 miles per hour) to the caged mosquitoes (each containing 25 adult females per cage) with treatment for 4 to 10 hours 5 seconds is carried out. The mosquitoes are then anesthetized with carbon dioxide (3 to 4 seconds) and transferred to storage cages. The treated mosquitoes are then relative in these storage cages at 29.4 + 0.55 ⁰ C (85 ⁰ F + 1) and a Moisture content of 4 6 + _ 2% The mortality is counted after 24 hours.

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

0 Π JiIi- .in; ρ

table

Determination of LC ₁ . Values of the investigated compounds in the control of adult female mosquitoes (Anopheles quadrimaculatus)

connection

CN

-CH-CO-O-CH-f ^ CH (CH ₃ ) ₂

percentage Concentration (ppm) the mortality * 0.5 10 1.0 10 2.0 5 3.0 5 5.0 52 15.0 95

approximate LC value (ppm)

^ CN -CH-CO-O-CH-, CH (CH_ ) _

CH (CH ₃ )

5.0 10.0 20.0 40.0 80.0

* Values determined in two different investigations ** described in South African Patent Application No. 73/4462 (1) = Study One (2) = Study Two

(D 10 (2) 6 14 26 66 60 62 78 92 90

(1) 21 (2) 18.8

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Example 5O

Residual insecticidal activity determined by applying the compounds to be tested in a small volume

The compounds to be tested are dispersed in such amounts in a mixture of 65% acetone and 35% water that in 19.31 l (5.1 gallons) of water there is an application dose of 0.08 kg of compound per active ingredient. Then, cotton plants are introduced into a spray room and sprayed from above with the aid of a stationary spray device while passing under the spray device.

After the leaves have dried, two leaves each of two plants are cut out and placed in Petri dishes (90 mm × 10 mm) on damp filter paper (9 cm, Whatman No. 1). Then put on each leaf five tobacco caterpillars in the third development stage and cover the Petri dish. The Petri dishes are then stored under constant lighting and at a temperature of 27 ⁰ C (80 ⁰ F) and a relative humidity of 50%. The counting of the killed larvae takes place 72 hours later.

The remaining plants are then transferred to the greenhouse and irradiated with intense light. Leaf samples are then re-examined at 3, 7, 10 and 14 days with third generation tobacco caterpillars. The numerical values obtained are summarized in the following Table XI.

T a b e 1 le XI

Residual insecticidal activity against tobacco caterpillars, determined by application of the active substances to be investigated

in small volumes on cotton plants _ ^ _

connection

order-

dose

Days remaining effect

10

(kg / ha) 12 1

CN

-CH-CO-O-CH-, CH (CH ₃ ) ₂

0.08 95 0.03 100 0 90 0.03 90 O 80 0.03

CN-CH-CO-O-CH-

0.08 95 0.1 90 3.0 8O 2.5 80 0.78 50. 1.6

control

0 92.5 0 88.5 0 87.5 30 41.3 0 67.5

1 = mean mortality percentage 20 TBW / point (72-hour mortality count)

2 = mean percentage damage / four repetitions

212 5 71

Example 51 Ixodicidal activity

The investigation method described in Example 22 is used to determine the ixodicidal activity of the compounds according to the invention in active compound concentrations of 12.5, 2.5, 0.5, 0.1, 0.02 and 0.004 ppm, respectively. The results obtained are shown in the following Table XII.

Table XII Percent mortality of tick larvae (Boophilus microplus) connection

Days after treatment

^ -Mortality at the concentration of (ppm) 12.5 2.5 0.5 0.1 0.02 0.004

_f0 -f \. _? -

CL 217,408

CN COO-CH

N = / CH

2 100 1OO 1OO 100 0 0 3 100 100 100 100 45 25

CL 217,407

-CH-COO-CII ₂ -

CH

2 100 100 100 0 0 0 3 100 100 100 20 15 15

-94 -

21257!

Example 52

The efficacy of the compounds of the invention is determined in the control of adult multi-host ticks (Rhipicephalus sanguineus (RS) and dermacentor variabilis (DV)) of dogs, using the following assay method, in which the test compound is prepared in the manner described in Example 4 5 described. The active ingredient is used in such an amount as to obtain solutions containing 100, 10 or 1 ppm of the compound to be tested.

Then, full-grown, saturated, female ticks are immersed in the solutions to be examined for 3 seconds, then placed in individual containers and stored for 48 hours at 27 ⁰ C (80 ⁰ F) and a relative humidity of 50%. Towards the end of the storage period, the ticks are examined and the ovipositions are counted. Mature female ticks that have not laid eggs are considered killed. The results obtained are summarized in the following Table XIII.

Table XIII

Ixodicidal activity against adult ticks, namely Rhipicephalus sanguineus (R.S.)

and Dermacentor variabilis (D.V.)

connection

Concentration (ppm)

Percent mortality

the adult ticks

R.S. D. V.

100

10 1

loo

100 100

100 90 60

212571

Example 53

Examination of the effect of the compounds of the invention in vitro against adult fleas of the species Ctenocehalides felis

In this study, 10 adult fleas of the species Ctenocephalides felis are sprayed for 30 seconds with an acetone / water solution containing 100, 50, 10 or 1 ppm of the compound to be tested. 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 mortality. The numerical values obtained are summarized in the following Table XIV.

Table XIV Effect of the tested compounds against fleas connection

Hours after treatmen development

Percent mortality at a concentration of (ppm)

ICO 50

10

CL 217,408

-CH-COOCH -

CH (CH ₃ )

CL 217,407

24 48

24

48

1OO 1OO

70 90

50 50

0 20

0 o

0 0

O O

'· JVt ~

- 99 - 212 5 71

The above examination is repeated with the difference that the investigated compound is used in a concentration of 80, 40, 20, 10, 5 or 2.5 ppm. The results obtained are summarized as mean values of two replicates at each dose, unless indicated otherwise, in the following Table XIVa.

Table XIVa

Effect of the tested compounds against fleas connection

Hours after treatmen development

Percent mortality at a concentration of (ppm)

80 4O 2O 10 5 2,5 0

F CHO-

-CH-CO-O-

CH (CH ₃ )

24

100 * 70 45 30 40 20 0

* Only one exam

212571

Example 54

The procedure of Example 52 is repeated except that male and female multipurpose ticks (Rhipicephalus sanguineus (R.S.) and Dermancentor variabilis (D.V.)) are used. The compounds to be tested are used in such an amount as to obtain solutions containing 1.0%, 0.1%, 0.01% or 0.001% of the compounds to be tested. The mortality counts are 24 and 48 hours after treatment.

The numerical values obtained are listed in the following Table XV.

on γ. 11 r- ·: η 7 π · ·, ο ο

Table XV

Ixocidal activity against eroded ticks, namely Rhipicephalus sanguineus (R.S.)

_ ^ _ ^ and Dermacentor varabilis (DV)

(The numerical values given are average values of two repetitions, unless stated otherwise).

F CHO-

connection

-CH-CO-O-CH-

CH (CH

% Mortality of the washed-out ticks

concentration R. sanguineus 48 hours D. variabilis 48 hours 100 * in percent 24 hours 24 hours 65 1.0 ICO * - lOO * 0.1 100 * 100 * 100 * 0.01 100 100 100 0.001 100 65

* Only one exam

- 4-Θ2 -

212571

Example 55

The effectiveness of the facial fly control compounds of the present invention (Musca autumnalis) is demonstrated by the following studies in which 1-day-old facial fly larvae can feed on cow dung, containing 0.13, 0.25 and 0.50 ppm, respectively Contains connection.

Two replicates are made per dose using 10 larvae each, and untreated controls are performed in the evaluation.

For each dose, add a solution of a suitable amount of the compound to be tested in acetone to 1 kg of fresh cow dung and mix for 1 minute with an electric mixer. The manure used for the control trials not treated with the active ingredient is treated in the same way, with the difference that only acetone is added. The manure samples are divided into four paper cups (paper souffle cups). At each dose (and controls), two beakers are infested with 1-day-old facial fly larvae. The cups are stored at a temperature of about 27 ⁰ C for 7 days (80 ⁰ F) and a relative humidity of 50%. Then the cups are examined for the pupae, which are then counted, weighed and transferred to plastic containers, where they hatch and die. After the flies have been killed, they are counted and the percentage of mortality is determined. The results obtained are shown in the following Table XVI.

Table XVI

In vitro evaluation of the effect of the compounds according to the invention as potential feed additives for controlling facial flies (Musca autumnalis) in manure

(The numerical values given are mean values of two repetitions)

Connection control

Concentration in manure (ppm)

face flies

Prevention of pupation %

0.0

Prevention of hatching of the dolls

0.0

0.13 0.25 0.50

86.8 78.9 97.3

90.6 84 _r 91.9

Claims (1)

- ¹⁰⁵ - 212571 invention claim Process for the preparation of phenylalkanoic acid m-phenoxybenzyl esters of the general formula I wherein the substituent of the formula RCF_X- in m- or
p-slope to the carbon atom to which the alkanoic acid ester group is bonded, and X is a sulfur atom, an oxygen atom, a sulfinyl group or a sulfonyl group, R is a hydrogen atom, a fluorine atom, a chlorine atom, a difluoromethyl group or a trifluoromethyl group, Rp is an ethyl group, an n-propyl group, an isopropyl group, a tert-butyl group or an isopropenyl group, and R-. represent a hydrogen atom or a cyano group, and the optical isomers of these compounds,
characterized in that a compound of the general formula in which A is a halogen atom and R and R have the meanings indicated, with an m-Phenyloxybenzylalkohol the general formula in which R_ has the meaning given, in the presence of a tertiary organic amine as acid acceptor and an inert organic solvent at a temperature of 10 to 30 ⁰ C. on AlIf: -i Q 7 Q * M Π >< ^: V, -I "