CS214717B2 - Fungicide means and method of making the active substances - Google Patents

Abstract

1. 1,2,4-triazolyl-enol ethers of the general formula I see diagramm : EP0024538,P14,F3 in which Ar represents phenyl and naphthyl, it being possible for these radicals to be substituted by halogen, alkyl with 1 to 6 carbon atoms and alkoxy with 1 to 4 carbon atoms, halogenoalkyl with 1 to 4 carbon atoms and 1 to 5 halogen atoms, furthermore by nitro or cyano and finally by optionally halogen-substituted phenyl, R represents alkyl with 1 to 4 carbon atoms and X represents oxygen or the methylene group, and acid addition compounds and metal salt addition compounds thereof.

Description

(54) Fungicidal composition and process for the manufacture of active substances

The present invention relates to novel 1,2A-triazolyl enol ethers, to a process for their preparation and to their use as fungicides.

It is known that 1,2,4 - rlazolylethery such as 1- ^{(4-chlorophenyl;} phenoxy) -2- (2,4-dichloro-benzyloxy) -3,3-dimethyl-1- (1,2 4-t-riazol-1-yl) butane as well as 1,2,4-triazolylpentanones, such as 1- (4-chlorophenyl-N-dimethylamino-1,2- (1,2-) 4-ethoxy-3-pentanone, have good fungicidal properties (see DOS No. 27 20 949 and DOS No. 27 34 426) However, the effect of these compounds, especially when used in lower amounts and concentrations is not always entirely satisfactory.

New 1,2,4-triazolylenol ethers of formula I have now been found

STEED

Ar-X-CsC-C (CH 3)

in which

Ar represents a phenyl group optionally substituted by halogen,

R 1 is C 1 -C 4 alkyl and

X is oxygen or methylene. as well as their acid addition salts.

The compounds of the formula I according to the invention are present in the form of the geometric isomers E (trans) and Z (cis). In the E, Z-no nomenclature, the substituents on the double bond are ranked according to decreasing priority according to the Cahn-Ingold-Prelog rule. If preferred substituents are on the same side. the double bonds, the Z configuration, if present on the opposite sides, the E configuration. Both the individual isomers and mixtures thereof are within the scope of the invention.

Further, it has been found that the 1,2,4-triazolyl-enol ethers of the formula I are obtained by reacting 1,2, z-riazolyl-etetones of the formula II _A CA

Ar-X-CH ~ C ~ C (CHA and ⁵ _N—

N ---- 'III'

in which

Ar and X are as defined above, reacted with alkyl sulphates or alkyl214717 halides in the presence of a base and in the presence of an organic diluent, or in an aqueous-organic biphasic system in the presence of a phase transfer catalyst, and optionally metal salt.

The novel 1,2,4-triazolyl-eiao-ethers of formula I have potent fungicidal properties. Surprisingly, the compounds according to the invention exhibit a considerably higher effect than the prior art known 1'-chlorothenoxy-2- (2,4-dichlorobenzyloxy) -3,3-dimethyl-1- (1,2, 4-dichlorobenzyloxy) -3- 4-para-1- (1-butan-1-butane) and 1- (4-chlorophenyl) -4,4-dimethylethyl (1,2,4-para-11-yl) -3-pentanone, which are The active substances according to the invention thus represent an enrichment of the prior art.

The present invention relates to a fungicidal composition, characterized in that it contains at least one of the .alpha.-triazolyl-1-ether of the above-mentioned formula (I) or an acid addition salt thereof, as well as a process for the preparation of said active compounds. .

Most preferred are those 1,2,4-triazolyl-enol ethers of formula I wherein Ar is a phenyl group optionally bearing one or two or the same or different substituents selected from fluoro, chloro, bromo and the like. iodo, R is methyl, ethyl, isopropyl, isobutyl or tert-butyl and X is as defined above.

If, for example, 1- (4-chlorophenoxy) -3,3-methyl-1- (1,2,4-riazol-1-yl) butan-2-one and dimethyl sulphate are used as starting materials, the reaction may be carried out. according to the invention described by the following reaction scheme:

base —-—>

The triazolyl ketoins used as starting materials in the process of the invention are generally defined by the above formula II. In this general formula, Ar and X preferably represent the same radicals as already mentioned. these substituents are named as preferred in the description of the compounds. . of formula I according to the invention.

1.2.4- Triazo ^ Уl ^; The compounds of formula (II) are known (cf. DAS No. 2 201 063 and DOS No. 2,734,426) and can be obtained according to the procedures described in these publications, for example by: the corresponding haloketones are reacted with 1,2,4,7-riazole in the presence of a diluent and in the presence of an acid-binding agent (see also Examples).

As next . The starting materials used by the alkyl sulphates or alkyl halides are generally known compounds in organic chemistry. As· . examples of these starting materials used. The process of the invention includes dimethyl sulfate, diethyl sulfate, methyl bromide, methyl iodide, ethyl bromide, ethyl iodide, isopropyl iodide and isobutyl iodide.

Suitable diluents for the process according to the invention are inert organic solvents, which preferably comprise aromatic hydrocarbons, such as benzene, toluene or xylene, halogenated hydrocarbons, such as methylene chloride, carbon tetrachloride, chloroform, or chlorobenzene, esters, esters, esters, and the like. These include ethyl acetate, formamides such as dimethylformamide, and dimethylsulfoxide.

The reaction of the invention is carried out in the presence of a base. All of the customary organic and, in particular, organic acids can be used for this purpose. inorganic bases, preferably alkali metal hydroxides or carbonates, such as sodium hydroxide and potassium hydroxide.

Reaction temperatures in the working manner. According to the invention, they can be moved within wide limits. .Obecně working at temperature between 0 and 100 · C, preferably between 20 · and 80 ^Q C.

In the process according to the invention,

1 mol of 1,2,4-riazolyl ketone of general formula

II preferably comprises 1 to 2 moles of alkyl sulphate or alkali metal halide. In this reaction, the compounds of formula I result in the form of a mixture of geometric isomers. The isolation of the individual geometric isomers is carried out by conventional methods, for example by varying the solubility of these isomers, using salt formation, Craig shaking or chromatographic separation, or combinations thereof. The unambiguous attribution of the structure. This is carried out on the basis of @ 1 H-NMR spectra, in particular using signal shifters. The signal shifts caused by these agents are the greater the smaller the spatial distance between the respective devices

With a tone and a central atom of the shift-causing agent involved in the formation of the complex (see also the Examples).

According to a preferred embodiment, the reaction according to the invention is carried out in a two-phase system, such as aqueous sodium or potassium hydroxide solution - toluene or methylene chloride, optionally with the addition of 0.1 to 1 mol of phase transfer catalyst, for example an ammonium or phosphonium compound. such as benzyldodecyldimethylammonium chloride or triethylbenzylammonium chloride (see also examples).

The compounds of formula I prepared by the process of the invention can be converted into acid addition salts.

The following acids are suitable for the preparation of physiologically tolerable acid addition salts of the compounds of the formula I:

hydrohalic acids such as hydrochloric acid and hydrobromic acid, in particular hydrochloric acid, further phosphoric acid, nitric acid, sulfuric acid, mono- and dibasic carboxylic and hydroxycarbonic acids, such as, for example, acetic acid, maleic acid, succinic acid, fumaric acid tartaric acid, citric acid, salicylic acid, sorbic acid, and lactic acid as well as sulfonic acids such as p-toluenesulfonic acid and 1,5-naphthalenedisulfonic acid. .

Acid addition salts of compounds of formula (I) may be obtained in a simple manner by conventional methods used to prepare salts, for example by dissolving a compound of formula (I) in a suitable inert solvent and adding an acid, for example hydrochloric acid. The resulting salts can be isolated in a conventional manner, for example by filtration, and optionally purified by washing with an inert organic solvent.

The active compounds according to the invention show a strong microbicidal action and can be used in practice to combat undesirable microorganisms. The active compounds described are suitable for use as plant protection agents.

Fungicides are used in plant protection to control fungi of the classes Oornycetes, Plasmodiophoromycetes, Chytridiomycetes, Zygomycetes, Ascomyceteis, Basidiomycetes and Deuteromycetes.

Since the plants of the active compound according to the invention are well tolerated in the concentrations necessary for combating fungal diseases of the plants, they can be used for the treatment of above-ground parts of plants, seedlings and seeds, and for the treatment of soil.

As plant protection agents, the active compounds according to the invention can be used with particularly good results for combating cereal diseases such as powdery mildew and powdery mildew, for controlling Podosphaera species, such as the causative agent of apple powdery mildew (Podosphaera leucotricha), as well as combating · Erysiphe species; such as cucumber powdery mildew (Erysiphe cichoracearum). Advantageously, the active compounds according to the invention have not only a protective effect, but are also partially systemically active, which makes it possible to protect the plants against fungal infections by feeding the active substance to the above-ground parts of the plant via soil and root system or through seed.

The active substances can be converted into conventional means such as solutions, emulsions, aerosols, natural and synthetic substances impregnated with active substances, small particles coated with polymeric substances. substances with flame retardants such as smoke cartridges, smoke jars, smoke spirals and the like, as well as compositions in the form of active substance concentrates. Cold or hot fog diffusers.

These compositions are prepared in a known manner, for example by mixing the active ingredient with fillers, i.e. liquid solvents, with liquefied gases present under pressure and / or ¹ solid carriers, optionally using surfactants, i.e. emulsifiers and / or dispersants and / or foaming agents. If water is used as a filler, it is also possible to use, for example, organic solvents as co-solvents. Suitable liquid solvents are, in principle, aromatics, such as xylene, toluene or alkylnaphthalenes, chlorinated aromatics or. Chlorinated aliphatic hydrocarbons such as chlorobenzenes, chlorethylenes or methylene chloride, aliphatic hydrocarbons such as cyclohexene or paraffins, for example petroleum fractions, alcohols such as butanol or glycol and their ethers and esters, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, strongly polar solvents such as dimethylformamide and dimethyl sulfoxide, as well as water. By liquefied gaseous fillers or carriers is meant those liquids which are gaseous at normal temperature and pressure, for example aerosol propellants, such as halogenated hydrocarbons, as well as butane, propane, nitrogen and carbon dioxide. As · solid carriers there are suitable: for example ground natural minerals, such as · kaolins, clays, talc, chalk, quartz, attapulgite, · m ^ι ontmoríllonit or diatomaceous earth, and ground synthetic minerals, such as · highly dispersed silicic acid, alumina and silicates. Suitable solid carriers for the preparation of granulates are, for example, crushed and fractionated natural stone materials such as limestone, marble, pumice, sepiolite and dolomite, as well as synthetic granules of inorganic and organic flours and granules of organic material, such as sawdust, coconut shells, corn cobs and tobacco stalks. Suitable emulsifiers and / or foaming agents are non-ionic and anonic emulsifiers, such as polyoxyethylene fatty acid esters, fatty alcohol polyoxyethylene ethers, for example alkylaryl polyglycol ether, alkylsulfonates, alkylsulfates. arylsulfonates. and protein hydrolysates, and the like. dlspergátory. for example lignin, sulfite waste liquors and methylcellulose.

The compositions of the invention may contain adhesives such as carboxymethylcellulose, natural and synthetic powdered, granular or latex polymers such as gum arabic, polyvinyl alcohol and polyvinyl acetate.

Furthermore, they may. means. contain dyes such as inorganic pigments, for example iron oxide, titanium dioxide and ferrocyanide blue, and organic. dyes such as alizarin dyes and metallic azo-phthalocyanine dyes, as well as trace elements such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc.

The concentrates generally contain between 0 ', 1 and 95% by weight, preferably between 0.5 and 90% by weight, of active ingredient.

The active compounds according to the invention may be present in the formulations in admixture with other active substances, such as fungicides, bactericides, insecticides, acaricides, nematicides, herbicides, preservatives, avian nutrients, growth agents, plant nutrients and texture-improving agents. soil.

The active compounds according to the invention can be applied as such, in general. in the form of concentrates or 'therefrom' by further diluting the ready-to-use dosage forms, such as ready-to-use solutions, emulsions, 'suspensions, powders,' pastes and granules. Application is carried out in a conventional manner, for example by watering, dipping, spraying by misting, evaporation, injection, flooding, painting, dusting, tossing, dry, wet pickling. wet or in suspension or incrustation.

In the treatment of aerial parts of plants, the concentrations of the active compounds in the application forms can be varied within wide limits. These concentrations generally lie between 1 and 0.0001% by weight, preferably between 0.5 and 0.001% by weight.

In the treatment of seed, it is generally necessary to use from 0.001 to 50 grams, preferably 0.01 to 10 g, of active compound per kilogram of seed.

For the treatment of the soil, it is necessary to use the active compounds in concentrations of 0.00001 to 0.1% by weight, preferably 0.0001 to 0.02%, depending on the type of effect desired.

In the examples below, the following compounds were used as comparators:

Example A

Protective test (treatment of shoots) for Erysiphe graminis var. Hordei (leaf-destroying mycosis)

To prepare a suitable active ingredient, 0.25 part by weight of the active compound is stirred in 25 parts by weight of dimethylformamide and 0.06 part by weight of alkylaryl polyglycol ether as emulsifier, and 975 parts by weight of water are added. The concentrate obtained is then diluted with water to the desired final concentration.

To determine the projective effect, young barley plants (Amsel species) in the single leaf stage are sprayed with the 'prepared' active ingredient 'and moistened with spores of Erysiphe graminis' var. hordei.

After six days of growing at 21-22 ° C and 80-90% air humidity, the extent of the disease on the plants is evaluated. The degree of infestation is expressed as the percentage of infestation of untreated control plants, with 0% representing no infestation and 100% of the same infestation as untreated control plants. The lower the degree of attack, the more effective the test substance is.

The test results are shown in the following table:

Table A

Protective test (shoot treatment) for Erysiphe graminis var. hordei (mycosis - destructive leaves)

Active substance

Concentration of active substance in spraying (% by weight)

Infestation in% attack of untreated control plants

0.001

72.5 (known)

C (CHJ _A c-chich ^ (3))

0.001

26.9

0.001

25.0

A n— ^J m

N ---- 1 12)

0.001

Example B

Test of systemic action on powdery mildew (Erysiphe graminis var. Hordei) - fungal disease of shoots - mobiles

The active ingredient is used in the form of powdered seed dressings. The mordant is prepared by mixing the respective active ingredient with a mixture of equal parts by weight of grease and diatomaceous earth to form a finely powdered mixture containing the active ingredient at the desired concentration.

The barley seed is treated by shaking with the prepared meridium in a closed glass container. The seed is then sieved (3X12 grains) 2 centimeters deep-flowered pots containing a mixture of one volume - part of standard peat soil - and one volume of quartz sand. Germination and emergence of grates takes place under favorable conditions in the greenhouse. 7 days after sowing, when the barley plants -flower -the first leaf -dusted with fresh -spores of Erysiphegraminis var. hordei-α are further cultured at a temperature of 21-22 ° C and 80-90% relative air humidity under a 16 hour illumination per day. Typical powdery mildew spots are formed on the leaves of the plants within 6 days.

The degree of infestation is expressed as the percentage of infestation of the untreated control plants, with 0% indicating no infestation and 100% the same infestation as untreated control plants. The more active the active substance, the lower the extent of the disease.

The test results are shown in the following table:

Table В

Test of systemic effect on powdery mildew (Eryslphe graminis var, roba of grain shoots) hordei) - mushroom cho- active substance Concentration Consumption Attack (example number) active substance mordants % of attacks in the stain (g / kg) untreated (w / o) • seeds.) control plant

(known)

(3)

С (СН _а ) _э О-СН (СН ^ с <сн _а ) _ъ 0 ^ Η ₅

С (СН _{3) 3}

О'СН ₃

12)

С (СН ₃ ) ₃ ° ~ ^с г.Н5Г

25 10 50.0 25 10 0.0 25 ilO 0.0 25 10 33.8

Cl

2'5 с = с.

о-с ₂ н ₅ (4)

0.0

Protective test for apple powdery mildew (Podosphaera)

Solvent:

4.7 parts by weight of acetone

Emulsifier:

0.3 parts by weight of alkylaryl polyglycol ether

Water:

95.0 parts by weight

The amount of active ingredient required to achieve the desired concentration of active ingredient in the spray is mixed with the indicated amount of solvent and the concentrate is diluted with the specified amount of water containing the above ingredients.

By spraying, young apple seedlings having 4-6 leaves are sprayed until wet.

The plants are kept in a greenhouse at 20 ° C and a relative humidity of 70 percent for 24 hours, then inoculated by dusting with conidia of Podospharea leucotricha (apple mildew) and placed in a greenhouse at 21-23 ° C and a relative air humidity of about 70%. .

days after inoculation, infestation of the seedlings under investigation is determined. The values obtained are converted to assault in%.

% means no infection, 100 percent represents complete infestation of plants.

The following table shows the active substances, the active substance concentrations and the results obtained:

Table. C

Protective test for apple powdery mildew (Podosphaera)

Active substance (example number) Infestation in% at active substance concentration 0.001%

(known)

C (CW _a ) ₃ * О-С _г Ну (3)

4 '

O-CHCHi (3)

C (CH ₃ ) ₃ O-CH ₃ (2)

Example D

Test for powdery mildew (Erysiphe) protective effect (cucumbers)

Solvent:

4.7 parts by weight of acetone

Emulsifier:

0.3 part by weight of alkylaryl polyglycol thera

Water: ..... 1

95.0 parts by weight

The amount of active ingredient required to achieve the desired concentration of active ingredient in the liquid spray is mixed with the indicated amount of solvent and the concentrate is diluted with the specified amount of water containing the above ingredients.

Young cucumber plants having about 3 true leaves are sprayed by liquid spray until dew. The plants are allowed to dry for 24 hours in a greenhouse and then inoculated by dusting with conidia of the fungus Erysiphe cichoracearum (powdery mildew). The plants were subsequently placed in a greenhouse at 23 to 24 ^O C, and about 75% relative humidity.

After 12 days, infestation of the plants with oc214717 rec. The values obtained are converted to infestation in%.

0 ' ^o / o .. means no attack, 100% Table D.

test for powdery mildew (Erysiphe) protective effect active substance (example number) names complete infestation of plants.

The test results are. in the following table:

(cucumbers) infestation in% at active substance concentration 0.0005%

CICHj

O-CHICH (3) a-c ^ s N - (1)

The preparation of the active compounds according to the invention is illustrated by the following examples.

EXAMPLE 1 (E) -form [alpha] ₄ (0/ _4- ^C- O-CH2-O)

N

K. 29.5 g (0.1 molar) 1- (4-chlorophenoxy) -3,3-dimethyl-1- (1,2,4-triazol-1-yl) butan-2-one 16 g (0.1 mol) of ethyl iodide and 0.5 g of benzyldodecyldimethylammonium chloride in 50 ml of dimethylsulfoxide were slowly added dropwise at room temperature to 4.4 g (0.11 mol) of sodium hydroxide. dissolved. in a small amount of water. Ongoing reaction is slightly exothermic (temperature rises up to about 50 ° C). The reaction mixture was stirred at room temperature for 3 hours, then poured into water, neutralized with acetic acid and extracted with methylene chloride. . The organic phase is shaken with water and dried. se. sodium sulphate. and evaporate. After separation by Craig shaking (countercurrent shaking), 6.0 g (22% of theory) of 1- (4-chlorophenoxy) -3,3-dimethyl-2-ethoxy-1- (1,2,4-triazole) were obtained. -lyl) -1-butene in the form of a mixture of isomers (Z / E = 1/3).

Preparative HPLC showed (Z) - and (E) 1- (4-chlorophenoxy) -3,3-dimethyl-2-ethoxy-1- (1,2,4-triazol-1-yl) form. 1-butene, the (E) form having a melting point of 57-62 ° C.

The attribution of the structure to both of these isomers was carried out by 1 H-NHR spectroscopy using Eu (TFC) with [tris- (3-fluoromethylhydroxymethylene) -d-camphoratoeuropium; see Merck, Constantine, workbook 2/1978, p. 9) as. signal shifting agents (VR-J). Measurements are made in deuterochloroform. The results are shown in the following table:

1β

Table

Offset values and offset differences of resonant signals when measured with and without reagent.

Fragment δ (ppm) excluding VR (Z) -isomer δ (ppm) ! S VR AS δ (ppm) excluding VR (E) -isomer δ (ppm) with VR AS С (СНз) з 1.00 2.77 1.77 1.15 2.16 1.01 СНз 1,22 1.80 0.58 1,02 2.70 1.68 CH2 4.02 5.10 1.08 3.33 6.45 .3,12 triaz. H 7.94 > 12 > 4 7.91 ,> 12 > 4 8.10 8.31 arom. H 7.02 7.80 0.78 6.9 (2, 7.58 0.66 7.25 8.60 1.35 7.19 8.46 1,27

Preparation of starting materials:

Dissolve 418 g (6,6 mol) of 1,2,4-triazole in 3000 ml of acetone, add 934 g (7.2 mol) of anhydrous powdered potassium carbonate to the solution, heat to boiling and add dropwise. 1565 g (6 mol) of 1- (4-chlorophenoxy) -1-chloro-3,3-dimethylbutan-2-one in 1500 ml of acetone at a rate such that the mixture boils under reflux without heating. to complete the reaction for 15 hours under reflux, the precipitate was filtered off, washed with acetone and discarded, the solvent was evaporated from the filtrate in a water-jet vacuum, the residue was taken up in 3000 ml of toluene and washed once with 100 g of 37% acid. The aqueous phase is separated and discarded, the organic phase is washed with 5000 ml of water and, after addition of another 4000 ml of toluene, stirred at room temperature with a solution of 145 g of sodium hydroxide in 3500 ml of water for 6 hours. The mixture was separated, washed with water until neutral, and the solvent was removed in a water pump vacuum. 1535 g (87% of theory) of 1- (4-chlorophenoxy) -3,3-dimethyl-1- (1,2,4-triazol-1-yl) butan-2-one are obtained. Deň: 32 ° C.

° ' ^CHr

CP

771 g (6 mol) of 4'-chlorophenol are dissolved in 3600 ml of acetone, 3 grams of anhydrous potassium iodide and 910 g (6.6 mol) of anhydrous powdered potassium carbonate are added thereto, and the mixture is added dropwise at reflux. 895 g (6.3 mol) of 94.6% monochlorpinacoline. After stirring at reflux for 2 hours, the precipitate formed is filtered off, washed with acetone and discarded. The filtrate was freed of solvent in a water pump vacuum, the white residue was taken up in 3000 ml of carbon tetrachloride and heated to 60 ° C. 891 g (6.6 mol) of sulfuryl chloride were added dropwise to the resulting solution without further heating at such a rate that gas evolution continued. After the addition was complete, the reaction mixture was heated under reflux for 15 hours, after which the solvent was distilled off in a water pump vacuum. 1565 g of 1- (4-chlorophenoxy) -1-chloro-3,3-dimethylbutan-2-one are obtained in quantitative yield, which can be used in the reaction described above without further purification.

Example 2 (E) -form

CÍCHjl,

O-CH3

C 146.5 g (0.5 mol) of 1- (4-chlorophenoxy) -3,3-dimethyl-1- (1,2,4-triazol-1-yl) butan-2-one in 250 ml of dimethylsulfoxide 30 grams of dissolved potassium hydroxide is added dropwise! in a small amount of water. After stirring for 1 hour, 65 g (0.51 mol) of dimethylsulfate was added dropwise while the temperature was maintained at about 40 ° C by ice cooling. The reaction mixture was stirred for 2 hours, then water was added, the crystalline precipitate was filtered off with suction and recrystallized from petroleum ether. 51 g (33% of theory) of (E) -1- (4-chlorophenoxy) 3,3-dimethyl-2-methoxy-1- (1,2,4-triazol-1-yl) - are obtained. 134 DEG-138 DEG C. butene.

The following compounds are obtained accordingly:

J

Melting point

° C)

OR i

Ar-XCCC (СН ₃ ) ₃ ig N ---- ¹ (I)

Example Ar number

3 0 1-C3H7 129—132 (E-form) 4 CH2 C2H5 103—105 (Z-form) 5 CH2 C2H5 n _D ² 2 = 1.5370 (E-form)

Claims (2)

I will invent the subject Fungicidal composition, characterized in that it contains at least one 1,2,4-triazolyl-enol ether of the formula I as active substance. STEED Ar-XC = CC (CH _s > _b from ⁿ 'N 1' η N ---- ¹ (I) in which Ar represents a phenyl group optionally substituted by halogen, R is C 1 -C 4 alkyl and X represents an oxygen atom or a methylene group, or an acid addition salt thereof. 2. A process for the preparation of the active compounds of the formula I according to claim 1 and their acid addition salts, characterized in that the 1,2,4-triazolyl ketones of the formula II are: O Ar-X-CH-C-ClCH3 iii IN— ¹ (in II in which Ar and X are as defined in point 1, reacted with alkyl sulfates and / or alkyl halides in the presence of a base and in the presence of an organic diluent, or in an aqueous-organic biphasic system in the presence of a base and in the presence of a phase transfer catalyst. optionally, an acid is added.